Septal Reduction Therapy Research Articles

Abstract 4126581: COVID-19 Impacted Septal Reduction Therapies in Hypertrophic Cardiomyopathy

Background: Coronavirus Disease-19 (COVID-19) pandemic had a significant impact on emergent and elective treatment strategies in patients with cardiovascular disease. We aimed to examine the impact of COVID-19 on septal reduction therapy (SRT) in hypertrophic cardiomyopathy (HCM). Methods: National Inpatient Sample 2019-2021 was queried to identify patients with HCM and SRT using appropriate ICD codes. Temporal trends for SRT were obtained before and after COVID-19 outset. Results: There was a significant decline in the number of SRT from 2019 to 2020 (1505 vs. 1180, p<0.001) with partial recovery in 2021 (1250 vs. 1180, p<0.001). Geographic differences existed with differential decrease in number of SM in midwestern and Western Unites States. In addition, the proportion of patients who underwent surgical myectomy (SM) decreased in 2020 (44.6 vs. 48.7%, p=0.008) in favor of alcohol septal ablation (ASA). Patients undergoing SRT in 2020 had higher prevalence of heart failure (39.5 vs. 29%, p=0.002). In-hospital complication rates for cardiogenic shock, bleeding requiring transfusion, acute kidney injury and admission to the critical care unit were higher in 2020 compared to 2019. Hospital length of stay (LOS) was not significantly different however there was an overall increase in LOS in septal myectomy group from 2019 to 2021 (9.1 vs. 10 days, p=0.028). The overall proportion of comorbidities and other in-hospital complications remain unchanged during this study period. Conclusions: Our data indicates that COVID-19 resulted in a significant decrease in total number of SRTs and a shift from surgical to percutaneous septal reduction therapy. Partial recovery of procedure numbers were noted in the year following the pandemic outset.

Abstract 4137810: Association of Sociodemographic Characteristics on Costs of Care in Patients with Obstructive Hypertrophic Cardiomyopathy

Introduction: No evidence exists on the impact of sociodemographic characteristics on costs of care for obstructive hypertrophic cardiomyopathy (oHCM). Therefore, we evaluated 5-year cumulative costs by age, sex, and race/ethnicity. Methods: Retrospective cohort study of adults diagnosed with oHCM (January 2013 to December 2021) using Optum claims and electronic medical record data. Patients with ≥2 claims for HCM (ICD-9 and-10) at least 30 days apart (index date = earliest oHCM claim) with ≥1 additional oHCM claim or septal reduction therapy, 6-months pre-index and 5-year post-index continuous enrollment were included. HCM-related cumulative costs (2022 CPI adjusted) were reported for medical (ambulatory [AB]: office [OV] visits, outpatient [OP] visits); emergency room [ER] visits; inpatient admissions (IP); and pharmacy (Rx). Results: Among 5,129 patients with oHCM, 52% were female (mean age 63.9 ± 14.3 years; 77.6% non-Hispanic White; 40% Medicare). Compared to females (Table), male patients had greater costs including total ($71,581 vs $63,710, p= 0.014), medical ($70,395 vs $62,455, p= 0.013), ambulatory ($16,024 vs $10,776, p<0.001), OV ($1,906 vs $1,573, p<0.001), and OP ($14,118 vs $9,202, p<0.001). Compared with White patients, Black patients had significantly greater IP costs ($54,572 vs $42,686, p= 0.01), Hispanic patients had greater ER costs ($1,724 vs $791, p<0.001), and Asian patients had greater OV costs ($2,094 vs $1,800, p<0.001). Patients aged 18-39 years had greater costs across all categories (p<0.001; IP=NS), except Rx. Patients aged 40-54 years had the highest Rx costs ($1,557, p<0.001), followed by 18-39, 55-64, 65-74, 75+ years ($1,528; $1,329; $1,197; $867), respectively. Conclusions: For oHCM patients , being male and age 18-39 years was associated with increased HCM-related healthcare costs. Differences in cost across race/ethnicity exist, including greater IP and ER costs for Black and Hispanic patients, respectively. Future research is required to understand the source of these differences among oHCM patients.

Abstract 4135259: Coronary Artery Anomalies Induce Myocardial Ischemia in Hypertrophic Cardiomyopathy

Background: Myocardial ischemia is a frequent finding in hypertrophic cardiomyopathy (HCM) and is often attributed to microvascular disease, extravascular compressive forces, reduced coronary flow reserve, hemodynamic abnormalities, and concomitant atherosclerotic coronary artery disease (CAD). The potential contribution of congenital coronary artery anomaly (CCAA) to myocardial ischemia in HCM has not been systematically explored. Research Question: We aimed to evaluate the spectrum and potential contribution of CCAA to myocardial ischemia in HCM. Methods: From June 1991 to March 2023 a total of 35 CCAA were reported in 29 adults [age 18-87 (47.9±19.9; 59% male; 35% obstructive, 21% apical variant). Clinical data on presence or absence of myocardial ischemia, mode of therapy, and outcomes of the patients were reviewed. Results: The individual CCAAs were graphically reproduced [Figure] and were categorized based on the number of coronary ostia present in the aorta [single ostium (n=11; 38%); 2 ostia (n=13; 45%); 3 ostia (n=4; 14%); 4 ostia (n=1; 3%)]. The anomalous coronary artery was the left main in 6 (17%); left anterior descending in 6 (17%); left circumflex in 8 (23%); right in 14 (40%) or the ramus intermedius in 1 (3%). Two patients (7%) with apical variant HCM also had coronary artery fistulae in a non-anomalous coronary artery. Of all 29 patients who presented, 12 (41%) showed objective evidence of myocardial ischemia and of those, a total of 6 (50%) had an anomalous coronary artery coursing between the great vessels. In addition, 1 of 5 patients with sudden cardiac arrest had a high-risk coronary anomaly. Pharmacologic treatment was offered to 11 (38%) patients and 3 (10%) patients underwent coronary artery surgery (bypass grafting in 2 and unroofing in 1). Septal reduction therapy was performed in 8 (28%). Follow up data was available in 14 patients including 2 of the 3 who underwent surgical correction. Symptomatic improvement was noted in all 14. Conclusion: Congenital coronary artery anomalies may be present in patients with HCM and may contribute to myocardial ischemia. Treatment options depend on the type of anomaly and presence of objective evidence of myocardial ischemia.

Diagnosis and management of hypertrophic cardiomyopathy: European vs. American guidelines.

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease, affecting 1:200 to 1:500 individuals worldwide. Guidelines on the diagnosis and management of HCM have been recently published by the European Society of Cardiology (ESC) and American societies. The ESC guidelines cover a broad range of cardiomyopathies, including HCM, with 119 recommendations, whereas the American guidelines focus exclusively on HCM with 141 specific recommendations. Both guidelines emphasize a comprehensive diagnostic approach, including imaging and genetic testing, but differ in some specific aspects. For example, sudden cardiac death (SCD) risk assessment is a primary point of divergence. The ESC guidelines advocate for the use of a validated Risk-SCD calculator, while the American guidelines rely on specific risk markers for individualized risk evaluation. Management strategies also vary: both guidelines prioritize beta-blockers and calcium channel blockers in patients with resting or provocable left ventricular outflow tract (LVOT) obstruction. If beta-blockers (or verapamil/diltiazem) are ineffective, either disopyramide or the myosin inhibitor mavacamten may be an option with slightly different indications among the two guidelines. Septal reduction therapy is recommended in ESC guidelines for symptomatic patients with significant LVOT gradients, while American guidelines suggest earlier myectomy for certain clinical factors and emphasize shared decision-making. The ESC guidelines recommend sequential atrioventricular pacing and dual-chamber defibrillators for reducing LVOT gradients. The American guidelines focus on genetic testing for risk assessment and suggest periodic cardiac magnetic resonance imaging. This paper provides a detailed comparison of these guidelines, highlighting key differences and areas needing further research and expert debate.

The Clinical Trajectory of NYHA Functional Class I Patients With Obstructive Hypertrophic Cardiomyopathy.

An improved understanding of the natural history in NYHA functional class I patients with obstructive hypertrophic cardiomyopathy (oHCM) is needed. Using a multicenter registry (SHaRe [Sarcomeric Human Cardiomyopathy Registry]), this study described the natural history in patients with oHCM who were classified as NYHA functional class I at the initial visit compared with patients classified as NYHA functional class II and reported baseline characteristics associated with incident clinical events. Incident events assessed included a composite of NYHA functional class III to IV symptoms, left ventricular ejection fraction<50%, atrial fibrillation, stroke, ventricular arrhythmias, septal reduction therapy, ventricular assist device or transplantation, or death. Factors associated with incident events were determined using Kaplan-Meier, Cox proportional hazards, and restricted cubic spline models. Of 7,964 patients with HCM in SHaRe, 1,239 patients with oHCM met inclusion criteria; 598 were in NYHA functional class I at the initial visit (age 48 ± 17 years; 31.1% female; peak gradient, 75 ± 40mmHg). At 5-year follow-up, the composite event rate of NYHA functional class I patients was 28% compared with 44% (P< 0.001) in 641 NYHA functional class II patients with oHCM (age 54 ± 16 years; 46.5% female; peak gradient, 83 ± 39mmHg). Left atrial (LA) diameter≥45mm (HR: 1.56 [95%CI: 1.14-2.12]; P = 0.005), female sex (HR: 1.61 [95%CI: 1.16-2.24]; P = 0.003), and older age (HR: 1.21 per 10 years [95%CI: 1.09-1.34]; P< 0.001), but not the magnitude of left ventricular outflow tract obstruction, were associated with a higher risk of the composite outcome in NYHA functional class I patients. Although NYHA functional class I patients with oHCM fared better than NYHA functional class II patients, more than one-fourth experienced adverse events over 5-year follow-up, especially if they were older, female, and/or had LA enlargement. Strategies to reduce the rate of clinical outcomes in NYHA functional class I patients warrant further study.

Efficacy of Cardiac Myosin Inhibition in Patients Post Septal Reduction Therapy

Efficacy of Cardiac Myosin Inhibition in Patients Post Septal Reduction Therapy

Symptoms trend in patients with obstructive hypertrophic cardiomyopathy treated with disopyramide

Abstract Background In obstructive hypertrophic cardiomyopathy (HOCM) medical intervention becomes necessary when symptoms coexist, whereas invasive septal reduction therapy (SRT) is indicated in presence of NYHA class &amp;gt;II, although optimized medical therapy. Thus, if SRT is avoided by medical therapy patient should be considered responder. However, due to inconsistency on definition of responders, effectiveness of medical therapy among data are conflicting. In addition, only short follow-up (FU) is available for analyses. Purpose To address this, we conducted a retrospective analysis in two HCM centers, both defining responders based on guidelines recommendations. Methods 62 symptomatic HOCM patients (43% women, age 52±14 years) with LVOTG ≥50 mmHg at rest or during provocation, were recruited from two HCM Italian centers. Disopyramide was added as second-line therapy. Responders were those reaching at least NYHA class II, if &amp;gt;II at baseline and those reaching NYHA class I or with stabilization of symptoms if in NYHA II class at baseline. Results At FU, (mean 4.4 years, IQR 1.1-6.6 years), 47 patients (76%) were responders, whereas 15(24%) patients were no-responders. Changes in NYHA class from baseline to follow-up are reported in the Figure. There were no differences at baseline of clinical and echocardiographic data between responders and no-responders, whereas at FU responders showed a significant lower LVOTG than no-responders (43 ±32 vs 66 ±28 mmHg, respectively, p=0.013), with LVOTG &amp;lt;50 mmHg more represented in responders than in no-responders (75% vs 25%, respectively; p=0.004) (Figure). No side effects indicating discontinuation of the therapy were recorded. Conclusion Patients treated with disopyramide as second-line therapy showed a reduction in symptoms in a quite long-follow-up, avoiding SRT in up to 70% of them. Patients who might benefit the most from the therapy are those who reached LVOTG &amp;lt;50 mmHg during treatment.

Assessing the alignment of obstructive hypertrophic cardiomyopathy pharmacological treatments with ESC guidelines in Germany

Abstract Introduction The European Society of Cardiology (ESC) recently updated treatment guidelines for hypertrophic cardiomyopathy (HCM). Purpose The aim of this study was to describe the treatment of obstructive HCM in Germany and assess alignment with the 2014 and 2023 ESC guidelines. Methods Adults with HCM were identified using a nationally representative administrative claims dataset (WIG2 Benchmark database) from several German Statutory Health Insurances between 2012 and 2018. Obstructive HCM was identified as any obstructive HCM diagnosis (ICD-10: I42.1) or any HCM diagnosis (I42.2, I42.9) with septal reduction therapy. The index date was defined as the date where the patient met all eligibility criteria for HCM. Minimum follow-up time was set to one year. Patients had at least 1 year of baseline data prior to the index HCM diagnosis and were followed up for at least 1 year after the diagnosis (or until death within 1 year). Patients with phenocopies were excluded. ESC guideline-directed pharmacological treatments for HCM included beta-blockers (BB), calcium channel blockers (CCB), disopyramide, and/or mavacamten (approved by EMA June 2023). While the 2014 ESC Guidelines on Diagnosis and Management of HCM were applicable during the study, recommendations pertaining to the use of non-vasodilating BBs and non-dihydropyridine (DHP) CCBs did not change in the 2023 ESC Guidelines for the Management of Cardiomyopathies; thus, this study applies to both. Results Out of 6793 patients with HCM analysed in the period 2012-2018, 1,141 had obstructive HCM. The average follow-up was 5 years. Patients were mostly male (62%) with a mean age of 60 years. Hypertension, hyperlipidaemia, coronary artery disease, heart failure, and atrial fibrillation were among the most common comorbidities; the mean Charlson Comorbidity Index score was 2.3. At index, 46% of patients were on BB monotherapy, 23% were on CCB monotherapy, &amp;lt;1% were on a combination of BBs or a combination of CCBs, 9% were on a combination of BBs and CCBs, and as many as 22% received no HCM treatment. Patients experienced 1615 unique treatment combinations throughout the study across all lines of therapy (Table 1). The most common treatments were bisoprolol (24%), metoprolol (19%), amlodipine (12%), and verapamil (12%). The use of propranolol was negligible (1%). 43% of pharmacological treatments were not in line with ESC guidelines. The most common reason for not aligning was using DHP-CCBs or vasodilating BBs. Conclusion This study shows that 57% of obstructive HCM treatments received by patients during the study were aligned with recommendations from the 2023 ESC guidelines on cardiomyopathies. Research is needed to investigate barriers and enablers to implementing the guideline including awareness of recommended treatments, as well as the management of comorbidities.

Is unsatisfactory outcome of alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy predictable?

Abstract Background Alcohol septal ablation (ASA) has been introduced for left ventricular outflow tract gradient (LVOTG) reduction in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, some patients may not profit from ASA. Thus, we identified characteristics of patients with unsatisfactory outcome of ASA in a large single-center cohort. Methods Consecutive ASAs between 1997 and 2023, performed at our institution, were retrospectively enrolled. Those ASAs performed in patients with missing follow-up (FU), previous septal reduction therapy (SRT), and atypical HOCM were excluded. Patients with unsatisfactory outcome (PUO) were defined as continuing to meet the guideline criteria for SRT (NYHA ≥III or NYHA ≥II with exertional syncope and resting/exercise-induced LVOTG ≥50mmHg). PUO were compared to patients with good outcome (PGO). Results are expressed in % or median and interquartile range (IQR). Pre-procedural predictors of poor hemodynamic outcome were identified using logistic regression analysis. Results 65 of 1003 patients were PUO (6.5%). Those were younger (48.0 years [40.5-61.8] vs. 57.0 years [IQR 47.0-67.0] in PGO; p=0.0030), more often reported syncope at baseline (35.4% vs. 22.2% in PGO; p=0.0214), and had lower body-mass-index (26.4kg/m2 [23.8-29.2] vs. 27.7kg/m2 [25.2-23.1] in PGO; p=0.0160). In PUO, resting LVOTG was higher at baseline (53.0mmHg [24.5-82.0]) than in PGO (40.0mmHg [22.0-75.0]; p=0.0292; Table 1). Differences in sex, family history of sudden cardiac death, dyspnoea, medication, and interventricular septum diameter (IVSD) were not observed at baseline (all p&amp;gt;0.05; Table 1). Age (OR 1.023; CI: 1.005-1.042; p=0.0129), syncope at baseline (OR 1.890; CI: 1.049-3.324; p=0.0296), and BMI (OR 1.072; CI: 1.007-1.145; p=0.0355) were found to independently influence poor hemodynamic response to ASA using multiple logistic regression controlling for confounders. However, sex, baseline IVSD, and LVOTG were not found to influence poor hemodynamic outcome (p&amp;gt;0.05). There were no differences with regard to the number of embolized branches (1 in both groups), the size of the balloon used to cover the septal branch (1.5mm in both groups), the volume of ethanol (PUO: 1.4ml [1.0-2.0]; PGO: 1.5ml [1.2-2.0]), or creatine kinase release (PUO: 879.0U/l [375.0-1187.0]; PGO: 842.0U/l [501.5 - 1234]) (all p&amp;gt;0.05). At 6-months-FU, PUO had significantly higher IVSD (18.0mm [13.5-22.0] vs. 16.0mm [12.0-19.0] in PGO; p=0.008), higher resting LVOTG (31.0mmHg [20.0-55.5] vs. 14.0mmHg [10.0-22.0] in PGO; p&amp;lt;0.0001) and higher exercise-induced LVOTG (105.0mmHg [84.5-143.0] vs. 35.0mmHg [22.0-64.0] in PGO; p&amp;lt;0.0001). Conclusion ASA was overall effective with only few patients experiencing unsatisfactory outcome. Syncope, age, and BMI were found predicting poor hemodynamic outcome.Baseline characteristics

Residual mitral leaflet length independently indicates left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

Abstract Background Due to its dynamic character, the diagnosis of left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) often requires extensive exercise testing. Mitral valve alterations represent structural parameters that are not affected by load or contractility and influence left ventricular outflow tract (LVOT) gradients. The residual portion of the mitral valve extending past its coaptation (RML) has been postulated as a necessity to exhibit LVOTO. Purpose This study aims to assess the impact of RML length on the likelihood of LVOTO in HCM patients. Methods This is a cross-sectional, multi-center, registry-based analysis conducted at two HCM referral centers. The study included HCM patients with valid standardized transthoracic echocardiographic examinations. Blinded investigators performed post-processing echocardiographic analyses. LVOTO was defined as resting or dynamic peak LVOT gradients ≥30 mmHg. Results Among 270 HCM patients studied (43% women, mean age 58±14 years), 131 patients (49%) exhibited LVOTO, with 76 (28%) having undergone septal reduction therapy (SRT). Patients with obstructive HCM exhibited a more pronounced end-diastolic interventricular septum (IVSd) thickness (2.2±0.4 vs. 1.8±0.5 cm; p&amp;lt;0.001) and higher left ventricular ejection fraction (LVEF) (65±9 vs. 62±10%; p=0.009) compared to those without LVOTO (nHCM). Obstructive HCM patients demonstrated longer anterior (29±4 vs. 26±4 mm; p&amp;lt;0.001), posterior (23±4 vs. 20±4 mm; p&amp;lt;0.001), and residual mitral leaflets (11±3 vs. 7±3 mm; p&amp;lt;0.001) than nHCM patients. Multivariable logistic regression analysis adjusting for age, IVSd thickness, LVEF, anterior, and posterior mitral leaflet length identified RML length as an independent predictor of LVOTO [OR=1.47 (95% CI 1.30-1.66); p&amp;lt;0.001]. The area under the receiver-operating characteristic curve for RML length in identifying LVOTO was 0.82 (95% CI 0.77-0.87). RML length ≥9 mm demonstrated 73% sensitivity and 77% specificity in identifying obstructive HCM patients. Notably, these results remained statistically significant in sensitivity analyses selectively performed in HCM patients who had previously undergone SRT as well as in those who were SRT-naïve, respectively. Conclusions This study indicates RML length as an independent predictor of LVOTO in HCM patients. Moreover, RML length demonstrated high diagnostic accuracy in identifying LVOTO among HCM patients. Prospective studies are warranted to assess the added value of RML length in the diagnostic work-up of HCM patients.Figure:Diagnostic Accuracy of RML

Real-world experience with mavacamten in obstructive hypertrophic cardiomyopathy: observations from a tertiary care center

Abstract Background In symptomatic obstructive hypertrophic cardiomyopathy (oHCM) patients, mavacamten is commercially approved to help improve left ventricular (LV) outflow tract (LVOT) gradients, symptoms, and reduce eligibility for septal reduction therapy (SRT) under the risk evaluation and mitigation strategy (REMS) program. We sought to prospectively report the initial real-world clinical experience with the use of commercially available mavacamten in a multi-hospital tertiary healthcare system. Methods We studied the first 150 consecutive oHCM patients (mean age 65 years, 53% women, 83% on betablockers and 61% in New York Heart Association [NYHA] class III) who were initiated on 5 mg of mavacamten with dose titrations using symptom assessment and echocardiographic measurements of LVOT gradient and LV ejection fraction (LVEF) measurements. We measured changes in NYHA class, LVEF, LVOT gradients (resting and Valsalva) at baseline, 4, 8 and 12 weeks. Results At 261±143 days (range of 31-571 days), 69 (46%) patients had ≥1 NYHA class, 27 (18%) additional patients had ≥2 NYHA class improvement and 40 (27%) reported a no change in symptoms. The mean LVOT gradient at rest decreased from 41±33 mmHg at baseline to 16±17 mmHg at 4 weeks, 16±16 mmHg at 8 weeks and 15±16 mmHg at 12 weeks. The mean drop in resting LVOT gradient from baseline to last follow-up was 26±3 mmHg (p&amp;lt;0.0001). The mean Valsalva LVOT gradient decreased from 72±43 mmHg at baseline to 29±31 mmHg at 4 weeks, 29±28 mmHg at 8 weeks and 30±29 mmHg at 12 weeks (p&amp;lt;0.001). The mean reduction in post Valsalva LVOT gradient from baseline to last follow-up was 43±4 mmHg (p&amp;lt;0.0001). At baseline, 100% patients had Valsalva LVOT gradients ≥ 30 mm Hg and 142 (95%) had ≥ 50 mm Hg. After initiation of mavacamten therapy, Valsalva LVOT gradient ≥ 30 mm Hg was observed in 44/150 (29%) at 4 weeks, 40/141 (28%) at 8 weeks and 41/136 (30%) at 12 weeks. In 40 patients who reported no symptomatic improvement, the mean Valsalva LVOT gradient decreased from 73±39 mmHg at baseline to 34± 27 mmHg at 4 weeks, 35±28 mmHg at 8 weeks and 30±24 mmHg at 12 weeks (P&amp;lt;0.001). The mean LVEF at baseline was 66±6% and changed to 64±5% at 4 weeks, 63±5% at 8 weeks and 62±7% at 12 weeks (p&amp;lt;0.0001). No patient underwent SRT, developed LVEF ≤30% or developed heart failure requiring admission. Three (2%) patients needed temporary interruption of mavacamten due to LVEF&amp;lt;50. During follow up, dose reduction or discontinuation of background HCM therapy (betablockers, calcium channel blockers and disopyramide) occurred in 33 (22%) patients. The breakdown of various drug doses of mavacamten, at last follow-up, is as follows: 2.5 mg (n=29, 19%), 5 mg (n=80, 53%), 10 mg (n=37, 25%) and 15 mg (n=3, 2%). Conclusions In a real-world study in symptomatic oHCM patients at a multi-hospital tertiary care referral center, we demonstrate the efficacy and safety of prescribing mavacamten under the REMS program.

Evaluation of clinical need, effectiveness, and safety of the first myosin inhibitor mavacamten in real world patients

Abstract Background Hypertrophic cardiomyopathy has a high burden of heart failure if obstruction in the left-ventricular outflow tract (HOCM) is present. Mavacamten is the first available myosin inhibitor specifically addressing the underlying pathophysiology of hypercontractility in HOCM. Based on positive results of respective approval studies, mavacamten is recommended for therapy of HOCM in recent ESC guidelines but clinical real world data are lacking. Methods In this ongoing study, consecutive patients with current or previous diagnosis of HOCM presenting at a single referral centre for hypertrophic cardiomyopathy from March 2023 to February 2024 were included and analysed by treatment modality. In patients initiating mavacamten therapy, clinical data of 4 weekly follow ups were assessed, including efficacy (NYHA class, LVOT gradient and biomarkers) and adverse events. Results A total of 72 patients were included (59.1 ± 13.0 years, 68% male). Mavacamten treatment was started in 30/72 (41.7%) patients, 3/72 (4.1%) were referred for transcatheter septal reduction therapy (SRT), and 39/72 (54.2%) did not require any escalation in their treatment due to low gradient with current treatment or few symptoms. Of the latter, 3/39 (7.7%) had previous SRT, 36/39 (92.3%) were stable on negative inotropic medication. The average age of patients selected for mavacamten therapy was 58.0 ± 13.0 years, 80% were male, and the average thickness of the interventricular septum was 18.8 ± 2.8 mm. 22/30 (73.3%) were on baseline therapy with beta-blockers, 3/30 (10.0%) with calcium channel blockers, 2/30 (6.7%) with both, and 4/30 (13.3%) had additional treatment with disopyramide. As shown in table 1, there was a significant decrease in the LVOT gradient under Valsalva maneuver observed 4 weeks after initiation of mavacamten treatment (p=0.006), while the reduction in peak exercise LVOT gradient was statistically significant after 8 weeks (p=0.02). Simultaneously, a significant decrease in Nt-pro-BNP levels was observed after 4 weeks of therapy (p&amp;lt;0.001). A significant drop in troponin T levels compared to baseline was only noted after 20 weeks of treatment (p=0.02). At baseline, 66.7% patients were classified as NYHA class III/IV, and 12.5% after 20 weeks of treatment. 75% of the patients improved ≥1 NYHA class after 20 weeks. Regarding adverse events, there was one case of ejection fraction dropping to &amp;lt;50%, which resolved after halting treatment. Additionally, there were two reports of dizziness and one reported syncope, all of which resolved without taking any actions. Conclusion In this real-world single centre HOCM cohort, 41.7% of patients had an indication for myosin inhibitor therapy. The safety and effectiveness in lowering the LVOT gradient and improving NYHA class were consistent with findings from the approval studies.

Serial changes in left and right ventricular global longitudinal strain in symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten: insights from VALOR-HCM trial

Abstract Background In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM phase 3 randomized, double-blind, placebo-controlled clinical trial demonstrated that mavacamten, reduces the need for septal reduction therapy with sustained improvement in left ventricular outflow tract gradients and symptoms. As a cardiac myosin inhibitor, mavacamten’s mechanism of action reduces myocardial hypercontractility. Global longitudinal strain (GLS), a measure of regional myocardial function, is a more sensitive marker of systolic function and can complement left ventricular ejection fraction (LVEF). Objective We sought to assess serial changes in LV and right ventricular (RV)-GLS in patients enrolled in the VALOR-HCM study. Methods VALOR-HCM included 112 symptomatic obstructive HCM patients (mean 60 years, 51% male, LVEF 68%). Patients assigned to mavacamten at baseline continued the drug for 56 weeks (n=56) and those assigned to placebo crossed over to mavacamten (n=52) from week 16-56 (40-week exposure). LV and RV-GLS assessment was performed according to the current American and European guideline recommendations using a vendor-neutral post processing software. Non-foreshortened apical (4, 3 and 2-chamber) views were used to obtain peak value of LV-GLS. For RV-GLS, RV focused 4-chamber view was used to calculate RV 4-chamber and free wall strain. A more negative strain value is favorable. Results Serial changes in LVEF, average LV-GLS, and RV-GLS (4-chamber and free wall) from baseline to week 56 are shown in the Figure. Despite preserved LVEF at baseline, average baseline LV-GLS was abnormal. There were significant and continued improvements in LV-GLS in the total group from baseline to week 56. 12 patients had transient reduction in LVEF (&amp;lt;50%) requiring temporary drug interruption (permanent discontinuation in 3). The LV-GLS in this subgroup was worse at baseline compared to the total study population, with no significant worsening from baseline through week 56. In the overall population, excluding these 12 patients, LV-GLS demonstrated an improvement sustained through week 56. Both free wall and 4-chamber RV-GLS were abnormal at baseline and remained unchanged from baseline to week 56. Conclusions In the VALOR-HCM trial, despite hypercontractile LVEF at baseline, average baseline LV-GLS was worse than normal reference values. Treatment with mavacamten resulted in an improvement in LV-GLS from baseline through Week 56 (with no significant worsening of LV-GLS in the subgroup who experienced any reduction in LVEF &amp;lt;50%), suggesting a favorable long-term impact on regional LV systolic function due to the reduction of cardiac hypercontractility. Additionally, there was no significant detrimental impact on RV systolic function on serial GLS assessment.Serial changes in LV and RV GLS in VALOR

Serial changes in left atrial strain in symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten: insights from VALOR-HCM trial

Abstract Background In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), the VALOR-HCM phase 3 randomized, double-blind, placebo-controlled clinical trial demonstrated that mavacamten, a cardiac myosin inhibitor, reduces the eligibility for septal reduction therapy with sustained improvement in left ventricular (LV) outflow tract gradients and symptoms. Mavacamten also resulted in favorable cardiac remodeling, including improvement in left atrial volume index (LAVI), LV diastolic function, and biomarkers (NT-proBNP and troponin T). However, the impact of mavacamten on LA function is not known. Objective We sought to assess serial changes in LA strain measures in patients enrolled in the VALOR-HCM trial. Methods VALOR-HCM included 112 symptomatic obstructive HCM patients (mean age 60 years, 51% male). Patients assigned to mavacamten at baseline (n=56) continued therapy for 56 weeks and those assigned to placebo crossed over to mavacamten (n=52) from week 16-56 (40-week exposure). Echocardiographic LA strain assessment was performed according to the current American and European guideline recommendations, using a vendor-neutral post processing software. For assessment of LA strain components (reservoir, conduit, and contraction), the non-foreshortened apical 4-chamber view was utilized. The zero reference was set at end-diastole. Results Serial changes in LAVI and all components of mean LA strain from baseline to week 56 are shown in the Figure. At baseline, LAVI and all mean LA strain values were worse than reported normal mean thresholds. There was a continued and significant improvement in all 3 LA strain values, from baseline to week 56, along with a significant reduction in LAVI. Improvement in LAVI was seen earlier than improvements in LA strain. There was a significant inverse correlation between change in mean LAVI and LA reservoir strain from baseline to week 56 (r= -0.42, p&amp;lt;0.001). Conclusions In the VALOR-HCM trial, average LAVI and baseline LA strain values were significantly worse than reported normal thresholds. Treatment with mavacamten resulted in an improvement in LAVI and LA strain values from baseline through week 56 suggesting a sustained favorable impact on cardiac remodeling. The advantageous cardiac remodeling associated with long-term treatment with mavacamten may in turn have a favorable impact on the observed high burden of atrial tachyarrhythmias in HCM.Serial changes in LA strain in VALOR-HCM

Effect of alcohol septal ablation on exercise hemodynamics, symptoms and quality of life in patients with obstructive hypertrophic cardiomyopathy

Abstract Background The comprehensive impact of septal reduction therapy in patients with obstructive hypertrophic cardiomyopathy (HCM), including exercise hemodynamics and quality of life (QoL), remains poorly understood. Purpose The aim of this study was to evaluate the effect of alcohol septal ablation (ASA) in mitigating left ventricular outflow tract (LVOT) obstruction, reducing filling pressures during exercise, and the effect on QoL in patients with obstructive HCM. Methods This prospective study enrolled 24 patients with obstructive HCM referred for ASA. Evaluations included right-heart catheterization and echocardiography performed at rest and during exercise, before and approximately six months post-ASA. The primary outcome was the difference in filling pressures assessed by pulmonary capillary wedge pressure (PCWP) at 75 Watt (W). Secondary outcome assessed LVOT gradients, New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and exercise capacity. Results ASA significantly reduced PCWP at 75 W (24 ± 10 mmHg vs 33 ± 9 mmHg; P = 0.0001) (Figure 1), decreased LVOT gradients at rest (49 mmHg (24-90) vs 17 mmHg (14-27); P=0.002), at peak exercise (45 mmHg (29-90) vs 32 mmHg (21-61); P = 0.02), and post-exercise (96 mmHg (34-161) vs 28 mmHg (21-62); P=0.004). The KCCQ-OSS score was also significantly reduced (75.6 ± 18.8 vs 64.7 ± 16; P = 0.006), without affecting peak oxygen consumption (19.9 ± 4.8 ml/kg/min vs 18.7 ± 3.6 ml/kg/min; P = 0.26). The improvement in the KCCQ score was confirmed by changes in NYHA functional class. Before ASA treatment, 54% of patients were in NYHA functional class III compared to 13% after ASA (P &amp;lt; 0.0005). Conclusion ASA substantially reduces exercise-induced filling pressures, reduces LVOT obstruction, and improves symptoms and QoL in obstructive HCM, without impacting maximal exercise capacity.

Mavacamten in a real-world hypertrophic cardiomyopathy population: how many may be eligible?

Abstract Introduction Mavacamten is a newly approved drug for obstructive hypertrophic cardiomyopathy (oHCM) and is currently being studied in non-obstructive HCM (nHCM). Our goal was to evaluate how often patients with oHCM and nHCM in a real-world cohort would be eligible for the main mavacamten trials: EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM. Methods Single-centre retrospective study enrolling consecutive patients with confirmed HCM, as per the 2023 ESC Guidelines, with at least yearly follow-up in our center, from 2017-2023. Key inclusion criteria from the three trials were considered: NYHA class II-III for all; obstructive forms (defined as peak left ventricle outflow tract [LVOT] gradient ≥50 mmHg at rest, after Valsalva manoeuvre or exercise) for EXPLORER-HCM and VALOR-HCM; left ventricular ejection fraction (LVEF) ≥55% for EXPLORER-HCM and MAVERICK-HCM; LVEF ≥60% and formal criteria for septal reduction therapy for VALOR-HCM, and NT-proBNP ≥300pg/mL for MAVERICK-HCM. Key exclusion criteria (estimated glomerular filtration rate [eGFR] &amp;lt;30mL/kg/1.73m2, QTc using the Fridericia’s formula &amp;gt;500ms, paroxysmal or intermittent atrial fibrillation present on screening electrocardiograph) were also considered. Results Overall, 410 patients were diagnosed with HCM, of whom 361 (88%) were alive at follow-up and included in the analysis: mean age of 63 ± 16 years, 196 (54%) were male, 272 (75%) with septal HCM and 60 (17%) with oHCM. According to the criteria of EXPLORER-HCM, VALOR-HCM and MAVERICK-HCM, 35 (10%), 6 (2%) and 27 (7%) patients would be eligible for enrolment, respectively. In patients with oHCM, 35 (58%) would be eligible for the EXPLORER-HCM trial. In the overall cohort, 65 (18%) would have criteria for at least one of the trials. The main reasons for exclusion were as follows: 191 (53%) NYHA I, 43 (12%) with NYHA IV, 12 (3%) had a LVEF &amp;lt;55%, 8 (2%) had both HCM and infiltrative myocardial disease and/or moderate-to-severe aortic stenosis and 8 (2%) had an eGFR &amp;lt;30mL/kg/1.73m2. In patients with nHCM, 16 (5%) would have been excluded due to NT-proBNP &amp;lt;300pg/mL and 8 (3%) due to paroxysmal atrial fibrillation. Conclusion In a real-word HCM cohort, we found that approximately 1 in every 5 patients would have criteria for either of the mavacamten trials, with more than half of oHCM being potential candidates for the EXPLORER-HCM. The main reasons for non-eligibility were NYHA I and LVEF &amp;lt;55%.

Procedural Volume and Outcomes After Septal Reduction Therapies in Hypertrophic Obstructive Cardiomyopathy.

Septal myectomy and alcohol septal ablation (ASA) are septal reduction therapies for patients with symptomatic obstructive hypertrophic cardiomyopathy. Operator and hospital volume may influence outcomes, but contemporary data on this relationship are limited. This retrospective cohort study used data from the Vizient Clinical Data Base (2016-2022). Patients with undergoing septal myectomy and ASA were identified using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes and stratified into low-, medium-, and high-volume groups based on annualized operator and hospital volumes. The outcomes were 30-day in-hospital mortality and 90-day readmission, analyzed using multivariable adjusted logistic and Cox models. Among 5725 patients with hypertrophic cardiomyopathy (3990 septal myectomy; 1735 ASA), most operators and hospitals performed <10 procedures annually. For septal myectomy, low-volume operators were associated with higher odds of 30-day mortality (adjusted odds ratio [aOR], 1.86 [95% CI, 1.11-3.15]) and greater risk for 90-day readmission (aOR, 1.51 [95% CI, 1.22-1.88]), and medium-volume operators had higher odds of 30-day mortality (aOR, 1.93 [95% CI, 1.05-3.55]). Medium-volume hospitals had higher 30-day mortality (aOR, 2.29 [95% CI, 1.32-3.99]), with low-volume hospitals showing greater risk for 90-day readmission (aOR, 1.60 [95% CI, 1.14-2.23]). For ASA, low- and medium-volume operators had increased 30-day mortality (aOR, 2.99 [95% CI, 1.15-7.75] and aOR, 3.86 [95% CI, 1.30-11.46]), but the risk of 90-day readmission was similar. Hospital volumes did not significantly impact outcomes for ASA. Low operator and hospital volumes were associated with worse outcomes for septal reduction therapies, emphasizing the need to refer patients with hypertrophic cardiomyopathy to high-volume centers with experienced operators.

Efficacy and Safety of Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by structural and functional abnormalities. Current management strategies, such as medications and septal reduction therapies, have significant limitations and risks. Recently, cardiac myosin inhibitors (CMIs) like mavacamten and aficamten have shown promise as noninvasive treatment options. This meta-analysis aims to evaluate the efficacy and safety of CMIs in HCM patients. PubMed/MEDLINE, Embase, the Cochrane Library, Ovid, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared CMIs to control treatments in HCM patients from inception till June 15, 2024. A random-effects model was used to pool odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes along with the corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using the χ2 test and Higgins I 2 statistic, and sensitivity and subgroup analyses were performed. Six RCTs involving 826 patients were included. CMI therapy significantly reduced resting left ventricular outflow tract (LVOT) gradient (MD, −37.64; 95% CI, −46.71 to −28.56), Valsalva LVOT gradient (MD, −46.04; 95% CI, −57.60 to −34.48), post-exercise LVOT peak gradient (MD, −48.64; 95% CI, −68.20 to −28.88), N-terminal pro-b-type natriuretic peptide levels (MD, −1.05; 95% CI, −1.64 to −0.47), and cardiac troponin I levels (MD, −7.96; 95% CI, −12.84 to −3.07). Improvements were observed in peak oxygen consumption (MD, 1.20; 95% CI, 0.23–2.17) and patient-reported outcomes (Kansas City Cardiomyopathy Questionnaire Clinical Summary Score: MD, 6.44; 95% CI, 3.50–9.37), with more patients achieving New York Heart Association class improvement &gt;1 (OR, 4.05; 95% CI, 2.61–6.30). Treatment-emergent adverse events were higher with CMI therapy (OR, 1.45; 95% CI, 1.02–2.05), but serious adverse events and other safety outcomes were comparable in both groups. CMIs, including mavacamten and aficamten, significantly improve clinical outcomes in HCM patients with a manageable safety profile. These results indicate that CMIs offer a promising noninvasive alternative to septal reduction therapies.

Hypertrophic Cardiomyopathy as a Form of Heart Failure with Preserved Ejection Fraction: Diagnosis, Drugs, and Procedures.

Hypertrophic cardiomyopathy (HCM) is a complex and heterogeneous cardiac disorder characterized by cardiac hypertrophy disproportionate to loading stimuli (e.g. hypertension or aortic stenosis). Diagnosing HCM requires a thorough examination of clinical symptoms, with echocardiography as the key initial imaging tool. Multimodality imaging further supports diagnosis, helps assess left ventricular outflow obstruction, and aids in risk stratification for sudden cardiac death. The cornerstone of HCM management remains pharmacological therapy with β-blockers and calcium channel blockers serving as first-line agents to alleviate symptoms and reduce left ventricular outflow tract obstruction. More recently, cardiac myosin inhibitors have revolutionized the treatment paradigm for obstructive HCM. Procedural interventions such as septal reduction therapy are reserved for refractory cases. Genetic testing and risk stratification for sudden cardiac death play a critical role in treatment decisions, guiding further testing in first-degree relatives and ICD implantation in high-risk individuals. Exercise recommendations have evolved based on recent data, challenging traditional restrictions and emphasizing individualized plans.

Long-Term Outcomes After Septal Reduction Therapies in Obstructive Hypertrophic Cardiomyopathy: Insights From the SHARE Registry.

Septal reduction therapy (SRT) provides substantial symptomatic improvement in patients with obstructive hypertrophic cardiomyopathy (HCM). However, long-term disease course after SRT and predictors of adverse outcomes have not been systematically examined. Data from 13 high clinical volume HCM centers from the international SHARE (Sarcomeric Human Cardiomyopathy Registry) were analyzed. Patients were followed from the time of SRT until last follow-up or occurrence of heart failure (HF) composite outcome (cardiac transplantation, implantation of a left ventricular assist device, left ventricular ejection fraction <35%, development of New York Heart Association class III or IV symptoms), ventricular arrhythmias composite outcome (sudden cardiac death, resuscitated cardiac arrest, or appropriate implantable cardioverter defibrillator therapy), or HCM-related death. Cox proportional hazards models were used to identify predictors of outcome. Of the 10 225 patients in SHARE, 1832 (18%; 968 [53%] male) underwent SRT, including 455 (25%) with alcohol septal ablation and 1377 (75%) with septal myectomy. The periprocedural 30-day mortality rate was 0.4% (8 of 1832) and 1499 of 1565 (92%) had a maximal left ventricular outflow tract gradient <50 mm Hg at 1 year. After 6.8 years (range, 3.4-9.8 years; 12 565 person-years) from SRT, 77 (4%) experienced HCM-related death (0.6% per year), 236 (13%) a composite HF outcome (1.9% per year), and 87 (5%) a composite ventricular arrhythmia outcome (0.7% per year). Among adults, older age at SRT was associated with a higher incidence of HCM death (hazard ratio, 1.22 [95 CI, 1.1-1.3]; P<0.01) and the HF composite (hazard ratio, 1.14 [95 CI, 1.1-1.2] per 5-year increase; P<0.01) in a multivariable model. Female patients also had a higher risk of the HF composite after SRT (hazard ratio, 1.4 [95 CI, 1.1-1.8]; P<0.01). De novo atrial fibrillation occurred after SRT in 387 patients (21%). Among pediatric patients followed for a median of 13 years after SRT, 26 of 343 (16%) developed the HF composite outcome, despite 96% being free of recurrent left ventricular outflow tract obstruction. Successful short- and long-term relief of outflow tract obstruction was observed in experienced multidisciplinary HCM centers. A subset of patients progressed to develop HF, but event-free survival at 10 years was 83% and ventricular arrhythmias were rare. Older age, female sex, and SRT during childhood were associated with a greater risk of developing HF.