Mechanisms of Effort Intolerance in Patients With Heart Failure and Borderline Ejection Fraction

Yan Topilsky*, Zach Rozenbaum, Shafik Khoury, Gregg S. Pressman, Yaniv Gura, Jack Sherez, Avi Man, Jason Shimiaie, Sanford Edwards, Joshua Berookhim, Thierry Le Tourneau, Amir Halkin, Simon Biner, Gad Keren, Galit Aviram

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Combining echocardiography and cardiopulmonary stress testing allows noninvasive assessment of hemodynamics, and oxygen extraction (A-VO2 difference). We evaluated mechanisms of effort intolerance in patients with heart failure with borderline (40% to 49%) left ventricular ejection fraction (EF) (HF and Borderline Ejection fraction). We included 89 consecutive patients with HF and Borderline Ejection fraction (n = 25; 63.6 ± 14 years, 64% men), control subjects (n = 22), patients with HF with preserved EF (n = 26; EF ≥50%), and patients with HF with reduced EF (n = 16; <40%). Various echo parameters (left ventricular volumes, EF, stroke volume, mitral regurgitation [MR] volume, e’, right ventricle end-diastolic area, and right ventricle end-systolic area), and ventilatory or combined parameters (peak oxygen consumption [VO2] and A-VO2 difference) were measured at 4 predefined activity stages. Effort-induced functional MR was frequent and more prevalent in HF and Borderline Ejection fraction than in all the other types of HF. In multivariable analysis heart rate response (p <0.0001), A-VO2 difference (p = 0.02), stroke volume (p = 0.002), and right ventricle end-systolic area were the only independent predictors of exercise capacity in HF and Borderline Ejection fraction but peak EF was not. In HF and Borderline Ejection fraction exercise intolerance is predominantly due to chronotropic incompetence, peripheral factors, and limited stroke volume reserve, which are related to right ventricle dysfunction and functional MR but not to left ventricular ejection fraction. Combined testing can be helpful in determining mechanisms of exercise intolerance in HF and Borderline Ejection fraction.

Original languageEnglish
Pages (from-to)416-422
Number of pages7
JournalAmerican Journal of Cardiology
Issue number3
StatePublished - 1 Feb 2017
Externally publishedYes


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