Determinants of Effort Intolerance in Patients With Heart Failure: Combined Echocardiography and Cardiopulmonary Stress Protocol

Jason Shimiaie, Jack Sherez, Galit Aviram, Ricki Megidish, Sami Viskin, Amir Halkin, Meirav Ingbir, Nahum Nesher, Simon Biner, Gad Keren, Yan Topilsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


Objectives: The purpose of this study was to assess individual mechanisms of effort intolerance in patients with heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), or normal cardiac function using combined echocardiography and cardiopulmonary stress testing. Background: Combined stress echocardiography and cardiopulmonary tests visualize cardiac chambers in 4 well-defined activity levels (rest, unloaded, anaerobic threshold, and peak), allowing noninvasive assessment of cardiac function, hemodynamics, and arterial venous oxygen content difference (AVo2Diff) during all stages. Methods: Left ventricular volumes, stroke volume (SV), S', E/e', oxygen consumption (Vo2), and AVo2Diff were measured in all effort stages using ramp semirecumbent cycle prolonged (≥8 min) exercise in 45 consecutive subjects evaluated for effort intolerance (14 normal cardiac function, 16 HFpEF, and 15 HFrEF patients; age 56.5 ± 16 years; 73% male). Results: In HFpEF and HFrEF, the changes in Vo2 were attenuated (between group p = 0.003; group by time interaction p < 0.0001), as well as peak heart rate (p = 0.0001; p = 0.0001) and SV (p = 0.006; p = 0.0001). End-diastolic volume to E/e' ratio (measure of compliance) was superior in HFrEF and normal patients at baseline but worsened in HFpEF and HFrEF at peak exercise (8.3 ± 4 vs. 11.6 ± 5 vs. 19.1 ± 8; p = 0.004; p = 0.01). Functional mitral regurgitation worsened even during the unloaded stage, mostly in patients with HFrEF, but also in several patients with HFpEF. In multivariable analysis, heart rate response (p = 0.007), and AVo2Diff (p < 0.0001) were the most significant independent predictors of effort capacity; SV was not. Conclusions: Combined tests are feasible and allow noninvasive evaluation of effort intolerance. In HFpEF and HFrEF patients, exercise intolerance is predominantly due to chronotropic incompetence and peripheral factors. Combined stress echocardiography and cardiopulmonary tests may have potential for clinical management and selection of patients for trials.

Original languageEnglish
Article number345
Pages (from-to)803-814
Number of pages12
JournalJACC: Heart Failure
Issue number10
StatePublished - Oct 2015
Externally publishedYes


  • Congestive heart failure
  • Echocardiography
  • Exercise testing


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