Author + information
- Oumhani Toubal, MD,
- Haifa Mahjoub, MD, PhD,
- Christophe Thébault, MD,
- Marie-Annick Clavel, PhD, DVM,
- Abdellaziz Dahou, MD, MSc,
- Julien Magne, PhD,
- Kim O’Connor, MD,
- Jonathan Beaudoin, MD,
- Mathieu Bernier, MD,
- Florent Le Ven, MD and
- Philippe Pibarot, PhD, DVM∗ ()
- ↵∗Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Chemin Sainte-Foy, Québec City G1V-4G5, Québec, Canada
Organic mitral regurgitation (OMR) has become the most frequent cause of severe MR leading to surgery in the Western world. However, the timing of surgery, in other words, early prophylactic surgery versus watchful waiting strategy, in patients with asymptomatic severe MR remains controversial.
We prospectively recruited and followed 111 asymptomatic patients (mean follow-up time: 2.74 ± 1.60 years) with at least moderate OMR in the PROGRAM (Predictors of Disease Progression and Outcomes in Patients With Asymptomatic Organic Mitral Regurgitation) study (NCT01835054). Doppler echocardiography was performed at rest and during a semisupine bicycle exercise using a stepwise protocol with 25-W increments.
Systolic pulmonary arterial pressure (SPAP) was determined at each stage of exercise by measuring the peak systolic gradient of tricuspid regurgitation and adding 10 mm Hg (1). The change in SPAP (ΔSPAP) between rest and the first stage of exercise was measured: the SPAP at the first stage (workload: 25 W) of the exercise protocol minus the SPAP at rest.
Patients were excluded if they had secondary MR, other valvulopathy ≥moderate, valvular surgery, significant coronary artery disease, pericardial disease, congenital disease, infective endocarditis, pregnancy, inability to exercise, or a class I or II indication for mitral valve surgery at the time of baseline echocardiography.
The study endpoint was the composite of the occurrence of mitral valve surgery, new onset of atrial fibrillation, heart failure, cardiac-related hospitalization, or cardiac death.
Among the 111 patients enrolled (61 ± 15 years of age, 53% men), 3% had diabetes, 24% had dyslipidemia, 24% were treated by beta-blockers, and 37% were treated by either angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers. The mean effective regurgitant orifice area was 29.5 ± 16.2 mm2, and 43 patients (39%) had severe MR at baseline. The mean SPAP was 34.2 ± 5.3 mm Hg at rest and 56.2 ± 9.4 mm Hg at peak exercise. Exercise-induced pulmonary hypertension (EIPH) (SPAP ≥60 mm Hg) was present in 21 patients (19%). Twenty-two patients (22%) harbored an early steep rise of SPAP, defined as ΔSPAP >15 mm Hg during the first stage of the exercise test.
Patients with ΔSPAP >15 mm Hg had similar baseline demographics, similar prevalence of cardiovascular risk factors, and clinical data except for systolic systemic arterial pressure, which was higher in this group (137 ± 17 mm Hg vs. 127 ± 16 mm Hg, p = 0.01). There were also more patients treated with beta-blockers in the group with ΔSPAP ≤15 mm Hg (15% vs. 9%; p = 0.02). Doppler echocardiographic data were similar among patients with ΔSPAP >15 mm Hg versus those with ΔSPAP ≤15 mm Hg. Of note, the proportion of patients who developed EIPH was similar in both groups (19.5% vs. 16.7%; p = 0.82).
Of patients with no evidence of PHT at rest, 22% had increased SPAP at a low level of exercise (Figure 1). Furthermore, 30% of patients with no EIPH exhibited a ΔSPAP >15 mm Hg in the early exercise phase, and 25% of patients with EIPH did not display a ΔSPAP >15 mm Hg at the first exercise stage. Patients with early ΔSPAP >15 mm Hg had similar SPAP at rest and peak exercise but higher SPAP at first stage of exercise compared with patients with ΔSPAP ≤15 mm Hg.
During a mean follow-up of 2.74 ± 1.60 years, there were 44 events (39%). Twenty-two percent of patients had a marked increase in SPAP during the first stage of exercise. The 3-year event rate was higher in patients with a ΔSPAP >15 mm Hg at low level of exercise than in those with ΔSPAP ≤15 mm Hg (42.74 ± 10.9% vs. 20.87 ± 4.7%; p = 0.03). ΔSPAP >15 mm Hg was associated with a 1.99-fold increase in the risk of cardiac events (hazard ratio: 1.99; 95% confidence interval: 1.01 to 3.77; p = 0.04). After adjustment for MR severity, indexed left atrial volume, left ventricular end-systolic diameter, and EIPH, a ΔSPAP >15 mm Hg during the first stage of exercise was independently associated with the risk of cardiovascular events (hazard ratio: 3.58; 95% confidence interval: 1.40 to 9.08; p = 0.005).
In summary, asymptomatic patients with OMR presenting an abrupt increase in SPAP >15 mm Hg at a low level of exercise have 2-fold increase in the risk of cardiac events. The early increase in ΔSPAP during exercise stress echocardiography may thus provide a simple and useful way to identify patients who may benefit from early surgery. Further prospective studies are needed to confirm these findings and determine whether the integration of this new parameter on a routine basis would improve risk stratification and therapeutic decision making in asymptomatic patients with moderate to severe OMR.
Please note: This study was funded by a grant from Canadian Institutes of Health Research, Ottawa, Ontario, Canada (MOP#102737 and FDN-143225). Dr. Toubal was supported by a scholarship from the Foundation of the Quebec Heart and Lung Institute. Dr. Pibarot holds the Canada Research Chair in Valvular Heart Diseases funded by the Canadian Institutes of Health Research. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation