Avishay Grupper

Role of ventricular assist therapy for patients with heart failure and restrictive physiology: Improving outcomes for a lethal disease.

BACKGROUND Restrictive cardiomyopathy (RCM) patients have poor prognosis due to progressive heart failure characterized by impaired ventricular filling of either or both ventricles. The goal of this study was to evaluate the outcome of end-stage RCM patients after left ventricular assist device (LVAD) implantation and to determine factors that may be associated with improved survival. METHODS This investigation is a retrospective study of prospectively collected data that include 28 consecutive patients with end-stage RCM who received continuous-flow LVADs at the Mayo Clinic, Rochester, Minnesota. Outcome was assessed by survival with LVAD support until heart transplantation or all-cause mortality. RESULTS The mean follow-up time post-LVAD implantation was 448 ± 425 days. The mean hospitalization time was 29 ± 19 days and was complicated mainly by post-operative right ventricular (RV) failure requiring short-term medical support. The short-term in-hospital mortality was 14%. Ten patients underwent heart transplantation with 100% survival post-transplant during the follow-up period. One-year survival for patients with LVADs without transplantation was 64%, and was not significantly different between amyloidosis and non-amyloidosis patients. Larger left ventricle (LV) end-diastolic and end-systolic dimensions were significantly associated with improved survival rates (RR = 0.94 and 0.95, p < 0.05, respectively), and left ventricular end-diastolic diameter (LVEDD) ≤46 mm was associated with increased mortality post-LVAD implantation. CONCLUSIONS LVAD is a feasible, life-saving therapy for end-stage heart failure related to RCM, especially as a bridge to transplant and in patients with larger LV dimensions.

Current Status of Left Ventricular Assist Device Therapy

Congestive heart failure (HF) remains a serious burden in the Western World. Despite advances in pharmacotherapy and resynchronization, many patients have progression to end-stage HF. These patients may be candidates for heart transplant or left ventricular assist device (LVAD) therapy. Heart transplants are limited by organ shortages and in some cases by patient comorbidities; therefore, LVAD therapy is emerging as a strategy of bridge to transplant or as a destination therapy in patients ineligible for transplant. Patients initially ineligible for a transplant may, in certain cases, become eligible for transplant after physiologic improvement with LVAD therapy, and a small number of patients with an LVAD may have sufficient recovery of myocardial function to allow device explantation. This clinically oriented review will describe (1) the most frequently used pump types and aspects of the continuous-flow physiology and (2) the clinical indications for and the shift toward the use of LVADs in less sick patients with HF. Additionally, we review complications of LVAD therapy and project future directions in this field. We referred to the Interagency Registry for Mechanically Assisted Circulatory Support, landmark trials, and results from recently published studies as major sources in obtaining recent outcomes, and we searched for related published literature via PubMed. This review focuses primarily on clinical practice for primary care physicians and non-HF cardiologists in the United States.

Reinnervation post-heart transplantation

Heart transplantation results in complete denervation of the donor heart with loss of afferent and efferent nerve connections. The majority of patients remain completely denervated during the first 6-12 months following transplantation. Evidence of reinnervation is usually found during the second year after transplantation and involve the myocardial muscle, sinoatrial node, and coronary vessels, but remains incomplete and regionally limited many years post-transplant. Restoration of cardiac innervation can improve exercise capacity as well as blood flow regulation in the coronary arteries, and hence improve quality of life. As yet, there is no evidence that the reinnervation process is associated with the occurrence of allograft-related events or survival.

Kidney transplantation as a therapeutic option for end-stage renal disease developing after heart transplantation.

BACKGROUND Progressive renal failure is a frequent complication after heart transplantation (HTx). It may result in end-stage renal disease (ESRD), prompting consideration of kidney Tx after HTx (KAH). METHODS We performed a retrospective single-center study of 268 HTx recipients to evaluate outcomes after KAH compared with HTx recipients with and without ESRD. RESULTS During a median follow-up of 76 months, ESRD developed in 51 patients (19), and 39 of them (76%) underwent KAH. The mean time from HTx to ESRD was 83 months. The incidence of switching to a calcineurin inhibitor (CNI)-free regimen based on sirolimus was significantly lower among recipients with ESRD (6% vs 57%, p = 0.0001), and prolonged exposure to CNI significantly increased the risk for ESRD (hazard ratio, 1.09; 95% confidence interval, 1.03-1.15; p < 0.005). Death-censored renal graft survival after KAH was 95%, 95%, and 83% at 1, 5, and 10 years, respectively. Median long-term survival of KAH patients was comparable to HTx recipients without ESRD (17.5 vs 17.1 years, p = 0.27) and significantly better compared with HTx recipients with ESRD (17.5 vs 7.3 years, p < 0.001). CONCLUSIONS Prolonged exposure to CNI immunosuppression medications significantly increases the risk for ESRD among HTx recipients. KAH is a good therapeutic option for HTx recipients with ESRD, with survival benefit comparable to HTx without ESRD.

Early Gains in Renal Function Following Implantation of HeartMate II Left Ventricular Assist Devices May not Persist to One Year

Renal function improves early after left ventricular assist device (LVAD) implantation but later decline has been observed. We sought to determine the occurrence and evaluate possible causes for this decline. In 62 consecutive patients with HeartMateII LVAD with available calculated glomerular filtration rate (GFR, ml/min/1.73 m2) 1 year after implant, GFR was assessed repeatedly and possible predictors for decline from 3 to 12 months were investigated. Post-mortem renal specimens for patients supported with an LVAD were evaluated. GFR 54.5 ± 19.5 at admission increased to 66.4 ± 22.3 preoperatively and to 79.2 ± 30.1 ~1 month after implantation. Subsequently at ~3 months GFR declined to 74.7 ± 25.4, at ~6 months to 68.8 ± 23.1, and ~1 year after implant to 63.9 ± 17.7. Glomerular filtration rate at 1 year was significantly lower (p < 0.0001, p < 0.0001, p = 0.005) than GFR 1, 3, and 6 months after implant. Early rise in GFR after surgery was not associated with late decline. Shorter bypass time (&bgr; = −0.09, p = 0.048) and higher albumin 3 months after LVAD (&bgr; = 14.4, p = 0.025) were significantly associated with less later decline in GFR. Arteriosclerosis was identified in autopsy renal specimens. In conclusion, early gains in renal function after LVAD implant are not sustained in many patients. Patient, device, and operative factors may influence long-term renal function in these patients.

Sex Related Differences in the Risk of Antibody-Mediated Rejection and Subsequent Allograft Vasculopathy Post-Heart Transplantation: A Single-Center Experience

Background Pregnancies may result in antibodies against HLA, a risk factor for antibody-mediated rejection (AMR) and subsequent cardiac allograft vasculopathy (CAV) after heart transplantation (HTx). The aim of this study was to evaluate sex differences in the incidence of AMR events and subsequent risk of CAV among HTx recipients. Methods The study comprised 160 patients (51 [32%] women) who underwent HTx in 2008 to 2014. The cumulative effect of AMR events was calculated by AMR score (sum of myocardial biopsy grading divided by number of biopsies taken during 3 years post-HTx). Results Females had higher levels of anti-HLA I antibodies pre-HTx compared to males which was associated with a history of pregnancies, total number of children and with a higher AMR score at 6 months post-HTx (P < 0.05). Women demonstrated a significant increase in the total incidence of AMR events (27 vs. 7%, P = 0.001) and in AMR scores at 6, 12, 24 and 36 months post-HTx compared to men (P < 0.05). There were no differences in cellular rejection between the groups. A history of AMR events was associated with a significantly increased risk of severe CAV onset (hazard ratio, 7.0; 95% confidence interval, 1.5-31.5; P = 0.012). Conclusions Women are at higher risk for AMR post-HTx which subsequently increases their risk for CAV. Females recipients may benefit from closer surveillance to identify AMR at an earlier stage post-HTx, and targeted immunosuppressive therapy to attenuate the development of CAV.

LEFT VENTRICULAR ASSIST DEVICE THERAPY IN PATIENTS WITH ADULT CONGENITAL HEART DISEASE

As a result of advancements in surgical repair and treatment, there are an increasing number of patients with congenital heart disease surviving into adulthood. Continuous flow left ventricular assist devices (LVAD) have been infrequently used in those patients that develop end stage heart failure,

Elevated ST2 levels are associated with antibody-mediated rejection in heart transplant recipients

Soluble ST2 (sST2) is a novel biomarker of inflammation and fibrosis. Elevated sST2 levels (≥35 ng/mL) are associated with worse outcomes in patients with heart failure (HF). There are sparse data regarding the significance of sST2 levels after heart transplantation (HTx). The study aims were to evaluate trends in soluble ST2 levels after the resolution of HF status with HTx and association between post‐HTx sST2 levels and outcomes. Plasma sST2 levels were measured at baseline (median [IQR] of 118 days pre‐HTx) and 12 months post‐HTx in 62 subjects who were stratified into two groups by post‐HTx sST2 levels < or ≥35 ng/mL: “Group 1” or “Group 2,” respectively. Plasma sST2 levels were elevated in 58% of patients pre‐HTx and in 50% of patients post‐HTx. There was no association between elevated sST2 levels before and after HTx, and no significant differences in baseline characteristics between Group 1 and Group 2 patients. Group 2 as compared to Group 1 HTx recipients had significantly higher incidence of antibody‐mediated rejection (AMR) for the entire post‐transplant follow‐up period (32% vs 4%, P = 0.006). There was no association between post‐HTx sST2 level status and other post‐HTx outcomes including survival. In conclusion, elevated plasma sST2 levels after HTx are associated with increased risk for AMR.

Cardiac Transplantation: Denervation, Reinnervation, and Myocardial Blood Flow

The intact heart is innervated by the parasympathetic and sympathetic fibers of the autonomic nervous system. Cardiac transplantation results in transection of the postganglionic neural axons innervating the heart. Axonal degeneration develops within days after transplantation and leads to total depletion of cardiac norepinephrine stores and eventual disappearance of nerve terminals in the transplanted tissue, resulting in total cardiac denervation.

Suspected ARVC in the Athlete: Do T-Wave Findings Really Help in Diagnosis?

Sudden cardiac death (SCD) associated with exercise in young athletes is a rare and tragic event. These deaths are usually due to a variety of cardiac diseases, which may be structural, electrical, or acquired abnormalities that are unsuspected and may become manifest in the setting of strenuous