Hypertrophic Cardiomyopathy Registry Research Articles

Protein Biomarkers of Adverse Clinical Features and Events in Sarcomeric Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a heterogeneous condition that can lead to atrial fibrillation, heart failure, and sudden cardiac death in many individuals but mild clinical impact in others. The mechanisms underlying this phenotypic heterogeneity are not well defined. The aim of this study was to use plasma proteomic profiling to help illuminate biomarkers that reflect or inform the heterogeneity observed in HCM. The Olink antibody-based proteomic platform was used to measure plasma proteins in patients with genotype positive (sarcomeric) HCM participating in the HCM Registry. We assessed associations between plasma protein levels with clinical features, cardiac magnetic resonance imaging metrics, and the development of atrial fibrillation. We measured 275 proteins in 701 patients with sarcomeric HCM. There were associations between late gadolinium enhancement with proteins reflecting neurohormonal activation (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and ACE2 [angiotensin-converting enzyme 2]). Metrics of left ventricular remodeling had novel associations with proteins involved in vascular development and homeostasis (vascular endothelial growth factor-D and TM [thrombomodulin]). Assessing clinical features, the European Society of Cardiology sudden cardiac death risk score was inversely associated with SCF (stem cell factor). Incident atrial fibrillation was associated with mediators of inflammation and fibrosis (MMP2 [matrix metalloproteinase 2] and SPON1 [spondin 1]). Proteomic profiling of sarcomeric HCM identified biomarkers associated with adverse imaging and clinical phenotypes. These circulating proteins are part of both established pathways, including neurohormonal activation and fibrosis, and less familiar pathways, including endothelial function and inflammatory proteins less well characterized in HCM. These findings highlight the value of plasma profiling to identify biomarkers of risk and to gain further insights into the pathophysiology of HCM.

Left atrial reservoir strain differentiates cardiac amyloidosis and hypertrophic cardiomyopathy

Abstract Aims Availability of mortality-reducing therapies for cardiac amyloidosis (CA) has led to an increase in referral rates to tertiary care centers. Investigations to improve diagnosis rates are urgently needed, as diagnosis of CA requires a multimodal approach and its early diagnosis is crucial due to high mortality in untreated patients. The aim of this study is to evaluate the accuracy of the left atrial reservoir strain (LASr) in differentiating CA patients from patients with hypertrophic cardiomyopathy (HCM). Methods This is a cross-sectional analysis from the Graz HCM Registry, a prospective single-center cohort study enrolling consecutive patients with a HCM phenotype. This analysis included HCM and CA patients with valid standardized transthoracic echocardiographic examinations. Blinded investigators performed post-processing echocardiographic analyses in 100 HCM and 95 CA patients. Results Compared to HCM patients, CA patients were more frequently male [79 (83%) vs. 54 (54%); p<0.001] and older [78 (73-81) vs. 58 (47-70) years; p<0.001]. Moreover, CA patients had a lower BMI [25.0 (22.8-26.9) vs. 26.5 (24.3-29.7) kg/m²; p=0.002] as well as lower systolic [134±20 vs. 142±25 mmHg; p=0.018] and diastolic blood pressure [78±12 vs. 84±12 mmHg; p<0.001]. Additionally, CA patients had higher NT-proBNP [2533.0 (1146.0-5016.0) vs. 543.0 (195.0-1381.0) pg/ml; p<0.001] and lower eGFR [58.4±19.1 vs. 80.1±22.2 ml/min/1.73m²; p<0.001]. LASr was significantly worse in CA patients compared to HCM patients [9.2 (5.6-13.0) vs. 21.7 (14.8-27.6) %; p<0.001]. Multivariable logistic regression analysis revealed LASr as an independent predictor of CA [OR=0.936 (95% CI 0.877-0.998)], adjusting for covariates. ROC analysis showed an AUC of 0.80 (95% CI 0.73-0.86) for LASr to discriminate CA from HCM. LASr ≤14.3% demonstrated a 80% sensitivity and 79% specificity for the identification of CA patients. Sensitivity analyses involving 74 sex- and age-matched patients yielded materially unchanged results. Conclusion Compared to HCM patients, LASr was diminished in CA patients and an independent predictor of CA. Moreover, LASr showed high diagnostic accuracy in differentiating CA and HCM patients. Prospective studies are needed to evaluate the added value of left atrial strain in the diagnostic work-up of CA patients.ROC curve of LASr

Preliminary Data of the Hypertrophic Cardiomyopathy Registry in Nonspecialized Centers of Argentina. Exploring Behind the Veils of Common Practice

Preliminary Data of the Hypertrophic Cardiomyopathy Registry in Nonspecialized Centers of Argentina. Exploring Behind the Veils of Common Practice

Abstract 17207: Usefulness of Polygenic Risk Score for Intraventricular Septal Diameter in Patients With Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant monogenic disease characterized by thickened heart muscles, particularly at the intraventricular septum (IVS), and an increased risk of arrythmias and sudden death. Recently, in addition to monogenic screening, the polygenic risk score (PRS) has been proposed as a potentially useful tool for risk stratification in several cardiovascular diseases. However, it remains unclear whether PRS is also beneficial for risk stratification of patients with HCM. Methods: We recruited and genotyped HCM patients from the Kanazawa University Mendelian Disease (KUMD) HCM registry and controls from the KUMD non-HCM familial hypercholesterolemia registry. The PRS was calculated from over 3 million genotyped with imputed variants of each participant for IVS diameter (PRS IVS ) using a publicly available summary statistic at the National Bioscience Database Center. We assessed the PRS IVS distributions among the monogenic HCM, causal variant negative HCM, and control groups. We also tested the associations of PRS IVS with the IVS diameters within each group. Results: We evaluated a total of 400 participants (267 HCM patients, including 79 with monogenic HCM and 188 with causal variant negative HCM, and 133 controls) for the analyses. Compared to the controls, PRS IVS was significantly higher in both monogenic HCM (0.12923 in Monogenic HCM vs. 0.09057 in controls, age- and sex-adjusted p = 0.02) and causal variant negative HCM patients (0.11127 in causal variant negative HCM vs. 0.09057 in controls, p = 9.9x10 -4 ). However, no associations were found between PRS IVS and IVS diameters in any of the groups. Conclusions: In this study, both the monogenic HCM and causal variant negative HCM groups demonstrated significantly higher PRS IVS than non-HCM controls. However, we found no evidence to suggest that PRS IVS might be useful for risk stratification in patients with HCM.

Abstract 18098: Prolonged Filtered QRS Duration on Signal Averaged Electrocardiogram is Associated With Structural Remodeling in Hypertrophic Cardiomyopathy

Background: Hypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy, electrical remodeling and fibrosis that lead to inhomogeneous ventricular depolarization and arrhythmias. Signal averaged ECG (SAECG) is useful for non-invasive risk stratification in ischemic cardiomyopathy. However, the association between SAECG and structural remodeling in HCM has not been investigated. Methods: We retrospectively studied 594 HCM patients from the Johns Hopkins HCM Registry, who underwent echocardiography and cardiac magnetic resonance (CMR) imaging within 12 months of SAECG or 12-lead ECG. Seventy-three patients underwent SAECG and were divided into 2 groups (Normal-SAECG, Abnormal-SAECG) based on filtered QRS duration and/or presence of late potentials . Results: Abnormal SAECG was seen in 50% of HCM patients (37/73). Of the 37 HCM patients with abnormal SAECG, 29 patients only had prolonged filtered QRS duration ( fQRS> 114ms ), and 8 patients had prolonged fQRS duration as well as late potentials ( LAS40 >38ms; RMS40 <20μV). Mean fQRS and LAS40 were significantly higher in the Abnormal-SAECG group ( fQRS : 125.7 vs 107msec, p<0.0001; LAS40 : 31.2 vs 22.9msec; p=0.002; RMS40 : 40 vs 54μV; p=0.07). HCM patients with abnormal SAECG also had 1) larger left atrial size (p=0.03), lower global LV peak systolic strain (p=0.04), systolic strain rate (p=0.008), early diastolic strain rate (p=0.01) by ECHO; 2) greater LV mass index (p=0.004) 3) Higher prevalence and amount of late gadolinium enhancement (LGE) reflecting LV-scar (p=0.045 and 0.01) by CMR; 4) higher prevalence of repolarization abnormalities on 12-lead ECG (p=0.02). Adverse outcomes (sustained-VT/VF, heart failure, death) were similar in the 2 groups. Filtered QRS duration (SAECG) was positively correlated with LV mass index (r=0.43, p=0.0002), QRS duration on 12-lead ECG (r=0.67, p=0.000), and negatively correlated with global LV early diastolic strain rate (r= -0.34, p=0.009) in our HCM cohort. Conclusion: In HCM, prolonged filtered QRS on SAECG reflects a greater degree of structural remodeling characterized by more LV hypertrophy, larger LA size, worse cardiac mechanics, and higher prevalence and amount of fibrosis.

Atrioventricular nodal ablation is an effective management strategy for atrial fibrillation in patients with hypertrophic cardiomyopathy

Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HCM) and can be challenging to manage. Atrioventricular nodal (AVN) ablation may be an effective management strategy for AF in these patients. The purpose of this study was to assess the efficacy of AVN ablation in HCM patients who have failed medical therapy and/or catheter ablation for AF. A multicenter study with retrospective analysis of a prospectively collated HCM registry was performed. AVN ablation patients were identified. Baseline characteristics and device and procedural indications were collected. Symptoms defined by New York Heart Association and European Heart Rhythm Association classification and echocardiographic findings during follow-up were assessed. Fifty-nine patients were included in the study. Indications for AVN ablation were 6 (10.2%) inappropriate implantable cardioverter-defibrillator shock, 35 (59.3%) ineffective rate control, and 18 (30.5%) to regularize rhythm for symptom improvement. During post-AVN ablation follow-up of 79.4 ± 61.1 months, left ventricular ejection fraction (LVEF) remained stable (pre-LVEF 48.9% ± 12.6% vs post-LVEF 50.1% ± 10.1%; P = .29), even in those without a cardiac resynchronization therapy (CRT) device (pre-LVEF 54.3% ± 8.0% vs post-LVEF 53.8% ± 8.0%; P = .65). Forty-nine patients (83.1%) reported an improvement in symptoms regardless of AF type (17/21 [81.0%] paroxysmal vs 32/38 [84.2%] persistent; P = 1.00), presence of baseline left ventricular impairment (22/26 [84.6%] LVEF ≤50% vs 27/33 [81.8%] LVEF ≥50%; P = 1.00) or CRT device (27/32 [84.4%] CRT vs 22/27 [81.5%] no CRT; P = 1.00). Symptoms improved in 16 patients (89.0%) who underwent AVN ablation to regularize rhythm. AVN ablation improved symptoms without impacting left ventricular function in the majority of patients. The data suggest that AVN ablation is an effective and safe management approach for AF in HCM and should be further evaluated in larger prospective studies.

Predictive Factors for Decreasing Left Ventricular Ejection Fraction and Progression to the Dilated Phase of Hypertrophic Cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HCM) may progress to the dilated phase (DHCM). This study aimed to identify the predictive factors for DHCM progression, including left ventricular (LV) ejection fraction (LVEF < 50%) or decreased LV contraction (LVEF < 60%). The study included 291 patients enrolled in our hospital's HCM registry who were grouped based on their poststudy LVEF (LVEF of ≥60%, 50-59%, and <50%). Predictive factors of an LVEF of <50% or <60% were determined. Further, the effects of percutaneous transluminal septal myocardial ablation (PTSMA) on long-term systolic LV function and DHCM development were investigated. LVEF was ≥60%, 50-59%, and <50% in 239, 33, and 19 patients, respectively, during the follow-up period (mean: 64.9 months). Multivariate analyses indicated baseline atrial fibrillation (AF), nonsustained ventricular tachycardia (NSVT), and left ventricular diameter at end-systole (LVDs) as significant predictors of DHCM. Using a scoring method based on AF, NSVT, and LVDs, patients with 2 and 3 points had a significantly higher risk of developing DHCM. PTSMA in 78 HCM patients demonstrated no significant effect on long-term LVEF changes or DHCM development. We concluded that AF, NSVT, and LVDs are significant predictors of DHCM development. However, a validation study with a larger population is required.

PO-02-158 PACE AND ABLATE IS AN EFFECTIVE MANAGEMENT STRATEGY FOR ATRIAL FIBRILLATION IN PATIENTS WITH HYPERTROPHIC CARDIOMYOPATHY

Atrial fibrillation (AF) is common in patients with hypertrophic cardiomyopathy (HCM). In this cohort, the sequel of rapid ventricular response and symptoms associated with an irregular rhythm can be challenging to manage with medical therapy and catheter ablation (CA). Pace and ablate (PAb) strategy may offer an effective treatment alternative. Assess the efficacy of PAb in patients with HCM who have failed medical therapy and/or catheter ablation for AF. Single centre study with retrospective analysis of a prospectively collated HCM registry. PAb patients were identified. Baseline characteristics, procedural indication and procedural data was collected and symptoms defined by NYHA and EHRA classification plus echocardiographic findings in follow-up assessed. Forty-two patients (17 (40%) male and age 67±11 years) were included (Table 1) of which 18 (43%) patients had undergone previous CA ablation. Indications for PAb: 5 (12%) inappropriate shock, 24 (57%) ineffective rate control and 13 (31%) to regularise rhythm to improve symptoms. Procedural parameters: procedure time 70±12mins and immediate success in 40 patients (95%) with no complications. During a follow-up time of 62±54 months, left ventricular ejection fraction (LVEF) post PAb remained stable (LVEF Pre 52±10%, LVEF Post 50±9%, p=0.6). Those without a CRT also had no change in LV function during follow-up post PAb (LVEF pre 55±8% vs post 51±19%, p=0.21). Thirty-three (83%) patients reported an improvement in symptoms post procedure. In patients with symptom improvement there was no difference in AF type (14/15, 93% paroxysmal vs. 19/25, 76% persistent AF; p=0.22), presence of at least moderate mitral regurgitation (MR) (12/33, 36% moderate MR. 1/7, 14% no moderate MR; p=0.39), LV impairment (10/11, 91% LVEF <50% vs. 23/29, 79% LVEF ≥50%; p=0.65) or CRT device in situ (22/24, 92% CRT vs. 11/16, 69% no CRT; p=0.09). Symptoms improved in 10 (76%) patients who underwent PAb to regularise rhythm. In the majority of patient with HCM and AF, PAb improves symptoms without impacting LV function regardless of AF type, device implanted or the presence of pre-existing LV impairment. PAb was also shown to effectively improve symptoms through regularising the rhythm. Post PAb, LV function remains stable regardless of the type of device implanted. PAb is an effective treatment strategy for AF in patients with HCM.

Genome-Wide Analysis of Left Ventricular Maximum Wall Thickness in the UK Biobank Cohort Reveals a Shared Genetic Background With Hypertrophic Cardiomyopathy.

Left ventricular maximum wall thickness (LVMWT) is an important biomarker of left ventricular hypertrophy and provides diagnostic and prognostic information in hypertrophic cardiomyopathy (HCM). Limited information is available on the genetic determinants of LVMWT. We performed a genome-wide association study of LVMWT measured from the cardiovascular magnetic resonance examinations of 42 176 European individuals. We evaluated the genetic relationship between LVMWT and HCM by performing pairwise analysis using the data from the Hypertrophic Cardiomyopathy Registry in which the controls were randomly selected from UK Biobank individuals not included in the cardiovascular magnetic resonance sub-study. Twenty-one genetic loci were discovered at P<5×10-8. Several novel candidate genes were identified including PROX1, PXN, and PTK2, with known functional roles in myocardial growth and sarcomere organization. The LVMWT genetic risk score is predictive of HCM in the Hypertrophic Cardiomyopathy Registry (odds ratio per SD: 1.18 [95% CI, 1.13-1.23]) with pairwise analyses demonstrating a moderate genetic correlation (rg=0.53) and substantial loci overlap (19/21). Our findings provide novel insights into the genetic underpinning of LVMWT and highlight its shared genetic background with HCM, supporting future endeavours to elucidate the genetic etiology of HCM.

3-Dimensional Strain Analysis of Hypertrophic Cardiomyopathy: Insights From the NHLBI International HCM Registry

BackgroundAbnormal global longitudinal strain (GLS) has been independently associated with adverse cardiac outcomes in both obstructive and nonobstructive hypertrophic cardiomyopathy. ObjectivesThe goal of this study was to understand predictors of abnormal GLS from baseline data from the National Heart, Lung, and Blood Institute (NHLBI) Hypertrophic Cardiomyopathy Registry (HCMR). MethodsThe study evaluated comprehensive 3-dimensional left ventricular myocardial strain from cine cardiac magnetic resonance in 2,311 patients from HCMR using in-house validated feature-tracking software. These data were correlated with other imaging markers, serum biomarkers, and demographic variables. ResultsAbnormal median GLS (> –11.0%) was associated with higher left ventricular (LV) mass index (93.8 ± 29.2 g/m2 vs 75.1 ± 19.7 g/m2; P < 0.0001) and maximal wall thickness (21.7 ± 5.2 mm vs 19.3 ± 4.1 mm; P < 0.0001), lower left (62% ± 9% vs 66% ± 7%; P < 0.0001) and right (68% ± 11% vs 69% ± 10%; P < 0.01) ventricular ejection fractions, lower left atrial emptying functions (P < 0.0001 for all), and higher presence and myocardial extent of late gadolinium enhancement (6 SD and visual quantification; P < 0.0001 for both). Elastic net regression showed that adjusted predictors of GLS included female sex, Black race, history of syncope, presence of systolic anterior motion of the mitral valve, reverse curvature and apical morphologies, LV ejection fraction, LV mass index, and both presence/extent of late gadolinium enhancement and baseline N-terminal pro–B-type natriuretic peptide and troponin levels. ConclusionsAbnormal strain in hypertrophic cardiomyopathy is associated with other imaging and serum biomarkers of increased risk. Further follow-up of the HCMR cohort is needed to understand the independent relationship between LV strain and adverse cardiac outcomes in hypertrophic cardiomyopathy.

Machine learning evaluation of LV outflow obstruction in hypertrophic cardiomyopathy using three-chamber cardiovascular magnetic resonance

Left ventricular outflow tract obstruction (LVOTO) is common in hypertrophic cardiomyopathy (HCM), but relationships between anatomical metrics and obstruction are poorly understood. We aimed to develop machine learning methods to evaluate LVOTO in HCM patients and quantify relationships between anatomical metrics and obstruction. This retrospective analysis of 1905 participants of the HCM Registry quantified 11 anatomical metrics derived from 14 landmarks automatically detected on the three-chamber long axis cine CMR images. Linear and logistic regression was used to quantify strengths of relationships with the presence of LVOTO (defined by resting Doppler pressure drop of > 30 mmHg), using the area under the receiver operating characteristic (AUC). Intraclass correlation coefficients between the network predictions and three independent observers showed similar agreement to that between observers. The distance from anterior mitral valve leaflet tip to basal septum (AML-BS) was most highly correlated with Doppler pressure drop (R2 = 0.19, p < 10–5). Multivariate stepwise regression found the best predictive model included AML-BS, AML length to aortic valve diameter ratio, AML length to LV width ratio, and midventricular septal thickness metrics (AUC 0.84). Excluding AML-BS, metrics grouped according to septal hypertrophy, LV geometry, and AML anatomy each had similar associations with LVOTO (AUC 0.71, 0.71, 0.68 respectively, p = ns), significantly less than their combination (AUC 0.77, p < 0.05 for each). Anatomical metrics derived from a standard three-chamber CMR cine acquisition can be used to highlight risk of LVOTO, and suggest further investigation if necessary. A combination of geometric factors is required to provide the best risk prediction.

Right Ventricular Enlargement and Dysfunction Are Associated With Increased All-Cause Mortality in Hypertrophic Cardiomyopathy

ObjectiveTo assess whether right ventricular enlargement (RVE) and right ventricular dysfunction (RVD) adversely affect prognosis in hypertrophic cardiomyopathy (HCM). Patients and MethodsData were retrieved from Mayo Clinic’s prospectively collected HCM registry between January 1, 2000, and September 30, 2012. Right ventricle (RV) size and function were semiquantitatively categorized via echocardiography as normal (RV-Norm) versus abnormal (RV-Abn) (RVE or RVD). All-cause mortality was the primary endpoint. ResultsOf 1878 HCM patients studied (mean age 53±15 years; 41.6% female), only 71 (3.8%) had RV-Abn (24 RVE, 28 RVD, 19 combined RVE and RVD). Compared with HCM patients with RV-Norm, RV-Abn patients were older (57±14 vs 53±15 years, P=.02), more symptomatic (New York Heart Association functional class III-IV in 62.0% vs 48.6%, P=.03), had more atrial fibrillation (53.5% vs 17.3%, P<.001), and more prior implantable cardioverter-defibrillator implantation (23.9% vs 11.3%, P=.02). Median follow-up was 9.4 years with 311 deaths. Patients who were RV-Abn had higher all-cause mortality compared with RV-Norm (log-rank P<.001); 24.1% (95% CI, 15.5% to 35.3%) vs 6.1% (95% CI, 5.1% to 7.3%) at 5 years. In multivariable Cox modeling, RV-Abn (hazard ratio, 1.89; 95% CI, 1.18 to 3.03; P=.008) was associated independently with all-cause mortality after adjusting for age, female sex, New York Heart Association functional class, atrial fibrillation, hypertension, coronary artery disease, implantable cardioverter-defibrillator implantation, beta blocker use, prior septal reduction therapy, resting LV outflow tract gradient, maximal LV wall thickness, and moderate or greater tricuspid regurgitation. ConclusionAlthough perturbations in RV size and function were observed in fewer than 5% of patients with HCM, they were associated with nearly two-fold higher all-cause mortality at long-term follow-up.

Sex Disaggregated Analysis of Risk Factors for Adverse Outcomes in Hypertrophic Cardiomyopathy

Patient sex has been associated with differences in disease penetrance and clinical expression in hypertrophic cardiomyopathy (HCM). We sought to investigate sex-disaggregated differences in risk factors for adverse outcomes in a large international HCM registry.

Abstract 13918: Prognostic Implication of Mitral Valve Disease in Patients With Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is a genetic disorder affecting not only the myocardium, but also the mitral valve (MV) and its apparatus. Hypothesis: MV disease would have a prognostic implication in patients with HCM. Methods: We reviewed MV function and structure in the indexed echocardiograms of 1,185 HCM patients (60 ±14 years, men 67%) who were included in a single-center longitudinal HCM registry. Patients were classified as obstructive (n=104) or non-obstructive (n=1,081) HCM. Clinical outcomes were defined as a composite of cardiovascular death, heart failure hospitalization, MV surgery or septal myectomy, and heart transplantation. Results: Overall, 278 patients (23.5%) showed at least mild mitral regurgitation (MR) on their indexed echocardiogram (Figure 1-1). MR, systolic anterior motion (SAM), and mitral annular calcification (MAC) were more prevalent in patients with obstructive HCM than in those with non-obstructive HCM. During a mean of 7.0 ± 4.0 years’ follow-up, Kaplan-Meier plots revealed that patients with MR showed poorer clinical outcomes (21.6% vs.7.3%, log-rank p &lt; 0.001) than those without MR (Figure 1-2). A multivariate Cox model revealed that MR was independently associated with clinical outcome (hazard ratio 1.57, 95% confidence interval 1.04-2.35, p=0.030) along with female sex, chronic kidney disease, atrial fibrillation, obstructive type HCM, and diastolic dysfunction. Conclusions: MV disease is not uncommon in patients with HCM. MR, SAM, and MAC are more prevalent in patients with obstructive HCM. The presence of MR is associated with a poor prognosis in patients with HCM.

Abstract 11959: Left Atrial Size and Function in Children and Young Adults With Obstructive vs. Nonobstructive Hypertrophic Cardiomyopathy

Introduction: Left atrial (LA) strain has been recently used to improve assessment of left atrial (LA) function. In adults with hypertrophic cardiomyopathy (HCM), increased LA size and decreased LA strain are associated with LVOT obstruction (LVOTO) and higher risk for adverse cardiovascular outcomes. Scant data exists on the association of LA strain and size in children with HCM, comparing those with and without obstruction. Methods: For this pilot study, all patients from an existing pediatric BCH stress echo HCM registry who had adequate echocardiographic images to assess both LA size and strain were consecutively enrolled and retrospectively reviewed. Post-processing LA size and strain (reservoir and conduit) were performed with use of Tomtec/Philips LV strain. Children with HCM were divided into 2 groups: those with resting LVOT gradients &lt;30 mm Hg (no obstruction) versus ≥30 mm Hg (obstruction). LA size, strain and diastolic indices were compared for those with and without obstruction. Results: A total of 48 children (63% male, median age 13 yrs, range 6-23yrs) with HCM and analyzable images from the registry formed the cohort. Patient demographics, LA size and strain, and diastolic indices are summarized in Table 1. HCM children with LVOTO had larger LA size (apical 4-chamber (A4C) cross sectional area: p&lt;0.001), lower LA conduit and reservoir strain (p&lt;0.05 for all), and increased diastolic dysfunction (p&lt;0.05 for all). Conclusions: Despite their younger age, children with obstructive HCM had larger LA size, lower LA reservoir and conduit strain, and increased diastolic dysfunction compared to children with nonobstructive HCM. Larger studies are needed with longer follow-up time to assess association of LA strain with cardiac events in children.

Myocardial Deformation Analysis in MYBPC3 and MYH7 Related Sarcomeric Hypertrophic Cardiomyopathy-The Graz Hypertrophic Cardiomyopathy Registry.

Accumulating evidence suggests that individuals with sarcomeric hypertrophic cardiomyopathy (HCM) carrying MYH7 mutations may have a worse prognosis than MYBPC3 mutation carriers. Myocardial deformation analysis is superior to standard echocardiography in detecting subtle myocardial dysfunction and scar formation, but studies evaluating the association with HCM genotype are scarce. We therefore aimed to compare myocardial strain parameters between MYBPC3 and MYH7 mutation carriers with proven HCM. Participants of the prospective Graz HCM Registry carrying at least one causative mutation in MYBPC3 (n = 39) or MYH7 (n = 18) were enrolled. MYBPC3 mutation carriers were older, predominantly male and more often treated with an implantable cardioverter-defibrillator (39% vs. 0%; p = 0.002). Using analyses of covariance, there were no significant differences between MYBPC3 and MYH7 mutation carriers with regard to left ventricular global longitudinal strain (estimated marginal means ± standard deviation: −16.9 ± 0.6% vs. −17.3 ± 0.9%; p = 0.807) and right ventricular 6-segments endocardial strain (−24.3 ± 1.0% vs. 26.3 ± 1.5%; p = 0.285). Our study suggests, that myocardial deformation analysis may not be helpful in concluding on the underlying HCM genotype, and vice versa.

Clinical significance of new-onset atrial fibrillation in patients with hypertrophic cardiomyopathy.

AimsThere is limited information about the clinical significance of atrial fibrillation (AF), particularly new‐onset AF, in patients with hypertrophic cardiomyopathy (HCM) in a community‐based patient cohort. This study was carried out to clarify the prevalence and prognostic impact of AF in Japanese HCM patients.Methods and resultsIn 2004, we established a cardiomyopathy registration network in Kochi Prefecture as a prospective study, and finally, 293 patients with HCM were followed. In the patients' cohort, we recently reported the clinical outcomes including mortality and HCM‐related morbid events. HCM‐related adverse cardiovascular events were defined in the following: (i) sudden cardiac death (SCD)‐relevant events including SCD, spontaneous sustained ventricular tachycardia, and appropriate implantable cardioverter defibrillator discharge; (ii) heart failure (HF) events with the composite of HF death and hospitalization for HF; and (iii) embolic events included embolic stroke‐related death and admission for embolic events. In the present study, we focused on AF and conducted a detailed investigation. At registration, the mean age of the patients was 63 ± 14 years, and 86 patients (29%) had documented AF including paroxysmal AF. Patients with AF at registration were characterized by worse clinical profiles including more advanced age, more symptomatic, more advanced left ventricular, and left atrial remodelling at registration. During a mean follow‐up period of 6.1 ± 3.2 years, a total of 77 HCM‐related adverse events occurred, and the presence of AF at registration was associated with an increased risk of HCM‐related adverse events, particularly heart failure events. During the follow‐up period, an additional 31 patients (11%) had documentation of AF for the first time, defined as new‐onset AF, with an annual incidence of approximately 1.8%, and finally, a total of 117 patients (40%) showed AF. The presence of palpitation and enlarged left atrial diameter, particularly left atrial diameter ≥50 mm, at registration were significant predictors of new‐onset AF. Importantly, the incidence of overall HCM‐related adverse events was further higher in patients with new‐onset AF observed from AF onset than in patients with AF at registration.ConclusionsIn our HCM registry in an aged Japanese community, a significant proportion developed AF. The presence of AF, particularly new‐onset AF, was associated with increased incidence of HCM‐related events. AF may not be just a marker of disease stage but an important trigger of adverse events.

Toward Replacing Late Gadolinium Enhancement With Artificial Intelligence Virtual Native Enhancement for Gadolinium-Free Cardiovascular Magnetic Resonance Tissue Characterization in Hypertrophic Cardiomyopathy.

Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging is the gold standard for noninvasive myocardial tissue characterization but requires intravenous contrast agent administration. It is highly desired to develop a contrast agent-free technology to replace LGE for faster and cheaper CMR scans. A CMR virtual native enhancement (VNE) imaging technology was developed using artificial intelligence. The deep learning model for generating VNE uses multiple streams of convolutional neural networks to exploit and enhance the existing signals in native T1 maps (pixel-wise maps of tissue T1 relaxation times) and cine imaging of cardiac structure and function, presenting them as LGE-equivalent images. The VNE generator was trained using generative adversarial networks. This technology was first developed on CMR datasets from the multicenter Hypertrophic Cardiomyopathy Registry, using hypertrophic cardiomyopathy as an exemplar. The datasets were randomized into 2 independent groups for deep learning training and testing. The test data of VNE and LGE were scored and contoured by experienced human operators to assess image quality, visuospatial agreement, and myocardial lesion burden quantification. Image quality was compared using a nonparametric Wilcoxon test. Intra- and interobserver agreement was analyzed using intraclass correlation coefficients (ICC). Lesion quantification by VNE and LGE were compared using linear regression and ICC. A total of 1348 hypertrophic cardiomyopathy patients provided 4093 triplets of matched T1 maps, cines, and LGE datasets. After randomization and data quality control, 2695 datasets were used for VNE method development and 345 were used for independent testing. VNE had significantly better image quality than LGE, as assessed by 4 operators (n=345 datasets; P<0.001 [Wilcoxon test]). VNE revealed lesions characteristic of hypertrophic cardiomyopathy in high visuospatial agreement with LGE. In 121 patients (n=326 datasets), VNE correlated with LGE in detecting and quantifying both hyperintensity myocardial lesions (r=0.77-0.79; ICC=0.77-0.87; P<0.001) and intermediate-intensity lesions (r=0.70-0.76; ICC=0.82-0.85; P<0.001). The native CMR images (cine plus T1 map) required for VNE can be acquired within 15 minutes and producing a VNE image takes less than 1 second. VNE is a new CMR technology that resembles conventional LGE but without the need for contrast administration. VNE achieved high agreement with LGE in the distribution and quantification of lesions, with significantly better image quality.

Time to Think Differently About Sarcomere-Negative Hypertrophic Cardiomyopathy.

Time to Think Differently About Sarcomere-Negative Hypertrophic Cardiomyopathy.

Management and outcomes of hypertrophic cardiomyopathy in young adults

Management of young adults with hypertrophic cardiomyopathy (HCM) is challenging. To evaluate the profile of young adults (16-25 years) with HCM included in the French prospective HCM registry. Patients were compared according to occurrence of major adverse cardiac events (MACE), comprising sudden cardiac death (SCD) events (implantable cardioverter defibrillator [ICD] discharge, SCD, sustained ventricular tachycardia), atrial fibrillation/embolic stroke, heart failure hospitalisation and unexplained syncope, at a mean follow-up of 4.4±2.2 years. At baseline, among 61 patients (20.5±3.0 years; 16 women, 26.2%), 13 (21.3%) had a prophylactic ICD, 24.6% a family history of SCD, 29.5% obstruction, 86.0% magnetic resonance imaging myocardial fibrosis, 11.8% abnormal exercise blood pressure and 52.8% a European Society of Cardiology (ESC) 5-year SCD score<4% (24.5%≥6%). At follow-up, 15 patients (24.6%; seven women; all with fibrosis) presented 17 MACE, comprising: SCD events (n=7, 41.2%; including three patients with an ICD, five with at least one SCD major classical risk factor and an ESC score≥5% and two with no risk factors and an ESC score<4%); atrial fibrillation/stroke (n=6, 35.3%); heart failure (n=1, 5.9%); syncope (n=3, 17.6%). An ICD was implanted in 11 patients (four for secondary prevention), but in only 61.5% of patients with a score≥6%. Only obstruction significantly increased MACE risk (odds ratio 3.96; P=0.035), with a non-significant trend towards a lower risk in men (OR 0.29; P=0.065). In young adults with HCM, MACE are common in the short term, especially in obstructive HCM and women, mostly arrhythmic in origin. Prophylactic ICD implantation is frequent and does not strictly follow the guidelines, while the use of European/USA guidelines is helpful but imperfect in identifying SCD risk.