Peter Dunselman

Effect of Moderate or Intensive Disease Management Program on Outcome in Patients With Heart Failure: Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH)

BACKGROUND Heart failure (HF) disease management programs are widely implemented, but data about their effect on outcome have been inconsistent. METHODS The Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH) was a multicenter, randomized, controlled trial in which 1023 patients were enrolled after hospitalization because of HF. Patients were assigned to 1 of 3 groups: a control group (follow-up by a cardiologist) and 2 intervention groups with additional basic or intensive support by a nurse specializing in management of patients with HF. Patients were studied for 18 months. Primary end points were time to death or rehospitalization because of HF and the number of days lost to death or hospitalization. RESULTS Mean patient age was 71 years; 38% were women; and 50% of patients had mild HF and 50% had moderate to severe HF. During the study, 411 patients (40%) were readmitted because of HF or died from any cause: 42% in the control group, and 41% and 38% in the basic and intensive support groups, respectively (hazard ratio, 0.96 and 0.93, respectively; P = .73 and P = .52, respectively). The number of days lost to death or hospitalization was 39 960 in the control group, 33 731 days for the basic intervention group (P = .81), and 34 268 for the intensive support group (P = .49). All-cause mortality occurred in 29% of patients in the control group, and there was a trend toward lower mortality in the intervention groups combined (hazard ratio, 0.85; 95% confidence interval, 0.66-1.08; P = .18). There were slightly more hospitalizations in the 2 intervention groups (basic intervention group, P = .89; and intensive support group, P = .60). CONCLUSIONS Neither moderate nor intensive disease management by a nurse specializing in management of patients with HF reduced the combined end points of death and hospitalization because of HF compared with standard follow-up. There was a nonsignificant, potentially relevant reduction in mortality, accompanied by a slight increase in the number of short hospitalizations in both intervention groups. Clinical Trial Registry http://trialregister.nl Identifier: NCT 98675639.

Effects of Controlled-Release Metoprolol on Total Mortality, Hospitalizations, and Well-being in Patients with Heart Failure: The Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure (MERIT-HF)

Åke Hjalmarson, MD, PhD Sidney Goldstein, MD Björn Fagerberg, MD, PhD Hans Wedel, PhD Finn Waagstein, MD, PhD John Kjekshus, MD, PhD John Wikstrand, MD, PhD Dia El Allaf, MD Jirı́ Vı́tovec, MD, PhD Jan Aldershvile, MD, PhD Matti Halinen, MD, PhD Rainer Dietz, MD Karl-Ludwig Neuhaus, MD András Jánosi, MD, DSc Gudmundur Thorgeirsson, MD, PhD Peter H. J. M. Dunselman, MD, PhD Lars Gullestad, MD Jerzy Kuch, MD Johan Herlitz, MD, PhD Peter Rickenbacher, MD Stephen Ball, MD, PhD Stephen Gottlieb, MD Prakash Deedwania, MD for the MERIT-HF Study Group

Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure).

OBJECTIVES We investigated whether plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction and prognosis measured in CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), could be used to identify the severity of heart failure at which statins become ineffective. BACKGROUND Statins reduce cardiovascular morbidity and mortality in many patients with ischemic heart disease but not, overall, those with heart failure. There must be a transition point at which treatment with a statin becomes futile. METHODS In CORONA, patients with heart failure, reduced left ventricular ejection fraction, and ischemic heart disease were randomly assigned to 10 mg/day rosuvastatin or placebo. The primary composite outcome was cardiovascular death, nonfatal myocardial infarction, or stroke. RESULTS Of 5,011 patients enrolled, NT-proBNP was measured in 3,664 (73%). The midtertile included values between 103 pmol/l (868 pg/ml) and 277 pmol/l (2,348 pg/ml). Log NT-proBNP was the strongest predictor (per log unit) of every outcome assessed but was strongest for death from worsening heart failure (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.71 to 2.30), was weaker for sudden death (HR: 1.69; 95% CI: 1.52 to 1.88), and was weakest for atherothrombotic events (HR: 1.24; 95% CI: 1.10 to 1.40). Patients in the lowest tertile of NT-proBNP had the best prognosis and, if assigned to rosuvastatin rather than placebo, had a greater reduction in the primary end point (HR: 0.65; 95% CI: 0.47 to 0.88) than patients in the other tertiles (heterogeneity test, p = 0.0192). This reflected fewer atherothrombotic events and sudden deaths with rosuvastatin. CONCLUSIONS Patients with heart failure due to ischemic heart disease who have NT-proBNP values <103 pmol/l (868 pg/ml) may benefit from rosuvastatin.

Prognostic value of heart rate variability during long-term follow-up in patients with mild to moderate heart failure

OBJECTIVES We sought to assess the prognostic value of heart rate variability measures, including Poincaré plots, in patients with mild to moderate chronic heart failure. BACKGROUND Mortality is high in patients with heart failure, and many of them die suddenly. However, identification of high risk patients, particularly those with an increased risk for sudden death, has remained difficult. METHODS We studied 95 patients with heart failure (mean [+/- SD] age 60 +/- 8 years, left ventricular ejection fraction 0.29 +/- 0.09, New York Heart Association functional class II [81%] and III [19%]) during up to 4 years of follow-up. Heart rate variability measures and Poincaré plots were obtained from 24-h Holter recordings. RESULTS During follow-up, 17 (18%) of the 95 patients died. In 15 patients, death was cardiac related (11 patients experienced sudden death). None of the conventional time and frequency domain measures of heart rate variability were related to survival. In contrast, abnormal Poincaré plots identified a significantly higher risk for all-cause cardiac death (Cox proportional hazards ratio 5.7, 95% confidence interval [CI] 1.6 to 20.6, univariate analysis) and for sudden cardiac death (hazards ratio 6.8, 95% CI 1.5 to 31.4) compared with those with normal Poincaré plots. Patients with abnormal Poincaré plots were shown to have a lower left ventricular ejection fraction (0.26 +/- 0.10 vs. 0.31 +/- 0.08, p < 0.05) and higher plasma norepinephrine concentrations (506 +/- 207 pg/ml vs. 411 +/- 175 pg/ml, p < 0.05). In multivariate analysis, abnormal Poincaré plots still had independent prognostic value, both for all-cause cardiac mortality and for sudden cardiac death (hazards ratio 5.3, 95% CI 1.2 to 17.1, hazards ratio 4.5, 95% CI 1.0 to 27.5, respectively. CONCLUSIONS Heart rate variability analysis, as assessed by Poincaré plots, has independent prognostic value in patients with mild to moderate chronic heart failure and identifies an increased risk for all-cause and sudden cardiac death in these patients.

Effects of Statin Therapy According to Plasma High-Sensitivity C-Reactive Protein Concentration in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) A Retrospective Analysis

Background— We examined whether the antiinflammatory action of statins may be of benefit in heart failure, a state characterized by inflammation in which low cholesterol is associated with worse outcomes. Methods and Results— We compared 10 mg rosuvastatin daily with placebo in patients with ischemic systolic heart failure according to baseline high sensitivity-C reactive protein (hs-CRP) <2.0 mg/L (placebo, n=779; rosuvastatin, n=777) or ≥2.0 mg/L (placebo, n=1694; rosuvastatin, n=1711). The primary outcome was cardiovascular death, myocardial infarction, or stroke. Baseline low-density lipoprotein was the same, and rosuvastatin reduced low-density lipoprotein by 47% in both hs-CRP groups. Median hs-CRP was 1.10 mg/L in the lower and 5.60 mg/L in the higher hs-CRP group, with higher hs-CRP associated with worse outcomes. The change in hs-CRP with rosuvastatin from baseline to 3 months was −6% in the low hs-CRP group (27% with placebo) and −33.3% in the high hs-CRP group (−11.1% with placebo). In the high hs-CRP group, 548 placebo-treated (14.0 per 100 patient-years of follow-up) and 498 rosuvastatin-treated (12.2 per 100 patient-years of follow-up) patients had a primary end point (hazard ratio of placebo to rosuvastatin, 0.87; 95% confidence interval, 0.77 to 0.98; P=0.024). In the low hs-CRP group, 175 placebo-treated (8.9 per 100 patient-years of follow-up) and 188 rosuvastatin-treated (9.8 per 100 patient-years of follow-up) patients experienced this outcome (hazard ratio, 1.09; 95% confidence interval, 0.89 to 1.34; P>0.2; P for interaction=0.062). The numbers of deaths were as follows: 581 placebo-treated (14.1 per 100 patient-years of follow-up) and 532 rosuvastatin-treated (12.6 per 100 patient-years) patients in the high hs-CRP group (hazard ratio, 0.89; 95% confidence interval, 0.79 to 1.00; P=0.050) and 170 placebo-treated (8.3 per 100 patient-years) and 192 rosuvastatin-treated (9.7 per 100 patient-years) patients in the low hs-CRP group (hazard ratio, 1.17; 95% confidence interval, 0.95 to 1.43; P=0.14; P for interaction=0.026). Conclusion— In this retrospective hypothesis-generating study, we found a significant interaction between hs-CRP and the effect of rosuvastatin for most end points whereby rosuvastatin treatment was associated with better outcomes in patients with hs-CRP ≥2.0 mg/L. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.

A statin in the treatment of heart failure? Controlled rosuvastatin multinational study in heart failure (CORONA): Study design and baseline characteristics

Previous prospective outcome studies of statins have not provided any guidance on benefit‐risk in patients with heart failure.

Predictors of fatal and non-fatal outcomes in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) : incremental value of apolipoprotein A-1, high-sensitivity C-reactive peptide and N-terminal pro B-type natriuretic peptide

Few prognostic models in heart failure have been developed in typically elderly patients treated with modern pharmacological therapy and even fewer included simple biochemical tests (such as creatinine), new biomarkers (such as natriuretic peptides), or, especially, both. In addition, most models have been developed for the single outcome of all‐cause mortality.

Effect of exercise training on quality of life in patients with chronic heart failure

The effect of exercise training on quality of life and exercise capacity was studied in 67 patients with mild to moderate chronic heart failure (CHF; age: 65.6+/-8.3 years; left ventricular ejection fraction: 26.5+/-9.6%). Patients were randomly allocated to either a training group or to a control group. After intervention a significantly larger decrease in Feelings of Being Disabled (a subscale of the Heart Patients Psychological Questionnaire) and a significantly larger increase in the Self-Assessment of General Well-Being (SAGWB) were observed in the training group. Exercise time and anaerobic threshold were increased in the training group only. The increase in exercise time was related to both Feelings of Being Disabled and SAGWB. We conclude that supervised exercise training improves both quality of life and exercise capacity and can be safely performed by chronic heart failure patients.

Presence and development of atrial fibrillation in chronic heart failure - Experiences from the MERIT-HF Study

Atrial fibrillation is common in heart failure, but data regarding beta‐blockade in these patients and its ability to prevent new occurrence of atrial fibrillation are scarce.

Coenzyme Q10, rosuvastatin, and clinical outcomes in heart failure: a pre-specified substudy of CORONA (controlled rosuvastatin multinational study in heart failure).

OBJECTIVES The purpose of this study was to determine whether coenzyme Q₁₀ is an independent predictor of prognosis in heart failure. BACKGROUND Blood and tissue concentrations of the essential cofactor coenzyme Q₁₀ are decreased by statins, and this could be harmful in patients with heart failure. METHODS We measured serum coenzyme Q₁₀ in 1,191 patients with ischemic systolic heart failure enrolled in CORONA (Controlled Rosuvastatin Multinational Study in Heart Failure) and related this to clinical outcomes. RESULTS Patients with lower coenzyme Q₁₀ concentrations were older and had more advanced heart failure. Mortality was significantly higher among patients in the lowest compared to the highest coenzyme Q₁₀ tertile in a univariate analysis (hazard ratio: 1.50, 95% confidence interval: 1.04 to 2.6, p = 0.03) but not in a multivariable analysis. Coenzyme Q₁₀ was not an independent predictor of any other clinical outcome. Rosuvastatin reduced coenzyme Q₁₀ but there was no interaction between coenzyme Q₁₀ and the effect of rosuvastatin. CONCLUSIONS Coenzyme Q₁₀ is not an independent prognostic variable in heart failure. Rosuvastatin reduced coenzyme Q₁₀, but even in patients with a low baseline coenzyme Q₁₀, rosuvastatin treatment was not associated with a significantly worse outcome. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310).