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Summary Introduction Inducible laryngeal obstruction is a common and challenging cause of exertional dyspnea. We report a case of an unanticipated cardiac condition that presented with symptoms suggestive of inducible laryngeal obstruction. Discussion A 55-year-old man was evaluated for progressive exertional dyspnea and throat tightness, unexplained after multiple medical evaluations. Resting laryngeal examination was suspicious for laryngopharyngeal reflux and mild vocal fold adduction during quiet expiration. Given progressive and refractory symptoms, maximal cardiopulmonary exercise testing with intermittent laryngeal examination was performed. This study excluded laryngeal causes of exercise limitation and led to an unexpected diagnosis of persistent atrial flutter and hypertrophic cardiomyopathy. Conclusion Cardiopulmonary exercise testing with laryngeal examination can identify unexpected and life-threatening mimics of inducible laryngeal obstruction that may be missed by unmonitored exercise challenges. Suspicion for inducible laryngeal obstruction at rest may not predict the true nature of exercise limitation on cardiopulmonary exercise testing.

Rare variants in JPH2 have been associated with a range of cardiac disease, including hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), arrhythmias, and sudden cardiac death (SCD); however, our understanding of how variants in JPH2 correspond to specific modes of inheritance and correlate clinical phenotypes has not been comprehensively explored. In this systematic review, we assess current case reports and series that describe patients with JPH2 variants and cardiac disease. We identified a total of 61 variant-positive individuals, approximately 80% of whom had some form of cardiac disease, including 47% HCM, 18% DCM, and 14% arrhythmia/SCD. In analyzing the 24 probands described in the studies, we found that autosomal recessive, loss-of-function variants are associated with severe, early onset DCM, while autosomal dominant missense variants are associated with a wider range of cardiac disease, including HCM, arrhythmia, SCD, and cardiac conduction disease.

To determine the potential impact of referral bias on short- and long-term outcomes following septal myectomy for hypertrophic cardiomyopathy.We reviewed 2303 adult patients who underwent transaortic septal myectomy for obstructive hypertrophic cardiomyopathy from January 1993 to April 2016. Patients were divided into 3 groups according to their permanent address: local (state) residents (n = 324), regional (surrounding 5 states) patients (n = 515), and national (outside 5 states) patients (n = 1464).Patient groups were similar for age, sex, preoperative New York Heart Association class, and left ventricular ejection fraction. Local patients had increased prevalence of diabetes mellitus (13%, 11%, 8%; P = .006), coronary artery disease (25%, 21%, 19%; P = .031), severe chronic lung disease (2.3%, 1.9%, 0.4%; P .001), and atrial fibrillation (24%, 18%, 19%; P = .045) when compared with regional and national patients. Echocardiographic features did not differ between the 3 groups, including prevalence of moderate or greater mitral regurgitation (59%, 61%, 56%; P = .161). Local and regional patients were more likely to undergo concomitant procedures than national patients (P .001). Mitral valve surgery was performed in 9.6% of the patients, more commonly in local and regional patients (12%, 12%, 8%; P = .018). There were 11 operative deaths (0.5%), and early mortality was similar among the groups. Geographic origin did not impact overall late survival.Compared with distant referrals, local patients who undergo septal myectomy at our institution have more comorbid conditions, and require more concomitant surgical procedures. Despite these differences, referral patterns did not impact early or late outcomes following transaortic septal myectomy.

Introduction The etiology of sudden cardiac death (SCD) in young people continues to attract much attention. This meta-analysis aimed to identify the most frequent causes of SCD in individuals aged ≤35 years, the differences between athletes and non-athletes and geographic areas. Methods Studies published between 01/01/1990 and 01/31/2020 and evaluating post-mortem the aetiology of SCD in young individuals (≤35 years) were included. Individuals were divided into athletes and non-athletes. Studies that did not report separate data between athletes and non-athletes were excluded. Results Thirty-four studies met the inclusion criteria, and a total population of 5,060 victims of SCD were analyzed (2,890 athletes, 2,170 non-athletes). Comparing the causes of SCD between athletes and non-athletes, non-ischemic left ventricular scar (NILVS) (5.1% vs. 1.1%, p=0.01) was more frequent in the former, while coronary artery disease (CAD) (19.6% vs. 9.1%, p=0.009), arrhythmogenic cardiomyopathy (ACM) (11.5% vs. 4.7%, p=0.03) and channelopathies (8.4% vs. 1.9%, p=0.02) were more frequent in the latter. In studies published in the last decade, hypertrophic cardiomyopathy (HCM) (p=0.002), dilated cardiomyopathy (p=0.047), and anomalous origin of coronary arteries (AOCA) (p=0.009) were more frequently the causes of SCD in athletes while aortic dissection (0.022) was the cause in non-athletes. HCM (p=0.01) and AOCA (p=0.004) were more frequently the causes of SCD in the US while ACM (p=0.001), structurally normal heart (p=0.02), and channelopathies (p=0.02) were more frequent in Europe. Conclusions Among the causes of SCD, NILVS was the more frequent cause in athletes, while CAD, ACM and channelopathies were more frequent causes in non-athletes. The causes of SCD differ between the US and Europe.

Hypertrophic cardiomyopathy is a complex disease with significant implications for patients and the physicians called upon to care for them during the perioperative period. In this article, the 2020 American Heart Association and American College of Cardiology clinical practice guidelines for the evaluation and management of pediatric and adult patients with hypertrophic cardiomyopathy are reviewed, with a particular focus on perioperative considerations for the anesthesiologist.

We present a case of an extreme preterm infant (Baby X) born at 24-week gestation. The echocardiogram showed evidence of hypertrophic cardiomyopathy (HCM) and a patent ductus arteriosus (PDA). There are a number of well-known causes of neonatal HCM including genetic, metabolic and endocrine. PDA is commonly present in preterm infants, and this can contribute to cardiac remodelling and result in cardiac changes mimicking HCM. Furthermore, medications such as steroids can also cause HCM through various mechanisms. A careful consideration of all the different aetiologies for HCM is important for appropriate management of such cases. This report examines the evidence in the literature for the above differential diagnoses and highlights the challenges in diagnosing the underlying cause of HCM in a preterm infant.

Hypertrophic cardiomyopathy (HCM) is genetically heterogeneous. Different variants associated with HCM have been identified in several cardiac sarcomeric protein genes. We identified the heterozygous missense variant c.2191 C>A p. Pro 731 Thr in the MYH7 gene and the heterozygous frameshift variant c.1091–1092 insTGAA p.Lys364fs*in the MYH6 gene in a Japanese family. Family members with the double variants demonstrated severe phenotypes, such as sudden cardiac-related death and heart failure. These double variants were well segregated and might be responsible for the severity of cardiovascular events in affected family members. These double variants are potentially associated with specific phenotypes in HCM. Further studies are needed to analyze specific gene functions.

Background MicroRNAs are small, endogenous, non-coding RNAs that regulate the expression of many genes. It has recently been shown that circulating microRNAs may be biomarkers of hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy (HCM). Objective To determine whether circulating levels of microRNAs involved in HCM are associated with electrocardiographic and echocardiographic parameters. Methods This study enrolled 20 patients with familial HCM and 20 blood donors. Peripheral serum levels of miR-29a-3p, miR-199a-5p and miR-451a were assessed by quantitative real-time polymerase chain reaction and compared with levels in the control group. Whether circulating levels of miRNAs in HCM patients correlated with electrocardiographic and echocardiographic parameters was also assessed. Results Median circulating levels of miR-29a and miR-451a were significantly higher in HCM than the control group. Median miR-199a levels did not differ between groups. However, circulating levels of miR-199a negatively correlated with corrected QT duration (Bazett formula). Median miR-29a levels positively correlated with QRS duration. In addition, circulating levels of miR-29a correlated with maximal wall thickness, left ventricular mass index and left atrial volume index. Conclusions The data suggested that serum levels of miR-29a and miR-451a were significantly increased in HCM patients. As the circulating level of miR-29a correlated with QRS duration, left ventricular hypertrophy and left atrial dilatation, the serum miR-199a level negatively correlated with corrected QT duration. These miRNAs may be seen as potential biomarkers for further research in HCM pathophysiology.

Objective Some patients with obstructive hypertrophic cardiomyopathy may remain limited after surgical relief of the subaortic obstruction. In this report, we describe experience in surgical management of patients with advanced diastolic heart failure symptoms after adequate transaortic septal myectomy for obstructive hypertrophic cardiomyopathy. Methods We identified adult patients who presented with heart failure symptoms after previous transaortic septal myectomy for obstructive hypertrophic cardiomyopathy and underwent repeat sternotomy for transapical myectomy to enlarge a small left ventricular cavity. Functional recovery after hospital dismissal was assessed through a questionnaire-based survey. Results Six patients with previous septal myectomy presented with New York Heart Association functional class III symptoms. Preoperative transthoracic Doppler echocardiography confirmed adequate relief of subaortic outflow tract obstruction with only trivial or mild mitral valve regurgitation; left atrial volume index was increased at 46 mL/m2 (range, 44-47 mL/m2). Following transapical myectomy, the left ventricular diameter was enlarged from 23 mm (range, 21-27 mm) to 29 mm (range, 27-31 mm) at end-systole and from 40 mm (range, 38-42 mm) to 43 mm (range, 42-50 mm) at end-diastole. All the patients were alive after a median follow-up of 0.6 years (range, 0.4-3.5 years), and 5 patients responded to a postoperative survey and indicated improvement in their heart condition compared with functional status before the repeat myectomy. Conclusions Patients with diastolic heart failure after septal myectomy for obstructive hypertrophic cardiomyopathy may present with systolic cavity obliteration due to excessive myocardial hypertrophy. Repeat transapical myectomy can enlarge the left ventricular chamber and augment the diastolic volume, which results in improved physical capacity and patient-perceived functional status.

Cleft-like indentations (CLIs) of the mitral valve (MV) are best assessed with three-dimensional (3D) transesophageal echocardiography (TEE). The present study examined the prevalence, characteristics, and surgical effect of MV CLIs in patients with hypertrophic cardiomyopathy (HCM).Prospective, observational, case-control study.Tertiary medical center.The study comprised 90 patients with HCM undergoing myectomy and 59 patients undergoing cardiac surgery for non-MV related indications.Intraoperative 3D TEE was used to evaluate the presence and characteristics of MV CLIs compared, with a random control group of 59 patients undergoing cardiac surgery for non-MV related indications. Ninety patients with HCM (mean age 54.8 ± 13.3 y, 67.8% male) were compared with 59 control patients (mean age 67 ± 12.7 y, 79.7% male). Three-dimensional TEE images were interpreted by consensus of two experienced echocardiographers. At least one MV CLI was present in 84 patients with HCM (93.3%), compared with 23 control patients (39%; p0.01). Compared with control patients, patients with HCM were more likely to have deep MV CLIs (85.6% v 25.4%; p0.01) and ≥2 CLIs (52.2% v 26.1%; p = 0.02). Six HCM patients (7%) appeared to have true congenital posterior leaflet clefts versus 0% in control patients (p = 0.08). Preoperative mitral regurgitation severity and jet direction were not associated with the presence of deep or multiple MV CLIs (all p0.2). None of the MV CLIs in the HCM group required MV surgical intervention or second pump runs for MV regurgitation correction after myectomy.Deep and multiple MV CLIs are common in patients with HCM undergoing septal myectomy, including possible true posterior clefts, but they are not associated with the premyectomy severity of mitral regurgitation or jet direction, and do not result in surgical MV intervention.

Obesity is highly prevalent in patients with obstructive hypertrophic cardiomyopathy (HCM). In this study, we investigated the impact of body mass index (BMI) in patients undergoing septal myectomy (SM) for obstructive HCM.We reviewed 2746 patients who underwent transaortic SM for obstructive HCM from February 1993 through September 2018. Patients were stratified into 3 groups based on BMI (normal weight,25 kg/mPreoperatively, the median left ventricular outflow tract gradient was 58 mm Hg, and there was no difference in gradients across BMI strata (P = .35). The percentage of obese patients with moderate or greater mitral valve regurgitation was lower (45.8%) compared with normal weight (52.9%) and overweight (55.4%) patients (P.001). However, patients with a higher BMI were more likely to have New York Heart Association Functional Classification III/IV limitation at presentation (P.001). After myectomy, anteroseptal thickness (P = .115) and left ventricular outflow tract gradient (P = .210) did not differ between groups. There were 14 (0.5%) deaths within 30 days postoperatively, and the risk was similar across BMI strata (P = .448). Model-estimated changes in average BMI at 10 years postprocedure showed stratum-specific increases ranging from 0.60 to 1.56 kg/mSM is safe and effective in HCM patients with obesity, but the risk of late death increased with increasing BMI. Attention to risk factor management through weight loss may improve late results after SM.

OBJECTIVES It is not uncommon to observe some discrepancy in hemodynamic values characterizing left ventricular outflow tract (LVOT) obstruction preoperatively and in the operating room in patients with hypertrophic obstructive cardiomyopathy. Interpretation of this discrepancy can be challenging. To clarify the extent of the discrepancy, the authors compared hemodynamic variables in patients undergoing septal myectomy at the time of preoperative and intraoperative evaluation. DESIGN Retrospective study. SETTING Single academic medical center. INTERVENTIONS Medical records review, study group-173 patients. MEASUREMENTS AND MAIN RESULTS While there was no statistically significant difference in resting peak LVOT gradients by preoperative transthoracic echocardiography (TTE) compared to intraoperative transesophageal echocardiography (46 mmHg [19-87 mmHg] v 36 mmHg [16-71 mmHg], p = 0.231), the former were higher compared to direct needle-resting LVOT gradient measurements before myectomy (49 mmHg [19-88 mmHg] v 32 mmHg [14-67 mmHg], p = 0.0022). The prevalence of systolic anterior motion was high (94.6% v 91.6%, P = 1.000) both on pre- and intraoperative evaluation. The incidence of moderate/severe mitral was higher intraoperatively (p < 0.0001). Pulmonary artery systolic pressures measured by pulmonary artery catheter provided higher values compared to preoperative TTE estimate (39 mmHg [34-45 mmHg] v 34 mmHg [28-41 mmHg], p < 0.0001). CONCLUSIONS Discrepancy between hemodynamic measurements in the cardiac laboratory and operating room is common and generally should not affect planned patients' care. These changes in hemodynamics might be explained by preoperative fasting, anesthetic agents, volume shifts while supine, and positive-pressure ventilation, as well as the difference in measurement techniques.

У статті розглядається проблема гіпертрофічної кардіоміопатії. Наведено клінічний випадок ефективності радіочастотної абляції в умовах 3D-кардіонавігаційної системи із забезпеченням зниження градієнта тиску на виносному тракті протягом року у хворого з недостатньою ефективністю двох алкогольних абляцій., В статье рассматривается проблема гипертрофической кардиомиопатии. Приведен клинический случай эффективности радиочастотной абляции в условиях 3D-кардионавигационной системы с обеспечением снижения градиента давления на выносящем тракте в течение года у больного с недостаточной эффективностью двух алкогольных абляций., The article deals with the problem of hypertrophic cardiomyopathy. A clinical case is presented on the efficiency of radiofrequency ablation using 3D cardionavigation system to reduce the pressure gradient in the outflow tract for a year in a patient with lack of efficacy of two alcohol ablations.

Мета роботи: вивчення прогностичної цінності рівня галектину-3 (Гал-3) у хворих з гіпертрофічною кардіоміопатією (ГКМП). Матеріали та методи. Вивчено клініко-анамнестичні та інструментальні дані у 90 пацієнтів з ГКМП, з яких 76 обстежені повторно через 12 ± 3 міс. лікування. Методи обстеження: електрокардіографія, ехокардіографія, добове моніторування електрокардіограми і визначення вмісту Гал-3 в сироватці крові імуноферментним методом. Результати. Повторне вивчення даних загальноклінічних та інструментальних досліджень, а також рівня Гал-3 в сироватці крові хворих з ГКМП через 12 ± 3 міс. після первинного огляду дозволило виділити дві групи хворих: зі стабільним і прогресуючим перебігом захворювання. Прогресуючий перебіг ГКМП частіше спостерігався при її обструктивному варіанті, наявності супутньої ішемічної хвороби серця, артеріальної гіпертензії, постійної форми фібриляції передсердь і тяжких форм серцевої недостатності. З даних інструментальних досліджень найбільш інформативними були показники ехокардіоскопії, які дозволили встановити, що при прогресуючому перебігу ГКМП відзначається розвиток систолічної та діастолічної дисфункції лівого шлуночка. Однак найбільш значущу кореляцію з прогресуючим перебігом ГКМП мало вихідне збільшення рівня Гал-3, що свідчить про прогностичне значення визначення даного показника у хворих з ГКМП. У підсумкову регресійну модель прогнозу перебігу ГКМП увійшли тяжка серцева недостатність, рівень Гал-3 і показники ехокардіоскопії, що характеризують систолічну і діастолічну функції лівого шлуночка. Ефективність запропонованої моделі прогнозу перебігу ГКМП становила 90,8 %, що свідчить про можливість її практичного застосування. Висновки. Початкове підвищення рівня Гал-3 у хворих з ГКМП асоційоване з прогресуючим перебігом захворювання, оцінка його рівня в комплексі з клініко-інструментальними показниками доцільна для прогнозування перебігу ГКМП.

У статті наведено опис клінічного випадку апікальної гіпертрофічної кардіоміопатії у пацієнта 60 років. Детально обговорюються діагностика і вибір тактики лікування з урахуванням даних досліджень, описаних у літературі.

Background: Heart failure is a hallmark of severe hypertrophic cardiomyopathy and dilated cardiomyopathy (DCM). Several mutations in the β-MYH7 gene lead to hypertrophic cardiomyopathy. Recently, causative mutations in the β-MYH7 gene have also been detected in DCM from different populations. Methods: Here, we sequenced the β-MYH7 gene in 137 Indian DCM patients and 167 ethnically matched healthy controls to detect the frequency of mutations and their association. Results: Our study revealed 27 variations, of which 7 mutations (8.0%) were detected exclusively in Indian DCM patients for the first time. These included 4 missense mutations—Arg723His, Phe510Leu, His358Leu, and Ser384Tyr (2.9%); a frameshift mutation—Asn676_T-del (1.5%); and 2 splice-site mutations (IVS17+2T) T>G and (IVS19-1G) G>A (3.6%). Remarkably, all 4 missense mutations altered evolutionarily conserved amino acids. All 4 missense mutations were predicted to be pathogenic by 2 bioinformatics tools—polymorphism phenotyping v2 (PolyPhen-2) and sorting intolerant from tolerant (SIFT). In addition, the 4 homology models of β-MYH7—p.Leu358, p.Tyr384, p.Leu510, and p.His723—displayed root-mean-square deviations of ∼2.55 Å, ∼1.24 Å, ∼3.36 Å, and ∼3.86 Å, respectively. Conclusions: In the present study, we detected numerous novel, unique, and rare mutations in the β-MYH7 gene exclusively in Indian DCM patients (8.0%). Here, we demonstrated how each mutant (missense) uniquely disrupts a critical network of non-bonding interactions at the mutation site (molecular level) and may contribute to development of dilated cardiomyopathy (DCM). Therefore, our findings may provide insight into the understanding of the molecular bases of disease and into diagnosis along with promoting novel therapeutic strategies (through personalized medicine). Résumé: Introduction: L’insuffisance cardiaque est une caractéristique de la cardiomyopathie hypertrophique grave et de la cardiomyopathie dilatée (CMD). Plusieurs mutations dans le gène β-MYH7 conduisent à la cardiomyopathie hypertrophique. Récemment, les mutations causales dans le gène β-MYH7 ont également été détectées au sein de différentes populations atteintes de CMD. Méthodes: Ici, nous avons séquencé le gène β-MYH7 de 137 patients indiens atteints de CMD et de 167 témoins sains appariés selon l’origine ethnique pour détecter la fréquence des mutations et leur association. Résultats: L’étude nous a permis de révéler 27 variations, dont sept mutations (8,0 %) étaient exclusivement détectées chez les patients indiens atteints de CMD pour la première fois. Parmi ces mutations, nous avons observé quatre mutations faux-sens—Arg723His, Phe510Leu, His358Leu et Ser384Tyr (2,9 %), une mutation par déphasage—Asn676_T-del (1,5 %) et deux mutations des sites d’épissage (IVS17+2T) T>G et (IVS19-1G) G>A (3,6 %). Étonnamment, les quatre mutations faux-sens changeaient les acides aminés évolutivement conservés. Selon deux outils bioinformatiques—PolyPhen-2 (de l’anglais, polymorphism phenotyping v2) et SIFT (de l’anglais, sorting intolerant from tolerant), les quatre mutations faux-sens devaient être pathogènes. De plus, les quatre modélisations de β-MYH7 par homologie—p.Leu358, p.Tyr384, p.Leu510 et p.His723—affichaient de façon respective des écarts quadratiques moyens de ∼2,55 Å, ∼1,24 Å, ∼3,36 Å et ∼3,86 Å. Conclusions: Dans la présente étude, nous avons détecté de nombreuses nouvelles mutations, uniques et rares, dans le gène β-MYH7, exclusivement chez les patients indiens atteints de CMD (8,0 %). Ici, nous avons démontré comment chaque mutant (faux-sens) perturbe de manière unique un réseau essentiel d’interactions non liantes au site de mutation (moléculaire) et peut contribuer à la survenue de la CMD. Par conséquent, les conclusions de notre étude peuvent donner un aperçu des bases moléculaires de la maladie et du diagnostic tout en favorisant la promotion de nouvelles stratégies thérapeutiques (par la médecine personnalisée).

Mitochondrial diseases (MD) include an heterogenous group of systemic disorders caused by sporadic or inherited mutations in nuclear or mitochondrial DNA (mtDNA), causing impairment of oxidative phosphorylation system. Hypertrophic cardiomyopathy is the dominant pattern of cardiomyopathy in all forms of mtDNA disease, being observed in almost 40% of the patients. Dilated cardiomyopathy, left ventricular noncompaction, and conduction system disturbances have been also reported. In this article, the authors discuss the current clinical knowledge on MD, focusing on diagnosis and management of mitochondrial diseases caused by mtDNA mutations.

Background The aim of our study was to assess the performance of the new American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines, with respect to sudden cardiac death (SCD) prevention, in comparison with the established risk score of the European Society of Cardiology (hypertrophic cardiomyopathy [HCM] Risk-SCD), in a large Mediterranean cohort of HCM patients. Methods The clinical and imaging characteristics of 784 HCM patients (mean age at first evaluation 52 ± 16 years, 67.2% males) were analyzed retrospectively. The sensitivity, specificity, and negative predictive value for SCD events of the presence of ≥1 risk factor for SCD according to the ACC/AHA Guidelines 2020 and of the HCM Risk-SCD≥6% and HCM Risk-SCD≥4% were estimated during follow-up. Results During follow-up, 47 (6%) patients suffered an SCD event. The presence of ≥1 major risk factor for SCD according to the new ACC/AHA Guidelines had 96% sensitivity (95% CI 85.5-99.5%) with modest specificity of 59% (95% CI 55-62.2%) and negative predictive value of 99.5% (95% CI 98.2-99.9%). On the contrary, HCM- Risk-SCD≥6% had a relatively low sensitivity (32%, 95% CI 19.1-47.1%) and high specificity of 95% (95% CI 93.1-96.4%), whereas, HCM-Risk-SCD≥4% had sensitivity of 60% (95% CI 44-74%) and specificity of 83.9% (95% CI 80-85.6%). Both the HCM Risk-SCD cut-off values demonstrated lower negative predictive value but higher accuracy than the ACC/AHA algorithm for SCD prediction. Conclusion The novel ACC/AHA proposed algorithm identifies most of the patients with an SCD event with the cost of numerous defibrillator implantations. HCM-Risk-SCD demonstrated higher specificity, whereas its sensitivity and negative predictive value are modest.

BACKGROUND: Few studies have demonstrated the performance of regional strain by cardiovascular magnetic resonance (CMR) feature tracking in hypertrophic cardiomyopathy (HCM) patients, and the prognostic value of segmental strain remains unknown. This study aimed to explore the prognostic implications of strain parameters generated by CMR feature tracking analysis in HCM patients. METHODS: In total, 104 clinically diagnosed HCM patients and 30 healthy volunteers were enrolled in this study, and all patients underwent a standard CMR examination. Global and regional strain was computed by short axis, 2-, 3-, and 4-chamber view cine MR imaging using specialized software. Cardiac structure, function, and myocardial strain were compared between the control group and HCM patients, and the event and event-free groups. Univariate and multivariate Cox regression analyses were performed to evaluate the correlations between clinical and CMR parameters and poor prognosis. RESULTS: During the follow-up time, 8 patients reached the primary end points and 14 patients reached secondary end points. Regional radial strain of hypertrophic segments (RRS) and regional circumferential strain of hypertrophic segments (RCS) were worse in HCM patients with primary and secondary end points. In univariate Cox regression analysis of RRS, RCS were associated with primary and secondary end points. Regional radial strain of hypertrophic segments [hazard ratio (HR) 1.64, 95% confidence interval (CI): 1.13–2.38] and RCS (HR 2.35, 95% CI: 1.20–4.59) were independent predictors of primary end points, and RRS (HR 1.71, 95% CI: 1.09–2.66) and RCS (HR 2.63, 95% CI: 1.20–5.75) remained independent predictors of secondary end points in multivariate analysis. Kaplan-Meier survival curves indicated patients with RRS

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a homozygous GAA triplet repeat expansion in the frataxin gene. Cardiac involvement, usually manifesting as hypertrophic cardiomyopathy, can range from asymptomatic cases to severe cardiomyopathy with progressive deterioration of the left ventricular ejection fraction and chronic heart failure. The management of cardiac involvement is directed to prevent disease progression and cardiovascular complications. However, direct-disease therapies are not currently available for FRDA. The present review aims to describe the current state of knowledge regarding cardiovascular involvement of FRDA, focusing on clinical-instrumental features and management of cardiac manifestation.

RASopathies are multisystemic disorders caused by germline mutations in genes linked to the RAS/mitogen-activated protein kinase pathway. Diagnosis of RASopathy can be triggered by clinical clues ("red flags") which may direct the clinician toward a specific gene test. Compared with sarcomeric hypertrophic cardiomyopathy, hypertrophic cardiomyopathy in RASopathies (R-HCM) is associated with higher prevalence of congestive heart failure and shows increased prevalence and severity of left ventricular outflow tract obstruction. Biventricular involvement and the association with congenital heart disease, mainly pulmonary stenosis, have been commonly described in R-HCM. The aim of this review is to assess the prevalence and unique features of R-HCM and to define the available therapeutic options.

Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage disease caused by pathogenic variants in the GLA gene. Cardiac involvement is common in FD and is responsible for impaired quality of life and premature death. The classic cardiac involvement is a nonobstructive form of hypertrophic cardiomyopathy, usually manifesting as concentric left ventricular hypertrophy, with subsequent arrhythmogenic intramural fibrosis. Treatment of patients with FD should be directed to prevent the disease progression to irreversible organ damage and organ failure. The aim of this review is to describe the current state of knowledge regarding cardiovascular involvement in FD, focusing on clinical and instrumental features, cardiovascular management, and targeted therapy.

Highlights • Knowledge of the genetic etiologies of cardiomyopathies has created novel opportunities for treatments. • Emerging treatments targets include gene therapy, myofilament function, protein quality control, and metabolism. • Consideration of the genetic cause, biophysical context, and cardiomyopathy disease stage will be critical to the success of these novel treatments., Summary The primary etiology of a diverse range of cardiomyopathies is now understood to be genetic, creating a new paradigm for targeting treatments on the basis of the underlying molecular cause. This review provides a genetic and etiologic context for the traditional clinical classifications of cardiomyopathy, including molecular subtypes that may exhibit differential responses to existing or emerging treatments. The authors describe several emerging cardiomyopathy treatments, including gene therapy, direct targeting of myofilament function, protein quality control, metabolism, and others. The authors discuss advantages and disadvantages of these approaches and indicate areas of high potential for short- and longer term efficacy., Central Illustration

The prevalence and contribution of cardiotropic viruses to various expressions of heart failure are increasing, yet primarily underappreciated and underreported due to variable clinical syndromes, a lack of consensus diagnostic standards and insufficient clinical laboratory tools. In this study, we developed an advanced methodology for identifying viruses across a spectrum of heart failure patients. We designed a custom tissue microarray from 78 patients with conditions commonly associated with virus-related heart failure, conditions where viral contribution is typically uncertain, or conditions for which the etiological agent remains suspect but elusive. Subsequently, we employed advanced, highly sensitive in situ hybridization to probe for common cardiotropic viruses: adenovirus 2, coxsackievirus B3, cytomegalovirus, Epstein–Barr virus, hepatitis C and E, influenza B and parvovirus B19. Viral RNA was detected in 46.4% (32/69) of heart failure patients, with 50% of virus-positive samples containing more than one virus. Adenovirus 2 was the most prevalent, detected in 27.5% (19/69) of heart failure patients, while in contrast to previous reports, parvovirus B19 was detected in only 4.3% (3/69). As anticipated, viruses were detected in 77.8% (7/9) of patients with viral myocarditis and 37.5% (6/16) with dilated cardiomyopathy. Additionally, viruses were detected in 50% of patients with coronary artery disease (3/6) and hypertrophic cardiomyopathy (2/4) and in 28.6% (2/7) of transplant rejection cases. We also report for the first time viral detection within a granulomatous lesion of cardiac sarcoidosis and in giant cell myocarditis, conditions for which etiological agents remain unknown. Our study has revealed a higher than anticipated prevalence of cardiotropic viruses within cardiac muscle tissue in a spectrum of heart failure conditions, including those not previously associated with a viral trigger or exacerbating role. Our work forges a path towards a deeper understanding of viruses in heart failure pathogenesis and opens possibilities for personalized patient therapeutic approaches., The prevalence and contribution of viruses to heart failure phenotypes are increasingly recognized, while still underappreciated and underreported. We designed a tissue microarray with cardiac muscle tissue from 78 heart failure patients and probed for common cardiotropic viruses via in situ hybridization. Viral RNA was detected in 46.4% of patients, higher than anticipated for these heart failure conditions that include those not previously associated with a viral trigger or an exacerbating role.

Background Myocardial replacement fibrosis is one of the major histologic features of hypertrophic cardiomyopathy (HCM), but its characteristics have not been well delineated. Purpose To clarify the characteristics of replacement fibrosis in HCM and to evaluate the prognostic value of the regional extent of fibrosis. Materials and Methods This prospective study evaluated participants with HCM who underwent contrast-enhanced cardiac MRI from March 2011 to April 2019. For each participant, global and 16-segment extent of late gadolinium enhancement (LGE) in the left ventricle (LV) at cardiac MRI was analyzed. The primary end point was all-cause death. Results Among the 798 study participants enrolled (median age, 49 years [interquartile range {IQR}: 38-59 years]; 508 men), 588 (74%) underwent whole-exome sequencing. Thirty-five participants (4%) experienced death from any cause during a median follow-up of 2.9 years (IQR: 1.5-4.7 years). Spearman analysis showed weak correlations between the extent of LGE and wall thickness (LGE of global LV and maximal LV wall thickness

Hypertrophic cardiomyopathy (HCM) is a complex disease characterized by thickening of the cardiac muscle. Common symptoms include chest pain, shortness of breath, palpitations, fatigue and syncope (fainting), which are often confused for other conditions. Clinical treatment focuses on the relief of symptoms with medical therapies, which provide adequate to more variable symptomatic relief. Patients may experience more severe complications that require surgical intervention, such as implantable cardioverter-defibrillator therapy or septal myectomy. Despite the potential impact on quality of life, the humanistic burden of HCM is not well established. Here, we present four patient testimonials that highlight challenges faced by patients and clinicians in diagnosing HCM and managing symptoms. These testimonials provide valuable information on the spectrum and expression of HCM across generations. Such testimonials can better inform disease diagnosis and monitoring, maximizing quality of life and improving disease outcome.

We report a case of rapidly progressed cardiac remodeling in a child with hypertrophic cardiomyopathy. Three and a half years after the diagnosis of hypertrophic cardiomyopathy, arrhythmia and heart failure due to aggravated septal hypertrophy and left ventricle apical aneurysm progressed, and a heart transplant was performed.

Broad cellular functions and diseases including muscular dystrophy, arrhythmogenic right ventricular cardiomyopathy (ARVC5) and cancer are associated with transmembrane protein43 (TMEM43/ LUMA). The study aimed to investigate biological roles of TMEM43 through genetic regulation, gene pathways and gene networks, candidate interacting genes, and up- or downstream regulators. Cardiac transcriptomes from 40 strains of recombinant inbred BXD mice and two parental strains representing murine genetic reference population (GRP) were applied for genetic correlation, functional enrichment, and coexpression network analysis using systems genetics approach. The results were validated in a newly created knock-in Tmem43-S358L mutation mouse model (Tmem43S358L) that displayed signs of cardiac dysfunction, resembling ARVC5 phenotype seen in humans. We found high Tmem43 levels among BXDs with broad variability in expression. Expression of Tmem43 highly negatively correlated with heart mass and heart rate among BXDs, whereas levels of Tmem43 highly positively correlated with plasma high-density lipoproteins (HDL). Through finding differentially expressed genes (DEGs) between Tmem43S358L mutant and wild-type (Tmem43WT) lines, 18 pathways (out of 42 found in BXDs GRP) that are involved in ARVC, hypertrophic cardiomyopathy, dilated cardiomyopathy, nonalcoholic fatty liver disease, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease were verified. We further constructed Tmem43-mediated gene network, in which Ctnna1, Adcy6, Gnas, Ndufs6, and Uqcrc2 were significantly altered in Tmem43S358L mice versus Tmem43WT controls. Our study defined the importance of Tmem43 for cardiac- and metabolism-related pathways, suggesting that cardiovascular disease-relevant risk factors may also increase risk of metabolic and neurodegenerative diseases via TMEM43-mediated pathways.

Hypertrophic cardiomyopathy (HCM) is a common cause of sudden cardiac death in athletes. Cardiac Magnetic Resonance (CMR) imaging is considered an excellent tool to differentiate between HCM and athlete's heart. The aim of this systematic review was to highlight the novel CMR-derived parameters with significant discriminative capacity between the two conditions. A systematic search in the MEDLINE, EMBASE and Cochrane Reviews databases was performed. Eligible studies were considered the ones comparing novel CMR-derived parameters on athletes and HCM patients. Therefore, studies that only examined Cine-derived volumetric parameters were excluded. Particular attention was given to binary classification results from multi-variate regression models and ROC curve analyses. Bias assessment was performed with the Quality Assessment on Diagnostic Accuracy Studies. Five (5) studies were included in the systematic review, with a total of 284 athletes and 373 HCM patients. Several novel indices displayed discriminatory potential, such as native T1 mapping and T2 values, LV global longitudinal strain, late gadolinium enhancement and whole-LV fractal dimension. Diffusion tensor imaging enabled quantification of the secondary eigenvalue angle and fractional anisotropy in one study, which also proved capable of reliably detecting HCM in a mixed athlete/patient sample. Several novel CMR-derived parameters, most of which are currently under development, show promising results in discerning between athlete's heart and HCM. Prospective studies examining the discriminatory capacity of all promising modalities side-by-side will yield definitive answers on their relative importance; diagnostic models can incorporate the best performing variables for optimal results.

We describe a 55 year old male diagnosed with cardiomyopathy due to Fabry disease. Biochemical testing of blood spot and plasma showed low-normal alpha-galactosidase A (α-Gal A) levels. Genetic testing revealed somatic mosaicism for GLA c.901C>T, p.(Arg301Ter). Usually, males with Fabry disease due to loss of function variants in GLA show symptoms of the multisystemic features of the condition early in life, and have very low levels of the α-Gal A enzyme. This demonstrates that the diagnosis of Fabry disease in males with cardiomyopathy should still be considered even in the context of a normal plasma enzyme assay.

Hypertrophic cardiomyopathy, one of the most common genetic cardiovascular conditions, will be encountered by nearly every health-care provider regardless of specialty. In 2020, new hypertrophic cardiomyopathy management guidelines were published, updating and evolving preceding versions. This Seminar provides a concise review and practical guide to the updated recommendations for patients with hypertrophic cardiomyopathy.

ObjectiveThis study describes the influence of sex and disease phenotype on the occurrence of cardiac events in Fabry disease (FD).MethodsCardiac events from birth to last visit (median age 50 years) were recorded for 213 patients with FD. Patients were categorised as follows : men with classical FD (n=57), men with non-classical FD (n=26), women with classical FD (n=98) and women with non-classical FD (n=32), based on the presence of classical FD symptoms, family history (men and women), biomarkers and residual enzyme activity (men). Event rates per 1000 patient-years after the age of 15 years and median event-free survival (EVS) age were presented. Influence of disease phenotype, sex and their interaction was studied using Firth’s penalised Cox regression.ResultsThe event rates of major cardiovascular events (combined endpoint cardiovascular death (CVD), heart failure (HF) hospitalisation, sustained ventricular arrhythmias (SVAs) and myocardial infarction) were 11.0 (95% CI 6.6 to 17.3) in men with classical FD (EVS 55 years), 4.4 (95% CI 2.5 to 7.1) in women with classical FD (EVS 70 years) and 5.9 (95% CI 2.6 to 11.6) in men with non-classical FD (EVS 70 years). None of these events occurred in women with non-classical FD. Sex and phenotype significantly influenced the risk of major adverse cardiovascular event. CVD was the leading cause of death (75%) to which HF contributed most (42%). The overall rate of SVA was low (14 events in nine patients (4%)).ConclusionsSex and phenotype greatly influence the risk and age of onset of cardiac events in FD. This indicates the need for patient group-specific follow-up and treatment.

Little is known about clinical symptomatology and genetics of juvenile onset Pompe disease (JOPD). The aims of this study were to analyze how these children are diagnosed, what clinical problems they have, and how phenotype is related to genotype. To accomplish this, we analyzed retrospectively data of 34 patients diagnosed after their first and before completion of their 18th birthday. Median age at diagnosis was 3.9 (range 1.1–17) years. Eight patients (23.5%) developed initial symptoms in the first year, 12 (35%) between 1 and 7 years, and 6 (18%) thereafter. Eight (23.5%) had no clinical symptoms at the time of diagnosis. Indications for diagnostics were a positive family history in three (9%), hyperCKemia in eight (23.5%), motor developmental delay in three (9%), and muscle weakness and/or pain in 17 (50%). Rare clinical signs were failure to thrive, recurrent diarrhea, and suspected hepatopathy with glycogen storage. Thirty-two different mutations were identified. Twenty-seven patients (79.5%) carried the milder c.32–13T > G mutation, known to be associated with a broad range of phenotypes. Three out of eight patients manifesting within the first year of life showed generalized muscle weakness, hypertrophic cardiomyopathy, and had to be ventilated during the course of disease, thereby demonstrating clinical overlap with infantile onset Pompe disease.These findings demonstrate that the phenotype of JOPD is broad and that the differential is not only restricted to neuromuscular disorders. Genotypic analysis was useful to delineate subjects with early onset JOPD from those with IOPD, but overall genotype–phenotype correlation was poor.

We report a case of a patient presenting with arrhythmogenic cardiomyopathy, myofibrillar myopathy, and multiorgan tumors. A 41-year-old woman with a history of hypertrophic cardiomyopathy, diagnosed at 6 years of age, developed scoliosis after puberty. Following spinal surgery to address the scoliosis, she developed recurrent severe arrhythmia and heart failure. She developed hypoventilation at age 29 years. Proximal dominant weakness and mild elevation of serum creatine kinase indicated possible myopathy. Myofibrillar myopathy was diagnosed by muscle biopsy at age 30 year. Acute abdomen was repeatedly reported from age 33 years, eventually leading to a diagnosis of gastric polyp and erosive ulcer. A urinary bladder tumor was found at age 35 years, and breast cancer was diagnosed at age 40 years. Whole exome sequencing detected a heterozygous missense mutation in Filamin C. Recent evidences suggest that filamins are associated with tumors, and this case further highlights the clinical spectrum of filaminopathy.

Aims The outcomes of patients with hypertrophic cardiomyopathy with left ventricular systolic dysfunction (HCM‐LVSD) undergoing left ventricular assist device (LVAD) implantation remain unclear. We retrospectively evaluated the clinical impact of LVAD implantation on clinical outcomes, including haemodynamics and brain natriuretic peptide (BNP) levels, in patients with HCM‐LVSD, in comparison with those with dilated cardiomyopathy (DCM). Methods and results In this retrospective, single‐centre, observational study conducted in Japan, the medical records of patients who underwent LVAD implantation in the National Cerebral and Cardiovascular Center between 2011 and 2020 were reviewed. We enrolled 96 patients with DCM (average age: 43.5 years; 73 men) and 24 patients with HCM‐LVSD (average age: 48.3 years; 16 men). The HCM‐LVSD group had smaller left ventricles with thicker ventricular walls than the DCM group, which became more prominent after LVAD implantation. Preoperatively, BNP values were comparable between both groups; however, 3 months post‐implantation, they were significantly higher in the HCM‐LVSD group. Pulmonary artery pulsatility index, right ventricular stroke work index, and cardiac index were lower, and right atrial pressure was higher, in the HCM‐LVSD group, suggesting subclinical impairment of right ventricular function. The HCM‐LVSD group demonstrated equivalent outcomes, including overall survival, cerebrovascular accidents, right ventricular failure, LVAD‐related infections, arrhythmia, and aortic insufficiency, post‐implantation. Conclusions Despite a decreased right ventricular function with higher BNP values, patients with HCM‐LVSD and DCM showed comparable outcomes post‐LVAD implantation.

Objective: In this study, we aimed to compare the functional adaptations of the left ventricle in variant forms of left ventricular hypertrophy (LVH) and to evaluate the use of two-dimensional speckle tracking echocardiography (2D-STE) in differential diagnosis and prognosis. Methods: This was a prospective cohort study of 68 patients with LVH, including 20 patients with non-obstructive hypertrophic cardiomyopathy (HCM), 23 competitive top-level athletes free of cardiovascular disease, and 25 patients with hypertensive heart disease (HHD). All the subjects underwent 2D transthoracic echocardiography (TTE) and 2D-STE. The primary endpoint was all-cause mortality. Global longitudinal strain (GLS) below −12.5% was defined as severely reduced strain, −12.5% to −17.9% as mildly reduced strain, and above −18% as normal strain. Results: The mean LV-GLS value was higher in athletes than in patients with HCM and HHD with the lowest value being in the HCM group (HCM: −11.4±2.2%; HHD: −13.6±2.6%; and athletes: −15.5±2.1%; p

A man in his 60s was referred to our clinic as a part of preoperative evaluation for non-cardiac surgery. The patient did not have any cardiovascular symptoms and had never been evaluated previously. Examination revealed a low volume pulse and an ejection systolic murmur best heard in the left parasternal region. An early diastolic murmur was also heard. The ejection systolic murmur decreased in intensity with Valsalva manoeuvre. ### Question The transthoracic echocardiogram is shown in figure 1 (online supplemental video). What is the diagnosis? ### Supplementary video [heartjnl-2021-319841supp001.mp4] Figure 1 Transthoracic echocardiography (A) Apical five-chamber view. (B) Colour Doppler imaging. 1. Hypertrophic cardiomyopathy (HCM) 2. Valvular aortic stenosis 3. Supravalvular aortic stenosis 4. Subaortic membrane The echocardiogram shows a discrete subaortic membrane causing subvalvular aortic stenosis. The colour Doppler across aortic …

Background: Hypertrophic cardiomyopathy (HCM) is a complex disease partly explained by the effects of individual gene variants on sarcomeric protein biomechanics. At the cellular level, HCM mutations most commonly enhance force production, leading to higher energy demands. Despite significant advances in elucidating sarcomeric structure–function relationships, there is still much to be learned about the mechanisms that link altered cardiac energetics to HCM phenotypes. In this work, we test the hypothesis that changes in cardiac energetics represent a common pathophysiologic pathway in HCM. Methods: We performed a comprehensive multiomics profile of the molecular (transcripts, metabolites, and complex lipids), ultrastructural, and functional components of HCM energetics using myocardial samples from 27 HCM patients and 13 normal controls (donor hearts). Results: Integrated omics analysis revealed alterations in a wide array of biochemical pathways with major dysregulation in fatty acid metabolism, reduction of acylcarnitines, and accumulation of free fatty acids. HCM hearts showed evidence of global energetic decompensation manifested by a decrease in high energy phosphate metabolites (ATP, ADP, and phosphocreatine) and a reduction in mitochondrial genes involved in creatine kinase and ATP synthesis. Accompanying these metabolic derangements, electron microscopy showed an increased fraction of severely damaged mitochondria with reduced cristae density, coinciding with reduced citrate synthase activity and mitochondrial oxidative respiration. These mitochondrial abnormalities were associated with elevated reactive oxygen species and reduced antioxidant defenses. However, despite significant mitochondrial injury, HCM hearts failed to upregulate mitophagic clearance. Conclusions: Overall, our findings suggest that perturbed metabolic signaling and mitochondrial dysfunction are common pathogenic mechanisms in patients with HCM. These results highlight potential new drug targets for attenuation of the clinical disease through improving metabolic function and reducing mitochondrial injury.

Objectives Septal myectomy remains the gold standard treatment for symptomatic left ventricular outflow tract obstruction refractory to medical treatment. It is recommended that this operation be performed in dedicated hypertrophic obstructive cardiomyopathy centres by experienced surgeons. The septal myectomy option remains unavailable to many patients based solely on geography, including those who would clearly benefit more substantially from surgery than other therapeutic options. Here, we share our experience in starting new hypertrophic cardiomyopathy programmes. Methods We retrospectively reviewed initial septal myectomy experiences at two hypertrophic cardiomyopathy programmes starting in 2014. Results Two-hundred septal myectomies were performed. Mean age was 58.8 years and 51% were females. Advanced heart failure symptoms were present in 95.5% of patients and 23.5% had experienced syncope. Mean maximal intraventricular gradient was 89 mmHg and 48.5% underwent concomitant procedures at the time of septal myectomy. There was no perioperative (in-hospital or 30 days) mortality. Ninety-two per cent had provoked left ventricular gradients of ≤ 15 mmHg and 97% had none/mild mitral regurgitation at post-operative assessment. In our contemporary cohort, there were 2 (1%) intraoperative ventricular septal defects and 5% required a permanent pacemaker. Conclusions Our early septal myectomy experience targeted a complex population, frequently in need of concomitant procedures. Abolition of left ventricular obstruction and resolution of systolic anterior motion mediated mitral regurgitation can be expected. The safety and efficacy of septal myectomy carried at hypertrophic cardiomyopathy centres by properly trained surgeons achieved the desired outcomes established by recent hypertrophic cardiomyopathy guidelines.

MicroRNAs (miRNAs) are single-stranded small non-coding RNA (18–25 nucleotides) that until a few years ago were considered junk RNA. In the last twenty years, they have acquired more importance thanks to the understanding of their influence on gene expression and their role as negative regulators at post-transcriptional level, influencing the stability of messenger RNA (mRNA). Approximately 5% of the genome encodes miRNAs which are responsible for regulating numerous signaling pathways, cellular processes and cell-to-cell communication. In the cardiovascular system, miRNAs control the functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts, playing a role in physiological and pathological processes and seeming also related to variations in contractility and hereditary cardiomyopathies. They provide a new perspective on the pathophysiology of disorders such as hypertrophy, fibrosis, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into the circulation and then detected. MiRNAs have become interesting for the development of new diagnostic and therapeutic tools for various diseases, including heart disease. In this review, the concept of miRNAs and their role in cardiomyopathies will be introduced, focusing on their potential as therapeutic and diagnostic targets (as biomarkers).

Objectives\udThe aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM).\ud\udBackground\udLeft ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD).\ud\udMethods\udA 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death.\ud\udResults\udMWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years’ experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range –59% to 117% [SD ±20%] and –61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk).\ud\udConclusions\udUsing the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM.

Objectives This study sought to identify predictors of major clinically important atrial fibrillation endpoints in hypertrophic cardiomyopathy. Background Atrial fibrillation (AF) is a common morbidity associated with hypertrophic cardiomyopathy (HCM). The HCMR (Hypertrophic Cardiomyopathy Registry) trial is a prospective natural history study of 2,755 patients with HCM with comprehensive phenotyping. Methods All patients received yearly telephone follow-up. Major AF endpoints were defined as requiring electrical cardioversion, catheter ablation, hospitalization for >24 h, or clinical decisions to accept permanent AF. Penalized regression via elastic-net methodology identified the most important predictors of major AF endpoints from 46 variables. This was applied to 10 datasets, and the variables were ranked. Predictors that appeared in all 10 sets were then used in a Cox model for competing risks and analyzed as time to first event. Results Data from 2,631 (95.5%) patients were available for analysis after exclusions. A total of 127 major AF endpoints events occurred in 96 patients over 33.3 ± 12.4 months. In the final model, age, body mass index (BMI), left atrial (LA) volume index, LA contractile percent (active contraction), moderate or severe mitral regurgitation (MR), and history of arrhythmia the most important. BMI, LA volume index, and LA contractile percent were age-dependent. Obesity was a stronger risk factor in younger patients. Increased LA volume, reduced LA contractile percent, and moderate or severe MR put middle-aged and older adult patients at increased risk. Conclusions The major predictors of major AF endpoints in HCM include older age, high BMI, moderate or severe MR, history of arrhythmia, increased LA volume, and reduced LA contractile percent. Prospective testing of a risk score based on these parameters may be warranted.

Hypertrophic cardiomyopathy (HC) is a common genetic heart disease. However, the number of gene mutation carriers who develop HC and manifest clinical symptoms is not well established. Our objective was to estimate annual prevalence and incidence rates of clinically diagnosed HC in the United States. Data from the HealthCore Integrated Research Database (HIRD) were interrogated for years 2013-2019 to identify patients with ≥1 claim of HC International Classification of Diseases, Clinical Modification Ninth and Tenth Revision diagnosis codes. In 2013, among 16,243,109 patients, 8,526 were identified with HC, yielding an estimated prevalence of clinically diagnosed HC of 0.052% (0.035% for obstructive [oHC], 0.017% for nonobstructive [nHC]). This prevalence yielded an estimated 164,403 patients with clinical diagnosis of HC. For the same year, the incidence of new HC diagnoses was 0.030% (0.020% for oHC, 0.010% for nHC). Over the following 6 years, prevalence and incidence of HC increased by 0.005%/year (p

Growing demand for genetic counselling and testing has created a need for innovative service delivery models to provide quality care in an efficient manner. The goal of this study was to develop and evaluate a patient-facing webinar providing pre-test genetic counselling to individuals with hypertrophic cardiomyopathy. A patient-facing webinar was developed and implemented between April 2019 and January 2021. It was evaluated using the Alberta Quality Matrix for Health framework, which considers the patient experience across the domains of effectiveness, appropriateness, acceptability, accessibility, and efficiency. The webinar group showed comparable scores to controls with regard to self-perceived knowledge and decisional conflict. The majority of patients reported that the webinar met their expectations and was an acceptable replacement for a 1:1 genetic counselling appointment. Finally, the webinar reduced genetic counsellor time to an average of 24 min per patient. Providing pre-test genetic counselling to index hypertrophic cardiomyopathy patients via a group webinar has achieved a high quality of care, and optimized use of provider and space resources. Supplementary Information The online version contains supplementary material available at 10.1007/s12687-021-00564-x.

Background Residual or new left ventricular outflow tract (LVOT) obstruction after an aortic valve replacement poses special challenges with respect to operative techniques. Our study assesses this gap. Methods From January 1993 to May 2019, 18 patients underwent a septal myectomy at Mayo Clinic for subaortic obstruction after aortic valve replacement. We evaluated their demographics, clinical presentation, and echocardiograms, and the type of prior valve replacement, need for repeat replacement, and their short- and long-term outcomes. The data were analyzed using descriptive statistics. Results All patients underwent septal myectomy for LVOT obstruction at a median interval of 7 years (interquartile range, 3-15 years) from their prior aortic valve procedure. Preoperatively, the median left ventricular outflow tract gradient was 57 mm Hg (interquartile range, 44-77 mm Hg); 10 patients (55.5%) had systolic anterior motion (SAM) of the mitral leaflets. Repeat replacement of the aortic valve at the time of myectomy was needed in 14 patients, and septal myectomy alone was performed in 4 patients. One hospital death occurred 34 days after myectomy and aortic valve replacement, and 2 patients needed permanent pacemaker placement for complete heart block. Conclusions Septal myectomy after aortic valve replacement may be performed with repeat replacement of the valve, if there is coexisting prosthetic dysfunction, through a normally functioning bioprosthesis or through an apical approach when visualization through the aortic prosthesis is poor. The complexity of reoperation supports a liberal approach to myectomy at the time of aortic valve replacement when there is significant subaortic septal hypertrophy.

The impact of mitral valve abnormality on the occurrence of non-sustained ventricular tachycardia (NSVT) in patients with hypertrophic cardiomyopathy (HC) has not been well determined. We sought to demonstrate the relation of mitral valve abnormalities with NSVT in patients with obstructive HC. Three hundred and sixteen adult patients with obstructive HC with at least 1 Holter electrocardiographic monitoring and cardiac magnetic resonance (CMR) from 2014 to 2018 were enrolled. CMR images and Holter electrocardiography were analyzed in all patients. NSVT occurred in 50 patients (16%). Compared with those without NSVT, anterior mitral leaflet and posterior mitral leaflet lengths was significantly increased in patients with NSVT (AML 32.0 ± 5.0mm vs. 26.1±4.8mm, p

Nicolaides–Baraitser syndrome is a rare, neuro-developmental disorder caused by heterozygous pathogenic variants in the SMARCA2 gene, involved with chromatin regulation. Cardinal features include intellectual disability, short stature, microcephaly, triangular facies, sparse hair, brachydactyly, prominent interphalangeal joints and seizures. Genetic testing demonstrated a loss within SMARCA2 at 9p24.3 inclusive of basepairs 2094861_2141830 (hg19) in our patient. This case highlights a child with Nicolaides–Baraiter syndrome, a SMARCA2 gene deletion and a novel association of hypertrophic obstructive cardiomyopathy.

This review presents the last literature data, concerning prevalence, clinical profile, diagnostic and treatment of apical hypertrophic cardiomyopathy (HCM), as less known among «classical» variants of HCM. It is also discussed the rare form of apical HCM — mid-ventricular HCM with apical aneurism formation.

Left atrial (LA) imaging is still not routinely used for diagnosis and risk stratification, although recent studies have emphasized its importance as an imaging biomarker. Cardiovascular magnetic resonance is able to evaluate LA structure and function, metrics that serve as early indicators of disease, and provide prognostic information, e.g. regarding diastolic dysfunction, and atrial fibrillation (AF). MR angiography defines atrial anatomy, useful for planning ablation procedures, and also for characterizing atrial shapes and sizes that might predict cardiovascular events, e.g. stroke. Long-axis cine images can be evaluated to define minimum, maximum, and pre-atrial contraction LA volumes, and ejection fractions (EFs). More modern feature tracking of these cine images provides longitudinal LA strain through the cardiac cycle, and strain rates. Strain may be a more sensitive marker than EF and can predict post-operative AF, AF recurrence after ablation, outcomes in hypertrophic cardiomyopathy, stratification of diastolic dysfunction, and strain correlates with atrial fibrosis. Using high-resolution late gadolinium enhancement (LGE), the extent of fibrosis in the LA can be estimated and post-ablation scar can be evaluated. The LA LGE method is widely available, its reproducibility is good, and validations with voltage-mapping exist, although further scan–rescan studies are needed, and consensus regarding atrial segmentation is lacking. Using LGE, scar patterns after ablation in AF subjects can be reproducibly defined. Evaluation of ‘pre-existent’ atrial fibrosis may have roles in predicting AF recurrence after ablation, predicting new-onset AF and diastolic dysfunction in patients without AF. LA imaging biomarkers are ready to enter into diagnostic clinical practice.