Moderate and severe diastolic dysfunction in patients who have normal systolic function increased all-cause mortality, according to a report in the June 27 issue of the Archives of Internal Medicine.
Such diastolic dysfunction is usually preclinical and often is identified on outpatient echocardiography that was done to assess nonspecific symptoms, ventricular or valvular function, arrhythmia, or ECG abnormalities. Its clinical significance has not been documented until now, said Dr. Carmel M. Halley of the Heart and Vascular Institute at the Cleveland Clinic, and her associates.
"Because the use of echocardiography as a clinical tool in the outpatient setting continues to increase ... our study provides the physician with a prognostic context when diastolic dysfunction is reported, especially because most procedures are requested by noncardiologists," the researchers noted (Arch. Intern. Med. 2011;171:1082-7).
Dr. Halley and her colleagues examined diastolic dysfunction in the absence of systolic dysfunction, because the clinical relevance of the condition has been questioned. Many medical disorders associated with diastolic dysfunction, such as hypertension, coronary artery disease, obesity, and diabetes, are themselves predictors of increased mortality, so it was unclear whether diastolic dysfunction was an independent contributor.
The researchers reviewed the records of consecutive patients who underwent outpatient echocardiography at the Cleveland Clinic and its satellite facilities between 1996 and 2005. They identified 36,261 patients (65,696 echocardiographic tests) who had normal ejection fractions signaling preserved systolic function.
The mean patient age was 58 years, and slightly more than half of the study subjects were women. The subjects were typical of patients usually referred for echocardiography – they frequently had cardiovascular risk factors such as dyslipidemia (35%), hypertension (15%), and diabetes (12%), but usually did not have established CV disease, such as congestive heart failure (4%), peripheral vascular disease (1%), or coronary artery disease (0.6%).
The most frequent indications for ordering the echocardiography were symptom assessment, assessment of ventricular or valvular function, evaluation of suspected or known CAD, and assessment of arrhythmia or ECG abnormalities.
The prevalence of diastolic dysfunction was high, at 65%. The dysfunction was mild in the majority of patients (nearly 60%), moderate in 4.8%, and severe in 0.4%.
During an average follow-up of 6 years, there were 5,789 deaths. Unadjusted all-cause mortality was higher with any degree of diastolic dysfunction than with normal diastolic function: 21% with mild diastolic dysfunction, 24% with moderate diastolic dysfunction, and 39% with severe diastolic dysfunction, compared with 7% in patients who had normal diastolic function.
However, because comorbidities that could confound the analyses were more common among patients with more severe diastolic dysfunction, propensity matching and statistical controlling for comorbidities were performed. Subsequent analysis showed that only moderate and severe diastolic dysfunction raised mortality risk.
Eight-year survival estimates were 78% for patients with normal diastolic function and 72% for mild diastolic dysfunction, compared with 68% for moderate diastolic dysfunction and 58% for severe diastolic dysfunction.
"For the first time, to our knowledge, moderate and severe diastolic dysfunction have been shown to be independent predictors of mortality rate," Dr. Halley and her associates said.
The mechanisms by which diastolic dysfunction raises mortality are not yet known, nor is it known whether therapies targeting such dysfunction can be developed, or whether they would reduce mortality. "However, our results suggest that an increased awareness of the clinical significance of advanced diastolic dysfunction may lead to earlier identification of those patients who are at risk, especially at a preclinical stage," the investigators noted.
They added that this study was limited in that it was retrospective and involved only a single institution.
This new study provides "an important piece of the puzzle," shedding light on the continuum from mild and asymptomatic to severe and symptomatic diastolic dysfunction, said Dr. Ileana L. Piña in remarks taken from her invited commentary that accompanied Dr. Halley’s report (Arch. Intern. Med. 2011;171:1088-9).
The findings that diastolic dysfunction is so common – affecting 65% of this study cohort – and that physicians must be alert to the prognostic value of more severe dysfunction are "novel and important for physicians."
In the future, it will be critical to elucidate the missing link between diagnosis of diastolic dysfunction on echocardiography and the later presentation of older patients, particularly older women, with acute decompensated heart failure in which systolic function is preserved, Dr. Piña of the departments of epidemiology and biostatistics at Case Western Reserve University, Cleveland, added.
One of Dr. Halley’s associates reported ties to GE Healthcare, Philips Healthcare, and Siemens AG. Dr. Piña reported no financial disclosures.