Impact of Progression of Diastolic Dysfunction on Mortality in Patients With Normal Ejection Fraction

Study Questions:

What is the impact of progression of diastolic dysfunction (DD) on all-cause mortality in patients initially evaluated as ambulatory outpatients?

Methods:

Clinical records and echocardiograms of 1,065 consecutive patients who underwent a baseline echocardiogram between January 1, 2005, and December 31, 2009, and who also had a follow-up echocardiogram within 6-24 months were reviewed. All-cause mortality was assessed by use of the Social Security Death Index. Diastolic function was labeled as normal, mild, moderate, or severe dysfunction corresponding to normal, and grade 1, 2, and 3 diastolic function.

Results:

Average patient age was 67.9 ± 13.9 years and 58% were male. Baseline DD was noted in 770 patients (72.3%), and was mild in 65.9% and moderate or severe in 7.4%. Clinical association with baseline DD included increasing age and hypertension. For the whole group, average time between echocardiograms was 1.1 ± 0.4 years and the average follow-up time was 1.6 ± 0.8 years. At baseline, all patients had normal left ventricular (LV) systolic function (LV ejection fraction [LVEF] ≥55%). Diastolic function remained stable in 783 patients (73%), worsened in 168 (16%), and improved in 14 (11%). A decrease in LVEF to <55% was noted in 88 patients (8.3%) of whom 60 had stable, 19 worsening, and 9 improved diastolic function. On follow-up, all-cause mortality was reported in 142 patients (13%), including 20 (27.6%) with normal diastolic function, 102 with mild DD (14.8%), and 20 (17.9%) with at least moderate DD (p = 0.01). All-cause mortality was 21% in patients with worsening DD versus 12% in those with stable DD (p = 0.001). Mortality was 11.4% in those with improved diastolic function (p = 0.88 compared to stable). On multivariable analysis, a decrease of LVEF to <55% and worsening diastolic function were independently associated with all-cause mortality (hazard ratio 1.78 for each, p = 0.02 and 0.003, respectively). The hazard ratio for conversion of diastolic function from normal to abnormal was 3.58 (p = 0.001), and was 2.13 for worsening from mild to moderate or severe DD (p = 0.01).

Conclusions:

In patients with normal baseline LV systolic function, development of DD or worsening of pre-existing DD independently predicts all-cause mortality.

Perspective:

Multiple studies have demonstrated the independent adverse impact of DD in patients with a broad spectrum of disease including congestive heart failure with or without concurrent systolic dysfunction. This large study evaluated a series of patients with preserved LV systolic function, all of whom were ambulatory outpatients at the time of enrollment, and nicely demonstrated an independent impact of subsequent development of DD on all-cause mortality. Data were not available to further stratify the mode of death with respect to cardiac versus noncardiac, or congestive heart failure versus other cardiac events. The mechanism by which diastolic function relates to adverse outcomes probably relates to progression of underlying disease whether it is ischemic heart disease, hypertensive cardiovascular disease, or other clinical entities. Whether more aggressive therapy in patients noted to have progression of DD on echocardiography would have an impact on prognosis remains conjectural.

Keywords: Prognosis, Myocardial Ischemia, Follow-Up Studies, Ventricular Function, Left, Outpatients, Heart Failure, Cardiovascular Diseases, Social Security, Diastole, Hypertension, Systole, Echocardiography


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