Discharge use of angiotensin receptor blockers provides comparable effects with angiotensin-converting enzyme inhibitors on outcomes in patients hospitalized for heart failure

Large-scale, placebo-controlled, randomized clinical trials have demonstrated that angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) reduce mortality and hospitalization in patients with heart failure (HF) caused by left ventricular systolic dysfunction (LVSD). However, it is unknown whether ACE inhibitors and ARBs have similar effects on the long-term outcomes in HF patients encountered in routine clinical practice. The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) enrolled HF patients hospitalized with worsening symptoms and they were followed during an average of 2.2 years. The outcome data were compared in patients with LVSD by echocardiography (ejection fraction <40%) according to the predischarge use of ACE inhibitors (n=356) or ARBs (n=372). The clinical characteristics were similar between patients with ACE inhibitor and ARB use except for higher prevalence of hypertensive etiology and diabetes mellitus. There was no significant difference between ACE inhibitor and ARB use in all cause death (adjusted hazard ratio [HR] 0.958, 95% CI 0.601-1.527, P=0.858) and rehospitalization (adjusted HR 0.964, 95% CI 0.683-1.362, P=0.836). The effects of ACE inhibitor and ARB use on the outcomes were generally consistent across all clinically relevant subgroups examined, including age, sex, etiology, EF, hypertension, diabetes mellitus, and β-blocker use. Discharge use of ARBs provided comparable effects with ACE inhibitors on outcomes in patients hospitalized for HF. These findings provide further support for guideline recommendations that ARBs can be used in patients with HF and LVSD as an alternative of ACE inhibitors

Increased myocardial NAD(P)H oxidase-derived superoxide causes the exacerbation of postinfarct heart failure in type 2 diabetes

Type 2 diabetes adversely affects the outcomes in patients with myocardial infarction (MI), which is associated with the development of left ventricular (LV) failure. NAD(P)H oxidase-derived superoxide (O2?) production is increased in type 2 diabetes. However, its pathophysiological significance in advanced post-MI LV failure associated with type 2 diabetes remains unestablished. We thus hypothesized that an inhibitor of NAD(P)H oxidase activation, apocynin, could attenuate the exacerbated LV failure after MI in high-fat diet (HFD)-induced obese mice with type 2 diabetes. Male C57BL/6J mice were fed on either HFD or normal diet (ND) for 8 wk. At 4 wk of feeding, MI was created in mice by ligating the left coronary artery. HFD-fed MI mice were treated with either 10 mmol/l apocynin or vehicle. HFD + MI had significantly greater LV end-diastolic diameter (LVEDD; 5.7 ± 0.1 vs. 5.3 ± 0.2 mm), end-diastolic pressure (12 ± 2 vs. 8 ± 1 mmHg), and lung weight/tibial length (10.1 ± 0.3 vs. 8.7 ± 0.7 mg/mm) than ND + MI, which was accompanied by an increased interstitial fibrosis of noninfarcted LV. Treatment of HFD + MI with apocynin significantly decreased LVEDD (5.4 ± 0.1 mm), LV end-diastolic pressure (9.7 ± 0.8 mmHg), lung weight/tibial length (9.0 ± 0.3 mg/mm), and concomitantly interstitial fibrosis of noninfarcted LV to the ND + MI level without affecting body weight, glucose metabolism, and infarct size. NAD(P)H oxidase activity and O2? production were increased in noninfarcted LV tissues from HFD + MI, both of which were attenuated by apocynin to the ND + MI level. Type 2 diabetes was associated with the exacerbation of LV failure after MI via increasing NAD(P)H oxidase-derived O2?, which may be a novel important therapeutic target in advanced heart failure with diabetes

Chronic Kidney Disease as an Independent Risk for Long-Term Adverse Outcomes in Patients Hospitalized With Heart Failure in Japan

Background: Previous studies have demonstrated that renal dysfunction is common in patients with heart failure (HF), but it is not known whether chronic kidney disease (CKD) is associated with increased risks of long-term adverse outcomes in unselected HF patients encountered in current routine clinical practice in Japan. Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) prospectively studied a broad sample of patients hospitalized with worsening HF and their outcomes with an average of 2.4 years of follow-up. The study cohort (n=2,013) were classified into 3 groups by estimated glomerular filtration rate (eGFR): ≥60 (n=579), 30-59 (n=1,025), and <30 ml · min-1 · 1.73 m-2 or patients with dialysis (n=409); 1,372 patients (70.3%) had an eGFR <60 ml · min-1 · 1.73 m-2 and 62 patients were treated with dialysis. The multivariable adjusted risk for all-cause death or rehospitalization increased with reduced eGFR; an adjusted hazard ratio (HR) 1.520 (95% confidence interval (CI) 1.186-1.949) for eGFR 30-59 ml · min-1 · 1.73 m-2 (P=0.001) and HR 2.566 (95%CI 1.885-3.492) for eGFR <30 ml · min-1 · 1.73 m-2 or patients with dialysis (P<0.001). Conclusions: CKD is common in HF and was independently associated with long-term adverse outcomes in a broad cohort of Japanese patients. (Circ J 2009; 73: 1442 - 1447

Effects of Atrial Fibrillation on Long-Term Outcomes in Patients Hospitalized for Heart Failure in Japan

Background: Atrial fibrillation (AF) is a common arrhythmia in patients with heart failure (HF), but its prognostic importance is controversial. The effect of AF on long-term outcomes, including mortality and rehospitalization, among unselected HF patients hospitalized with HF in routine clinical practice in Japan was assessed in the present study. Methods and Results: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) prospectively studied the characteristics and treatment strategies of a broad sample of patients hospitalized with worsening HF and the outcomes were followed with an average of 2.4 years of follow-up. The study cohort (n=2,659) was grouped according to the presence (n=937; 35.2%) or absence (n=1,722; 64.8%) of AF at baseline. After multivariable adjustment, patients with and without AF had a comparable risk for all-cause death (adjusted hazard ratio (HR) 0.931, 95% confidence interval (CI) 0.690-1.258, P=0.643), cardiac death (adjusted HR 0.949, 95%CI 0.655-1.377, P=0.784), rehospitalization because of the worsening HF (adjusted HR 1.028, 95%CI 0.816-1.295, P=0.816), and all-cause death or rehospitalization (adjusted HR 1.039, 95%CI 0.842-1.281, P=0.722). Conclusions: Among patients hospitalized for HF in Japan, AF was common, but was not an independent risk for long-term adverse outcomes, including death or rehospitalization, in routine clinical practice. (Circ J 2009; 73: 2084-2090