Mode and Characteristics of Arrhythmia Initiation in Idiopathic Ventricular Fibrillation: A THESIS Substudy.

BACKGROUND: There is limited information on the mode of arrhythmia initiation in idiopathic ventricular fibrillation (IVF). A non-pause-dependent mechanism has been suggested to be the rule. OBJECTIVES: The aim of this study was to assess the mode and characteristics of initiation of polymorphic ventricular tachycardia (PVT) in patients with short or long-coupled PVT/IVF included in THESIS (THerapy Efficacy in Short or long-coupled idiopathic ventricular fibrillation: an International Survey), a multicenter study involving 287 IVF patients treated with drugs or radiofrequency ablation. METHODS: We reviewed the initiation of 410 episodes of ≥1 PVT triplet in 180 patients (58.3% females; age 39.6 ± 13.6 years) with IVF. The incidence of pause-dependency arrhythmia initiation (prolongation by >20 ms of the preceding cycle length) was assessed. RESULTS: Most arrhythmias (n = 295; 72%) occurred during baseline supraventricular rhythm without ambient premature ventricular complexes (PVCs), whereas 106 (25.9%) occurred during baseline rhythm including PVCs. Nine (2.2%) arrhythmias occurred during atrial/ventricular pacing and were excluded from further analysis. Mode of PVT initiation was pause-dependent in 45 (15.6%) and 64 (60.4%) of instances in the first and second settings, respectively, for a total of 109 of 401 (27.2%). More than one type of pause-dependent and/or non-pause-dependent initiation (mean: 2.6) occurred in 94.4% of patients with ≥4 events. Coupling intervals of initiating PVCs were <350 ms, 350-500 ms, and >500 ms in 76.6%, 20.72%, and 2.7% of arrhythmia initiations, respectively. CONCLUSIONS: Pause-dependent initiation occurred in more than a quarter of arrhythmic episodes in IVF patients. PVCs having long (between 350 and 500 ms) and very long (>500 ms) coupling intervals were observed at the initiation of nearly a quarter of PVT episodes.

2023 Cardiac Society of Australia and New Zealand Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation.

Catheter ablation for atrial fibrillation (AF) has increased exponentially in many developed countries, including Australia and New Zealand. This Expert Position Statement on Catheter and Surgical Ablation for Atrial Fibrillation from the Cardiac Society of Australia and New Zealand (CSANZ) recognises healthcare factors, expertise and expenditure relevant to the Australian and New Zealand healthcare environments including considerations of potential implications for First Nations Peoples. The statement is cognisant of international advice but tailored to local conditions and populations, and is intended to be used by electrophysiologists, cardiologists and general physicians across all disciplines caring for patients with AF. They are also intended to provide guidance to healthcare facilities seeking to establish or maintain catheter ablation for AF.

Predicting Adverse Outcomes Following Catheter Ablation Treatment for Atrial Flutter/Fibrillation.

BACKGROUND & AIM: To develop prognostic survival models for predicting adverse outcomes after catheter ablation treatment for non-valvular atrial fibrillation (AF) and/or atrial flutter (AFL). METHODS: We used a linked dataset including hospital administrative data, prescription medicine claims, emergency department presentations, and death registrations of patients in New South Wales, Australia. The cohort included patients who received catheter ablation for AF and/or AFL. Traditional and deep survival models were trained to predict major bleeding events and a composite of heart failure, stroke, cardiac arrest, and death. RESULTS: Out of a total of 3,285 patients in the cohort, 177 (5.3%) experienced the composite outcome-heart failure, stroke, cardiac arrest, death-and 167 (5.1%) experienced major bleeding events after catheter ablation treatment. Models predicting the composite outcome had high-risk discrimination accuracy, with the best model having a concordance index >0.79 at the evaluated time horizons. Models for predicting major bleeding events had poor risk discrimination performance, with all models having a concordance index <0.66. The most impactful features for the models predicting higher risk were comorbidities indicative of poor health, older age, and therapies commonly used in sicker patients to treat heart failure and AF and AFL. DISCUSSION: Diagnosis and medication history did not contain sufficient information for precise risk prediction of experiencing major bleeding events. Predicting the composite outcome yielded promising results, but future research is needed to validate the usefulness of these models in clinical practice. CONCLUSIONS: Machine learning models for predicting the composite outcome have the potential to enable clinicians to identify and manage high-risk patients following catheter ablation for AF and AFL proactively.

Clinical Management of Brugada Syndrome: Commentary From the Experts.

Although there is consensus on the management of patients with Brugada Syndrome with high risk for sudden cardiac arrest, asymptomatic or intermediate-risk patients present clinical management challenges. This document explores the management opinions of experts throughout the world for patients with Brugada Syndrome who do not fit guideline recommendations. Four real-world clinical scenarios were presented with commentary from small expert groups for each case. All authors voted on case-specific questions to evaluate the level of consensus among the entire group in nuanced diagnostic and management decisions relevant to each case. Points of agreement, points of controversy, and gaps in knowledge are highlighted.

Provocation testing in congenital long QT syndrome: A practical guide.

Congenital long QT syndrome (LQTS) is a hereditary cardiac channelopathy with an estimated prevalence of 1 in 2500. A prolonged resting QT interval corrected for heart rate (QTc interval) remains a key diagnostic component; however, the QTc value may be normal in up to 40% of patients with genotype-positive LQTS and borderline in a further 30%. Provocation of QTc prolongation and T-wave changes may be pivotal to unmasking the diagnosis and useful in predicting genotype. LQTS provocation testing involves assessment of repolarization during and after exercise, in response to changes in heart rate or autonomic tone, with patients with LQTS exhibiting a maladaptive repolarization response. We review the utility and strengths and limitations of 4 forms of provocation testing-stand-up test, exercise stress test, epinephrine challenge, and mental stress test-in diagnosing LQTS and provide some practical guidance for performing provocation testing. Ultimately, exercise testing, when feasible, is the most useful form of provocation testing when considering diagnostic sensitivity and specificity.

The New South Wales Sudden Cardiac Arrest Registry: A Data Linkage Cohort Study.

BACKGROUND: Sudden cardiac arrest (SCA) in young people aged 1 to 50 years often occurs with no presenting symptoms or risk factors prompting screening for cardiovascular disease prior to their cardiac arrest. Approximately 3,000 young Australians suffer from sudden cardiac death (SCD) each year, making this a major public health issue. However, there is significant variation in the way incidence is estimated resulting in discrepancy across reporting which impacts our ability to understand and prevent these devastating events. We describe the New South Wales (NSW) Sudden Cardiac Arrest Registry: a retrospective, data linkage study which will identify all SCAs in the young in NSW from 2009 through to June 2022. OBJECTIVE: To determine the incidence, demographic characteristics and causes of SCA in young people. We will develop an NSW-based registry that will contribute to a greater understanding of SCA including risk factors and outcomes. METHODS: The cohort will include all people who experience a SCA in the NSW community aged between 1 to 50 years. Cases will be identified using the following three datasets: the Out of Hospital Cardiac Arrest Register housed at NSW Ambulance, the NSW Emergency Department Data Collection, and the National Coronial Information System. Data from eight datasets will be collected, anonymised and linked for the entire cohort. Analysis will be undertaken and reported using descriptive statistics. CONCLUSIONS: The NSW SCA registry will be an important resource for the improved understanding of SCA and inform the widespread impacts it has on individuals, their families and society.

Prognostic benefit of catheter ablation of atrial fibrillation in heart failure: An updated meta-analysis of randomized controlled trials.

Background: The prognostic role of catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) remains uncertain, with guideline recommendations largely based on a single trial. We conducted a meta-analysis of randomized controlled trials (RCTs) assessing the prognostic impact of AF ablation in patients with HF. Methods: Electronic databases were searched for RCTs comparing 'AF ablation' versus 'other care' (medical therapy and/or atrioventricular node ablation with pacing) in patients with HF. Primary endpoints were ≥1-year mortality, HF hospitalization and change in left ventricular ejection fraction (LVEF). Meta-analyses were performed using random-effects modelling. Results: Nine RCTs (n = 1462) met inclusion criteria. Compared to 'other care', AF ablation significantly reduced ≥1-year mortality (relative risk [RR] 0.65; 95% confidence intervals [CI], 0.49-0.87) and HF hospitalization (RR 0.64; 95% CI, 0.51-0.81). AF ablation demonstrated significantly greater improvement in LVEF (mean difference [MD] 5.4; 95% CI, 4.4-6.4), 6-min walk test distance (MD 21.5 meters; 95% CI, 4.6-38.4) and quality of life as measured by Minnesota Living with Heart Failure Questionnaire score (MD 7.2; 95% CI, 2.8-11.7). Meta-regression analyses showed the beneficial impact of AF ablation on LVEF was significantly blunted by higher prevalence of ischaemic cardiomyopathy. Conclusions: Our meta-analysis demonstrates AF ablation is superior to 'other care' in improving mortality, HF hospitalization, LVEF and quality of life in patients with HF. However, the highly selected study populations in included RCTs and effect modification mediated by etiology of HF suggests these benefits do not uniformly apply across the HF population.

Longitudinal assessment of structural phenotype in Brugada syndrome using cardiac magnetic resonance imaging.

Background: Despite historically being considered a channelopathy, subtle structural changes have been reported in Brugada syndrome (BrS) on histopathology and cardiac magnetic resonance (CMR) imaging. It is not known if these structural changes progress over time. Objective: The study sought to assess if structural changes in BrS evolve over time with serial CMR assessment and to investigate the utility of parametric mapping techniques to identify diffuse fibrosis in BrS. Methods: Patients with a diagnosis of BrS based on international guidelines and normal CMR at least 3 years prior to the study period were invited to undergo repeat CMR. CMR images were analyzed de novo and compared at baseline and follow-up. Results: Eighteen patients with BrS (72% men; mean age at follow-up 47.4 ± 8.9 years) underwent serial CMR with an average of 5.0 ± 1.7 years between scans. No patients had late gadolinium enhancement (LGE) on baseline CMR, but 4 (22%) developed LGE on follow-up, typically localized to the right ventricular (RV) side of the basal septum. RV end-systolic volume increased over time (P = .04) and was associated with a trend toward reduction in RV ejection fraction (P = .07). Four patients showed a reduction in RV ejection fraction >10%. There was no evidence of diffuse myocardial fibrosis observed on parametric mapping. Conclusions: Structural changes may evolve over time with development of focal fibrosis, evidenced by LGE on CMR in a significant proportion of patients with BrS. These findings have implications for our understanding of the pathological substrate in BrS and the longitudinal evaluation of patients with BrS.

Novel Epicardial Access Technique Facilitated by Carbon Dioxide Insufflation of the Pericardium for Ablation of Ventricular Arrhythmias: Lessons From the Early Experience From a Single Centre in Australia.

INTRODUCTION: Epicardial access for mapping and ablation of the epicardial substrate may be required in catheter ablation of ventricular tachycardias (VT). However, high complication rates are associated with the standard epicardial access approach. Recently, a novel method of intentional coronary vein (CV) exit with pericardial CO2 insufflation to facilitate epicardial access has been described. This study describes our initial experience with this technique. METHODS: Patients undergoing epicardial VT ablation between 1 February 2021 to 31 May 2022 at the Royal Prince Alfred Hospital, Sydney, NSW, were included in this study. Via femoral venous access, a branch of the coronary sinus was sub-selected and intentional CV exit was performed with a high tip load coronary angioplasty wire. A microcatheter was then advanced over the wire into the pericardial space, followed by pericardial CO2 insufflation, facilitating subxiphoid pericardial puncture. RESULTS: Five (5) patients underwent epicardial access for VT mapping and ablation. All patients had successful intentional CV exit and CO2 facilitated epicardial access. The mean time to successful epicardial access was 37.2±17.5 minutes. With increasing operator experience, there was improvement in epicardial access times, with the fifth case requiring only 13 minutes. There was one case of inadvertent right ventricular puncture (without haemodynamic or ventilatory compromise) due to inappropriate CO2 insufflation into the right ventricle. Epicardial access was successful on the second attempt. CONCLUSION: This is the first case series of epicardial access facilitated by CO2 insufflation in Australia. This technique enabled successful epicardial access in all patients in our early experience, with no adverse outcomes from epicardial access. With increasing operator experience, this technique may allow for more widespread adoption of up-front epicardial access for the treatment of VT.

The role of genetic testing in diagnosis and care of inherited cardiac conditions in a specialised multidisciplinary clinic.

BACKGROUND: The diagnostic yield of genetic testing for inherited cardiac diseases is up to 40% and is primarily indicated for screening of at-risk relatives. Here, we evaluate the role of genomics in diagnosis and management among consecutive individuals attending a specialised clinic and identify those with the highest likelihood of having a monogenic disease. METHODS: A retrospective audit of 1697 consecutive, unrelated probands referred to a specialised, multidisciplinary clinic between 2002 and 2020 was performed. A concordant clinical and genetic diagnosis was considered solved. Cases were classified as likely monogenic based on a score comprising a positive family history, young age at onset, and severe phenotype, whereas low-scoring cases were considered to have a likely complex aetiology. The impact of a genetic diagnosis was evaluated. RESULTS: A total of 888 probands fulfilled the inclusion criteria, and genetic testing identified likely pathogenic or pathogenic (LP/P) variants in 330 individuals (37%) and suspicious variants of uncertain significance (VUS) in 73 (8%). Research-focused efforts identified 46 (5%) variants, missed by conventional genetic testing. Where a variant was identified, this changed or clarified the final diagnosis in a clinically useful way for 51 (13%). The yield of suspicious VUS across ancestry groups ranged from 15 to 20%, compared to only 10% among Europeans. Even when the clinical diagnosis was uncertain, those with the most monogenic disease features had the greatest diagnostic yield from genetic testing. CONCLUSIONS: Research-focused efforts can increase the diagnostic yield by up to 5%. Where a variant is identified, this will have clinical utility beyond family screening in 13%. We demonstrate the value of genomics in reaching an overall diagnosis and highlight inequities based on ancestry. Acknowledging our incomplete understanding of disease phenotypes, we propose a framework for prioritising likely monogenic cases to solve their underlying cause of disease.

Concealed Cardiomyopathy in Autopsy-Inconclusive Cases of Sudden Cardiac Death and Implications for Families.

BACKGROUND: Genetic testing following sudden cardiac death (SCD) is currently guided by autopsy findings, despite the inherent challenges of autopsy examination and mounting evidence that malignant arrhythmia may occur before structural changes in inherited cardiomyopathy, so-called "concealed cardiomyopathy" (CCM). OBJECTIVES: The authors sought to identify the spectrum of genes implicated in autopsy-inconclusive SCD and describe the impact of identifying CCM on the ongoing care of SCD families. METHODS: Using a standardized framework for adjudication, autopsy-inconclusive SCD cases were identified as having a structurally normal heart or subdiagnostic findings of uncertain significance on autopsy. Genetic variants were classified for pathogenicity using the American College of Medical Genetics and Genomics guidelines. Family follow-up was performed where possible. RESULTS: Twenty disease-causing variants were identified among 91 autopsy-inconclusive SCD cases (mean age 25.4 ± 10.7 years) with a similar rate regardless of the presence or absence of subdiagnostic findings (25.5% vs 18.2%; P = 0.398). Cardiomyopathy-associated genes harbored 70% of clinically actionable variants and were overrepresented in cases with subdiagnostic structural changes at autopsy (79% vs 21%; P = 0.038). Six of the 20 disease-causing variants identified were in genes implicated in arrhythmogenic cardiomyopathy. Nearly two-thirds of genotype-positive relatives had an observable phenotype either at initial assessment or subsequent follow-up, and 27 genotype-negative first-degree relatives were released from ongoing screening. CONCLUSIONS: Phenotype-directed genetic testing following SCD risks under recognition of CCM. Comprehensive evaluation of the decedent should include assessment of genes implicated in cardiomyopathy in addition to primary arrhythmias to improve diagnosis of CCM and optimize care for families.

Congenital Long QT Syndrome.

Congenital long QT syndrome (LQTS) encompasses a group of heritable conditions that are associated with cardiac repolarization dysfunction. Since its initial description in 1957, our understanding of LQTS has increased dramatically. The prevalence of LQTS is estimated to be ∼1:2,000, with a slight female predominance. The diagnosis of LQTS is based on clinical, electrocardiogram, and genetic factors. Risk stratification of patients with LQTS aims to identify those who are at increased risk of cardiac arrest or sudden cardiac death. Factors including age, sex, QTc interval, and genetic background all contribute to current risk stratification paradigms. The management of LQTS involves conservative measures such as the avoidance of QT-prolonging drugs, pharmacologic measures with nonselective ß-blockers, and interventional approaches such as device therapy or left cardiac sympathetic denervation. In general, most forms of exercise are considered safe in adequately treated patients, and implantable cardioverter-defibrillator therapy is reserved for those at the highest risk. This review summarizes our current understanding of LQTS and provides clinicians with a practical approach to diagnosis and management.

An Observational Study of Clinical and Health System Factors Associated With Catheter Ablation and Early Ablation Treatment for Atrial Fibrillation in Australia.

OBJECTIVE: To investigate clinical and health system factors associated with receiving catheter ablation (CA) and earlier ablation for non-valvular atrial fibrillation (AF). METHODS: We used hospital administrative data linked with death registrations in New South Wales, Australia for patients with a primary diagnosis of AF between 2009 and 2017. Outcome measures included receipt of CA versus not receiving CA during follow-up (using Cox regression) and receipt of early ablation (using logistic regression). RESULTS: Cardioversion during index admission (hazard ratio [HR] 1.96; 95% CI 1.75-2.19), year of index admission (HR 1.07; 95% CI 1.05-1.10), private patient status (HR 2.65; 95% CI 2.35-2.97), and living in more advantaged areas (HR 1.18; 95% CI 1.13-1.22) were associated with a higher likelihood of receiving CA. A history of congestive heart failure, hypertension, diabetes, and myocardial infarction were associated with a lower likelihood of receiving CA. Private patient status (odds ratio [OR] 2.04; 95% CI 1.59-2.61), cardioversion during index admission (OR 1.25; 95% CI 1.0-1.57), and history of diabetes (OR 1.6; 95% CI 1.06-2.41) were associated with receiving early ablation. CONCLUSIONS: Beyond clinical factors, private patients are more likely to receive CA and earlier ablation than their public counterparts. Whether the earlier access to ablation procedures in private patients is leading to differences in outcomes among patients with atrial fibrillation remains to be explored.

Systematic review of electrophysiology procedures in patients with obstruction of the inferior vena cava.

AIMS: The objective of the study was to conduct a systematic review to describe and compare the different approaches for performing cardiac electrophysiology (EP) procedures in patients with interrupted inferior vena cava (IVC) or equivalent entities causing IVC obstruction. METHODS: We conducted a structured search to identify manuscripts reporting EP procedures with interrupted IVC or IVC obstruction of any aetiology published up until August 2020. No restrictions were applied in the search strategy. We also included seven local cases that met inclusion criteria. RESULTS: The analysis included 142 patients (mean age 48.9 years; 48% female) undergoing 143 procedures. Obstruction of the IVC was not known before the index procedure in 54% of patients. Congenital interruption of IVC was the most frequent cause (80%); and, associated congenital heart disease (CHD) was observed in 43% of patients in this setting. The superior approach for ablation was the most frequently used strategy (52%), followed by inferior approach via the azygos or hemiazygos vein (24%), transhepatic approach (14%), and retroaortic approach (10%). Electroanatomical mapping (58%), use of long sheaths (41%), intracardiac echocardiography (19%), transesophageal echocardiography (15%) and remote controlled magnetic navigation (13%) were used as adjuncts to aid performance. Ablation was successful in 135 of 140 procedures in which outcomes were reported. Major complications were only reported in patients undergoing AF ablation, including two patients with pericardial effusion, one of whom required surgical repair, and another patient who died after inadvertent entry into an undiagnosed atrioesophageal fistula from a previous procedure. CONCLUSION: The superior approach is most frequent approach for performing EP procedures in the setting of obstructed IVC. Transhepatic approach is a feasible alternative, and may provide a "familiar approach" for transseptal access when it is required. Adjunctive use of long sheaths, intravascular echocardiography, electro-anatomical mapping and remote magnetic navigation may be helpful, especially if there is associated complex CHD. With careful planning, EP procedures can usually be successfully performed with a low risk of complications.

A unique case report of relapsing eosinophilic myocarditis causing atrial myopathy and persistent sinus arrest.

BACKGROUND: Eosinophilic myocarditis (EM) is a rare and devastating condition. The underlying cause of EM is unknown, and the natural history is not well understood. CASE SUMMARY: A 20-year-old male presented in cardiogenic shock with preceding 24-h history of pleuritic chest pain associated with nausea and vomiting. Electrocardiogram showed sinus tachycardia with widespread ST elevation, significantly raised high-sensitivity troponin T, and raised white cell count with eosinophilia. Transthoracic echocardiogram demonstrated severe left ventricular (LV) impairment and a moderate-sized pericardial effusion. Right ventricular (RV) endomyocardial biopsy and bone marrow biopsy were performed, with both demonstrating prominent eosinophilia. He was initiated on pulse methylprednisolone leading to rapid clinical improvement with normalization of LV function. Day 9 after discharge, he was readmitted to hospital with presyncope and right heart failure. Electrocardiogram revealed junctional escape rhythm, and cardiac magnetic resonance imaging showed scarring confined to the atria. The patient was treated with mepolizumab and underwent an electrophysiology study with electroanatomical mapping, demonstrating sinus arrest and the absence of electrical activity throughout the right atrium. After much deliberation, an implantable cardioverter-defibrillator was implanted with a deep septal RV pacing lead and an apical RV defibrillator lead. DISCUSSION: We present a unique case of EM with two distinct phases: the first marked by severe LV impairment resolving with immunosuppression; the second characterized by atrial cardiomyopathy leading to persistent symptomatic sinus arrest necessitating permanent pacing. Close follow-up of EM after initial remission is essential to monitor for further complications including heart failure and arrhythmias.

Electrocardiographic QRS duration is influenced by body mass index and sex.

BACKGROUND: Electrocardiogram (ECG) measured QRS duration has been shown to influence cardiovascular outcomes. However, there is paucity of data on whether ECG QRS duration is influenced by obesity and sex in large populations. METHODS: All ECGs performed by a pathology provider over a 2-year period were included. ECGs with confounding factors and those not in sinus rhythm were excluded from the primary analysis. RESULTS: Of the 76,220 who met the inclusion criteria, 41,685 (55%) were females. The median age of the study cohort was 61 years (interquartile [IQR] range 48-71 years). The median QRS duration was 86 ms (IQR 80-94 ms). The median BMI was 27.6 kg/m2 (IQR 24.2-31.8 kg/m2). When stratified according to the World Health Organization classification of BMI < 18.50 kg/m2, 18.50-24.99 kg/m2, 25.00-29.99 kg/m2, and ≥ 30.00 kg/m2, the median QRS durations were 82 ms (IQR 76-88 ms), 86 ms (IQR 80-92 ms), 88 ms (IQR 80-94 ms) and 88 ms (IQR 82-94 ms), respectively (p < 0.001 for linear trend). Median QRS duration for females was 84 ms (IQR 78-88 ms); for males, it was 92 ms (IQR 86-98 ms), p < 0.001. Compared to males, females had narrower QRS complexes at similar age and similar BMI. In multiple linear regression analysis, BMI correlated positively with QRS duration (standardized beta 0.095, p < 0.001) independent of age, sex, and heart rate. CONCLUSIONS: In this large cohort there was a positive association between increasing BMI and QRS duration. Females had narrower QRS duration than males at similar age and similar BMI.

Management of Congenital Long-QT Syndrome: Commentary From the Experts.

While published guidelines are useful in the care of patients with long-QT syndrome, it can be difficult to decide how to apply the guidelines to individual patients, particularly those with intermediate risk. We explored the diversity of opinion among 24 clinicians with expertise in long-QT syndrome. Experts from various regions and institutions were presented with 4 challenging clinical scenarios and asked to provide commentary emphasizing why they would make their treatment recommendations. All 24 authors were asked to vote on case-specific questions so as to demonstrate the degree of consensus or divergence of opinion. Of 24 authors, 23 voted and 1 abstained. Details of voting results with commentary are presented. There was consensus on several key points, particularly on the importance of the diagnostic evaluation and of ß-blocker use. There was diversity of opinion about the appropriate use of other therapeutic measures in intermediate-risk individuals. Significant gaps in knowledge were identified.

"Concealed cardiomyopathy" as a cause of previously unexplained sudden cardiac arrest.

BACKGROUND: Genetic heart disease is a common cause of sudden cardiac arrest (SCA) in the young and those without an ischaemic precipitant. Identifying a cause of SCA in these patients allows for targeted care and family screening. Current guidelines recommend limited, phenotype-guided genetic testing in SCA survivors where a specific genetic condition is suspected and genetic testing is not recommended in clinically-idiopathic SCA survivors. OBJECTIVE: To investigate the diagnostic utility of broad, multi-phenotype genetic testing in clinically-idiopathic SCA survivors. METHODS: Clinically-idiopathic SCA survivors underwent analysis of genes known to be associated with either cardiomyopathy or primary arrhythmia syndromes, following referral to a specialised genetic heart disease clinic in Sydney, Australia between 1997 and 2019. Comprehensive review of clinical records, investigations and re-appraisal of genetic data according to current variant classification criteria was performed. RESULTS: In total, 22% (n = 8/36) of clinically-idiopathic SCA survivors (mean age 36.9 ± 16.9 years, 61% male) had a disease-causing variant identified on broad genetic testing. Of these, 7 (88%) variants resided in cardiomyopathy-associated genes (ACTN2, DES, DSP, MYBPC3, MYH7, PKP2) despite structurally normal hearts or sub-diagnostic structural changes at the time of arrest, so-called "concealed cardiomyopathy". Only one SCA survivor had a variant identified in a channelopathy associated gene (SCN5A). CONCLUSION: Extended molecular analysis with multi-phenotype genetic testing can identify a "concealed cardiomyopathy", and increase the diagnosis rate for clinically-idiopathic SCA survivors.

Long-Term Follow-Up of Mortality and Heart Failure Hospitalisation in Patients With Intracardiac Device-Related Tricuspid Regurgitation.

INTRODUCTION: Tricuspid regurgitation (TR) is a known complication of cardiac implantable electronic devices (CIED). A better understanding of the patient population affected by this complication and their outcomes is needed. The aims of our study were to: 1) describe the incidence of CIED-related tricuspid regurgitation; 2) identify patient characteristics conferring risk; 3) assess the long-term risk of hospitalisation for heart failure and mortality in patients with this complication. METHODS: This was a retrospective cohort study of 2,265 patients that had a de novo device implantation at a tertiary referral centre between January 2010 and December 2017. Patients with echocardiograms prior to and at least 3 months after device implantation were included. Patients with moderate or severe TR at baseline were excluded. RESULTS: Following screening of medical records, 165 patients were analysed. Forty-four (44) (27%) patients developed new-onset moderate or severe device-related TR, without a significant difference between patients with permanent pacemaker (PPM) and implantable cardioverter-defibrillator (ICD). Patients with CIED-related tricuspid regurgitation had a higher rate of hospitalisation for heart failure than those without (63.6% vs 34.7%, p=0.001) during a median follow-up of 29 months (IQR 13-60 months). Subsequent analyses showed that the association between CIED-related TR and heart failure hospitalisation only became significant in the period beyond 12 months following CIED implantation. Piecewise Cox regression analysis stratified at 12 months of follow-up showed that CIED-related TR was associated with an increased risk of heart failure hospitalisation beyond 12 months after adjustment for differences in baseline characteristics (HR 1.99, 95% CI 1.05-3.76, p=0.03). There was a higher mortality rate in the group with CIED-related TR; however, this did not reach significance (36.3% vs 22.3%, p=0.09). CONCLUSION: CIED-related TR is common and clinically significant with serious implications for long-term outcomes, especially congestive heart failure.