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This Article Figures Only Full Text Full Text (PDF) View Investigators and staff participating in CHARMES All Versions of this Article: j.jacc.2006.08.062v1 49/6/687    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Persson, H. Search for Related Content PubMed Articles by Persson, H. Related Collections Related Article

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, Magnus Edner, MD, PhD^_*, Lawrence Baruch, MD, Chim C. Lang, MD, John J. Morton, PhD^||, Jan Östergren, MD, PhD^¶, Robert S. McKelvie, MD, PhD for the Investigators of the CHARM Echocardiographic Substudy–CHARMES

^_* Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital Department of Cardiology, Stockholm, Sweden
Population Health Research Institute and McMaster University, Hamilton, Canada
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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