Search

The sudden death (SD) risk stratification algorithm in hypertrophic cardiomyopathy (HCM) has evolved, underscored recently by novel cardiac magnetic resonance (CMR)-based risk markers (left ventricular apical aneurysm, extensive late gadolinium enhancement, and end-stage disease with systolic dysfunction) incorporated into the 2020 American Heart Association (AHA)/American College of Cardiology (ACC) HCM guidelines.The purpose of this study was to assess the specific impact of newer, predominantly CMR-based risk markers in a large multicenter HCM population that underwent primary prevention implantable cardioverter-defibrillator (ICD) implants.Longitudinal study of 1149 consecutive HCM patients from 6 North American and European HCM centers prospectively judged to be at high SD risk based on ≥1 AHA/ACC individual risk markers and prophylactically implanted with an ICD was performed. European Society of Cardiology (ESC) risk score was retrospectively analyzed with respect to the known clinical outcome.Of 1149 patients with an ICD, 162 (14%) experienced device therapy terminating ventricular tachycardia/ventricular fibrillation 4.6 ± 4.2 years after implant. CMR-based markers solely or in combination led to ICD implantation in 49 of the 162 patients (30%) experiencing device therapy. Particularly low ESC scores (4%/5 years) would have excluded an ESC ICD recommendation for 67 patients who nevertheless experienced appropriate ICD therapy, including 26 with the CMR-based risk markers not part of the ESC formula.Identification and incorporation of novel guideline-supported CMR-based risk markers enhance selection of HCM patients for SD prevention with ICDs. Absence of CMR-based markers from the ESC risk score accounts, in part, for it not identifying many HCM patients with SD events. These data support inclusion of CMR as a routine part of HCM patient evaluation and risk stratification.

Objectives This study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making. Background Myocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM. Methods A total of 157 patients with HCM were enrolled in this study, with 2 sequential CMR scans separated by an interval of 4.7 ± 1.9 years. Results At the first CMR session (CMR-1), 70% of patients had LGE compared with 85% at CMR-2 (p = 0.001). The extent of LGE extent increased between the 2 CMR procedures, from 4.0 ± 5.6% to 6.3 ± 7.4% (p 8% of LV mass, indexed LV mass >100 g/m2, maximal wall thickness ≥20 mm, LVEF ≤60%, and apical aneurysm. There was a significant correlation between the magnitude of LGE progression and future implantation of insertable cardioverter-defibrillators (p = 0.004), EF deterioration to ≤50% (p Conclusions Myocardial fibrosis in patients with HCM is a slowly progressive process. Progression of LGE is significantly correlated with a number of clinical outcomes such as progression to EF ≤50% and heart failure admission. Judicious use of serial CMR with LGE can provide valuable information to help patient management.

Surgical myectomy remains the time-honored primary treatment for hypertrophic cardiomyopathy patients with drug refractory limiting symptoms due to LV outflow obstruction. Based ongt;50 years experience, surgery reliably reverses disabling heart failure by permanently abolishing mechanical outflow impedance and mitral regurgitation, with normalization of LV pressures and preserved systolic function. A consortium of 10 international currently active myectomy centers report about 11,000 operations, increasing significantly in number over the most recent 15 years. Performed in experienced multidisciplinary institutions, perioperative mortality for myectomy has declined to 0.6%, becoming one of the safest currently performed open-heart procedures. Extended myectomy relieves symptoms ingt;90% of patients by ≥ 1 NYHA functional class, returning most to normal daily activity, and also with a long-term survival benefit; concomitant Cox-Maze procedure can reduce the number of atrial fibrillation episodes. Surgery, preferably performed in high volume clinical environments, continues to flourish as a guideline-based and preferred high benefit: low treatment risk option for adults and children with drug refractory disabling symptoms from obstruction, despite prior challenges: higher operative mortality/skepticism in 1960s/1970s; dual-chamber pacing in 1990s, alcohol ablation in 2000s, and now introduction of novel negative inotropic drugs potentially useful for symptom management.

Identifying patients with hypertrophic cardiomyopathy (HCM) who warrant a primary prevention implantable cardioverter-defibrillator (ICD) is crucial. ICDs are effective in terminating life-threatening arrhythmias; however, ICDs carry risks of complications.The purpose of this study was to assess the incidence and predictors of appropriate ICD therapies, inappropriate shocks, and device-related complications in patients with HCM and primary prevention ICDs.All patients with HCM who underwent primary prevention ICD implantation at Toronto General Hospital between September 2000 and December 2017 were identified. Therapies (shocks or antitachycardia pacing) for ventricular tachycardia180 beats/min or ventricular fibrillation were considered appropriate.Three hundred two patients were followed for a mean 6.1 ± 4.3 years (1801 patient-years of follow-up). Thirty-eight patients (12.6%) received at least 1 appropriate ICD therapy (2.3%/y); the 5-year cumulative probability of receiving appropriate ICD therapy was 9.6%. None of the conventional risk factors nor the European Society of Cardiology risk score was associated with appropriate ICD therapy. In multivariable analysis, age40 years at implantation and atrial fibrillation were independent predictors of appropriate ICD therapy. In a subgroup of patients who had undergone cardiac magnetic resonance imaging before ICD implantation, severe late gadolinium enhancement was the strongest predictor of appropriate ICD therapies. ICD-related complications or inappropriate shocks occurred in 87 patients (28.8%), with an inappropriate shock rate of 2.1%/y; the 5-year cumulative probability was 10.7%.The incidence of appropriate ICD therapies in patients with HCM and primary prevention ICDs is lower than previously reported; a high proportion of patients suffer from an ICD-related complication. Traditional risk factors have low predictive utility. Severe late gadolinium enhancement, atrial fibrillation, and young age are important predictors of ventricular tachyarrhythmias in HCM.

In this study, we aimed to assess a large cohort of nonapical hypertrophic cardiomyopathy (HC) patients who have undergone 2 serial cardiac magnetic resonance studies to examine morphological dynamics and their correlation to patient characteristics and clinical outcomes. A total of 214 patients with nonapical HC were enrolled in this study, with 2 sequential cardiac magnetic resonance studies separated by a mean interval of 4.8 ± 2.1 years. Progression of indexed left ventricular mass (LVMI) was correlated with lower LVMI at baseline (p 0.00001) and older age50 years. In terms of maximal wall thickness (MWT), progression was associated with lower baseline MWT and with the presence of LV outflow tract obstruction. No association was demonstrated between the degree of progression of LVMI or MWT and baseline LV volumes, the severity of mitral regurgitation, gender, or the presence of pathogenic HC variants. Progression of left atrial size was significantly associated with the development of atrial fibrillation (p = 0.014; odds ratio 1.18, confidence interval 1.03 to 1.35) and admission for heart failure (p = 0.018; odds ratio 1.18, confidence interval 1.03 to 1.36). No correlation was demonstrated between changes in LV mass or MWT and clinical outcomes of admission for heart failure, progression to New York Heart Association 2/3, progression to end-stage HC, or implantable cardioverter-defibrillator implantation. In conclusion, our study provides novel insights into the natural history of HC from a morphological perspective. It shows that HC is a dynamic disease in which LV morphology and hypertrophy extent change over time, with the presence of risk factors associated with disease progression.

Background Significant left-ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM) may result in symptoms and is associated with adverse outcomes. Although disopyramide can reduce resting gradients, nearly 30% of HCM patients do not respond. We sought to study the clinical and echocardiographic variables associated with disopyramide-induced LVOT-gradient reduction. Methods Forty-one disopyramide-treated HCM patients (average daily-dose 305 mg) were subdivided into two groups: (1) nineteen responders, with a reduction of LVOT-gradients of at least 30% from baseline, and (2) twenty-two non-responders, in whom LVOT-gradients did not change or increased following treatment. All patients had a thorough clinical and echocardiographic assessment pre- and post-treatment initiation. Results Patients who responded to disopyramide had better pretreatment left ventricular (LV) systolic function (LV ejection fraction of 67.9 ± 5.6% vs. 59.7 ± 5.8%, p = 0.0001), better LV global longitudinal strain (−17.9 ± 2.3% vs. −16.1 ± 2.5%, p = 0.048), less mitral regurgitation, smaller LV size (indexed LV end-systolic volume of 16.2 ± 5.1 ml/m2 vs. 23.2 ± 6.8 ml/m2, p = 0.001), and lower LV maximal wall thickness (17.2±3 mm vs.19.2 ± 3.4 mm, p = 0.046). Baseline left atrial (LA) volumes were significantly lower in the responders, with higher indices of LA ejection fraction (62 ± 11.2% vs. 50.5 ± 12.2%, p = 0.005), systolic LA strain (34 ± 12.4% vs. 25.8 ± 10.6%, p = 0.04), and LA strain-rate (1.34 ± 0.49%/sec vs. 0.99 ± 0.24%/sec, p = 0.012). In multivariable analysis, the presence of reduced LV systolic function and systolic LA strain-rate remained independently associated with poor response to disopyramide. Conclusions Obstructive HCM patients with more severe disease at baseline tend to respond less to disopyramide treatment. In those patients, early referral for alcohol septal ablation or myectomy surgery should be considered.

Background Unlike T‐wave alternans (TWA), the relation between QRS alternans (QRSA) and ventricular arrhythmia (VA) risk has not been evaluated in hypertrophic cardiomyopathy (HCM). We assessed microvolt QRSA/TWA in relation to HCM risk factors and late VA outcomes in HCM. Methods and Results Prospectively enrolled patients with HCM (n=130) with prophylactic implantable cardioverter‐defibrillators underwent digital 12‐lead ECG recordings during ventricular pacing (100–120 beats/min). QRSA/TWA was quantified using the spectral method. Patients were categorized as QRSA+ and/or TWA+ if sustained alternans was present in ≥2 precordial leads. The VA end point was appropriate implantable cardioverter‐defibrillator therapy over 5 years of follow‐up. QRSA+ and TWA+ occurred together in 28% of patients and alone in 7% and 7% of patients, respectively. QRSA magnitude increased with pacing rate (1.9±0.6 versus 6.2±2.0 µV; P =0.006). Left ventricular thickness was greater in QRSA+ than in QRSA− patients (22±7 versus 20±6 mm; P =0.035). Over 5 years follow‐up, 17% of patients had VA. The annual VA rate was greater in QRSA+ versus QRSA− patients (5.8% versus 2.0%; P =0.006), with the QRSA+/TWA− subgroup having the greatest rate (13.3% versus 2.6%; P P =0.001). Separate Cox models revealed QRSA+ (hazard ratio [HR], 2.9 [95% CI, 1.2–7.0]; P =0.019) and QRSA+/TWA− (HR, 7.9 [95% CI, 2.9–21.7]; P Conclusions In HCM, microvolt QRSA is a novel, rate‐dependent phenomenon that can exist without TWA and is associated with greater left ventricular thickness. QRSA increases VA risk 3‐fold in all patients, whereas the absence of QRSA confers low VA risk in patients with Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02560844.

Left ventricular (LV) apical aneurysms in hypertrophic cardiomyopathy (HCM) are a recognized risk marker for adverse cardiovascular events. There is variable practice among clinicians and discordance between international guidelines regarding treatment recommendations and prognostication for this important phenotype.The authors sought to describe the morphology, clinical course, and risk of adverse events in a large single-center cohort of HCM patients with LV apical aneurysms.This study analyzed 160 HCM patients with an LV apical aneurysm who were evaluated in our dedicated HCM clinic between January 1997 and April 2021.Mean age was 59.1 ± 13.6 years, and 71% of these patients were male. Mean aneurysm size was 1.77 ± 1.04 cm. Over 6.2 ± 4.8 years, 14 (9%) patients had a sudden cardiac death (SCD) event, including appropriate therapy from an implantable cardioverter-defibrillator (ICD) or resuscitation from cardiac arrest (annualized event rate 1.77%/y), 39 (24%) had either a thromboembolic stroke or apical thrombus formation (2.9%/y), and 14 (9%) developed LV systolic dysfunction with an ejection fraction (EF) 50% (1.28%/y). HRs for SCD, stroke or thrombus, and EF 50% per 1-cm increase in aneurysm size were 1.69 (P = 0.007), 1.60 (P = 0.0002), and 1.63 (P = 0.01), respectively. Aneurysm size ≥2 cm was associated with a 5-year SCD rate of 9.7%, compared with 2.9% for aneurysm size 2 cm (log-rank P = 0.037). This subgroup also had higher risk of stroke/thrombus formation (HR: 2.20; P = 0.002), with an annualized event rate of 2.7%/year. A total of 39 (24%) patients reached the combined end point of SCD, stroke, or LV dysfunction (2.12%/y) with an HR of 1.47/cm increase in aneurysm size (P = 0.003) and an HR of 2.22 for patients with aneurysm size ≥2 cm (P = 0.02).Increasing aneurysm size confers poorer prognosis. Aneurysm size ≥2 cm should alert potential consideration for prophylactic anticoagulation and primary prevention ICDs.

Hypertrophic cardiomyopathy (HCM), a relatively common, globally distributed, and often inherited primary cardiac disease, has now transformed into a contemporary highly treatable condition with effective options that alter natural history along specific personalized adverse pathways at all ages. HCM patients with disease-related complications benefit from: matured risk stratification in which major markers reliably select patients for prophylactic defibrillators and prevention of arrhythmic sudden death; low risk to high benefit surgical myectomy (with percutaneous alcohol ablation a selective alternative) that reverses progressive heart failure caused by outflow obstruction; anticoagulation prophylaxis that prevents atrial fibrillation-related embolic stroke and ablation techniques that decrease the frequency of paroxysmal episodes; and occasionally, heart transplant for end-stage nonobstructive patients. Those innovations have substantially improved outcomes by significantly reducing morbidity and HCM-related mortality to 0.5%/y. Palliative pharmacological strategies with currently available negative inotropic drugs can control symptoms over the short-term in some patients, but generally do not alter long-term clinical course. Notably, a substantial proportion of HCM patients (largely those identified without outflow obstruction) experience a stable/benign course without major interventions. The expert panel has critically appraised all available data and presented management insights and recommendations with concise principles for clinical decision-making.

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), associated with impaired quality of life, risk for embolic stroke, and unpredictable onset. We sought to create a predictive model to identify risk for AF development in HCM. Methods: A cohort of 1900 patients with HCM followed for newly diagnosed AF in the Tufts HCM center was used for model development. A cohort of 387 patients from Toronto General Hospital was used for external validation. Data in the development cohort generated the HCM-AF score, a point score to predict AF probability at 2 and 5 years: left atrial dimension (+2 points per 6 mm increase), age at clinical evaluation (+3 points per 10-year increase), age at initial HCM diagnosis (−2 points per 10-year increase), and heart failure symptoms (+3 points if symptomatic). Results: The HCM-AF score stratifies risk as low (2.0%/y; score ≥22) for AF development for individual patients. Concordance of the HCM-AF score was 0.70 in the development cohort and 0.68 in the external validation cohort. In the development cohort, 17.2% of high-risk patients developed AF (rate 3.4%/y), while only 3.3% of low-risk patients developed AF (rate 0.7%/y) at 5 years ( P Conclusions: The HCM-AF score is a novel externally validated predictive tool to identify AF risk in HCM. This score can reliably stratify patients with HCM to risk of newly diagnosed AF and offers the opportunity to inform expectations regarding future clinical course.

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

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

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.

IMPORTANCE: Patients with hypertrophic obstructive cardiomyopathy (HOCM) and drug-refractory symptoms and outflow gradients have limited nonsurgical treatment options. The feasibility of percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) has been reported previously; however, procedural and medium-term outcomes are unknown. OBJECTIVE: To describe the safety and medium-term outcomes of PIMSRA in a large patient cohort with drug-refractory HOCM. DESIGN, SETTING, AND PARTICIPANTS: This was a single-arm, open-label study of PIMSRA in patients with drug-refractory HOCM. Patients presenting to the Xijing Hospital in Xi’an, China, between October 2016 to June 2020 with hypertrophic cardiomyopathy. Of 1314 patients presenting with HOCM, 244 fulfilled inclusion criteria of severe resting/provoked outflow gradients of 50 mm Hg or higher, and symptoms of New York Heart Association functional class of II or higher refractory to maximum tolerated medications. After discussion among the heart team, 40 patients underwent surgical or alcohol septal reduction therapy and 4 required treatment of significant coronary artery disease. INTERVENTIONS: PIMSRA performed in patients. MAIN OUTCOMES AND MEASURES: The primary outcome was 30-day major adverse clinical events: death, emergency surgery, severe effusion requiring intervention, procedure-related stroke, bleeding, and stroke. Secondary outcomes included 30-day technical success and 90-day improvement in outflow obstruction. RESULTS: The mean (SD) age of 200 patients was 46.9 (14.0) years, and 125 (62.5%) were men. Resting or provoked left ventricular outflow tract gradients were 50 mm Hg or higher. The median (IQR) follow-up for all patients was 19 (6-50) months. Thirty-day major adverse clinical events rate was 10.5% (n = 21): there were 2 in-hospital/30-day deaths (1.0%), 7 patients (3.5%) with pericardial effusion requiring mini-thoracotomy, 12 patients (6%) with pericardial effusion requiring pericardiocentesis, and no bleeding or strokes. Other periprocedural complications included permanent right bundle branch block in 5 patients (2.5%), resuscitated ventricular fibrillation in 2 (1.0%), and septal branch aneurysm in 2 (1.0%). There were no permanent pacemaker implantations. At follow-up, maximum septal thickness was reduced from a mean (SD) of 24.0 (5.1) mm to 17.3 (4.4) mm (P

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.

Background Left ventricular (LV) apical aneurysm is a unique morphological entity and novel adverse risk marker existing within the broad phenotypic spectrum of hypertrophic cardiomyopathy (HCM). Its true prevalence in the HCM population is likely underestimated because of inherent limitations of conventional noncontrast echocardiography. The authors hypothesized that contrast echocardiography is a reliable imaging technique compared with cardiovascular magnetic resonance (CMR) for the detection of apical aneurysms. The aim of this study was to assess the effectiveness of contrast echocardiography in the detection of LV apical aneurysms in patients with HCM in comparison with the gold standard, CMR. Methods One hundred twelve patients with HCM identified from an institutional clinical database, who underwent echocardiographic and CMR examinations within 12 months and had LV apical aneurysms identified on either or both imaging modalities, were retrospectively analyzed. Discordant cases were reviewed by an expert panel, and a consensus was reached regarding the presence or absence of an apical aneurysm. The reason for any discrepancy was recorded. Results The mean age of the patients was 59 ± 13 years, and 73% were men. Sixty-four (57%) underwent contrast echocardiography. The median interval between echocardiography and CMR was 118 days (interquartile range, 61–237 days). Thirty-nine patients (35%) had discordance between echocardiographic and CMR findings, of whom 20 had aneurysms reported on echocardiography but not CMR and 19 vice versa. Upon reanalysis by the expert panel, aneurysms were initially missed on CMR in 16 patients (80%), largely because of interpretation error secondary to small aneurysms, with a mean aneurysm size of 0.82 ± 0.38 cm in these cases. Before secondary review by the expert panel, contrast echocardiography had sensitivity of 97% compared with 85% for CMR (P = .0198) and 64% for noncontrast echocardiography (P = .0001). After secondary review, contrast echocardiography had sensitivity of 98% compared with 67% for noncontrast echocardiography (P = .0001) and 97% for CMR (P = 1.00). Conclusions Contrast echocardiography has high sensitivity for detecting LV apical aneurysms and should be used routinely in the evaluation and risk stratification of patients with HCM.

Hypertrophic cardiomyopathy (HCM) is a relatively common often inherited global heart disease, with complex phenotypic and genetic expression and natural history, affecting both genders and many races and cultures. Prevalence is 1:200-1:500, largely based on the disease phenotype with imaging, inferring that 750,000 Americans may be affected by HCM. However, cross-sectional data show that only a fraction are clinically diagnosed, suggesting under-recognition, with most clinicians exposed to small segments of the broad disease spectrum. Highly effective HCM management strategies have emerged, altering clinical course and substantially lowering mortality and morbidity rates. These advances underscore the importance of reliable HCM diagnosis with echocardiography and cardiac magnetic resonance. Family screening with noninvasive imaging will identify relatives with the HCM phenotype, while genetic analysis recognizes preclinical sarcomere gene carriers without left ventricular hypertrophy, but with the potential to transmit disease. Comprehensive initial patient evaluations are important for reliable diagnosis, accurate portrayal of HCM and family history, risk stratification, and distinguishing obstructive versus nonobstructive forms.

Background We report characteristics and outcomes of elderly patients with hypertrophic cardiomyopathy (HCM) with basal septal hypertrophy and dynamic left ventricular outflow tract obstruction. Methods and Results We studied 1110 consecutive elderly patients with HCM (excluding moderate or greater aortic stenosis or subaortic membrane, age 80±5 years [range, 75–92 years], 66% women), evaluated at our center between June 2002 and December 2018. Clinical and echocardiographic data, including maximal left ventricular outflow tract gradient, were recorded. The primary outcome was death and appropriate internal defibrillator discharge. Hypertension was observed in 72%, with a Society of Thoracic Surgeons (STS) score (8.6±6); while 80% had no HCM‐related sudden cardiac death risk factors. Left ventricular mass index, basal septal thickness, and maximal left ventricular outflow tract gradient were 127±43 g/m2, 1.7±0.4 cm, and 49±31 mm Hg, respectively. A total of 597 (54%) had a left ventricular outflow tract gradient >30 mm Hg, of which 195 (33%) underwent septal reduction therapy (SRT; 79% myectomy and 21% alcohol ablation). At 5.1±4 years, 556 (50%) had composite events (273 [53%] in nonobstructive, 220 [55%] in obstructive without SRT, and 63 [32%] in obstructive subgroup with SRT). One‐ and 5‐year survival, respectively were 93% and 63% in nonobstructive, 90% and 63% in obstructive subgroup without SRT, and 94% and 84% in the obstructive subgroup with SRT. Following SRT, there were 5 (2.5%) in‐hospital deaths (versus an expected Society of Thoracic Surgeons mortality of 9.2%). Conclusions Elderly patients with HCM have a high prevalence of traditional cardiovascular rather than HCM risk factors. Longer‐term outcomes of the obstructive SRT subgroup were similar to a normal age‐sex matched US population.

Aims We explored the early effects of bariatric surgery on subclinical myocardial function in individuals with severe obesity and preserved left ventricular (LV) ejection fraction. Methods Thirty-eight patients with severe obesity [body mass index (BMI) ≥35 kg/m2] and preserved LV ejection fraction (≥50%) who underwent bariatric surgery (biliopancreatic diversion with duodenal switch [BPD-DS]) (Surgery group), 19 patients with severe obesity managed with usual care (Medical group), and 18 age and sex-matched non-obese controls (non-obese group) were included. Left ventricular global longitudinal strain (LV GLS) was evaluated with echocardiography speckle tracking imaging. Abnormal myocardial function was defined as LV GLS Results Age of the participants was 42 ± 11 years with a BMI of 48 ± 8 kg/m2 (mean ± standard deviation); 82% were female. The percentage of total weight loss at 6 months after bariatric surgery was 26.3 ± 5.2%. Proportions of hypertension (61 vs. 30%, P = 0.0005), dyslipidemia (42 vs. 5%, P = 0.0001) and type 2 diabetes (40 vs. 13%, P = 0.002) were reduced postoperatively. Before surgery, patients with obesity displayed abnormal subclinical myocardial function vs. non-obese controls (LV GLS, 16.3 ± 2.5 vs. 19.6 ± 1.7%, P 0.05). In a multivariate model, losing visceral fat mass was independently associated with improved subclinical myocardial function. Conclusions Bariatric surgery was associated with significant improvement in the metabolic profile and in subclinical myocardial function. Early improvement in subclinical myocardial function following bariatric surgery was related to a greater mobilization of visceral fat depot, linked to global fat dysfunction and cardiometabolic morbidity.

Introduction: Accurate and reproducible scar quantification of late gadolinium enhancement (LGE) images from cardiac magnetic resonance imaging (CMR) is important in risk stratifying hypertrophic cardiomyopathy (HCM) patients. Previous machine learning algorithms for CMR LGE quantification deployed three-dimensional convolutional neural network (CNN) architecture, which required image cropping and custom graphic processing units (GPUs) to function, thus limiting their general applicability. We aim to develop a deep two-dimensional (2D) CNN model that contours the left ventricle (LV) endo- and epicardial borders and quantifies LGE. Hypothesis: We hypothesize that a deep 2D CNN model, which uses commercially available GPUs, could be used to efficiently and accurately contour LV endo- and epicardial borders and quantify CMR LGE in HCM patients. Methods: We retrospectively studied 296 HCM patients (2423 images) from the University Health Network (Toronto, Canada) and Tufts Medical Center (Boston, USA). LGE images were manually segmented by an expert reader. Scar was defined as 5 standard deviations higher than the mean of the annotated normal region pixels. A 2D U-net CNN variant was used to train a model on 80% of the datasets. Testing was performed on the remaining 20%. We applied a 5-folds cross validation algorithm for training to improve model robustness. Model performance was assessed using the Dice Similarity Coefficient (DSC). Results: We were able to develop a deep learning model that could successfully perform both LV segmentation and scar quantification using a generally available GPU card. Our algorithm did not require image cropping and processed one image every 60 milliseconds. DSC scores averaged across the 5-folds was excellent at 0.89+0.22 for the endocardium and 0.81+0.17 for the epicardium, and good at 0.57+0.31 for scar. Conclusions: Using novel 2D CNN methods, we have successfully developed an automatic algorithm that rapidly provides LV endo- and epicardial contours and scar quantification on LGE CMR images that is superior to previously published studies. Unlike previous algorithms, our program does not require the use of custom CPUs or image cropping, potentially allowing it to be integrated into routine clinical practice.

Introduction: Strategies for reliable selection of high-risk hypertrophic cardiomyopathy (HCM) patients for prevention of sudden cardiac death (SCD) with implantable cardioverter-defibrillators (ICDs) continue to be debated. Objective: Assess the sensitivity of sudden death risk strategies in predicting SCD events (appropriate ICD shocks, sudden death or out of hospital cardiac arrest) among a large multicenter cohort of high-risk HCM patients. Methods: Observational longitudinal study from 6-HCM centers in North America and Europe to determine outcomes in consecutive HCM patients considered high risk for sudden death based on an enhanced ACC/AHA (U.S./Canada) guidelines-based risk factor algorithm with primary prevention ICD placement. ESC risk score was retrospectively calculated in this cohort and compared to ACC/AHA risk factor method for predicting SCD events. Results: Of 1185 patients with primary prevention ICDs implanted based on ≥ 1 major risk marker, 162 (14%) experienced device therapy terminating VT/VF episodes at 49 ± 18 years of age and 4.6 ± 4.2 years after device implant. Within the 6 HCM centers, only 28 other patients not implanted with ICD died suddenly or had resuscitated cardiac arrests, including 19 (68%) with risk-markers who declined ICDs. Of these 190 high risk patients with SCD or SCD events, 67 (35%) had ESC risk-scores scores ≥6%/5-years, considered sufficient to recommend a prophylactic ICD, while 83 (44%) had low risk scores ( Conclusion: In this large multicenter study of high-risk HCM patients, an enhanced ACC/AHA risk factor strategy was superior to the ESC risk score in identifying patients at greatest risk for SCD events.

This study examined fibrosis progression in hypertrophic cardiomyopathy (HCM) patients, as well as its relationship to patient characteristics, clinical outcomes, and its effect on clinical decision making.Myocardial fibrosis, as quantified by late gadolinium enhancement (LGE) in cardiac magnetic resonance (CMR), provides valuable prognostic information in patients with HCM.A total of 157 patients with HCM were enrolled in this study, with 2 sequential CMR scans separated by an interval of 4.7 ± 1.9 years.At the first CMR session (CMR-1), 70% of patients had LGE compared with 85% at CMR-2 (p = 0.001). The extent of LGE extent increased between the 2 CMR procedures, from 4.0 ± 5.6% to 6.3 ± 7.4% (p 0.0001), with an average LGE progression rate of 0.5 ± 1.0%/year. LGE mass progression was correlated with higher LGE mass and extent on CMR-1 (p = 0.0017 and p = 0.007, respectively), greater indexed left ventricular (LV) mass (p 0.0001), greater LV maximal wall thickness (p 0.0001), apical aneurysm at CMR-1 (p 0.0001), and lower LV ejection fraction (EF) (p = 0.029). Patients who were more likely to have a higher rate of LGE progression presented with more severe disease at baseline, characterized by LGE extent8% of LV mass, indexed LV mass100 g/mMyocardial fibrosis in patients with HCM is a slowly progressive process. Progression of LGE is significantly correlated with a number of clinical outcomes such as progression to EF ≤50% and heart failure admission. Judicious use of serial CMR with LGE can provide valuable information to help patient management.

Background Genetic testing is helpful for diagnosis of hypertrophic cardiomyopathy (HCM) mimics. Little data are available regarding the yield of such testing and its clinical impact. Methods The HCM genetic database at our center was used for identification of patients who underwent HCM-directed genetic testing including at least 1 gene associated with an HCM mimic ( GLA , TTR , PRKAG2 , LAMP2 , PTPN11 , RAF1 , and DES ). Charts were retrospectively reviewed and genetic and clinical data extracted. Results There were 1731 unrelated HCM patients who underwent genetic testing for at least 1 gene related to an HCM mimic. In 1.45% of cases, a pathogenic or likely pathogenic variant in one of these genes was identified. This included a yield of 1% for Fabry disease, 0.3% for familial amyloidosis, 0.15% for PRKAG2 -related cardiomyopathy, and 1 patient with Noonan syndrome. In the majority of patients, diagnosis of the HCM mimic based on clinical findings alone would have been challenging. Accurate diagnosis of an HCM mimic led to change in management (eg, enzyme replacement therapy) or family screening in all cases. Conclusions Genetic testing is helpful in the diagnosis of HCM mimics in patients with no or few extracardiac manifestations. Adding these genes to all HCM genetic panels should be considered.

Background There is little understanding of whether a physician's tendency to order an inappropriate cardiac service is associated with the use of other cardiac services and clinical outcomes in their patients with heart failure (HF). Methods and Results We conducted a secondary analysis of 35 Ontario‐based cardiologists who participated in the control arm of the Echo WISELY (Will Inappropriate Scenarios for Echocardiography Lessen Significantly) trial. Transthoracic echocardiograms, ordered during the trial, were classified as rarely appropriate ( rA ), appropriate, or maybe appropriate on the basis of the 2011 appropriate use criteria. Cardiologists were grouped into tertiles of rA transthoracic echocardiogram ordering frequency: low ordering (bottom tertile), n=11; moderate ordering, n=12; or high ordering (top tertile), n=12. The main outcomes were measures of cardiac service use, including cardiology‐related physician visits, tests, and medications. Among 1677 patients with heart failure and an outpatient visit to 1 of 35 cardiologists, we found no significant association between rA transthoracic echocardiogram ordering frequency (by tertile) and cardiac testing use, although patients of cardiologists in the high ordering group had fewer physician visits, on average, than patients seen by low ordering cardiologists. In addition, patients of cardiologists in the highest rA ordering tertile had significantly lower odds of receiving potentially effective interventions, such as β blockers (odds ratio, 0.62; 95% CI , 0.43–0.89), than the low ordering group. Conclusions Although patients of cardiologists who frequently order rA transthoracic echocardiograms do not appear more (or less) likely to have subsequent cardiac tests, these patients have fewer follow‐up visits and lower odds of receiving evidence‐based medications. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02038101.

Background: The relationship between ordering frequency of rarely appropriate transthoracic echocardiograms on healthcare utilization and patient outcomes in coronary artery disease (CAD) is not known. Our objective was to investigate practice patterns of cardiologists who order a high frequency of low-value transthoracic echocardiograms in patients with CAD and whether practice behavior influences patient outcomes. Methods and Results: A retrospective cohort of outpatient CAD patients was accrued by identifying patients with at least 1 visit to 1 of 35 Ontario-based cardiologists in the EchoWISELY randomized clinical trial (Will Inappropriate Scenarios for Echocardiography Lessen Significantly) control group. The main outcomes of interest were patient-level receipt of diagnostic tests, physician visits, medication prescriptions, and clinical outcomes at 1 year. Our cohort consisted of 3966 patients with CAD (mean [SD] age, 67.8 [12.0] years; 72% men), with an outpatient visit to 1 of 35 eligible cardiologists, stratified into 3 ordering tertiles. Patients of cardiologists in the top ordering tertile of rarely appropriate transthoracic echocardiograms had significantly lower odds of receiving the following services at 1 year compared with patients in the low ordering group: cholesterol assessment (odds ratio [OR], 0.77 [95% CI, 0.65–0.91]); hemoglobin A1c assessment (OR, 0.79 [95% CI, 0.66–0.94]); β-blocker prescription (OR, 0.70 [95% CI, 0.55–0.90]); and aldosterone receptor antagonist prescription (OR, 0.46 [95% CI, 0.22–0.98]). Patients of high ordering cardiologists had greater odds of all-cause mortality at 1 year (OR, 1.54 [95% CI, 1.04–2.28]), although all other outcomes were similar. Conclusions: Patients with CAD seen by cardiologist who ordered a high rate of rarely appropriate transthoracic echocardiograms were less likely to receive potentially high-value screening tests and evidence-based medications than low ordering cardiologists. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02038101.

The appropriate use criteria (AUC) is intended to facilitate rationale of cardiovascular imaging and aid quality improvement efforts [(1,2)][1]. Despite emerging research regarding the role of AUC for transthoracic echocardiography (TTE) in clinical practice, little data exist regarding the

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

Background Appropriate use criteria (AUC) have defined transthoracic echocardiogram (TTE) indications for which there is a clear lack of benefit as rarely appropriate (rA). Objectives This study sought to investigate the impact of an AUC-based educational intervention on outpatient TTE ordering by cardiologists and primary care providers. Methods The authors conducted a prospective, investigator-blinded, multicenter, randomized controlled trial of an AUC-based educational intervention aimed at reducing rA outpatient TTEs. The study was conducted at 8 hospitals across 2 countries. The authors randomized cardiologists and primary care providers to receive either intervention or control (no intervention). The primary outcome measure was the proportion of rA TTEs. Results One hundred and ninety-six physicians were randomized, and 179 were included in the analysis. From December 2014 to April 2016, the authors assessed 14,697 TTEs for appropriateness, of which 99% were classifiable using the 2011 AUC. The mean proportion of rA TTEs was significantly lower in the intervention versus the control group (8.8% vs. 10.1%; odds ratio [OR]: 0.75; 95% confidence interval [CI]: 0.57 to 0.99; p = 0.039). In physicians who ordered, on average, at least 1 TTE per month, there was a significantly lower proportion of rA TTEs in the intervention versus the control group (8.6% vs. 11.1%; OR: 0.76; 95% CI: 0.57 to 0.99; p = 0.047). There was no difference in the TTE ordering volume between the intervention and control groups (mean 77.7 ± 89.3 vs. 85.4 ± 111.4; p = 0.83). Conclusions An educational intervention reduced the number of rA TTEs ordered by attending physicians in a variety of ambulatory care environments. This may prove to be an effective strategy to improve the use of imaging. (A Multi-Centered Feedback and Education Intervention Designed to Reduce Inappropriate Transthoracic Echocardiograms [Echo WISELY]; NCT02038101)

Background Left atrial (LA) size is a marker of prognosis in severe aortic stenosis (AS). The aims of this retrospective study were to assess the impact of transcatheter aortic valve implantation (TAVI) on the recovery of LA phasic function and to assess the relationship between LA function and new-onset atrial fibrillation (NAF) after TAVI. Methods In this retrospective cohort study, LA function was measured using biplane volumes and 2-dimensional (2D) speckle tracking echocardiography (STE) in 52 patients (median age, 81 years) with severe AS before TAVI and at midterm follow-up. Twenty healthy individuals ≥ 75 years were used as controls. Results Before TAVI, the 3 phasic volumetric emptying fractions and all STE-derived parameters of LA function were significantly reduced. At 5 ± 3 months after TAVI, there was an improvement in LA reservoir and contractile function. However, LA phasic volumes and emptying fractions showed minimal changes. Fourteen patients had NAF in the early postprocedural period after TAVI. These patients experienced longer hospitalization (11 days vs 6 days; P = 0.002). By bivariable logistic regression analysis, the use of a transapical approach and the LA early diastolic strain rate (SR) before TAVI were significantly associated with NAF immediately after TAVI. Conclusions Severe AS is associated with LA dysfunction. Intrinsic LA compliance and LA contractile properties by STE improved at midterm follow-up after TAVI. Preprocedural LA early diastolic SR may predict the development of NAF after TAVI pending confirmation by larger prospective evaluations.

Hypertrophic cardiomyopathy is a common genetic disorder with a prevalence of 1:500 in the general population. Amongst a varied spectrum of clinical presentations, the most feared complication of this cardiac disorder is sudden cardiac death. Although only a minority of patients with hypertrophic cardiomyopathy who suffer sudden cardiac death or resuscitated cardiac arrest do so during exercise, strenuous physical activity is regarded as an important trigger for these tragic outcomes. Furthermore, during exercise, patients with hypertrophic cardiomyopathy may develop augmentation of left ventricular outflow tract obstruction, myocardial ischemia, diastolic dysfunction and/or inappropriate vasodilation in non-exercising vascular beds. This in turn may lead to exertional dyspnea, chest pain or syncope. Accordingly, patients with hypertrophic cardiomyopathy are disqualified from competitive sports and in many cases are recommended to avoid strenuous physical activity of any kind. Nevertheless, avoidance of physical activity comes with a price. The positive effects of regular exercise have been extensively reported to convey a wide range of benefits including reduced cardiovascular events, weight reduction and improved wellbeing. Therefore, finding the right exercise level that will offer some of the benefits of physical activity without increasing the risk of sudden cardiac death is of utmost importance. In this review, we discuss the current evidence for and against exercise in this patient population and review national guideline recommendations. We also propose alternative fitness strategies including a novel fitness program implemented by our hypertrophic cardiomyopathy center which may be of particular usefulness for hypertrophic cardiomyopathy patients.

Importance Genetic testing is a valuable tool for managing inherited cardiovascular disease in patients and families, including hypertrophic, dilated, and arrhythmogenic cardiomyopathies and inherited arrhythmias. By identifying the molecular etiology of disease, genetic testing can improve diagnostic accuracy and refine family management. However, unique features associated with genetic testing affect the interpretation and application of results and differentiate it from traditional laboratory-based diagnostics. Clinicians and patients must have accurate and realistic expectations about the yield of genetic testing and its role in management. Familiarity with the rationale, implications, benefits, and limitations of genetic testing is essential to achieve the best possible outcomes. Observations Successfully incorporating genetic testing into clinical practice requires (1) recognizing when inherited cardiovascular disease may be present, (2) identifying appropriate individuals in the family for testing, (3) selecting the appropriate genetic test, (4) understanding the complexities of result interpretation, and (5) effectively communicating the results and implications to the patient and family. Obtaining a detailed family history is critical to identify families who will benefit from genetic testing, determine the best strategy, and interpret results. Instead of focusing on an individual patient, genetic testing requires consideration of the family as a unit. Consolidation of care in centers with a high level of expertise is recommended. Clinicians without expertise in genetic testing will benefit from establishing referral or consultative networks with experienced clinicans in specialized multidisciplinary clinics. Conclusions and Relevance Genetic testing provides a foundation for transitioning to more precise and individualized management. By distinguishing phenotypic subgroups, identifying disease mechanisms, and focusing family care, gene-based diagnosis can improve management. Successful integration of genetic testing into clinical practice requires understanding of the complexities of testing and effective communication of the implications to patients and families.

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). 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.

Hypertrophic cardiomyopathy (HCM) is estimated to affect 1:500 individuals. It may develop at any age but typically develops during adolescence or early adulthood. Mortality rates in HCM are lower than initially suspected, especially in treated patients, but remain higher than those in the general population. Although the majority of HCM patients develop few or no symptoms, a significant minority will develop advanced heart failure, atrial fibrillation, or stroke. The presence of left ventricular outflow tract obstruction, development of systolic dysfunction (i.e., end-stage HCM), and possibly apical aneurysms has been associated with worse outcomes.