Events In Hypertrophic Cardiomyopathy Research Articles

Abstract 4143227: Incidence of Hemorrhagic Stroke in Hypertrophic Cardiomyopathy

Background: Individuals with hypertrophic cardiomyopathy (HCM) have an elevated risk of ischemic stroke, primarily driven by the increased risk of atrial fibrillation (AF) development in this patient population. This risk remains elevated regardless of CHADS2VASC score; thus, anticoagulation is recommended for all HCM patients with AF. Given the known association between anticoagulant medications and hemorrhagic events, there is likely an assumed risk of hemorrhagic stroke in these individuals. Currently, the incidence of hemorrhagic stroke in HCM and its relationship to AF and anticoagulation has not been well-established in the literature. The goal of this study was to establish the presence of and risk factors for hemorrhagic stroke in individuals with HCM. Methods: A retrospective review of all HCM patients ages 18 and older in our institution’s health system was performed from 2019-2023. ICD 10 codes were used to identify individuals with hemorrhagic stroke. Patient charts were reviewed for additional data including demographics, comorbid conditions, anticoagulant prescription, and other inciting factors prior to the hemorrhagic event. Results: The study cohort comprised 343 HCM patients, of which 47.1% were female and 72.7% were Caucasian. Concurrently, 30% (n=103) had a diagnosis of AF. The overall incidence of hemorrhagic stroke was 2.9% (5.8%, n=6 in those with AF vs 1.7%, n=4 in those without AF); furthermore, AF was associated with a non-statistically significant increased risk of hemorrhagic stroke (RR = 3.36, 95% CI 0.97-11.7). Anticoagulant use at the time of hemorrhagic event was observed in 4 individuals (67%) with AF and 1 individual (25%) without AF. Head trauma and falls were frequently observed as precipitating events prior to hospital admission for hemorrhagic stroke, occurring in 83% (n = 5) of patients with AF and 50% (n = 2) of those without AF. Conclusions: While ischemic stroke and anticoagulant use are commonly studied in those with HCM, the incidence of hemorrhagic stroke in this population is not negligible. Risk of hemorrhagic events in HCM appears largely influenced by anticoagulant use, particularly in those with concurrent AF, and by head trauma. Given the known benefits of anticoagulation on ischemic stroke risk in the HCM population, appropriate counseling and careful attention to individual patient factors may be warranted in the administration of anticoagulants.

Left atrial strain predicts adverse events in hypertrophic cardiomyopathy: preliminary results from a CMR study

Abstract Background Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of major adverse cardiovascular events (MACE), however, current risk stratification methods are imperfect. Left atrial global longitudinal strain (LA GLS) is an increasingly acknowledged predictive parameter, yet its potential role in HCM is not well defined. Purpose This study aims to investigate the prognostic role of cardiac magnetic resonance (CMR)-derived LA GLS for the occurrence of MACE in patients with HCM. Methods A retrospective, single-centre, CMR study of HCM patients was conducted. Clinical data was collected from electronic medical record and CMR images were analysed by two blinded investigators. LA GLS was derived from CMR two-chamber cine images by a semiautomatic method, and was categorized according to its median value. The endpoint was a composite of MACE, including all-cause death, sudden cardiac death (SCD), sustained and non-sustained ventricular tachycardias (VT), appropriate implantable cardiac defibrillator (ICD) shocks, heart failure (HF) hospitalization, and new-onset atrial fibrillation (AF). Cox regression analysis was performed. The preliminary results of the study are now reported. Results A total of 54 HCM patients were included, mean age was 58.5 years ± 15.9 and 38.9% were female. Average maximal wall thickness (MWT) was 18.0 mm ± 3.9, 37% had left ventricular outflow obstruction (LVOTO) and 45.1% had positive late gadolinium enhancement (LGE). After a mean follow-up of 6.9 ± 3.0 years, 26 patients (48.1%) experienced the composite endpoint. Figure 1 shows the clinical and CMR differences according to the occurrence of MACE. LA GLS was significantly lower in patients with MACE compared to those without (26.5 ± 19% vs 36.7 ± 13%, p=0.026), with a moderate predictive value (AUC = 0.68, Figure 2A). Multivariate Cox regression analysis revealed that a decrease in LA GLS (HR 1.09 per each 1% decrease, 95% CI 1.03-1.15, p=0.002), the presence of LGE (HR 6.9, 95% CI 1.7-28, p=0.007), the presence of LVOTO (HR 3.4, 95% CI 1.12-10.2, p=0.031) and an increase in MWT (HR 1.23 per each 1mm increase, 95% CI 1.05-1.45, p=0.011) were independently associated with MACE. Among low-risk HCM patients (absence of LGE or LVOTO, or MWT below our median value), LA GLS had an additional prognostic role, and those with an LA GLS above the median value (LA GLS>29.7%) presented a remarkably favourable prognosis (Figure 2B-D). Conclusions CMR-derived LA GLS is a predictor of outcomes in HCM beyond established imaging prognostic factors. Particularly, LA GLS appears to be useful in risk-stratifying low-risk HCM patients: those with normal LA GLS show an excellent prognosis. If confirmed in larger studies, LA GLS could be used to individualise HCM management.Figure 2

The prognostic and incremental value of T1 mapping for predicting adverse events in hypertrophic cardiomyopathy

Abstract Background In patients with hypertrophic cardiomyopathy (HCM), the prognostic value of native T1 and extracellular volume fraction (ECV) for adverse cardiovascular events has not been well defined. Methods Consecutive 663 participants with HCM who underwent cardiovascular magnetic resonance (CMR) were recruited. The follow-up endpoints included heart failure (HF)-related death and sudden cardiac death (SCD) or aborted SCD. Results During the median follow-up time of 44 months (interquartile range [IQR]: 23 to 66.0 months), 56 (8.4%) participants reached composite endpoints including 38 (5.7%) with SCD or aborted SCD, 16 (2.4%) with HF-related death and 2 (0.3%) with heart transplantation. On multivariable Cox proportional hazards regression analyses, native T1 including late gadolinium enhancement (LGE) from three short axes were significantly associated with cardiac death (basal native T1: hazard ratio [HR], 1.06 per 10 ms increase; 95% confidence interval [CI], 1.02 to 1.09; middle native T1: HR, 1.05 per 10 ms increase; 95% CI, 1.01 to 1.09; apical native T1: HR, 1.04 per 10 ms increase; 95% CI, 1.02 to 1.07; all P < 0.05) after adjustment for non-sustained ventricular tachycardia, history of syncope, the extent of LGE, left atrial size, and NYHA class. Conversely, only basal ECV was associated with cardiac death (basal ECV including LGE area: HR, 1.08 per 1% increase, 95%CI, 1.03 to 1.13, P = 0.001; basal ECV excluding LGE: HR, 1.1 per 1% increase; 95%CI, 1.04 to 1.16; P < 0.001) In addition, participants with increased mean native T1 (≥1349.4 ms) or basal ECV(≥ 29.4%) were more likely to suffer from cardiac death in the entire study cohort or the subgroup with low LGE extent (<15%) or low ESC risk score (<6%) (all P < 0.05). Furthermore, the addition of mean LV native T1 (≥1349.4 ms) or basal ECV (≥ 29.4%) to current risk factors in the guidelines could further improve prediction for the composite endpoint (C-index increased to 0.719 from 0.521 for the AHA/ACC risk model, P < 0.001; C index increased to 0.709 from 0.514 for the ESC risk model; P < 0.001). Conclusions In this study of patients with HCM, mean native T1 of three short axes and basal ECV were independently associated with cardiac death and added incremental value to conventional clinical predictors for patients with HCM.Figure 1.Demonstrative images.Figure 2 Incremental Value of T1 mapping

Kiosk 8R-FA-02 - Predictive Value of Left Atrial Fast Long-axis Strain for Thrombotic Events in Hypertrophic Cardiomyopathy

Kiosk 8R-FA-02 - Predictive Value of Left Atrial Fast Long-axis Strain for Thrombotic Events in Hypertrophic Cardiomyopathy

Late gadolinium enhancement entropy as a new measure of myocardial tissue heterogeneity for prediction of adverse cardiac events in patients with hypertrophic cardiomyopathy

ObjectivesEntropy is a new late gadolinium enhanced (LGE) cardiac magnetic resonance (CMR)–derived parameter that is independent of signal intensity thresholds. Entropy can be used to measure myocardial tissue heterogeneity by comparing full pixel points of tissue images. This study investigated the incremental prognostic value of left ventricular (LV) entropy in patients with hypertrophic cardiomyopathy (HCM).MethodsThis study enrolled 337 participants with HCM who underwent 3.0-T CMR. The LV entropy was obtained by calculating the probability distribution of the LV myocardial pixel signal intensities of the LGE sequence. Patients who underwent CMR imaging were followed up for endpoints. The primary endpoint was defined as readmission to the hospital owing to heart failure. The secondary endpoint was the composite of the primary endpoint, sudden cardiac death and non-cardiovascular death.ResultsDuring the median follow-up of 24 months ± 13 (standard deviation), 43 patients who reached the primary and secondary endpoints had a higher entropy (6.20 ± 0.45, p < 0.001). The patients with increased entropy (≥ 5.587) had a higher risk of the primary and secondary endpoints, compared with HCM patients with low entropy (p < 0.001 for both). In addition, Cox analysis showed that LV entropy provided significant prognostic value for predicting both primary and secondary endpoints (HR: 1.291 and 1.273, all p < 0.001). Addition of LV entropy to the multivariable model improved model performance and risk reclassification (p < 0.05).ConclusionLV entropy assessed by CMR was an independent predictor of primary and secondary endpoints. LV entropy assessment contributes to improved risk stratification in patients with HCM.Critical relevance statementMyocardial heterogeneity reflected by entropy the derived parameter of LGE has prognostic value for adverse events in HCM. The measurement of LV entropy helped to identify patients with HCM who were at risk for heart failure and sudden cardiac death.Key points• Left ventricular entropy can reflect myocardial heterogeneity in HCM patients.• Left ventricular entropy was significantly higher in HCM patients who reached endpoint events.• Left ventricular entropy helps to predict the occurrence of heart failure and death in HCM patients.Graphical

High-risk imaging characteristics in left ventricular apex for the life-threatening arrhythmic events in Japanese hypertrophic cardiomyopathy patients.

Left ventricular (LV) apical aneurysm is known to be associated with the life-threatening arrhythmic events in hypertrophic cardiomyopathy (HCM). However, the current 2014 ESC guideline has not included apical aneurysm as a major risk factor for sudden cardiac death and 2018 JCS guideline includes it only as a modulator, while it has been included as a new major risk marker in 2020 AHA/ACC guideline. Therefore, we sought to identify high-risk imaging characteristics in LV apex which is associated with a higher occurrence of ventricular tachycardia/fibrillation (VT/VF). In 99 consecutive Japanese HCM patients (median age, 65years; 59 males) undergoing implantable cardioverter-defibrillator (ICD) implantation for primary prevention following cardiac magnetic resonance including late gadolinium enhancement (LGE), the occurrence of appropriate ICD interventions for VT/VF was evaluated for 6.2 (median) years after ICD implantation. Overall, appropriate ICD interventions occurred in 43% with annual rates of 7.0% for appropriate interventions. Kaplan-Meier analysis demonstrated that the presence of LV apical aneurysm was significantly associated with a higher occurrence of appropriate interventions (annual rates 18.9% vs. 6.4%, P = 0.013). Similarly, patients with high LV mid-to-apex pressure gradient (annual rates 14.9% vs. 6.2%, P = 0.022) and presence of apical LGE (annual rates 10.9% vs. 4.0%, P = 0.001) experienced appropriate interventions more frequently. An aneurysm, high-pressure gradient, and LGE in an apex are associated with VT/VF. These characteristics in apex should be kept in mind when implanting ICD in Japanese HCM patients as a primary prevention.

Signaling Pathways Associated With Prior Cardiovascular Events in Hypertrophic Cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. A subset of patients experience major adverse cardiovascular events (MACEs), including arrhythmias, strokes and heart failure. However, the molecular mechanisms underlying MACEs in HCM are still not well understood. Therefore, we conducted a multicenter case-control study of patients with HCM, comparing those with and without prior histories of MACEs to identify dysregulated signaling pathways through plasma proteomics profiling. MethodsWe performed plasma proteomics profiling of 4986 proteins. We developed a proteomics-based discrimination model in patients enrolled at 1 institution (training set) and externally validated the model in patients enrolled at another institution (test set). We performed pathway analysis of proteins dysregulated in patients with prior MACEs. ResultsA total of 402 patients were included, with 278 in the training set and 124 in the test set. In this cohort, 257 (64%) patients had prior MACEs (172 in the training set and 85 in the test set). Using the proteomics-based model from the training set, the area under the receiver operating characteristic curve was 0.82 (95% confidence interval, 0.75–0.90) in the test set. Patients with prior MACEs demonstrated dysregulation in pathways known to be associated with MACEs (eg, TGF-β) and novel pathways (eg, Ras-MAPK and associated pathways). ConclusionsIn this multicenter study of 402 patients with HCM, we identified both known and novel pathways dysregulated in a subset of patients with more advanced disease.

Evidence for microstructural alteration and microvascular disease in subclinical and overt hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation - Clinical Research Training Fellowship Background Disarray and microvascular disease (MVD) are implicated in adverse events in hypertrophic cardiomyopathy (HCM). Advances in CMR permit quantification of microstructural indices reflecting disarray, and microvascular disease. As novel myosin inhibitors provide promise for disease modification, early and disease-specific biomarkers are a rapidly emerging clinical priority. Purpose Using latest imaging techniques, we investigated MVD and disarray in 3 HCM groups: overt disease, either genotype positive (G+LVH+) or negative (G-LVH+), and subclinical HCM (G+LVH-), exploring relationships to electrical changes and genetic substrate. Methods A 207 subject, multi-centre consortium: 102 patients with overt HCM (52 G+LVH+, 50 G-LVH+), 77 subclinical (G+LVH-) and 28 matched healthy volunteers (HV). All underwent ECG, quantitative perfusion (measuring myocardial blood flow (MBF), perfusion reserve (MPR) and perfusion defects) and cardiac diffusion tensor imaging (cDTI) to investigate for evidence of disarray, measured as fractional anisotropy (FA – the directional variability of diffusion, reflecting myocyte disarray), mean diffusivity (MD – reflecting myocyte packing and intra- and extracellular volume) and absolute second eigenvector angle (E2A –measuring orientation of sheetlets, functional units of myocytes that re-orientate to facilitate wall-thickening). Results Compared to HV, overt HCM had evidence of microstructural alteration (lower FA (suggestive of disarray), higher MD and higher E2A, all p&amp;lt;0.001) and MVD (lower stress MBF and MPR p&amp;lt;0.001). Compared to G+LVH+, G-LVH+ had elevated E2A (64.4°(58.7–66.5) vs 60.1°(55.6–63.7 p = 0.006)). Perfusion defects were found in all G+ but not all G- overt disease (100%(52/52) vs 82%(41/50) p = 0.001). Compared to HV, subclinical HCM (G+LVH-) had evidence of microstructural alteration (lower FA suggestive of disarray, higher MD and higher E2A, all p&amp;lt;0.001) and MVD (reduced stress MBF (2.43±0.52 vs 2.77±0.62ml/g/min p = 0.006) with perfusion defects in 29% (vs 0 HV p = 0.001)). Microstructural markers and MVD were independently associated, in both overt and subclinical disease (overt: E2A and stress MBF: β=-0.29, p = 0.002; subclinical: those with perfusion defects (vs without) had lower FA &amp; higher E2A). Disarray markers and MVD independently associated with pathological ECG abnormalities in both overt and subclinical disease, after adjustment for degree of fibrosis and LVH (overt: FA odds ratio (OR) for abnormal ECG=3.2, p = 0.014; stress MBF OR=2.8, p = 0.013; subclinical: FA OR=3.4, p = 0.006, MPR OR=4.0 p = 0.008). Conclusions In Hypertrophic Cardiomyopathy, sarcomere mutation carriers without hypertrophy have microstructural alterations and microvascular disease that are detectable, correlate, and associate with pathological ECG changes. These are more prominent once LVH is present, with genotype positive and genotype negative overt disease patients having differing phenotypes.

Machine learning approach based on echocardiographic data to improve prediction of cardiovascular events in hypertrophic cardiomyopathy

Structural changes and myocardial fibrosis quantification by cardiac imaging have become increasingly important to predict cardiovascular events in hypertrophic cardiomyopathy patients. In this setting, it is likely that a supervised approach, using machine learning, may improve their risk assessment. We retrospectively included patients with confirmed HCM (n = 265, 52 ± 17 years) through clinical and echocardiographic. A supervised machine learning prognosis algorithm, based on echocardiographic data, was obtained to predict cardiovascular (CV) outcomes, and subsequently investigated for their association with myocardial fibrosis (n = 185) assessed by CMR imaging. At follow-up at 57 months, 13 (4.9%) of patients died and 114 (43%) had been hospitalized for CV events. Patient with CV events had higher indexed LV mass, worse diastolic dysfunction, and more severe LV obstruction. HCM-patients with myocardial fibrosis have more severe LV hypertrophy (OR: 3.1; P = 0.003) and longitudinal myocardial deformation (OR: 0.8; P = 0.008). Prognosis algorithm established using machine learning identified left atrium area (> 24 cm2), mechanical dispersion (> 49 ms), posterior wall thickness (> 1.8 cm), and TAPSE (27 mm) as the four most relevant variables to correctly predict cardiovascular events. Our findings suggest that a simple algorithm based on four key variables (posterior wall thickness, mechanical dispersion, LA area and TAPSE) may help risk stratification and decision-making in patients with HCM. Using new treatments to target these parameters might improve outcomes in HCM-patients (Fig. 1).

Myocardial Activity at 18F-FAPI PET/CT and Risk for Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

Background Myocardial fibrosis contributes to adverse cardiovascular events in hypertrophic cardiomyopathy (HCM). Purpose To explore the characteristics of cardiac fibroblast activation protein inhibitor (FAPI) PET/CT imaging and its relationship with the risk of sudden cardiac death (SCD) in HCM. Materials and Methods In this prospective study from July 2021 to January 2022, participants with HCM and healthy control participants underwent cardiac fluorine 18 (18F)-labeled FAPI PET/CT imaging. Myocardial FAPI activity was quantified as intensity (target-to-background uptake ratio), extent (the percent of FAPI-avid myocardium of the left ventricle [LV]), and amount (the percent of FAPI-avid myocardium of LV × target-to-background ratio). Regional wall thickness was analyzed at cardiac MRI. The 5-year SCD risk score was calculated from the 2014 European Society of Cardiology guidelines. Univariable and multivariable linear regression analyses were used to identify factors related to the FAPI amount. The correlation between FAPI amount and 5-year SCD risk was explored. Results Fifty study participants with HCM (mean age, 43 years ± 13 [SD]; 32 men) and 22 healthy control participants (mean age, 45 years ± 17; 14 men) were included. All participants with HCM had intense and inhomogeneous cardiac FAPI activity in the LV myocardium that was higher than that in healthy control participants (median target-to-background ratio, 8.8 vs 2.1, respectively; P < .001). In HCM, more segments with FAPI activity were detected than the number of hypertrophic segments (median, 14 vs five, respectively; P < .001); 84% of nonhypertrophic segments showed FAPI activity. Log-transformed FAPI amount had a positive relationship with log-transformed N-terminal probrain natriuretic peptide, high-sensitive troponin I, and left atrial diameter and a negative relationship with LV ejection fraction z-score. Degree of FAPI activity positively correlated with the 5-year SCD risk score (r = 0.32; P = .03). Conclusion Fibroblast activation protein inhibitor (FAPI) PET/CT imaging indicated intense and heterogeneous activity in hypertrophic cardiomyopathy, and FAPI uptake was associated with 5-year risk of sudden cardiac death. © RSNA, 2022 Online supplemental material is available for this article.

Left Atrial Reservoir Strain-Based Left Ventricular Diastolic Function Grading and Incident Heart Failure in Hypertrophic Cardiomyopathy

The echocardiographic assessment of left ventricular (LV) diastolic dysfunction (LVDD) in patients with hypertrophic cardiomyopathy is complex and not well-established. We investigated whether the left atrial reservoir strain (LARS) could be used to categorize LVDD and whether this grading is predictive of heart failure (HF) events in hypertrophic cardiomyopathy. A total of 414 patients with hypertrophic cardiomyopathy (aged 58.3±12.8 years; 65.7% male) were categorized using LARS-defined LVDD (LARS-DD) grades: ≥35% (grade 0), ≥24% to <35%, ≥19% to <24%, and <19% (grade 3). Patients were followed for a median of 6.9 years to assess hospitalization for HF or HF-related death. An increase in LARS-DD grade was associated with worse conventional echocardiographic parameters of LVDD, such as lower e', higher E/e' ratio, greater maximum tricuspid regurgitation velocity, and restrictive mitral inflow pattern. Higher LARS-DD grade was also associated with parameters reflecting increased LV filling pressure, such as greater LV wall thickness, greater extent of fibrosis, obstructive physiology, and decreased LV longitudinal strain. Furthermore, higher LARS-DD grade was associated with worse HF-free survival (log-rank P<0.001). Patients with LARS-DD grades 0, 1, 2, and 3 showed 10-year HF-free survival of 100%, 91.6%, 84.1%, and 67.5%, respectively. LARS-DD grade was an independent predictor of HF events after adjusting for clinical and echocardiographic variables (hazard ratio, 1.53 [95% CI, 1.03-2.28], per 1-grade increase). The LARS-DD grade also had incremental prognostic value for incident HF events over the traditional echocardiographic LVDD parameters and grading system. The prognostic value of advanced LARS-DD grade was consistent in sensitivity analyses and various patient subgroups. LARS can be used as a simple single or supplemental index to categorize LV diastolic function and predict HF events in hypertrophic cardiomyopathy.

Absent fourth heart sound as a marker of adverse events in hypertrophic cardiomyopathy with sinus rhythm.

BackgroundPatients with hypertrophic cardiomyopathy (HCM) in sinus rhythm commonly show the fourth heart sound (S4). The lack of S4 may be a marker of impaired atrial function in HCM patients with sinus rhythm.Methods and ResultsThis retrospective study consisted of 47 patients with HCM who had undergone phonocardiography and a cardiopulmonary exercise test. The primary outcome was a composite of cardiac death, stroke, hospitalization for worsening heart failure, and newly developed atrial fibrillation (AF). S4 was detected in 38 of 43 patients with sinus rhythm (88%). Peak oxygen consumption was the highest in 38 sinus rhythm patients with S4 (23.6 ± 5.6 mL/kg/min), middle in five sinus rhythm patients without S4 (19.3 ± 6.7 mL/kg/min), and lowest in four patients with AF (15.7 ± 3.3 mL/kg/min, p = 0.01). After a median of 40.5 months, the incidence of the primary outcome was higher in patients without S4 than in those with S4 (33% vs. 8%; hazard ratio, 6.17; 95% confidence interval, 1.02 – 37.4; p = .04) and higher in sinus rhythm patients without S4 than in those with S4 (60% vs. 8%; hazard ratio, 12.05; 95% confidence interval, 2.31 – 71.41; p = .007).ConclusionsThe absence of S4 on phonocardiography was associated with impaired exercise tolerance and adverse cardiac events in HCM patients with sinus rhythm.

The impact of cardiopulmonary exercise-derived scoring on prediction of cardio-cerebral outcome in hypertrophic cardiomyopathy.

Sudden cardiac death (SCD) and stroke-related events accompanied by atrial fibrillation (AF) can affect morbidity and mortality in hypertrophic cardiomyopathy (HCM). This study sought to evaluate a scoring system predicting cardio-cerebral events in HCM patients using cardiopulmonary exercise testing (CPET). We investigated the role of a previous prediction model based on CPET, the HYPertrophic Exercise-derived Risk score for Heart Failure-related events (HyperHF), which is derived from peak circulatory power ventilatory efficiency and left atrial diameter (LAD), for predicting a composite of SCD-related (SCD, serious ventricular arrhythmia, death from cardiac cause, heart failure admission) and stroke-related (new-onset AF, acute stroke) events. The Novel HyperHF risk model using left atrial volume index (LAVI) instead of LAD was proposed and compared with the previous HCM Risk-SCD model. A total of 295 consecutive HCM patients (age 59.9±13.2, 71.2% male) who underwent CPET was included in the present study. During a median follow-up of 742 days (interquartile range 384-1047 days), 29 patients (9.8%) experienced an event (SCD-related event: 14 patients (4.7%); stroke-related event: 17 patients (5.8%)). The previous model for SCD risk score showed fair prediction ability (AUC of HCM Risk-SCD 0.670, p = 0.002; AUC of HyperHF 0.691, p = 0.001). However, the prediction power of Novel HyperHF showed the highest value among the models (AUC of Novel HyperHF 0.717, p<0.001). Both conventional HCM Risk-SCD score and CPET-derived HyperHF score were useful for prediction of overall risk of SCD-related and stroke-related events in HCM. Novel HyperHF score using LAVI could be utilized for a better prediction power.

Feature-tracking cardiac magnetic resonance method: a valuable marker of replacement fibrosis in hypertrophic cardiomyopathy.

PurposeLeft ventricular (LV) replacement fibrosis is a marker of adverse cardiac events in hypertrophic cardiomyopathy (HCM). We aimed to assess the efficacy of the feature-tracking cardiac magnetic resonance (FT-CMR) in the detection of LV replacement fibrosis.Material and methodsFifty-one patients with HCM (51% female, mean age = 21 ± 5.2 years) and significant myocardial hypertrophy, who underwent CMR between February 2018 and December 2019 were enrolled. Functional and 3D FT-CMR parameters were measured. LV global longitudinal strain, global radial strain (GRS), and global circumferential strain (GCS) were recorded. The percentage of enhanced myocardial mass was calculated. Univariate and multivariate regression analyses were performed to determine the predictors of fibrosis. A p-value of less than 0.05 was considered significant.ResultsThe mean enhanced mass percentage was 15.2 ± 10.53%. Among LV volumetric parameters, end-systolic and end-diastolic volume indices predicted fibrosis (fitness [F] = 8.11 and p = 0.006 vs. F = 6.6 and p = 0.012, correspondingly). The univariate linear regression demonstrated that GCS and GRS predicted total enhanced mass (%) (F = 12.29 and p = 0.001 vs. F = 7.92 and p = 0.007, respectively). After the inclusion of all volumetric and deformation parameters, the multivariate analysis identified the model of a combination of LV end-diastolic volume index (LV EDVI) and LV GCS as a robust predictor of the fibrosis percentage (F = 8.86 and p = 0.005).ConclusionsNon-contrast CMR parameters including LV GCS and LV EDVI are valuable markers of replacement fibrosis in HCM patients with notable myocardial hypertrophy.

Mean Scar Entropy by Late Gadolinium Enhancement Cardiac Magnetic Resonance Is Associated With Ventricular Arrhythmias Events in Hypertrophic Cardiomyopathy.

Background: Ventricular arrhythmias are associated with sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). Previous studies have found the late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) was independently associated with ventricular arrhythmia (VA) in HCM. The risk stratification of VA remains complex and LGE is present in the majority of HCM patients. This study was conducted to determine whether the scar heterogeneity from LGE-derived entropy is associated with the VAs in HCM patients.Materials and Methods: Sixty-eight HCM patients with scarring were retrospectively enrolled and divided into VA (31 patients) and non-VA (37 patients) groups. The left ventricular ejection fraction (LVEF) and percentage of the LGE (% LGE) were evaluated. The scar heterogeneity was quantified by the entropy within the scar and left ventricular (LV) myocardium.Results: Multivariate analyses showed that a higher scar [hazard ratio (HR) 2.682; 95% CI: 1.022–7.037; p = 0.039] was independently associated with VA, after the adjustment for the LVEF, %LGE, LV maximal wall thickness (MWT), and left atrium (LA) diameter.Conclusion: Scar entropy and %LGE are both independent risk indicators of VA. A high scar entropy may indicate an arrhythmogenic scar, an identification of which may have value for the clinical status assessment of VAs in HCM patients.

Abstract 9571: Major Adverse Cardiac Events in Hypertrophic Cardiomyopathy Among Index Patients and Their Affected Relatives

Introduction: The incidence of major adverse cardiac events (MACE) is well established among index patients with hypertrophic cardiomyopathy (HCM) carrying pathogenic sequence variants in recognized HCM genes. However, MACE among their affected relatives is unknown. It was the aim to compare the incidence of MACE among index patients with HCM and their affected relatives. Methods: Clinical and genetic investigations were performed in consecutive index patients with HCM. Genetic investigations by next-generation sequencing were made in 116 recognized and likely HCM genes, and variants were classified by American College of Medical Genetics and Genomics criteria. Relatives at risk of having HCM were invited for clinical investigations (echocardiography, ECG-recording, and genetic testing when relevant). MACE was defined as a composite endpoint of sudden cardiac death, death due to end-stage heart failure or stroke, and heart transplant. Results: A total of 453 HCM families underwent clinical and genetic investigations, of whom 40% (183/453) carried pathogenic variants. Among relatives, 383 carried the same variant as the index-patient, and the penetrance of HCM in those was 42% (160/383). The median age of diagnosis was 47 years (p=0.13) in relatives and index patients. MACE occurred in 18% (33/183) of index patients, 18% (28/160) of relatives with HCM, and 0% (0/223) of healthy variant carriers. The median age of MACE was 43 years for index patients and relatives (p=0.48). During eight years of follow-up, incidence rates of MACE were not significantly different between index patients and relatives (1.2%/year vs. 1.5%/year p=0.2). Conclusions: Affected Relatives in HCM families who carried pathogenic sequence variants in recognized HCM genes had the same risk of MACE as index patients. This finding emphasized the importance of family screening, follow-up, and continuous risk stratification to possibly avoid adverse disease complications and sudden death.

Vectorcardiography as a prognostic tool in hypertrophic cardiomyopathy

BackgroundVectorcardiography (VCG) has demonstrated diagnostic value in the assessment of hypertrophic cardiomyopathy (HCM), however, determining its prognostic value over time has not yet been investigated. This study sought to assess the correlation of VCG parameters with the progression of HCM. MethodsA retrospective chart review of 119 pediatric patients with diagnosis of HCM at the University of Minnesota. Eighty-three cases were excluded because of age, presence of congenital heart disease, not meeting criteria for HCM or negative phenotype. Sample was divided into 2 groups based on the presence or not of cardiac events (ventricular tachycardia, cardiac arrest, ventricular assist device, heart transplant). Derived vectorcardiography from standard 12‑lead ECG was obtained for the first ECG and last available or prior to sentinel event. ResultsOf the 36 cases that met inclusion criteria, 9 (25%) developed a sentinel event. The median age for the event group was 10.1 ± 7.5 years and for the non-event group was 8.7 ± 6.35 years. There was no significant difference in age or sex between the groups.The T wave vector magnitude value was significantly smaller in the event group than in the non-event group (0.302 ± 0.146 mV Vs. 0.561 ± 0.305 mV, p 0.002), with a hazard ratio of 0.651 (95% CI 0.463 to 0.915). No other parameter showed significant difference between the two groups. ConclusionsThe T wave vector magnitude may predict sentinel events in HCM. Prospective studies are necessary to evaluate the utility of the evolution of VCG parameters.

Cardiac magnetic resonance strain as a predictor of clinical events in hypertrophic cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Hypertrophic cardiomyopathy (HCM) is a relatively prevalent condition associated with cardiovascular death and heart failure. Several tools are currently available to identify which HCM patients are at risk of developing these events. Purpose We aimed to evaluate the association of new Tissue Tracking strain analysis by cardiac magnetic resonance (CMR) and the development of clinical events in patients with HCM. Methods We prospectively analyzed 136 consecutive patients with HCM diagnosis (established according to current clinical practice guidelines) from January 2006 to October 2017. Heart failure hospital admissions and death on follow-up were included in a combined clinical outcome. CMR studies were performed following our predefined CMR protocol for HCM with 1.5T magnets. Cine images were obtained with standard, retrospectively gated, steady-state free-precession (SSFP) sequences in 2, 3 and 4 chambers views and in 10–15 contiguous short-axis slices covering the ventricles from the base to the apex, with breath holding. The strain evaluation was performed by a commercially available Tissue Tracking analysis software, manually defining the endocardial border in short axis, 4, 3 and 2 chambers views and, after verifying adequate identification of the different structures, running the strain analysis (Figure 1, displaying myocardium identification by the strain analysis software). Results Mean follow-up was 49 ± 45 months. Mean age was 61 ± 15.33 years old (p 0.024) and 31% of patients were women (p 0.01). 20% had atrial fibrillation (p 0.154). Mean ejection fraction was 69 ± 9.21% (p 0.762) and mean HCM-SCD (hypertrophic cardiomyopathy sudden cardiac death) risk score was 2.20 ± 1.35 (p 0.885). Mean global radial systolic strain rate (GRSsr) was -1,33 ± 0.59 s-1 (p 0.083). During follow-up, 12 heart failure hospital admissions and 14 death from any cause were registered. GRSsr showed an area under de ROC curve of 0.63 (95% confidence interval -CI- 0.51 – 0.75) predicting clinical events. The value of 1.40 s−1 was selected as the best sensitivity/specificity cutoff point. Three variables (sex, age, and previous history of atrial fibrillation) were chosen (through the allsets method) and included as adjusting variables together with &amp;lt;1,40 s−1/≥1.40 s−1 in a multivariate Cox’s regression model (p 0.002; AIC 99.7; Harrell C index 0.82). Patients with GRSsr &amp;lt;1.40 s−1 showed more clinical evens on follow-up vs those with GRSsr ≥1.40 s−1 (adjusted HR 6.57; 95% CI 2.01 – 21.49; p 0.002; Figure 2, displaying Kaplan-Meier survival estimates). Conclusions A GRSsr &amp;lt;1.40 s−1 emerges as a novel independent predictor of worse clinical outcomes in patients with HCM and preserved ejection fraction.

The prognostic value of novel myocardial deformation parameters for sudden events in hypertrophic cardiomyopathy

Abstract Background Data about the implications of two-dimensional (2D) speckle tracking myocardial deformation parameter for predicting sudden arrhythmic events in hypertrophic cardiomyopathy (HCM) are limited. Purpose The aim of our study was to prospectively evaluate the predictive value of novel myocardial deformation parameters with regard to 2D speckle tracking echocardiography in patients with HCM. Methods This was a prospective study that included HCM patients without concomitant severe valvular heart disease, without prior myocardial infarction and with sinus rhythm at index evaluation. A total of 317 patients were screened and 67 subjects were excluded. Finally, the study sample consisted of 250 patients (mean age 50.8±15.8, 67.2% male). Global longitudinal strain (GLS), left atrial (LA) strain, radial strain, circumferential strain, and mechanical dispersion of the left ventricle ((MD)-the standard deviation of time to peak negative strain in 18 left ventricular segments) were examined. The primary outcome of the study was sudden arrhythmic events including sudden cardiac death, sustained ventricular tachycardia, resuscitated cardiac arrest and appropriate impantable cardioverter defibrillator discharges. Results During a mean follow-up of 2.4±1.2 years, 19 patients suffered a sudden arrhythmic event. GLS, LA strain, MD and radial strain significantly predicted sudden events among our cohort. The optimal cut-off values obtained from receiver-operator characteristic curves were for GLS &amp;gt;−14%, for LA strain &amp;lt;12%, for radial strain &amp;lt;21% and for MD &amp;gt;67ms. However, only GLS &amp;gt;−14% and LA strain &amp;lt;12% displayed a significant additive predictive value on top of the European Society Of Cardiology risk score (HCMRisk-SCD) (C statistic from 0.757 to 0.831, p=0.03 including GLS &amp;gt;−14% in the survival model and to 0.839, p=0.009 including LA strain &amp;lt;12% in the model). (Table) Conclusion GLS and LA strain conferred a significant additional prognostic value to HCMRisc-SCD score for predicting sudden arrhythmic events in HCM patients. Funding Acknowledgement Type of funding source: None

Myocardial tissue characterization by gadolinium-enhanced cardiac magnetic resonance imaging for risk stratification of adverse events in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy with a wide spectrum of clinical manifestations. Patients can be asymptomatic or suffer major adverse events including sudden cardiac death, ventricular arrhythmias, and heart failure. Identification of individuals with HCM who are at risk for these complications remains challenging. While echocardiography remains the mainstay of diagnostic evaluation, cardiac magnetic resonance imaging (CMR) is an important adjunctive diagnostic modality with emerging applications for risk-stratification of adverse events in the HCM population. Although not included in current guidelines for HCM management, there is increasing evidence to support the use of CMR for routine prognostic assessment of HCM patients. In this review we discuss the use of CMR techniques, including late gadolinium enhancement, T1 mapping, and quantification of extracellular volume fraction, for the risk stratification of three major adverse events in HCM: sudden cardiac death, ventricular arrhythmias, and congestive heart failure.