Predictors of death and transplant in patients with a mechanical circulatory support device: a multi-institutional study.

BACKGROUND: INTERMACS is a registry of FDA-approved durable mechanical circulatory support (MCS) devices used for the strategies of destination therapy (DT) and bridge to transplantation (BTT) or recovery. This study identifies predictors for death and transplantation based on initial results from INTERMACS. METHODS: From June 23, 2006 to December 31, 2007, 420 patients from 75 institutions were prospectively entered into the INTERMACS database in which pre-implant data, indication for MCS device use, adverse events, demographics, hemodynamics, laboratory values and outcomes were recorded. Using competing outcomes methodology, risk factors were identified for the events of death and transplantation. RESULTS: The devices included 314 left ventricular assist devices (LVADs), 5 right VADs (RVADs), 77 biventricular VADs (biVADs) and 24 total artificial hearts (TAHs) for a total of 497 pumps in 420 patients. Among the BTT patients at 6 months, 33% were alive with a device in place, 42% were transplanted, 22% had died, and 3% were explanted for recovery. Among the DT patients at 6 months, 68% were alive with a device in place, 5% were transplanted, 25% had died, and 2% were explanted for recovery. The risk factors identified for death across all patient groups include older age (relative risk [RR] = 1.41, p < 0.001), ascites (RR = 2.04, p = 0.003), increased bilirubin (RR = 1.49, p < 0.05) and INTERMACS Level 1 (cardiogenic shock) (RR = 1.59, p = 0.02). The most common causes of death were central nervous system (CNS) event (18.3% of deaths), multiple-organ failure (16.4%) and cardiac cause (right ventricular failure and arrhythmias, 15.4%). CONCLUSIONS: Cardiogenic shock, advanced age and severe right heart failure manifested as ascites or increased bilirubin are risk factors for death after MCS therapy. BTT patients who require biVAD support have a transplant rate similar to that of LVAD-only patients, but their mortality at 6 and 12 months exceeds that of LVAD-only patients. Consideration should be given to MCS referral before the sequelae of right ventricular failure dominate the advanced heart failure syndrome.

Tricuspid annular motion as a predictor of severe right ventricular failure after left ventricular assist device implantation.

BACKGROUND: Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is associated with a high rate of morbidity and mortality. We sought to determine pre-operative right heart echocardiographic predictors of post-LVAD severe RV failure. METHODS: RV failure, defined as the need for inotropic support or pulmonary vasodilators for >or=14 days post-operatively, was evaluated in 33 patients (age 54 +/- 13 years) with LVADs. Preoperative RV systolic and diastolic echocardiographic parameters, including RV fractional area change, tricuspid annular motion, right atrial volume index, RV index of myocardial performance, hepatic vein Doppler velocities, tricuspid regurgitation severity, and RV systolic pressures (RVSPs) in patients with and without RV failure were compared. RESULTS: Of the 33 patients evaluated, 11 (33%) had post-LVAD RV failure (2 needed RVAD support). Patients with post-LVAD RV failure had significantly lower pre-operative tricuspid annular motion (8 +/- 4 vs 15 +/- 6 mm, p < 0.01) and higher RVSPs (60 +/- 14 vs 46 +/- 11 mm Hg, p = 0.02). In 13 patients (39%) with moderate tricuspid regurgitation, pre-operative tricuspid annular motion remained significantly reduced (6.0 +/- 0.5 vs 13.5 +/- 5.0 mm, p = 0.045). Other echocardiographic parameters were not significantly different between patients. Tricuspid annular motion of <7.5 mm provides 91% specificity and 46% sensitivity in predicting post-LVAD RV failure. CONCLUSION: Tricuspid annular motion is a predictor of post-LVAD RV failure. Using tricuspid annular motion in addition to conventional criteria may aid in early identification of patients with prolonged inotropic support or severe RV failure and allow for better pre-operative planning.

Hyperhomocysteinemia in patients with heart failure referred for cardiac transplantation: preliminary observations.

BACKGROUND: Hyperhomocysteinemia is becoming recognized as a risk factor for cardiovascular disease, yet there are limited data on the prevalence of hyperhomocysteinemia in patients with heart failure. HYPOTHESIS: The purpose of this study was to examine the prevalence of hyperhomocysteinemia in patients with severe heart failure and to correlate serum homocysteine levels with factors that may affect homocysteine metabolism. METHODS: Serum homocysteine levels were measured at the time of cardiac transplant evaluation in 89 consecutive patients with severe heart failure. Homocysteine levels for patients with ischemic cardiomyopathy (ICM) were compared with levels obtained in patients with nonischemic cardiomyopathy (NICM), and homocysteine levels were correlated with demographic and hemodynamic parameters as well as functional status. RESULTS: The mean plasma homocysteine level was increased (14.3 +/- 5.3 micromol/l, normal <9.0 micromol/l) and was equivalent between patients with ICM versus NICM (14.7 +/- 5.8 micromol/l vs. 13.8 +/- 4.5 micromol/l, p = 0.44). Elevated homocysteine levels were seen in a large proportion (89%) of patients and were equally common to patients with NICM (94%) and ICM (85%). Serum homocysteine levels correlated with serum creatinine (r = 0.51, p < 0.001), with a history of diabetes (p = 0.028), and with a history of peripheral vascular disease (p = 0.045). Only 6% of patients were receiving folic acid therapy at the time of transplant referral. CONCLUSION: Hyperhomocysteinemia is common in patients with severe heart failure, and plasma homocysteine levels are uniformly elevated regardless of the etiology of heart failure. Elevated plasma homocysteine levels are likely a consequence of heart failure-related renal insufficiency.

Comparison of dobutamine versus milrinone therapy in hospitalized patients awaiting cardiac transplantation: a prospective, randomized trial.

BACKGROUND: The use of dobutamine or milrinone for inotropic support in patients with heart failure awaiting cardiac transplantation is largely arbitrary and based on institutional preference. The costs and effectiveness of these drugs have yet to be compared in a prospective, randomized study. METHODS: We compared clinical outcomes and costs associated with the use of dobutamine or milrinone in 36 hospitalized patients awaiting cardiac transplantation. Patients were randomly assigned to receive either dobutamine or milrinone at the time of initial hospitalization and were followed until death, transplantation, or placement of mechanical cardiac support (intra-aortic balloon pump or left ventricular assist device). RESULTS: Seventeen patients were randomly assigned to receive dobutamine (mean dose 4.1 +/- 1.4 microg/kg/min) and 19 patients received milrinone (mean dose 0.39 +/- 1.0 microg/kg/min). Therapy lasted 50 +/- 46 days for those in the dobutamine group and 63 +/- 45 days in the milrinone group. We did not detect differences between the 2 groups in right heart hemodynamics, death, need for additional vasodilator/inotropic therapy, or need for mechanical cardiac support before transplantation. Ventricular arrhythmias requiring increased antiarrhythmic therapy occurred frequently in both groups. Total acquisition cost of milrinone was significantly higher than that of dobutamine (16,270 dollars +/- 1334 vs 380 dollars +/- 533 P <.00001). CONCLUSIONS: Both dobutamine and milrinone can be used successfully as pharmacologic therapy for a bridge to heart transplantation. Despite similar clinical outcomes, treatment with milrinone incurs greater cost.

Percutaneous coronary intervention versus medical therapy for coronary allograft vasculopathy. One center's experience.

BACKGROUND: Coronary allograft vasculopathy, a rapidly progressive form of atherosclerosis, remains the limiting factor in the long-term survival of heart transplant recipients. Some centers have attempted percutaneous coronary intervention to slow the disease process and thereby reduce mortality in these patients, but long-term follow-up data are scarce. We compared clinical outcomes in heart transplant recipients with coronary allograft vasculopathy who were treated either with percutaneous coronary intervention or with aggressive medical therapy alone. METHODS: A retrospective analysis of all heart transplant recipients at our institution who underwent surveillance coronary angiography for coronary allograft vasculopathy between 1995 and 2000 was performed. Patients with coronary allograft vasculopathy were stratified according to whether they received medical therapy or percutaneous coronary intervention. Baseline demographics, results of re-vascularization procedures and outcomes were analyzed. RESULTS: From 1995 to 2000, 301 patients underwent 602 coronary angiograms. Of the 79 patients who had angiographic evidence of coronary allograft vasculopathy, 53 were treated with aggressive medical therapy, while 26 underwent percutaneous coronary intervention in addition to aggressive medical therapy. At baseline, patients treated with aggressive medical therapy tended to be younger (54.6 +/- 13.8 years) than patients treated with percutaneous coronary intervention (62.6 +/- 7.6 years; p = 0.0079). Ejection fraction at time of diagnosis of coronary allograft vasculopathy was similar for both groups (medical therapy group, 44.4 +/- 13.4% vs percutaneous coronary intervention group, 47.2 +/- 12.7%; p = 0.38). In our cohort, heart transplant recipients with coronary allograft vasculopathy demonstrated greater mortality than heart transplant recipients without coronary allograft vasculopathy (p = 0.016). Patients who underwent percutaneous coronary intervention had a 60% re-stenosis rate at 6 months if they were treated with coronary angioplasty and an 18% re-stenosis rate if they received a coronary stent. Kaplan-Meier analysis showed no significant difference in survival in either treatment group at 1 year (80% for medical therapy group vs 95% for percutaneous coronary intervention group) or 3 years (68% for medical therapy group vs 79% for percutaneous coronary intervention group) after the angiographic diagnosis of coronary allograft vasculopathy. CONCLUSION: In this non-randomized trial, heart transplant recipients with coronary allograft vasculopathy were less likely to survive than patients without it. In addition, we found no statistical difference in mortality in heart transplant recipients with coronary allograft vasculopathy, regardless of whether they received percutaneous coronary intervention or aggressive medical therapy alone.