Ablation versus anti-arrhythmic therapy for reducing all hospital episodes from recurrent atrial fibrillation: a prospective, randomized, multi-centre, open label trial.

AIMS: There is rising healthcare utilization related to the increasing incidence and prevalence of atrial fibrillation (AF) worldwide. Simplifying therapy and reducing hospital episodes would be a valuable development. The efficacy of a streamlined AF ablation approach was compared to drug therapy and a conventional catheter ablation technique for symptom control in paroxysmal AF. METHODS AND RESULTS: We recruited 321 patients with symptomatic paroxysmal AF to a prospective randomized, multi-centre, open label trial at 13 UK hospitals. Patients were randomized 1:1:1 to cryo-balloon ablation without electrical mapping with patients discharged same day [Ablation Versus Anti-arrhythmic Therapy for Reducing All Hospital Episodes from Recurrent (AVATAR) protocol]; optimization of drug therapy; or cryo-balloon ablation with confirmation of pulmonary vein isolation and overnight hospitalization. The primary endpoint was time to any hospital episode related to treatment for atrial arrhythmia. Secondary endpoints included complications of treatment and quality-of-life measures. The hazard ratio (HR) for a primary endpoint event occurring when comparing AVATAR protocol arm to drug therapy was 0.156 (95% CI, 0.097-0.250; P < 0.0001 by Cox regression). Twenty-three patients (21%) recorded an endpoint event in the AVATAR arm compared to 76 patients (74%) within the drug therapy arm. Comparing AVATAR and conventional ablation arms resulted in a non-significant HR of 1.173 (95% CI, 0.639-2.154; P = 0.61 by Cox regression) with 23 patients (21%) and 19 patients (18%), respectively, recording primary endpoint events (P = 0.61 by log-rank test). CONCLUSION: The AVATAR protocol was superior to drug therapy for avoiding hospital episodes related to AF treatment, but conventional cryoablation was not superior to the AVATAR protocol. This could have wide-ranging implications on how demand for AF symptom control is met. TRIAL REGISTRATION: Clinical Trials Registration: NCT02459574.

Chronic reduction of store operated Ca2+ entry is viable therapeutically but is associated with cardiovascular complications.

Loss of function mutations in store-operated Ca2+ entry (SOCE) are associated with severe paediatric disorders in humans, including combined immunodeficiency, anaemia, thrombocytopenia, anhidrosis and muscle hypotonia. Given its central role in immune cell activation, SOCE has been a therapeutic target for autoimmune and inflammatory diseases. Treatment for such chronic diseases would require prolonged SOCE inhibition. It is, however, unclear whether chronic SOCE inhibition is viable therapeutically. Here we address this issue using a novel genetic mouse model (SOCE hypomorph) with deficient SOCE, nuclear factor of activated T cells activation, and T cell cytokine production. SOCE hypomorph mice develop and reproduce normally and do not display muscle weakness or overt anhidrosis. They do, however, develop cardiovascular complications, including hypertension and tachycardia, which we show are due to increased sympathetic autonomic nervous system activity and not cardiac or vascular smooth muscle autonomous defects. These results assert that chronic SOCE inhibition is viable therapeutically if the cardiovascular complications can be managed effectively clinically. They further establish the SOCE hypomorph line as a genetic model to define the therapeutic window of SOCE inhibition and dissect toxicities associated with chronic SOCE inhibition in a tissue-specific fashion. KEY POINTS: A floxed stromal interaction molecule 1 (STIM1) hypomorph mouse model was generated with significant reduction in Ca2+ influx through store-operated Ca2+ entry (SOCE), resulting in defective nuclear translocation of nuclear factor of activated T cells, cytokine production and inflammatory response. The hypomorph mice are viable and fertile, with no overt defects. Decreased SOCE in the hypomorph mice is due to poor translocation of the mutant STIM1 to endoplasmic reticulum-plasma membrane contact sites resulting in fewer STIM1 puncta. Hypomorph mice have similar susceptibility to controls to develop diabetes but exhibit tachycardia and hypertension. The hypertension is not due to increased vascular smooth muscle contractility or vascular remodelling. The tachycardia is not due to heart-specific defects but rather seems to be due to increased circulating catecholamines in the hypomorph. Therefore, long term SOCE inhibition is viable if the cardiovascular defects can be managed clinically.

Diagnostic role of head-up tilt test in patients with cough syncope.

AIMS: The aim of this study was to describe the head-up tilt (HUT) test and carotid sinus massage (CSM) responses, and the occurrence of syncope with coughing during HUT in a large cohort of patients. METHODS AND RESULTS: A total of 5133 HUT were retrospectively analysed to identify patients with cough syncope. Head-up tilt followed by CSM were performed. Patients were made to cough on two separate occasions in an attempt to reproduce typical clinical symptoms on HUT. Patients with cough syncope were compared with 29 age-matched control patients with syncope unrelated to coughing. A total of 29 patients (26 male, age 49 ± 14 years) with cough syncope were identified. Coughing during HUT reproduced typical prodromal symptoms of syncope in 16 (55%) patients and complete loss of consciousness in 2 (7%) patients, with a mean systolic blood pressure reduction of 45 ± 26 mmHg, and a mean increase in heart rate of 13 ± 8 b.p.m. No syncope or symptoms after coughing were observed in the control group. The HUT result was positive in 13 (48%) patients with the majority of positive HUT responses being vasodepressor (70% of positive HUT). Carotid sinus massage was performed in 18 patients being positive with a vasodepressor response causing mild pre-syncopal symptoms in only 1 patient. CONCLUSION: Syncope during coughing is a result of hypotension, rather than bradycardia. Coughing during HUT is a useful test in patients suspected to have cough syncope but in whom the history is not conclusive.

Cardiac rehabilitation for participants with implantable cardiac devices: A systematic review and meta-analysis.

Aim: The aim is to discuss efficacy and safety of exercise-based cardiac rehabilitation (CR) programmes in participants with implantable cardiac devices compared with usual care. Methods: MEDLINE, EMBASE and Cochrane databases were searched from inspection till July 15, 2022. Randomized controlled trials were included if they enrolled adult participants with implantable cardiac devices and tested exercise-based CR interventions in comparison with any control. Risk of bias was assessed, and endpoints data were pooled using random-effects model. Results: Sixteen randomized trials enrolling 2053 participants were included. Study interventions differed between studies in terms of programme components, setting, exercise intensity, and follow-up. All studies included physical exercise component. In both implantable cardioverter defibrillators (ICD) and cardiac resynchronization therapy (CRT) groups, exercise training in CR programmes improved peak oxygen uptake (VO2) [(mean difference (MD) 2.08 ml/kg/min; 95 % CI: 1.44-2.728, p < 0.0001; I2 = 99 %) and (MD 2.24 ml/kg/min; 95 % CI: 1.43-3.04, p < 0.0001; I2 = 96 %), respectively] and 6-min walk test in ICD group (MD 41.51 m; 95 % CI: 15.19-67.82 m, p = 0.002; I2 = 95 %) compared with usual care. In CRT group, there was no statistically significant improvement in left ventricular ejection fraction change between comparison groups. The results were consistent in subgroup analysis according to high or low-to-moderate exercise intensity for change in peak VO2 and ejection fraction in CRT group. There was no difference in number of ICD shocks between the comparators. Conclusion: Exercise-based CR programmes appear to be safe when enrolling participants with implantable cardiac devices and leading to favourable functional outcomes.

Malfunction of subpectorally implanted cardiac resynchronization therapy defibrillators due to weakened header bond.

BACKGROUND: Implantable cardioverter defibrillator (ICD) implantation has increased significantly over the last 10 years. Concerns about the safety and reliability of ICD systems have been raised, with premature lead failure and battery malfunctions accounting for the majority of reported adverse events. We describe the unique mode of presentation, diagnosis, and management of cardiac resynchronization therapy defibrillators (CRT-D) malfunctions that were caused by weakened bonding between the generator and header. METHODS AND RESULTS: Between June 2008 and December 2009, 22 Teligen™ ICDs and 24 Cognis™ CRT-Ds were implanted subpectorally at our institution, until a product advisory was issued. Of 24 Cognis™ CRT-D implants, 3 patients presented with CRT-D malfunctions. All our cases presented with initially intermittent and then persisting increases in shock lead impedance, associated with nonphysiological noise in the shock electrogram channels. These issues were rectified by generator change. Postexplant laboratory analysis confirmed inadequate bonding between device header and titanium casing in all cases, resulting in loosening and rocking of the header followed by fatigue-induced fracture of the shock circuitry. CONCLUSION: Weakened bonding between the header and generator casing of subpectorally implanted CRT-Ds can result in fractures and malfunction of the HV circuit. Physicians monitoring patients with devices affected by the product advisory should remain vigilant in order to diagnose and manage similar device malfunction expediently.

Robotic assistance and general anaesthesia improve catheter stability and increase signal attenuation during atrial fibrillation ablation.

AIMS: Recurrent arrhythmias after ablation procedures are often caused by recovery of ablated tissue. Robotic catheter manipulation systems increase catheter tip stability which improves energy delivery and could produce more transmural lesions. We tested this assertion using bipolar voltage attenuation as a marker of lesion quality comparing robotic and manual circumferential pulmonary vein ablation for atrial fibrillation (AF). METHODS AND RESULTS: Twenty patients were randomly assigned to robotic or manual AF ablation at standard radiofrequency (RF) settings for our institution (30 W 60 s manual, 25 W 30 s robotic, R30). A separate group of 10 consecutive patients underwent robotic ablation at increased RF duration, 25 W for 60 s (R60). Lesions were marked on an electroanatomic map before and after ablation to measure distance moved and change in bipolar electrogram amplitude during RF. A total of 1108 lesions were studied (761 robotic, 347 manual). A correlation was identified between voltage attenuation and catheter movement during RF (Spearman's rho -0.929, P < 0.001). The ablation catheter was more stable during robotic RF; 2.9 ± 2.3 mm (R30) and 2.6 ± 2.2 mm (R60), both significantly less than the manual group (4.3 ± 3.0 mm, P < 0.001). Despite improved stability, there was no difference in signal attenuation between the manual and R30 group. However, there was increased signal attenuation in the R60 group (52.4 ± 19.4%) compared with manual (47.7 ± 25.4%, P = 0.01). When procedures under general anaesthesia (GA) and conscious sedation were analysed separately, the improvement in signal attenuation in the R60 group was only significant in the procedures under GA. CONCLUSIONS: Robotically assisted ablation has the capability to deliver greater bipolar voltage attenuation compared with manual ablation with appropriate selection of RF parameters. General anaesthesia confers additional benefits of catheter stability and greater signal attenuation. These findings may have a significant impact on outcomes from AF ablation procedures.

Safety and outcome of nurse-led syncope clinics and implantable loop recorder implants.

BACKGROUND: Implantable loop recorders (ILRs) are effective in achieving symptom-rhythm correlation. Data on the diagnostic yield of ILRs, on nurse-led syncope clinics, and on nurse-led ILR implants are limited. OBJECTIVE: We evaluated the safety and efficacy of our nurse-led syncope clinic and nurse-led ILR implants. METHODS: A retrospective study of all consecutive patients undergoing nurse-led ILR implantations was performed between April 2016 and April 2018. Patients were referred from both nurse-led and physician-led clinics. Data were collected on baseline demographic characteristics, referral source, symptom-rhythm correlation, ILR findings, and subsequent changes to management. All ILRs were enrolled into remote monitoring with automatic arrhythmia detection, and all immediate (≤24 hours) ILR implant complications were recorded. Comparisons were made between nurse-led and physician-led clinics and subsequent outcomes. RESULTS: A total of 432 patients with an ILR were identified: 164 (38%) from nurse-led and 268 (62%) from physician-led clinics; 200 (46%) were women (mean age 66.5 ± 18.2 years; mean follow-up duration 28.9 ± 9.5 months). Primary ILR indications were syncope (n = 251 [58%]), presyncope (n = 33 [7%]), palpitation (n = 39 [9%]), cryptogenic stroke (n = 78 [18%]), and other reasons (n = 31 [7%]). No immediate ILR implant complications occurred. Overall, 156 patients (36%) had a change in management as a direct result of ILR findings, with no overall differences between nurse-led and physician-led clinics (35% vs 36%; P = .7). More patients had newly diagnosed atrial fibrillation in physician-led clinics (15% vs 7%; P = .01), and more patients had pacemaker implants for bradycardia in nurse-led clinics (23% vs 13%; P < .01). CONCLUSION: Nurse-led ILR implantation was safe and effective. Nurse-led syncope clinics achieved good symptom-rhythm correlation with resultant significant changes to management in comparison to physician-led clinics. Larger prospective studies are needed to evaluate their longer-term impact.

Protocol update for a randomised controlled feasibility trial of exercise rehabilitation for people with postural tachycardia syndrome: the PULSE study.

BACKGROUND: The PULSE (PostUraL tachycardia Syndrome Exercise) study is a randomised controlled trial assessing the feasibility of conducting a multicentre RCT testing supervised exercise rehabilitation with behavioural and motivational support, compared to best-practice usual care, for people with Postural Tachycardia Syndrome (PoTS). The original trial protocol was published in BMC Pilot & Feasibility Studies (accessible at https://doi.org/10.1186/s40814-020-00702-1 ). The PULSE intervention consists of (1) individual assessment; (2) 12-week, twice-weekly, supervised exercise training; (3) behavioural and motivational support; and (4) guided lifestyle physical activity. The control intervention is best-practice usual care with a single 30-min, one-to-one practitioner appointment, and general advice on safe and effective physical activity. Sixty-two people (aged 18-60 years) with a confirmed diagnosis of PoTS will be invited to enrol on a feasibility RCT with an embedded qualitative study. The primary outcome will be feasibility; process-related measures will include eligibility, recruitment, randomisation and withdrawal rates, along with indicators of exercise programme adherence and acceptability. Secondary physiological, clinical and health-related outcomes will be assessed. In response to the COVID-19 pandemic, here we describe amendments to the trial protocol. METHODS: Restrictions imposed by the COVID-19 pandemic meant it was necessary to change the delivery of the PULSE and control interventions. These changes reflected the need to limit the risk of COVID-19 transmission in a clinical population, some of whom were at increased risk of contracting the virus and suffering serious illness. The major change was that the originally intended centre-based PULSE and control interventions would now be delivered remotely on-line. Subsequently, there were minor changes to the participant eligibility criteria. These decisions followed an on-line co-creation session with people affected by PoTS, and relevant public and professional stakeholders. CONCLUSIONS: We present an update of the original trial protocol in response to the COVID-19 pandemic. No participants were recruited to the original protocol; thus, results will reflect the on-line delivery of the intervention. PULSE will be the first randomised trial to assess the feasibility of conducting a definitive multi-centre RCT testing supervised on-line exercise rehabilitation with behavioural and motivational support, compared to best-practice usual care, for people with PoTS. TRIAL REGISTRATION: ISRCTN45323485 registered on 7 April 2020.

Coronary flow reserve assessed by myocardial contrast echocardiography predicts mortality in patients with heart failure.

AIMS: the aim of the study was to assess whether myocardial contrast echocardiography (MCE) can predict mortality in patients with heart failure. Myocardial viability, ischaemia, and coronary flow reserve (CFR) are predictors of mortality in patients with heart failure. MCE can assess myocardial viability, ischaemia, and CFR at the bedside. However, its prognostic value is unknown in patients with heart failure. METHODS AND RESULTS: eighty-seven patients (age: 68 ± 10 years, 62% male) with heart failure [left ventricular ejection fraction (LVEF): 35% ± 13] underwent low-power intermittent MCE at rest and 2 min after dipyridamole infusion. Resting and stress perfusion score index were derived qualitatively. CFR (MBF at stress/MBF at rest) was calculated by a quantitative method. All patients underwent coronary arteriography. Patients were followed up for mortality. Of the 87 patients, 43 (49%) patients had coronary artery disease. There were 28 (32%) deaths during a mean follow-up of 4.1 ± 1.7 years. Type 2 diabetes [P = 0.02, hazard ratios (HR) 2.43, confidence interval (CI) 1.13-5.22] and CFR (P = 0.001, HR 0.15, CI 0.05-0.45) were independent predictors of mortality. A CFR ≤ 1.5 had a significantly (P < 0.0001) higher mortality of 49 vs. 10% in patients with CFR > 1.5 over the 4 year follow-up period. CONCLUSION: CFR determined by MCE is a powerful predictor of mortality in patients with heart failure.

Impact of a high-density grid catheter on long-term outcomes for structural heart disease ventricular tachycardia ablation.

BACKGROUND: Substrate mapping has highlighted the importance of targeting diastolic conduction channels and late potentials during ventricular tachycardia (VT) ablation. State-of-the-art multipolar mapping catheters have enhanced mapping capabilities. The purpose of this study was to investigate whether long-term outcomes were improved with the use of a HD Grid mapping catheter combining complementary mapping strategies in patients with structural heart disease VT. METHODS: Consecutive patients underwent VT ablation assigned to either HD Grid, Pentaray, Duodeca, or point-by-point (PbyP) RF mapping catheters. Clinical endpoints included recurrent anti-tachycardia pacing (ATP), appropriate shock, asymptomatic non-sustained VT, or all-cause death. RESULTS: Seventy-three procedures were performed (33 HD Grid, 22 Pentaray, 12 Duodeca, and 6 PbyP) with no significant difference in baseline characteristics. Substrate mapping was performed in 97% of cases. Activation maps were generated in 82% of HD Grid cases (Pentaray 64%; Duodeca 92%; PbyP 33% (p = 0.025)) with similar trends in entrainment and pace mapping. Elimination of all VTs occurred in 79% of HD Grid cases (Pentaray 55%; Duodeca 83%; PbyP 33% (p = 0.04)). With a mean follow-up of 372 ± 234 days, freedom from recurrent ATP and shock was 97% and 100% respectively in the HD Grid group (Pentaray 64%, 82%; Duodeca 58%, 83%; PbyP 33%, 33% (log rank p = 0.0042, p = 0.0002)). CONCLUSIONS: This study highlights a step-wise improvement in survival free from ICD therapies as the density of mapping capability increases. By using a high-density mapping catheter and combining complementary mapping strategies in a strict procedural workflow, long-term clinical outcomes are improved.

Safety and cost-effectiveness of same-day complex left atrial ablation.

BACKGROUND: Catheter ablation for complex left-atrial arrhythmia is increasing worldwide with many centres admitting patients overnight. Same-day procedures using conscious sedation carry significant benefits to patients/healthcare providers but data are limited. We evaluated the safety and cost-effectiveness of same-day complex left-atrial arrhythmia ablation. METHOD: Multi-centre retrospective cohort study of all consecutive complex elective left-atrial ablation procedures performed between January 2011 and December 2019. Data were collected on planned same-day discharge versus overnight stay, baseline parameters, procedure details/success, ablation technology, post-operative complications, unplanned overnight admissions/outcomes at 4-months and mortality up to April 2020. A cost analysis of potential savings was also performed. RESULTS: A total of 967 consecutive patients underwent complex left-ablation using radiofrequency (point-by-point ablation aided by 3D-mapping or PVAC catheter ablation with fluoroscopic screening) or cryoballoon-ablation (mean age: 60.9 ± 11.6 years, range 23-83 yrs., 572 [59%] females). The majority of patients had isolation of pulmonary veins alone (n = 846, 87%) and most using conscious-sedation alone (n = 921, 95%). Of the total cohort, 414 (43%) had planned same-day procedure with 35 (8%) admitted overnight due to major (n = 5) or minor (n = 30) complications. Overall acute procedural success-rate was 96% (n = 932). Complications in planned overnight-stay/same-day cohorts were low. At 4-month follow-up there were 62 (6.4%) readmissions (femoral haematomas, palpitation, other reasons); there were 3 deaths at mean follow-up of 42.0 ± 27.6 months, none related to the procedure. Overnight stay costs £350; the same-day ablation policy over this period would have saved £310,450. CONCLUSIONS: Same-day complex left-atrial catheter ablation using conscious sedation is safe and cost-effective with significant benefits for patients and healthcare providers. This is especially important in the current financial climate and Covid-19 pandemic.

Epilepsy and Brugada Syndrome: Association or Uncommon Presentation?

Brugada syndrome (BrS) is a rare genetic disease, of which its clinical manifestations include, but not limited to, syncope or sudden cardiac death. A 30-year-old Bangladeshi male patient with a past medical history of epilepsy was admitted following successful resuscitation from an out of hospital cardiac arrest secondary to ventricular fibrillation. Electrocardiogram (ECG) upon admission was suggestive of BrS type I. His old medical record showed similar ECG 2 months earlier when he had presented with syncope and was diagnosed with seizure. The correlation between BrS and epilepsy has been reported in the literature, discussing whether seizure is an uncommon presentation of BrS or whether epilepsy and BrS share similar genetic mutations that have the potential to cause both arrhythmia and seizures in some patients. Patients who present with seizure and ECG suggestive of Brugada pattern should be evaluated to rule out associated or underlying cardiac arrhythmia.

The Impact of a Nurse-Led Syncope Clinic: Experience from a single UK tertiary center.

BACKGROUND: Syncope is a leading cause of hospital admission and is associated with significant morbidity and mortality. Our Syncope Clinic commenced in 2014 and we sought to evaluate its impact on outcomes (1-yr mortality and syncope re-hospitalization) in patients discharged following syncope admission. METHODS: A single-center study of all consecutive patients discharged with syncope (ICD-10 R55) between April 2012 and 2017. Patient demographics, comorbidities, hospital stay, syncope re-hospitalization, and mortality at one-year were collected. Those subsequently referred and seen in Syncope Clinic were compared with those who were not and predictors of poor outcome were evaluated. RESULTS: In total 2950 patients were discharged from hospital with syncope (median age: 73years, 51% male) with 1220 (41%) discharged same-day; after commencement of Syncope Clinic 231were subsequently reviewed here. Overall mortality was 11%, which was lower in the Syncope Clinic group (3% vs 12%, P < .001). Temporal analysis revealed reduced re-hospitalization following commencement of Syncope Clinic (2% vs 6%, P = .027). Independent predictors of mortality were increasing age (HR 1.03, 95% CI 1.03-1.04), AF (HR 1.6, 95% CI 1.2-2.1), HF (HR 2.2, 95% CI 1.6-3.0), COPD (HR 1.9, 95% CI 1.4-2.7), and CHADS2 score ≥ 1 (HR 1.45, 95% CI 1,12-1.87). Syncope Clinic attendance was associated with reduced mortality (HR 0.3, 95% CI 0.1-0.6). CONCLUSIONS: Syncope patients discharged from hospital had reduced 1yr mortality if seen in subsequent Syncope Clinic. Independent predictors of mortality were COPD, HF, AF, and CHADS2 ≥1. Prospective randomized trials of Syncope Clinics are warranted.

Brugada Syndrome: Clinical Features, Risk Stratification, and Management.

In 1992, the Brugada brothers published a patient series of aborted sudden death, who were successfully resuscitated from ventricular fibrillation (VF). These patients had a characteristic coved ST-segment elevation in the right precordial leads on their 12-lead electrocardiogram with no apparent structural heart abnormality. This disease was referred to as "right bundle branch block, persistent ST-segment elevation, and sudden death syndrome." The term Brugada syndrome (BrS) was first coined for this new arrhythmogenic entity in 1996. BrS is more prevalent in Southeast Asian ethnic groups and was considered a familial disease due to the presence of syncope and/or sudden deaths in several members of the same family, however, the genetic alteration was only noted in 1998. The genetic characterization of BrS has proven to be challenging. The most common and well-established BrS genotype involves loss-of-function mutations in the SCN5A gene, but only represents between 15% and 30% of the diagnosed patients. Patients with BrS can present with a range of symptoms which can include syncope, seizures, and nocturnal agonal breathing due to polymorphic ventricular tachycardia or VF. If these arrhythmias are sustained, sudden cardiac death may result. Despite the significant progress on the understanding of BrS over the last two decades, there remain a number of uncertainties and challenges; we present an update review on the subject.

Protocol for a randomised controlled feasibility trial of exercise rehabilitation for people with postural tachycardia syndrome: the PULSE study.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is an autonomic nervous system disorder causing an abnormal cardiovascular response to upright posture. It affects around 0.2% of the population, most commonly women aged 13 to 50 years. POTS can be debilitating; prolonged episodes of pre-syncope and fatigue can severely affect activities of daily living and health-related quality of life (HRQoL). Medical treatment is limited and not supported by randomised controlled trial (RCT) evidence. Lifestyle interventions are first-line treatment, including increased fluid and salt intake, compression tights and isometric counter-pressure manoeuvres to prevent fainting. Observational studies and small RCTs suggest exercise training may improve symptoms and HRQoL in POTS, but evidence quality is low. METHODS: Sixty-two people (aged 18-40 years) with a confirmed diagnosis of POTS will be invited to enrol on a feasibility RCT with embedded qualitative study. The primary outcome will be feasibility; process-related measures will include the number of people eligible, recruited, randomised and withdrawn, along with indicators of exercise programme adherence and acceptability. Secondary physiological, clinical and health-related outcomes including sub-maximal recumbent bike exercise test, active stand test and HRQoL will be measured at 4 and 7 months post-randomisation by researchers blinded to treatment allocation. The PostUraL tachycardia Syndrome Exercise (PULSE) intervention consists of (1) individual assessment; (2) 12-week, once to twice-weekly, supervised out-patient exercise training; (3) behavioural and motivational support; and (4) guided lifestyle physical activity. The control intervention will be best-practice usual care with a single 30-min, one-to-one practitioner appointment, and general advice on safe and effective physical activity. For the embedded qualitative study, participants (n = 10 intervention, n = 10 control) will be interviewed at baseline and 4 months post-randomisation to assess acceptability and the feasibility of progressing to a definitive trial. DISCUSSION: There is very little high-quality research investigating exercise rehabilitation for people with POTS. The PULSE study will be the first randomised trial to assess the feasibility of conducting a definitive multicentre RCT testing supervised exercise rehabilitation with behavioural and motivational support, compared to best-practice usual care, for people with POTS. TRIAL REGISTRATION: ISRCTN45323485 registered on 7 April 2020.

Tissue Doppler-Derived Left Ventricular Systolic Velocity Is Associated with Lethal Arrhythmias in Cardiac Device Recipients Irrespective of Left Ventricular Ejection Fraction.

BACKGROUND: Life-threatening arrhythmias (LTAs) can trigger sudden cardiac death or provoke implantable cardioverter-defibrillator (ICD) discharges that escalate morbidity and mortality. Longitudinal myofibrils predominate in the subendocardium, which is uniquely sensitive to arrhythmogenic triggers. In this study, we test the hypothesis that mitral annular systolic velocity (S'), a simple routinely obtained tissue Doppler index of LV long-axis systolic function, might predict lethal arrhythmias irrespective of left ventricular ejection fraction (LVEF). METHODS: This is a retrospective analysis of data from 302 patients (mean age, 68 years; LVEF, 32%; 77% male; 52% ischemic; 35% primary prevention; and 53% cardiac resynchronization therapy defibrillator [CRT-D]) who were followed up (median, 15 months) at two centers after receipt of an ICD or CRT-D for diverse indications. S', averaged from tissue Doppler-derived medial and lateral mitral annular velocities, was correlated with the primary outcome of time to sustained ventricular tachycardia (VT) or fibrillation (VF) needing device therapy. RESULTS: The median S' was 5.1 (interquartile range, 4.0-6.2) cm/sec and lower in CRT-D than ICD subjects (4.5 [3.8-5.6] cm/sec vs 5.5 [4.8-6.8] cm/sec, P < .001). Fifty-six (19%) subjects had LTA. Each 1 cm/sec higher S' correlated to a 30% decreased risk of LTA (hazard ratio = 0.70; 95% CI, 0.57-0.87; P = .001) independently of age, sex, ß-blocker use, center, ICD use, and LVEF. Adding S' to the baseline Cox model improved net reclassification (P = .02). An S' > 5.6 cm/sec was the best cutoff and linked to a 58% lower LTA risk than an S' ≤ 5.6 cm/sec (95% CI, 0.23-0.85; P = .02). CONCLUSIONS: A higher S' is associated with a reduced probability of LTA in cardiac device recipients irrespective of LVEF and may have the potential to be used clinically to titrate medical, device, and ablative therapies to mitigate future arrhythmic risk.

Enhanced ventricular tachycardia substrate resolution with a novel omnipolar high-density mapping catheter: the omnimapping study.

BACKGROUND: Defining diastolic slow-conduction channels within the borderzone (BZ) of scar-dependent re-entrant ventricular tachycardia (VT) is key for effective mapping and ablation strategies. Understanding wavefront propagation is driving advances in high-density (HD) mapping. The newly developed Advisor™ HD Grid Mapping Catheter (HD GRID) has equidistant spacing of 16, 1 mm electrodes in a 4 × 4 3 mm interspaced arrangement allowing bipolar recordings along and uniquely across the splines (orthogonal vector) to facilitate substrate mapping in a WAVE configuration (WAVE). The purpose of this study was to determine the relative importance of the WAVE configuration compared to the STANDARD linear-only bipolar configuration (STANDARD) in defining VT substrate. METHODS: Thirteen patients underwent VT ablation at our institution. In all cases, a substrate map was constructed with the HD GRID in the WAVE configuration (conWAVE) to guide ablation strategy. At the end of the procedure, the voltage map was remapped in the STANDARD configuration (conSTANDARD) using the turbo-map function. Detailed post-hoc analysis of the WAVE and STANDARD maps was performed blinded to the configuration. Quantification of total scar area, BZ and dense scar area with assessment of conduction channels (CC) was performed. RESULTS: The substrate maps conSTANDARD vs conWAVE showed statistically significant differences in the total scar area (56 ± 32 cm2 vs 51 ± 30 cm2; p = 0.035), dense scar area (36 ± 25 cm2 vs 29 ± 22 cm2; p = 0.002) and number of CC (3.3 ± 1.6 vs 4.8 ± 2.5; p = 0.026). conWAVE collected more points than the conSTANDARD settings (p = 0.001); however, it used fewer points in map construction (p = 0.023). CONCLUSIONS: The multipolar Advisor™ HD Grid Mapping Catheter in conWAVE provides more efficient point acquisition and greater VT substrate definition of the borderzone particularly at the low-voltage range compared to conSTANDARD. This greater resolution within the low-voltage range facilitated CC definition and quantification within the scar, which is essential in guiding the ablation strategy.

Treatment of ruptured coronary aneurysm with a novel covered stent.

Coronary artery aneurysms are relatively rare but have been diagnosed with increasing frequency since the advent of coronary arteriography. Their reported incidence varies from 1.5% to 5% with male dominance and a predilection for the right coronary artery (RCA), accounting for over 40% of all cases. The most common etiology amongst adults remains atherosclerosis accounting for 50% of coronary aneurysms. We describe the first use of a novel flexible pericardium covered stent for successful treatment of a ruptured coronary aneurysm in 76 year old lady.

Improved prediction of outcome by contrast echocardiography determined left ventricular remodelling parameters compared to unenhanced echocardiography in patients following acute myocardial infarction.

AIMS: Contrast echocardiography has been shown to be a more accurate method of assessing left ventricular (LV) remodelling compared with unenhanced echocardiography after acute myocardial infarction (AMI). However, whether this translated into improved prediction of outcome is not known. METHODS AND RESULTS: Accordingly, a total of 89 consecutive patients undergoing contrast echocardiography and unenhanced echocardiography 7 to 10 days after AMI and reperfusion therapy were followed up for cardiac death (CD) and AMI. LV ejection fraction (LVEF), LV end-systolic volume (ESV), and LV end-diastolic volume were assessed by the two methods independently. Outcome data were obtained (mean 46 +/- 16 months).There were 15 (17%) events (eight CDs and seven AMIs). LVEF and ESV with contrast echocardiography were found to be independent multivariable predictors of CD (P = 0.04 and P = 0.02, respectively) and CD or AMI (P = 0.02 and P = 0.01, respectively). Furthermore, LVEF and ESV with contrast echocardiography provided incremental information for the prediction of CD (P = 0.004 and P = 0.004, respectively) and CD or AMI (P = 0.02 and P = 0.03, respectively). CONCLUSION: Contrast echocardiography provided improved prediction of outcome compared with unenhanced echocardiography following AMI.

Long-term follow-up of normal and structural heart ventricular tachycardia catheter ablation: real-world experience from a UK tertiary centre.

Background: Ventricular tachycardia (VT) is associated with increased morbidity and mortality. There is growing evidence for the effectiveness of catheter ablation in improving outcomes in patients with recurrent VT. Consequently the threshold for referral for VT ablation has fallen over recent years, resulting in increased number of procedures. Objective: To evaluate the effectiveness and safety of VT ablation in a real-world tertiary centre setting. Methods: This is a prospective analysis of all VT ablation cases performed at University Hospital Coventry. Follow-up data were obtained from review of electronic medical records and patient interview. The primary endpoint for normal heart VT was death, cardiovascular hospitalisation and VT recurrence, and for structural heart VT was arrhythmic death, VT storm (>3 episodes within 24 hours) or appropriate shock. Results: Forty-seven patients underwent 53 procedures from January 2012 to January 2018. The mean age ±SD was 57±15 years, 68% were male, 81% were Caucasian and 66% were elective cases. The aetiology of VT included normal heart (49%), ischaemic cardiomyopathy (ICM, 36%), dilated cardiomyopathy (9%), hypertrophic cardiomyopathy (4%) and valvular heart disease (2%). Procedural success occurred in 83%, with six major complications. After a median follow-up of 231 days (lower quartile 133, upper quartile 631), the primary outcome occurred in 28% of patients. There were two non-arrhythmic deaths (4%). At a median follow-up of 193 days (129-468), the primary outcome occurred in 19% of patients with ICM, while VT storm/appropriate shocks occurred in three patients (17%). Conclusions: Our real-world registry confirms that VT ablation is safe, and is associated with high acute procedural success and long-term outcomes comparable with randomised controlled studies.