The Role of Pulmonary Hypertension in the Decision to Intervene in Degenerative Mitral Regurgitation

By Michael H. Crawford, MD, Editor

SYNOPSIS: A retrospective observational study of patients with degenerative mitral valve regurgitation has shown that Doppler echocardiographic-determined elevated pulmonary artery systolic pressure is related to mortality independent of the severity of mitral regurgitation, and that this excess mortality can be attenuated by mitral valve surgery.

SOURCE: Essayagh B, Benfari G, Antoine C, et al. Reappraisal of the concept and implications of pulmonary hypertension in degenerative mitral regurgitation. JACC Cardiovasc Imaging 2024; Jun 14. doi: 10.1016/j.jcmg.2024.05.006. [Online ahead of print].

The value of estimating systolic pulmonary artery pressure (SPAP) by Doppler echocardiography in the timing of surgical intervention for degenerative mitral regurgitation (DMR) is not well defined. Thus, this international multicenter (United States, France, and Israel) observational study is of interest.

Essayagh et al included 3,712 adults between 2003 and 2020 with isolated DMR as the result of prolapse or flail leaflets with at least moderate mitral regurgitation (MR) defined as a continuous wave Doppler-estimated effective regurgitant orifice area (EROA) of ≥ 0.20 cm². Excluded were those with concomitant moderate or more aortic valve disease, mitral stenosis, cardiomyopathy, previous valve surgery, significant pericardial disease, or other potential causes of pulmonary hypertension (PH). SPAP was estimated using continuous wave Doppler of the tricuspid regurgitation (TR) jet without contrast per guidelines and was categorized as no PH if < 35 mmHg, moderate if 35 mmHg to 50 mmHg, and severe if ≥ 50 mmHg. The primary outcome was all-cause mortality under medical management, or until surgery or the end of the study. The secondary endpoint was postoperative survival.

Essayagh et al enrolled 3,172 patients (mean age 67 years, 36% women): 1,668 patients without PH, 1,128 patients with moderate PH, and 916 patients with severe PH. Most of the baseline characteristics of the patients became significantly different in the PH groups compared to the no PH group as SPAP increased. Significant associations were found with increasing age, female sex, symptoms, the presence of atrial fibrillation (AF), higher surgical risk scores, systolic left ventricular (LV) function, left atrial (LA) volume, and the severity of MR and TR. LV dimensions were almost identical in the SPAP groups and, thus, were irrelevant.

Adjusted multivariable analyses showed that PH was significantly associated with age > 65 years, female sex, E/e’ ≥ 14, and MR EROA. The mean follow-up was five years, during which 2,214 (60%) of the patients had surgery and 910 patients died (69% under medical management and 31% after surgery). Survival post-surgery was 91% at five years and 83% at 10 years. The risk of mortality under medical management with 10 mmHg increases in SPAP was 1.43 (95% confidence interval [CI], 1.38-1.49; P < 0.0001), which was not changed when correcting for European Society of Cardiology (ESC) guidelines class I and II recommendations for surgery.

Although the risk of mortality after mitral valve surgery for increasing SPAP was higher (1.30 [95% CI, 1.23-1.30; P < 0.0001]), it was attenuated. When these comparisons were done for the moderate and severe PH groups alone, the risks were higher. The authors concluded that Doppler echocardiographic-determined SPAP in patients with DMR shows that SPAP affects mortality independent of the severity of MR and that early surgery (less than three months from diagnosis) attenuates this risk.

COMMENTARY

The decision on when to recommend mitral valve surgery for DMR remains challenging. The most recent guidelines are from the ESC in 2021.¹ In patients with severe MR, the class I indications for surgery are symptoms and LV systolic dysfunction (LVEF ≤ 60% or LV end systolic dimension ≥ 40 mm). Class IIa recommendations are the presence of AF, resting SPAP > 50 mmHg, LA volume > 60 mL/m², or diameter > 55 mm. Essayagh et al are suggesting that resting SPAP > 50 mmHg should be moved up to a class I indication for surgery. Also, they showed that resting SPAP between 35 mmHg and 50 mmHg contributes to risk stratification and perhaps should be a class II indication.

Estimation of SPAP by Doppler echocardiography has been criticized for not always accurately predicting invasive measurements of pulmonary artery pressure. In the Essayagh et al study, only 4% had SPAP measured invasively, so the predictive ability of SPAP was based largely on Doppler echocardiographic data. In addition, their study included patients with moderate MR, which raises the question of whether the guidelines for intervention should apply to these patients as well. Many believe that earlier intervention in those with moderate MR is justified by current data.

Essayagh et al showed that surgery within three months of the diagnosis of moderate to severe MR reduced mortality at all levels of SPAP. Part of the problem here is the difficulty of accurately estimating MR severity by Doppler echocardiography in DMR because of eccentric jets and the range of LA sizes and LA pressures. Finally, even though Essayagh et al eliminated patients with other causes of PH, the pathophysiology of PH in patients with DMR likely is complex and not just the result of the severity of MR, yet SPAP is an independent predictor of mortality and surgical success.

Strengths of the Essayagh et al study are that the researchers used the best Doppler echocardiographic quantitative techniques for determining MR severity. They did not use contrast to enhance detection of TR, but many would consider that acceptable since contrast can overestimate TR jet velocity. There also are limitations. It is a retrospective observational study, but so were all the studies that informed the guidelines. It is not clear exactly how SPAP was estimated because details of inferior vena cava characteristics are not included in the report. The decision to label pressure SPAP > 35 mmHg as moderate PH is contrary to the common belief that estimated SPAP up to 35 mmHg is within normal limits. Thus, they have not defined a separate mildly elevated SPAP range.

Exercise SPAP, which is believed by many to provide additional information of prognostic value, was not considered. They present data on diastolic function measured as mitral Doppler E/e’, but since MR can markedly increase E, most do not believe diastolic function can be determined accurately in patients with significant MR. The quantitation of MR is complex and EROA cannot always be determined. This was handled by excluding patients in whom EROA and SPAP could not be measured, which amounted to 14% of the patients with moderate to severe MR who were identified in the database.

In summary, Essayagh et al make a strong case for the value of estimating resting SPAP in the management of patients with more than mild DMR and suggest guideline committees consider this information in the future.

REFERENCE

1. Vahanian A, Beyersdorf F, Praz F, et al; ESC/EACTS Scientific Document Group. 2021 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J 2022;43:561-632.