Mavacamten to treat patients with obstructive HCM in Portugal: an interim analysis of the MAVA-PT cohort

Background Mavacamten, a selective cardiac myosin inhibitor, reduces left ventricular outflow tract obstruction (LVOTO) and improves exercise capacity and symptoms in patients with obstructive hypertrophic cardiomyopathy (oHCM). As a drug becomes more widely used, generating real-world data is important to assess its effectiveness and safety. MAVA-PT is an observational multicentre registry aiming to assess patient characteristics, treatment patterns, and longitudinal outcomes in patients receiving mavacamten. Aim To describe the real-world experience with the use of mavacamten in symptomatic oHCM across Portuguese centres. Methods All consecutive adult patients with symptomatic (NYHA III) oHCM enrolled in the Early Access Program at 3 centres were analysed in this interim analysis. Baseline characteristics, clinical outcomes, and safety were compared with the EXPLORER-HCM and VALOR-HCM trials. Results Overall, ninety-three patients were included [mean age 65 ± 12 years; 31% male; 91% on beta-blocker at baseline; 6 patients with prior septal reduction therapy]. Pathogenic or likely pathogenic variants were identified in 18% of those genotyped (16/87/Y). Only two patients were poor CYP2C19 metabolizers. MAVA-PT patients presented with a higher symptom burden and LVOTO than those in the EXPLORER-HCM and VALOR-HCM. Seventy-three patients had received at least one month of mavacamten and were included for further analysis. At a median follow-up of 9 (3-14) months, a significant improvement was noted in functional capacity (NYHA I: 0 vs. 73%; p<0.001), NT-proBNP (1012 [301-2368] vs. 235 [103-491] pg/mL; p<0.001), maximal LVOTO (99 ± 41 vs. 24 ± 30 mmHg; p<0.001) and maximal wall thickness (18 [16-21] vs. 16 [15-18] mm; p<0.001). Maximal LVOTO below 30 mmHg and 50 mmHg was achieved in 48 (66%) and 60 (82%) of the patients at last follow-up, respectively, all of whom had an improvement of at least one NYHA class. These changes were comparable to those in observed in the EXPLORER-HCM and VALOR-HCM trials (central figure). Mavacamten was well-tolerated, with low adverse event rates. There was a mild reduction in left ventricular ejection fraction (LVEF) (67 ± 8% vs. 63 ± 8%; p<0.001). Nine patients discontinued mavacamten due to a LVEF <50%, all of whom had fully recovered LVEF after 4 weeks and seven of whom were restarted on treatment. Three additional patients stopped the drug: one due to planned pregnancy, one due to generalized muscle weakness and one for a non-cardiovascular death. There were no reported arrhythmic events. Conclusion MAVA-PT is the first real-world study characterizing the use of mavacamten in patients with oHCM in Portugal. This interim analysis provides insight of the national experience with the drug, showing substantial clinical and structural improvements and a favourable safety profile.