Left heart failure with a normal ejection fraction: Identification of different pathophysiologic mechanisms

Mathew S. Maurer, Donald L. King, Lyna El-Khoury Rumbarger, Milton Packer, Daniel Burkhoff

Research output: Contribution to journalArticlepeer-review

165 Scopus citations


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 (Ees,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 (Ees,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 Ees,sb (4.23 ± 0.54 versus 2.1 ± 0.7 mm Hg/mL) and 1 with normal Ees,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.

Original languageEnglish (US)
Pages (from-to)177-187
Number of pages11
JournalJournal of Cardiac Failure
Issue number3
StatePublished - Apr 2005


  • Diastole
  • Echocardiography
  • Heart failure
  • Hemodynamics

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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