Left Heart Failure With a Normal Ejection Fraction: Identification of Different Pathophysiologic Mechanisms

doi:10.1016/j.cardfail.2004.10.006

Journal of Cardiac Failure

Volume 11, Issue 3, April 2005, Pages 177-187

https://doi.org/10.1016/j.cardfail.2004.10.006 Get rights and content

Abstract

Background

Although heart failure with a normal ejection fraction (HFNEF) is a clinically heterogeneous syndrome, a single pathophysiologic mechanism, diastolic dysfunction, is often ascribed to explain this condition. In view of the clinical heterogeneity of these patients, we hypothesized that subgroups of HFNEF patients may have different underlying pathophysiologic mechanisms.

Methods and Results

Freehand 3-dimensional echocardiography was used to measure left ventricular end-systolic and end-diastolic volumes in 99 asymptomatic normal controls and 2 groups with chronic heart failure: 35 patients with normal ejection fraction with longstanding hypertension (hypertensive HFNEF) and 11 patients with hypertrophic cardiomyopathy without a history of hypertension (nonhypertensive HFNEF). These data, combined with cuff sphygmomanometry and Doppler estimates of LV end-diastolic pressure (EDP) yielded estimated pressure-volume loops and slope (E_es,sb) of the end-systolic pressure-volume relationship, a load independent index of chamber contractility. Nonhypertensive HFNEF patients required high EDPs (21 ± 2 versus 15 ± 3 mm Hg in normals, P < .0001) to achieve normal EDVs (98 ± 25 versus 95 ± 21 mL in normals, P = NS). Although systolic function (E_es,sb) did not differ from normal, systolic blood pressure was lower than normal in these patients (114 ± 10 versus 124 ± 14 mm Hg in normals, P < .05). Hypertensive HFNEF patients also had increased EDP (20 ± 2 mm Hg), but this was observed at higher than normal EDVs (118 ± 29 mL, P < .05). Among patients with hypertensive HFNEF, 2 subgroups emerged, 1 with a high E_es,sb (4.23 ± 0.54 versus 2.1 ± 0.7 mm Hg/mL) and 1 with normal E_es,sb (2.31 ± 0.51 mm Hg/mL). The former group was composed of elderly women with small body size (body surface area 1.7 ± 0.2 versus 1.9 ± 0.2 m², P = .02) who had concentrically remodeled ventricles and low stroke volumes. The latter group was more diverse in age, body size, and included patients of both genders with increases in ventricular volumes, stroke volume, and mass consistent with a volume overload state.

Conclusion

Although HFNEF is commonly thought of as being the result of a single hemodynamic mechanism, these data indicate that subgroups exist with distinctly different underlying pathophysiologies.

Section snippets

Study Patients

All patients provided informed consent forms and were evaluated as outpatients while medically stable and clinically euvolemic (no rales, lower extremity edema, or ascites), according to a protocol approved by the Institutional Review Board of Columbia University. The main group of patients (n = 56) comprised subjects with heart failure and a normal ejection fraction (by 2-dimensional [2D] echocardiography) referred by their primary cardiologists with a diagnosis of diastolic heart failure. For

Clinical Characteristics

Consistent with previous reports,6, 35, 36 patients with hypertensive HFNEF were primarily elderly women, whereas patients with nonhypertensive HFNEF did not differ significantly from controls with regard to age or gender distribution (Table 1). All groups were reasonably similar with regard to body surface area. Diabetes mellitus was prevalent in all heart failure groups. Coronary artery disease defined by presence of electrocardiographic evidence of a prior myocardial infarction or documented

Discussion

Theory predicts (Fig. 1) and our measurements of ventricular size and function support (Fig. 2) the hypothesis that the mechanisms leading to heart failure in the setting of a normal ejection fraction differ among patient subgroups. Using a simple clinical variable, the presence or absence of elevated blood pressure or clinical history of hypertension, and echocardiographic measures of ventricular size and function, we identified 2 distinct subgroups of subjects with HFNEF: (1) nonhypertensive

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: M.S.M. supported by a Career Development Award (K23) from the National Institute on Aging (AG-00966).

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Clinical InvestigationLeft Heart Failure With a Normal Ejection Fraction: Identification of Different Pathophysiologic Mechanisms

Abstract

Background

Methods and Results

Conclusion

Section snippets

Study Patients

Clinical Characteristics

Discussion

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Clinical Investigation
Left Heart Failure With a Normal Ejection Fraction: Identification of Different Pathophysiologic Mechanisms