Background Right ventricular (RV) failure after left ventricular assist device (LVAD) placement is a serious complication and is difficult to predict. In the era of destination therapy and the total artificial heart, predicting post-LVAD RV failure requiring mechanical support is extremely important. Methods We reviewed patient characteristics, laboratory values, and hemodynamic data from 266 patients who underwent LVAD placement at the University of Pennsylvania from April 1995 to June 2007. Results Of 266 LVAD recipients, 99 required RV assist device (BiVAD) placement (37%). We compared 36 parameters between LVAD (n=167) and BiVAD patients (n=99) to determine preoperative risk factors for RV assist device (RVAD) need. By univariate analysis, 23 variables showed statistically significant differences between the two groups (P ≤ 0.05). By multivariate logistic regression, cardiac index ≤ 2.2 L/min·m2 (odds ratio [OR] 5.7), RV stroke work index ≤ 0.25 mmHg·mL/m2 (OR 5.1), severe preoperative RV dysfunction (OR 5.0), preoperative creatinine ≥ 1.9 mg/dL (OR 4.8), previous cardiac surgery (OR 4.5), and systolic blood pressure ≤ 96 mmHg (OR 2.9) were the best predictors of RVAD need. Conclusions The most significant predictors for RVAD need were cardiac index, RV stroke work index, severe preoperative RV dysfunction, creatinine, previous cardiac surgery, and systolic blood pressure. Using these, we constructed an algorithm which can predict which LVAD patients will require RVAD with greater than 80% sensitivity and specificity.

Objective It is generally accepted that patients who require biventricular mechanical support (BiVAD) have poorer outcomes than those requiring isolated left ventricular support (LVAD). However, it is unknown how the timing of BiVAD insertion affects outcomes. We hypothesized that planned BiVAD insertion improves survival compared to delayed conversion of LVAD to BiVAD. Methods We reviewed and compared outcomes of 266 patients undergoing LVAD or BiVAD placement at the University of Pennsylvania from April 1995 to June 2007. We subdivided BiVAD patients into planned BiVAD (P-BiVAD) and delayed BiVAD (D-BiVAD) groups, based on the timing of RVAD insertion. We defined D-BiVAD as any failure of isolated LVAD support. Results Of 266 LVAD patients, 99 required BiVAD (37%). We compared preoperative characteristics, successful bridging to transplant, survival to hospital discharge, and Kaplan-Meier one-year survival between P-BiVAD (n=71) and D-BiVAD (n=28) groups. Preoperative comparison showed that patients who ultimately require biventricular support have similar preoperative status. LVAD (n=167) outcomes in all categories exceeded both P-BiVAD and D-BiVAD outcomes. Further, P-BiVAD patients had superior survival to discharge than D-BiVAD patients (51% v 29% p<0.05). One-year and long-term Kaplan-Meier survival distribution confirmed this finding. There was also a trend towards improved bridging to transplant in P-BiVAD (n=55) vs. D-BiVAD (n=22) patients (65% v 45% p=0.10). Conclusion When patients at risk for isolated LVAD support failure are identified, proceeding directly to BiVAD implantation is advised, as early institution of biventricular support results in dramatic improvement in survival.

Abbreviations used: CHO -Chinese hamster ovary; DTT -dithiothreitol; EDTAethylenediaminotetraacetic acid; EIA -enzyme immunoassay; LAD -left anterior descending; SDS -sodium dodecyl sulphate Abstract: Apelin interacts with the APJ receptor to enhance inotropy. In heart failure, apelin-APJ coupling may provide a means of enhancing myocardial function. The alterations in apelin and APJ receptor concentrations with ischemic cardiomyopathy are poorly understood. We investigated the compensatory changes in endogenous apelin and APJ levels in the setting of ischemic cardiomyopathy. Male, Lewis rats underwent LAD ligation and progressed into heart failure over 6 weeks. Corresponding animals underwent sham thoracotomy as control. Six weeks after initial surgery, the animals underwent hemodynamic functional analysis in the presence of exogenous apelin-13 infusion and the hearts were explanted for western blot and enzyme immunoassay analysis. Western blot analysis of myocardial APJ concentration demonstrated increased APJ receptor protein levels with heart failure (1890750±133500 vs. 901600±143120 intensity units, n=8, p=0.00001). Total apelin protein levels increased with ischemic heart failure as demonstrated by enzyme immunoassay (12.0±4.6 vs. 1.0±1.2 ng/ml, n=5, p=0.006) and western blot (1579400±477733 vs. 943000±157600 intensity units, n=10, p=0.008). Infusion of apelin-13 significantly enhanced myocardial function in sham and failing hearts. We conclude that total myocardial apelin and APJ receptor levels increase in compensation for ischemic cardiomyopathy. ISCHEMIC HEART FAILURE ENHANCES ENDOGENOUS MYOCARDIAL APELIN AND APJ RECEPTOR EXPRESSION

Background-Heart failure is a global health concern. As a novel therapeutic strategy, the induction of endogenous myocardial regeneration was investigated by initiating cardiomyocyte mitosis by expressing the cell cycle regulator cyclin A2. Methods and Results-Lewis rats underwent left anterior descending coronary artery ligation followed by peri-infarct intramyocardial delivery of adenoviral vector expressing cyclin A2 (n ϭ32) or empty adeno-null (n ϭ32). Cyclin A2 expression was characterized by Western Blot and immunohistochemistry. Six weeks after surgery, in vivo myocardial function was analyzed using an ascending aortic flow probe and pressure-volume catheter. DNA synthesis was analyzed by proliferating cell nuclear antigen (PCNA), Ki-67, and BrdU. Mitosis was analyzed by phosphohistone-H3 expression. Myofilament density and ventricular geometry were assessed. Cyclin A2 levels peaked at 2 weeks and tapered off by 4 weeks.