Sacubitril/valsartan improves mitral regurgitation severity in certain patients with HFrEF
NATIONAL HARBOR, Md. — Among PROVE-HF trial participants with HF with reduced ejection fraction and moderate to severe mitral regurgitation at baseline, sacubitril/valsartan improved mitral regurgitation severity in about half, a speaker reported.
However, those who improved in mitral regurgitation severity had similar baseline characteristics as those who did not, according to the researchers.
Additionally, reduced mitral regurgitation severity with sacubitril/valsartan (Entresto, Novartis) was associated with reverse remodeling, reduced N-terminal pro-B-type natriuretic peptide and improved Kansas City Cardiomyopathy Questionnaire (KCCQ) score, according to findings presented at the Heart Failure Society of America Annual Scientific Meeting and simultaneously published in Circulation.

“Mitral regurgitation severity is an important determinant of symptom burden and prognosis in patients with HFrEF,” G. Michael Felker, MD, MHS, professor of medicine at Duke University School of Medicine and member in the Duke Clinical Research Institute, said during a presentation. “Based on the COAPT trial, percutaneous mitral repair has improved outcomes in selected patients with HFrEF. But critically, optimizing [guideline-directed medical therapy] may also reduce [mitral regurgitation] severity and obviate the need for mitral repair. Prior data suggests that this might be true with sacubitril/valsartan.”
As Healio previously reported, in the main results of PROVE-HF, a single-arm, open-label study that enrolled 794 patients with HFrEF (mean age, 65 years; 29% women), sacubitril/valsartan promoted reverse cardiac remodeling and was associated with improvements in NT-proBNP.
The present analysis was conducted to examine the association between sacubitril/valsartan and change in mitral regurgitation among PROVE-HF participants.
Echocardiography was performed at baseline, 6 months and 12 months, and mitral regurgitation severity was graded and categorized on a scale of 0 (none), 1+ (trace), 2+ mild, 3+ (moderate) and 4+ (severe).
At baseline, 5.8% of PROVE-HF participants had moderate mitral regurgitation and 9.1% had severe mitral regurgitation.
At 12 months, the prevalence of moderate and severe mitral regurgitation decreased to 8.4%, correlating to a relative reduction of 44.7%.
Among participants with moderate and severe mitral regurgitation at baseline that was reduced to mild or less by 12 months (responders), researchers noted similar baseline clinical characteristics — vital signs, guideline-directed therapy at baseline or prior cardiac resynchronization therapy — compared with those with persistent moderate and severe mitral regurgitation at 12 months (nonresponders).
Baseline left ventricular ejection fraction and LV volumes were similar between patients with persistent compared with improved mitral regurgitation severity, according to the presentation.
Twelve-month improvement in LVEF was greater in among responders compared with nonresponders (11% vs. 7.6%; P = .05) and responders had lower final LV end-diastolic volume index (85.2 vs. 96.9 mL/kg2; P = .02), LV end-systolic volume index (56.5 vs. 66 mL/kg2; P = .04), left atrial volume index (33.4 vs 42.3 mL/kg2; P < .001), E/e’ ratio (12.6 vs. 15.8; P = .04) and LV mass index (125.7 vs. 152.2 g/m2) than nonresponders, according to the presentation.
Moreover, responders had lower median NT-proBNP (912 vs. 1,512 pg/mL; P = .01) and higher median KCCQ overall summary scores (82.3 vs 72.9; P = .04) at 12 months compared with nonresponders.
“Among patients with HFrEF who were initiated and uptitrated on sacubitril/valsartan, we noted a substantial reduction in 3+ to 4+ [mitral regurgitation]. This was associated with greater reduction in NT-proBNP, improved measures of health status and favorable reverse cardiac remodeling,” Felker said during the presentation. “Importantly, the baseline clinical and echocardiographic characteristics did not identify those who would or would not improve their severity of mitral regurgitation. This has important implications for how long we want to look at and how aggressively we want to try with optimizing [guideline-directed medical therapy] prior to considering mitral intervention.”