Bio


My long-term research interests involve development of algorithms using computational methods for early detection of coronary pathophysiology including, endothelial dysfunction and microvascular dysfunction (MVD) and/or a myocardial bridge (MB) in patients with angina and no obstructive coronary artery disease (NOCAD) and the identification of novel target therapies for primary prevention and improved prognosis in these patients. Under the mentorship of Dr. Jennifer Tremmel in Cardiovascular medicine at Stanford, I have been systematically studying to better understand the underlying pathophysiology of these patients, as well as the optimal use of diagnostic testing and treatment using the angina and no-obstructive CAD Registry at Stanford. In collaboration with other investigators in this field, we have published multiple scientific articles highlighting the limitations of current testing in this population and identification of novel diagnostic tools for early diagnosis and management of patients with angina and no obstructive CAD. My research also focuses on myocardial infarction (MI) in women, particularly spontaneous coronary artery dissection (SCAD). I have been involved in the design and execution of the first international collaborative study in SCAD, investigating peripartum vs. non-peripartum SCAD. This is analyzing the largest cohort of patients recruited from multiple US and non-US sites to understand the pathophysiological differences in these patient cohorts.

Institute Affiliations


Honors & Awards


  • CVI Travel Award, Stanford Cardiovascular Institute (Sept 11, 2017)
  • Outstanding Research Poster Award, Stanford Cardiovascular Institute (Oct 20, 2016)

Education & Certifications


  • MBBS, Maharashtra University of Health Sciences, India, Medicine (2012)

All Publications


  • 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; 309: 8–13
  • Dose-Response Relationship Between Intracoronary Acetylcholine and Minimal Lumen Diameter in Coronary Endothelial Function Testing of Women and Men With Angina and No Obstructive Coronary Artery Disease. Circulation. Cardiovascular interventions Pargaonkar, V. S., Lee, J. H., Chow, E. K., Nishi, T., Ball, R. L., Kobayashi, Y., Kimura, T., Lee, D. P., Stefanick, M. L., Fearon, W. F., Yeung, A. C., Tremmel, J. A. 2020; 13 (4): e008587

    Abstract

    BACKGROUND: Intracoronary acetylcholine (Ach) provocation testing is the gold standard for assessing coronary endothelial function. However, dosing regimens of Ach are quite varied in the literature, and there are limited data evaluating the optimal dose. We evaluated the dose-response relationship between Ach and minimal lumen diameter (MLD) by sex and studied whether incremental intracoronary Ach doses given during endothelial function testing improve its diagnostic utility.METHODS: We evaluated 65 men and 212 women with angina and no obstructive coronary artery disease who underwent endothelial function testing using the highest tolerable dose of intracoronary Ach, up to 200 mug. Epicardial endothelial dysfunction was defined as a decrease in MLD >20% after intracoronary Ach by quantitative coronary angiography. We used a linear mixed effects model to evaluate the dose-response relationship. Deming regression analysis was done to compare the %MLD constriction after incremental doses of intracoronary Ach.RESULTS: The mean age was 53.5 years. Endothelial dysfunction was present in 186 (68.1%). Among men with endothelial dysfunction, there was a significant decrease in MLD/10 g of Ach at doses above 50 mug and 100 g, while this decrease in MLD was not observed in women (P<0.001). The %MLD constriction at 20 mug versus 50 mug and 50 mug versus 100 mug were not equivalent while the %MLD constriction at 100 mug versus 200 mug were equivalent.CONCLUSIONS: Women and men appear to have different responses to Ach during endothelial function testing. In addition to having a greater response to intracoronary Ach at all doses, men also demonstrate an Ach-MLD dose-response relationship with doses up to 200 mug, while women have minimal change in MLD with doses above 50 g. An incremental dosing regimen during endothelial function testing appears to improve the diagnostic utility of the test and should be adjusted based on the sex of the patient.

    View details for DOI 10.1161/CIRCINTERVENTIONS.119.008587

    View details for PubMedID 32279562

  • 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

  • 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

  • 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

  • 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

  • Long-Term Prognosis of Early Repolarization With J-Wave and QRS Slur Patterns on the Resting Electrocardiogram: A Cohort Study. Annals of internal medicine Pargaonkar, V. S., Perez, M. V., Jindal, A., Mathur, M. B., Myers, J., Froelicher, V. F. 2015; 163 (10): 747-755

    Abstract

    The prognostic value of early repolarization with J waves and QRS slurs remains controversial. Although these findings are more prevalent in patients with idiopathic ventricular fibrillation, their ability to predict cardiovascular death has varied across studies.To test the hypothesis that J waves and QRS slurs on electrocardiograms (ECGs) are associated with increased risk for cardiovascular death.Retrospective cohort.Veterans Affairs Palo Alto Health Care System.Veterans younger than 56 years who had resting 12-lead electrocardiography, 90.5% of whom were men.Electrocardiograms were manually measured and visually coded using criteria of 0.1 mV or greater in at least 2 contiguous leads. J waves were measured at the peak of an upward deflection or notch at the end of QRS, and QRS slurs were measured at the top of conduction delay on the QRS downstroke. Absolute risk differences at 10 years were calculated to study the associations between J waves or QRS slurs and the primary outcome of cardiovascular death.Over a median follow-up of 17.5 years, 859 cardiovascular deaths occurred. Of 20 661 ECGs, 4219 (20%) had J waves or QRS slurs in the inferior and/or lateral territories; of these, 3318 (78.6%) had J waves or QRS slurs in inferior leads and 1701 (40.3%) in lateral leads. The upper bound of differences in risk for cardiovascular death from any of the J-wave or QRS slur patterns suggests that an increased risk can be safely ruled out (inferior, -0.77% [95% CI, -1.27% to -0.27%]; lateral, -1.07% [CI, -1.72% to -0.43%]).The study consisted of predominantly men, and deaths could be classified as cardiovascular but not arrhythmic.J waves and QRS slurs did not exhibit a clinically meaningful increased risk for cardiovascular death in long-term follow-up.None.

    View details for DOI 10.7326/M15-0598

    View details for PubMedID 26501238

  • 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
  • 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

  • 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

  • Antegrade Dissection Re-Entry AfterSubintimal Wiring of an Occluded VesselFrom Spontaneous Coronary Artery Dissection. JACC. Case reports Daniels, D. V., Pargaonkar, V. S., Nishi, T., Tremmel, J. A. 2020; 2 (1): 72-76

    Abstract

    Percutaneous management of spontaneous coronary artery dissection (SCAD) is challenging, with high procedural failurerates. We present a case of successful revascularization using antegrade dissection re-entry after failing to wirethetrue lumen in occlusive SCAD. Utilizing such alternative strategies may improve procedural success in this poorlyunderstood patient subset. (Level of Difficulty: Advanced.).

    View details for DOI 10.1016/j.jaccas.2019.12.001

    View details for PubMedID 34316968

  • 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

  • Improving risk stratification in heart failure with preserved ejection fraction by combining two validated risk scores. Open heart Boralkar, K. A., Kobayashi, Y., Moneghetti, K. J., Pargaonkar, V. S., Tuzovic, M., Krishnan, G., Wheeler, M. T., Banerjee, D., Kuznetsova, T., Horne, B. D., Knowlton, K. U., Heidenreich, P. A., Haddad, F. 2019; 6 (1): e000961

    Abstract

    Introduction: The Intermountain Risk Score (IMRS) was developed and validated to predict short-term and long-term mortality in hospitalised patients using demographics and commonly available laboratory data. In this study, we sought to determine whether the IMRS also predicts all-cause mortality in patients hospitalised with heart failure with preserved ejection fraction (HFpEF) and whether it is complementary to the Get with the Guidelines Heart Failure (GWTG-HF) risk score or N-terminal pro-B-type natriuretic peptide (NT-proBNP).Methods and results: We used the Stanford Translational Research Integrated Database Environment to identify 3847 adult patients with a diagnosis of HFpEF between January 1998 and December 2016. Of these, 580 were hospitalised with a primary diagnosis of acute HFpEF. Mean age was 76±16 years, the majority being female (58%), with a high prevalence of diabetes mellitus (36%) and a history of coronary artery disease (60%). Over a median follow-up of 2.0 years, 140 (24%) patients died. On multivariable analysis, the IMRS and GWTG-HF risk score were independently associated with all-cause mortality (standardised HRs IMRS (1.55 (95% CI 1.27 to 1.93)); GWTG-HF (1.60 (95% CI 1.27 to 2.01))). Combining the two scores, improved the net reclassification over GWTG-HF alone by 36.2%. In patients with available NT-proBNP (n=341), NT-proBNP improved the net reclassification of each score by 46.2% (IMRS) and 36.3% (GWTG-HF).Conclusion: IMRS and GWTG-HF risk scores, along with NT-proBNP, play a complementary role in predicting outcome in patients hospitalised with HFpEF.

    View details for DOI 10.1136/openhrt-2018-000961

    View details for PubMedID 31217994

  • Asymmetric dimethylarginine predicts impaired epicardial coronary vasomotion in patients with angina in the absence of obstructive coronary artery disease. International journal of cardiology Parikh, R. V., Pargaonkar, V. n., Ball, R. L., Kobayashi, Y. n., Kimura, T. n., Yeung, A. C., Cooke, J. P., Tremmel, J. A. 2019

    Abstract

    Impaired epicardial coronary vasomotion is a potential mechanism of angina and a predictor of adverse cardiovascular outcomes in patients without angiographic evidence of obstructive coronary artery disease (CAD). We sought to evaluate the association of asymmetric dimethylarginine (ADMA)-a marker of nitric oxide-mediated vascular dysfunction-with epicardial coronary vasomotor dysfunction in this select population.Invasive testing for epicardial vasomotor dysfunction was performed using intracoronary acetylcholine in the left anterior descending coronary artery. Impaired vasomotor response was defined as a luminal constriction of >20% on quantitative coronary angiography. Plasma ADMA levels were measured using high performance liquid chromatography. A robust multivariate linear mixed-effect model approach and Akaike information criterion were used to determine predictors of vasomotor dysfunction.In 191 patients with angina in the absence of obstructive CAD, abnormal epicardial vasomotion was observed in 137 (71.7%) patients. Median ADMA rose as the extent of impairment progressed: none (0.48 [0.44-0.59] μM), any (0.51 [0.46-0.60] μM, p = 0.12), focal (0.54 [0.49,0.61] μM, p = 0.17), and diffuse (0.55 [0.49,0.63] μM, p = 0.02). In unadjusted analysis, ADMA was highly predictive of vasomotor dysfunction (χ2=15.1, p = 0.002). Notably, ADMA remained a significant predictor even after adjusting for other factors in the best fit model (χ2=10.0, p = 0.02).ADMA is an independent predictor of epicardial coronary vasomotor dysfunction in patients with angina in the absence of obstructive CAD. These data support a very early mechanistic role of ADMA in the continuum of atherosclerotic heart disease.

    View details for DOI 10.1016/j.ijcard.2019.07.062

    View details for PubMedID 31416658

  • Association of Endothelin-1 with Accelerated Cardiac Allograft Vasculopathy and Late Mortality Following Heart Transplantation. Journal of cardiac failure Parikh, R. V., Khush, K., Pargaonkar, V. S., Luikart, H., Grimm, D., Yu, M., Akada, K., Honda, Y., Yeung, A. C., Valantine, H., Fearon, W. F. 2018

    Abstract

    BACKGROUND: Endothelin-1 (ET-1) has been implicated in the development of post-heart transplantation (HT) cardiac allograft vasculopathy (CAV), but has not been well-studied in humans.METHODS AND RESULTS: In 90 HT patients, plasma ET-1 was measured within 8 weeks of HT (baseline) via a competitive enzyme-linked immunosorbent assay. 3D volumetric intravascular ultrasound of the left anterior descending artery was performed at baseline and at 1 year. Accelerated CAV (lumen volume loss) was defined using the 75th percentile as a cutoff. Patients were followed beyond the first year post-HT for late death or re-transplantation. A receiver operative characteristic curve demonstrated that a baseline ET-1 concentration of 1.75 pg/mL provided the best accuracy for diagnosis of accelerated CAV at 1 year [area under the curve=0.69 (0.57-0.82), p=0.007]. In multivariate logistic regression, a higher baseline ET-1 concentration was independently associated with accelerated CAV [odds ratio (OR)=2.13, 95% confidence interval (CI): 1.15-3.94; p=0.01]; this relationship persisted when ET-1 was dichotomized at 1.75 pg/mL (OR=4.88, 95% CI: 1.69-14.10; p=0.003). Eighteen deaths occurred during a median follow-up period of 3.99 (2.51-9.95) years. Treated as a continuous variable, baseline ET-1 was not associated with late mortality in multivariate Cox regression [hazard ratio (HR)=1.22, 95% CI: 0.72-2.05; p=0.44]. However, ET-1 >1.75 pg/mL conferred a significantly lower cumulative event-free survival on Kaplan-Meier analysis (p=0.047), and was independently associated with late mortality (HR=2.94, 95% CI: 1.12-7.72; p=0.02).CONCLUSIONS: Elevated ET-1 early after HT is an independent predictor of accelerated CAV and late mortality, suggesting that ET-1 has durable prognostic value in the HT arena.

    View details for PubMedID 30543947

  • 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

  • THE COMPLEMENTARY VALUE OF THE GET WITH THE GUIDELINES: HEART FAILURE RISK SCORE AND LABORATORY MARKERS AT DISCHARGE IN PREDICTING MORTALITY IN PATIENTS HOSPITALIZED WITH HEART FAILURE WITH PRESERVED EJECTION FRACTION Boralkar, K., Kobayashi, Y., Pargaonkar, V., Moneghetti, K., Tuzovic, M., Krishnan, G., Amsallem, M., Kouznetsova, T., Horne, B., Knowlton, K., Heidenreich, P., Haddad, F. ELSEVIER SCIENCE INC. 2018: 839
  • SUBCLINICAL LEFT VENTRICULAR DYSFUNCTION IN WOMEN WITH ANGINA IN THE ABSENCE OF OBSTRUCTIVE CORONARY ARTERY DISEASE: A COMPREHENSIVE INVASIVE AND ECHOCARDIOGRAPHIC STUDY Bouajila, S., Pargaonkar, V., Kobayashi, Y., Kobayashi, Y., Haddad, F., Tremmel, J. ELSEVIER SCIENCE INC. 2018: 132
  • 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
  • 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
  • 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

  • Impact of Asymmetric Dimethylarginine on Coronary Physiology Early After Heart Transplantation. The American journal of cardiology Parikh, R. V., Khush, K. K., Luikart, H. n., Pargaonkar, V. S., Kobayashi, Y. n., Lee, J. H., Sinha, S. n., Cohen, G. n., Valantine, H. A., Yeung, A. C., Fearon, W. F. 2017

    Abstract

    Cardiac allograft vasculopathy is a major cause of long-term graft failure following heart transplantation. Asymmetric dimethylarginine (ADMA), a marker of endothelial dysfunction, has been mechanistically implicated in the development of cardiac allograft vasculopathy, but its impact on coronary physiology early after transplantation is unknown. Invasive indices of coronary physiology, namely, fractional flow reserve (FFR), the index of microcirculatory resistance, and coronary flow reserve, were measured with a coronary pressure wire in the left anterior descending artery within 8 weeks (baseline) and 1 year after transplant. Plasma levels of ADMA were concurrently assayed using high-performance liquid chromatography. In 46 heart transplant recipients, there was a statistically significant correlation between elevated ADMA levels and lower FFR values at baseline (r = -0.33; p = 0.024); this modest association persisted 1 year after transplant (r = -0.39; p = 0.0085). Patients with a baseline FFR <0.90 (a prognostically validated cutoff) had significantly higher baseline ADMA levels (0.63 ± 0.16 vs 0.54 ± 0.12 µM; p = 0.034). Baseline ADMA (odds ratio 1.80 per 0.1 µM; 95% confidence interval 1.07 to 3.03; p = 0.027) independently predicted a baseline FFR <0.90 after multivariable adjustment. Even after dichotomizing ADMA (≥0.60 µM, provides greatest diagnostic accuracy by receiver operating characteristic curve), this association remained significant (odds ratio 7.52, 95% confidence interval 1.74 to 32.49; p = 0.006). No significant relationship between ADMA and index of microcirculatory resistance or coronary flow reserve was detected. In conclusion, baseline ADMA was a strong independent predictor of FFR <0.90, suggesting that elevated ADMA levels are associated with abnormal epicardial function soon after heart transplantation.

    View details for PubMedID 28754566

  • Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease JACC-CARDIOVASCULAR INTERVENTIONS Kobayashi, Y., Fearon, W. F., Honda, Y., Tanaka, S., Pargaonkar, V., Fitzgerald, P. J., Lee, D. P., Stefanick, M., Yeung, A. C., Tremmel, J. A. 2015; 8 (11): 1433-1441

    Abstract

    This study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease.Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation.We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn) (an inverse correlate to absolute flow) at rest and hyperemia.All patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting Tmn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic Tmn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn.Despite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.

    View details for DOI 10.1016/j.jcin.2015.03.045

    View details for Web of Science ID 000361757600013

  • Effect of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease. JACC. Cardiovascular interventions Kobayashi, Y., Fearon, W. F., Honda, Y., Tanaka, S., Pargaonkar, V., Fitzgerald, P. J., Lee, D. P., Stefanick, M., Yeung, A. C., Tremmel, J. A. 2015; 8 (11): 1433-41

    Abstract

    This study investigated sex differences in coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) in patients with angina in the absence of obstructive coronary artery disease.Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR) are 2 methods of assessing the coronary microcirculation.We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive coronary artery disease. We performed CFR, IMR, fractional flow reserve, and quantitative coronary angiography in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn) (an inverse correlate to absolute flow) at rest and hyperemia.All patients had minimal atherosclerosis by quantitative coronary angiography (% diameter stenosis: 23.2 ± 12.3%), and epicardial disease was milder in women (fractional flow reserve: 0.88 ± 0.04 vs. 0.87 ± 0.04; p = 0.04). IMR was similar between the sexes (20.7 ± 9.8 vs. 19.1 ± 8.0; p = 0.45), but CFR was lower in women (3.8 ± 1.6 vs. 4.8 ± 1.9; p = 0.004). This was primarily due to a shorter resting Tmn in women (p = 0.005), suggesting increased resting coronary flow, whereas hyperemic Tmn was identical (p = 0.79). In multivariable analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn.Despite similar microvascular function in women and men by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The effect of sex differences should be considered in interpretation of physiological indexes using resting coronary flow.

    View details for DOI 10.1016/j.jcin.2015.03.045

    View details for PubMedID 26404195

  • Examining QRS amplitude criteria for electrocardiographic left ventricular hypertrophy in recommendations for screening criteria in athletes. Journal of electrocardiology Singla, V., Jindal, A., Pargaonkar, V., Soofi, M., Wheeler, M., Froelicher, V. 2015; 48 (3): 368-372

    Abstract

    Current guidelines for interpretation of the ECGs of athletes recommend that isolated R and S wave amplitudes that exceed traditional criteria for left ventricular hypertrophy be accepted as a physiological response to exercise training. This is based on training and echocardiographic studies but not on long term follow up. Demonstration of the prognostic characteristics of the amplitude criteria in a non-athletic population could support the current guidelines.To evaluate the prognostic value of the R and S wave voltage criteria for electrocardiographic left ventricular hypertrophy (ECG-LVH) in an ambulatory clinical population.The target population consisted of 20,903 ambulatory subjects who had ECGs recorded between 1987 and 1999 and were followed for cardiovascular death until 2013. During the mean follow up of 17years, there were 881 cardiovascular deaths.The mean age was 43±10, 91% were male and 16% were African American. Of the 2482 (12%) subjects who met the Sokolow-Lyon criteria, 241 (1.2%) subjects with left ventricular (LV) strain had an HR of 5.4 (95% CI 4.1-7.2, p<0.001), while 2241 (11%) subjects without strain had an HR of 1.4 (95% CI 1.2-1.8, p<0.001). Of the 4836 (23%) subjects who met the Framingham voltage criteria, 350 (2%) subjects with LV strain had an HR of 5.1 (95% CI 4.0-6.5, p<0.001), while 4486 (22%) subjects without strain had an HR of 1.1 (95% CI 0.9-1.3, p=0.26). The individual components of the Romhilt-Estes had HRs ranging from 1.4 to 3.6, with only the voltage component not being significant (HR 1.1, 95% CI 0.9-1.5, p=0.35).This study demonstrates that the R and S wave voltage criteria components of most of the original classification schema for electrocardiographic left ventricular hypertrophy are not predictive of CV mortality. Our findings support the current guidelines for electrocardiographic screening of athletes.

    View details for DOI 10.1016/j.jelectrocard.2014.12.012

    View details for PubMedID 25661864

  • A New Electrocardiographic Left Ventricular Hypertrophy Prognostic Score AMERICAN JOURNAL OF CARDIOLOGY Jindal, A., Singla, V., Pargaonkar, V., Froelicher, V. 2015; 115 (7): 982-985

    Abstract

    This report determines if the classic Romhilt-Estes score would predict better if points for its components were determined using a Cox hazard model and if the Cornell voltage criteria should replace the original criteria. Of the 20,903 subjects, the mean age was 43 ± 10 years and 90.6% were men. The mean follow-up for the population was 17 years, with 881 cardiovascular deaths; they were tested from 1987 to 1999 and followed until 2013. The new score was created with multipliers based on the Cox hazards of its elements with age bracket and gender included. The Cornell criteria were analyzed individually using Cox hazards with and without adjustments for age, gender, and African-American ethnicity and subsequently incorporated into the new score for analysis. For the new score, all 7 components were significant predictors of cardiovascular mortality with gender producing the greatest hazard ratio (HR) and left axis deviation and QRS duration >110 ms producing the lowest. For the original Romhilt-Estes score, 367 patients (1.8%) met the "definite" cutoff and had an HR of 5.6 (95% confidence interval 4.3 to 7.1). For the new score, 208 patients (1.0%) met the "definite" left ventricular hypertrophy cutoff and had an HR of 13.6 (95% confidence interval 10.8 to 17.3). The Romhilt-Estes had an area under the curve of 0.63, whereas the new score and new score with Cornell voltage both had an area under the curve of 0.7. In conclusion, our modified Romhilt-Estes score with new multipliers and without voltage criteria outperformed the original score.

    View details for DOI 10.1016/j.amjcard.2015.01.028

    View details for Web of Science ID 000352253000022

    View details for PubMedID 25700803