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Dalane W. Kitzman, MD; William C. Little, MD; Peter H. Brubaker, PhD; Roger T. Anderson, PhD; W. Gregory Hundley, MD; Christian T. Marburger, MD; Bridget Brosnihan, PhD; Timothy M. Morgan, PhD; Kathryn P. Stewart, RT, RDMS

JAMA. 2002;288:2144-2150.

Context  Many older patients with symptoms of congestive heart failure have a preserved left ventricular ejection fraction (LVEF). However, the pathophysiology of this disorder, presumptively termed diastolic heart failure (DHF), is not well characterized and it is unknown whether it represents true heart failure.

Objective  To assess the 4 key pathophysiological domains that characterize classic heart failure by systematically performing measurements in older patients with presumed DHF and comparing these results with those from age-matched healthy volunteers and patients with classic systolic heart failure (SHF).

Design and Setting  Observational clinical investigation conducted in 1998 in a general community and teaching hospital in Winston-Salem, NC.

Participants  A total of 147 subjects aged at least 60 years. Fifty-nine had isolated DHF defined as clinically presumed heart failure, LVEF of at least 50%, and no evidence of significant coronary, valvular, or pulmonary disease. Sixty had typical SHF (LVEF 35%). Twenty-eight were age-matched healthy volunteer controls.

Main Outcome Measures  Left ventricular structure and function, exercise capacity, neuroendocrine function, and quality of life.

Results  By echocardiography, mean (SE) LVEF was 60% (2%) in patients with DHF vs 31% (2%) in those with SHF and 54% (2%) in controls. Mean (SE) LV mass-volume ratio was markedly increased in patients with DHF (2.12 [0.14] g/mL) vs those with SHF (1.22 [0.14] g/mL) (P<.001) and vs controls (1.49 [0.17] g/mL) (P = .002). Peak oxygen consumption by expired gas analysis during cycle ergometry was similar in the DHF and SHF groups (14.2 [0.5] and 13.1 [0.5] mL/kg per minute, respectively; P = .40) and in both was markedly reduced compared with healthy controls (19.9 [0.7] mL/kg per minute) (P = .001 for both). Ventilatory anaerobic threshold was similar in the DHF and SHF groups (9.1 [0.3] and 8.7 [0.3] mL/kg per minute, respectively; P<.001) and in both was reduced compared with healthy controls (11.5 [0.4] mL/kg per minute) (P<.001). Norepinephrine levels were similar in the DHF (306 [64] pg/mL) and SHF (287 [62] pg/mL) groups (P = .56) and in both were markedly increased vs healthy controls (169 [80] pg/mL) (P = .007 and .03, respectively). Brain natriuretic peptide was substantially increased in both the DHF (56 [30] pg/mL) and the SHF (154 [28] pg/mL) groups compared with healthy controls (3 [38] pg/mL) (P = .02 and .001, respectively). Quality-of-life decrement score as assessed by the Minnesota Living with Heart Failure Questionnaire was substantially increased from the benchmark score of 10 in both groups (SHF: 43.8 [3.9]; DHF: 24.8 [4.4]).

Conclusion  Patients with isolated DHF have similar though not as severe pathophysiologic characteristics compared with patients with typical SHF, including severely reduced exercise capacity, neuroendocrine activation, and impaired quality of life.

Author Affiliations: Sections of Cardiology (Drs Kitzman, Little, and Hundley, and Ms Stewart) and Gerontology (Dr Marburger), Department of Internal Medicine; Department of Public Health Sciences (Drs Anderson and Morgan); and Division of Surgery (Dr Brosnihan), Wake Forest University School of Medicine; and Department of Health and Exercise Sciences (Dr Brubaker), Wake Forest University, Winston-Salem, NC.

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