Nisha A. Gilotra

Evaluation of the Role of Endomyocardial Biopsy in 851 Patients With Unexplained Heart Failure From 2000–2009

Background—Endomyocardial biopsy (EMB) is often considered when the pathogenesis of heart failure cannot be determined by noninvasive testing. Uncertainty remains about the diagnostic and clinical use of EMB in various clinical scenarios. Methods and Results—We examined the characteristics of a cohort of patients with unexplained heart failure who underwent EMB at a tertiary care medical center. We categorized each patient into a clinical scenario as outlined by the 2007 AHA/ACC/ESC guidelines and determined the number of times EMB provided a diagnosis or altered the clinical course. A total of 851 patients underwent EMB from 2000–2009. Overall, 25.5% of EMBs provided a diagnosis and 22.7% of EMBs changed clinical course. Heart failure associated with unexplained restrictive cardiomyopathy was the most common clinical scenario, comprising 33.6% (286/851) of EMBs, and 84 (29.4%) of these EMBs were diagnostic. EMB for unexplained heart failure of <2 weeks duration had a diagnostic yield at 35% (39/109). There were 4 uncommon scenarios where EMB had a high diagnostic and clinical yield. There were 16 complications for an overall rate of 1.9%. Conclusions—We confirm that EMB is useful in acute onset unexplained cardiomyopathy. We demonstrate a role for EMB in suspected infiltrative disease and in the management of rare clinical scenarios, such as suspected hypersensitivity myocarditis, anthracycline cardiomyopathy, cardiac tumors, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Our results suggest low use of EMB in chronic heart failure that responds to usual care.

Clinician's Guide to the Updated ABCs of Cardiovascular Disease Prevention

To facilitate the guideline-based implementation of treatment recommendations in the ambulatory setting and to encourage participation in the multiple preventive health efforts that exist, we have organized several recent guideline updates into a simple ABCDEF approach. We would remind clinicians that evidence-based medicine is meant to inform recommendations but that synthesis of patient-specific data and use of appropriate clinical judgment in each individual situation is ultimately preferred.

Eosinophil-derived IL-4 drives progression of myocarditis to inflammatory dilated cardiomyopathy

Inflammatory dilated cardiomyopathy (DCMi) is a major cause of heart failure in children and young adults. DCMi develops in up to 30% of myocarditis patients, but the mechanisms involved in disease progression are poorly understood. Patients with eosinophilia frequently develop cardiomyopathies. In this study, we used the experimental autoimmune myocarditis (EAM) model to determine the role of eosinophils in myocarditis and DCMi. Eosinophils were dispensable for myocarditis induction but were required for progression to DCMi. Eosinophil-deficient &Dgr;dblGATA1 mice, in contrast to WT mice, showed no signs of heart failure by echocardiography. Induction of EAM in hypereosinophilic IL-5Tg mice resulted in eosinophilic myocarditis with severe ventricular and atrial inflammation, which progressed to severe DCMi. This was not a direct effect of IL-5, as IL-5Tg&Dgr;dblGATA1 mice were protected from DCMi, whereas IL-5−/− mice exhibited DCMi comparable with WT mice. Eosinophils drove progression to DCMi through their production of IL-4. Our experiments showed eosinophils were the major IL-4–expressing cell type in the heart during EAM, IL-4−/− mice were protected from DCMi like &Dgr;dblGATA1 mice, and eosinophil-specific IL-4 deletion resulted in improved heart function. In conclusion, eosinophils drive progression of myocarditis to DCMi, cause severe DCMi when present in large numbers, and mediate this process through IL-4.

Patient selection for mechanical circulatory support.

Heart failure continues to be associated with high morbidity and mortality. Over the past decade, left ventricular assist devices have been shown to improve the survival and quality of life. However, it is quite clear that very sick patients do not do as well, and it is therefore imperative to select patients at the proper time. In this article, we review both the indications for considering left ventricular assist device therapy as well as discuss the considerations and therapy that should be done pre-operatively to possibly improve post-insertion outcomes.

Increased lipofuscin on endomyocardial biopsy predicts greater cardiac improvement in adolescents and young adults

BACKGROUND The presence of interstitial fibrosis and lipofuscin in endomyocardial biopsies may indicate the chronicity of heart failure. Fibrosis is known to increase in the failing heart. Lipofuscin increases with age, but its relationship to heart function is unknown. This study investigated whether lipofuscin or fibrosis had predictive utility in indicating function or adverse event (death, transplant, assist device placement) at 1 year postbiopsy in adolescents and young adults. METHODS A retrospective analysis was performed on nontransplant endomyocardial biopsies between 2000 and 2009 from individuals aged 10-40 years. Clinical and demographic information including ejection fraction (EF), EF at 1 year, and adverse events were obtained as available. Lipofuscin and fibrosis were scored retrospectively in a blinded fashion for 201 biopsies. Linear regression and Cox proportional hazard models were used for multivariable analysis. RESULTS Increasing lipofuscin strongly correlated with patient age (P<.0001). Higher lipofuscin levels were correlated with a better EF at 1 year (P=.02). This remained significant (P=.04) after adjusting for age. The degree of fibrosis did not associate with any clinical variable and had no predictive capabilities in this study. CONCLUSIONS This is the first study to incorporate lipofuscin in predicting future heart function. We found that more lipofuscin correlates with better EFs at 1 year, suggesting that lipofuscin is a marker for improved cardiac compensation. This information can help clinicians devise treatment plans for individuals in this age group.

Arginine vasopressin as a target in the treatment of acute heart failure

Congestive heart failure (CHF) is one of the most common reasons for hospitalization in the United States. Despite multiple different beneficial medications for the treatment of chronic CHF, there are no therapies with a demonstrated mortality benefit in the treatment of acute decompensated heart failure. In fact, studies of inotropes used in this setting have demonstrated more harm than good. Arginine vasopressin has been shown to be up regulated in CHF. When bound to the V1a and/or V2 receptors, vasopressin causes vasoconstriction, left ventricular remodeling and free water reabsorption. Recently, two drugs have been approved for use that antagonize these receptors. Studies thus far have indicated that these medications, while effective at aquaresis (free water removal), are safe and not associated with increased morbidity such as renal failure and arrhythmias. Both conivaptan and tolvaptan have been approved for the treatment of euvolemic and hypervolemic hyponatremia. We review the results of these studies in patients with heart failure.

Pre-operative proteinuria in left ventricular assist devices and clinical outcome

BACKGROUND This study evaluated the association of pre-operative proteinuria before continuous flow left ventricular assist device (CF-LVAD) implantation in relation to mortality and the need for renal replacement therapy (RRT) during the first year of follow-up. METHODS This retrospective, multicenter cohort study evaluated all patients (n = 241) who underwent CF-LVAD implantation in the 2 participating tertiary referral centers. Patients were included if a urine dipstick was performed within 7 days before CF-LVAD implantation. Proteinuria was defined as trace or higher. RESULTS In total, 173 patients (72%) were included (78% men; mean age, 52.3 ± 13.3; mean estimated glomerular filtration rate, 60.1 ± 25.9 mL/min/1.73 m2), and 42 patients (24%) had pre-operative proteinuria. The observed survival in patients with proteinuria vs without proteinuria was 57% vs 86% at 3 months and 52% vs 78% at 1 year (log-rank p < 0.001), respectively. In addition, during the first year after implantation, 32% of the patients with proteinuria and 15% of the patients without proteinuria required RRT (log-rank p = 0.02). Multivariate Cox regression analysis confirmed that pre-operative proteinuria was an independent predictor for mortality (adjusted hazard ratio, 2.09; 95% confidence interval, 1.10-3.80, p = 0.02) and for the need of RRT during the first year (adjusted hazard ratio, 2.23; 95% confidence interval, 1.13-4.84; p = 0.02). CONCLUSIONS Proteinuria, which was present in 25% of all tested LVAD patients, predicts worse outcome in all-cause mortality and need of RRT in patients with a CF-LVAD. This warrants the use of proteinuria in risk stratification when selecting patients for CF-LVAD therapy.

Patients Commonly Believe Their Heart Failure Hospitalizations Are Preventable and Identify Worsening Heart Failure, Nonadherence, and a Knowledge Gap as Reasons for Admission

BACKGROUND There are few data describing patient-identified precipitants of heart failure (HF) hospitalization. We hypothesized a patients perception of reason for or preventability of an admission may be related to 30-day readmission rates. METHODS AND RESULTS Ninety-four patients admitted with decompensated HF from July 2014 to March 2015 completed a brief questionnaire regarding circumstances leading to admission. Thirty-day outcomes were assessed via telephone call and chart review. Mean age was 58 ± 14 years, with 60% blacks (n = 56) and 41% females (n = 39). Median left ventricular ejection fraction was 30%; 27 had preserved ejection fraction. Seventy-two patients identified their hospitalization to be due to HF (± another condition). Most common patient-identified precipitants of admission were worsening HF (n = 37) and dietary nonadherence (n = 11). Readmitted patients tended to have longer time until first follow-up appointment (21 vs 8 days). Seven of the 42 patients who identified their hospitalization as preventable were readmitted compared with 21/49 who believed their hospitalization was unpreventable (P = .012). On multivariate regression analysis, patients who thought their hospitalization was preventable were less likely to be readmitted (odds ratio 0.31; 95% confidence interval 0.10-0.91; P = .04). CONCLUSION Almost 50% of patients believe their HF hospitalization is preventable, and these patients appear to be less likely to be readmitted within 30 days. Notably, patients cite nonadherence and lack of knowledge as reasons hospitalizations are preventable. These results lend insight into possible interventions to reduce HF readmissions.

Acute kidney injury and 1-year mortality after left ventricular assist device implantation

BACKGROUND Data on the consequences of acute kidney injury (AKI) after continuous-flow left ventricle assist device (LVAD) implantation are scarce and inconsistent. In this study, we evaluated the incidence, predictors and the impact of AKI on mortality and renal function in the first year after LVAD implantation. METHODS A retrospective, multicenter cohort study was conducted, including all patients (age ≥18 years) undergoing LVAD implantation (91% with a HeartMate II device and 9% with a HeartWare device). The definition proposed by the Kidney Disease Improving Global Outcome (KDIGO) criteria was used to define AKI. RESULTS Overall, 241 patients (mean age 52.4 ± 12.9 years, 76% males) were included in the study. AKI criteria were met in 169 (70%) patients, of whom 109 (45%) were in AKI Stage I, 22 (9%) in Stage II and 38 (16%) in Stage III. Two factors, the need for pre-operative inotropic support and pre-existent chronic kidney disease Stage ≤II (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2), were independently associated with the development of AKI and the severity of AKI stages. One-year mortality rates in patients without AKI and AKI Stages I, II and III were 18.7%, 26.4%, 23%, and 51%, respectively (log rank, p = 0.001). In the multivariable analysis, AKI Stage ≥II was independently associated with mortality (hazard ratio 2.2 [95% confidence interval 1.1 to 4.5], p = 0.027) and worse renal function (β = -7.4 [95% confidence interval -12.6 to -2.1], p < 0.01) at 1 year. CONCLUSION AKI is highly frequent after LVAD implantation. More severe AKI stages are associated with higher mortality rates and impaired renal function at 1 year after LVAD implantation.

Baseline Characteristics Predict the Presence of Amyloid on Endomyocardial Biopsy

BACKGROUND Recent studies have suggested a high prevalence of cardiac amyloidosis (CAm) in heart failure (HF) patients. CAm might be underdiagnosed owing to low clinical suspicion. METHODS AND RESULTS We performed retrospective analysis of 259 patients with HF and ejection fraction (EF) ≥50% referred for endomyocardial biopsy. Seventy-three (28%) had CAm. Multivariable independent predictors of CAm were identified. Over a mean follow-up of 2.6 ± 3.3 years, CAm patients had worse survival than those without (1.5 y vs 6.3 y; log rank P < .0001). CONCLUSIONS Clinicians should be suspicious of CAm in patients with EF 50%-75%, >50 years of age, BMI <30 kg/m2, peripheral neuropathy, Sokolow-Lyon index ≤15 mm, and septal wall thickness ≥1.4 cm.