Pre-stroke anticoagulation for atrial fibrillation in primary English speakers and non-primary English speakers: a multicentre retrospective cohort study.

BACKGROUND: Anticoagulation can prevent most strokes in individuals with atrial fibrillation (AF); however, many people presenting with stroke and known AF are not anticoagulated. Language barriers and poor health literacy have previously been associated with decreased patient medication adherence. The association between language barriers and initiation of anticoagulation therapy for AF is uncertain. AIMS: The aims of this study were to determine whether demographic factors, including non-English primary language, were (1) associated with not being initiated on anticoagulation for known AF prior to admission with stroke, and (2) associated with non-adherence to anticoagulation in the setting of known AF prior to admission with stroke. METHODS: A multicentre retrospective cohort study was conducted for consecutive individuals admitted to the three South Australian tertiary hospitals with stroke units over a 5-year period. RESULTS: There were 6829 individuals admitted with stroke. These cases included 5835 ischaemic stroke patients, 1333 of whom had pre-existing AF. Only 40.0% presenting with ischaemic stroke in the setting of known pre-existing AF were anticoagulated. When controlling for demographics, socioeconomic status and past medical history (including the components of the CHADS2VASC score and anticoagulation contraindications), having a primary language other than English was associated with a lower likelihood of having been commenced on anticoagulant for known pre-stroke AF (odds ratio: 0.52, 95% confidence interval: 0.36-0.77, P = 0.001), but was not associated with a differing likelihood of anticoagulation adherence. CONCLUSIONS: A significant proportion of patients with stroke have pre-existing unanticoagulated AF; these rates are substantially higher if the primary language is other than English. Targeted research and interventions to minimise evidence-treatment gaps in this cohort may significantly reduce stroke burden.

Optimizing electrophysiology studies to prevent sudden cardiac death after myocardial infarction.

AIMS: This study assessed associations of minimum final extrastimulus coupling interval utilized within electrophysiology study (EPS) after myocardial infarction (MI) and possible site of origin of induced ventricular tachycardia (VT) with long-term occurrence of spontaneous ventricular tachyarrhythmia and long-term survival. METHODS AND RESULTS: This prospective study recruited consecutive patients with left ventricular ejection fraction (LVEF) ≤ 40% who underwent EPS days 3-5 after MI between 2004 and 2017. Positive EPS was defined as sustained monomorphic VT cycle length ≥200 ms for ≥10 s or shorter duration if haemodynamic compromise occurred. Each of the four extrastimuli was shortened by 10 ms at a time, until it failed to capture the ventricle (ventricular refractoriness) or induced ventricular tachyarrhythmia. Outcomes included spontaneous ventricular tachyarrhythmia occurrence and all-cause mortality. Shorter coupling interval length of final extrastimulus that induced VT was associated with higher risk of spontaneous ventricular tachyarrhythmia (P < 0.001). Significantly higher rates of spontaneous ventricular tachyarrhythmia (65.2% vs. 23.2%; P < 0.001) were observed for final coupling interval at EPS <200 ms vs. >200 ms. Right bundle branch block (RBBB) morphology of induced VT, with possible site of origin from the left ventricle, was associated with all-cause mortality [hazard ratio (HR) 3.2, P = 0.044] and a composite of spontaneous ventricular tachyarrhythmia recurrence or mortality (HR 1.8, P = 0.043). CONCLUSION: Ventricular tachycardia induced with shorter coupling intervals was associated with higher risk of spontaneous ventricular tachyarrhythymia on follow-up, indicating that the final extrastimulus coupling interval at EPS early after MI should be determined by ventricular refractoriness. Induced VT with possible origin from left ventricle was associated with increased risk of spontaneous ventricular tachyarrhythmia recurrence or death.

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.

Renal Artery Denervation in Resistant Hypertension: The Good, The Bad and The Future.

Early studies of renal artery denervation (RAD) demonstrated efficacy in treating resistant hypertension patients with significant reduction in office blood pressure (BP). This resulted in a growing enthusiasm in the field and a rapid evolution of technology with expanding procedural indications. However, the first randomised sham-controlled trial, Symplicity HTN-3, failed to demonstrate a significant difference in BP reduction between the RAD and the sham control arm, which subsequently led to a major reduction in the clinical application of this procedure. Additionally, the results generated further interest into understanding the mechanism and factors affecting procedural success and identifying the limitations within the field. Many lessons were learned from Symplicity HTN-3 trial, and with recent evidence emerging for RAD in hypertension treatment, the field continues to be refined.

Influence of BMI on Short and Long-Term Outcomes in Patients With STEMI and LV Dysfunction.

BACKGROUND: Recent studies suggest an obesity paradox in individuals with myocardial infarction with better outcomes in obese relative to normal weight patients. We assessed the influence of body mass index (BMI) on early and long-term outcomes in patients with ST elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction. METHODS: Outcomes were assessed according to BMI status in 478 consecutive patients with STEMI and LV dysfunction (ejection fraction [EF]<40%) admitted to Westmead Hospital between 1 January 2004 and 16 April 2014. Normal weight, overweight and obesity were defined as BMI < 25, 25-29.9, and ≥30 kg/m2, respectively. RESULTS: Obese patients were significantly younger (p = 0.01) and were more likely to have hypertension and diabetes (p = 0.04 and 0.001 respectively). In hospital outcomes and 30-day major adverse cardiac events (MACE) were similar in all three groups. There was no difference in recurrent myocardial infarction (MI) and target vessel revascularisation (TVR) during long-term follow-up (mean follow-up 809 days). Overall mortality following hospital discharge was significantly lower in overweight and obese patients. Adjusted hazard ratio for all-cause mortality in normal weight patients compared to overweight patients was 2.4 (95% C.I 1.1-5.3, p= -0.03). The adjusted hazard ratio for all-cause mortality in normal weight patients in comparison to obese patients was 2.7 (95% C.I, 1 -7.4, p = 0.05). Left ventricular ejection fraction (LVEF) and age were other predictors of all-cause mortality. CONCLUSIONS: Normal weight, overweight and obese patients with STEMI and LV dysfunction had similar in hospital outcomes and 30-day outcomes. Long-term all-cause mortality was, however, higher in normal weight patients suggesting the presence of an obesity paradox in this cohort.

Influence of Body Mass Index on Recurrence of Ventricular Arrhythmia, Mortality in Defibrillator Recipients With Ischaemic Cardiomyopathy.

BACKGROUND: Obesity is associated with increased risk of cardiovascular disease. There is little known, however, about the influence of body mass index (BMI) on spontaneously occurring ventricular arrhythmias in patients with ischaemic heart disease. We sought to examine the effect of BMI on the ventricular arrhythmia (VA) recurrence and mortality in defibrillator recipients with ischaemic cardiomyopathy. METHODS: Consecutive patients (n = 123) with ischaemic cardiomyopathy (left ventricular ejection fraction (LVEF) ≤ 40%) and a primary or secondary prevention defibrillator were included. Patients were classified according to their BMI as being normal (18.5-24.99, n = 54/ 43.9%), overweight (2 -29.99, n = 43/ 35%) or obese (>30, n = 26/20.3%). RESULTS: The primary combined endpoint of VA recurrence and mortality occurred in 36%, 5.4% and 11.5% of patients with normal, overweight and obese BMI (p = 0.001). When adjusting for risk factors such as ejection fraction, age and triple vessel disease, on multivariable analysis, normal BMI remained a significant predictor for the primary outcome (Hazard Ratio, Normal vs Overweight = 7.1, 95% CI 1.8-25, p = 0.002: Hazard Ratio, Normal vs Obese = 5.5, 95% CI 1.11-25, p = 0.033). There was a non-significant trend towards reduced survival in patients with normal weight in comparison to overweight and obese patients (p = 0.08). CONCLUSION: In defibrillator recipients with ischaemic cardiomyopathy, BMI appears to be a significant predictor for the combined primary outcome of spontaneously occurring ventricular arrhythmias and mortality. Normal BMI, compared to overweight and obese patients had worse outcomes, suggesting the presence of the obesity paradox in ventricular arrhythmogenesis late post infarction.

Sex Differences in Electrophysiology, Ventricular Tachyarrhythmia, Cardiac Arrest and Sudden Cardiac Death Following Acute Myocardial Infarction.

BACKGROUND: Women experience less appropriate implantable cardioverter-defibrillator (ICD) interventions and are underrepresented in randomised ICD trials. Sex-differences in inducible and spontaneous ventricular tachycardia/fibrillation (VT/VF), cardiac arrest and sudden cardiac death (SCD) early post-myocardial infarction (MI) require further study. METHODS: Consecutive ST-elevation MI patients with left ventricular ejection fraction (LVEF)≤40% underwent electrophysiology study (EPS) to target early prevention of SCD. An ICD was implanted for a positive (inducible monomorphic VT) but not a negative (no arrhythmia or inducible VF) EPS. The combined primary endpoint of VT/VF (spontaneous or ICD-treated), cardiac arrest or SCD was assessed using competing risk survival analysis in women versus men with adjustment for confounders. Logistic regression was used to determine independent predictors of inducible VT at EPS. RESULTS: A total of 403 patients (16.9% female) underwent EPS. Women were significantly older than men but with similar LVEF (31.5 ± 6.3 versus 31.6 ± 6.4%, p = 0.91). Electrophysiology study was positive for inducible VT in 22.1% and 33.4% (p = 0.066) and an ICD implanted in 25.0% and 33.4% (p = 0.356) of women versus men. Appropriate ICD activations (VT/VF) occurred in 5.9% of women and 36.6% of men (p = 0.012). The adjusted cumulative primary endpoint incidence was significantly lower in women than men (1.6% versus 26.5%, p = 0.03). Female sex was not an independent predictor of inducible VT at EPS (HR 0.63, 95% CI 0.33-1.23, p = 0.178). CONCLUSIONS: Women with early post-MI cardiomyopathy had lower VT/VF, cardiac arrest and SCD, compared to men. In ICD recipients the rate of appropriate activations was six-fold less in women compared to men.

Renal Artery Branch Denervation: Evaluation of Lesion Characteristics Using a Thermochromic Liquid Crystal Phantom Model.

BACKGROUND: Lately, combined main vessel and branch ablation has been recommended during radiofrequency (RF) renal artery denervation. Utilising a validated renal artery phantom model, we aimed (1) to determine thermal injury extent (lesion depth, width and circumferential coverage) and electrode-tissue interface temperature for branch renal artery ablation, and (2) to compare the extent of thermal injury for branch versus main vessel ablation using the same RF System. METHODS: We employed a gel based renal artery phantom model simulating variable vessel diameter and flow, which incorporated a temperature sensitive thermochromic-liquid-crystal (TLC) film for assessing RF ablation thermodynamics. Ablations in a branch renal artery model (n = 32) were performed using Symplicity Spyral (Medtronic, Minneapolis, MN, USA). Lesion dimensions defined by the 51 °C isotherm, circumferential injury coverage, and electrode-tissue interface temperature were measured for all ablations at 60 seconds. RESULTS: Lesion dimensions were 2.13 ± 0.13 mm and 4.13 ± 0.18 mm for depth and width, respectively, involving 23% of the vessel circumference. Maximum electrode-tissue interface temperature was 68.31 ± 2.29 °C. No significant difference in lesion depth between branch and main vessel ablations was found (Δ = 0.02 mm, p = 0.60). However, lesions were wider in the branch (Δ=0.49 mm, p < 0.001) with a larger circumferential coverage compared to main vessel (arc angle of 82.02±3.27° versus 54.90±4.36°, respectively). CONCLUSIONS: In the phantom model, branch ablations were of similar depth but had larger width and circumferential coverage compared to main vessel ablations. Concerning safety, no overheating at the electrode-tissue interface was observed.

Retinal microvascular changes in microvascular angina: Findings from the Australian Heart Eye Study.

OBJECTIVE: Microvascular changes in microvascular angina are poorly understood due to difficulties in imaging the coronary microcirculation in vivo. The retinal microvasculature may reflect changes in coronary microcirculation. We assessed microvascular changes in the retina in patients with microvascular angina and compared them with patients with angiographically proven coronary artery disease. METHODS: We performed retinal photography and coronary angiography on 915 patients. Retinal vessel calibers were measured using a validated computer-assisted method; coronary artery disease was graded from coronary angiograms. Microvascular angina was defined as angina with <25% stenosis in all coronary epicardial arteries. RESULTS: A total of 139 patients (15.2%) had microvascular angina, while 776 (84.8%) had coronary artery disease. Participants with microvascular angina and coronary artery disease had similar retinal arteriolar and venular calibers. After adjustment for age, ethnicity, mean arterial pressure, diabetes, current smoking, body mass index, and fellow vessel caliber, women with smaller venules were threefold more likely to have microvascular angina than women with larger venules (multivariable-adjusted odds ratio 3.54, 95% confidence interval 1.35 to 9.24, P < 0.01). This difference was not observed in men. CONCLUSIONS: Microvascular angina in women was associated with microvascular changes distinct from those in coronary artery disease.

Comparison of two different radiofrequency ablation systems for renal artery denervation: Evaluation of short-term and long-term follow up.

OBJECTIVES: To assess the clinical efficacy of renal artery denervation (RAD) in our center and to compare the efficacy of two different radiofrequency (RF) systems. BACKGROUND: Several systems are available for RF renal denervation. Whether there is a difference in clinical efficacy among various systems remains unknown. METHODS: Renal artery denervation was performed on 43 patients with resistant hypertension using either the single electrode Symplicity Flex (n = 20) or the multi-electrode EnligHTN system (n = 23). Median post-procedural follow-up was 32.93 months. The primary outcome was post-procedural change in office blood pressure (BP) within 1 year (short-term follow-up). Secondary outcomes were change in office BP between 1 and 4 years (long-term follow-up) and the difference in office BP reduction between the two systems at each follow-up period. RESULTS: For the total cohort, mean baseline office BP (systolic/diastolic) was 174/94 mmHg. At follow-up, mean changes in office BP from baseline were -19.70/-11.86 mmHg (P < 0.001) and -21.90/-13.94 mmHg (P < 0.001) for short-term and long-term follow-up, respectively. The differences in office BP reduction between Symplicity and EnligHTN groups were 8.96/1.23 mmHg (P = 0.42 for systolic BP, P = 0.83 for diastolic BP) and 9.56/7.68 mmHg (P = 0.14 for systolic BP, P = 0.07 for diastolic BP) for short-term and long-term follow-up, respectively. CONCLUSIONS: In our cohort, there was a clinically significant office BP reduction after RAD, which persisted up to 4 years. No significant difference in office BP reduction between the two systems was found.

Clinical safety of the ProMRI implantable cardioverter-defibrillator systems during head and lower lumbar magnetic resonance imaging at 3 T: results of the ProMRI 3T ENHANCED Master study.

AIMS: There have been no published studies on the safety of magnetic resonance imaging (MRI) at 3 Tesla (3 T) in patients with MRI-conditional implantable cardioverter-defibrillators (ICDs). The aim of this study was to assess clinical safety of the Biotronik ProMRI ICD system during non-diagnostic head and lower lumbar scans under 3 T MRI conditions. METHODS AND RESULTS: The study enrolled 129 patients at 12 sites in Australia, Singapore, and Europe. Predefined head and lower lumbar MR scans (total duration ≈30 min) were performed in 112 patients. Three primary endpoints were evaluated from the pre-MRI to the 1-month post-MRI visit: (i) freedom from serious adverse device effects (SADEs) related to MRI (hypothesized to be >90%); (ii) pacing threshold invariance for all leads (geometric mean of the patient-wise ratios for 1 month vs. pre-MRI was hypothesized to be <1.07); and (iii) sensing amplitude invariance (geometric mean of the ratios was hypothesized to be >0.993). No MRI-related SADE occurred (SADE-free rate 100%, 95% confidence interval 95.98-100%). Pacing threshold and sensing amplitudes fulfilled the invariance hypotheses with high statistical significance (P < 0.0013). No threshold increase >0.5 V or sensing amplitude decrease by >50% was observed (secondary endpoints). Lead impedances, battery capacity, and detection and treatment of arrhythmias by ICDs were not affected by MRI scans. CONCLUSION: The head and lower lumbar scans under specific 3 T MRI conditions were safe in the investigated MR-conditional ICD systems. There was no evidence of harm to the patients or any negative influence of the MRI scan on the implanted systems.

ST-elevation myocardial infarction in a migrant population: a registry-based study of patient treatment and outcomes.

BACKGROUND: Internationally, a growing number of studies has identified race-related disparities in the presentation, treatment and outcomes of patients with ST-elevation myocardial infarction (STEMI). With a large migrant population, Australia presents a unique microcosm in which to study the impact of migrant status and ethnicity in STEMI patients. AIM: To investigate if first-generation migrants differed in presentation, treatment or outcomes following STEMI compared with the Australian-born population. METHODS: We conducted a retrospective observational study using data from a clinician-initiated registry. The study involved 2154 patients who presented to 12 hospitals between 2004 and 2012. Our main outcome measures included time to reperfusion, 30-day mortality and complications. RESULTS: Migrants (n = 1035, 48.8%) were more likely to be older (61 vs 58 years, P < 0.001), diabetic (29.3 vs 21.5%, P < 0.001) and have a prolonged symptom to door time (102 vs 91 min, P = 0.04). Despite lower rates of previous known ischaemic heart disease (22.5 vs 26.6%, P = 0.03), migrants had more diffuse disease (triple vessel or left main (3VD/LM): 29.8 vs 22.0%, P < 0.001) and higher troponin values (3.77 vs 3.22 µg/L, P = 0.01). We found no significant differences in hospital treatment times, intervention types or rates. Multivariate regression identified age, diabetes, female gender and multi-vessel disease as predictors of complications and death at 30 days. CONCLUSIONS: Migrants had longer pre-hospital delays and exhibited different cardiovascular risk profiles than Australian-born patients but received comparable treatment in the acute hospital setting. Higher rates of diabetes and multi-vessel coronary artery disease were seen among migrant patients, indicating a relatively higher risk population.

Sudden Death Risk-Stratification in 2018-2019: The Old and the New.

Sudden Cardiac Death (SCD) is a major public health issue, accounting for half of all cardiovascular deaths world-wide. The implantable cardioverter-defibrillator (ICD) has been solidified as the cornerstone therapy in primary prevention of SCD in ischaemic and non-ischaemic cardiomyopathy. However, what has become increasingly clear is that the left ventricular ejection fraction (LVEF) is an inadequate tool to select patients for a prophylactic ICD, despite its widespread use for this purpose. Use of LVEF alone has poor specificity for arrhythmic versus non-arrhythmic death. In addition, the vast majority of sudden deaths occur in patients with more preserved cardiac function. Alternate predictors of sudden death include electrophysiology study, non-invasive markers of electrical instability, myocardial fibrosis, genetic and bio-markers. The challenge for the future is finding a risk stratification test, or combination of tests, that adequately select patients at high risk of SCD with low competing risk of non-sudden death.

Early and long-term outcomes after manual and remote magnetic navigation-guided catheter ablation for ventricular tachycardia.

Aims: Remote magnetic navigation (RMN) is a safe and effective means of performing ventricular tachycardia (VT) ablation. It may have advantages over manual catheter ablation due to ease of manoeuvrability and catheter stability. We sought to compare the safety and efficacy of RMN vs. manual VT ablation. Methods and results: Retrospective study of procedural outcomes of 139 consecutive VT ablation procedures (69 RMN, 70 manual ablation) in 113 patients between 2009 and 2015 was performed. Remote magnetic navigation was associated with overall higher acute procedural success (80% vs. 60%, P = 0.01), with a trend to fewer major complications (3% vs. 9% P = 0.09). Seventy-nine patients were followed up for a median of 17.0 [interquartile range (IQR) 3.0-41.0] months for the RMN group and 15.5 (IQR 6.5-30.0) months for manual ablation group. In the ischaemic cardiomyopathy subgroup, RMN was associated with longer survival from the composite endpoint of VT recurrence leading to defibrillator shock, re-hospitalization or repeat catheter ablation and all-cause mortality; single-procedure adjusted hazard ratio (HR) 0.240 (95% CI 0.070-0.821) P = 0.023, multi-procedure HR 0.170 (95% CI 0.046-0.632) P = 0.002. In patients with implanted defibrillators, multi-procedure VT-free survival was superior with RMN, HR 0.199 (95% CI 0.060-0.657) P = 0.003. Conclusion: Remote magnetic navigation may improve clinical outcomes after catheter ablation of VT in patients with ischaemic cardiomyopathy. Further prospective clinical studies are required to confirm these findings.

The Use of Intravenous Sotalol in Cardiac Arrhythmias.

Sotalol is a non-selective beta-adrenergic blocking agent without intrinsic sympathomimetic activity. It has the additional unique property of producing pronounced prolongation of the cardiac action potential duration. Sotalol therapy has been indicated for the management of supraventricular arrhythmias, refractory life threatening ventricular arrhythmias and atrial fibrillation/flutter. Until recently, sotalol was only available in the oral form, however, it was approved for intravenous administration by the US Food & Drug Administration (FDA). The current recommendations are for sotalol 75-150mg to be administered intravenously over 5hours. This rate of administration does not reflect the majority of the research that has been performed with regards to intravenous sotalol. Also, the safety of intravenous bolus dosing of 100mg over 1 and 5minutes has previously been demonstrated. The antiarrhythmic action of sotalol depends on its ability to prolong refractoriness in the nodal and extra nodal tissue. Hence, by giving a lower dose over a long duration, patients may not necessarily benefit from its anti-arrhythmic potential. The purpose of this article is to review the research that has been conducted with regards to dosage and safety of intravenous sotalol, its electrophysiological effects and finally the spectrum of arrhythmias in which it has been used to date.