Hypertrophic Cardiomyopathy Population Research Articles

Clinical characteristics and outcome of end stage hypertrophic cardiomyopathy: Role of age and heart failure phenotypes

BackgroundA minority of patients with hypertrophic cardiomyopathy (HCM) presents advanced heart failure (HF) during their clinical course, in the context of left ventricular (LV) remodeling with reduced LV ejection fraction (LVEF), or of severe diastolic dysfunction without impaired LVEF. Aim of this study was to describe a multicentric end stage (ES) HCM population and analyze clinical course and outcome among its different phenotypes. MethodsData of all HCM patients from 7 Italian referral centres were retrospectively evaluated. ES was diagnosed in presence of: LVEF <50% (ES-rEF) or NYHA functional class ≥II with severe diastolic dysfunction (ES-pEF). Outcomes were: HCM-related and all-cause mortality; combined arrhythmic events; advanced HF treatments. ResultsStudy population included 331 ES patients; 87% presented ES-rEF and 13% ES-pEF. At ES recognition, patients with ES-pEF were more commonly females, had more frequently NYHA III/IV, atrial fibrillation and greater maximal LV wall thickness. Over a median follow-up of 5.6 years, 83 (25%) patients died, 46 (15%) experienced arrhythmic events and (26%) 85 received advanced HF treatments. Incidence of HCM-related and all-cause mortality, and of combined arrhythmic events did not differ in ES-pEF and ES-rEF patients, but ES-pEF patients were less likely to receive advanced HF treatments. Older age at ES recognition was an independent predictor of increased HCM-related mortality (p = 0.01) and reduced access to advanced HF treatments (p < 0.0001). ConclusionsTwo different HCM-ES phenotypes can be recognized, with ES-pEF showing distinctive features at ES recognition and receiving less frequently advanced HF treatments. Older age at ES recognition has a major impact on outcomes.

Cancer Treatment–Related Complications in Patients With Hypertrophic Cardiomyopathy

ObjectiveTo describe the potential clinical cardiotoxicity of oncological treatments in a cohort of consecutive patients with hypertrophic cardiomyopathy (HCM), systematically followed-up at two national referral centers for HCM. Cardiotoxicity relates to the direct effects of cancer-related treatment on heart function, commonly presenting as left ventricular contractile dysfunction. However, limited data are available regarding cardiotoxic effects on HCM as most studies have not specifically analyzed the effects of oncological treatment in HCM populations. This gap in knowledge may lead to unjustified restriction of HCM patients from receiving curative cancer treatments. MethodsWe retrospectively analyzed clinical and instrumental data of all consecutive HCM patients who underwent oncological treatment between January 2000 and December 2020 collected in a centralized database. ResultsOf 3256 HCM patients, 121 (3.7%) had cancer; 110 (90.9%) underwent oncological surgery, 45 (37.2%) received chemotherapy, and 22 (18.2%) received chest radiation therapy (cRT). After a median follow-up of 5.2 years (Q1-Q3: 2-13 years) from oncological diagnosis, 32 patients died. The cumulative survival at 5 years was 79.9%. The cause of death was mainly attributed to the oncological condition, whereas four patients died of sudden cardiac death without receiving previous chemotherapy or cRT. No patient interrupted or reduced the dose of oncological treatment due to cardiac dysfunction. No sustained ventricular tachyarrhythmia was induced by chemotherapy or radiation therapy. ConclusionCancer treatment was well tolerated in HCM patients. In our consecutive series, none died of cardiovascular complications induced by chemotherapy or cRT and they did not require interruption or substantial treatment tapering due to cardiovascular toxic effects. Although a multidisciplinary evaluation is necessary and regimens must be tailored individually, the diagnosis of HCM per se should not be considered a contraindication to receive optimal curative cancer treatment.

Kiosk 1R-TC-10 - Identification of Fabry Disease Cardiac Phenotype in Hypertrophic Cardiomyopathy Population with Cardiac Magnetic Resonance

Kiosk 1R-TC-10 - Identification of Fabry Disease Cardiac Phenotype in Hypertrophic Cardiomyopathy Population with Cardiac Magnetic Resonance

Abstract 15036: Identification of Fabry Disease Cardiac Phenotype in Hypertrophic Cardiomyopathy With Cardiac Magnetic Resonance Imaging Technology

Introduction: Cardiac magnetic resonance(CMR), especially T1 mapping, has an important role in the diagnosis of Fabry disease, but the differential value in myocardial diseases with hypertrophic phenotype needs further study. More importantly, there has been no systematic study of the difference between different CMR techniques indistinguishing Fabry cardiomyopathy from hypertrophic cardiomyopathy (HCM). Hypothesis: Myomapping technology can be a parameter in distinguishing Fabry cardiomyopathy from HCM. Methods: We continuously included patients with clinically diagnosed hypertrophic cardiomyopathy, completed systematic magnetic resonance imaging, and used genetic testing as the diagnostic criteria. We reported the prevalence rate in the population of HCM, and deeply conducted comparative studies on the differences in magnetic resonance characteristics between Fabry disease and HCM. We also analyzed the diagnostic value of magnetic resonance imaging in distinguishing Fabry cardiomyopathy from HCM. Results: We continuously included patients diagnosed with hypertrophic cardiomyopathy at West China Hospital from 2012 to 2022 and completed systematic magnetic resonance imaging examinations. We reported the prevalence of Fabry cardiomyopathy in the population using genetic testing as the diagnostic criteria, and deeply conducted comparative studies on the differences in CMR features between Fabry disease and HCM. We also analyzed the diagnostic value of CMR in distinguishing Fabry cardiomyopathy from HCM. Conclusions: We found a prevalence of 13 (2.6%) cases of Fabry disease in the hypertrophic cardiomyopathy cohort (494 cases). Our further analysis found that there were no significant differences in the degree of hypertrophy, overall cardiac function and size of Fabry patients compared with patients with HCM, as well as strain analysis. NativeT1 was significantly reduced in Fabry disease, and segmental analysis found that the basal and middle ventricular septum and anterior wall were the most obvious. ECV differed significantly between the two groups. There was no difference in T2 between the two groups. ROC analysis showed that T1 had the most discriminating value

Abstract 11317: Comprehensive Plasma Proteomics Profiling Identifies Signaling Pathways Dysregulated in Genotype-Positive versus Genotype-Negative Patients With Hypertrophic Cardiomyopathy

Introduction: Only a subset of patients with hypertrophic cardiomyopathy (HCM) have positive genotype. Although genotype-positive patients with HCM are known to have worse prognosis than genotype-negative patients, the underlying mechanism is unclear. Hypothesis/Aims: To test the hypothesis that plasma proteomics profiling identifies signaling pathways that are dysregulated in genotype-positive patients with HCM compared with those with negative genotype. Methods: In this multi-center study, we conducted plasma proteomics profiling of 4986 proteins in patients with HCM who underwent genetic testing. The outcome measure was positive genotype, defined as having a mutation that is pathogenic or likely pathogenic for HCM. We identified plasma proteins with significant (univariable P&lt;0.05) differences in concentration between patients with positive and negative genotype in HCM using the Mann-Whitney-Wilcoxon test. Using these proteins, we performed pathway analysis to determine dysregulated pathways with false discovery rate &lt;0.05. Results: A total of 340 patients with HCM underwent genotyping and 103 patients (30%) had positive genotype for HCM. Among the 4986 proteins, 844 (17%) had significant differences between patients with positive and negative genotypes - a larger percentage than what is expected by chance. Pathway analysis exhibited that both pathways known to be associated with poor prognosis (e.g., TGF-β, metabolic, and inflammation) and novel pathways (e.g., Ras-MAPK and associated pathways such as Pl3K-Akt and JAK-STAT) were dysregulated in genotype-positive patients with HCM compared to those who were genotype-negative ( Figure ). Conclusions: This study serves as the first to apply comprehensive proteomics profiling to identify signaling pathways that are differentially regulated in patients with positive genotype in the HCM population, elucidating dysregulation of both known (e.g., TGF-β) and novel (e.g., Ras-MAPK) pathways.

Hypertrophic Cardiomyopathy in Underrepresented Populations: Clinical and Genetic Landscape Based on a Russian Single-Center Cohort Study.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder characterized by marked clinical and genetic heterogeneity. Ethnic groups underrepresented in studies may have distinctive characteristics. We sought to evaluate the clinical and genetic landscape of Russian HCM patients. A total of 193 patients (52% male; 95% Eastern Slavic origin; median age 56 years) were clinically evaluated, including genetic testing, and prospectively followed to document outcomes. As a result, 48% had obstructive HCM, 25% had HCM in family, 21% were asymptomatic, and 68% had comorbidities. During 2.8 years of follow-up, the all-cause mortality rate was 2.86%/year. A total of 5.7% received an implantable cardioverter-defibrillator (ICD), and 21% had septal reduction therapy. A sequencing analysis of 176 probands identified 64 causative variants in 66 patients (38%); recurrent variants were MYBPC3 p.Q1233* (8), MYBPC3 p.R346H (2), MYH7 p.A729P (2), TPM1 p.Q210R (3), and FLNC p.H1834Y (2); 10 were multiple variant carriers (5.7%); 5 had non-sarcomeric HCM, ALPK3, TRIM63, and FLNC. Thin filament variant carriers had a worse prognosis for heart failure (HR = 7.9, p = 0.007). In conclusion, in the Russian HCM population, the low use of ICD and relatively high mortality should be noted by clinicians; some distinct recurrent variants are suspected to have a founder effect; and family studies on some rare variants enriched worldwide knowledge in HCM.

The predictive value of cardiac MRI strain parameters in hypertrophic cardiomyopathy patients with preserved left ventricular ejection fraction and a low fibrosis burden: a retrospective cohort study.

Prompt interventions prevent adverse events (AE) in hypertrophic cardiomyopathy (HCM). We evaluated the pattern and the predictive role of feature tracking (FT)-cardiac magnetic resonance (CMR) imaging parameters in an HCM population with a normal left ventricular ejection fraction (LVEF) and a low fibrosis burden. The CMR and clinical data of 170 patients, consisting of 142 HCM (45 ± 15.7 years, 62.7% male) and 28 healthy (42.2 ± 11.26 years, 50% male) subjects, who were enrolled from 2015 to 2020, were evaluated. HCM patients had a normal LVEF with a late gadolinium enhancement (LGE) percentage below 15%. Between-group differences were described, and the potent predictors of AE were determined. A P-value below 0.05 was considered significant. LV global longitudinal, circumferential, and radial strains (GLS, GCS, and GRS, respectively) and the LV myocardial mass index (MMI) were different between the healthy and HCM cases (all Ps < 0.05). Strains were significantly impaired in the HCM patients with a normal MMI. A progressive decrease in LVGLS and a distinct fall in LVGCS were noted with a rise in MMI. AE were predicted by LVGLS, LVGCS, and the LGE percentage, and LVGCS was the single robust predictor (HR, 1.144; 95% CI, 1.080-1.212; P = 0.001). An LVGCS below 16.2% predicted AE with 77% specificity and 58% sensitivity. LV strains were impaired in HCM patients with a normal EF and a low fibrosis burden, even in the presence of a normal MMI. CMR parameters, especially FT-CMR values, predicted AE in our HCM patients.

Clinical Application of the HCM-AF Risk Score in the Prediction of Clinical Outcomes of Polish Patients with Hypertrophic Cardiomyopathy.

The recently introduced HCM-AF Risk Calculator allows the prognosis of atrial fibrillation (AF) occurrence in hypertrophic cardiomyopathy (HCM) patients. The aim of this study was to assess the clinical application of the HCM-AF Risk Score in the prediction of the clinical outcomes of Polish patients. The study included 92 patients (50.0% female, median age 55 years), with a baseline sinus rhythm diagnosed between 2013 and 2018. The analysis involved the incidence of clinical characteristics and outcomes, total mortality, rehospitalisation, and the course of heart failure (HF). According to the HCM-AF Risk Score, the HCM population was stratified into three subgroups, with a low (13/14.2%), intermediate (30/32.6%), and high risk of AF (49/53.2%). Subgroups differed significantly: the high-risk subgroup was older, had a higher body mass index (BMI), and more advanced signs of left ventricular (LV) hypertrophy and left atrium (LA) dilatation. The registered AF incidence was 31.5% and 43.5% in the 2- and 5-year follow-ups, and it was significantly higher than in the HCM-AF Risk Score population, which had 4.6% in the 2-year follow-up, and 10.7% in the 5-year follow-up. In the whole population, the AF incidence in both the 2- and 5-year follow-ups revealed a strong correlation with the HCM-AF Risk Score (r = 0.442, p < 0.001; r = 0.346, p < 0.001, respectively). The clinical outcomes differed among the subgroups: the total mortality was 15.4% vs. 20.0% vs. 42.9% (p < 0.05); rehospitalisation was 23.1% vs. 53.3% vs. 71.4% (p < 0.05). The highest HF progression was in the high-risk subgroup (36.7%). Regardless of the high results of the HCM-Risk Score in Polish patients, the score underestimates the real-life high level of AF incidence. The HCM-AF Risk Score seems to be useful in the prediction of the general clinical outcomes in HCM patients.

Apical Hypertrophic Cardiomyopathy: Diagnosis, Natural History, and Management.

Apical hypertrophic cardiomyopathy (ApHCM) represents a rare variant of hypertrophic cardiomyopathy (HCM) with distinct phenotypic characteristics. The prevalence of this variant varies according to each study's geographic region. The leading imaging modality for the diagnosis of ApHCM is echocardiography. Cardiac magnetic resonance, however, is the gold standard for ApHCM diagnosis in case of poor acoustic windows or equivocal echocardiographic findings but also in cases of suspected apical aneurysms. The prognosis of ApHCM was reported to be relatively benign, although more recent studies seem to contradict this, demonstrating similar incidence of adverse events compared with the general HCM population. The aim of this review is to summarize the available evidence for the diagnosis of ApHCM, highlight distinctions in comparison to more frequent forms of HCM with regards to its natural history, prognosis, and management strategies.

Outcomes of concomitant myectomy and left ventricular apical aneurysm repair in patients with hypertrophic cardiomyopathy

ObjectivesHypertrophic cardiomyopathy with left ventricular apical aneurysm is a phenotype associated with a 4-fold increase in the risk for sudden cardiac death. In this study, we describe the surgical outcome of concomitant apical aneurysm repair in patients undergoing transapical myectomy for hypertrophic cardiomyopathy. MethodsWe identified 67 patients with left ventricular apical aneurysms who underwent transapical myectomy and apical aneurysm repair between July 2000 and August 2020. Long-term survival was compared with that of 2746 consecutive patients undergoing transaortic septal myectomy for obstructive hypertrophic cardiomyopathy with subaortic obstruction. ResultsTransapical myectomy was indicated for midventricular obstruction (n = 44) or left ventricular remodeling for diastolic heart failure (n = 29). Preoperatively, 74.6% (n = 50) of patients were in New York Heart Association class III/IV heart failure, and 34.3% (n = 23) of patients had experienced syncope or presyncope. Atrial fibrillation was documented in 22 patients (32.8%), and episodes of ventricular arrhythmias were recorded in 30 patients (44.8%). Thrombus was present in the apical aneurysm in 6 patients. During a median (interquartile range) follow-up of 4.9 (1.8-7.6) years, the estimated 1- and 5-year survivals were 98.5% and 94.5%, respectively, which were not significantly different from that of patients undergoing transaortic septal myectomy for obstructive hypertrophic cardiomyopathy (P = .52) or an age- and sex-matched US general population (P = .40). ConclusionsApical aneurysm repair in conjunction with septal myectomy is a safe procedure, and the good long-term survival of patients suggests that the procedure may reduce cardiac-related death in this high-risk hypertrophic cardiomyopathy population.

High-Sensitivity Cardiac Troponin T Elevation in Hypertrophic Cardiomyopathy Is Associated With Ventricular Arrhythmias

ObjectiveTo investigate the relationship between high-sensitivity cardiac troponin T (hs-cTnT) levels and sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). MethodsA referral HCM population with prospectively obtained hs-cTnT concentration from March 1, 2018, to April 23, 2020, was reviewed. Patients with end-stage renal disease or an abnormal hs-cTnT level not collected in an outpatient protocolled fashion were excluded. The hs-cTnT level was compared with demographic characteristics, comorbidities, conventional HCM-associated SCD risk factors, imaging, exercise testing, and prior cardiac events. ResultsOf 112 included patients, 69 (62%) had an elevated hs-cTnT concentration. The level of hs-cTnT correlated with known risk factors for SCD, including nonsustained ventricular tachycardia (P=.049) and septal thickness (P=.02). When patients were stratified by having a normal vs an elevated hs-cTnT concentration, patients with elevated hs-cTnT concentration were more likely to have experienced an implantable cardioverter-defibrillator discharge for ventricular arrhythmia, ventricular arrhythmia with hemodynamic instability, or cardiac arrest (incidence rate ratio, 2.96; 95% CI, 1.11 to 10.2). When sex-specific hs-cTnT cutoffs were removed, this association was no longer present (incidence rate ratio, 1.50; 95% CI, 0.66 to 3.60). ConclusionIn a protocolized, outpatient HCM population, hs-cTnT elevations were common and were associated with more arrhythmic expressivity of the HCM substrate as indicated by previous ventricular arrhythmias and appropriate implantable cardioverter-defibrillator shocks only when sex-specific hs-cTnT cutoffs were used. Further research should use different hs-cTnT reference values by sex to determine whether an elevated hs-cTnT value is an independent risk factor for SCD in patients with HCM.

A Cardiac Magnetic Resonance Study: Comparison of Biventricular Longitudinal Function in Hypertrophic Cardiomyopathy Patients and Normal Individuals.

Hypertrophic cardiomyopathy (HCM) is a genetic disease with an incidence of0.2%-0.5%. It has a wide range of clinical presentations varying from coincidental diagnoses to heart failure, ventricular arrhythmias and sudden cardiac death.Mitral annular plane systolic excursion (MAPSE) and tricuspid annular plane systolic excursion (TAPSE) are M-mode-derivedpractical and reproduciblemeasurements of systolic longitudinal displacement of the annular plane. These two measuresmay be used as markers of the left ventricular and right ventricular longitudinal functions. Currently, there are only a fewstudies on cardiac magnetic resonance (CMR)-derived TAPSE and MAPSE measurement comparison between the HCM group andnormal control group. The aim of our study is to show the differences in CMR-derived TAPSE and MAPSE valuesbetween the HCM and normal population. We evaluatedCMR exams of patients diagnosed with HCM andof normal individuals scanned between 2020 and 2021 retrospectively. The patients were from our own institution's and other hospitals'in- and out-patient departments. Data was collected on36 HCMpatients and 34 adults with no known history ofcardiac and non-cardiac diseases. All CMR exams were performed on a 1.5 T (Magnetom Avanto, Siemens Healthcare, Erlangen, Germany) scanner.CMR-derived MAPSE and TAPSE were measured on standard four-chamber steady-state free precession (SSFP) cine images and given in millimeters. From February 2020to December 2021, a total of 150 patients were diagnosed with hypertrophic cardiomyopathy. After exclusion, 36 patients with HCM were included in the study and the normal control group comprised 34 individuals. The mean age of the HCM groupwas 43.2+ 13.5 years, while it was 37.5 + 11.3 in the control group. The female ratio of the HCM group was found to be 36%, while it was56% in the healthy control group.MAPSEvalues were significantly higher in the normal control group when compared to the HCM patient group (MAPSE: 14.5 ± 2.9 mm vs. 11.7 ± 3.2 mm; p<0.001), while TAPSE values did not depict a significant difference between the two groups (p=0.627). This study suggests that MAPSE values are significantly lower in the HCM patient group in comparison with the normal control group on CMRscans. Although not statistically significant, TAPSE values are also lower in the HCMgroup.

751 CANCER TREATMENT RELATED COMPLICATIONS IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

Abstract Introduction Cardiotoxicity involves direct effects of cancer related treatment on heart function, commonly presenting as left ventricular contractile dysfunction. However, limited data are available regarding cardiotoxicity on hypertrophic cardiomyopathy (HCM), because most studies and registries have not specifically analyzed the effects of oncological treatment in HCM populations. This gap in knowledge may lead to unjustified restriction of HCM patients to radical cancer treatments. Aim We aimed at describing the potential clinical cardiotoxicity of oncological treatments in a cohort of consecutive HCM patients, systematically followed up at two national referral centres for HCM. Methods We retrospectively analysed all clinical and instrumental data of all consecutive HCM patients who underwent oncological treatment between January 2000 and December 2020, collected in a centralized database. Results Of 3256 HCM patients, 121 (3.7%) had a reported diagnosis of cancer; 109 (90.1%) patients underwent oncological surgery, 45 (37.2%) chemotherapic treatment, 22 (18.2%) chest radiotherapy. After a median follow up of 5 (2-13) years from oncological diagnosis, 32 of the 121 patients (26.4%) died. The cause of death was mainly attributed to the oncological condition, while 4 (12.5%) patients died of sudden cardiac death without previous chemotherapy or chest radiotherapy. No patient interrupted or reduced the dose of oncological treatment due to cardiac dysfunction. No sustained ventricular tachyarrhythmia was induced by chemotherapy or radiotherapy. Conclusions Cancer treatment is well tolerated in HCM patients. In our oncology series, none died of cardiovascular complications induced by chemotherapy or chest radiotherapy and none required interruption or substantial tapering of treatment due to cardiovascular side effects. Although expert multidisciplinary evaluation is mandatory and regimens must be tailored individually, the diagnosis of HCM per se should not be considered a contraindication to radical cancer treatment.

Hypertrophic cardiomyopathy and atrial fibrillation: the Cardiomyopathy/Myocarditis registry of the EURObservational Research Programme of the European Society of Cardiology

Abstract Background Current guidelines for AF management underline a complex approach to detecting and treating atrial fibrillation (AF). Hypertrophic cardiomyopathy (HCM) is commonly associated with AF. Purpose To assess the clinical characteristic and prognosis in patients with HCM and AF. Methods and results Overall, 1739 adult patients with HCM (711/40.9% female; median age at diagnosis: 55.5 years) were enrolled in the EURObservational Research Programme – Cardiomyopathy/Myocarditis Long-Term Registry. Baseline clinical characteristics and adverse cardiovascular endpoints at 1-year follow-up were analysed. Results At baseline, AF was found in 478 (27.5%) subjects (paroxysmal: 54.7%, persistent: 17.6%, permanent: 27.7%). Newly diagnosed AF was identified during 1-year follow-up in 48 (2.8%) subjects with HCM. The presence of AF was associated with higher age (59.6±13.8 vs 50.8±16.1, p&amp;lt;0.001); BMI (27.7±5.1 vs 26.6±4.6 kg/m2, p&amp;lt;0.001); more advanced NYHA class (NYHA I/II and III/IV: 75.1 and 24.9 vs 86.2 and 13.8%, p&amp;lt;0.001); more frequent history of diabetes (14.6 vs 8.4%, p&amp;lt;0.001); arterial hypertension 43.4 vs 34.6%, p&amp;lt;0.001); renal impairment (15.4 vs 6.35%, p&amp;lt;0.001); and history of sustained VT (10.8 vs 6.35%, p&amp;lt;0.001). AF patients were characterized by lower left ventricular ejection fraction (LV EF) (59±12 vs 63±11%, P&amp;lt;0.001), left atrium (LA) dilatation (48.9±9.1 vs 42.4±7.7%, p&amp;lt;0.001), increased pulmonary artery systolic pressure (37.8±13.7 vs 29.6±12.6 mmHg, p&amp;lt;0.001), distribution of LV hypertrophy (p=0.032) and more advanced LV diastolic dysfunction (p&amp;lt;0.001). On multivariate logistic regression analysis, independent predictors of AF in the HCM population were: age at enrolment (OR 1.068, P&amp;lt;0.001); LVEF (OR 0.978, p&amp;lt;0.001); and LA diameter (OR 1.094, p&amp;lt;0.001). Oral anticoagulation (OAC) was administered in 69.5% of patients with AF (vitamin K antagonist: 48.5%; direct OAC: 21%). ICD was implanted in 26.8% in AF and 16.9% in non-AF subjects (p&amp;lt;0.001). PVI was performed in 9.9% of AF patients only. The annual incidence of stroke/TIA was higher in AF than in the non-AF population (2.64 vs 0.85%, p=0.009). There was a trend towards increased death from any cause in the AF population (3.39 vs 1.74%, p=0.05). There were no differences in SCD-risk score between AF and non-AF subjects. Conclusion The study reveals a high prevalence of AF in patients with HCM that corresponds with more advanced symptoms, increased prevalence of comorbidities, structural and functional heart remodelling along with inadequate anticoagulation and a significant increase in the risk of stroke. The clinical characteristics of HCM-AF patients indicate that the ESC recommended complex AF approach “CC To ABC” is appropriate in this population. Funding Acknowledgement Type of funding sources: None.

Ischaemic events in hypertrophic cardiomyopathy patients with and without atrial fibrillation: a systematic review and meta-analysis.

Hypertrophic cardiomyopathy predisposes to acute cerebrovascular events including ischaemic stroke, transient ischaemic attack and systemic thromboembolism. Atrial fibrillation confers even higher risk. We aim to report the incidence of these complications and to investigate the impact of atrial fibrillation on the ischaemic risk in patients with hypertrophic cardiomyopathy. A literature search was performed on PubMed, Scopus, Embase/Ovid and Cochrane library from inception to 20th March 2021. We compared the incidence of ischaemic strokes, transient ischaemic attack, non-specified thromboembolism events and systemic thromboembolism in hypertrophic cardiomyopathy patients with or without atrial fibrillation. Non-specified thromboembolism events in our paper referred to thromboembolic events whereby types were not specified in the studies. Meta-analysis was performed using StataSE 16 software, and heterogeneity was assessed using I2 test. A total of 713 studies were identified. Thirty-five articles with 42,570 patients were included. The pooled incidence of stroke/ transient ischaemic attack was 7.45% (95% confidence interval [CI] 5.80-9.52, p < 0.001) across 24 studies with a total of 37,643 hypertrophic cardiomyopathy patients. Atrial fibrillation significantly increased the risk of total stroke/ transient ischaemic attack (Risk Ratio 3.26, 95% CI 1.75-6.08, p < 0.001, I2 = 76.0). The incidence of stroke/ transient ischaemic attack was 9.30% (95% CI 6.64-12.87, p = 0.316) in the apical hypertrophic cardiomyopathy subgroup. Concomitant atrial fibrillation in hypertrophic cardiomyopathy increases the risk of thromboembolic events including ischaemic stroke and transient ischaemic attack. The apical subgroup shows a similar risk of acute cerebrovascular events as the overall hypertrophic cardiomyopathy population.

Nationwide screening of Fabry disease in patients with hypertrophic cardiomyopathy in Czech Republic.

Fabry disease (FD) is a rare X-linked genetic disorder caused by α-galactosidase A (AGALA) deficiency. Whereas 'classic' variant has multisystemic manifestation, the more recently described 'later-onset' variant is characterized by predominant cardiac involvement that often mimics hypertrophic cardiomyopathy (HCM). Consecutive unrelated patients with HCM were screened for FD in 16 (out of 17) cardiac centres in the Czech Republic covering specialized cardiology care from June 2017 to December 2018. AGALA activity and globotriaosylsphingosine (lyso-Gb3 ) levels were measured in all subjects using the dry blood spot method. FD was suspected in male patients with AGALA activity <1.2μmol/h/L and in females with either low AGALA activity or lyso-Gb3 >3.5ng/mL. Positive screening results were confirmed by genetic testing. We evaluated 589 patients (390 males, 66%) with HCM (mean maximal myocardial thickness 19.1±4.3mm). The average age was 58.4±14.7years. In total, 17 patients (11 males, 6 females) had a positive screening result, and subsequently, six of them (four males and two females) had a genetically confirmed pathogenic GLA mutation (total prevalence of 1.02%). Five of these patients were carrying the p.N215S mutation known to cause a typical later-onset cardiac FD. We confirmed the prevalence of FD repeatedly reported in previous screening programmes (approximately 1% irrespective of gender) in a non-selected HCM population in Central Europe. Our findings advocate a routine screening for FD in all adult patients with HCM phenotype including both genders. The dry blood spot method used led to identification of clearly pathogenic variants.

Abstract P027: Yamaguchi Syndrome Presenting With Atrial Fibrillation And Heart Failure Diagnosed With Contrast Echocardiography

Yamaguchi syndrome or apical hypertrophic cardiomyopathy (ApHCM), is a rare variant of hypertrophic cardiomyopathy (HCM), prevalence of about 3% among HCM population in the United States. Generally considered a benign condition but can be potentially life-threatening. A 84 year old female with history of mitral regurgitation with mitra-clip, paroxysmal atrial fibrillation (pAF) presented to ED with dyspnea and leg swelling. She was tachypneic with bibasilar rales, jugular venous distention. BNP 1,086 pg/l with cardiomegaly and pulmonary edema on chest x-ray. She was managed for acute decompensated cardiac failure (NYHA class III) using IV furosemide with symptom improvement. EKG revealed AF with abnormal deep T-wave inversion most prominent in precordial leads (V4-V6). Contrast echocardiogram revealed ApHCM, missed on prior echocardiograms. Patient’s dose of metoprolol was doubled, and outpatient follow-up was scheduled. Conclusion: ApHCM commonly presents with heart failure symptoms, chest pain, palpitation, or syncope. Undiagnosed/untreated ApHCM can lead to complications including diastolic dysfunction, left atrial enlargement causing atrial fibrillation, apical clots formation with subsequent thromboembolism, ventricular wall aneurysm, arrhythmias, and myocardial infarction. In our case, contrast echocardiogram was able to diagnose ApHCM. A presentation of heart failure symptoms at NYHA class II or higher is a known predictor of poor prognosis in patients with ApHCM. Missing diagnosis on normal echocardiogram without use of ultrasound contrast is very common. Diagnosing with proper use of modality can help to improve outcomes in these patients.

Prognostic significance of serum alkaline phosphatase for all-cause mortality in patients with hypertrophic cardiomyopathy: A cohort of the hospitalized population.

Higher levels of serum alkaline phosphatase (ALP) as a novel risk factor was recently found associated with mortality in different population, whereas, the relationship remains unknown in hypertrophic cardiomyopathy (HCM) population. In this study, we hypothesized that increased ALP could predict all-cause mortality in the adult HCM population. In this cohort study, retrospective data from 538 HCM patients consecutively recruited in West China Hospital were collected. Patients were divided into two groups by baseline ALP with 80IU/L as the cutoff. All-cause mortality was set as the endpoint. Subgroup analysis was conducted in patients with normal liver function. In total, 461 adult HCM patients were included. After a median follow-up of 4.7 years, 91 patients died. Alkaline phosphatase was an independent predictor of all-cause mortality since patients in the higher ALP group had an increased risk (adjusted HR 2.0, 95% CI: 1.3-3.3, P < 0.01) compared with those in the lower ALP group. In subgroup analysis, the relationship was consistent with the overall (adjusted HR: 3.0, 95% CI: 1.7-5.3, P < 0.01 for the higher ALP group). In the Chinese cohort study of HCM patients, serum ALP is independently associated with all-cause mortality. Patients with a measured value above 80IU/L had an increased risk of all-cause mortality and this cutoff might help with risk stratification in HCM population.

The use of artificial intelligence and deep learning methods in subcutaneous implantable cardioverter defibrillator screening to optimise selection in special patient populations

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Dr.Mohamed ElRefai is receiving an unrestricted grant from Boston Scientific. Introduction Adult congenital heart disease (ACHD) and hypertrophic cardiomyopathy (HCM) patients who require defibrillator therapy are often relatively young and may require several generator replacements in their lifetime. The increased risk of complications associated with transvenous ICDs make the subcutaneous (S-ICD) a valuable alternative. However, higher S-ICD ineligibility rates (20-40% in ACHD and 7-38% in HCM) and higher inappropriate shock rates (10.5% in ACHD and 12.5% in HCM) are observed in these populations. Unfavourable T:R ratios and dynamic changes in the R and T wave amplitudes are the primarily factors behind ineligibility and inappropriate shocks, which are most commonly caused by T wave over-sensing. Purpose We report a novel application of deep learning methods used to autonomously screen patients for S-ICD eligibility over a longer period than conventional screening. We hypothesise that this screening approach might achieve better patient selection and optimise S-ICD vector selection in challenging patient cohorts. Methods Adult patients with ACHD or HCM and a control group of normal subjects were fitted with a 24-hour ambulatory ECG with the leads placed to record their S-ICD vectors. T: R ratio throughout the recordings was analysed utilising phase space reconstruction matrices to convert the ECG signal into compressed pixel images. Whilst a convolutional neural network model was trained to provide an in-depth description of the T: R variation plot for each vector T: R variation was compared statistically using a one-way ANOVA test. Results 20 patients (age 44.1 ±11.68, 60% male, 7 HCM, 6 ACHD and 7 control subjects) were enrolled. A significant difference was observed in the mean and median T: R values between the three groups (p&amp;lt;0.001). There was no difference observed in the standard deviation of T: R between the control subjects and HCM group. However, there was a statistically significant difference in the standard deviation of T: R between the control subjects and the ACHD group (p= 0.01). [see Figure]. Conclusions T:R ratio, a main determinant for S-ICD eligibility, is significantly higher in ACHD and HCM when compared to normal hearts and it also has more tendency to fluctuate in ACHD patients when compared to HCM and normal hearts populations. We hypothesise that our novel model could be used to select S-ICD eligible patients by better characterisation of T:R ratio reducing the risk of T wave oversensing and inappropriate shocks particularly in the ACHD patients’ cohort.

The Genetic Architecture of Hypertrophic Cardiomyopathy in Hungary: Analysis of 242 Patients with a Panel of 98 Genes.

Hypertrophic cardiomyopathy (HCM) is a primary disease of the myocardium most commonly caused by mutations in sarcomeric genes. We aimed to perform a nationwide large-scale genetic analysis of a previously unreported, representative HCM cohort in Hungary. A total of 242 consecutive HCM index patients (127 men, 44 ± 11 years) were studied with next generation sequencing using a custom-designed gene-panel comprising 98 cardiomyopathy-related genes. A total of 90 patients (37%) carried pathogenic/likely pathogenic (P/LP) variants. The percentage of patients with P/LP variants in genes with definitive evidence for HCM association was 93%. Most of the patients with P/LP variants had mutations in MYBPC3 (55 pts, 61%) and in MYH7 (21 pts, 23%). Double P/LP variants were present in four patients (1.7%). P/LP variants in other genes could be detected in ≤3% of patients. Of the patients without P/LP variants, 46 patients (19%) carried a variant of unknown significance. Non-HCM P/LP variants were identified in six patients (2.5%), with two in RAF1 (p.Leu633Val, p.Ser257Leu) and one in DES (p.Arg406Trp), FHL1 (p.Glu96Ter), TTN (p.Lys23480fs), and in the mitochondrial genome (m.3243A>G). Frameshift, nonsense, and splice-variants made up 82% of all P/LP MYBPC3 variants. In all the other genes, missense mutations were the dominant form of variants. The MYBPC3 p.Gln1233Ter, the MYBPC3 p.Pro955ArgfsTer95, and the MYBPC3 p.Ser593ProfsTer11 variants were identified in 12, 7, and 13 patients, respectively. These three variants made up 36% of all patients with identified P/LP variants, raising the possibility of a possible founder effect for these mutations. Similar to other HCM populations, the MYBPC3 and the MYH7 genes seemed to be the most frequently affected genes in Hungarian HCM patients. The high prevalence of three MYBPC3 mutations raises the possibility of a founder effect in our HCM cohort.