The Prevalence and Association of Exercise Test Abnormalities With Sudden Cardiac Death and Transplant-Free Survival in Childhood Hypertrophic Cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) can be associated with an abnormal exercise response. In adults with HCM, abnormal results on exercise stress testing are predictive of heart failure outcomes. Our goal was to determine whether an abnormal exercise response is associated with adverse outcomes in pediatric patients with HCM. METHODS: In an international cohort study including 20 centers, phenotype-positive patients with primary HCM who were <18 years of age at diagnosis were included. Abnormal exercise response was defined as a blunted blood pressure response and new or worsened ST- or T-wave segment changes or complex ventricular ectopy. Sudden cardiac death (SCD) events were defined as a composite of SCD and aborted sudden cardiac arrest. Using Kaplan-Meier survival, competing outcomes, and Cox regression analyses, we analyzed the association of abnormal exercise test results with transplant and SCD event-free survival. RESULTS: Of 724 eligible patients, 630 underwent at least 1 exercise test. There were no major differences in clinical characteristics between those with or without an exercise test. The median age at exercise testing was 13.8 years (interquartile range, 4.7 years); 78% were male and 39% were receiving beta-blockers. A total of 175 (28%) had abnormal test results. Patients with abnormal test results had more severe septal hypertrophy, higher left atrial diameter z scores, higher resting left ventricular outflow tract gradient, and higher frequency of myectomy compared with participants with normal test results (P<0.05). Compared with normal test results, abnormal test results were independently associated with lower 5-year transplant-free survival (97% versus 88%, respectively; P=0.005). Patients with exercise-induced ischemia were most likely to experience all-cause death or transplant (hazard ratio, 4.86 [95% CI, 1.69-13.99]), followed by those with an abnormal blood pressure response (hazard ratio, 3.19 [95% CI, 1.32-7.71]). Exercise-induced ischemia was also independently associated with lower SCD event-free survival (hazard ratio, 3.32 [95% CI, 1.27-8.70]). Exercise-induced ectopy was not associated with survival. CONCLUSIONS: Exercise abnormalities are common in childhood HCM. An abnormal exercise test result was independently associated with lower transplant-free survival, especially in those with an ischemic or abnormal blood pressure response with exercise. Exercise-induced ischemia was also independently associated with SCD events. These findings argue for routine exercise testing in childhood HCM as part of ongoing risk assessment.

Left Ventricular Systolic Dysfunction in Patients Diagnosed With Hypertrophic Cardiomyopathy During Childhood: Insights From the SHaRe Registry.

BACKGROUND: The development of left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM) is rare but serious and associated with poor outcomes in adults. Little is known about the prevalence, predictors, and prognosis of LVSD in patients diagnosed with HCM as children. METHODS: Data from patients with HCM in the international, multicenter SHaRe (Sarcomeric Human Cardiomyopathy Registry) were analyzed. LVSD was defined as left ventricular ejection fraction <50% on echocardiographic reports. Prognosis was assessed by a composite of death, cardiac transplantation, and left ventricular assist device implantation. Predictors of developing incident LVSD and subsequent prognosis with LVSD were assessed using Cox proportional hazards models. RESULTS: We studied 1010 patients diagnosed with HCM during childhood (<18 years of age) and compared them with 6741 patients with HCM diagnosed as adults. In the pediatric HCM cohort, median age at HCM diagnosis was 12.7 years (interquartile range, 8.0-15.3), and 393 (36%) patients were female. At initial SHaRe site evaluation, 56 (5.5%) patients with childhood-diagnosed HCM had prevalent LVSD, and 92 (9.1%) developed incident LVSD during a median follow-up of 5.5 years. Overall LVSD prevalence was 14.7% compared with 8.7% in patients with adult-diagnosed HCM. Median age at incident LVSD was 32.6 years (interquartile range, 21.3-41.6) for the pediatric cohort and 57.2 years (interquartile range, 47.3-66.5) for the adult cohort. Predictors of developing incident LVSD in childhood-diagnosed HCM included age <12 years at HCM diagnosis (hazard ratio [HR], 1.72 [CI, 1.13-2.62), male sex (HR, 3.1 [CI, 1.88-5.2), carrying a pathogenic sarcomere variant (HR, 2.19 [CI, 1.08-4.4]), previous septal reduction therapy (HR, 2.34 [CI, 1.42-3.9]), and lower initial left ventricular ejection fraction (HR, 1.53 [CI, 1.38-1.69] per 5% decrease). Forty percent of patients with LVSD and HCM diagnosed during childhood met the composite outcome, with higher rates in female participants (HR, 2.60 [CI, 1.41-4.78]) and patients with a left ventricular ejection fraction <35% (HR, 3.76 [2.16-6.52]). CONCLUSIONS: Patients with childhood-diagnosed HCM have a significantly higher lifetime risk of developing LVSD, and LVSD emerges earlier than for patients with adult-diagnosed HCM. Regardless of age at diagnosis with HCM or LVSD, the prognosis with LVSD is poor, warranting careful surveillance for LVSD, especially as children with HCM transition to adult care.

Improved Cardiac Performance and Decreased Arrhythmia in Hypertrophic Cardiomyopathy With Non-ß-Blocking R-Enantiomer Carvedilol.

BACKGROUND: Hypercontractility and arrhythmia are key pathophysiologic features of hypertrophic cardiomyopathy (HCM), the most common inherited heart disease. ß-Adrenergic receptor antagonists (ß-blockers) are the first-line therapy for HCM. However, ß-blockers commonly selected for this disease are often poorly tolerated in patients, where heart-rate reduction and noncardiac effects can lead to reduced cardiac output and fatigue. Mavacamten, myosin ATPase inhibitor recently approved by the US Food and Drug Administration, has demonstrated the ability to ameliorate hypercontractility without lowering heart rate, but its benefits are so far limited to patients with left ventricular (LV) outflow tract obstruction, and its effect on arrhythmia is unknown. METHODS: We screened 21 ß-blockers for their impact on myocyte contractility and evaluated the antiarrhythmic properties of the most promising drug in a ventricular myocyte arrhythmia model. We then examined its in vivo effect on LV function by hemodynamic pressure-volume loop analysis. The efficacy of the drug was tested in vitro and in vivo compared with current therapeutic options (metoprolol, verapamil, and mavacamten) for HCM in an established mouse model of HCM (Myh6R403Q/+ and induced pluripotent stem cell (iPSC)-derived cardiomyocytes from patients with HCM (MYH7R403Q/+). RESULTS: We identified that carvedilol, a ß-blocker not commonly used in HCM, suppresses contractile function and arrhythmia by inhibiting RyR2 (ryanodine receptor type 2). Unlike metoprolol (a ß1-blocker), carvedilol markedly reduced LV contractility through RyR2 inhibition, while maintaining stroke volume through α1-adrenergic receptor inhibition in vivo. Clinically available carvedilol is a racemic mixture, and the R-enantiomer, devoid of ß-blocking effect, retains the ability to inhibit both α1-receptor and RyR2, thereby suppressing contractile function and arrhythmias without lowering heart rate and cardiac output. In Myh6R403Q/+ mice, R-carvedilol normalized hyperdynamic contraction, suppressed arrhythmia, and increased cardiac output better than metoprolol, verapamil, and mavacamten. The ability of R-carvedilol to suppress contractile function was well retained in MYH7R403Q/+ iPSC-derived cardiomyocytes. CONCLUSIONS: R-enantiomer carvedilol attenuates hyperdynamic contraction, suppresses arrhythmia, and at the same time, improves cardiac output without lowering heart rate by dual blockade of α1-adrenergic receptor and RyR2 in mouse and human models of HCM. This combination of therapeutic effects is unique among current therapeutic options for HCM and may particularly benefit patients without LV outflow tract obstruction.

Evolving Contemporary Management of Atrial Fibrillation in Hypertrophic Cardiomyopathy.

Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM) with clinical and subclinical episodes occurring in nearly one-half of patients. AF in HCM historically has been characterized as a decisive disease complication associated with substantial risk for thromboembolic stroke and increased morbidity and mortality. However, there have been many advances in treatment strategy resulting in improved outcomes for this patient group. For example, stroke risk in HCM has been greatly reduced by using systemic oral anticoagulation initiated after the first clinical (symptomatic) AF episode, usually with preference given to direct anticoagulants over warfarin. In contrast, stroke risk scoring systems (such as CHA2DS2-VASc score) are not informative in HCM given the substantial potential for stroke events in patients with low scores, and therefore should not be used for anticoagulation decisions in this disease. A novel risk score specifically designed for HCM (HCM-AF score) can reliably identify most patients with HCM at risk for future AF. Although a strategy focused on controlling ventricular rate is effective in asymptomatic (or minimally symptomatic) patients with AF, restoring and maintaining sinus rhythm is required for most patients with marked AF symptom burden and impaired quality of life. Several antiarrhythmic drugs such as sotalol, disopyramide, and amiodarone, can be effective in suppressing AF episodes; albeit safe, long-term efficacy is supported by only limited data. Catheter AF ablation has emerged as an important treatment option for some patients, although freedom from AF after a single ablation is relatively low (35% at 3 years), multiple ablations and the concomitant use of antiarrhythmic drugs can control AF with more than two-thirds of patients maintaining sinus rhythm at 5 years. Surgical AF ablation with biatrial Cox-Maze IV performed as an adjunctive procedure during myectomy can reduce symptomatic AF episodes (70% of patients free from AF at 5 years). For the vast majority of patients who have HCM with AF, the implementation of contemporary therapies has allowed for improved quality of life and low HCM-related mortality.

Myocardial bridging in obstructive hypertrophic cardiomyopathy: a risk factor for myocardial fibrosis.

BACKGROUND: Myocardial bridging (MB) is common in patients with hypertrophic cardiomyopathy (HCM). There are sparse data on the impact of MB on myocardial fibrosis in HCM. This study was designed to evaluate the relationship between MB and myocardial fibrosis in patients with obstructive HCM. METHODS: In this cohort study, retrospective data were collected from a high-volume HCM center. Patients with obstructive HCM who underwent septal myectomy and preoperative cardiac magnetic resonance (CMR) were screened from 2011 to 2018. RESULTS: Finally, 492 patients were included in this study, with an average age of 45.7 years. Of these patients, 76 patients had MB. MB occurred mostly in the left anterior descending artery (73/76). The global extent of late gadolinium enhancement (LGE) was correlated with the degree of systolic compression (r = 0.33, p = 0.003). Multivariable linear regression analysis revealed that the degree of systolic compression was an independent risk factor for LGE (ß = 0.292, p = 0.007). The LGE fraction of basal and mid anteroseptal segments in patients with severe MB (compression ratio ≥ 80%) was significantly greater than that in patients with mild to moderate MB (compression ratio < 80%). During a median follow-up of 28 (IQR: 15-52) months, 15 patients died. Kaplan-Meier analysis did not identify differences in all-cause death (log-rank p = 0.63) or cardiovascular death (log-rank p = 0.72) between patients undergoing MB-related surgery and those without MB. CONCLUSIONS: MB with severe systolic compression was significantly associated with a high extent of fibrosis in patients with obstructive HCM. Concomitant myotomy or coronary artery bypass grafting might provide excellent survival similar to that of patients without MB. Identification of patients with severe MB and providing comprehensive management might help improve the prognosis of patients with HCM.

Assessing the impact of atrial fibrillation on symptoms and quality of life in hypertrophic cardiomyopathy.

INTRODUCTION: In hypertrophic cardiomyopathy (HCM), atrial fibrillation (AF) has historically been regarded to have a deleterious impact on clinical course, strongly associated with progressive heart failure (HF) symptoms. However, there is a paucity of information regarding the impact of AF on HCM employing validated quality of life (QoL) surveys. Therefore, we evaluated the impact of AF on QoL utilizing patient reported outcome measures (PROMs). METHODS: 218 consecutive HCM patients with or without AF at the Lahey HCM center in 2022 completed PROMs at their most recent visit evaluating HF (Kansas City Cardiomyopathy Questionnaire [KCCQ]) and AF symptoms (AF Effect on QoL [AFEQT]). RESULTS: Among the 218 patients, 50 (23%) had a history of AF and comprise the primary study cohort. AF was diagnosed at 55 ± 10 years of age, median of 5.5 years before PROM, with 66% of patients treated with a rhythm control strategy with antiarrhythmic drug and/or AF ablation. AFEQT indicated that 52% of patients experienced no or minimal AF-related disability, mild to moderate in 22%, and severe in 26%. There was no substantial difference in HCM phenotype in patients with no or minimal AF disability compared to those with severe disability. HF symptoms for most HCM patients with prior AF history was consistent with no or minimal (59%) or only mild (27%) disability as measured by KCCQ overall summary scores. In addition, with multivariate analysis, AF history was associated with less HF symptoms and improved QoL (OR 0.4, p = 0.02). CONCLUSION: In contrast to prior perceptions, HCM patients with prior AF history were less likely to incur HF symptoms impairing QoL compared to HCM patients without AF. After treatment, prior history of AF did not substantially impact current QoL. These data provide a realistic appraisal for the impact that AF has on HCM patients and also offers a measure of reassurance for this patient subgroup.

Current perspectives of sudden cardiac death management in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder characterized by left ventricular hypertrophy. Sudden cardiac death (SCD) is a rare but the most catastrophic complication in patients with HCM. Implantable cardioverter-defibrillators (ICDs) are widely recognized as effective preventive measures for SCD. Individualized risk stratification and early intervention in HCM can significantly improve patient prognosis. In this study, we review the latest findings regarding pathogenesis, risk stratification, and prevention of SCD in HCM patients, highlighting the clinic practice of cardiovascular magnetic resonance imaging for SCD management.

The impact of diabetes mellitus on cardiac function assessed by magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

BACKGROUND: The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM). METHODS: A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression. RESULTS: Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P < 0.05). In terms of the LA parameters, HCM-DM patients presented impaired LA reservoir and conduit strain/strain rate (all P < 0.05). Among all HCM patients, comorbidity with diabetes was independently associated with a low LV ejection fraction (ß = - 6.05, P < 0.001) and impaired global longitudinal strain (ß = 1.40, P = 0.007). Moreover, compared with the isolated HCM controls, HCM-DM patients presented with more myocardial fibrosis according to late gadolinium enhancement, which was an independent predictor of impaired LV global radial strain (ß = - 45.81, P = 0.008), LV global circumferential strain (ß = 18.25, P = 0.003), LA reservoir strain (ß = - 59.20, P < 0.001) and strain rate (ß = - 2.90, P = 0.002). CONCLUSIONS: Diabetes has adverse effects on LV and LA function in HCM patients, which may be important contributors to severe manifestations and outcomes in those patients. The present study strengthened the evidence of the prevention and management of diabetes in HCM patients.

Association between left atrial myopathy and sarcomere mutation in patients with hypertrophic cardiomyopathy: insights into left atrial strain by MRI feature tracking.

OBJECTIVES: Left atrial (LA) myopathy, characterized by LA enlargement and mechanical dysfunction, is associated with worse prognosis in hypertrophic cardiomyopathy (HCM) while the impact of sarcomere mutation on LA myopathy remains unclear. We aimed to assess the association between LA myopathy and sarcomere mutation and to explore the incremental utility of LA strain in mutation prediction. METHODS: A total of 105 consecutive HCM patients (mean age 47.8 ± 11.9 years, 71% male) who underwent HCM-related gene screening and cardiac MRI were retrospectively enrolled. LA volume, ejection fraction and strain indices in reservoir, conduit, and booster-pump phases were investigated respectively. RESULTS: Fifty mutation-positive patients showed higher LA maximal volume index (59.4 ± 28.2 vs 43.8 ± 18.1 mL/m2, p = 0.001), lower reservoir (21.3 ± 7.9 vs 26.2 ± 6.6%, p < 0.001), and booster-pump strain (12.1 ± 5.4 vs 17.1 ± 5.0%, p < 0.001) but similar conduit strain (9.2 ± 4.5 vs 9.1 ± 4.5%, p = 0.909) compared with mutation-negative patients. In multivariate logistic regression, LA booster-pump strain was associated with sarcomere mutation (odds ratio = 0.86, 95% confidence interval: 0.77-0.96, p = 0.010) independent of maximal wall thickness, late gadolinium enhancement, and LA volume. Furthermore, LA booster-pump strain showed incremental value for mutation prediction added to Mayo II score (AUC 0.798 vs 0.709, p = 0.024). CONCLUSIONS: In HCM, mutation-positive patients suffered worse LA enlargement and worse reservoir and booster-pump functions. LA booster-pump strain was a strong factor for sarcomere mutation prediction added to Mayo II score. CLINICAL RELEVANCE STATEMENT: The independent association between sarcomere mutation and left atrial mechanical dysfunction provide new insights into the pathogenesis of atrial myopathy and is helpful to understand the adverse prognosis regarding atrial fibrillation and stroke in mutation-positive patients. KEY POINTS: • In patients with hypertrophic cardiomyopathy, left atrial (LA) reservoir and booster-pump function, but not conduit function, were significantly impaired in mutation-positive patients compared with mutation-negative patients. • LA booster-pump strain measured by MRI-derived feature tracking is feasible to predict sarcomere mutation with high incremental value added to Mayo II score.

Scar architecture affects the electrophysiological characteristics of induced ventricular arrhythmias in hypertrophic cardiomyopathy.

AIMS: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) detects myocardial scarring, a risk factor for ventricular arrhythmias (VAs) in hypertrophic cardiomyopathy (HCM). The LGE-CMR distinguishes core, borderzone (BZ) fibrosis, and BZ channels, crucial components of re-entry circuits. We studied how scar architecture affects inducibility and electrophysiological traits of VA in HCM. METHODS AND RESULTS: We correlated scar composition with programmed ventricular stimulation-inducible VA features using LGE intensity maps. Thirty consecutive patients were enrolled. Thirteen (43%) were non-inducible, 6 (20%) had inducible non-sustained, and 11 (37%) had inducible sustained mono (MMVT)- or polymorphic VT/VF (PVT/VF). Of 17 induced VA, 13 (76%) were MMVT that either ended spontaneously, persisted as sustained monomorphic, or degenerated into PVT/VF. Twenty-seven patients (90%) had LGE. Of these, 17 (57%) had non-sustained or sustained inducible VA. Scar mass significantly increased (P = 0.002) from non-inducible to inducible non-sustained and sustained VA patients in both the BZ and core components. Borderzone channels were found in 23%, 67%, and 91% of non-inducible, inducible non-sustained, and inducible sustained VA patients (P = 0.003). All 13 patients induced with MMVT or monomorphic-initiated PVT/VF had LGE. The origin of 10/13 of these VTs matched scar location, with 8/10 of these LGE regions showing BZ channels. During follow-up (20 months, interquartile range: 7-37), one patient with BZ channels and inducible PVT had an ICD shock for VF. CONCLUSION: Scar architecture determines inducibility and electrophysiological traits of VA in HCM. Larger studies should explore the role of complex LGE patterns in refining risk assessment in HCM patients.

Understanding the incidence of atrial fibrillation and stroke in hypertrophic cardiomyopathy patients: insights from Danish nationwide registries.

AIMS: The treatment of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) can be challenging since AF aggravates symptoms and increases the risk of stroke. Which factors contribute to the development of AF and stroke in HCM remains unknown. The aim of this study was to determine the incidence of AF and stroke in HCM patients and identify the risk factors. METHODS AND RESULTS: Using Danish national registries, all HCM patients from 2005 to 2018 were included. The association between HCM, incident AF, and stroke was investigated using multivariable Cox proportional hazards analysis. Cumulative incidences were calculated using the Aalen-Johansen estimator. Among the 3367 patients without prevalent AF, 24% reached the endpoint of incident AF with death as a competing risk. Median follow-up time was 4 years. Atrial fibrillation incidence was equal between sexes and increased for patients with ischaemic heart disease [IHD; hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.08-1.63], hypertension (HT) (HR 1.36, 95% CI 1.14-1.67), and obstructive HCM (HR 1.27, 95% CI 1.05-1.52). Seven per cent developed stroke, with no difference detected stratifying for the presence of AF. Sub-analysis revealed that when AF was treated with oral anticoagulants (OACs), stroke was less likely (HR 0.4, 95% CI 0.18-0.86, P = 0.02). However, 34% of patients were not receiving adequate anticoagulation following AF diagnosis. CONCLUSION: Obstructive HCM, HT, and IHD were associated with increased risk of AF. Prevalent AF alone was not predictive of stroke; however, AF patients treated with OAC were significantly less likely to develop stroke, suggesting that this development is driven by the protective effect of OAC. Despite this, 34% of patients did not receive OAC.

Comparison Between Heart Failure Without Left Ventricular Systolic Dysfunction and Progression to End-Stage in Hypertrophic Cardiomyopathy.

BACKGROUND: The incidence and prognostic predictors of heart failure (HF) without left ventricular systolic dysfunction (LVSD) in hypertrophic cardiomyopathy (HCM), particularly their differences in terms of developing LVSD (progression to end-stage) or sudden cardiac death (SCD), are not fully elucidated. METHODS AND RESULTS: This study included 330 consecutive HCM patients with left ventricular ejection fraction (LVEF) ≥50%. HF hospitalization without LVSD and development of LVSD were evaluated as main outcomes. During a median follow-up of 7.3 years, the incidence of HF hospitalization without LVSD was 18.8%, which was higher than the incidence of developing LVSD (10.9%) or SCD (8.8%). Among patients who developed LVSD, only 19.4% experienced HF hospitalization without LVSD before developing LVSD. Multivariable analysis showed that predictors for HF hospitalization without LVSD (higher age, atrial fibrillation, history of HF hospitalization, and higher B-type natriuretic peptide concentrations) were different from those of developing LVSD (male sex, lower LVEF, lower left ventricular outflow tract gradient, and higher tricuspid regurgitation pressure gradient). Known risk factors for SCD did not predict either HF without LVSD or developing LVSD. CONCLUSIONS: In HCM with LVEF ≥50%, HF hospitalization without LVSD was more frequently observed than development of LVSD or SCD during mid-term follow-up. The overlap between HF without LVSD and developing LVSD was small (19.4%), and these 2 HF events had different predictors.

Tailored Planning of Surgical Myectomy in Obstructive Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic myocardial disease characterized by abnormal thickening of the myocardium caused by myocardial disarray and interstitial fibrosis. HCM is associated with sudden cardiac-related events, such as ventricular fibrillation, tachycardia, and syncope. Moreover, left ventricular or midcavity obstruction due to the thickened myocardium can result in severe heart failure and mortality in patients with HCM. Surgical myectomy is a standard treatment option for patients with symptomatic obstructive HCM; however, it is a complex procedure that requires careful planning and execution to avoid complications, such as residual flow obstruction, persistent obliteration of the left ventricular cavity in systole, or iatrogenic ventricular septal defects. Therefore, a thorough understanding of the mechanics of HCM and precise evaluation of the location and extent of the hypertrophic myocardium to be removed are crucial for preoperative planning. Multiphase cardiac CT postprocessing is important for preoperative evaluation and planning of surgical myectomy in patients with HCM. In this review, the authors highlight use of multiphase cardiac CT with step-by-step postprocessing methods to simulate successful surgical myectomy. The transaortic surgeon's view on end-diastolic phase images accurately represents the surgical field. Moreover, myocardial segmentation can be used to generate volume-rendered images and three-dimensional printing. CT evaluation can also assist in identifying concurrent abnormalities, such as mitral valve or papillary muscle abnormalities. In addition to CT, other imaging modalities for preoperative evaluation of HCM and postmyectomy evaluation methods are presented. ©RSNA, 2023 Test Your Knowledge questions in the supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Association between postoperative nadir platelet count and postoperative cardiovascular complications following septal myectomy in patients with hypertrophic cardiomyopathy: a retrospective cohort study.

BACKGROUND: Platelet count is associated with cardiovascular risk and mortality in several cardiovascular diseases, but the association of the nadir platelet counts post-septal myectomy with the cardiovascular complication risk in hypertrophic obstructive cardiomyopathy patients remains unclear. METHODS: This retrospective cohort study reviewed all adult patients who underwent septal myectomy at a single tertiary referral center over a 5-year period. Postoperative nadir platelet count was defined as the lowest platelet count in the first 4 postoperative days or until hospital discharge. The composite outcome included cardiovascular death, myocardial infarction, heart failure, malignant arrhythmia, cardiac tamponade, and major bleeding events within 30 days postoperatively. Univariable and multivariable logistic regression and restricted cubic spline models were used to assess the association between postoperative nadir platelet count and the 30-day postoperative cardiovascular complication risk. RESULTS: Among the 113 enrolled patients, 23 (20.4%) developed cardiovascular events within 30 days postoperatively. The incidence of postoperative cardiovascular complications was significantly higher in patients with a nadir platelet count ≤ 99 × 109/L than in those with a nadir platelet count > 99 × 109/L (33.3% vs. 7.1%, crude risk ratio: 4.67, 95% confidence interval: 1.69-12.85, P < 0.001). Multivariable logistic regression revealed that postoperative nadir platelet count was negatively associated with 30-day postoperative cardiovascular complications (adjusted odds ratio: 0.97; 95% confidence interval: 0.95-0.99; P = 0.005) and the association was linear (Pnonlinearity = 0.058) after full adjustment. The association between nadir platelet count and cardiovascular complications within 30 days post-surgery was consistent in all predefined subgroups (Pinteraction > 0.05). CONCLUSION: The postoperative nadir platelet count was significantly associated with the 30-day post-myectomy risk of cardiovascular complications in hypertrophic obstructive cardiomyopathy patients. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT04275544).

A novel pathogenic variant in the carnitine transporter gene, SLC22A5, in association with metabolic carnitine deficiency and cardiomyopathy features.

BACKGROUND: Primary carnitine deficiency (PCD) denotes low carnitine levels with an autosomal recessive pattern of inheritance. Cardiomyopathy is the most common cardiac symptom in patients with PCD, and early diagnosis can prevent complications. Next-generation sequencing can identify genetic variants attributable to PCD efficiently. OBJECTIVE: We aimed to detect the genetic cause of the early manifestations of hypertrophic cardiomyopathy and metabolic abnormalities in an Iranian family. METHODS: We herein describe an 8-year-old boy with symptoms of weakness and lethargy diagnosed with PCD through clinical evaluations, lab tests, echocardiography, and cardiac magnetic resonance imaging. The candidate variant was confirmed through whole-exome sequencing, polymerase chain reaction, and direct Sanger sequencing. The binding efficacy of normal and mutant protein-ligand complexes were evaluated via structural modeling and docking studies. RESULTS: Clinical evaluations, echocardiography, and cardiac magnetic resonance imaging findings revealed hypertrophic cardiomyopathy as a clinical presentation of PCD. Whole-exome sequencing identified a new homozygous variant, SLC22A5 (NM_003060.4), c.821G > A: p.Trp274Ter, associated with carnitine transport. Docking analysis highlighted the impact of the variant on carnitine transport, further indicating its potential role in PCD development. CONCLUSIONS: The c.821G > A: p.Trp274Ter variant in SLC22A5 potentially acted as a pathogenic factor by reducing the binding affinity of organic carnitine transporter type 2 proteins for carnitine. So, the c.821G > A variant may be associated with carnitine deficiency, metabolic abnormalities, and cardiomyopathic characteristics.

Pregnancy related complications in women with hypertrophic cardiomyopathy: a nationwide population-based cohort study.

BACKGROUND: The impact of hypertrophic cardiomyopathy (HCM) on cardiovascular and obstetrical outcomes in pregnant women remains unclear, particularly in Asian populations. This study aimed to evaluate the maternal cardiovascular and obstetrical outcomes in Korean women with HCM. METHODS: Using data from the Korean National Health Insurance Service database, we identified women who gave birth via cesarean section or vaginal delivery after being diagnosed with HCM between 2006 and 2019. Maternal cardiovascular and obstetrical outcomes were assessed based on the trimester of pregnancy. RESULTS: This study included 122 women and 158 pregnancies. No maternal deaths were noted; however, 21 cardiovascular events, such as hospital admission for cardiac problems, including heart failure and atrial fibrillation (AF), new-onset AF or ventricular tachycardia (VT) occurred in 14 pregnancies (8.8%). Cardiac events occurred throughout pregnancy with a higher occurrence in the third trimester. Cesarean sections were performed in 49.3% of the cases, and all cardiovascular outcomes occurring after delivery were observed in patients who had undergone cesarean sections. Seven cases involved preterm delivery, and two of these cases were accompanied by cardiac events, specifically AF. Pre-existing arrhythmia (AF: odds ratio (OR): 7.44, 95% confidence interval (CI): 2.61-21.21, P < 0.001; VT: OR: 31.61, 95% CI: 5.85-172.77, P < 0.001) was identified as a predictor for composite outcomes of cardiovascular events or preterm delivery. CONCLUSIONS: Most pregnant women with HCM were well-tolerated. However, cardiovascular complications could occur in some patients. Therefore, planned delivery may be necessary for selected patients, especially the women with pre-existing arrhythmias.

Recurrent atrial flutter after radiofrequency ablation for atrial fibrillation in a patient with hypertrophic obstructive cardiomyopathy undergoing repetitive transcoronary ablation of septal hypertrophy.

INTRODUCTION: We described the clinical characteristics of a patient with hypertrophic obstructive cardiomyopathy (HOCM) who had undergone transcoronary ablation of septal hypertrophy (TASH) twice and developed atrial flutter after radiofrequency ablation for atrial fibrillation (AF) due to pulmonary vein reconnection. This case of HOCM is unique because of its complex complications and multiple complex atrial arrhythmias. The treatment of HOCM was successful and the postoperative follow-up results was good. METHODS AND RESULTS: A 71-year-oldfemale, developed exertional dyspnea with palpitations 12 years ago, with a valid diagnosis of HOCM according to the echocardiography which showed an absolute increase in the interventricular septum thickness (22.8 mm). She underwent two rounds of TASH and only the second round was successful. During a visit due to recurrent palpitations, the patient was diagnosed with AF based on electrocardiographic examination. Circumferential pulmonary vein isolation (CPVI) was performed to treat AF. However, the recurrence of atrial flutter was detected on her electrocardiograms (ECGs) three years after the operation. Since the patient had an interstitial lung injury, there were relative contraindications for antiarrhythmic drugs. Due to restrictive use of antiarrhythmic drugs and continuous palpitation, the patient agreed to receive a second radiofrequency ablation. Left-sided macroreentrant circuits were identified via high-density mapping and successful ablation was performed at the isthmus. CONCLUSIONS: Performing catheter ablation and TASH respectively in patients with HOCM associated with AF would be tricky. But taking such a comprehensive and respective clinical treatment would be beneficial to patients in the long term.

Catheter ablation versus antiarrhythmic drug therapy for sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM. METHODS: A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up. RESULTS: Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10-0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12-0.95]; P = 0.029). CONCLUSIONS: In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD.

Evaluating convolutional neural network-enhanced electrocardiography for hypertrophic cardiomyopathy detection in a specialized cardiovascular setting.

The efficacy of convolutional neural network (CNN)-enhanced electrocardiography (ECG) in detecting hypertrophic cardiomyopathy (HCM) and dilated HCM (dHCM) remains uncertain in real-world applications. This retrospective study analyzed data from 19,170 patients (including 140 HCM or dHCM) in the Shinken Database (2010-2017). We evaluated the sensitivity, positive predictive rate (PPR), and F1 score of CNN-enhanced ECG in a ''basic diagnosis'' model (total disease label) and a ''comprehensive diagnosis'' model (including disease subtypes). Using all-lead ECG in the "basic diagnosis" model, we observed a sensitivity of 76%, PPR of 2.9%, and F1 score of 0.056. These metrics improved in cases with a diagnostic probability of ≥ 0.9 and left ventricular hypertrophy (LVH) on ECG: 100% sensitivity, 8.6% PPR, and 0.158 F1 score. The ''comprehensive diagnosis'' model further enhanced these figures to 100%, 13.0%, and 0.230, respectively. Performance was broadly consistent across CNN models using different lead configurations, particularly when including leads viewing the lateral walls. While the precision of CNN models in detecting HCM or dHCM in real-world settings is initially low, it improves by targeting specific patient groups and integrating disease subtype models. The use of ECGs with fewer leads, especially those involving the lateral walls, appears comparably effective.

Hypertrophic Cardiomyopathy: Preadolescence, Mitral Valve Disease, and Midventricular Obstruction.

Septal myectomy is indicated in patients with obstructive hypertrophic cardiomyopathy (HCM) who have persistent symptoms despite medical therapy, intolerance of medication side effects, or severe resting or provocable gradients. Septal myectomy at high volume centers is safe, with low operative mortality (1%) and low rates of complications such as complete heart block or ventricular septal defect (3% and 0.5%, respectively). Additionally, improved survival following myectomy has been observed when compared to patients with obstructive HCM managed medically or those with nonobstructive HCM. As a longstanding, quaternary referral center for septal myectomy, our institution has built significant experience and expertise in the surgical and medical management of HCM, including atypical HCM, defined as preadolescent patients, those with mitral valve disease, and those with isolated midventricular obstruction. The most important factor of septal myectomy in achieving complete resolution of obstruction and avoiding recurrence is the apical extent of the myectomy trough, which must extend to the septum opposite the papillary muscles. If this cannot be fully achieved via a transaortic exposure, especially in preadolescents and patients with midventricular obstruction, then a transapical approach may be needed. Mitral valve repair is rarely necessary as SAM-mediated MR resolves with adequate myectomy alone, but mitral repair is performed in cases of intrinsic valvular disease. In this manuscript we provide a summary of current operative techniques and outcomes data from our institution on the management of these various categories of HCM.