Physicians pursue a less aggressive management approach to coronary disease in women than in men, despite greater cardiac disability in women.

BACKGROUND Atrial natriuretic factor (ANF) is a peptide hormone secreted from cardiac atria in response to increased atrial pressure. Because of a longer half-life and greater stability, the N-terminal of ANF prohormone (N-terminal proANF) may be a better integrator of atrial peptide secretion than ANF itself. After myocardial infarction, elevation of ANF and other neurohormones has been associated with a poor prognosis. However, when left ventricular ejection fraction (LVEF) and other important clinical variables are included in multivariate analysis, the independent predictive value of these neurohormones has been reduced markedly. METHODS AND RESULTS To test the prognostic value of N-terminal proANF after myocardial infarction, its plasma concentration was measured a mean of 12 days after infarction in 246 patients in the Survival and Ventricular Enlargement (SAVE) Study. N-terminal proANF was a much stronger predictor of survival than ANF itself. Furthermore, in multivariate analysis of cardiovascular mortality and development of heart failure, N-terminal proANF in contrast to ANF and other neurohormones was still a powerful and independent predictor when the model included age, gender, prior myocardial infarction, hypertension, diabetes, use of thrombolysis, Killip class, infarct location, and LVEF. CONCLUSIONS The measurement of N-terminal proANF supplements presently used clinical and objective assessments and provides an important independent predictor of prognosis with respect to cardiovascular mortality and development of heart failure.

Aims CONCERT‐HF is an NHLBI‐sponsored, double‐blind, placebo‐controlled, Phase II trial designed to determine whether treatment with autologous bone marrow‐derived mesenchymal stromal cells (MSCs) and c‐kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy. Methods and results Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (−22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6‐min walking distance, and peak oxygen consumption did not differ significantly among groups. Conclusions This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline‐directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients.

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URL: http://www.clinicaltrials.gov. Unique identifier: NCT02501811.