Prospective evaluation of elastic restraint to lessen the effects of heart failure (PEERLESS-HF) trial.

BACKGROUND: Left ventricular (LV) remodeling predicts poor outcomes in heart failure (HF) patients. The HeartNet(®) cardiac restraint device (Paracor Medical Inc., Sunnyvale, CA) may reduce LV remodeling and improve functional capacity, quality of life, and outcomes in HF patients. To evaluate the safety and efficacy of the HeartNet Ventricular Support System in HF patients receiving optimal medical therapy. METHODS AND RESULTS: Prospective, randomized, controlled, multicenter trial in patients with symptomatic HF and LV ejection fraction ≤35% on optimal medical and device therapy. The primary efficacy end points were changes in peak VO(2), 6-minute walk (6MW) distance, and Minnesota Living with Heart Failure (MLWHF) quality of life score at 6 months. The primary safety end point was all-cause mortality at 12 months. Because the planned adaptive interim analysis of the first 122 subjects with a completed 6-month follow-up indicated futility to reach the peak VO(2) end point, trial enrollment was suspended. Hence, the results on the 96 treatment and 114 control subjects are reported. Groups were similar at baseline. At 6 months, responder frequency for a prespecified improvement was similar between groups for peak VO(2) (P = .502) and MLWHF score (P = .184) but borderline higher for improvement in 6MW distance in the treatment compared with the control group (33 [38%] vs. 25 [25%]; P = .044). At 6 months, the treatment group had a significantly greater improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) (P < .001) and decrease in LV mass (P = .032), LV end-diastolic diameter (P = .015), LV end-systolic diameter (P = .032), and LV end-diastolic volume (P = .031) as compared with controls. At 12 months, all-cause mortality and responder rates were similar in the 2 groups. Success rate for the HeartNet implantation was 99%. CONCLUSION: Enrollment in the trial was stopped because an interim analysis showed futility of reaching the peak VO(2) end point. However, because of the device safety and favorable signals for LV remodeling and quality of life, further investigation of this device is warranted.

Assessing historical compliance with medical recommendations among transplant candidates: preliminary findings.

CONTEXT: Noncompliance with medical recommendations by transplant candidates and recipients carries serious consequences for morbidity and mortality. Few patient-specific, objective measures for assessing historical compliance exist. OBJECTIVE: To address this gap, a psychometric and exploratory analysis of an interview-based, global measure of clinician-rated judgment of historical compliance was undertaken. METHODS: All findings are based on a retrospective chart review of the medical and psychosocial evaluations of 96 consecutive potential heart transplant candidates seen at a large Southeastern academic medical center. RESULTS: Preliminary results demonstrated adequate interrater reliability and discriminant validity for the measure. Additionally, results from hierarchical multivariable regression analysis revealed years of education to be positively associated with clinician-rated judgment of historical compliance. CONCLUSIONS: This study provides preliminary psychometric support for the use of a measure of historical compliance among heart transplant candidates. Findings from this study also are consistent with the literature to date and may be reflective of a psychobiological process that mediates the relationship between socioeconomic status and health outcomes.

Bradycardia and syncope as a presentation of cardiac allograft rejection involving the conducting system.

Post-heart transplantation bradycardic syncope and arrest could be due to preferential rejection of the conduction system. We present six heart transplant patients with this presentation, two of whom died. The autopsy of one of those patients demonstrated severe rejection of the conduction system, with only mild rejection throughout the rest of the myocardium. We postulate that aggressive therapy for rejection and pacemaker placement may result in improved survival in heart transplant recipients with this clinical presentation.

Safety and efficacy of ibutilide in heart transplant recipients.

In this report we describe our experience with ibutilide, a relatively new Class III anti-arrhythmic agent, in 8 heart transplant patients with supraventricular tachycardia in various settings (3 patients with rejection, 2 after endomyocardial biopsy). Ibutilide treatment was successful in all patients, with the arrhythmia recurring early in 1 patient. There were no complications.

Treprostinil-based therapy in the treatment of moderate-to-severe pulmonary arterial hypertension: long-term efficacy and combination with bosentan.

BACKGROUND: Treprostinil, a long-acting prostacyclin analog, diminished the symptoms of pulmonary arterial hypertension (PAH) in controlled 12-week clinical efficacy studies. This retrospective, single-center, open-label study was designed to assess the efficacy of long-term, subcutaneously administered, treprostinil-based therapy alone or in combination with bosentan for the treatment of moderate-to-severe PAH. METHODS: Thirty-eight patients with pulmonary hypertension treated with subcutaneous treprostinil were followed up for a mean (+/-SD) duration of 984+/-468 days (range, 165 to 1,847 days). Oral bosentan was added to the treprostinil regimen if patients remained in New York Heart Association (NYHA) functional class III or II with intolerable prostacyclin side effects that limited therapy. Hemodynamic studies, Borg dyspnea score evaluations, 6-min walk (6MW) tests, and NYHA functional class determinations were performed at approximately 6-month intervals. RESULTS: Mean pulmonary artery pressure decreased from 59.7 to 50.5 mm Hg (p<0.001). Significant and sustained improvement in 6MW distance (p=0.022) and Borg dyspnea score (p=0.023) were observed. At the final observation, the mean dose of treprostinil was 37.8 ng/kg/min (range, 7.5 to 115 ng/kg/min). At baseline, 5% of patients were in NYHA functional class 2 or lower vs 58% at the last follow-up. Bosentan was added to the regimens of 19 patients. In those patients, significant additional improvement occurred in the pulmonary arterial pressure (p<0.001), 6MW distance (p=0.001), and Borg dyspnea scale (p=0.020) compared to baseline. CONCLUSIONS: Long-term treatment with subcutaneous treprostinil-based therapy improved functional parameters and hemodynamics in patients with moderate-to-severe PAH. In patients requiring combination therapy, the addition of oral bosentan to treprostinil-based therapy was safe, well-tolerated, and associated with further clinical improvements.

Worldwide surgical experience with the Paracor HeartNet cardiac restraint device.

OBJECTIVE: An elastic ventricular restraint device has been developed for patients with heart failure who remain symptomatic despite treatment with standard therapies. The safety and efficacy of this device are under clinical investigation. Six-month data for the first 51 patients treated worldwide are reported. We hypothesize that the Paracor HeartNet device (Paracor Medical, Sunnyvale, Calif), placed through a minithoracotomy in patients with severe dilated cardiomyopathy, improves clinical and functional status. METHODS: Fifty-one patients with an ejection fraction of 35% or less, with a New York Heart Association class II or III, and receiving optimal medical therapy for at least 3 months, were selected at 15 sites (3 in Europe, 12 in the United States) to undergo implantation of the HeartNet device through a minithoracotomy. Patients were evaluated at baseline and at 6-month follow-up by echocardiography, the 6-minute walk test, cardiopulmonary exercise testing (partial oxygen pressure in mixed venous blood), New York Heart Association class, and (in the United States) the Minnesota Living with Heart Failure questionnaire. RESULTS: The average age was 52 years (30-73 years), with a preponderance of men and nonischemic cause of heart failure. Implantation was accomplished in 50 of 51 patients (98%). Adverse events included 2 in-hospital deaths secondary to pulmonary complications (4%), additional pulmonary complications in 7 patients (14%), arrhythmia in 14 patients (27%), epicardial laceration in 2 patients (4%), and empyema in 1 patient (2%). Six-month data demonstrated significant improvement in the 6-minute walk test (+65.7, P = .002) and Minnesota Living with Heart Failure scores (-15.7, P = .002) and improvement in echocardiographic findings. CONCLUSION: The Paracor HeartNet device can be reliably implanted in patients with heart failure and marked reduction of left ventricular function. These data suggest a functional and clinical benefit, with a trend toward reverse remodeling, and support the conduct of a randomized controlled pivotal trial.

Post-heart transplant diastolic dysfunction is a risk factor for mortality.

OBJECTIVES: The purpose of this study was to evaluate the incidence and prognostic implication of diastolic dysfunction (DD) occurring in the first year after transplant. BACKGROUND: Diastolic dysfunction is a recognized complication in heart transplant recipients, but its true incidence and natural history has been poorly characterized. We studied the prognostic implication of DD, as defined by elevated filling pressures with normal systolic function, occurring in the first year after transplant. METHODS: Between June 1992 and June 2002, all patients who underwent heart transplantation at a single institution were included in the study (231 at 6 weeks and 250 at 6 months and 1 year). Diastolic dysfunction was defined as right atrial pressure (RAP) >/=15 mm Hg (right ventricular [RV] DD) or pulmonary capillary wedge pressure >/=18 mm Hg (left ventricular [LV] DD) with normal systolic function by echocardiogram and without severe mitral or tricuspid insufficiency. In addition, RV DD was defined by a RAP/stroke volume (SV) ratio. RESULTS: The incidence of DD was 22%, 8%, and 12% at 6 weeks, 6 months, and 1 year, respectively. The incidence of LV DD was more frequent than that of RV DD at any time point (p < 0.0001). By multivariable analysis RV DD, as manifested by an elevated RAP/SV, but not LV DD was a strong predictor of cardiac mortality at all time points. CONCLUSIONS: Diastolic dysfunction is common early after transplant, and its incidence decreases during the first year. Right ventricular DD, as measured by an elevated RAP/SV ratio, but not LV DD is a strong predictor of cardiac mortality. Further studies are needed to evaluate the functional status of patients with RV or LV DD and whether aggressive medical therapy for early DD could alter outcome.

Device therapy for remodeling in congestive heart failure.

Heart failure is a progressive condition which begins after an inciting event that leads to neurohormonal activation and cardiac remodeling. Medical therapy with beta-blockers and angiotensin-converting enzyme inhibitors has been shown to attenuate neurohormonal changes and left ventricular remodeling. Despite optimal medical therapy, patients often progress, and other therapeutic modalities have been sought to interrupt and reverse the process of remodeling. Various devices have been developed and entered into clinical trials with the intent of promoting reverse remodeling by directly altering the mechanical properties or shape of the left ventricle. This article reviews devices currently undergoing clinical trials.

Initial United States experience with the Paracor HeartNet myocardial constraint device for heart failure.

OBJECTIVE: This study was undertaken to review the initial results and surgical safety data for the US Food and Drug Administration safety and feasibility trial of the Paracor HeartNet (Paracor Medical, Inc, Sunnyvale, Calif.) myocardial constraint device. METHODS: Patients with New York Heart Association functional class II or III heart failure underwent device implantation (n = 21) through a left minithoracotomy. RESULTS: The average age was 53 years (31-72 years). There were 18 men and 3 women, and 17 patients had nonischemic etiology of heart failure. Mean heart failure duration was 8.3 years (1.4-18.8 years). Average ejection fraction was 22% (11%-33%), with an average left ventricular end-diastolic dimension of 74 mm (55-94 mm). Previous medical therapy included angiotensin-converting enzyme inhibitors, beta-blockers, diuretics, digoxin, and aldosterone receptor blockers. At implantation, 17 patients had implantable electronic devices: 1 biventricular pacemaker, 11 biventricular pacemakers with cardioverter-defibrillators, and 5 implantable cardioverter-defibrillators. Patient comorbidities included hypertension in 10 cases, diabetes mellitus in 8, myocardial infarction in 1, and ventricular tachycardia in 8. Mean operative time was 68 minutes (42-102 minutes), and implantation time averaged 15 minutes (5-51 minutes). The average time to ambulation was 1.6 days (1-4 days). The intensive care unit stay averaged 3.3 days (1-16 days), and hospital stay averaged 6.3 days (4-16 days). Atrial fibrillation occurred in 2 patients, and there were 2 in-hospital deaths. CONCLUSIONS: The Paracor device can be implanted in patients with heart failure and reduced left ventricular function with a high degree of success. Significant surgical complications were infrequent. The initial US experience supports the conduct of a randomized, controlled, pivotal trial.

A phase 1-2 dose-escalating study evaluating the safety and tolerability of istaroxime and specific effects on electrocardiographic and hemodynamic parameters in patients with chronic heart failure with reduced systolic function.

Istaroxime (PST2744) is a luso-inotrope that stimulates the sarcoplasmic reticulum calcium adenosine triphosphatase isoform 2a without chronotropic effects. Additionally, it has beneficial effects on myocardial energetics. This phase 1-2 clinical trial in patients with chronic stable heart failure (HF) is the first evaluation of istaroxime in humans. Three cohorts of 6 patients each were exposed to 4 sequentially increasing 1-hour infusions with a random placebo. Doses were 0.005-5.0 micro/kg per min. Safety and hemodynamics were evaluated by impedance cardiography, digital Holter recorder, and electrocardiography. Pharmacokinetic data were obtained for 1 hour during treatment and for 6 hours after dosing. The mean age was 53+/-7 years, and the mean left ventricular ejection fraction was 0.27+/-0.08. Impedance cardiography demonstrated enhanced contractility as measured by the acceleration index, left cardiac work index, cardiac index, and pulse pressure at doses>or=1 micro/kg per min, with evidence of activity at doses of 0.5 micro/kg per min. Istaroxime shortened QTc. After infusion, the hemodynamic effect rapidly dissipated over 1-2 hours. Istaroxime was pharmacologically active and well tolerated at doses up to 3.33 micro/kg per min. Side effects were related to gastrointestinal symptoms and injection site pain at higher doses, which dissipated within minutes after the infusion ended. Ventricular ectopy was not altered. This study suggests that istaroxime is potentially useful in the treatment of HF and may offer a unique treatment for systolic and/or diastolic dysfunction. Additional studies are under way to further define its utility in acute HF.

Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure.

BACKGROUND: Treatment of decompensated heart failure often includes the use of intravenous vasoactive medications, but the effect on outcome has not been clearly defined. METHODS: Data from 433 patients enrolled in the ESCAPE trial were analyzed to determine 6-month risks of all-cause mortality and all-cause mortality plus rehospitalization associated with the use of vasodilators, inotropes, and their combination. Patients had a mean left ventricular ejection fraction of 19%, 6-minute walk distance of 414 ft, and systolic blood pressure of 106 mm Hg. The main outcome measure was multivariable risk-adjusted 6-month hazard ratios (HRs). RESULTS: Overall 6-month mortality was 19%. Risk-adjusted HRs were not statistically significant for vasodilators (1.39, 95% CI 0.64-3.00), but were significant for inotropes (2.14, 95% CI 1.10-4.15) and the combination (4.81, 95% CI 2.34-9.90). Risk-adjusted 6-month mortality plus rehospitalization HRs were not significant for vasodilators (1.20, 95% CI 0.81-1.78, P = .37), but were significant for inotropes (1.96, 95% CI 1.37-2.82, P < .001) and their combination (2.90, 95% CI 1.88-4.48, P = .001). The decision to use vasodilators or inotropes was determined by hemodynamic parameters and renal function, but the main factor was treatment site. CONCLUSIONS: In ESCAPE, the choice of medications was mainly determined by the treatment site. Use of inotropic agents was associated with adverse outcomes, whereas the use of vasodilators was not. Inotropes in combination with vasodilators identified a group with the highest mortality. Prospective studies are needed to establish the appropriate use of vasoactive medications in this population.

Efficacy of bosentan in a small cohort of adult patients with pulmonary arterial hypertension related to congenital heart disease.

OBJECTIVES: This study was designed to assess the tolerability and efficacy of the oral endothelin receptor antagonist bosentan in adult patients with pulmonary arterial hypertension (PAH) related to congenital heart disease (CHD). BACKGROUND: Severe PAH in the setting of CHD is a debilitating syndrome for which there are limited treatment options. This is the first long-term study experience in adults reporting on the tolerability and efficacy of therapy with bosentan for this patient population. METHODS: A 12-month single-center experience with 19 women and 5 men with PAH associated with CHD (79% in New York Heart Association [NYHA] class III) was analyzed. Hemodynamic responses, exercise capacity, and Borg dyspnea index were assessed prior to the administration of bosentan, and again at 3, 6, and 12 months after the study began. Clinical assessments were performed monthly for up to 12 months. The change from baseline was tested using the Wilcoxon pairs test. RESULTS: There was significant improvement in hemodynamics from baseline to 12 months (mean [+/- SD] systolic pulmonary arterial pressure, 99 +/- 30 to 87 +/- 28 mm Hg [p

Response of doxorubicin-induced cardiomyopathy to the current management strategy of heart failure.

BACKGROUND: Doxorubicin (D) (Adriamycin) is a potent and efficacious chemotherapeutic agent in the treatment of various forms of cancer, but its use has been limited by the development of cardiac toxicity. Historically, D-induced cardiomyopathy (CMP) has been refractory to therapy. We report our experience with this form of CMP at the University of Alabama at Birmingham. METHODS: Twenty-five patients (20 women, 5 men) with a clinical diagnosis of D-CMP were referred to our program from 1990 to 2003. Patient data were extracted from office charts. RESULTS: Patients were followed-up for 71 +/- 58 months. On presentation, the average left ventricular ejection fraction (LVEF) was 26 +/- 9.2%, and 88% of patients were New York Heart Association (NYHA) Class III or IV. Patients were treated with angiotensin-converting enzyme inhibitors (ACEi; n = 23) or angiotensin-receptor blocker (ARB; n = 2), and 15 were treated with a combination of ACEi and beta-blockers (BB). With medical therapy, LVEF improved significantly (26 +/- 9.2% vs 35 +/- 16.5%, p = 0.022), as did the NYHA class (p < 0.003). All survivors (n = 19) were NYHA Class I or II with medical therapy, with 10 (53%) being Class I. In the group of patients treated with ACEi + BB, there was a statistically significant improvement in LVEF (26 +/- 10.0% vs 37 +/- 17.6%, p = 0.028), which not seen in the ACEi group, with a strong trend toward normalization of LV function (47% vs 10%, p = 0.054). CONCLUSIONS: In the current era of management of heart failure, D-CMP carries a better prognosis than previously described. Early addition of BB may further improve LVEF.

Multi-organ transplantation: is there a protective effect against acute and chronic rejection?

BACKGROUND: Heart-lung transplantation (Tx) is known to offer a protective effect against acute cardiac rejection. This study was undertaken to evaluate acute and chronic heart and/or lung rejection in the setting of multiple-transplanted organs from the same donor compared with single-organ transplantation. METHODS: Acute (treated rejection episodes of heart or lungs) and chronic (allograft vasculopathy in hearts and bronchiolitis obliterans syndrome [BOS] in lungs) rejection events were analyzed in 348 heart transplant (H) recipients, 24 heart-lung (HL) recipients, 82 double-lung (L) recipients and 8 heart-kidney (HK) recipients >18 years of age, who were transplanted between 1990 and 2002. RESULTS: Survival at 3 years differed among groups as follows: HK, 100%; H, 82%; HL, 74%; and L, 70%. The probability of acute rejection within the first 3 months was higher in H recipients than in HL (81% vs 22%; p < 0.0001) or HK (81% vs 12%; p = 0.00009) recipients. Acute cardiac rejection occurred more frequently during the first 2 years in isolated H recipients compared with HL (2.8 vs 0.27 episodes; p < 0.0001) and HK (2.8 vs 0.54; p < 0.001) recipients. Acute lung rejection occurred more frequently in the first 2 years in L than HL (2.4 vs 1.0 episodes; p = 0.02) recipients. Chronic cardiac rejection (allograft vasculopathy) was more likely within 3 years after H compared with HL (32% vs 16%; p = 0.04) or HK (32% vs 0%; p = 0.14). The onset of chronic lung rejection (BOS) within 3 years was similar in HL and L recipients (39% vs 40%; p = 0.9). CONCLUSIONS: Recipients of multiple organs from a single donor undergo less acute rejection of the heart or lungs compared with isolated heart or lung transplant recipients. Cardiac allograft vasculopathy is decreased significantly when cardiac transplantation is combined with a lung allograft. A lower incidence of cardiac allograft vasculopathy is observed when cardiac transplantation is combined with a renal allograft, and may prove statistically significant when more cases have been accumulated. These phenomena may result from immune modulation of the recipient by simultaneous transplant of disparate tissues or introduction of immune-modulating hematopoietic elements.

Statin use and risks of death or fatal rejection in the Heart Transplant Lipid Registry.

Although small, randomized trials have shown that statin use is associated with decreased risks of mortality and severe rejection, no study has examined statin therapy as used in actual practice in large numbers of heart transplant recipients. We analyzed data from the Heart Transplant Lipid Registry (n = 12 centers). Patients were included if they underwent transplantation between 1995 and 1999, survived >/=30 days after transplantation, and had >/=30 days of Registry follow-up. Multivariable Cox regression models, with propensity scoring performed to adjust for nonrandom allocation of statin therapy, were performed to determine the association of statin therapy with death and fatal rejection. The study included 1,186 patients, with a mean follow-up of 580 +/- 469 days; 937 patients (79%) received statin therapy. Overall, 71 patients (6%) died and 40 (3.4%) had fatal rejection. The statin group had a lower frequency of death (4% vs 13.7%, p <0.0001) and fatal rejection (2.4% vs 7.2%, p = 0.0001). Using multivariable Cox regression, with propensity scoring included to adjust for likelihood of receiving statin therapy, statin use was the only factor associated with lower risk of death (hazard ratio 0.29, 95% confidence interval 0.13 to 0.67) and fatal rejection (hazard ratio 0.27, 95% confidence interval 0.09 to 0.78). This study represents the largest population of heart transplant recipients analyzed for the relation between statin therapy and clinical outcomes in actual practice. Statin therapy was significantly associated with lower risk of death and fatal rejection, benefits that were independent of lipid values.

Infection in ventricular assist devices: prevention and treatment.

Infection is one of the most important challenges to the use of implanted mechanical circulatory support systems (MCSS), particularly as we enter the era of permanent device use in patients who are not candidates for cardiac transplantation. This paper describes the pathogenesis of MCSS infection, with particular attention to the role of biofilm-forming bacteria. Suggestions are presented for the prevention and treatment of infections in implanted MCSS.

Beraprost therapy for pulmonary arterial hypertension.

OBJECTIVES: The purpose of this study was to assess the safety and efficacy of the oral prostacyclin analogue beraprost sodium during a 12-month double-blind, randomized, placebo-controlled trial in patients with pulmonary arterial hypertension (PAH). BACKGROUND: Pulmonary arterial hypertension is a progressive disease that ultimately causes right heart failure and death. Despite the risks from its delivery system, continuous intravenous epoprostenol remains the most efficacious treatment currently available. METHODS: A total of 116 patients with World Health Organization (WHO) functional class II or III primary pulmonary hypertension or PAH related to either collagen vascular diseases or congenital systemic to pulmonary shunts were enrolled. Patients were randomized to receive the maximal tolerated dose of beraprost sodium (median dose 120 microg four times a day) or placebo for 12 months. The primary end point was disease progression; i.e., death, transplantation, epoprostenol rescue, or >25% decrease in peak oxygen consumption (VO(2)). Secondary end points included exercise capacity assessed by 6-min walk test and peak VO(2), Borg dyspnea score, hemodynamics, symptoms of PAH, and quality of life. RESULTS: Patients treated with beraprost exhibited less evidence of disease progression at six months (p = 0.002), but this effect was not evident at either shorter or longer follow-up intervals. Similarly, beraprost-treated patients had improved 6-min walk distance at 3 months by 22 m from baseline and at 6 months by 31 m (p = 0.010 and 0.016, respectively) compared with placebo, but not at either 9 or 12 months. Drug-related adverse events were common and were related to the disease and/or expected prostacyclin adverse events. CONCLUSIONS: These data suggest that beneficial effects may occur during early phases of treatment with beraprost in WHO functional class II or III patients but that this effect attenuates with time.

Mechanical circulatory support for myocarditis: how much recovery should occur before device removal?

A 12-year-old girl with presumed myocarditis was supported with right and left ventricular assist devices for 68 days before device removal. During this time, the patient underwent echocardiography and right heart catheterization for evaluation of cardiac recovery. This case report serves as the basis for a discussion of criteria for deciding when to terminate mechanical circulatory support in a patient with recovery after acute myocarditis.

Treatment of end-stage heart disease with outpatient ventricular assist devices.

BACKGROUND: Initiating outpatient therapy with ventricular assist devices (VAD) was important in the progress of mechanical circulatory support. This article reviews our experience with VAD therapy from the start of our outpatient program until the present. METHODS: Medical records of patients who received a Thoratec para-corporeal VAD, HeartMate vented electrical VAD, or HeartMate pneumatic VAD between 12/1/97 and 9/1/01 were reviewed. Variables included age, type of devices, total duration of VAD support, discharge status, duration of outpatient support, outcome (transplanted, died on support, ongoing), in-hospital length of stay after transplantation, and complications during VAD support. RESULTS: There were 53 device implants in 46 patients. The cumulative patient-days of VAD support was 7,468 (mean duration of support, 138 +/- 195 days; median, 95 days; range, 2 to 948 days). Twenty of the 46 patients were discharged with a VAD. The cumulative outpatient days was 3,600 (mean outpatient duration, 157 +/- 164 days; median, 83 days; maximum, 560 days). Of the 20 outpatients, 11 received cardiac transplantation, 5 died, and 4 are ongoing as of 9/1/01. Major complications that occurred in the outpatient setting included 5 deaths after hospital readmission (1 sepsis, 1 conduit tear, 3 neurologic events); 4 device infections (3 sepsis, 1 pouch infection); and 3 device malfunctions that required reoperation for pump replacement (1 HeartMate pneumatic and 2 HeartMate vented electrical). No deaths occurred in an outpatient setting. CONCLUSIONS: Ventricular assist devices effectively support outpatients for months to years. The anticipated time for postoperative recovery and VAD training before discharge is approximately 14 to 21 days, although shorter times may be possible in the future. Establishing a successful outpatient VAD program is a crucial step toward VAD as definitive therapy for end-stage heart disease.