By Michael H. Crawford, MD, Editor
A large tertiary center retrospective observational study of patients with moderate to severe aortic regurgitation showed that 14% had significant pulmonary hypertension (PH) and that it was associated with symptoms and higher mortality. Aortic valve replacement abrogated PH in most patients by hospital discharge and improved survival regardless of the presence of PH.
Anand V, Scott CG, Lee AT, et al. Prevalence and prognostic implications of pulmonary hypertension in patients with severe aortic regurgitation. JACC Adv 2024;3:100827.
Little is known about the prevalence of pulmonary hypertension (PH) and its effect on outcomes in hemodynamically significant chronic aortic regurgitation. Thus, Anand et al from the Mayo Clinic performed a retrospective observational study of patients with moderate to severe aortic regurgitation (AR) between 2004 and 2019 who had an echocardiogram. Patients with acute AR, endocarditis, or other diseases that would affect the left ventricle (LV) or pulmonary pressure were excluded. PH by echocardiography was categorized as none (estimated right ventricular systolic pressure < 40 mmHg), mild to moderate (41 mmHg to 59 mmHg), and severe (≥ 60 mmHg). Of the 1,100 patients screened, a tricuspid regurgitation (TR) signal was not present in 25%, leaving 821 patients (mean age 61 years; 20% women) in the final analysis.
AR severity was determined by integrating the qualitative appearance of the color flow jet and quantitative methods. Elevated LV filling pressure was defined as a septal E/e’ of > 15. The diameter of the aorta at the sinus of Valsalva and mid ascending aorta was measured. The primary outcome was all-cause mortality. Secondary outcomes were the effect of PH on symptoms and the change in right ventricular (RV) systolic pressure (SP) pre- and post-surgical aortic valve replacement (SAVR). Mild to moderate PH was present in 11% of patients and severe PH was present in 3% of patients. Multivariable analysis showed that PH was associated with larger LV size, elevated LV filling pressures, and moderate or more TR.
During a median follow-up of seven years, there were 188 deaths. Multivariable analysis of mortality showed that moderate to severe PH was a strong predictor of mortality (hazard ratio [HR], 2.90; 95% confidence interval [CI], 1.63-5.15; P < 0.001), as was New York Heart Association functional class III or IV (HR, 2.84; 95% CI, 1.88-4.30; P < 0.001). The only factor associated with reduced mortality was SAVR (HR, 0.64; 95% CI, 0.45-0.91; P = 0.014). PH was present in 57 of the 396 patients who underwent SAVR, but survival improved similarly in those with or without PH. Finally, among patients with preoperative PH, 63% exhibited regression of PH (≥ 8 mmHg) post-SAVR before discharge.
The authors concluded that PH was infrequent in patients with significant AR but was associated with higher mortality and symptoms. Also, the survival benefit of SAVR was similar whether the patient had PH and that in about two-thirds of AR patients with PH, it had regressed significantly post-operatively before hospital discharge.
COMMENTARY
An estimated resting RV systolic pressure > 50 mmHg at rest or > 60 mmHg during exercise by echocardiography is a class II-B indication for mitral valve replacement in the guidelines, but not an indication for AV replacement. This Mayo Clinic study suggests that perhaps it should be. The argument for this concept is that LV size and filling pressure elevations are strongly associated with PH in both LV valve regurgitations. This suggests that it is post-capillary and, therefore, alleviating the regurgitation will lead to lower pulmonary pressures as it largely did in this study.
Current guidelines list symptoms (an LVEF < 55%, an LV end-diastolic diameter of > 65 mm, or end-systolic diameter > 50 mm) as indications for SAVR in chronic AR. Patients who presumably met these guidelines who did not have PH had similar surgical outcomes as those with PH. Thus, there may be nothing to gain by including PH as a criterion for SAVR. Since PH in this study was associated with LV size, filling pressures, and symptoms, the current guidelines may capture all those in whom SAVR would improve outcomes.
This study has several limitations in addition to the potential biases of a retrospective study. PH was not confirmed by right heart catheterization. There was no follow-up past one year for 13% of the patients. PH was not systematically reevaluated post-hospital discharge in the SAVR patients. In the initial cohort, 25% of the patients had no TR jet and had to be excluded. If these patients did not have PH, then the incidence would be even lower. There was no comprehensive search for primary or other secondary causes of PH. LV filling pressures were estimated by medial E/e’ only. Thus, at this time, a large prospective study will be needed to entertain modifying the guidelines to include PH as an indication for SAVR in AR.
