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This article presents a case of diagnosis and treatment of a rare form of left ventricular (LV) hypertrophic cardiomyopathy (HCMP), asymmetric topical HCMP without obstruction of the LV outflow tract, and raises the issue of diagnosis and treatment of rare forms of this disease. In the Federal Center for Cardiovascular Surgery in 2019-2020, 5 cases of asymmetric hypertrophic apical cardiomyopathy were observed and documented with echocardiography (EchoCG), cardiac magnetic resonance imaging (MRI), and Holter ECG monitoring. A 60-year-old female patient underwent a comprehensive evaluation, including physical examination, EchoCG, MRI, Holter ECG monitoring, and coronary angiography. Apical HCMP was detected. The clinical picture was explainable from the perspective of functional and structural alterations in the LV myocardium, where full obstruction of the cardiac apex develops during systole. The small LV cavity is unable to provide effective hemodynamics. Changed small coronary arteries also contribute to this disorder, which, in results, affects myocardial oxygen supply. The administered therapy included antiplatelets, beta-blockers, angiotensin II receptor blockers, diuretics, and ranolazine. The effect of therapy was assessed as positive. Risk of sudden death, according to European Guidelines, 2014 was 0.86 %.

Aims: CMR feature tracking strain (CMR-FT) provides prognostic information. However, there is a paucity of data in hypertrophic cardiomyopathy (HCM). We sought to analyze global CMR-FT parameters in all four cardiac chambers and to assess associations with NT-proBNP and cardiac troponin T (hsTnT) in patients with HCM., Methods: This retrospective study included 144 HCM patients and 16 healthy controls with CMR at 1.5 T. Analyses were performed on standard steady-state free precession cine (SSFP) CMR data using a commercially available software. Global left ventricular (LV) strain was assessed as longitudinal (LV LAX- GLS), circumferential (LV LAX- GCS) and radial strain (LV LAX- GRS) on long -axis (LAX) and as LV SAX -GCS and LV SAX -GRS on short- axis (SAX). Right ventricular (RV-GLS), left atrial (LA-GLS) and right atrial (RA-GLS) strain were assessed on LAX., Results: We found LV LAX -GLS [- 18.9 (- 22.0, - 16.0), - 23.5 (- 25.5, - 22.0) %, p = 0.0001), LV SAX -GRS [86.8 (65.9-115.5), 119.6 (91.3-143.7) %, p = 0.001] and LA LAX -GLS [LA 2CH -GLS 29.2 (19.1-37.7), LA 2CH -GLS 38.2 (34.3-47.1) %, p = 0.0036; LA 4CH -GLS 22.4 (14.6-30.7) vs. LA 4CH -GLS 33.4 (28.4-37.3) %, p = 0.0033] to be impaired in HCM compared to healthy controls despite normal LVEF. Furthermore, LV and LA strain parameters were impaired in HCM with elevated NT-proBNP and/or hsTnT, despite preserved LVEF compared to HCM with normal biomarker levels. There was a moderate correlation of LV and LA CMR-FT with levels of NT-proBNP and hsTnT., Conclusion: CMR-FT reveals LV and LA dysfunction in HCM despite normal LVEF. The association between impaired LV strain and elevated NT-proBNP and hsTnT indicates a link between unapparent functional abnormalities and disease severity in HCM. Typical CMR-FT findings in patients with hypertrophic cardiomyopathy., (© 2021. The Author(s).)

Background Inherited cardiomyopathies display variable penetrance and expression, and a component of phenotypic variation is genetically determined. To evaluate the genetic contribution to this variable expression, we compared protein coding variation in the genomes of those with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). Methods and Results Nonsynonymous single-nucleotide variants (nsSNVs) were ascertained using whole genome sequencing from familial cases of HCM (n=56) or DCM (n=70) and correlated with echocardiographic information. Focusing on nsSNVs in 102 genes linked to inherited cardiomyopathies, we correlated the number of nsSNVs per person with left ventricular measurements. Principal component analysis and generalized linear models were applied to identify the probability of cardiomyopathy type as it related to the number of nsSNVs in cardiomyopathy genes. The probability of having DCM significantly increased as the number of cardiomyopathy gene nsSNVs per person increased. The increase in nsSNVs in cardiomyopathy genes significantly associated with reduced left ventricular ejection fraction and increased left ventricular diameter for individuals carrying a DCM diagnosis, but not for those with HCM. Resampling was used to identify genes with aberrant cumulative allele frequencies, identifying potential modifier genes for cardiomyopathy. Conclusions Participants with DCM had more nsSNVs per person in cardiomyopathy genes than participants with HCM. The nsSNV burden in cardiomyopathy genes did not correlate with the probability or manifestation of left ventricular measures in HCM. These findings support the concept that increased variation in cardiomyopathy genes creates a genetic background that predisposes to DCM and increased disease severity.

We describe characteristics and outcomes of contemporary pediatric hypertrophic cardiomyopathy (PHC) patients. We studied 398 consecutive pediatric HC patients (<18 years, median 14 years, 65% boys) seen at our center between 2002 and 2018. Baseline clinical and pediatric echocardiographic data was collected. Left ventricular outflow tract gradient (LVOTG), LV fractional shortening and Z-score for left ventricular (LV) wall thickness were calculated. Sudden cardiac death (SCD), appropriate internal defibrillator discharge (ICD), myectomy, and orthotopic heart transplant (OHT) were composite primary endpoint. A total of 133 (33%) had symptoms (71 [18%] dyspnea, 77 [19%] angina, and 19 [5%] syncope), 109 (27%) were on beta-blockers; 179 (45%) had family history of HC. A total of 146 (37%) underwent genetic testing (of which 91 (62%) were HC-gene positive). Basal septal LV thickness, septal LV z-score and fractional shortening were 1.2 ± 0.6 cm, 4.8 ± 5.6, and 42% ± 8, whereas 23% had extreme LV hypertrophy (z-score > 6) and 8% had LVOTG >30 mm Hg (range 0 to 139 mm Hg). At a median of 5.9 years (interquartile range 2.4, 9), there were 23 (6%) ICD's placed, and 47 (12%) primary composite events (9 [2%] deaths, 3 [1%] appropriate ICD discharge, 29 [7%] myectomy, and 8 [2%] OHT). There were no in hospital deaths following myectomy/OHT. Presence of symptoms (Hazard ratio or HR 2.45), ventricular tachycardia (HR 1.52), and higher basal septal LV z-score (HR 1.10) were independently associated with primary composite outcomes. LV septal z-score >4 was independently associated with events on spline analysis. Rate of SCD/appropriate ICD discharge was 0.5%/year. In conclusion, contemporary PHC patients seen at an experienced center have excellent outcomes with presence of symptoms and higher LV septal thickness associated with primary composite events., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Left ventricular maximum wall thickness (MWT) is central to diagnosis and risk stratification of hypertrophic cardiomyopathy, but human measurement is prone to variability. We developed an automated machine learning algorithm for MWT measurement and compared precision (reproducibility) with that of 11 international experts, using a dataset of patients with hypertrophic cardiomyopathy., Methods: 60 adult patients with hypertrophic cardiomyopathy, including those carrying hypertrophic cardiomyopathy gene mutations, were recruited at three institutes in the UK from August, 2018, to September, 2019: Barts Heart Centre, University College London Hospital (The Heart Hospital), and Leeds Teaching Hospitals NHS Trust. Participants had two cardiovascular magnetic resonance scans (test and retest) on the same day, ensuring no biological variability, using four cardiac MRI scanner models represented across two manufacturers and two field strengths. End-diastolic short-axis MWT was measured in test and retest by 11 international experts (from nine centres in six countries) and an automated machine learning method, which was trained to segment endocardial and epicardial contours on an independent, multicentre, multidisease dataset of 1923 patients. Machine learning MWT measurement was done with a method based on solving Laplace's equation. To assess test-retest reproducibility, we estimated the absolute test-retest MWT difference (precision), the coefficient of variation (CoV) for duplicate measurements, and the number of patients reclassified between test and retest according to different thresholds (MWT >15 mm and >30 mm). We calculated the sample size required to detect a prespecified MWT change between pairs of scans for machine learning and each expert., Findings: 1440 MWT measurements were analysed, corresponding to two scans from 60 participants by 12 observers (11 experts and machine learning). Experts differed in the MWT they measured, ranging from 14·9 mm (SD 4·2) to 19·0 mm (4·7; p<0·0001 for trend). Machine learning-measured mean MWT was 16·8 mm (4·1). Machine learning precision was superior, with a test-retest difference of 0·7 mm (0·6) compared with experts, who ranged from 1·1 mm (0·9) to 3·7 mm (2·0; p values for machine learning vs expert comparison ranging from <0·0001 to 0·0073) and a significantly lower CoV than for all experts (4·3% [95% CI 3·3-5·1] vs 5·7-12·1% across experts). On average, 38 (64%) patients were designated as having MWT greater than 15 mm by machine learning compared with 27 (45%) to 50 (83%) patients by experts; five (8%) patients were reclassified in test-retest by machine learning compared with four (7%) to 12 (20%) by experts. With a cutoff point of more than 30 mm for implantable cardioverter-defibrillator, three experts would have changed recommendations between tests a total of four times, but machine learning was consistent. Using machine learning, a clinical trial to detect a 2 mm MWT change would need 2·3 times (range 1·6-4·6) fewer patients., Interpretation: In this preliminary study, machine learning MWT measurement in hypertrophic cardiomyopathy is superior to human experts with potential implications for diagnosis, risk stratification, and clinical trials., Funding: European Regional Development Fund and Barts Charity., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

There is sparse Indian data on whether fetal echocardiography among pregnant diabetics would be useful to predict adverse perinatal/neonatal outcome., Objectives: To study fetal cardiac changes in diabetic mothers and non-diabetic controls from 24 weeks gestation until the neonatal period; correlate them with maternal glycemic control; study their implications on adverse perinatal/neonatal outcome., Methodology: Prospective observational cohort study. Pregnant diabetics (17 overt, 66 gestational) recruited beyond 24 weeks, divided as well (39) and poorly (44) controlled, based on American Diabetes Association 2016 criteria. Controls were 102 healthy non-diabetic pregnancies. Fetal echocardiography performed at weeks 24-32, 32-36, >37, and between 4 and 7 days on neonates. The thickness of Interventricular septum (IVS), Right Ventricle (RV), and Left ventricle (LV) assessed with M mode. E/A ratio across Tricuspid/Mitral valves and Tei index determined. TDI(Tissue Doppler imaging) used to assess tissue annular velocities across IVS, RV, and LV. Maternal glycemic control and various perinatal/neonatal adverse outcomes were recorded., Results: Significant myocardial hypertrophy seen among fetuses of diabetic mothers versus controls, most severe at term among the poorly controlled diabetics. Structural changes persisted in the neonate. At term, fetal myocardial dysfunction was evident among diabetic pregnancies only as poor annular systolic velocity across IVS, RV using TDI. However, Tissue Doppler changes could not predict adverse perinatal/neonatal outcome. Myocardial dysfunction could not be demonstrated in the neonates. Myocardial hypertrophy at term was a surrogate marker for suboptimal glycemic control, and it could predict important neonatal morbidities like hypoglycaemia, hyperbilirubinemia, prolonged NICU stays, and persistent foetal cardiac shunts., Conclusion: Our study shows a significant association between fetal myocardial hypertrophy and maternal glycemic control among GDM pregnancies. There also seems to be an association between fetal myocardial hypertrophy and some of the adverse perinatal events including hypoglycemia. However these newborns were not found to have clinically relevant cardiac comorbidities even though there was significant septal hypertrophy in utero., Competing Interests: Conflicts of interest None., (Copyright © 2020 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

Objectives: This study aimed to evaluate the feasibility and reproducibility of using cardiovascular magnetic resonance feature tracking (CMR-FT) for analysis of bi-ventricular strain and strain rate (SR) in hypertrophic cardiomyopathy (HCM) patients as well as to explore the correlation between right ventricular (RV) and left ventricular (LV) deformation., Methods: A total of 60 HCM patients and 48 controls were studied. Global and segmental peak values of bi-ventricular longitudinal, circumferential, radial strain, and systolic SR were analyzed. Pearson analysis was performed to investigate the correlation of RV and LV deformation. Intra-observer and inter-observer reproducibility were also assessed., Results: LV mass in the HCM group was significantly higher than that in the control group. LV end-systolic and end-diastolic volume and RV end-systolic and end-diastolic volume in the HCM group were all significantly lower than the correlated parameters in the control group (p < 0.001, respectively), whereas no statistical difference was found in ejection fraction (p > 0.05). Global longitudinal strain (GLS), global longitudinal strain rate (GLSR), global circumferential strain (GCS), global circumferential strain rate (GCSR), global radial strain (GRS), and global radial strain rate (GRSR) of the LV and RV were all significantly lower than the control group, and segmental strain and SR were also true (p < 0.001, respectively). Bi-ventricular strain and SR measurements were highly reproducible at both intra- and inter-observer levels. Additionally, Pearson analysis showed RV GCS, GLS, and GRS positively correlated with LV GCS, GLS, and GRS (r = 0.713, p < 0.001; r = 0.728, p < 0.001; r = 0.730, p < 0.001, respectively)., Conclusions: CMR-FT is a promising approach to analyze impairment of global and segmental myocardium deformation in HCM patients non-invasively and quantitatively., Key Points: • CMR-FT allows for advanced myocardial characterization with high reproducibility. • As compared with controls, HCM patients have significant differences in CMR-FT strain analysis while ejection fraction was similar. • CMR-FT may serve as an early biomarker of HCM in subjects at risk.

The systematic development of early age talent in sports academies has led to the professionalization of pediatric sport and the sports physician need to be aware of pediatric cardiological problems. Research into the medical cardiac care and assessment of the pediatric athlete are accumulating, but specific pediatric international guidelines are not available yet and reference data for ECG and echocardiography are incomplete, in particular for the age group <12 years of age. This article is an introduction to the physiological and diagnostics specifics of the pediatric athlete. The focus lies in the differences in presentation and diagnosis between pediatric and adult athletes for the most common pathologies. Reference data for electrical and structural adaptations to intensive exercise are sparse particularly in athletes aged below 12 years old. Training related changes include decrease of resting heart rate, increase of cardiac output, ventricular cavity size, and wall thickness. Cardiac hypertrophy is less pronounced in pediatric athletes, as HR mediated cardiac output increase to endurance exercise is the dominant mechanism in peripubertal children. As in adults, the most pronounced cardiovascular adaptations appear in classical endurance sports like rowing, triathlon, and swimming, but the specifics of pediatric ECG and echocardiographic changes need to be considered., (© 2020 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Hypertrophic cardiomyopathy (HC) is associated with a well-recognized risk for unexpected sudden death (SD). Most such reported patients have been referred to dedicated centers and/or expert cardiologists for risk stratification, with the number of SDs decreasing sharply due to penetration of the implantable cardioverter-defibrillator (ICDs) into HC practice. However, the clinical circumstances, and morphologic features of HC patients who incur SD without the opportunity to be considered for preventive intervention with ICDs are largely undefined. Using the long-standing unique Jesse Edwards Registry (St. Paul, Minnesota), we studied 86 selected heart specimens from young HC patients who died suddenly and unexpectedly without prior clinical evaluation, ages 31 ± 16 years. The patients were predominantly male (87%) with only modest phenotypic expression and maximum LV wall thickening of only 18 ± 4 mm. SD events occurred predominantly with sedentary/mild activities (66%) often in bed or asleep (32%), but also during physical activity (22%) including with organized competitive sports. This largely unappreciated sub-population of patients with HC (and SD) is characterized by mild-to-moderate degree of LV hypertrophy, representing a clinical challenge which is particularly relevant in the current ICD era for HC, with the potential for SD prevention., (Copyright © 2020. Published by Elsevier Inc.)

Interstitial fibrosis is a histopathological hallmark of hypertrophic cardiomyopathy (HCM). Although extracellular matrix (ECM) biomarkers, including matrix metalloproteinases, are overexpressed in HCM patients, they do not correlate with sudden cardiac death (SCD) risk. The objective of this study was to determine whether scleraxis, a transcription factor that regulates collagen gene expression, is detectable in HCM patients and correlates with disease burden. Between 2017 and 2018, a total of 46 HCM patients were enrolled (58 ± 14 years (31 males, 15 females)) with a mean 5 year SCD risk of 2.3% ± 1.3%. Cardiac MRI confirmed HCM in all patients with a mean interventricular septal thickness of 20 ± 2 mm. Late gadolinium enhancement (LGE) was present in 32 (70%) study participants occupying 18% ± 7% of the left ventricular (LV) myocardium. Serum scleraxis levels were significantly higher in the HCM patients by approximately twofold as compared to controls (0.76 ± 0.06 versus 0.32 ± 0.02 ng/mL, p < 0.05). No correlation was demonstrated between serum scleraxis levels and markers of disease severity in HCM patients, including maximum LV wall thickness, %LGE, and SCD risk factors. Serum scleraxis is elevated in the HCM population. Future studies are warranted to evaluate the prognostic value of scleraxis in identifying high-risk HCM patients who require aggressive management for prevention of SCD.

Hypertrophic cardiomyopathy (HCM) is the most common non-ischemic cardiomyopathy, characterized by increased left ventricular wall thickness. Echocardiographic studies are essential for establishing the diagnosis, evaluating the extent of disease, and risk stratification. Echocardiography is also recommended in regular screening of the genotype-positive relatives. Two-dimensional, M-mode, and Doppler echocardiography are standard modalities in HCM diagnosis. Newer echocardiographic techniques as tissue Doppler, strain, and three-dimensional echocardiography are now widely used and can reveal subtle changes in the HCM patients. Echocardiography has given us a better understanding of the disease. In this review, we briefly profile the echocardiographic management of HCM in a clinical perspective.

To assess the global and regional right ventricular (RV) deformation in hypertrophic cardiomyopathy (HCM) patients with preserved right ventricular ejection fraction (RVEF) using 3.0-T cardiovascular magnetic resonance tissue tracking (CMR-TT). Eighty-two HCM patients and 32 age- and sex-matched healthy controls were enrolled. HCM patients were divided into groups depending on the presence or absence of right ventricular hypertrophy (RVH), RV late gadolinium enhancement (RV-LGE), and left ventricular outflow tract obstruction (LVOTO), respectively. The RV global and apical longitudinal peak strain (LPS) in HCM patients with RVH were significantly lower than that in HCM patients without RVH and controls (P < 0.05). The global, apical and mid-ventricular LPS in HCM patients with RV-LGE were significantly lower than that in HCM patients without RV-LGE and controls (P < 0.05). Lower LPS was demonstrated in HCM patients without RV-LGE compared with controls in apical and mid-ventricular levels (P < 0.05). No significant difference was found regarding global and regional LPS in HCM patients with LVOTO compared without LVOTO (all P > 0.05). CMR-TT was able to detect subclinical RV myocardial deformation prior to RVEF impairment, which was more severe in the presence of RVH and RV-LGE.

Background: Left ventricular (LV) diastolic dysfunction is a prominent feature of hypertrophic cardiomyopathy (HCM). Prediction of LV filling pressure using the ratio between early diastolic transmitral flow and mitral annular velocity (E/e') had proved a good accuracy., Aim of This Study: We investigated the value of E/e' to predict cardiovascular (CV) mortality in patients with HCM., Methods: A total of 243 patients with HCM had E/e' measured in combination with clinical evaluation, conventional echocardiographic measurements, cardiopulmonary exercise evaluation, and Holter monitoring., Results: During a mean follow-up of (3.2 ± 1.2 years), 17 (7%) patients died. Non survivors had significantly higher SBP, DBP, left ventricular outflow tract obstruction (LVOTO) gradient, mitral E, and E/e', but lower e' of mitral annulus and more prevalent restrictive filling pattern. E/e' was directly correlated with age (r = .24, P < .005), left atrial volume index (r = .44, P < .0001), LVMI (r=0.23,P<.005), LVOT gradient (r = .43, P < .0001), NYHA class (r = .19, P < .006), pulmonary artery pressure (r = .24, P < .005), positive family history of HCM (r = .22, P < .005), and inversely related to peak systolic velocity (S) (r = .44, P < .0001). By multivariate analysis, only LVOTO ([RR] 4.11, 95% CI 1.002 to 1.148, P < .04) and E/e' were independent predictors for overall mortality in HCM (relative risk [RR] 5.27, 95% CI 1.002 to 1.024, P < .02). The risk of dying increased with increasing E/e' ratio, being approximately 4 times higher for patients in the highest quartile (HR 3.8 (CI 1.38-5.12, log-rank < 0.002))., Conclusions: In hypertrophic cardiomyopathy, the E/e' ratio remains a powerful predictor of all-cause mortality, particularly if it is associated with LVOT obstruction., (© 2019 Wiley Periodicals, Inc.)

Introduction: Apical Hypertrophic Cardiomyopathy (Apical HCM) is an uncommon variant of hypertrophic cardiomyopathy, but it is relatively more common in Asian countries. This is a retrospective, non-randomised, single centre study of patients with Apical HCM focusing on their diastolic dysfunction grading, echocardiographic parameters and electrocardiograms (ECG)., Methods: All Apical HCM patients coming for clinic visits at the Institut Jantung Negara from September 2017 to September 2018 were included. We assessed their echocardiography images, grade their diastolic function and reviewed their ECG on presentation., Results: Fifty patient were included, 82% (n=41) were males and 18% (n=9) females. The diastolic function grading of 37 (74%) patients were able to be determined using the updated 2016 American Society of Echocardiography (ASE) diastolic guidelines. Fifty percent (n=25) had the typical ace-ofspades shape left ventricle (LV) appearance in diastole and 12% (n=6) had apical pouch. All patients had T inversion in the anterior leads of their ECG, and only 52% (n=26) fulfilled the ECG left ventricular hypertrophy (LVH) criteria. Majority of our patients presented with symptoms of chest pain (52%, n=26) and dyspnoea (42%, n=21)., Conclusion: The updated 2016 ASE guideline makes it easier to evaluate LV diastolic function in most patients with Apical HCM. It also helps in elucidating the aetiology of dyspnoea, based on left atrial pressure. Clinicians should have a high index of suspicion for Apical HCM when faced with deep T inversion on ECG, in addition to a thick LV apex with an aceof- spades appearance during diastole.

Background: The concept of "red flags" has been particularly useful in the etiologic diagnosis of cardiomyopathies such as Fabry disease, as early detection is often essential for treatment response and outcomes. The present study sought to describe the echocardiographic features that may differentiate Fabry cardiomyopathy from sarcomeric hypertrophic cardiomyopathy (HCM)., Methods: Forty patients with left ventricular (LV) hypertrophy were prospectively included and divided into two groups: the Fabry group (20) and the sarcomeric HCM group (20). The two groups were matched for LV hypertrophy (similar maximum wall thickness and indexed LV mass) and age. All patients underwent full echocardiographic evaluation including ventricular strain analysis., Results: The Fabry group had significantly lower LV ejection fraction (63 ± 7 vs 72 ± 7%, P = .001) and higher LV end-systolic diameter (28 ± 7 vs 22 ± 5 mm, P = .004). LV hypertrophy in Fabry patients was more often concentric, with a significantly lower interventricular septum/posterior wall ratio (1.22 ± 0.63 vs 1.55 ± 0.66, P = .001). Fabry patients had more reduced regional longitudinal strain in the inferolateral part of the LV (-9 ± 5 vs -16 ± 7%), and RV free wall longitudinal strain was also worse in Fabry patients (-23 ± 6 vs -28 ± 5%, P = .027)., Conclusion: These parameters are promising echocardiographic features to identify patients with Fabry cardiomyopathy and may help for the detection and subsequent management of these patients., (© 2019 Wiley Periodicals, Inc.)

Background: Whether mitral leaflet elongation is a primary phenotype of hypertrophic cardiomyopathy (HCM) is controversial. We investigated the genetic relevance and determinants of mitral leaflet size by performing extensive gene analyses in patients with HCM., Methods: Anterior mitral leaflet (AML) lengths were measured in HCM patients (n = 211) and age- and sex-matched controls (n = 30) using echocardiography with hemodynamic and chamber geometric assessments. We analyzed 82 nuclear DNA (8 sarcomeric genes, 74 other HCM-associated genes) and mitochondrial DNA. Cardiac magnetic resonance imaging (CMR) was performed in the 132 HCM patients., Results: Average indexed AML was significantly longer for HCM than for controls (17.2 ± 2.3 vs. 13.3 ± 1.6 mm/m 2 , P <  0.001). Average AML length correlated with body surface area (BSA), left ventricular (LV) end-systolic volume (P <  0.001) and LV mass by CMR (P < 0.001). Average indexed AML by BSA of pure-apical HCM was significantly shorter than other typed HCM (16.6 ± 2.0 vs. 17.4 ± 2.4 mm/m 2 , P = 0.025). Indexed AML was independently correlated with left atrial wall stress. The thin filament mutation group showed larger average AML (31.9 ± 3.8 vs. 29.6 ± 3.8 mm, P = 0.045), but this was not significant with the indexed value. No difference in AML size among subgroups was observed based on the presence of sarcomere protein or mitochondria-related gene variants (P > 0.05)., Conclusion: AML elongation was a unique finding of HCM. However, the leaflet size was more related to chamber geometry and hypertrophy pattern rather than genetic factors within overt HCM.

Sudden cardiac death (SCD) is the most life-threating complication of hypertrophic cardiomyopathy. Guidelines of the European Society of Cardiology (ESC) suggest the implantation of an implantable cardioverter defibrillator in primary prevention according to a 5-year risk SCD score ≥6%. The aim of the study is to evaluate the prognostic role of late gadolinium enhancement (LGE) in patients with a 5-year risk SCD score <6%. In this multicenter study, we performed cardiac magnetic resonance in 354 consecutive hypertrophic cardiomyopathy patients (257 males, range of age 54 ± 17) with a risk SCD score <6% (302 with <4% and 52 with ≥4 and <6% risk). Hard cardiac events, including SCD, resuscitated cardiac arrest, appropriate implantable cardioverter defibrillator interventions, sustained ventricular tachycardia, occurred in 22 patients. LGE was detected in a high proportion (92%) of patients with hard cardiac events (p = 0.002). At receiver-operating characteristic curve analysis, LGE extent ≥10% was the best threshold to predict major arrhythmic events (area under the curve: 0.74). Kaplan-Meier curves showed that patients with LGE ≥10% had a worse prognosis than those with lower extent (p < 0.0001). LGE extent was the best independent predictor of hard cardiac events (hazard ratio 1.05; 95% confidence interval [CI] 1.03 to 107; p < 0.0001). The estimates 5-year risk of hard cardiac event was 2.5% (95% CI 0.8 to 4.2) in patients with LGE extent <10% and 23.4% (95% CI 10.2 to 36.5) for those with LGE extent ≥10%. In conclusion, this study demonstrates as the extent of LGE ≥10% is able to recognize additional patients at increased risk for malignant arrhythmic episodes in a population with low-to-intermediate ESC SCD risk score., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Myocardial disarray is a likely focus for fatal arrhythmia in hypertrophic cardiomyopathy (HCM). This microstructural abnormality can be inferred by mapping the preferential diffusion of water along cardiac muscle fibers using diffusion tensor cardiac magnetic resonance (DT-CMR) imaging. Fractional anisotropy (FA) quantifies directionality of diffusion in 3 dimensions. The authors hypothesized that FA would be reduced in HCM due to disarray and fibrosis that may represent the anatomic substrate for ventricular arrhythmia., Objectives: This study sought to assess FA as a noninvasive in vivo biomarker of HCM myoarchitecture and its association with ventricular arrhythmia., Methods: A total of 50 HCM patients (47 ± 15 years of age, 77% male) and 30 healthy control subjects (46 ± 16 years of age, 70% male) underwent DT-CMR in diastole, cine, late gadolinium enhancement (LGE), and extracellular volume (ECV) imaging at 3-T., Results: Diastolic FA was reduced in HCM compared with control subjects (0.49 ± 0.05 vs. 0.52 ± 0.03; p = 0.0005). Control subjects had a mid-wall ring of high FA. In HCM, this ring was disrupted by reduced FA, consistent with published histology demonstrating that disarray and fibrosis invade circumferentially aligned mid-wall myocytes. LGE and ECV were significant predictors of FA, in line with fibrosis contributing to low FA. Yet FA adjusted for LGE and ECV remained reduced in HCM (p = 0.028). FA in the hypertrophied segment was reduced in HCM patients with ventricular arrhythmia compared to patients without (n = 15; 0.41 ± 0.03 vs. 0.46 ± 0.06; p = 0.007). A decrease in FA of 0.05 increased odds of ventricular arrhythmia by 2.5 (95% confidence interval: 1.2 to 5.3; p = 0.015) in HCM and remained significant even after correcting for LGE, ECV, and wall thickness (p = 0.036)., Conclusions: DT-CMR assessment of left ventricular myoarchitecture matched patterns reported previously on histology. Low diastolic FA in HCM was associated with ventricular arrhythmia and is likely to represent disarray after accounting for fibrosis. The authors propose that diastolic FA could be the first in vivo marker of disarray in HCM and a potential independent risk factor., (Copyright © 2019. Published by Elsevier Inc.)

Objective: To determine whether abnormal blood pressure response (ABPR), with or without left ventricular outflow tract obstruction (LVOTO), is associated with adverse heart failure and arrhythmia outcomes in hypertrophic cardiomyopathy (HCM)., Methods: A retrospective, single-center analysis was performed for adult HCM patients who underwent exercise stress testing., Results: Of 589 patients included in the study, 192 (33%) demonstrated ABPR. A similar proportion of patients with ABPR had LVOTO compared to those without ABPR (56% vs 63%, p = 0.11). Patients with ABPR demonstrated lower percent predicted VO2 and METs achieved than those with LVOTO (16.9 ± 6.8 vs 21.6 ± 7.9, p = 0.002 and 5.3 ± 2.4 vs 7.4 ± 3.1, p < 0.001). In a subgroup of 17 patients with LVOTO and ABPR who subsequently underwent successful myectomy, 5 (30%) demonstrated persistent ABPR. 23 patients (3.8%) experienced sudden cardiac death or ventricular arrhythmias, which were not associated with ABPR, regardless of age group. In multivariable analysis, syncope (p = 0.04), left ventricular hypertrophy (p = 0.02) and left atrial diameter (p = 0.006) were significantly associated with the composite outcome of sudden death or severe ventricular arrhythmia, whereas ABPR was not (p = 0.38). In contrast, ABPR was associated with subsequent heart failure hospitalization (p = 0.002), regardless of presence or absence of LVOTO (p = 0.04, p = 0.02)., Conclusions: ABPR is associated with reduced functional capacity in HCM regardless of the presence of LVOTO but is not associated with adverse arrhythmia outcomes. Patients with ABPR have a higher incidence of subsequent heart failure hospitalization., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Few data are available regarding the prevalence and clinical significance of right ventricular systolic dysfunction (RVSD) in hypertrophic cardiomyopathy (HC) patients. This study aimed to evaluate right ventricular (RV) systolic function by cardiovascular magnetic resonance and explore the prevalence and prognostic significance of RVSD in HC patients. A total of 226 patients with HC assessed by cardiovascular magnetic resonance were included in this retrospective study. RVSD was defined by RV ejection fraction (RVEF) ≤45% and was present in 26 (11.5%) patients. Association between RVSD, clinical characteristics, and outcomes were analyzed. RVEF was significantly lower in patients with RVSD than without RVSD (36.2 ± 7.0% vs 60.5 ± 7.4%, p < 0.001). There was a positive correlation between RVEF and left ventricular ejection fraction (r = 0.45; p < 0.001). During a mean follow-up of 30.5 ± 23.9 months, there were 22 (9.7 %) all-cause mortality, including 12 (5.3%) cardiovascular death. Kaplan-Meier analysis showed a significantly higher risk for cardiovascular mortality in patients with RVSD (p = 0.026), but no significant difference in all-cause mortality (p = 0.118) and heart failure related rehospitalization (p = 0.485). On multivariate Cox regression analysis, RVSD (hazard ratio 5.36; confidence interval 1.39 to 20.77; p = 0.015) and RVEF (hazard ratio 0.94; confidence interval 0.89 to 0.98; p = 0.011) were independent predictors of cardiovascular mortality. In conclusion, RVSD is a common phenotype and a strong independent predictor of cardiovascular mortality in HC patients., (Copyright © 2018. Published by Elsevier Inc.)

In hypertrophic cardiomyopathy (HC), a process of left ventricular (LV) remodeling carrying an adverse prognosis has been described. Conversely, a gradual and benign LV wall thinning has been suggested but never investigated. Therefore, we studied a HC cohort over a long period of time to evaluate the occurrence of a LV remodeling with a benign clinical course. Data of HC patients aged 18 to 65 years and without any condition known to influence LV remodeling were analyzed over a mean follow-up of 7.6 ± 5.7 years. Of 231 HC patients (65% males, mean age 46 ± 12 years), 47 (20%) developed LV remodeling, of whom 23 (10%) had a thinning ≥15% of LV maximal wall thickness from baseline without systolic dysfunction (MWT thinning); 13 (6%) progressed to a LV ejection fraction <50% (end-stage HC) and 11 (5%) developed an apical aneurysm. Follow-up length (odds ratio 1.07, 95% confidence interval 1.00 to 1.15, p = 0.06) and maximal LV wall thickness at baseline (odds ratio 1.14, 95% confidence interval 1.04 to 1.25, p = 0.004) were the main predictors of MWT thinning. Compared with patients with end-stage HC and apical aneurysm, those with MWT thinning showed lower HC-related morbidity (92% and 36% vs 22%, p = 0.003) and mortality (31% and 27% vs 4%, p = 0.02). Furthermore, they showed a combined HC-related morbidity and mortality similar to patients without LV remodeling (incidence 29/1000 vs 26/1000 patient-year, p = 0.77). In conclusion, a process of LV wall thinning with a benign outcome can occur over the long term in patients with HC. The prognostic importance of LV remodeling varies in relation to the different changes in LV morphology and function., (Copyright © 2018. Published by Elsevier Inc.)

It is unknown whether the presence of a sarcomeric mutation alone is sufficient to result in abnormal myocardial force generation, or whether additional changes in myocardial architecture (hypertrophy, disarray, and fibrosis) are required to impair systolic function. Speckle tracking echocardiography allows quantification of global strain/strain rates, twist, and dyssynchrony. In the present study we sought to further elucidate early abnormalities of myocardial mechanics in sarcomeric mutation carriers without evidence of clinical disease. Sixty genotype-positive left ventricular hypertrophy-negative (G+left ventricular hypertrophy [LVH]-) patients and 60 normal controls were studied. Velocity vector imaging was applied retrospectively to echocardiographic images to quantify global longitudinal and circumferential strain/strain rate, and rotation parameters. The G+LVH- group demonstrated both smaller left ventricular diastolic cavity dimensions (4.5 ± 0.6 cm vs 4.8 ± 0.4 cm) and a higher LVEF (66 ± 6% vs 60 ± 5%) compared with controls. An increase in circumferential subendocardial systolic strain (-30 ± 5 vs -27 ± 3%) and both systolic and diastolic subendocardial strain rate was seen in the G+LVH- group. Peak rotation angles were higher at the base and apex, with an increase in total twist (9.0 ± 3.8 vs 6.9 ± 2.9). In the control group, global and average segmental strain were similar, suggesting no/minimal dyssynchrony (global mechanical synchrony index [GMSi] 0.97-0.98). In the G+LVH- group GMSi was significantly lower (subendocardial GMSi 0.95; subepicardial GMSi 0.60), suggesting increasing subendocardial to subepicardial dyssynchrony. In conclusion, utilizing multilayer strain analysis, we demonstrate that G+LVH- subjects have enhanced subendocardial systolic strain rate and twist, as well as mechanical dyssynchrony within the left ventricular myocardium. These results demonstrate that abnormalities in myocardial mechanics precede the development of clinical hypertrophy., (Copyright © 2018. Published by Elsevier Inc.)

The influence of shunts between the coronary artery (CA) and the left ventricle (LV), on chest pain (CP) in patients with hypertrophic cardiomyopathy (HCM) is unknown. We examined the incidence of CA-LV shunts and their influence on CP in HCM patients. Twenty normal control subjects (NCS), 3 with CP due to CA-LV shunts (CP patients), and 60 with HCM participated. Interventricular septal wall thickness (IVST), LV posterior wall thickness (LVPWT), cardiac and stroke indexes (CI and SI), LV end-diastolic pressure (LVEDP), and proximal diameters of the CA were measured. Twenty-five HCM patients had a CA-LV shunt (41.7%). Both IVST and LVPWT were greater in the HCM patients than in NCS and CP patients. These values showed no significant differences between the HCM with shunt and HCM without shunt groups. CI and SI were lower in the HCM patients than in NCS and CP patients. LVEDP was higher in the HCM and CP patients than in NCS. CA diameters were larger in the HCM and CP patients than in NCS. CP was found in 32 HCM patients (53%). The incidence of CP was greater in the HCM with shunt group than in HCM without shunt group (80 vs. 34%, p < 0.0005). There was no significant difference in CA diameters between the HCM patients with CP and those without CP. CA-LV shunts are often found in HCM patients and are closely related to CP. Thus, CA-LV shunts are an important factor behind CP in HCM patients.

Background: Identification of a subclinical cardiomyopathy in pediatric patients with Friedreich's ataxia (FA) has not been well-described., Methods: We performed echocardiography (Echo), cardiac magnetic resonance imaging (cMRI), and neurologic assessment in a cross-sectional analysis of 48 genetically confirmed FA subjects aged 9-17 years with moderate neurologic impairment but without a cardiovascular history. Echo- and cMRI-determined left ventricular mass were indexed (LVMI) to height in grams/m 2.7 . LV remodeling was categorized as concentric remodeling (CR), concentric hypertrophy (CH), or eccentric hypertrophy based upon Echo- determined relative LV wall thickness., Results: Echo LVMI exceeded age-based normal values in 85% of subjects, and cMRI-determined LVMI correlated with depression of both diastolic and systolic tissue Doppler velocity (E': r = -0.65, P < .001, S': r = -0.46, P < .001) as well as increased early diastolic Doppler flow velocity/tissue velocity ratio (r= 0.55, P < .001), a marker of elevated LV filling pressure. Similar associations were found with echo-determined LV mass. Evidence of depressed LV relaxation and increased LV stiffness were observed in 88% and 71%, of subjects, respectively, despite a normal LV ejection fraction in almost all cases (mean = 60% + 7%). CR and CH were present in 40% and 44% of the study group, respectively, although significant depressions of E' and S' were observed only in subjects with CH (P < .005)., Conclusions: A subclinical hypertrophic cardiomyopathy is common in pediatric FA patients and CH is associated with both diastolic and systolic dysfunction., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Atrial fibrillation (AF) is a common complication in patients with hypertrophic cardiomyopathy (HCM) and may contribute to high cardiovascular morbidity and mortality. Therefore, it is important to assess parameters associated with AF in HCM patients., Hypothesis: The aim of the study was to evaluate AF prevalence in patients with HCM and to investigate risk factors for AF., Methods: Five hundred and forty-six HCM patients aged below 65 were included into analysis. Clinical and echocardiographic parameters were analyzed., Results: In 141 patients (25.8%) AF episodes were recorded. The following factors were identified as risk factors for AF in patients with HCM: age ≥ 45 years (OR 2.38, CI 1.40-4.05, P = 0.001), past history of presyncope or syncope (OR 2.25, CI 1.35-3.74, P = 0.002), non-sustained ventricular tachycardia (nsVT) (OR 2.70, CI 1.60-4.57, P < 0.001), left atrium diameter during first assessment (OR 1.065, CI 1.03-1.11, P = 0.001), left atrium diameter at the last assessment before AF occurrence (OR 1.10, CI 1.06-1.14, P < 0.001) and left ventricular ejection fraction at the last assessment before AF occurrence (CI 0.96, CI 0.94-0.98, P = 0.001)., Conclusions: We confirm that AF is a common complication for patients with HCM. Identification of patients with high risk for AF and implementation of preventive strategies may reduce AF occurrence and its complications., (© 2018 Wiley Periodicals, Inc.)

We used peak longitudinal strain (PLS) on TTE in HCM patients to differentiate LV myocardium (LVM) into the following 4 groups: group 1-no fibrosis or hypertrophy (≥ 13 mm), group 2-no fibrosis but hypertrophy evident, group 3-fibrosis present but without hypertrophy, and group 4-both fibrosis and hypertrophy. Seventeen HCM patients (13 males, 56 ± 16 years) underwent both 1.5 T CMR and TTE. On TTE, PLS (absolute values) for each LVM segment from 17 AHA-defined lesions was calculated. Of 289 LVM lesions, the numbers in each group, 1-4, were 156, 53, 39, and 41, respectively. PLS for LVM segments in group 1 (13.6 ± 6.4%) were significantly greater than those in group 2 (8.5 ±  4.9%, P < 0.001), group 3 (10.4 ± 5.0%, P = 0.006), and group 4 (7.1 ± 4.4%, P < 0.001). PLS for LVM segments in group 3 was significantly greater than those in group 4 (P = 0.016). However, significant differences in PLS in LVM between groups 2 and 3, and between 2 and 4 were not observed. Using regional PLS, we demonstrate successful differentiation of LVM in HCM patients for group 1 (LVM with zero fibrosis or hypertrophy) from LVM belonging to groups 2-4 and we also demonstrate successful differentiation of LVM with fibrosis present but without hypertrophy from LVM with both fibrosis and hypertrophy. However, it is not possible to differentiate between LVM with no fibrosis but hypertrophy evident and those with fibrosis present but without hypertrophy and also between LVM with no fibrosis but hypertrophy evident and those with both fibrosis and hypertrophy. Our findings have significant implications for the management of HCM patients.

Only few studies aimed at identifying predictors of heart failure (HF) in hypertrophic cardiomyopathy (HC) patients. Furthermore, serial echocardiographic analyses are lacking in these patients and little is known about the natural progression of left ventricular (LV) abnormalities and their association with HF development. Aim of this study was to assess the prognostic value of LV global longitudinal strain (GLS) and other clinical and echocardiographic characteristics for the development of HF in patients with nonobstructive HC; furthermore, changes in echocardiographic parameters over time were correlated with HF development. Echocardiography was performed in 236 HC patients (68% men, age: 50 ± 14 years) at their initial visit and during follow-up (6.5(4.1 to 9.8) years). The end point of new HF development or progression to New York Heart Association class III/IV was noted and echocardiographic changes over time were compared among patients with and without HF using linear mixed model analysis. In total, 40 patients reached the HF end point. Multivariable cox regression analysis showed that age (HR 1.04(1.01 to 1.06), p = 0.016), New York Heart Association class (HR 2.30(1.07 to 4.95), p = 0.033), GLS (HR 1.15(1.05 to 1.22), p = 0.001), and left atrial volume (LAVI, HR 2.22(1.10 to 4.50), p = 0.027) were independently associated with the HF end point. Echocardiographic parameters, including GLS and LAVI, remained stable over time in patients without HF end point, but changed significantly in patients who developed HF (group-time interaction, p = 0.042 for GLS and p = 0.027 for LAVI). In conclusion, LV dysfunction is a progressive phenomenon in nonobstructive HC patients which can be detected by repeated echocardiography. Importantly, GLS and LAVI at baseline as well as their changes over time are associated with HF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In nonhigh risk patients with hypertrophic cardiomyopathy (HC), the presence of extensive late gadolinium enhancement (LGE ext ) at cardiovascular magnetic resonance (CMR) imaging has been proposed as a risk modifier in the decision process for implantable cardioverter defibrillator implantation. With a pretest risk of about 10%, a strategy that alters the likelihood of LGE ext could markedly affect efficacious CMR imaging. Our aim was to study the potential of clinical variables and biomarkers to predict LGE ext . In 98 HC patients without any clear indication for implantable cardioverter defibrillator implantation, we determined the discriminative values of a set of clinical variables and a panel of biomarkers (hs-cTnT, NTproBNP, GDF-15, and Gal-3, CICP) for LGE ext , that is, LGE ≥15% of the left ventricular mass. LGE ext was present in 10% (10/98) of patients. The clinical prediction model contained a history of nonsustained ventricular tachycardia, maximal wall thickness and reduced systolic function (c-statistic: 0.868, p <0.001). Of all biomarkers, only hs-cTnT was associated with LGE ext , in addition to the improved clinical model of diagnostic accuracy (p = 0.04). A biomarker-only strategy allowed the exclusion of LGE ext in half of the cohort, in case of a hs-cTnT concentration less than the optimal cutoff (Youden index; 8 ng/L-sensitivity 100%, specificity 54%). In conclusion, in this nonhigh risk HC cohort, the pretest likelihood of LGE ext can be altered using clinical variables and the addition of hs-cTnT. The promising findings with the use of hs-cTnT only call for new initiatives to study its impact on efficacious CMR imaging in a larger HC population, either with or without additional use of clinical variables., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The transapical approach has been utilized in adult HCM patients with either midventricular obstruction or a small LV cavity; however, there are little data on its use in children., Methods: We retrospectively reviewed all patients (age <21 years) with HCM who underwent a transapical myectomy from January 2002 to December 2016. Indication for surgery was midventricular obstruction in 19/23 (83%) and small LV cavity in 4 (17%). Preoperative symptoms included: dyspnea (96%), chest pain (65%), presyncope (61%), and syncope (35%). The mean age at the time of operation was 14 ± 4.0 years (range, 4-20)., Results: Overall, 23 patients (12 males) underwent transapical myectomy. A concomitant transaortic approach was performed in 16/19 (84%) with obstruction. The intraventricular gradient decreased from 71 mm Hg (IQR 44-92 mm Hg) preoperatively to 18 mm Hg (IQR 8-34 mm Hg, P < .0001) after myectomy. In patients with a small LV cavity, the mean left ventricular end diastolic dimension (LVEDD) increased from 40 ± 3 mm to 46 ± 3 mm (P = .05) after myectomy. There were no early deaths. Postoperative morbidity included complete heart block in 3 patients, 2 of which required pacemakers. Median follow up was 3.5 years (IQR 1.6-5.6). Symptoms improved in 95% of patients; the number of patients in NYHA class 3 or 4 heart failure decreased from 10/23 (43%) preoperatively to 3/23 (13%) postoperatively (P < .0001). Overall survival at 5 years postsurgery was 100%. Transplant-free survival was 91% and 87% at 1 and 5 years, respectively., Conclusion: In children with HCM, transapical myectomy is an effective adjunct to a transaortic approach to abolish midventricular obstruction and it effectively increases LV stroke volume in patients with small LV cavities and nonobstructive HCM. It may be beneficial for these patients with significant symptoms and who have failed medical therapy as a treatment alternative to cardiac transplantation., (© 2018 Wiley Periodicals, Inc.)

Myocardial perfusion-single-photon emission computed tomography (MP-SPECT) is used to evaluate microvascular dysfunction and coexisting coronary artery disease in patients with hypertrophic cardiomyopathy (HCM). Phase analysis in gated MP-SPECT can provide additional information on left ventricular (LV) dyssynchrony, while the extent of late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging is an important prognostic factor in patients with HCM. We, therefore, sought to investigate the relationship of dyssynchrony by phase analysis on gated MP-SPECT and LGE on CMR imaging in 22 patients with HCM who underwent both stress/rest-gated MP-SPECT and contrast-enhanced CMR imaging. LV dyssynchrony parameters [phase standard deviation (SD) and histogram bandwidth] from gated MP-SPECT were compared with LGE parameters from CMR imaging [L/C contrast and %LGE calculated, respectively, as LGE intensity/LV cavity intensity and (LGE volume/myocardial volume) × 100]. Phase SD and histogram bandwidth showed strong correlation with %LGE (r = 0.73, p < 0.0001 and r = 0.73, p < 0.0001, respectively), although they did not significantly correlate with L/C contrast (r = 0.30, p = 0.17 and r = 0.26, p < 0.25, respectively). The LV dyssynchrony derived from gated MP-SPECT strongly correlated with the extent of LGE on CMR imaging. In conclusion, our investigation suggests that gated MP-SPECT may be useful not only for the assessment of myocardial ischemia but also the extent of myocardial replacement fibrosis.

Two-dimensional speckle tracking echocardiography represents a novel, simple, and reproducible technique for the estimation of left ventricular myocardial deformation (strain) and the evaluation of left ventricular twist mechanics. During the last few years, its clinical and prognostic implications in cardiomyopathies and hypertrophic cardiomyopathy (HCM), in particular, have been rapidly increasing. Reduced global longitudinal strain is associated with more severe disease and confers an increased risk for major cardiac events, independently of other clinical and echocardiographic risk factors. Left ventricular dyssynchrony also seems promising as a risk factor for sudden cardiac events. With respect to left atrial mechanics, left atrial reservoir, conduit, and contractile strain may also confer an increased prognostic value for atrial fibrillation, major cardiac events, and even sudden death. Although right ventricular global longitudinal strain is impaired in HCM compared with healthy controls and individuals with physiological hypertrophy, its prognostic significance is currently unknown. Conclusively, 2-dimensional speckle tracking imaging seems promising for HCM. However, future studies are needed to incorporate this new imaging technique in the standard evaluation of an HCM individual.

Background: The association between athletic participation and alteration in diastolic function is not well established. The aims of this study were to determine the spectrum of Doppler parameters of left ventricular (LV) diastolic function in a large cohort of healthy athletes and to quantify the overlap between physiologic LV hypertrophy and hypertrophic cardiomyopathy (HCM)., Methods: A retrospective analysis of indices of LV diastolic function was performed in 1,510 healthy athletes (mean age, 22 ± 5 years; range, 13-33 years; 72% men). The results were compared with those from 58 young patients with HCM., Results: Septal E' < 7 cm/sec and lateral E' < 10 cm/sec were found in five (0.3%) and eight (0.5%) athletes, respectively. Septal E' was >14.6 cm/sec in 170 (11%) and lateral E' was >19.9 cm/sec in 430 (28%) athletes. Athletes aged >25 years showed lower E' velocities compared with younger athletes (mean septal E', 11.8 ± 6.1 vs 12.9 ± 5.9 cm/sec [P < .001]; mean lateral E', 17.1 ± 3.6 vs 19.3 ± 4.1 cm/sec [P < .001]). Athletes with high indexed LV end-diastolic diameters (>32 mm/m 2 ) exhibited lower septal E' compared with athletes with normal indexed LV end-diastolic diameters (mean septal E', 11.9 ± 6 vs 12.7 ± 6 cm/sec; P = .002). Septal E' < 10 cm/sec and lateral E' < 12 cm/sec showed the best accuracy in differentiating between HCM and athlete's heart., Conclusions: Reduced septal and lateral E' are rarely observed in young elite athletes. Tissue Doppler velocities tend to decrease with increasing age and LV size, and values representative of supernormal diastolic function are found in less than one-third of young athletes. Cutoff thresholds for Doppler parameters of diastolic function should be corrected for multiple demographic and clinical variables to differentiate cardiac adaptation to exercise from HCM in young individuals., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Exercise intolerance is the most common symptom in hypertrophic cardiomyopathy (HCM). We examined whether inability to augment myocardial mechanics during exercise would influence functional performance and clinical outcomes in HCM., Methods: Ninety-five HCM patients (32 nonobstructive, 32 labile-obstructive, 31 obstructive) and 26 controls of similar age and gender distribution were recruited prospectively. They underwent rest and treadmill stress strain echocardiography, and 61 of them underwent magnetic resonance imaging. Mechanical reserve (MRES) was defined as percent change in systolic strain rate (SR) immediately postexercise., Results: Global strain and SR were significantly lower in HCM patients at rest (strain: nonobstructive, -15.6 ± 3.0; labile-obstructive, -15.9 ± 3.0; obstructive, -13.8 ± 2.9; control, -17.7% ± 2.1%, P < .001; SR: nonobstructive, -0.92 ± 0.20; labile-obstructive, -0.94 ± 0.17; obstructive, -0.85 ± 0.18; control, -1.04 ± 0.14 s -1 , P = .002); and immediately postexercise (strain: nonobstructive, -15.6 ± 3.0; labile-obstructive, -17.6 ± 3.6; obstructive, -15.6 ± 3.6; control, -19.2 ± 3.1%; P = .001; SR: nonobstructive, -1.41 ± 0.37; labile-obstructive, -1.64 ± 0.38; obstructive, -1.32 ± 0.29; control, -1.82 ± 0.29 s -1 , P < .001). MRES was lower in nonobstructive and obstructive compared with labile-obstructive and controls (51% ± 29%, 54% ± 31%, 78% ± 38%, 77% ± 30%, P = .001, respectively). Postexercise SR and MRES were associated with exercise capacity (r = 0.47 and 0.42, P < .001 both, respectively). When adjusted for age, gender, body mass index, E/e', and resting peak instantaneous systolic gradient, postexercise SR best predicted exercise capacity (r = 0.74, P = .003). Postexercise SR was correlated with extent of late gadolinium enhancement (r = 0.34, P = .03). By Cox regression, exercise SR and MRES predicted ventricular tachycardia/ventricular fibrillation (VT/VF) even after adjustment for age, gender, family history of sudden cardiac death, septum ≥ 3 cm and abnormal blood pressure response (P = .04 and P = .046, respectively)., Conclusions: Nonobstructive and obstructive patients have reduced MRES compared with labile-obstructive and controls. Postexercise SR correlates with LGE and exercise capacity. Exercise SR and MRES predict VT/VF., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

A diastolic paradoxical jet flow, often seen in patients with hypertrophic cardiomyopathy, is a unique flow from the apex toward the base of the left ventricle during isovolumic relaxation. To date, this phenomenon appears to have been noninvasively detected only on echocardiograms. We report the case of a 43-year-old man with hypertrophic cardiomyopathy and a diastolic paradoxical jet flow, in whom cardiac auscultation revealed a soft S 4 , a systolic ejection murmur, and a low-pitched early diastolic murmur immediately after S 2 at the apex. On comparing his echocardiographic findings with those on phonocardiograms and apexcardiograms, we confirmed that the unusual murmur coincided with the diastolic jet flow. To our knowledge, this is the first case in which heart murmurs associated with a diastolic paradoxical jet flow have been clearly described. Because these flows can increase the risk of adverse outcomes, detecting any associated murmurs by methods other than echocardiography is worthwhile, even in the era of advanced imaging techniques.

Hypertrophic cardiomyopathy has a range of clinical severity in children. Treatment options are limited, mainly on account of small patient size. Disopyramide is a sodium channel blocker with negative inotropic properties that effectively reduces left ventricular outflow tract gradients in adults with hypertrophic cardiomyopathy, but its efficacy in children is uncertain. A retrospective chart review of patients ⩽21 years of age with hypertrophic cardiomyopathy at our institution and treated with disopyramide was performed. Left ventricular outflow tract Doppler gradients before and after disopyramide initiation were compared as the primary outcome measure. Nine patients received disopyramide, with a median age of 5.6 years (range 6 days-12.9 years). The median left ventricular outflow tract Doppler gradient before initiation of disopyramide was 81 mmHg (range 30-132 mmHg); eight patients had post-initiation echocardiograms, in which the median lowest recorded Doppler gradient was 43 mmHg (range 15-100 mmHg), for a median % reduction of 58.2% (p=0.002). With median follow-up of 2.5 years, eight of nine patients were still alive, although disopyramide had been discontinued in six of the nine patients. Reasons for discontinuation included septal myomectomy (four patients), heart transplantation (one patient), and side effects (one patient). Disopyramide was effective for the relief of left ventricular outflow tract obstruction in children with hypertrophic cardiomyopathy, although longer-term data suggest that its efficacy is not sustained. In general, it was well tolerated. Further study in larger patient populations is warranted.

Background: The association between bicuspid aortic valve (BAV) and hypertrophic cardiomyopathy (HCM) has been reported but its true prevalence is unknown. This study investigated the prevalence and clinical impact of coexistent BAV in a large referral HCM population., Methods: Retrospective analysis of 3765 echocardiograms between 2004 and 2014 in 2640 consecutive patients with HCM was performed to assess for BAV. Patients with coexistent conditions were studied., Results: Twenty-three patients (0.9%) were identified with coexisting BAV and HCM. Mean age was 52±16years, 18 males (78%), 16 with NYHA functional class I/II at initial evaluation (70%). A family history of HCM was present in five patients (22%); none had a family history of BAV or aortopathy. Maximal left ventricular wall thickness was 24±6mm; the majority had either reverse curve or sigmoid septal morphology. Moderate or greater aortic valve dysfunction was present in seven patients (30%), BAV-related aortopathy in 18 patients (78%) and dynamic left ventricular outflow tract (LVOT) obstruction in nine patients (39%). Three patients had combined LVOT obstruction and aortic stenosis. Median time from diagnosis of BAV or HCM to last follow-up was 11±12.5years. At last follow-up, 22% had undergone BAV-related surgeries, 30% had septal reduction therapy (SRT), and 17% had combined SRT and BAV-related surgeries. Overall survival was 95% at 10 years., Conclusions: This study reported a 0.9% prevalence of BAV among HCM population, similar to the general population. Aortopathy and LVOT obstruction were common, necessitating cardiac interventions in over one-third of cases. Long-term survival appeared favourable., (Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Implantable cardioverter-defibrillator (ICD) is effective to prevent sudden death in HCM patients. We reviewed ICD records to analyze the relation between life-threatening arrhythmia and late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) in Japanese hypertrophic cardiomyopathy (HCM) patients. In 102 consecutive patients (median age 63 years, 63 males) implanted with an ICD after CMR with gadolinium enhancement (median follow-up 2.8 years), the outcome of life-threatening arrhythmic events (appropriate ICD interventions for ventricular tachycardia or ventricular fibrillation) was examined. Appropriate interventions rate were 10.3% per year for secondary prevention and 7.4% per year for primary prevention. The annualized ICD-related complication rate was 3.7%. 43/91 patients (47%) implanted ICD for primary prevention had maximum wall thickness ≥20 mm plus LGE in ≥4 of 17 left ventricular segments (cut-off value obtained from ROC curve); the appropriate ICD intervention rate was significantly higher in this group than in other patients group (annualized event rate, 11.1 vs. 4.6%; log-rank P = 0.038). A combination of myocardial hypertrophy and LGE is a useful outcome predictive factor for life-threatening ventricular arrhythmia in Japanese HCM patients.

Objective: Diastolic dysfunction is common in hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HHD), but its relationships with left ventricular (LV) parameters have not been well studied. Our objective was to assess the relationship of various measures of diastolic function, and maximum left ventricular wall thickness (MLVWT) and left ventricular mass index (LVMI) in HCM, HHD and normal controls using cardiac magnetic resonance imaging (CMR). We also assessed LV parameters and diastolic function in relation to late gadolinium enhancement (LGE) and right ventricular (RV) hypertrophy in HCM., Methods: 41 patients with HCM, 21 patients with HHD and 20 controls were studied. Peak filling rate (PFR), time to peak filling (TPF), MLVWT and LVMI were measured using CMR. LGE and RV morphology were assessed in HCM patients., Results: MLVWT correlated with TPF in HCM (r=0.38; p=0.02), HHD (r=0.58; p=0.01) and controls (r=0.54; p=0.01); correlation between MLVWT and TPF was weaker in HCM than HHD. LVMI did not correlate with diastolic function. In HCM, LGE extent correlated with MLVWT (τ=0.41; p=0.002) and with TPF (τ=0.29; p=0.02). The HCM patients with RV hypertrophy had higher MLVWT (p<0.001) and TPF (p=0.03) than patients without RV hypertrophy., Conclusion: MLVWT correlates with diastolic function (TPF) in HCM, HHD and controls. LVMI did not show significant correlation with TPF. The diastolic dysfunction in HCM is not entirely explained by wall thickening. LGE and RV involvement are associated with worse LV diastolic function, suggesting that these may be markers of more severe underlying myocardial disarray and fibrosis that contribute to diastolic dysfunction., (Copyright © 2016. Published by Elsevier B.V.)

Guidelines recommend exercise stress echocardiogram (ESE) for patients with hypertrophic cardiomyopathy (HC) if a 50 mm Hg gradient is not present at rest or provoked with Valsalva or amyl nitrite, to direct medical and surgical management. However, no study has directly compared all 3 methods. We sought to evaluate efficacy and degree of provocation of left ventricular outflow gradients by ESE, and compare with Valsalva and amyl nitrite. In patients with HC between 2002 and 2015, resting echocardiograms and ESEs within 1 year were retrospectively reviewed. Gradients elicited by each provocation method were compared. Rest and ESE were available in 97 patients (mean age 54 ± 18 years, 57% male); 78 underwent Valsalva maneuver and 41 amyl nitrite provocation. Median gradients (interquartile range) were 10 mm Hg (7,19) at rest, 16 mm Hg (9,34) with Valsalva, 23 mm Hg (13,49) with amyl nitrite, and 26 mm Hg (13,58) with ESE. ESE and amyl nitrite were able to provoke obstruction (≥30 mm Hg) and severe obstruction (≥50 mm Hg) more frequently than Valsalva. In patients with resting gradient <30 mm Hg (n = 83), provocation maneuvers demonstrated dynamic obstruction in 51%; in those with Valsalva gradient <30 mm Hg (n = 57), ESE or amyl nitrite provoked a gradient in 44%; and in those with amyl nitrite gradient <30 mm Hg (n = 20), ESE provoked a gradient in 29%. No demographic or baseline echocardiographic parameter predicted provocable obstruction. In conclusion, ESE is clinically useful; however, different provocation maneuvers may be effective in different patients with HC, and all maneuvers may be required to provoke dynamic obstruction in symptomatic patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The coexistence of sleep-disordered breathing (SDB) and hypertrophic obstructive cardiomyopathy (HOCM) has widely been recognized; however, the impact of percutaneous transluminal septal myocardial ablation (PTSMA) for HOCM on SDB remains unknown. Herein, we examine cardiorespiratory polygraph parameters in patients with drug-refractory HOCM before and after PTSMA. Forty consecutive drug-refractory HOCM patients, admitted to Keio University Hospital, and who underwent cardiorespiratory polygraphy were retrospectively analyzed. Cardiorespiratory polygraphy was performed before and after PTSMA if patients underwent PTSMA. Patients with an apnea-hypopnea index (AHI) ≥5/h were considered to have SDB. The total number of central sleep apneas, obstructive sleep apneas, and hypopnea events was evaluated. Thirty-two out of 40 patients (80%) with drug-refractory HOCM had SDB. All patients experienced relief of heart failure-associated symptoms after PTSMA. The severity of SDB was found to be correlated with left atrial diameter. The AHI decreased after PTSMA [before 15.4 (range 10.9-23.5)/h vs. after 13.1 (8.3-17.8)/h, P = 0.02]. Especially, the hypopnea index decreased after PTSMA. The average and lowest arterial oxygen saturation also increased after PTSMA (94.2 ± 1.9-95.7 ± 1.6%, P = 0.009; 81.3 ± 5.7-85.8 ± 4.8%, P = 0.012, respectively). In patients with drug-refractory HOCM, PTSMA decreased the AHI and improved arterial oxygen saturation measures. Thus, invasive treatment of the left ventricular obstruction ameliorates the severity of SDB, in addition to improving heart failure status.

Apical hypertrophic cardiomyopathy (HCM) is an uncommon variant of HCM characterized by apical hypertrophy without the septal predominance seen in the majority of HCM cases. In 2% of patients, a concomitant left ventricular apical aneurysm is observed, which increases the risk of sudden death and adverse HCM-related events. Multimodality imaging is helpful for appropriate identification of this particular morphologic pattern. Herein, we present a case of apical HCM with a left ventricular apical aneurysm, exemplifying the utility of a multimodality approach from resting electrocardiogram, transthoracic echocardiogram, left ventriculography, and cardiac magnetic resonance imaging, for proper risk stratification and treatment planning., (© 2017, Wiley Periodicals, Inc.)

Background: Atrial fibrillation (AF) is the most common arrhythmic event in patients with hypertrophic cardiomyopathy (HCM). The aim of this study was to identify the clinical impact and prognostic significance of AF on a large cohort of patients with HCM., Methods: Echocardiographic and clinical correlates, risk factors for AF and thromboembolic stroke and the prognostic significance of AF were evaluated in 509 patients with an established diagnosis of HCM., Results: A total of 119 patients (23.4%) were diagnosed with AF during the index evaluation visit. AF patients had a higher prevalence of stroke and presented with worse functional impairment. Left atrial diameter (LA size) was a common independent predictor of the arrhythmia (OR: 2.2, 95% CI 1.6-3.3) and thromboembolic stroke (OR: 1.6, 95% CI 1.01-2.40). AF was an important risk factor for overall mortality (HR=3.4, 95% CI: 1.7-6.5), HCM-related mortality (HR=3.9, 95% CI: 1.8-8.2) and heart failure-related mortality (HR=6.0, 95% CI: 2.0-17.9), even after adjusting for statistically significant clinical and demographic risk factors. However, AF did not affect the risk for sudden death., Conclusions: LA size is an independent predictor of both AF and thromboembolic stroke. Moreover, patients with AF, regardless of type, have significantly higher mortality rates than patients without AF., (Copyright © 2017 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.)

Background: Preserved left ventricular (LV) ejection fraction (EF) and reduced myocardial strain are reported in patients with hypertrophic cardiomyopathy, ischemic heart disease, diabetes mellitus, and more., Objectives: The authors performed a combined mathematical and echocardiographic study to understand the inconsistencies between EF and strains., Methods: An analytical equation showing the relationship between EF and the 4 parameters, global longitudinal strain (GLS), global circumferential strain (GCS), wall thickness, and short-axis diameter, was derived from an elliptical LV model. The equation was validated by measuring the 4 parameters by echocardiography in 100 subjects with EF ranging from 16% to 72% and comparing model-predicted EF with measured EF. The effect of the different parameters on EF was explored in the model and compared with findings in the patients., Results: Calculated EF had very good agreement with measured EF (r = 0.95). The model showed that GCS contributes more than twice as much to EF than GLS. A significant reduction of GLS could be compensated by a small increase of GCS or wall thickness or reduced diameter. The model further demonstrated how EF can be maintained in ventricles with increased wall thickness or reduced diameter, despite reductions in both longitudinal and circumferential shortening. This was consistent with similar EF in 20 control subjects and 20 hypertrophic cardiomyopathy patients with increased wall thickness and reductions in both circumferential and longitudinal shortening (all p < 0.01)., Conclusions: Reduced deformation despite preserved EF can be explained through geometric factors. Due to geometric confounders, strain better reflects systolic function in patients with preserved EF., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)