Structural and Functional Phenotyping of the Failing Heart: Is the Left Ventricular Ejection Fraction Obsolete?

Abstract

Diagnosis, prognosis, treatment, and development of new therapies for diseases or syndromes depend on a reliable means of identifying phenotypes associated with distinct predictive probabilities for these various objectives. Left ventricular ejection fraction (LVEF) provides the current basis for combined functional and structural phenotyping in heart failure by classifying patients as those with heart failure with reduced ejection fraction (HFrEF) and those with heart failure with preserved ejection fraction (HFpEF). Recently the utility of LVEF as the major phenotypic determinant of heart failure has been challenged based on its load dependency and measurement variability. We review the history of the development and adoption of LVEF as a critical measurement of LV function and structure and demonstrate that, in chronic heart failure, load dependency is not an important practical issue, and we provide hemodynamic and molecular biomarker evidence that LVEF is superior or equal to more unwieldy methods of identifying phenotypes of ventricular remodeling. We conclude that, because it reliably measures both left ventricular function and structure, LVEF remains the best current method of assessing pathologic remodeling in heart failure in both individual clinical and multicenter group settings. Because of the present and future importance of left ventricular phenotyping in heart failure, LVEF should be measured by using the most accurate technology and methodologic refinements available, and improved characterization methods should continue to be sought.

Keywords: ejection fraction; gene expression; heart failure; left ventricular function; left ventricular structure; phenotyping.

Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

FIGURE 1. Remodeling of a Normal Heart Into an HFrEF Phenotype

Remodeling of a normal heart into a HFrEF phenotype (LV or RV) characterized by contractile dysfunction and eccentric hypertrophy as detected by a reduction in EF. ARVC = arrhythmogenic right ventricular cardiomyopathy; COPD = chronic obstructive pulmonary disease; CRT = cardiac resynchronization therapy; EDV = end diastolic volume; ESV = end systolic volume; HFrEF = heart failure with reduced ejection fraction; HTN = hypertension; IDC = idiopathic dilated cardiomyopathy; LV = left ventricle; LVF = left ventricle failure; MI = myocardial infarction; PAH = pulmonary arterial hypertension; RV = right ventricle; VHD = valvular heart disease.

FIGURE 2. LVEF, Ventricular Volume (EDVI and ESVI), and SVI Relationships

(A) LVEF, ventricularvolume (EDVIand ESVI), and SVIrelationships are shownin 32nonischemicDCM patients treated for 3(n = 5)and12(n = 27)months with metoprolol, metoprolol plus doxazosin or carvedilol (18,19). EF and volume measurements were made by radionuclide SPECT imaging (18). (B) Change from baseline (%) in patient and parameters shown in A. DCM = dilated cardiomyopathies; EDVI = end diastolic volume index; ESVI = end systolic volume index; LVEF = left ventricle ejection fraction; SPECT = single-photon emission computed tomography; SVI = stroke volume index.

CENTRAL ILLUSTRATION. Natural History of HFrEF Phenotype

Natural history of a HFrEF phenotype as assessed by serial LVEF measurements. Following initial damage to or loss of sarcomere, compensatory mechanisms are activated to support myocardial function, but these compensatory mechanisms eventually lead to progression of remodeling and heart failure natural history (16). C.O. = cardiac output; ECM = extracellular matrix; EDV = end diastolic volume; HFrEF = heart failure with reduced ejection fraction; LVEF = left ventricle ejection fraction; RAAS = renin-angiotensin-aldosterone systems; SV = stroke volume.