Burhan Mohamedali

Frequency and pattern of left ventricular dysfunction in potential heart donors: implications regarding use of dysfunctional hearts for successful transplantation.

To the Editor: Cardiac transplantation is a widely accepted treatment for patients with advanced heart failure. Unfortunately only 1 in 8 hearts offered for donation is accepted for transplantation ([1][1]). Some donor hearts may be rejected due to left ventricular systolic dysfunction (LVSD) noted

Clinical Benefits of Stem Cells for Chronic Symptomatic Systolic Heart Failure A Systematic Review of the Existing Data and Ongoing Trials.

The benefits of stem cell therapy for patients with chronic symptomatic systolic heart failure due to ischemic and nonischemic cardiomyopathy (ICM and NICM, respectively) are unclear. We performed a systematic review of major published and ongoing trials of stem cell therapy for systolic heart failure and compared measured clinical outcomes for both types of cardiomyopathy. The majority of the 29 published studies demonstrated clinical benefits of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs). Left ventricular ejection fraction (LVEF) was improved in the majority of trials after therapy. Cell delivery combined with coronary artery bypass grafting was associated with the greatest improvement in LVEF. Left ventricular end-systolic volume (or diameter), New York Heart Association functional classification, quality of life, and exercise capacity were also improved in most studies after cell therapy. Most ICM trials demonstrated a significant improvement in perfusion defects, infarct size, and myocardial viability. Several larger clinical trials that are in progress employ alternative delivery modes, cell types, and longer follow-up periods. Stem cells are a promising therapeutic modality for patients with heart failure due to ICM or NICM. More data are required from larger blinded trials to determine which combination of cell type and delivery mode will yield the most benefit with avoidance of harm in these patient populations.

Changes in Spirometry After Left Ventricular Assist Device Implantation.

Left ventricular assist devices (LVADs) are increasingly being used as life-saving therapy in patients with end-stage heart failure. The changes in spirometry following LVAD implantation and subsequent unloading of the left ventricle and pulmonary circulation are unknown. In this study, we explored long-term changes in spirometry after LVAD placement. In this retrospective study, we compared baseline preoperative pulmonary function test (PFT) results to post-LVAD spirometric measurements. Our results indicated that pulmonary function tests were significantly reduced after LVAD placement (forced expiratory volume in one second [FEV1 ]: 1.9 vs.1.7, P = 0.016; forced vital capacity [FVC]: 2.61 vs. 2.38, P = 0.03; diffusing capacity of the lungs for carbon monoxide [DLCO]: 14.75 vs. 11.01, P = 0.01). Subgroup analysis revealed greater impairment in lung function in patients receiving HeartMate II (Thoratec, Pleasanton, CA, USA) LVADs compared with those receiving HeartWare (HeartWare, Framingham, MA, USA) devices. These unexpected findings may result from restriction of left anterior hemi-diaphragm; however, further prospective studies to validate our findings are warranted.

Mean Arterial Pressure to Central Venous Pressure Ratio: A Novel Marker for Right Ventricular Failure After Left Ventricular Assist Device Placement

BACKGROUND Early right ventricular failure (RVF) is common after left ventricular assist device (LVAD) implantation and often leads to increased morbidity and mortality. It is difficult to predict early RVF on the basis of clinical and hemodynamic parameters. We investigated the utility of mean arterial pressure (MAP) to central venous pressure (CVP) ratio in predicting early RVF. METHODS AND RESULTS We analyzed a retrospective cohort of 212 consecutive patients who underwent hemodynamic assessment before destination-therapy LVAD implantation. Patients were followed for early RVF and mortality. Receiver operating characteristic (ROC) analysis was used to determine discriminative capacity of MAP/CVP and tested the diagnostic and prognostic value of median MAP/CVP threshold. The ROC analysis demonstrated that pre-LVAD MAP/CVP was associated with an area under the ROC curve of 0.65 (95% confidence interval 0.58-0.73; P < .001). MAP/CVP threshold <7.5 (simple nearest-to-median value) was associated with 70% sensitivity and 56% specificity for early RV failure. Patients with MAP/CVP <7.5 had a higher incidence of post-LVAD RVF than those with a ratio ≥7.5 (44% vs 23%, respectively; P = .001). Right ventricular assist device requirement was higher in the MAP/CVP <7.5 group (11% vs 2%; P = .01). All-cause mortality was higher in the MAP/CVP <7.5 group (annualized mortality 26% vs 16%; log-rank P = .017). MAP-CVP ratio provided incremental prognostic value for RVF and all-cause mortality beyond established Heartmate II and RVF risk scores. CONCLUSIONS Our findings suggest that pre-LVAD MAP/CVP <7.5 is associated with early RVF and increased mortality risk. This novel parameter can be used in risk stratification of LVAD candidates. Prospective validation of our findings is needed.

The Influence of Pre-Left Ventricular Assist Device (LVAD) Implantation Glomerular Filtration Rate on Long-Term LVAD Outcomes

BACKGROUND Chronic kidney disease (CKD) is a known predictor for adverse outcomes in patients with advanced heart failure requiring left ventricular assist devices (LVADs). The effect of pre-LVAD glomerular filtration rate (GFR) on post-LVAD outcomes in CKD patients is not completely understood. Additionally, a subset of patients improve their GFR after LVAD placement. In this study we sought to determine the effects of pre-LVAD GFR on post-LVAD outcomes. METHODS Two hundred and seventy consecutive patients with LVADs were enrolled. Patients were stratified based on a GFR cut-off of 60mL/min/1.73m2. Patients with preoperative GFR <60 were further divided into two subgroups based post-LVAD discharge GFR of 60. Post-LVAD major adverse effects were analysed. RESULTS Patients with pre-implant GFR <60 had higher all cause mortality than patients with pre-implant GFR ≥60 (45% vs. 27%, p=0.006). These patients also had higher incidence of early right ventricular failure and congestive heart failure hospitalisations. Kaplan-Meier survival analysis confirmed poor survival in this group. When the subgroup analysis of patients in the GFR <60 cohort was performed, the above findings were heavily weighted towards patients who did not improve their GFR to ≥60 post-LVAD. CONCLUSION Pre-implant GFR is an important prognostic marker in LVAD patients. Patients with pre-implant GFR <60 are at higher risk of cardiovascular morbidity and mortality. Our findings suggest that the patients who do not improve their GFR post-LVAD are at the highest risk.

Acute Cellular Rejection and C4d Positivity in Heart Transplantation A Manifestation of Asymptomatic Antibody-Mediated Rejection?

OBJECTIVES The role of routine C4d staining in endomyocardial biopsy specimens is uncertain. The implications of a diagnosis of acute cellular rejection (ACR) with a positive C4d with or without any evidence of antibody-mediated rejection (AMR) are unclear. This study sought to evaluate a distinct phenotype of ACR+/C4d+ in AMR- patients. METHODS Data on C4d, ACR, and AMR were collected. Donor-specific antibody (DSA), panel-reactive antibody (PRA), flow crossmatch, and data on ACR and AMR episodes were also reviewed. RESULTS Thirty-five patients were followed. Group I with C4d+ biopsy specimens was compared with group II with C4d- biopsy specimens. ACR greater than 1R was higher in group I compared with group II (50% vs 7.4%; P = .01). Clinical suspicion of AMR, positive retrospective crossmatches, and detection of de novo DSA were also higher in group I. CONCLUSIONS Our result indicate that C4d and ACR positivity in posttransplant patients may be a harbinger of a subclinical form of asymptomatic AMR.

Cardiomyopathy in the Potential Kidney Transplant Candidate

Chronic kidney disease is a risk factor for cardiovascular disease and is an independent risk factor for development of cardiomyopathy even after controlling for coronary artery disease, hypertension, and diabetes. Congestive heart failure, both systolic and diastolic, in patients with end-stage renal disease is a poor prognostic marker with over 80% of patients dying within 3 years of the diagnosis. The pathophysiology of cardiomyopathy is thought to be a complex with multiple traditional risk factors (such as volume overload, hypertension, anemia) and nontraditional risk factors (such uremic toxin, inflammation, oxidative stress) being implicated. The current treatment approach is centered on treating both, the cardiomyopathy, and chronic kidney disease using guideline directed treatment algorithms focused on treating pressure and volume overload, anemia, secondary parathyroidism, and uremia. The field of transplant in patients with both congestive heart failure and end-stage renal disease is evolving. In the absence of genetic conditions or systemic infiltrative disease, most patients with isolated diastolic congestive heart failure may be listed for kidney transplantation. The work up of patients with systolic dysfunction is controversial due to a perceived high-risk candidacy. Consensus is lacking whether these patients should be listed for single organ or double organ heart/kidney transplantation. Although a majority of systolic heart failure patients will have improvement in their ejection fraction after kidney transplantation, a subset of patients has high mortality. The survival disadvantage is driven by patients who fail to improve their ejection fraction after kidney transplantation, suggesting a need for prospective trials to identify these patients.