Ingela Schnittger, MD

All Publications

• Impact of myocardial bridging on coronary artery plaque formation and long-term mortality after heart transplantation. International journal of cardiology Tanaka, S., Okada, K., Kitahara, H., Luikart, H., Yock, P. G., Yeung, A. C., Schnittger, I., Tremmel, J. A., Fitzgerald, P. J., Khush, K. K., Fearon, W. F., Honda, Y. 2023

  Abstract

  OBJECTIVES: This study aimed to explore the impact of myocardial bridging (MB) on early development of cardiac allograft vasculopathy and long-term graft survival after heart transplantation.BACKGROUND: MB has been reported to be associated with acceleration of proximal plaque development and endothelial dysfunction in native coronary atherosclerosis. However, its clinical significance in heart transplantation remains unclear.METHODS: In 103 heart-transplant recipients, serial (baseline and 1-year post-transplant) volumetric intravascular ultrasound (IVUS) analyses were performed in the first 50 mm of the left anterior descending (LAD) artery. Standard IVUS indices were evaluated in 3 equally divided LAD segments (proximal, middle, and distal segments). MB was defined by IVUS as an echolucent muscular band lying on top of the artery. The primary endpoint was death or re-transplantation, assessed for up to 12.2 years (median follow-up: 4.7 years).RESULTS: IVUS identified MB in 62% of the study population. At baseline, MB patients had smaller intimal volume in the distal LAD than non-MB patients (p = 0.002). During the first year, vessel volume decreased diffusely irrespective of the presence of MB. Intimal growth diffusely distributed in non-MB patients, whereas MB patients demonstrated significantly augmented intimal formation in the proximal LAD. Kaplan-Meier analysis revealed significantly lower event-free survival in patients with versus without MB (log-rank p = 0.02). In multivariate analysis, the presence of MB was independently associated with late adverse events [hazard ratio 5.1 (1.6-22.2)].CONCLUSION: MB appears to relate to accelerated proximal intimal growth and reduced long-term survival in heart-transplant recipients.

  View details for DOI 10.1016/j.ijcard.2023.03.014

  View details for PubMedID 36893856

• Symptomatic Myocardial Bridging in D-Transposition of the Great Arteries Post-Arterial Switch JACC: Case Reports, Vol 8, Iss , Pp 101730- (2023) Vaikunth, S. S., Murphy, D. J., Tremmel, J. A., Schnittger, I., Mitchell, R. S., Maeda, K., Rogers, I. S. 2023

  View details for DOI 10.1016/j.jaccas.2022.101730

• Colocalization of Coronary Plaque with Wall Shear Stress in Myocardial Bridge Patients. Cardiovascular engineering and technology Khan, M. O., Nishi, T., Imura, S., Seo, J., Wang, H., Honda, Y., Nieman, K., Rogers, I. S., Tremmel, J. A., Boyd, J., Schnittger, I., Marsden, A. 2022

  Abstract

  PURPOSE: Patients with myocardial bridges (MBs) have a higher prevalence of atherosclerosis. Wall shear stress (WSS) has previously been correlated with plaque in coronary artery disease patients, but such correlations have not been investigated in symptomatic MB patients. The aim of this paper was to use a multi-scale computational fluid dynamics (CFD) framework to simulate hemodynamics in MB patient, and investigate the co-localization of WSS and plaque.METHODS: We identified N = 10 patients from a previously reported cohort of 50 symptomatic MB patients, all of whom had plaque in the proximal vessel. Dynamic 3D models were reconstructed from coronary computed tomography angiography (CCTA), intravascular ultrasound (IVUS) and catheter angiograms. CFD simulations were performed to compute WSS proximal to, within and distal to the MB. Plaque was quantified from IVUS images in 2 mm segments and registered to CFD model. Plaque area was compared to absolute and patient-normalized WSS.RESULTS: WSS was lower in the proximal segment compared to the bridge segment (6.1 ± 2.9 vs. 16.0 ± 7.1 dynes/cm2, p value < 0.01). Plaque area and plaque burden measured from IVUS peaked at 1-3 cm proximal to the MB entrance, coinciding with the first diagonal branch. Normalized WSS showed a statistically significant moderate correlation with plaque area (r = 0.41, p < 0.01).CONCLUSION: WSS may be obtained non-invasively in MB patients and provides a surrogate marker of plaque area. Using CFD, it may be possible to non-invasively assess the extent of plaque area, and identify patients who could benefit from frequent monitoring or medical management.

  View details for DOI 10.1007/s13239-022-00616-4

  View details for PubMedID 35296987

• Relationship Between Coronary Atheroma, Epicardial Adipose Tissue Inflammation, and Adipocyte Differentiation Across the Human Myocardial Bridge. Journal of the American Heart Association McLaughlin, T., Schnittger, I., Nagy, A., Zanley, E., Xu, Y., Song, Y., Nieman, K., Tremmel, J. A., Dey, D., Boyd, J., Sacks, H. 2021: e021003

  Abstract

  Background Inflammation in epicardial adipose tissue (EAT) may contribute to coronary atherosclerosis. Myocardial bridge is a congenital anomaly in which the left anterior descending coronary artery takes a "tunneled" course under a bridge of myocardium: while atherosclerosis develops in the proximal left anterior descending coronary artery, the bridged portion is spared, highlighting the possibility that geographic separation from inflamed EAT is protective. We tested the hypothesis that inflammation in EAT was related to atherosclerosis by comparing EAT from proximal and bridge depots in individuals with myocardial bridge and varying degrees of atherosclerotic plaque. Methods and Results Maximal plaque burden was quantified by intravascular ultrasound, and inflammation was quantified by pericoronary EAT signal attenuation (pericoronary adipose tissue attenuation) from cardiac computed tomography scans. EAT overlying the proximal left anterior descending coronary artery and myocardial bridge was harvested for measurement of mRNA and microRNA (miRNA) using custom chips by Nanostring; inflammatory cytokines were measured in tissue culture supernatants. Pericoronary adipose tissue attenuation was increased, indicating inflammation, in proximal versus bridge EAT, in proportion to atherosclerotic plaque. Individuals with moderate-high versus low plaque burden exhibited greater expression of inflammation and hypoxia genes, and lower expression of adipogenesis genes. Comparison of gene expression in proximal versus bridge depots revealed differences only in participants with moderate-high plaque: inflammation was higher in proximal and adipogenesis lower in bridge EAT. Secreted inflammatory cytokines tended to be higher in proximal EAT. Hypoxia-inducible factor 1a was highly associated with inflammatory gene expression. Seven miRNAs were differentially expressed by depot: 3192-5P, 518D-3P, and 532-5P were upregulated in proximal EAT, whereas miR 630, 575, 16-5P, and 320E were upregulated in bridge EAT. miR 630 correlated directly with plaque burden and inversely with adipogenesis genes. miR 3192-5P, 518D-3P, and 532-5P correlated inversely with hypoxia/oxidative stress, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG1a), adipogenesis, and angiogenesis genes. Conclusions Inflammation is specifically elevated in EAT overlying atherosclerotic plaque, suggesting that EAT inflammation is caused by atherogenic molecular signals, including hypoxia-inducible factor 1a and/or miRNAs in an "inside-to-out" relationship. Adipogenesis was suppressed in the bridge EAT, but only in the presence of atherosclerotic plaque, supporting cross talk between the vasculature and EAT. miR 630 in EAT, expressed differentially according to burden of atherosclerotic plaque, and 3 other miRNAs appear to inhibit key genes related to adipogenesis, angiogenesis, hypoxia/oxidative stress, and thermogenesis in EAT, highlighting a role for miRNA in mediating cross talk between the coronary vasculature and EAT.

  View details for DOI 10.1161/JAHA.121.021003

  View details for PubMedID 34726081

• Impact of Diastolic Vessel Restriction on Quality of Life in Symptomatic Myocardial Bridging Patients Treated With Surgical Unroofing: Preoperative Assessments With Intravascular Ultrasound and Coronary Computed Tomography Angiography. Circulation. Cardiovascular interventions Hashikata, T., Honda, Y., Wang, H., Pargaonkar, V. S., Nishi, T., Hollak, M. B., Rogers, I. S., Nieman, K., Yock, P. G., Fitzgerald, P. J., Schnittger, I., Boyd, J. H., Tremmel, J. A. 2021; 14 (10): e011062

  Abstract

  [Figure: see text].

  View details for DOI 10.1161/CIRCINTERVENTIONS.121.011062

  View details for PubMedID 34665656

• Abnormal shear stress and residence time are associated with proximal coronary atheroma in the presence of myocardial bridging. International journal of cardiology Yong, A. S., Pargaonkar, V. S., Wong, C. C., Javadzdegan, A., Yamada, R., Tanaka, S., Kimura, T., Rogers, I. S., Sen, I., Kritharides, L., Schnittger, I., Tremmel, J. A. 2021

  Abstract

  BACKGROUND: Atheromatous plaques tend to form in the coronary segments proximal to a myocardial bridge (MB), but the mechanism of this occurrence remains unclear. This study evaluates the relationship between blood flow perturbations and plaque formation in patients with an MB.METHODS AND RESULTS: A total of 92 patients with an MB in the mid left anterior descending artery (LAD) and 20 patients without an MB were included. Coronary angiography, intravascular ultrasound, and coronary physiology measurements were performed. A moving-boundary computational fluid dynamics algorithm was used to derive wall shear stress (WSS) and peak residence time (PRT). Patients with an MB had lower WSS (0.46 ± 0.21 vs. 0.96 ± 0.33 Pa, p < 0.001) and higher maximal plaque burden (33.6 ± 15.0 vs. 14.2 ± 5.8%, p < 0.001) within the proximal LAD compared to those without. Plaque burden in the proximal LAD correlated significantly with proximal WSS (r = -0.51, p < 0.001) and PRT (r = 0.60, p < 0.001). In patients with an MB, the site of maximal plaque burden occurred 23.4 ± 13.3 mm proximal to the entrance of the MB, corresponding to the site of PRT.CONCLUSIONS: Regions of low WSS and high PRT occur in arterial segments proximal to an MB, and this is associated with the degree and location of coronary atheroma formation.

  View details for DOI 10.1016/j.ijcard.2021.08.011

  View details for PubMedID 34375705

• Myocardial Bridge in Pregnancy: Beyond a 'Normal Anatomic Variant'. Joudi, N., Datoc, I., Leonard, S., Lee, C., Schnittger, I., Khandelwal, A., Bianco, K. SPRINGER HEIDELBERG. 2021: 267A

  View details for Web of Science ID 000675441000561

• IMPACT OF DIASTOLIC VESSEL RESTRICTION ON CLINICAL SYMPTOMS IN PATIENTS WITH SYMPTOMATIC MYOCARDIAL BRIDGING Hashikata, T., Honda, Y., Wang, H., Pargaonkar, V., Hollak, M., Rogers, I. S., Yock, P., Fitzgerald, P., Schnittger, I., Boyd, J., Tremmel, J. ELSEVIER SCIENCE INC. 2021: 165

  View details for Web of Science ID 000647487500165

• Invasive Assessment of Myocardial Bridging in Patients with Angina and No Obstructive Coronary Artery Disease. EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology Pargaonkar, V. S., Kimura, T., Kameda, R., Tanaka, S., Yamada, R., Schwartz, J. G., Perl, L., Rogers, I. S., Honda, Y., Fitzgerald, P., Schnittger, I., Tremmel, J. A. 2020

  Abstract

  AIMS: Angina and no obstructive CAD (ANOCA) is common. A potential cause of angina in this patient population is a myocardial bridge (MB). We studied the anatomical and hemodynamic characteristics of an MB in patients with angina and no obstructive CAD.METHODS AND RESULTS: Using intravascular ultrasound (IVUS), we identified 184 MBs in 154 patients. We evaluated MB length, arterial compression, and halo thickness. MB muscle index (MMI) was defined as MB length*halo thickness. Hemodynamic testing of the MB was performed using an intracoronary pressure/Doppler flow wire at rest and during dobutamine stress. We defined an abnormal diastolic fractional flow reserve (dFFR) as ≤0.76 during stress. The median MB length was 22.9 mm, arterial compression 30.9%, and halo thickness 0.5mm. The median MMI was 12.1. Endothelial and microvascular dysfunction were present in 85.4% and 22.1%, respectively. At peak dobutamine stress, 94.2% of patients had a dFFR≤0.76 within and/or distal to the MB. MMI was associated with an abnormal dFFR.CONCLUSIONS: In select patients with ANOCA who have an MB by IVUS, a majority have evidence of a hemodynamically significant dFFR during dobutamine stress, suggesting the MB as a cause of their angina. A comprehensive invasive assessment of such patients during coronary angiography provides important diagnostic information that can guide management.

  View details for DOI 10.4244/EIJ-D-20-00779

  View details for PubMedID 33074153

• Effect of ranolazine on symptom and quality of life in patients with angina in the absence of obstructive coronary artery disease: A case control study. International journal of cardiology Pargaonkar, V. S., Tremmel, J. A., Schnittger, I., Khandelwal, A. 2020

  Abstract

  BACKGROUND: More than 20% of patients presenting to the catheterization lab have no significant obstructive coronary artery disease (CAD) despite having angina. Several occult coronary abnormalities, including endothelial dysfunction, microvascular dysfunction (MVD), and/or a myocardial bridge (MB), may explain their symptoms. We studied the effect of ranolazine on symptoms and quality of life (QOL) in these patients.METHODS: We retrospectively studied 53 patients prescribed with ranolazine, matched on sex and age, with 106 patients on standard of care who underwent comprehensive invasive testing. Endothelial dysfunction was defined as a decrease in luminal diameter of >20% after intracoronary acetylcholine, MVD as an index of microvascular resistance ≥25, and a MB as an echolucent half-moon sign and/or ≥10% systolic compression on intravascular ultrasound. A Seattle Angina Questionnaire (SAQ) and SF-12 questionnaire were completed at baseline and follow-up.RESULTS: Median follow-up was 1.9 (1.7-2.2) years. Endothelial dysfunction was present in 109 (69%), MVD in 36 (23%), and an MB in 86 (54%). Both groups had significant improvement in all dimensions of the SF-12 and SAQ with the exception of treatment satisfaction. We found no significant difference in change in SAQ and SF-12 scores between the groups, although the ranolazine group had significantly lower baseline SAQ scores.CONCLUSION: In patients with angina and no obstructive CAD, ranolazine is no different than standard of care in symptomatic and QOL improvement. Further randomized trials are warrented to confirm our findings and identify novel medical therapies in this patient population.

  View details for DOI 10.1016/j.ijcard.2020.02.014

  View details for PubMedID 32220488

• Accuracy of a novel stress echocardiography pattern for myocardial bridging in patients with angina and no obstructive coronary artery disease - A retrospective and prospective cohort study. International journal of cardiology Pargaonkar, V. S., Rogers, I. S., Su, J., Forsdahl, S. H., Kameda, R., Schreiber, D., Chan, F. P., Becker, H., Fleischmann, D., Tremmel, J. A., Schnittger, I. 2020

  Abstract

  BACKGROUND: Myocardial bridge (MB) may cause angina in patients with no obstructive coronary artery disease (CAD). We previously reported a novel stress echocardiography (SE) pattern of focal septal buckling with apical sparing in the end-systolic to early-diastolic phase that is associated with the presence of an MB. We evaluated the diagnostic accuracy of this pattern, and prospectively validated our results.METHODS: The retrospective cohort included 158 patients with angina who underwent both SE and coronary CT angiography (CCTA). The validation cohort included 37 patients who underwent CCTA in the emergency department for angina, and prospectively underwent SE. CCTA was used as a reference standard for the presence/absence of an MB, and also confirmed no obstructive CAD.RESULTS: In the retrospective cohort, an MB was present in 107 (67.7%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 91.6%, 70.6%, 86.7% and 80%, respectively. On logistic regression, focal septal buckling and Duke treadmill score were associated with an MB. In the validation cohort, an MB was present in 31 (84%). The sensitivity, specificity PPV and NPV were 90.3%, 83.3%, 96.5% and 62.5%, respectively. On logistic regression, focal septal buckling was associated with an MB.CONCLUSION: Presence of focal septal buckling with apical sparing on SE is an accurate predictor of an MB in patients with angina and no obstructive CAD. This pattern can reliably be used to screen patients who may benefit from advanced non-invasive/invasive testing for an MB as a cause of their angina.

  View details for DOI 10.1016/j.ijcard.2020.02.006

  View details for PubMedID 32145938

• Off-Pump Mini Thoracotomy Versus Sternotomy for Left Anterior Descending Myocardial Bridge Unroofing. The Annals of thoracic surgery Wang, H. n., Pargaonkar, V. S., Hironaka, C. E., Bajaj, S. S., Abbot, C. J., O'Donnell, C. T., Miller, S. L., Honda, Y. n., Rogers, I. S., Tremmel, J. A., Fischbein, M. P., Mitchell, R. S., Schnittger, I. n., Boyd, J. H. 2020

  Abstract

  Myocardial bridge (MB) of the left anterior descending (LAD) coronary artery occurs in approximately 25% of the population. For patients with a symptomatic, hemodynamically significant MB who fail medical therapy, MB unroofing represents the optimal surgical management. Here, we evaluated minimally invasive MB unroofing in selected patients compared with sternotomy.MB unroofing was performed in 141 adult patients via sternotomy on-pump (ST-on, n=40), sternotomy off-pump (ST-off, n=62), or mini thoracotomy off-pump (MT, n=39). Angina symptoms were assessed preoperatively and 6-months postoperatively using the Seattle Angina Questionnaire. Matching included all MT patients and 31 ST-off patients with similar MB characteristics, no previous cardiac surgery or coronary interventions, and no concomitant procedures.MT patients tended to have a shorter MB length than ST-on and ST-off patients (2.57 vs 2.93 vs 3.09 cm, p=0.166). ST-on patients had a longer hospital stay than ST-off and MT patients (5.0 vs 4.0 vs 3.0 days, p<0.001), and more blood transfusions (15.2% vs 0.0% vs 2.6%, p=0.002). After matching, MT patients had a shorter hospital stay than ST-off patients (3.0 vs 4.0 days, p=0.005). No deaths or major complications occurred in any group. In all groups, MB unroofing yielded significant symptomatic improvement regarding physical limitation, angina stability, angina frequency, treatment satisfaction, and quality of life.We report the largest experience of off-pump minimally invasive MB unroofing, which may be safely performed in carefully selected patients, yielding dramatic improvements in angina symptomatology at 6 months after surgery.

  View details for DOI 10.1016/j.athoracsur.2020.11.023

  View details for PubMedID 33333083

• Computed Tomographic Angiography-Based Fractional Flow Reserve Compared With Catheter-Based Dobutamine-Stress Diastolic Fractional Flow Reserve in Symptomatic Patients With a Myocardial Bridge and No Obstructive Coronary Artery Disease. Circulation. Cardiovascular imaging Jubran, A. n., Schnittger, I. n., Tremmel, J. n., Pargaonkar, V. n., Rogers, I. n., Becker, H. C., Yang, S. n., Mastrodicasa, D. n., Willemink, M. n., Fleischmann, D. n., Nieman, K. n. 2020; 13 (2): e009576

  View details for DOI 10.1161/CIRCIMAGING.119.009576

  View details for PubMedID 32069114

• A Step Back in the Diagnosis and Management of Myocardial Bridging. The Annals of thoracic surgery Schnittger, I., Boyd, J. H., Tremmel, J. A. 2019

  View details for DOI 10.1016/j.athoracsur.2019.09.051

  View details for PubMedID 31706871

• Impact of Myocardial Bridging on Long-Term Outcomes After Heart Transplantation: Risk Stratification With IVUS-Determined Anatomical Properties Okada, K., Nishi, T., Tanaka, S., Luikart, H., Yock, P. G., Yeung, A. C., Hibi, K., Kimura, K., Schnittger, I., Khush, K., Fearon, W., Honda, Y. ELSEVIER SCIENCE INC. 2019: B342

  View details for Web of Science ID 000487306300343

• EXPRESS: Myocardial Bridge - An Unrecognized Cause of Chest Pain in Pulmonary Arterial Hypertension. Pulmonary circulation Rajmohan, D. n., Sung, Y. K., Kudelko, K. n., Perez, V. i., Haddad, F. n., Tremmel, J. n., Schnittger, I. n., Zamanian, R. T., Spiekerkoetter, E. F. 2019: 2045894019860738

  View details for DOI 10.1177/2045894019860738

  View details for PubMedID 31187693

• Surgical unroofing of hemodynamically significant myocardial bridges in a pediatric population. The Journal of thoracic and cardiovascular surgery Maeda, K., Schnittger, I., Murphy, D. J., Tremmel, J. A., Boyd, J. H., Peng, L., Okada, K., Pargaonkar, V. S., Hanley, F. L., Mitchell, R. S., Rogers, I. S. 2018

  Abstract

  BACKGROUND: Although myocardial bridges (MBs) are traditionally regarded as incidental findings, it has been reported that adult patients with symptomatic MBs refractory to medical therapy benefit from unroofing. However, there is limited literature in the pediatric population. The aim of our study was to evaluate the indications and outcomes for unroofing in pediatric patients.METHODS: We retrospectively reviewed all pediatric patients with MB in our institution who underwent surgical relief. Clinical characteristics, relevant diagnostic data, intraoperative findings, and postoperative outcomes were evaluated.RESULTS: Between 2012 and 2016, 14 pediatric patients underwent surgical unroofing of left anterior descending artery MBs. Thirteen patients had anginal symptoms refractory to medical therapy, and 1 patient was asymptomatic until experiencing aborted sudden cardiac arrest during exercise. Thirteen patients underwent exercise stress echocardiography, all of which showed mid-septal dys-synergy. Coronary computed tomography imaging confirmed the presence of MBs in all patients. Intravascular ultrasound imaging confirmed the length of MBs: 28.2±16.3mm, halo thickness: 0.59±0.24mm, and compression of left anterior descending artery at resting heart rate: 33.0±11.6%. Invasive hemodynamic assessment with dobutamine confirmed the physiologic significance of the MBs with diastolic fractional flow reserve: 0.59±0.13. Unroofing was performed with the patient under cardiopulmonary bypass (CPB) in the initial 9 cases and without CPB in the subsequent 5 cases. All patients were discharged without complications. The 13 symptomatic patients reported resolution of symptoms on follow-up, and improvement in symptoms and quality of life was documented using the Seattle Angina Questionnaire version 7.CONCLUSIONS: Unroofing of MBs can be safely performed in pediatric patients, with or without use of CPB. In symptomatic patients, unroofing can provide relief of symptoms refractory to medical therapy.

  View details for PubMedID 30005887

• MYOCARDIAL BRIDGE MUSCLE INDEX (MMI): A MARKER OF DISEASE SEVERITY AND ITS RELATIONSHIP WITH ENDOTHELIAL DYSFUNCTION AND SYMPTOMATIC OUTCOME IN PATIENTS WITH ANGINA AND A HEMODYNAMICALLY SIGNIFICANT MYOCARDIAL BRIDGE Pargaonkar, V., Schnittger, I., Rogers, I., Tanaka, S., Yamada, R., Kimura, T., Boyd, J., Tremmel, J. ELSEVIER SCIENCE INC. 2018: 160

  View details for DOI 10.1016/S0735-1097(18)30701-0

  View details for Web of Science ID 000429659701010

• Myocardial bridging is associated with exercise-induced ventricular arrhythmia and increases in QT dispersion. Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc Nishikii-Tachibana, M. n., Pargaonkar, V. S., Schnittger, I. n., Haddad, F. n., Rogers, I. S., Tremmel, J. A., Wang, P. J. 2017

  Abstract

  A myocardial bridge (MB) has been associated with ventricular arrhythmia and sudden death during exercise. QT dispersion (QTd) is a measure of abnormal repolarization and may predict ventricular arrhythmia. We investigated the frequency of ventricular arrhythmias during exercise and the QTd at rest and after exercise, in patients with an MB compared to a normal cohort.We studied the rest and stress ECG tracings of patients with an MB suspected by focal septal buckling on exercise echocardiography (EE) (Echo-MB group, N = 510), those with an MB confirmed by another examination (MB group, N = 110), and healthy controls (Control group, N = 198).The frequency of exercise-induced premature ventricular contractions (PVCs) was significantly higher in the Echo-MB and MB groups compared with the Control group (both p < .001). In all, 25 patients (4.9%) in the Echo-MB group, seven patients (6.4%) in the MB group and no patients in the Control group had exercise-induced non-sustained ventricular tachycardia (NSVT). There was no difference in the baseline QTd between the groups. In the Echo-MB and MB groups, QTd postexercise increased significantly when compared with baseline (both p < .001). Patients with NSVT had a higher frequency of male gender and an even greater increase in QTd with exercise compared with the non-NSVT group.There is an increased frequency of exercise-induced PVCs and NSVT in patients with MBs. Exercise significantly increases QTd in MB patients, with an even greater increase in QTd in MB patients with NSVT. Exercise in MB patients results in ventricular arrhythmias and abnormalities in repolarization.

  View details for PubMedID 28921787

• Myocardial Bridges on Coronary Computed Tomography Angiography　- Correlation With Intravascular Ultrasound and Fractional Flow Reserve. Circulation Journal Forsdahl, S. H., Rogers, I. S., Schnittger, I., et al 2017

  View details for DOI 10.1253/circj.CJ-17-0284

• Myocardial bridges: Overview of diagnosis and management. Congenital heart disease Rogers, I. S., Tremmel, J. A., Schnittger, I. n. 2017

  Abstract

  A myocardial bridge is a segment of a coronary artery that travels into the myocardium instead of the normal epicardial course. Although it is general perception that myocardial bridges are normal variants, patients with myocardial bridges can present with symptoms, such as exertional chest pain, that cannot be explained by a secondary etiology. Such patients may benefit from individualized medical/surgical therapy. This article describes the prevalence, clinical presentation, classification, evaluation, and management of children and adults with symptomatic myocardial bridges.

  View details for PubMedID 28675696

• Surgical Unroofing of Hemodynamically Significant Left Anterior Descending Myocardial Bridges. Annals of thoracic surgery Boyd, J. H., Pargaonkar, V. S., Scoville, D. H., Rogers, I. S., Kimura, T., Tanaka, S., Yamada, R., Fischbein, M. P., Tremmel, J. A., Mitchell, R. S., Schnittger, I. 2016

  Abstract

  Left anterior descending artery myocardial bridges (MBs) range from clinically insignificant incidental angiographic findings to a potential cause of sudden cardiac death. Within this spectrum, a group of patients with isolated, symptomatic, and hemodynamically significant MBs despite maximally tolerated medical therapy exist for whom the optimal treatment is controversial. We evaluated supraarterial myotomy, or surgical unroofing, of the left anterior descending MBs as an isolated procedure in these patients.In 50 adult patients, we prospectively evaluated baseline clinical characteristics, risk factors, and medications for coronary artery disease, relevant diagnostic data (stress echocardiography, computed tomography angiography, stress coronary angiogram with dobutamine challenge for measurement of diastolic fractional flow reserve, and intravascular ultrasonography), and anginal symptoms using the Seattle Angina Questionnaire. These patients then underwent surgical unroofing of their left anterior descending artery MBs followed by readministration of the Seattle Angina Questionnaire at 6.6-month (range, 2 to 13) follow-up after surgery.Dramatic improvements were noted in physical limitation due to angina (52.0 versus 87.1, p < 0.001), anginal stability (29.6 versus 66.4, p < 0.001), anginal frequency (52.1 versus 84.7, p < 0.001), treatment satisfaction (76.1 versus 93.9, p < 0.001), and quality of life (25.0 versus 78.9, p < 0.001), all five dimensions of the Seattle Angina Questionnaire. There were no major complications or deaths.Surgical unroofing of carefully selected patients with MBs can be performed safely as an independent procedure with significant improvement in symptoms postoperatively. It is the optimal treatment for isolated, symptomatic, and hemodynamically significant MBs resistant to maximally tolerated medical therapy.

  View details for DOI 10.1016/j.athoracsur.2016.08.035

  View details for PubMedID 27745841

• Myocardial Bridge and Acute Plaque Rupture. Journal of investigative medicine high impact case reports Perl, L., Daniels, D., Schwartz, J., Tanaka, S., Yeung, A., Tremmel, J. A., Schnittger, I. 2016; 4 (4): 2324709616680227-?

  Abstract

  A myocardial bridge (MB) is a common anatomic variant, most frequently located in the left anterior descending coronary artery, where a portion of the coronary artery is covered by myocardium. Importantly, MBs are known to result in a proximal atherosclerotic lesion. It has recently been postulated that these lesions predispose patients to acute coronary events, even in cases of otherwise low-risk patients. One such mechanism may involve acute plaque rupture. In this article, we report 2 cases of patients with MBs who presented with acute coronary syndromes despite having low cardiovascular risk. Their presentation was life-risking and both were treated urgently and studied with coronary angiographies and intravascular ultrasound. This latter modality confirmed a rupture of an atherosclerotic plaque proximal to the MB as a likely cause of the acute events. These cases, of unexplained acute coronary syndrome in low-risk patients, raise the question of alternative processes leading to the event and the role MB play as an underlying cause of ruptured plaques. In some cases, an active investigation for this entity may be warranted, due to the prognostic implications of the different therapeutic modalities, should an MB be discovered.

  View details for DOI 10.1177/2324709616680227

  View details for PubMedID 28251167

• Functional Versus Anatomic Assessment of Myocardial Bridging by Intravascular Ultrasound: Impact of Arterial Compression on Proximal Atherosclerotic Plaque JOURNAL of AMERICAN HEART ASSOCIATON Yamada, R., Tremmel, J., Tanaka, S., Lin, S., Kobayashi, Y., Hollak, M., Yock, P., Fitzgerald, P., Schnittger, I., Honda, Y. 2016; 20 (5(4))
• Exercise Strain Echocardiography in Patients With a Hemodynamically Significant Myocardial Bridge Assessed by Physiological Study. Journal of the American Heart Association Kobayashi, Y., Tremmel, J. A., Kobayashi, Y., Amsallem, M., Tanaka, S., Yamada, R., Rogers, I. S., Haddad, F., Schnittger, I. 2015; 4 (11)

  Abstract

  Although a myocardial bridge (MB) is often regarded as a benign coronary variant, recent studies have associated MB with focal myocardial ischemia. The physiological consequences of MB on ventricular function during stress have not been well established.We enrolled 58 patients with MB of the left anterior descending artery, diagnosed by intravascular ultrasound. Patients underwent invasive physiological evaluation of the MB by diastolic fractional flow reserve during dobutamine challenge and exercise echocardiography. Septal and lateral longitudinal strain (LS) were assessed at rest and immediately after exercise and compared with strain of matched controls. Absolute and relative changes in strain were also calculated. The mean age was 42.5±16.0 years. Fifty-five patients had a diastolic fractional flow reserve ≤0.76. At rest, there was no significant difference between the 2 groups in septal LS (19.0±1.8% for patients with MB versus 19.2±1.5% for control, P=0.53) and lateral LS (20.1±2.0% versus 20.0±1.6%, P=0.83). With stress, compared with controls, patients with MB had a lower peak septal LS (18.9±2.6% versus 21.7±1.6%, P<0.001) and lower absolute (-0.1±2.1% versus 2.5±1.3%, P<0.001) and relative change (-0.6±11.2% versus 13.1±7.8%, P<0.001) in septal LS, whereas there was no significant difference in lateral LS. In multivariate analysis, diastolic fractional flow reserve and length were independent determinants of lower changes in septal LS.Patients with a hemodynamically significant MB, determined by invasive diastolic fractional flow reserve, have significantly lower change in septal LS on exercise echocardiography, suggesting that septal LS may be useful for noninvasively assessing the hemodynamic significance of an MB.

  View details for DOI 10.1161/JAHA.115.002496

  View details for PubMedID 26581225

• Invasive physiologic and anatomic multimodality assessment of myocardial bridging Coronary Artery Disease Schwartz, J., Tanaka, S., Schnittger, I., Tremmel, J., et al 2015: 38-40

  View details for DOI 10.1097/MCA.0000000000000206

• Myocardial bridging. Journal of the American College of Cardiology Tremmel, J. A., Schnittger, I. 2014; 64 (20): 2178-2179

  View details for DOI 10.1016/j.jacc.2014.07.993

  View details for PubMedID 25457408

• Histological characteristics of myocardial bridge with an ultrasonic echolucent band. Comparison between intravascular ultrasound and histology. Circulation Journal Yamada, R., Turcott, R., Connolly, A., McConnell, M., Schnittger, I., et al 2014; 78 (2): 502-4
• A novel stress echocardiography pattern for myocardial bridge with invasive structural and hemodynamic correlation. Journal of the American Heart Association Lin, S., Tremmel, J. A., Yamada, R., Rogers, I. S., Yong, C. M., Turcott, R., McConnell, M. V., Dash, R., Schnittger, I. 2013; 2 (2)

  Abstract

  Patients with a myocardial bridge (MB) and no significant obstructive coronary artery disease (CAD) may experience angina presumably from ischemia, but noninvasive assessment has been limited and the underlying mechanism poorly understood. This study seeks to correlate a novel exercise echocardiography (EE) finding for MBs with invasive structural and hemodynamic measurements.Eighteen patients with angina and an EE pattern of focal end-systolic to early-diastolic buckling in the septum with apical sparing were prospectively enrolled for invasive assessment. This included coronary angiography, left anterior descending artery (LAD) intravascular ultrasound (IVUS), and intracoronary pressure and Doppler measurements at rest and during dobutamine stress. All patients were found to have an LAD MB on IVUS. The ratios of diastolic intracoronary pressure divided by aortic pressure at rest (Pd/Pa) and during dobutamine stress (diastolic fractional flow reserve [dFFR]) and peak Doppler flow velocity recordings at rest and with stress were successfully performed in 14 patients. All had abnormal dFFR (≤0.75) at stress within the bridge, distally or in both positions, and on average showed a more than doubling in peak Doppler flow velocity inside the MB at stress. Seventy-five percent of patients had normalization of dFFR distal to the MB, with partial pressure recovery and a decrease in peak Doppler flow velocity.A distinctive septal wall motion abnormality with apical sparing on EE is associated with a documented MB by IVUS and a decreased dFFR. We posit that the septal wall motion abnormality on EE is due to dynamic ischemia local to the compressed segment of the LAD from the increase in velocity and decrease in perfusion pressure, consistent with the Venturi effect.

  View details for DOI 10.1161/JAHA.113.000097

  View details for PubMedID 23591827

• Relationship Between Severity of Ischemia and Coronary Artery Disease for Different Stress Test Modalities in the ISCHEMIA Trial. Circulation. Cardiovascular interventions Reynolds, H. R., Page, C. B., Shaw, L. J., Berman, D. S., Chaitman, B. R., Picard, M. H., Kwong, R. Y., Min, J. K., Leipsic, J., Mancini, G. B., Budoff, M. J., Hague, C. J., Senior, R., Szwed, H., Bhargava, B., Celutkiene, J., Gadkari, M., Bainey, K. R., Doerr, R., Ramos, R. B., Ong, P., Naik, S. R., Steg, P. G., Goetschalckx, K., Chow, B. J., Scherrer-Crosbie, M., Phillips, L., Mark, D. B., Spertus, J. A., Alexander, K. P., O'Brien, S. M., Boden, W. E., Bangalore, S., Stone, G. W., Maron, D. J., Hochman, J. S. 2024; 17 (12): e013743

  Abstract

  The relationship between the extent and severity of stress-induced ischemia and the extent and severity of anatomic coronary artery disease (CAD) in patients with obstructive CAD is multifactorial and includes the intensity of stress achieved, type of testing used, presence and extent of prior infarction, collateral blood flow, plaque characteristics, microvascular disease, coronary vasomotor tone, and genetic factors. Among chronic coronary disease participants with site-determined moderate or severe ischemia, we investigated associations between ischemia severity on stress testing and the extent of CAD on coronary computed tomography angiography.Clinically indicated stress testing included nuclear imaging, echocardiography, cardiac magnetic resonance imaging, or nonimaging exercise tolerance test. Among those with preserved renal function who underwent coronary computed tomography angiography, we examined relationships between ischemia and CAD by coronary computed tomography angiography, overall, and by stress test modality, regardless of subsequent randomization. Core laboratories categorized ischemia as severe, moderate, mild, or none, while the extent and severity of anatomic CAD were categorized based on the modified Duke prognostic index.Among 3601 participants with interpretable stress tests and coronary computed tomography angiography, ischemia severity was weakly associated with CAD extent/severity (r=0.27), with modest variability in strength of association by modality: nuclear (n=1532; r=0.40), echocardiography (n=827; r=0.15), cardiac magnetic resonance imaging (n=108; r=0.31), and exercise tolerance test (n=1134; r=0.18). The extent of infarction on nuclear imaging and echocardiography was weakly associated with CAD extent/severity.Overall, ischemia severity on stress testing showed weak to moderate associations with the anatomic extent of CAD in this cohort with moderate or severe ischemia on local interpretation and controlled symptoms.URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

  View details for DOI 10.1161/CIRCINTERVENTIONS.123.013743

  View details for PubMedID 39689188

• Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial. Circulation. Cardiovascular interventions Pracoń, R., Spertus, J. A., Broderick, S., Bangalore, S., Rockhold, F. W., Ruzyllo, W., Demchenko, E., Nageh, T., Grossman, G. B., Mavromatis, K., Manjunath, C. N., Smanio, P. E., Stone, G. W., Mancini, G. B., Boden, W. E., Newman, J. D., Reynolds, H. R., Hochman, J. S., Maron, D. J. 2024: e013435

  Abstract

  ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease.Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use.Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography.Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease.URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

  View details for DOI 10.1161/CIRCINTERVENTIONS.123.013435

  View details for PubMedID 38629312

• Sex Differences in Revascularization, Treatment Goals, and Outcomes of Patients With Chronic Coronary Disease: Insights From the ISCHEMIA Trial. Journal of the American Heart Association Reynolds, H. R., Cyr, D. D., Merz, C. N., Shaw, L. J., Chaitman, B. R., Boden, W. E., Alexander, K. P., Rosenberg, Y. D., Bangalore, S., Stone, G. W., Held, C., Spertus, J., Goetschalckx, K., Bockeria, O., Newman, J. D., Berger, J. S., Elghamaz, A., Lopes, R. D., Min, J. K., Berman, D. S., Picard, M. H., Kwong, R. Y., Harrington, R. A., Thomas, B., O'Brien, S. M., Maron, D. J., Hochman, J. S., ISCHEMIA Research Group *, Mavromatis, K., Linefsky, J., Miller, T., Banerjee, S., Reynolds, H. R., Newman, J. D., Bangalore, S., Donnino, R. M., Phillips, L. M., Saric, M., Abdul-Nour, K., Stone, P. H., Jang, J. J., Yee, G., Weitz, S., Arnold, S., O'Keefe, J. H., Shapiro, M. D., El-Hajjar, M., Sidhu, M. S., Fein, S. A., Torosoff, M. T., Lyubarova, R., Mookherjee, S., Drzymalski, K., McFalls, E. O., Garcia, S. A., Bertog, S. C., Siddiqui, R. A., Ishani, A., Hansen, R. A., Khouri, M. G., Goldberg, J. L., Goldweit, R., Cohen, R. A., Mirrer, B., Navarro, V., Winchester, D. E., Kronenberg, M., Rogal, P., McFarren, C., Heitner, J. F., Dauber, I. M., Cannan, C., Sudarshan, S., Mehta, P. K., McDaniel, M., Lerakis, S., Quyyumi, A., Wenger, N. K., Hedgepeth, C. M., Hurlburt, H., Rosen, A., Sahul, Z., Booth, D., Leung, S., Abdel-Latif, A., Reda, H., Ziada, K., Setty, S., Barua, R. S., Hage, F., Caldeira, C., Davies, J. E., Leesar, M., Heo, J., Iskandrian, A., Al Solaiman, F., Singh, S., Dajani, K., El-Hajjar, M., Der Mesropian, P., Sacco, J., McCandless, B., Orgera, M., Sidhu, M. S., Arif, I., Kerr, H., Trejo Gutierrez, J. F., Fletcher, G., Lane, G. E., Neeson, L. M., Parikh, P. P., Pollak, P. M., Shapiro, B. P., Landolfo, K., Gemignani, A., O'Rourke, D., Meadows, J. L., Call, J. T., Hannan, J., Bojar, R., Kumar, D., Mukai, J., Martin, E. T., Vorobiof, G., Moorman, A., Kinlay, S., Hamburger, R. J., Rocco, T. P., Bhatt, D. L., Croce, K., Quin, J. A., Anumpa, J., Zenati, M., Faxon, D. P., Rayos, G., Seedhom, A., Sullenberger, L., Kumkumian, G., Sedlis, S. P., Donnino, R. M., Lorin, J., Tamis-Holland, J. E., Kornberg, R., Leber, R., Saba, S., Lee, M. W., Small, D. R., Nona, W., Alexander, P. B., Rehman, I., Badami, U., Marzo, K., Robbins, I. H., Levite, H. A., Shetty, S., Patel, M., Hamroff, G. S., Little, R. W., Zimbelman, B. D., Lui, C. Y., Smith, B. R., Vezina, D. P., Khor, L. L., Abraham, J. D., Bull, D. A., McKellar, S. H., Booth, D., Kotter, J., Abdel-Latif, A., Hu, B., Labovitz, A. J., Berlowitz, M., Rogal, P., McFarren, C., Matar, F., Caldeira, C., Maron, D. J., Rodriguez, F., Schnittger, I., Fearon, W. F., Deedwania, P., Reddy, K., Sweeny, J., Spizzieri, C., Hochberg, C. P., Salerno, W. D., Wyman, R., Zarka, A., Shah, A. V., Haldis, T., Kohn, J. A., Girotra, S., Almousalli, O., Krishnam, M. S., Milliken, J. C., Patel, P. M., Seto, A. H., Harley, K. T., Gibson, M. A., Allen, B. J., Coram, R., Thomas, S., Schwartz, R. G., Chen, W., El Shahawy, M., Stafford, J., Abernethy, W. B., Zurick, A., Meyer, T. M., Morford, R. G., Rutkin, B., Bokhari, S., Sokol, S. I., Meisner, J., Hamzeh, I., Misra, A., Wall, M., De Rosen, V. L., Alam, M., Turner, M. C., Mulhearn, T. J., Good, A. P., Shammas, N. W., Chilton, R., Nguyen, P. K., Jezior, M., Gordon, P. C., Crain, T., Stenberg, R., Pedalino, R. P., Wiesel, J., Juang, G. J., Al-Amoodi, M., Wohns, D., Lader, E. W., Mumma, M., Dharmarajan, L., McGarvey, J. F., Downes, T. R., Luckasen, G. J., Cheong, B., Potluri, S., Mastouri, R. A., Breall, J. A., Revtyak, G. E., Bazeley, J. W., Li, D., Giedd, K., Old, W., Burt, F., Sokhon, K., Gopal, D., Valeti, U. S., Kobashigawa, J., Govindan, S. C., Nair, R. G., Manjunath, C. N., Moorthy, N., Manjunath, S. C., Narayanappa, S., Pandit, N., Nath, R. K., Dwivedi, S. K., Narain, V. S., Chandra, S., Wander, G. S., Tandon, R., Ralhan, S., Aslam, N., Goyal, A., Bhargava, B., Karthikeyan, G., Ramakrishnan, S., Seth, S., Yadav, R., Singh, S., Roy, A., Parakh, N., Verma, S. K., Narang, R., Mishra, S., Naik, N., Sharma, G., Choudhary, S. K., Patel, C., Gulati, G., Sharma, S., Bahl, V. K., Mathew, A., Punnoose, E., Gadkari, M. A., Gadage, S., Pillay, T. U., Satheesh, S., Mathur, A., Kaul, U., Christopher, J., Menon, R., Kumar, N., Oomman, A., Mao, R., Solomon, H., Naik, S., Khan, S. P., Christopher, J., Kumar, N., Grant, P., Kachru, R., Ajit Kumar, V. K., Ganapathi, S., Jayakumar, K., Sivadasanpillai, H., Sasidharan, B., Kapilamoorthy, T. R., Christopher, J., Polamuri, P., Kaul, U., Senior, R., Elghamaz, A., Gurunathan, S., Karogiannis, N., Shah, B. N., Trimlett, R. H., Rubens, M. B., Nicol, E. D., Mittal, T. K., Hampson, R., Gamma, R. A., de Belder, M. A., Thambyrajah, J., Nageh, T., Davies, J. R., Lindsay, S. J., Kurian, J., Jamil, H., Raheem, O., Hoye, A., Donnelly, P., Valecka, B., Chauhan, A., Barr, C., Alfakih, K., Byrne, J., Webb, I., Henriksen, P., OKane, P., de Silva, R., Conway, D. S., Sirker, A. A., Hoole, S. P., Witherow, F. N., Johnston, N., Harbinson, M., Walsh, S., Douglas, H., Luckie, M., Sobolewska, J., Jeetley, P., Patel, N., Kotecha, T., Travill, C., Karimullah, I., Al-Bustami, M., Braganza, D., Henderson, R., Pointon, K., Naik, S., Mathew, T., Berry, C., Collison, D., Roditi, G., Moriarty, A. J., Glover, J. D., Pradhan, J., Mikhail, G., Francis, D. P., Gosselin, G., Diaz, A., Rheault, P., Barrero, M., Gagne, C., Pepin-Dubois, Y., Costa, R., Sia, Y. T., Lemay, C., Gisbert, A., Gervais, P., Rheault, A., Phaneuf, D. C., Gosselin, G., Garg, P., Chow, B. J., Hessian, R. C., Beanlands, R. S., Davies, R. F., Bainey, K. R., Cheema, A. N., Bagai, A., Wald, R., Goodman, S., Graham, J. J., Peterson, M., Chow, C., Abramson, B., Cheema, A. N., Vakani, M. T., Cha, J., Howarth, A. G., Wong, G., Uxa, A., Galiwango, P., Kassam, S., Mukherjee, A., Ricci, A. J., Lam, A., Mehta, S., Udell, J., Genereux, P., Hameed, A., Daba, L., Hueb, W., Rezende, P. C., Silva, E. E., Hueb, A. C., Smanio, P. E., de Quadros, A. S., Kalil, R. A., da Costa Vieira, J. L., Grossmann, G., de Oliveira, P. P., Bridi, L., Savaris, S., Vitola, J. V., Cerci, R. J., Farias, F. R., Fernandes, M. M., Marin-Neto, J. A., Schmidt, A., de Oliveira Lima Filho, M., Oliveira, R. M., Chierice, J. R., Polanczyk, C. A., Furtado, M. V., Smidt, L. F., Carvalho, A. C., Pucci, G., Lyra, F., Junior, A. R., Dracoulakis, M. D., Lima, R. G., Figueiredo, E., Caramori, P. R., Tumelero, R., Dall'Orto, F., Mesquita, C. T., Colafranseschi, A. S., Oliveira, A. C., Carvalho, L. A., Palazzo, I. C., Sousa, A. S., da Silva, E. E., de Barros, P. G., de Padua Silva Baptista, L., Rodrigues, M. J., de Resende, M. V., Saraiva, J. F., Costantini, C., Demkow, M., Pracon, R., Kepka, C., Teresinska, A., Kryczka, K., Henzel, J., Solecki, M., Kaczmarska, E., Mazurek, T., Drozdz, J., Czarniak, B., Frach, M., Szymczyk, K., Niedzwiecka, I., Sobczak, S., Ciurus, T., Jakubowski, P., Misztal-Teodorczyk, M., Teodorczyk, D., Fratczak, A., Szkopiak, M., Lebioda, P., Wlodarczyk, M., Plachcinska, A., Kusmierek, J., Miller, M., Marciniak, H., Wojtczak-Soska, K., Luczak, K., Tarchalski, T., Cichocka-Radwan, A., Szwed, H., Szulczyk, G. A., Witkowski, A., Kukula, K., Celinska-Spodar, M., Zalewska, J., Gajos, G., Bury, K., Pruszczyk, P., Roik, M., Loboz-Grudzien, K., Sokalski, L., Brzezinska, B., Lesiak, M., Lanocha, M., Reczuch, K. W., Kalarus, Z., Swiatkowski, A., Szulik, M., Musial, W. J., Bockeria, L., Petrosyan, K., Trifonova, T., Chernyavskiy, A. M., Kretov, E. I., Grazhdankin, I. O., Bershtein, L. L., Sayganov, S. A., Kuzmina-Krutetskaya, A. M., Zbyshevskaya, E. V., Katamadze, N. O., Demchenko, E. A., Kozlov, P. S., Kozulin, V. Y., Lubinskaya, E. I., Lopez-Sendon, J., Castro, A., Salicio, E. R., Guzman, G., Galeote, G., Valbuena, S., Peteiro, J., Martinez-Ruiz, M. D., Perez-Fernandez, R., Cuenca-Castillo, J. J., Flores-Rios, X., Prada-Delgado, O., Barge-Caballero, G., Juanatey, J. R., Bayarri, M. S., Nunez, V. P., Sanchez, R. O., Alvarez, B. C., Gil, C. P., Monzonis, A. M., Sionis, A., Perales, M. V., Padro, J. M., Penaranda, A. S., Picart, J. G., Iglesias, A. G., Marimon, X. G., Llado, G. P., Costa, F. C., Miro, V., Diez, J. L., Calvillo, P., Ortuno, F. M., Chavarri, M. V., Montolliu, A. T., Bermudez, E. P., De La Morena, G., Blancas, M. G., Luena, J. E., Fernandez-Aviles, F., Chen, J., Wu, Y., Ma, Y., Yang, Y., Ji, Z., Yang, X., Lin, W., Zeng, H., Fu, X., Yang, B., Wang, S., Cheng, G., Zhao, Y., Fang, X., Zeng, Q., Su, X., Li, Q., Nie, S., Yu, Q., Wang, J., Zhang, S., Liu, Z., Perna, G. P., Marini, M., Gabrielli, G., Provasoli, S., Verna, E., Monti, L., Nardi, B., Di Chiara, A., Mortara, A., Galvani, M., Ottani, F., Sicuro, M., Calabro, P., Formisano, T., Tarantini, G., Cucchini, U., Andres, A. L., Racca, E., Briguori, C., Amati, R., Vergoni, W., Russo, A., Fanelli, R., Poh, K., Chai, P., Lau, T., Loh, J. P., Tay, E. L., Teoh, K., Teo, L. L., Ong, C., Wong, R. C., Loh, P., Kofidis, T., Chan, W. X., Chan, K. H., Foo, D., Kong, J. L., Er, C. M., Jafary, F. H., Chua, T., Doerr, R., Stumpf, J., Matschke, K., Simonis, G., Kadalie, C. T., Sechtem, U., Ong, P., Schulze, P. C., Goebel, B., Lenk, K., Nickenig, G., Schuchlenz, H., Weikl, S., Lang, I. M., Huber, K., Jakl-Kotauschek, G., Vertes, A., Varga, A., Fontos, G., Merkely, B., Kerecsen, G., Hinic, S., Zdravkovic, M., Mudrenovic, V., Crnokrak, B., Beleslin, B. D., Boskovic, N. N., Petrovic, M. T., Dobric, M. R., Markovic, Z. Z., Mladenovic, A. S., Cemerlic-Adjic, N., Davidovic, G., Vucic, R., Dekleva, M. N., Stankovic, G., Apostolovic, S., Escobedo, J., Baleon-Espinosa, R., Campos-Santaolalla, A. S., Duran-Cortes, E., Flores-Palacios, J. M., Garcia-Rincon, A., Jimenez-Santos, M., Penafiel, J. V., Ortega-Ramirez, J. A., Valdespino-Estrada, A., Rosas, E. A., Selvanayagam, J. B., Joseph, M. X., Thambar, S. T., Beltrame, J. F., Hillis, G. S., Thuaire, C., Dutoiu, T., Steg, P. G., Juliard, J., Slama, M. S., El Mahmoud, R., Nicollet, E., Goube, P., Barone-Rochette, G., Furber, A., Biere, L., Laucevicius, A., Celutkiene, J., Kedhi, E., Timmer, J., Hermanides, R., Kaplan, E., Riezebos, R. K., Samadi, P., van Dongen, E., Niehe, S. R., Suryapranata, H., van Vugt, S., Ramos, R., Cacela, D., Santana, A., Fiarresga, A., Sousa, L., Marques, H., Patricio, L., Bernanrdes, L., Rio, P., Carvalho, R., Ferreira, R., Silva, T., Rodrigues, I., Modas, P., Portugal, G., Fragata, J., Pinto, F. J., Menezes, M. N., Lopes, G. C., Almeida, A. G., Silva, P. C., Nobre, A., Francisco, A. R., Ferreira, N., Lopes, R. L., Guzman, L., Figal, J. C., Mendiz, O., Cortes, C., Favaloro, R. R., Alvarez, C., Courtis, J., Zeballos, G., Schiavi, L., Rubio, M., Devlin, G. P., Fisher, R., Stewart, R. A., White, H. D., Benatar, J., Kedev, S., Mitevska, I. P., Kostovska, E. S., Pejkov, H., Held, C., Eggers, K., Frostfelt, G., Johnston, N., Olsowka, M., Akerblom, A., Soveri, I., Aspberg, J., Sharir, T., Elian, D., Kerner, A., Massalha, S., Fukuda, K., Kohsaka, S., Yasuda, S., Nishimura, S., Goetschalckx, K., Van de Werf, F., Claes, K., Hung, C., Yun, C., Hou, C. J., Kuo, J., Yeh, H., Hung, T., Li, J., Chien, C., Tsai, C., Liu, C., Yu, F., Lin, Y., Lan, W., Yen, C., Tsai, J., Sung, K., Ntsekhe, M., Pandie, S., Viljoen, C. A., De Andrade, M., Moccetti, T., Rossi, M. G., Abdelhamid, M., Adel, A., Kamal, A., Mahrous, H., El Kaffas, S., El Fishawy, H., Pop, C., Claudia, M., Popescu, B. A., Ginghina, C., Deleanu, D., Iliescu, V. A., Al-Mallah, M. H., Aljzeeri, A., Najm, H., Alghamdi, A., Ramos, W. E., Kuanprasert, S., Prommintikul, A., Nawarawong, W., Woragidpoonpol, S., Tepsuwan, T., Taksaudom, N., Rimsukcharoenchai, C., Euathrongchit, J., Wannasopha, Y., Yamwong, S., Sritara, P., Aramcharoen, S., Meemuk, K., Khairuddin, A., Hadi, H. A., Yahaya, S. A. 2024: e029850

  Abstract

  BACKGROUND: Women with chronic coronary disease are generally older than men and have more comorbidities but less atherosclerosis. We explored sex differences in revascularization, guideline-directed medical therapy, and outcomes among patients with chronic coronary disease with ischemia on stress testing, with and without invasive management.METHODS AND RESULTS: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial randomized patients with moderate or severe ischemia to invasive management with angiography, revascularization, and guideline-directed medical therapy, or initial conservative management with guideline-directed medical therapy alone. We evaluated the primary outcome (cardiovascular death, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest) and other end points, by sex, in 1168 (22.6%) women and 4011 (77.4%) men. Invasive group catheterization rates were similar, with less revascularization among women (73.4% of invasive-assigned women revascularized versus 81.2% of invasive-assigned men; P<0.001). Women had less coronary artery disease: multivessel in 60.0% of invasive-assigned women and 74.8% of invasive-assigned men, and no ≥50% stenosis in 12.3% versus 4.5% (P<0.001). In the conservative group, 4-year catheterization rates were 26.3% of women versus 25.6% of men (P=0.72). Guideline-directed medical therapy use was lower among women with fewer risk factor goals attained. There were no sex differences in the primary outcome (adjusted hazard ratio [HR] for women versus men, 0.93 [95% CI, 0.77-1.13]; P=0.47) or the major secondary outcome of cardiovascular death/myocardial infarction (adjusted HR, 0.93 [95% CI, 0.76-1.14]; P=0.49), with no significant sex-by-treatment-group interactions.CONCLUSIONS: Women had less extensive coronary artery disease and, therefore, lower revascularization rates in the invasive group. Despite lower risk factor goal attainment, women with chronic coronary disease experienced similar risk-adjusted outcomes to men in the ISCHEMIA trial.REGISTRATION: URL: http://wwwclinicaltrials.gov. Unique identifier: NCT01471522.

  View details for DOI 10.1161/JAHA.122.029850

  View details for PubMedID 38410945

• Precision of Echocardiographic Measurements. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Pillai, B., Salerno, M., Schnittger, I., Cheng, S., Ouyang, D. 2024

  View details for DOI 10.1016/j.echo.2024.01.001

  View details for PubMedID 38199333

• Reference change value of global longitudinal strain in clinical practice: A test-rest quality implementation project. Echocardiography (Mount Kisco, N.Y.) Tuzovic, M., Tang, X., Francisco, N., Sell, A., Drew, R., Paloma, A., Chow, J., Liang, D., Heidenreich, P., Salerno, M., Schnittger, I., Haddad, F. 2022

  Abstract

  BACKGROUND: Reference change value (RCV) is used to assess the significance of the difference between two measurements after accounting for pre-analytic, analytic, and within-subject variability. The objective of the current study was to define the RCV for global longitudinal strain (GLS) using different semi-automated software in standard clinical practice.METHODS: Using a test-retest study design, we quantified the median coefficient of variation (CV) for GLS using AutoStrain and Automated Cardiac Motion Quantification (aCMQ) by Philips. Triplane left-ventricular ejection fraction (LVEF) was measured for comparison. Multivariable regression analysis was performed to determine factors influencing test-retest CV including image quality and the presence of segmental wall motion abnormalities (WMA). RCV was reported using a standard formula assuming two standard deviations for repeated measurements; results were also translated into Bayesian probability. Total measurement variation was described in terms of its three different components: pre-analytic (acquisition), analytic (measuring variation), and within-subject (biological) variation.RESULT: Of the 44 individuals who were screened, 41 had adequate quality for strain quantification. The mean age of the cohort was 56.4±16.8 years, 41% female, LVEF was 55.8±9.8% and the median and interquartile range for LV GLS was -17.2 [-19.3 to -14.8]%. Autostrain was more time efficient (80% less analysis time) and had a lower total median CV than aCMQ (CV=7.4%vs. 17.6%, p <.001). The total CV was higher in patients with WMA (6.4%vs. 13.2%, p=.035). In non-segmental disease, the CV translates to a RCV of 15% (corresponding to a probability of real change of 80%). Assuming a within-subject variability of 4.0%, the component analysis identified that inter-reader variability accounts for 3.7% of the CV, while acquisition variability accounts for 4.0%.CONCLUSION: Using test-retest analysis and CVs, we find that an RCV of 15% for GLS represents an optimistic estimate in routine clinical practice. Based on our results, a higher RCV of 17%-21% is needed in order to provide a high probability of clinically meaningful change in GLS in all comers. The methodology presented here for determining measurement reproducibility and RCVs is easily translatable into clinical practice for any imaging parameter.

  View details for DOI 10.1111/echo.15482

  View details for PubMedID 36376263

• High-Throughput Precision Phenotyping of Left Ventricular Hypertrophy With Cardiovascular Deep Learning. JAMA cardiology Duffy, G., Cheng, P. P., Yuan, N., He, B., Kwan, A. C., Shun-Shin, M. J., Alexander, K. M., Ebinger, J., Lungren, M. P., Rader, F., Liang, D. H., Schnittger, I., Ashley, E. A., Zou, J. Y., Patel, J., Witteles, R., Cheng, S., Ouyang, D. 2022

  Abstract

  Importance: Early detection and characterization of increased left ventricular (LV) wall thickness can markedly impact patient care but is limited by under-recognition of hypertrophy, measurement error and variability, and difficulty differentiating causes of increased wall thickness, such as hypertrophy, cardiomyopathy, and cardiac amyloidosis.Objective: To assess the accuracy of a deep learning workflow in quantifying ventricular hypertrophy and predicting the cause of increased LV wall thickness.Design, Settings, and Participants: This cohort study included physician-curated cohorts from the Stanford Amyloid Center and Cedars-Sinai Medical Center (CSMC) Advanced Heart Disease Clinic for cardiac amyloidosis and the Stanford Center for Inherited Cardiovascular Disease and the CSMC Hypertrophic Cardiomyopathy Clinic for hypertrophic cardiomyopathy from January 1, 2008, to December 31, 2020. The deep learning algorithm was trained and tested on retrospectively obtained independent echocardiogram videos from Stanford Healthcare, CSMC, and the Unity Imaging Collaborative.Main Outcomes and Measures: The main outcome was the accuracy of the deep learning algorithm in measuring left ventricular dimensions and identifying patients with increased LV wall thickness diagnosed with hypertrophic cardiomyopathy and cardiac amyloidosis.Results: The study included 23 745 patients: 12 001 from Stanford Health Care (6509 [54.2%] female; mean [SD] age, 61.6 [17.4] years) and 1309 from CSMC (808 [61.7%] female; mean [SD] age, 62.8 [17.2] years) with parasternal long-axis videos and 8084 from Stanford Health Care (4201 [54.0%] female; mean [SD] age, 69.1 [16.8] years) and 2351 from CSMS (6509 [54.2%] female; mean [SD] age, 69.6 [14.7] years) with apical 4-chamber videos. The deep learning algorithm accurately measured intraventricular wall thickness (mean absolute error [MAE], 1.2 mm; 95% CI, 1.1-1.3 mm), LV diameter (MAE, 2.4 mm; 95% CI, 2.2-2.6 mm), and posterior wall thickness (MAE, 1.4 mm; 95% CI, 1.2-1.5 mm) and classified cardiac amyloidosis (area under the curve [AUC], 0.83) and hypertrophic cardiomyopathy (AUC, 0.98) separately from other causes of LV hypertrophy. In external data sets from independent domestic and international health care systems, the deep learning algorithm accurately quantified ventricular parameters (domestic: R2, 0.96; international: R2, 0.90). For the domestic data set, the MAE was 1.7 mm (95% CI, 1.6-1.8 mm) for intraventricular septum thickness, 3.8 mm (95% CI, 3.5-4.0 mm) for LV internal dimension, and 1.8 mm (95% CI, 1.7-2.0 mm) for LV posterior wall thickness. For the international data set, the MAE was 1.7 mm (95% CI, 1.5-2.0 mm) for intraventricular septum thickness, 2.9 mm (95% CI, 2.4-3.3 mm) for LV internal dimension, and 2.3 mm (95% CI, 1.9-2.7 mm) for LV posterior wall thickness. The deep learning algorithm accurately detected cardiac amyloidosis (AUC, 0.79) and hypertrophic cardiomyopathy (AUC, 0.89) in the domestic external validation site.Conclusions and Relevance: In this cohort study, the deep learning model accurately identified subtle changes in LV wall geometric measurements and the causes of hypertrophy. Unlike with human experts, the deep learning workflow is fully automated, allowing for reproducible, precise measurements, and may provide a foundation for precision diagnosis of cardiac hypertrophy.

  View details for DOI 10.1001/jamacardio.2021.6059

  View details for PubMedID 35195663

• Deep learning evaluation of biomarkers from echocardiogram videos. EBioMedicine Hughes, J. W., Yuan, N., He, B., Ouyang, J., Ebinger, J., Botting, P., Lee, J., Theurer, J., Tooley, J. E., Nieman, K., Lungren, M. P., Liang, D. H., Schnittger, I., Chen, J. H., Ashley, E. A., Cheng, S., Ouyang, D., Zou, J. Y. 2021; 73: 103613

  Abstract

  BACKGROUND: Laboratory testing is routinely used to assay blood biomarkers to provide information on physiologic state beyond what clinicians can evaluate from interpreting medical imaging. We hypothesized that deep learning interpretation of echocardiogram videos can provide additional value in understanding disease states and can evaluate common biomarkers results.METHODS: We developed EchoNet-Labs, a video-based deep learning algorithm to detect evidence of anemia, elevated B-type natriuretic peptide (BNP), troponin I, and blood urea nitrogen (BUN), as well as values of ten additional lab tests directly from echocardiograms. We included patients (n=39,460) aged 18 years or older with one or more apical-4-chamber echocardiogram videos (n=70,066) from Stanford Healthcare for training and internal testing of EchoNet-Lab's performance in estimating the most proximal biomarker result. Without fine-tuning, the performance of EchoNet-Labs was further evaluated on an additional external test dataset (n=1,301) from Cedars-Sinai Medical Center. We calculated the area under the curve (AUC) of the receiver operating characteristic curve for the internal and external test datasets.FINDINGS: On the held-out test set of Stanford patients not previously seen during model training, EchoNet-Labs achieved an AUC of 0.80 (0.79-0.81) in detecting anemia (low hemoglobin), 0.86 (0.85-0.88) in detecting elevated BNP, 0.75 (0.73-0.78) in detecting elevated troponin I, and 0.74 (0.72-0.76) in detecting elevated BUN. On the external test dataset from Cedars-Sinai, EchoNet-Labs achieved an AUC of 0.80 (0.77-0.82) in detecting anemia, of 0.82 (0.79-0.84) in detecting elevated BNP, of 0.75 (0.72-0.78) in detecting elevated troponin I, and of 0.69 (0.66-0.71) in detecting elevated BUN. We further demonstrate the utility of the model in detecting abnormalities in 10 additional lab tests. We investigate the features necessary for EchoNet-Labs to make successful detection and identify potential mechanisms for each biomarker using well-known and novel explainability techniques.INTERPRETATION: These results show that deep learning applied to diagnostic imaging can provide additional clinical value and identify phenotypic information beyond current imaging interpretation methods.FUNDING: J.W.H. and B.H. are supported by the NSF Graduate Research Fellowship. D.O. is supported by NIH K99 HL157421-01. J.Y.Z. is supported by NSF CAREER 1942926, NIH R21 MD012867-01, NIH P30AG059307 and by a Chan-Zuckerberg Biohub Fellowship.

  View details for DOI 10.1016/j.ebiom.2021.103613

  View details for PubMedID 34656880

• Effect of ranolazine on symptom and quality of life in patients with angina in the absence of obstructive coronary artery disease: A case control study INTERNATIONAL JOURNAL OF CARDIOLOGY Pargaonkar, V. S., Tremmel, J. A., Schnittger, I., Khandelwal, A. 2020; 309: 8–13

  View details for Web of Science ID 000531868300003

• Initial Invasive or Conservative Strategy for Stable Coronary Disease. The New England journal of medicine Maron, D. J., Hochman, J. S., Reynolds, H. R., Bangalore, S. n., O'Brien, S. M., Boden, W. E., Chaitman, B. R., Senior, R. n., López-Sendón, J. n., Alexander, K. P., Lopes, R. D., Shaw, L. J., Berger, J. S., Newman, J. D., Sidhu, M. S., Goodman, S. G., Ruzyllo, W. n., Gosselin, G. n., Maggioni, A. P., White, H. D., Bhargava, B. n., Min, J. K., Mancini, G. B., Berman, D. S., Picard, M. H., Kwong, R. Y., Ali, Z. A., Mark, D. B., Spertus, J. A., Krishnan, M. N., Elghamaz, A. n., Moorthy, N. n., Hueb, W. A., Demkow, M. n., Mavromatis, K. n., Bockeria, O. n., Peteiro, J. n., Miller, T. D., Szwed, H. n., Doerr, R. n., Keltai, M. n., Selvanayagam, J. B., Steg, P. G., Held, C. n., Kohsaka, S. n., Mavromichalis, S. n., Kirby, R. n., Jeffries, N. O., Harrell, F. E., Rockhold, F. W., Broderick, S. n., Ferguson, T. B., Williams, D. O., Harrington, R. A., Stone, G. W., Rosenberg, Y. n. 2020

  Abstract

  Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain.We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction.Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32).Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

  View details for DOI 10.1056/NEJMoa1915922

  View details for PubMedID 32227755

• Incremental value of diastolic stress test in identifying subclinical heart failure in patients with diabetes mellitus. European heart journal cardiovascular Imaging Nishi, T. n., Kobayashi, Y. n., Christle, J. W., Cauwenberghs, N. n., Boralkar, K. n., Moneghetti, K. n., Amsallem, M. n., Hedman, K. n., Contrepois, K. n., Myers, J. n., Mahaffey, K. W., Schnittger, I. n., Kuznetsova, T. n., Palaniappan, L. n., Haddad, F. n. 2020

  Abstract

  Resting echocardiography is a valuable method for detecting subclinical heart failure (HF) in patients with diabetes mellitus (DM). However, few studies have assessed the incremental value of diastolic stress for detecting subclinical HF in this population.Asymptomatic patients with Type 2 DM were prospectively enrolled. Subclinical HF was assessed using systolic dysfunction (left ventricular longitudinal strain <16% at rest and <19% after exercise in absolute value), abnormal cardiac morphology, or diastolic dysfunction (E/e' > 10). Metabolic equivalents (METs) were calculated using treadmill speed and grade, and functional capacity was assessed by percent-predicted METs (ppMETs). Among 161 patients studied (mean age of 59 ± 11 years and 57% male sex), subclinical HF was observed in 68% at rest and in 79% with exercise. Among characteristics, diastolic stress had the highest yield in improving detection of HF with 57% of abnormal cases after exercise and 45% at rest. Patients with revealed diastolic dysfunction during stress had significantly lower exercise capacity than patients with normal diastolic stress (7.3 ± 2.1 vs. 8.8 ± 2.5, P < 0.001 for peak METs and 91 ± 30% vs. 105 ± 30%, P = 0.04 for ppMETs). On multivariable modelling found that age (beta = -0.33), male sex (beta = 0.21), body mass index (beta = -0.49), and exercise E/e' >10 (beta = -0.17) were independently associated with peak METs (combined R2 = 0.46). A network correlation map revealed the connectivity of peak METs and diastolic properties as central features in patients with DM.Diastolic stress test improves the detection of subclinical HF in patients with diabetes mellitus.

  View details for DOI 10.1093/ehjci/jeaa070

  View details for PubMedID 32386203

• Health-Status Outcomes with Invasive or Conservative Care in Coronary Disease. The New England journal of medicine Spertus, J. A., Jones, P. G., Maron, D. J., O'Brien, S. M., Reynolds, H. R., Rosenberg, Y. n., Stone, G. W., Harrell, F. E., Boden, W. E., Weintraub, W. S., Baloch, K. n., Mavromatis, K. n., Diaz, A. n., Gosselin, G. n., Newman, J. D., Mavromichalis, S. n., Alexander, K. P., Cohen, D. J., Bangalore, S. n., Hochman, J. S., Mark, D. B. 2020

  Abstract

  In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients.We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency.At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina).In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

  View details for DOI 10.1056/NEJMoa1916370

  View details for PubMedID 32227753

• Time based versus strain based myocardial performance indices in hypertrophic cardiomyopathy, the merging role of left atrial strain EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING Kobayashi, Y., Moneghetti, K. J., Bouajila, S., Stolfo, D., Finocchiaro, G., Kuznetsova, T., Liang, D., Schnittger, I., Ashley, E., Wheeler, M., Haddad, F. 2019; 20 (3): 334–42

  View details for DOI 10.1093/ehjci/jey097

  View details for Web of Science ID 000481422400015

• Time based versus strain based myocardial performance indices in hypertrophic cardiomyopathy, the merging role of left atrial strain. European heart journal cardiovascular Imaging Kobayashi, Y., Moneghetti, K. J., Bouajila, S., Stolfo, D., Finocchiaro, G., Kuznetsova, T., Liang, D., Schnittger, I., Ashley, E., Wheeler, M., Haddad, F. 2018

  Abstract

  Aims: The myocardial performance index (MPI) is a time-based index of global myocardial performance. In this study, we sought to compare the prognostic value of the MPI with other strain and remodelling indices in hypertrophic cardiomyopathy (HCM).Methods and results: We enrolled 126 patients with HCM and 50 age- and sex-matched controls. Along with traditional echocardiographic assessment, MPI, left ventricular global longitudinal strain (LVGLS), E/e' ratio, and total left atrial (LA) global strain (LAS) were also measured. Time-based MPI was calculated from flow or tissue-based pulse wave Doppler (PWD and TDI) as the (isovolumic-relaxation and contraction time)/systolic-time. We used hierarchical clustering and network analysis to better visualize the relationship between parameters. The primary endpoint was the composite of all-cause death, heart transplantation, left ventricular assist device implantation, and clinical worsening. Left ventricular outflow tract (LVOT) obstruction was present in 56% of patients. Compared with controls, patients with HCM had worse LVGLS (-14.0±3.4% vs. -19.6±1.5%), higher E/e' (12.9±7.2 vs. 6.1±1.5), LA volume index (LAVI) (36.4±13.8ml/m2 vs. 25.6±6.7ml/m2), and MPI (0.55±0.17 vs. 0.40±0.11 for PWD and 0.59±0.22 vs. 0.46±0.09 for TDI) (all P<0.001). During a median follow-up of 55months, 47 endpoints occurred. PWD or TDI-based MPI was not associated with outcome, while LAVI, LAS, LVGLS, and E/e' were (all P<0.01). On multivariable analysis, LVOT obstruction (P<0.001), LAS (P<0.001), and E/e' (P=0.02) were retained as independent associates. They were in different clusters suggesting complemental relationship between them.Conclusion: Time-based index is less predictive of outcome than strain or tissue Doppler indices. LAS may be a promising prognostic marker in HCM.

  View details for PubMedID 30060097

• Optimizing right ventricular focused four-chamber views using three-dimensional imaging, a comparative magnetic resonance based study. The international journal of cardiovascular imaging Amsallem, M., Lu, H., Tang, X., Do Couto Francisco, N. L., Kobayashi, Y., Moneghetti, K., Shiran, H., Rogers, I., Schnittger, I., Liang, D., Haddad, F. 2018

  Abstract

  Obtaining focused right ventricular (RV) apical view remains challenging using conventional two-dimensional (2D) echocardiography. This study main objective was to determine whether measurements from RV focused views derived from three-dimensional (3D) echocardiography (3D-RV-focused) are closely related to measurements from magnetic resonance (CMR). A first cohort of 47 patients underwent 3D echocardiography and CMR imaging within 2h of each other. A second cohort of 25 patients had repeat 3D echocardiography to determine the test-retest characteristics; and evaluate the bias associated with unfocused RV views. Tomographic views were extracted from the 3D dataset: RV focused views were obtained using the maximal RV diameter in the transverse plane, and unfocused views from a smaller transverse diameter enabling visualization of the tricuspid valve opening. Measures derived using the 3D-RV-focused view were strongly associated with CMR measurements. Among functional metrics, the strongest association was between RV fractional area change (RVFAC) and ejection fraction (RVEF) (r=0.92) while tricuspid annular plane systolic excursion moderately correlated with RVEF (r=0.47), all p<0.001. Among RV size measures, the strongest association was found between RV end-systolic area (RVESA) and volume (r=0.87, p<0.001). RV unfocused views led on average to 10% underestimation of RVESA. The 3D-RV-focused method had acceptable test-retest characteristics with a coefficient of variation of 10% for RVESA and 11% for RVFAC. Deriving standardized RV focused views using 3D echocardiography strongly relates to CMR-derived measures and may improve reproducibility in RV 2D measurements.

  View details for PubMedID 29654480

• EFFECT OF RANOLAZINE ON SYMPTOMS AND QUALITY OF LIFE IN PATIENTS WITH ANGINA IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE: A RETROSPECTIVE COHORT STUDY Pargaonkar, V., Tremmel, J., Schnittger, I., Khandelwal, A. ELSEVIER SCIENCE INC. 2018: 161

  View details for DOI 10.1016/S0735-1097(18)30702-2

  View details for Web of Science ID 000429659701011

• Long-term prognostic value of invasive and non-invasive measures early after heart transplantation. International journal of cardiology Kobayashi, Y. n., Kobayashi, Y. n., Yang, H. M., Bouajila, S. n., Luikart, H. n., Nishi, T. n., Choi, D. H., Schnittger, I. n., Valantine, H. A., Khush, K. K., Yeung, A. C., Haddad, F. n., Fearon, W. F. 2018; 260: 31–35

  Abstract

  Invasively assessed coronary microvascular resistance early after heart transplantation predicts worse long-term outcome; however, little is known about the relationship between microvascular resistance, left ventricular function and outcomes in this setting.A total of 100 cardiac transplant recipients had fractional flow reserve (FFR) and the index of microcirculatory resistance (IMR) measured in the left anterior descending artery and echocardiographic assessment of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) at 1 year after heart transplantation. The primary endpoint was the composite of death and retransplantation occurring beyond the first post-operative year.The mean FFR, IMR, LVEF, and GLS values at 1 year were 0.87 ± 0.06, 21.3 ± 17.3, 60.4 ± 5.4%, and 14.2 ± 2.4%, respectively. FFR and IMR had no significant correlation with LVEF and GLS. During a mean follow-up of 6.7 ± 4.2 years, the primary endpoint occurred in 24 patients (24.0%). By ROC curve analysis, IMR = 19.3 and GLS = 13.3% were the best cutoff values for predicting death or retransplantation. Cumulative event-free survival was significantly lower in patients with higher IMR (log-rank p = 0.02) and lower GLS (log-rank p < 0.001). Cumulative event-free survival can be further stratified by the combination of IMR and GLS (long-rank p < 0.001). By multivariable Cox proportional hazards model, higher IMR and lower GLS were independently associated with long-term death or retransplantation (elevated IMR, hazard ratio = 2.50, p = 0.04 and reduced GLS, hazard ratio = 3.79, p = 0.003, respectively).Invasively assessed IMR does not correlate with GLS at 1 year after heart transplantation. IMR and GLS determined at 1 year may be used as independent predictors of late death or retransplantation.

  View details for PubMedID 29622448

• Accuracy of non-invasive stress testing in women and men with angina in the absence of obstructive coronary artery disease. International journal of cardiology Pargaonkar, V. S., Kobayashi, Y. n., Kimura, T. n., Schnittger, I. n., Chow, E. K., Froelicher, V. F., Rogers, I. S., Lee, D. P., Fearon, W. F., Yeung, A. C., Stefanick, M. L., Tremmel, J. A. 2018

  Abstract

  While >20% of patients presenting to the cardiac catheterization laboratory with angina have no obstructive coronary artery disease (CAD), a majority (77%) have an occult coronary abnormality (endothelial dysfunction, microvascular dysfunction (MVD), and/or a myocardial bridge (MB)). There are little data regarding the ability of noninvasive stress testing to identify these occult abnormalities in patients with angina in the absence of obstructive CAD.We retrospectively evaluated 155 patients (76.7% women) with angina and no obstructive CAD who underwent stress echocardiography and/or electrocardiography before angiography. We evaluated Duke treadmill score, heart rate recovery (HRR), metabolic equivalents, and blood pressure response. During angiography, patients underwent invasive testing for endothelial dysfunction (decrease in epicardial coronary artery diameter >20% after intracoronary acetylcholine), MVD (index of microcirculatory resistance ≥25), and intravascular ultrasound for the presence of an MB.Stress echocardiography and electrocardiography were positive in 58 (43.6%) and 57 (36.7%) patients, respectively. Endothelial dysfunction was present in 96 (64%), MVD in 32 (20.6%), and an MB in 83 (53.9%). On multivariable logistic regression, stress echo was not associated with any abnormality, while stress ECG was associated with endothelial dysfunction. An abnormal HRR was associated with endothelial dysfunction and MVD, but not an MB.Conventional stress testing is insufficient for identifying occult coronary abnormalities that are frequently present in patients with angina in the absence of obstructive CAD. A normal stress test does not rule out a non-obstructive coronary etiology of angina, nor does it negate the need for comprehensive invasive testing.

  View details for DOI 10.1016/j.ijcard.2018.10.073

  View details for PubMedID 30527992

• Long-Term Prognostic Value of Invasive and Non-Invasive Measures Early after Heart Transplantation Kobayashi, Y., Kobayashi, Y., Luikart, H., Nishi, T., Choi, D., Schnittger, I., Fearon, W. ELSEVIER SCIENCE INC. 2017: B273

  View details for Web of Science ID 000413459200664

• Load Adaptability in Patients With Pulmonary Arterial Hypertension. The American journal of cardiology Amsallem, M., Boulate, D., Aymami, M., Guihaire, J., Selej, M., Huo, J., Denault, A. Y., McConnell, M. V., Schnittger, I., Fadel, E., Mercier, O., Zamanian, R. T., Haddad, F. 2017; 120 (5): 874-882

  Abstract

  Right ventricular (RV) adaptation to pressure overload is a major prognostic factor in patients with pulmonary arterial hypertension (PAH). The objectives were first to define the relation between RV adaptation and load using allometric modeling, then to compare the prognostic value of different indices of load adaptability in PAH. Both a derivation (n = 85) and a validation cohort (n = 200) were included. Load adaptability was assessed using 3 approaches: (1) surrogates of ventriculo-arterial coupling (e.g., RV area change/end-systolic area), (2) simple ratio of function and load (e.g., tricuspid annular plane systolic excursion/right ventricular systolic pressure), and (3) indices assessing the proportionality of adaptation using allometric pressure-function or size modeling. Proportional hazard modeling was used to compare the hazard ratio for the outcome of death or lung transplantation. The mean age of the derivation cohort was 44 ± 11 years, with 80% female and 74% in New York Heart Association class III or IV. Mean pulmonary vascular resistance index (PVRI) was 24 ± 11 with a wide distribution (1.6 to 57.5 WU/m2). Allometric relations were observed between PVRI and RV fractional area change (R2 = 0.53, p < 0.001) and RV end-systolic area indexed to body surface area right ventricular end-systolic area index (RVESAI) (R2 = 0.29, p < 0.001), allowing the derivation of simple ratiometric load-specific indices of RV adaptation. In right heart parameters, RVESAI was the strongest predictor of outcomes (hazard ratio per SD = 1.93, 95% confidence interval 1.37 to 2.75, p < 0.001). Although RVESAI/PVRI0.35 provided small incremental discrimination on multivariate modeling, none of the load-adaptability indices provided stronger discrimination of outcome than simple RV adaptation metrics in either the derivation or the validation cohort. In conclusion, allometric modeling enables quantification of the proportionality of RV load adaptation but offers small incremental prognostic value to RV end-systolic dimension in PAH.

  View details for DOI 10.1016/j.amjcard.2017.05.053

  View details for PubMedID 28705377

• Incremental value of right heart metrics and exercise performance to well-validated risk scores in dilated cardiomyopathy. European heart journal cardiovascular Imaging Moneghetti, K. J., Giraldeau, G., Wheeler, M. T., Kobayashi, Y., Vrtovec, B., Boulate, D., Kuznetsova, T., Schnittger, I., Wu, J. C., Myers, J., Ashley, E., Haddad, F. 2017

  Abstract

  Risk stratification in heart failure (HF) relies on several established clinical risk scores, however, myocardial deformation, right heart metrics, and exercise performance have not usually been considered. This study sought to assess the incremental value of advanced echocardiographic and cardiopulmonary exercise testing (CPX) parameters to validated risk scores in HF.The Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) and Metabolic Exercise Test Data Combined with Cardiac and Kidney Indexes (MECKI) scores were applied to 208 ambulatory patients with dilated cardiomyopathy (DCM) who completed echocardiography in conjunction with CPX as part of the Stanford Exercise Testing registry. Patients were followed for the composite end point of death, heart transplant, left ventricular device implantation, and hospitalization for acute HF. Mean age, left ventricular ejection fraction (LVEF), and left ventricular global longitudinal strain (LVGLS) were 47 ± 13 years, 33 ± 13%, and -10.6 ± 4.4%, respectively, while right ventricular free-wall longitudinal strain was -18.8 ± 5.5%. Partial correlation mapping identified strong correlations between LVEF, LVGLS, and LV systolic strain rate, with a moderate correlation between these metrics and peak VO2. Over a median follow up of 5.3 years, the composite end point occurred in 60 patients. Cox proportional hazards identified MAGGIC score [hazard ratio (HR) (2.04 [1.39-3.01], P < 0.01], peak VO2 HR (0.52 [0.28-0.97], P = 0.04), and right atrial volume indexed (RAVI) HR (1.31 [1.07-1.61], P < 0.01) as independent correlates of outcome. RAVI remained an independent correlate when combined with the MECKI score (2.21 [1.59-3.07]), P < 0.01, RAVI, 1.33 [1.06-1.67], P = 0.01).Our study demonstrates that RAVI is complementary to well-validated HF risk scores and highlights the importance of exercise performance in DCM.

  View details for DOI 10.1093/ehjci/jex187

  View details for PubMedID 28977353

• Right Heart End-Systolic Remodeling Index Strongly Predicts Outcomes in Pulmonary Arterial Hypertension: Comparison With Validated Models. Circulation. Cardiovascular imaging Amsallem, M., Sweatt, A. J., Aymami, M. C., Kuznetsova, T., Selej, M., Lu, H., Mercier, O., Fadel, E., Schnittger, I., McConnell, M. V., Rabinovitch, M., Zamanian, R. T., Haddad, F. 2017; 10 (6)

  Abstract

  Right ventricular (RV) end-systolic dimensions provide information on both size and function. We investigated whether an internally scaled index of end-systolic dimension is incremental to well-validated prognostic scores in pulmonary arterial hypertension.From 2005 to 2014, 228 patients with pulmonary arterial hypertension were prospectively enrolled. RV end-systolic remodeling index (RVESRI) was defined by lateral length divided by septal height. The incremental values of RV free wall longitudinal strain and RVESRI to risk scores were determined. Mean age was 49±14 years, 78% were female, 33% had connective tissue disease, 52% were in New York Heart Association class ≥III, and mean pulmonary vascular resistance was 11.2±6.4 WU. RVESRI and right atrial area were strongly connected to the other right heart metrics. Three zones of adaptation (adapted, maladapted, and severely maladapted) were identified based on the RVESRI to RV systolic pressure relationship. During a mean follow-up of 3.9±2.4 years, the primary end point of death, transplant, or admission for heart failure was reached in 88 patients. RVESRI was incremental to risk prediction scores in pulmonary arterial hypertension, including the Registry to Evaluate Early and Long-Term PAH Disease Management score, the Pulmonary Hypertension Connection equation, and the Mayo Clinic model. Using multivariable analysis, New York Heart Association class III/IV, RVESRI, and log NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) were retained (χ(2), 62.2; P<0.0001). Changes in RVESRI at 1 year (n=203) were predictive of outcome; patients initiated on prostanoid therapy showed the greatest improvement in RVESRI. Among right heart metrics, RVESRI demonstrated the best test-retest characteristics.RVESRI is a simple reproducible prognostic marker in patients with pulmonary arterial hypertension.

  View details for DOI 10.1161/CIRCIMAGING.116.005771

  View details for PubMedID 28592589

• Dynamic changes in aortic impedance after transcatheter aortic valve replacement and its impact on exploratory outcome. international journal of cardiovascular imaging Kobayashi, Y., Kim, J. B., Moneghetti, K. J., Kobayashi, Y., Zhang, R., Brenner, D. A., O'Malley, R., Schnittger, I., Fischbein, M., Miller, D. C., Yeung, A. C., Liang, D., Haddad, F., Fearon, W. F. 2017

  Abstract

  Valvulo-arterial impedance (Zva) has been shown to predict worse outcome in medically managed aortic stenosis (AS) patients. We aimed to investigate the association between Zva and left ventricular (LV) adaptation and to explore the predictive value of Zva for cardiac functional recovery and outcome after transcatheter aortic valve replacement (TAVR). We prospectively enrolled 128 patients with AS who underwent TAVR. Zva was calculated as: (systolic blood pressure + mean transaortic gradient)/stroke volume index). Echocardiographic assessment occurred at baseline, 1-month and 1-year after TAVR. The primary endpoints were to investigate associations between Zva and global longitudinal strain (GLS) at baseline as well as GLS change after TAVR. The secondary was to compare all-cause mortality after TAVR between patients with pre-defined Zva (=5 mmHg m(2)/ml), stroke volume index (=35 ml/m(2)), and GLS (=-15%) cutoffs. The mean GLS was reduced (-13.0 ± 3.2%). The mean Zva was 5.2 ± 1.6 mmHg*m(2)/ml with 55% of values ≥5.0 mmHg*m(2)/ml, considered to be abnormally high. Higher Zva correlated with worse GLS (r = -0.33, p < 0.001). After TAVR, Zva decreased significantly (5.1 ± 1.6 vs. 4.5 ± 1.6 mmHg*m(2)/ml, p = 0.001). A reduction of Zva at 1-month was associated with GLS improvement at 1-month (r = -0.31, p = 0.001) and at 1-year (r = -0.36 and p = 0.001). By Kaplan-Meier analysis, patients with higher Zva at baseline had higher mortality (Log-rank p = 0.046), while stroke volume index and GLS did not differentiate outcome (Log-rank p = 0.09 and 0.25, respectively). As a conclusion, Zva is correlated with GLS in AS as well as GLS improvement after TAVR. Furthermore, a high baseline Zva may have an additional impact to traditional parameters on predicting worse mortality after TAVR.

  View details for DOI 10.1007/s10554-017-1155-6

  View details for PubMedID 28516313

• Left atrial function and phenotypes in asymmetric hypertrophic cardiomyopathy. Echocardiography (Mount Kisco, N.Y.) Kobayashi, Y., Wheeler, M., Finocchiaro, G., Ariyama, M., Kobayashi, Y., Perez, M. V., Liang, D., Kuznetsova, T., Schnittger, I., Ashley, E., Haddad, F. 2017

  Abstract

  Few studies have analyzed changes in left atrial (LA) function associated with different phenotypes of asymmetric hypertrophic cardiomyopathy (HCM). We sought to demonstrate the association of impairments in LA function with disease phenotype in patients with obstructive and nonobstructive HCM.From Stanford Cardiomyopathy Registry, we randomly selected 50 age-/sex-matched healthy controls, 35 patients with nonobstructive HCM (HCM 1), 35 patients with obstructive HCM (HCM 2), and 35 patients with obstructive HCM requiring septal reduction therapy (HCM 3). Echocardiography was performed to evaluate left ventricular (LV) strain as well as LA function including LA emptying fraction and LA strain.The mean age was 51±14 years and 57% were male. LA volume index differed among all four predefined groups (25.6±6.7 mL/m(2) in controls, 32.2±13.3 mL/m(2) in HCM 1, 42.0±12.9 mL/m(2) in HCM 2, 52.4±15.2 mL/m(2) for HCM 3, and P<.05 all between groups). All measurement of LA function was impaired in patients with HCM than controls. Total and passive LA function was further impaired in HCM 2 or 3 compared with HCM 1, while active LA function was not different among the three groups. Among LV strains, only septal longitudinal strain differed among all groups (-18.5±1.9% in controls, -14.5±1.9% in HCM 1, -13.3±1.8% in HCM 2, -11.6±2.3% in HCM 3, and P<.05 all between groups).LA function was impaired in patients with HCM even in minimally symptomatic nonobstructive phenotype. Total and passive LA function was further impaired in patients with obstructive HCM.

  View details for DOI 10.1111/echo.13533

  View details for PubMedID 28370331

• Investigating the value of right heart echocardiographic metrics for detection of pulmonary hypertension in patients with advanced lung disease. The international journal of cardiovascular imaging Amsallem, M., Boulate, D., Kooreman, Z., Zamanian, R. T., Fadel, G., Schnittger, I., Fadel, E., McConnell, M. V., Dhillon, G., Mercier, O., Haddad, F. 2017

  Abstract

  This study determined whether novel right heart echocardiography metrics help to detect pulmonary hypertension (PH) in patients with advanced lung disease (ALD). We reviewed echocardiography and catheterization data of 192 patients from the Stanford ALD registry and echocardiograms of 50 healthy controls. Accuracy of echocardiographic right heart metrics to detect PH was assessed using logistic regression and area under the ROC curves (AUC) analysis. Patients were divided into a derivation (n = 92) and validation cohort (n = 100). Experimental validation was assessed in a piglet model of mild PH followed longitudinally. Tricuspid regurgitation (TR) was not interpretable in 52% of patients. In the derivation cohort, right atrial maximal volume index (RAVI), ventricular end-systolic area index (RVESAI), free-wall longitudinal strain and tricuspid annular plane systolic excursion (TAPSE) differentiated patients with and without PH; 20% of patients without PH had moderate to severe RV enlargement by RVESAI. On multivariate analysis, RAVI and TAPSE were independently associated with PH (AUC = 0.77, p < 0.001), which was confirmed in the validation cohort (0.78, p < 0.001). Presence of right heart metrics abnormalities did not improve detection of PH in patients with interpretable TR (p > 0.05) and provided moderate detection value in patients without TR. Only two patients with more severe PH (mean pulmonary pressure 35 and 36 mmHg) were missed. The animal model confirmed that right heart enlargement discriminated best pigs with PH from shams. This study highlights the frequency of right heart enlargement and dysfunction in ALD irrespectively from presence of PH, therefore limiting their use for detection of PH.

  View details for DOI 10.1007/s10554-017-1069-3

  View details for PubMedID 28120156

• Incremental value of right heart metrics and exercise performance to well-validated risk scores in dilated cardiomyopathy European Heart Journal - Cardiovascular Imaging Moneghetti , K. J., Giraldeau, G., Wheeler, M. T., Kobayashi , Y., Vrtovec, B., Boulate, D., Kuznetsova, T., Schnittger, I., Wu, J. C., Myers, J., Ashely, E., Haddad , F. 2017

  View details for DOI 10.1093/ehjci/jex187

• Load Adaptability in Patients With Pulmonary Arterial Hypertension. Am J Cardiol Amsallem, M., et al 2017: 874–82

  Abstract

  Right ventricular (RV) adaptation to pressure overload is a major prognostic factor in patients with pulmonary arterial hypertension (PAH). The objectives were first to define the relation between RV adaptation and load using allometric modeling, then to compare the prognostic value of different indices of load adaptability in PAH. Both a derivation (n = 85) and a validation cohort (n = 200) were included. Load adaptability was assessed using 3 approaches: (1) surrogates of ventriculo-arterial coupling (e.g., RV area change/end-systolic area), (2) simple ratio of function and load (e.g., tricuspid annular plane systolic excursion/right ventricular systolic pressure), and (3) indices assessing the proportionality of adaptation using allometric pressure-function or size modeling. Proportional hazard modeling was used to compare the hazard ratio for the outcome of death or lung transplantation. The mean age of the derivation cohort was 44 ± 11 years, with 80% female and 74% in New York Heart Association class III or IV. Mean pulmonary vascular resistance index (PVRI) was 24 ± 11 with a wide distribution (1.6 to 57.5 WU/m2). Allometric relations were observed between PVRI and RV fractional area change (R2 = 0.53, p < 0.001) and RV end-systolic area indexed to body surface area right ventricular end-systolic area index (RVESAI) (R2 = 0.29, p < 0.001), allowing the derivation of simple ratiometric load-specific indices of RV adaptation. In right heart parameters, RVESAI was the strongest predictor of outcomes (hazard ratio per SD = 1.93, 95% confidence interval 1.37 to 2.75, p < 0.001). Although RVESAI/PVRI0.35 provided small incremental discrimination on multivariate modeling, none of the load-adaptability indices provided stronger discrimination of outcome than simple RV adaptation metrics in either the derivation or the validation cohort. In conclusion, allometric modeling enables quantification of the proportionality of RV load adaptation but offers small incremental prognostic value to RV end-systolic dimension in PAH.

  View details for DOI 10.1016/j.amjcard.2017.05.053

• GDF-15 (Growth Differentiation Factor 15) Is Associated With Lack of Ventricular Recovery and Mortality After Transcatheter Aortic Valve Replacement. Circulation. Cardiovascular interventions Kim, J. B., Kobayashi, Y. n., Moneghetti, K. J., Brenner, D. A., O'Malley, R. n., Schnittger, I. n., Wu, J. C., Murtagh, G. n., Beshiri, A. n., Fischbein, M. n., Miller, D. C., Liang, D. n., Yeung, A. C., Haddad, F. n., Fearon, W. F. 2017; 10 (12)

  Abstract

  Recent data suggest that circulating biomarkers may predict outcome in patients undergoing transcatheter aortic valve replacement (TAVR). We examined the association between inflammatory, myocardial, and renal biomarkers and their role in ventricular recovery and outcome after TAVR.A total of 112 subjects undergoing TAVR were included in the prospective registry. Plasma levels of B-type natriuretic peptide, hs-TnI (high-sensitivity troponin I), CRP (C-reactive protein), GDF-15 (growth differentiation factor 15), GAL-3 (galectin-3), and Cys-C (cystatin-C) were assessed before TAVR and in 100 sex-matched healthy controls. Among echocardiographic parameters, we measured global longitudinal strain, indexed left ventricular mass, and indexed left atrial volume. The TAVR group included 59% male, with an average age of 84 years, and 1-year mortality of 18%. Among biomarkers, we found GDF-15 and CRP to be strongly associated with all-cause mortality (P<0.001). Inclusion of GDF-15 and CRP to the Society of Thoracic Surgeons score significantly improved C index (0.65-0.79; P<0.05) and provided a category-free net reclassification improvement of 106% at 2 years (P=0.01). Among survivors, functional recovery in global longitudinal strain (>15% improvement) and indexed left ventricular mass (>20% decrease) at 1 year occurred in 48% and 22%, respectively. On multivariate logistic regression, lower baseline GDF-15 was associated with improved global longitudinal strain at 1 year (hazard ratio=0.29; P<0.001). Furthermore, improvement in global longitudinal strain at 1 month correlated with lower overall mortality (hazard ratio=0.45; P=0.03).Elevated GDF-15 correlates with lack of reverse remodeling and increased mortality after TAVR and improves risk prediction of mortality when added to the Society of Thoracic Surgeons score.

  View details for PubMedID 29222133

• Incremental Value of Deformation Imaging and Hemodynamics Following Heart Transplantation: Insights From Graft Function Profiling. JACC. Heart failure Kobayashi, Y. n., Sudini, N. L., Rhee, J. W., Aymami, M. n., Moneghetti, K. J., Bouajila, S. n., Kobayashi, Y. n., Kim, J. B., Schnittger, I. n., Teuteberg, J. J., Khush, K. K., Fearon, W. F., Haddad, F. n. 2017; 5 (12): 930–39

  Abstract

  This study investigated to define graft dysfunction and to determine its incremental association with long-term outcome after heart transplantation (HT).Although graft failure is an established cause of late mortality after HT, few studies have analyzed the prognostic value of graft dysfunction at 1- and 5-year follow-up of HT.Patients who underwent HT and completed their first annual evaluation with right heart catheterization and echocardiography at Stanford University between January 1999 and December 2011 were included in the study. Hierarchical clustering was used to identify modules to capture independent features of graft dysfunction at 1 year. The primary endpoint for analysis consisted of the composite of cardiovascular mortality, re-transplantation, or heart failure hospitalization within 5 years of HT. The study further explored whether changes in graft dysfunction between 1 and 5 years were associated with 10-year all-cause mortality.A total of 215 HT recipients were included in the study. Using hierarchical clustering, 3 functional modules were identified; among them, left ventricular global longitudinal strain (LVGLS), stroke volume index, and right atrial pressure (RAP) or pulmonary capillary wedge pressure (PCWP) captured key features of graft function. Graft dysfunction based on pre defined LVGLS in absolute value <14%, stroke volume index <35 ml/m2, RAP >10 mm Hg, or PCWP >15 mm Hg were present in 41%, 36%, and 27%, respectively. The primary endpoint at 5 years occurred in 52 patients (24%), whereas 10-year all-cause mortality occurred in 30 (27%) of 110 patients alive at 5 years. On multivariate analysis, RAP (standardized hazard ratio: 1.63), LVGLS (standardized hazard ratio: 1.39), and a history of hemodynamically compromising rejection within 1 year (hazard ratio: 2.18) were independent predictors of 5-year outcome. RAP at 5 years, as well as change in RAP from 1 to 5 years, was predictive of 10-year all-cause mortality.RAP and LVGLS at the first annual evaluation provide complementary prognostic information in predicting 5-year outcome after HT.

  View details for PubMedID 29191301

• Myocardial Bridges on Coronary Computed Tomography Angiography　- Correlation With Intravascular Ultrasound and Fractional Flow Reserve. Circulation journal : official journal of the Japanese Circulation Society Forsdahl, S. H., Rogers, I. S., Schnittger, I. n., Tanaka, S. n., Kimura, T. n., Pargaonkar, V. S., Chan, F. P., Fleischmann, D. n., Tremmel, J. A., Becker, H. C. 2017

  Abstract

  Myocardial bridges (MB) are commonly seen on coronary CT angiography (CCTA) in asymptomatic individuals, but in patients with recurrent typical angina symptoms, yet no obstructive coronary artery disease (CAD), evaluation of their potential hemodynamic significance is clinically relevant. The aim of this study was to compare CCTA to invasive coronary angiography (ICA), including intravascular ultrasound (IVUS), to confirm MB morphology and estimate their functional significance in symptomatic patients.Methods and Results:We retrospectively identified 59 patients from our clinical databases between 2009 and 2014 in whom the suspicion for MB was raised by symptoms of recurrent typical angina in the absence of significant obstructive CAD on ICA. All patients underwent CCTA, ICA and IVUS. MB length and depth by CCTA agreed well with length (0.6±23.7 mm) and depth (CT coverage) as seen on IVUS. The product of CT length and depth (CT coverage), (MB muscle index (MMI)), ≥31 predicted an abnormal diastolic fractional flow reserve (dFFR) ≤0.76 with a sensitivity and specificity of 74% and 62% respectively (area under the curve=0.722).In patients with recurrent symptoms of typical angina yet no obstructive CAD, clinicians should consider dynamic ischemia from an MB in the differential diagnosis. The product of length and depth (i.e., MMI) by CCTA may provide some non-invasive insight into the hemodynamic significance of a myocardial bridge, as compared with invasive assessment with dFFR.

  View details for PubMedID 28690285

• Challenging the complementarity of different metrics of left atrial function: insight from a cardiomyopathy-based study. European heart journal cardiovascular Imaging Kobayashi, Y., Moneghetti, K. J., Boralkar, K., Amsallem, M., Tuzovic, M., Liang, D., Yang, P. C., Narayan, S., Kuznetsova, T., Wu, J. C., Schnittger, I., Haddad, F. 2016

  Abstract

  Left ventricular (LV) strain provides incremental values to LV ejection fraction (LVEF) in predicting outcome. We sought to investigate if similar relationship is observed between left atrial (LA) emptying fraction and LA strain.In this study, we selected 50 healthy subjects, 50 patients with dilated, 50 hypertrophic, and 50 infiltrative (light-chain (AL) amyloidosis) cardiomyopathy (CMP). Echocardiographic measures included LVEF and LA emptying fraction as well as LV and LA longitudinal strain (LVLS and LALS). After regression analysis, comparison of least square means of LA strain among aetiologies was performed. Intraclass correlation coefficient (ICC) and coefficient of variation (COV) were used in the assessment of variability and reproducibility of LV and LA metrics. The mean LVLS and all LA metrics were impaired in patients with all CMP compared with healthy subjects. In contrast to the moderate relationship between LVEF and LVLS (r = -0.51, P < 0.001), there was a strong linear relationship between LA emptying fraction and LA strain (r = 0.87, P < 0.001). In multiple regression analysis, total LA strain was associated with LVLS (β = -0.48, P < 0.001), lateral E/e' (β = -0.24, P < 0.001), age (β = -0.21, P < 0.001), and heart rate (β = -0.14, P = 0.02). The least square mean of LA strain adjusted for the parameters was not different among aetiologies (ANOVA P = 0.82). The ICC (>0.77) and COV (<13) were acceptable.In contrast to LV measures, there is a strong linear relationship between volumetric and longitudinal deformation indices of left atrium irrespective of CMP aetiology. Either LA emptying fraction or LA strain could be used as an important parameter in predictive models.

  View details for PubMedID 27638850

• Impact and pitfalls of scaling of left ventricular and atrial structure in population-based studies JOURNAL OF HYPERTENSION Kuznetsova, T., Haddad, F., Tikhonoff, V., Kloch-Badelek, M., Ryabikov, A., Knez, J., Malyutina, S., Stolarz-Skrzypek, K., Thijs, L., Schnittger, I., Wu, J. C., Casiglia, E., Narkiewicz, K., Kawecka-Jaszcz, K., Staessen, J. A. 2016; 34 (6): 1186-1194

  Abstract

  Several allometric methods for indexing cardiac structures to body size have been proposed but the optimal way for normalization of cardiac structures is still controversial. We aimed to estimate the allometric exponents that best describe the relationships between cardiac dimensions and body size, propose normative values, and analyze how the different scaling metrics influence the prevalence of left ventricular hypertrophy (LVH) and chambers enlargement as well as predictive models for cardiovascular outcome in the community.We measured left ventricular end-diastolic dimension, end-diastolic volume, left ventricular mass, and left atrial volume in randomly recruited population cohorts (n = 1509; 52.8% women; mean age, 47.8 years).In a healthy subgroup (n = 656), the allometric exponents that described the relationships between left ventricular end-diastolic dimension and body size were 1, 0.5, and 0.33 for body height, body surface area (BSA), and estimated lean body mass, respectively. With regard to left ventricular end-diastolic volume, left ventricular mass, and left atrial volume the allometric exponents for body height were 2.9, 2.7, and 2.0, respectively; for BSA, they ranged from 1.7 to 1.8; for estimated lean body mass all exponents were around 1. These exponents were used to appropriately scale the cardiac dimensions to body size and derived sex-specific cut-off limits for different indexed cardiac dimensions. The hazard ratios of cardiovascular outcome were highest for LVH defined by left ventricular mass/height.Our study resulted in a proposal for thresholds for various indexed cardiac dimensions. Left ventricular mass indexed to height was sensitive in detection of LVH associated with obesity and slightly better predicted outcome.

  View details for DOI 10.1097/HJH.0000000000000922

  View details for Web of Science ID 000375146000024

  View details for PubMedID 27035735

• Impact of Septal Reduction on Left Atrial Size and Diastole in Hypertrophic Cardiomyopathy ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Finocchiaro, G., Haddad, F., Kobayashi, Y., Lee, D., Pavlovic, A., Schnittger, I., Sinagra, G., Magavern, E., Myers, J., Froelicher, V., Knowles, J. W., Ashley, E. 2016; 33 (5): 686-694

  Abstract

  Both myectomy and alcohol septal ablation (ASA) can substantially reduce left ventricular (LV) outflow obstruction, relieve symptoms, and improve outcomes in hypertrophic cardiomyopathy (HCM). It is unclear whether septal reduction decreases left atrial (LA) size and improves diastolic function. The aim of this study was to analyze the consequences of septal reduction on LA size and diastolic function in a cohort of patients with HCM.Forty patients (mean age: 50 ± 14, male sex 64%) with HCM who underwent septal reduction (myectomy or alcohol septal ablation) were studied. Retrospective analyses of echocardiograms preprocedure, postprocedure, and at 1 year of follow-up were performed.Thirty-one patients had septal myectomy and 9 ASA. The degree of reduction in rest peak LV outflow tract gradient was significant (57 ± 32 vs. 23 ± 20 mmHg at 1 year, P < 0.001). Maximal interventricular septal thickness decreased from 22 ± 6 mm preprocedure to 19 ± 4 mm postprocedure (P < 0.001); moderate-to-severe mitral regurgitation (MR) was initially present in 34% of the sample and only 2% after the procedure. Average LA volume index (LAVI) decreased from 63 ± 20 to 55 ± 20 mL/m(2) at the 1-year follow-up (P < 0.001). We did not observe a significant improvement in diastolic function at Doppler (E/A 1.2 ± 0.4 vs. 1.1 ± 0.5, P = 0.07; E' 7.6 ± 3.6 vs. 6.9 ± 3.0, P = 0.4) pre- and postprocedure, respectively). At 1 year, only 5% of the patients were severely symptomatic (NYHA III). On multivariate analysis, a significant change in the LVOT gradient during stress (Δ gradient ≥30 mmHg) was the only variable independently associated with LAVI reverse remodeling >10 mL/m(2) [OR = 6.4 (CI 95% 1.12-36.44), P = 0.04].Septal reduction is effective in the relief of LV obstruction and symptoms in patients with HCM. The hemodynamic changes result in a significant LA reverse remodeling, but not in an improvement of diastolic function in these patients.

  View details for DOI 10.1111/echo.13158

  View details for PubMedID 26926154

• Functional Versus Anatomic Assessment of Myocardial Bridging by Intravascular Ultrasound: Impact of Arterial Compression on Proximal Atherosclerotic Plaque. Journal of the American Heart Association Yamada, R., Tremmel, J. A., Tanaka, S., Lin, S., Kobayashi, Y., Hollak, M. B., Yock, P. G., Fitzgerald, P. J., Schnittger, I., Honda, Y. 2016; 5 (4)

  Abstract

  The presence of a myocardial bridge (MB) has been shown to promote atherosclerotic plaque formation proximal to the MB, presumably because of hemodynamic disturbances provoked by retrograde blood flow toward this segment in cardiac systole. We aimed to determine the anatomic and functional properties of an MB related to the extent of atherosclerosis assessed by intravascular ultrasound.We enrolled 100 patients with angina but no significant obstructive coronary artery disease who had an intravascular ultrasound-detected MB in the left anterior descending artery (median age 54 years, 36% male). The MB was identified with intravascular ultrasound by the presence of an echolucent band (halo). Anatomically, the MB length was 22±13 mm, and halo thickness was 0.7±0.6 mm. Functionally, systolic arterial compression was 23±12%. The maximum plaque burden up to 20 mm proximal to the MB entrance was significantly greater than the maximum plaque burden within the MB segment. Among the intravascular ultrasound-defined MB properties, arterial compression was the sole MB parameter that demonstrated a significant positive correlation with maximum plaque burden up to 20 mm proximal to the MB entrance (r=0.254, P=0.011 overall; r=0.545, P<0.001 low coronary risk). In multivariate analysis, adjusting for clinical characteristics and coronary risk factors, arterial compression was independently associated with maximum plaque burden up to 20 mm proximal to the MB entrance.In patients with an MB in the left anterior descending artery, the percentage of arterial compression is related directly to the burden of atherosclerotic plaque located proximally to the MB, particularly in patients who otherwise have low coronary risk. This may prove helpful in identifying high-risk MB patients.

  View details for DOI 10.1161/JAHA.114.001735

  View details for PubMedID 27098967

• Comparison of left ventricular manual versus automated derived longitudinal strain: implications for clinical practice and research INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING Kobayashi, Y., Ariyama, M., Kobayashi, Y., Giraldeau, G., Fleischman, D., Kozelj, M., Vrtovec, B., Ashley, E., Kuznetsova, T., Schnittger, I., Liang, D., Haddad, F. 2016; 32 (3): 429-437

  Abstract

  Systolic global longitudinal strain (GLS) is emerging as a useful metric of ventricular function in heart failure and usually assessed using post-processing software. The purpose of this study was to investigate whether longitudinal strain (LS) derived using manual-tracings of ventricular lengths (manual-LS) can be reliable and time efficient when compared to LS obtained by post-processing software (software-LS). Apical 4-chamber view images were retrospectively examined in 50 healthy controls, 100 patients with dilated cardiomyopathy (DCM), and 100 with hypertrophic cardiomyopathy (HCM). We measured endocardial and mid-wall manual-LS and software-LS, using peak of average regional curve [software-LS(a)] and global ventricular lengths [software-LS(l)] according to definition of Lagragian strain. We compared manual-LS and software-LS by using Bland-Altman plot and coefficient of variation (COV). In addition, test-retest was also performed for further assessment of variability in measurements. While manual-LS was obtained in all subjects, software-LS could be obtained in 238 subjects (95 %). The time spent for obtaining manual-LS was significantly shorter than for the software-LS (94 ± 39 s vs. 141 ± 79 s, P < 0.001). Overall, manual-LS had an excellent correlation with both software-LS (a) (R(2) = 0.93, P < 0.001) and software-LS(l) (R(2) = 0.84, P < 0.001). The bias (95 %CI) between endocardial manual-LS and software-LS(a) was 0.4 % [-2.8, 3.6 %] in absolute and 3.5 % [-17.0, 24.0 %] in relative difference while it was 0.4 % [-2.5, 3.3 %] and 3.4 % [-16.2, 23.1 %], respectively with software-LS(l). Mid-wall manual-LS and mid-wall software-LS(a) also had good agreement [a bias (95 % CI) for absolute value of 0.1 % [-2.1, 2.5 %] in HCM, and 0.2 % [-2.2, 2.6 %] in controls]. The COV for manual and software derived LS were below 6 %. Test-retest showed good variability for both methods (COVs were 5.8 and 4.7 for endocardial and mid-wall manual-LS, and 4.6 and 4.9 for endocardial and mid-wall software-LS(a), respectively. Manual-LS appears to be as reproducible as software-LS; this may be of value especially when global strain is the metric of interest.

  View details for DOI 10.1007/s10554-015-0804-x

  View details for Web of Science ID 000370166100008

  View details for PubMedID 26578468

• Regional right ventricular dysfunction in acute pulmonary embolism: relationship with clot burden and biomarker profile INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING Tuzovic, M., Adigopula, S., Amsallem, M., Kobayashi, Y., Kadoch, M., Boulate, D., Krishnan, G., Liang, D., Schnittger, I., Fleischmann, D., McConnell, M. V., Haddad, F. 2016; 32 (3): 389-398

  Abstract

  Regional right ventricular (RV) dysfunction (RRVD) is an echocardiographic feature in acute pulmonary embolism (PE), primarily reported in patients with moderate-to-severe RV dysfunction. This study investigated the clinical importance of RRVD by assessing its relationship with clot burden and biomarkers. We identified consecutive patients admitted to the emergency department between 1999 and 2014 who underwent computed tomographic angiography, echocardiography, and biomarker testing (troponin and NT-proBNP) for suspected acute PE. RRVD was defined as normal excursion of the apex contrasting with hypokinesis of the mid-free wall segment. RV assessment included measurements of ventricular dimensions, fractional area change, free-wall longitudinal strain and tricuspid annular plane systolic excursion. Clot burden was assessed using the modified Miller score. Of 82 patients identified, 51 had acute PE (mean age 66 ± 17 years, 43 % male). No patient had RV myocardial infarction. RRVD was present in 41 % of PEs and absent in all patients without PE. Among patients with PE, 86 % of patients with RRVD had central or multi-lobar PE. Patients with RRVD had higher prevalence of moderate-to-severe RV dilation (81 vs. 30 %, p < 0.01) and dysfunction (86 vs. 23 %, p < 0.01). There was a strong trend for higher troponin level in PE patients with RRVD (38 vs. 13 % in PE patients without RRVD, p = 0.08), while there was no significant difference for NT-proBNP (67 vs. 73 %, p = 0.88). RRVD showed good concordance between readers (87 %). RRVD is associated with an increased clot burden in acute PE and is more prevalent among patients with moderate-to-severe RV enlargement and dysfunction.

  View details for DOI 10.1007/s10554-015-0780-1

  View details for PubMedID 26428674

• Addressing the Controversy of Estimating Pulmonary Arterial Pressure by Echocardiography JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Amsallem, M., Sternbach, J. M., Adigopula, S., Kobayashi, Y., Vu, T. A., Zamanian, R., Liang, D., Dhillon, G., Schnittger, I., McConnell, M. V., Haddad, F. 2016; 29 (2): 93-102

  Abstract

  There is currently controversy over whether echocardiography provides reliable estimations of pulmonary pressures. The objective of this study was to determine the factors influencing the accuracy and reliability of estimating right ventricular systolic pressure (RVSP) using echocardiography in patients with advanced lung disease or pulmonary arterial hypertension.Between January 2001 and December 2012, 667 patients with advanced lung disease or pulmonary arterial hypertension underwent right heart catheterization and transthoracic echocardiography. Of those, 307 had both studies within 5 days of each other. The correlation and bias in estimating RVSP according to tricuspid regurgitation (TR) signal quality and reader expertise were retrospectively determined. Reasons for under- and overestimation were analyzed. The diagnostic performance of estimated RVSP, relative right ventricular size, eccentricity index, and tricuspid annular plane systolic excursion was compared for classifying patients with pulmonary hypertension (mean pulmonary artery pressure ≥ 25 mm Hg).Invasive mean and systolic pulmonary artery pressures were strongly correlated (R(2) = 0.95, P < .001), with mean pulmonary artery pressure = 0.60 × systolic pulmonary artery pressure + 2.1 mm Hg. Among patients undergoing right heart catheterization and transthoracic echocardiography within 5 days, level 3 readers considered only 61% of TR signals interpretable, compared with 72% in clinical reports. Overestimation in the clinical report was related mainly to not assigning peak TR velocity at the modal frequency and underestimation to overreading of uninterpretable signals. When the TR signal was interpretable, the areas under the curve for classifying pulmonary hypertension were 0.97 for RVSP and 0.98 for RVSP and eccentricity index (P > .05). When TR signals were uninterpretable, eccentricity index and right ventricular size were independently associated with pulmonary hypertension (area under the curve, 0.77).Echocardiography reliably estimates RVSP when attention is given to simple quality metrics.

  View details for DOI 10.1016/j.echo.2015.11.001

  View details for Web of Science ID 000369168700003

• Impact and pitfalls of scaling of left ventricular and atrial structure in population-based studies JOURNAL of HYPERTENSION Kuznetsova, T., Haddad, F., Tikhonoff, V., Kloch-Badelek, M., Ryabikov, A., Knez, J., Malyutina, S., Stolarz-Skrzypek, K., Thijs, L., Schnittger, I., Wu, J., Casiglia, E., Narkiewicz, K., Kawecka-Jaszcz, K., Staessen, J. 2016; 34 (5): 1186-94
• Impact of Septal Reduction on Left Atrial Size and Diastole in Hypertrophic Cardiomyopathy ECHOCARDIOGRAPHY Finocchiaro, G., Haddad, F., Kobayashi, Y., Lee, D., Pavlovic, A., Schnittger, I., Sinagra, G., Magavern, E., Myers, J., Froelicher, V., Knowles, J., Ashley, E. 2016; 33 (5): 686-94
• Addressing the Controversy of Estimating Pulmonary Arterial Pressure by Echocardiography. J Am Soc Echocardiogr Ansallem, M., Sternbach, J., Adigopula, S., Kobayashi, Y., Vu, T., Zamanian, R., Liang, D., Dhillon, G., Schnittger, I., McConnell, M., Haddad, F. 2016; 29 (2): 93-102
• Addressing the Controversy of Estimating Pulmonary Arterial Pressure by Echocardiography. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Amsallem, M., Sternbach, J. M., Adigopula, S., Kobayashi, Y., Vu, T. A., Zamanian, R., Liang, D., Dhillon, G., Schnittger, I., McConnell, M. V., Haddad, F. 2015

  Abstract

  There is currently controversy over whether echocardiography provides reliable estimations of pulmonary pressures. The objective of this study was to determine the factors influencing the accuracy and reliability of estimating right ventricular systolic pressure (RVSP) using echocardiography in patients with advanced lung disease or pulmonary arterial hypertension.Between January 2001 and December 2012, 667 patients with advanced lung disease or pulmonary arterial hypertension underwent right heart catheterization and transthoracic echocardiography. Of those, 307 had both studies within 5 days of each other. The correlation and bias in estimating RVSP according to tricuspid regurgitation (TR) signal quality and reader expertise were retrospectively determined. Reasons for under- and overestimation were analyzed. The diagnostic performance of estimated RVSP, relative right ventricular size, eccentricity index, and tricuspid annular plane systolic excursion was compared for classifying patients with pulmonary hypertension (mean pulmonary artery pressure ≥ 25 mm Hg).Invasive mean and systolic pulmonary artery pressures were strongly correlated (R(2) = 0.95, P < .001), with mean pulmonary artery pressure = 0.60 × systolic pulmonary artery pressure + 2.1 mm Hg. Among patients undergoing right heart catheterization and transthoracic echocardiography within 5 days, level 3 readers considered only 61% of TR signals interpretable, compared with 72% in clinical reports. Overestimation in the clinical report was related mainly to not assigning peak TR velocity at the modal frequency and underestimation to overreading of uninterpretable signals. When the TR signal was interpretable, the areas under the curve for classifying pulmonary hypertension were 0.97 for RVSP and 0.98 for RVSP and eccentricity index (P > .05). When TR signals were uninterpretable, eccentricity index and right ventricular size were independently associated with pulmonary hypertension (area under the curve, 0.77).Echocardiography reliably estimates RVSP when attention is given to simple quality metrics.

  View details for DOI 10.1016/j.echo.2015.11.001

  View details for PubMedID 26691401

• Gender Differences in Ventricular Remodeling and Function in College Athletes, Insights from Lean Body Mass Scaling and Deformation Imaging AMERICAN JOURNAL OF CARDIOLOGY Giraldeau, G., Kobayashi, Y., Finocchiaro, G., Wheeler, M., Perez, M., Kuznetsova, T., Lord, R., George, K. P., Oxborough, D., Schnittger, T., Froelicher, V., Liang, D., Ashley, E., Haddad, F. 2015; 116 (10): 1610-1616

  Abstract

  Several studies suggest gender differences in ventricular dimensions in athletes. Few studies have, however, made comparisons of data indexed for lean body mass (LBM) using allometry. Ninety Caucasian college athletes (mixed sports) who were matched for age, ethnicity, and sport total cardiovascular demands underwent dual-energy x-ray absorptiometry scan for quantification of LBM. Athletes underwent comprehensive assessment of left and right ventricular and atrial structure and function using 2-dimensional echocardiography and deformation imaging using the TomTec analysis system. The mean age of the study population was 18.9 ± 1.9 years. Female athletes (n = 45) had a greater fat free percentage (19.4 ± 3.7%) compared to male athletes (11.5 ± 3.7%). When scaled to body surface area, male had on average 19 ± 3% (p <0.001) greater left ventricular (LV) mass; in contrast, when scaled to LBM, there was no significant difference in indexed LV mass -1.4 ± 3.0% (p = 0.63). Similarly, when allometrically scaled to LBM, there was no significant gender-based difference in LV or left atrial volumes. Although female athletes had mildly higher LV ejection fraction and LV global longitudinal strain in absolute value, systolic strain rate and allometrically indexed stroke volume were not different between genders (1.5 ± 3.6% [p = 0.63] and 0.0 ± 3.7% [p = 0.93], respectively). There were no differences in any of the functional atrial indexes including strain or strain rate parameters. In conclusion, gender-related differences in ventricular dimensions or function (stroke volume) appear less marked, if not absent, when indexing using LBM allometrically.

  View details for DOI 10.1016/j.amjcard.2015.08.026

  View details for PubMedID 26456207

• Exercise Strain Echocardiography in Patients With a Hemodynamically Significant Myocardial Bridge Assessed by Physiological Study JOURNAL OF THE AMERICAN HEART ASSOCIATION Kobayashi, Y., Tremmel, J. A., Kobayashi, Y., Amsallem, M., Tanaka, S., Yamada, R., Rogers, I. S., Haddad, F., Schnittger, I. 2015; 4 (11)

  Abstract

  Although a myocardial bridge (MB) is often regarded as a benign coronary variant, recent studies have associated MB with focal myocardial ischemia. The physiological consequences of MB on ventricular function during stress have not been well established.We enrolled 58 patients with MB of the left anterior descending artery, diagnosed by intravascular ultrasound. Patients underwent invasive physiological evaluation of the MB by diastolic fractional flow reserve during dobutamine challenge and exercise echocardiography. Septal and lateral longitudinal strain (LS) were assessed at rest and immediately after exercise and compared with strain of matched controls. Absolute and relative changes in strain were also calculated. The mean age was 42.5±16.0 years. Fifty-five patients had a diastolic fractional flow reserve ≤0.76. At rest, there was no significant difference between the 2 groups in septal LS (19.0±1.8% for patients with MB versus 19.2±1.5% for control, P=0.53) and lateral LS (20.1±2.0% versus 20.0±1.6%, P=0.83). With stress, compared with controls, patients with MB had a lower peak septal LS (18.9±2.6% versus 21.7±1.6%, P<0.001) and lower absolute (-0.1±2.1% versus 2.5±1.3%, P<0.001) and relative change (-0.6±11.2% versus 13.1±7.8%, P<0.001) in septal LS, whereas there was no significant difference in lateral LS. In multivariate analysis, diastolic fractional flow reserve and length were independent determinants of lower changes in septal LS.Patients with a hemodynamically significant MB, determined by invasive diastolic fractional flow reserve, have significantly lower change in septal LS on exercise echocardiography, suggesting that septal LS may be useful for noninvasively assessing the hemodynamic significance of an MB.

  View details for DOI 10.1161/JAHA.115.002496

  View details for Web of Science ID 000366615600020

  View details for PubMedID 26581225

• Invasive physiologic and anatomic multimodality assessment of myocardial bridging. Coronary artery disease Schwartz, J. G., Tanaka, S., Schnittger, I., Tremmel, J. A. 2015; 26: e38-40

  View details for DOI 10.1097/MCA.0000000000000206

  View details for PubMedID 26247269

• Right Heart Score for Predicting Outcome in Idiopathic, Familial, or Drug- and Toxin-Associated Pulmonary Arterial Hypertension JACC-CARDIOVASCULAR IMAGING Haddad, F., Spruijt, O. A., Denault, A. Y., Mercier, O., Brunner, N., Furman, D., Fadel, E., Bogaard, H. J., Schnittger, I., Vrtovec, B., Wu, J. C., Perez, V. D., Vonk-Noordegraaf, A., Zamanian, R. T. 2015; 8 (6): 627-638

  View details for DOI 10.1016/j.jcmg.2014.12.029

  View details for Web of Science ID 000356560600001

  View details for PubMedID 25981508

• Prevalence and Prognostic Role of Right Ventricular Involvement in Stress-Induced Cardiomyopathy JOURNAL OF CARDIAC FAILURE Finocchiaro, G., Kobayashi, Y., Magavern, E., Zhou, J. Q., Ashley, E., Sinagra, G., Schnittger, I., Knowles, J. W., Fearon, W. F., Haddad, F., Tremmel, J. A. 2015; 21 (5): 419-425

  Abstract

  Stress-induced cardiomyopathy (SCM) is a reversible cardiomyopathy observed in patients without significant coronary disease. The aim of this study was to assess the incidence and clinical significance of right ventricular (RV) involvement in SCM.We retrospectively analyzed echocardiograms from 40 consecutive patients who presented with SCM at Stanford University Medical Center from September 2000 to November 2010. The primary end point was overall mortality. RV involvement was observed in 20 patients (50%; global RV hypokinesia in 15 patients and focal RV apical akinesia in 5 patients). The independent correlates of RV involvement were older age (odds ratio [OR] 1.09, 95% confidence interval [CI] 1.02-1.7two, P = .01) and LVEF (per 10% decrease: OR 3.60, CI 1.77-7.32; P = .02). At a mean follow-up of 44 ± 32 months, 12 patients (30%) died (in-hospital death in 3 patients). At multivariate analysis, the presence of an RV fractional area change <35% emerged as an independent predictor of death (OR 3.6, CI 1.06-12.41; P = .04).RV involvement is a common finding in SCM, and may present as either global or focal RV apical involvement. Both older age and lower LVEF are associated with a higher risk of RV involvement, which appears to be a major predictor of death.

  View details for DOI 10.1016/j.cardfail.2015.02.001

  View details for PubMedID 25704104

• Cardiopulmonary responses and prognosis in hypertrophic cardiomyopathy: a potential role for comprehensive noninvasive hemodynamic assessment. JACC. Heart failure Finocchiaro, G., Haddad, F., Knowles, J. W., Caleshu, C., Pavlovic, A., Homburger, J., Shmargad, Y., Sinagra, G., Magavern, E., Wong, M., Perez, M., Schnittger, I., Myers, J., Froelicher, V., Ashley, E. A. 2015; 3 (5): 408-418

  Abstract

  This study sought to discover the key determinants of exercise capacity, maximal oxygen consumption (oxygen uptake [Vo2]), and ventilatory efficiency (ventilation/carbon dioxide output [VE/Vco2] slope) and assess the prognostic potential of metabolic exercise testing in hypertrophic cardiomyopathy (HCM).The intrinsic mechanisms leading to reduced functional tolerance in HCM are unclear.The study sample included 156 HCM patients consecutively enrolled from January 1, 2007 to January 1, 2012 with a complete clinical assessment, including rest and stress echocardiography and cardiopulmonary exercise test (CPET) with impedance cardiography. Patients were also followed for the composite outcome of cardiac-related death, heart transplant, and functional deterioration leading to septal reduction therapy (myectomy or septal alcohol ablation).Abnormalities in CPET responses were frequent, with 39% (n = 61) of the sample showing a reduced exercise tolerance (Vo2 max <80% of predicted) and 19% (n = 30) characterized by impaired ventilatory efficiency (VE/Vco2 slope >34). The variables most strongly associated with exercise capacity (expressed in metabolic equivalents), were peak cardiac index (r = 0.51, p < 0.001), age (r = -0.25, p < 0.01), male sex (r = 0.24, p = 0.02), and indexed right ventricular end-diastolic area (r = 0.31, p = 0.002), resulting in an R(2) of 0.51, p < 0.001. Peak cardiac index was the main predictor of peak Vo2 (r = 0.61, p < 0.001). The variables most strongly related to VE/VCO2 slope were E/E' (r = 0.23, p = 0.021) and indexed left atrial volume index (LAVI) (r = 0.34, p = 0.005) (model R(2) = 0.15). The composite endpoint occurred in 21 (13%) patients. In an exploratory analysis, 3 variables were independently associated with the composite outcome (mean follow-up 27 ± 11 months): peak Vo2 <80% of predicted (hazard ratio: 4.11; 95% confidence interval [CI]: 1.46 to 11.59; p = 0.008), VE/Vco2 slope >34 (hazard ratio: 3.14; 95% CI: 1.26 to 7.87; p = 0.014), and LAVI >40 ml/m(2) (hazard ratio: 3.32; 95% CI: 1.08 to 10.16; p = 0.036).In HCM, peak cardiac index is the main determinant of exercise capacity, but it is not significantly related to ventilatory efficiency. Peak Vo2, ventilatory inefficiency, and LAVI are associated with an increased risk of major events in the short-term follow-up.

  View details for DOI 10.1016/j.jchf.2014.11.011

  View details for PubMedID 25863972

• Septal curvature is marker of hemodynamic, anatomical, and electromechanical ventricular interdependence in patients with pulmonary arterial hypertension. Echocardiography (Mount Kisco, N.Y.) Haddad, F., Guihaire, J., Skhiri, M., Denault, A. Y., Mercier, O., Al-Halabi, S., Vrtovec, B., Fadel, E., Zamanian, R. T., Schnittger, I. 2014; 31 (6): 699-707

  Abstract

  The objective of this study was to determine the factors independently associated with septal curvature in patients with pulmonary arterial hypertension (PAH).Eighty-five consecutive patients with PAH who had an echocardiogram and a right heart catheterization within 24 hours of each others were included in the study. Septal curvature was assessed at the mid-papillary level using the eccentricity index (EI). Marked early systolic septal anterior motion was defined as a change in EI > 0.2 between end-diastole and early systole. Inter-ventricular mechanical delay was calculated as the percent time difference between right ventricular (RV) to left ventricular (LV) end-ejection time normalized for the RR interval.Average age was 45 ± 11 years and the majority of patients were women (75%). Mean right atrial pressure was 11 ± 7 mmHg, mean PAP was 52 ± 13 mmHg, relative RV area 1.8 ± 0.9, and RV fractional area change 24 ± 8%. End-diastolic EI was 1.6 ± 0.4 and systolic EI was 2.5 ± 0.8. On multivariate analysis relative pulmonary pressure, relative RV area, and inter-ventricular mechanical delay were independently associated with systolic EI (R(2)  = 0.72, P < 0.001). Independent determinants of diastolic EI included relative RV area and mean PAP (R(2)  = 0.69, P < 0.001). A systolic EI >1.08 differentiated patients with PAH from healthy controls with an AUC = 0.99. Patients with early systolic septal anterior motion (44% of subjects) had lower exercise capacity, more extensive ventricular remodeling, and worst ventricular function.Septal curvature is a useful marker of structural, hemodynamic, and electromechanical ventricular interdependence in PAH.

  View details for DOI 10.1111/echo.12468

  View details for PubMedID 24372843

• Exercise capacity and paroxysmal atrial fibrillation in patients with hypertrophic cardiomyopathy. Heart Azarbal, F., Singh, M., Finocchiaro, G., Le, V., Schnittger, I., Wang, P., Myers, J., Ashley, E., Perez, M. 2014; 100 (8): 624-630

  Abstract

  Atrial fibrillation (AF) is the most common arrhythmia among patients with hypertrophic cardiomyopathy (HCM). The relationship between paroxysmal AF and exercise capacity in this population is incompletely understood.Patients with HCM underwent symptom-limited cardiopulmonary testing with expired gas analysis at Stanford Hospital between October 2006 and October 2012. Baseline demographics, medical histories and resting echocardiograms were obtained for all subjects. Diagnosis of AF was established by review of medical records and baseline ECG. Those with paroxysmal AF were in sinus rhythm at the time of cardiopulmonary testing with expired gas analysis. Exercise intolerance was defined as peak VO2<20 mL/kg/min. We used multivariate logistic regression to evaluate the association between exercise intolerance and paroxysmal AF.Among the 265 patients recruited, 55 had AF (28 paroxysmal and 27 permanent). Compared with those without AF, subjects with paroxysmal AF were older, more likely to use antiarrhythmic and anticoagulant medications, and had larger left atria. Patients with paroxysmal AF achieved lower peak VO2 (21.9±9.2 mL/kg/min vs 26.9±10.8 mL/kg/min, p=0.02) and were more likely to have exercise intolerance (61% vs 28%, p<0.001) compared with those without AF. After adjustment for age, sex and body mass index (BMI) exercise intolerance remained significantly associated with paroxysmal AF (OR 4.65, 95% CI 1.83 to 11.83, p=0.001).Patients with HCM and paroxysmal AF demonstrate exercise intolerance despite being in sinus rhythm at the time of exercise testing.

  View details for DOI 10.1136/heartjnl-2013-304908

  View details for PubMedID 24326897

• Latent obstruction and left atrial size are predictors of clinical deterioration leading to septal reduction in hypertrophic cardiomyopathy. Journal of cardiac failure Finocchiaro, G., Haddad, F., Pavlovic, A., Sinagra, G., Schnittger, I., Knowles, J. W., Perez, M., Magavern, E., Myers, J., Ashley, E. 2014; 20 (4): 236-243

  Abstract

  Exercise echocardiography is a reliable tool to assess left ventricular (LV) dynamic obstruction in hypertrophic cardiomyopathy (HCM). The aim of this study was to determine the role of exercise echocardiography in the evaluation of latent obstruction and in predicting clinical deterioration in HCM patients.We considered 283 HCM patients studied with exercise echocardiography. The end point was clinical deterioration leading to septal reduction (myectomy or alcohol septal ablation). LV latent obstruction was present at enrollment in 67 patients (24%). During a mean follow-up of 42 ± 31 months, 42 patients had clinical deterioration leading to septal reduction therapy: in 12/67 (22%) patients with a latent obstruction at enrollment, in 28/84 (33%) patients with obstruction at rest, and in 2/132 (1.5%) with obstruction neither at rest or during stress. Multivariate analysis identified the following variables as independently associated with the end point: LV gradient >30 mm Hg at rest (hazard ratio [HR] 2.56, 95% CI 1.27-5.14; P = .009), LV gradient >30 mm Hg during stress (HR 4.96, 95% CI 1.81-13.61; P = .002), and indexed left atrial volume (LAVi ) >40 mL/m(2) (HR 2.86, 95% CI 1.47-5.55; P = .002). In patients with a latent obstruction, the strongest independent predictor of outcome was LAVi >40 mL/m(2) (HR 3.75, 95% CI 1.12-12.51; P = .032).Assessment of LV gradient during stress with exercise echocardiography is an important tool for the evaluation of latent obstruction in HCM and may have a role in risk stratification of these patients.

  View details for DOI 10.1016/j.cardfail.2014.01.014

  View details for PubMedID 24486928

• Histological characteristics of myocardial bridge with an ultrasonic echolucent band. Comparison between intravascular ultrasound and histology. Circulation journal Yamada, R., Turcott, R. G., Connolly, A. J., Ikeno, F., McConnell, M. V., Schnittger, I., Fitzgerald, P. J., Honda, Y. 2014; 78 (2): 502-504

  View details for PubMedID 24172077

• Race differences in ventricular remodeling and function among college football players. American journal of cardiology Haddad, F., Peter, S., Hulme, O., Liang, D., Schnittger, I., Puryear, J., Gomari, F. A., Finocchiaro, G., Myers, J., Froelicher, V., Garza, D., Ashley, E. A. 2013; 112 (1): 128-134

  Abstract

  Athletic training is associated with increases in ventricular mass and volume. Recent studies have shown that left ventricular mass increases proportionally in white athletes with a mass/volume ratio approaching unity. The objective of this study was to compare the proportionality in ventricular remodeling and ventricular function in black versus white National Collegiate Athletic Association Division I football players. From 2008 to 2011, football players at Stanford University underwent cardiovascular screening with a 12-point history and physical examination, electrocardiography, and focused echocardiography. Compared with white players, black players had on average higher left ventricular mass indexes (77 ± 11 vs 71 ± 11 g/m(2), p = 0.009), higher mass/volume ratios (1.18 ± 0.16 vs 1.06 ± 0.09 g/ml, p <0.001), and higher QRS vector magnitudes (3.2 ± 0.7 vs 2.7 ± 0.8, p = 0.002). Black race had an odds ratio of 14 (95% confidence interval 5 to 42, p <0.001) for a mass/volume ratio >1.2. Mass/volume ratio was inversely related to early diastolic tissue Doppler velocity e' (r = -0.50, p <0.001) but not to QRS vector magnitude (r = 0.065, p = 0.034). With regard to systolic indexes, there was no significant difference in the left ventricular ejection fraction, velocity of circumferential shortening, and isovolumic acceleration. In conclusion, black college football players exhibit more concentric ventricular remodeling, lower early diastolic annular velocities, and increased ventricular voltage compared with white players. Ventricular mass increases proportionally to volume in white players but not in black players.

  View details for DOI 10.1016/j.amjcard.2013.02.065

  View details for PubMedID 23602691

• A novel stress echocardiography pattern for myocardial bridge with invasive structural and hemodynamic correlation. Journal of the American Heart Association Lin, S., Tremmel, J. A., Yamada, R., Rogers, I. S., Yong, C. M., Turcott, R., McConnell, M. V., Dash, R., Schnittger, I. 2013; 2 (2)

  View details for DOI 10.1161/JAHA.113.000097

  View details for PubMedID 23591827

• PAROXYSMAL ATRIAL FIBRILLATION IS ASSOCIATED WITH EXERCISE INTOLERANCE AMONG INDIVIDUALS WITH HYPERTROPHIC CARDIOMYOPATHY 62nd Annual Scientific Session of the American-College-of-Cardiology Azarbal, F., Singh, M., Finocchiaro, G., Le, V., Schnittger, I., Wang, P., Myers, J., Perez, M., Ashley, E. ELSEVIER SCIENCE INC. 2013: E1617–E1617

  View details for Web of Science ID 000316555201722

• Clinical and Functional Correlates of Early Microvascular Dysfunction After Heart Transplantation CIRCULATION-HEART FAILURE Haddad, F., Khazanie, P., Deuse, T., Weisshaar, D., Zhou, J., Nam, C. W., Vu, T. A., Gomari, F. A., Skhiri, M., Simos, A., Schnittger, I., Vrotvec, B., Hunt, S. A., Fearon, W. F. 2012; 5 (6): 759-768

  Abstract

  Microvascular dysfunction is emerging as a strong predictor of outcome in heart transplant recipients. At this time, the determinants and consequences of early microvascular dysfunction are not well established. The objective of the study was to determine the risk factors and functional correlates associated with early microvascular dysfunction in heart transplant recipients.Sixty-three heart transplant recipients who had coronary physiology assessment, right heart catheterization, and echocardiography performed at the time of their first annual evaluation were included in the study. Microvascular dysfunction was assessed using the recently described index of microcirculatory resistance. The presence of microvascular dysfunction, predefined by an index of microcirculatory resistance >20, was observed in 46% of patients at 1 year. A history of acute rejection and undersized donor hearts were associated with microvascular dysfunction at 1 year, with odds ratio of 4.0 (1.3-12.8) and 3.6 (1.2-11.1), respectively. Patients with microvascular dysfunction had lower cardiac index (3.1±0.7 versus 3.5±0.7 L/min per m(2); P=0.02) and mild graft dysfunction measured by echocardiography-derived left and right myocardial performance indices ([0.54±0.09 versus 0.43±0.09; P<0.01] and [0.47±0.14 versus 0.32±0.05; P<0.01], respectively). Microvascular dysfunction was also associated with a higher likelihood of death, graft failure, or allograft vasculopathy at 5 years after transplant (hazard ratio, 2.52 [95% CI, 1.04-5.91]).A history of acute rejection during the first year and smaller donor hearts were identified as risk factors for early microvascular dysfunction. Microvascular dysfunction assessed using index of microcirculatory resistances at 1 year was also associated with worse graft function and possibly worse clinical outcomes.

  View details for DOI 10.1161/CIRCHEARTFAILURE.111.962787

  View details for PubMedID 22933526

• Characteristics and Outcome After Hospitalization for Acute Right Heart Failure in Patients With Pulmonary Arterial Hypertension CIRCULATION-HEART FAILURE Haddad, F., Peterson, T., Fuh, E., Kudelko, K. T., Perez, V. D., Skhiri, M., Vagelos, R., Schnittger, I., Denault, A. Y., Rosenthal, D. N., Doyle, R. L., Zamanian, R. T. 2011; 4 (6): 692-699

  Abstract

  Although much is known about the risk factors for poor outcome in patients hospitalized with acute heart failure and left ventricular dysfunction, much less is known about the syndrome of acute heart failure primarily affecting the right ventricle (acute right heart failure).By using Stanford Hospital's pulmonary hypertension database, we identified consecutive acute right heart failure hospitalizations in patients with PAH. We used longitudinal regression analysis with the generalized estimating equations method to identify factors associated with an increased likelihood of 90-day mortality or urgent transplantation. From June 1999 to September 2009, 119 patients with PAH were hospitalized for acute right heart failure (207 episodes). Death or urgent transplantation occurred in 34 patients by 90 days of admission. Multivariable analysis identified a higher respiratory rate on admission (>20 breaths per minute; OR, 3.4; 95% CI, 1.5-7.8), renal dysfunction on admission (glomerular filtration rate <45 mL/min per 1.73 m2; OR, 2.7; 95% CI, 1.2-6.3), hyponatremia (serum sodium ≤136 mEq/L; OR, 3.6; 95% CI, 1.7-7.9), and tricuspid regurgitation severity (OR, 2.5 per grade; 95% CI, 1.2-5.5) as independent factors associated with an increased likelihood of death or urgent transplantation.These results highlight the high mortality after hospitalizations for acute right heart failure in patients with PAH. Factors identifiable within hours of hospitalization may help predict the likelihood of death or the need for urgent transplantation in patients with PAH.

  View details for DOI 10.1161/CIRCHEARTFAILURE.110.949933

  View details for PubMedID 21908586

• Stress-induced cardiomyopathy associated with a transfusion reaction: A case of potential crosstalk between the histaminic and adrenergic systems EXPERIMENTAL & CLINICAL CARDIOLOGY Zhou, J. Q., Choe, E., Ang, L., Schnittger, I., Rockson, S. G., Tremmel, J. A., Haddad, F. 2011; 16 (1): 30-32

  Abstract

  The adrenergic and histaminergic systems have been reported to have analogous effects on the heart. A case of transient ventricular dysfunction with echocardiographic findings characteristic of stress-induced cardiomyopathy (also known as takotsubo cardiomyopathy) in a patient who had an urticarial transfusion reaction is described. The effect of histamine on ventricular function and its interaction with the adrenergic system are discussed.

  View details for Web of Science ID 000300518800008

  View details for PubMedID 21523205

  View details for PubMedCentralID PMC3076164

• A comparison of echocardiographic measures of diastolic function for predicting all-cause mortality in a predominantly male population AMERICAN HEART JOURNAL Nguyen, P. K., Schnittger, I., Heidenreich, P. A. 2011; 161 (3): 530-537

  Abstract

  Prior studies demonstrating the prognostic value of echocardiographic measures of diastolic function have been limited by sample size, have included only select clinical populations, and have not incorporated newer measures of diastolic function nor determined their independent prognostic value. The objective of this study is to determine the independent prognostic value of established and new echocardiographic parameters of diastolic function.We included 3,604 consecutive patients referred to 1 of 3 echocardiography laboratories over a 2-year period. We obtained measurements of mitral inflow velocities, pulmonary vein filling pattern, mitral annulus motion (e'), and propagation velocity (V(p)). The primary end point was 1-year all-cause mortality.The mean age of the patients was 68 years, and 95% were male. There were 277 deaths during a mean follow-up of 248 ± 221 days. For patients with reduced left ventricular ejection fraction (LVEF), all measured parameters except for e' were associated with mortality (P < .05) on univariate analysis. For patients with preserved LVEF, the E-wave velocity was significantly associated with mortality (P < .05) on univariate analysis. The deceleration time/E-wave velocity ratio, V(p), and pulmonary vein filling pattern were borderline significant (P < .10). With multivariate analysis, only V(p) was associated with survival for both reduced (P = .02) and preserved LVEF groups (P = .01).In a large, clinically diverse population, most measures of diastolic function were predictive of all-cause mortality without adjustment for patient characteristics. On multivariate analysis, only V(p) was independently associated with total mortality. This association with mortality may be related to factors other than diastolic function and warrants further investigation.

  View details for DOI 10.1016/j.ahj.2010.12.010

  View details for Web of Science ID 000288156400018

  View details for PubMedID 21392608

• Mechanisms of exercise intolerance in patients with hypertrophic cardiomyopathy AMERICAN HEART JOURNAL Le, V., Perez, M. V., Wheeler, M. T., Myers, J., Schnittger, I., Ashley, E. A. 2009; 158 (3): E27-E34

  Abstract

  To determine the relation between echocardiogram findings and exercise capacity in hypertrophic cardiomyopathy (HCM).Sixty-three patients (48 +/- 15 years) were referred for cardiopulmonary testing and exercise echocardiography. They were classified by morphology: proximal (n = 11), reverse curvature (n = 32), apical (n = 7), and concentric HCM (n = 13). There were more women in proximal and reverse curvature groups. Proximal HCM patients were older. Maximal left ventricular thickness was highest in reverse curvature group. At peak exercise, concentric HCM achieved the lowest percent predicted maximal Vo2. Excluding apical group, no significant differences in gradient were noted between groups. Overall, no statistically significant correlation was found between peak Vo2, wall thickness, and gradient. Significant correlations were noted between peak Vo2 and indexed left atrial (LA) volume (r = -0.52), lateral E' (r = 0.50), and lateral E/E' ratio (r = -0.46). A multivariate model including age, lateral E', indexed LA volume, and mitral A wave explained 46% of the variance in peak Vo2 (P = .01).Lateral E' and indexed LA volume are negatively correlated with functional capacity. Although patients with concentric morphology achieved the lowest peak Vo2, wall thickness and gradient did not predict exercise capacity.

  View details for DOI 10.1016/j.ahj.2009.06.006

  View details for Web of Science ID 000269641200027

  View details for PubMedID 19699847

• Multiplanar Reconstruction of Three-Dimensional Transthoracic Echocardiography Improves the Presurgical Assessment of Mitral Prolapse JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Beraud, A., Schnittger, I., Miller, D. C., Liang, D. H. 2009; 22 (8): 907-913

  Abstract

  The aim of this study was to evaluate the value and accuracy of multiplanar reconstruction (MPR) of three-dimensional (3D) transthoracic echocardiographic data sets in assessing mitral valve pathology in patients with surgical mitral valve prolapse (MVP).Sixty-four patients with surgical MVP and preoperative two-dimensional (2D) and 3D transthoracic echocardiography were analyzed. The descriptions obtained by 3D MPR and 2D were compared in the context of the surgical findings.Two-dimensional echocardiography correctly identified the prolapsing leaflets in 32 of 64 patients and 3D MPR in 46 of 64 patients (P=.016). Among the 27 patients with complex pathology (ie, more than isolated middle scallop of the posterior leaflet prolapse), 3D MPR identified 20 correctly, as opposed to 6 with 2D imaging (P<.001).Interpretation of 3D transthoracic echocardiographic images with MPR improved the accuracy of the description of the MVP compared with 2D interpretation. This added value of 3D MPR was most important in extensive and/or commissural prolapse.

  View details for DOI 10.1016/j.echo.2009.05.007

  View details for PubMedID 19553082

• A Novel Non-Invasive Method of Estimating Pulmonary Vascular Resistance in Patients With Pulmonary Arterial Hypertension JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Haddad, F., Zamanian, R., Beraud, A., Schnittger, I., Feinstein, J., Peterson, T., Yang, P., Doyle, R., Rosenthal, D. 2009; 22 (5): 523-529

  Abstract

  The assessment of pulmonary vascular resistance (PVR) plays an important role in the diagnosis and management of pulmonary arterial hypertension (PAH). The main objective of this study was to determine whether the noninvasive index of systolic pulmonary arterial pressure (SPAP) to heart rate (HR) times the right ventricular outflow tract time-velocity integral (TVI(RVOT)) (SPAP/[HR x TVI(RVOT)]) provides clinically useful estimations of PVR in PAH.Doppler echocardiography and right-heart catheterization were performed in 51 consecutive patients with established PAH. The ratio of SPAP/(HR x TVI(RVOT)) was then correlated with invasive indexed PVR (PVRI) using regression and Bland-Altman analysis. Using receiver operating characteristic curve analysis, a cutoff value for the Doppler equation was generated to identify patients with PVRI > or = 15 Wood units (WU)/m2.The mean pulmonary arterial pressure was 52 +/- 15 mm Hg, the mean cardiac index was 2.2 +/- 0.6 L/min/m2, and the mean PVRI was 20.5 +/- 9.6 WU/m2. The ratio of SPAP/(HR x TVI(RVOT)) correlated very well with invasive PVRI measurements (r = 0.860; 95% confidence interval, 0.759-0.920). A cutoff value of 0.076 provided well-balanced sensitivity (86%) and specificity (82%) to determine PVRI > 15 WU/m2. A cutoff value of 0.057 increased sensitivity to 97% and decreased specificity to 65%.The novel index of SPAP/(HR x TVI(RVOT)) provides useful estimations of PVRI in patients with PAH.

  View details for DOI 10.1016/j.echo.2009.01.021

  View details for PubMedID 19307098

• An unusual case of partial anomalous pulmonary venous drainage: Utility of the cardiac MRI INTERNATIONAL JOURNAL OF CARDIOLOGY Kapoor, J. R., Katikireddy, C., Rubin, G., Schnittger, I., McConnell, M. V. 2009; 133 (1): E35-E36

  View details for DOI 10.1016/j.ijcard.2007.08.113

  View details for Web of Science ID 000263950100046

  View details for PubMedID 18164082

• Left Atrial Volume and E/E' Ratio are Most Predictive of Exercise Capacity in Hypertrophic Cardiomyopathy 81st Annual Scientific Session of the American-Heart-Association Le, V., Perez, M., Wheeler, M., Schnittger, I., Ashley, E. LIPPINCOTT WILLIAMS & WILKINS. 2008: S641–S641

  View details for Web of Science ID 000262104502032

• Predictive value of the index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Fearon, W. F., Shah, M., Ng, M., Brinton, T., Wilson, A., Trernmel, J. A., Schnittger, I., Lee, D. P., Vagelos, R. H., Fitzgerald, P. J., Yock, P. G., Yeung, A. C. 2008; 51 (5): 560-565

  Abstract

  The objective of this study is to evaluate the predictive value of the index of microcirculatory resistance (IMR) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI).Despite adequate epicardial artery reperfusion, a number of patients with STEMI have a poor prognosis because of microvascular damage. Assessing the status of the microvasculature in this setting remains challenging.In 29 patients after primary PCI for STEMI, IMR was measured with a pressure sensor/thermistor-tipped guidewire. The Thrombolysis In Myocardial Infarction (TIMI) myocardial perfusion grade, TIMI frame count, coronary flow reserve, and ST-segment resolution were also recorded.The IMR correlated significantly with the peak creatinine kinase (CK) (R = 0.61, p = 0.0005) while the other measures of microvascular dysfunction did not. In patients with an IMR greater than the median value of 32 U, the peak CK was significantly higher compared with those having values 32 U compared with

  View details for DOI 10.1016/j.jacc.2007.08.062

  View details for PubMedID 18237685

• Yield of transesophageal echocardiography in ischemic stroke patients by age and lesion pattern on diffusion-weighted MRI 33rd International Stroke Conference Campbell, D. M., Beraud, A., Mlynash, M., Schnittger, I., Eyngorn, I., Kumar, M. A., Tong, D. C., Moseley, M., Albers, G. W., Wijman, C. A. LIPPINCOTT WILLIAMS & WILKINS. 2008: 575–76

  View details for Web of Science ID 000252726100246

• MRI-based diagnostic evaluation has substantial impact on final stroke diagnosis 33rd International Stroke Conference Kumar, M. A., Campbell, D. M., Vangala, H. L., Eyngorn, I., Olivot, J. M., Beraud, A. S., Belgude, A., Lansberg, M. G., Schnittger, I., Wijman, C. A., Tong, D. C., Mlynash, M., Albers, G. W., Moseley, M. LIPPINCOTT WILLIAMS & WILKINS. 2008: 569–69

  View details for Web of Science ID 000252726100222

• Multiplanar visualization in 3D transthoracic echocardiography for precise delineation of mitral valve pathology ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Liang, D., Paloma, A., Kuppahally, S. S., Miller, D. C., Schnittger, I. 2008; 25 (1): 84-87

  Abstract

  A novel multiplanar reformatting (MPR) technique in three-dimensional transthoracic echocardiography (3D TTE) was used to precisely localize the prolapsed lateral segment of posterior mitral valve leaflet in a patient symptomatic with mitral valve prolapse (MVP) and moderate mitral regurgitation (MR) before undergoing mitral valve repair surgery. Transesophageal echocardiography was avoided based on the findings of this new technique by 3D TTE. It was noninvasive, quick, reproducible and reliable. Also, it did not need the time-consuming reconstruction of multiple cardiac images. Mitral valve repair surgery was subsequently performed based on the MPR findings and corroborated the findings from the MPR examination.

  View details for DOI 10.1111/j.1540-8175.2007.00566.x

  View details for PubMedID 18186784

• Comparison of three-dimensional echocardiography to two-dimensional echocardiography and fluoroscopy for monitoring of endomyocardial biopsy AMERICAN JOURNAL OF CARDIOLOGY Amitai, M. E., Schnittger, I., Popp, R. L., Chow, J., Brown, P., Liang, D. H. 2007; 99 (6): 864-866

  Abstract

  Real-time 3-dimensional echocardiography (RT3DE) offers the rapid acquisition of quantitative and qualitative anatomic data without the use of geometric assumptions. This study was designed to test the feasibility and potential superiority of RT3DE versus 2-dimensional echocardiography (2DE) and standard fluoroscopy for monitoring endomyocardial biopsies (EMBs). Thirty-eight consecutive EMBs performed under fluoroscopic guidance in 26 patients were monitored using 2DE and RT3DE alternately. Two reviewers scored each biopsy pass for visualization of the tip of the bioptome and location of the actual biopsy. Overall image quality was noted as good or poor, and the effect of image quality on tip localization was analyzed. A total of 243 biopsy attempts were made during 38 EMBs. The location of the biopsy was determined in 74% of the biopsies monitored with RT3DE, whereas 2DE demonstrated the location with certainty in only 43% of the biopsies (p <0.0001). On a procedure-by-procedure comparison, RT3DE was found to show the bioptome tip better in 23 of 38 biopsies, compared with 1 of 38 for 2DE (p = 0.001). In 14 of 38 EMBs, neither method was clearly better. In conclusion, RT3DE improves the ability to see the location of the bioptome during EMB compared with 2DE and fluoroscopy.

  View details for DOI 10.1016/j.amjcard.2006.10.050

  View details for Web of Science ID 000245289200027

  View details for PubMedID 17350384

• Clinical dilemmas in treating left ventricular thrombus. International journal of cardiology Leeper, N. J., Gupta, A., Schnittger, I., Wu, J. C. 2007; 114 (3): e118-9

  View details for PubMedID 17049652

• Screening for coronary artery disease after mediastinal irradiation for Hodgkin's disease JOURNAL OF CLINICAL ONCOLOGY Heidenreich, P. A., Schnittger, I., Strauss, H. W., Vagelos, R. H., Lee, B. K., Mariscal, C. S., Tate, D. J., Horning, S. J., Hoppe, R. T., Hancock, S. L. 2007; 25 (1): 43-49

  Abstract

  Incidental cardiac irradiation during treatment of thoracic neoplasms has increased risks for subsequent acute myocardial infarction or sudden cardiac death. Identifying patients who have a high risk for a coronary event may decrease morbidity and mortality. The objective of this study was to evaluate whether stress imaging can identify severe, unsuspected coronary stenoses in patients who had prior mediastinal irradiation for Hodgkin's disease.We enrolled 294 outpatients observed at a tertiary care cancer treatment center after mediastinal irradiation doses 35 Gy for Hodgkin's disease who had no known ischemic cardiac disease. Patients underwent stress echocardiography and radionuclide perfusion imaging at one stress session. Coronary angiography was performed at the discretion of the physician.Among the 294 participants, 63 (21.4%) had abnormal ventricular images at rest, suggesting prior myocardial injury. During stress testing, 42 patients (14%) developed perfusion defects (n = 26), impaired wall motion (n = 8), or both abnormalities (n = 8). Coronary angiography showed stenosis 50% in 22 patients (55%), less than 50% in nine patients (22.5%), and no stenosis in nine patients (22.5%). Screening led to bypass graft surgery in seven patients. Twenty-three patients developed coronary events during a median of 6.5 years of follow-up, with 10 acute myocardial infarctions (two fatal).Stress-induced signs of ischemia and significant coronary artery disease are highly prevalent after mediastinal irradiation in young patients. Stress testing identifies asymptomatic individuals at high risk for acute myocardial infarction or sudden cardiac death.

  View details for DOI 10.1200/JCO.2006.07.0805

  View details for Web of Science ID 000243725900009

  View details for PubMedID 17194904

• Index of microcirculatory resistance: A novel measure for predicting myocardial damage in patients with acute myocardial infarction 79th Annual Scientific Session of the American-Heart-Association Shah, M., Tremmel, J., Brinton, T., Wilson, A., Schnittger, I., Lee, D. P., Yeung, A. C., Fearon, W. F. LIPPINCOTT WILLIAMS & WILKINS. 2006: 586–87

  View details for Web of Science ID 000241792803637

• Index of microcirculatory resistance: A novel measure for predicting myocardial damage in patients with acute myocardial infarction 55th Annual Scientific Session of the American-College-of-Cardiology Shah, M. G., Tremmel, J., Brinton, T., Wilson, A., Schnittger, I., Lee, D. P., Yeung, A. C., Fearon, W. F. ELSEVIER SCIENCE INC. 2006: 182A–182A

  View details for Web of Science ID 000235530401102

• Diastolic dysfunction after mediastinal irradiation AMERICAN HEART JOURNAL Heidenreich, P. A., Hancock, S. L., Vagelos, R. H., Lee, B. K., Schnittger, I. 2005; 150 (5): 977-982

  Abstract

  Mediastinal irradiation is known to cause cardiac disease, but its effect on left ventricular diastolic function is unknown. The purpose of this study was to determine the prevalence of diastolic dysfunction and its association with prognosis in asymptomatic patients after mediastinal irradiation.We recruited 294 patients who had received at least 35 Gy to the mediastinum for treatment of Hodgkin disease. Each patient underwent resting echocardiography, stress echocardiography, and nuclear scintigraphy. Survival free from cardiac events was determined during 3.2 years of follow-up.The mean age of the included patients was 42 years, and 49% were male. Adequate measurements of diastolic function were obtained in 282 (97%) patients. Diastolic dysfunction was considered mild in 26 (9%) and moderate in 14 (5%). Exercise-induced ischemia was more common in patients with diastolic dysfunction (23%) than those with normal diastolic function (11%, P = .008). After adjustment for patient demographics, clinical characteristics, and radiation history, patients with diastolic dysfunction had worse event-free survival than patients with normal function (hazard ratio 1.66, 95% CI 1.06-2.4).There is a high prevalence of diastolic dysfunction in asymptomatic patients after mediastinal irradiation, and the presence of diastolic dysfunction is associated with stress-induced ischemia and a worse prognosis. Screening with Doppler echocardiography may be helpful in identifying patients at risk for subsequent cardiac events.

  View details for DOI 10.1016/j.ahj.2004.12.026

  View details for Web of Science ID 000233478800024

  View details for PubMedID 16290974

• A systolic murmur is a common presentation of aortic regurgitation detected by echocardiography - P. A. Heidenreich, I. Schnittger, S. L. Hancock, J. E. Atwood: Clin cardiol 2004;27 : 502-506 - Reply CLINICAL CARDIOLOGY Heidenreich, P. A., Schnittger, I., Hancock, S. L., Atwood, J. E. 2005; 28 (3): A30-A30

  View details for Web of Science ID 000227460800002

• A systolic murmur is a common presentation of aortic regurgitation detected by echocardiography CLINICAL CARDIOLOGY Heidenreich, P. A., Schnittger, I., Hancock, S. L., Atwood, J. E. 2004; 27 (9): 502-506

  Abstract

  The finding of aortic regurgitation at a classical examination is a diastolic murmur.Aortic regurgitation is more likely to be associated with a systolic than with a diastolic murmur during routine screening by a noncardiologist physician.In all, 243 asymptomatic patients (mean age 42 +/- 10 years) with no known cardiac disease but at risk for aortic valve disease due to prior mediastinal irradiation (> or = 35 Gy) underwent auscultation by a noncardiologist followed by echocardiography. A systolic murmur was considered benign if it was grade < or = II/VI, not holosystolic, was not heard at the apex, did not radiate to the carotids, and was not associated with a diastolic murmur.Of the patients included, 122 (49%) were male, and 86 (35%) had aortic regurgitation, which was trace in 20 (8%), mild in 52 (21%), and moderate in 14 (6%). A systolic murmur was common in patients with aortic regurgitation, occurring in 12 (86%) with moderate, 26 (50%) with mild, 6 (30%) with trace, and 27 (17%) with no aortic regurgitation (p < 0.0001). The systolic murmurs were classified as benign in 21 (78%) patients with mild and 8 (67%) with moderate aortic regurgitation. Diastolic murmurs were rare, occurring in two (14%) with moderate, two (4%) with mild, and three (2%) with no aortic regurgitation (p=0.15).An isolated systolic murmur is a common auscultatory finding by a noncardiologist in patients with moderate or milder aortic regurgitation. A systolic murmur in patients at risk for aortic valve disease should prompt a more thorough physical examination for aortic regurgitation.

  View details for Web of Science ID 000223604300004

  View details for PubMedID 15471160

• Real-time three-dimensional echocardiography is superior to two-dimensional echocardiography and fluoroscopy in guidance of endomyocardial biopsy 53rd Annual Scientific Session of the American-College-of-Cardiology Amitai, M. E., Schnittger, I., Chow, J., BROWN, P., Liang, D. H. ELSEVIER SCIENCE INC. 2004: 355A–355A

  View details for Web of Science ID 000189388501504

• Asymptomatic cardiac disease following mediastinal irradiation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Heidenreich, P. A., Hancock, S. L., Lee, B. K., Mariscal, C. S., Schnittger, I. 2003; 42 (4): 743-749

  Abstract

  This study was designed to evaluate the potential benefit of screening previously irradiated patients with echocardiography.Mediastinal irradiation is known to cause cardiac disease. However, the prevalence of asymptomatic cardiac disease and the potential for intervention before symptom development are unknown.We recruited 294 asymptomatic patients (mean age 42 +/- 9 years, 49% men, mean mantle irradiation dose 43 +/- 0.3 Gy) treated with at least 35 Gy to the mediastinum for Hodgkin's disease. After providing written consent, each patient underwent electrocardiography and transthoracic echocardiography. Valvular disease was common and increased with time following irradiation. Patients who had received irradiation more than 20 years before evaluation had significantly more mild or greater aortic regurgitation (60% vs. 4%, p < 0.0001), moderate or greater tricuspid regurgitation (4% vs. 0%, p = 0.06), and aortic stenosis (16% vs. 0%, p = 0.0008) than those who had received irradiation within 10 years. The number needed to screen to detect one candidate for endocarditis prophylaxis was 13 (95% confidence interval [CI] 7 to 44) for patients treated within 10 years and 1.6 (95% CI 1.3 to 1.9) for those treated at least 20 years ago. Compared with the Framingham Heart Study population, mildly reduced left ventricular fractional shortening (<30%) was more common (36% vs. 3%), and age- and gender-adjusted left ventricular mass was lower (90 +/- 27 g/m vs. 117 g/m) in irradiated patients.There is a high prevalence of asymptomatic heart disease in general, and aortic valvular disease in particular, following mediastinal irradiation. Screening echocardiography should be considered for patients with a history of mediastinal irradiation.

  View details for DOI 10.1016/S0735-1097(03)00759-9

  View details for Web of Science ID 000184780600027

  View details for PubMedID 12932613

• Accuracy of hand-carried ultrasound ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES Liang, D., Schnittger, I. 2003; 20 (5): 487-490

  Abstract

  Hand-carried ultrasound introduces a new group of devices, operators and usage patterns to echocardiography. This may have significant impact on the accuracy of the findings obtained with hand-carried ultrasound. Although reasonable agreement can be obtained with standard echocardiography in certain circumstances, limitations in imaging modes, device image quality, operator experience, and study completeness may significantly limit the diagnostic accuracy of hand carried ultrasound. Despite this, hand-carried ultrasound has the potential to improve significantly upon the data obtained by physical examination.

  View details for Web of Science ID 000183844800015

  View details for PubMedID 12848872

• Clinical use of cardiac ultrasound performed with a hand-carried device in patients admitted for acute cardiac care AMERICAN JOURNAL OF CARDIOLOGY Rugolotto, M., CHANG, C. P., Hu, B., Schnittger, I., Liang, D. H. 2002; 90 (9): 1040-?

  View details for Web of Science ID 000178991100033

  View details for PubMedID 12398985

• Rapid assessment of cardiac anatomy and function with a new hand-carried ultrasound device (OptiGo): a comparison with standard echocardiography. European journal of echocardiography Rugolotto, M., Hu, B. S., Liang, D. H., Schnittger, I. 2001; 2 (4): 262-269

  Abstract

  The aim of this study was to evaluate image quality and accuracy of a new hand-carried ultrasound device, OptiGo (Agilent Technologies) when compared to standard echocardiography in the setting of a focused examination in the assessment of cardiac anatomy and function.One-hundred and twenty-one patients were prospectively enrolled. Image quality and accuracy in assessment of chamber sizes, left ventricular (LV) wall thickness and contractility, right ventricular (RV) function, mitral and aortic leaflet thickening, mitral annular calcification, pericardial effusion and valvular regurgitation were assessed. Two-dimensional (2D) findings were graded on a four-point scale, except for LV function (six-point) and valvular leaflet opening (two-point). Colour Doppler assessment of valvular regurgitation was graded on a seven-point scale. A one-point difference was considered minor; a two or more point difference was considered major. There was no statistically significant difference in image quality between the two devices. For 2D data, the number of total (minor and major) differences between the hand-carried and standard echocardiograph examinations was significantly greater than the inter-observer variability (14.3% vs 10.7%, P< 0.05), however, major differences alone were not statistically different. For the colour Doppler assessment of regurgitation there was a significant difference between the devices for total (minor and major) differences, (40.0% vs 31.8%,P < 0.007) however, the number of major differences is explained by inter-observer variability.Image quality and diagnostic accuracy of the hand-carried device, OptiGo, was adequate for the purpose of performing a focused assessment of a limited number of 2D and Doppler parameters for the evaluation of cardiac anatomy and function.

  View details for PubMedID 11888820

• Bedside point-of-care echocardiography performed with a new generation hand-carried device: impact on the management of patients hospitalized for acute cardiac care Rugolotto, M., Liang, D. H., Hu, B. S., CHANG, C. P., Schnittger, I. OXFORD UNIV PRESS. 2001: 707–707

  View details for Web of Science ID 000170988302707

• Validation of new small portable ultrasound device (SPUD): A comparison study with standard echocardiography. Rugolotto, M., Hu, B. S., Liang, D. H., Popp, R. L., Schnittger, I. LIPPINCOTT WILLIAMS & WILKINS. 2000: 364–64

  View details for Web of Science ID 000090072301773

• Contrast echocardiography is superior to tissue harmonics for assessment of left ventricular function in mechanically ventilated patients AMERICAN HEART JOURNAL Kornbluth, M., Liang, D. H., BROWN, P., Gessford, E., Schnittger, I. 2000; 140 (2): 291-296

  Abstract

  Assessment of left ventricular function by echocardiography is frequently challenging in mechanically ventilated patients. We evaluated the potential value of contrast-enhanced imaging and tissue harmonic imaging over standard fundamental imaging for endocardial border detection (EBD) in these patients.Fifty patients underwent standard transthoracic 2D echocardiography and were imaged in fundamental and tissue harmonic modes and subsequently with intravenous contrast (Optison). Two echocardiographers reviewed all studies for ease of visualization of endocardial border segments and scoring of wall motion. EBD for each wall segment was graded from 1 to 4 (1 = excellent EBD). Wall motion was scored by a standard 16-segment model and 1 to 5 scale. Studies were categorized as nondiagnostic if 4 of 6 segments in the apical 4-chamber view were either poorly seen or not seen (EBD score 3 or 4). Quantification of ejection fraction was independently performed offline. Visualization of 68% of all segments improved with contrast echocardiography versus 17% improvement with tissue harmonics compared with fundamental mode. Significant improvement (poor/not seen to good/excellent) occurred in 60% of segments with contrast echocardiography versus 18% with tissue harmonics. A total of 850 segments were deemed poor/not seen, 78% of which improved to good/excellent with contrast echocardiography versus 23% with tissue harmonics. Interobserver agreement on EBD was 64% to 70%. Conversion of nondiagnostic to diagnostic studies occurred in 85% of patients with contrast echocardiography versus 15% of patients with tissue harmonics. Scoring of wall motion with fundamental mode, tissue harmonics, and contrast echocardiography was possible in 61%, 74%, and 95% of individual segments, respectively (P <.001). Wall motion scoring was altered in 17% of segments with contrast echocardiography and in 8% with tissue harmonics. Interobserver agreement on wall motion scoring was 84% to 88%. Contrast echocardiography permitted measurement of ejection fraction 45% (P =.003) more often over fundamental mode versus a 27% (P =.09) increase with tissue harmonics.Contrast echocardiography is superior to tissue harmonic imaging for EBD, wall motion scoring, and quantification of ejection fraction in mechanically ventilated patients.

  View details for Web of Science ID 000088739900018

  View details for PubMedID 10925345

• Clinical outcome in the Marfan syndrome with ascending aortic dilatation followed annually by echocardiography AMERICAN JOURNAL OF CARDIOLOGY Kornbluth, M., Schnittger, I., Eyngorina, I., Gasner, C., Liang, D. H. 1999; 84 (6): 753-?

  Abstract

  This study reviewed the utility of echocardiography in following patients with the Marfan syndrome for whom cardiovascular complications, especially aortic root dilatation, dissection and rupture, are the major causes of morbidity and mortality. We conclude that echocardiography can be used to follow asymptomatic patients with the Marfan syndrome.

  View details for Web of Science ID 000082536100027

  View details for PubMedID 10498154

• Echocardiography in emergency medicine: A policy statement by the American Society of Echocardiography and the American College of Cardiology JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Stewart, W. J., Douglas, P. S., Sagar, K., Seward, J. B., Armstrong, W. F., Zoghbi, W., Kronzon, I., Mays, J. M., Pearlman, A. S., Schnittger, I., St Vrain, J. A., Kerber, R. E. 1999; 33 (2): 586-588

  View details for Web of Science ID 000079179200041

  View details for PubMedID 9973044

• Echocardiography in emergency medicine: A policy statement by the American Society of Echocardiography and the American College of Cardiology JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Stewart, W. J., Douglas, P. S., Sagar, K., Seward, J. B., Armstrong, W. F., Zoghbi, W., Kronzon, I., Mays, J. M., Schnittger, I., Vrain, J. A., Kerber, R. E. 1999; 12 (1): 82-84

  View details for Web of Science ID 000078117100016

• Echocardiography in emergency medicine: a policy statement by the American Society of Echocardiography and the American College of Cardiology. The Task Force on Echocardiography in Emergency Medicine of the American Society of Echocardiography and the Echocardiography TPEC Committees of the American College of Cardiology. Journal of the American Society of Echocardiography Stewart, W. J., Douglas, P. S., Sagar, K., Seward, J. B., Armstrong, W. F., Zoghbi, W., Kronzon, I., Mays, J. M., Pearlman, A. S., Schnittger, I., St Vrain, J. A., Kerber, R. E. 1999; 12 (1): 82-84

  View details for PubMedID 9882784

• Native tissue harmonic imaging improves endocardial border definition and visualization of cardiac structures JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Kornbluth, M., Liang, D. H., Paloma, A., Schnittger, I. 1998; 11 (7): 693-701

  Abstract

  The purpose of this study was to examine the impact of native tissue harmonic imaging on endocardial border definition, wall motion scoring, and visualization of intracardiac structures.For wall motion analysis, 60 consecutive patients underwent standard transthoracic echocardiograms in both harmonic and fundamental modes. Three experienced echocardiographers reviewed each echocardiogram. Endocardial border definition for each wall segment was graded from 1 to 4 (1 = excellent endocardial definition). Wall motion was scored by using a standard 16-segment model and 1 to 5 scale. For visualization of cardiac structures, 50 consecutive patients were studied. Two experienced interpreters reviewed each echocardiogram for both normal and abnormal structures by using the following scoring scale: (1) harmonic is much better than fundamental, (2) harmonic is slightly better than fundamental, (3) harmonic and fundamental are equivalent, (4) fundamental is slightly better than harmonic, and (5) fundamental is much better than harmonic. Visualization of 64% (95% confidence interval [CI] 0.61 to 0.66) of all segments improved in harmonic mode, with 26% (95% CI 0.24 to 0.29) improving from poor/not seen to good/excellent. Of 444 segments deemed poor/not seen, visualization of 312 (70%) (95% CI 0.66 to 0.75) improved to good/excellent with harmonic mode. Of these 312 segments, 55% comprised the lateral and anterior walls on apical views. Interobserver agreement on endocardial border definition was 82% to 86%. Scoring of wall motion was altered in 171 of 1075 (16%) of segments by harmonic mode. This was significantly greater than the interobserver disagreement, which was only 10% (p<0.002). Mitral valve chordae and papillary muscles were visualized slightly/much better with harmonic mode in 40 of 50 echocardiograms. Left atrial boundaries were seen slightly/much better in harmonic mode in 29 of 50 studies. Abnormal structures were seen slightly/much better in harmonic mode in 12 of 14 cases.Native tissue harmonic imaging has significant impact on endocardial border definition and wall motion scoring and improves the visualization of both normal and abnormal cardiac structures.

  View details for Web of Science ID 000074885200003

  View details for PubMedID 9692526

• Automatic cardiac output measurement (ACOM): Clinical applications of a new noninvasive tool INTERNATIONAL JOURNAL OF CARDIAC IMAGING Trindade, P. T., BROWN, P., Puryear, J. V., Popylisen, S., Schnittger, I. 1998; 14 (3): 147-154

  Abstract

  This study sought to validate a new noninvasive method to measure cardiac output, in the clinical setting, using color Doppler flow integration. This method, the automatic cardiac output measurement (ACOM), using color Doppler was recently developed and validated in vitro. ACOM was performed at the aortic valve and in the left ventricular outflow tract in 106 subjects (60 men, mean age 52 +/- 18) and compared with the echocardiographic pulsed-wave Doppler and a 2-D volume method. In 14 patients the noninvasive methods were correlated with the thermodilution technique. ACOM was feasible in 101 subjects (95%). The correlation factor between the values obtained with ACOM in the apical 5-chamber view and apical long-axis view was 0.75 at the aortic valve and 0.74 in the left ventricular outflow tract. Interoperator variability for ACOM in the apical 5-chamber and apical long-axis views were 0.93 and 0.75, respectively. The best comparison of ACOM with the pulsed-wave echo-Doppler technique occurred in the apical long-axis view (n = 79, r = 0.62), whereas the correlation with the 2-D volume method was poor. The most favorable comparison of ACOM with the thermodilution technique (n = 14) was also obtained in the apical long-axis view (5.408 +/- 1.72 vs. 3.356 +/- 1.281/min. [mean +/- SD], r = 0.71). Assuming the thermodilution technique as 'gold standard', the pulsed-wave echo-Doppler technique showed a better correlation (5.408 +/- 1.72 vs. 4.664 +/- 1.281/min., r = 0.84). ACOM is a useful, reproducible, noninvasive tool for rapid automated measurements of cardiac output. There is, however, an underestimation when compared with the pulsed-wave Doppler echocardiography and the thermodilution techniques. Good 2-D echocardiographic images, adequate color filling of the outflow tract and high frame rates are prerequisites for accurate values. Further refinements of this new technique are needed to enhance its clinical value in the future.

  View details for Web of Science ID 000076691200002

  View details for PubMedID 9813750

• Mediastinal irradiation accelerates age-related diastolic dysfunction Heidenreich, P. A., Lee, B., Mariscol, C. S., Tate, D. J., Puryear, J. V., Hancock, S. L., Schnittger, I. ELSEVIER SCIENCE INC. 1998: 243A–243A

  View details for Web of Science ID 000071920601027

• Native tissue harmonic imaging improves endocardial border definition and wall motion scoring Kornbluth, M., Liang, D. H., Schnittger, I. ELSEVIER SCIENCE INC. 1998: 76A–76A

  View details for Web of Science ID 000071920600305

• Silent ischemia following mediastinal irradiation. Heidenreich, P. A., Lee, B., Mariscol, C. S., Tate, D. J., Strauss, W. H., Schnittger, I., Hancock, S. L. LIPPINCOTT WILLIAMS & WILKINS. 1997: 527–27

  View details for Web of Science ID A1997YC88000526

• Lossy digital image compression (MPEG-2) preserves the diagnostic accuracy of echocardiograms Liang, D. H., Schnittger, I., Tovey, D., Hu, B. S. LIPPINCOTT WILLIAMS & WILKINS. 1997: 2633–33

  View details for Web of Science ID A1997YC88002619

• Assessment of left ventricular wall motion abnormalities with the use of color kinesis: A valuable visual and training aid JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Lau, Y. S., Puryear, J. V., Gan, S. C., Fowler, M. B., Vagelos, R. H., Popp, R. L., Schnittger, I. 1997; 10 (6): 665-672

  Abstract

  Accurate interpretation of left ventricular segmental wall motion by echocardiography is an important yet difficult skill to learn. Color-coded left ventricular wall motion (color kinesis) is a tool that potentially could aid in the interpretation and provide semiquantification. We studied the usefulness of color kinesis in 42 patients with a history of congestive cardiomyopathy who underwent two-dimensional echocardiograms and a color kinesis study. The expert's reading of the two-dimensional wall motion served as a reference for comparison of color kinesis studies interpreted by the expert and a cardiovascular trainee. Correlation between two-dimensional echocardiography and the expert's and trainee's color coded wall motion scores were r = 0.83 and r = 0.67, respectively. Reproducibility between reviewers and between operators was also assessed. Interobserver variability for color-coded wall motion showed a correlation of r = 0.78. Correlation between operators was also good; r = 0.84. Color kinesis is reliable and appears promising as an adjunct in the assessment of wall motion abnormalities by echocardiography. It is both a valuable visual aid, as well as a training aid for the cardiovascular trainee.

  View details for Web of Science ID A1997XR35200011

  View details for PubMedID 9282356

• Accuracy of biplane and multiplane transesophageal echocardiography in diagnosis of typical acute aortic dissection and intramural hematoma JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Keren, A., Kim, C. B., Hu, B. S., Eyngorina, I., Billingham, M. E., Mitchell, R. S., Miller, D. C., Popp, R. L., Schnittger, I. 1996; 28 (3): 627-636

  Abstract

  The purpose of this study was to evaluate the diagnostic accuracy of biplane and multiplane transesophageal echocardiography in patients with suspected aortic dissection, including intramural hematoma.Transesophageal echocardiography is a useful technique for rapid bedside evaluation of patients with suspected acute aortic dissection. The sensitivity of transesophageal echocardiography is high, but the diagnostic accuracy of biplane and multiplane transesophageal echocardiography for dissection and intramural hematoma is less well defined.We studied 112 consecutive patients at a major referral center who had undergone biplane or multiplane transesophageal echocardiography to identify aortic dissection. The presence, absence and type of aortic dissection (type A or B, typical dissection or intramural hematoma) were confirmed by operation or autopsy in 60 patients and by other imaging techniques in all. The accuracy of transesophageal echocardiography for ancillary findings of aortic dissection (intimal flap, fenestration and thrombosis) was assessed in the 60 patients with available surgical data.Of the 112 patients, aortic dissection was present in 49 (44%); 10 of these had intramural hematoma (5 with and 5 without involvement of the ascending aorta). Of the remaining 63 patients without dissection, 33 (29%) had aortic aneurysm and 30 (27%) had neither dissection nor aneurysm. The overall sensitivity and specificity of transesophageal echocardiography for the presence of dissection were 98% and 95%, respectively. The specificity for type A and type B dissection was 97% and 99%, respectively. The sensitivity and specificity for intramural hematoma was 90% and 99%, respectively. The accuracy of transesophageal echocardiography for diagnosis of acute significant aortic regurgitation and pericardial tamponade was 100%.Biplane and multiplane transesophageal echocardiography are highly accurate for prospective identification of the presence and site of aortic dissection, its ancillary findings and major complications in a large series of patients with varied aortic pathology. Intramural hematoma carries a high complication rate and should be treated identically with aortic dissection.

  View details for PubMedID 8772749

• Wegener's granulomatosis presenting as dilated cardiomyopathy WESTERN JOURNAL OF MEDICINE Day, J. D., Ellison, K. E., Schnittger, I., Perlroth, M. G. 1996; 165 (1-2): 64-66

  View details for PubMedID 8855696

• Upper airway resistance syndrome, nocturnal blood pressure monitoring, and borderline hypertension CHEST Guilleminault, C., Stoohs, R., Shiomi, T., Kushida, C., Schnittger, I. 1996; 109 (4): 901-908

  Abstract

  Upper airway resistance syndrome (UARS) is a sleep-disordered breathing syndrome characterized by complaints of daytime fatigue and/or sleepiness, increased upper airway resistance during sleep, frequent transient arousals, and no significant hypoxemia. Of a population of 110 subjects (58 men) diagnosed as having UARS, we investigated acute systolic and diastolic BP changes seen during sleep in two different samples. First, six patients from the original subject pool were found to have untreated chronic borderline high BP, and were subjected to 48 h of continuous ambulatory BP monitoring before treatment and another 48 h of BP monitoring 1 month after the start of nasal-continuous positive airway pressure (N-CPAP) treatment. Five of six subjects used their equipment on a regular basis and had their chronic borderline high BP completely controlled. No change in BP values was seen in the last subject, who discontinued N-CPAP after 3 days. A second protocol investigated seven normotensive subjects drawn from the initial subject pool. Continuous radial artery BP recording was performed during nocturnal sleep with simultaneous polygraphic recording of sleep/wake variables and respiration. BP changes were studied during periods of increased respiratory efforts and at the time of alpha EEG arousals. Increases in systolic and diastolic BP were noted during the breaths with the greatest inspiratory efforts without significant hypoxemia. A further increase in BP was noted in association with arousals. Three of these subjects also underwent echocardiography during sleep, which demonstrated a leftward shift of the interventricular septum with pulsus paradoxus in association with peak end-inspiratory esophageal pressure more negative than -35 cm H2O. Our study indicates that, in the absence of classic apneas, hypopneas, and repetitive significant drops in oxygen saturation (below 90%), repetitive increases in BP can occur as a result of increased airway resistance during sleep. It also shows that, in some patients with both UARS and borderline high BP, high BP can be controlled with treatment of UARS. We conclude that abnormal upper airway resistance during sleep, often associated with snoring, can play a role in the development of hypertension.

  View details for PubMedID 8635368

• Valvular Strands. Cardiogenic Embolism. Baltimore:Williams & Wilkins, Schnittger I. 1996: 129-135
• VALUE OF TRANSESOPHAGEAL ECHOCARDIOGRAPHY BEFORE DC CARDIOVERSION IN PATIENTS WITH ATRIAL-FIBRILLATION - ASSESSMENT OF EMBOLIC RISK BRITISH HEART JOURNAL Schnittger, I. 1995; 73 (4): 306-309

  View details for Web of Science ID A1995QU53500004

  View details for PubMedID 7756062

• EPIDURAL AIR INJECTION ASSESSED BY TRANSESOPHAGEAL ECHOCARDIOGRAPHY REGIONAL ANESTHESIA Jaffe, R. A., Siegel, L. C., Schnittger, L., PROPST, J. W., BROCKUTNE, J. G. 1995; 20 (2): 152-155

  Abstract

  The object of this study, using transesophageal echocardiography (TEE) in anesthetized patients, was to investigate the occurrence of venous air embolism (VAE) when air is injected into the epidural space.Six patients between the ages of 18 and 50 years (ASA I-II) undergoing general anesthesia in a supine position for nonthoracic surgical procedures were studied. Prior to general anesthesia, an epidural catheter was placed into the epidural space using a Tuohy needle and a standard saline loss-of-resistance technique. Following verification of proper catheter placement, general anesthesia was induced and the trachea intubated. Thereafter, a TEE probe was inserted into the esophagus. After a 10-minute control period, and during continuous TEE videotape recording, 5 mL of air was rapidly injected into the epidural space through the epidural catheter. This was followed 10 minutes later by the epidural injection of 5 mL of room-temperature preservative-free saline. Microbubble echo targets were quantified in a range from 0 to 4+.Venous air microbubble emboli appeared in the circulation within 15 seconds after injecting either air or saline into the epidural space.No evidence of clinically significant VAE was seen in any patient. The results suggest that drugs injected into the epidural space may have unexpectedly easy access to the venous circulation with a potential to produce unwanted systemic effects. Clinicians should be alert to the possibility that local anesthetics, or any other drug placed epidurally, may rapidly enter the systemic circulation even without the intravenous placement of an epidural catheter.

  View details for Web of Science ID A1995QP69300012

  View details for PubMedID 7605763

• On-line estimation of cardiac output with a new automated border detection system using transesophageal echocardiography: a preliminary comparison with thermodilution. Journal of cardiothoracic and vascular anesthesia Pinto, F. J., Siegel, L. C., Chenzbraun, A., Schnittger, I. 1994; 8 (6): 625-630

  Abstract

  Continuous estimation of cardiac output would be extremely useful for hemodynamic monitoring of patients in the operating room and intensive care settings. A recently developed echocardiographic imaging system provides real-time automated border detection (ABD) with the ability to measure cyclic changes in cavity area, and thus calculate changes in intracavitary volumes. Eight patients undergoing cardiac surgery were studied with intraoperative transesophageal (TEE), and cardiac outputs obtained with this new imaging system were compared with thermodilution (TD). Triplicate measurements were obtained simultaneously at five intraoperative times, three before and two after cardiopulmonary bypass. The 91 of 120 measurements with adequate TEE and TD data were analyzed. The average difference between the two techniques (bias) was -0.2 +/- 1.3 L/min. The limits of agreement (bias +/- 2 SD) were -2.8 L/min to 2.4 L/min. The average of the absolute value of the difference between measurements made with the two techniques was 0.9 +/- 0.8 L/min. Linear regression yielded the equation: ABD = 0.64TD + 1.57 L/min (r = 0.71). The average difference between the two techniques (bias) for detecting changes in cardiac output between sequential intraoperative times was 0.1 +/- 1.1 L/min. With further development, this new method shows promise for measurement of cardiac output in selected patient care settings.

  View details for PubMedID 7880989

• TRANSESOPHAGEAL ECHOCARDIOGRAPHY IN THE INTENSIVE-CARE UNIT - IMPACT ON DIAGNOSIS AND DECISION-MAKING CLINICAL CARDIOLOGY Chenzbraun, A., Pinto, F. J., Schnittger, I. 1994; 17 (8): 438-444

  Abstract

  Transesophageal echocardiography (TEE) is widely used in the management of patients in intensive care units. The present study assesses the specific value of this technique in various categories of these patients. We reviewed 113 studies performed in 100 such patients for: suspected aortic dissection (25), suspected endocarditis (33), source of emboli assessment (19), hemodynamic instability (15), and miscellaneous (21). TEE provided diagnostic information in all patients with aortic dissection, in 53% of the cases with hemodynamic instability, in 50% of the cases with septic states with high likelihood of endocarditis, and in 29% of the cases where the question was the source of emboli. When the clinical probability for endocarditis was low, all transesophageal echocardiograms performed in septic patients were negative. The information provided by TEE was considered crucial in one-third of the positive cases; in about one-half of these special cases, the results were instrumental for further surgical management. There were no significant side effects related to the procedure. TEE is easily performed in the intensive care unit setting and yields useful information in almost half of the cases. Special benefit is expected in suspected aortic disease, hemodynamic instability, suspected endocarditis, and embolic events. The overall yield as screening procedure in febrile patients is low.

  View details for Web of Science ID A1994NZ09500006

  View details for PubMedID 7955591

• EXERCISE ECHOCARDIOGRAPHY IN HEAT TRANSPLANT RECIPIENTS - A COMPARISON WITH ANGIOGRAPHY AND INTRACORONARY ULTRASONOGRAPHY JOURNAL OF HEART AND LUNG TRANSPLANTATION COLLINGS, C. A., Pinto, F. J., Valantine, H. A., Popylisen, S., Puryear, J. V., Schnittger, I. 1994; 13 (4): 604-613

  Abstract

  Transplant coronary artery disease is the leading cause of allograft failure in heart transplant recipients surviving beyond 1 year. Coronary angiography still remains the major technique for surveillance of these patients, with recent use of intracoronary ultrasonography to detect the early stages of intimal thickening. We evaluated exercise echocardiography to screen for the presence or absence of angiographic evidence of transplant coronary artery disease in any vessel, defined as follows: absent; stenosis 39% or less = mild; stenosis 40% to 69% = moderate; or stenosis > or = 70%, or more = severe. Fifty-one consecutive heart transplant recipients undergoing routine annual evaluation were included in the study. Of thirty-seven patients with no coronary artery disease, thirty-two had a normal and five had an abnormal exercise echocardiogram. Fourteen patients (27%) had transplant coronary artery disease by angiographic criteria; six had mild, six had moderate, and two had severe stenosis. One patient with mild and the two patients with severe transplant coronary artery disease had abnormal exercise echocardiograms. None of the patients with moderate disease had an abnormal exercise echocardiogram (false negative). Of forty-three patients with no or mild stenosis, 19 patients had moderate to severe intimal proliferation as seen with intracoronary ultrasonography. Of eight patients with moderate or severe stenosis, four were tested with intracoronary ultrasonography and all had moderate to severe intimal proliferation. Six patients had a "false positive" exercise echocardiogram, and of four who were tested with intracoronary ultrasonography, two had mild and two had moderate to severe intimal thickening. In summary, exercise echocardiography correctly excluded the presence of transplant coronary artery disease in 86% of patients but was associated with a high false negative rate for detection of moderate coronary stenosis. A false positive exercise echocardiogram was associated with intimal proliferation by intracoronary ultrasonography in several patients and suggests that coronary angiography may underestimate significant coronary artery disease.

  View details for Web of Science ID A1994PA31000005

  View details for PubMedID 7947876

• FILLING PATTERNS IN LEFT-VENTRICULAR HYPERTROPHY - A COMBINED ACOUSTIC QUANTIFICATION AND DOPPLER STUDY JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Chenzbraun, A., Pinto, F. J., Popylisen, S., Schnittger, I., Popp, R. L. 1994; 23 (5): 1179-1185

  Abstract

  The purpose of this study was to evaluate the potential of acoustic quantification compared with Doppler echocardiography for assessment of left ventricular diastolic dysfunction.Diastolic dysfunction usually accompanies left ventricular hypertrophy. Although Doppler echocardiography is widely used, it has known limitations in the diagnosis of diastolic abnormalities. The ventricular area-change waveform obtained with acoustic quantification technology may provide an alternative to assess diastolic dysfunction.Potential acoustic quantification variables (peak rate of area change and mean slope of area change rate during rapid filling, amount of relative area change during rapid filling and atrial contraction) were obtained and compared with widely used Doppler indexes of ventricular filling (isovolumetric relaxation time, pressure half-time, peak early diastolic velocity/peak late diastolic velocity ratio, rapid filling, atrial contribution to filling) in 16 healthy volunteers and 30 patients with left ventricular hypertrophy.Criteria for abnormal relaxation were present in 68% of patients by acoustic quantification and in 64% of patients by Doppler echocardiography. However, abnormal relaxation was identified in 80% of patients by one or both methods. Acoustic quantification indicated abnormal relaxation in the presence of completely normalized Doppler patterns and in patients with mitral regurgitation or abnormal rhythm with unreliable Doppler patterns.Acoustic quantification potentially presents a new way to assess diastolic dysfunction. This technique may be regarded as complementary to Doppler echocardiography. The combined use of the methods may improve the diagnosis of left ventricular relaxation abnormalities.

  View details for Web of Science ID A1994PH37100028

  View details for PubMedID 8144786

• COMPARISON OF ACOUSTIC QUANTIFICATION AND DOPPLER-ECHOCARDIOGRAPHY IN ASSESSMENT OF LEFT-VENTRICULAR DIASTOLIC VARIABLES BRITISH HEART JOURNAL Chenzbraun, A., Pinto, F. J., Popylisen, S., Schnittger, I., Popp, R. L. 1993; 70 (5): 448-456

  Abstract

  To assess the haemodynamic correlations of the waveforms of left ventricular area change obtained by automated boundary detection with newly developed acoustic quantification technology.The timing of events in the cardiac cycle was identified on the wave-form automated boundary detection and was correlated with the corresponding timing derived from pulsed wave Doppler flow velocity traces of the mitral valve and left ventricular outflow tract. The amounts of area change during the rapid filling phase and during atrial contraction were correlated with the time-velocity integrals of early and late diastolic ventricular filling obtained from Doppler tracings of the mitral inflow.A university medical school echocardiography laboratory.16 healthy volunteers and 19 patients referred for echocardiographic studies.A significant correlation was found between the methods for measurement of the time from the R wave to mitral valve opening (r = 0.72, p < 0.01), isovolumic relaxation time (r = 0.62, p < 0.01), and ejection time (r = 0.54, p < 0.01). The change of total area that occurred during rapid filling and atrial filling phases measured from the acoustic waveform correlated with the time-velocity integrals of the early and late diastolic mitral valve inflow velocity derived from Doppler echocardiography (r = 0.60 and r = 0.80, respectively).The waveform of left ventricular area obtained by the automated boundary detection technique identifies the phases of the cardiac cycle and correlates with Doppler values of left ventricular diastolic function. Therefore, this new method of automated boundary detection has potential uses in the assessment of left ventricular diastolic function.

  View details for Web of Science ID A1993MF26800012

  View details for PubMedID 8260277

• SEGMENTAL WALL-MOTION ABNORMALITIES IN PATIENTS UNDERGOING TOTAL HIP-REPLACEMENT - CORRELATIONS WITH INTRAOPERATIVE EVENTS ANESTHESIA AND ANALGESIA PROPST, J. W., Siegel, L. C., Schnittger, I., FOPPIANO, L., Goodman, S. B., BROCKUTNE, J. G. 1993; 77 (4): 743-749

  Abstract

  We examined the effect of methylmethacrylate cement on venous embolization and cardiac function in 20 patients having total hip arthroplasty under general anesthesia. Segmental wall motion abnormalities and intracardiac targets (presumably emboli) were investigated by making videotaped recordings of the transgastric short axis and longitudinal 4-chamber views of the heart with transesophageal echocardiography at different points during surgery. The incidence of segmental wall motion abnormalities was the most frequent during insertion of cemented femoral prostheses (8 of 14 patients had wall motion abnormalities). This was significantly different from baseline measurements taken at the beginning of surgery (P < 0.05). In addition, there were also significantly more segmental wall motion abnormalities in patients having a cemented femoral component compared to those having an uncemented femoral prosthesis (P < 0.05). The incidence of wall motion abnormalities during acetabular and femoral reaming and during wound closure was not significantly different from baseline. Intracardiac targets (emboli) were seen in all 20 patients during surgery. The largest number of emboli occurred during reaming of the femur and during insertion of the femoral prosthesis. Significantly more emboli were seen with cemented components (P < 0.02). Most emboli were small (< 2 mm) and appeared similar to the microbubbles produced by agitating saline with a small amount of air. Six patients also had larger (> 5 mm) emboli that appeared to be solid material. One patent foramen ovale was detected (5% incidence). There were no adverse cardiac or neurologic events, and heart rate and arterial blood pressure remained within normal limits throughout surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 8214658

• OBSTRUCTED BREATHING IN CHILDREN DURING SLEEP MONITORED BY ECHOCARDIOGRAPHY ACTA PAEDIATRICA Shiomi, T., Guilleminault, C., Stoohs, R., Schnittger, I. 1993; 82 (10): 863-871

  Abstract

  Six 3 to 14-year-old boys with snoring and obstructive sleep apnea syndrome were monitored polygraphically during sleep with and without nasal continuous positive airway pressure with simultaneous recording of esophageal pressure (Pes) and M-mode and two-dimensional echocardiograms. Continuous non-invasive blood pressure monitoring was performed in two older children. Three of the six children demonstrated a diastolic leftward shift of the interventricular septum related to the negativity of Pes. Progressively more negative Pes correlated significantly with an increase in right ventricular internal end-diastolic dimension and a decrease in left ventricular internal end-diastolic dimension, with at times left ventricular "collapse". One of the subjects with blood pressure monitoring demonstrated pulsus paradoxus with leftward shift of the interventricular septum. Nasal continuous positive airway pressure normalized all changes. Pulsus paradoxus and leftward shift of the interventricular septum are related to the mechanical changes associated with heavy snoring during sleep, regardless of the amount of oxygen desaturation.

  View details for PubMedID 8241648

• Biplane transesophageal echocardiography in the diagnosis of patent foramen ovale. Journal of the American Society of Echocardiography Chenzbraun, A., Pinto, F. J., Schnittger, I. 1993; 6 (4): 417-421

  Abstract

  Patent foramen ovale is associated with unexplained systemic embolic events or persistent hypoxemia. The diagnosis of a patient foramen ovale is based on the existence of an interatrial right-to-left shunt. Biplane transesophageal echocardiography with its increased ability to provide accurate anatomic detail may allow the visualization of the actual opening of the patent foramen ovale. In 19 patients with transesophageal positive contrast studies, we assessed the value of the vertical versus the horizontal plane in the diagnosis of a patent foramen ovale. The patent foramen ovale opening could be seen and sized in the vertical plane in 10 studies (53%). In none of these 10 cases was the opening seen also in the horizontal plane. We conclude that in a significant number of cases, biplane transesophageal echocardiography adds morphological detail to the diagnosis of patent foramen ovale. The ability to size the actual opening may have therapeutic implications.

  View details for PubMedID 8217208

• ABNORMAL POSTOPERATIVE INTERVENTRICULAR MOTION - NEW INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHIC EVIDENCE SUPPORTS A NOVEL HYPOTHESIS AMERICAN HEART JOURNAL Wranne, B., Pinto, F. J., Siegel, L. C., Miller, D. C., Schnittger, I. 1993; 126 (1): 161-167

  Abstract

  Abnormal interventricular septal motion is a frequent finding after cardiac surgery. However, the time course and underlying mechanisms are not well understood. Nineteen patients, mean age 54 years (range 20 to 82 years), were studied with intraoperative transesophageal echocardiography at five specific times: with the chest closed (baseline), with the chest open and the pericardium closed, with both chest and pericardium open, after cardiopulmonary bypass with the chest open, and after cardiopulmonary bypass with the chest closed. In each patient interventricular septal motion was recorded from the transgastric view; tricuspid annular motion and Doppler color flow mapping of tricuspid regurgitation were obtained from the four-chamber view. All the echocardiographic data were stored on videotape and were later viewed in random sequence by one investigator who was aware of the baseline stage but was blinded to the other stages. All patients had normal septal motion before cardiopulmonary bypass. After cardiopulmonary bypass, with the chest still open, 5 of 17 patients (29%) with adequate recordings had abnormal septal motion while 13 of 17 patients (76%) with adequate recordings had abnormal tricuspid annular motion. After chest closure, only three patients (14%) had normal septal motion and one patient (6%) had normal tricuspid annular motion. Significant tricuspid regurgitation was an infrequent finding in all cases. It is concluded that abnormal interventricular septal motion occurs after cardiopulmonary bypass and is related to abnormal tricuspid annular motion. We hypothesize that suboptimal right ventricular myocardial preservation impairs the motion pattern of the right ventricle, including the tricuspid annulus.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for PubMedID 8322660

• ASPECTS OF MECHANICAL VENTILATION AFFECTING INTERATRIAL SHUNT FLOW DURING GENERAL-ANESTHESIA ANESTHESIA AND ANALGESIA Jaffe, R. A., Pinto, F. J., Schnittger, I., Siegel, L. C., Wranne, B., BROCKUTNE, J. G. 1992; 75 (4): 484-488

  Abstract

  Intraoperative transesophageal echocardiography was used to study the incidence of flow-patent foramen ovale in 33 normal, healthy patients (ASA physical status I) undergoing general anesthesia in the supine position for nonthoracic surgical procedures. Echocardiographic contrast was injected intravenously during mechanical ventilation in the presence of 0, 5, 10, 15, or 19 cm H2O positive end-expiratory pressure (PEEP). A final test was performed during the release of 19 cm H2O PEEP. The presence of a flow-patent foramen ovale was detected when the injected echo targets were observed crossing the interatrial septum from right to left. Most interesting, 3 of 33 patients developed a right-to-left shunt that was first detected with the steady application of 10 (1 patient) or 15 cm H2O PEEP (2 patients). In all three cases, the shunt flow was accentuated on the release of PEEP; however, no additional cases were detected using this respiratory maneuver. These cases represent the first demonstration of right-to-left interatrial shunting evoked as the result of the sustained application of PEEP. This study also revealed a lower than expected incidence of flow-patent foramen ovale (9%) when measured during general anesthesia and positive pressure ventilation with or without PEEP.

  View details for Web of Science ID A1992JP53400003

  View details for PubMedID 1530158

• ABNORMAL LEFT-VENTRICULAR FILLING PATTERNS - ONLINE RECOGNITION USING ACOUSTIC QUANTIFICATION Chenzbraun, A., Pinto, F. J., Milton, S., Schnittger, I., Popp, R. L. LIPPINCOTT WILLIAMS & WILKINS. 1992: 449–49

  View details for Web of Science ID A1992JT66001810

• INFLUENCE OF MITRAL-VALVE MORPHOLOGY ON MITRAL BALLOON COMMISSUROTOMY - IMMEDIATE AND 6-MONTH RESULTS FROM THE NHLBI BALLOON VALVULOPLASTY REGISTRY AMERICAN HEART JOURNAL Reid, C. L., Otto, C. M., Davis, K. B., Labovitz, A., Kisslo, K. B., McKay, C. R., Diver, D. J., Berman, A., Safian, R. D., Grossman, W., Come, P. C., Douglas, P., McKay, R. G., Slater, A., Williams, D. O., DREW, T. M., Carnevale, R., Cimini, D., HARDINK, D., Cannon, P., Homma, S., Berke, A., Keller, A., ESCALA, E., TRESGALLO, M., Bashore, T. M., Davidson, C. J., Harrison, J. K., Kisslo, J., Kisslo, K., Brinker, J. A., Weiss, J. L., Raqueno, J., DOWGER, B., Lambrew, C. T., Cutler, J., SZE, K., TOOKER, N., Holmes, D. R., Nishimura, R., Reeder, G., MATHESON, S. J., SCHREIFELS, S., Meyer, L., Block, P. C., Palacios, I. F., Weyman, A., Block, E. H., Petitclerc, R., BROUILLETE, M., Slater, J. N., Feit, F., Kronzon, I., Attubato, M. J., GINDEA, A., BILYK, F., Kern, M. J., Labovitz, A., Stonner, T., Mechem, C., Alderman, E. L., Schnittger, I., Schwarzkopf, A., ROD, J. L., Comess, K., Ferguson, J., Massumi, A., Treistman, B., Hernandez, G., Wilansky, S., Harlan, M., Dean, L. S., Baxley, W., Nanda, N., Kirklin, J. W., Saenz, C., Helmcke, F. R., MELUCH, F. T., Buchbinder, M., Peterson, K., Dittrich, H., Daily, E., Hill, J., Miranda, A., Pepine, C., Geiser, E., SCOTTFRANCO, E., DeMaria, A. N., Wisenbaugh, T., Berk, M., Obrien, M., Weiner, B. H., Pape, L., Borbone, M. L., Nabel, E. G., Armstrong, W. F., GALEANA, A., Buda, A., GALEANA, A., Rahimtoola, S. H., Kawanishi, D. T., Reid, C., Chandraratna, P. A., Morrison, E., Powers, E. R., Smucker, M., Gibson, R., Tedesco, C., Stewart, D. K., ONEIL, W., Hauser, A., DUDLETS, P., PAVILEDES, G., Margulis, A., Vanderberg, B., Waller, B. F., Kennedy, J. W., Gillespie, M. J., Mickel, M., Solomon, R. E. 1992; 124 (3): 657-665

  View details for Web of Science ID A1992JL61500016

• SYSTEMIC VENOUS FLOW DURING CARDIAC-SURGERY EXAMINED BY INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHY AMERICAN JOURNAL OF CARDIOLOGY Pinto, F. J., Wranne, B., STGOAR, F. G., Siegel, L. C., Haddow, G., Schnittger, I., Popp, R. L. 1992; 69 (4): 387-393

  Abstract

  Patterns of systemic venous return change after cardiac surgery. However, the exact timing and underlying mechanisms are not well understood. To analyze these changes transesophageal echocardiography was used to evaluate 21 patients (mean age 56 +/- 17 years) during cardiac surgery. Eleven patients underwent coronary bypass grafting, 2 had ablation of accessory bundles, 4 had mitral and 4 had aortic valve replacements. All were in sinus rhythm and were undergoing their first cardiac operation. Hepatic and pulmonary venous flow, tricuspid annular motion, and signs of tricuspid regurgitation were recorded sequentially 5 times: (A) with chest closed, (B) with chest open and pericardium closed, (C) with both chest and pericardium open, (D) after cardiopulmonary bypass with chest open, and (E) after cardiopulmonary bypass with chest closed. The hepatic venous Doppler flow velocity integrals (cm) changed, from stage A to stage E: systolic flow decreased from 5.9 +/- 5.2 to 2.2 +/- 1.4 (p less than 0.01); diastolic flow increased from 3.1 +/- 1.5 to 4.8 +/- 3.3 (p less than 0.001); and systolic to diastolic ratio decreased from 2.0 +/- 1.2 to 0.7 +/- 0.6 (p less than 0.001). Reversed flow at the end of ventricular systole was present in 9 patients (43%) at stage A and in all patients at stage E. Decreased tricuspid annular motion was noted in all but 1 patient after cardiopulmonary bypass. No patient presented significant tricuspid regurgitation at any stage. In conclusion, the significant change in the pattern of systemic venous return after open heart surgery is not due to opening of the chest wall or parietal pericardium, or to tricuspid regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1992HB24800018

  View details for PubMedID 1734654

• TRANSESOPHAGEAL ECHOCARDIOGRAPHY FOR STUDY OF BIOPROSTHESES IN THE AORTIC-VALVE POSITION AMERICAN JOURNAL OF CARDIOLOGY Pinto, F. J., Wranne, B., Schnittger, I. 1992; 69 (3): 274-276

  View details for Web of Science ID A1992GZ65200028

  View details for PubMedID 1731474

• LEFTWARD SHIFT OF THE INTERVENTRICULAR SEPTUM AND PULSUS PARADOXUS IN OBSTRUCTIVE SLEEP-APNEA SYNDROME CHEST Shiomi, T., Guilleminault, C., Stoohs, R., Schnittger, I. 1991; 100 (4): 894-902

  Abstract

  Echocardiograms were taken from the parasternal long axis view during nocturnal sleep in ten patients diagnosed with OSAS. A table designed to support the echocardiographic probe prevented significant sleep disturbances during monitoring and allowed continuous data collection with and without nasal CPAP administration. In five of ten patients, there was before CPAP treatment a diastolic LSIVS during NREM sleep, inducing a flattening of the left ventricle. Arterial blood pressure recordings showed pulsus paradoxus when LSIVS was occurring. Nasal CPAP led to normal, unobstructed breathing, significant decrease in Pes nadir and disappearance of LSIVS and pulsus paradoxus. Increase in left ventricular afterload and increase in total peripheral resistance could lead to hypertrophy and hypertension in some OSAS patients. The presence of pulsus paradoxus in OSAS indicates a marked increase in Pes nadir, and its disappearance with nasal CPAP may be one of the signs of effective treatment of OSAS.

  View details for PubMedID 1914603

• Transesophageal echo-Doppler echocardiographic assessment of pulmonary venous flow patterns. Journal of the American Society of Echocardiography BARTZOKIS, T., LEE, R., YEOH, T. K., GROGIN, H., Schnittger, I. 1991; 4 (5): 457-464

  Abstract

  Fifty-eight of 61 consecutive patients undergoing transesophageal echo-Doppler echocardiography provided excellent signals to permit assessment of pulmonary venous blood low patterns. Normal antegrade pulmonary venous flow during ventricular systole was biphasic and was characterized by a short, low velocity (28 +/- 17 cm/sec), early systolic jet (P1), and longer, higher velocity (41 +/- 23 cm/sec), late systolic jet (P2). Antegrade pulmonary venous flow during ventricular diastole (P3) was of moderate velocity (34 +/- 17 cm/sec) and was monophasic; during atrial contraction there was transient, low velocity (-17 +/- 11 cm/sec) and reversal of flow (P4). The early systolic antegrade venous flow (P1) was absent or reversed in rhythm disorders, which interrupted normal synchronized atrioventricular activation. These rhythm disorders also were associated with diminished peak flow velocities during late systole (P2). Abnormalities in systolic left ventricular function and mitral regurgitation also had this effect. Diastolic flow velocities (P3) remained constant, except in patients with mitral regurgitation. In these patients diastolic peak flows were significantly increased above normal. In cases of atrial fibrillation or ventricular pacing the late diastolic reversal of flow resulting from atrial contraction (P4) was absent. Conclusions: Transesophageal echo-Doppler echocardiography gives high quality signals of pulmonary venous inflow to help assess function of the left ventricle and left atrium. Multiple factors affect the patterns. This study suggests caution in the interpretation of abnormal patterns, particularly of reduced systolic pulmonary vein flow in the presence of left ventricular dysfunction, atrial fibrillation, ventricular pacing, and mitral regurgitation.

  View details for PubMedID 1742033

• INTRAOPERATIVE VENTILATOR-INDUCED RIGHT-TO-LEFT INTRACARDIAC SHUNT ANESTHESIOLOGY Jaffe, R. A., Pinto, F. J., Schnittger, I., BROCKUTNE, J. G. 1991; 75 (1): 153-155

  View details for Web of Science ID A1991FU01700027

  View details for PubMedID 2064044

• FREQUENCY AND MECHANISM OF BRADYCARDIA IN CARDIAC TRANSPLANT RECIPIENTS AND NEED FOR PACEMAKERS AMERICAN JOURNAL OF CARDIOLOGY Dibiase, A., Tse, T. M., Schnittger, I., Wexler, L., Stinson, E. B., Valantine, H. A. 1991; 67 (16): 1385-1389

  Abstract

  Orthotopic cardiac transplantation is occasionally complicated by unexplained bradyarrhythmias. Sinus node injury as a consequence of operation or acute rejection has anecdotally been linked to the development of bradycardia early after transplantation. These arrhythmias are empirically managed by pacemaker implantation, the indications for which remain poorly defined. This retrospective study examined the 20-year experience of our institution with bradyarrhythmias after transplantation to determine the predisposing factors and indications for pacemaker implantation. Forty-one of 556 patients in our cardiac transplant program (7.4%) received permanent pacemakers between 1969 and 1989. The predominant rhythm disturbances were junctional rhythm (46%), sinus arrest (27%) and sinus bradycardia (17%). Most patients were asymptomatic (61%), and presented in the early post-transplant period (73%). Four possible predisposing factors were evaluated: (1) graft ischemic time, (2) rejection history, (3) use of bradycardia-inducing drugs, and (4) anatomy of blood supply to the sinoatrial (SA) node. No significant differences existed between patients with and without pacemakers with regard to the first 3 variables. However, after transplantation angiograms showed that prevalence of abnormal SA nodal arteries was greater in patients with than without pacemakers (p less than 0.02). Pacemaker follow-up at 3, 6 and 12 months showed persistent bradycardia (60 to 90 beats/min) in 88, 75 and 50% of patients, respectively. The most common pacemaker complication (15%) was lead displacement at time of biopsy. These results suggest that disruption of the SA nodal blood supply may be an important predisposing factor in the development of bradycardias.

  View details for Web of Science ID A1991FR02000014

  View details for PubMedID 2042569

• ENHANCED DETECTION OF INTRACARDIAC SOURCES OF CEREBRAL EMBOLI BY TRANSESOPHAGEAL ECHOCARDIOGRAPHY STROKE Lee, R. J., BARTZOKIS, T., YEOH, T. K., GROGIN, H. R., Choi, D., Schnittger, I. 1991; 22 (6): 734-739

  Abstract

  We performed transesophageal echocardiography in 50 consecutive hospitalized patients with recent transient ischemic attack or stroke of embolic origin to determine whether transesophageal echocardiography is more sensitive than transthoracic echocardiography in detection of possible intracardiac sources of embolism. Twenty-six of 50 patients with a negative transthoracic echocardiogram for potential source of emboli had a transesophageal echocardiography study that demonstrated at least one intracardiac abnormality. Abnormalities noted by transesophageal echocardiography included five of 50 patients with either a left atrial or left atrial appendage clot, four patients with a patent foramen ovale, and nine patients with spontaneous echocardiographic contrast. In 11 of 50 patients with no other source of embolism, we found highly mobile filamentous strands on the mitral valve, which have not been described previously. These mitral valve echo strands may represent a fissured surface or fibrosis that can serve as a nidus for thrombus formation. We detected no unexpected left ventricular thrombus or left atrial myxoma. Factors significantly associated with a greater likelihood of a positive transesophageal echocardiography study included left atrial enlargement, atrial fibrillation, and a calcified or thickened mitral valve. Our study suggests that transesophageal echocardiography is a valuable addition to transthoracic echocardiography in investigating potential intracardiac sources of embolism.

  View details for Web of Science ID A1991FQ99800004

  View details for PubMedID 2057971

• HEPATIC VENOUS FLOW ASSESSED BY TRANSESOPHAGEAL ECHOCARDIOGRAPHY JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Pinto, F. J., Wranne, B., STGOAR, F. G., Schnittger, I., Popp, R. L. 1991; 17 (7): 1493-1498

  Abstract

  Systemic venous flow patterns are easily assessed by transthoracic echocardiography for evaluation of right heart dynamics. However, the transthoracic approach cannot be used in patients undergoing thoracic surgery. The present study describes a method for obtaining hepatic venous flow velocity with transesophageal Doppler echocardiography. Twenty-nine patients were studied with transthoracic echocardiography just before cardiac surgery and with transesophageal echocardiography during surgery. Hepatic venous flow velocity recordings were obtained in 14 of 29 patients with the transthoracic and in all 29 with the transesophageal approach. Timing of flow pattern was similar with the two methods, but recordings obtained with transesophageal echocardiography were inverted compared with those obtained with transthoracic echocardiography as a result of the difference in probe location in relation to flow direction. The time-velocity integrals obtained with the two techniques did not differ significantly; for the transthoracic and transesophageal approaches, they were, respectively, 7.3 +/- 3.4 versus 5.7 +/- 4.4 for systolic flow; 1.0 +/- 1.0 versus 0.5 +/- 0.6 for end-systolic flow reversal; 4.7 +/- 2.3 versus 3.7 +/- 1.7 for diastolic flow; 2.0 +/- 1.8 versus 1.5 +/- 1.5 for atrial flow reversal and 1.9 +/- 1.0 versus 1.7 +/- 1.1 for systolic/diastolic ratio. In conclusion, hepatic venous flow values are obtained more frequently and with better quality by transesophageal than by transthoracic echocardiography. The flow patterns and velocity integrals are similar with both methods and previous experience with transthoracic echocardiography should be applicable to the transesophageal technique. Transesophageal Doppler echocardiography therefore has potential for studying right heart dynamics during anesthesia and surgery.

  View details for Web of Science ID A1991FQ22900008

  View details for PubMedID 2033181

• ECHOCARDIOGRAPHIC STUDIES IN ADULTS AND CHILDREN PRESENTING WITH OBSTRUCTIVE SLEEP-APNEA OR HEAVY SNORING SYMP ON SLEEP AND CARDIORESPIRATORY CONTROL Guilleminault, C., Shiomi, T., Stoohs, R., Schnittger, I. INST NATL SANTE RECHERCHE MEDICALE. 1991: 95–103

  View details for Web of Science ID A1991BU22W00012

• ASSESSMENT OF HEPATIC VENOUS FLOW USING TRANSESOPHAGEAL ECHOCARDIOGRAPHY Pinto, F. J., Wranne, B., STGOAR, F. G., Schnittger, I., Popp, R. L. LIPPINCOTT WILLIAMS & WILKINS. 1990: 722–22

  View details for Web of Science ID A1990EC76402873

• SYSTEMIC VENOUS FLOW CHANGES DURING OPEN-HEART-SURGERY - TIMING AND MECHANISMS Pinto, F. J., Wranne, B., STGOAR, F. G., Siegel, L. C., Haddow, G., Schnittger, I., Popp, R. L. LIPPINCOTT WILLIAMS & WILKINS. 1990: 723–23

  View details for Web of Science ID A1990EC76402879

• LEFT-VENTRICULAR DIASTOLIC FUNCTION - DOPPLER ECHOCARDIOGRAPHIC CHANGES SOON AFTER CARDIAC TRANSPLANTATION CIRCULATION STGOAR, F. G., Gibbons, R., Schnittger, I., Valantine, H. A., Popp, R. L. 1990; 82 (3): 872-878

  Abstract

  In acute cardiac rejection, left ventricular diastolic function is altered, and a restrictive ventricular filling pattern occurs. Doppler echocardiographic indexes of mitral inflow have been proposed as sensitive markers of the rejection process. As rejection progresses, the restrictive ventricular filling pattern is reflected by a shortening of isovolumic relaxation time and mitral valve pressure half-time and by an increase in early transmitral filling velocity. Diastolic function is also compromised in the nonrejecting cardiac transplant recipient during the early postoperative period. This study examined the progression in Doppler-derived mitral filling indexes in 25 recent cardiac transplant recipients who demonstrated no histological evidence of transplant rejection. Isovolumic relaxation time, mitral valve pressure half-time, and early transmitral filling velocity were measured at postoperative weeks 1, 2, 4, and 6 on the day that surveillance right ventricular endomyocardial biopsies were performed. The initial indexes were comparable to previously described restrictive parameters and over the 6-week study period evolved into a nonrestrictive filling pattern. This evolution reflects a progressive improvement in postoperative diastolic function and a decrease in left heart filling pressures. None of the evaluated clinical characteristics, including preoperative pulmonary pressures, total ischemic time of the transplanted heart, cardiopulmonary bypass time, and age of the donor heart, correlated with this process. Given the increasing use of Doppler echocardiography as a means of screening for transplant rejection, it is important to have a thorough understanding of normal postoperative changes in left ventricular diastolic function.

  View details for Web of Science ID A1990DY27700018

  View details for PubMedID 2394008

• SERIAL MEASUREMENT OF INTEGRATED ULTRASONIC BACKSCATTER IN HUMAN CARDIAC ALLOGRAFTS FOR THE RECOGNITION OF ACUTE REJECTION CIRCULATION Masuyama, T., Valantine, H. A., Gibbons, R., Schnittger, I., Popp, R. L. 1990; 81 (3): 829-839

  Abstract

  Cyclic variation of integrated ultrasonic backscatter (IB) was noninvasively measured in the septum and left ventricular posterior wall using a quantitative IB imaging system to assess the alterations in the acoustic properties of myocardium associated with acute cardiac allograft rejection. The study population consisted of 23 cardiac allograft recipients and 18 normal subjects. In each cardiac allograft recipient, one to eight (mean, four) IB studies were performed, each within 24 hours of right ventricular endomyocardial biopsy performed for rejection surveillance. The magnitude of the cyclic variation of IB in the posterior wall was 5.9 +/- 0.9 dB in normal subjects and 6.2 +/- 1.3 dB in the cardiac allograft recipients without previous or current histological evidence of acute rejection (n = 17, p = NS vs. normal subjects). The magnitude of cyclic variation of IB in the septum was 4.8 +/- 1.1 dB in normal subjects and 3.8 +/- 2.0 dB in the cardiac allograft recipients (n = 15, p = NS vs. normal subjects). A significant decrease in the septal IB measure was observed in cardiac allograft recipients with left ventricular hypertrophy (wall thickness of at least 13 mm) (2.6 +/- 1.7 dB, n = 8, p less than 0.05 vs. normal subjects). IB studies were done before and during moderate acute rejection in 11 recipients (14 episodes). During moderate acute cardiac rejection, the magnitude of the cyclic variation in IB decreased from 6.7 +/- 1.3 to 5.1 +/- 1.4 dB in the posterior wall (n = 14, p less than 0.05) and from 4.2 +/- 2.1 dB to 2.9 +/- 1.8 dB in the septum (n = 12, p less than 0.05). These data suggest 1) the magnitude of the cyclic variation in IB of the septum is different in cardiac allografts with cardiac hypertrophy and normal subjects, possibly reflecting regionally depressed myocardial contractile performance and 2) acute cardiac rejection in humans is accompanied by an alteration in the acoustic properties of the myocardium. This change is detectable by serial measurement of the magnitude of the cyclic variation in IB, both in the septum and in the posterior wall.

  View details for Web of Science ID A1990CT01400012

  View details for PubMedID 2306834

• Flow velocity acceleration in the left ventricle: a useful Doppler echocardiographic sign of hemodynamically significant mitral regurgitation. Journal of the American Society of Echocardiography Appleton, C. P., Hatle, L. K., Nellessen, U., Schnittger, I., Popp, R. L. 1990; 3 (1): 35-45

  Abstract

  Doppler echocardiography is a sensitive method to detect mitral regurgitation in patients with both native and prosthetic valves. However, estimates of the amount of mitral regurgitation remain semiquantitative, and even severe mitral regurgitation may be underestimated in the presence of markedly eccentric regurgitant jets or acoustic shadowing of the left atrium by mitral or aortic prostheses. This report describes the Doppler findings in 10 patients with severe native valve mitral regurgitation (angiographic grade III or IV) and in 15 patients with severe bioprosthetic mitral regurgitation that required valve replacement. An increase in peak mitral flow velocity above normal values was seen in eight of 10 patients with severe native valve mitral regurgitation (greater than or equal to 130 cm per second) and 11 of 15 patients with severe prosthetic valve mitral regurgitation (greater than or equal to 210 cm per second). One of 10 patients with a native valve and four of 15 patients with a bioprosthetic valve appeared to have only a localized left atrial systolic flow disturbance, incorrectly suggesting that the mitral regurgitation was mild. However, in all patients with severe mitral regurgitation, a low velocity (less than 100 cm per second) flow signal could be recorded in the left ventricle that was directed toward the mitral valve in systole. This flow signal showed a gradual increase in velocity as the sample volume was moved toward the mitral valve, with an abrupt further increase on entry into the left atrium. This signal was continuous with antegrade mitral flow and had the same orientation as mitral regurgitation recorded by continuous wave technique from the apex. A similar flow signal was not recorded in the left ventricle of any individual in a control group of 30 patients who had no mitral regurgitation or who had angiographic grade I or II mitral regurgitation. These findings suggest that acceleration of left ventricle flow toward the mitral valve in systole is only recorded when there is hemodynamically significant mitral regurgitation that is approximately equal to angiographic grade III or IV. Recognition of this Doppler finding may help in the estimation of mitral regurgitation severity, especially in difficult diagnostic situations.

  View details for PubMedID 2310590

• ULTRASONIC TISSUE CHARACTERIZATION WITH A REAL-TIME INTEGRATED BACKSCATTER IMAGING-SYSTEM IN NORMAL AND AGING HUMAN HEARTS JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Masuyama, T., Nellessen, U., Schnittger, I., Tye, T. L., Haskell, W. L., Popp, R. L. 1989; 14 (7): 1702-1708

  Abstract

  Experimental studies have shown that variation in the magnitude of integrated ultrasonic backscatter during the cardiac cycle represents acoustic properties of myocardium that are affected by pathologic processes; however, there are few clinical studies using integrated backscatter. Forty subjects without cardiovascular disease (aged 22 to 71 years, mean 41) were studied with use of a new M-mode format integrated backscatter imaging system to characterize the range of cyclic variation of integrated backscatter in normal subjects. Cyclic variation in integrated backscatter was noted in both the septum and the posterior wall in all subjects. The magnitude of the cyclic variation of integrated backscatter and the interval from the onset of the QRS wave of the electrocardiogram to the minimal integrated backscatter value were measured using an area of interest of variable size for integrated backscatter sampling and a software resident in the ultrasound scanner. The magnitude of cyclic variation was larger for the posterior wall than for the septum (6.3 +/- 0.8 versus 4.9 +/- 1.3 dB, p less than 0.01). The interval to the minimal integrated backscatter value was 328 +/- 58 ms for the septum and 348 +/- 42 ms for the posterior wall (p = NS). There was a weak correlation between the magnitude of cyclic variation of integrated backscatter and subject age for the posterior wall (r = -0.47, p less than 0.01), but this was not significant for the septum (r = -0.21) (partially because of inability to exclude specular septal echoes) and septal endocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1989CE08600019

  View details for PubMedID 2685077

• TRANSESOPHAGEAL ECHOCARDIOGRAPHY - AN INTRODUCTION FOR ULTRASONOGRAPHERS JOURNAL OF DIAGNOSTIC MEDICAL SONOGRAPHY Tye, T. L., Nellessen, U., Schnittger, I., Popp, R. 1989; 5 (6): 316-321

  View details for Web of Science ID A1989CF11400005

• ULTRASONIC TISSUE CHARACTERIZATION OF HUMAN HYPERTROPHIED HEARTS INVIVO WITH CARDIAC CYCLE-DEPENDENT VARIATION IN INTEGRATED BACKSCATTER CIRCULATION Masuyama, T., STGOAR, F. G., Tye, T. L., Oppenheim, G., Schnittger, I., Popp, R. L. 1989; 80 (4): 925-934

  Abstract

  Integrated ultrasonic backscatter (IB) is a noninvasive measure of the acoustic properties of myocardium. Previous experimental studies have indicated that altered acoustic properties of the myocardium are reflected by the magnitude of variation of IB during the cardiac cycle. In our study, cardiac cycle-dependent variation of IB was noninvasively measured using a quantitative IB imaging system in 12 patients with uncomplicated pressure-overload hypertrophy and 13 patients with hypertrophic cardiomyopathy. Sixteen normal subjects served as a control. The magnitude of cardiac cycle-dependent variation of IB for the posterior wall was 6.0 +/- 0.9 dB in normal subjects, 5.7 +/- 0.8 dB in the patients with uncomplicated pressure-overload hypertrophy, and 6.7 +/- 2.1 dB in the patients with hypertrophic cardiomyopathy. There were no significant differences among any of these groups. In contrast, the magnitude of cardiac cycle-dependent variation of IB for the septum was significantly smaller in the patients with uncomplicated pressure-overload hypertrophy (2.8 +/- 1.3 dB) and in the patients with hypertrophic cardiomyopathy (3.1 +/- 2.3 dB) than in normal subjects (4.9 +/- 1.0 dB). The magnitude of cardiac cycle-dependent variation of IB was smaller as the wall-thickness index increased (r = -0.53, p less than 0.01, n = 82 for all data). This IB measure also correlated with percent-systolic thickening of the myocardium (r = 0.67, p less than 0.01, n = 82). Thus, alteration in the magnitude of cardiac cycle-dependent variation of IB was observed in hypertrophic hearts and showed apparent regional myocardial differences.

  View details for Web of Science ID A1989AW00100020

  View details for PubMedID 2529060

• LONG-TERM RESULTS OF ANTITACHYCARDIA PACING IN PATIENTS WITH SUPRAVENTRICULAR TACHYCARDIA PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY Schnittger, I., Lee, J. T., Hargis, J., Wyndham, C. R., ECHT, D. S., Swerdlow, C. D., Griffin, J. C. 1989; 12 (6): 936-941

  Abstract

  Between 1979 and 1984 the Cybertach-60, (Intermedics, Inc. Model 262-01), a programmable, automatic antitachycardia pacemaker was implanted in 11 patients who had drug-refractory supraventricular tachycardia (SVT). The patients have been followed for a total of 64-108 (mean 84 months). All patients were symptomatic and had failed two or more drugs and six patients had required prior DC cardioversion. The mechanism of supraventricular tachycardia was atrioventricular (AV) nodal reentry in six patients, AV reentry in four patients, and atrial tachycardia in one patient. Preoperatively all patients had reliable termination of the tachycardia without induction of atrial fibrillation by pacing methods available to Cybertach-60. Postimplant, Cybertach-60 reliably terminated all episodes of tachycardia without ancillary drug therapy. Nevertheless, at long-term follow-up antitachycardia pacing was effective and safe in the minority (36%), with only four patients out of eleven still using a pacemaker for supraventricular tachycardia. One of these four patients required additional drug therapy. In one of the patients, the Cybertach-60 was replaced after 78 months by a more advanced device, (Intertach, Intermedics, Inc.) because of a depleted Cybertach-60 battery. In seven patients who no longer use antitachycardia pacing for termination of tachycardia, one patient developed atrial fibrillation during tachycardia termination (at 58 months postimplant). Three patients experienced induction of tachycardia or atrial fibrillation by the pacemaker due to undersensing of sinus P waves (at 36, 48, and 51 months).(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1989AK02100009

  View details for PubMedID 2472621

• Doppler diagnosis of left ventricle to coronary sinus fistula: an unusual complication of mitral valve replacement. Journal of the American Society of Echocardiography YEE, G. W., NAASZ, C., Hatle, L., PIPKIN, R., Schnittger, I. 1988; 1 (6): 458-462

  View details for PubMedID 3272796

• TRANS-ESOPHAGEAL TWO-DIMENSIONAL ECHOCARDIOGRAPHY AND COLOR DOPPLER FLOW VELOCITY MAPPING IN THE EVALUATION OF CARDIAC-VALVE PROSTHESES CIRCULATION Nellessen, U., Schnittger, I., Appleton, C. P., Masuyama, T., Bolger, A., Fischell, T. A., Tye, T., Popp, R. L. 1988; 78 (4): 848-855

  Abstract

  To determine the value of transesophageal ultrasound in the assessment of cardiac valve prostheses, 14 patients with clinically suspected mitral prosthesis malfunction were studied by transthoracic and transesophageal two-dimensional imaging as well as by color Doppler flow velocity mapping (color Doppler). Patients underwent left ventricular angiography (n = 13), surgery (n = 11), or both angiography and surgery (n = 10). Nine patients had only mitral valve replacement, four patients had both mitral and aortic valve replacement, and one patient had mitral, aortic, and tricuspid valve replacement. There were 16 biological and four mechanical prostheses. The degree of mitral regurgitation was graded by both transthoracic and transesophageal color Doppler according to the area of the regurgitant jet visualized and was compared with a three-point classification of mitral regurgitation by left ventricular angiography judged by observers blinded to the echocardiographic results. All transesophageal studies were performed without complication and were well tolerated. The pathological morphology of the mitral prosthesis was additionally or more clearly visualized by transesophageal two-dimensional imaging and subsequently proven at surgery in three patients with flail leaflets and one patient with a vegetation compared with images obtained by the transthoracic approach. Valvular regurgitation was graded by the transthoracic approach as absent in four patients, mild in two patients, moderate in five patients, and severe in only three patients. The transesophageal assessment showed absence of mitral regurgitation in two patients, moderate regurgitation in two patients, and severe regurgitation in 10 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

  View details for Web of Science ID A1988Q654900007

  View details for PubMedID 3168192

• DIASTOLIC MITRAL AND TRICUSPID REGURGITATION BY DOPPLER ECHOCARDIOGRAPHY IN PATIENTS WITH ATRIOVENTRICULAR-BLOCK - NEW INSIGHT INTO THE MECHANISM OF ATRIOVENTRICULAR VALVE CLOSURE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Schnittger, I., Appleton, C. P., Hatle, L. K., Popp, R. L. 1988; 11 (1): 83-88

  Abstract

  The purpose of this study was to prospectively determine the incidence of diastolic mitral and tricuspid regurgitation in atrioventricular (AV) block using Doppler echocardiography. The temporal relation between mitral and tricuspid diastolic insufficiency and the diastolic murmur recorded in patients with complete heart block was also investigated. Twenty-two consecutive patients with AV block (referred to the Echo-Doppler laboratory for routine clinical studies), aged 18 to 87 years, were enrolled in the study. Eleven patients had third degree AV block and a ventricular-inhibited (VVI) pacemaker, two patients had second degree AV block, seven patients had first degree AV block, one patient had blocked premature atrial complexes and one patient had atrial flutter with 4:1 AV block. Diastolic mitral regurgitation was detected in 20 patients, and diastolic tricuspid regurgitation in 21. A mid-diastolic murmur was detected in all patients except in the three youngest. The murmur occurred before diastolic regurgitation and coincided with peak forward flow through the AV valve after atrial contraction. M-mode mitral valve echocardiograms obtained in nine patients demonstrated near closure of some portions of the mitral valve after atrial contraction. Effective closure of the valve, however, did not occur unless ventricular systole supervened. In conclusion, diastolic mitral and tricuspid regurgitation are almost universally present in patients with AV block and are associated with a diastolic murmur. The murmur coincides with forward AV valve flow. Diastolic regurgitation is silent. Effective AV valve closure is not established until ventricular systole occurs, as demonstrated by M-mode echocardiographic recording of the mitral valve.

  View details for Web of Science ID A1988L604800013

  View details for PubMedID 3335709

• LONG-TERM FOLLOW-UP OF PATIENTS WITH PACEMAKERS FOR THE MANAGEMENT OF SUPRAVENTRICULAR TACHYCARDIA Schnittger, I., Lee, J., Hargis, J., Wyndham, C., Echt, D., Swerdlow, C., Griffin, J. C. FUTURA PUBL CO. 1987: 439–39

  View details for Web of Science ID A1987G329700149

• DIAGNOSTIC CHALLENGES FOLLOWING CARDIAC TRANSPLANTATION RADIOLOGIC CLINICS OF NORTH AMERICA GUTHANER, D. F., Schnittger, I., Wright, A., Wexler, L. 1987; 25 (2): 367-376

  Abstract

  It is now almost two decades since the first human cardiac transplantation was performed. Recipients will require close follow-up by their referring physicians outside of the main referral centers. This article is intended to assist the referring physician in choosing the most appropriate diagnostic studies throughout the posttransplant period.

  View details for Web of Science ID A1987G568700014

  View details for PubMedID 3547483

• Ultrasonic characterization of acute cardiac rejection from temporal evolution of echocardiograms. journal of heart transplantation Wear, K. A., Schnittger, I., DIRECTOR, B. A., Dawkins, K. D., Haverich, A., Billingham, M. E., Jamieson, S. W., Popp, R. L. 1986; 5 (6): 425-429

  Abstract

  Two ultrasonic parameters that characterize cardiac contractile performance were tested for their ability to detect the early stages of acute rejection. Five dogs received heart transplants with a heterotopic abdominal model and were given echographic examinations 1, 4, and 8 days after surgery. The ultrasonic measurements were extracted from pairs of cross-sectional echocardiograms, separated in time by approximately half of a cardiac cycle. The contraction-related changes in the portions of the images corresponding to myocardium were characterized by ratio of mean video amplitude and image-pair correlation. Full-thickness biopsies were taken from the left and right ventricles after each examination so that the correlations between the ultrasonic measurements and the histologic state of the tissue could be determined. Each biopsy was ranked according to the following scale of increasing levels of rejection: 0 (normal), 1 (lymphocyte infiltration), 2 (focal necrosis), 3 (diffuse necrosis), 4 (presence of hemorrhages). The average histologic state for the left ventricle increased from 0.2 +/- 0.4 for the first examination, to 2.0 +/- 0.7 for the second, and 3.6 +/- 0.5 for the third. Similar results were obtained for the right ventricle. The progressions of mean amplitude ratio and correlation were 1.55 +/- 0.14, 1.49 +/- 0.17, 1.19 +/- 0.15, and 0.22 +/- 0.10, 0.28 +/- 0.10, 0.74 +/- 0.25, respectively. Thus in this experiment, these parameters were useful for distinguishing advanced stages of rejection from the normal state and from mild rejection.

  View details for PubMedID 3302175

• TIMING OF ABNORMAL INTERVENTRICULAR SEPTAL MOTION AFTER CARDIOPULMONARY BYPASS OPERATIONS - LACK OF INJURY PROVED BY PREOPERATIVE, INTRAOPERATIVE, AND POSTOPERATIVE ECHOCARDIOGRAPHY JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Schnittger, I., Keren, A., Yock, P. G., Allen, M. D., Modry, D. L., Zusman, D. R., Mitchell, R. S., Miller, D. C., Popp, R. L. 1986; 91 (4): 619-623

  Abstract

  Abnormal interventricular septal motion after cardiopulmonary bypass is a widely known occurrence. The cause and exact timing of this phenomenon remain unclear. We have studied 21 patients prospectively with preoperative, intraoperative, and postoperative two-dimensional and M-mode echocardiograms. Intraoperative studies were obtained with the pericardium closed and open and after completion of procedures performed with cardiopulmonary bypass. Fourteen patients had coronary artery bypass graft operations alone. Six patients had valve replacement with or without coronary bypass, and one patient had removal of a left atrial myxoma. All patients had normal interventricular septal motion before the operation, and none had abnormal septal motion intraoperatively. Four to eight days postoperatively, the septum still thickened normally in all patients, with five patients having normal, nine patients abnormal, and seven patients paradoxical interventricular septal motion. Studies in 11 patients 1 to 4 months postoperatively showed no change from the early postoperative study. The pericardium was left open postoperatively in all patients. Six patients were studied a few hours after sternal closure and all had abnormal interventricular septal motion. We conclude that abnormal interventricular septal motion after cardiac operations is not due to injury of the septum, adhesion formation, or loss of pericardial constraint. Closure of the chest wall itself, with the pericardium left open, is associated with this abnormality.

  View details for Web of Science ID A1986A823600019

  View details for PubMedID 3959582

• ESOPHAGEAL ELECTROCARDIOGRAPHY - A NEW TECHNOLOGY REVIVES AN OLD TECHNIQUE AMERICAN JOURNAL OF CARDIOLOGY Schnittger, I., Rodriguez, I. M., WINKLE, R. A. 1986; 57 (8): 604-607

  Abstract

  This study evaluates the clinical use of an easily swallowed bipolar electrode for recording an esophageal electrocardiogram (ECG). Fourteen patients were selected for bedside diagnosis (ECG group) because of arrhythmias difficult to evaluate using a standard 12-lead ECG. A second group of 27 non-selected patients scheduled for routine 24-hour ambulatory electrocardiographic recordings (ambulatory ECG group) had an esophageal ECG recorded as the "third channel." All 14 patients (100%) in the ECG group had excellent-quality tracings, and the esophageal ECG was diagnostic in 12 cases (86%). Of 27 patients in the ambulatory ECG group, 19 (70%) had fairly good to excellent-quality 24-hour esophageal pill tracings, with the esophageal ECG contributing to correct arrhythmia diagnosis in 11 patients (41%). It is concluded that this easily swallowed esophageal electrode provides an excellent-quality short-term ECG and often permits proper arrhythmia diagnosis in selected patients with arrhythmias. Good-quality 24-hour esophageal ambulatory electrocardiographic recordings can also be obtained that contribute to arrhythmia diagnosis in a limited number of unselected patients, and should be even more clinically useful in carefully selected patients.

  View details for Web of Science ID A1986A393000019

  View details for PubMedID 3953447

• ULTRASONIC CHARACTERIZATION OF ACUTE CARDIAC REJECTION FROM TEMPORAL EVOLUTION OF ECHOCARDIOGRAMS Wear, K. A., Schnittger, I., DIRECTOR, B. A., Haverich, A., Billingham, M. E., Popp, R. L. ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS. 1986: 37–37

  View details for Web of Science ID A1986C266900006

• ULTRASONIC TISSUE CHARACTERIZATION - DETECTION OF ACUTE MYOCARDIAL ISCHEMIA IN DOGS CIRCULATION Schnittger, I., Vieli, A., Heiserman, J. E., DIRECTOR, B. A., Billingham, M. E., Ellis, S. G., Kernoff, R. S., Takamoto, T., Popp, R. L. 1985; 72 (1): 193-199

  Abstract

  Ultrasonic tissue characterization is a new area of investigation in the field of cardiac ultrasound. The amplitude and frequency of the ultrasound signal are normally altered as the signal penetrates through tissue. It is assumed that the amplitude distribution and frequency shift of diseased or edematous tissue are different than those of normal tissue. A statistical approach to the analysis of the unprocessed radiofrequency signal in the amplitude domain was used to study the effect of acute myocardial ischemia on the parameter mean amplitude/standard deviation of the amplitude (MSR). Ten dogs were anesthetized and underwent left lateral thoracotomy. Baseline mean MSR from the interventricular septum was 1.99 +/- 0.05, but increased by 30 min after coronary artery occlusion and started to plateau at 1 hr (mean 2.24 +/- 0.06). Reproducibility in noninfarcted myocardium (left ventricular inferoposterior wall) was good, with a mean MSR of 2.00 +/- 0.05 at baseline and 1.98 +/- 0.04 3 to 4 hr later. There was no difference in mean MSR when data were obtained through chest wall and when they were obtained directly from the surface of the heart. We conclude that statistical analysis in the amplitude domain of the unprocessed radiofrequency signal can detect acute myocardial ischemia within 30 min after coronary artery occlusion, provides reproducible measurements, and is unaffected by chest wall filtering.

  View details for Web of Science ID A1985ALE0300025

  View details for PubMedID 3891130

• DOPPLER COLOR FLOW MAPPING - UTILITY IN VALVULAR REGURGITATION Yock, P. G., Segal, J., Teirstein, P. S., Schnittger, I., Popp, R. L. LIPPINCOTT WILLIAMS & WILKINS. 1984: 38–38

  View details for Web of Science ID A1984TN45400161

• COMPUTERIZED QUANTITATIVE-ANALYSIS OF LEFT-VENTRICULAR WALL MOTION BY TWO-DIMENSIONAL ECHOCARDIOGRAPHY CIRCULATION Schnittger, I., Fitzgerald, P. J., Gordon, E. P., Alderman, E. L., Popp, R. L. 1984; 70 (2): 242-254

  Abstract

  Quantitative detection of left ventricular segmental wall motion abnormalities by any modality depends on the reference system used because of the dynamic geometry of contraction and cardiac motion within the thorax. To assess the feasibility and accuracy of quantitative analysis of left ventricular wall motion by two-dimensional echocardiography, we studied 61 subjects with the use of 44 different reference methods in each of three echocardiographic views: the parasternal short-axis view at the levels of the mitral valve and of the papillary muscles and an apical four-chamber view. The three major groups of reference systems used were those with a fixed external reference, a floating reference correcting for translation, and systems correcting for both translation and rotation. In the first part of this study the end-diastolic and end-systolic outlines of 20 normal subjects were stored in a computer and composite data of these 20 subjects were plotted to obtain a 95% confidence interval for measured normal fractional change for each reference method. In the second part of the project an additional prospective group of 10 normal subjects and a group of 31 "abnormal" patients had their left ventricular wall motion analyzed by similar methods and the results were compared with all the confidence intervals. One reference method was selected for each two-dimensional echocardiographic view based on the highest sensitivity and specificity found by statistical analysis; a floating-reference system including translation was found to be optimal for the apical four-chamber and parasternal short-axis views at the level of the mitral valve and a fixed external reference system was optimal for the short-axis view at the papillary level. The percent fractional shortening of radial dimensions (radial methods) and the percent fractional change in area measurements (area methods) during the cardiac cycle were also calculated at 5, 10, 20, 30 and 45 degree intervals around the outline perimeter for each subject according to each of the 44 different methods. Area methods yielded the same specificity and sensitivity as radial dimension analysis methods at 5 to 45 degree intervals. Ten normal subjects underwent repeat echocardiography within 2 days of their first study to examine day-to-day variation. Average change in mean contraction from day to day was 7% to 9% for radial methods and 9% to 13% for area methods. In conclusion, we present a computerized system for unbiased selection of optimal methods of analysis of left ventricular wall motion by two-dimensional echocardiography.(ABSTRACT TRUNCATED AT 400 WORDS)

  View details for Web of Science ID A1984TB41300013

  View details for PubMedID 6733880

• IS CONTINUOUS WAVE DOPPLER TOO SENSITIVE IN DIAGNOSING PATHOLOGIC VALVULAR REGURGITATION Yock, P. G., Schnittger, I., Popp, R. L. LIPPINCOTT WILLIAMS & WILKINS. 1984: 381–81

  View details for Web of Science ID A1984TN45401530

• AN IMPROVED STOCHASTIC APPROACH TO RF AMPLITUDE ANALYSIS IN ULTRASONIC CARDIAC TISSUE CHARACTERIZATION ULTRASONIC IMAGING Vieli, A., Heiserman, J., Schnittger, I., Popp, R. L. 1984; 6 (2): 139-151

  Abstract

  We carried out a series of studies to improve the reproducibility of methods for ultrasonic myocardial tissue characterization using a stochastic approach to amplitude analysis of radiofrequency signals previously reported from our laboratory. Analysis of transducer scanner characteristics, data acquisition and processing, and data display from studies in tissue phantoms permit us to define some features of a parameter for expression of tissue character. The ratio of mean to standard deviation of the amplitude histogram from our system is explored as now implemented in our laboratory for reproducible measurements. The theoretical basis for understanding the utility of this method in defining tissue architecture and pathologic conditions requires further work.

  View details for Web of Science ID A1984SU51800003

  View details for PubMedID 6539976

• DOPPLER TRICUSPID AND PULMONIC REGURGITATION IN NORMALS - IS IT REAL Yock, P. G., NAASZ, C., Schnittger, I., Popp, R. L. LIPPINCOTT WILLIAMS & WILKINS. 1984: 40–40

  View details for Web of Science ID A1984TN45400168

• COMPUTERIZED QUANTITATIVE-ANALYSIS OF LEFT-VENTRICULAR WALL MOTION BY TWO-DIMENSIONAL ECHOCARDIOGRAPHY Schnittger, I., Fitzgerald, P. J., Gordon, E. P., Alderman, E. L., Popp, R. L. ELSEVIER SCIENCE INC. 1983: 581–81

  View details for Web of Science ID A1983QD14000018

• RAPID, SEMIAUTOMATED TECHNIQUE FOR ESTIMATING LEFT-VENTRICULAR VOLUME AMERICAN HEART JOURNAL KANTROWITZ, N. E., Schnittger, I., Schwarzkopf, A., Fitzgerald, P. J., Popp, R. L. 1983; 106 (3): 521-527

  Abstract

  A new system for rapidly quantitating left ventricular volume using two-dimensional echocardiography is tested. This system relies on a microprocessor built into a sector scanner that immediately calculates the length, area, and volume of the chamber being imaged using the mathematical model of an ellipsoid of revolution. The calculations are made after the observer superimposes a smooth calibrated ellipse outline on the endocardium imaged with the sector scanner. We report our experience with this system in 50 patients with a variety of cardiac disorders and compare the left ventricular volumes measured with those obtained using cineangiography, M-mode, and more detailed light pen tracing techniques. Correlations between volumes measured with the elliptical calipers and angiography were good (r = 0.820, SEE +/- 38.8 ml) (n = 100), but not as good as that between light pen tracing of the echo images and angiography (r = 0.847, SEE +/- 27.8 ml) (n = 22). M-mode correlated less well with angiography (r = 0.789; SEE +/- 42.1 ml) (n = 90). We conclude that the calibrated ellipse system is rapid and simple to use, while its accuracy matches previous studies using two-dimensional echocardiography to quantitate left ventricular volume.

  View details for Web of Science ID A1983RE66300014

  View details for PubMedID 6881026

• REPRODUCIBILITY OF LEFT-VENTRICULAR VOLUMES BY TWO-DIMENSIONAL ECHOCARDIOGRAPHY JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Gordon, E. P., Schnittger, I., Fitzgerald, P. J., Williams, P., Popp, R. L. 1983; 2 (3): 506-513

  Abstract

  Reproducibility may be as important as absolute accuracy in assessing the utility of an echocardiographic method of left ventricular volume estimation for epidemiologic or physiologic studies. The magnitude of differences between measurements in the same subjects from day to day must be defined before any quantitative technique can be used reliably to document "real" changes in heart volume over time. Two-dimensional echocardiograms were performed serveral days apart in 30 subjects, including 20 normal subjects and 10 patients with stable coronary heart disease. Analyses of light-pen tracings provided measurements of end-diastolic volume, endsystolic volume and derived ejection fraction on both days, and differences in individual subjects between days were quantitated. Beat to beat, interobserver and intraobserver variability also were assessed. Although group values changed little from day to day, individual volume changes were substantial in some cases. Confidence limits for individual measurements were derived from analyses of intrasubject variability and were as follows: end-diastolic volume +/- 15%, end-systolic volume +/- 25%, ejection fraction +/- 10%. Confidence limits in a larger group of subjects were narrower; in a group of 30 subjects, changes of greater than 2% in end-diastolic volume, 5% in end-systolic volume and 2% in ejection fraction most likely represent real change. Intraobserver variability was minimal, but interobserver and beat to beat variability were of sufficient magnitude to suggest that serial measurements on a given subject be made ideally by a single person and that several cycles be averaged for a given measurement.

  View details for Web of Science ID A1983RE86300014

  View details for PubMedID 6875114

• STANDARDIZED INTRACARDIAC MEASUREMENTS OF TWO-DIMENSIONAL ECHOCARDIOGRAPHY JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Schnittger, I., Gordon, E. P., Fitzgerald, P. J., Popp, R. L. 1983; 2 (5): 934-938

  Abstract

  Thirty-five healthy adults were studied by two-dimensional echocardiography to attempt to standardize a simple method for measurement of intracardiac dimensions. Both ventricles and the atria and aorta were measured in five different views: parasternal long-axis, parasternal short-axis at the level of the aortic valve, the chordae tendineae and the papillary muscles and an apical four chamber view. The minor axis of each chamber was measured in all five views; the major axis in the apical four chamber view also was measured. All measurements are presented as a range of values (mean and 2 standard deviations about the mean); the mean value is given as well as the absolute range of values measured. Normalization according to body surface area is also presented. Data from these multiple views allow assessment of asymmetry of cardiac chambers in normal subjects. The mean minor axis dimension at end-diastole of the right ventricle in the parasternal long-axis view (1.9 to 3.8 cm) was 13.6% smaller than in the four chamber view (2.2 to 4.4 cm), whereas the minor axis dimension of the left ventricle in the parasternal long-axis view (3.5 to 6.0 cm) was only 1.1% larger than in the four chamber view (3.3 to 6.0 cm). Therefore, the right ventricular minor axis dimensions are not interchangeable. Reproducibility in 10 subjects for all dimensions showed a maximal variability of 4.8%. These values permit a standardized and expeditious method for measuring intracardiac dimensions by two-dimensional echocardiography.

  View details for Web of Science ID A1983RN88600019

  View details for PubMedID 6630768

• ULTRASONIC TISSUE CHARACTERIZATION FOR DETECTION OF ACUTE MYOCARDIAL ISCHEMIA Schnittger, I., Vieli, A., Heiserman, J. E., DIRECTOR, B. A., Billingham, M. E., Kernoff, R. S., Takamoto, T., Popp, R. L. AMER HEART ASSOC. 1983: 330–30

  View details for Web of Science ID A1983RJ59301329

• REFERENCE SYSTEMS FOR ECHOCARDIOGRAPHIC SEGMENTAL WALL MOTION ANALYSIS Fitzgerald, P. J., Schnittger, I., Gordon, E. P., Popp, R. L. LIPPINCOTT WILLIAMS & WILKINS. 1982: 339–39

  View details for Web of Science ID A1982PH11401361

• REPRODUCIBILITY OF LEFT-VENTRICULAR VOLUME MEASUREMENT BY 2 DIMENSIONAL ECHOCARDIOGRAPHY Gordon, E. P., Schnittger, I., Fitzgerald, P. J., Popp, R. L. LIPPINCOTT WILLIAMS & WILKINS. 1982: 338–38

  View details for Web of Science ID A1982PH11401356

• LIMITATIONS OF COMPARING LEFT-VENTRICULAR VOLUMES BY 2 DIMENSIONAL ECHOCARDIOGRAPHY, MYOCARDIAL MARKERS AND CINEANGIOGRAPHY AMERICAN JOURNAL OF CARDIOLOGY Schnittger, I., Fitzgerald, P. J., Daughters, G. T., Ingels, N. B., KANTROWITZ, N. E., Schwarzkopf, A., MEAD, C. W., Popp, R. L. 1982; 50 (3): 512-519

  View details for Web of Science ID A1982PE99400013

  View details for PubMedID 7113934

• ACCURATE ASSESSMENT OF LEFT-VENTRICULAR VOLUMES BY TWO-DIMENSIONAL ECHOCARDIOGRAPHY Schnittger, I., Fitzgerald, P. J., Daughters, G. T., Ingels, N. B., SCHWARTZKOPF, A., Mead, C., KANTROWITZ, N. E., Popp, R. L. LIPPINCOTT WILLIAMS & WILKINS. 1981: 129–29

  View details for Web of Science ID A1981MJ18900486

• TIME DEPENDENCY OF VENTRICULAR-FIBRILLATION THRESHOLDS DETERMINED USING TRAINS OF STIMULI AMERICAN JOURNAL OF PHYSIOLOGY WINKLE, R. A., Jaillon, P., Griffin, J. C., Schnittger, I. 1980; 239 (4): H457-H463

  Abstract

  When determining ventricular fibrillation threshold (VFT), considerable time elapses from beginning a VFT measurement until the actual occurrence of ventricular fibrillaion (VF). We have defined this elapsed time as the "time to VF" and examined the effect of varying time to VF on the measured value of VFT. We induced VF in anesthetized dogs with a 100-Hz train of 16 4-ms stimuli applied to the right ventricular epicardium. The time to VF was varied by changing either the increment of fibrillation current increase (0.5, 1.0, or 2.0 mA) from one train to the next and/or the number of atrial paced beats between trains (6-192 beats). For 0.5-mA current increments, as time to VF increased from 66 to 454 s, VFT fell progressively from 15.3 +/- 4.8 to 6.7 +/- 1.1 mA. When time to VF exceeded 454 s, VFT increased again. Current increments of 1.0 and 2.0 mA had a similar time dependency of VFT. For any time to VF the VFT was lower when small current increments (i.e., more trains) were used to induce VF. Pretreatment with reserpine in six dogs abolished the time dependency. We conclude that time elapsed from the beginning of a VFT determination until VF actually occurs and the total number of trains used are important determinants of the VFT, probably because of local catecholamine release by the stimuli.

  View details for Web of Science ID A1980KN02900027

  View details for PubMedID 7425137

• THE RELATIONSHIP BETWEEN THE REPETITIVE EXTRA-SYSTOLE THRESHOLD AND THE VENTRICULAR-FIBRILLATION THRESHOLD IN THE DOG - NON-PARALLEL CHANGES FOLLOWING PHARMACOLOGICAL INTERVENTION CIRCULATION RESEARCH Jaillon, P., Schnittger, I., Griffin, J. C., WINKLE, R. A. 1980; 46 (5): 599-605

  View details for Web of Science ID A1980JQ42600001

  View details for PubMedID 7363409

• ECHOCARDIOGRAPHY-PERICARDIAL THICKENING AND CONSTRICTIVE PERICARDITIS AMERICAN JOURNAL OF CARDIOLOGY Schnittger, I., BOWDEN, R. E., Abrams, J., Popp, R. L. 1978; 42 (3): 388-395

  Abstract

  A total of 167 patients with pericardial thickening noted on M node echocardiography were studied retrospectively. After the echocardiogram, 72 patients underwent cardiac surgery, cardiac catheterization or autopsy for various heart diseases; 96 patients had none of these procedures. In 49 patients the pericardium was directly visualized at surgery or autopsy; 76 percent of these had pericardial thickening or adhesions. In another 8 percent, pericardial adhesions were absent, but no comment had been made about the appearance of the pericardium itself. In the remaining 16 percent, no comment had been made about the pericardium or percardial space. Cardiac catheterization in 64 patients revealed 24 with hemodynamic findings of constrictive pericarditis or effusive constrictive disease. Seven echocardiographic patterns consistent with pericardial adhesions or pericardial thickening are described and related when possible to the subsequent findings at heart surgery or autopsy. The clinical diagnoses of 167 patients with pericardial thickening are presented. The hemodynamic diagnosis of constrictive pericardial disease was associated with the echocardiographic finding of pericardial thickening, but there were no consistent echocardiographic patterns of pericardial thickening diagnostic of constriction. However, certain other echocardiographic abnormalities of left ventricular posterior wall motion and interventricular septal motion and a high E-Fo slope were suggestive of constriction.

  View details for Web of Science ID A1978FQ60000008

  View details for PubMedID 685851

• IS REPETITIVE EXTRA-SYSTOLE THRESHOLD AN INDEX OF VENTRICULAR-FIBRILLATION THRESHOLD Jaillon, P., Schnittger, I., Griffin, J. C., WINKLE, R. A. AMER HEART ASSOC. 1978: 46–46

  View details for Web of Science ID A1978FR51900174

• EFFECTS OF TOCAINIDE ON VENTRICULAR-FIBRILLATION THRESHOLD - COMPARISON WITH LIDOCAINE AMERICAN JOURNAL OF CARDIOLOGY Schnittger, I., Griffin, J. C., Hall, R. J., MEFFIN, P. J., WINKLE, R. A. 1978; 42 (1): 76-81

  View details for Web of Science ID A1978FG42000014

  View details for PubMedID 677040

• BOTH ACEBUTOLOL AND ITS ACETYL METABOLITE INCREASE VENTRICULAR-FIBRILLATION THRESHOLD Schnittger, I., Griffin, J. C., MEFFIN, P. J., Kernoff, R. S., WINKLE, R. A. SLACK INC. 1978: A295–A295

  View details for Web of Science ID A1978EU89400505

• EVIDENCE FOR A CATECHOLAMINE-MEDIATED TIME DEPENDENCY WHICH AFFECTS VENTRICULAR-FIBRILLATION THRESHOLD DETERMINATIONS WINKLE, R. A., Jaillon, P., Griffin, J. C., Schnittger, I. AMER HEART ASSOC. 1978: 65–65

  View details for Web of Science ID A1978FR51900251

• EFFECTS OF TOCAINIDE ON VENTRICULAR-FIBRILLATION THRESHOLD Griffin, J., Schnittger, I., Peters, F., MEFFIN, P. J., Hall, R., Kernoff, R., WINKLE, R. A. LIPPINCOTT WILLIAMS & WILKINS. 1977: 158–58

  View details for Web of Science ID A1977DX48400623