A Systematic Review of Diastolic Stress Tests in Heart Failure with Preserved Ejection Fraction, with Proposals from the EU-FP7 MEDIA Study Group

AIMS: Cardiac function should be assessed during stress in patients with suspected heart failure with preserved ejection fraction (HFPEF), but it is unclear how to define impaired diastolic reserve. METHODS AND RESULTS: We conducted a systematic review to identify which pathophysiological changes serve as appropriate targets for diagnostic imaging. We identified 38 studies of 1111 patients with HFPEF (mean age 65 years), 744 control patients without HFPEF, and 458 healthy subjects. Qualifying EF was >45-55%; diastolic dysfunction at rest was a required criterion in 45% of studies. The initial workload during bicycle exercise (25 studies) varied from 12.5 to 30 W (mean 23.1 ± 4.6), with increments of 10-25 W (mean 19.9 ± 6) and stage duration 1-5 min (mean 2.5 ± 1); targets were submaximal (n = 8) or maximal (n = 17). Other protocols used treadmill exercise, handgrip, dobutamine, lower body negative pressure, nitroprusside, fluid challenge, leg raising, or atrial pacing. Reproducibility of echocardiographic variables during stress and validation against independent reference criteria were assessed in few studies. Change in E/e' was the most frequent measurement, but there is insufficient evidence to establish this or other tests for routine use when evaluating patients with HFPEF. CONCLUSIONS: To meet the clinical requirements of performing stress testing in elderly subjects, we propose a ramped exercise protocol on a semi-supine bicycle, starting at 15 W, with increments of 5 W/min to a submaximal target (heart rate 100-110 b.p.m., or symptoms). Measurements during submaximal and recovery stages should include changes from baseline in LV long-axis function and indirect echocardiographic indices of LV diastolic pressure.