Slide 1: Effect of Aficamten Compared with Metoprolol on Cardiac Structure and Function in Symptomatic oHCM
Effect of Aficamten Compared with Metoprolol on Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy: A prespecified analysis of MAPLE-HCM Sheila M. Hegde, MD MPH1,2, Xiaowen Wang, MD, MPH, Pablo Garcia-Pavia, MD, PhD, Stoyan Getchevski, MD, Ahmad Masri, MD, Bela Mer
Slide 2: Background, Baseline Characteristics and Primary Endpoint
Background Baseline Characteristics • Beta-blockers have served as the first-line therapy for symptomatic obstructive HCM (oHCM) for decades • 175 participants • Mean age: 58 ± 13 years • Aficamten is an investigational, next-in-class CMI, a small- • 42% Female molecule selective inhibitor of the ca
Slide 3: Systolic Function and Gradients
Systolic Function and Gradients Resting LVOT Gradient Valsalva LVOT Gradient P < 0.001 80 P < 0.001 Valsalva LVOT Gradient (mmHg) 80 Resting LVOT Gradient (mmHg) 70 70 60 60 50 50 40 Resting LVOT-G 40 30 30 Valsalva LVOT-G 20 20 10 10 0 Washout 0 Washout 0 2 4 6 8 12 16 20 24 28 0 2 4 6 8 12 16 20 2
Slide 4: Cardiac Structure
Cardiac Structure Maximal Wall Thickness Inferolateral Wall Thickness LV ESVi Maximal Wall Inferolateral Wall Thickness (mm) Maximum Wall Thickness (mm) 22 16 16 P = 0.02 P = 0.04 P < 0.001 Thickness LV End Systolic Volume 21 15 15 Inferolateral Wall Index (ml/m2) 20 14 14 19 LV ESVi 13 13 18 12 12
Slide 5: Diastolic Function
Diastolic Function LAVi Lateral E/e′ Septal E/e′ P < 0.001 P < 0.001 P < 0.001 Left Atrial Volume Index (mm2) 45 20 20 18 LAVi 18 Lateral e′ Lateral E/e’ Septal E/e’ 40 16 16 Septal e′ 35 14 14 Lateral E/e′ 12 12 Septal E/e′ 30 Washout 10 Washout 10 Washout 0 12 24 28 0 12 24 28 0 12 24 28 Weeks Wee
Slide 6: Results: Change in Mitral Valve Function
Results: Change in Mitral Valve Function Systolic Anterior Motion Mitral Regurgitation Metoprolol No SAM SAM SAM + Septal contact None Mild Moderate Severe 100 Baseline 17 35 49 15 14 14 23 80 % of Participants Week 24 13 35 53 28 31 25 60 Aficamten 54 40 36 44 41 Baseline 16 43 41 20 Week 24 34 55
Slide 7: Conclusions
Conclusions • Compared with metoprolol, aficamten demonstrated significant improvement in multiple measures of cardiac structure and function • A modest decline in measures of LV systolic function occurred (LVEF, LV GCS), yet they remained within normal range, reflecting less hypercontractility • Su
Slide 8: Acknowledgments
Acknowledgments The MAPLE-HCM trial is funded by Cytokinetics, Incorporated. Simultaneously We thank the following individuals for their contributions to this clinical trial: published in • Participants and their families. • Investigators and study site staff • Brigham and Women’s Hospital Cardiovas