Congestive Heart Failure Trial Research Articles

Left Ventricular Assist Device Destination Therapy Versus Extended Criteria Cardiac Transplant

End-stage heart failure is a growing problem associated with a high mortality using conventional medical care. Although cardiac transplantation is an excellent treatment option, it is a limited resource and most patients are ineligible for cardiac transplantation using standard listing criteria. Increasingly, newer surgical options for these patients include the usage of marginal donor organs in an extended criteria-alternate list heart transplant program (EC-AL), or left ventricular assist devices as destination therapy (DT-LVAD). The purpose of this study was to compare baseline characteristics and outcomes after EC-AL versus DT-LVAD. From March 2000 to August 2008, 153 consecutive patients who had been turned down for standard heart transplantation underwent either EC-AL or DT-LVAD. The most common reasons for standard heart transplant ineligibility for both groups were advanced age, diabetes mellitus with end-organ dysfunction, and significant renal insufficiency. Patients in the alternate list program received a donor organ that had been turned down by all other centers for standard list recipients. The most common reasons for donor heart refusal were decreased left ventricular function, left ventricle hypertrophy, or coronary artery disease. Outcomes for both groups were retrospectively reviewed after Institutional Review Board permission was obtained. Comparisons were also made between patients that had been matched by propensity score analysis. In all, 93 patients underwent EC-AL, and 60 underwent DT-LVAD. Baseline preoperative characteristics of both groups were similar except that 87% of DT-LVAD patients (52 of 60) required preoperative mechanical or inotropic support whereas only 51% of EC-AL patients (47 of 93) required support (p<0.0001). Thirty-day operative mortality and 1-year survival were 2.5% and 82.2% for EC-AL and 6.7% and 77.5% DT-LVAD, respectively (p=0.2411 and p=0.5036). Overall survival at 3 years was better for EC-AL versus DT-LVAD. The DT-LVAD patients had improved survival compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial DT-LVAD cohort, a historical control. These findings were corroborated in the analysis of propensity-matched patients. Preoperatively, the DT-LVAD cohort was more unstable, with greater need for inotropes or mechanical support. Despite this, perioperative and 1-year mortality was similar for the two groups. Three-year survival was better for EC-AL. The DT-LVAD patient survival was better than that of the REMATCH DT-LVAD cohort.

Triage After Hospitalization With Advanced Heart Failure: The ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) Risk Model and Discharge Score

Identifying high-risk heart failure (HF) patients at hospital discharge may allow more effective triage to management strategies. Heart failure severity at presentation predicts outcomes, but the prognostic importance of clinical status changes due to interventions is less well described. Predictive models using variables obtained during hospitalization were created using data from the ESCAPE (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) trial and internally validated by the bootstrapping method. Model coefficients were converted to an additive risk score. Additionally, data from FIRST (Flolan International Randomized Survival Trial) was used to externally validate this model. Patients discharged with complete data (n = 423) had 6-month mortality and death and rehospitalization rates of 18.7% and 64%, respectively. Discharge risk factors for mortality included BNP, per doubling (hazard ratio [HR]: 1.42, 95% confidence interval [CI]: 1.15 to 1.75), cardiopulmonary resuscitation or mechanical ventilation during hospitalization (HR: 2.54, 95% CI: 1.12 to 5.78), blood urea nitrogen, per 20-U increase (HR: 1.22, 95% CI: 0.96 to 1.55), serum sodium, per unit increase (HR: 0.93, 95% CI: 0.87 to 0.99), age >70 years (HR: 1.05, 95% CI: 0.51 to 2.17), daily loop diuretic, furosemide equivalents >240 mg (HR: 1.49, 95% CI: 0.68 to 3.26), lack of beta-blocker (HR: 1.28, 95% CI: 0.68 to 2.41), and 6-min walk, per 100-foot increase (HR: 0.955, 95% CI: 0.99 to 1.00; c-index 0.76). A simplified discharge score discriminated mortality risk from 5% (score = 0) to 94% (score = 8). Bootstrap validation demonstrated good internal validation of the model (c-index 0.78, 95% CI: 0.68 to 0.83). The ESCAPE study discharge risk model and score refine risk assessment after in-hospital therapy for advanced decompensated systolic HF, allowing clinicians to focus surveillance and triage for early life-saving interventions in this high-risk population. (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness [ESCAPE]; NCT00000619).

Atrial Fibrillation in the Setting of Heart Failure

In the treatment and management of atrial fibrillation (AF), the debate over ‘rate versus rhythm’ has largely been answered by several large randomised prospective clinical trials that have shown no distinct advantage for one strategy over the other in terms of clinical outcomes. Prior to the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial, these studies were largely conducted on patients without heart failure (HF) and included patients with paroxysmal AF. Notably, only 23% of patients enrolled in the largest rate versus rhythm AF trial to date, Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM), had HF. However, the treatment of patients with both AF and HF remains a specific challenge. While anticoagulation treatment is necessary in all cases, the definition of the optimal therapy prescribed to control arrhythmia itself is much more difficult. There appear to be specific advantages of sinus rhythm in patients who have AF and HF. These might include a salutary effect of sinus rhythm due to at least three factors: regularisation of the rhythm, physiological rate control and restoration of atrial contribution to cardiac output. It would be prudent to assess carefully whether patients presenting with both AF and HF will benefit from improved outcomes following restoration and maintenance of sinus rhythm, whether achieved by drug therapy or catheter ablation.

Hemodynamics, diuretics, and nesiritide: a retrospective VMAC analysis.

Hypotension has been proposed as the cause of nesiritide-associated increases in serum creatinine (SCr); however, this hypothesis has not been tested. This retrospective evaluation of patients who had a pulmonary artery catheter and received nesiritide in the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) trial assessed hypotension, SCr elevation, concomitant therapy, and mortality. Patients were categorized by baseline pulmonary capillary wedge pressure (PCWP) and analyzed both for overall population and by diuretic dose. Compared with patients with PCWP > 23 mm Hg (n = 105), patients with PCWP < or = 23 mm Hg (n = 49) had more hypotension within 24 hours of initiating nesiritide (16% vs 7%), but neither more SCr elevation by nominal day 30 (29% vs 28%) nor higher mortality (30 days: 8.2% vs 7.7%; 6 months: 29.0% vs 29.3%). The risk of hypotension was directly related to high dose diuretics (25% vs 6%; relative risk [RR]: 4.2; 95% confidence interval [CI]: 1.10-15.82) and was not significantly increased in patients without this concomitant treatment (10% vs 7%; RR: 1.4; 95% CI: 0.34-5.93). Additionally, high dose diuretics significantly increased the risk of SCr elevation (RR: 2.6; 95% CI: 1.03-6.64) and 6 month mortality (hazard ratio: 3.6; 95% CI: 1.19-10.63) in patients with PCWP < or = 23 mm Hg. Hypotension is not the primary etiology for nesiritide-associated increases in SCr. High dose diuretics increase the risk of adverse outcomes in patients with PCWP < or = 23 mm Hg and should be reserved for patients in whom PCWPs are known to be markedly elevated.

Correlation of impedance cardiography with invasive hemodynamic measurements in patients with advanced heart failure: The BioImpedance CardioGraphy (BIG) substudy of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) Trial

Impedance cardiography (ICG) is a noninvasive modality that uses changes in impedance across the thorax to assess hemodynamic parameters, including cardiac output (CO). The utility of ICG in patients hospitalized with heart failure is uncertain. The BioImpedance CardioGraphy in Advanced Heart Failure study was a prospective substudy of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness. A total of 170 subjects underwent blinded ICG measurements using BioZ (CardioDynamics, San Diego, CA); of these, 82 underwent right heart catheterization. We compared ICG with invasively measured hemodynamics by simple correlation and compared overall ICG hemodynamic profiles ("wet" [thoracic fluid content > or =47/kOhm in men and > or =37/kOhm in women] and "cold" [cardiac index < or =2.2 L min(-1)m(-2)) versus those determined by invasive measurements (wet [pulmonary capillary wedge pressure > or =22 mm Hg] and cold [cardiac index < or =2.2 L min(-1)m(-2)). We also determined whether ICG measurements were associated with subsequent death or hospitalization within 6 months. There was modest correlation between ICG and invasively measured CO (r = 0.4 to 0.6 on serial measurement). Thoracic fluid content measured by ICG was not a reliable measure of pulmonary capillary wedge pressure. There was poor agreement between ICG and invasively measured hemodynamic profiles (kappa < or =0.1). No ICG variable alone or in combination was associated with outcome. In hospitalized patients with advanced heart failure, ICG provides some information about CO but not left-sided filling pressures. Impedance cardiography did not have prognostic utility in this patient population.

Effect of pulmonary hypertension on clinical outcomes in advanced heart failure: Analysis of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) database

Pulmonary hypertension has been shown to predict hospitalizations and mortality in patients with heart failure. We aimed to define the prevalence of mixed pulmonary hypertension (MPH; mean pulmonary artery pressure > or = 25 mm Hg, pulmonary capillary wedge pressure >15 mm Hg, and pulmonary vascular resistance > or = 3 Wood units), identify clinical predictors of MPH, and determine whether MPH predicts adverse outcomes in patients hospitalized with severe heart failure. This is a subgroup analysis of patients assigned to pulmonary artery catheter placement in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Patients with and without MPH were compared with respect to baseline characteristics and clinical outcomes, including NYHA class, 6-minute walk distance, quality of life, days hospitalized, and 6-month mortality. Of the 171 patients studied, 80 (47%) had MPH. Older age was the only significant predictor of MPH. MPH patients had lower cardiac index (1.8 +/- 0.5 L/min vs 2.1 +/- 0.5 L/min, P = .001) and higher systemic vascular resistance index (3,179 +/- 1,454 vs 2,550 +/- 927 dynes x s/cm5 x m2, P < .001) compared to those without MPH. Importantly, right ventricular function was relatively preserved (median RVSWI 8.7 gm-m/m2/beat) in MPH patients. There were no significant differences in clinical outcomes between the two groups. Mixed pulmonary hypertension is common in patients hospitalized with advanced heart failure and is not associated with adverse short-term clinical outcomes over and above the poor prognosis of ADHF patients without MPH.

Enhanced external counterpulsation for the treatment of stable angina and heart failure: a systematic review and economic analysis

To determine the clinical effectiveness and cost-effectiveness of enhanced external counterpulsation (EECP) compared with usual care and placebo for refractory stable angina and heart failure, and to undertake analyses of the expected value of information to assess the potential value of future research on EECP. Major electronic databases were searched between November 2007 and March 2008. A systematic review of the literature was undertaken and a decision model developed to compare EECP treatment with no treatment in adults with chronic stable angina. Five studies were included in the review. In the Multicenter Study of Enhanced External Counterpulsation (MUST-EECP), time to greater than or equal to 1-mm ST segment depression (exercise-induced ischaemia) was statistically significantly improved in the EECP group compared with the control group (sham EECP), mean difference (MD) 41 seconds [95% confidence interval (CI) 9.10-73.90]. However, there was no statistically significant difference between the EECP and control groups in the change in exercise duration from baseline to end of treatment, self-reported angina episodes or daily nitroglycerin use, and the clinical significance of the limited benefits was unclear. There was also a lack of data on long-term outcomes. There were more withdrawals due to adverse events in the EECP group than in the control group, as well as a greater proportion of patients with adverse events [relative risk (RR) 2.13, 95% CI 1.35-3.38]. The three non-randomised studies compared EECP with elective percutaneous coronary intervention (PCI) and usual care. There was a high risk of selection bias in all three studies and the results should be treated with considerable caution. The study comparing an EECP registry with a PCI registry reported similar 1-year all-cause mortality in both groups. In the Prospective Evaluation of EECP in Congestive Heart Failure (PEECH) trial, patients with heart failure were randomised to EECP or to usual care (pharmacotherapy only). At 6 months post treatment, the proportion of patients achieving at least a 60-second increase in exercise duration was higher in the EECP group (RR 1.39, 95% CI 0.89-2.16), but the proportion with an improvement in peak VO2 was similar in both groups. The clinical significance of this is unclear. The proportion of patients in the EECP group with an improvement in New York Heart Association classification was higher (RR 2.25, 95% CI 1.25-4.06) at 6 months, as was mean exercise duration, MD 34.6 (95% CI -4.86 to 74.06). There were more withdrawals in the EECP group than in the control group as a result of adverse events (RR 1.05, 95% CI 0.67-1.66). There were limitations in the generalisability of results of the trial and, again, a lack of data on long-term outcomes. The review of cost-effectiveness evidence found only one unpublished study but demonstrated that the long-term maintenance of quality of life benefits of EECP is central to the estimate of its cost-effectiveness. The incremental cost-effectiveness ratio of EECP was 18,643 pounds for each additional quality-adjusted life-year (QALY), with a probability of being cost-effective of 0.44 and 0.70 at cost-effectiveness thresholds of 20,000 pounds and 30,000 pounds per QALY gained respectively. Results were sensitive to the duration of health-related quality of life (HRQoL) benefits from treatment. The results from a single randomised controlled trial (MUST-EECP) do not provide firm evidence of the clinical effectiveness of EECP in refractory stable angina or in heart failure. High-quality studies are required to investigate the benefits of EECP, whether these outweigh the common adverse effects and its long-term cost-effectiveness in terms of quality of life benefits.

Left ventricular device as destination therapy: are we there yet?

Mechanical circulatory assistance is evolving from bridge-to-transplant to destination therapy for end-stage heart failure patients. Recent studies document the evolution in outcomes following destination therapy achieved subsequent to the landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial, as well as the outcomes of second-generation left ventricular assist devices (LVADs). Post-Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure destination therapy patients receiving first-generation pulsatile flow devices have benefited from some improvement in 2-year outcomes and some reduction in the incidence of adverse events including device failure and sepsis. Despite these improvements, survival at 2 years remains poor and adverse events continue to portend significant morbidity and mortality. Second-generation continuous axial flow devices have demonstrated superior device durability and reliability as well as significant reductions in the incidence of sepsis and device-related infections in bridge-to-transplant patients. Second-generation axial flow devices have significantly improved the adverse-event profile of LVAD therapy and are anticipated to offer substantial device longevity. Destination therapy is clearly an option for some patients with end-stage heart failure. As devices and experience evolve, outcomes will improve, which begs the question of whether these devices will have a role in the treatment of patients not as ill as those in the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial.

Atrial fibrillation and congestive heart failure

The present review will examine the prognostic importance of atrial fibrillation and heart failure, explore the different therapeutic options for treating atrial fibrillation and present the results of the Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial. The Atrial Fibrillation and Congestive Heart Failure trial was a randomized trial involving patients with both atrial fibrillation and heart failure. The trial was designed to compare the maintenance of sinus rhythm with the control of ventricular rate in patients with left ventricular dysfunction, heart failure and a history of atrial fibrillation. There was no significant difference in the rate of death from cardiovascular causes in the rhythm-control group as compared with the rate-control strategy. In addition, there was no significant difference in any of the secondary outcomes including death from any cause, worsening heart failure or stroke. The rate-control strategy eliminated the need for repeated cardioversion and reduced rates of hospitalization. The results of the Atrial Fibrillation and Congestive Heart Failure trial indicate that a routine strategy of rhythm control does not reduce rate of death and suggest that rate control should be considered a primary approach for patients with atrial fibrillation and heart failure.

Atrial Fibrillation in Heart Failure Patients

There is a sinister synergism between atrial fibrillation (AF) and heart failure (HF). These common cardiovascular conditions often co-exist and result in significant morbidity and mortality. Despite the extensive amount of research and literature about each of these disorders separately, randomised controlled clinical trial data concerning the management of AF in patients with HF are lacking. The recently published Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial elucidated the matter of rhythm versus rate control. In addition, non-pharmacological treatment approaches such as catheter ablation of AF and cardiac resynchronisation therapy are rapidly growing and are likely to alter AF management in HF patients in the near future.

Atrial fibrillation and congestive heart failure: should we aim to control the heart's rate or its rhythm?

The Atrial Fibrillation and Congestive Heart Failure trial, which was conducted in patients with a reduced left ventricular ejection fraction, demonstrates that prognosis is independent of whether treatment is targeted towards controlling the heart's rate or its rhythm. The study also showed that other factors, such as use of beta-blockers, angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, oral anticoagulants, and implantable cardioverter-defibrillators, can have a major influence on prognosis. Antiarrhythmic drugs (primarily amiodarone) were well tolerated, and adequate rate control was achieved with adjusted doses of beta-blockers combined with digoxin. Future studies should focus on the clinical importance of radiofrequency ablation for atrial fibrillation, versus that of traditional approaches to treatment.

Association of Weight Change With Subsequent Outcomes in Patients Hospitalized With Acute Decompensated Heart Failure

The association of weight loss achieved through various decongestive strategies with clinical outcomes in patients with acute decompensated heart failure (HF) is not well described. The aim of this study was to determine the relation between weight change during hospitalization and subsequent clinical events in patients with decompensated HF. Data from 433 patients hospitalized with advanced HF enrolled in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial were evaluated. The influence of change in weight during hospitalization to clinical outcomes (days alive out of the hospital in the first 6 months; death; death or rehospitalization; and death, rehospitalization, or cardiac transplantation) was evaluated. On average, patients lost approximately 3.6 kg during hospitalization. When categorized into 3 weight loss tertiles, those in the highest tertile were more likely to be older, women, and smokers, with higher body weights, previous percutaneous coronary interventions, baseline heart rates, and brain natriuretic peptide and blood urea nitrogen values but lower ejection fractions and peak oxygen consumption. No significant differences were observed between weight change and any in-hospital or follow-up events (days well: hazard ratio 0.995, 95% confidence interval 0.975 to 1.016; 180-day death: hazard ratio 1.012, 95% confidence interval 0.969 to 1.057; death or rehospitalization at 180 days: hazard ratio 1.014, 95% confidence interval 0.990 to 1.038). In conclusion, weight loss in patients with acute decompensated HF during hospitalization was not related to clinical end points. These data challenge the merit of using weight as a surrogate end point for more important clinical events (i.e., death and/or rehospitalization) in patients with HF in the design of treatment strategies for novel therapeutic agents in randomized controlled clinical trials.

Destination Therapy: Current Results and Future Promise

The landmark Randomized Evaluation of Mechanical Assistance in the Treatment of Congestive Heart Failure (REMATCH) trial demonstrated that the implantation of left ventricular assist devices (LVADs) as an alternative to heart transplantation, or destination therapy (DT) is superior to any known medical therapy in patients with end-stage heart failure who are not eligible for transplantation. In this article, we review results of the first United States and European clinical trials of DT, including the REMATCH, the Investigation of the Non-Transplant Eligible Patients who are Inotrope Dependent (INTREPID), and the Clinical Utility Baseline Study (CUBS) trials, as well as the outcomes of the first DT implantations in the post-REMATCH era in the United States. The article summarizes the current state of knowledge and future directions in the field of permanent mechanical circulatory support therapy as an alternative to heart transplantation.

The Cost of Medical Management in Advanced Heart Failure During the Final Two Years of Life

Objective To examine patterns of resource use and the cost of care for patients with advanced heart failure treated with medical management (MM) during the final 2 years of life. Methods and Results The study population (n = 47, mean age 70.4 years ± 7.06) included patients randomized to the MM arm of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. Inpatient and outpatient use data were obtained from the clinical dataset and Centers for Medicare and Medicaid Services (beginning January 1, 1998). Cost and resource use were tracked from the date of death (t d) backward in 3-month intervals (eg, t d-1, t d-2). In the primary analysis, costs were summed across intervals. The mean cost of MM in the final 2 years of life was $156,169, with 50.5% ($78,880.39) expended in the final 6 months. The mean quarterly cost increased ( P < .01) 4.9-fold from t d-8 ($8,816 ± $14,270) to t d-1 ($42,836 ± $41,407). The number of inpatient days increased ( P < .01) 6.6-fold from 3.8 ± 4.7 days to 22.2 ± 23.5 days during the same time intervals. Conclusion This current economic analysis extends on previous findings by demonstrating that medical therapy in advanced and end-stage heart failure is associated with significant costs and resource consumption; these costs and resource consumption increase significantly as death approaches.

Effect of repeated intracoronary injection of bone marrow cells in patients with ischaemic heart failure☆ The Danish Stem Cell study—Congestive Heart Failure trial (DanCell‐CHF)

It has been suggested that myocardial regeneration may be achieved by a single intracoronary bone marrow derived stem cell infusion in selected patients with ischaemic heart disease. The effect is uncertain in patients with chronic ischaemic heart failure and it is not known whether repeated infusions would have additional positive effects. To assess whether two treatments of intracoronary infusion of bone marrow stem cells, administered 4 months apart, could improve left ventricular (LV) systolic function in patients with chronic ischaemic heart failure. The study was prospective and non-randomised, comprising an observational baseline period of 4 months followed by an interventional period of 12 months. Intracoronary bone marrow cell infusion was performed at the end of the baseline period and repeated 4 months later. 32 patients were included. LV ejection fraction remained unchanged (33+/-9% vs. 34+/-10% after 8 months, p=0.30). Likewise, there was no significant change in LV end-systolic volume, wall motion score index (WMSI) or contractile reserve. At 12 months, a decrease in target vessel WMSI was seen (2.17+/-0.34 vs. 2.06+/-0.46, p=0.02). Furthermore, NYHA class improved (p<0.0001). No deaths were observed. In this non-randomised study, no change in LV ejection fraction could be demonstrated after repeated intracoronary bone marrow stem cell treatment in patients with chronic ischaemic heart failure.

Preliminary report on the effects of ultrafiltration in severe heart failure: the Continuous Ultrafiltration for cOngestive heaRt failurE (CUORE) trial

Preliminary report on the effects of ultrafiltration in severe heart failure: the Continuous Ultrafiltration for cOngestive heaRt failurE (CUORE) trial

Improving outcomes with long-term “destination” therapy using left ventricular assist devices

Destination therapy experience using long-term left ventricular assist devices was analyzed relative to the benchmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial to evaluate the potential for improving outcomes with this groundbreaking therapy for advanced heart failure. The largest single-center experience with destination therapy in the United States (Utah Artificial Heart Program, LDS Hospital, Salt Lake City, UT) was retrospectively analyzed. All destination therapy recipients (n = 23) presented with chronic, advanced heart failure, meeting indications for destination therapy adopted from the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. All received HeartMate left ventricular assist devices (Thoratec Corp, Pleasanton, Calif), with 87% receiving an improved XVE model. Advanced practice guidelines were implemented using a multidisciplinary approach. Survivals (Kaplan-Meier, log-rank analyses) and adverse events (Poisson regression) were compared with those of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device group (n = 68). Survival in the destination therapy group was significantly increased (P = .007), with an overall reduction in mortality of 66%. The 2-year survival was 77% for destination therapy compared with 29% for the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device group (P < .0001). The 1-year survival was 77% for destination therapy compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device rate of 52% (P = .036). Adverse events decreased by 38% (3.90 per patient-year in the destination therapy group compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device rate of 6.32). Factors related to severity of illness met Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure-like criteria for both groups. This analysis provides evidence that long-term destination therapy can be improved well beyond the pioneering experience of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. With continued evolution of devices, management, and patient selection, outcomes approaching those of heart transplantation may be possible.

Outcomes of Left Ventricular Assist Device Implantation as Destination Therapy in the Post-REMATCH Era

The landmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial first demonstrated that implantation of left ventricular assist devices (LVADs) as destination therapy (DT) can provide survival superior to any known medical treatment in patients with end-stage heart failure who are ineligible for transplantation. In the present study, we describe outcomes of DT in the post-REMATCH era in the United States. The present study included 280 patients who underwent HeartMate XVE LVAD implantation between November 2001 and December 2005. A preoperative risk score for in-hospital mortality after LVAD implantation was established in 222 patients with complete data. All patients were followed up until death or December 2006. The 1-year survival after LVAD implantation was 56%. The in-hospital mortality after LVAD surgery was 27%. The main causes of death included sepsis, right heart failure, and multiorgan failure. The most important determinants of in-hospital mortality were poor nutrition, hematological abnormalities, markers of end-organ or right ventricular dysfunction, and lack of inotropic support. Stratification of DT candidates into low (n=65), medium (n=111), high (n=28), and very high (n=18) risk on the basis of the risk score calculated from these predictors corresponded with 1-year survival rates of 81%, 62%, 28%, and 11%, respectively. Appropriate selection of candidates and timing of LVAD implantation are critical for improved outcomes of DT. Patients with advanced heart failure who are referred for DT before major complications of heart failure develop have the best chance of achieving an excellent 1-year survival with LVAD therapy.

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

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. 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. 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 of pulmonary artery catheters in advanced heart failure

Randomized trials have demonstrated that use of the pulmonary artery catheter does not improve outcomes in patients with critical illness. Despite this, pulmonary artery catheters continue to be used, especially in heart failure. This review addresses recent clinical trials evaluating the safety and efficacy of the pulmonary artery catheter. It also offers guidelines on when pulmonary artery catheter use could be considered in patients with advanced heart failure. A meta-analysis demonstrated that use of the pulmonary artery catheter in critically ill patients had no significant impact on morbidity or mortality. In the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial, the addition of the pulmonary artery catheter to careful clinical assessment also had neutral impact. The results of the study are limited, however, by the patient population that was selected for the study, and there still may be a role for the pulmonary artery catheter in advanced heart failure. Based on the results of the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial and the meta-analysis, there is no indication for routine use of pulmonary artery catheters to adjust therapy during hospitalization for decompensation of chronic heart failure. There remain many specific clinical situations in heart failure in which the pulmonary artery catheter may be useful, however.