Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy.

BACKGROUND AND AIMS: Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten. METHODS: Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion. RESULTS: At the latest data cut-off, 211 (91.3%) of 231 patients originally enrolled in MAVA-LTE still received mavacamten. Median (range) time on study was 166.1 (6.0-228.1) weeks; 185 (80.1%) and 99 (42.9%) patients had completed the week 156 and 180 visits, respectively. Sustained reductions from baseline to week 180 occurred in left ventricular outflow tract gradients (mean [standard deviation]: resting, -40.3 [32.7] mmHg; Valsalva, -55.3 [33.7] mmHg), NT-proBNP (median [interquartile range]: -562 [-1162.5, -209] ng/L), and EQ-5D-5L score (mean [standard deviation]: 0.09 [0.17]). Mean left ventricular ejection fraction (LVEF) decreased from 73.9% (baseline) to 66.6% (week 24) and 63.9% (week 180). At week 180, 74 (77.9%) of 95 patients improved by at least one New York Heart Association class from baseline. Over 739 patient-years exposure, 20 patients (8.7%; exposure-adjusted incidence: 2.77/100 patient-years) experienced 22 transient reductions in LVEF to <50% resulting in temporary treatment interruption (all recovered LVEF of ≥50%). Five (2.2%) patients died (all considered unrelated to mavacamten). CONCLUSIONS: Long-term mavacamten treatment resulted in sustained improvements in cardiac function and symptoms in patients with obstructive HCM, with no new safety concerns identified. Transient, reversible reductions in LVEF were observed in a small proportion of patients during long-term follow-up.

A systematic review and meta-analysis of the efficacy and safety of Mavacamten therapy in international cohort of 524 patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro-B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events. Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients.

Angiographic microvascular resistance in patients with obstructive hypertrophic cardiomyopathy.

BACKGROUND: Coronary microvascular dysfunction (CMD) is an important feature of obstructive hypertrophic cardiomyopathy (oHCM). Angiographic microvascular resistance (AMR) offers a potent means for assessing CMD. This study sought to evaluate the prognostic value of CMD burden calculated by AMR among oHCM patients. METHODS: We retrospectively screened all patients diagnosed with oHCM from Fuwai Hospital between January 2017 and November 2021. Off-line AMR assessments were performed for all 3 major coronary vessels by the independent imaging core laboratory. Patients were followed every 6 months post discharge via office visit or telephone contacts. The primary outcome was major adverse cardiovascular events (MACE), including all-cause death, and unplanned rehospitalization for heart failure. RESULTS: A total of 342 patients presented with oHCM diseases enrolled in the present analyses. Mean age was 49.7, 57.6 % were men, mean 3-vessel AMR was 6.9. At a median follow-up of 18 months, high capability of 3-vessel AMR in predicting MACE was identified (AUC: 0.70) with the best cut-off value of 7.04. The primary endpoint of MACE was significantly higher in high microvascular resistance group (3-vessel AMR ≥ 7.04) as compared with low microvascular resistance group (56.5 % vs. 16.5 %; HR: 5.13; 95 % CI: 2.46-10.7; p < 0.001), which was mainly driven by the significantly higher risk of heart failure events in high microvascular resistance group. Additionally, 3-vessel AMR (HR: 4.37; 95 % CI: 1.99-9.58; p < 0.001), and age (per 1 year increase, HR: 1.03; 95 % CI: 1.01-1.06; p = 0.02) were independently associated with MACE. CONCLUSION: The present retrospective study demonstrated that the novel angiography-based AMR was a useful tool for CMD evaluation among patients with oHCM. High microvascular resistance as identified by 3-vessel AMR (≥7.04) was associated with worse prognosis.

Acute Left Ventricular Ballooning: Tools to Differentiate Hypertrophic Cardiomyopathy with Outflow Obstruction from Neurohumoral Takotsubo Syndrome.

Despite considerable interest in the syndrome of acute left ventricular (LV) ballooning, its pathophysiology has remained ill-defined. In this review, we explore observational data describing two etiologies of acute LV ballooning: neurohumoral classic Takotsubo Syndrome (TTS), and acute severe unrelenting left ventricular outflow tract (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (HCM). We describe the clinical presentation and varying pathophysiology of these presentations, explore how echocardiography and cardiac catheterization may help differentiate between the two etiologies, and detail differences in management. We highlight the significant overlap as well as key differentiating features of these conditions, with the aim to improve diagnostic awareness and accuracy and appropriately tailor therapy.

Left Bundle Branch Pacing for Bradycardia in Non-obstructive Hypertrophic Cardiomyopathy Patients: Feasibility, Safety, and Effect.

PURPOSE: Left bundle branch pacing (LBBP) is as an innovative physiological pacing approach. The research on LBBP in non-obstructive hypertrophic cardiomyopathy (NOHCM) patients is scarce. This study aimed to assess the feasibility, safety, and effect of LBBP in bradycardia NOHCM patients with permanent pacemaker (PPM) implantation indication. METHODS: Thirteen consecutive patients with NOHCM who received LBBP were retrospectively enrolled as a hypertrophic cardiomyopathy (HCM) group. Following 1:3 matching, 39 patients without HCM were randomly matched as a control group. Echocardiographic index and pacing parameters were collected. RESULTS: The successful LBBP was achieved in 96.2% of all cases (50/52), and the success rate of the HCM group was 92.3% (12/13). In the HCM group, the paced QRS duration (from the pacing stimulus to QRS end) was 145.6±20.8 ms. The stimulus to left ventricular activation time (s-LVAT) was 87.4±15.2 ms. In the control group, the paced QRS duration was 139.4±17.2 ms, and the s-LVAT was 79.9±14.1 ms. During the implantation, R-wave sensing and the pacing threshold of the HCM group were significantly higher than the control group (20.2±10.5 vs 12.5±5.9 mV, P < 0.05; 0.8±0.3 vs 0.6±0.2V/0.4 ms, P < 0.05). In addition, the fluoroscopic duration and procedural duration were longer in the HCM group (14.8±8.3 vs 10.3±6.6min, P = 0.07; 131.8±50.5 vs 101.4±41.6 min, P < 0.05). The lead insertion depth was 15±2 mm in the HCM group, and no procedure-related complications occurred. During the 12-month follow-up, pacing parameters remained stable and were of no significance in the two groups. The cardiac function did not deteriorate, and the left ventricular outflow tract gradient (LVOTG) did not increase in the follow-up. CONCLUSION: LBBP might be feasible and safe for NOHCM patients with conventional bradycardia pacing indication, and there is no deterioration in cardiac function and LVOTG of patients with NOHCM.

[Mitral valve replacement in patients with obstructive hypertrophic cardiomyopathy]. / Protezirovanie mitral'nogo klapana u bol'nykh obstruktivnoi gipertroficheskoi kardiomiopatiei.

OBJECTIVE: To analyze the incidence and causes of mitral valve replacement in patients with obstructive hypertrophic cardiomyopathy (HCM). MATERIAL AND METHODS: There were 172 patients (98 women and 74 men) with obstructive HCM and severe mitral valve insufficiency between November 2017 and May 2023. All patients complained of chronic heart failure NYHA class III. Surgical correction of left ventricular outflow tract (LVOT) obstruction and mitral valve repair with elimination of systolic anterior motion were technically successful in 160 (93.0%) patients. RESULTS: The need for mitral valve replacement was noted in 12 (7.0%) patients. Mean cardiopulmonary bypass time was 83.5±19.2 min (94; 127), aortic cross-clamping - 62.8±14.3 min (70; 102). In 5 cases, primary mitral valve replacement was scheduled due to obvious organic lesion of the mitral valve (tearing of chords, rheumatic lesion with leaflet restriction). In 7 patients, valve replacement was forced after ineffective primary septal myectomy (LVOT pressure gradient, severe mitral insufficiency). CONCLUSION: Mitral valve replacement is an involuntary strategy after ineffective myectomy with severe mitral insufficiency and high LVOT pressure gradient.

Left ventricular outflow obstruction occurs immediately after exercise in patients with non-obstructive hypertrophic cardiomyopathy.

We evaluated the hemodynamic and geometric determinants of latent obstruction (LO, trans-left ventricular outflow tract (LVOT) gradient ≥30 mmHg with provocation) in patients with non-obstructive hypertrophic cardiomyopathy (HCMP). A total of 35 patients with non-obstructive HCMP underwent stepwise supine bicycle exercise echocardiography. Trans-LVOT pressure gradients, mitral geometric parameters, left ventricular ejection fractions (LVEF) and left ventricular end-systolic and diastolic dimensions (LVESD, LVEDD) were measured at each stage. The highest peak LVOT pressure gradient predominantly occurred immediately after exercise (n = 32, 91.3%) rather than during peak exercise (n = 3, 8.7%). Significant LO developed in nine patients (25%). No significant differences were found in resting echocardiographic parameters. Compared to the remaining patients, however, patients with LO had longer residual mitral leaflets (defined as residual portions of leaflets after coaptation; 4 ± 4 vs. 13 ± 4 mm, respectively; p = 0.001) and higher resting LVOT pressure gradients (7.4 ± 3.7 vs. 12.9 ± 5.8 mmHg, respectively; p = 0.001). Substantial decreases in mitral annular diameters from peak exercise to recovery after exercise were observed in the LO group, while mitral annular diameters increased after exercise in the non-LO group. In conclusion, the highest peak LVOT pressure gradient predominantly occurred immediately after exercise rather than during peak exercise, regardless of LO. Abrupt decrease of mitral annular diameter immediately after exercise, a longer residual mitral leaflet and a higher resting LVOT pressure gradient at rest might be related to LO.

Outcomes of hypertrophic obstructive cardiomyopathy patients undergoing alcohol septal ablation with a standard 3 mL dose of ethanol: Focus on long-term safety.

OBJECTIVES: The objective of this research was to assess the long-term results of alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy (HOCM), with all of them receiving a standard 3 mL ethanol dose. BACKGROUND: Generally, ethanol (0.5-3 mL) is infused depending on a septal artery width or interventricular septum (IVS) thickness during alcohol septal ablation. We injected 3 mL of ethanol irrespective of IVS thickness or perforator width in all cases. METHODS: Between 2000 and 2017, 150 HOCM patients (78 males, 72 females) underwent alcohol septal ablation procedures. In all cases we intentionally used the constant dose of ethanol (3 mL). The median of age was 52 (interquartile range: 41-60) years. RESULTS: The median of follow-up was 71 (interquartile range: 36-110) months. Hospital mortality was 0.67% (one patient died of sepsis). Perioperative high-grade atrioventricular blocks required permanent pacemaker implantations-18 (12%). Long-term survival rates were as follows: 95.1% (95% confidence interval [CI]: 92.7-97.5%), 85.8% (95% CI: 83.7-87.0%), and 81.7% (95% CI: 79.7-83.7%) at 5-, 10-, and 15-year follow-up, respectively. One-sample log-rank test revealed no significant differences in 15-year survival rates between the alcohol septal ablation cohort and age- and sex-matched Russian population. CONCLUSIONS: Alcohol septal ablation with the standard (3 mL) ethanol dose is safe and efficient. Survival rates after alcohol septal ablation are comparable with those in age- and sex-matched general Russian population.

Effectiveness of Bokeria-Boldyrev ACH Solution in Surgerical Treatment of Adult Patients with Obstructive Hypertrophic Cardiomyopathy.

The study examined effectiveness of pharmaco-cold cardioplegia employing solutions of enhanced buffer capacity during surgery of obstructive hypertrophic cardiomyopathy in adult patients (N=51) operated during 2013-2018. In group 1 (N=28), the cardioplegia was performed with HTK (Custodiol) solution, whereas in group 2 (N=23), it was carried out with Bokeria-Boldyrev ACH solution. The mean, minimum, and maximum ages in group 1 were 46, 21, and 64 years, respectively; in group 2 - 42, 14, and 70 years, respectively. In both groups, the patients were subjected to myoectomy of exit pathway in the left ventricle according to Bokeria-Morrow operation and annuloplasty of tricuspid valve accompanied by reconstructive surgery (or replacement) of mitral valve. Atrial fibrillation (if any) was suppressed with cryoablation (-60°Ð¡) of the openings of the right and left pulmonary veins. The surgery was carried out in hypothermic mode at 28°C. The significant intergroup differences were observed in the asystole latent period after the onset of antegrade or retrograde injection of cardioplegic solution. In group 1, the asystole latent periods determined after antegrade or retrograde injection were 53±7 or 170±30 sec, respectively; in group 2 - 32±6 and 97±11 sec (p<0.0001), respectively. The mean times of aortic cross-clumping in groups 1 and 2 were 66±8 and 64±6 min, respectively; the electromechanical action of the heart restored after aortic unclamping in 35±7 and 30±6 sec, respectively. The biochemical and clinical data revealed no significant intergroup differences. Overall, novel Bokeria-Boldyrev ACH cardioplegic solution secured effective protection of the myocardium against intraoperative ischemia in adult patients with obstructive hypertrophic cardiomyopathy and significantly decreased the asystole latent period.

[Alcohol septal ablation for obstructive hypertrophic cardiomopathy]. / Alcoolisation septale dans la cardiomyopathie hypertrophique obstructive.

Alcohol septal ablation has become an attractive alternative to surgical myomectomy in symptomatic patients with obstructive hypertrophic cardiomyopathy. Its purpose is to achieve a therapeutic infarction in the sub-aortic territory responsible of the obstruction. It is indicated in symptomatic patients resistant to optimal medical treatment and having a left intraventricular gradient equal or higher than 50 mmHg, spontaneous or with exercise. The selection of candidates must be rigorous and the procedure must be performed in an experienced center, associating interventionalists and echocardiographists. Alcohol septal ablation is preferred in cases of favourable coronary anatomy, sub-aortic obstruction and absence of associated mitral valve defect. The septal alcohol technique is fast, effective and safe. The per-procedural contrast echocardiography helps identifying whether the myocardial segment is vascularized by the septal branch to be occluded. The benefits of alcohol septal ablation are comparable to those seen with surgical myectomy in terms of functional class, exercise capacity, and gradient regression. The morbidity and mortality observed in the short and mid terms are globally equivalent to that of the surgical intervention. The major complication is dominated by the occurrence of complete atrioventricular block requiring the implantation of a definitive pacemaker, a complication in sharp decline since the contrast ultrasound-guided technique has become widespread.

L'alcoolisation du septum par voie percutanée est devenue une alternative séduisante à l'intervention de myomectomie chirurgicale chez les patients symptomatiques porteurs d'une cardiomyopathie hypertrophique obstructive. Son but est de réaliser un infarctus thérapeutique dans le territoire septal basal responsable de l'obstruction. Elle est indiquée chez les patients symptomatiques, résistant au traitement médical optimal et présentant un gradient intraventriculaire gauche égal ou supérieur à 50 mmHg, spontané ou à l'effort. La sélection des candidats doit être rigoureuse et la procédure doit être confiée à un centre expérimenté, associant cardiologues interventionnels et échocardiographistes. L'alcoolisation septale est à privilégier en cas d'obstruction sous-aortique avec anatomie coronaire favorable et absence d'anomalie associée de l'appareil sous-valvulaire mitral. La technique d'alcoolisation septale est rapide, efficace et sûre. L'échocardiographie de contraste per-procédure permet aisément de repérer la branche septale à alcooliser. Les bénéfices de cette technique sont comparables à ceux observés avec la myectomie chirurgicale en termes de classe fonctionnelle, de capacité à l'effort et de régression du gradient. La morbi-mortalité observée, à court et moyen termes, est globalement équivalente à celle de l'intervention chirurgicale. La complication majeure est dominée par la survenue d'un bloc auriculo-ventriculaire complet nécessitant l'implantation d'un pacemaker définitif, complication en net recul depuis que la technique échoguidée s'est généralisée.

[Surgical treatment of patients with obstructive hypertrophic cardiomyopathy]. / Khirurgicheskie i anesteziologicheskie aspekty lecheniia bol'nykh s gipertroficheskoi kardiomiopatiei.

OBJECTIVE: To analyze in-hospital results of surgical treatment of patients with obstructive hypertrophic cardiomyopathy. MATERIAL AND METHODS: There were 15 patients (8 women and 6 men) with obstructive hypertrophic cardiomyopathy and severe mitral insufficiency for the period from November 2017 to March 2019. Mean age of patients was 55.9±7.1 years. All patients had chronic heart failure NYHA class III and secondary coronary insufficiency. RESULTS: Surgical correction of LVOT obstruction and mitral valve repair with elimination of systolic anterior motion were technically successful in all cases. There was no need for mitral valve replacement in all patients. Heart failure NYHA class I-II in early postoperative period was observed in all cases. CONCLUSION: Careful preoperative planning with a comprehensive analysis of hemodynamic and anatomical features of LV and certain surgical experience are essential for adequate correction of LVOT obstruction without atrioventricular node injury and mitral valve repair.

[Atrial fibrillation in patients with obstructive hypertrophic cardiomyopathy: clinical characteristics and risk factors].

Objective: To evaluate the clinical characteristics and risk factors for atrial fibrillation(AF)in patients with obstructive hypertrophic cardiomyopathy(OHCM). Methods: Patients with OHCM hospitalized in Fuwai Hospital from March 2011 to January 2016 were enrolled in the present study. Each patient underwent examinations including transthoracic echocardiography, body surface electrocardiograph or dynamic electrocardiogram (Holter). Cardiac troponin I (cTNI) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP)levels were tested and clinical profiles were collected.The subjects were divided into two groups (the AF group and non-AF group). Risk factors for AF in patients with OHCM were assessed by multivariate logistic regression analysis. Results: A total of 309 patients were evaluated in the study. Among them, 17.5%( 54/309) patients were with AF.Age[(51.2±10.1)years vs (43.1 ± 14.4)years], New York Heart Association class(NYHA class)(2.8±0.5 vs 2.6±0.6), disease duration[6.0(4.0, 10.0)years vs 3.0(1.0, 6.0)years], left atrial (LA) dimension[(45.1±7.0)mm vs(42.6 ± 7.4)mm]and NT-pro-BNP levels[2 007(1 565, 3 199)pmol/L vs 1 509(729, 2 921)pmol/L]in the AF group were significantly higher than those in the non-AF group (all P<0.05). Multivariate logistic regression analysis indicated that advanced age(OR=1.04, 95% CI 1.01-1.08, P<0.01), higher NYHA class(OR=2.00, 95% CI 1.08-3.70, P<0.05)and longer disease duration(OR=1.08, 95% CI 1.01-1.15, P<0.05)were independent risk factors for AF in patients with OHCM, in which advanced age(OR=1.05, 95% CI 1.02-1.09, P<0.01), higher NYHA class(OR=3.39, 95% CI 1.53-7.54, P<0.01), LA dimension(OR=1.06, 95% CI 1.01-1.12, P<0.05)and longer clinical course(OR=1.12, 95% CI 1.04-1.20, P<0.01)were associated with AF in male patients, and advanced age (OR=1.05, 95% CI 1.01-1.09, P<0.05)and longer disease duration(OR=1.14, 95% CI 1.01-1.28, P<0.01)were associated with AF in female patients when stratified by gender. Conclusion: Advanced age , higher NYHA class and longer clinical duration are independent risk factors for AF in OHCM patients.

Evaluation of left ventricular diastolic function by global strain rate imaging in patients with obstructive hypertrophic cardiomyopathy: a simultaneous speckle tracking echocardiography and cardiac catheterization study.

BACKGROUND: Impaired left ventricular (LV) diastolic function is a common pathophysiological feature of patients with hypertrophic cardiomyopathy (HCM). The noninvasive evaluation of diastolic function in these patients remains a challenge. Speckle tracking echocardiography (STE) provides direct information on intrinsic myocardial function and may improve the diagnostic of diastolic dysfunction in HCM patients. METHODS AND RESULTS: We retrospectively analyzed 51 patients with obstructive HCM (HOCM). Strain rate (SR) curves were obtained for 18 different segments of the LV myocardium. The peak SR during the isovolumic relaxation period (SRIVR ) and the peak early diastolic strain rate (SRE ) were measured for each segment. Cardiac catheterization was performed within 24 hours after echocardiographic analysis. LV end-diastolic pressure (LVEDP) was measured and time constant of myocardial relaxation (τ) was calculated. We therefore correlated STE-derived with invasive indices and compared it with flow and tissue Doppler measurements. SRIVR and SRE were significantly reduced in all 51 HOCM patients (0.16 ± 0.09%/sec and 0.71 ± 0.25%/sec).The ratio of peak early mitral inflow velocities to SRIVR and SRE (E/SRIVR and E/SRE ) correlated well with LVEDP (r = 0.760, P < 0.001; r = 0.401, P = 0.004). Receiver operating characteristic analysis shown E/SRE ratio had the largest under curve area in predicting HOCM patients with seriously elevated LVEDP. In addition, SRIVR and SRE significantly related with τ (r = -0.611, P < 0.001; r = -0.369, P = 0.008). CONCLUSIONS: Diastolic function was seriously impaired in HOCM patients. The E/SRE ratio can be used to predict LVEDP with acceptable accurate in HOCM patients. In addition, SRIVR is a reliable parameter to assess LV relaxation in patients with HOCM.

A systematic review of present and future pharmaco-structural therapies for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM.

Exercise Capacity in Patients With Obstructive Hypertrophic Cardiomyopathy: SEQUOIA-HCM Baseline Characteristics and Study Design.

Patients with obstructive hypertrophic cardiomyopathy (oHCM) have increased risk of arrhythmia, stroke, heart failure, and sudden death. Contemporary management of oHCM has decreased annual hospitalization and mortality rates, yet patients have worsening health-related quality of life due to impaired exercise capacity and persistent residual symptoms. Here we consider the design of clinical trials evaluating potential oHCM therapies in the context of SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). This large, phase 3 trial is now fully enrolled (N = 282). Baseline characteristics reflect an ethnically diverse population with characteristics typical of patients encountered clinically with substantial functional and symptom burden. The study will assess the effect of aficamten vs placebo, in addition to standard-of-care medications, on functional capacity and symptoms over 24 weeks. Future clinical trials could model the approach in SEQUOIA-HCM to evaluate the effect of potential therapies on the burden of oHCM. (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM [SEQUOIA-HCM]; NCT05186818).

Mavacamten in real-life practice: Initial experience at a hypertrophic cardiomyopathy centre.

AIMS: In clinical trials, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved symptoms in patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). We aimed to share our real-world experience with the efficacy and safety of mavacamten in this patient population. METHODS AND RESULTS: This retrospective, single-centre study included patients with symptomatic oHCM from March 2023 to November 2023. Inclusion criteria were oHCM, age >18 years, significant LVOTO (gradient >50 mmHg at rest or with Valsalva), New York Heart Association (NYHA) class ≥II despite maximally tolerated medical therapy, and left ventricular ejection fraction (LVEF) >55%. Patients were evaluated by echocardiography, NYHA class, electrocardiography and Holter monitor on each monthly visit for 3 months. A total of 31 patients were included in this study. The mean (SD) age was 58 (16.5) years, and 14 (45%) were female. Mean provoked left ventricular outflow tract gradient (LVOTG) reduced by -49.4 mmHg (P < 0.001) at 4 weeks, -59.2 mmHg (P < 0.001) at 8 weeks, and -60.8 mmHg (P < 0.001) at 12 weeks. Twenty-six of the 31 patients (83.8%) achieved an LVOTG ≤30 mmHg at Week 12. No major side effects were reported. Sixty-seven percent experienced ≥2 NYHA class improvements, LVEF remained above 55% and no dose titration was made. CONCLUSIONS: Our real-world experience aligns with established mavacamten trial outcomes. Continuous vigilance and longitudinal investigations are needed to further assess potential long-term impacts.

Radiofrequency ablation in obstructive hypertrophic cardiomyopathy: a case report.

Background: We report endocardial radiofrequency (RF) ablation as an alternative treatment approach for a symptomatic patient with obstructive hypertrophic cardiomyopathy (oHCM), who is not suitable for surgical septal myectomy or alcohol septal ablation. Endocardial RF ablation, with detailed 3D mapping of the intrinsic conducting system, offers the possibility of reducing the risk of complete heart block rates and of effectively relieving symptoms. Case summary: We present a symptomatic 51-year-old female patient with oHCM and a maximum left ventricular outflow tract (LVOT) gradient of 148 mmHg. Because of alcohol septal ablation failure, endocardial RF ablation in combination with detailed mapping of the intrinsic conduction system and intraprocedural imaging was performed. The 6-month follow-up showed a significant improvement in exercise tolerance, no relevant dynamic LVOT obstruction with a gradient of 22 mmHg under Valsalva. Discussion: In the current case report, endocardial RF ablation persistently reduced LVOT gradients in a patient with oHCM. Pre-interventional imaging, detailed 3D mapping of the conduction system, and correlation to intracardiac and transthoracic echocardiography were key for an effective and safe ablation of a small target zone.

LA-to-LV Valved Conduit for Relief of Mitral Stenosis in Patients With HCM and Severe MAC.

A left atrium-to-left ventricle valved conduit is an alternative to conventional mitral valve (MV) replacement in patients with MV stenosis associated with a heavily calcified annulus. We describe a series of 6 patients with hypertrophic cardiomyopathy who received a valved conduit to bypass a stenotic MV, with or without concomitant septal myectomy.