Hypertrophic Cardiomyopathy-Related Sudden Cardiac Death in Young People in Ontario.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is considered a leading cause of sudden cardiac death (SCD) in younger people. The incidence of HCM-related SCD and its relationship to exercise have not been well studied in large comprehensive studies outside of tertiary care settings. This study sought to estimate the incidence of HCM-related SCD and its association with exercise in a large unselected population. METHODS: Using the Office of the Chief Coroner of Ontario database encompassing all deaths attended by the coroner, we identified all HCM-related SCDs in individuals 10 to 45 years of age between 2005 and 2016 (70 million person-years). Confirmation of HCM was based on typical macroscopic and microscopic features (definite HCM-related SCD). Sudden deaths with a prior clinical diagnosis of HCM but no autopsy were considered probable HCM-related SCDs. Cases with typical features but no myofiber disarray were considered possible HCM. The completeness of data was verified in a subset of patients in the Toronto area with the use of a registry of all emergency medical services-attended cardiac arrests, with an autopsy rate of 94%. To estimate the number of HCM-related aborted cardiac arrests and lives potentially saved by implantable cardioverter-defibrillators, all de novo implantations for secondary prevention and all implantations and appropriate shocks for primary prevention in patients with HCM 10 to 45 years of age, respectively, were identified with the use of a registry containing data on implantable cardioverter-defibrillator implantations from all implanting sites throughout Ontario. RESULTS: Forty-four, 3, and 6 cases of definite, probable, and possible HCM-related SCDs, respectively, were identified, corresponding to estimated annual incidence rates of 0.31 per 1000 HCM person-years (95% CI, 0.24-0.44) for definite HCM-related SCD, 0.33 per 1000 HCM person-years (95% CI, 0.34-0.62) for definite or probable HCM-related SCD, and 0.39 per 1000 HCM person-years (95% CI, 0.28-0.49) for definite, probable, or possible HCM-related SCD (estimated 140 740 HCM person-years of observation). The estimated annual incidence rate for HCM-related SCD plus aborted cardiac arrest and HCM-related life-threatening arrhythmia (SCD, aborted cardiac arrest, and appropriate implantable cardioverter-defibrillator shocks) was 0.84 per 1000 HCM person-years (95% CI, 0.70-1.0). The majority (70%) of SCDs occurred in previously undiagnosed individuals. Most SCDs occurred during rest (64.8%) or light activity (18.5%). CONCLUSIONS: The incidence of HCM-related SCD in the general population 10 to 45 years of age is substantially lower than previously reported, with most cases occurring in previously undiagnosed individuals. SCDs are infrequently related to exercise.

The relationship between the quantitative extent of late gadolinium enhancement and burden of nonsustained ventricular tachycardia in hypertrophic cardiomyopathy: A delayed contrast-enhanced magnetic resonance study.

OBJECTIVES: To examine the relationship between late gadolinium enhancement (LGE) extent and nonsustained ventricular tachycardia (NSVT) characteristics in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: NSVT has been shown to be independently associated with sudden cardiac death (SCD) in HCM. Previous studies have found LGE on cardiac magnetic resonance (CMR) to be independently associated with NSVT. METHODS: Seventy-three patients who had 14-day Holter monitoring for either risk stratification for SCD (n = 62) or evaluation of atrial fibrillation (n = 11) on a CMR study were included. Areas of LGE in left ventricle (LV) were visually identified and analyzed quantitatively for both high (≥6 SD above the mean signal intensity of normal myocardium) and intermediate (≥4 but <6 SD) LGE signal intensity. RESULTS: Patients with more extensive LGE had longer (P = 0.0028) and more frequent (P = 0.02) episodes of NSVT. In univariate analyses, frequency of NSVT was associated with LGE extent (rs = 0.43, P = 0.001), LV ejection fraction (rs = -0.38, P < 0.001), LV mass (rs = 0.32, P = 0.005), LV maximal wall thickness (rs = 0.28, P = 0.016), and left atrium diameter (rs = 0.29, P = 0.001); maximal length of NSVT was associated with LGE extent (rs = 0.52, P < 0.001), LV ejection fraction (rs = -0.44, P < 0.001), LV mass (rs = 0.37, P = 0.001), and left atrium diameter (rs = 0.3, P < 0.001). In multivariable analyses, LGE extent remained the sole variable independently associated with frequency (P = 0.001) and maximal length of episodes of NSVT (P = 0.001). No significant association was found between the rate of NSVT and LGE extent. CONCLUSIONS: LGE extent is independently associated with a greater burden and longer episodes of NSVT in HCM. These findings support the association between myocardial fibrosis as represented by LGE and ventricular tachyarrhythmias in HCM.

Cardiovascular Magnetic Resonance Provides Evidence of Abnormal Myocardial Strain and Primary Cardiomyopathy in Marfan syndrome.

OBJECTIVE: Marfan syndrome is an autosomal-dominant genetic disorder caused by mutations in the fibrillin-1 gene. The condition is a connective tissue disease that frequently involves the cardiovascular system. The existence of a primary cardiomyopathy in Marfan syndrome, however, is controversial. The aims of this study were to investigate the prevalence of left ventricular dysfunction with both transthoracic echocardiography and cardiovascular magnetic resonance (CMR) in a cohort of Marfan syndrome patients and to investigate patterns of myocardial strain across the cohort. METHODS: We used an institutional database to identify all patients with a firm diagnosis of Marfan syndrome based on Ghent criteria. Inclusion required left ventricular ejection fraction (LVEF) to have been measured by both CMR and transthoracic echocardiography within 12 months of each other. Normal LVEF was defined as a value of >55% when measured by CMR. Velocity vector imaging was used to measure left ventricular longitudinal strain patterns by application of feature tracking to cine magnetic resonance images. Results were compared with data from 20 age-matched control subjects. RESULTS: Sixty-nine Marfan syndrome patients met the inclusion criteria. The mean age was 35.4 ± 15.0 years, and 56.5% were male. The mean LVEF was 59.0% ± 7.0% by CMR and 59.1% ± 5.8% by echo. One-fifth of Marfan syndrome patients (15/69; 21.7%) had reduced function with LVEF ≤55% by CMR, but only 5 of these were identified by echo. Furthermore, echo identified 5 Marfan syndrome patients as having reduced LVEF in the presence of a normal LVEF by CMR. Some Marfan syndrome patients had abnormal longitudinal strain patterns even with LVEF within the reference range. CONCLUSIONS: These data provide support for a primary cardiomyopathy in some Marfan syndrome patients. Cardiovascular magnetic resonance is more sensitive than echo for identifying cases with mild systolic dysfunction. Strain analysis may be more sensitive than simple LVEF assessment for identifying at-risk individuals.

Left atrial remodeling postseptal myectomy for severe obstructive hypertrophic cardiomyopathy: Analysis by two-dimensional speckle-tracking echocardiography.

BACKGROUND: Septal myectomy relieves left ventricular outflow obstruction (LVOTO) and is associated with excellent long-term outcomes. LVOTO is associated with diastolic dysfunction and increased left atrial (LA) size. We sought to investigate the changes in LA volumes and function postmyectomy and the association between these changes with clinical outcomes postmyectomy. METHODS: Sixty-six hypertrophic cardiomyopathy patients undergoing myectomy were retrospectively studied. Preprocedural and 6- to 18-month postmyectomy follow-up transthoracic echocardiographic images were obtained. LA volumes and strain were assessed by two-dimensional speckle-tracking echocardiography. RESULTS: Left atrial volumes, that is, indexed maximal, minimal, and pre-A volumes reduced postmyectomy, yet remained increased compared to controls (105.6 ± 34.5 mL vs 84.9 ± 26.7 mL, 45.2 ± 25.7 mL vs 35.4 ± 22.6 mL, 70.1 ± 31.4 mL vs 35.4 ± 22.6 mL, respectively, P < 0.05). The total emptying index did not improve postmyectomy and remained lower than controls (58.6 ± 12.4 vs 59.9 ± 12.8, P = NS) whereas atrial contraction improved, yet did not normalize (active emptying index 36.1 ± 14.9 vs 41.1 ± 16.2, P < 0.05). The conduit volume remained reduced postmyectomy (18.6 ± 13.3 mL vs 16.6 ± 15.1 mL, P = NS). LA strain also did not improve postmyectomy (26.8 ± 7.3 vs 28.5 ± 8.8, P = NS). A multivariable logistic regression identified preprocedural E/e' ratio and indexed maximal LA volume, as independent predictors for LA volume reduction ≥20% postmyectomy. During a mean follow-up of 4.9 ± 2.3 years postmyectomy, 24.2% of the patients developed atrial fibrillation and <5% of patients were severely symptomatic. We found no associations between LA volumes/function and atrial fibrillation or symptoms postmyectomy. CONCLUSION: Postmyectomy LA volumes decreased, and the contractile function improved. There was no association between LA volumes/function and clinical outcomes postmyectomy. Notably, the LA remained enlarged (though to a lesser degree) with reduced strain and emptying fraction, suggesting possible atrial myopathy.

Evaluation of Hypertrophic Cardiomyopathy: Newer Echo and MRI Approaches.

PURPOSE OF REVIEW: This review discusses the basic and evolving echocardiographic and cardiac magnetic resonance (CMR) approaches in the diagnosis and management of patients with hypertrophic cardiomyopathy (HCM). RECENT FINDINGS: Newer imaging technologies and techniques in both echocardiography and CMR have proved to add incremental value to our understanding of HCM. 3D reconstruction in echocardiography and CMR allows for more accurate morphological and volumetric assessment of the left ventricle. Echocardiographic and CMR-based left atrial assessment, including for its mechanical properties, has been shown to be correlated to outcomes and development of atrial fibrillation. Tissue characterization and scar burden quantification by late gadolinium enhancement on CMR has revolutionized our understanding of fibrotic processes in HCM and their contribution to disease severity and clinical outcomes. Cardiac imaging plays a crucial role in HCM patients. Using echocardiography and CMR as complementary modalities allows for improved diagnostics, optimization of treatment, and better prognostication.

Prevention of sudden death in hypertrophic cardiomyopathy: bridging the gaps in knowledge.

Sudden cardiac death (SCD) is the most devastating complication of hypertrophic cardiomyopathy (HCM). Although the annual rate of SCD in the general HCM population is <1% per year according to contemporary series, there is still a small subset of patients who are at increased risk of SCD. The greatest challenge in the management of HCM is identifying those at increased risk as an implantable cardioverter defibrillator is a potentially life-saving therapy. In this review, we sought to summarize the available data on SCD in HCM and provide a clinical perspective on the current differing and somewhat conflicting European and American recommendations on risk stratification, with balanced guidance with regards to rational clinical decision making. Additionally, we sought to learn more on the actual implementation of the guidelines by HCM experts worldwide.

Patterns of CMR measured longitudinal strain and its association with late gadolinium enhancement in patients with cardiac amyloidosis and its mimics.

BACKGROUND: Regional variability of longitudinal strain (LS) has been previously described with echocardiography in patients with cardiac amyloidosis (CA), however, the reason for this variability is not completely evident. We sought to describe regional patterns in LS using feature-tracking software applied to cardiovascular magnetic resonance (CMR) cine images in patients with CA, hypertrophic cardiomyopathy (HCM), and Anderson-Fabry's disease (AFD) and to relate these patterns to the distribution of late gadolinium enhancement (LGE). METHODS: Patients with CA (n = 45) were compared to LV mass indexed matched patients with HCM (n = 19) and AFD (n = 19). Peak systolic LS measurements were obtained using Velocity Vector Imaging (VVI) software on CMR cine images. A relative regional LS ratio (RRSR) was calculated as the ratio of the average of the apical segmental LS divided by the sum of the average basal and mid-ventricular segmental LS. LGE was quantified for the basal, mid, and apical segments using a threshold of 5SD above remote myocardium. A regional LGE ratio was calculated similar to RRSR. RESULTS: Patients with CA had significantly had worse global LS (-15.7 ± 4.6%) than those with HCM (-18.0 ± 4.6%, p = 0.046) and AFD (-21.9 ± 5.1%, p < 0.001). The RRSR was higher in patients with CA (1.00 ± 0.31) than in AFD (0.79 ± 0.24; p = 0.018) but not HCM (0.84 ± 0.32; p = 0.114). In CA, a regional difference in LGE burden was noted, with lower LGE in the apex (31.5 ± 19.1%) compared to the mid (38.2 ± 19.0%) and basal (53.7 ± 22.7%; p < 0.001 for both) segments. The regional LGE ratio was not significantly different between patients with CA (0.33 ± 0.15) and AFD (0.47 ± 0.58; p = 0.14) but lower compared to those with HCM (0.72 ± 0.43; p < 0.0001). LGE percentage showed a significant impact on LS (p < 0.0001), with a 0.9% decrease in absolute LS for every 10% increase in LGE percentage. CONCLUSION: The presence of marked "relative apical sparing" of LS along with a significant reduction in global LS seen in patients with CA on CMR cine analysis may provide an additional tool to differentiate CA from other cause of LVH. The concomitant presence of a base to apex gradient in quantitative LGE burden suggests that the regional strain gradient may be at least partially explained by the burden of amyloid deposition and fibrosis.

Complementary Role of Echocardiography and Cardiac Magnetic Resonance in Hypertrophic Cardiomyopathy.

PURPOSE OF REVIEW: This review discusses the complementary roles of echocardiography and cardiac magnetic resonance in the diagnosis and management of patients with hypertrophic cardiomyopathy (HCM). RECENT FINDINGS: Imaging using novel echocardiographic techniques and cardiac magnetic resonance (CMR) imaging in HCM has demonstrated incremental utility in diagnosis and management guidance. Application of 3-D imaging has improved assessment of left ventricular (LV) mass and volume by echocardiography. Quantification of myocardial mechanics has shown promise for clarification of diagnosis, prognosis, and assessment of LV dysfunction. CMR permits 3-D tomographic characterization of cardiac structure and tissue characterization which has shown utility for assessing the diverse phenotypes in HCM and quantification of left ventricular fibrosis, an increasingly recognized poor prognostic marker. Non-invasive cardiac imaging remains central for the evaluation of HCM patients. An approach integrating echocardiography and CMR as complementary modalities allows for improved diagnostic and prognostic assessment.

Rapid Device-Detected Nonsustained Ventricular Tachycardia in the Risk Stratification of Hypertrophic Cardiomyopathy.

BACKGROUND: Nonsustained ventricular tachycardia (NSVT) detected by ambulatory Holter (Holter NSVT) is a major risk factor for sudden cardiac death in hypertrophic cardiomyopathy (HCM). We hypothesized that the prognostic utility of Holter NSVT in HCM would improve with prolonged monitoring and a higher heart rate cut-off for detection. METHODS: We enrolled 60 patients (44 ± 14 years) with HCM, who had a prophylactic implantable cardioverter defibrillator (ICD). Positive Holter NSVT (prior to implant) was defined as ≥3 beats at ≥120 beats per minute (bpm). We assessed the prevalence of rapid NSVT (RNSVT) detected by their ICD within 12 months of its implant, defined as 4-16 beats at ≥150-200 bpm. The primary outcome was appropriate ICD therapy (antitachycardia pacing and shocks) for sustained ventricular arrhythmia (VA). RESULTS: Holter NSVT was detected in 34 patients. RNSVT occurred in 21 (35%) patients of whom five did not have Holter NSVT. Over a median follow-up of 61 (interquartile range 29, 129) months after ICD implant, nine patients had VA. RNSVT, but not Holter NSVT, was significantly associated with VA (hazard ratio 6.2, 95% confidence interval [1.3-30], P = 0.01) by multivariable Cox regression analysis that included conventional risk factors. Receiver operating characteristic analysis for RNSVT (area under curve 0.80, P = 0.005) showed that the occurrence of ≥2 episodes of RNSVT discriminated patients for VA optimally (sensitivity 78%, specificity 84%, positive predictive value 47%, negative predictive value 96%). CONCLUSIONS: In this pilot study, RNSVT detected by continuous monitoring independently predicted VA in HCM and offered superior discrimination of VA risk compared to conventional risk factors, including Holter NSVT. Future studies are needed to validate these findings in a larger, unselected HCM cohort.

Left atrial and ventricular systolic and diastolic myocardial mechanics in patients with end-stage renal disease.

BACKGROUND: Diastolic cardiac dysfunction is an important complication of end-stage renal disease (ESRD), but quantification remains a challenge. Given that diastolic dysfunction is reflected in both left atrial (LA) and ventricular (LV) function, we aimed to identify abnormalities in LV and LA volume and function using measures of myocardial mechanics. METHODS: We retrospectively studied 53 incident ESRD patients (46±16 y/o 44% male) and compared them to 85 normal controls. LA phasic volumes and functional parameters were obtained from the apical 4CH view. Global ventricular peak longitudinal and circumferential strain, strain rate (GLS, GL-SR, CS), and rotation were obtained from apical and short-axis views. LA and LV measurements were taken off line using dedicated software (eSie VVI). RESULTS: ESRD patients had abnormal systolic function with lower LV ejection fraction and peak endocardial strain parameters (mean: GLS -16.6% vs -19.9%, GL-SR -0.91 vs -1.04, and CS -25.6% vs 27.9%, P≤.01 for all). Traditional Doppler parameters remained similar between groups, while diastolic mechanics were abnormal in ESRD. Reduced LV-derived diastolic parameters, fractional early reverse rotation, a marker of ventricular relaxation (P<.006), and ratio of early diastolic SR to systolic SR (P<.04) denote significant diastolic dysfunction. Increased LA volumes (P<.001), decreased LA reservoir (P<.001), conduit (P<.0004), and contractile (P<.02) function reflect diastolic dysfunction. CONCLUSION: Myocardial strain measurements quantitated the abnormalities in both LV diastolic and LA function associated with the uremic state. The distinct abnormal diastolic parameters were suggestive of abnormal relaxation and increased filling pressures. Early and accurate assessment of diastolic function may help tailor patient management ESRD.

Prognostic value of quantitative contrast-enhanced cardiovascular magnetic resonance for the evaluation of sudden death risk in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in the young, although not all patients eligible for sudden death prevention with an implantable cardioverter-defibrillator are identified. Contrast-enhanced cardiovascular magnetic resonance with late gadolinium enhancement (LGE) has emerged as an in vivo marker of myocardial fibrosis, although its role in stratifying sudden death risk in subgroups of HCM patients remains incompletely understood. METHODS AND RESULTS: We assessed the relation between LGE and cardiovascular outcomes in 1293 HCM patients referred for cardiovascular magnetic resonance and followed up for a median of 3.3 years. Sudden cardiac death (SCD) events (including appropriate defibrillator interventions) occurred in 37 patients (3%). A continuous relationship was evident between LGE by percent left ventricular mass and SCD event risk in HCM patients (P=0.001). Extent of LGE was associated with an increased risk of SCD events (adjusted hazard ratio, 1.46/10% increase in LGE; P=0.002), even after adjustment for other relevant disease variables. LGE of ≥15% of LV mass demonstrated a 2-fold increase in SCD event risk in those patients otherwise considered to be at lower risk, with an estimated likelihood for SCD events of 6% at 5 years. Performance of the SCD event risk model was enhanced by LGE (net reclassification index, 12.9%; 95% confidence interval, 0.3-38.3). Absence of LGE was associated with lower risk for SCD events (adjusted hazard ratio, 0.39; P=0.02). Extent of LGE also predicted the development of end-stage HCM with systolic dysfunction (adjusted hazard ratio, 1.80/10% increase in LGE; P<0.03). CONCLUSIONS: Extensive LGE measured by quantitative contrast enhanced CMR provides additional information for assessing SCD event risk among HCM patients, particularly patients otherwise judged to be at low risk.

Design and methods of the Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen SignificantlY) study: An investigator-blinded randomized controlled trial of education and feedback intervention to reduce inappropriate echocardiograms.

BACKGROUND: Appropriate use criteria (AUC) for transthoracic echocardiography (TTE) were developed to address concerns regarding inappropriate use of TTE. A previous pilot study suggests that an educational and feedback intervention can reduce inappropriate TTEs ordered by physicians in training. It is unknown if this type of intervention will be effective when targeted at attending level physicians in a variety of clinical settings. AIMS: The aim of this international, multicenter study is to evaluate the hypothesis that an AUC-based educational and feedback intervention will reduce the proportion of inappropriate echocardiograms ordered by attending physicians in the ambulatory environment. METHODS: In an ongoing multicentered, investigator-blinded, randomized controlled trial across Canada and the United States, cardiologists and primary care physicians practicing in the ambulatory setting will be enrolled. The intervention arm will receive (1) a lecture outlining the AUC and most recent available evidence highlighting appropriate use of TTE, (2) access to the American Society of Echocardiography mobile phone app, and (3) individualized feedback reports e-mailed monthly summarizing TTE ordering behavior including information on inappropriate TTEs and brief explanations of the inappropriate designation. The control group will receive no education on TTE appropriate use and order TTEs as usual practice. CONCLUSIONS: The Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly in an education RCT) study is the first multicenter randomized trial of an AUC-based educational intervention. The study will examine whether an education and feedback intervention will reduce the rate of outpatient inappropriate TTEs ordered by attending level cardiologists and primary care physicians (www.clinicaltrials.gov identifier NCT02038101).

The role of echocardiography in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a disease with a constellation of unique clinical, hemodynamic and echocardiographic features. Over the past decades, echocardiography has played a pivotal role in our understanding of the epidemiology, pathophysiology and prognosis of the condition. Recent advances in echocardiographic techniques have not only expanded our knowledge base but have also extrapolated the role of imaging from that of diagnosis, screening and non-invasive serial assessment to identification of poor prognostic markers, differentiation from phenocopies of HCM and guidance of intraprocedural decision-making in both septal ethanol ablation and surgical myectomy. This article summarizes the recent advances in echocardiography pertaining to HCM.

Significance of left ventricular apical-basal muscle bundle identified by cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy.

AIMS: Cardiovascular magnetic resonance (CMR) has improved diagnostic and management strategies in hypertrophic cardiomyopathy (HCM) by expanding our appreciation for the diverse phenotypic expression. We sought to characterize the prevalence and clinical significance of a recently identified accessory left ventricular (LV) muscle bundle extending from the apex to the basal septum or anterior wall (i.e. apical-basal). METHODS AND RESULTS: CMR was performed in 230 genotyped HCM patients (48 ± 15 years, 69% male), 30 genotype-positive/phenotype-negative (G+/P-) family members (32 ± 15 years, 30% male), and 126 controls. Left ventricular apical-basal muscle bundle was identified in 145 of 230 (63%) HCM patients, 18 of 30 (60%) G+/P- family members, and 12 of 126 (10%) controls (G+/P- vs. controls; P < 0.01). In HCM patients, the prevalence of an apical-basal muscle bundle was similar among those with disease-causing sarcomere mutations compared with patients without mutation (64 vs. 62%; P = 0.88). The presence of an LV apical-basal muscle bundle was not associated with LV outflow tract obstruction (P = 0.61). In follow-up, 33 patients underwent surgical myectomy of whom 22 (67%) were identified to have an accessory LV apical-basal muscle bundle, which was resected in all patients. CONCLUSION: Apical-basal muscle bundles are a unique myocardial structure commonly present in HCM patients as well as in G+/P- family members and may represent an additional morphologic marker for HCM diagnosis in genotype-positive status.

Deep basal inferoseptal crypts occur more commonly in patients with hypertrophic cardiomyopathy due to disease-causing myofilament mutations.

PURPOSE: To determine the relationship between deep basal inferoseptal crypts and disease-causing gene mutations in hypertrophic cardiomyopathy (HCM). MATERIALS AND METHODS: Institutional research and ethics board approval was obtained for this retrospective study, and the requirement to obtain informed consent was waived. Two readers, who were blinded to genetic status, independently assessed cardiac magnetic resonance (MR) images obtained in 300 consecutive unrelated genetically tested patients with HCM. Readers documented the morphologic phenotype, the presence of deep basal inferoseptal crypts, and the imaging plane in which crypts were first convincingly visualized. The Student t test, the Fisher exact test, and multivariate logistic regression were used for comparisons and to evaluate the relationship between these crypts and the detection of disease-causing mutations. RESULTS: The frequency of deep basal inferoseptal crypts was significantly higher in patients with disease-causing mutations than in those without disease-causing mutations (36% and 4%, respectively; P < .001). The presence of crypts was a stronger predictor of disease-causing mutations than was reverse septal curvature (P = .025). Patients with these crypts had a higher likelihood of having disease-causing mutations than non-disease-causing mutations (P < .001). Thirty-one of the 34 patients with both deep basal inferoseptal crypts and reverse septal curvature (91%) had disease-causing mutations (sensitivity, 26%; specificity, 98%). The presence of deep basal inferoseptal crypts (odds ratio: 6.64; 95% confidence interval: 2.631, 16.755; P < .001) and reverse septal curvature (odds ratio: 4.8; 95% confidence interval: 2.552, 9.083; P < .001) were predictive of disease-causing mutations. Both observers required additional imaging planes to identify approximately half of all crypts. CONCLUSION: Deep basal inferoseptal crypts occur more commonly in patients with HCM with disease-causing mutations than in those with genotype-negative HCM.

Interpretable machine learning for automated left ventricular scar quantification in hypertrophic cardiomyopathy patients.

Scar quantification on cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) images is important in risk stratifying patients with hypertrophic cardiomyopathy (HCM) due to the importance of scar burden in predicting clinical outcomes. We aimed to develop a machine learning (ML) model that contours left ventricular (LV) endo- and epicardial borders and quantifies CMR LGE images from HCM patients.We retrospectively studied 2557 unprocessed images from 307 HCM patients followed at the University Health Network (Canada) and Tufts Medical Center (USA). LGE images were manually segmented by two experts using two different software packages. Using 6SD LGE intensity cutoff as the gold standard, a 2-dimensional convolutional neural network (CNN) was trained on 80% and tested on the remaining 20% of the data. Model performance was evaluated using the Dice Similarity Coefficient (DSC), Bland-Altman, and Pearson's correlation. The 6SD model DSC scores were good to excellent at 0.91 ± 0.04, 0.83 ± 0.03, and 0.64 ± 0.09 for the LV endocardium, epicardium, and scar segmentation, respectively. The bias and limits of agreement for the percentage of LGE to LV mass were low (-0.53 ± 2.71%), and correlation high (r = 0.92). This fully automated interpretable ML algorithm allows rapid and accurate scar quantification from CMR LGE images. This program does not require manual image pre-processing, and was trained with multiple experts and software, increasing its generalizability.

Association of duration and intensity of exercise with phenotypic expression in hypertrophic cardiomyopathy.

OBJECTIVES: There is limited data regarding the impact of exercise on phenotypic expression in hypertrophic cardiomyopathy (HCM). We aimed to investigate whether such an association exists in a cohort of genotype-positive HCM patients. METHODS: In this cross-sectional study of genotype-positive HCM families, we used structured questionnaires to obtain data regarding intensity and duration of exercise of participants starting at the age of 10, as well as data regarding exercise recommendations and their impact on quality of life (QOL). The association of cumulative metabolic-equivalent hours of exercise at different ages with different measures of phenotypic expression (maximal wall thickness, left atrial diameter, extent of late gadolinium enhancement) was analyzed. RESULTS: The study included 109 patients from 55 families, including 43 male (39%) and 90 (83%) phenotype-positive. No association was identified between exercise duration or intensity with any of the phenotypic markers with the exception of greater cumulative exercise associated with younger age at presentation. Similar results were obtained when analysis was limited to exercise until the age of 20, until the age of 30 or only after 30. Among phenotype-positive patients, 89% recalled receiving recommendations regarding exercise restriction, 29% noted reduction in exercise level following such recommendations and 25% noted this having a significant impact on their QOL. CONCLUSION: We found no association between exercise intensity or duration and phenotypic expression in genotype-positive HCM patients. These findings are important for physician-patient discussions and support the recent trend towards more permissive exercise restrictions in HCM.

Clinical Significance of Postoperative Atrial Fibrillation in Hypertrophic Cardiomyopathy Patients Undergoing Septal Myectomy.

BACKGROUND: The optimal management of hypertrophic cardiomyopathy (HCM) patients with postoperative atrial fibrillation (POAF) after surgical myectomy remains unknown. We sought to investigate the association between POAF and atrial fibrillation (AF) or cardioembolic events during follow-up to bridge this gap. METHODS: Patients undergoing surgical myectomy at 2 HCM referral centres in North America from 2002 to 2020 were included in this study. Patients with preoperative AF were excluded. POAF was defined as any episode of AF within 30 days after surgery. RESULTS: Of 1176 patients, 375 (31.9%) had POAF. Age (adjusted hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.03-1.06; P < 0.001), premyectomy left atrial diameter (LAD; adjusted HR 1.6, 95% CI 1.32-2.02; P < 0.001), and smoking (adjusted HR 1.60, 95% CI 1.17-2.20; P = 0.001) were associated with POAF on multivariable analysis. Of 934 patients with follow-up data, of duration 4.3 ± 4.1 years, AF was detected in 86 (9.2%). Only POAF (HR 4.20, 95% CI 2.44-7.23; P < 0.001), previous history of stroke (HR 4.81, 95% CI 1.63-14.17; P = 0.01), and postmyectomy LAD (HR 1.80, 95% CI 1.21-2.70; P = 0.004) were associated with AF incidence during follow-up. Cardioembolic events occurred in only 15 patients (1.6%). POAF was not associated with increased cardioembolic risk, with only 3 patients with POAF suffering such an event, all more than 4 years after surgery. CONCLUSIONS: POAF is common in HCM patients undergoing myectomy and is a predictor of AF during follow-up. Over long-term follow-up, cardioembolic events are uncommon. These findings suggest that routine long-term anticoagulation for all HCM patients with postmyectomy AF is not justified after the initial postoperative period.