Sacubitril/Valsartan Associated With Reduced Mitral Regurgitation Severity in HFrEF

Use of sacubitril/valsartan for 12 months is associated with lesser degrees of mitral regurgitation (MR) in patients with heart failure with reduced ejection fraction (HFrEF), according to a study in Circulation.

Investigators evaluated the association between treatment with sacubitril/valsartan and change in MR in participants from the PROVE-HF (Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure; ClinicalTrial.gov: NCT02887183) study.

A total of 794 patients with HF and left ventricular ejection fraction (LVEF) of less than 40% received sacubitril/valsartan titrated to the maximum tolerated dose. They received an echocardiogram at baseline, 6 months, and 12 months.

The participants had a mean age of 65.0±12.4 years, and 76.4% were receiving an ACE inhibitor (ACEi) or angiotensin II receptor blocker (ARB) at baseline. They also had the following characteristics:

• LV end diastolic volume (LVEDV) index of 87.2 mL/kg²
• Median LVEF of 28.3%
• LV end systolic volume index (LVESVi) of 61.8 mL/kg²
• E/e’ of 11.3
• Left atrial volume index (LAVi) of 37.6 mL/kg²
• LV mass index (LVMi) of 125.2 g/m²

In addition, 5.8% and 9.1% of patients had 3+ and 4+ MR, respectively, at baseline.

Improvement in MR among the participants was observed from baseline through 12 months. At 6 months, the prevalence of 3 to 4+ MR decreased to 8.2% (relative 45.0% reduction), and at 12 months the prevalence was 8.4% (relative 44.7% reduction).

Participants with 3 to 4+ MR at baseline and a reduction to 2+ or less by 12 months (responders; n=52) had similar baseline clinical characteristics (including vital signs, baseline guideline-directed medical therapy, or previous cardiac resynchronization therapy) compared with those who had persistent MR grade 3 to 4+ at 12 months (nonresponders, n=33). Responders had a lower baseline LAVi (43.9 vs 49.3 mL/kg²; P =.01) and LVMi (145.0 vs 166.0 g/m²; P =.02) vs nonresponders.

Responders and nonresponders had an average sacubitril/valsartan dose of 276 vs 277 mg/day, respectively (P =.57). LVEF improvement was greater at 12 months for responders vs nonresponders (+11.0 vs +7.6%; P =.05). Responders had lower final LVEDV index (85.2 vs 96.9 mL/kg²; P =.02), LVESVi (56.5 vs 66.0 mL/kg²; P =.04), LAVi (33.4 vs 42.3 mL/kg²; P <.001), E/e’ (12.6 vs 15.8; P =.04), and LVMi (125.7 vs 152.2 g/m²) compared with nonresponders.

At 12 months, responders had a lower median N-terminal pro-B type natriuretic peptide (NT-proBNP) level (912 vs 1512 pg/mL; P =.01) and higher median Kansas City Cardiomyopathy Questionnaire Overall Summary Scores (82.3 vs 72.9; P =.04) vs nonresponders, although the results were similar for both measures at baseline.

Study limitations include the single-arm, observational design, as improvement in MR could have resulted from factors other than use of sacubitril/valsartan.

“…despite the majority of study participants previously receiving ACEi or ARB, we observed a substantial shift to lesser degrees of MR following 12 months of treatment with sacubitril/valsartan, including a nearly 50% reduction in 3-4+ MR,” the study authors wrote. “Reduction in MR from 3-4+ was associated with considerable reverse cardiac remodeling, reduced NT-proBNP, and improved health status.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.