A Prospective, Multicentre Randomised Controlled Trial Comparing Catheter Ablation Versus Antiarrhythmic Drugs in Patients With Structural Heart Disease Related Ventricular Tachycardia: The CAAD-VT Trial Protocol.

IMPORTANCE: Randomised trials have shown that catheter ablation (CA) is superior to medical therapy for ventricular tachycardia (VT) largely in patients with ischaemic heart disease. Whether this translates to patients with all forms and stages of structural heart disease (SHD-e.g., non-ischaemic heart disease) is unclear. This trial will help clarify whether catheter ablation offers superior outcomes compared to medical therapy for VT in all patients with SHD. OBJECTIVE: To determine in patients with SHD and spontaneous or inducible VT, if catheter ablation is more efficacious than medical therapy in control of VT during follow-up. DESIGN: Randomised controlled trial including 162 patients, with an allocation ratio of 1:1, stratified by left ventricular ejection fraction (LVEF) and geographical region of site, with a median follow-up of 18-months and a minimum follow-up of 1 year. SETTING: Multicentre study performed in centres across Australia. PARTICIPANTS: Structural heart disease patients with sustained VT or inducible VT (n=162). INTERVENTION: Early treatment, within 30 days of randomisation, with catheter ablation (intervention) or initial treatment with antiarrhythmic drugs only (control). MAIN OUTCOMES, MEASURES, AND RESULTS: Primary endpoint will be a composite of recurrent VT, VT storm (≥3 VT episodes in 24 hrs or incessant VT), or death. Secondary outcomes will include each of the individual primary endpoints, VT burden (number of VT episodes in the 6 months preceding intervention compared to the 6 months after intervention), cardiovascular hospitalisation, mortality (including all-cause mortality, cardiac death, and non-cardiac death) and LVEF (assessed by transthoracic echocardiography from baseline to 6-, 12-, 24- and 36-months post intervention). CONCLUSIONS AND RELEVANCE: The Catheter Ablation versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT) trial will help determine whether catheter ablation is superior to antiarrhythmic drug therapy alone, in patients with SHD-related VT. TRIAL REGISTRY: Australian New Zealand Clinical Trials Registry (ANZCTR) TRIAL REGISTRATION ID: ACTRN12620000045910 TRIAL REGISTRATION URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377617&isReview=true.

Concurrent Transcatheter Aortic Valve Replacement and Leadless Pacemaker Implantation in a Patient With Aortic Stenosis and Tachycardia-Bradycardia Syndrome.

We present a patient with symptomatic severe aortic stenosis and atrial fibrillation complicated by tachycardia-bradycardia syndrome, deemed too high-risk for surgical valve replacement and referred for transcatheter aortic valve replacement. We show that concurrent implantation of a leadless pacemaker system can be performed successfully with minimal additional risk to the patient, and also, that it can be used to rapidly pace the ventricles to assist in balloon valvuloplasty and prosthetic aortic valve deployment.

Nous présentons le cas d'un patient ayant une sténose aortique symptomatique grave et une fibrillation auriculaire compliquée par un syndrome tachycardie-bradycardie, jugé comme présentant un risque trop élevé pour être candidat à un remplacement valvulaire chirurgical, et orienté pour subir un remplacement valvulaire aortique par cathéter. Nous démontrons que l'implantation concomitante d'un système de stimulateur cardiaque sans fil peut être réalisée avec succès tout en entraînant un risque additionnel minime pour le patient, et que celui-ci peut être utilisé pour stimuler rapidement les ventricules afin de faciliter la valvuloplastie par ballonnet et le déploiement de la prothèse valvulaire aortique.

Human Connexin40 Mutations Slow Conduction and Increase Propensity for Atrial Fibrillation.

BACKGROUND: Patch clamping studies using non-cardiomyocytes revealed that the human connexin40 mutations P88S, G38D, and A96S are associated with reduced gap junction conductances compared to wild type connexin40 (wtCx40). Their effects within myocytes however are unclear. We aimed to characterise P88S, G38D, and A96S after expression in rat hearts and primary cardiomyocyte cultures. METHODS: Adult Sprague-Dawley rat atria were transduced with a lentivector containing a transgene encoding wtCx40, P88S, G38D, A96S, or eGFP (n=6 per transgene). Electrophysiology studies (EPS) were performed just prior to and 7 days after surgery. Left atria were assessed for connexin expression, mRNA levels, inflammation and fibrosis. Primary cardiomyocyte cultures were also transduced with the abovementioned vectors (n=6 per transgene) and monolayer conduction velocities (CV) and protein expression were assessed at 96hours. RESULTS: At day 7 EPS, P wave and induced atrial fibrillation (AF) durations were significantly longer in the mutant groups when compared to wtCx40 controls (p<0.05). There were no significant differences in inflammation, fibrosis, or heart to body weight ratios. Monolayer CV's were reduced in the A96S group compared to the wtCx40 group. While similar to wtCx40 controls, P88S velocities were reduced compared to eGFP controls. G38D monolayers possessed spontaneous fibrillatory activity and could not be paced. Immunofluorescence revealed that P88S and G38D reduced native connexin43 myocyte coupling while A96S appeared to co-localise with connexin43 in gap junctions. Connexin43 mRNA levels were similar between groups. CONCLUSIONS: The A96S, G38D, and P88S Cx40 mutations slow conduction and increased the propensity for inducible AF.

Twelve-lead ambulatory electrocardiographic monitoring in Brugada syndrome: Potential diagnostic and prognostic implications.

BACKGROUND: Patients with Brugada syndrome (BrS) are diagnosed and risk stratified on the basis of a spontaneous or drug-induced type 1 electrocardiographic (ECG) pattern, often at single time points not accounting for variation throughout the day. OBJECTIVES: The purpose of this study was to prospectively assess the overall burden of type 1 Brugada ECG changes using 12-lead 24-hour Holter monitoring and evaluate association with cardiac events. METHODS: From July 1, 2013 to December 31, 2015, patients with BrS were recruited from 3 Australian centers and the Australian Genetic Heart Disease Registry. All patients underwent clinical review, baseline ECG, and 12-lead 24-hour Holter assessment with precordial leads placed in the left and right second, third, and fourth intercostal spaces. The frequency, temporal, and spatial burden of type 1 BrS ECG pattern were analyzed and assessed for association with cardiac events. RESULTS: A total of 54 patients with BrS were recruited (n=44, 81% men; mean age 44 ± 13 years); the mean follow-up was 2.3 ± 2.5 years. Eleven of 32 patients (34%) initially classified as "drug-induced BrS" demonstrated a spontaneous type 1 pattern at least once over 24 hours. Patients with cardiac events had a significantly higher temporal burden of type 1 ST-segment elevation in the 24-hour monitoring period (total area under the curve 21% vs 15%; P = .008), being most pronounced between the hours of 1600 and 2400 (P = .027). CONCLUSION: Patients with BrS traditionally classified as drug-induced can exhibit spontaneous ECG changes with longer-term monitoring, particularly in the evening. Temporal burden on 12-lead Holter monitor was associated with cardiac events. Ambulatory 12-lead ECG monitoring may have potential utility in the diagnosis and risk stratification of patients with BrS.

Novel insight into the natural history of short QT syndrome.

OBJECTIVES: This study intends to gain further insights into the natural history, the yield of familial and genetic screening, and the arrhythmogenic mechanisms in the largest cohort of short QT syndrome (SQTS) patients described so far. BACKGROUND: SQTS is a rare genetic disorder associated with life-threatening arrhythmias, and its natural history is incompletely ascertained. METHODS: Seventy-three SQTS patients (84% male; age, 26 ± 15 years; corrected QT interval, 329 ± 22 ms) were studied, and 62 were followed for 60 ± 41 months (median, 56 months). RESULTS: Cardiac arrest (CA) was the most frequent presenting symptom (40% of probands; range, <1 month to 41 years). The rate of CA was 4% in the first year of life and 1.3% per year between 20 and 40 years; the probability of a first occurrence of CA by 40 years of age was 41%. Despite the male predominance, female patients had a risk profile superimposable to that of men (p = 0.49). The yield of genetic screening was low (14%), despite familial disease being present in 44% of kindreds. A history of CA was the only predictor of recurrences at follow-up (p < 0.0000001). Two patterns of onset of ventricular fibrillation were observed and were reproducible in patients with multiple occurrences of CA. Arrhythmias occurred mainly at rest. CONCLUSIONS: SQTS is highly lethal; CA is often the first manifestation of the disease with a peak incidence in the first year of life. Survivors of CA have a high CA recurrence rate; therefore, implantation of a defibrillator is strongly recommended in this group of patients.

Intramyocardial adiposity after myocardial infarction: new implications of a substrate for ventricular tachycardia.

BACKGROUND: Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. METHODS AND RESULTS: Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI-; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT-; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass-independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation (r) with conduction velocity (r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude (r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups (P>0.29). However, the MI+VT+ group demonstrated a significant (all P≤0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT- group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength (P<0.001). CONCLUSIONS: Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI.

Percutaneous left atrial appendage closure using a PFO closure device.

Percutaneous left atrial appendage (LAA) occlusion is commonly performed using umbrella-shaped devices. However, the utility of such devices is highly dependent on the underlying anatomy of the appendage. For the first time, we report the use of an Occlutech PFO closure device to successfully occlude a left atrial appendage that possessed a circumferential ridge at its mouth. PFO closure devices would also be suitable for the occlusion of left atrial appendages when an incomplete surgical closure results in a circumferential ridge.

Early exercise stress testing is safe after primary percutaneous coronary intervention.

BACKGROUND: The optimal timing of exercise stress testing post primary percutaneous coronary intervention is uncertain with anecdotal evidence suggesting an increased risk of acute myocardial infarction and/or death if performed too early. This has translated into a delayed return to normal life activities following an acute myocardial infarction resulting in an increase in socio-economic burden. AIMS: We hypothesize that early (within 7 days of primary percutaneous coronary intervention) exercise stress testing is safe. METHODS: A prospective study of consecutive patients enrolled into the Cardiac Rehabilitation Program at a tertiary referral centre that underwent primary percutaneous coronary intervention, and who were able to perform a treadmill stress test were recruited. Timing of exercise stress testing was within 7 days post primary percutaneous coronary intervention and outcomes of death, acute myocardial infarction and other major adverse cardiac event were assessed 24 hours post exercise stress testing. RESULTS: Recruited patients (n=230) aged between 29 and 78 (mean age 56 ± 10 years) with 191 being males (83%) and 39 being females (17%). While 28 patients had a positive stress test (12.2%), there were no deaths, acute myocardial infarction or any other major adverse cardiac event within 24 hours of performing the exercise stress testing. Mean METS achieved were 8.1 ± 2.3. CONCLUSIONS: Early exercise stress testing after primary percutaneous coronary intervention appears safe.