Severe Mitral Regurgitation: More than Pulmonary Congestion

Abstract

Several decades ago, Braunwald and colleagues observed that a subset of highly symptomatic (predominantly rheumatic) patients with severe mitral regurgitation (MR) exhibited paradoxically low mean left atrial pressure (LAP) and diminutive V-waves. They attributed this hemodynamic phenomenon to the ability of the left atrium to remodel through chamber dilation and enhanced compliance. In their informative single-center retrospective analysis, Breen and colleagues from the Mayo Clinic assessed patients undergoing mitral valve transcatheter edge to edge repair (TEER) and hypothesized that individuals with normal invasively measured LAP, compared to those with elevated LAP, would exhibit similar improvement in heart failure symptoms and similar mortality at 30 days and 12 months. The primary study findings indeed suggested an immediate and persistent treatment benefit regardless of LAP. Patients with severe MR and normal LAP at the time of TEER were previously noted by the authors to exhibit a higher burden of comorbid lung disease and associated higher non-cardiac mortality at 1 year. These observations, when viewed through a competing risks framework, motivated an analysis as to whether TEER would benefit patients with severe MR and low LAP, and moreover, whether mean LAP measurement can identify a subset of patients who would perhaps not benefit from TEER. The group with reduced LAP, compared to those with elevated LAP, exhibited distinct epidemiologic and physiologic characteristics including lower rates of coronary artery disease and atrial fibrillation, equivalent rates of chronic lung disease, and a relatively higher proportion of degenerative or mixed MR compared to functional MR. Left atrial volume and right ventricular systolic pressure were significantly elevated in both groups, though comparatively less among the patients with lower LAP. An additional sub-analysis with LAP defined as normal (LAP < 13 mmHg) versus abnormal (LAP ≥ 13 mmHg) did capture (like the prior study) a higher proportion of patients with lung disease and supplemental oxygen use. Indeed, this second group of patients also demonstrated a favorable treatment response based on NYHA functional class at 30 days and 1 year. Despite the retrospective nature of this study and the attendant methodological biases, the quality and completeness of the diagnostic and procedural data were robust up to 12 months. Patients were evaluated with diagnostic rigor and a subset were enrolled in the comprehensive, multicenter, randomized COAPT trial with core lab review. The procedural results were similar between the experimental groups in terms of number of clips, degree of MR reduction, and hospitalization/ICU duration. Procedural success was high and few patients in both groups required subsequent surgical mitral valve replacement or redo-TEER. This investigation contributes much to the ongoing challenge of distinguishing patients likely to benefit from TEER from those in whom treatment is futile. The most immediate and useful observation is that patients with severe MR experience a similar symptomatic benefit following TEER regardless of baseline LAP. As such, normal LAP (or pulmonary capillary wedge pressure) is consistent with symptomatic MR and should not preclude life-saving mitral valve repair. The hemodynamic details are informative: The median LAP for the entire cohort of 302 patients was a modest 18 mmHg, and among the 149 patients with a LAP below the median, the mean LAP was a relatively normal 13.6 mmHg. In the lower LAP cohort, quantitative MR assessment by comprehensive echocardiography yielded a mean MR grade of 3.7 (± 0.5) with numerous secondary signs that MR was hemodynamically significant: Left atria were severely enlarged (mean volume 67 ± 26 mL/m), right ventricular systolic pressure was elevated (mean 48.4 ± 13.8 mmHg), and mean N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) was severely elevated (4704 ± 8615). These analyses suggest that unlike LAP, LA volume, PA pressure, and NT-proBNP can independently and collectively be used to evaluate the hemodynamic significance of MR, inform patient prognosis, and inform the potential treatment benefit from TEER. Invasive hemodynamic monitoring including LAP assessment plays an important role in guiding medical and device therapy. Device-induced LAP elevation during TEER may indicate physiologic mitral stenosis and is associated with worse clinical outcomes. These study results in no way diminish the value of invasive hemodynamic monitoring, but rather, enhance our understanding of how to use these data. The key message is that left atrial hemodynamic data should not be used to select patients with severe MR for