Background-The role of QTc interval prolongation in heart failure remains poorly defined. To better understand it, we analyzed the QTc interval duration in patients with heart failure with high B-type natriuretic peptide (BNP) levels and analyzed the combined prognostic impact of prolonged QTc and elevated BNP. Methods and Results-QTc intervals were measured in 241 patients with heart failure who had BNP levels Ͼ400 pg/mL.QT interval duration was determined by averaging 3 consecutive beats through leads II and V 4 on a standard 12-lead ECG and corrected by using the Bazett formula. QTc intervals were prolonged (Ͼ440 ms) in 122 (51%) patients and normal in 119 (49%). The BNP levels in these 2 groups were not significantly different (786Ϯ321 pg/mL in the prolonged QTc group versus 733Ϯ274 pg/mL in the normal QTc group, Pϭ0.13). During 6 months of follow-up, 46 patients died, 9 underwent transplantation, and 17 underwent left ventricular assist device implantation. The deaths were attributed to pump failure (nϭ24, 52%), sudden cardiac death (nϭ18, 39%), or noncardiac causes (nϭ4, 9%). Kaplan-Meier survival rates were 3 times higher in the normal QTc group than in the prolonged QTc group (PϽ0.0001).On multivariate analysis, prolonged QTc interval was an independent predictor of all-cause death (Pϭ0.0001), cardiac death (Pϭ0.0001), sudden cardiac death (Pϭ0.004), and pump failure death (Pϭ0.0006). Conclusions-Prolonged QTc interval is a strong, independent predictor of adverse outcome in patients with heart failure with BNP levels Ͼ400 pg/mL.

Background-Progression of heart failure after initial myocardial injury is mediated in part by various redundant inflammatory mediators, including the widely expressed cyclooxygenase-2 (COX-2). Because COX-2 inhibitors are useful in treating many inflammation-mediated diseases, we asked whether COX-2 inhibition can attenuate heart failure progression. Methods and Results-Heart failure was experimentally induced in 100 mice by administration of doxorubicin (4 mg · kg Ϫ1 · wk Ϫ1 for 6 weeks). Beginning at day 42, mice were fed daily with either COX-2 inhibitor-containing mice chow (nϭ50) or plain mice chow (controls; nϭ50). Left ventricular ejection fraction was evaluated as a measure of heart failure by a novel method of transthoracic echocardiography (with intravascular ultrasound catheters) at baseline and on days 42, 56, and 70. From baseline to study termination, left ventricular ejection fraction in COX-2 inhibitor-treated mice decreased significantly less than in control mice (9% versus 29%, PϽ0.01). Mortality was significantly lower for COX-2 inhibitor-treated mice than for control mice (18% versus 38%, PϽ0.01). These results were confirmed in a revalidation study in COX-2 inhibitor-treated mice (nϭ25) and controls (nϭ25). That study revealed that the hearts from control mice weighed roughly the same as hearts from COX-2 inhibitor-treated mice but showed more extensive signs of cardiomyopathy (as determined by pathological analysis by an independent, blinded observer) and higher levels of COX-2 proteins (as determined by immunoblotting [6442Ϯ1635 versus 4300Ϯ2408 arbitrary units, PϽ0.022]). Conclusions-COX-2 inhibitors can attenuate the progression of heart failure in a murine model of doxorubicin-induced heart failure.

No abstract

No abstract