Myocardial Injury on CMR in Patients With COVID-19 and Suspected Cardiac Involvement.

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.

Reappraisal of electrocardiographic criteria for localization of idiopathic outflow region ventricular arrhythmias.

BACKGROUND: Electrocardiographic (ECG) criteria have been proposed to localize the site of origin of outflow region ventricular arrhythmias (VAs). Many factors influence the QRS morphology of VAs and may limit the accuracy of these criteria. OBJECTIVE: The purpose of this study was to assess the accuracy of ECG criteria that differentiate right from left outflow region VAs and localize VAs within the aortic sinus of Valsalva (ASV). METHODS: One hundred one patients (mean age 52 ± 16 years; 55 [54%] women) undergoing catheter ablation of right ventricular outflow tract (RVOT) or ASV VAs with a left bundle branch block, inferior axis morphology were studied. ECG measurements including V2 transition ratio, transition zone index, R-wave duration index, R/S amplitude index, V2S/V3R index, V1-3 QRS morphology, R-wave amplitude in the inferior leads were tabulated for all VAs. Comparisons were made between the predicted site of origin using these criteria and the successful ablation site. RESULTS: Patients had successful ablation of 71 RVOT and 38 ASV VAs. For the differentiation of RVOT from ASV VAs, the positive predictive values and negative predictive values for all tested ECG criteria ranged from 42% to 75% and from 71% to 82%, respectively, with the V2S/V3R index having the largest area under the curve of 0.852. Morphological QRS criteria in leads V1 through V3 did not localize ASV VAs. The maximum R-wave amplitude in the inferior leads was the sole criterion demonstrating a significant difference between right ASV, right-left ASV commissure, and left ASV sites. CONCLUSION: ECG criteria for differentiating right from left ventricular outflow region VAs and for localizing ASV VAs have a limited accuracy.

Novel Echocardiographic Algorithm for Right Ventricular Mass Quantification: Cardiovascular Magnetic Resonance and Clinical Prognosis Validation.

BACKGROUND: Right ventricular hypertrophy (RVH) provides a key remodeling index alterable by pulmonary hypertension. Although echocardiography commonly integrates linear wall thickness and chamber dimensions to quantify left ventricular remodeling, the utility of an equivalent right ventricular (RV)-based approach is unknown. METHODS: This was a retrospective analysis of 200 patients undergoing transthoracic echocardiography and cardiac magnetic resonance (CMR) within 30 days (median = 3 days; interquartile range, 15 days), stratified by echocardiography-quantified pulmonary artery systolic pressure (<35, 35 to <55, 55 to <75, or ≥75 mm Hg). Echocardiographic assessment included RV linear dimensions in parasternal long-axis and apical four-chamber views and wall thicknesses in parasternal long-axis, four-chamber, and subcostal views. Subcostal wall thickness was integrated with chamber diameters to calculate RV mass, which was tested in relation to CMR-quantified RV mass and all-cause mortality. RESULTS: Echocardiography-based quantification of all linear dimensions was feasible in 95% of patients (190 of 200). RV wall thicknesses in all orientations increased in relation to pulmonary artery systolic pressure (P < .001) and was greater among patients with, versus those without, CMR-evidenced RVH (P < .001 for all). Correlations between echocardiography and CMR were greatest for RV basal diameter (r = 0.73), RV subcostal wall thickness (r = 0.71), and global RV mass (r = 0.82; P < .001 for all). Echocardiography-derived global RV mass cutoffs were established in a derivation cohort and tested in a validation cohort. Results demonstrated good sensitivity and specificity (75.5% and 74.0%, respectively) in relation to CMR-quantified RVH. During follow-up (median, 4.2 years), 18% of patients (n = 36) died. Echocardiography-evidenced RVH (hazard ratio, 1.98; 95% CI, 1.09-3.88; P = .048) conferred similar mortality risk compared with RVH on CMR (hazard ratio, 2.41; 95% CI, 1.22-4.78; P = .01). CONCLUSIONS: Echocardiography-quantified RV parameters provide a robust index of RV afterload. Global RV mass calculated using a novel echocardiographic formula based on readily available linear indices yields good diagnostic performance for CMR-evidenced RVH and confers increased mortality risk.

Ischemia-Mediated Dysfunction in Subpapillary Myocardium as a Marker of Functional Mitral Regurgitation.

OBJECTIVES: The goal of this study was to test whether ischemia-mediated contractile dysfunction underlying the mitral valve affects functional mitral regurgitation (FMR) and the prognostic impact of FMR. BACKGROUND: FMR results from left ventricular (LV) remodeling, which can stem from myocardial tissue alterations. Stress cardiac magnetic resonance can assess ischemia and infarction in the left ventricle and papillary muscles; relative impact on FMR is uncertain. METHODS: Vasodilator stress cardiac magnetic resonance was performed in patients with known or suspected coronary artery disease at 7 sites. Images were centrally analyzed for MR etiology/severity, mitral apparatus remodeling, and papillary ischemia. RESULTS: A total of 8,631 patients (mean age 60.0 ± 14.1 years; 55% male) were studied. FMR was present in 27%, among whom 16% (n = 372) had advanced (moderate or severe) FMR. Patients with ischemia localized to subpapillary regions were more likely to have advanced FMR (p = 0.003); those with ischemia localized to other areas were not (p = 0.17). Ischemic/dysfunctional subpapillary myocardium (odds ratio: 1.24/10% subpapillary myocardium; confidence interval: 1.17 to 1.31; p < 0.001) was associated with advanced FMR controlling for infarction. Among a subgroup with (n = 372) and without (n = 744) advanced FMR matched (1:2) on infarct size/distribution, patients with advanced FMR had increased adverse mitral apparatus remodeling, paralleled by greater ischemic/dysfunctional subpapillary myocardium (p < 0.001). Although posteromedial papillary ischemia was more common with advanced FMR (p = 0.006), subpapillary ischemia with dysfunction remained associated (p < 0.001), adjusting for posteromedial papillary ischemia (p = 0.074). During follow-up (median 5.1 years), 1,473 deaths occurred in the overall cohort; advanced FMR conferred increased mortality risk (hazard ratio: 1.52; 95% confidence interval: 1.25 to 1.86; p < 0.001) controlling for left ventricular ejection fraction, infarction, and ischemia. CONCLUSIONS: Ischemic and dysfunctional subpapillary myocardium provides a substrate for FMR, which predicts mortality independent of key mechanistic substrates.

Prognostic Utility of Right Ventricular Remodeling Over Conventional Risk Stratification in Patients With COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a growing pandemic that confers augmented risk for right ventricular (RV) dysfunction and dilation; the prognostic utility of adverse RV remodeling in COVID-19 patients is uncertain. OBJECTIVES: The purpose of this study was to test whether adverse RV remodeling (dysfunction/dilation) predicts COVID-19 prognosis independent of clinical and biomarker risk stratification. METHODS: Consecutive COVID-19 inpatients undergoing clinical transthoracic echocardiography at 3 New York City hospitals were studied; images were analyzed by a central core laboratory blinded to clinical and biomarker data. RESULTS: In total, 510 patients (age 64 ± 14 years, 66% men) were studied; RV dilation and dysfunction were present in 35% and 15%, respectively. RV dysfunction increased stepwise in relation to RV chamber size (p = 0.007). During inpatient follow-up (median 20 days), 77% of patients had a study-related endpoint (death 32%, discharge 45%). RV dysfunction (hazard ratio [HR]: 2.57; 95% confidence interval [CI]: 1.49 to 4.43; p = 0.001) and dilation (HR: 1.43; 95% CI: 1.05 to 1.96; p = 0.02) each independently conferred mortality risk. Patients without adverse RV remodeling were more likely to survive to hospital discharge (HR: 1.39; 95% CI: 1.01 to 1.90; p = 0.041). RV indices provided additional risk stratification beyond biomarker strata; risk for death was greatest among patients with adverse RV remodeling and positive biomarkers and was lesser among patients with isolated biomarker elevations (p ≤ 0.001). In multivariate analysis, adverse RV remodeling conferred a >2-fold increase in mortality risk, which remained significant (p < 0.01) when controlling for age and biomarker elevations; the predictive value of adverse RV remodeling was similar irrespective of whether analyses were performed using troponin, D-dimer, or ferritin. CONCLUSIONS: Adverse RV remodeling predicts mortality in COVID-19 independent of standard clinical and biomarker-based assessment.

Left ventricular end-diastolic volume predicts exercise capacity in patients with a normal ejection fraction.

BACKGROUND: Exercise capacity is a powerful predictor of all-cause mortality. The duration of exercise with treadmill stress testing is an important prognostic marker in both healthy subjects and patients with cardiovascular disease. Left ventricular (LV) structure is known to adapt to sustained changes in level of physical activity. HYPOTHESIS: Poor exercise capacity in patients with a preserved LV ejection fraction (LVEF) should be reflected in smaller LV dimensions, and a normal exercise capacity should be associated with larger LV dimensions, irrespective of comorbidities. METHODS: This hypothesis was first tested in a cross-sectional analysis of 201 patients with normal chamber dimensions and preserved LVEF who underwent a clinically indicated treadmill stress echocardiogram using the Bruce protocol (derivation cohort). The best LV dimensional predictor of exercise capacity was then tested in 1285 patients who had a Bruce-protocol treadmill exercise stress test and a separate transthoracic echocardiogram (validation cohort). RESULTS: In the derivation cohort, there was a strong positive relationship between exercise duration and LV end-diastolic volume deciles (r 2 = 0.85; P < 0.001). Regression analyses of several LV dimensional parameters revealed that the body surface area-based LV end-diastolic volume index was best suited to predict exercise capacity (P < 0.0001). In a large validation cohort, LV end-diastolic volume was confirmed to predict exercise capacity (P < 0.0001). CONCLUSIONS: Among patients referred for outpatient stress echocardiography who have a preserved LVEF and no evidence of myocardial ischemia, we found a strong positive association between LV volume and exercise capacity.

ß-Blockers in myocardial infarction and coronary artery disease with a preserved ejection fraction: recommendations, mechanisms, and concerns.

ß-Blockers are a recommended therapy in patients with acute myocardial infarction and coronary artery disease. ß-Blockers markedly and unequivocally reduce mortality in patients with myocardial infarction and coronary artery disease with heart failure and a reduced ejection fraction. However, the mortality effects of ß-blockers in patients with a preserved ejection fraction are not established even though they represent the majority of patients with coronary artery disease. In this review, we will assess the evidence basis of the recommendations for ß-blockers in the US guidelines and discuss emerging concerns about the use of ß-blockers and other heart rate-lowering medications in patients with a preserved ejection fraction that suggest that their long-term adverse outcomes may outweigh their antianginal benefits.

Plausible Role of Acute HIV Infection Mediated Immune Activation in Causing Renal Allograft Rejection: A Case Report.

Current research states that AIDS pathogenesis has its roots in a chronic activation of immune system secondary to human immunodeficiency virus (HIV)-induced proliferation of T cells, B cells, NK cells, and macrophages. Immune activation due to acute HIV infection can be highly detrimental to allograft survival in a renal transplant recipient. In this report, we describe a 32-year-old African-American male patient who underwent a second live donor renal transplant, following which he developed acute allograft rejection coincident with newly acquired HIV seropositivity.

Type VI Choledochal Cyst-An Unusual Presentation of Jaundice.

Choledochal cysts involving the cystic duct are extremely rare, and are usually associated with cystic dilatations of the extrahepatic biliary tract. We describe a patient who presented with jaundice and was found to have a dilatation of the common bile duct on computed tomographic imaging, consistent with a choledochal cyst. He underwent a laparoscopic-converted-to-open cholecystectomy with excision of the choledochal cyst which was found to involve the cystic duct. Choledochal cysts involving the cystic duct are notably missing from the Todani classification. Although exceedingly rare, new cases of these types of cysts are being reported, in part due to advancement of diagnostic imaging modalities. We discuss the current classification scheme for choledochal cysts and we propose an expansion of this scheme.

Promiscuous binding of extracellular peptides to cell surface class I MHC protein.

Algorithms derived from measurements of short-peptide (8-10 mers) binding to class I MHC proteins suggest that the binding groove of a class I MHC protein, such as K(b), can bind well over 1 million different peptides with significant affinity (<500 nM), a level of ligand-binding promiscuity approaching the level of heat shock protein binding of unfolded proteins. MHC proteins can, nevertheless, discriminate between similar peptides and bind many of them with high (nanomolar) affinity. Some insights into this high-promiscuity/high-affinity behavior and its impact on immunodominant peptides in T-cell responses to some infections and vaccination are suggested by results obtained here from testing a model developed to predict the number of cell surface peptide-MHC complexes that form on cells exposed to extracellular (exogenous) peptides.

Obesity, physical activity and the development of metabolic syndrome: the Atherosclerosis Risk in Communities study.

BACKGROUND: The objective of this study is to determine the impact of body weight and physical activity on the development of metabolic syndrome (MetS). DESIGN AND METHODS: We used the public use data from the Atherosclerosis Risk in Communities study. From the baseline cohort, we identified, as the study population, 9359 individuals who did not have MetS and who completed the second follow-up examination in 1993-1995. RESULTS: In 6 years of follow-up, 1970 individuals (25%) developed MetS. Compared with normal weight group [body mass index (BMI)<25 kg/m], the odds ratios [95% confidence interval (CI)] of incident MetS were 2.81 (95% CI: 2.50-3.17) and 5.24 (95% CI: 4.50-6.12) for the overweight (BMI: 25-30 kg/m) and the obese groups (BMI>or=30 kg/m), respectively. Compared with persons in the lowest quartile of leisure-time physical activity, the odds ratios (95% CI) of incident MetS were 0.80 (95% CI: 0.71-0.91) and 0.92 (95% CI: 0.81-1.04) for persons in the highest and the middle quartiles of leisure-time physical activity, respectively. Our results indicated that at any level of physical activity, there is a graded increase in the risk of incident MetS with an increase in BMI, in contrast to a lack of graded association between physical activity and the incidence of MetS in all categories of BMI. CONCLUSION: This study highlights the need to target obesity more than physical activity in preventing the development of MetS.