Sex-Related Differences in Patients With Hypertrophic Cardiomyopathy Undergoing Alcohol Septal Ablation.

BACKGROUND: Previous studies have shown that women with hypertrophic obstructive cardiomyopathy (HCM) have worse long-term outcomes irrespective of intervention. However, the outcomes of patients undergoing alcohol septal ablation (ASA) based on sex have not been described. Hence, this study aimed to evaluate pressure changes and long-term mortality in patients with HCM undergoing ASA based on sex. METHODS AND RESULTS: This is a single-center retrospective study evaluating hemodynamic changes and long-term mortality in patients with HCM treated with ASA according to sex. A total of 259 patients were included (aged 68.4±11.9 years, 62.2% women). Women had higher age and baseline pressures at the time of ASA, with a greater percent reduction in mean left atrial pressure (men versus women: 2.2% versus 15.9%, respectively; P=0.02). Women had better survival (median survival rate of men versus women: 8.6 versus 12.5 years, respectively; P=0.011). On Cox multivariable regression, predictors of mortality were age (per group change <60 years, 61-70 years, 71-80 years, and >80 years; hazard ratio [HR], 1.45 [95% CI, 1.10-1.91], P=0.008), female sex (HR, 0.59 [95% CI, 0.35-0.99], P=0.048), chronic kidney disease (HR, 1.88 [95% CI, 1.06-3.33], P=0.031), and left ventricular outflow tract gradient reduction ≤86% (HR, 1.91 [95% CI, 1.14-3.19], P=0.014). CONCLUSIONS: Women with HCM undergoing ASA are older and have higher left-sided baseline pressures compared with men yet have better survival. Further studies exploring the mechanisms of differential outcomes according to sex in patients with HCM undergoing ASA are needed.

Outcomes of Surgical Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy After Prior Septal Reduction Therapy.

OBJECTIVE: To compare early and late outcomes of septal myectomy in patients with obstructive hypertrophic cardiomyopathy who presented with residual or recurrent left ventricular outflow tract (LVOT) obstruction following prior septal reduction therapy (SRT). METHODS: From January 1989 to March 2022, 145 patients underwent reintervention by septal myectomy for residual LVOT obstruction following prior SRT; 72 patients had prior alcohol septal ablation (ASA), and 73 had prior surgical septal myectomy (SM). Baseline patient characteristics, echocardiographic parameters, and surgical outcomes were compared between these two groups. RESULTS: Patients who had prior ASA were more likely to be male (50.0% vs 30.1%; P=0.015), older (median age 57.5 years vs. 48.3 years; P<0.001) and have a greater body mass index (32.7 kg/m2vs. 30.0 kg/m2; P=0.011). After repeat SRT by septal myectomy, there was no significant difference in the incidence of postoperative complete heart block (CHB), necessitating permanent pacemaker, between the two groups (8.3% vs. 2.7%; P=0.151). One (0.7%) patient died within 30 days of surgery. Over a median follow-up of 7.5 years (IQR 3.0-13.8), there were 20 deaths. Kaplan-Meier 5-, 10-, and 15-year survival rates were 100%, 91%, and 76% for the prior SM group, and 93%, 81%, and 64% for the prior ASA group (P=0.207). CONCLUSION: Septal myectomy for residual or recurrent LVOT obstruction in patients who had prior ASA is safe with an acceptably low rate of postoperative CHB. Surgical outcomes and late survival rates in patients with prior ASA were satisfactory and comparable to patients who underwent repeat myectomy.

Invasive Cardiac Hemodynamics in Apical Hypertrophic Cardiomyopathy.

BACKGROUND: Symptomatic limitations in apical hypertrophic cardiomyopathy may occur because of diastolic dysfunction with resultant elevated left ventricular filling pressures, cardiac output limitation to exercise, pulmonary hypertension (PH), valvular abnormalities, and/or arrhythmias. In this study, the authors aimed to describe invasive cardiac hemodynamics in a cohort of patients with apical hypertrophic cardiomyopathy. METHODS AND RESULTS: Patients presenting to a comprehensive hypertrophic cardiomyopathy center with apical hypertrophic cardiomyopathy were identified (n=542) and those who underwent invasive hemodynamic catheterization (n=47) were included in the study. Of these, 10 were excluded due to postmyectomy status or incomplete hemodynamic data. The mean age was 56±18 years, 16 (43%) were women, and ejection fraction was preserved (≥50%) in 32 (91%) patients. The most common indication for catheterization was dyspnea (48%) followed by suspected PH (13%), and preheart transplant evaluation (10%). Elevated left ventricular filling pressures at rest or exercise were present in 32 (86%) patients. PH was present in 30 (81%) patients, with 6 (20%) also having right-sided heart failure. Cardiac index was available in 25 (86%) patients with elevated resting filling pressures. Of these, 19 (76%) had reduced cardiac index and all 6 with right-sided heart failure had reduced cardiac index. Resting hemodynamics were normal in 8 of 37 (22%) patients, with 5 during exercise; 3 of 5 (60%) patients had exercise-induced elevation in left ventricular filling pressures. CONCLUSIONS: In patients with apical hypertrophic cardiomyopathy undergoing invasive hemodynamic cardiac catheterization, 86% had elevated left ventricular filling pressures at rest or with exercise, 81% had PH, and 20% of those with PH had concomitant right-sided heart failure.

Obstruction in Hypertrophic Cardiomyopathy: Many Faces.

Hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, exhibits left ventricular hypertrophy not secondary to other causes, with varied phenotypic expression. Enhanced actin-myosin interaction underlies excessive myocardial contraction, frequently resulting in dynamic obstruction within the left ventricle. Left ventricular outflow tract obstruction, occurring at rest or with provocation in 75% of HCM patients, portends adverse prognosis, contributes to symptoms, and is frequently a therapeutic target. Transthoracic echocardiography plays a crucial role in the screening, initial diagnosis, management, and risk stratification of HCM. Herein, we explore echocardiographic evaluation of HCM, emphasizing Doppler assessment for obstruction. Echocardiography informs management strategies through noninvasive hemodynamic assessment, which is frequently obtained with various provocative maneuvers. Recognition of obstructive HCM phenotypes and associated anatomical abnormalities guides therapeutic decision-making. Doppler echocardiography allows monitoring of therapeutic responses, whether it be medical therapies (including cardiac myosin inhibitor therapy) or septal reduction therapies, including surgical myectomy and alcohol septal ablation. This article discusses the hemodynamics of obstruction and practical application of Doppler assessment in HCM. In addition, it provides a visual atlas of obstruction in HCM, including high-quality figures and complementary videos that illustrate the many facets of dynamic obstruction.

A Multi-Omics Atlas of Sex-Specific Differences in Obstructive Hypertrophic Cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease. Women with HCM tend to have a later onset but more severe disease course. However, the underlying pathobiological mechanisms for these differences remain unknown. Methods: Myectomy samples from 97 patients (53 males/44 females) with symptomatic obstructive HCM and 23 control cardiac tissues were included in this study. RNA-sequencing was performed on all samples. Mass spectrometry-based proteomics and phosphoproteomics was performed on a representative subset of samples. Results: The transcriptome, proteome, and phosphoproteome was similar between sexes and did not separate on PCA plotting. Overall, there were 482 differentially expressed genes (DEGs) between control females and control males while there were only 53 DEGs between HCM females and HCM males. There were 1963 DEGs between HCM females and control females compared to 1064 DEGs between HCM males and control males. Additionally, there was increased transcriptional downregulation of hypertrophy pathways in HCM females and in HCM males. HCM females had 119 differentially expressed proteins compared to control females while HCM males only had 27 compared to control males. Finally, the phosphoproteome showed females had 341 differentially phosphorylated proteins (DPPs) compared to controls while males only had 184. Interestingly, there was hypophosphorylation and inactivation of hypertrophy pathways in females but hyperphosphorylation and activation in males. Conclusion: There are subtle, but biologically relevant differences in the multi-omics profile of HCM. This study provides the most comprehensive atlas of sex-specific differences in the transcriptome, proteome, and phosphoproteome present at the time of surgical myectomy for obstructive HCM.

Re-evaluating the Incidence and Prevalence of Clinical Hypertrophic Cardiomyopathy: An Epidemiological Study of Olmsted County, Minnesota.

OBJECTIVE: To contemporaneously reappraise the incidence-rate, prevalence, and natural history of hypertrophic cardiomyopathy (HCM) in Olmsted County, Minnesota, from 1984 to 2015. PATIENTS AND METHODS: A validated medical-record linkage system collecting information for residents of Olmsted County was used to identify all cases of HCM between January 1, 1984, and December 31, 2015. After adjudication of records from Mayo Clinic and Olmsted Medical Center, data relating to diagnoses and outcomes were abstracted. The calculated incidence rate and prevalence were standardized to the US 1980 White population (age- and sex-adjusted) and compared with a prior study examining the years 1975-1984. RESULTS: Two hundred seventy subjects with HCM were identified. The age- and sex-adjusted incidence rate was 6.6 per 100,000 person-years, and the point prevalence of HCM on January 1, 2016, was 89 per 100,000 population. The incidence rate and point prevalence of HCM on January 1, 2016, standardized to the US 1980 White population (age- and sex-adjusted), were 6.7 (95% CI, 7.1 to 8.8) per 100,000 person-years and 81.5 per 100,000 population, respectively. The incidence rate of HCM increased each decade since the index study. Individuals with HCM had a higher overall standardized mortality rate than the general population with an observed to expected HR of 1.44 (95% CI, 1.21 to 1.71; P<.001) which improved by each decade. CONCLUSION: The incidence and prevalence of HCM are higher than rates reported from a prior study in the same community examining the years 1975-1984, but lower than other study cohorts. The risk of mortality in HCM remains higher than expected, albeit with improvement in rates of mortality observed each decade during the study period.

Improvement in gastrointestinal bleeding after septal myectomy for hypertrophic cardiomyopathy.

OBJECTIVE: Patients with obstructive hypertrophic cardiomyopathy may have occult gastrointestinal bleeding. In this study, we analyzed outcomes of septal myectomy in patients who had a history of gastrointestinal bleeding preoperatively to understand patient characteristics and impact of septal reduction on recurrent gastrointestinal bleeding. METHODS: We analyzed 73 adult patients who had a history of gastrointestinal bleeding before transaortic septal myectomy for obstructive hypertrophic cardiomyopathy and compared outcomes to 219 patients without gastrointestinal bleeding preoperatively. RESULTS: Patients with preoperative history of gastrointestinal bleeding were older (median (IQR) age, 65 (59-69) years, P < .001) and were more likely to have systemic hypertension (70% vs 53%, P = .020) and coronary artery disease (25% vs 13%, P = .026). Preoperatively, patients with gastrointestinal bleeding had a larger left atrial volume index (median, 53 mL/m2; interquartile range, 42-67; P = .006) and greater right ventricular systolic pressure (median, 36 mm Hg; interquartile range, 32-49; mm Hg, P = .005) but no significant difference in severity of outflow tract obstruction (P = .368). There were no perioperative deaths. The estimated 5- and 10-year survivals were 96.6% and 81.8%, respectively. At a median of 3.4 (interquartile range, 1.9-9.1) years after septal myectomy, 11 patients (15%) had recurrence of gastrointestinal bleeding, which was attributed to angiodysplasia or unknown causes in 6 patients (8%). CONCLUSIONS: Patients with a preoperative history of gastrointestinal bleeding have favorable short- and long-term outcomes after septal myectomy for obstructive hypertrophic cardiomyopathy. Remission of gastrointestinal bleeding was observed in 85% of patients postprocedure, and only 8% of the patients had recurrent gastrointestinal bleeding due to angiodysplasia or unknown causes.

Cardiovascular Testing in the United States during the COVID-19 Pandemic: Volume Recovery and Worldwide Comparison.

Purpose: To characterize the recovery of diagnostic cardiovascular procedure volumes in U.S. and non-U.S. facilities in the year following the initial COVID-19 outbreak. Materials and Methods: The International Atomic Energy Agency (IAEA) coordinated a worldwide study called the IAEA Noninvasive Cardiology Protocols Study of COVID-19 2 (INCAPS COVID 2), collecting data from 669 facilities in 107 countries, including 93 facilities in 34 U.S. states, to determine the impact of the pandemic on diagnostic cardiovascular procedure volumes. Participants reported volumes for each diagnostic imaging modality used at their facility for March 2019 (baseline), April 2020, and April 2021. This secondary analysis of INCAPS COVID 2 evaluated differences in changes in procedure volume between U.S. and non-U.S. facilities and among U.S. regions. Factors associated with return to prepandemic volumes in the United States were also analyzed in a multivariable regression analysis. Results: Reduction in procedure volumes in April 2020 compared with baseline was similar for U.S. and non-U.S. facilities (-66% vs -71%, P = .27). U.S. facilities reported greater return to baseline in April 2021 than did all non-U.S. facilities (4% vs -6%, P = .008), but there was no evidence of a difference when comparing U.S. facilities with non-U.S. high-income country (NUHIC) facilities (4% vs 0%, P = .18). U.S. regional differences in return to baseline were observed between the Midwest (11%), Northeast (9%), South (1%), and West (-7%, P = .03), but no studied factors were significant predictors of 2021 change from prepandemic baseline. Conclusion: The reductions in cardiac testing during the early pandemic have recovered within a year to prepandemic baselines in the United States and NUHICs, while procedure volumes remain depressed in lower-income countries.Keywords: SPECT, Cardiac, Epidemiology, Angiography, CT Angiography, CT, Echocardiography, SPECT/CT, MR Imaging, Radionuclide Studies, COVID-19, Cardiovascular Imaging, Diagnostic Cardiovascular Procedure, Cardiovascular Disease, Cardiac Testing Supplemental material is available for this article. © RSNA, 2023.

Persistence of left atrial thrombus in patients with hypertrophic cardiomyopathy and atrial fibrillation.

BACKGROUND: We recently demonstrated that patients with atrial fibrillation (AF) and hypertrophic cardiomyopathy (HCM) have an increased risk of left atrial (LA) thrombus. In this study, we aimed to evaluate thrombus management, thrombus persistence, and thromboembolic events for HCM and non-HCM patients with AF and LA thrombus. METHODS: From a cohort of 2,155 AF patients undergoing transesophageal echocardiography (TEE) for any indication, this study included 122 patients with LA thrombus (64 HCM patients and 58 non-HCM controls). RESULTS: There was no difference in mean CHA2DS2-VASc scores between HCM and control patients (3.9 ± 2.2 vs 3.8 ± 2.0, p = 0.88). Ten (16%) and 4 (7%) patients in the HCM and control groups, respectively, were in sinus rhythm at the time of TEE identifying the LA thrombus (p = 0.13). In all patients, the anticoagulation strategy was modified after the LA thrombus diagnosis. A total of 36 (56%) HCM patients and 34 (59%) control patients had follow-up TEE at median 90 and 62 days, respectively, after index TEE. The HCM group had significantly higher 90-day rates of persistent LA thrombus compared to the control group (88% vs 29%; p < 0.001). In adjusted models, HCM was independently associated with LA thrombus persistence. Among patients with LA thrombus, the 5-year cumulative incidence of thromboembolic events was 11% and 2% in HCM and control groups, respectively (p = 0.22). CONCLUSIONS: Among patients with AF with LA thrombus identified by TEE, those with HCM appear to have a higher risk of LA thrombus persistence than non-HCM patients despite anticoagulation.

Art and science of risk stratification of sudden cardiac death in hypertrophic cardiomyopathy: Current state, unknowns, and future directions.

The progress in the management of hypertrophic cardiomyopathy (HCM) over the last several decades has resulted in great improvements in quality of life and overall survival for HCM patients. Yet, sudden cardiac death (SCD) due to ventricular tachyarrhythmias is among the common causes of HCM-related mortality. SCD risk stratification is a central and often challenging domain in the care of the HCM patient. Distinguishing the individuals most likely to benefit from a primary prevention implantable-cardioverter defibrillator (ICD) from those truly at a low risk of SCD in whom an ICD is not necessary is a nuanced process. Clinicians need to carefully balance the potential benefit and risks of ICDs, particularly in young patients. Because of intense investigations in diverse HCM cohorts globally, two main approaches to SCD risk stratification in HCM have emerged, one based on major SCD risk factors and one based on a mathematically derived risk score. In this overview, we discuss the current state, latest advances and remaining unknowns about established and novel markers of risk of SCD in HCM. We also review how the risk factor- and risk score-based assessments can and should be used in conjunction to enhance rather than contradict each other in facilitating informed ICD decision-making in contemporary clinical practice.

Hemodynamic Predictors of Outcome Following Alcohol Septal Ablation for Hypertrophic Obstructive Cardiomyopathy.

BACKGROUND: Alcohol septal ablation (ASA) is a minimally invasive treatment for drug-refractory obstructive hypertrophic cardiomyopathy. Detailed assessment of pressure changes and predictors of mortality and procedure success are not well defined. METHODS: This is a single-center study evaluating pressure changes and predictors of mortality and procedure success in transseptal ASA. Survival analysis and predictors of mortality were assessed using the Kaplan-Meier analysis and Cox regression, respectively. RESULTS: A total of 156 patients were included (mean age, 67.3 years; 46.8% women). Left atrial (LA) pressure and left ventricular outflow tract (LVOT) gradient decreased, whereas aortic pulse pressure (PP) increased post-ASA. Patients with lower baseline mean LA pressure (82% (gradient change median), and PP increase >19% (PP change median) had superior survival. On Cox univariable regression, baseline mean LA pressure >median (19 mm Hg; hazard ratio [HR], 2.09 [95% CI, 1.05-4.18]; P=0.036), residual LVOT gradient (HR, 1.02 [95% CI, 1.01-1.03]; P=0.003), and LVOT gradient percent reduction median (28 mm Hg; HR, 2.36 [95% CI, 1.17-4.76]; P=0.016), baseline mean LA pressure >median (19 mm Hg; HR, 2.70 [95% CI, 1.33-5.50]; P=0.006), percentage reduction in gradient

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.

Ultrasound Enhancing Agents with Transthoracic Echocardiography for Maximal Wall Thickness in Hypertrophic Cardiomyopathy.

Objectives: To determine whether ultrasound enhancing agent (UEA) changes maximal wall thickness (WT) in hypertrophic cardiomyopathy (HCM), and if it improves correlation with magnetic resonance imaging (MRI). Patients and Methods: A total of 107 patients with HCM were prospectively enrolled at a single tertiary referral center between July 10, 2014, and August 31, 2017, and underwent transthoracic echocardiography (TTE) with and without UEA and MRI. Maximal WT measurements were compared, and variability among the 3 modalities was evaluated using a simple linear regression analysis and paired t tests and Bland-Altman plots. Interobserver variability for each technique was assessed. Results: Most (63%) of cardiac imagers found UEA helpful in determining maximal WT by TTE, with 49% reporting change in WT. Of 52 patients where UEA changed WT measurement, 32 (62%) reported an increase and 20 (38%) reported a decrease in WT. The UEA did not alter the median discrepancy in WT between MRI and TTE. However, where UEA increased reported WT, the difference between MRI and TTE improved in 79% of cases (P=.001) from 2.0-0.5mm. In those with scar on MRI, UEA improved agreement of WT between TTE and MRI compared with that of TTE without UEA (79% vs 39%; P=.011). Interclass correlation coefficient for WT for TTE without UEA, with UEA, and MRI was 0.84; (95% CI, 0.61-0.92), 0.88; (95%CI, 0.82-0.92), and 0.97; (95%CI, 0.96-0.98), respectively. Conclusion: Although use of UEA did not eliminate differences in WT discrepancy between modalities, the addition of UEA to TTE aided in WT determination and improved correlation with MRI in those with greater WT and in all patients with myocardial scars.

Aortic valve regurgitation following transaortic septal myectomy for obstructive hypertrophic cardiomyopathy: Incidence and influence on late outcomes.

OBJECTIVE: In this study, we describe the incidence, sites of valve injury, and the influence of aortic valve regurgitation (AR) on outcomes of septal myectomy for obstructive hypertrophic cardiomyopathy. METHODS: We analyzed patients who underwent transaortic septal myectomy for obstructive hypertrophic cardiomyopathy from 2001 to 2022. The primary study end point was incidence of procedure-related AR, defined as the need for an unplanned aortic valve (AV) procedure or new-onset moderate AR on early postoperative echocardiography. RESULTS: There were 2807 patients who underwent transaortic septal myectomy for hypertrophic cardiomyopathy and had pre- and postoperative transthoracic echocardiograms. Procedure-related AR was observed in 55 (2%) patients; 27 (1%) required unplanned AV procedures at the time of myectomy, and 29 (1%) additional patients developed moderate AR postoperatively. During follow-up, 9 total patients underwent late AV reoperation, 1 patient who developed new moderate AR postoperatively required late AVR due to severe calcific AS, and none of the patients who had unplanned AV procedures required late reoperation. The overall cumulative incidence of AV reoperation at 10 and 15 years was 1% and 5%. The predicted probability of moderate or severe AR at 5 and 10 years was 1.4% and 1.8%, respectively. There was no difference in survival comparing patients with or without early postoperative mild or worse AR (P = .69). CONCLUSIONS: Procedure-related AR was observed in 2% of patients undergoing transaortic septal myectomy, and unplanned AV procedures were necessary for half of these patients. Intraoperative identification and valve repair mitigate the impact of cusp injury on late reintervention and survival.