One-point carotid wave intensity predicts cardiac mortality in patients with congestive heart failure and reduced ejection fraction.

Wave intensity (WI) is a hemodynamic index used to evaluate the interaction between the heart and the arterial system, measured with an echo-Doppler system at the level of the common carotid artery. WI has two peaks: W1 during early systole that represents left ventricular (LV) contractility, and W2 in late systole that is related to the inertia force during isovolumetric relaxation. The aim of this study was to determine whether WI parameters improve the prediction of poor outcome in patients with heart failure and reduced ejection fraction (HFrEF). Sixty-two patients (mean age 69.4 ± 11.5 years) in NYHA class II-III were followed up for 43.5 months. They underwent routine clinical work-up, transthoracic echocardiography and WI measurement. A stratified survival analysis was conducted using the Kaplan-Meier method. During follow-up, 23 patients died from cardiovascular causes. Survivors and non-survivors were similar in age, blood pressure, heart rate and echocardiographic parameters, except for LV end-diastolic volume indexed to body surface area, E/A ratio (higher in non-survivors) and deceleration time (lower in non-survivors). W2 (1950 ± 1006 vs 1117 ± 708 mmHg m/s(3), p = 0.001) was significantly lower in non-survivors, whereas W1 (6951 ± 4119 vs 5748 ± 3891 mmHg m/s(3), p = NS) was similar. At the end of follow-up, cardiovascular mortality was higher in patients with W1 ≤ 3900 mmHg m/s(3) (p = 0.02) and W2 ≤ 1000 mmHg m/s(3) (p = 0.0002). Only E/A (cut-off 1.5) was predictive of mortality (p = 0.05). In patients with HFrEF, WI parameters derived from the carotid artery better identified patients with poor prognosis and were significant predictors of cardiovascular mortality.

Hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin prevents cardiac hypertrophy induced by pressure overload and inhibits p21ras activation.

BACKGROUND: Patients with cardiac hypertrophy are at increased cardiovascular risk. It has been hypothesized that hydroxymethylglutaryl coenzyme A reductase inhibitors may exert beneficial effects other than their cholesterol-lowering actions. The aims of the study were to assess the in vivo effects of simvastatin (SIM) on cardiac hypertrophy and on Ras signaling in rats with ascending aorta banding. METHODS AND RESULTS: Wistar rats were randomized to receive either treatment with SIM or placebo, and then short-term (group I) and long-term (group II) left ventricular pressure overload was performed by placing a tantalum clip on ascending aorta. At the end of treatment period, left and right ventricular weight, body weight, and tibial length were measured and echocardiographic evaluations were performed. Ras signaling was investigated by analyzing Ras membrane localization and activation, ERK2 phosphorylation, and p27(kip1) and cdk4 levels. In SIM-treated rats, a significant reduction of left ventricular weight/body weight, echocardiographic left ventricular mass, and left ventricular end-diastolic diameter and end-diastolic pressure was found. In rats with pressure overload, SIM treatment significantly reduced Ras membrane targeting, Ras in vivo activation, ERK2 phosphorylation, and the ratio cdk4/p27(kip1). CONCLUSIONS: HMG CoA inhibitor SIM inhibits in vivo Ras signaling and prevents left ventricular hypertrophy development in aortic-banded animals.