E.C. DePasquale

Outcomes of adults with restrictive cardiomyopathy after heart transplantation

BACKGROUND Restrictive cardiomyopathy (RCM) represents a spectrum of disorders with a common physiology but divergent etiologies. RCM commonly leads to progressive heart failure and the need for heart transplantation (HTx). Pediatric RCM is a more homogeneous disorder with post-HTx outcomes comparable to those for non-RCM patients. However, post-HTx outcomes in adult RCM patients have not been studied to date. METHODS Demographic, clinical and survival outcomes of 38,190 adult HTx-only recipients from 1987 to 2010 were acquired from the registry of the United Network of Organ Sharing. The study population included 544 RCM patients (1.4%) and 37,646 non-RCM patients (98.6%). RCM diagnoses included idiopathic (n = 227, 42%), amyloid (n = 142, 26%), sarcoid (n = 81, 15%), radiation/chemotherapy (XRT) (n = 35, 6%) and other (n = 59, 11%). RESULTS Follow-up began at the time of HTx (74±64 months). During the follow-up period, 224 (41%) patients in the RCM group died, whereas 18,791 (50%) in the non-RCM group died. Crude 1-, 5- and 10-year survival for RCM patients was 84%, 66% and 45%, and for non-RCM patients was 85%, 70% and 50%, respectively. The overall unadjusted hazard ratio of RCM vs non-RCM for all-cause mortality was 1.07 (confidence interval [CI] 0.93 to 1.22). Multivariate Cox proportional hazards regression analysis yielded a hazard ratio of 1.06 (CI 0.91 to 1.25). RCM subgroup analysis showed decreased survival at 1, 5 and 10 years in the XRT (71%, 47% and 32%) and amyloid (79%, 47% and 28%) patient groups. The unadjusted hazard ratio for the XRT and amyloid subgroups vs RCM for all-cause mortality was 1.81 (p = 0.002) and 1.85 (p = 0.0004), respectively. CONCLUSIONS Outcomes for RCM patients post-HTx are comparable to those of non-RCM patients. However, RCM subgroup analysis suggests increased mortality for XRT and amyloid subgroups. Further analysis is warranted to understand the contributing factors.

Hypertrophic cardiomyopathy: diagnosis, risk stratification and treatment

Hypertrophic cardiomyopathy is a common inherited cardiomyopathy, occurring in about 1 in 500 individuals.[1][1] The first gene mutation for this condition was identified in a large French Canadian family cohort in 1989.[2][2] Clinical presentation typically includes left ventricular hypertrophy in

A contemporary review of adult heart transplantation: 2012 to 2013

Important developments have occurred during the past 2 years in the field of heart transplantation. These include refinements in donor management, preservation, and allocation, and evaluation of immunosuppression strategies for rejection and for allograft vascular disease. Finally, long-term outcomes addressing areas of significant morbidity for patients, including renal dysfunction and cancer, have seen important advances. This contemporary review will highlight the key articles for 2012 to 2013.

Team-Based Care for Outpatients with Heart Failure

Management of heart failure requires a multidisciplinary team-based approach that includes coordination of numerous team members to ensure guideline-directed optimization of medical therapy, frequent and regular assessment of volume status, frequent education, use of cardiac rehabilitation, continued assessment for the use of advanced therapies, and advance care planning. All of these are important aspects of the management of this complex condition.

Heart Failure Therapies for End-Stage Chemotherapy–Induced Cardiomyopathy

With ongoing advancements in cancer-related treatments, the number of cancer survivors continues to grow globally, with numbers in the United States predicted to reach 18 million by 2020. As a result, it is expected that a greater number of patients will present with chemotherapy-related side effects. One entity in particular, chemotherapy-related cardiomyopathy (CCMP), is a known cardiotoxic manifestation associated with agents such as anthracyclines, trastuzumab, and tyrosine kinase inhibitors. Although such effects have been described in the medical literature for decades, concrete strategies for screening, prevention, and management of CCMP continue to be elusive owing to limited studies. Late recognition of CCMP is associated with a poorer prognosis, including a lack of clinical response to pharmacologic therapy, and end-stage heart failure. A number of advanced cardiac therapies, including cardiac resynchronization therapy, ventricular assist devices, and orthotopic cardiac transplantation, are available to for end-stage heart failure; however, the role of these therapies in CCMP is unclear. In this review, management of end-stage CCMP with the use of advanced therapies and their respective effectiveness are discussed, as well as clinical characteristics of patients undergoing these treatments. The relative paucity of data in this field highlights the importance and need for larger-scale longitudinal studies and long-term registries tracking the outcomes of cancer survivors who have received cardiotoxic cancer therapy to determine the overall incidence of end-stage CCMP, as well as prognostic factors that will ultimately guide such patients toward receiving appropriate end-stage care.

Temporary Venoarterial Extracorporeal Membrane Oxygenation Ten-Year Experience at a Cardiac Transplant Center

Objective: Advances in extracorporeal membrane oxygenation (ECMO) have enabled rapid deployment in a wide range of clinical settings. We report our experience with venoarterial (VA) ECMO in adult patients over 10 years and aim to identify predictors of mortality. Design: This is a retrospective analysis of all adult patients undergoing VA ECMO at a tertiary care center from January 1, 2004, to December 31, 2013. Results: A total of 224 consecutive cases were reviewed. Eighty (35.7%) patients survived to discharge and 144 (64.3%) patients died. Patients requiring ECMO for heart transplant graft failure had lower mortality (51.6%) compared to all other etiologies (69.1%; P = .02). Forty-two percent (94 of the 224) of the patients required cardiopulmonary resuscitation (CPR) preceding ECMO and had higher rate of in-hospital mortality (74.5%) compared with patients without cardiac arrest (56.9%; P = .01). Patients with less than 30 minutes of CPR had a mortality rate of 40.0% compared to 91.4% for CPR > 30 minutes (P = .001). In all, 24.1% of patients (54 of the 224) experienced ECMO-associated complications without significant increase in mortality, and 22.3% (50 of the 224) of the patients were transitioned to ventricular assist devices (VADs) or transplant. Patients bridged to a VAD including left ventricular assist devices and biventricular assist devices had a mortality rate of 56.1% versus 22.2% when bridged directly to transplant (P = .01). Paradoxically, patients with an ejection fraction (EF) > 35% had a higher mortality compared to patients with an EF < 35% (75.3% vs 49.4%, respectively, P = .001). Conclusion: Extracorporeal membrane oxygenation in patients with heart transplant graft failure had the best outcome. In patients who had cardiac arrest, prolonged CPR > 30 minutes was associated with very high mortality. Paradoxically, patients with EF > 35% had a higher mortality than patients with EF < 35%, likely reflecting patients with diastolic heart failure or noncardiac causes necessitating ECMO. For transplant candidates, direct bridge from ECMO to transplant could achieve a very good outcome.

Familial dilated cardiomyopathy diagnosis is commonly overlooked at the time of transplant listing

BACKGROUND The prevalence and clinical characteristics of familial dilated cardiomyopathy (FDCM) among patients with end stage heart failure (ESHF) has yet to be elucidated. We sought to determine the prevalence of FDCM in ESHF in the United Network for Organ Sharing (UNOS) registry and compare this with center specific data from a large tertiary teaching hospital. Patients with a banked UNOS diagnosis of dilated cardiomyopathy (DCM) whose care originated at our center then underwent detailed pedigree analysis in order to determine the true prevalence of FDCM. METHODS AND RESULTS A total of 16,091 patients with DCM from all centers were identified in the UNOS registry of whom 492 carried the diagnosis of FDCM (3.1%). Patients with the diagnosis of FDCM tended to be younger (42 versus 49 years old in idiopathic dilated cardiomyopathy (IDCM), p=0.001), were less likely to have diabetes (7.8% versus 16.5% in IDCM, p<0.0001), had slightly lower creatinine (1.2 versus 1.4 in IDCM, p=0.0001) and were more likely to have a panel reactive antibody level ≥ 20% (62.1% versus 44.7% in IDCM, p<0.0001). Consecutive living adult patients with ESHF were identified from the UNOS registry that had been treated at the Yale Center for Advanced Heart Failure (YCAHF). After excluding all diagnoses that did not include any form of non-ischemic DCM, 73 patients met the inclusion criteria. Center-specific UNOS data showed pre-pedigree analysis diagnosis of FDCM in 4.12% of patients (3 out of 73), consistent with that found in the UNOS database for all centers. However, after detailed family history and pedigree analysis, 19 (26%) of 73 patients were found to have FDCM, while the remaining 54 were found to have IDCM. Echocardiographic findings including mitral regurgitation, mitral valve annulus and left ventricular end diastolic dimension were not significantly different between groups when adjusting for multiple testing. CONCLUSIONS The diagnosis of FDCM was missed in the majority of patients with end stage heart failure enrolled in the UNOS database, as sampled from a large, tertiary care teaching hospital in the United States. Echocardiographic findings are unlikely to aid in the differentiation between DCM and FDCM. Detailed pedigree analysis can successfully identify undiagnosed FDCM and should be encouraged prior to transplant listing as it has important implications for early detection and treatment of disease in family members.

Survival After Heart Transplantation in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

BACKGROUND Outcomes of arrhythmogenic right ventricular cardiomyopathy (ARVC) patients after heart transplantation have not been well studied. Diagnostic criteria were established in 1994 and subsequently revised in 2010. We sought to better characterize this population in a national cohort. METHODS A total of 35,138 heart transplant-only recipients were identified from the United Network for Organ Sharing (UNOS) Thoracic Registry (1994-2011); 73 had ARVC. The non-ARVC group included ischemic cardiomyopathy, restrictive cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, and other. Survival was censored at 12 years. Multivariate Cox proportional hazard regression analysis was adjusted for age, sex, DM, race, ischemia time, dialysis, life support, wait time, and HLA mismatch. RESULTS There were 73 ARVC and 35,065 non-ARVC patients. The ARVC cohort was associated with less ventricular assist device use (P = .001) and significantly decreased pulmonary arterial and capillary wedge pressures (P < .001). Survivals at 1, 5, and 10 years were, respectively, ARVC 87%, 81%, and 77%, and non-ARVC 87%, 72%, and 53% (log rank P = .07). The ARVC unadjusted hazard ratio for all-cause mortality was 0.59 (95% confidence interval [CI] 0.34-1.04; P = .073). Multivariate analysis yielded a hazard ratio of 0.68 (95% CI 0.35-1.30; P = .25). ARVC survival was similar to restrictive, hypertrophic, and dilated cardiomyopathies and significantly better than ischemic cardiomyopathy. CONCLUSIONS This is the largest reported series of ARVC after heart transplantation, of which 11% were pediatric. Survival was similar to the non-ARVC cohort, with improved survival over ischemic and restrictive etiologies.

INFLUENCE OF PRE-TRANSPLANT CHRONIC KIDNEY DISEASE ON OUTCOMES OF ADULT HEART TRANSPLANT-ONLY RECIPIENTS: UNOS REGISTRY ANALYSIS

Renal dysfunction severity is considered for heart transplant (HT) candidacy. However, acceptable level of dysfunction is not well defined. The influence of Chronic Kidney Disease (CKD) stage on post-HT outcomes is unknown. 30437 HT patients (pts) were identified from UNOS (1987-2011) & stratified

Impact of Atrial Fibrillation on Outcomes in Heart Failure

The prevalence of atrial fibrillation (AF) and heart failure increases with advancing age. It is estimated that the annual incidence of AF in the general heart failure population is approximately 5%, whereas as many as 40% of patients with advanced heart failure have AF. The goals of therapy in patients with heart failure and AF are symptom control and prevention of arterial thromboembolism. The adverse hemodynamic events of AF may lead to symptom deterioration and reduced exercise capacity. This review addresses the impact of AF on heart failure outcomes as they pertain to prognosis and management.