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J Am Coll Cardiol, 2007; 49:687-694, doi:10.1016/j.jacc.2006.08.062 (Published online 25 January 2007).
© 2007 by the American College of Cardiology Foundation
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CLINICAL RESEARCH: HEART FAILURE

Diastolic Dysfunction in Heart Failure With Preserved Systolic Function: Need for Objective Evidence

Results From the CHARM Echocardiographic Substudy–CHARMES

Hans Persson, MD, PhD*,*, Eva Lonn, MD, MSc{dagger}, Magnus Edner, MD, PhD*, Lawrence Baruch, MD{ddagger}, Chim C. Lang, MD§, John J. Morton, PhD||, Jan Östergren, MD, PhD, Robert S. McKelvie, MD, PhD{dagger} for the Investigators of the CHARM Echocardiographic Substudy–CHARMES

* Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital Department of Cardiology, Stockholm, Sweden
{dagger} Population Health Research Institute and McMaster University, Hamilton, Canada
{ddagger} Bronx Veterans Affairs Medical Center, Mt. Sinai School of Medicine, Bronx, New York
§ Ninewells Hospital and Medical School, Dundee, United Kingdom
|| Western Infirmary, University of Glasgow, Glasgow, United Kingdom
Department of Medicine, Karolinska University Hospital, Solna, Stockholm, Sweden.

Manuscript received July 7, 2006; revised manuscript received August 8, 2006, accepted August 30, 2006.

* Reprint requests and correspondence: Dr. Hans Persson, Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital Department of Cardiology, Stockholm, Sweden. (Email: hans.persson{at}ds.se).

Objectives: We tested the hypothesis that diastolic dysfunction (DD) was an important predictor of cardiovascular (CV) death or heart failure (HF) hospitalization in a subset of patients (ejection fraction [EF] >40%) in the CHARM-Preserved study.

Background: More than 40% of hospitalized patients with HF have preserved systolic function (HF-PSF), suggesting that DD may be responsible for the clinical manifestations of HF.

Methods: Patients underwent Doppler echocardiographic examination that included assessment of pulmonary venous flow or determination of plasma NT-pro-brain natriuretic peptide ≥14 months after randomization to candesartan or placebo. The patients were classified into 1 of 4 diastolic function groups: normal, relaxation abnormality (mild dysfunction), pseudonormal (moderate dysfunction), and restrictive (severe dysfunction).

Results: There were 312 patients in the study, mean age was 66 ± 11 years, EF was 50 ± 10%, and 34% were women. The median follow-up was 18.7 months. Diastolic dysfunction was found in 67% of classified patients (n = 293), and moderate and severe DD were identified in 44%. Moderate and severe DD had a poor outcome compared with normal and mild DD (18% vs. 5%, p < 0.01). Diastolic dysfunction, age, diabetes, previous HF, and atrial fibrillation were univariate predictors of outcome. In multivariate analysis, moderate (hazard ratio [HR] 3.7, 95% confidence interval [CI] 1.2 to 11.1) and severe DD (HR 5.7, 95% CI 1.4 to 24.0) remained the only independent predictors (p = 0.003).

Conclusions: Objective evidence of DD was found in two-thirds of HF-PSF patients. Moderate and severe DD, which were found in less than one-half of the patients, were important predictors of adverse outcome. The results demonstrate the prognostic significance and need for objective evidence of DD in HF-PSF patients.

Abbreviations and Acronyms
  CI = confidence interval
  CV = cardiovascular
  DD = diastolic dysfunction
  EF = ejection fraction
  HF = heart failure
  HF-PSF = heart failure and preserved systolic function
  HR = hazard ratio
  LAVI = left atrial volume index
  LV = left ventricular
  NT-proBNP = N-terminal pro-brain natriuretic peptide


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