CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Hans Persson, MD, PhD*,
Eva Lonn, MD, MSc,
Robert S. McKelvie, MD, PhD for the Investigators of the CHARM Echocardiographic Substudy—CHARMES
* Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, Stockholm, SE-182 88, Sweden (Email: hans.persson{at}ds.se).
We thank Dr. Kolias for his congratulatory letter to us for our echocardiographic substudy in CHARM (Candesartan in Heart Failure—Assessment of Reduction in Mortality and Morbidity) Preserved—the CHARMES trial, recently published in JACC (1). His comments are appreciated, and we would agree with him that it is important to consider abandoning the "black box" term of "heart failure with preserved systolic function" and that efforts would be better directed toward striving to improve the detailed assessment of diastolic function. We have been able to reclassify the patients in CHARMES to respond to the relevant question posed by Dr. Kolias. In the revised analysis we have retrieved data for a conventional Doppler-echocardiographic evaluation of 181 of the 312 patients entered in the trial, thus not using the N-terminal part of the pro-B-type natriuretic peptide (NT-proBNP) to distinguish between normal and pseudonormal diastolic function. We have used a non–age-related classification of diastolic function following the current guideline from the Mayo Clinic (2). The present analysis is a secondary, post hoc analysis in a smaller subset; therefore, the results have to be interpreted with caution.
The results do show that the proportion of patients with normal diastolic function is similar to the previous results in CHARMES, with 1 out of 3 patients being normal (see Table 1). The proportion of patients with mild diastolic dysfunction is slightly higher, although the proportion with normal and mild diastolic dysfunction is not significantly different from the original CHARMES study (60% vs. 55%). We can still show a graded relationship between severity of diastolic dysfunction and outcome. The relative risk for moderate to severe diastolic versus mild diastolic dysfunction is approximately 2, both for the end point of cardiovascular death or readmission for heart failure (CV1) and for the combined end point of cardiovascular mortality, rehospitalization for heart failure, myocardial infarction, and stroke (CV2). The relative risk for moderate to severe diastolic dysfunction versus mild dysfunction and normal function is 3.8 for CV1 and 3.9 for CV2. Mild diastolic dysfunction in this subset carries a similar prognosis as in the full study (7% vs. 6%), whereas the normal group has a nonsignificantly better prognosis (0% vs. 4%).
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Table 1 Diastolic Function Groups in CHARMES and Subset: Cardiovascular Events in CHARMES Subset by Diastolic Function Group
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Thus, using a non–age-adjusted Doppler-echocardiographic classification of diastolic function, we can conclude that normal diastolic function and mild diastolic dysfunction are seen in 60% of the patients, and the relationship is graded between severity of diastolic dysfunction and outcome, with a 4-fold risk increase for moderate to severe diastolic dysfunction compared to normal diastolic function and mild diastolic dysfunction and 2-fold when comparing moderate and severe to mild dysfunction. The recalculations do not suggest a different picture from the previous primary analysis.
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References
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- Persson H, Lonn E, Edner M, et al. Investigators of the CHARM Echocardiographic Substudy—CHARMES Diastolic dysfunction in heart failure with preserved systolic function: need for objective evidence: results from the CHARM Echocardiographic Substudy—CHARMES J Am Coll Cardiol 2007;49:687-694.[Abstract/Free Full Text]
- Redfield M, Jacobsen S, Burnett J, Mahoney D, Bailey K, Rodeheffer R. Burden of systolic and diastolic ventricular dysfunction in the community JAMA 2003;289:194-202.[Abstract/Free Full Text]
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