JAMA: Heart Failure Topic Collection

Strategies and Opportunities for Drug Development in Heart Failure Drug Development in Heart Failure

Butler J, Fonarow GC, Gheorghiade M. — Wed, 17 Apr 2013 00:00:00 GMT

More than a million hospitalizations for heart failure (HHF) occur annually in the United States, with mortality and readmission rates up to 50% within 60 to 90 days after discharge. The annual costs for HF care exceed $40 billion, with the majority spent on HHF. Hospital reimbursement is now tied to 30-day readmission rates among patients with HF. Most HHF patients have worsening chronic HF and are receiving recommended therapies. Despite improved signs or symptoms by discharge, postdischarge event rates remain high. About half of the HHF patients have preserved left ventricular ejection fraction for which there is no evidence-based treatment.

Long-term Outcomes of Left Anterior Fascicular Block in the Absence of Overt Cardiovascular Disease

Mandyam MC, Soliman EZ, Heckbert SR, et al. — Wed, 17 Apr 2013 00:00:00 GMT

To the Editor: Left anterior fascicular block (LAFB) is considered a benign electrocardiographic (ECG) finding, but its long-term consequences have not been comprehensively studied. Conduction blocks occur due to conduction system fibrosis and are associated with myocardial fibrosis, even in the absence of other cardiovascular disease. Therefore, LAFB may be an immediately accessible marker of left heart fibrosis, a substrate for atrial fibrillation (AF) and congestive heart failure (CHF). We investigated the long-term outcomes of participants with LAFB in the absence of manifest cardiovascular disease in the Cardiovascular Health Study (CHS).

Effect of Shock Wave–Facilitated Intracoronary Cell Therapy on LVEF in Patients With Chronic Heart Failure The CELLWAVE Randomized Clinical Trial Intracoronary Cell Therapy and LVEF

Assmus B, Walter DH, Seeger FH, et al. — Wed, 17 Apr 2013 00:00:00 GMT

Importance

The modest effects of clinical studies using intracoronary administration of autologous bone marrow–derived mononuclear cells (BMCs) in patients with chronic postinfarction heart failure may be attributed to impaired homing of BMCs to the target area. Extracorporeal shock wave treatment has been experimentally shown to increase homing factors in the target tissue, resulting in enhanced retention of applied BMCs.

Objective

To test the hypothesis that targeted cardiac shock wave pretreatment with subsequent application of BMCs improves recovery of left ventricular ejection fraction (LVEF) in patients with chronic heart failure.

Design, Setting, and Participants

The CELLWAVE double-blind, randomized, placebo-controlled trial conducted among patients with chronic heart failure treated at Goethe University Frankfurt, Germany, between 2006 and 2011.

Interventions

Single-blind low-dose (n = 42), high-dose (n = 40), or placebo (n = 21) shock wave pretreatment targeted to the left ventricular anterior wall. Twenty-four hours later, patients receiving shock wave pretreatment were randomized to receive double-blind intracoronary infusion of BMCs or placebo, and patients receiving placebo shock wave received intracoronary infusion of BMCs.

Main Outcomes and Measures

Primary end point was change in LVEF from baseline to 4 months in the pooled groups shock wave + placebo infusion vs shock wave + BMCs; secondary end points included regional left ventricular function assessed by magnetic resonance imaging and clinical events.

Results

The primary end point was significantly improved in the shock wave + BMCs group (absolute change in LVEF, 3.2% [95% CI, 2.0% to 4.4%]), compared with the shock wave + placebo infusion group (1.0% [95% CI, −0.3% to 2.2%]) (P = .02). Regional wall thickening improved significantly in the shock wave + BMCs group (3.6% [95% CI, 2.0% to 5.2%]) but not in the shock wave + placebo infusion group (0.5% [95% CI, −1.2% to 2.1%]) (P = .01). Overall occurrence of major adverse cardiac events was significantly less frequent in the shock wave + BMCs group (n = 32 events) compared with the placebo shock wave + BMCs (n = 18) and shock wave + placebo infusion (n = 61) groups (hazard ratio, 0.58 [95% CI, 0.40-0.85]; P = .02).

Conclusions and Relevance

Among patients with postinfarction chronic heart failure, shock wave–facilitated intracoronary administration of BMCs vs shock wave treatment alone resulted in a significant, albeit modest, improvement in LVEF at 4 months. Determining whether the increase in contractile function will translate into improved clinical outcomes requires confirmation in larger clinical end point trials.

Trial Registration

clinicaltrials.gov Identifier: NCT00326989