Summary Background Cardiosphere-derived cells (CDCs) reduce scarring after myocardial infarction, increase viable myocardium, and boost cardiac function in preclinical models. We aimed to assess safety of such an approach in patients with left ventricular dysfunction after myocardial infarction. Methods In the prospective, randomised CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial, we enrolled patients 2–4 weeks after myocardial infarction (with left ventricular ejection fraction of 25–45%) at two medical centres in the USA. An independent data coordinating centre randomly allocated patients in a 2:1 ratio to receive CDCs or standard care. For patients assigned to receive CDCs, autologous cells grown from endomyocardial biopsy specimens were infused into the infarct-related artery 1·5–3 months after myocardial infarction. The primary endpoint was proportion of patients at 6 months who died due to ventricular tachycardia, ventricular fibrillation, or sudden unexpected death, or had myocardial infarction after cell infusion, new cardiac tumour formation on MRI, or a major adverse cardiac event (MACE; composite of death and hospital admission for heart failure or non-fatal recurrent myocardial infarction). We also assessed preliminary efficacy endpoints on MRI by 6 months. Data analysers were masked to group assignment. This study is registered with ClinicalTrials.gov, NCT00893360. Findings Between May 5, 2009, and Dec 16, 2010, we randomly allocated 31 eligible participants of whom 25 were included in a per-protocol analysis (17 to CDC group and eight to standard of care). Mean baseline left ventricular ejection fraction (LVEF) was 39% (SD 12) and scar occupied 24% (10) of left ventricular mass. Biopsy samples yielded prescribed cell doses within 36 days (SD 6). No complications were reported within 24 h of CDC infusion. By 6 months, no patients had died, developed cardiac tumours, or MACE in either group. Four patients (24%) in the CDC group had serious adverse events compared with one control (13%; p=1·00). Compared with controls at 6 months, MRI analysis of patients treated with CDCs showed reductions in scar mass (p=0·001), increases in viable heart mass (p=0·01) and regional contractility (p=0·02), and regional systolic wall thickening (p=0·015). However, changes in end-diastolic volume, end-systolic volume, and LVEF did not differ between groups by 6 months. Interpretation We show intracoronary infusion of autologous CDCs after myocardial infarction is safe, warranting the expansion of such therapy to phase 2 study. The unprecedented increases we noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes. Funding US National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center.

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Normal limits of ascending and descending aortic dimensions by noncontrast gated cardiac CT have been defined by age, gender, and BSA in a large, low-risk population of subjects undergoing CAC scanning.

In this large observational series with long-term follow-up, patients with significant ischaemia and without extensive scar were likely to realize a survival benefit from early revascularization. In contrast, the survival of patients with minimal ischaemia was superior with medical therapy without early revascularization.

The findings of this study demonstrate that assessment of perfusion data alone by visual or quantitative SPECT MPI analysis underestimates the magnitude of left main CAD. The combination of perfusion and nonperfusion abnormalities on gated MPI identifies high risk in most patients with left main CAD.

Over the past 2 decades, the frequency and severity of abnormal stress SPECT-MPI studies has progressively decreased. Notably, the frequency of abnormal SPECT-MPI is now very low among exercising patients without typical angina. These findings suggest the need for developing more cost-effective strategies for the initial work-up of patients who are presently at low risk for manifesting inducible myocardial ischemia during cardiac imaging procedures.

AimsThe mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling.Materials and resultsRandomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD [invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI)]. Short-term oral ranolazine 500–1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (−3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041).ConclusionsIn this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects.Trial registrationclinicaltrials.gov Identifier: NCT01342029.

OBJECTIVE We conducted a prospective randomized trial to compare the clinical impact of conventional risk factor modification to that associated with coronary artery calcium (CAC) scanning. BACKGROUND Although CAC scanning predicts cardiac events, its impact on subsequent medical management and CAD risk is not known. METHODS We assigned 2,137 volunteers to groups that did versus did not undergo CAC scanning before risk factor counseling. The primary end-point was 4-year change in CAD risk factors and Framingham Risk Score (FRS). We also compared the groups for differences in downstream medical resource utilization. RESULTS Compared to the no-scan group, the scan group showed a net favorable change in systolic blood pressure (p=0.02), LDL-cholesterol (p=0.04), waist circumference for those with increased abdominal girth (p=0.01), and tendency to weight loss among overweight subjects (p=0.07). While mean FRS rose in the no-scan group, it remained static in the scan group (0.7±5.1 versus 0.002±4.9, p=0.003). Within the scan group, increasing baseline CAC score was associated with a dose-response improvement in systolic and diastolic blood pressure (p<0.001), total cholesterol (p<0.001), LDL-cholesterol (p<0.001), triglycerides (p<0.001), weight (p<0.001) and FRS (p=0.003). Downstream medical testing and costs in the scan group were comparable versus the no-scan group, balanced by lower and higher resource utilization for those with normal CAC scans and CAC scores ≥400, respectively. CONCLUSIONS As compared to no scanning, randomization to CAC scanning was associated with superior CAD risk factor control without increasing downstream medical testing. Further study of CAC scanning for improvement of cardiovascular outcomes may be warranted. (ClinicalTrials.gov, number NCT00927693).