SPC365

Genetic Status and Response Patterns to Mavacamten in oHCM: An Echocardiographic Signature of Reverse Remodeling From 3 Portuguese Centers

Session: Sessão de Comunicações Orais 14 – Mavacamten na MCH obstrutiva: preditores de resposta, remodelagem e dados de vida real
Speaker: Inês Pereira De Miranda

Congress: CPC 2026
Topic: F. Valvular, Myocardial, Pericardial, Pulmonary, Congenital Heart Disease
Theme: 17. Myocardial Disease
Subtheme: 17.4 Myocardial Disease – Treatment
Session Type: Comunicações Orais
FP Number: ---
Authors: Inês Pereira de Miranda; Débora Correia; Julien Lopes; Filipa Gerardo; Rodrigo Brandão; Sérgio Maltês; José Viegas; Tânia Laranjeira; Sílvia Aguiar Rosa; Bruno Rocha; João Bicho Augusto

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-family:&quot;Calibri&quot;,sans-serif">Background: </span></strong><span style="font-family:&quot;Calibri&quot;,sans-serif">Mavacamten is an effective targeted therapy for symptomatic obstructive hypertrophic cardiomyopathy (oHCM). However, real-world data on the extent and trajectory of cardiac reverse remodeling, based on comprehensive echocardiography, remains scarce. Additionally, the influence of genetic background on treatment response is still incompletely understood.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-family:&quot;Calibri&quot;,sans-serif">Objective:</span></strong><span style="font-family:&quot;Calibri&quot;,sans-serif"> To characterize echocardiographic markers of reverse remodeling in mavacamten-treated oHCM patients from three Portuguese centres and to assess whether genotype influences treatment response patterns.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:&quot;Times New Roman&quot;,serif"><strong><span style="font-family:&quot;Calibri&quot;,sans-serif">Methods: </span></strong><span style="font-family:&quot;Calibri&quot;,sans-serif">A retrospective multicentre study was conducted including consecutive mavacamten-treated oHCM patients across three Portuguese centres. Clinical, laboratory, ECG, cardiopulmonary exercise, and multimodality imaging (echocardiography and CMR when available) data were collected at baseline, weeks 4, 8, and 12, and at each patient&rsquo;s optimal dose. Measurements included maximal wall thickness, left ventricular (LV) mass index, LV outflow tract (LVOT) gradients (rest and Valsalva), systolic and diastolic function (LVEF, GLS, E/e&prime; ratio), and left atrial size. A composite response endpoint was defined as (i) haemodynamic improvement (normalization or marked LVOT gradient reduction) or (ii) clinical response (improvement of at least 1 NYHA class). Associations between genotype and response were assessed using contingency analyses and logistic regression.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif"><strong>Results:</strong>&nbsp;A total of 83 patients were included (mean age 65 &plusmn; 12 years; 68.7% female). Baseline functional status was poor (all patients NYHA III), improving markedly <span style="font-family:&quot;Calibri&quot;,sans-serif">at follow-up</span> (NYHA I-II). Genetic testing results were available for 73 patients (88%), of whom 57 (78%) were negative and 16 (22%) had a P/LP variant. </span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">Mavacamten was associated with progressive structural reverse remodeling: (1) maximal wall thickness decreased at 12 weeks (-1.7 mm, p&lt;0.001) and further at optimal dosing (-2.9 mm, p&lt;0.001), (2) indexed LV mass decreased significantly at 12 weeks (-16.8 g/m&sup2;, p=0.006) and at optimal dose (-24.5 g/m&sup2;, p=0.002). Hemodynamics improved significantly: resting LVOT gradient fell by -26.4mmHg at 12 weeks and -59.9mmHg at optimal dosing, while provoked gradients decreased by -43.0 mmHg and -92.3 mmHg, respectively (all p&lt;0.001). Diastolic unloading was evident through reductions in E/e&prime; at 12 weeks (-2.9) and at optimal dose (-4.3) (both p&lt;0.001). LVEF and GLS showed small reductions but remained within clinically preserved ranges. </span></span></p>

<p style="text-align:justify"><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">The composite response rate was high across both genotype groups: 93.0% in the negative/VUS group vs 100% in the P/LP group (p=0.57).</span></span></p>

<p style="text-align:justify"><strong><span style="font-size:12.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Conclusion: </span></span></strong><span style="font-size:12.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">Mavacamten led to substantial and progressive improvements in symptoms, haemodynamics, and cardiac structure, with similarly strong responses across all genotypic groups and no </span></span><span style="font-size:12.0pt"><span style="font-family:&quot;Calibri&quot;,sans-serif">evidence </span></span><span style="font-size:12pt"><span style="font-family:Calibri,sans-serif">of reduced efficacy regardless of genotype.</span></span></p>