SPC365

Mavacamten use in a real-world cohort of obstructive Hypertrophic Cardiomyopathy patients: Insights from the initial centre experience

Session: SESSÃO DE COMUNICAÇÕES ORAIS 16 – AVANÇOS NO DIAGNÓSTICO E TRATAMENTO DAS MIOCARDIOPATIAS
Speaker: Maria Rita Lima

Congress: CPC 2025
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: Maria Rita Giestas Lima; Débora Silva Correia; Rita Carvalho; Rita Amador; Tânia Laranjeira; Pedro Lopes; Sérgio Maltês; Gonçalo Cunha; Miguel Mendes; Regina Ribeiras; Bruno Rocha; Carlos Aguiar

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:&quot;Times New Roman&quot;,serif">Introduction</span></strong></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Aptos,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">Mavacamten&nbsp;was recently approved for the treatment of obstructive hypertrophic cardiomyopathy (HOCM) in patients who remain symptomatic despite first-line medical therapy. We aimed to describe the first real-world experience of this drug in a Portuguese cohort of patients with HOCM.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:&quot;Times New Roman&quot;,serif">Methods</span></strong></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Aptos,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">Single-centre prospective study enrolling patients with HOCM [peak left ventricle outflow tract obstruction (LVOTO)&ge;50mmHg] treated with mavacamten. All patients fulfilled the following criteria: moderate symptoms (NYHA III) despite first-line medical treatment with beta-blockers (BB) and/or calcium channel blockers (CCB), or who were intolerant to or had a contraindication for BB/CCB therapy; LV&nbsp;ejection fraction (LVEF)&gt;55%. Following treatment, patients underwent transthoracic echocardiography at 1, 2, 3 and, thereafter, every 3 months. Cardiopulmonary exercise testing (CPET) and quality-of-life assessment using SF-36v2 score were performed at baseline and at 6 months. Efficacy and safety endpoints were evaluated in patients with at least 6 months follow-up.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:&quot;Times New Roman&quot;,serif">Results</span></strong></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Aptos,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">Overall, 20 patients with symptomatic HOCM initiated treatment with mavacamten: 15&nbsp;(75%) were female; median age 65 (58-71) years; and 2 patients (10%) had significant residual LVOTO despite prior surgical myectomy. Genetic testing showed positive sarcomeric mutations in 7 patients (50%) and negative results in another 7 (50%). CYP2C19 genotyping revealed normal metabolizers in all but&nbsp;2 patients (10%) which were intermediate metabolizers. At baseline, 19 patients (95%) were treated with BB (bisoprolol equivalent mean dose 7&plusmn;3mg), and 4 (20%) discontinued CCB before starting mavacamten. All patients were at NYHA III, with median SF-36v2 score 104&plusmn;14,&nbsp;median NT-proBNP 1250 (296&ndash;2909)pg/mL, with a mean LVEF 65&plusmn;6% and maximal LVOTO 105&plusmn;39mmHg. Treatment began at a median dose of 2.5 (2.5&ndash;5)mg and was significantly titrated up to 5 (5&ndash;10)mg at a median follow-up of 7 (1&ndash;11) months. Follow-up data (at 6-months) was available in 10 (50%) patients. Mavacamten associated with an improvement in cardiac symptoms (NYHA I: 0 <em>vs</em>&nbsp;50%, p&lt;0.001), SF-36v2 score (104&plusmn;14 <em>vs</em>&nbsp;109&plusmn;9; p=0.180) and LVOTO (113&plusmn;36 <em>vs</em>. 49&plusmn;40mmHg; p=0.008), without remarkable changes in NT-proBNP, LVEF or global longitudinal strain. CPET showed a significant improvement in peak VO<sub>2</sub>&nbsp;(17&plusmn;6 <em>vs</em>&nbsp;21&plusmn;6; p=0.043) with 10 (50%) patients having met the primary efficacy endpoint of EXPLORER-HCM. No patient stopped the drug due to adverse events: none had LVOTO&lt;20mmHg during the initiation phase (1-3months) nor LVEF&lt;50% at any time. One patient discontinued treatment at 6-months due to planned pregnancy.</span></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Aptos,sans-serif"><strong><span style="font-family:&quot;Times New Roman&quot;,serif">Conclusion</span></strong></span></span></p>

<p style="text-align:justify"><span style="font-size:11pt"><span style="font-family:Aptos,sans-serif"><span style="font-family:&quot;Times New Roman&quot;,serif">Treatment with mavacamten in selected patients with symptomatic HOCM was safe and associated with significant clinical improvement, thus reproducing the main findings of the EXPLORER-HCM trial in a real-world setting.</span></span></span></p>