Abstract

Phenotyping heart failure represents a major challenge for both research studies and clinical practice. Large-scale clinical trials have failed to achieve meaningful improvement in clinical outcomes with different pharmacological agents in patients with heart failure and preserved left ventricular ejection fraction. Therefore, an alternative scheme for phenotyping heart failure is needed, which is both pathophysiologically distinct and practical for routine clinical application. Heart failure is a syndromic diagnosis broadly based on clinical features, physical findings, and serum biomarkers. Although the assessment of exercise hemodynamics and invasive estimation of filling pressures may be necessary, it is typically confirmed and phenotyped by the imaging data. Phenotyping heart failure represents a major challenge despite decades of ongoing research, vast clinical experience in the field, and multiple iterations of published guidelines. Left ventricular ejection fraction (LVEF) remains the major phenotyping tool endorsed by multiple cardiology societies. However, it has multiple limitations especially in patients with heart failure with preserved LVEF (HFpEF), and many have questioned the current approach to phenotyping of heart failure but no alternative, widely accepted, scheme (which is both clinically relevant and practical) has been offered.1 The existing phenotyping approach to heart failure is based on the premise of LVEF as a surrogate marker for left ventricular systolic performance and, in turn, prognosis. Heart failure patients with reduced LVEF (HFrEF) are assumed to have systolic heart failure, whereas many heart failure patients have preservation of LVEF and are commonly labeled as HFpEF. This assumption makes LVEF the primary marker of heart failure and excludes other important abnormalities that can create the heart failure syndrome. Furthermore, LVEF is an imperfect marker even for assessment of systolic function: it has high interobserver variability, it mainly reflects radial shortening, it is load dependent, and it does not reflect the remodeling pattern of the …

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