2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.

2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy" provides recommendations to guide clinicians in the management of patients with hypertrophic cardiomyopathy. METHODS: A comprehensive literature search was conducted from September 14, 2022, to November 22, 2022, encompassing studies, reviews, and other evidence on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through May 23, 2023, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. STRUCTURE: Hypertrophic cardiomyopathy remains a common genetic heart disease reported in populations globally. Recommendations from the "2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy" have been updated with new evidence to guide clinicians.

Treatment Strategies for Hypertrophic Cardiomyopathy: Alcohol Septal Ablation and Procedural Step-by-Step Technique.

Alcohol septal ablation (ASA) is a well-established procedure for septal reduction therapy in patients with obstructive hypertrophic cardiomyopathy, significant at rest or provocable outflow tract gradients, and medically refractory symptoms. This percutaneous approach to relief of obstruction and eventual cardiac remodeling involves the infusion of a small quantity of ethanol into an appropriately targeted septal artery that is feeding the basal septum to create an iatrogenic and controlled focal infarction. Early akinesia is followed by subsequent thinning and remodeling, which widens the outflow tract, reducing or eliminating the obstruction. Historically, the use of ASA was reserved primarily for high-risk surgical candidates; however, more contemporary data suggest similar outcomes in the short-term and long-term safety of the procedure and overall effectiveness in relieving obstructive symptoms when it is performed in broader populations at experienced centers. Therefore, the current guidelines published in 2020 support ASA as a class 1 indication, similar to its open-heart surgical counterpart, surgical myectomy, when no concomitant significant coronary or valve surgical indication exists. This article summarizes contemporary management of patients with hypertrophic cardiomyopathy who were selected for ASA and details procedural methods and outcomes.

Treatment of Acute Myocardial Infarction and Cardiogenic Shock: Outcomes of the RECOVER III Postapproval Study by Society of Cardiovascular Angiography and Interventions Shock Stage.

BACKGROUND: The Society for Cardiovascular Angiography and Interventions proposed a staging system (A-E) to predict prognosis in cardiogenic shock. Herein, we report clinical outcomes of the RECOVER III study for the first time, according to Society for Cardiovascular Angiography and Interventions shock classification. METHODS AND RESULTS: The RECOVER III study is an observational, prospective, multicenter, single-arm, postapproval study of patients with acute myocardial infarction with cardiogenic shock undergoing percutaneous coronary intervention with Impella support. Patients enrolled in the RECOVER III study were assigned a baseline Society for Cardiovascular Angiography and Interventions shock stage. Staging was then repeated within 24 hours after initiation of Impella. Kaplan-Meier survival curve analyses were conducted to assess survival across Society for Cardiovascular Angiography and Interventions shock stages at both time points. At baseline assessment, 16.5%, 11.4%, and 72.2% were classified as stage C, D, and E, respectively. At ≤24-hour assessment, 26.4%, 33.2%, and 40.0% were classified as stage C, D, and E, respectively. Thirty-day survival among patients with stage C, D, and E shock at baseline was 59.7%, 56.5%, and 42.9%, respectively (P=0.003). Survival among patients with stage C, D, and E shock at ≤24 hours was 65.7%, 52.1%, and 29.5%, respectively (P<0.001). After multivariable analysis of impact of shock stage classifications at baseline and ≤24 hours, only stage E classification at ≤24 hours was a significant predictor of mortality (odds ratio, 4.8; P<0.001). CONCLUSIONS: In a real-world cohort of patients with acute myocardial infarction with cardiogenic shock undergoing percutaneous coronary intervention with Impella support, only stage E classification at ≤24 hours was significantly predictive of mortality, suggesting that response to therapy may be more important than clinical severity of shock at presentation.

Outcomes in non-ST-segment elevation myocardial infarction complicated by in-hospital cardiac arrest based on management strategy.

BACKGROUND: There are limited data on in-hospital cardiac arrest (IHCA) complicating non-ST-segment-elevation myocardial infarction (NSTEMI) based on management strategy. METHODS: We used National Inpatient Sample (2000-2017) to identify adults with NSTEMI (not undergoing coronary artery bypass grafting) and concomitant IHCA. The cohort was stratified based on use of early (hospital day 0) or delayed (≥hospital day 1) coronary angiography (CAG), percutaneous coronary intervention (PCI), and medical management. Outcomes included incidence of IHCA, in-hospital mortality, adverse events, length of stay, and hospitalization costs. RESULTS: Of 6,583,662 NSTEMI admissions, 375,873 (5.7 %) underwent early CAG, 1,133,143 (17.2 %) received delayed CAG, 2,326,391 (35.3 %) underwent PCI, and 2,748,255 (41.7 %) admissions were managed medically. The medical management cohort was older, predominantly female, and with higher comorbidities. Overall, 63,085 (1.0 %) admissions had IHCA, and incidence of IHCA was highest in the medical management group (1.4 % vs 1.1 % vs 0.7 % vs 0.6 %, p < 0.001) compared to early CAG, delayed CAG and PCI groups, respectively. In adjusted analysis, early CAG (adjusted OR [aOR] 0.67 [95 % confidence interval {CI} 0.65-0.69]; p < 0.001), delayed CAG (aOR 0.49 [95 % CI 0.48-0.50]; p < 0.001), and PCI (aOR 0.42 [95 % CI 0.41-0.43]; p < 0.001) were associated with lower incidence of IHCA compared to medical management. Compared to medical management, early CAG (adjusted OR 0.53, CI: 0.49-0.58), delayed CAG (adjusted OR 0.34, CI: 0.32-0.36) and PCI (adjusted OR 0.19, CI: 0.18-0.20) were associated with lower in-hospital mortality (all p < 0.001). CONCLUSION: Early CAG and PCI in NSTEMI was associated with lower incidence of IHCA and lower mortality among NSTEMI-IHCA admissions.

Ultrasound Guidance for Vascular Access for Coronary Angiogram: A Meta-Analysis of Randomized Controlled Trials.

Obtaining vascular access during percutaneous coronary intervention is necessary to facilitate the procedure but carries procedural risks that impact patient outcomes. Historically, vascular access has been accomplished using anatomic landmarks, pulsation, and/or fluoroscopic guidance. Ultrasound (US) guidance has emerged as a modality for achieving vascular access in a multitude of interventional procedures including those in the cardiac catheterization laboratory. US use has been demonstrated in randomized controlled trials and meta-analyses to be associated with an increased success rate for vascular access with fewer complications, although the data are mixed. We aimed to re-evaluate the totality of evidence in an updated meta-analysis to compare the ease of access and complications rates between US-guided and manual vascular access. A meta-analysis of 8 randomized controlled trials including 5,170 patients was performed. The primary outcome evaluated was the rate of access failure, and the secondary outcomes included hematomas and access site bleeding. US-guided arterial access was associated with a significantly higher rate of first-attempt success and a decreased risk of venipuncture. US use had a trend toward a lower total number of attempts, but the results were not significant. This updated meta-analysis further supports the use of US for vascular access for coronary angiography because of higher rates of first-attempt success and reduced venipuncture. However, there was no significant difference in vascular complications such as hematoma, pseudoaneurysm, and bleeding complications. Because of the high morbidity of bleeding complications associated with coronary angiography, further research should be done to reduce these complications.

Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 56 Results From the VALOR-HCM Randomized Clinical Trial.

Importance: There is an unmet need for novel medical therapies before recommending invasive therapies for patients with severely symptomatic obstructive hypertrophic cardiomyopathy (HCM). Mavacamten has been shown to improve left ventricular outflow tract (LVOT) gradient and symptoms and may thus reduce the short-term need for septal reduction therapy (SRT). Objective: To examine the cumulative longer-term effect of mavacamten on the need for SRT through week 56. Design, Setting, and Participants: This was a double-blind, placebo-controlled, multicenter, randomized clinical trial with placebo crossover at 16 weeks, conducted from July 2020 to November 2022. Participants were recruited from 19 US HCM centers. Included in the trial were patients with obstructive HCM (New York Heart Association class III/IV) referred for SRT. Study data were analyzed April to August 2023. Interventions: Patients initially assigned to mavacamten at baseline continued the drug for 56 weeks, and patients taking placebo crossed over to mavacamten from week 16 to week 56 (40-week exposure). Dose titrations were performed using echocardiographic LVOT gradient and LV ejection fraction (LVEF) measurements. Main Outcome and Measure: Proportion of patients undergoing SRT, remaining guideline eligible or unevaluable SRT status at week 56. Results: Of 112 patients with highly symptomatic obstructive HCM, 108 (mean [SD] age, 60.3 [12.5] years; 54 male [50.0%]) qualified for the week 56 evaluation. At week 56, 5 of 56 patients (8.9%) in the original mavacamten group (3 underwent SRT, 1 was SRT eligible, and 1 was not SRT evaluable) and 10 of 52 patients (19.2%) in the placebo crossover group (3 underwent SRT, 4 were SRT eligible, and 3 were not SRT evaluable) met the composite end point. A total of 96 of 108 patients (89%) continued mavacamten long term. Between the mavacamten and placebo-to-mavacamten groups, respectively, after 56 weeks, there was a sustained reduction in resting (mean difference, -34.0 mm Hg; 95% CI, -43.5 to -24.5 mm Hg and -33.2 mm Hg; 95% CI, -41.9 to -24.5 mm Hg) and Valsalva (mean difference, -45.6 mm Hg; 95% CI, -56.5 to -34.6 mm Hg and -54.6 mm Hg; 95% CI, -66.0 to -43.3 mm Hg) LVOT gradients. Similarly, there was an improvement in NYHA class of 1 or higher in 51 of 55 patients (93%) in the original mavacamten group and in 37 of 51 patients (73%) in the placebo crossover group. Overall, 12 of 108 patients (11.1%; 95% CI, 5.87%-18.60%), which represents 7 of 56 patients (12.5%) in the original mavacamten group and 5 of 52 patients (9.6%) in the placebo crossover group, had an LVEF less than 50% (2 with LVEF ≤30%, one of whom died), and 9 of 12 patients (75%) continued treatment. Conclusions and Relevance: Results of this randomized clinical trial showed that in patients with symptomatic obstructive HCM, mavacamten reduced the need for SRT at week 56, with sustained improvements in LVOT gradients and symptoms. Although this represents a useful therapeutic option, given the potential risk of LV systolic dysfunction, there is a continued need for close monitoring. Trial Registration: ClinicalTrials.gov Identifier: NCT04349072.

Pulmonary Artery Catheter Use and Outcomes in Patients With ST-Elevation Myocardial Infarction and Cardiogenic Shock Treated With Impella (a Nationwide Analysis from the United States).

The role of continuous hemodynamic assessment with pulmonary artery (PA) catheter placement in cardiogenic shock (CS) remains debated. We aimed to assess the association between PA catheter placement and clinical outcomes in patients with CS secondary to ST-elevation myocardial infarction (STEMI) treated with an intravascular microaxial flow pump. We identified patients hospitalized with STEMI complicated by CS on mechanical circulatory support with an intravascular microaxial flow pump (Impella, Abiomed, Danvers, Massachusetts) using the National Inpatient Sample database and compared the outcomes in those treated with and without PA catheters. The primary outcome was in-hospital mortality. The secondary outcomes included in-hospital complications, hospital length of stay, inpatient costs, and temporal trends. The total cohort included 14,635 hospitalizations for STEMI complicated by CS treated with Impella between 2016 and 2020, of whom 5,505 (37.6%) received PA catheters. Over the study period, the use of PA catheters increased significantly from 25.9% to 41.8% (ptrend <0.01). Similarly, the use of Impella increased from 9.9% to 18.9% (ptrend <0.01). After adjustment for baseline characteristics using a multivariate logistic regression analysis, PA catheter use was associated with lower in-hospital mortality (adjusted odds ratio 0.80, 95% confidence interval 0.67 to 0.96, p = 0.01) and similar cardiovascular, neurologic, renal, and hematologic complications; length of stay; and inpatient costs compared with no PA catheter use. In conclusion, PA catheter use in patients with STEMI complicated by CS treated with Impella is associated with reduced in-hospital mortality and similar complication rates. Given the mortality benefit, further research is necessary to optimize PA catheter use in patients with STEMI with CS.

Frequency and clinicoeconomic impact of delays to definitive diagnosis of obstructive hypertrophic cardiomyopathy in the United States.

AIMS: The diagnostic history in the years leading up to the definitive diagnosis of patients with obstructive hypertrophic cardiomyopathy (HCM) has not been studied. METHODS: Patients with a delay in the definitive diagnosis of obstructive HCM from January 2009 to March 2019 were identified in the US IBM MarketScan Commercial and Medicare Supplemental Databases if they had an alternative diagnosis indicating a misdiagnosis during the 24 months before the definitive obstructive HCM diagnosis. Resource use and costs associated with the delay were estimated during the same period. RESULTS: Of 3,888 eligible patients with obstructive HCM, 59.5% had a delay in definitive diagnosis. Patients received a mean of 4.0 misdiagnoses before the definitive obstructive HCM diagnosis, most of which were other cardiovascular conditions. Consequently, 15.7% of patients may have received inappropriate treatment. Approximately 78.4% of patients visited a cardiologist (mean 4.7 visits) before the definitive obstructive HCM diagnosis. Additionally, 26.8% and 32.1% of patients had an inpatient and emergency room visit, respectively. Annualized healthcare costs associated with the delay were $4,379 per patient. LIMITATIONS: The current study used administrative claims data for a commercially insured population. Therefore, the results may not be generalizable to other populations (e.g. those insured by Medicare or Medicaid and the uninsured). Like other database studies, the current study may have suffered from miscoding or undercoding, which may have caused misclassification of patients. Owing to insufficient data, the study could not evaluate all potential consequences of a delay in definitive diagnosis. CONCLUSIONS: Most patients with obstructive HCM had a delay of ≤ 2 years before receiving the definitive diagnosis. The diagnostic journey involved multiple potential misdiagnoses, predominantly cardiovascular, as well as a substantial clinical and economic burden on patients and the healthcare system.

Exercise and cardiovascular health: A state-of-the-art review.

Cardiovascular (CV) disease (CVD) is the leading cause of global morbidity and mortality, and low levels of physical activity (PA) is a leading independent predictor of poor CV health and associated with an increased prevalence of risk factors that predispose to CVD development. In this review, we evaluate the benefits of exercise on CV health. We discuss the CV adaptations to exercise, focusing on the physiological changes in the heart and vasculature. We review the impact and benefits of exercise on specific CV prevention, including type II diabetes, hypertension, hyperlipidemia, coronary artery disease, and heart failure, in addition to CVD-related and all-cause mortality. Lastly, we evaluate the current PA guidelines and various modes of exercise, assessing the current literature for the effective regimens of PA that improve CVD outcomes.

Contemporary Diagnosis and Management of Patients with MINOCA.

PURPOSE OF REVIEW: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is defined as acute myocardial infarction (MI) with angiographically no obstructive coronary artery disease or stenosis ≤ 50%. MINOCA is diagnostically challenging and complex, making it difficult to manage effectively. This condition accounts for 6-8% of all MI and poses an increased risk of morbidity and mortality after diagnosis. Prompt recognition and targeted management are essential to improve outcomes and our understanding of this condition, but this process is not yet standardized. This article offers a comprehensive review of MINOCA, delving deep into its unique clinical profile, invasive and noninvasive diagnostic strategies for evaluating MINOCA in light of the lack of widespread availability for comprehensive testing, and current evidence surrounding targeted therapies for patients with MINOCA. RECENT FINDINGS: MINOCA is not uncommon and requires comprehensive assessment using various imaging modalities to evaluate it further. MINOCA is a heterogenous working diagnosis that requires thoughtful approach to diagnose the underlying disease responsible for MINOCA further.

Clinical Outcomes, Resource Utilization, and Treatment Over the Disease Course of Symptomatic Obstructive Hypertrophic Cardiomyopathy in the United States.

We sought to describe the clinical outcomes, resource utilization, and treatment options for patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) over the course of their disease. Adults with obstructive HCM who were symptomatic were identified from the IBM MarketScan Commercial and Medicare supplemental database (January 2009 to March 2019). The index date was the initial obstructive HCM diagnosis date. Patients were required to have ≥12-month continuous eligibility before and after the index date. Incidence rates (IRs) and cumulative risk of cardiovascular events, healthcare resource utilization, and pharmacotherapy were assessed after index and compared with matched controls. Among 4,617 eligible patients with obstructive HCM, 2,917 (63.2%, mean age 60, 47.2% women) were symptomatic at index date. The most common cardiovascular events were atrial fibrillation/flutter (IR:1.421 per person-year [PPY], heart failure (IR: 0.895 PPY), and dyspnea (IR:0.797 PPY). Patients incurred higher resource use with frequent tests and monitoring, hospitalizations (0.454 PPY), and emergency room visits (0.611 PPY). The use of pharmacotherapy increased from 61.2% in the 6-month preindex period to 83.9% in the 6-month postindex period and remained stable after diagnosis. These events ranged from 3 to over 60-fold higher compared with controls, with the largest difference observed in arrhythmic events. The majority of patients were symptomatic at the time of obstructive HCM diagnosis, resulting in significantly increased cardiovascular complications and frequent disease monitoring after diagnosis versus controls. In conclusion, healthcare resource utilization was substantial, and these findings suggest a higher clinical and economic burden over the disease course among patients with symptomatic obstructive HCM, despite current treatment.

Multi-modality management of hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited condition defined by left ventricular wall thickness greater than 15 mm in the absence of other conditions that could explain that degree of hypertrophy. Obstructive HCM associated with left ventricular outflow tract obstruction is defined by an intraventricular systolic pressure gradient greater than or equal to 30 mm Hg. Over the past couple of decades, there has been an expansion of both invasive and pharmacotherapeutic options for patients with HCM, with recent guidelines calling for a melody of invasive and non-invasive treatment strategies. There are several invasive therapies including proven therapies such as alcohol septal ablation and septal myectomy. Novel invasive therapies such as MitraClip, radiofrequency septal ablation and SESAME procedure have more recently been promoted. Pharmacological therapy has also dramatically evolved and includes conventional medications such as beta-blockers, calcium channel blockers, and disopyramide. Mavacamten, a novel cardiac myosin inhibitor, may significantly change management. Other myosin inhibitors and modulators are also being developed and tested in large clinical trials. Given significant phenotypical variability in patients with HCM, clinical management can be challenging, and often requires an individualized approach with a combination of invasive and non-invasive options.

The Effect of Yoga on Cardiovascular Disease Risk Factors: A Meta-Analysis.

Yoga has been increasingly popular yet has shown inconsistent benefits on cardiovascular disease (CVD) risk factors. We aimed to systematically analyze the effect of yoga on modifiable CVD risk factors. We systematically searched Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception in 1966 through June 2022 for studies evaluating the association between yoga and blood pressure, lipid profile, HbA1c and body mass index (BMI). Two investigators independently reviewed data. Conflicts were resolved through consensus. Random-effects meta-analyses were used. 64 RCTs including a total of 16,797 participants were eligible for inclusion in the meta-analysis. Yoga therapy improved both systolic as well as diastolic blood pressure (weight mean difference [WMD] (95% Confidence interval [CI]) of -4.56 [-6.37, -2.75] mm Hg, WMD [95% CI] - 3.39 [-5.01, -1.76] mm Hg respectively). There was also an improvement in BMI as well as hemoglobin A1c (HbA1c) (WMD [95% CI] of -0.57 [-1.05, -0.10] kg/m2, WMD [95% CI] of -0.14 [-0.24, -0.030] mmol/L respectively) . In addition, all parameters of the lipid profile, including low-density lipoprotein cholesterol (LDL-C) showed a significant improvement with yoga therapy (WMD [95% CI] -7.59 [-12.23, -2.95] mg/dL for LDL-C). Yoga has a modest yet positive effect on blood pressure, BMI, lipid profile and HbA1c and, therefore, may play an ancillary role in primary prevention of CVD.

Meta-analysis Comparing the Efficacy of Dobutamine Versus Milrinone in Acute Decompensated Heart Failure and Cardiogenic Shock.

This study aims to evaluate the difference between dobutamine and milrinone in patients presenting with acute decompensated heart failure (AHF). Inotropes are indicated for treating AHF, especially in patients with concomitant hypoperfusion indicative of cardiogenic shock. However, previous studies have not identified the optimal inotrope. We sought to compare outcomes associated with milrinone versus dobutamine in patients with AHF. A systematic literature search was performed to identify relevant trials from inception to August 2021. Our primary outcome of interest was mortality. Analysis was sub-categorized according to subpopulation, including AHF, AHF with cardiogenic shock (AHF-shock), AHF with a bridge to transplantation, and AHF with destination therapy. Summary effects were calculated using a fixed-effects model as risk ratio or mean difference with 95% confidence intervals for all the clinical endpoints. Ten studies, including one randomized controlled trial with 21,106 patients, were included in the analysis (4918 patients were in the Milrinone group, while 15188 were in the Dobutamine group). Milrinone was associated with a lower risk of mortality in patients with AHF (relative risk 0.87; confidence interval :0.79-0.97; P < 0.05, heterogeneity I²â€¯= 0%) with event rates of 9.4% vs 9.8% (number needed to treat of 250). Milrinone was also associated with improved mortality with relative risk 0.76 (0.79-0.95; P < 0.05) in patients with AHF with destination therapy. There was a non-significant trend towards improved mortality in AHF-shock patients. However, AHF with a bridge to transplantation patients had a non-significant trend towards improved mortality with dobutamine. There was no difference between the 2 strategies for the outcomes of acute kidney injury, initiation of renal replacement therapy, mechanical ventilation, arrhythmias, symptomatic hypotension, and length of hospital stay in the overall population. Intensive care unit length of hospital stay was lower in AHF-shock patients in the milrinone group, whereas dobutamine was associated with a lower length of intensive care unit stay in AHF patients. The cumulative data comparing milrinone with dobutamine indicate an overall marginal benefit of milrinone compared to dobutamine in the totality of patients with AFH with or without cardiogenic shock, and whether or not they are bridged to transplantation or destination assist device. More appropriately powered prospective studies are needed to identify a conclusive benefit of one inotrope over another.

Dose-Blinded Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy: Outcomes Through 32 Weeks.

BACKGROUND: Septal reduction therapy (SRT) in patients with intractable symptoms from obstructive hypertrophic cardiomyopathy (oHCM) is associated with variable morbidity and mortality. The VALOR-HCM trial (A Study to Evaluate Mavacamten in Adults with Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy) examined the effect of mavacamten on the need for SRT through week 32 in oHCM. METHODS: A double-blind randomized placebo-controlled multicenter trial at 19 US sites included patients with oHCM on maximal tolerated medical therapy referred for SRT with left ventricular outflow tract gradient ≥50 mm Hg at rest or provocation (enrollment, July 2020-October 2021). The group initially randomized to mavacamten continued the drug for 32 weeks, and the placebo group crossed over to dose-blinded mavacamten from week 16 to week 32. Dose titrations were based on investigator-blinded echocardiographic assessment of left ventricular outflow tract gradient and left ventricular ejection fraction. The principal end point was the proportion of patients proceeding with SRT or remaining guideline eligible at 32 weeks in both treatment groups. RESULTS: From the 112 randomized patients with oHCM, 108 (mean age, 60.3 years; 50% men; 94% in New York Heart Association class III/IV) qualified for week 32 evaluation (56 in the original mavacamten group and 52 in the placebo cross-over group). After 32 weeks, 6 of 56 patients (10.7%) in the original mavacamten group and 7 of 52 patients (13.5%) in the placebo cross-over group met SRT guideline criteria or elected to undergo SRT. After 32 weeks, a sustained reduction in resting left ventricular outflow tract gradient (-33.0 mm Hg [95% CI, -41.1 to -24.9]) and Valsalva left ventricular outflow tract gradient (-43.0 mm Hg [95% CI, -52.1 to -33.9]) was observed in the original mavacamten group. A similar reduction in resting (-33.7 mm Hg [95% CI, -42.2 to -25.2]) and Valsalva (-52.9 mm Hg [95% CI, -63.2 to -42.6]) gradients was quantified in the cross-over group after 16 weeks of mavacamten. After 32 weeks, improvement by ≥1 New York Heart Association class was observed in 48 of 53 patients (90.6%) in the original mavacamten group and 35 of 50 patients (70%) after 16 weeks in the cross-over group. CONCLUSIONS: In severely symptomatic patients with oHCM, 32 weeks of mavacamten treatment showed sustained reduction in the proportion proceeding to SRT or remaining guideline eligible, with similar effects observed in patients who crossed over from placebo after 16 weeks. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04349072.