BackgroundA thorough analysis of noncardiac determinants of mortality in heart failure (HF) is missing. Furthermore, evidence conflicts on the outcome of patients with HF and no or mild systolic dysfunction. We aimed to investigate the prevalence of noncardiac and cardiac causes of death in a cohort of chronic HF patients, covering the whole spectrum of systolic function.Methods and ResultsWe enrolled 2791 stable HF patients, classified into HF with reduced ejection fraction (HFrEF; left ventricular ejection fraction [EF] <40%), HR with midrange EF (HFmrEF; left ventricular EF 41–49%), or HF with preserved EF (HFpEF; left ventricular EF ≥50%), and followed up for all‐cause, cardiac, and noncardiac mortality (adjudicated as due to cancer, sepsis, respiratory disease, renal disease, or other causes). Over follow‐up of 39 months, adjusted mortality was lower in HFpEF and HFmrEF versus HFrEF (hazard ratio: 0.75 [95% CI, 0.67–0.84], P<0.001 for HFpEF; hazard ratio: 0.78 [95% CI, 0.63–0.96], P=0.017 for HFmrEF). HFrEF had the highest rates of cardiac death, whereas noncardiac mortality was similar across left ventricular EF categories. Noncardiac causes accounted for 62% of deaths in HFpEF, 54% in HFmrEF and 35% in HFrEF; cancer was twice as frequent as a cause of death in HFpEF and HFmrEF versus HFrEF. Yearly rates of noncardiac death exceeded those of cardiac death since the beginning of follow‐up in HFpEF and HFmrEF.ConclusionsNoncardiac death is a major determinant of outcome in stable HF, exceeding cardiac‐related mortality in HFpEF and HFmrHF. Comorbidities should be regarded as main therapeutic targets and objects of dedicated quality improvement initiatives, especially in patients with no or mild systolic dysfunction.

In CRT-D patients, pre-implant CHA2DS2-VASc score is an independent predictor of major clinical events at 30-month follow-up.

Mitochondrial modulation in CHF is an intriguing example of translational research and a potentially rewarding field.

No abstract

Right or left axis deviation in the presence of LBBB in HF patients undergoing CRT are independent predictors of poor prognosis.