Aetiology, ejection fraction and mortality in chronic heart failure: a mediation analysis

Area of Science:

• Cardiology
• Clinical Research
• Heart Failure Management

Background:

• Clinical decision-making in chronic heart failure (CHF) primarily relies on left ventricular ejection fraction (LVEF).
• The underlying etiology of CHF is considered secondary in current treatment strategies.
• Understanding the interplay between etiology, LVEF, and mortality is essential for optimizing patient care.

Purpose of the Study:

• To investigate the mediating role of LVEF in the relationship between CHF etiology and patient mortality.
• To quantify the direct and indirect effects of various CHF etiologies on overall mortality.
• To determine the relative importance of etiology versus LVEF in predicting mortality.

Main Methods:

• Analysis of data from 2056 Austrian CHF patients with a mean follow-up of 8.8 years.
• Utilized multivariable-adjusted linear and Cox regression models to assess effects of etiology on LVEF and mortality.
• Employed causal mediation analyses to decompose the total effect of etiology on mortality into direct and indirect pathways through LVEF.

Main Results:

• The effect of LVEF on mortality was consistent across analyzed etiologies (e.g., dilated cardiomyopathy, hypertrophic cardiomyopathy, ischemic heart disease, hypertensive heart disease, cardiac amyloidosis).
• Cardiac amyloidosis (CA) showed the highest mortality, with a significant indirect effect mediated through LVEF.
• For most etiologies, less than 20% of the total mortality effect was mediated through LVEF, indicating a dominant direct effect of etiology.

Conclusions:

• The direct impact of CHF etiology on mortality is more significant than the indirect effect mediated by LVEF.
• Clarifying the specific etiology of chronic heart failure is as critical as measuring LVEF for accurate prognosis.
• These findings underscore the need to integrate etiological assessment into clinical decision-making for CHF patients.