Numerous studies have reported that the presence of FMR immediately after acute myocardial infarction detected by either physical examination [1–8], echocardiography [9] or left ventriculography [3, 10], is associated with a significant increase in the risk of death (Fig. 3.1). Although old ventriculography studies of patients with FMR after myocardial infarction observed that only moderate or severe regurgitation was associated with an increased risk of death [3, 11], more recent ventriculography and echocardiography data provided evidence that even milder degrees of mitral regurgitation detected early after myocardial infarction predict adverse outcomes [2, 12, 13]. It is difficult to generalize results of clinical trials performed in patients referred to tertiary centers to the entire community of patients with systolic dysfunction, but a population-based cohort study from Olmsted County extended the results of these series to the community [4]. The investigators have found that there was a strong graded, positive association between severity of MR and heart failure (Fig. 3.2a), and that MR was associated with a >3-fold excess risk of heart failure, independently of age, gender, EF, and Killip class, underscoring the importance of FMR as a separate indicator of risk in the context of acute myocardial infarction. Furthermore, a similar relationship was observed between MR and death (Fig. 3.2b). After adjustment for age, gender, and EF, the presence of moderate or severe MR was associated with a 45 % increase in the risk of death. For all end points, adjustment for hypertension, diabetes, non–ST-elevation MI, and co-morbidity did not attenuate these associations. Similar results were found in the SAVE study, in which individuals with mitral regurgitation had a higher incidence of severe heart failure as compared to those without regurgitation [2]. However, these findings were not investigated further with multivariable analysis.

In a case–control study, Grigioni et al. [5] demonstrated that patients with FMR detected in the chronic phase after Q-wave myocardial infarction (more than 16 days after the index myocardial infarction), have worse survival compared to the controls [5]. Patients without MR were matched to those with MR for age, sex, and LV ejection fraction to ensure baseline comparability of these major determinants of outcome. Color flow imaging was used to determine presence or absence of MR, but in all patients with MR, degree of MR was graded with quantitative measurements. Despite identical age and EF, Patients with FMR experienced higher long-term mortality rates than those without MR (Fig. 3.3). In multivariate analysis, independent baseline predictors of overall survival were age, EF, New York Heart Association (NYHA) class III or IV, diabetes, atrial fibrillation, and renal failure. When FMR presence was added into the model, it negatively and independently influenced outcome, with adjusted RR of 1.88.

Notably, FMR remained independently predictive of survival, adjusting for diastolic dysfunction, co-morbidity index, extent of coronary disease, and for all variables showing baseline differences between patients with and without IMR. The assumption that patients with FMR had a “true” EF decreased by 4 %, 8 %, or even 10 % did not eliminate the FMR effect on overall mortality.

The same group of researchers observed that FMR in the chronic post-myocardial infarction phase was also associated with higher risk of heart failure [14] of a magnitude similar to that reported by Bursi et al. in the community [4].

In a very large recent multi-center study [7], the investigators found that quantitatively estimated FMR was strongly associated with the outcome of patients with heart failure, independently of LV systolic or diastolic function. Interestingly, their cohort included more than 400 patients with non-ischemic dilated cardiomyopathy. They found that severe FMR, defined as regurgitant volume >30 ml or ERO >0.2 cm² or vena contracta >0.4 cm, is associated with a twofold increased risk of adverse events after adjustment for LV ejection fraction and diastolic mitral inflow restrictive filling pattern in patients with heart failure due to non-ischemic dilated cardiomyopathy (see Fig. 3.4).

On the other hand, in a recent analysis, performed in patients with advanced heart failure followed in a tertiary large heart failure clinic, FMR was found to be common, but the severity of MR did not provide independent prognostic information [15]. The investigators selected only patients who had advanced symptoms (NYHA class III or IV) and markedly reduced systolic function (EF <35 %) resulting from either ischemic or idiopathic dilated cardiomyopathy. Routine assessment of MR incorporated mostly semi-quantitative methods, and quantitative methods were used in less than half of patients, mostly those with severe MR. They found that among patients with hemodynamically significant (severe, moderate-severe, or moderate) MR mean survival time was shorter than for those with non-significant MR (mild-moderate, mild, or trace/no). However, in multivariate analysis controlling for age, sex, cause of LV dysfunction, NYHA functional class, and EF, the severity of MR was not an independent predictor of overall survival. These findings were similar when patients with ischemic or idiopathic causes were considered separately. A smaller study of patients with idiopathic dilated cardiomyopathy also found that FMR was not an independent predictor of mortality [16].