Vigorous Exercise in Patients With Hypertrophic Cardiomyopathy.

Importance: Whether vigorous intensity exercise is associated with an increase in risk of ventricular arrhythmias in individuals with hypertrophic cardiomyopathy (HCM) is unknown. Objective: To determine whether engagement in vigorous exercise is associated with increased risk for ventricular arrhythmias and/or mortality in individuals with HCM. The a priori hypothesis was that participants engaging in vigorous activity were not more likely to have an arrhythmic event or die than those who reported nonvigorous activity. Design, Setting, and Participants: This was an investigator-initiated, prospective cohort study. Participants were enrolled from May 18, 2015, to April 25, 2019, with completion in February 28, 2022. Participants were categorized according to self-reported levels of physical activity: sedentary, moderate, or vigorous-intensity exercise. This was a multicenter, observational registry with recruitment at 42 high-volume HCM centers in the US and internationally; patients could also self-enroll through the central site. Individuals aged 8 to 60 years diagnosed with HCM or genotype positive without left ventricular hypertrophy (phenotype negative) without conditions precluding exercise were enrolled. Exposures: Amount and intensity of physical activity. Main Outcomes and Measures: The primary prespecified composite end point included death, resuscitated sudden cardiac arrest, arrhythmic syncope, and appropriate shock from an implantable cardioverter defibrillator. All outcome events were adjudicated by an events committee blinded to the patient's exercise category. Results: Among the 1660 total participants (mean [SD] age, 39 [15] years; 996 male [60%]), 252 (15%) were classified as sedentary, and 709 (43%) participated in moderate exercise. Among the 699 individuals (42%) who participated in vigorous-intensity exercise, 259 (37%) participated competitively. A total of 77 individuals (4.6%) reached the composite end point. These individuals included 44 (4.6%) of those classified as nonvigorous and 33 (4.7%) of those classified as vigorous, with corresponding rates of 15.3 and 15.9 per 1000 person-years, respectively. In multivariate Cox regression analysis of the primary composite end point, individuals engaging in vigorous exercise did not experience a higher rate of events compared with the nonvigorous group with an adjusted hazard ratio of 1.01. The upper 95% 1-sided confidence level was 1.48, which was below the prespecified boundary of 1.5 for noninferiority. Conclusions and Relevance: Results of this cohort study suggest that among individuals with HCM or those who are genotype positive/phenotype negative and are treated in experienced centers, those exercising vigorously did not experience a higher rate of death or life-threatening arrhythmias than those exercising moderately or those who were sedentary. These data may inform discussion between the patient and their expert clinician around exercise participation.

Prevalence and diagnostic significance of de-novo 12-lead ECG changes after COVID-19 infection in elite soccer players.

BACKGROUND AND AIM: The efficacy of pre-COVID-19 and post-COVID-19 infection 12-lead ECGs for identifying athletes with myopericarditis has never been reported. We aimed to assess the prevalence and significance of de-novo ECG changes following COVID-19 infection. METHODS: In this multicentre observational study, between March 2020 and May 2022, we evaluated consecutive athletes with COVID-19 infection. Athletes exhibiting de-novo ECG changes underwent cardiovascular magnetic resonance (CMR) scans. One club mandated CMR scans for all players (n=30) following COVID-19 infection, despite the absence of cardiac symptoms or de-novo ECG changes. RESULTS: 511 soccer players (median age 21 years, IQR 18-26 years) were included. 17 (3%) athletes demonstrated de-novo ECG changes, which included reduction in T-wave amplitude in the inferior and lateral leads (n=5), inferior leads (n=4) and lateral leads (n=4); inferior T-wave inversion (n=7); and ST-segment depression (n=2). 15 (88%) athletes with de-novo ECG changes revealed evidence of inflammatory cardiac sequelae. All 30 athletes who underwent a mandatory CMR scan had normal findings. Athletes revealing de-novo ECG changes had a higher prevalence of cardiac symptoms (71% vs 12%, p<0.0001) and longer median symptom duration (5 days, IQR 3-10) compared with athletes without de-novo ECG changes (2 days, IQR 1-3, p<0.001). Among athletes without cardiac symptoms, the additional yield of de-novo ECG changes to detect cardiac inflammation was 20%. CONCLUSIONS: 3% of athletes demonstrated de-novo ECG changes post COVID-19 infection, of which 88% were diagnosed with cardiac inflammation. Most affected athletes exhibited cardiac symptoms; however, de-novo ECG changes contributed to a diagnosis of cardiac inflammation in 20% of athletes without cardiac symptoms.

Cardiopulmonary Exercise Test in Patients with Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with chronic diseases frequently adapt their lifestyles to their functional limitations. Functional capacity in Hypertrophic Cardiomyopathy (HCM) can be assessed by stress testing. We aim to review and analyze the available data from the literature on the value of Cardiopulmonary Exercise Test (CPET) in HCM. Objective measurements from CPET are used for evaluation of patient response to traditional and new developing therapeutic measurements. METHODS: A systematic review of the literature was conducted in PubMed, Web of Science and Cochrane in Mar-20. The original search yielded 2628 results. One hundred and two full texts were read after the first screening, of which, 69 were included for qualitative synthesis. Relevant variables to be included in the review were set and 17 were selected, including comorbidities, body mass index (BMI), cardiac-related symptoms, echocardiographic variables, medications and outcomes. RESULTS: Study sample consisted of 69 research articles, including 11,672 patients (48 ± 14 years old, 65.9%/34.1% men/women). Treadmill was the most common instrument employed (n = 37 studies), followed by upright cycle-ergometer (n = 16 studies). Mean maximal oxygen consumption (VO2max) was 22.3 ± 3.8 mL·kg-1·min-1. The highest average values were observed in supine and upright cycle-ergometer (25.3 ± 6.5 and 24.8 ± 9.1 mL·kg-1·min-1; respectively). Oxygen consumption in the anaerobic threshold (ATVO2) was reported in 18 publications. Left ventricular outflow tract gradient (LVOT) > 30 mmHg was present at baseline in 31.4% of cases. It increased to 49% during exercise. Proportion of abnormal blood pressure response (ABPRE) was higher in severe (>20 mm) vs. mild hypertrophy groups (17.9% vs. 13.6%, p < 0.001). Mean VO2max was not significantly different between severe vs. milder hypertrophy, or for obstructive vs. non-obstructive groups. Occurrence of arrhythmias during functional assessment was higher among younger adults (5.42% vs. 1.69% in older adults, p < 0.001). Twenty-three publications (9145 patients) evaluated the prognostic value of exercise capacity. There were 8.5% total deaths, 6.7% cardiovascular deaths, 3.0% sudden cardiac deaths (SCD), 1.2% heart failure death, 0.6% resuscitated cardiac arrests, 1.1% transplants, 2.6% implantable cardioverter defibrillator (ICD) therapies and 1.2 strokes (mean follow-up: 3.81 ± 2.77 years). VO2max, ATVO2, METs, % of age-gender predicted VO2max, % of age-gender predicted METs, ABPRE and ventricular arrhythmias were significantly associated with major outcomes individually. Mean VO2max was reduced in patients who reached the combined cardiovascular death outcome compared to those who survived (-6.20 mL·kg-1·min-1; CI 95%: -7.95, -4.46; p < 0.01). CONCLUSIONS: CPET is a valuable tool and can safely perform for assessment of physical functional capacity in patients with HCM. VO2max is the most common performance measurement evaluated in functional studies, showing higher values in those based on cycle-ergometer compared to treadmill. Subgroup analysis shows that exercise intolerance seems to be more related to age, medication and comorbidities than HCM phenotype itself. Lower VO2max is consistently seen in HCM patients at major cardiovascular risk.

Differentiation between athlete's heart and dilated cardiomyopathy in athletic individuals.

OBJECTIVE: Distinguishing early dilated cardiomyopathy (DCM) from physiological left ventricular (LV) dilatation with LV ejection fraction <55% in athletes (grey zone) is challenging. We evaluated the role of a cascade of investigations to differentiate these two entities. METHODS: Thirty-five asymptomatic active males with DCM, 25 male athletes in the 'grey zone' and 24 male athletes with normal LV ejection fraction underwent N-terminal pro-brain natriuretic peptide (NT-proBNP) measurement, ECG and exercise echocardiography. Grey-zone athletes and patients with DCM underwent cardiovascular magnetic resonance (CMR) and Holter monitoring. RESULTS: Larger LV cavity dimensions and lower LV ejection fraction were the only differences between grey-zone and control athletes. None of the grey-zone athletes had abnormal NT-proBNP, increased ectopic burden/complex arrhythmias or pathological late gadolinium enhancement on CMR. These features were also absent in 71%, 71% and 50% of patients with DCM, respectively. 95% of grey-zone athletes and 60% of patients with DCM had normal ECG. During exercise echocardiography, 96% grey-zone athletes increased LV ejection fraction by >11% from baseline to peak exercise compared with 23% of patients with DCM (p<0.0001). Peak LV ejection fraction was >63% in 92% grey-zone athletes compared with 17% patients with DCM (p<0.0001). Failure to increase LV ejection fraction >11% from baseline to peak exercise or achieve a peak LV ejection fraction >63% had sensitivity of 77% and 83%, respectively, and specificity of 96% and 92%, respectively, for predicting DCM. CONCLUSION: Comprehensive assessment using a cascade of routine investigations revealed that exercise stress echocardiography has the greatest discriminatory value in differentiating between grey-zone athletes and asymptomatic patients with DCM. Our findings require validation in larger studies.

The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy.

Sudden cardiac death (SCD) is often associated with structural abnormalities of the heart during autopsy. This study sought to compare the diagnostic yield of postmortem genetic testing in (1) cases with structural findings of uncertain significance at autopsy to (2) cases with autopsy findings diagnostic of cardiomyopathy. We evaluated 57 SCD cases with structural findings at cardiac autopsy. Next-generation sequencing using a panel of 77 primary electrical disorder and cardiomyopathy genes was performed. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. In 29 cases (51%) autopsy findings of uncertain significance were identified whereas in 28 cases (49%) a diagnosis of cardiomyopathy was established. We identified a pathogenic or likely pathogenic variant in 10 cases (18%); in 1 (3%) case with non-specific autopsy findings compared with 9 (32%) cases with autopsy findings diagnostic of cardiomyopathy (p = 0.0054). The yield of genetic testing in SCD cases with autopsy findings consistent with cardiomyopathy is comparable with the yield in cardiomyopathy patients that are alive. Genetic testing in cases with findings of uncertain significance offers lower clinical utility than in cardiomyopathy, with lower yields than detected previously. This highlights the need for stringent evaluation of variant pathogenicity.

The Diagnostic Yield of Brugada Syndrome After Sudden Death With Normal Autopsy.

BACKGROUND: Familial evaluation after a sudden death with negative autopsy (sudden arrhythmic death syndrome; SADS) may identify relatives at risk of fatal arrhythmias. OBJECTIVES: This study aimed to assess the impact of systematic ajmaline provocation testing using high right precordial leads (RPLs) on the diagnostic yield of Brugada syndrome (BrS) in a large cohort of SADS families. METHODS: Three hundred three SADS families (911 relatives) underwent evaluation with resting electrocardiogram using conventional and high RPLs, echocardiography, exercise, and 24-h electrocardiogram monitor. An ajmaline test with conventional and high RPLs was undertaken in 670 (74%) relatives without a familial diagnosis after initial evaluation. Further investigations were guided by clinical suspicion. RESULTS: An inherited cardiac disease was diagnosed in 128 (42%) families and 201 (22%) relatives. BrS was the most prevalent diagnosis (n = 85, 28% of families; n = 140, 15% of relatives). Ajmaline testing was required to unmask the BrS in 97% of diagnosed individuals. The use of high RPLs showed a 16% incremental diagnostic yield of ajmaline testing by diagnosing BrS in an additional 49 families. There were no differences of the characteristics between individuals and families with a diagnostic pattern in the conventional and the high RPLs. On follow-up, a spontaneous type 1 Brugada pattern and/or clinically significant arrhythmic events developed in 17% (n = 25) of the concealed BrS cohort. CONCLUSIONS: Systematic use of ajmaline testing with high RPLs increases substantially the yield of BrS in SADS families. Assessment should be performed in expert centers where patients are counseled appropriately for the potential implications of provocation testing.

Individualized surgical strategies for left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

OBJECTIVES: Surgical strategies to treat drug refractory left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy include septal myectomy (SM) and, less frequently, mitral valve (MV) repair or replacement. The primary aim of this study was to report the surgical technique and management outcomes in a consecutive group of patients with variable phenotypes of hypertrophic cardiomyopathy in a broad national specialist practice. METHODS: A total of 203 consecutive patients, 132 men (mean age 48.6 ± 14.6 years) underwent surgery for the management of LVOTO. Surgical approaches included SM (n = 159), SM with MV repair (n = 25), SM with MV replacement (n = 9) and MV replacement alone (n = 10). Specific surgical approaches were performed based on the underlying mechanism of obstruction. Eleven (5.4%) patients had previous alcohol septal ablation for the management of LVOTO. Concomitant non-mitral cardiac procedures were carried out in 22 (10.8%) patients. RESULTS: Operative survival rate was 99.0% with 2 deaths within 30 days. The mean bypass time was 92.9 ± 47.8 min, with a mean length of hospital stay of 10.5 ± 7.8 days. Surgical complications included 3 ventricular septal defects requiring repair (1.5%), 1 Gerbode defect surgically repaired, 2 aortic valve repairs (1.0%), 2 transient ischaemic attacks (1.0%) and 4 strokes (2.0%). Thirty-nine (19.2%) patients had perioperative new-onset atrial fibrillation and 8 (3.9%) patients had unexpected atrioventricular block requiring a permanent pacemaker. Mean resting left ventricular outflow tract gradient improved from 70.6 ± 40.3 mmHg preoperatively to 11.0 ± 10.5 mmHg at 1 year postoperatively (P < 0.001). Mean New York Heart Association class improved from 2.6 ± 0.5 preoperatively to 1.6 ± 0.6 at 1 year after the procedure. CONCLUSIONS: In variable phenotypes of LVOTO in hypertrophic cardiomyopathy, an individualized surgical approach provided effective reductions in left ventricular outflow tract gradients and good symptomatic relief with acceptable mortality and morbidity.

Long-term outcomes for different surgical strategies to treat left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

AIMS: Surgical intervention is used to treat dynamic left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy. This study assesses the effect of different surgical strategies on long-term mortality and morbidity. METHODS AND RESULTS: In total, 347 patients underwent surgical intervention for LVOTO (1988-2015). Group A (n = 272) underwent septal myectomy; Group B (n = 33), septal myectomy and mitral valve (MV) repair; Group C (n = 22), myectomy and MV replacement; and Group D (n = 20), MV replacement alone. Median follow-up was 5.2 years (interquartile range 1.9-7.9). The mean resting LVOT gradient improved post-operatively from 71.9 ± 39.6 mmHg to 13.4 ± 18.5 mmHg (P < 0.05). Overall, 72.4% of patients improved by >1 New York Heart Association (NYHA) class; 58.9% of patients undergoing MV replacement alone did not improve their NYHA class. There were 5 perioperative deaths and 20 late deaths (>30 days). Survival rates at 1, 5 and 10 years respectively were 98.4, 96.9, 91.9% in Group A; 97.0, 92.4, 61.6% in Group B; 100.0, 100.0, 55.6% in Group C; and 94.7, 85.3, 85.3% in Group D (log-rank, P < 0.05). Long-term (>30 days) complications included atrial fibrillation (29.6%), transient ischaemic attack/stroke (2.4%) and heart failure hospitalisation (3.2%). There were 16 repeat surgical interventions at 3.0 years. CONCLUSION: Septal myectomy is a safe procedure resulting in symptomatic improvement in the majority of patients. The annual incidence of non-fatal disease-related complications after surgical treatment of LVOTO is relatively high. Patients who underwent MV replacements had poorer outcomes with less symptomatic benefit in spite of a similar reduction in LVOT gradients.

Early and medium-term outcomes of Alfieri mitral valve repair in the management of systolic anterior motion during septal myectomy.

BACKGROUND: This report studies the early and medium-term clinical and echocardiographic outcomes of the Alfieri edge-to-edge mitral valve repair, as adjunctive therapy, to prevent and treat systolic anterior motion (SAM) at the time of septal myectomy (SM) for left ventricular outflow tract obstruction in hypertrophic cardiomyopathy. METHODS: From 2009-2015, 11 consecutive patients had a trans-atrial Alfieri repair, to prevent (n = 7) or treat (n = 4) SAM at the time of SM. RESULTS: No patients were lost to follow-up. There were no perioperative or late deaths. Pre-bypass, the mean left ventricular outflow tract gradient, measured directly by simultaneous needle insertion, was 40.7 ± 19.9 mmHg at rest and 115.8 ± 30.4 mmHg on provocation with Isoproterenol, which reduced after SM and Alfieri repair and discontinuation of bypass, to a mean gradient of 8.3 ± 9.8 mmHg at rest and 25.8 ± 9.2 mmHg on provocation. One patient who required mitral valve replacement on day 4, was hospitalized at 2.7 years with heart failure requiring diuresis and remains well at 6 years. One patient developed postoperative atrial fibrillation. There were no other early or late complications. At a median follow-up of 6.6 years (international quartile range 1.2-7.4), clinical and echocardiographic data demonstrated maintained improvement in mean New York Heart Association class from 2.6 ± 0.9 preoperatively to 1.7 ± 0.4 and reduction in mean grade of mitral regurgitation from 2.7 ± 0.8 preoperatively to 0.7 ± 0.6. CONCLUSIONS: The Alfieri repair, as adjunctive therapy, for the prevention or treatment of SAM at the time of SM demonstrates satisfactory early and medium-term clinical and echocardiographic outcomes supporting the ongoing utility of this approach.

Inter-Rater Reliability and Downstream Financial Implications of Electrocardiography Screening in Young Athletes.

BACKGROUND: Preparticipation screening for cardiovascular disease in young athletes with electrocardiography is endorsed by the European Society of Cardiology and several major sporting organizations. One of the concerns of the ECG as a screening test in young athletes relates to the potential for variation in interpretation. We investigated the degree of variation in ECG interpretation in athletes and its financial impact among cardiologists of differing experience. METHODS AND RESULTS: Eight cardiologists (4 with experience in screening athletes) each reported 400 ECGs of consecutively screened young athletes according to the 2010 European Society of Cardiology recommendations, Seattle criteria, and refined criteria. Cohen κ coefficient was used to calculate interobserver reliability. Cardiologists proposed secondary investigations after ECG interpretation, the costs of which were based on the UK National Health Service tariffs. Inexperienced cardiologists were more likely to classify an ECG as abnormal compared with experienced cardiologists (odds ratio, 1.44; 95% confidence interval, 1.03-2.02). Modification of ECG interpretation criteria improved interobserver reliability for categorizing an ECG as abnormal from poor (2010 European Society of Cardiology recommendations; κ=0.15) to moderate (refined criteria; κ=0.41) among inexperienced cardiologists; however, interobserver reliability was moderate for all 3 criteria among experienced cardiologists (κ=0.40-0.53). Inexperienced cardiologists were more likely to refer athletes for further evaluation compared with experienced cardiologists (odds ratio, 4.74; 95% confidence interval, 3.50-6.43) with poorer interobserver reliability (κ=0.22 versus κ=0.47). Interobserver reliability for secondary investigations after ECG interpretation ranged from poor to fair among inexperienced cardiologists (κ=0.15-0.30) and fair to moderate among experienced cardiologists (κ=0.21-0.46). The cost of cardiovascular evaluation per athlete was $175 (95% confidence interval, $142-$228) and $101 (95% confidence interval, $83-$131) for inexperienced and experienced cardiologists, respectively. CONCLUSIONS: Interpretation of the ECG in athletes and the resultant cascade of investigations are highly physician dependent even in experienced hands with important downstream financial implications, emphasizing the need for formal training and standardized diagnostic pathways.

Disease Severity and Exercise Testing Reduce Subcutaneous Implantable Cardioverter-Defibrillator Left Sternal ECG Screening Success in Hypertrophic Cardiomyopathy.

BACKGROUND: The features of the hypertrophic cardiomyopathy (HCM) ECG make it a challenge for subcutaneous implantable cardioverter-defibrillator (S-ICD) screening. We aimed to investigate the causes of screening failure at rest and on exercise to inform optimal S-ICD ECG vector development. METHODS AND RESULTS: One hundred and thirty-one HCM patients (age, 50±16 years; 92 males and 39 females) with ≥1 HCM risk factor for sudden death underwent S-ICD ECG screening at rest and on exercise. Fifty patients (38%) were ineligible for S-ICD because of screening failure in every lead vector: 33 (66%) failed in the supine position, 12 (24%) failed in the standing position, and 5 (10%) failed on exercise. In patients who could exercise and passed screening at rest, 31 (44%) had 1 vector safety, 16 (23%) had 2 vector safety, and 24 (33%) had 3 vector safety. Increased R:T wave ratio in the S-ICD screening ECG (odds ratio, 4.0; confidence interval, 3.0-5.3; P<0.001) was associated with screening failure, while R/T ratio <3 in aVF (odds ratio, 0.3; confidence interval, 0.12-0.69; P=0.006) and increasing age (odds ratio, 0.97; confidence interval, 0.95-0.99; P=0.03) was associated with reduced screening failure. European Society of Cardiology risk score was higher in those failing screening (risk score 5.5% [interquartile range, 3.2-8.7] in failed versus 4.5% [interquartile range, 2.9-7.4] in passed; P=0.04). CONCLUSIONS: HCM patients have a significant incidence of screening failure, which is determined primarily by the increased R:T ratio on the screening ECG and lead aVF. High-risk patients have an increased screening failure rate. Optimization of sensing algorithms is required to ensure that the highest risk HCM patients can benefit from S-ICD implantation.

Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.

BACKGROUND: Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. OBJECTIVES: This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives. METHODS: We evaluated 302 expertly validated SADS cases with suitable DNA (median age: 24 years; 65% males) who underwent next-generation sequencing using an extended panel of 77 primary electrical disorder and cardiomyopathy genes. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. The yield of combined molecular autopsy and clinical evaluation in 82 surviving families was evaluated. A gene-level rare variant association analysis was conducted in SADS cases versus controls. RESULTS: A clinically actionable pathogenic or likely pathogenic variant was identified in 40 of 302 cases (13%). The main etiologies established were catecholaminergic polymorphic ventricular tachycardia and long QT syndrome (17 [6%] and 11 [4%], respectively). Gene-based rare variants association analysis showed enrichment of rare predicted deleterious variants in RYR2 (p = 5 × 10-5). Combining molecular autopsy with clinical evaluation in surviving families increased diagnostic yield from 26% to 39%. CONCLUSIONS: Molecular autopsy for electrical disorder and cardiomyopathy genes, using ACMG guidelines for variant classification, identified a modest but realistic yield in SADS. Our data highlighted the predominant role of catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, especially the RYR2 gene, as well as the minimal yield from other genes. Furthermore, we showed the enhanced utility of combined clinical and genetic evaluation.

Relationship between aetiology and left ventricular systolic dysfunction in hypertrophic cardiomyopathy.

BACKGROUND: Severe left ventricular (LV) systolic dysfunction is an uncommon complication of hypertrophic cardiomyopathy (HCM) that is associated with poor prognosis. Small observational series suggest that patients with rare causes of HCM are more likely to develop systolic impairment than those with idiopathic disease or mutations in cardiac sarcomeric protein genes. The aim of this study was to test this hypothesis by comparing the prevalence of systolic dysfunction and its impact on prognosis in patients with different causes of HCM. METHODS AND RESULTS: 1697 patients (52 (40-63) years, 1160 (68%) males) with HCM followed at two European referral centres were studied. Diagnosis of specific aetiologies was made on the basis of clinical examination, cardiac imaging and targeted genetic and biochemical testing. The primary survival outcome was all-cause mortality or heart transplantation (HTx) for end-stage heart failure (HF). Secondary outcomes were HF-related death, sudden cardiac death, stroke-related death and non-cardiovascular death. Systolic dysfunction (LV ejection fraction <50% by two-dimensional (2D) echocardiography) at first evaluation was more frequent in rare phenocopies than in idiopathic or sarcomeric HCM (105/409 (26%) vs 40/1288 (3%), respectively (p<0.0001)). All-cause death/HTx and HF-related death were more frequent in rare phenocopies compared with idiopathic or sarcomeric HCM (p<0.0001). All-cause mortality and HF-related death were highest in patients with cardiac amyloidosis (p<0.0001). CONCLUSIONS: In adults with HCM, LV systolic dysfunction is more frequent in those with rare phenocopies. When combined with age at presentation, it is a marker for specific aetiologies and is associated with poorer long-term survival.

Psychosocial adjustment and quality of life in children undergoing screening in a specialist paediatric hypertrophic cardiomyopathy clinic.

OBJECTIVE: This study aimed to assess the psychological well-being and quality of life in children with hypertrophic cardiomyopathy and the potential psychosocial impact of screening. METHODS: A total of 152 children (aged 3-18 years) attending a specialist paediatric hypertrophic cardiomyopathy clinic, and their parents completed the Generic Core Scales and Cardiac Module of the Paediatric Quality of Life Inventory (PedsQL) questionnaire as well as the Strengths and Difficulties Questionnaire; 21 patients (14%) had hypertrophic cardiomyopathy (group A); 23 children (15%) harboured hypertrophic cardiomyopathy-causing sarcomeric mutations with normal echocardiograms (group G); and 108 children (71%) had a family history of hypertrophic cardiomyopathy with normal investigations and attended for clinical cardiological screening (group S). RESULTS: In group A, mean PedsQLTM total scores reported by children and parents were lower than those reported by unaffected children (p<0.001). There was no significant difference between unaffected and gene-positive patients. Mean Cardiac module PedsQLTM total scores by children and parents were lower in children with hypertrophic cardiomyopathy compared with unaffected patients [mean child-reported total score 86.4 in group S versus 72.3 in group A (p<0.001) and 80.2 in group G (p=0.25); mean parent-reported total score 91.6 in group S versus 71.4 in group A (p<0.001) and 87 in group G (p=0.4)]. There was no significant difference between group S and group G on any of the scales, or between the three groups of patients in the mean Strengths and Difficulties Questionnaire scores. CONCLUSIONS: Children with hypertrophic cardiomyopathy have a significantly reduced quality of life. Importantly, Quality-of-Life scores among unaffected children attending for screening were not different compared with scores from a normative UK population.

The influence of aortoseptal angulation on provocable left ventricular outflow tract obstruction in hypertrophic cardiomyopathy.

OBJECTIVES: Aortoseptal angulation (AoSA) can predict provocable left ventricular outflow tract obstruction (LVOTO) in patients with symptomatic hypertrophic cardiomyopathy (HCM). Lack of a standardised measurement technique in HCM without the need for complex three-dimensional (3D) imaging limits its usefulness in routine clinical practice. This study aimed to validate a simple measurement of AoSA using 2D echocardiography and cardiac MR (CMR) imaging as a predictor of LVOTO. METHODS: We retrospectively assessed 160 patients with non-obstructive HCM, referred for exercise stress echocardiography. AoSA was measured using resting 2D echocardiography in all patients, and CMR in 29. Twenty-five controls with normal echocardiograms were used for comparison. RESULTS: Patients with HCM had a reduced AoSA compared with controls (113°±12 vs 126°±6), p<0.0001. Sixty (38%) patients had provocable LVOTO, with smaller angles than non-obstructive patients (108°±12 vs 116°±12, p<0.0001). AoSA, degree of mitral valvular regurgitation and incomplete systolic anterior motion (SAM) were associated with peak left ventricular outflow tract gradient (r=0.508, p<0.0001). An angle ≤100° had 27% sensitivity, 91% specificity and 59% positive predictive value for predicting provocable LVOTO. When combined with SAM, specificity was 99% and positive predictive value 88%. Intraclass correlation coefficient of AoSA measured by two observers was 0.901 (p<0.0001). Bland-Altman analysis of echocardiographic AoSA showed good agreement with the CMR-derived angle. CONCLUSIONS: Measurement of AoSA using echocardiography in HCM is easy, reproducible and comparable to CMR. Patients with provocable LVOTO have reduced angles compared with non-obstructive patients. AoSA is highly specific for provocable LVOTO and should prompt further evaluation in symptomatic patients without resting obstruction.

Arrhythmogenic right ventricular cardiomyopathy mimics: role of cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is commonly used in patients with suspected arrhythmogenic right ventricular cardiomyopathy (ARVC) based on ECG, echocardiogram and Holter. However, various diseases may present with clinical characteristics resembling ARVC causing diagnostic dilemmas. The aim of this study was to explore the role of CMR in the differential diagnosis of patients with suspected ARVC. METHODS: 657 CMR referrals suspicious for ARVC in a single tertiary referral centre were analysed. Standardized CMR imaging protocols for ARVC were performed. Potential ARVC mimics were grouped into: 1) displacement of the heart, 2) right ventricular overload, and 3) non ARVC-like cardiac scarring. For each, a judgment of clinical impact was made. RESULTS: Twenty patients (3.0%) fulfilled imaging ARVC criteria. Thirty (4.6%) had a potential ARVC mimic, of which 25 (3.8%) were considered clinically important: cardiac displacement (n=17), RV overload (n=7) and non-ARVC like myocardial scarring (n=4). One patient had two mimics; one patient had dual pathology with important mimic and ARVC. RV overload and scarring conditions were always thought clinically important whilst the importance of cardiac displacement depended on the degree of displacement from severe (partial absence of pericardium) to epiphenomenon (minor kyphoscoliosis). CONCLUSIONS: Some patients referred for CMR with suspected ARVC fulfil ARVC imaging criteria (3%) but more have otherwise unrecognised diseases (4.6%) mimicking potentially ARVC. Clinical assessment should reflect this, emphasising the assessment and/or exclusion of potential mimics in parallel with the detection of ARVC major and minor criteria.