Dr. Clark completed a 4-year MD/MPH program at the University of Texas Health Science Center in San Antonio. He subsequently completed all of his post-graduate training at Vanderbilt University Medical Center (VUMC), including Internal Medicine-Pediatrics, Adult Cardiology, and Adult Congenital Heart Disease (ACHD). Additionally, he served as Chief Fellow of the Vanderbilt Cardiovascular Medicine Fellowship, trained in multimodality cardiovascular imaging, and conducted clinical research during a two-year NIH-funded T32 research fellowship at VUMC.
Prior to joining the Stanford ACHD faculty, he was appointed Instructor of Cardiovascular Medicine at Vanderbilt and read cardiac magnetic resonance (CMR) imaging as an attending for two years. He is appointed Assistant Professor of Medicine and Pediatrics at Stanford University School of Medicine.
His academic and investigative interests focus on advanced cardiovascular imaging for ACHD patients, particularly the application of CMR in this population. During the COVID-19 pandemic, Dr. Clark pivoted his scholarly efforts to focus on studying the cardiovascular effects of COVID-19 with CMR. His current clinical investigations include understanding the CMR-derived diastolic patterns of Fontan physiology and the effect of cardiac rehabilitation on functional status among patients with Fontan failure.
- Cardiovascular Disease
Honors & Awards
SCMR Case of the Year: https://scmr.org/general/custom.asp?page=COW2003, Society of Cardiac Magnetic Resonance (SCMR) (2022)
Cardiovascular Medicine Rhodes' Scholarly Award, Vanderbilt University Medical Center (2020)
Cardiovascular Fellow Teacher of the Year, Vanderbilt University Medical Center (2019)
Fellow Teacher of the Year, Vanderbilt University Medical Center (2018)
Housestaff Clinical Teaching Award (awarded to 5 housestaff annually), Vanderbilt School of Medicine (2017)
Member, Alpha Omega Alpha (AOA) (2019)
Member, Gold Humanism Honor Society (2017)
Member, Delta Omega Honorary Society (2013)
Boards, Advisory Committees, Professional Organizations
Member, American College of Cardiology Competency Management Committee Multi-societal Writing Committee on Advanced Training in Cardiovascular Imaging (2022 - Present)
Editorial Board Member, Circulation Cardiovascular Imaging (2022 - Present)
Early Career Editorial Board Member, Journal of the American Heart Association (2022 - Present)
Fellow, American College of Cardiology (2022 - Present)
Board certification:, Cardiovascular Magnetic Resonance, Certification Board of Cardiac Magnetic Resonance (CBCMR) (2020 - Present)
Board Certification:, American Board of Internal Medicine, Cardiovascular Disease (2020 - Present)
Board certification:, American Board of Internal Medicine, Internal Medicine (2017 - Present)
Fellowship: Vanderbilt University Adult Congenital Heart Disease Fellowship Pgm (2022) TN
Board Certification: American Board of Internal Medicine, Cardiovascular Disease (2020)
Fellowship: Vanderbilt University Medical Center Cardiovasular Fellowship (2020) TN
Board Certification: American Board of Internal Medicine, Internal Medicine (2017)
Residency: Vanderbilt University Internal Medicine Residency (2017) TN
Medical Education: University of Texas at San Antonio (2013) TX
Fellowship, Vanderbilt University Medical Center, Adult Congenital Heart Disease (2022)
Research Fellow, Vanderbilt University Medical Center, T32 HL007411-39 NIH grant (2021)
Chief Fellow, Vanderbilt University Medical Center, Cardiovascular Medicine (2020)
Fellowship, Vanderbilt University Medical Center, Cardiovascular Medicine (2020)
Residency, Vanderbilt University Medical Center, Internal Medicine-Pediatrics (2017)
MPH, University of Texas Health Science Center San Antonio, Global Health (2013)
MD, University of Texas Health Science Center San Antonio, Medicine (2013)
B.S., Northwestern University, Social Policy (2007)
Curriculum and Instruction
REHAB Fontan Failure: RCT of the Effects of Cardiac reHABilitation versus Tadalafil among patients with Fontan Failure, Stanford University, Vanderbilt University (10/1/2022 - 9/30/2023)
Pharmacologic and therapeutic interventions for patients with Fontan failure are limited and poorly studied. Patient-reported outcome (PROs) metrics of quality of life (QOL) are crucial for aligning patient-centered goals regarding a meaningful improvement in their QOL and are currently underutilized in Fontan research. This proposal will address an urgent clinical need to better understand patient-reported outcome (PROs) metrics of quality of life (QOL), quantitative functional and frailty testing, and a direct comparison of two accessible, but underutilized therapeutic interventions among patients with failing Fontan physiology. A multicenter, randomized controlled trial (1:1) will test the central hypothesis that cardiac rehabilitation will result in improved peak VO2, frailty, and a validated, congenital heart disease-specific PROs (ACHD PROs) over a 12-week duration compared to PDE-5 inhibitor (Tadalafil).
- Jonathan Menachem, Director, Advanced Congenital Cardiac Therapies (ACCT), Vanderbilt University Medical Center
Metabolic Signatures of Cardiac Dysfunction, Multimorbidity, and Post-Transcatheter Aortic Valve Implantation Death.
Journal of the American Heart Association
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
2023; 81 (22): 2161-2171
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
2023; 81 (22): 2149-2160
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.
2023; 132 (10): 1387-1404
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
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
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
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.
2022; 57 (9): 561-566
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
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) 2022; 108 (18): 1437-1500
Reduced Circumferential Strain in Athletes with Prior COVID-19.
Radiology. Cardiothoracic imaging
2022; 4 (4): e210310
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
- Case Series Conference: Anesthetic Management in Parturients With Fontan Physiology. Journal of cardiothoracic and vascular anesthesia 2022
Characteristics of COVID-19 Myocarditis With and Without Multisystem Inflammatory Syndrome.
The American journal of cardiology
2022; 168: 135-141
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
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
2022; 28 (3): 415-421
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
2022; 4 (1): 49-53
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
2022; 8: e09
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
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 2021; 10 (22): e023731
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
2021; 23 (1): 108
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
2021; 23 (1): 106
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.
2021; 42 (6): 1425-1432
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
2021; 162 (2): 422-428.e1
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 2021; 4 (5): e2110323
No survival benefit associated with waiting for non-lung donor heart transplants for adult recipients with congenital heart disease.
2021; 35 (5): e14266
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
2021; 15 (3): e0009199
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 2021; 143 (6): 609-612
COVID-19 Myocardial Pathology Evaluated Through scrEening Cardiac Magnetic Resonance (COMPETE CMR).
medRxiv : the preprint server for health sciences
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
2020; 11 (3): 368-369
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
2020; 2 (3): 420-425
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
2020; 35 (3): 603-608
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
2020; 25 (2): 131-136
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
CardioMEMS Implantation in Patient With a Systemic Right Ventricle.
JACC. Case reports
2019; 1 (3): 394-395
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
2019; 14 (5): 765-771
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
2019; 100 (1): 83-89
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
2018; 37 (12): 1227-1234
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
Management of Kawasaki disease in adults.
Heart (British Cardiac Society)
2017; 103 (22): 1760-1769
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
2016; 10 (2): e0004407
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