AimsHigh-sensitivity cardiac troponin I (cTnI) assays hold promise in detecting the transition from hypertrophy to heart failure in aortic stenosis. We sought to investigate the mechanism for troponin release in patients with aortic stenosis and whether plasma cTnI concentrations are associated with long-term outcome.Methods and resultsPlasma cTnI concentrations were measured in two patient cohorts using a high-sensitivity assay. First, in the Mechanism Cohort, 122 patients with aortic stenosis (median age 71, 67% male, aortic valve area 1.0 ± 0.4 cm2) underwent cardiovascular magnetic resonance and echocardiography to assess left ventricular (LV) myocardial mass, function, and fibrosis. The indexed LV mass and measures of replacement fibrosis (late gadolinium enhancement) were associated with cTnI concentrations independent of age, sex, coronary artery disease, aortic stenosis severity, and diastolic function. In the separate Outcome Cohort, 131 patients originally recruited into the Scottish Aortic Stenosis and Lipid Lowering Trial, Impact of REgression (SALTIRE) study, had long-term follow-up for the occurrence of aortic valve replacement (AVR) and cardiovascular deaths. Over a median follow-up of 10.6 years (1178 patient-years), 24 patients died from a cardiovascular cause and 60 patients had an AVR. Plasma cTnI concentrations were associated with AVR or cardiovascular death HR 1.77 (95% CI, 1.22 to 2.55) independent of age, sex, systolic ejection fraction, and aortic stenosis severity.ConclusionsIn patients with aortic stenosis, plasma cTnI concentration is associated with advanced hypertrophy and replacement myocardial fibrosis as well as AVR or cardiovascular death.

Objective:Determine the effects of dapagliflozin in patients with heart failure(HF) and type 2 diabetes(T2DM) on left ventricular(LV) remodelling using cardiac MRI. Research Design and Methods:We randomized 56 patients with T2DM and HF with LV systolic dysfunction to dapagliflozin 10mg daily or placebo for one year, on top of usual therapy. Primary endpoint was difference in LV end-systolic volume(LVESV) using cardiac MRI. Key secondary endpoints included other measures of LV remodelling, clinical and biochemical parameters. Results:In our cohort, Dapagliflozin had no effect on LVESV or any other parameter of LV remodelling. It however, reduced diastolic BP and loop diuretic requirements, while increasing hemoglobin, hematocrit and ketone bodies. There was a trend towards lower weight. Conclusions:We were unable to determine with certainty if dapagliflozin in patients with T2DM and HF had any effect on LV remodelling. Whether the benefits of dapagliflozin in HF are due to remodelling or other mechanisms remains unknown.

Potentially arrhythmogenic QT abnormalities during quinidine treatment and in CHF can be nearly normalized by modest elevation of serum potassium.

AimWe tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes.Methods and resultsWe randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference −1.37 (95% confidence interval: −2.63 to −0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study.ConclusionMetformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials.