부산대학교 도서관

Background: Secondary mitral regurgitation (MR) is a serious and frequent complication of dilated cardiomyopathy and/or coronary artery disease. In patients with left-sided valvular heart disease, exercise pulmonary hypertension (ExPHT) was recently identified as a powerful marker of advanced risk of cardiac event. In secondary MR, exercise PHT is mainly determined by dynamic MR,which is involved in the pathogenesis of acute pulmonary edema (APE). Nevertheless, the impact of ExPHT on outcome in patients with secondary MR is unknown. We hypothesized that ExPHT is an independent predictor of the occurrence of APE, cardiac event and overall mortality. Method and Results: All patients with secondary MR, sinus rhythms, narrow QRS (<120ms) and referred for exercise stress echocardiography with quantifiable exercise systolic pulmonary arterial pressure (SPAP), were included in this study (n=159, 65 ± 11 years, 66% of male). Resting and ExPHT were defined as a systolic pulmonary arterial pressure (SPAP) >50mmHg and >60mmHg, respectively. ExPHT was more frequent than resting PHT (40% vs. 13%, p<0.0001). There was no significant difference between patients with or without ExPHT regarding demographic and clinical data, as well as medication. Using multiple linear regression, exercise SPAP was determined by resting SPAP (β=0.94 ± 0.1, p<0.0001), exercise MR severity as assessed using regurgitant volume (β=0.58 ± 0.1, p<0.0001), and resting e'-wave velocity (β=-1.3 ± 0.4, p=0.004). During a mean follow-up of 35 ± 11 months, 26 APE, 12 myocardial infarction and 23 deaths occurred. The incidence of combined cardiac event was significantly higher in patients with ExPHT as compared to those without ExPHT (2-year: 11 ± 3 vs. 28 ± 6%; 4-year: 20 ± 5 vs. 40 ± 7%, p<0.0001). Similarly, patients with ExPHT demonstrated significantly reduced survival (2-year: 88 ± 4 vs. 99 ± 1%; 4-year: 62 ± 8% vs. 94 ± 2%, p<0.0001). In multivariate Cox proportional Hazard model, after adjustment for age, sex, left ventricular volumes, both resting and exercise diastolic function and resting MR severity, ExPHT remains significantly associated with high risk of combined cardiac event (Hazard ratio=3.7, 95% of CI: 1.9-7.2, p<0.0001). Conclusion: In patients with secondary MR, ExPHT may be frequent and mainly determined by resting SPAP, LV diastolic burden markers and exercise MR severity. ExPHT is a powerful predictor of poor outcome and is associated with a 3.7-fold increase in risk of cardiac event. These results further highlight the usefulness of exercise stress echocardiography for the management and the risk stratification of these patients.