Prevalence of illicit drug use in young patients with sudden cardiac death.

BACKGROUND: Illicit drug use may accelerate coronary disease and cardiac hypertrophy or stimulate arrhythmias. Rates of illicit drug use in young patients with sudden cardiac death (SCD) are uncertain. OBJECTIVE: The purpose of this study was to identify rates of illicit drug use in young patients with SCD. METHODS: A prospective statewide registry identified out-of-hospital patients with cardiac arrest aged 18-50 years from April 2019 to April 2021. Clinical characteristics were compared between patients with and without illicit drug use (defined by toxicological results or reported regular use). Illicit drugs included amphetamine-type substances, cocaine, heroin, cannabis, and other drugs. RESULTS: A total of 554 (40.2%) of 1378 patients had confirmed cardiac cause of out-of-hospital cardiac arrest, with 523 undergoing toxicological assessment. There were 170 patients (32.5%) having either positive toxicology for illicit drugs (n = 138) or negative toxicology but reported regular drug use (n = 32). Patients with SCD and illicit drug use were more commonly male (81.2% vs 72.3%; P = .028), smokers (38.8% vs 19.8%; P ≤ .0001), and excess alcohol drinkers (30.6% vs 20.6%; P = .012) and had a psychiatric diagnosis (38.8% vs 25.7%; P = .002), lower body mass index (29.4 kg/m2 vs 31.7 kg/m2; P = .0063), and lower rates of hypertension (10.6% vs 18.6%; P = .019). Death commonly occurred while sedentary (47.5%) or during sleep (45.8%). Accounting for these baseline differences, there were no differences in rates of coronary disease or cardiomyopathy. Cannabis (n = 106) was the most common illicit drug identified and polysubstance abuse occurred frequently (n = 25). CONCLUSION: Approximately one-third of young patients with SCD have positive toxicology at the time of death or reported frequent use of illicit drugs, with high rates of polysubstance abuse.

Sudden cardiac death in the young: A qualitative study of experiences of family members with cardiogenetic evaluation.

Sudden cardiac death (SCD) is a devastating event for the family and the community, especially when it occurs in a young person (<45 years). Genetic heart diseases, including cardiomyopathies and primary arrhythmia syndromes, are an important cause of SCD in the young. Although cardiogenetic evaluation, that is, clinical evaluation, genetic testing, and psychological support, is increasingly performed after SCD, it is unknown how suddenly bereaved family members experience the process. We aimed to explore the experiences of family members with cardiogenetic evaluation after SCD, and their perception of the process and care received. In-depth interviews were conducted with 18 family members of young people (<45 years old) who died suddenly, including parents, siblings, and partners. The interviews were thematically analyzed by two researchers independently. In total, 18 interviews were conducted from 17 families. The following themes were identified: (1) Experiences with postmortem genetic testing including managing expectations and psychological impact, (2) appreciation of care such as access to genetic counseling and relief following cardiac evaluation of relatives, and (3) need for support including unmet psychological support needs and better coordination of care immediately after the death. Although participants appreciated the opportunity for cardiogenetic evaluation, they also experienced a lack of coordination of cardiogenetic and psychological care. Our findings stress the importance of access to expert multidisciplinary teams, including psychological care, to adequately support these families after a SCD in a young family member.

European Society of Cardiology quality indicators for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death.

To develop a suite of quality indicators (QIs) for the management of patients with ventricular arrhythmias (VA) and the prevention of sudden cardiac death (SCD). The Working Group comprised experts in heart rhythm management including Task Force members of the 2022 European Society of Cardiology (ESC) Clinical Practice Guidelines for the management of patients with VA and the prevention of SCD, members of the European Heart Rhythm Association, international experts, and a patient representative. We followed the ESC methodology for QI development, which involves (i) the identification of the key domains of care for the management of patients with VA and the prevention of SCD by constructing a conceptual framework of care, (ii) the development of candidate QIs by conducting a systematic review of the literature, (iii) the selection of the final set of QIs using a modified-Delphi method, and (iv) the evaluation of the feasibility of the developed QIs. We identified eight domains of care for the management of patients with VA and the prevention of SCD: (i) structural framework, (ii) screening and diagnosis, (iii) risk stratification, (iv) patient education and lifestyle modification, (v) pharmacological treatment, (vi) device therapy, (vii) catheter ablation, and (viii) outcomes, which included 17 main and 4 secondary QIs across these domains. Following a standardized methodology, we developed 21 QIs for the management of patients with VA and the prevention of SCD. The implementation of these QIs will improve the care and outcomes of patients with VA and contribute to the prevention of SCD.

Analysis of athlete QT intervals by age: Fridericia and Hodges heart rate corrections outperform Bazett for athlete ECG screening.

BACKGROUND: Cardiac screening of elite athletes including a 12­lead electrocardiogram (ECG) is recommended by numerous international bodies. Current athlete ECG interpretation guidelines recommend the Bazett method to correct the QT interval (QTc). OBJECTIVE: This study sought to investigate normative QTc changes by age using athlete screening ECGs and different QT correction methods in a population of elite cricketers. METHODS: Initial cardiac screening ECGs from an existing database of elite Australian cricketers aged 14-35 years were examined. Average QT interval, QTcB (corrected QT-Bazett), QTcF (Fridericia), QTcH (Hodges), and heart rate (HR) were analyzed by age and sex. RESULTS: A total of 1310 athletes (66% male, 34% female) were included with mean age 19.1 years and mean heart rate 66.9 bpm (range 38-121 bpm). With increasing age, HR decreased and absolute QT increased. The pattern of QTc change with age differed depending on the method of correction: Bazett correction (QTcB) demonstrated a "dish-shaped" or broad U-shaped appearance; while Fridericia and Hodges corrections showed a linear increase in QTc from young to older age. The Bazett method had a stronger correlation of HR with QTc (R2 = 0.32) than either Fridericia (R2 = 0.0007) or Hodges (R2 = 0.009) methods. CONCLUSIONS: The Bazett method is not the most accurate QT correction in athletes, especially during adolescence. In elite cricketers, QTcB revealed a drop in QTc from adolescence to early adulthood due to mis-correction of the QT interval. The Fridericia method has the smoothest correction of HR and least QT variation by age and may be preferred for athlete screening.

Reduced death rates of elite Australian Rules footballers compared to age-matched general population.

OBJECTIVES: To determine age-matched death rates of current and retired elite male Australian football players (Australian and/or Victorian Football League) with the general population. DESIGN: Analysis of publicly-available birth, debut and death data for all Australian Victorian Football/Victorian Football League players who debuted prior to (and were still alive at) the start of 1971 or debuted 1971-2020. METHODS: Wikipedia was used to source the dates of death (or record that the player was alive in 2021) for the cohort. New players became part of the cohort for analysis on debut and existing cohort members left it at death. Actual death rates (per year and per decade) were then compared to expected deaths, based on age-specific population death rates. RESULTS: There were 5400 players and ex-players in the cohort at the start of 1971 (average age 47.3) and a further 4532 players debuted between 1971 and 2020 inclusive (a total of 9932 players). The expected deaths for the cohort in this 50-year period were 4955, but only 3914 deaths occurred (Standardized Mortality Ratio 0.79, 95 %CI 0.76-0.82). For younger members of the cohort (age <50) the discrepancy between expected (222) and actual (98) deaths was also significant (Standardized Mortality Ratio 0.44, 95 %CI 0.35-0.56). CONCLUSIONS: We conclude that the death rates of elite male Australian footballers are lower than the reference general population, similar to other studies of elite athletes. Some of this may be explained by "healthy cohort" selection bias, a limitation which affects almost all studies in this genre.

Obesity in young sudden cardiac death: Rates, clinical features, and insights into people with body mass index >50kg/m2.

Objective: To contextualize obesity rates in young sudden cardiac death (SCD) against the age-matched national population, and identify clinical and pathologic features in WHO class II and III obesity. Methods: A prospective state-wide out-of-hospital cardiac arrest registry included all SCDs in Victoria, Australia from 2019-2021. Body mass indices (BMIs) of patients 18-50 years were compared to age-referenced general population. Characteristics of SCD patients with WHO Class II obesity (BMI ≥30kg/m2) and non-obesity (BMI<30kg/m2) were compared. Clinical characteristics of people with BMI>50kg/m2 were assessed. Results: 504 patients were included. Obesity was strongly over-represented in young SCD compared to the age-matched general population (55.0% vs 28.7%, p<0.0001). Obese SCD patients more frequently had hypertension, diabetes and obstructive sleep apnoea (p<0.0001, p=0.009 and p=0.001 respectively), ventricular fibrillation as their arrest rhythm (p=0.008) and left ventricular hypertrophy (LVH) (p<0.0001). Obese patients were less likely to have toxicology positive for illicit substances (22.0% vs 32.6%, p=0.008) or history of alcohol abuse (18.8% vs 26.9%, p=0.030). Patients with BMI>50 kg/m2 represented 8.5% of young SCD. LVH (n=26, 60.5%) was their predominant cause of death and only 10 (9.3%) patients died from coronary disease. Conclusion: Over half of young Australian SCD patients are obese, with all obesity classes over-represented compared to the general population. Obese patients had more cardiac risk factors. Almost two thirds of patients with BMI>50 kg/m2 died from LVH, with fewer than 10% dying from coronary disease.

Use of a smartphone electrocardiogram to diagnose arrhythmias during exercise in athletes: a case series.

Background: While athletes are generally very fit, intense exercise can increase the risk of atrial fibrillation. Moreover, other arrhythmias such as atrial flutter or supraventricular tachycardia can cause distressing, exercise-related symptoms. Given symptoms are infrequent and may occur during intense exertion, traditional monitoring devices are often impractical to use during exercise. Smartphone electrocardiograms (ECGs) such as the Alivecor Kardia device may be the portable and reliable tool required to help identify arrhythmias in this challenging population. This case series highlights the use of such devices in aiding the diagnosis of arrhythmias in the setting of exercise-related symptoms in athletes. Case summary: The six cases in this series included one elite non-endurance athlete, two elite cricketers, one amateur middle-distance runner, and two semi-elite ultra-endurance runners, with an age range of 16-48 years. An accurate diagnosis of an arrhythmia was obtained in five cases (atrial fibrillation/flutter and supraventricular tachycardias) using the smartphone ECG, which helped guide definitive treatment. No arrhythmia was identified in the final case despite using the device during multiple symptomatic events. Discussion: The smartphone ECG was able to accurately detect arrhythmias and provide a diagnosis in cases where traditional monitoring had not. The utility of detecting no arrhythmia during symptoms in one case was also highlighted, providing the athlete with the confidence to continue exercising. This reassurance and confidence across all cases is perhaps the most valuable aspect of this device, where clinicians and athletes can be more certain of reaching a diagnosis and undertaking appropriate management.

Comparison between a 6­lead smartphone ECG and 12­lead ECG in athletes.

Athletes sometimes experience transient arrhythmias during intense exercise, which may be difficult to capture with traditional Holter monitors. New and highly portable technology, such as smartphone electrocardiogram (ECG) devices, may be useful in documenting and contribute to diagnosis of exercise-induced arrhythmias. There are little data available regarding the new Kardia 6 lead device (6L) and no data regarding its use in athletic populations. In this short communication, we present pilot data from 30 healthy athletes who underwent a 12­lead ECG and subsequent 6L reading. Our pilot data show relatively high levels of agreement for QTc and PR interval and QRS duration, with the 6L readings slightly but significantly shorter on average.

Harmonizing the Collection of Clinical Data on Genetic Testing Requisition Forms to Enhance Variant Interpretation in Hypertrophic Cardiomyopathy (HCM): A Study from the ClinGen Cardiomyopathy Variant Curation Expert Panel.

Diagnostic laboratories gather phenotypic data through requisition forms, but there is no consensus as to which data are essential for variant interpretation. The ClinGen Cardiomyopathy Variant Curation Expert Panel defined a phenotypic data set for hypertrophic cardiomyopathy (HCM) variant interpretation, with the goal of standardizing requisition forms. Phenotypic data elements listed on requisition forms from nine leading cardiomyopathy testing laboratories were compiled to assess divergence in data collection. A pilot of 50 HCM cases was implemented to determine the feasibility of harmonizing data collection. Laboratory directors were surveyed to gauge potential for adoption of a minimal data set. Wide divergence was observed in the phenotypic data fields in requisition forms. The 50-case pilot showed that although demographics and assertion of a clinical diagnosis of HCM had 86% to 98% completion, specific phenotypic features, such as degree of left ventricular hypertrophy, ejection fraction, and suspected syndromic disease, were completed only 24% to 44% of the time. Nine data elements were deemed essential for variant classification by the expert panel. Participating laboratories unanimously expressed a willingness to adopt these data elements in their requisition forms. This study demonstrates the value of comparing and sharing best practices through an expert group, such as the ClinGen Program, to enhance variant interpretation, providing a foundation for leveraging cumulative case-level data in public databases and ultimately improving patient care.

Disease-specific variant pathogenicity prediction significantly improves variant interpretation in inherited cardiac conditions.

PURPOSE: Accurate discrimination of benign and pathogenic rare variation remains a priority for clinical genome interpretation. State-of-the-art machine learning variant prioritization tools are imprecise and ignore important parameters defining gene-disease relationships, e.g., distinct consequences of gain-of-function versus loss-of-function variants. We hypothesized that incorporating disease-specific information would improve tool performance. METHODS: We developed a disease-specific variant classifier, CardioBoost, that estimates the probability of pathogenicity for rare missense variants in inherited cardiomyopathies and arrhythmias. We assessed CardioBoost's ability to discriminate known pathogenic from benign variants, prioritize disease-associated variants, and stratify patient outcomes. RESULTS: CardioBoost has high global discrimination accuracy (precision recall area under the curve [AUC] 0.91 for cardiomyopathies; 0.96 for arrhythmias), outperforming existing tools (4-24% improvement). CardioBoost obtains excellent accuracy (cardiomyopathies 90.2%; arrhythmias 91.9%) for variants classified with >90% confidence, and increases the proportion of variants classified with high confidence more than twofold compared with existing tools. Variants classified as disease-causing are associated with both disease status and clinical severity, including a 21% increased risk (95% confidence interval [CI] 11-29%) of severe adverse outcomes by age 60 in patients with hypertrophic cardiomyopathy. CONCLUSIONS: A disease-specific variant classifier outperforms state-of-the-art genome-wide tools for rare missense variants in inherited cardiac conditions ( https://www.cardiodb.org/cardioboost/ ), highlighting broad opportunities for improved pathogenicity prediction through disease specificity.

Can post-mortem coronary artery calcium scores aid diagnosis in young sudden death?

This study sought to explore the feasibility and utility of post-mortem coronary artery calcium (CAC) scoring in identifying patients with ischemic heart disease as cause of sudden death. 100 deceased patients aged 18-50 years underwent post-mortem examination in the setting of sudden death. At post-mortem, fifty cases were determined to have ischemic heart disease, and fifty had death attributed to trauma or unascertained causes. The CAC score was calculated in a blinded manner from post-mortem CTs performed on all cases. CAC scores were assessable in 97 non-decomposed cases (feasibility 97%). The median CAC score was 88 Agatston units [IQR 0-286] in patients deceased from ischemic heart disease vs 0 [IQR 0-0] in patients deceased from other causes (p < 0.0001). Presence of any coronary calcification differed significantly between ischemic heart disease and non-ischemic groups (adjusted odds ratio 10.7, 95% CI 3.2-35.5). All cases with a CAC score > 100 (n = 22) had ischemic heart disease as the cause of death. Fifteen cases had a CAC score of zero but severe coronary disease at post-mortem examination. Post-mortem CAC scoring is highly feasible. An elevated CAC score in cases 18-50 years old with sudden death predicts ischemic heart disease at post-mortem examination. However, a CAC score of zero does not exclude significant coronary artery disease. Post-mortem CAC score may be considered as a further assessment tool to help predict likely cause of death when there is an objection to or unavailability of post-mortem examination.

Audit of a cardiac screening policy for elite Australian cricketers.

OBJECTIVES: To report the compliance and results of an electrocardiogram (ECG) cardiac screening program in male and female elite Australian cricketers. DESIGN: cross-sectional study. METHODS: Elite cricketers were offered screening in accordance with Cricket Australia policy. Players who consented provided a personal and family history, physical examination and resting 12-lead ECG. An audit (1 February 2019) examined all cardiac screening records for male and female players in all Australian Cricket state squads from 16 years upwards. Data extracted from the Cricket Australia database included the number of players who underwent screening; signed waivers opting out; and had follow-up tests. ECGs were re-reviewed according to the International Criteria. RESULTS: 710 players were included in the cohort (mean age 20.4±4.9 years, 62% male). 692 (97.5%) players underwent recommended cardiac screening or signed a waiver opting out (1.1%). 173 (24.4%) players were screened (or signed a waiver) more than once. Follow-up testing was conducted for 59 (6.9%) cases. No players were excluded from sport due to a cardiac problem and no major cardiac incidents occurred to any player in the audit cohort. Review of 830 ECGs showed benign athlete heart changes, including sinus bradycardia (33.5%), left ventricular hypertrophy (16.3%), and incomplete/partial right bundle branch block (8.4%), were common but abnormal screening ECGs were uncommon (2.0%). CONCLUSIONS: An audit of a cardiac screening program in elite Australian cricketers found excellent compliance. A small proportion required follow-up testing and no player was excluded from sport due to a cardiac problem. ECG analysis suggested cricket is a sport of moderate cardiac demands, with benign athlete heart changes common.

Prevalence of Anderson-Fabry disease in a cohort with unexplained late gadolinium enhancement on cardiac MRI.

INTRODUCTION: Fabry disease is a rare X-linked genetic disorder in which cardiac manifestations include LVH, contractile dysfunction, and fibrosis, visible on cardiac MRI (cMRI) as late gadolinium enhancement (LGE) of the myocardium. Fabry's disease is an important diagnosis to make as treatment is available as lifelong replacement of the deficient enzyme. AIM: To define the prevalence of Fabry disease in a cohort of patients with unexplained LGE on cMRI. METHODS: The study population was recruited from patients aged >16 years who had cMRI performed between 2010 and 2018 to investigate LVH, idiopathic LV dysfunction and/or idiopathic ventricular arrhythmia. Patients with 'unexplained' LGE i.e. without a genetic diagnosis of an alternate cardiomyopathy such as HCM or biopsy-proven infiltrative cardiomyopathy such as sarcoid or amyloid, were tested for Fabry disease by either genetic testing or the Dried Blood Spot test (Sanofi-Genzyme). RESULTS: Of the 79 patients with unexplained LGE on cMRI, 2 patients tested positive for Fabry disease, both using genetic sequencing techniques. The prevalence of Fabry disease in this selected cohort was 2.5%. Specifically, 1 patient was a 65 year old male and the other patient a 75 year old female. In both cases, the pattern and distribution of LGE on cMRI was of patchy mid-wall enhancement in the inferoseptum. CONCLUSION: Unexplained LGE on cMRI may be an isolated manifestation of late-onset Fabry disease. This finding should prompt testing for Fabry disease given this is a potentially treatable condition.

Assessment of myocardial oxygenation, strain, and diastology in MYBPC3-related hypertrophic cardiomyopathy: a cardiovascular magnetic resonance and echocardiography study.

AIMS: Myocardial oxygenation is impaired in hypertrophic cardiomyopathy (HCM) patients with left ventricular hypertrophy (LVH), and possibly also in HCM gene carriers without LVH. Whether these oxygenation changes are also associated with abnormalities in diastolic function or left ventricular (LV) strain are unknown. METHODS AND RESULTS: We evaluated 60 subjects: 20 MYBPC3 gene positive patients with LVH (G+LVH+), 18 MYBPC3 gene positive without LVH (G+LVH-), 11 gene negative siblings (G-), and 11 normal controls (NC). All subjects underwent 2D transthoracic echocardiography and cardiovascular magnetic resonance imaging for assessment of ventricular volumes, mass, and myocardial oxygenation at rest and adenosine stress using the blood oxygen level dependent (BOLD) technique. Maximal septal thickness was 20 mm in the G+LVH+ group, vs. 9 mm for the G+LVH- group. As expected, the G+LVH+ group had a more blunted myocardial oxygenation response to stress when compared with the G+LVH- group (-5% ± 3% vs. 2% ± 4%, P < 0.05), G- siblings (-5% ± 3% vs. 11% ± 4%, P < 0.0001) and NC (-5% ± 3% vs. 15% ± 4%, P < 0.0001). A blunted BOLD response to stress was also seen in G+LVH- subjects when compared with gene negative siblings (2% ± 4% vs. 11% ± 4%, P < 0.05) and NC (15% ± 4%, P < 0.050). G+LVH+ patients exhibited abnormal diastolic function including lower E', higher E to E' ratio and greater left atrial area compared with the G+LVH- subjects who all had normal values for these indices. CONCLUSION: Myocardial deoxygenation during stress is observed in MYBPC3 HCM patients, even in the presence of normal LV diastolic function, LV global longitudinal strain, and LV wall thickness.

Long-Term Outcomes of Hypertrophic Cardiomyopathy Diagnosed During Childhood: Results From a National Population-Based Study.

BACKGROUND: Late survival and symptomatic status of children with hypertrophic cardiomyopathy have not been well defined. We examined long-term outcomes for pediatric hypertrophic cardiomyopathy. METHODS: The National Australian Childhood Cardiomyopathy Study is a longitudinal population-based cohort study of children (0-10 years of age) diagnosed with cardiomyopathy between 1987 and 1996. The primary study end point was time to death or cardiac transplantation. RESULTS: There were 80 patients with hypertrophic cardiomyopathy, with a median age at diagnosis of 0.48 (interquartile range, 0.1, 2.5) years. Freedom from death/transplantation was 86% (95% confidence interval [CI], 77.0-92.0) 1 year after presentation, 80% (95% CI, 69.0-87.0) at 10 years, and 78% (95% CI, 67.0-86.0) at 20 years. From multivariable analyses, risk factors for death/transplantation included symmetrical left ventricular hypertrophy at the time of diagnosis (hazard ratio, 4.20; 95% CI, 1.60-11.05; P=0.004), Noonan syndrome (hazard ratio, 2.88; 95% CI, 1.02-8.08; P=0.045), higher posterior wall thickness z score (hazard ratio, 1.45; 95% CI, 1.22-1.73; P<0.001), and lower fractional shortening z score (hazard ratio, 0.84; 95% CI, 0.74-0.95; P=0.005) during follow-up. Nineteen (23%) subjects underwent left ventricular myectomy. At a median of 15.7 years of follow-up, 27 (42%) of 63 survivors were treated with ß-blocker, and 13 (21%) had an implantable cardioverter-defibrillator. CONCLUSIONS: The highest risk of death or transplantation for children with hypertrophic cardiomyopathy is within 1 year after diagnosis, with low attrition rates thereafter. Many subjects receive medical, surgical, or device therapy.

NOS1AP Polymorphisms Modify QTc Interval Duration But Not Cardiac Arrest Risk in Hypertrophic Cardiomyopathy.

INTRODUCTION: The accurate prediction of the risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains elusive. Corrected QT interval (QTc) duration is a known risk factor in various cardiac conditions. Single nucleotide polymorphisms (SNPs) have been linked to QTc length, and to SCD. Here we investigated the role of 21 candidate SNPs in QTc duration and SCD events in patients with HCM. METHODS AND RESULTS: This HCM registry-based study included patients with an ECG, medical history, first SCD event data, and DNA available. Each individual SNP was assessed using logistic regression for associations with 2 outcomes: a prolonged QTc ( ≥440 milliseconds), and first SCD event (SCD, resuscitated cardiac arrest, and appropriate implantable cardioverter defibrillator (ICD) shock for ventricular fibrillation/ventricular tachycardia (VF/VT). In 272 HCM patients, there were 31 SCD events (8 SCD, 9 resuscitated cardiac arrest, 14 ICD shocks for VF/VT; 11%). A QTc ≥ 500 milliseconds was associated with SCD events on multivariate analysis (odds ratio [OR] = 4.0, 95% confidence interval [CI], 1.19-12.02, P = 0.016). In 228 Caucasian patients, 2 SNPs in the NOS1AP gene (rs10494366 and rs12143842) were associated with a prolonged QTc after correction for multiple testing. This remained significant after adjustment for current age, sex, and ≥1 SCD risk factor (OR 1.59 per copy of the minor allele, 95% CI 1.08-2.39, P = 0.022, and OR 1.63, 95% CI 1.09-2.49, P = 0.020, respectively). No SNPs were directly associated with SCD events. CONCLUSION: SNPs in the NOS1AP gene influence QTc interval duration but we have not demonstrated a direct association with the risk of SCD.

Surgery for hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetically determined cardiac disease characterised by otherwise unexplained myocardial hypertrophy of the left ventricle, and may result in left ventricular outflow tract obstruction. It is the most common cause of sudden cardiac death in young adults due to arrhythmias. Septal myectomy is a surgical treatment for HCM with moderate to severe outflow tract obstruction, and is indicated for patients with severe symptoms refractory to medical therapy. The surgical approach involves obtaining access to the interventricular septum via transaortic, transapical or transmitral approaches, and excising a portion of the hypertrophied myocardium to relieve the outflow tract obstruction. Large, contemporary series from centres experienced in septal myectomy patients have demonstrated a low early mortality of <2 %, excellent long-term survival that matches the general population, and durable relief of symptoms.

Impact of new task force criteria in the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy that can lead to sudden cardiac death. The diagnostic criterion has recently been revised and through the use of cardiac magnetic resonance (CMR) imaging this study aimed to assess the clinical impact of comparing the original 1994 task force (TF) criterion to the revised 2010 criterion. METHODS: We evaluated 173 consecutive CMR scans of patients referred with clinical suspicion of ARVC between 2008 and 2011. We then compared the prevalence of major and minor CMR criteria by applying the two criteria. RESULTS: Using the 1994 TF criterion, 13 (7.5%) patients had definite, 11 (6.4%) had borderline, and 39 (22.5%) had possible ARVC. Using the 2010 TF criterion, 10 (5.8%) patients had definite, 1 had borderline, and 7 had (0.04%) possible ARVC. With the 1994 criterion, 81 patients satisfied CMR criterion, of which 36 (44%) had major and 45 (56%) had minor criteria. Upon reclassification with the revised criterion, 61 of the 81 patients were not assigned any criteria, even though many patients had significant risk factors. The negative predictive values (NPV) for both CMR criteria were 100% but the positive predictive values (PPV) for combined CMR major or minor criteria improved from 23% to 55%. CONCLUSIONS: Revision of the criterion has enhanced the diagnostic capabilities of CMR but has resulted in a large cohort of patients not classified. In these patients, there is presently no official consensus on imaging or clinical strategy for surveillance of the evolution of pathology over time.

No association of G-protein-coupled receptor kinase 5 or ß-adrenergic receptor polymorphisms with Takotsubo cardiomyopathy in a large Australian cohort.

AIMS: Takotsubo cardiomyopathy (TC) is an increasingly recognized syndrome in which patients present with chest pain and ST changes, and are observed to have reversible LV apical ballooning in the absence of angiographically significant coronary artery stenosis. Although the pathophysiology remains unclear, the syndrome occurs almost exclusively in women, and is often triggered by stress. Recent small studies have reported association of TC with functional variants in the G-protein-coupled receptor kinase 5 (GRK5) gene, as well as in the ß1-adrenergic receptor (ß1AR) and ß2AR. METHODS AND RESULTS: We tested these associations in a larger cohort of 92 TC patients. In addition we examined for the association of polymorphisms in the oestrogen receptor α (ERα) and catechol-O-methyl transferase (COMT) with the occurrence of TC, by comparing the allele frequency of these variants in the TC cohort with that in previously genotyped large Caucasian cohorts. Ninety-two patients with TC were recruited from four Australian centres; they had an age range of 41-90 years (mean ± SD = 66.3 ± 9) and 89/92 were female. There were no significant differences in allelic frequency in the TC group vs. the historic control database for any of the loci. CONCLUSION: In the largest genotyped TC cohort in the literature, we have found no association of genetic variants in the ERα, ß1AR, ß2AR, or COMT genes, or with the previously implicated GRK5, with occurrence of the syndrome.