Septal Reduction Therapy Research Articles

Role of Regulating Myosin in Incidence and Progression of Obstructive Hypertrophic Cardiomyopathy in Iraqi Patients

Patients diagnosed with obstructive hypertrophic cardiomyopathy who have not responded favorably to medical treatment may be good candidates for septal reduction therapy. The purpose of this study was to discover whether or not the Patients who take the oral myosin inhibitor mavacamten have the ability to improve to the point where they no longer require septal reduction treatment. This is true regardless of whether or not the patients opt to abandon the medicine completely. Methods: Patients who satisfied the requirements for septal reduction therapy and had a left ventricular outflow tract gradient of 47 mm Hg at rest or during provocation were randomly assigned, in a double-blind fashion, to receive either 5 milligrams of mavacamten per day or a placebo. Patients needed to have a gradient in their left ventricular outflow tract that was 47 mm Hg in order for them to be eligible for the treatment. The patients' left ventricular outflow gradients and ejection fractions were used to determine how much of the dose should be increased up to 15 mg. The primary outcome was a composite measure that was taken after 20 weeks of treatment to determine the proportion of patients who either got septal reduction therapy or fulfilled the eligibility requirements. Results: Totally, 121 individuals with obstructive hypertrophic cardiomyopathy participated. The patients' mean age was 58, 66% were men, and 88% had a left ventricular outflow gradient of 84 mm Hg or more after exercise. 43 of 56 placebo patients (68.4%) met guideline criteria or received septal reduction treatment after 20 weeks, whereas only 10 of 56 mavacamten patients (17.9%) did, a 45.4% difference (95 percent confidence interval: 33.4 percent -80.4 percent; P 0.03). Secondary testing found statistically significant differences (P less than 0.001). Conclusion: After 20 weeks of treatment, mavacamten decreased the number of obstructive hypertrophic cardiomyopathy patients with refractory symptoms who needed septal reduction. Septal reduction therapy may be unnecessary in the long term.

Single Center Experience of Percutaneous Septal Ablation in Patients With Hypertrophic Cardiomyopathy With A Novel Agent: Polidocanol

Septal reduction therapy is recommended in patients with obstructive hypertrophic cardiomyopathy (HCM) who remain symptomatic under maximally tolerated optimal medical treatment. Alcohol septal ablation is a favorable option, especially in patients with high surgical risk or who refuse surgery. Alcohol; causes scar-related ventricular arrhythmias and advanced heart blocks more frequently than surgical myectomy. Therefore, novel, safer agents are required for percutaneous septal ablation therapy. All the patients who underwent percutaneous septal ablation between January 2017 and June 2021 with polidocanol because of ongoing symptoms related to HCM despite maximally tolerated medical treatment were enrolled. Data were obtained retrospectively from the hospital electronic database. A total of 28 patients were included. Median age was 61 years (43.5-67), and 19 (67.8%) patients were male. Most of the patients underwent index procedures; however, only 2 cases had history of previous septal ablation. Median follow-up was 3.5 months (0.25 to 12.25). Median left ventricular outflow tract (LVOT) gradient at rest was 68.5 (37-80) mmHg, and after Valsalva maneuver median LVOT gradient was 95.5 (75-125) mmHg. Median volume of polidocanol used in procedures was 2 (2-3.37) ml, and mean procedure time was 28.1±2.5minutes. LVOT gradient invasively measured was significantly reduced (mean 76.5mm Hg vs mean 30mm Hg; p<0.001) immediately after the septal ablation. Conduction defects developed in 18 patients (64.2%); however, de novo permanent cardiac implantable electronic device implantation was required in only 4 (14.3%) cases. Leakage of polidocanol and mortality did not occur in any cases. Pericardial effusion developed in only 1 case, and it resolved with medical treatment. After mean 3.5months follow-up, both LVOT gradient and New York Heart Association functional class parameters were better than baseline values. In conclusion, polidocanol is a safe and effective agent for septal ablation in patients with HCM. Outcomes and complication rates are similar with alcohol septal ablation.

185 BETA-BLOCKERS OR CALCIUM CHANNEL BLOCKERS IN HYPERTROPHIC CARDIOMYOPATHY

Abstract Background Guidelines recommend betablockers (BB) as first line therapy in symptomatic patients with hypertrophic cardiomyopathy (HCM). A secondary role in the therapeutic algorithm is assigned to non-dihydropyridine calcium channel blockers (ND-CCB). Since no randomized comparison trials between the two drugs have been made so far, the aim of the present analysis was to evaluate the prognostic impact of BB and ND-CCB in a cohort of patients with HCM, either obstructive or not. Methods From a cohort of 1434 patients with a diagnosis of HCM included in the French register REMY, we retrospectively analysed 601 individuals treated with BB or ND-CCB. Patients taking both BB and ND-CCB or none, patients who already had an implantable cardioverter defibrillator or a pacemaker and who had already undergone a procedure of atrial fibrillation (AF) ablation or of septal reduction therapy were excluded. Results Out of 601 HCM patients, 545 (91%) were treated with BB and 56 (9%) with ND-CCB. At 8-year follow-up no differences were observed as regard the composite endpoint of cardiovascular death, hospitalization for heart failure and hospitalization for AF (133 [24%] vs. 9 [16%] for patients taking BB or ND-CCB respectively, HR 1.84, 95% CI 0.94–3.63). Patients taking ND-CCB were less symptomatic at long-term follow-up but experienced more drug interruptions or changes. Conclusions In a real-world cohort of patients with HCM, ND-CCB therapy was not associated with a higher incidence of adverse events compared to BB therapy.

Costs and Healthcare Resource Utilization for Obstructive Hypertrophic Cardiomyopathy With Septal Reduction Therapy.

Patients with obstructive hypertrophic cardiomyopathy (oHCM) and severe refractory symptoms may require invasive septal reduction therapies (SRTs), either surgical septal myectomy (SM) or transcatheter alcohol septal ablation (ASA). The main objective of this study was to quantify all-cause and oHCM-related healthcare resource utilization (HCRU) and costs for patients receiving SM or ASA. This retrospective study utilized medical and pharmacy claims submitted during 2012-2020. HCRU and costs for 119 adults with oHCM who had at least 1 SM (n = 95) or ASA (n = 24) were compared for baseline and follow-up periods. The mean inpatient hospitalization stay was longer for SM (8.3 days) than ASA (6.0 days). Postprocedure HCM-related medication usage was greater following SM (98%) than ASA (88%). The mean number of HCM-related outpatient visits increased from pre- to post procedure (12.2 vs 15.9 in the SM group; 7.2 vs 9.5 in the ASA group), with most patients having at least 1 cardiology visit post procedure (86% of the SM group; 83% of the ASA group). Total mean HCM-related costs (reported in United States currency) increased with both procedures ($27,045 vs $119,772 in the SM group; $11,278 vs $54,351 in the ASA group), driven by increased inpatient hospitalization ($10,325 vs $112,923 in the SM group; $5509 vs $47,450 in the ASA group) and surgical costs ($6665 vs $92,031 in the SM group; $52 vs $44,815 in the ASA group). Our results indicate increasing costs for patients undergoing SRT, driven by inpatient hospitalizations and surgical costs. Commercially insured and Medicare Advantage patients with oHCM experience high healthcare costs and economic burden attributable to SRT.

MSR97 Systematic Literature Review of the Efficacy and Safety of Pharmacological Treatments and Septal Reduction Therapies for Obstructive Hypertrophic Cardiomyopathy

To systematically identify studies evaluating the efficacy and safety of pharmacological interventions and septal reduction therapies (SRT) used to treat obstructive hypertrophic cardiomyopathy (HCM).

The Risk of Ventricular Arrhythmias between Alcohol Septal Ablation and Septal Myectomy in Hypertrophic Cardiomyopathy: A Meta-Analysis on Septal Reduction Therapy.

Alcohol septal ablation (ASA) has been more commonly applied in medical refractory hypertrophic obstructive cardiomyopathy (HOCM) compared with septal myectomy (SM), however its potential to create a proarrhythmic substrate is increased. A systematic search was performed in PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to October 2020. Fixed or random effects models were used to estimate the risk ratios (RR) for ventricular arrhythmia events or other outcomes between the SM and ASA cohorts. Twenty studies with 8025 patients were included. Pool analysis showed that the incidence of ventricular tachycardia (VT)/ventricular fibrillation (VF), which included appropriate implantable cardioverter defibrillator (ICD) intervention, was significantly higher in the ASA cohort than that in the SM cohort (ASA vs SM: 10% (345/3312) vs 5% (161/3227) (RR = 1.98, 95% CI (confidence interval), 1.65-2.37; p 0.00001, = 0%). In both groups, more than 90% of VT/VF events occurred in the early phase (during the procedure, during hospitalization or within 30 days after the procedure) (ASA: 94.20%; SM: 94.41%). Further subgroup analysis also showed that the ASA group had a higher incidence of VT/VF in both the early phase (RR = 1.94, 95% CI, 1.61-2.33; p 0.0001, = 0%) and the late phase (RR = 2.80, 95% CI, 1.00-7.89; p = 0.05, = 33%). Furthermore, although the risks of sudden cardiac death (SCD) were similar between the ASA and SM groups, a higher incidence of sudden cardiac arrest (SCA), which included SCD and resuscitated SCA, was observed in the ASA group (RR = 2.30, 95% CI, 1.35-3.94; p = 0.002, = 0%). In patients with HOCM, those who received ASA showed a higher incidence of VF/VT and SCD combined with resuscitated SCA. The majority of VT/VF occurred in the early phase.

Abstract 11215: Comparative Effectiveness of Alcohol Septal Ablation versus Septal Myectomy on Mortality in Patients With Hypertrophic Cardiomyopathy

Introduction: Alcohol septal ablation (ASA) and septal myectomy (SM) are two options of septal reduction therapy (SRT) for patients with medication-resistant symptomatic obstructive hypertrophic cardiomyopathy (HCM). The 2020 AHA/ACC HCM Guideline recommends SM as the first-line choice and ASA as the second-line option to be conducted only if SM is contraindicated or surgical risk is high. However, little is known about the effectiveness of ASA versus SM for HCM on mortality in the real-world settings. Objective: To compare mortality between patients with HCM who underwent ASA and those who had SM using population-based databases. Methods: We identified patients with HCM who underwent an SRT from 2007 through 2014 using the SPARC database — a comprehensive, all-payer claims database that includes record of every inpatient stay and outpatient visit in New York State. We compared mortality at 15, 30, 180, and 360 days after SRT between the ASA group and the SM group (the reference group) using unadjusted analysis, propensity score matching (PSM), and inverse probability weighting (IPW). In the PSM and IPW models, we adjusted for age, sex, race/ethnicity, insurance type, and each item in the Elixhauser Comorbidity Index. Results: We identified 755 patients with HCM who underwent an SRT, including 348 in the ASA group and 407 in the SM group. In the unadjusted analysis, mortality in the ASA group was lower than that in the SM group (crude mortality at 360 days, 3.7% vs. 7.4%; Figure ). Using the PSM method, mortality was lower in the ASA group in the 180-day and 360-day post-SRT periods (adjusted odds ratio [aOR] = 0.31 at 360 days; 95% confidence interval [CI], 0.09-0.93; P = 0.049). The IPW model showed consistent findings with the PSM model (aOR = 0.44 at 360 days; 95% CI, 0.21-0.88; P = 0.02). Conclusions: Patients with HCM who underwent ASA had lower mortality than those who had SM during a 1-year post-SRT period in this population-based study.

Abstract 12354: Novel Coronavirus Disease 2019 Infection in a Cohort of Patients With Phenotypic Hypertrophic Cardiomyopathy: An Extended Report

Background: Patients with preexisting heart disease suffer more severe outcomes after COVID-19. Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac conditions. We previously reported incidence and outcomes of COVID-19 in HCM in early days of the pandemic. We report results from an expanded and extended HCM cohort. Methods: 343 patients with HCM [age 59±17 years, 55% men, 19% NYHA class &gt;1, 63% obstructive, 14% septal reduction therapy, 24% positive family history, 42% selectively genotyped (43% positive for pathogenic mutations), 22% implantable cardioverter-defibrillator (ICD) implants, 27% paroxysmal or permanent atrial fibrillation (AF), 4% AF ablation] were evaluated for COVID-19 from December 2019 to May 2022. Results. Overall, 54 (16%) patients were diagnosed with COVID-19 [56% men, age 55±17 years, 60% obstructive HCM, 5.5% dilated phase HCM, 28% positive family history, 15% genotype positive, 28% with ICD, 17% NYHA class &gt;1, 31% AF]. There were 289 patients without COVID-19 [55% men, age 58±17 years, 63% obstructive HCM, 3% dilated phase HCM, 23% positive family history, 17% genotype positive, 21% with ICD, 19% NYHA class &gt;1, 27% AF]. Patients with COVID-19 were slightly younger (55±17 vs 58±17 years, p 0.046) and more often had dilated phase HCM (5.5% vs 3%) and more often had ICD (28% vs 21%). Eleven (20%) patients with COVID-19 were hospitalized and 1 (2%) died of the disease. Compared to those with mild disease, hospitalized patients with COVID-19 were more often men (82% vs 49%, p 0.04), older (age 59±15 vs. 54±18 years), with obstructive phenotype (73% vs 56%) and with NYHA class &gt;1 symptoms (27% vs 12%). In the studied patient cohort 70% had at least one dose of COVID-19 vaccine. Prior to the infection 63% of patients had no vaccination against SARS-CoV2. Among hospitalized patients 9 (82%) had no vaccination and 2 (18%) were vaccinated and had mild disease. Conclusions. Although Covid-19 infection rate (16%) in studied cohort was slightly lower than in general US population (~25%), hospitalization rate was higher (20% vs 9%) with similar death rates (1-2%). Older man with symptomatic obstructive HCM phenotype noted to have higher risk for hospitalization. Patients with vaccination against SARS-Cov2 tended to require less hospitalization.

Abstract 15848: Prognostic Value of Left Ventricular Diastolic Function in Patients With Hypertrophic Cardiomyopathy

Background: Diastolic dysfunction (DD) is frequently present in patients with hypertrophic cardiomyopathy (HCM) due to abnormal left ventricular (LV) relaxation, wall hypertrophy, increased LV filling pressures and myocardial disarray and fibrosis, even though ejection fraction (EF) remains preserved until late stages. Our aim was to investigate in a large cohort whether contemporary markers of DD and increased filling pressures are associated with outcomes in these patients. Methods: We screened consecutive patients with HCM who had transthoracic echocardiography and no significant valvular heart disease. The associations of septal/lateral e’ velocity, E/e’, left atrial volume index (LAVi), and tricuspid regurgitant velocity (TR) with all-cause mortality were tested. A diastolic score (DS) was also calculated (1 point for each abnormality in e’, E/e’, TR, LAVi). Results: 1,496 patients with HCM were studied (mean age 52±15 yrs; 61% men; LV EF 69±7%; Table). Diastolic abnormalities were highly prevalent in these patients ( Table ). In the subset without septal reduction therapy (SRT; n=900), at a median followup of 9 years (IQR 7-11 yrs; n=78 deaths), increased E/e’ and DS were strongly associated with mortality (log-rank P &lt;.0001 for both; Figure ). However, E/e’ did not remain significant in multivariable models after adjustment for known cardiac risk factors or other significant confounders ( Table ). In contrast, DS &gt;2 remained independently associated with ~2-fold higher mortality risk (adjusted HR 1.91 [1.14-3.20, P =.01]; n=693; Table). In patients who underwent SRT (n=596), these associations showed the same trend but attenuated. Conclusion: In HCM patients who did not require SRT, the severity of DD was associated with mortality, independent of cardiac pump function or known cardiac risk factors. The composite score was more powerful than E/e’. Further studies are needed to fully understand the impact of DD in these patients with and without SRT.

Abstract 11462: Alcohol Septal Ablation vs Surgical Myectomy for Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis

Introduction: Surgical Myectomy (SM) is the gold standard treatment for hypertrophic obstructive cardiomyopathy (HOCM). However, alcohol septal ablation (ASA) has emerged as an alternative option for selected patients. Nonetheless, the long-term efficacy and safety of ASA have been debated in recent years. The aim of this metanalysis is to evaluate the long-term outcomes of ASA vs SM in HOCM patients. Hypothesis: ASA is a safe and effective alternative to SM in HOCM. Methods: : Unrestricted searches of the PubMed, EMBASE, and Cochrane databases from inception till June 1, 2022, for studies comparing long-term outcomes of ASA with SM in HOCM patients. Relevant data were extracted and analyzed using Revman 5.3 software. Odds Ratio (OR) and 95% Confidence interval (CI) were calculated using the random-effects model. Results: : A total of 12 retrospective studies were included examining 7,599 HOCM patients (2,010 ASA vs 5,589 SM). After a mean follow-up of 5.04 years, all-cause mortality was similar between the two groups (OR 1.18; 95% CI 0.60-2.29). However, ASA was associated with high rates of reinterventions (OR 15.68; 95% CI 6.71-36.61), and pacemaker insertion (OR 2.74; 95% CI 1.39-5.41). Conclusions: Although there was no difference in mortality between ASA and SM, ASA was associated with higher rates of reinterventions and pacemaker insertion in long-term follow-up. Therefore, the selection of septal reduction therapy in HOCM should be individualized and should be performed in a comprehensive center after detailed risk and benefits discussions with an experienced team.

Abstract 12577: Effect of Mavacamten on Diastolic Function in Patients With Obstructive Hypertrophic Cardiomyopathy: Insights From the VALOR-HCM Study

Introduction: In the randomized VALOR-HCM study of symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM), mavacamten reduced the need for septal reduction therapy at 16 weeks. Because mavacamten is a cardiac myosin inhibitor that may improve ventricular compliance, this sub-study hypothesized that mavacamten would favorably impact diastolic function. Methods: Symptomatic patients on maximally-tolerated medical therapy referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo. Echocardiographic assessment was performed by an independent, blinded core laboratory. Diastolic grade was determined according to ASE guidelines. Between-group comparisons were made from baseline to week 16. Results: Among 112 enrolled patients, baseline left atrial volume index (LAVi) was similar (Table). At 16 weeks, mavacamten treatment resulted in a significant reduction in LAVi (-5.2 vs -0.5 with placebo, p = .003). Similarly, although lateral E/e’ and septal E/e’ were comparable at baseline, patients treated with mavacamten demonstrated a significant reduction at week 16 (lateral E/e’: -3.5 vs 0.7, p &lt;0.001; septal E/e’: -3.3 vs 0.7, p &lt; 0.001)(Table). Patients treated with mavacamten were also more likely to improve their diastolic dysfunction grade (31.4% vs 12.8%, p = 0.032) (Figure). Conclusions: After only 16 weeks of therapy, in a highly symptomatic oHCM population with echocardiographic-guided drug titration, mavacamten improved measures of diastolic function.

Abstract 14365: In-Hospital Outcomes of Septal Myectomy versus Alcohol Septal Ablation for Hypertrophic Cardiomyopathy - An Update and Insights From the National Inpatient Sample

Introduction: Septal Myectomy (SM) and Alcohol Septal Ablation (ASA) improve symptoms in patients with Hypertrophic Cardiomyopathy (HCM), however, outcomes data in this population is predominantly from specialized centers. Methods: The National Inpatient Database was queried from 2011- 2019 for relevant ICD-9 and -10 diagnostic and procedural codes. Baseline characteristics and in-hospital outcomes of patients with HCM who underwent SM vs. ASA were compared. A p-value &lt;0.001 was considered statistically significant. Results: We identified 17,245 patients who underwent septal reduction therapies, of whom 62.5% underwent SM and 37.5% underwent ASA. Patients who underwent SM had higher all-cause mortality (OR:2.2 [1.7-2.9]), post procedure ischemic stroke (OR: 2.4 [1.8-3.2]), acute kidney injury (OR: 1.9 [1.7-2.2]), vascular complications (OR: 4 [2.8-5.7]), ventricular septal defect (OR: 4.6 [3.5-6.1]), aortic dissection/aneurysm (OR: 1.6 [1.3-2.1]), cardiogenic shock (OR: 2 [1.5-2.6]), sepsis (OR:5.2 [3.3-8.1]), and left bundle branch block (OR: 3.2 [2.8-3.7]) (p&lt;0.001 for all), compared to ASA. Patients who underwent ASA had higher post procedure complete heart block (OR: 1.2 [1.1-1.4]), 2 nd -degree AV Block (OR: 2 [1.4-3]), right bundle branch block (OR: 6.4 [5.3-7.8]), ventricular tachycardia (OR:2 [1.8-2.3]), supraventricular tachycardia (OR: 1.4 [1.2-1.7]), and more commonly required pacemaker (OR: 1.4 [1.2-1.6]) or implantable cardioverter-defibrillator (OR: 1.3 [1.1-1.5]) (p&lt;0.001 for all) insertion compared to SM. Conclusions: This nationwide analysis evidenced patients undergoing SM had higher in-hospital mortality and periprocedural complications compared to ASA, however, those undergoing ASA had higher post-procedure conduction abnormalities and pacemaker or ICD implantation. The implications of these findings warrant further investigation in regards to patient selection strategies for these therapies.

Abstract 12598: Effect of Mavacamten on Systolic Anterior Motion of the Mitral Valve and Mitral Regurgitation in Patients With Obstructive Hypertrophic Cardiomyopathy: Insights From the VALOR-HCM Study

Introduction: In the randomized VALOR-HCM study of symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM), mavacamten reduced the need for septal reduction therapy at 16 weeks. The current sub-study sought to assess the impact of mavacamten on systolic anterior motion (SAM) of the mitral valve and associated mitral regurgitation (MR). Methods: Patients on maximally-tolerated medical therapy referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo. Echocardiographic assessment was performed by an independent, blinded core laboratory. SAM was assessed as none, mild (anterior leaflet &gt;/= 1 cm from the septum), moderate (anterior leaflets &lt;1cm from the septum), and severe (anterior leaflet in contact with septum). MR was assessed according to ASE guidelines. Results: Among 112 enrolled patients, 23.2% (n=27) had at least moderate (2+) MR. Most (92.9%, n=104) had at least moderate resting SAM, of whom 55.4% (n = 62) had severe SAM. At 16 weeks, 53.7% of patients treated with mavacamten had at least one level improvement in resting SAM compared to 21.6% of patients treated with placebo ( p = 0.001), and 35.2% had at least a two level improvement in SAM compared with 11.8% of placebo patients ( p = 0.007)(Figure 1A). Similarly, patients treated with mavacamten had an improvement of -36.0 + 28.8 mmHg in resting left ventricular outflow tract gradient at week 16 compared to -1.5 + 26.5 mmHg with placebo (&lt;0.001). At week 16, 48.1% of patients treated with mavacamten had at least a one grade improvement in MR, and 23.1% had at least a two grade improvement compared to 12.2% and 6.1% of patients treated with placebo ( p &lt;0.001 and 0.025, respectively)(Figure 1B). Conclusions: In highly symptomatic patients with oHCM, treatment with mavacamten reduced resting SAM with an improvement in associated MR.

Percutaneous Septal Reduction Therapy in a Patient with Severely Symptomatic Hypertrophic Obstructive Cardiomyopathy: An experience from a tertiary care centre.

NONE

Population estimates of obstructive and non-obstructive hypertrophic cardiomyopathy in the UK and Germany

Abstract Background While numerous publications have estimated the prevalence of diagnosed hypertrophic cardiomyopathy (HCM), none have quantified the real-world proportion of obstructive and non-obstructive HCM using nationally representative data sources in any European countries. Purpose To estimate the prevalence of diagnosed HCM and its subtypes in the UK and Germany. Methods Patients with HCM were identified in the UK from 01 Apr 2009 to 30 Oct 2020 and Germany from 2011 to 2019. UK patients with HCM were identified using electronic health records from the Clinical Practice Research Datalink (CPRD) primary care data linked with Hospital Episode Statistics (HES) secondary care data using ICD-10 (I42.1, I42.2), Read, Medcode, SNOMED, and OPCS codes. German patients with HCM were identified using a nationally representative administrative claims data pool (WIG2 Benchmark database) from several German Statutory Health Insurance (SHI)-insurances using ICD-10 and OPS codes. Obstructive HCM was identified as any obstructive HCM diagnosis, any HCM diagnosis with septal reduction therapy, and any HCM diagnosis and left ventricular outflow tract obstruction (LVOTO; not in German claims data). Non-obstructive HCM was any non-obstructive or unspecified HCM diagnosis without evidence of any obstructive HCM. Annual prevalence was calculated for each year in the respective study periods and average annual prevalence across the study period. Results The average annual prevalence rate of HCM was 4.15/10,000 in the UK and 8.61/10,000 in Germany, while the average annual prevalence rate of obstructive HCM was 2.84/10,000 in the UK and 4.18/10,000 in Germany (Table). The proportion of HCM that was obstructive HCM was 68% in the UK and 49% in Germany. The prevalence rates of diagnosed HCM and obstructive HCM tended to increase over time (Figure). Conclusion The prevalence of HCM, obstructive HCM and the proportion of HCM that is obstructive varied between the UK and Germany. The prevalence of HCM was generally consistent with previously published estimates. Although there are limitations with coding in administrative data, it is important to differentiate obstructive HCM from non-obstructive HCM given their unique treatments and disease progression and management, especially since at least 49–68% of HCM is obstructive. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bristol Myers-Squibb

Representativeness of EXPLORER-HCM trial and prevalence of eligibility criteria for Mavacamten in a nationwide cohort

Abstract Introduction The EXPLORER-HCM trial evaluated the safety and efficacy of Mavacamten, a cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy (HCM). Mavacamten improved symptoms, exercise capacity and left ventricular outflow tract (LVOT) obstruction. However, the proportion of patients eligible for this therapy in real practice remains unclear. Purpose To determine the prevalence of eligibility criteria for Mavacamten and to describe the profile of patients complying with EXPLORER-HCM criteria in a nationwide cohort. Methods Cross-sectional study including all HCM patients enrolled in a European country-based nationwide registry. Presence of EXPLORER-HCM inclusion [≥18 years, obstructive HCM (LVOT gradient ≥50 mmHg), left ventricular ejection fraction (LVEF) ≥55%, New York Heart Association (NYHA) class II–III] and exclusion criteria [syncope or sustained ventricular tachycardia with exercise] were analyzed. Results Of 1042 patients included in this analysis (57.8% male, mean age at diagnosis 52 years, 39.6% obstructive HCM), 45 met the EXPLORER-HCM inclusion criteria and, after applying exclusion criteria, 30 patients were eligible for therapy with Mavacamten. Eligible patients were all Caucasian, mostly female (63.3%), with a mean age at diagnosis of 58±14 years. All patients presented with heart failure symptoms, and were mostly in NYHA class II (83.3%); 4 patients (13.3%) presented with atrial fibrillation. In the baseline echocardiogram, mean LVEF was 68±9%; mean interventricular septum thickness was 20±4 mm; most patients presented with systolic anterior motion of the mitral valve (96.7%) and mitral regurgitation (96.7%). In cardiac magnetic resonance imaging evaluation, maximal wall thickness was 22±4 mm and 76.9% had late gadolinium enhancement. A pathogenic or likely pathogenic HCM gene variant was identified in 5 patients (MYH7 and MYBPC3 gene mutations). In this group, 86.2% of patients were treated with beta-blockers and 34.5% with calcium channel antagonists. Only 1 patient was on Disopyramide. Septal reduction techniques were used in 43.3% of patients: alcohol septal ablation and septal myectomy were performed in 7 (23.3%) and 6 (20.0%) patients, respectively. Cardioverter-defibrillators were implanted in 2 patients for primary prevention of sudden cardiac death, and 6 patients received a pacemaker for bradycardia indications. Conclusion Specific therapies remain an unmet need in HCM. In this large nationwide cohort, only 2.9% of patients were eligible for therapy with Mavacamten according to EXPLORER-HCM criteria. Among patients complying with the study criteria, invasive septal reduction therapies were offered to a high proportion of patients. Further real-world data are warranted to estimate the proportion of HCM patients that will benefit from Mavacamten. Funding Acknowledgement Type of funding sources: None.

Current therapies for hypertrophic cardiomyopathy: a systematic review and meta-analysis of the literature.

The aim of this study was to synthesize the evidence on the effect of the current therapies over the pathophysiological and clinical characteristics of patients with hypertrophic cardiomyopathy (HCM). A systematic review and meta-analysis of 41 studies identified from 1383 retrieved from PubMed, Web of Science, and Cochrane was conducted. Therapies were grouped in pharmacological, invasive and physical exercise. Pharmacological agents had no effect on functional capacity measured by VO2max (1.11mL/kg/min; 95% CI: -0.04, 2.25, P<0.05). Invasive septal reduction therapies increased VO2max (+3.2mL/kg/min; 95% CI: 1.78, 4.60, P<0.05). Structured physical exercise programmes did not report contraindications and evidenced the highest increases on functional capacity (VO2max+4.33mL/kg/min; 95% CI: 0.20, 8.45, P<0.05). Patients with left ventricular outflow tract (LVOT) obstruction at rest improved their VO2max to a greater extent compared with those without resting LVOT obstruction (2.82mL/kg/min; 95% CI: 1.97, 3.67 vs. 1.18; 95% CI: 0.62, 1.74, P<0.05). Peak LVOT gradient was reduced with the three treatment options with the highest reduction observed for invasive therapies. Left ventricular ejection fraction was reduced in pharmacological and invasive procedures. No effect was observed after physical exercise. Symptomatic status improved with the three options and to a greater extent with invasive procedures. Invasive septal reduction therapies increase VO2max, improve symptomatic status, and reduce resting and peak LVOT gradient, thus might be considered in obstructive patients. Physical exercise emerges as a coadjuvant therapy, which is safe and associated with benefits on functional capacity. Pharmacological agents improve reported NYHA class, but not functional capacity.

Thin filament cardiomyopathies: A review of genetics, disease mechanisms, and emerging therapeutics.

All muscle contraction occurs due to the cyclical interaction between sarcomeric thin and thick filament proteins within the myocyte. The thin filament consists of the proteins actin, tropomyosin, Troponin C, Troponin I, and Troponin T. Mutations in these proteins can result in various forms of cardiomyopathy, including hypertrophic, restrictive, and dilated phenotypes and account for as many as 30% of all cases of inherited cardiomyopathy. There is significant evidence that thin filament mutations contribute to dysregulation of Ca2+ within the sarcomere and may have a distinct pathomechanism of disease from cardiomyopathy associated with thick filament mutations. A number of distinct clinical findings appear to be correlated with thin-filament mutations: greater degrees of restrictive cardiomyopathy and relatively less left ventricular (LV) hypertrophy and LV outflow tract obstruction than that seen with thick filament mutations, increased morbidity associated with heart failure, increased arrhythmia burden and potentially higher mortality. Most therapies that improve outcomes in heart failure blunt the neurohormonal pathways involved in cardiac remodeling, while most therapies for hypertrophic cardiomyopathy involve use of negative inotropes to reduce LV hypertrophy or septal reduction therapies to reduce LV outflow tract obstruction. None of these therapies directly address the underlying sarcomeric dysfunction associated with thin-filament mutations. With mounting evidence that thin filament cardiomyopathies occur through a distinct mechanism, there is need for therapies targeting the unique, underlying mechanisms tailored for each patient depending on a given mutation.

TCT-355 Lifetime Costs of Septal Reduction Therapies are Substantially Lower Compared to Mavacamten in Patients With Obstructive Hypertrophic Cardiomyopathy

TCT-355 Lifetime Costs of Septal Reduction Therapies are Substantially Lower Compared to Mavacamten in Patients With Obstructive Hypertrophic Cardiomyopathy

Twenty years of experience with alcohol septal ablation (ASA) for hypertrophic obstructive cardiomyopathy in Chile

Septal reduction therapies for patients with hypertrophic obstructive cardiomyopathy (HOCM) are accepted in patients with symptoms and LV outflow tract gradient >50 mmHg who do not respond to medical treatment. Alcohol septal ablation is a minimally invasive procedure with promising short- and long-term results