Mechanisms of Effort Intolerance in Patients With Rheumatic Mitral Stenosis: Combined Echocardiography and Cardiopulmonary Stress Protocol

Michal Laufer-Perl, Yaniv Gura, Jason Shimiaie, Jack Sherez, Gregg S. Pressman, Galit Aviram, Simon Maltais, Ricki Megidish, Amir Halkin, Meirav Ingbir, Simon Biner, Gad Keren, Yan Topilsky*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Objectives This study sought to evaluate mechanisms of effort intolerance in patients with rheumatic mitral stenosis (MS). Background Combined stress echocardiography and cardiopulmonary testing allows assessment of cardiac function, hemodynamics, and oxygen extraction (A–VO2 difference). Methods Using semirecumbent bicycle exercise, 20 patients with rheumatic MS (valve area 1.36 ± 0.4 cm2) were compared to 20 control subjects at 4 pre-defined activity stages (rest, unloaded, anaerobic threshold, and peak). Various echocardiographic parameters (left ventricular volumes, ejection fraction, stroke volume, mitral valve gradient, mitral valve area, tissue s′ and e′) and ventilatory parameters (peak oxygen consumption [VO2] and A–VO2 difference) were measured during 8 to 12 min of graded exercise. Results Comparing patients with MS to control subjects, significant differences (both between groups and for group by time interaction) were seen in multiple parameters (heart rate, stroke volume, end-diastolic volume, ejection fraction, s′, e′, VO2, and tidal volume). Exercise responses were all attenuated compared to control subjects. Comparing patients with MS and poor exercise tolerance (<80% of expected) to other subjects with MS, we found attenuated increases in tidal volume (p = 0.0003), heart rate (p = 0.0009), and mitral area (p = 0.04) in the poor exercise tolerance group. These patients also displayed different end-diastolic volume behavior over time (group by time interaction p = 0.05). In multivariable analysis, peak heart rate response (p = 0.01), tidal volume response (p = 0.0001), and peak A–VO2 difference (p = 0.03) were the only independent predictors of exercise capacity in patients with MS; systolic pulmonary pressure, mitral valve gradient, and mitral valve area were not. Conclusions In patients with rheumatic MS, exercise intolerance is predominantly the result of restrictive lung function, chronotropic incompetence, limited stroke volume reserve, and peripheral factors, and not simply impaired valvular function. Combined stress echocardiography and cardiopulmonary testing can be helpful in determining mechanisms of exercise intolerance in patients with MS.

Original languageEnglish
Pages (from-to)622-633
Number of pages12
JournalJACC: Cardiovascular Imaging
Issue number6
StatePublished - Jun 2017


  • congestive heart failure
  • echocardiography
  • exercise testing


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