Acceptability and psychometric properties of the Minnesota Living With Heart Failure Questionnaire among patients undergoing heart valve surgery: validation and comparison with SF-36.

BACKGROUND: Health-related quality of life (HQOL) enhancement is a major objective of valvular surgery (VS), but assessments have been limited primarily to generic measures that may not be optimally responsive to intervention. Disease-specific instruments have been used in heart failure (HF), commonly associated with valve disease, but have been neither validated nor routinely applied among patients undergoing VS. METHODS AND RESULTS: We administered the Minnesota Living with Heart Failure (MLHFQ) and SF-36 questionnaires preoperatively (T(0)) to 50 patients undergoing VS and at 1 (T(1)) and 6 months (T(2)) after VS. Performance of MLHFQ was evaluated and compared with SF-36. MLHFQ completion rates were >98% (NS vs. SF-36); Cronbach's alpha was > or = 0.9 (total score, dimensions), supporting internal reliability. Confirmatory factor analysis verified good model fit for physical/emotional domain items (relative chi-squares < 3.0, critical ratios > 2.0, both instruments), supporting structural validity. Spearman coefficients correlating MLHFQ with parallel SF-36 domains were moderate to high (0.6-0.9; P < or = .001: T(0)-T(2)), supporting convergent validity. Baseline HQOL was poorest in patients with HF (P < or = .05 [both instruments]), supporting criterion validity. Responsiveness (proportional HQOL change scores: T(0) vs. T(2)) to VS was greater with MLHFQ vs. SF-36 (P < or = .002). CONCLUSIONS: Among patients undergoing VS, the MLHFQ is highly acceptable and maintains good psychometric properties, comparing favorably with SF-36. These findings suggest its utility for measuring disease-specific HQOL changes after VS.

Evidence for the continued safety and tolerability of fixed-dose isosorbide dinitrate/hydralazine in patients with chronic heart failure (the extension to African-American Heart Failure Trial).

The benefits of fixed-dose combination isosorbide dinitrate plus hydralazine (ID/H) in African-Americans with heart failure (HF) were established by the African-American Heart Failure Trial (A-HeFT), which was terminated early because of a significant survival benefit of ID/H. The Extension to A-HeFT trial (X-A-HeFT), designed to make ID/H available for ethical reasons after A-HeFT termination, afforded an opportunity to further observe responsiveness and compliance with ID/H. In total 198 patients completing the A-HeFT took ID/H for an additional 209 +/- 116 days. Their age (57 +/- 13 years), cause and duration of HF, and HF medications were not different from all A-HeFT patients. New York Heart Association class at X-A-HeFT baseline was > or =III in 51% of patients versus 100% of all patients at A-HeFT baseline, remained unchanged in most patients, improved in 24%, and worsened in only 9% during X-A-HeFT. The average number of ID/H tablets taken during X-A-HeFT was 3.7 +/- 1.8 per day with compliance averaging 87 +/- 25%. The most common adverse events, headache (34%) and dizziness (16%), were less than in patients taking ID/H in A-HeFT, with only 6% discontinuations for adverse events. The 6% annualized mortality rate in X-A-HeFT was the same as for ID/H in A-HeFT. There were no statistically significant differences in baseline characteristics or outcomes in X-A-HeFT patients analyzed according to their A-HeFT randomization. In conclusion, these results confirm the good compliance, tolerability, and responsiveness, with low mortality and improved symptoms, during treatment with ID/H observed in A-HeFT.

Beta-blocker dosing in community-based treatment of heart failure.

BACKGROUND: Community patients with heart failure (HF) are older, less often treated by HF specialists, and have more comorbidity than those in randomized clinical trials. These differences might affect beta-blocker prescribing in HF. METHODS: To explore patterns of beta-blocker prescribing for HF in the community and their association with outcomes, we determined carvedilol doses at end titration in 4113 patients from a community-based beta-blocker HF registry according to physician and patient characteristics, HF severity, and rates of hospitalization and death. RESULTS: Female sex, age > or = 65 years, and left ventricular ejection fraction > or = 35% were associated with lower beta-blocker doses. Average daily dose of beta-blocker was lower with worse baseline New York Heart Association class. More patients of cardiologists achieved carvedilol doses > or = 25 mg twice daily, whereas in those of noncardiologists lower doses were more common. Relative risk of HF hospitalizations or all-cause death was significantly lower with higher doses of beta-blocker. CONCLUSIONS: Beta-blocker dosing in community HF appears lower than in randomized clinical trials, especially when prescribed by noncardiologists. At all doses, patients taking the beta-blocker carvedilol have a lower incidence of death and HF hospitalization than those discontinuing it, regardless of physician type in the community setting.

Comparison of outcomes and usefulness of carvedilol across a spectrum of left ventricular ejection fractions in patients with heart failure in clinical practice.

Heart failure (HF) in the community differs meaningfully from that in clinical trials, particularly the higher prevalence of patients with preserved left ventricular (LV) ejection fraction (EF) typically excluded from clinical trials, thus limiting knowledge of their responsiveness to beta-blocker therapy. From a community-based registry of 4,280 patients with HF starting treatment with the beta blocker carvedilol, we compared characteristics, carvedilol titration, and outcomes of patients according to LVEF >40% or <40% (as in clinical trials) and across the spectrum of LVEF <21%, 21% to 30%, 31% to 40%, and >40%. Patients with preserved EF (LVEF >40%) were older and more often women and hypertensive. Lower LVEF was associated with worse functional class and more HF hospitalizations in the previous year. Carvedilol dose decreased with increasing LVEF. Hospitalization rates for HF related inversely to LVEF before starting carvedilol therapy and decreased from the previous year in all LVEF groups during follow-up. Although 1-year mortality rate decreased from 8% with LVEF < or =20% to 6% with LVEF >40%, adjusted hazard ratios were not significantly different across LVEF groups. Thus, characteristics of community patients with HF vary across the spectrum of LVEF. Patients with HF and preserved EF treated with carvedilol in the community improve symptomatically and experience fewer HF hospitalizations after initiating carvedilol. In conclusion, without a control group, the effect of carvedilol on outcomes is not conclusive and trials of carvedilol in patients with HF and preserved EF should be undertaken.

Tolerability, safety, and efficacy of beta-blockade in black patients with heart failure in the community setting: insights from a large prospective beta-blocker registry.

Heart failure (HF) clinical trials suggest different responses of blacks and whites to beta-blockers. Differences between clinical trial and community settings may also have an impact. The Carvedilol Heart Failure Registry (COHERE) observed experience with carvedilol in 4280 patients with HF in a community setting. This analysis compares characteristics, outcomes, and carvedilol dosing of blacks and whites in COHERE. Compared with whites (n=3433), blacks (n=523) had more severe HF symptoms despite similar systolic function. At similar carvedilol maintenance doses, symptoms improved in 33% of blacks vs 28% of whites, while worsening in 10% and 11%, respectively (both nonsignificant), and HF hospitalization rates were reduced comparably in both groups (-58% vs -56%, respectively; both P<.001). Incidence and hazard ratios of death were similar in blacks and whites (6.9% vs 7.5%, hazard ratio 1.2 vs 1.0, P=.276). Thus carvedilol was similarly effective in blacks and whites with HF in the community setting, consistent with carvedilol clinical trials.

Heart failure in community practice: relationship to age and sex in a beta-blocker registry.

Women and the elderly are underrepresented in clinical trials of heart failure (HF). The authors analyzed, by sex and age groups, a registry of 4280 community patients initiating carvedilol for HF. Women (n=1485) were older than men (n=2793) and had worse functional class with higher left ventricular ejection fraction and blood pressure. Women also had more HF hospitalizations, less use of angiotensin-converting enzyme inhibitors, and lower doses of carvedilol. Nevertheless, during 1-year follow-up, both groups experienced greater than 40% reductions in HF hospitalizations (P<.001), with mortality of 7.3% in women vs 9.1% in men (P=.085). With increasing age, left ventricular ejection fraction, blood pressure, and functional class increased, whereas angiotensin-converting enzyme inhibitor use and carvedilol doses decreased. HF hospitalizations fell at least 40% in all age groups after starting carvedilol (P<.001). Characteristics of women and the elderly with HF in the community suggest increased risk, but both populations respond well after initiating carvedilol.

Fixed combination isosorbide dinitrate-hydralazine for nitric-oxide-enhancing therapy in heart failure.

The major advances in our understanding and management of heart failure (HF) in recent decades have not fully benefited all segments of our population. HF still represents a growing epidemic, especially for African-Americans, in whom the burden of HF is even greater. The recently reported beneficial effects of the fixed combination of isosorbide dinitrate and hydralazine (ISDN+HYD) in the African-American Heart Failure Trial (A-HeFT), has led to both the FDA approval of this agent and its endorsement by the latest HF guidelines. The properties of ISDN+HYD are well known as its components are mature agents, readily available in generic formulations that have been used for decades in other indications. However, fixed-dose ISDN+HYD represents the first drug to undergo targeted clinical development and to be approved for use in a specific ethnic group. As such, A-HeFT and the approval of ISDN+HYD represent landmark events that merit further scrutiny.

Predictors of clinical outcomes in patients given carvedilol for heart failure.

Risk factors for outcomes in heart failure (HF) were derived from populations in clinical trials, at hospital discharge, or in localized geographic or socioeconomic strata before the widespread use of beta blockers. This study observed 4,280 patients in a community-based HF registry for 1 year after completing carvedilol titration. Independent risk factors for death, hospitalization for HF, or hospitalization for cardiovascular reasons other than HF were first identified by age-, gender-, and race-adjusted analyses, then by multivariate analysis adjusted simultaneously for all factors. Over this period, 7% of patients died, 11% were hospitalized for HF, 12% were hospitalized for other cardiovascular reasons, and 27% had > or =1 of these events. The most significant outcome predictors were New York Heart Association class III or IV, history of hospitalization for HF or other cardiovascular reasons, and angina pectoris, all associated with increased odds of having an adverse outcome (all p < or =0.001). The left ventricular ejection fraction was not a significant outcome predictor by multivariate analysis. The odds ratio for an adverse outcome was significantly reduced for patients with hypertensive or idiopathic causes of HF and for those whose physicians had graduated from medical school > or =24 years earlier compared with <14 years earlier (all p <0.005). In conclusion, easily obtained historical information predicts clinical outcomes in patients with HF in the year after initiating carvedilol. In this unselected community population, these historical factors were better predictors of risk than the left ventricular ejection fraction.

Beta-blocker therapy for heart failure outside the clinical trial setting: findings of a community-based registry.

BACKGROUND: beta-Blockers reduce morbidity and mortality rates in heart failure (HF) clinical trials, but it is unknown whether these findings persist in the community setting. METHODS: A registry was created to survey tolerability and outcomes during initiation and 1-year follow-up of beta-blocker treatment with carvedilol in patients with HF treated by cardiologists (CARD) and primary care physicians (PCP) in the community. RESULTS: A total 4280 patients were enrolled (3121 by 259 CARD, 1159 by 129 PCP). Patient age averaged 67 +/- 13 years; 35% were women and 12% were black. The left ventricular ejection fraction averaged 31 +/- 12; New York Heart Association class was II-III in 86% and IV in 3%. Patients of PCP had higher left ventricular ejection fraction, were older, and more frequently were female, black, diabetic, hypertensive, and in New York Heart Association class III/IV. Minimal difficulty titrating carvedilol was noted by >80% of CARD and PCP. Significantly more CARD-treated patients reached carvedilol doses of 25 mg twice daily (49% vs 27%). Kaplan-Meier all-cause mortality rate was 8.5% at 1 year and did not differ between CARD-treated and PCP-treated patients (8.2% vs 9.3%, P =.254). At least one HF hospitalization occurred in 11% of patients during follow-up, compared with 28% in the preceding year. CONCLUSIONS: Community-based physicians use carvedilol with success approaching that of clinical trials. Overall mortality rates and HF hospitalizations were in the same low range as in clinical trials. Thus, it appears that results of clinical trials with carvedilol for HF can be translated to the community setting.

The potential role of community-based registries to complement the limited applicability of clinical trial results to the community setting: heart failure as an example.

BACKGROUND: Clinical trials do not represent community settings, making widespread implementation of evidence-based medicine problematic. New heart failure treatments are an example, as results comparable to those of clinical trials have not been observed in the community. Alternatives to clinical trials could provide useful complementary information. OBJECTIVES AND METHODS: To review the clinical trials and community experiences in heart failure management by searching Pubmed with key words "observational studies," "clinical trials," and "heart failure," to present the preliminary results of a community-based heart failure registry as a complementary database, and to assess the potential value and limitations of the registry approach. RESULTS: Recent advances in the treatment of heart failure led to guidelines using clinical trial evidence as the rationale for transferring newer therapeutic technologies to the community practice setting. Implementation of such guidelines is slow, reflecting concerns over applicability of clinical trial results to the community setting. A community-based registry of beta-blocker treatment for heart failure showed outcomes comparable to those of clinical trials, despite significant differences between physicians and their patients in these settings. CONCLUSION: Registries can complement clinical trials to expedite technology transfer to the community setting.

The African-American Heart Failure Trial: background, rationale and significance.

New treatments have improved outcomes in heart failure (HF), but applicability of these advances may be limited in African Americans. Analysis of previous trials has shown that a combination of hydralazine (H) plus isosorbide dinitrate (ISDN) may be especially beneficial in African Americans with HF. The African American Heart Failure Trial (A-HeFT) is a double-blind, randomized, and placebo-controlled trial in African American patients with stable NYHA Class III-IV HF while on standard therapy. Randomization to addition of BiDil, a fixed combination of H+ISDN, or placebo, will be stratified for beta-blocker usage, and all patients will be treated and followed until the last patient entered has completed six months of follow-up. The primary efficacy endpoint will be a composite score including quality of life, deaths, and hospitalizations for HF. At least 600 patients will be randomized. The first patient was randomized in June, 2001. Besides additional testing of H+ISDN in HF, A-HeFT will be the first HF trial aimed at a subgroup of African American patients, as well as the first to use a new composite HF score as its primary efficacy endpoint.

African-American Heart Failure Trial (A-HeFT): rationale, design, and methodology.

BACKGROUND: Hydralazine and isosorbide dinitrate combination (H+ISDN), angiotensin-converting enzyme inhibitors, and beta-blockers have improved outcomes in heart failure (HF). Analysis of previous trials has shown that H+ISDN appears especially beneficial in African American patients. METHODS AND RESULTS: The African-American Heart Failure Trial (A-HeFT) is double-blind, placebo-controlled, and includes African American patients with stable New York Heart Association Class III-IV HF on standard therapy. Patients must have prior HF-related events and left ventricular ejection fraction (LVEF) < or = 35% or LVEF <45% with left ventricular internal diastolic dimension >2.9 cm/m(2). Randomization to addition of placebo or BiDil (Nitro Med, Inc., Bedford, MA), a fixed combination of H+ISDN, is stratified for beta-blocker usage. All patients are treated and followed until the last patient entered completes 6 months of follow-up. The primary efficacy endpoint is a composite score including quality of life, death, and hospitalization for HF. At least 600 patients will be randomized; the first was randomized in June 2001. CONCLUSIONS: In addition to providing additional information on BiDil efficacy in HF, A-HeFT is the first HF trial aimed at a selected subgroup of patients and the first to use a new composite HF score as its primary efficacy endpoint.