Daniel Clark, MD, MPH

All Publications

• Democratizing Congenital Heart Disease Management: The Potential for AI-Enabled Care and Necessary Future Directions. Journal of the American College of Cardiology Jain, S. S., Elias, P., Clark, D. E. 2024; 84 (9): 829-831

  View details for DOI 10.1016/j.jacc.2024.06.019

  View details for PubMedID 39168569

• Vitamin D Status and Cardiovascular Disease in College Athletes After SARS-CoV-2 Infection. Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine Hollabaugh, W. L., Hymel, A., Pennings, J. S., Clark, D. E., Soslow, J. H., Karpinos, A. R. 2024

  Abstract

  To evaluate the association between vitamin D status and CV disease after COVID-19 in college athletes.Retrospective cohort study.National College Athletic Association Division-I college athletes from a single academic institution.A total of 157 athletes (60 female; median age: 20 years) from 9 sports with a positive SARS-CoV-2 test, cardiac magnetic resonance imaging (CMR), and vitamin D level.Serum 25-hydroxyvitamin D level (primary); age, sex (regression models).Differences in age, sex, race, ethnicity, myocarditis, pericarditis, and CMR metrics by vitamin D status were analyzed. Regression models were used to assess the relationship between vitamin D status and CMR metrics accounting for age and sex.Low vitamin D (LVD) was found in 33 (21.0%) of athletes, particularly Black males (P < 0.001). Athletes with LVD had higher biventricular and lower mid-ventricular extracellular volumes, but these differences were not significant when corrected for age and sex. Athletes with LVD had higher left ventricle (LV) mass (P < 0.001) and LV mass index (P = 0.001) independent of age and sex. Differences in global circumferential strain were noted but are likely clinically insignificant. Vitamin D status did not associate with myocarditis and pericarditis (P = 0.544).LVD is common in athletes, particularly in Black males. Although athletes with LVD had higher LV mass, cardiac function and tissue characterization did not differ by vitamin D status. Future studies are needed to determine if the differences in LV mass and LV mass index by vitamin D status are clinically significant. This study suggests that vitamin D status does not impact the development of myocarditis or pericarditis after COVID-19 infection.

  View details for DOI 10.1097/JSM.0000000000001253

  View details for PubMedID 38980665

• Quantifying the impact of post-acute sequelae of coronavirus on the cardiopulmonary endurance of athletes. Pulmonary circulation Lubarsky, D., Clark, D. E., Crum, K., Karpinos, A., Austin, E. D., Soslow, J. H. 2024; 14 (3): e12413

  Abstract

  Post-acute sequelae of Coronavirus (PASC), or Long COVID, has emerged as a critical health concern. The clinical manifestations of PASC have been described, but studies have not quantified the cardiopulmonary effects. The goal of this study was to quantify PASC cardiopulmonary changes among endurance athletes. Endurance athletes were recruited via social media; 45 met inclusion criteria, 32 had PASC and 13 were asymptomatic at 3 months (control). Comprehensive interviews were conducted to assess: cardiopulmonary symptoms at 3 months; quantitative and qualitative changes in cardiovascular endurance; exercise hours per week at baseline and 3 months; and Modified Oslo, Dyspnea, and EQ-5D-5L scales. All collected data was based on self-reported symptoms. Wilcoxon rank sum compared PASC with control to distinguish the effects of PASC vs effects of COVID infection/lockdown. PASC subjects were more likely to be female (Table). The most common 3-month symptoms in PASC were fatigue and shortness of breath. Based on self-reported data, subjects endorsed a median decrease of 27% in cardiopulmonary endurance levels compared with 0% in controls (p = 0.0019). PASC subjects exercised less hours and had worse self-reported health as compared with controls. PASC subjects also had significantly worse Modified Oslo, Dyspnea, and EQ-5D-5L scores. Of the 32 PASC patients, 10 (31%) reported a complete inability to engage in any cardiovascular endurance exercise at 3 months. PASC leads to a significant, quantifiable decrease in cardiopulmonary health and endurance.

  View details for DOI 10.1002/pul2.12413

  View details for PubMedID 39022309

  View details for PubMedCentralID PMC11252491

• The role of comprehensive stress cardiac MRI in autoimmune rheumatic disease: A review. International journal of cardiology. Heart & vasculature Varghese, B., Gustafson, A., Chew, E., Chew, C., Frech, T., El-Harasis, M. A., Kumar, A., Shoemaker, B., Chrispin, J., Mukherjee, M., Dendy, J. M., Hughes, S. G., Clark, D. E. 2024; 52: 101381

  Abstract

  Cardiovascular disease is the leading cause of morbidity and mortality in patients with autoimmune rheumatic diseases. Much of this may be attributed to systemic inflammation resulting in coronary atherosclerosis and myocarditis. Cardiac magnetic resonance imaging is the gold standard for the evaluation of cardiac structure and function, including tissue characterization, which allows for detection of myocardial edema, inflammation, and fibrosis. Advances in parametric mapping and coronary flow reserve measurement techniques have the potential to change the diagnosis, risk stratification, and management of patients with autoimmune rheumatic diseases. We provide an overview of the current evidence and suggest potential future roles for the use of comprehensive cardiac magnetic resonance in patients with autoimmune rheumatic diseases in the field of cardio-rheumatology.

  View details for DOI 10.1016/j.ijcha.2024.101381

  View details for PubMedID 38854746

• INVESTIGATING THE PREDICTIVE UTILITY OF DOSIMETRY AND IMAGING FOR GRADE ≥3 CARDIAC EVENTS AFTER BREAST CANCER RADIOTHERAPY Guo, F., No, H., Butler, S., Jackson, S., Rhee, J., Clark, D., Marquez, C., Horst, K., Binkley, M. ELSEVIER SCIENCE INC. 2024: 2658

  View details for Web of Science ID 001324901502692

• A case report of successful primary percutaneous coronary intervention to an occluded anomalous left main coronary artery arising from the right coronary sinus. European heart journal. Case reports Wong, C. C., Pogatchnik, B. P., Clark, D. E., Sharma, R. P. 2024; 8 (4): ytae192

  Abstract

  Background: Anomalous aortic origin of a coronary artery from the opposite sinus is a rare congenital abnormality that may be encountered during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).Case summary: A 65-year-old man presented with chest pain and signs of heart failure. Electrocardiogram demonstrated atrial fibrillation with ST elevation in the high lateral leads, and he was taken emergently to the cardiac catheterization laboratory for primary PCI. Coronary angiography identified the culprit to be an occluded anomalous left main coronary artery (LMCA) arising from the right coronary cusp, and primary PCI was successfully performed in the LMCA and the left anterior descending artery (LAD). Computed tomography angiography confirmed a benign retroaortic course of the anomalous LMCA with no additional high-risk features, as well as a new left atrial appendage thrombus. He subsequently developed deep venous thrombosis, acute pulmonary embolism, and acute kidney injury secondary to renal artery embolism with associated infarction. Workup for patent foramen ovale and thrombophilia were negative, and he was discharged in a stable condition. At 2-month follow-up, he was asymptomatic with no evidence of myocardial ischaemia on stress cardiac magnetic resonance imaging.Discussion: We present the first reported case of an occluded anomalous LMCA arising from the right coronary sinus in a patient presenting with STEMI. Rapid recognition of this congenital anomaly and selection of an appropriate guide catheter were keys to achieving timely reperfusion and a good outcome in this case.

  View details for DOI 10.1093/ehjcr/ytae192

  View details for PubMedID 38665427

• Percutaneous Closure of a Ruptured Sinus of Valsalva Aneurysm under Transesophageal Echocardiography Guidance. CASE (Philadelphia, Pa.) Li, X. E., McElhinney, D. B., Lui, G. K., Clark, D. E., Woo, J. P. 2024; 8 (3Part A): 186-192

  Abstract

  • SOVA is a rare cardiac anomaly. • Ruptured SOVA carries a high mortality rate. • SOVA often coexists with other congenital lesions, most commonly VSD and bicuspid AV. • Ruptured SOVA needs repair; percutaneous repair is a safe alternative to surgery. • Echo plays a vital role in both diagnosing SOVA and guiding percutaneous closure.

  View details for DOI 10.1016/j.case.2023.12.006

  View details for PubMedID 38524988

  View details for PubMedCentralID PMC10954579

• Multimodality Imaging in Management of Adults with Dextro-Transposition of the Great Arteries Post Arterial Switch Operation. CASE (Philadelphia, Pa.) Conrad, D. R., Woo, J. P., Lui, G. K., Clark, D. E. 2024; 8 (3Part A): 162-166

  Abstract

  • Echo is an essential tool for monitoring long-term complications of D-TGA with ASO. • Multimodality imaging is complementary to echo in the assessment of complications. • 4D flow CMR can assess supravalvular PS post ASO. • Branch pulmonary arteries after LeCompte maneuver can be challenging to image.

  View details for DOI 10.1016/j.case.2023.12.028

  View details for PubMedID 38524978

  View details for PubMedCentralID PMC10954704

• Clinical prediction model: Multisystem inflammatory syndrome in children versus Kawasaki disease. Journal of hospital medicine Starnes, L. S., Starnes, J. R., Stopczynski, T., Amarin, J. Z., Charnogursky, C., Hayek, H., Talj, R., Parra, D. A., Clark, D. E., Patrick, A. E., Katz, S. E., Howard, L. M., Peetluk, L., Rankin, D., Spieker, A. J., Halasa, N. B. 2024

  Abstract

  Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious complication of severe acute respiratory syndrome coronavirus 2 infection. Features of MIS-C overlap with those of Kawasaki disease (KD).The study objective was to develop a prediction model to assist with this diagnostic dilemma.Data from a retrospective cohort of children hospitalized with KD before the coronavirus disease 2019 pandemic were compared to a prospective cohort of children hospitalized with MIS-C. A bootstrapped backwards selection process was used to develop a logistic regression model predicting the probability of MIS-C diagnosis. A nomogram was created for application to individual patients.Compared to children with incomplete and complete KD (N = 602), children with MIS-C (N = 105) were older and had longer hospitalizations; more frequent intensive care unit admissions and vasopressor use; lower white blood cell count, lymphocyte count, erythrocyte sedimentation rate, platelet count, sodium, and alanine aminotransferase; and higher hemoglobin and C-reactive protein (CRP) at admission. Left ventricular dysfunction was more frequent in patients with MIS-C, whereas coronary abnormalities were more common in those with KD. The final prediction model included age, sodium, platelet count, alanine aminotransferase, reduction in left ventricular ejection fraction, and CRP. The model exhibited good discrimination with AUC 0.96 (95% confidence interval: [0.94-0.98]) and was well calibrated (optimism-corrected intercept of -0.020 and slope of 0.99).A diagnostic prediction model utilizing admission information provides excellent discrimination between MIS-C and KD. This model may be useful for diagnosis of MIS-C but requires external validation.

  View details for DOI 10.1002/jhm.13290

  View details for PubMedID 38282424

• Society for Cardiovascular Magnetic Resonance 2022 Cases of SCMR case series. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Johnson, J. N., Pouraliakbar, H., Mahdavi, M., Ranjbar, A., Pfirman, K., Mehra, V., Ahmed, S., Ba-Atiyah, W., Galal, M. O., Zahr, R. A., Hussain, N., Tadikamalla, R. R., Farah, V., Dzelebdzic, S., Muniz, J. C., Lee, M., Williams, J., Lee, S., Aggarwal, S. K., Clark, D. E., Hughes, S. G., Ganigara, M., Nagiub, M., Hussain, T., Kwok, C., Lim, H. S., Nolan, M., Kikuchi, D. S., Goulbourne, C. A., Sahu, A., Sievers, B., Sievers, B., Sievers, B., Garg, R., Armas, C. R., Paleru, V., Agarwal, R., Rajagopal, R., Bhagirath, P., Kozor, R., Aneja, A., Tunks, R., Chen, S. S. 2023; 26 (1): 100007

  Abstract

  "Cases of SCMR" is a case series on the SCMR website (https://www.scmr.org) for the purpose of education. The cases reflect the clinical presentation, and the use of cardiovascular magnetic resonance (CMR) in the diagnosis and management of cardiovascular disease. The 2022 digital collection of cases are presented in this manuscript.

  View details for DOI 10.1016/j.jocmr.2023.100007

  View details for PubMedID 38211509

• Predicting Adverse Cardiac Events After Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer. JACC. CardioOncology No, H. J., Guo, F. B., Park, N. J., Kastelowitz, N., Rhee, J. W., Clark, D. E., Chin, A. L., Vitzthum, L. K., Horst, K. C., Moding, E. J., Loo, B. W., Diehn, M., Binkley, M. S. 2023; 5 (6): 775-787

  Abstract

  Radiotherapy may cause grade ≥3 cardiac events, necessitating a better understanding of risk factors. The potential predictive role of imaging biomarkers with radiotherapy doses for cardiac event occurrence has not been studied.The aim of this study was to establish the associations between cardiac substructure dose and coronary artery calcium (CAC) scores and cardiac event occurrence.A retrospective cohort analysis included patients with locally advanced non-small cell lung cancer treated with radiotherapy (2006-2018). Cardiac substructures, including the left anterior descending coronary artery, left main coronary artery, left circumflex coronary artery, right coronary artery, and TotalLeft (left anterior descending, left main, and left circumflex coronary arteries), were contoured. Doses were measured in 2-Gy equivalent units, and visual CAC scoring was compared with automated scoring. Grade ≥3 adverse cardiac events were recorded. Time-dependent receiver-operating characteristic modeling, the log-rank statistic, and competing-risk models were used to measure prediction performance, threshold modeling, and the cumulative incidence of cardiac events, respectively.Of the 233 eligible patients, 61.4% were men, with a median age of 68.1 years (range: 34.9-90.7 years). The median follow-up period was 73.7 months (range: 1.6-153.9 months). Following radiotherapy, 22.3% experienced cardiac events, within a median time of 21.5 months (range: 1.7-118.9 months). Visual CAC scoring showed significant correlation with automated scoring (r = 0.72; P < 0.001). In a competing-risk multivariable model, TotalLeft volume receiving 15 Gy (per 1 cc; HR: 1.38; 95% CI: 1.11-1.72; P = 0.004) and CAC score >5 (HR: 2.51; 95% CI: 1.08-5.86; P = 0.033) were independently associated with cardiac events. A model incorporating age, TotalLeft CAC (score >5), and volume receiving 15 Gy demonstrated a higher incidence of cardiac events for a high-risk group (28.9%) compared with a low-risk group (6.9%) (P < 0.001).Adverse cardiac events associated with radiation occur in more than 20% of patients undergoing thoracic radiotherapy within a median time of <2 years. The present findings provide further evidence to support significant associations between TotalLeft radiotherapy dose and cardiac events and define CAC as a predictive risk factor.

  View details for DOI 10.1016/j.jaccao.2023.08.007

  View details for PubMedID 38205000

  View details for PubMedCentralID PMC10774791

• Metabolic Signatures of Cardiac Dysfunction, Multimorbidity, and Post-Transcatheter Aortic Valve Implantation Death. Journal of the American Heart Association Perry, A. S., Zhao, S., Murthy, V., Gupta, D. K., Fearon, W. F., Kim, J. B., Kapadia, S., Kumbhani, D. J., Gillam, L., Whisenant, B., Quader, N., Zajarias, A., Mallugari, R. R., Clark, D. E., Patel, J. N., Gonzales, H., Welt, F. G., Bavry, A. A., Coylewright, M., Piana, R. N., Vatterott, A., Jackson, N., Gerszten, R. E., Lindman, B. R., Shah, R., Elmariah, S. 2023: e029542

  Abstract

  Background Studies in mice and small patient subsets implicate metabolic dysfunction in cardiac remodeling in aortic stenosis, but no large comprehensive studies of human metabolism in aortic stenosis with long-term follow-up and characterization currently exist. Methods and Results Within a multicenter prospective cohort study, we used principal components analysis to summarize 12 echocardiographic measures of left ventricular structure and function pre-transcatheter aortic valve implantation in 519 subjects (derivation). We used least absolute shrinkage and selection operator regression across 221 metabolites to define metabolic signatures for each structural pattern and measured their relation to death and multimorbidity in the original cohort and up to 2 validation cohorts (N=543 for overall validation). In the derivation cohort (519 individuals; median age, 84years, 45% women, 95% White individuals), we identified 3 axes of left ventricular remodeling, broadly specifying systolic function, diastolic function, and chamber volumes. Metabolite signatures of each axis specified both known and novel pathways in hypertrophy and cardiac dysfunction. Over a median of 3.1years (205 deaths), a metabolite score for diastolic function was independently associated with post-transcatheter aortic valve implantation death (adjusted hazard ratio per 1 SD increase in score, 1.54 [95% CI, 1.25-1.90]; P<0.001), with similar effects in each validation cohort. This metabolite score of diastolic function was simultaneously associated with measures of multimorbidity, suggesting a metabolic link between cardiac and noncardiac state in aortic stenosis. Conclusions Metabolite profiles of cardiac structure identify individuals at high risk for death following transcatheter aortic valve implantation and concurrent multimorbidity. These results call for efforts to address potentially reversible metabolic biology associated with risk to optimize post-transcatheter aortic valve implantation recovery, rehabilitation, and survival.

  View details for DOI 10.1161/JAHA.123.029542

  View details for PubMedID 37345820

• Morbidity and Mortality in Adult Fontan Patients After Heart or Combined Heart-Liver Transplantation. Journal of the American College of Cardiology Lewis, M. J., Reardon, L. C., Aboulhosn, J., Haeffele, C., Chen, S., Kim, Y., Fuller, S., Forbess, L., Alshawabkeh, L., Urey, M. A., Book, W. M., Rodriguez, F., Menachem, J. N., Clark, D. E., Valente, A. M., Carazo, M., Egbe, A., Connolly, H. M., Krieger, E. V., Angiulo, J., Cedars, A., Ko, J., Jacobsen, R. M., Earing, M. G., Cramer, J. W., Ermis, P., Broda, C., Nugaeva, N., Ross, H., Awerbach, J. D., Krasuski, R. A., Rosenbaum, M. 2023; 81 (22): 2161-2171

  Abstract

  An increasing number of adult Fontan patients require heart transplantation (HT) or combined heart-liver transplant (CHLT); however, data regarding outcomes and optimal referral time remain limited.The purpose of this study was to define survivorship post-HT/CHLT and predictors of post-transplant mortality, including timing of referral, in the adult Fontan population.A retrospective cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers in the United States and Canada was performed. Inclusion criteria included the following: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at the time of referral. Date of "failing" Fontan was defined as the earliest of the following: worsening fluid retention, new ascites, refractory arrhythmia, "failing Fontan" diagnosis by treating cardiologist, or admission for heart failure.A total of 131 patients underwent transplant, including 40 CHLT, from 1995 to 2021 with a median post-transplant follow-up time of 1.6 years (Q1 0.35 years, Q3 4.3 years). Survival was 79% at 1 year and 66% at 5 years. Survival differed by decade of transplantation and was 87% at 1 year and 76% at 5 years after 2010. Time from Fontan failure to evaluation (HR/year: 1.23 [95% CI: 1.11-1.36]; P < 0.001) and markers of failure, including NYHA functional class IV (HR: 2.29 [95% CI: 1.10-5.28]; P = 0.050), lower extremity varicosities (HR: 3.92 [95% CI: 1.68-9.14]; P = 0.002), and venovenous collaterals (HR: 2.70 [95% CI: 1.17-6.20]; P = 0.019), were associated with decreased post-transplant survival at 1 year in a bivariate model that included transplant decade.In our multicenter cohort, post-transplant survival improved over time. Late referral after Fontan failure and markers of failing Fontan physiology, including worse functional status, lower extremity varicosities, and venovenous collaterals, were associated with post-transplant mortality.

  View details for DOI 10.1016/j.jacc.2023.03.422

  View details for PubMedID 37257951

• Clinical Outcomes of Adult Fontan-Associated Liver Disease and Combined Heart-Liver Transplantation. Journal of the American College of Cardiology Lewis, M. J., Reardon, L. C., Aboulhosn, J., Haeffele, C., Chen, S., Kim, Y., Fuller, S., Forbess, L., Alshawabkeh, L., Urey, M. A., Book, W. M., Rodriguez, F., Menachem, J. N., Clark, D. E., Valente, A. M., Carazo, M., Egbe, A., Connolly, H. M., Krieger, E. V., Angiulo, J., Cedars, A., Ko, J., Jacobsen, R. M., Earing, M. G., Cramer, J. W., Ermis, P., Broda, C., Nugaeva, N., Ross, H., Awerbach, J. D., Krasuski, R. A., Rosenbaum, M. 2023; 81 (22): 2149-2160

  Abstract

  The impact of Fontan-associated liver disease (FALD) on post-transplant mortality and indications for combined heart-liver transplant (CHLT) in adult Fontan patients remains unknown.The purpose of this study was to assess the impact of FALD on post-transplant outcomes and compare HT vs CHLT in adult Fontan patients.We performed a retrospective-cohort study of adult Fontan patients who underwent HT or CHLT across 15 centers. Inclusion criteria were as follows: 1) Fontan; 2) HT/CHLT referral; and 3) age ≥16 years at referral. Pretransplant FALD score was calculated using the following: 1) cirrhosis; 2) varices; 3) splenomegaly; or 4) ≥2 paracenteses.A total of 131 patients (91 HT and 40 CHLT) were included. CHLT recipients were more likely to be older (P = 0.016), have a lower hemoglobin (P = 0.025), require ≥2 diuretic agents pretransplant (P = 0.051), or be transplanted in more recent decades (P = 0.001). Postmatching, CHLT demonstrated a trend toward improved survival at 1 year (93% vs 74%; P = 0.097) and improved survival at 5 years (86% vs 52%; P = 0.041) compared with HT alone. In patients with a FALD score ≥2, CHLT was associated with improved survival (1 year: 85% vs 62%; P = 0.044; 5 years: 77% vs 42%; P = 0.019). In a model with transplant decade and FALD score, CHLT was associated with improved survival (HR: 0.33; P = 0.044) and increasing FALD score was associated with worse survival (FALD score: 2 [HR: 14.6; P = 0.015], 3 [HR: 22.2; P = 0.007], and 4 [HR: 27.8; P = 0.011]).Higher FALD scores were associated with post-transplant mortality. Although prospective confirmation of our findings is necessary, compared with HT alone, CHLT recipients were older with higher FALD scores, but had similar survival overall and superior survival in patients with a FALD score ≥2.

  View details for DOI 10.1016/j.jacc.2023.03.421

  View details for PubMedID 37257950

• Multimodality Cardiac Imaging in COVID. Circulation research Holby, S. N., Richardson, T. L., Laws, J. L., McLaren, T. A., Soslow, J. H., Baker, M. T., Dendy, J. M., Clark, D. E., Hughes, S. G. 2023; 132 (10): 1387-1404

  Abstract

  Infection with SARS-CoV-2, the virus that causes COVID, is associated with numerous potential secondary complications. Global efforts have been dedicated to understanding the myriad potential cardiovascular sequelae which may occur during acute infection, convalescence, or recovery. Because patients often present with nonspecific symptoms and laboratory findings, cardiac imaging has emerged as an important tool for the discrimination of pulmonary and cardiovascular complications of this disease. The clinician investigating a potential COVID-related complication must account not only for the relative utility of various cardiac imaging modalities but also for the risk of infectious exposure to staff and other patients. Extraordinary clinical and scholarly efforts have brought the international medical community closer to a consensus on the appropriate indications for diagnostic cardiac imaging during this protracted pandemic. In this review, we summarize the existing literature and reference major societal guidelines to provide an overview of the indications and utility of echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging for the diagnosis of cardiovascular complications of COVID.

  View details for DOI 10.1161/CIRCRESAHA.122.321882

  View details for PubMedID 37167354

• Myocardial Injury on CMR in Patients With COVID-19 and Suspected CardiacInvolvement. JACC. Cardiovascular imaging Vidula, M. K., Rajewska-Tabor, J., Cao, J. J., Kang, Y., Craft, J., Mei, W., Chandrasekaran, P. S., Clark, D. E., Poenar, A., Gorecka, M., Malahfji, M., Cowan, E., Kwan, J. M., Reinhardt, S. W., Al-Tabatabaee, S., Doeblin, P., Villa, A. D., Karagodin, I., Alvi, N., Christia, P., Spetko, N., Cassar, M. P., Park, C., Nambiar, L., Turgut, A., Azad, M. R., Lambers, M., Wong, T. C., Salerno, M., Kim, J., Elliott, M., Raman, B., Neubauer, S., Tsao, C. W., LaRocca, G., Patel, A. R., Chiribiri, A., Kelle, S., Baldassarre, L. A., Shah, D. J., Hughes, S. G., Tong, M. S., Pyda, M., Simonetti, O. P., Plein, S., Han, Y. 2022

  Abstract

  BACKGROUND: Myocardial injury in patients with COVID-19 and suspected cardiac involvement is not well understood.OBJECTIVES: The purpose of this study was to characterize myocardial injury in a multicenter cohort of patients with COVID-19 and suspected cardiac involvement referred for cardiac magnetic resonance (CMR).METHODS: This retrospective study consisted of 1,047 patients from 18 international sites with polymerase chain reaction-confirmed COVID-19 infection who underwent CMR. Myocardial injury was characterized as acute myocarditis, nonacute/nonischemic, acute ischemic, and nonacute/ischemic patterns on CMR.RESULTS: In this cohort, 20.9% of patients had nonischemic injury patterns (acute myocarditis: 7.9%; nonacute/nonischemic:13.0%), and 6.7% of patients had ischemic injury patterns (acute ischemic: 1.9%; nonacute/ischemic: 4.8%). In a univariate analysis, variables associated with acute myocarditis patterns included chest discomfort (OR: 2.00; 95%CI: 1.17-3.40, P=0.01), abnormal electrocardiogram (ECG) (OR: 1.90; 95%CI: 1.12-3.23; P=0.02), natriuretic peptide elevation (OR: 2.99; 95%CI: 1.60-5.58; P=0.0006), and troponin elevation (OR: 4.21; 95%CI: 2.41-7.36; P< 0.0001). Variables associated with acute ischemic patterns included chest discomfort (OR: 3.14; 95%CI: 1.04-9.49; P=0.04), abnormal ECG (OR: 4.06; 95%CI: 1.10-14.92; P=0.04), known coronary disease (OR: 33.30; 95%CI: 4.04-274.53; P=0.001), hospitalization (OR: 4.98; 95%CI: 1.55-16.05; P=0.007), natriuretic peptide elevation (OR: 4.19; 95%CI: 1.30-13.51; P=0.02), and troponin elevation (OR: 25.27; 95%CI: 5.55-115.03; P< 0.0001). In a multivariate analysis, troponin elevation was strongly associated with acute myocarditis patterns (OR: 4.98; 95%CI: 1.76-14.05; P=0.003).CONCLUSIONS: In this multicenter study of patients with COVID-19 with clinical suspicion for cardiac involvement referred for CMR, nonischemic and ischemic patterns were frequent when cardiac symptoms, ECG abnormalities, and cardiac biomarker elevations were present.

  View details for DOI 10.1016/j.jcmg.2022.10.021

  View details for PubMedID 36752429

• A Diagnostic Prediction Model to Distinguish Multisystem Inflammatory Syndrome in Children. ACR open rheumatology Clark, M. T., Rankin, D. A., Peetluk, L. S., Gotte, A., Herndon, A., McEachern, W., Smith, A., Clark, D. E., Hardison, E., Esbenshade, A. J., Patrick, A., Halasa, N. B., Connelly, J. A., Katz, S. E. 2022

  Abstract

  Features of multisystem inflammatory syndrome in children (MIS-C) overlap with other syndromes, making the diagnosis difficult for clinicians. We aimed to compare clinical differences between patients with and without clinical MIS-C diagnosis and develop a diagnostic prediction model to assist clinicians in identification of patients with MIS-C within the first 24 hours of hospital presentation.A cohort of 127 patients (<21 years) were admitted to an academic children's hospital and evaluated for MIS-C. The primary outcome measure was MIS-C diagnosis at Vanderbilt University Medical Center. Clinical, laboratory, and cardiac features were extracted from the medical record, compared among groups, and selected a priori to identify candidate predictors. Final predictors were identified through a logistic regression model with bootstrapped backward selection in which only variables selected in more than 80% of 500 bootstraps were included in the final model.Of 127 children admitted to our hospital with concern for MIS-C, 45 were clinically diagnosed with MIS-C and 82 were diagnosed with alternative diagnoses. We found a model with four variables-the presence of hypotension and/or fluid resuscitation, abdominal pain, new rash, and the value of serum sodium-showed excellent discrimination (concordance index 0.91; 95% confidence interval: 0.85-0.96) and good calibration in identifying patients with MIS-C.A diagnostic prediction model with early clinical and laboratory features shows excellent discrimination and may assist clinicians in distinguishing patients with MIS-C. This model will require external and prospective validation prior to widespread use.

  View details for DOI 10.1002/acr2.11509

  View details for PubMedID 36319189

• Global Longitudinal Strain and Biomarkers of Cardiac Damage and Stress as Predictors of Outcomes After Transcatheter Aortic Valve Implantation. Journal of the American Heart Association Perry, A. S., Stein, E. J., Biersmith, M., Fearon, W. F., Elmariah, S., Kim, J. B., Clark, D. E., Patel, J. N., Gonzales, H., Baker, M., Piana, R. N., Mallugari, R. R., Kapadia, S., Kumbhani, D. J., Gillam, L., Whisenant, B., Quader, N., Zajarias, A., Welt, F. G., Bavry, A. A., Coylewright, M., Gupta, D. K., Vatterott, A., Jackson, N., Huang, S., Lindman, B. R. 2022: e026529

  Abstract

  Background Global longitudinal strain (GLS) is a sensitive measure of left ventricular function and a risk marker in severe aortic stenosis. We sought to determine whether biomarkers of cardiac damage (cardiac troponin) and stress (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) could complement GLS to identify patients with severe aortic stenosis at highest risk. Methods and Results From a multicenter prospective cohort of patients with symptomatic severe aortic stenosis who underwent transcatheter aortic valve implantation, we measured absolute GLS (aGLS), cardiac troponin, and NT-proBNP at baseline in 499 patients. Left ventricular ejection fraction <50% was observed in 19% and impaired GLS (aGLS <15%) in 38%. Elevations in cardiac troponin and NT-proBNP were present in 79% and 89% of those with impaired GLS, respectively, as compared with 63% and 60% of those with normal GLS, respectively (P<0.001 for each). aGLS <15% was associated with increased mortality in univariable analysis (P=0.009), but, in a model with both biomarkers, aGLS, and clinical covariates included, aGLS was not associated with mortality; elevation in each biomarker was associated with an increased hazard of mortality (adjusted hazard ratio, >2; P≤0.002 for each) when the other biomarker was elevated, but not when the other biomarker was normal (interaction P=0.015). Conclusions Among patients with symptomatic severe aortic stenosis undergoing transcatheter aortic valve implantation, elevations in circulating cardiac troponin and NT-proBNP are more common as GLS worsens. Biomarkers of cardiac damage and stress are independently associated with mortality after transcatheter aortic valve implantation, whereas GLS is not. These findings may have implications for risk stratification of asymptomatic patients to determine optimal timing of valve replacement.

  View details for DOI 10.1161/JAHA.122.026529

  View details for PubMedID 36172966

• Myocardial Tissue Oxygenation and Microvascular Blood Volume Measurement Using a Contrast Blood Oxygenation Level-Dependent Imaging Model. Investigative radiology Dendy, J. M., Hughes, S. G., Soslow, J. H., Clark, D. E., Paschal, C. B., Gore, J. C. 2022; 57 (9): 561-566

  Abstract

  We propose a method of quantitatively measuring drug-induced microvascular volume changes, as well as drug-induced changes in blood oxygenation using calibrated blood oxygen level-dependent magnetic resonance imaging (MRI). We postulate that for MRI signals there is a contribution to R2* relaxation rates from static susceptibility effects of the intravascular blood that scales with the blood volume/magnetic field and depends on the oxygenation state of the blood. These may be compared with the effects of an intravascular contrast agent. With 4 R2* measurements, microvascular blood volume (MBV) and tissue oxygenation changes can be quantified with the administration of a vasoactive drug.The protocol examined 12 healthy rats in a prospective observational study. R2* maps were acquired with and without infusion of adenosine, which increases microvascular blood flow, or dobutamine, which increases myocardial oxygen consumption. In addition, R2* maps were acquired after the intravenous administration of a monocrystalline iron oxide nanoparticle, with and without adenosine or dobutamine.Total microvascular volume was shown to increase by 10.8% with adenosine and by 25.6% with dobutamine ( P < 0.05). When comparing endocardium versus epicardium, both adenosine and dobutamine demonstrated significant differences between endocardial and epicardial MBV changes ( P < 0.05). Total myocardial oxygenation saturation increased by 6.59% with adenosine and by 1.64% with dobutamine ( P = 0.27). The difference between epicardial and endocardial oxygenation changes were significant with each drug (adenosine P < 0.05, dobutamine P < 0.05).Our results demonstrate the ability to quantify microvascular volume and oxygenation changes using calibrated blood oxygen level-dependent MRI, and we demonstrate different responses of adenosine and dobutamine. This method has clinical potential in examining microvascular disease in various disease states without the administration of radiopharmaceuticals or gadolinium-based contrast agents.

  View details for DOI 10.1097/RLI.0000000000000871

  View details for PubMedID 35438656

  View details for PubMedCentralID PMC9355912

• Syncope in an elderly man with hypertrophic obstructive cardiomyopathy HEART Curkovic, N. B., Clark, D. E., Hughes, S. G. 2022; 108 (18): 1437-+

  View details for Web of Science ID 000913792400005

• Syncope in an elderly man with hypertrophic obstructive cardiomyopathy. Heart (British Cardiac Society) Curkovic, N. B., Clark, D. E., Hughes, S. G. 2022; 108 (18): 1437-1500

  View details for DOI 10.1136/heartjnl-2022-321222

  View details for PubMedID 36007934

• Reduced Circumferential Strain in Athletes with Prior COVID-19. Radiology. Cardiothoracic imaging Wassenaar, J. W., Clark, D. E., Dixon, D. D., George-Durrett, K., Parikh, A., Li, D. L., Baker, M. T., Gupta, D. K., Hughes, S. G., Soslow, J. H., Dendy, J. M. 2022; 4 (4): e210310

  Abstract

  To characterize global and segmental circumferential systolic strain (CS) measured by cardiac MRI in athletes after SARS-CoV-2 infection.This retrospective observational cohort study included 188 soldiers and collegiate athletes referred for cardiac MRI after SARS-CoV-2 infection (C19+) between July 2020 and February 2021 and a control group of 72 soldiers, collegiate, and high school athletes who underwent cardiac MRI from May 2019 to February 2020, prior to the first SARS-CoV-2 case detected in our region (C19-). Global and segmental CS were measured by feature tracking, then compared between each group using unadjusted and multivariable- adjusted models. Acute myocarditis was diagnosed according to the modified Lake Louise criteria and the location of pathologic late gadolinium enhancement (LGE) was ascertained.Among the 188 C19+ athletes (median age, 25 years [IQR, 23-30]; 131 men), the majority had mild illness. Global CS significantly differed between C19+ and C19- groups, with a median of -24.0 (IQR -25.8, -21.4) versus. -25.0 (-28.0, -22.4), respectively (p = .009). This difference in CS persisted following adjustment for age, sex, body mass index, heart rate, and systolic blood pressure β coefficient 1.29 [95% CI: 0.20, 2.38], p = .02). In segmental analysis, the basal- and mid- inferoseptal, septal and inferolateral segments were significantly different (p < .05), which had a higher frequency of post-COVID late gadolinium enhancement. The global and segmental differences were similar after exclusion of athletes with myocarditis.Among athletes, SARS-CoV-2 infection was associated with a small but statistically significant reduced CS.

  View details for DOI 10.1148/ryct.210310

  View details for PubMedID 35996735

  View details for PubMedCentralID PMC9387168

• Prevalence and clinical implications of persistent or exertional cardiopulmonary symptoms following SARS-CoV-2 infection in 3597 collegiate athletes: a study from the Outcomes Registry for Cardiac Conditions in Athletes (ORCCA). British journal of sports medicine Petek, B. J., Moulson, N., Baggish, A. L., Kliethermes, S. A., Patel, M. R., Churchill, T. W., Harmon, K. G., Drezner, J. A. 2022; 56 (16): 913-918

  Abstract

  To assess the prevalence and clinical implications of persistent or exertional cardiopulmonary symptoms in young competitive athletes following SARS-CoV-2 infection.This observational cohort study from the Outcomes Registry for Cardiac Conditions in Athletes included 3597 US collegiate athletes after SARS-CoV-2 infection. Clinical characteristics, advanced diagnostic testing and SARS-CoV-2-associated sequelae were compared between athletes with persistent symptoms >3 weeks, exertional symptoms on return to exercise and those without persistent or exertional symptoms.Among 3597 athletes (mean age 20 years (SD, 1 year), 34% female), data on persistent and exertional symptoms were reported in 3529 and 3393 athletes, respectively. Persistent symptoms >3 weeks were present in 44/3529 (1.2%) athletes with 2/3529 (0.06%) reporting symptoms >12 weeks. Exertional cardiopulmonary symptoms were present in 137/3393 (4.0%) athletes. Clinical evaluation and diagnostic testing led to the diagnosis of SARS-CoV-2-associated sequelae in 12/137 (8.8%) athletes with exertional symptoms (five cardiac involvement, two pneumonia, two inappropriate sinus tachycardia, two postural orthostatic tachycardia syndrome and one pleural effusion). No SARS-CoV-2-associated sequelae were identified in athletes with isolated persistent symptoms. Of athletes with chest pain on return to exercise who underwent cardiac MRI (CMR), 5/24 (20.8%) had probable or definite cardiac involvement. In contrast, no athlete with exertional symptoms without chest pain who underwent CMR (0/20) was diagnosed with probable or definite SARS-CoV-2 cardiac involvement.Collegiate athletes with SARS-CoV-2 infection have a low prevalence of persistent or exertional symptoms on return to exercise. Exertional cardiopulmonary symptoms, specifically chest pain, warrant a comprehensive evaluation.

  View details for DOI 10.1136/bjsports-2021-104644

  View details for PubMedID 34725052

  View details for PubMedCentralID PMC8561826

• Case Series Conference: Anesthetic Management in Parturients With Fontan Physiology. Journal of cardiothoracic and vascular anesthesia Clark, D. E., Staudt, G., Byrne, R. D., Jelly, C., Christian, K., Dumas, S. D., Healan, S., Frischhertz, B. P., Thompson, J., Weingarten, A. J., Eagle, S. 2022

  View details for DOI 10.1053/j.jvca.2022.07.009

  View details for PubMedID 35953405

• Cardiovascular Outcomes in Collegiate Athletes After SARS-CoV-2 Infection: 1-Year Follow-Up From the Outcomes Registry for Cardiac Conditions in Athletes. Circulation Petek, B. J., Moulson, N., Drezner, J. A., Harmon, K. G., Kliethermes, S. A., Churchill, T. W., Patel, M. R., Baggish, A. L. 2022; 145 (22): 1690-1692

  View details for DOI 10.1161/CIRCULATIONAHA.121.058272

  View details for PubMedID 35545946

• Characteristics of COVID-19 Myocarditis With and Without Multisystem Inflammatory Syndrome. The American journal of cardiology Li, D. L., Davogustto, G., Soslow, J. H., Wassenaar, J. W., Parikh, A. P., Chew, J. D., Dendy, J. M., George-Durrett, K. M., Parra, D. A., Clark, D. E., Hughes, S. G. 2022; 168: 135-141

  Abstract

  Multisystem inflammatory syndrome (MIS) is a severe complication described in a minority of patients with COVID-19. Myocarditis has been reported in patients with COVID-19, including MIS. In this study, we compared the clinical characteristics and cardiac magnetic resonance (CMR) findings of COVID-19 myocarditis in patients with and without MIS. In the 330 patients with COVID-19 who were referred for CMR at our institution between July 24, 2020, to March 31, 2021, 40 patients were identified as having myocarditis, MIS myocarditis (n = 21) and non-MIS myocarditis (n = 19). MIS myocarditis was characterized by global myocardial inflammation/edema with significantly elevated native T1, whereas only regional inflammation, and edema were noted in the non-MIS group. Distinct late gadolinium enhancement (LGE) patterns-inferior myocardial involvement in non-MIS myocarditis and septal involvement in MIS myocarditis-were identified. The LGE burden was comparable between the 2 groups (5.9% vs 6.6%, MIS vs non-MIS group, p = 0.83). Myocarditis was diagnosed more frequently by CMR in the MIS group (70% vs 6.3%, MIS vs non-MIS, p <0.001). In the 20 patients with a sequential CMR study at a median 102-day follow-up, 25% had persistent myocardial edema. The LGE burden improved over time, from a median of 5.0% (interquartile range 3.4% to 7.3%) to 3.2% (interquartile range 2.0% to 3.8%; p <0.001). In conclusion, MIS and non-MIS myocarditis exhibit distinct characteristics by CMR. Persistent LGE and edema were common at follow-up CMR examination in both groups.

  View details for DOI 10.1016/j.amjcard.2021.12.031

  View details for PubMedID 35058054

  View details for PubMedCentralID PMC8767902

• Left Ventricular Hypertrophy and Biomarkers of Cardiac Damage and Stress in Aortic Stenosis. Journal of the American Heart Association Stein, E. J., Fearon, W. F., Elmariah, S., Kim, J. B., Kapadia, S., Kumbhani, D. J., Gillam, L., Whisenant, B., Quader, N., Zajarias, A., Welt, F. G., Bavry, A. A., Coylewright, M., Piana, R. N., Mallugari, R. R., Clark, D. E., Patel, J. N., Gonzales, H., Gupta, D. K., Vatterott, A., Jackson, N., Huang, S., Lindman, B. R. 2022: e023466

  Abstract

  Background Left ventricular hypertrophy (LVH) is associated with increased mortality risk and rehospitalization after transcatheter aortic valve replacement among those with severe aortic stenosis. Whether cardiac troponin (cTnT) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) risk stratify patients with aortic stenosis and without LVH is unknown. Methods and Results In a multicenter prospective registry of 923 patients with severe aortic stenosis undergoing transcatheter aortic valve replacement, we included 674 with core-laboratory-measured LV mass index, cTnT, and NT-proBNP. LVH was defined by sex-specific guideline cut-offs and elevated biomarker levels were based on age and sex cut-offs. Adjusted Cox proportional hazards models evaluated associations between LVH and biomarkers and all-cause death out to 5years. Elevated cTnT and NT-proBNP were present in 82% and 86% of patients with moderate/severe LVH, respectively, as compared with 66% and 69% of patients with no/mild LVH, respectively (P<0.001 for each). After adjustment, compared with no/mild LVH, moderate/severe LVH was associated with an increased hazard of mortality (adjusted hazard ratio [aHR], 1.34; 95% CI 1.01-1.77, P=0.043). cTnT and NT-proBNP each risk stratified patients with moderate/severe LVH (P<0.05). In a model with both biomarkers and LVH included, elevated cTnT (aHR, 2.08; 95% CI 1.45-3.00, P<0.001) and elevated NT-proBNP (aHR, 1.46; 95% CI 1.00-2.11, P=0.049) were each associated with increased mortality risk, whereas moderate/severe LVH was not (P=0.15). Conclusions Elevations in circulating cTnT and NT-proBNP are more common as LVH becomes more pronounced but are also observed in those with no/minimal LVH. As measures of maladaptive remodeling and cardiac injury, cTnT and NT-proBNP predict post-transcatheter aortic valve replacement mortality better than LV mass index. These findings may have important implications for risk stratification and treatment of patients with aortic stenosis.

  View details for DOI 10.1161/JAHA.121.023466

  View details for PubMedID 35301869

• Exception-Status Listing: A Critical Pathway to Heart Transplantation for Adults With Congenital Heart Diseases. Journal of cardiac failure Rali, A. S., Ranka, S., Mazurek, J. A., Brinkley, M. D., Cedars, A., Clark, D., Do, N., Lazzara, G. E., Punnoose, L., Sandhaus, E., Shah, A., Taduru, S., Wigger, M., Zalawadiya, S., Rogers, J., Lindenfeld, J., Schlendorf, K., Menachem, J. N. 2022; 28 (3): 415-421

  Abstract

  Adults with congenital heart diseases may not be candidates for conventional therapies to control ventricular systolic dysfunction, including mechanical circulatory support, which moves potential heart-transplantation recipients to a listing status of higher priority. This results in longer waitlist times and greater mortality rates. Exception-status listing allows a pathway for this complex and anatomically heterogenous group of patients to be listed for heart transplantation at appropriately high listing status. Our study queried the United Network for Organ Sharing registry to evaluate trends in the use of exception-status listing among adults with congenital heart diseases awaiting heart transplantation. Uptrend in the use of exception-status listing precedes the new allocation system, but it has been greatest since changes were made in the allocation system. It continues to remain a vital pathway for adults with congenital heart disease (whose waitlist mortality rates are often not characterized adequately by using the waitlist-status criteria) timely access to heart transplantation.

  View details for DOI 10.1016/j.cardfail.2021.10.004

  View details for PubMedID 34670174

• Toxin-Mediated Myocarditis From a Brown Recluse Spider Bite. JACC. Case reports Sims, R. A., Fish-Trotter, H. L., Clark, D. E., Gayle, K. A., Hughes, S. G., Brittain, E. L. 2022; 4 (1): 49-53

  Abstract

  We describe a case of myocarditis associated with a brown recluse spider bite in a 31-year-old man. Cardiac magnetic resonance revealed late gadolinium enhancement in the lateral wall and inferior wall. There was also regional elevation of the myocardial T2 and extracellular volume indicative of myocardial edema. (Level of Difficulty: Intermediate.).

  View details for DOI 10.1016/j.jaccas.2021.10.003

  View details for PubMedID 35036944

  View details for PubMedCentralID PMC8743809

• Cardiac Magnetic Resonance in the Evaluation of COVID-19. Cardiac failure review Clark, D. E., Aggarwal, S. K., Phillips, N. J., Soslow, J. H., Dendy, J. M., Hughes, S. G. 2022; 8: e09

  Abstract

  Cardiovascular involvement following COVID-19 is heterogeneous, prevalent and is often missed by echocardiography and serum biomarkers (such as troponin I and brain natriuretic peptide). Cardiac magnetic resonance (CMR) is the gold standard non-invasive imaging modality to phenotype unique populations after COVID-19, such as competitive athletes with a heightened risk of sudden cardiac death, patients with multisystem inflammatory syndrome, and people suspected of having COVID-19 vaccine-induced myocarditis. This review summarises the key attributes of CMR, reviews the literature that has emerged for using CMR for people who may have COVID-19-related complications after COVID-19, and offers expert opinion regarding future avenues of investigation and the importance of reporting findings.

  View details for DOI 10.15420/cfr.2021.20

  View details for PubMedID 35399549

  View details for PubMedCentralID PMC8978025

• Austin Powers' Steamroller: Lessons Learned to Benefit Patients with Congenital Heart Disease. Journal of cardiac failure Menachem, J. N., Clark, D., Cedars, A. 2021

  Abstract

  A structural crisis is brewing in advanced care for patients with congenital heart disease (CHD)-specifically, single-ventricle patients palliated by the Fontan procedure. The largest study evaluating management practices in pediatric cardiac teams found that 93% of providers believe that after the Fontan procedure, patients "will eventually have signs/symptoms of heart failure (HF) and will need a heart transplant (HT) at some point in their lives."1 Despite this, the majority either disagreed about (45%) or were undecided about (24%) "whether routine evaluation by a HF/HT cardiologist is needed." This may be, in part, attributable to the lack of an HF/HT subspecialty in the American College of Pediatrics, but these findings highlight a concerning disconnect in the minds of providers caring for patients undergoing the Fontan procedure, for whom the providers' preparation seems incongruous in terms of the anticipated endpoint. This disconnect would likely be even worse had the survey been conducted in adult providers, given that the providers of care for adults with congenital heart disease (ACHD) have limited required HF/HT training, and adult HF/HT cardiologists have little required training in CHD.

  View details for DOI 10.1016/j.cardfail.2021.12.015

  View details for PubMedID 34974182

• The Bright Side of Myocardial Edema. Journal of the American Heart Association Clark, D. E., Hughes, S. G. 2021; 10 (22): e023731

  View details for DOI 10.1161/JAHA.121.023731

  View details for PubMedID 34779232

  View details for PubMedCentralID PMC8751949

• Society for Cardiovascular Magnetic Resonance 2020 Case of the Week series. Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Johnson, J. N., Mandell, J. G., Christopher, A., Olivieri, L. J., Loke, Y. H., Campbell, M. J., Darty, S., Kim, H. W., Clark, D. E., Frischhertz, B. P., Fish, F. A., Bailey, A. L., Mikolaj, M. B., Hughes, S. G., Oneugbu, A., Chung, J., Burdowski, J., Marfatia, R., Bi, X., Craft, J., Umairi, R. A., Kindi, F. A., Williams, J. L., Campbell, M. J., Kharabish, A., Gutierrez, M., Arzanauskaite, M., Ntouskou, M., Ashwath, M. L., Robinson, T., Chiang, J. B., Lee, J. C., Lee, M. S., Chen, S. S. 2021; 23 (1): 108

  Abstract

  The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). Case of the week is a case series hosted on the SCMR website ( https://www.scmr.org ) that demonstrates the utility and importance of CMR in the clinical diagnosis and management of cardiovascular disease. Each case consists of the clinical presentation and a discussion of the condition and the role of CMR in diagnosis and guiding clinical management. The cases are all instructive and helpful in the approach to patient management. We present a digital archive of the 2020 Case of the Week series of 11 cases as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.

  View details for DOI 10.1186/s12968-021-00799-0

  View details for PubMedID 34629101

  View details for PubMedCentralID PMC8504030

• Cardiovascular magnetic resonance evaluation of soldiers after recovery from symptomatic SARS-CoV-2 infection: a case-control study of cardiovascular post-acute sequelae of SARS-CoV-2 infection (CV PASC). Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance Clark, D. E., Dendy, J. M., Li, D. L., Crum, K., Dixon, D., George-Durrett, K., Parikh, A. P., Wassenaar, J. W., Hughes, S. G., Soslow, J. H. 2021; 23 (1): 106

  Abstract

  Myocarditis is a potential complication after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and a known cause of sudden cardiac death. Given the athletic demands of soldiers, identification of myocarditis and characterization of post-acute sequelae of SARS-CoV-2 infection with cardiovascular symptoms (CV PASC) may be critical to guide return-to-service. This study sought to evaluate the spectrum of cardiac involvement among soldiers with cardiopulmonary symptoms in the late convalescent phase of recovery from SARS-CoV-2 compared to a healthy soldier control group, and to determine the rate of progression to CV PASC.All soldiers referred for cardiovascular magnetic resonance (CMR) imaging for cardiopulmonary symptoms following COVID-19 were enrolled and matched by age, gender, and athletic phenotype 1:1 to soldiers undergoing CMR in the year prior to the first case of COVID-19 at our institution. Demographic, clinical, laboratory, and imaging parameters were compared between groups. The diagnosis of acute myocarditis was made using modified Lake Louise criteria. Wilcoxon rank sum and chi-squared tests were used for comparison of continuous and categorical variables, respectively.Fifty soldier cases and 50 healthy soldier controls were included. The median time from SARS-CoV-2 detection to CMR was 71 days. The majority of cases experienced moderate symptoms (N = 43, 86%), while only 10% required hospitalization. The right ventricular (RV) ejection fraction (RVEF) was reduced in soldier cases compared to controls (51.0% vs. 53.2%, p = 0.012). Four cases were diagnosed with myocarditis (8%), 1 (2%) was diagnosed with Takotsubo cardiomyopathy, and 1 (2%) had new biventricular systolic dysfunction of unclear etiology. Isolated inferior RV septal insertion late gadolinium enhancement (LGE) was present in 8 cases and 8 controls (16% vs. 24%, p = 0.09). Seven of the 19 (37%) cases that completed an intermediate-term follow-up survey reported CV PASC at a median of 139 days of follow-up. Two of the 7 soldiers (29%) with CV PASC had a pathological clinical diagnosis (myocarditis) on CMR.Cardiovascular pathology was diagnosed in 6 symptomatic soldiers (12%) after recovery from SARS-CoV-2, with myocarditis found in 4 (8%). RVEF was reduced in soldier cases compared to controls. CV PASC occurred in over one-third of soldiers surveyed, but did not occur in any soldiers with asymptomatic acute SARS-CoV-2 infection.

  View details for DOI 10.1186/s12968-021-00798-1

  View details for PubMedID 34620179

  View details for PubMedCentralID PMC8495668

• Sizing Up Fontan Failure: Association with Increasing Weight in Adulthood. Pediatric cardiology Byrne, R. D., Weingarten, A. J., Clark, D. E., Healan, S. J., Richardson, T. L., Huang, S., Menachem, J. N., Frischhertz, B. P. 2021; 42 (6): 1425-1432

  Abstract

  Obesity has become increasingly recognized in adults with Fontan palliation, yet the relationship between weight changes in adulthood and Fontan failure is not clearly defined. We hypothesize that increasing weight in adulthood among Fontan patients is associated with the development of Fontan failure. Single-center data from adults with Fontan palliation who were not in Fontan failure at their first clinic visit in adulthood and who received ongoing care were retrospectively collected. Fontan failure was defined as death, transplant, diagnosis of protein losing enteropathy, predicted peak VO2 less than 50%, or new loop diuretic requirement. Anthropometric data including weight and BMI were collected. Change in weight was compared between those that developed Fontan failure, and those that remained failure-free. To estimate the association between weight change during adulthood and the risk of developing Fontan failure, a survival analysis using multiple Cox's proportional hazards regression model was performed. Overall, 104 patients were included in the analysis. Those that developed Fontan failure had a larger associated median weight gain than those who remained failure-free (7.8 kg vs. 4.9 kg, respectively; p = 0.011). In multivariable Cox regression analysis, increased weight during adulthood was associated with increased likelihood of developing Fontan failure (HR 1.36; CI 1.07-1.73; p = 0.011). Weight gain in adulthood is associated with the development of Fontan failure.

  View details for DOI 10.1007/s00246-021-02628-8

  View details for PubMedID 33948709

• Sizing heart transplant donors in adults with congenital heart disease. The Journal of thoracic and cardiovascular surgery Clark, D. E., Byrne, R. D., Mazurek, J. A., Opotowsky, A. R., Schlendorf, K. H., Xu, M., Zalawadiya, S., Menachem, J. N. 2021; 162 (2): 422-428.e1

  Abstract

  Optimal donor sizing for heart transplantation (HT) in adults with congenital heart disease (CHD) remains unclear, given the propensity for pulmonary hypertension related to shunting, staged repairs, and periods of pulmonary overcirculation. We studied HT outcomes related to donor size matching in the adult CHD population.We conducted a retrospective cohort analysis of patients with CHD undergoing HT in the United States from January 1, 2000, to December 31, 2015. Patients were selected from the United Network for Organ Sharing database; 827 patients met inclusion criteria and were analyzed.At a median follow-up of 1462 days, 548 (66.3%) subjects were alive and 279 (33.7%) were deceased. All-cause mortality did not differ based on donor sizing (by predicted heart mass ratio: hazard ratio, 1.03; confidence interval, 0.86-1.23; P = .74). Pulmonary hypertension was not significantly associated with survival (by predicted heart mass ratio, χ2 = 2.01, P = .73).Our data demonstrate that donor oversizing, to the extent used in current practice, does not affect survival after HT in adults with CHD. Our findings from the United Network for Organ Sharing database demonstrate that donor oversizing in these patients is not associated with improved mortality.

  View details for DOI 10.1016/j.jtcvs.2020.01.099

  View details for PubMedID 32222406

• Characteristics Associated With Multisystem Inflammatory Syndrome Among Adults With SARS-CoV-2 Infection. JAMA network open Davogustto, G. E., Clark, D. E., Hardison, E., Yanis, A. H., Lowery, B. D., Halasa, N. B., Wells, Q. S. 2021; 4 (5): e2110323

  View details for DOI 10.1001/jamanetworkopen.2021.10323

  View details for PubMedID 34009351

  View details for PubMedCentralID PMC8134998

• No survival benefit associated with waiting for non-lung donor heart transplants for adult recipients with congenital heart disease. Clinical transplantation Diamant, M. J., Fox, A. L., Modi, V. A., Joshi, A. A., Clark, D. E., Bichell, D. P., Cedars, A., Fowler, R., Frischhertz, B. P., Mazurek, J. A., Schlendorf, K. H., Shah, A. S., Zalawadiya, S. K., Lindenfeld, J., Menachem, J. N. 2021; 35 (5): e14266

  Abstract

  Adults with congenital heart disease (CHD) awaiting heart transplant (HT) have higher mortality and waitlist removal due to clinical deterioration than those without CHD. The selective use of non-lung donors (NLD) to recover donor pulmonary vasculature to assist in graft implantation may be a contributing factor and is supported by consensus statements despite the recent use of pericardium or graft material as an alternative in pulmonary vascular reconstruction. The impact of selecting NLD for CHD recipients on wait time and mortality has not been evaluated.In the United Network for Organ Sharing (UNOS) Registry, 1271 HT recipients age ≥ 18 with CHD were identified between 1987 and 2016, 68% of which had NLDs. Prior to HT, NLD recipients were significantly less likely to be listed UNOS Status 1A, require mechanical ventilation, or intra-aortic balloon pump support. There was no difference in mean waitlist time (254 vs. 278 days, p = .31), 1-year mortality (82% vs. 80%, p = .81; adjusted odds ratio 1.32, 95% confidence interval [CI] 0.96-1.83, p = .08), or overall mortality (adjusted hazard ratio 1.08, 95% CI 0.86-1.36, p = .48) between recipients from NLD and concomitant lung donors.Adult CHD patients who are less critically ill or listed at a lower status are more likely to receive HT from NLD. There is no overall mortality benefit associated with this practice. While specific cases may necessitate waiting for NLD, programs need to re-evaluate whether this should remain a more widespread practice among CHD patients.

  View details for DOI 10.1111/ctr.14266

  View details for PubMedID 33615562

• Detection of toxoplasmic encephalitis in HIV positive patients in urine with hydrogel nanoparticles. PLoS neglected tropical diseases Steinberg, H. E., Bowman, N. M., Diestra, A., Ferradas, C., Russo, P., Clark, D. E., Zhu, D., Magni, R., Malaga, E., Diaz, M., Pinedo-Cancino, V., Ramal Asayag, C., Calderón, M., Carruthers, V. B., Liotta, L. A., Gilman, R. H., Luchini, A. 2021; 15 (3): e0009199

  Abstract

  Diagnosis of toxoplasmic encephalitis (TE) is challenging under the best clinical circumstances. The poor clinical sensitivity of quantitative polymerase chain reaction (qPCR) for Toxoplasma in blood and CSF and the limited availability of molecular diagnostics and imaging technology leaves clinicians in resource-limited settings with few options other than empiric treatment.Here we describe proof of concept for a novel urine diagnostics for TE using Poly-N-Isopropylacrylamide nanoparticles dyed with Reactive Blue-221 to concentrate antigens, substantially increasing the limit of detection. After nanoparticle-concentration, a standard western blotting technique with a monoclonal antibody was used for antigen detection. Limit of detection was 7.8pg/ml and 31.3pg/ml of T. gondii antigens GRA1 and SAG1, respectively. To characterize this diagnostic approach, 164 hospitalized HIV-infected patients with neurological symptoms compatible with TE were tested for 1) T. gondii serology (121/147, positive samples/total samples tested), 2) qPCR in cerebrospinal fluid (11/41), 3) qPCR in blood (10/112), and 4) urinary GRA1 (30/164) and SAG1 (12/164). GRA1 appears to be superior to SAG1 for detection of TE antigens in urine. Fifty-one HIV-infected, T. gondii seropositive but asymptomatic persons all tested negative by nanoparticle western blot and blood qPCR, suggesting the test has good specificity for TE for both GRA1 and SAG1. In a subgroup of 44 patients, urine samples were assayed with mass spectrometry parallel-reaction-monitoring (PRM) for the presence of T. gondii antigens. PRM identified antigens in 8 samples, 6 of which were concordant with the urine diagnostic.Our results demonstrate nanoparticle technology's potential for a noninvasive diagnostic test for TE. Moving forward, GRA1 is a promising target for antigen based diagnostics for TE.

  View details for DOI 10.1371/journal.pntd.0009199

  View details for PubMedID 33651824

  View details for PubMedCentralID PMC7954332

• COVID-19 Myocardial Pathology Evaluation in Athletes With Cardiac Magnetic Resonance (COMPETE CMR). Circulation Clark, D. E., Parikh, A., Dendy, J. M., Diamond, A. B., George-Durrett, K., Fish, F. A., Slaughter, J. C., Fitch, W., Hughes, S. G., Soslow, J. H. 2021; 143 (6): 609-612

  View details for DOI 10.1161/CIRCULATIONAHA.120.052573

  View details for PubMedID 33332151

  View details for PubMedCentralID PMC7864610

• Congenital Heart Disease in Children Richardson , T., Clark , D., Frischhertz , B. McGraw-Hill Education. New York, NY. 2021

  Abstract

  Vanderbilt Internal Medicine/Pediatric Curriculum

• Pediatric Hypertension: Part 1 Diagnosis Richardson , T., Clark , D., VanDeVoorde, R., Frischhertz , B. McGraw-Hill Education. New York, NY. 2021

  Abstract

  AccessMedicine. Vanderbilt Internal Medicine/Pediatric Curriculum

• COVID-19 Myocardial Pathology Evaluated Through scrEening Cardiac Magnetic Resonance (COMPETE CMR). medRxiv : the preprint server for health sciences Clark, D. E., Parikh, A., Dendy, J. M., Diamond, A. B., George-Durrett, K., Fish, F. A., Fitch, W., Hughes, S. G., Soslow, J. H. 2020

  Abstract

  Background Myocarditis is a leading cause of sudden cardiac death among competitive athletes and may occur without antecedent symptoms. COVID-19-associated myocarditis has been well-described, but the prevalence of myocardial inflammation and fibrosis in young athletes after COVID-19 infection is unknown. Objectives This study sought to evaluate the prevalence and extent of cardiovascular involvement in collegiate athletes that had recently recovered from COVID-19. Methods We conducted a retrospective cohort analysis of collegiate varsity athletes with prior COVID-19 infection, all of whom underwent cardiac magnetic resonance (CMR) prior to resumption of competitive sports in August 2020. Results Twenty-two collegiate athletes with prior COVID-19 infection underwent CMR. The median time from SARS-CoV-2 infection to CMR was 52 days. The mean age was 20.2 years. Athletes represented 8 different varsity sports. This cohort was compared to 22 healthy controls and 22 tactical athlete controls. Most athletes experienced mild illness (N=17, 77%), while the remainder (23%) were asymptomatic. No athletes had abnormal troponin I, electrocardiograms, or LVEF < 50% on echocardiography. Late gadolinium enhancement was found in 9% of collegiate athletes and one athlete (5%) met formal criteria for myocarditis. Conclusions Our study suggests that the prevalence of myocardial inflammation or fibrosis after an asymptomatic or mild course of ambulatory COVID-19 among competitive athletes is modest (9%), but would be missed by ECG, Ti, and strain echocardiography. Future investigation is necessary to further phenotype cardiovascular manifestations of COVID-19 in order to better counsel athletes on return to sports participation.

  View details for DOI 10.1101/2020.08.31.20185140

  View details for PubMedID 32908996

  View details for PubMedCentralID PMC7480048

• HeartMate 3 in a ccTGA patient. World journal for pediatric & congenital heart surgery Clark, D. E., Richardson, T. L., Byrne, R. D., Klausner, R. E., Frischhertz, B. P., Zalawadiya, S. K., Mettler, B. A., Danter, M. R., Menachem, J. N. 2020; 11 (3): 368-369

  Abstract

  A 49-year-old female with congenitally corrected (or levo-) transposition of the great arteries complicated by nonischemic cardiomyopathy presented for worsening heart failure despite guideline-directed medical therapy and was found to be in cardiogenic shock. She successfully underwent ventricular assist device placement with a HeartMate III to her systemic right ventricle as a bridge to transplantation.

  View details for DOI 10.1177/2150135119897901

  View details for PubMedID 32294004

• Human Monocytic Ehrlichiosis Associated With Myocarditis and Hemophagocytic Lymphohistiocytosis. JACC. Case reports Dahm, C. N., Yang, B. Q., Clark, D. E., Armstrong, W. C., Stevenson, L. W. 2020; 2 (3): 420-425

  Abstract

  We present 3 cases at a single institution of human monocytic ehrlichiosis resulting in myocarditis and hemophagocytic lymphohistiocytosis. Contrary to previously published studies in which case fatalities were only as high as 1%, 2 of the 3 patients we discuss experienced a fulminant course resulting in death despite appropriate doxycycline treatment. Human monocytic ehrlichiosis is rarely a cause of myocarditis and hemophagocytic lymphohistiocytosis, but a high degree of suspicion is important because early empirical therapy may decrease morbidity and mortality. (Level of Difficulty: Intermediate.).

  View details for DOI 10.1016/j.jaccas.2019.12.042

  View details for PubMedID 34317254

  View details for PubMedCentralID PMC8311717

• Heart transplantation and in-hospital outcomes in adult congenital heart disease patients with Fontan: A decade nationwide analysis from 2004 to 2014. Journal of cardiac surgery Hernandez, G. A., Lemor, A., Clark, D., Blumer, V., Burstein, D., Byrne, R., Fowler, R., Frischhertz, B., Sandhaus, E., Schlendorf, K., Zalawadiya, S., Lindenfeld, J., Menachem, J. N. 2020; 35 (3): 603-608

  Abstract

  Treatment of adult congenital heart disease patients who require advanced therapies remains challenging due to high perioperative and wait-list mortality and limited donors. Patients palliated with Fontan are at the highest risk of early mortality due to multiorgan involvement and few centers able to safely transplant them. We sought to evaluate the early outcomes of heart transplants in these adult Fontan patients.Using the Nationwide Inpatient Sample database, we identified all adults aged at least 18 years old who underwent heart transplantation across U.S. hospitals from 2004 to 2014. We then identified those with specific ICD-9 codes to include tricuspid atresia, hypoplastic left heart syndrome and common ventricle. Multivariate regression models were created to adjust for potential confounders.A total of 93 Fontan patients underwent heart transplant during the study time (0.5% of all heart transplants). Compared to non-Fontan heart transplantations, Fontan patients were younger, with a higher incidence of liver disease and coagulopathy. Fontan patients receiving heart transplant had higher mortality during transplant hospitalization compared to non-Fontan patients (26.3% vs 5.3% OR, 18.10, CI, 5.06-65.0 P < .001). Extracorporeal membrane oxygenator (ECMO) usage and bleeding were also higher in the Fontan cohort with an OR of 5.30 (P = .016) and 5.32 (P = .015) for ECMO and bleeding, respectively. The remaining outcomes were similar for both cohorts.Adults with Fontan palliation undergoing heart transplantation have exceptionally high inpatient mortality, which is nearly five times that of non-Fontan heart transplant recipients, perhaps related to a delayed referral, surgical complexity, and coexistent, underrecognized liver failure.

  View details for DOI 10.1111/jocs.14430

  View details for PubMedID 31971277

• Biomarker-specific differences between transpulmonary and peripheral arterial-venous blood sampling in patients with pulmonary hypertension. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals Meoli, D. F., Clark, D. E., Davogustto, G., Su, Y. R., Brittain, E. L., Hemnes, A. R., Monahan, K. 2020; 25 (2): 131-136

  Abstract

  Purpose: Transpulmonary biomarkers may provide insight into pulmonary hypertension (PH) pathophysiology, but require cardiac catheterization. We investigated whether the peripheral arterial-venous ratio (PR) could substitute for the transpulmonary ratio (TPR).Materials and methods: Blood from the pulmonary artery (PA), pulmonary arterial wedge (PAW), peripheral venous, and peripheral arterial positions was analysed for ET-1, NT-pro-BNP and cAMP levels in subjects with no PH (n = 18) and PH due to left heart disease (PH-LHD), which included combined pre- and post-capillary PH (Cpc-PH; n = 7) and isolated post-capillary PH (Ipc-PH; n = 9). Bland-Altman comparisons were made between peripheral venous and PA samples and between peripheral arterial and PAW samples. TPR was defined as [PAW]/[PA].Results: For ET-1, Bland-Altman analysis indicated negative bias (-24%) in peripheral arterial compared to PAW concentration and positive bias (23%) in peripheral venous compared to PA concentration. There was <10% absolute bias for NT-pro-BNP and cAMP. For ET-1, there was no difference in PR between Cpc-PH and Ipc-PH (0.87 ± 0.4 vs. 0.94 ± 0.6, p = 0.8), whereas there was a difference in TPR (2.2 ± 1.1 vs. 1.1 ± 0.2, p < 0.05).Conclusions: In PH-LHD, peripheral samples may be inadequate surrogates for transpulmonary samples, particularly when measuring mediators with prominent pulmonary secretion or clearance, such as ET-1.

  View details for DOI 10.1080/1354750X.2019.1710256

  View details for PubMedID 31903794

• CMR detects endocardial fibroelastosis in an ACHD patient with ventricular tachycardia Clark , D., Frischhertz , B., Fish , F., Bailey , A., Mikolaj , M., Hughes , S. SCMR Case of the Week, Number 20-03. 2020
• RVOT thrombosis without valvular extension in a repaired tetralogy of Fallot patient Aggarwal , S., Clark , D., Hughes , S. SCMR Case of the Week, Number 22-07. 2020
• CardioMEMS Implantation in Patient With a Systemic Right Ventricle. JACC. Case reports Clark, D. E., Fowler, R., Zalawadiya, S., Lindenfeld, J., Menachem, J. N. 2019; 1 (3): 394-395

  Abstract

  A 42-year-old woman with repaired, complex cyanotic congenital heart disease complicated by systemic right ventricular dysfunction presented for worsening heart failure. She successfully underwent CardioMEMS implantation and has since remained out of the hospital with improved functional class. (Level of Difficulty: Beginner.).

  View details for DOI 10.1016/j.jaccas.2019.07.016

  View details for PubMedID 34316833

  View details for PubMedCentralID PMC8289149

• More than the heart: Hepatic, renal, and cardiac dysfunction in adult Fontan patients. Congenital heart disease Byrne, R. D., Weingarten, A. J., Clark, D. E., Huang, S., Perri, R. E., Scanga, A. E., Menachem, J. N., Markham, L. W., Frischhertz, B. P. 2019; 14 (5): 765-771

  Abstract

  Fontan-associated liver disease universally affects adults with single ventricle heart disease. Chronic kidney disease is also highly prevalent in adult Fontan patients. In this study, we evaluate the relationship of Fontan hemodynamics invasively and noninvasively with extra-cardiac dysfunction as measured by MELD and MELD-XI.We hypothesize that invasive and noninvasive measures of Fontan circuit congestion and ventricular dysfunction are associated with increased MELD and MELD-XI scores.Single-center data from adults with Fontan palliation who had ongoing care, including cardiac catheterization, were retrospectively collected. Hemodynamic data from cardiac catheterization and echocardiographic assessment of ventricular and atrioventricular valve function were tested for association with serum creatinine, MELD, and MELD-XI. Linear regression was used to perform multivariable analysis in the echocardiogram cohort.Fifty-seven patients had congruent lab and catheterization data for analysis. Sixty-three and sixty-nine patients had congruent lab and echocardiogram data for MELD and MELD-XI, respectively. Of the hemodynamic variables analyzed, only decreased systemic oxygen saturation had significant correlation with elevated MELD and MELD-XI (P = .045). Patients with moderately or severely reduced ejection fraction by echocardiogram had significantly higher MELD and MELD-XI scores compared to those with normal or mildly depressed systolic ventricular function (P = .008 and P < .001 for MELD and MELD-XI, respectively). Significant differences in creatinine were also found among the ventricular dysfunction groups (P = .02).In adults following Fontan palliation, systolic ventricular dysfunction and decreased oxygen saturation were associated with hepatic and renal dysfunction as assessed by elevated serum creatinine, MELD, and MELD-XI scores.

  View details for DOI 10.1111/chd.12820

  View details for PubMedID 31282062

• Development of a Novel Protocol Based on Blood Clot to Improve the Sensitivity of qPCR Detection of Toxoplasma gondii in Peripheral Blood Specimens AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE Gutierrez-Loli, R., Ferradas, C., Diestra, A., Traianou, A., Bowman, N., Bok, J., Reimer-McAtee, M., Ramal, C., Ticona, E., Steinberg, H., Mayta, H., Calderon, M., Calla-Choque, J. S., Sterling, C., Gilman, R. H., Pinedo, L., Valencia, G., Sanchez, L., Malaga, E., Zhu, D., Jimenez, J., Bern, C., Angulo, N., Schiaffino, F., Acosta, J., Holtz, M., Clark, D., Clark, T., Trompeter, G., Choi, J., Gandarilla, O., Dorn, M., Fortuny, E., Galdos, G., Colanzi, R., Toxoplasmosis Working Grp Peru Bol 2019; 100 (1): 83-89

  Abstract

  Quantitative polymerase chain reaction (qPCR) for Toxoplasma gondii multicopy genes has emerged as a promising strategy for sensitive detection of parasite DNA. qPCR can be performed from blood samples, which are minimally invasive to collect. However, there is no consensus about what type of blood specimen yields the best sensitivity. The development of a novel protocol for qPCR detection of T. gondii using blood clot, involving an appropriate DNA extraction method and the use of an internal amplification control to monitor the reaction is presented in the current study. Assays directed to the B1 and REP529 genes were performed in spiked specimens of whole blood, guanidine-ethylenediaminetetraacetic acid blood, and clot. The clot-based qPCR was shown to be more sensitive when compared with other types of specimens, detecting five and 0.05 T. gondii genomes, using B1 and REP529 targets, respectively. Finally, a comparative analysis with samples from HIV patients with clinical suspicion of toxoplasmosis was performed, demonstrating the detection of four positive suspected cases with clots compared with only one using guanidine-ethylenediaminetetraacetic acid blood. The high analytical sensitivity and the cost-effective advantages offered by clot supports this methodology as a good laboratory tool to monitor parasite burden.

  View details for DOI 10.4269/ajtmh.17-0920

  View details for Web of Science ID 000455207700019

  View details for PubMedID 30457102

  View details for PubMedCentralID PMC6335924

• Predictors of Intravenous Immunoglobulin Nonresponse and Racial Disparities in Kawasaki Disease. The Pediatric infectious disease journal Clark, D. E., Denby, K. J., Kaufman, L. M., Fill, M. A., Piya, B., Krishnaswami, S., Fonnesbeck, C., Halasa, N. 2018; 37 (12): 1227-1234

  Abstract

  Kawasaki disease (KD) is the most common cause of acquired heart disease in American children. Intravenous immunoglobulin (IVIG) nonresponse is a known risk factor for cardiac sequelae. Previously reported risk factors for nonresponse include age, male sex and laboratory abnormalities. We set out to identify additional risk factors for IVIG nonresponse in a racially diverse KD population.We conducted a retrospective chart review at a referral center in the Southeastern United States of children meeting ICD-9 (International Statistical Classification of Disease and Related Health Problems) criteria for KD and being treated with IVIG.Four-hundred and fifty-nine children met inclusion criteria, 67 were excluded for subsequent rheumatologic diagnosis, unknown race, or failure to meet the American Heart Association guideline criteria. Our final cohort consisted of 392 subjects, with median age of 2.7 years, 65.1% male, 66.1% White, 24.2% Black, 4.9% Asian and 82.9% responded to a single dose of IVIG. Coronary ectasia or aneurysm developed in 27%; 7.4% developed aneurysms and 2.3% giant coronary aneurysms. Nonresponders were more likely to be Black, have higher white blood cell, erythrocyte sedimentation rate and C-reactive protein, lower hemoglobin, develop ectasia or aneurysm and require critical care and hospital readmission. Responders achieved echocardiographic normalization more often compared with nonresponders (81.3% vs. 60.9%, P = 0.002) and coronary artery pseudonormalization (87.2% vs. 69.7%, P = 0.03) at 1 year. Black nonresponders had the slowest normalization at 1 year (52.9%, P = 0.02).Nonresponders have higher rates and greater severity of coronary involvement than responders. Our study uniquely demonstrates Black race as a risk factor for nonresponse and for delayed normalization of cardiac involvement at 1-year follow-up.

  View details for DOI 10.1097/INF.0000000000002019

  View details for PubMedID 29570178

• Nutrition for the School-age Child and Teenager Clark , D., El-Sourady , M. McGraw-Hill Education. New York, NY. 2018

  Abstract

  AccessMedicine. Vanderbilt Internal Medicine/Pediatric Curriculum

• Discipline for Young Children Moutsios , S., Clark , D. McGraw-Hill Education. New York, NY. 2018

  Abstract

  Vanderbilt Internal Medicine/Pediatric Curriculum

• Nutrition for Toddlers Clark , D., Moutsios , S., Miller , M., El-Sourady , M. McGraw-Hill Education. New York, NY. 2018

  Abstract

  AccessMedicine. Vanderbilt Internal Medicine/Pediatric Curriculum

• Management of Kawasaki disease in adults. Heart (British Cardiac Society) Denby, K. J., Clark, D. E., Markham, L. W. 2017; 103 (22): 1760-1769

  Abstract

  Kawasaki disease is the most common childhood vasculitis in the USA and the most common cause of acquired cardiac disease in children in developed countries. Since the vast majority of Kawasaki disease initially presents at <5 years of age, many adult cardiologists are unfamiliar with the pathophysiology of this disease. This vasculitis has a predilection for coronary arteries with a high complication rate across the lifespan for those with medium to large coronary artery aneurysms. An inflammatory cascade produces endothelial dysfunction and damage to the vascular wall, leading to aneurysmal dilatation. Later, pseudonormalisation of the vascular lumen occurs through vascular remodelling and layering thrombus, but this does not necessarily indicate resolution of disease or reduction of risk for future complications. There is a growing prevalence of Kawasaki disease, making it increasingly relevant for adult cardiologists as this population transitions into adulthood. As the 2017 American Heart Association (AHA) and 2014 Japanese Circulation Society (JCS) guidelines emphasise, Kawasaki disease requires rigorous follow-up with cardiac stress testing and non-invasive imaging to detect progressive stenosis, thrombosis and luminal occlusion that may lead to myocardial ischaemia and infarction. Due to differences in disease mechanisms, coronary disease due to Kawasaki disease should be managed with different pharmacological and non-pharmacological treatment algorithms than atherosclerotic coronary disease. This review addresses gaps in the current knowledge of the disease and its optimal treatment, differences in the AHA and JCS guidelines, targets for future research and obstacles to transition of care from adolescence into adulthood.

  View details for DOI 10.1136/heartjnl-2017-311774

  View details for PubMedID 28751537

• Use of a Chagas Urine Nanoparticle Test (Chunap) to Correlate with Parasitemia Levels in T. cruzi/HIV Co-infected Patients. PLoS neglected tropical diseases Castro-Sesquen, Y. E., Gilman, R. H., Mejia, C., Clark, D. E., Choi, J., Reimer-McAtee, M. J., Castro, R., Valencia-Ayala, E., Flores, J., Bowman, N., Castillo-Neyra, R., Torrico, F., Liotta, L., Bern, C., Luchini, A. 2016; 10 (2): e0004407

  Abstract

  Early diagnosis of reactivated Chagas disease in HIV patients could be lifesaving. In Latin America, the diagnosis is made by microscopical detection of the T. cruzi parasite in the blood; a diagnostic test that lacks sensitivity. This study evaluates if levels of T. cruzi antigens in urine, determined by Chunap (Chagas urine nanoparticle test), are correlated with parasitemia levels in T. cruzi/HIV co-infected patients.T. cruzi antigens in urine of HIV patients (N = 55: 31 T. cruzi infected and 24 T. cruzi serology negative) were concentrated using hydrogel particles and quantified by Western Blot and a calibration curve. Reactivation of Chagas disease was defined by the observation of parasites in blood by microscopy. Parasitemia levels in patients with serology positive for Chagas disease were classified as follows: High parasitemia or reactivation of Chagas disease (detectable parasitemia by microscopy), moderate parasitemia (undetectable by microscopy but detectable by qPCR), and negative parasitemia (undetectable by microscopy and qPCR). The percentage of positive results detected by Chunap was: 100% (7/7) in cases of reactivation, 91.7% (11/12) in cases of moderate parasitemia, and 41.7% (5/12) in cases of negative parasitemia. Chunap specificity was found to be 91.7%. Linear regression analysis demonstrated a direct relationship between parasitemia levels and urine T. cruzi antigen concentrations (p<0.001). A cut-off of > 105 pg was chosen to determine patients with reactivation of Chagas disease (7/7). Antigenuria levels were 36.08 times (95% CI: 7.28 to 64.88) higher in patients with CD4+ lymphocyte counts below 200/mL (p = 0.016). No significant differences were found in HIV loads and CD8+ lymphocyte counts.Chunap shows potential for early detection of Chagas reactivation. With appropriate adaptation, this diagnostic test can be used to monitor Chagas disease status in T. cruzi/HIV co-infected patients.

  View details for DOI 10.1371/journal.pntd.0004407

  View details for PubMedID 26919324

  View details for PubMedCentralID PMC4768913