Exercise capacity in HFpEF unaffected by reduced diastolic filling time

Using chronotropic response as a reference, study authors from Japan examined the potential influence of exercise-induced heart rate on cardiac output and exercise capacity in a cohort of heart failure patients with conserved ejection fraction (HFpEF).

Neither exercise capacity nor cardiac output reserve were impaired in heart failure patients with preserved ejection fraction (HFpEF) after cycling exercise echocardiography and expired gas analysis, despite reduced diastolic filling time, according to study results published in Journal of the American Heart Association.

“We sought to determine the association between heart rate, diastolic filling time, hemodynamics and exercise capacity in HFpEF,” the authors wrote.

The 173 study participants were divided into 2 groups: 66 in the HFpEF group and 107 in the non-HF cohort. They underwent exercise cardiography in the echocardiography laboratory of Gunma University Hospital, Maebashi, Japan, between October 2019 and September 2021. The stress test consisted of 20 W steps of 3 minutes each up to the subject’s reported exhaustion. Control group participants were unable to have a heart-related cause of shortness of breath.

Overall total median maximum exercise load was 33% lower in the HFpEF cohort versus control group, at 40 (range, 40-60) versus 60 (range, 40-80) and mean exercise time was 13% shorter, at 532 (178 ) vs. 614 (196) seconds. However, the mean respiratory exchange ratios were similar: 1.12 (0.15) versus 1.10 (0.17), respectively. Furthermore, the median exertion and dyspnea scores were higher in the HFpEF cohort versus the control group: 0.32 (range 0.25-0.43) vs 0.25 (range 0.20-0.32) and 0.13 (range 0.08-0.18) vs 0.09 (range, 0.05-0.13), respectively.

Patients in the HFpEF cohort were older than controls (mean [SD] age, 74 [8] against 63 [13] years), had a higher rate of hypertension (83% vs 66%), had a 4-fold increase in -blocker use (33% vs 7%), and had a reduced estimated glomerular filtration rate (63 [23] against 67 [21] ml/min/1.73 m2† In addition, their mean baseline E wave and A wave were increased compared to the control group:

  • E-wave: 74 (26) vs 63 (16) cm/s
  • A-wave: 91 (27) vs 76 (21) cm/s

On a scale of 0 to 60 W, the overlap time for both groups increased continuously, concomitantly with an increase in heart rate, with the control group numbers being slightly higher than the HFpEF group (0, 20, 40, 60 W) at all points. This increase in overlap time indicated a shorter diastolic filling time.

In turn, the higher heart rate in both groups during peak exercise had a positive correlation with higher cardiac output (r = 0.51; p < .0001) and oxygen consumption (r = 0.50; p < .0001). In addition, the shortened diastolic filling time had a positive correlation with higher cardiac output (r = 0.47; p < .0001), as well as peak oxygen consumption (r = 0.38; p = .007).

A positive relationship was also seen between longer overlap time and both mitral velocity A (r = 0.53; p < .0001) and left atrial booster pump voltage (r = 0.42; p < .0001).

“These data suggest that shortening the diastolic filling interval in combination with an increased heart rate during exercise does not limit cardiac output reserve or exercise capacity in patients with HFpEF,” the authors wrote. “Our data indicate a compensatory mechanism for the reduction of the diastolic filling period by improving the contractile function of the left atrium.”

They also note that because recent research indicates that beta-blockers may exacerbate the chronotropic response to cardiac output-limiting exercise and increase left ventricular wall stress, the option of discontinuing their use in patients with reduced exercise capacity and chronotropic incompetence should be explored.

“Further studies are needed to increase our understanding of the underlying pathophysiological mechanisms and to investigate the optimal treatment of this syndrome,” they concluded.


Kagami K, Obokata M, Harada T, et al. Diastolic filling time, chronotropic response and exercise capacity in heart failure and preserved ejection fraction with sinus rhythm. J Am Hart Assoc. Published online June 29, 2022. doi:10.1161/JAHA.121.026009

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