Randomized controlled trial of ventricular elastic support therapy in the treatment of symptomatic heart failure: rationale and design.

BACKGROUND: Despite the current drug and device therapies, heart failure remains associated with high rates of disability, morbidity, and mortality. There is a need for newer therapies. One investigational approach is the use of ventricular support devices. These devices reduce ventricular wall stress leading to decreases in left ventricular (LV) volumes, dimensions, and mass. Ventricular support devices have been shown to reverse pathological ventricular remodeling, improve systolic function, and improve symptoms of heart failure. The Prospective Evaluation of Elastic Restraint to LESSen the effects of Heart Failure (PEERLESS-HF) trial was designed to further evaluate the safety and efficacy of one such device, the HeartNet (Paracor Medical, Sunnyvale, CA). METHODS: The HeartNet is an elastic ventricular restraint device formed from nitinol and covered in silicone, implanted using a minimally invasive approach. The aim of this randomized controlled trial is to compare optimal heart failure drug and device therapy plus the HeartNet (treatment group) to optimal drug and device therapy alone (control group) in patients with advanced systolic heart failure (LV ejection fraction ≤35% and LV end diastolic diameter <85 mm). Primary efficacy end points include the change in peak VO(2), quality of life score, and 6-minute hall walk distance from baseline to 6 months. The primary safety objective is to demonstrate noninferiority for all-cause mortality at 12 months. Planned enrollment is for 272 patients at approximately 35 centers in North America. CONCLUSIONS: The PEERLESS-HF trial will evaluate the safety and efficacy of ventricular elastic support in advanced systolic heart failure, advancing our knowledge of this investigational approach to heart failure therapy.

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.

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.

Left ventricular collapse secondary to pericardial effusion treated with pericardicentesis and percutaneous pericardiotomy in severe pulmonary hypertension.

A 61-year-old white female, a Jehovah's Witness, with severe pulmonary hypertension, presented with worsening heart failure symptoms. She had a pericardial effusion with left ventricular (LV) diastolic collapse on transthoracic echocardiography. She was not a candidate for surgical pericardial window and therefore underwent pericardiocentesis and percutaneous balloon pericardiotomy with remarkable improvement in her clinical condition and with no recurrence of the effusion. LV diastolic collapse, an atypical presentation of cardiac tamponade, is commonly seen in postoperative patients with localized pericardial effusions. However, outside the surgical setting, isolated LV diastolic collapse is rare. Our case is one of the first cases described in the literature of LV diastolic collapse in the setting of severe pulmonary hypertension treated successfully with pericardiocentesis and percutaneous balloon pericardiotomy.

Rationale, design, and methods for the Transplant-Eligible MAnagement of Congestive Heart Failure (TMAC) trial: a multicenter clinical outcomes trial using nesiritide for TMAC.

BACKGROUND: Urgent heart transplant candidates classified as United Network for Organ Sharing status 1B who require continuous infusions of inotropic agents for hemodynamic stability often have hemodynamic, electrical, or multisystem decompensation. This multicenter trial will study both traditional safety and efficacy parameters and the physiologic mechanisms of benefit of the addition to conventional therapy of nesiritide, a recombinant analog of brain-type natriuretic peptide, in this population. METHODS: TMAC is a prospective, randomized, parallel, multicenter, double-blind, placebo-controlled study in patients awaiting heart transplantation who meet United Network for Organ Sharing status 1B criteria (N = 120) and receive continuous dobutamine or milrinone through a double-lumen central catheter for at least 3 consecutive days before randomization. Patients will receive standard care and continuous intravenous inotrope therapy plus a 28-day continuous infusion of nesiritide or placebo. There will be up to 6 months of follow-up. Primary efficacy end point will be days alive after treatment without renal, hemodynamic, or electrical worsening at completion. Secondary analyses will evaluate effects on hemodynamics, echocardiographic parameters, endogenous brain-type natriuretic peptide levels, modification of diet in renal disease-calculated glomerular filtration rate, and all-cause and cardiovascular mortality. Two mechanistic substudies will evaluate the effect on iohexol-determined glomerular filtration rate and assess changes in lung mechanics. CONCLUSION: This investigation will provide key data for clinical profiles of heart transplant candidates bound to inotropic support. It will investigate the efficacy and safety (especially renal) of nesiritide and provide mechanistic insight into benefits of its use for the relief of breathlessness.

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.

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.

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

Palliation of allograft vasculopathy with transluminal angioplasty: a decade of experience.

OBJECTIVES: The goal of this study was to examine the outcomes of percutaneous coronary interventions (PCI) and the predictors for restenosis after cardiac transplantation. BACKGROUND: The role of PCI as definitive therapy for allograft coronary disease (ACD) remains contentious. METHODS: Between January 1, 1990 and December 31, 2000, 62 patients (1.5 to 15.5 years after transplant) underwent 151 procedures resulting in PCIs of 219 lesions. Follow-up after PCI angiography was usually obtained at three and six months, then yearly. Repeat PCI was routinely done to lesions with >60% restenosis. RESULTS: The primary procedural success was 97%. Repeat PCI occurred in 74 of 219 lesions (34%); PCI-related mortality was 2.6% (4 of 151). The freedom from re-PCI (of same vessel site) was 75% at six months, 65% at one year, and 57% at four years. The freedom from restenosis was 95% at one month, 81% at three months, and 57% at six months. Multivariate predictors of freedom from restenosis were the use of stents, higher anti-proliferative immunosuppressant dose, and an era effect. In the setting of one-vessel disease at first PCI, the two-year freedom for ACD death or graft loss was 74%, compared with 75% for two-vessel and 27% for three-vessel disease (p = 0.009). CONCLUSIONS: Despite the increasing effectiveness of PCI for localized ACD, the survival after development of advanced ACD remains poor. Stents appear to increase effectiveness of PCI for ACD, but other factors in the current era contribute to improved outcomes.

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.

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.

Relationship between bridging with ventricular assist device on rejection after heart transplantation.

BACKGROUND: Ventricular assist devices (VADs) are commonly used to bridge patients to heart transplantation. Recipients of VADs may develop anti-human histocompatibility leukocyte antigen antibodies, as reflected by elevated panel-reactive antibodies (PRA). The purpose of this study was to evaluate the relationship between bridging with VAD before heart transplantation and development of cellular rejection, humoral rejection, and allograft vasculopathy after transplantation. METHODS: Data on all patients who underwent cardiac transplantation between July 1994 and February 2001 at Rush Presbyterian St Luke's Medical Center were retrospectively reviewed. Data collected included sex, age, etiology of cardiomyopathy, percentage panel reactive antibodies (by cytotoxic method), type and duration of mechanical circulatory support, transfusion history, rejection history (both cellular and humoral) after cardiac transplantation, and development of allograft vasculopathy. Cellular rejection was treated when International Society of Heart and Lung and Transplantation Grade 2 or greater in the first 12 months after transplant and Grade 3 or greater after 12 months and treated with intensification of immunosuppression. Humoral rejection was defined clinically as allograft dysfunction by echocardiography without evidence of cellular rejection on endomyocardial biopsy or allograft vasculopathy. Allograft vasculopathy was defined by presence of any degree of luminal narrowing or pruning of distal vessels by coronary arteriography. Statistical analyses were performed by chi-square test, Fisher's exact test, and Wilcoxon rank sum test, as appropriate. RESULTS: Ninety-eight patients underwent cardiac transplantation during the study period (87 men, mean age 49 years, 46 ischemic etiology). Of these, 48 were bridged with HeartMate VAD (20 patients received vented electric device, 28 received pneumatic device). Nineteen percent of VAD patients had a peak pretransplant PRA > or =10% vs 2% of patients without VAD (p = 0.014). PRA > or =10%, use of VAD, or duration of VAD support did not predict development of humoral rejection. Use of VAD did not predict development of cellular rejection or allograft vasculopathy. VAD use was not associated with sudden death after heart transplantation. In the entire group of 98 patients, neither humoral nor cellular rejection predicted development of allograft vasculopathy. Longer ischemic time correlated with increased cellular rejection and humoral rejection after transplantation (p = 0.01). CONCLUSIONS: Some patients bridged to cardiac transplantation with VADs have increased PRA before heart transplantation, but this does not appear to translate into increased risk of either humoral or cellular rejection after transplantation or development of allograft vasculopathy as detected by coronary angiography.

Prediction of heart transplant rejection with a breath test for markers of oxidative stress.

The Heart Allograft Rejection: Detection with Breath Alkanes in Low Levels study evaluated a breath test for oxidative stress in heart transplant recipients, and we report here a mathematical model predicting the probability of grade 3 rejection. The breath test divided the heart transplant recipients into 3 groups: positive for grade 3 rejection, negative for grade 3 rejection, and intermediate. The test was 100% sensitive for grade 3 heart transplant rejection when the p value was >/=0.98, and 100% specific when the p value was

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.

Heart allograft rejection: detection with breath alkanes in low levels (the HARDBALL study).

BACKGROUND: We evaluated a new marker of heart transplant rejection, the breath methylated alkane contour (BMAC). Rejection is accompanied by oxidative stress that degrades membrane polyunsaturated fatty acids, evolving alkanes and methylalkanes, which are excreted in the breath as volatile organic compounds (VOCs). METHODS: Breath VOC samples (n = 1,061) were collected from 539 heart transplant recipients before scheduled endomyocardial biopsy. Breath VOCs were analyzed by gas chromatography and mass spectroscopy, and BMAC was derived from the abundance of C4-C20 alkanes and monomethylalkanes. The "gold standard" of rejection was the concordant set of International Society for Heart and Lung Transplantation (ISHLT) grades in biopsies read by 2 reviewers. RESULTS: Concordant biopsies were: Grade 0, 645 of 1,061 (60.8%); 1A, 197 (18.6%); 1B, 84 (7.9%); 2, 93 (8.8%); and 3A, 42 (4.0%). A combination of 9 VOCs in the BMAC identified Grade 3 rejection (sensitivity 78.6%, specificity 62.4%, cross-validated sensitivity 59.5%, cross-validated specificity 58.8%, positive predictive value 5.6%, negative predictive value 97.2%). Site pathologists identified the same cases with sensitivity of 42.4%, specificity 97.0%, positive predictive value 45.2% and negative predictive value 96.7%. CONCLUSIONS: A breath test for markers of oxidative stress was more sensitive and less specific for Grade 3 heart transplant rejection than a biopsy reading by a site pathologist, but the negative predictive values of the 2 tests were similar. A screening breath test could potentially identify transplant recipients at low risk of Grade 3 rejection and reduce the number of endomyocardial biopsies.

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.

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.

Strategies for minimizing hyperlipidemia after cardiac transplantation.

Allograft coronary artery disease represents a major limitation to long-term survival after cardiac transplantation. Hyperlipidemias have been linked to the development of native coronary atherosclerosis, and hyperlipidemic states have correlated with the severity of allograft coronary artery disease. Heart transplant recipients typically manifest increases in plasma levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and triglycerides within the first 3-12 months following transplantation. Factors known to promote post-transplant hyperlipidemia include the use of corticosteroids, cyclosporine (interference with clearance and increased oxidizability of LDL), sirolimus (hypertriglyceridemia), and patient-specific causes of hyperlipidemia which contributed to their underlying heart disease. Hydroxymethylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors are the foundation of antilipid therapy following cardiac transplantation. Pravastatin is effective in lowering plasma cholesterol levels and is associated with a decreased incidence and progression of allograft coronary artery disease. All HMG-CoA reductase inhibitors except pravastatin are metabolized by the hepatic cytochrome P450 system which metabolizes cyclosporine, increasing the risk of myostitis when they are used in large dosages with cyclosporine. Simvastatin, atorvastatin and fluvastatin have been studied in heart transplant recipients. Gemfibrozil has proved effective in transplant recipients when there is isolated marked elevation of plasma triglyceride levels. When hyperlipidemia persists despite therapy, some benefit may result with conversion from cyclosporine to tacrolimus. Although a definitive link between hyperlipidemia and allograft coronary disease has yet to be proven, available evidence points to abnormal lipid metabolism as part of the complex etiologic machinery driving the process of 'chronic rejection'. Consensus exists within the transplant community that a HMG-CoA reductase inhibitor such as pravastatin, should be part of the routine post-transplant drug regimen, and persistent hyperlipidemia should be aggressively treated.

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.