JAMA: Does all diastolic dysfunction in HF lead to death?
Moderate or severe diastolic dysfunction (DD) was an independent predictor of mortality in patients with a normal ejection fraction who presented for outpatient echocardiography, according to a study published June 27 in the Journal of the American Medical Association.

“Severe DD has been associated with an increased risk of mortality in many conditions, including post–acute MI, amyloidosis, hypertension, chronic renal failure and systolic impairment and even in the presence of normal systolic function in some populations,” wrote Carmel M. Halley, MD, of the Heart and Vascular Institute at Cleveland Clinic, and colleagues. DD also has been linked to increased mortality.

Because few trials have evaluated the effect of DD in patients with normal systolic function, Halley and colleagues performed a single-center study of 36,261 patients who underwent outpatient echo and had an ejection fraction greater than or equal to 55 percent from Jan. 1, 1996 through Dec. 31, 2005.

The patients had a mean age of 58.3 years and 54.4 percent were female. Mean follow-up time was 6.2 years. Cardiovascular risk factors, such as dyslipidemia, hypertension and diabetes mellitus, were seen in 35.3 percent, 14.9 percent, and 11.6 percent of patients, respectively.

The authors reported that DD was present in 65.2 percent of the study population and mild DD was the most prevalent type of dysfunction. Sixty percent of patients had mild DD, 4.8 percent had moderate DD and 0.4 percent had severe DD. Patients with DD were more likely to be male, older than 65, obese and have a greater number of CV risk factors.

During the study’s follow-up period, 5,789 deaths occurred: 842 in the normal diastolic function group, 4,469 in the mild DD group, 429 in the moderate DD group and 49 in the severe DD group. The authors reported that the unadjusted survival rate was worse according to the presence and degree of DD; however, after propensity matching only, moderate and severe DD were associated with an increased mortality risk.

“For the first time, to our knowledge, moderate and severe DD have been shown to be independent predictors of mortality rate, although mild DD has not shown this characteristic after adjusting for common cardiovascular risk factors and existing comorbidities in a large cohort of outpatients with normal ejection fraction,” the authors wrote.

“This finding has important clinical implications, especially given the high prevalence of mild DD in the population studied.”

The authors noted that the potential mechanisms by which moderate and severe DD are independently linked to mortality risk will require further study. “However, our results suggest that an increased awareness of the clinical significance of advanced DD may lead to earlier identification of those patients who are at risk, especially at a preclinical stage,” the authors concluded.

In an invited JAMA commentary, Ileana L. Piña, MD, MPH, of the Case Western Reserve University in Cleveland, asked: “Does DD exist that does not progress to HF?

“The continuum of DD from mild and asymptomatic to severe and symptomatic is being constructed by pieces, as is a puzzle,” Piña wrote. While many studies have been undertaken, the prevalence of DD and HF varies significantly among studies depending on the population studied.

“These observations lend credence to the complexity of [HF with normal systolic function] beyond mere DD and of the ways patients ultimately progress to frank HF,” Piña wrote. “The missing link between DD diagnosed via echocardiographic testing and the acute presentation of older women with [this condition] is yet to be elucidated. Further work will help solve this puzzle.”