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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BackgroundAlthough the association between coronary artery calcium (CAC) and future heart failure (HF) has been shown previously, the value of CAC progression in the prediction of HF has not been investigated. In this study, we investigated the association of CAC progression with subclinical left ventricular (LV) dysfunction and incident HF in the Multi‐Ethnic Study of Atherosclerosis.Methods and ResultsThe Multi‐Ethnic Study of Atherosclerosis is a population‐based study consisting of 6814 men and women aged 45 to 84, free of overt cardiovascular disease at enrollment, who were recruited from 4 ethnicities. We included 5644 Multi‐Ethnic Study of Atherosclerosis participants who had baseline and follow‐up cardiac computed tomography and were free of HF and coronary heart disease before the second cardiac computed tomography. Mean (±SD) age was 61.7±10.2 years and 47.2% were male. The Cox proportional hazard models and multivariable linear regression models were deployed to determine the association of CAC progression with incident HF and subclinical LV dysfunction, respectively. Over a median follow‐up of 9.6 (interquartile range: 8.8–10.6) years, 182 participants developed incident HF. CAC progression of 10 units per year was associated with 3% of increased risk of HF independent of overt coronary heart disease (P=0.008). In 2818 participants with available cardiac magnetic resonance images, CAC progression was associated with increased LV end diastolic volume (β=0.16; P=0.03) and LV end systolic volume (β=0.12; P=0.006) after excluding participants with any coronary heart disease.Conclusions CAC progression was associated with incident HF and modestly increased LV end diastolic volume and LV end systolic volume at follow‐up exam independent of overt coronary heart disease.

Background Hypertrophic cardiomyopathy is defined as unexplained left ventricular ( LV ) hypertrophy (wall thickness ≥15 mm) and is prevalent in 0.2% of adults (1:500) in population‐based studies using echocardiography. Cardiac magnetic resonance imaging ( MRI ) allows for more accurate wall thickness measurement across the entire ventricle than echocardiography. The prevalence of unexplained LV hypertrophy by cardiac MRI is unknown. MESA (Multi‐Ethnic Study of Atherosclerosis) recruited individuals without overt cardiovascular disease 45 to 84 years of age. Methods and Results We studied 4972 individuals who underwent measurement of regional LV wall thickness by cardiac MRI as part of the MESA baseline exam. American Heart Association criteria were used to define LV segments. We excluded participants with hypertension, LV dilation (≥95% predicted end‐diastolic volume) or dysfunction (ejection fraction ≤50%), moderate‐to‐severe left‐sided valve lesions by cardiac MRI , severe aortic valve calcification by cardiac computed tomography (aortic valve Agatston calcium score >1200 in women or >2000 in men), obesity (body mass index >35 kg/m 2 ), diabetes mellitus, and current smoking. Sixty‐seven participants (aged 64±10 years, 9% female) had unexplained LV hypertrophy (wall thickness ≥15 mm in at least 2 adjacent LV segments), representing 1.4% (1 in 74) participants, 2.6% of men and 0.2% of women. Prevalence was similar across categories of race/ethnicity. Hypertrophy was focal in 17 (25.4%), intermediate in 44 (65.7%), and diffuse in 5 (7.5%) participants. Conclusions The prevalence of unexplained LV hypertrophy in a population‐based cohort using cardiac MRI was 1.4%. This may have implications for the diagnosis of patients with hypertrophic cardiomyopathy and will require further study.