Noncardiac Versus Cardiac Mortality in Heart Failure With Preserved, Midrange, and Reduced Ejection Fraction

Area of Science:

• Cardiology
• Internal Medicine
• Public Health

Background:

• A comprehensive understanding of noncardiac mortality determinants in heart failure (HF) is lacking.
• Conflicting evidence exists regarding the prognosis of HF patients with no or mild systolic dysfunction.
• This study addresses the prevalence of cardiac and noncardiac death causes across the full spectrum of systolic function in chronic HF.

Purpose of the Study:

• To investigate the prevalence of noncardiac and cardiac causes of death in a stable chronic heart failure cohort.
• To analyze mortality across different left ventricular ejection fraction (EF) categories: reduced (HFrEF), midrange (HFmrEF), and preserved (HFpEF).
• To compare the contribution of noncardiac factors to overall mortality in HF subtypes.

Main Methods:

• Enrolled 2791 stable HF patients categorized by LVEF (<40% for HFrEF, 41-49% for HFmrEF, ≥50% for HFpEF).
• Followed patients for all-cause, cardiac, and noncardiac mortality over 39 months.
• Adjudicated noncardiac deaths due to cancer, sepsis, respiratory, renal, or other causes.

Main Results:

• Adjusted mortality was significantly lower in HFpEF and HFmrEF compared to HFrEF.
• Noncardiac mortality rates were similar across LVEF categories, while cardiac death predominated in HFrEF.
• Noncardiac causes constituted 62% of deaths in HFpEF, 54% in HFmrEF, and 35% in HFrEF; cancer was a more frequent cause in HFpEF/HFmrEF.

Conclusions:

• Noncardiac death is a primary determinant of outcome in stable HF, surpassing cardiac mortality in HFpEF and HFmrEF.
• Comorbidities represent key therapeutic targets and quality improvement areas, particularly for patients with no or mild systolic dysfunction.
• This highlights the need for integrated management strategies addressing both cardiac and noncardiac conditions in heart failure care.