Left Ventricular Outflow Tract Gradient Research Articles

Prediction of new-onset atrial fibrillation in patients with hypertrophic cardiomyopathy using machine learning.

Atrial fibrillation (AF) is the most common sustained arrhythmia among patients with hypertrophic cardiomyopathy (HCM), leading to increased symptom burden and risk of thromboembolism. The HCM-AF score was developed to predict new-onset AF in patients with HCM, though sensitivity and specificity of this conventional tool are limited. Thus, there is a need for more accurate tools to predict new-onset AF in HCM. The objective of the present study was to develop a better model to predict new-onset AF in patients with HCM using machine learning (ML). In this prospective, multicentre cohort study, we enrolled 1069 patients with HCM without a prior history of AF. We built a ML model (logistic regression with Lasso regularization) using clinical variables. We developed the ML model using the cohort from one institution (training set) and applied it to an independent cohort from a separate institution (test set). We used the HCM-AF score as a reference model. We compared the area under the receiver-operating characteristic curve (AUC) between the ML model and the reference model using the DeLong's test. Median follow-up time was 2.1 years, with 128 (12%) patients developing new-onset AF. Using the ML model developed in the training set to predict new-onset AF, the AUC in the test set was 0.84 (95% confidence interval [CI] 0.77-0.91). The ML model outperformed the reference model (AUC 0.64; 95% CI 0.54-0.73; DeLong's p < 0.001). The ML model had higher sensitivity (0.82; 95% CI 0.65-0.93) than that of the reference model (0.67; 95% CI 0.52-0.88). The ML model also had higher specificity (0.76; 95% CI 0.71-0.81) than that of the reference model (0.57; 95% CI 0.41-0.70). Among the most important clinical variables included in the ML-based model were left atrial volume and diameter, left ventricular outflow tract gradient with exercise stress and at rest, late gadolinium enhancement on cardiac magnetic resonance imaging, peak heart rate during exercise stress, age at diagnosis, positive genotype, diabetes mellitus, and end-stage renal disease. Our ML model showed superior performance compared to the conventional HCM-AF score for the prediction of new-onset AF in patients with HCM.

The Diagnosis and Treatment of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) with or without left ventricular outflow tract (LVOT) obstruction is a common primary myocardial disease, with a prevalence of 1:500. It is characterized by thickening of the myocardium. Its diagnostic evaluation includes history-taking and physical examination, genetic studies, transthoracic echocardiography, and cardiac MRI. When optimally treated, it carries a mortality of less than 1% per year. This review is based on pertinent publications retrieved by a selective literature search, including the current guidelines. In symptomatic patients with high LVOT gradients (≥ 50 mm Hg), the treatment of first choice is pharmacotherapy with non-vasodilating beta-blockers or non-dihydropyridine-type calcium channel antagonists. Common side effects include bradycardia and hypotension, and there is a risk of AV nodal blockade. Both substance classes lower the LVOT gradient. Beta-blockers alleviate dyspnea and improve patients' quality of life. Verapamil can increase physical resilience. A further option is mavacamten, a myosin inhibitor that gained approval in Germany in mid-2023: it, too, lowers the LVOT gradient and improves quality of life. In 7-10% of patients, there is a reversible reduction of the left ventricular ejection fraction to less than 50%. Septal reduction treatments can be considered if drug therapy fails. Attention must also be paid to the management of sequelae such as atrial fibrillation, malignant arrhythmias, and mitral valve insufficiency. Patients with HCM have a near-normal life expectancy if the disease is diagnosed early and treated according to the guidelines. The treatment of HCM and HOCM (hypertrophic obstructive cardiomyopathy) have been studied in no more than a few clinical trials, and randomized studies with clinical endpoints are needed.

Radiofrequency Ablation for Patients with Hypertrophic Obstructive Cardiomyopathy Accompanied by Severe Left Ventricular Outflow Tract Obstruction.

Patients with hypertrophic obstructive cardiomyopathy (HOCM) have few available nonsurgical treatment options. The feasibility of CARTOSound-guided catheter radiofrequency ablation (RFA) has been reported previously; however, relevant data are limited. The objective is to retrospectively evaluate the effectiveness and safety of CARTOSound-guided RFA for patients with HOCM. Thirty-seven patients with successive HOCM accompanied by severe left ventricular outflow tract (LVOT) obstruction underwent CARTOSound-guided RFA were reviewed. The intracardiac echocardiography (ICE) images obtained were merged with the CARTO system to create a shell of the left ventricle. The systolic anterior motion-septal contact area marked from the ICE images was considered the target area for the current delivery of RFA. Follow-up data of the LVOT gradient examined before, 1 month, 6 months, 1 year, and every year after catheter-mediated RFA were accessed. The symptoms of 30 patients (81.1%) improved during the follow-up after RFA. The symptoms of all 30 patients were alleviated from the New York Heart Association (NYHA) class IV/III/II to the NYHA class II/I. A sustained and significant gradient reduction was observed in 28 patients (75.7%). The invasive pressure gradient of LVOT was 84.43 ± 27.55 mm Hg before RFA and 42.78 ± 36.38 mm Hg after RFA (P < .001), with a decrease of 41.65 ± 19.72 mm Hg. The median drop in pressure gradient was 36.0% (1.0-67.0%). Catheter-mediated RFA is an effective and safe treatment for patients with HOCM. However, its long-term efficacy and safety should be validated in the future by conducting multicenter clinical trials with large sample sizes.

Long-term clinical outcomes after alcohol septal ablation for hypertrophic obstructive cardiomyopathy in Japan: a retrospective study.

Hypertrophic cardiomyopathy is characterized by significant left ventricular wall thickening, often leading to obstructive symptoms. Alcohol septal ablation (ASA) has emerged as an effective treatment for patients with hypertrophic obstructive cardiomyopathy (HOCM) who remain symptomatic despite maximal medical therapy. However, the detailed long-term effects of ASA in Japanese patients with HOCM remain unclear. Therefore, this study aimed to investigate the long-term effects of ASA for HOCM by evaluating changes in symptoms, pressure gradient, hemodynamics, prognosis, and predictive factors for cardiovascular events over time. In this retrospective study, we examined 239 highly symptomatic patients (age, 64 ± 13years; median follow-up, 6.9years) treated with ASA for drug-refractory HOCM between 1998 and 2021. Patients were assessed using transthoracic echocardiography, magnetic resonance imaging, and cardiac catheterization. Follow-up evaluations included clinical assessments, electrocardiography, and echocardiography. Data analysis included descriptive statistics, Kaplan-Meier analysis, and multivariate regression. ASA reduced the left ventricular outflow tract gradient from 90.5 ± 52.8 to 14.4 ± 17.1mmHg (P < 0.01) and New York Heart Association (NYHA) class from 3 [2.5-3] to 1 [1-2] at 10years after ASA (P < 0.01). The 30-day mortality rate following ASA was 1%. Overall, 31 patients (13%) died during the follow-up period. The survival rates at 1, 5, 10, and 15years after ASA were 97.4%, 89.9%, 83.7%, and 77.6%, respectively. Multivariable analysis revealed NYHA functional class before ASA (odds ratio [OR], 3.09; 95% confidence interval [CI], 1.40-6.82; P = 0.005), beta-blocker use (OR, 0.25; 95% CI, 0.07-0.91; P = 0.036), and class Ia agent use (OR, 0.31; 95% CI, 0.13-0.75; P = 0.009) as independent predictors of all-cause mortality. This study demonstrated low periprocedural and long-term mortality rates following ASA in patients with HOCM, suggesting that ASA provides durable symptomatic relief and reduces left ventricular outflow tract obstruction in selected highly symptomatic patients with HOCM.

National experience of alcohol septal ablation in patients with obstructive hypertrophic cardiomyopathy: A long-term multicenter retrospective study

ObjectivesHypertrophic cardiomyopathy (HCM) is a widespread disease with an incidence of 1:200 in the general population and its surgical and interventional treatment is well-developed in western countries. This study is focusing on outcomes of HCM patients after alcohol septal ablation in Russian Federation. MethodsWe conducted a multicenter registry to evaluate outcomes of obstructive hypertrophic cardiomyopathy (oHCM) patients after ASA.Our study was focused on the following outcomes: (i) 30-day mortality, (ii) 30-day permanent pacemaker implantations, (iii) a residual obstruction occurrence, (iv) final maximal left ventricular outflow tract gradient, (v) long-term mortality, (vi) final heart failure functional class, (vii) freedom from sudden cardiac death. We conducted secondary analysis to assess outcomes in patients with single versus repeated ASA. The mean follow-up was 71±47 months. ResultsA total of 597 consecutive patients (54.9% female) were enrolled in the Russian Alcohol Septal Reduction (RASA) registry from three interventional groups. The mean age was 56±14 years. Thirty-day mortality rate was 0.7% (4 patients). Permanent pacemakers were implanted in 42 (7%) cases in 30-days follow-up. The resting LVOT gradient reduced from 64±28 to 20±13 mmHg (P<0.0001), and the mean NYHA class decreased from 2.3±0.7 to 1.3±0.5 (P<0.001). Long-term survival rates were as follows: 97.4 (95%CI: 96.2-98.7) %, 93.2 (95%CI: 91.0-95.3) %, 84.9 (95%CI: 80.7-89.4) % at 1-, 5-, 10-year follow-up, respectively. Patients after repeated ASAhad similar long-term survival comparing to those who underwent single ASA (weighted log rank P value = 0.254). Heart failure class in the long-term and final gradient at the last follow-up were not statistically different between groups under study (P>0.05). ConclusionsIn our registry, alcohol septal ablation in patients with obstructive hypertrophic cardiomyopathy was safe in the short- and long-term follow-up. Outcomes of patients underwent repeated ASA were non-inferior to those after single ASA.

Mavacamten in Patients With Hypertrophic Cardiomyopathy Referred for Septal Reduction: Week 128 Results from VALOR-HCM

Background: In severely symptomatic patients with obstructive hypertrophic cardiomyopathy (HCM), VALOR-HCM trial (Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy [URL: https://clinicaltrials.gov; Unique identifier: NCT04349072]) reported that mavacamten reduced the short-term need for septal reduction therapy (SRT). The current report examined the longer-term effect of mavacamten through end of treatment at week 128. Methods: A double-blind randomized placebo-controlled multicenter trial at 19 sites in the United States included symptomatic obstructive HCM patients referred for SRT (enrollment July 2020 through October 2021). The group initially randomized to mavacamten continued the drug for 128 weeks and the placebo to mavacamten group from week 16 to 128 (112-week exposure). Dose titrations were performed using echocardiographic left ventricular outflow tract gradient and left ventricular ejection fraction measurements. The principal end point was proportion of patients proceeding with SRT or remaining guideline-eligible at week 128. Results: At week 128, 17 of 108 (15.7%) patients in the total study sample met the composite end point (7 underwent SRT, 1 was SRT-eligible, and 9 SRT-status unevaluable). Additionally, 87 of 108 (80.5%) patients demonstrated ≥1 New York Heart Association class improvement by week 128, and 52 of 108 (48.1%) demonstrated ≥2, with a sustained reduction in resting and Valsalva left ventricular outflow tract gradients of 38.2 mm Hg and 59.4 mm Hg, respectively. Ninety-five of 108 (88%) patients transitioned to commercial mavacamten. Overall, 15 of 108 (13.8%) patients (5.41 per 100 patient-years) had an left ventricular ejection fraction &lt;50% (2 with left ventricular ejection fraction ≤30%; 1 death). Of these, 12 of 15 (80%) continued treatment. New-onset atrial fibrillation occurred in 11 (10.2%) patients (4.55 per 100 patient-years). Conclusions: In severely symptomatic obstructive HCM patients, sustained freedom from SRT was observed at 128 weeks, with nearly 90% patients remaining on long-term mavacamten.

Abstract 4140118: Identification of Obstructive and Non-Obstructive Hypertrophic Cardiomyopathy Patients Using Natural Language Processing in a Large Integrated Healthcare System

Introduction: Accurately identifying and characterizing patients with hypertrophic cardiomyopathy (HCM) is critical for population management and care optimization. Research Question: To develop natural language processing (NLP) algorithms to identify and characterize obstructive (oHCM) and non-obstructive (nHCM) HCM patients directly from echocardiograms, and to compare with the presence or absence of HCM-related diagnosis codes. Methods: We developed and validated NLP algorithms to identify HCM from all adult (age≥18yrs) echocardiograms performed from 2010-2019 in Kaiser Permanente Northern CA (KPNC), capturing measures of any HCM, HCM subtype, hypertrophy subtype, septal and posterior LV wall thickness, resting and stress/Valsalva LVOT gradients, and systolic anterior motion. We developed a rules-based algorithm (following AHA/ACC criteria) to classify patients as having HCM, including oHCM or nHCM subtypes, and possible HCM (defined as wall thickness ≥2cm without other criteria meeting an HCM definition). We evaluated the presence of HCM-related ICD-9/10 diagnosis codes among patients classified as HCM/non-HCM from echocardiograms using NLP, and linked baseline demographics and clinical parameters from our integrated electronic medical record. Results: Among 472,405 adults with echocardiograms, we identified 2,892 patients with HCM based upon NLP-derived measures (all NLP measures achieved &gt;95% positive predictive value and &gt;95% negative predictive value), including 1,585 (55%) with oHCM, 1,145 (40%) with nHCM, and 162 (6%) which could not be classified (Figure). Among those 2,892 patients, 1,283 did not have any associated HCM ICD-9/10 diagnosis codes (Table). Among 469,513 patients with no identified HCM from NLP-based algorithms, HCM ICD-9/10 diagnosis codes existed in 1,567 patients (Table). We also identified 4,593 patients with possible HCM by NLP, only 4.5% of whom had an associated HCM code. Among confirmed HCM patients by NLP, oHCM patients were slightly older (66 vs 61 yrs), more likely female (53% vs 43%), had similar mean septal wall thickness (1.7cm vs 1.7cm), but were more likely to have a septal hypertrophy subtype (46% vs 28%) compared to nHCM patients. Conclusions: Echocardiogram-based NLP methods can improve the identification of and care for HCM patients. Many patients with possible HCM may be underdiagnosed, representing an opportunity for quality improvement.

Abstract 4138690: A Case of Hypertrophic Cardimyopathy: Digenic Variants of Uncertain Significance Mutations in MHY7 and RYR2 Genes

Introduction: Hypertrophic Cardiomyopathy (HCM) is primarily a disease caused by mutations in single genes, but around 5% of HCM patients, exhibit 2 (digenic) or more (oligogenic) causal mutations in the same gene or in different genes. We present a case of familial HCM with variants of uncertain significance (VUS) mutations in the MYH7 and RYR2 genes, highlighting the complexity of genetic inheritance and its implications on disease severity. Case presentation: A 40-year-old male presented with a history of hypertension, HCM, and two prior myocardial infarctions. He had syncope, non-sustained ventricular tachycardia, and a family history of sudden cardiac death (SCD) in his maternal grandfather. A dual-chamber ICD was placed for primary prevention of SCD because of his high-risk profile. Echocardiography demonstrated normal LV size and function with moderate asymmetric septal hypertrophy. Cardiac MRI indicated diffuse asymmetric hypertrophy and a 10.9% LV myocardial scar burden. Left heart catheterization revealed normal coronary arteries with LVOT gradient up to 60 mmHg, consistent with HCM. Genetic testing revealed VUS in the MYH7 (c.1305G&gt;A, p.Met435Ile) and RYR2 (c.10528C&gt;A, p.Arg3510Ser) genes (Figure 1). Further family genetic testing confirmed these VUS mutations in multiple relatives (Figure 2). Discussion: The identification of VUS mutations in MYH7 and RYR2 genes in multiple family members highlights the complexity of genetic inheritance in HCM. These findings underscore the challenges in clinical interpretation and risk stratification, as the co-occurrence of mutations in different genes may have synergistic effects on disease severity and phenotype expression. Comprehensive genetic evaluation, including family studies, is crucial for understanding the clinical significance of these mutations and guiding personalized management strategies. Further research is needed to elucidate the impact of VUS mutations on the clinical outcomes of HCM patients.

Abstract 4138268: The Use of Mavacamten for Management of Post TAVR Obstruction: A Novel Approach to Treatment

Background: Treatment of left ventricular outflow tract (LVOT) obstruction involves a combination of negative inotropic agents. However, these therapies have limitations which may result in insufficient control of symptoms, leading to more invasive options such as surgical septal myectomy or septal alcohol ablation. Mavacamten, a cardiac myosin inhibitor, is currently approved for the treatment of patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). We present a case of a patient treated with mavacamten in addition to β-blockers (BB) for management of post-TAVR LVOT obstruction. Case: A 76 year old female with a past medical history of hypertension, severe aortic stenosis, and coronary artery disease underwent a Medtronic Evolut TAVR in March 2022. Her TTE post TAVR showed LVOT peak gradient greater than 100 mm Hg, LVEF 75% and severe eccentric mitral regurgitation secondary to systolic anterior motion (SAM) of the mitral valve (MV). After multidisciplinary discussion, the patient was discharged on maximally tolerated BB therapy. Follow up TTE showed persistent obstruction and gradients, so diltiazem was added to her regimen. Her subsequent TTE showed a peak LVOT &gt; 100 mmHg at rest, and severe MR. Given persistent findings, she was started on mavacamten, continued on metoprolol, and tapered off of diltiazem. Her TTE two months after initiation of mavacamten revealed resolution of LVOT gradients, reduction of MR to mild and normal LV and TAVR function. She tolerated the therapy well and endorsed ongoing symptomatic improvement on subsequent follow up. Discussion: With the increasing use of TAVR therapy, there has been a corresponding rise in cases of post-TAVR obstruction that must be managed. As demonstrated by this case, management with BB therapy alone may be suboptimal. Although mavacamten is currently approved in patients with HCM, the obstruction in post-TAVR patients is functionally similar. Thus, this medication was trialed as a supplemental treatment in this patient and yielded positive results. This case highlights the potential benefit of extending use of mavacamten alongside β-blocker therapy for this patient population and suggests the need for future studies.

Abstract 4132223: Mavacamten in adolescent patients with symptomatic obstructive hypertrophic cardiomyopathy: design of the Phase 3 SCOUT-HCM trial

Background: While most current treatments can improve symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM), they may be poorly tolerated and do not target the underlying pathophysiology. Mavacamten is the first and only cardiac myosin inhibitor approved for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive HCM but has not been evaluated in a pediatric age group. SCOUT-HCM (Study of MavaCamten in AdOlescents with Symptomatic ObstrUcTive HCM; NCT06253221) will evaluate the efficacy, safety, and pharmacokinetics of mavacamten in adolescents with symptomatic obstructive HCM. Methods: SCOUT-HCM is a randomized, double-blind, placebo-controlled, international phase 3 clinical trial that will enroll 40 adolescents (age 12 to &lt;18 years) with obstructive HCM ( Figure ). Patients will receive mavacamten or placebo during the first 28 weeks, followed by a 28-week double-blind active treatment period. Inclusion criteria include a diagnosis of HCM with presence of symptoms and left ventricular outflow tract (LVOT) obstruction. Patients with HCM phenocopies, LVEF &lt;50% at rest in the past 6 months, planned escalation in HCM therapy or upcoming intervention (eg, major cardiac surgery) will be excluded. The primary endpoint is change in Valsalva LVOT gradient from baseline to week 28. Key secondary endpoints include other echocardiographic parameters, safety, pharmacokinetics, and exercise capacity. Conclusions: SCOUT-HCM is the first randomized controlled trial evaluating a targeted myosin inhibitor in adolescents with symptomatic obstructive HCM. The results will inform the utility of mavacamten in adolescent patients with symptomatic obstructive HCM.

Abstract 4135212: An Overlap Between Takotsubo Cardiomyopathy and Hypertrophic Obstructive Cardiomyopathy Causing Dynamic Left Ventricular Outflow Tract Obstruction: A Unique Case Report

Background: Takotsubo cardiomyopathy (TC) can cause dynamic left ventricular outflow tract (LVOT) obstruction leading to cardiogenic shock. Due to differential wall-motion abnormalities, flow acceleration in the LVOT can lead to systolic anterior motion (SAM) of the mitral valve which worsens LVOT obstruction and leads to hemodynamic compromise. We present a case of overlap between TC and hypertrophic obstructive cardiomyopathy (HOCM) with worsening LVOT obstruction leading to cardiogenic shock. Case: A 76-year-old female presented with typical chest pain, nausea, and worsening shortness of breath. On examination, she was hypotensive and cold to touch. EKG showed T-wave inversions in lateral leads with elevated cardiac troponins. Coronary angiogram showed non-obstructive coronary artery disease, and right heart catheterization revealed elevated filling pressures. Transthoracic echocardiogram (TTE) showed septal hypertrophy and SAM of the mitral valve causing dynamic LVOT obstruction (Figure 1) and ejection fraction (EF) of 20%. TTE with contrast showed apical ballooning consistent with TC (Figure 2). Decision Making: Initially with diuresis, she became hypotensive so it was stopped and she received controlled intravenous fluids along with phenylephrine to reduce LVOT obstruction. Her blood pressure improved and she was started on low-dose metoprolol succinate along with ivabradine to reduce heart rate. She tolerated this therapy and hemodynamics stabilized. Conclusion: Cardiogenic shock can be a severe complication of TC. Early detection of LVOT obstruction in cardiogenic shock is important as traditional management strategies of increased inotropy and reduction of afterload can be fatal in these cases. The treatment strategy focuses on reducing the LVOT gradient and includes fluid administration to increase preload, beta-blockers to increase diastolic filling time, and vasopressors to raise afterload.

Abstract 4123391: CardioMEMS and Mavacamten: A Synergistic Approach in Managing Hypertrophic Obstructive Cardiomyopathy with HFpEF Phenotype

Introduction: Mavacamten is a cardiac myosin inhibitor that has been approved for obstructive hypertrophic cardiomyopathy (oHCM). The CardioMEMS PA (pulmonary artery) sensor allows remote pulmonary artery diastolic (PAD) pressure monitoring to adjust diuresis in heart failure with preserved ejection fraction (HFpEF). We present the case of a patient with oHCM and HFpEF where data extrapolated from CardioMEMS provided valuable insight to the hemodynamic impact of cardiac myosin inhibitors. Case: A 66-year-old female with hypertension, obesity and oHCM presented with worsening dyspnea and was evaluated for septal myectomy. However, surgery was deferred because of decompensated HFpEF, as evidenced by significant leg edema on exam, and severely elevated left and right-side filling pressure, with restrictive physiology on right heart catheterization. A CardioMEMS PA sensor was implanted to guide decongestion, however, escalation of diuresis was limited due to severe left ventricular outflow tract (LVOT) obstruction. PAD remained elevated at 20-30 mmHg. Due to the refractory LVOT obstruction and despite the use of maximally tolerated beta blockers, Mavacamten was initiated and escalated according to protocol. LVOT obstruction resolved on follow up echocardiogram. Without any adjustment in her diuretic regimen, her PAD decreased to 15-20 mmHg. On follow-up visit, the patient reported improvement in dyspnea and reduction in lower extremity edema. Discussion: Managing oHCM is challenging, particularly when complicated by HFpEF. Mavacamten has shown promise in reducing LVOT gradients and improving symptoms in oHCM. However, managing fluid status in these patients can be difficult due to the risk of exacerbating LVOT obstruction while optimizing filling pressures. Our case provides direct evidence that treating LVOT obstruction with a cardiac myosin inhibitor leads to improvement in decompensated heart failure, as evidenced by the reduction in PAD. Conclusion: Addressing LVOT obstruction is key to decongesting and managing heart failure in oHCM patients. In our case, the use of CardioMEMS PA sensor system allowed a novel perspective of assessing hemodynamic impact of cardiac myosin inhibitors.

Abstract 4112926: Echocardiography in Hypertrophic Cardiomyopathy: Virtual Continuing Medical Education Advances Physician Knowledge and Confidence

Purpose: This study examined whether online CME could improve the knowledge and confidence of cardiologists regarding the use of echocardiography for HCM diagnosis and management. Methods: The CME intervention comprised of a series of 6 online interviews between 1 moderator and 2 expert faculty. Educational effect was assessed using a repeated-pair design with pre-/post-assessment. 3 multiple choice questions assessed knowledge, and 1, rated on a Likert-type scale, assessed confidence. A paired samples t-test was conducted on overall average number of correct responses and for confidence rating, and a McNemar’s test was conducted at the question level (significance level, P &lt; .05). Data were collected August 8-September 8, 2023. Results: 165 cardiologists answered all assessment questions during the study period. Analysis of pre- vs. post-intervention responses demonstrated a significant improvement in overall knowledge; average correct responses increased from 48% pre-assessment to 74% post-assessment ( P &lt;.001). Specific areas of improvement include: Knowledge of the quantification of LVOT gradients, MR, and LVEF in the echocardiographic workup of HCM: 21% improved and 62% reinforced; the correct response increased (P&lt;.001) from 65% (pre) to 84% (post). Knowledge of the utility of echocardiography for follow-up and monitoring response to HCM treatment: 48% improved and 35% reinforced; the correct response increase (P&lt;.001) from 39% (pre) to 70% (post). Post-education, 48% of cardiologists had a measurable increase in their ability to diagnose HCM using echocardiographic parameters, resulting in 43% who were mostly or very confident after education (24% pre vs 43% post; P&lt;.001). Conclusion: This study demonstrated the success of online CME at improving the knowledge and confidence of cardiologists related to the use of echocardiography to identify and manage HCM.

Contemporary Clinical Characteristics, Imaging, Management, and Surgical and Nonsurgical Outcomes of Adult Patients With Subaortic Stenosis.

Subaortic stenosis (SAS) is characterized by a fibromuscular membrane located just below the aortic valve, causing fixed outflow tract obstruction. There is a paucity of studies evaluating this condition. This cohort study reviewed the contemporary characteristics and outcomes of SAS in adult patients in a single large referral center. We retrospectively studied adult patients with SAS evaluated at our center during 2011 to 2022. The primary outcome was all-cause mortality and heart failure hospitalizations during follow-up, with secondary end points including recurrence of SAS and repeat surgery after initial SAS surgery. Among 484 patients with SAS, key characteristics included mean age 55±18 years, 67.5% female, left ventricular outflow tract peak velocity 352±140 cm/s and gradient 57±40 mm Hg, left ventricular ejection fraction 60%±14%, 54.8% had prior SAS surgery, and 45.1% had surgery during follow-up. Over a median follow-up of 5.5 (1.5-12.3) years, 11.5% (n=56) died, 6.8% (n=33) had heart failure hospitalizations, 8.0% (n=39) experienced SAS recurrence, and 14 (5.9%) underwent repeat SAS surgery. Multivariable analyses identified older age per 10-years (hazard ratio [HR], 1.37 [95% CI, 1.12-1.68]) and baseline New York Heart Association class (HR, 2.48 [95% CI, 1.54-3.99]) to be statistically significantly associated with the primary end point; higher body mass index, New York Heart Association class, and peak left ventricular outflow tract gradient were also statistically significantly associated with SAS recurrence and redo surgery. Almost half of patients with SAS had surgery in the past or during follow-up, and a significant minority had mortality or morbidity events during follow-up. Identified prognosticators warrant further research to guide management.

Mavacamten: Real-World Experience from 22 Months of the Risk Evaluation and Mitigation Strategy (REMS) Program.

Background: Mavacamten is the only cardiac myosin inhibitor approved by the US FDA for treatment of symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) patients. Under the risk evaluation and mitigation strategy (REMS) program for mavacamten, patients are required to be monitored for development of systolic heart failure, and reduction of left ventricular ejection fraction (LVEF) to <50%. We report results from the mavacamten REMS database (28-Apr-2022 to 27-Feb-2024). Methods: Data on healthcare providers and pharmacy certification, patient monitoring (from Patient Status Forms, based partly on echocardiograms), and screening for drug interactions prior to each dispense were collected. Results: Of 6,299 patients who received ≥1 dose of mavacamten, 60.0% were women; 64.6% were >60 years of age. Of 5,573 patients with submitted Patient Status Forms, 256 (4.6%) developed LVEF <50% and 71 (1.3%) experienced heart failure requiring hospitalization (HFH). On the 29,111 status forms in these patients, each representing an assessment of an echocardiogram, LVEF <50% was reported on 276 (0.9%) and HFH was reported on 86 (0.3%). Of 1,929 patients with ≥1 year of treatment, 78 (4.0%) had an LVEF reduction to <50% and 4 (0.2%) experienced LVEF <50% + HFH but later resumed treatment. Of 3,228 patients initiated on 5 mg/day mavacamten and were treated for at least 6 months, 2,391 (74.1%) remained at 5 or 10 mg/day. At 3- and 6-months following mavacamten treatment initiation, 57.2% and 70.3%, respectively, demonstrated post-Valsalva LV outflow tract gradient <30 mmHg. Conclusions: We describe the feasibility and experience of the first 22 months of the REMS program for prescribing mavacamten in >6,000 symptomatic obstructive HCM patients. The need for temporary interruption for LVEF <50% was low, including for patients on therapy ≥1 year, with even fewer LVEF reductions associated with HFH.

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

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

Loss of quality of life and increased societal costs in patients with hypertrophic cardiomyopathy: the AFFECT-HCM study.

Hypertrophic cardiomyopathy (HCM) is the most prevalent inherited cardiac disease. The impact of HCM on quality of life (QoL) and societal costs remains poorly understood. This prospective multi-centre burden of disease study estimated QoL and societal costs of genotyped HCM patients and genotype-positive phenotype-negative (G+/P-) subjects. Participants were categorized into three groups based on genotype and phenotype: 1) G+/P- (left ventricular (LV) wall thickness <13 mm), 2) non-obstructive HCM (nHCM, LV outflow tract (LVOT) gradient <30 mmHg), and 3) obstructive HCM (oHCM, LVOT gradient ≥30 mmHg). We assessed QoL with EQ-5D-5L and Kansas City Cardiomyopathy Questionnaires (KCCQ). Societal costs were measured using medical consumption (iMCQ) and productivity cost (iPCQ) questionnaires. We performed subanalyses within three age groups: <40, 40-59, and ≥60 years. From three Dutch hospitals, 506 subjects were enrolled (84 G+/P-, 313 nHCM, 109 oHCM; median age 59 years, 39% female). HCM (both nHCM and oHCM) patients reported reduced QoL vs G+/P- subjects (KCCQ: 88 vs 98, EQ-5D-5L: 0.88 vs 0.96; both p<0.001). oHCM patients reported lower KCCQ scores than nHCM patients (83 vs 89, p=0.036). Societal costs were significantly higher in HCM patients (€19,035/year vs €7,385/year) compared to G+/P- controls, mainly explained by higher healthcare costs and productivity losses. Being symptomatic and of younger age (<60 years) particularly led to decreased QoL and increased costs. HCM is associated with decreased QoL and increased societal costs, especially in younger and symptomatic patients. oHCM patients were more frequently symptomatic than nHCM patients. This study highlights the substantial disease burden of HCM and can aid in assessing new therapy cost-effectiveness for HCM in the future.

Phase 3 Open-Label Study Evaluating the Efficacy and Safety of Mavacamten in Japanese Adults With Obstructive Hypertrophic Cardiomyopathy - The HORIZON-HCM Study.

Mavacamten, a cardiac myosin inhibitor, significantly improved symptoms and cardiac function vs. placebo in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in EXPLORER-HCM. However, the efficacy and safety profiles of mavacamten in Japanese patients are unclear. HORIZON-HCM is a Phase 3 single-arm study in Japanese patients with symptomatic obstructive HCM. The mavacamten starting dose was 2.5 mg; individualized dose titration occurred in Weeks 6-20 based on Valsalva left ventricular outflow tract (LVOT) gradient and resting left ventricular ejection fraction (LVEF). Overall, 38 patients were treated; 36 completed the 30-week primary treatment analysis period. Clinically significant improvements in postexercise LVOT gradient were observed after 30 weeks of treatment (mean change from baseline -60.7 mmHg). Improvements in N-terminal pro B-type natriuretic peptide, New York Heart Association class, and Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score were observed over 30 weeks, and mean LVEF was ≥74% at all visits. Treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 63.2% and 7.9% of patients, respectively; none resulted in treatment discontinuation. One patient experienced a transient asymptomatic reduction in LVEF to <50%. No deaths occurred during the study. In Japanese patients with obstructive HCM, mavacamten was associated with similar improvements in LVOT gradients, cardiac biomarkers, and symptoms to those observed in EXPLORER-HCM. Treatment was well tolerated with no new safety concerns.

Prevention of left ventricular outflow tract obstruction in transapical mitral valve replacement: the MitraCut procedure.

The MitraCut procedure employs beating heart transapical (TA) cannulation and endoscopic scissors for dividing the anterior mitral leaflet (AML) to prevent left ventricular outflow tract (LVOT) obstruction in transapical transcatheter mitral valve replacement (TA-TMVR). We present the first multicentre experience of the MitraCut procedure prior to TA-TMVR to prevent LVOT obstruction. In 6 European centres, the clinical outcomes of all 13 high-risk patients who had undergone the MitraCut procedure during TA-TMVR procedures were retrospectively reviewed regarding technical success, procedural details and outcome. The MitraCut procedure was successfully completed in 11 patients with 1 cutting attempt, while 2 patients had 2 cutting attempts, with an average procedure duration of 9.0±5.4 min. No patient demonstrated postoperative LVOT obstruction, and all mitral valve (MV) prostheses were competent throughout the follow-up period. However, 1 patient developed a MitraCut-related paravalvular leak (PVL; technical success rate: 12/13). The mean LVOT gradient was 3.9±4.4 mmHg directly after valve expansion and 3.6±3.1 mmHg at follow-up. In-hospital and 30-day mortality were 0%. One patient experiencing MitraCut-related PVL was successfully treated by interventional PVL closure (reintervention rate: n=1). One patient died at 47 days due to cardiac arrhythmia, unrelated to the AML-directed procedure. The mean follow-up at the time of data analysis was 52±34 days. The MitraCut procedure was effective and reproducible for preventing potential LVOT obstruction in TA-TMVR patients during its initial exploration in 6 European hospitals. Considerations regarding the scissors' characteristics, their handling and cut length are mandatory for safe performance of the procedure.

Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy: A Patient with a High LVOT Gradient

Background: Hypertrophic obstructive cardiomyopathy is a type of cardiomyopathy. The presence of a pressure gradient between the mid ventricle and LVOT on the hemodynamic evaluation revealed by echocardiography serves as the basis for the diagnosis. Objective: To Perform Alcohol Septal Ablation in patient with Hypertrophic Cardiomyopathy Method: Under both Echocardiography and Fluoroscopy first septal branch of LAD is identified and alcohol is injected to cause necrosis of the selected myocardial tissue to reduce the outflow gradient. Result: A reduction of the outflow gradient measured after the procedure indicates that it wassuccessful. J Inv Clin Cardiol 2023; 5(2): 56-59