Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Neuroprotection provided by hypothermia initiated with high transnasal flow with ambient air in a model of pediatric cardiac arrest.

Clinical trials of hypothermia after pediatric cardiac arrest (CA) have not seen robust improvement in functional outcome, possibly because of the long delay in achieving target temperature. Previous work in infant piglets showed that high nasal airflow, which induces evaporative cooling in the nasal mucosa, reduced regional brain temperature uniformly in half the time needed to reduce body temperature. Here, we evaluated whether initiation of hypothermia with high transnasal airflow provides neuroprotection without adverse effects in the setting of asphyxic CA. Anesthetized piglets underwent sham-operated procedures (n=7) or asphyxic CA with normothermic recovery (38.5°C; n=9) or hypothermia initiated by surface cooling at 10 (n=8) or 120 (n=7) minutes or transnasal cooling initiated at 10 (n=7) or 120 (n=7) minutes after resuscitation. Hypothermia was sustained at 34°C with surface cooling until 20 hours followed by 6 hours of rewarming. At four days of recovery, significant neuronal loss occurred in putamen and sensorimotor cortex. Transnasal cooling initiated at 10 minutes significantly rescued the number of viable neurons in putamen, whereas levels in putamen in other hypothermic groups remained less than sham levels. In sensorimotor cortex, neuronal viability in the four hypothermic groups was not significantly different from the sham group. These results demonstrate that early initiation of high transnasal airflow in a pediatric CA model is effective in protecting vulnerable brain regions. Because of its simplicity, portability, and low cost, transnasal cooling potentially could be deployed in the field or emergency room for early initiation of brain cooling after pediatric CA.

Safety of ventricular arrhythmia radiofrequency ablation with half-normal saline irrigation.

AIMS: Failure of radiofrequency (RF) ablation of ventricular arrhythmias is often due to inadequate lesion size. Irrigated RF ablation with half-normal saline (HNS) has the potential to increase lesion size and reduce sodium delivery to the patient if the same volume of RF irrigant were used for normal saline (NS) and HNS but could increase risks related to steam pops and lesion size. This study aims to assess periprocedural complications and acute ablation outcome of ventricular arrhythmias ablation with HNS. METHODS AND RESULTS: Prospective assessment of outcomes was performed in 1024 endocardial and/or epicardial RF ablation procedures in 935 consecutive patients (median age 64 years, 71.2% men, 73.4% cardiomyopathy, 47.2% sustained ventricular tachycardia). Half-normal saline was selected at the discretion of the treating physician. Radiofrequency ablation power was generally titrated to a ≤15â€…Ω impedance fall with intracardiac echocardiography monitoring. Half-normal saline was used in 900 (87.9%) and NS in 124 (12.1%) procedures. Any adverse event within 30 days occurred in 13.0% of patients treated with HNS RF ablation including 4 (0.4%) strokes/transient ischaemic attacks and 34 (3.8%) pericardial effusions requiring treatment (mostly related to epicardial access). Two steam pops with perforation required surgical repair (0.2%). Patients who received NS irrigation had less severe disease and arrhythmias. In multivariable models, adverse events and acute success of the procedure were not related to the type of irrigation. CONCLUSION: Half-normal saline irrigation RF ablation with power guided by impedance fall and intracardiac echocardiography has an acceptable rate of complications and acute ablation success while administering half of the saline load expected for NS irrigation.

Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Study.

BACKGROUND: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. METHODS: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. RESULTS: Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (P<0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P<0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P<0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value. CONCLUSIONS: PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.

Sex and Race Differences in Cardiac Sarcoidosis Presentation, Treatment and Outcomes.

BACKGROUND: Although sex- and race-based patterns have been described in the extracardiac organ involvement of sarcoidosis, cardiac sarcoidosis (CS)-specific studies are lacking. METHODS: We studied CS presentation, treatment and outcomes based on sex and race in a tertiary-center cohort. Multivariable adjusted Cox proportional hazards and survival analyses were performed for primary composite outcomes (left ventricular assist device, heart transplantation, all-cause death) and for secondary outcomes (ventricular arrhythmia and all-cause death. RESULTS: We identified 252 patients with CS (108 female, 109 Black). At presentation with CS, females vs males (P = 0.001) and Black vs White individuals (P = 0.001) more commonly had symptomatic heart failure (HF), with HF most common in Black females (ANOVA P < 0.001). Treatment differences included more corticosteroid use (90% vs 79%; P = 0.020), higher 1-year prednisone dosage (13 vs 10 mg; P = 0.003) and less frequent early steroid-sparing agent use in males (29% vs 40%; P = 0.05). Black participants more frequently received a steroid-sparing agent (75% vs 60%; P = 0.023). Composite outcome-free survival did not differ by sex or race. Male sex had an adjusted hazard ratio of 2.34 (95% CI 1.13, 4.80; P = 0.021) for ventricular arrhythmia. CONCLUSION: CS course may differ by sex and race and may contribute to distinct clinical CS phenotypes.

Determinants of acute irreversible electroporation lesion characteristics after pulsed field ablation: the role of voltage, contact, and adipose interference.

AIMS: Pulsed field ablation (PFA) is a non-thermal ablative approach in which cardiomyocyte death is obtained through irreversible electroporation (IRE). Data correlating the biophysical characteristics of IRE and lesion characteristics are limited. The aim of this study was to assess the effect of different procedural parameters [voltage, number of cycles (NoCs), and contact] on lesion characteristics in a vegetal and animal model for IRE. METHODS AND RESULTS: Two hundred and four Russet potatoes were used. Pulsed field ablation lesions were delivered on 3 cm cored potato specimens using a multi-electrode circular catheter with its dedicated IRE generator. Different voltage (from 300 to 1200 V) and NoC (from 1 to 5×) protocols were used. The impact of 0.5 and 1 mm catheter-to-specimen distances was tested. A swine animal model was then used to validate the results observed in the vegetable model. The association between voltage, the NoCs, distance, and lesion depth was assessed through linear regression. An almost perfect linear association between lesion depth and voltage was observed (R2 = 0.95; P < 0.001). A similarly linear relationship was observed between the NoCs and the lesion depth (R2 = 0.73; P < 0.001). Compared with controls at full contact, a significant dampening on lesion depth was observed at 0.5 mm distance (1000 V 2×: 2.11 ± 0.12 vs. 0.36 ± 0.04, P < 0.001; 2.63 ± 0.10 vs. 0.43 ± 0.08, P < 0.001). No lesions were observed at 1.0 mm distance. CONCLUSION: In a vegetal and animal model for IRE assessment, PFA lesion characteristics were found to be strongly dependent on voltage settings and the NoCs, with a quasi-linear relationship. The lack of catheter contact was associated with a dampening in lesion depth.

Minimizing Shivering During Targeted Normothermia: Comparison Between Novel Transnasal and Surface Temperature-Modulating Devices.

BACKGROUND: Shivering is a common adverse effect of achieving and maintaining normothermia in neurocritical care patients. We compared the burden of shivering and shivering-related interventions between a novel transnasal temperature-modulating device (tnTMD) and surface cooling temperature-modulating devices (sTMDs) during the first 24 h of targeted normothermia in mechanically ventilated febrile neurocritical care patients. METHODS: This is a case-control study controlling for factors that impact shiver burden: age, sex, body surface area. All patients underwent transnasal cooling (CoolStat, KeyTech, Inc.) as part of an ongoing multicenter clinical trial (NCT03360656). Patients undergoing treatment with sTMDs were selected from consecutively treated patients during the same time period. Data collected included the following: core body temperature (every 2 h), bedside shivering assessment scale (BSAS) score (every 2 h), and administration of antishivering medication for a BSAS score > 1. Time to normothermia (≤ 37.5 °C), as well as temperature burden > 37.5 °C (°C × h), were compared between groups using Student's t-test for mean differences. The proportion of patients requiring interventions, as well as the number of interventions per patient, was compared using the χ2 test. Significance was determined based on a p value < 0.05. RESULTS: There were 10 tnTMD patients and 30 sTMD patients included in the analysis (mean age: 62 ± 4, 30% women, body surface area = 1.97 ± 0.25). There were no differences between groups in temperature at cooling initiation (tnTMD: 38.5 ± 0.2 °C vs. sTMD: 38.7 ± 0.5 °C, p = 0.3), time to ≤ 37.5 °C (tnTMD: 1.8 ± 1.5 h vs. sTMD: 2.9 ± 1.4 h, p = 0.1), or temperature burden > 37.5 (tnTMD: - 0.4 ± 1.13 °C × h vs. sTMD median [IQR]: - 0.57 ± 0.58 °C × h, p = 0.67). The number of tnTMD patients who received pharmacologic shivering interventions was lower than the number of controls (20 vs. 67%, p = 0.01). tnTMD patients also had fewer shivering interventions per patient (0 [range: 0-3] vs. 4 [range: 0-23], p < 0.001). CONCLUSIONS: A transnasal cooling approach achieved similar time to normothermia and temperature burden with less shivering than surface cooling. This approach may be a feasible option to consider for mechanically ventilated febrile neurocritical care patients.

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.3% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).

Clinical characteristics and risk stratification of desmoplakin cardiomyopathy.

AIMS: Desmoplakin (DSP) cardiomyopathy is an increasingly recognized form of arrhythmogenic cardiomyopathy. With a genotype-specific approach, we characterized the diagnosis, natural history, and risk for ventricular arrhythmia and heart failure in DSP cardiomyopathy. METHODS AND RESULTS: We followed 91 individuals [45 probands, 34% male, median age 27.5 years (interquartile interval 20.0-43.9)] with pathogenic or likely pathogenic DSP variants for a median of 4.3 years. Regarding the ventricular involvement, left predominance was most common (n = 22, 28%) followed by bi-ventricular in 12 (15%) and right predominance in 5 (6%). Myocardial injury (chest pain, elevated troponin, normal coronary angiogram) occurred in 20 (22%) individuals. Incidence rates of sustained ventricular arrhythmia and heart failure (ventricular dysfunction ± symptoms) were 5.9 [95% confidence interval (CI): 3.9-9.1] and 6.7 (95% CI: 4.5-9.8) per 100 person-years, respectively. In univariate regression, myocardial injury was associated with sustained ventricular arrhythmia [hazard ratio (HR) 2.53, 95% CI: 1.05-6.11] and heart failure (HR 7.53, 95% CI: 3.10-18.26). After adjustment, left ventricular ejection fraction <35% and right ventricular dysfunction were prognostic for sustained ventricular arrhythmia while proband status and myocardial injury were prognostic for heart failure (all P < 0.05). The sensitivity of the arrhythmogenic right ventricular cardiomyopathy Task Force Criteria in diagnosing left dominant disease was 0.73; 5/22 (23%) of patients with sustained ventricular arrhythmias did not meet these criteria. CONCLUSION: DSP cardiomyopathy affects both ventricles and carries high risk for ventricular arrhythmia and heart failure. Myocardial injury is associated with worse disease outcomes. Both diagnosis and risk stratification of DSP cardiomyopathy need refinement.

Non-invasive localization of premature ventricular focus: A prospective multicenter study.

BACKGROUND: Accurate localization of premature ventricular contractions (PVC) focus is a prerequisite to successful catheter ablation. OBJECTIVE: The objective was to evaluate the software View Into Ventricular Onset (VIVO) accuracy at locating the anatomical origins for premature ventricular contractions. The VIVO device noninvasively creates a model of the patient's heart and torso, with exact locations of 12­lead ECG electrodes, and applies a mathematical algorithm from surface signals to determine the origin of the arrhythmia. We sought to compare the agreement between VIVO-predicted locations to invasive electroanatomical mapping results. METHODS: 51 consecutive patients who presented for PVC ablations at the study centers were recruited. VIVO images were collected at baseline preprocedure and all patients underwent invasive electroanatomical activation mapping of the clinical arrhythmia. Pacing was performed in pre-specified locations in the right and/or left ventricle. The successful sites of ablation and the pacing locations were compared to VIVO predicted locations. The results were adjudicated by physician experts in a blinded fashion. RESULTS: Seven patients were excluded from analyses. VIVO accurately identified the origin of the clinical premature ventricular contractions in 44/44 patients (100.00%). The accuracy in identifying the paced location for all patients (right and left sides of the heart) was 99.5% using the VIVO system. No adverse events were reported. CONCLUSIONS: VIVO is a novel noninvasive system that could be used to help guide ablation procedures with a high degree of accuracy. The VIVO algorithm is easy to use and may be useful in the workflow for ventricular arrhythmia ablation.

Efficacy of catheter ablation for premature ventricular contractions in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Premature ventricular contractions (PVCs) may be found in any stage of arrhythmogenic right ventricular cardiomyopathy (ARVC) and have been associated with the risk of sustained ventricular tachycardia (VT). OBJECTIVE: To investigate the role of PVC ablation in ARVC patients. METHODS: We studied consecutive ARVC patients who underwent PVC ablation due to symptomatic high PVC burden. Mean daily PVC burden and antiarrhythmic drug (AAD) use were assessed before and after the procedure. Complete long-term success was defined as more than 80% reduction in PVC burden off of membrane-active AADs. RESULTS: Eight patients (37 ± 15 years; 4 males) underwent PVC ablation. The mean daily PVC burden before ablation ranged from 5.4% to 24.8%. A total of 7 (87.5%) patients underwent epicardial ablation. Complete acute elimination of PVCs was achieved in 4 (50%) patients (no complications). The mean daily PVC burden variation ranged from an 87% reduction to a 26% increase after the procedure. Over a median follow-up of 345 days (range: 182-3004 days), only one (12.5%) patient presented complete long-term success, and 6 (75%) patients either maintained or increased the need for Class I or Class III AADs. A total of 2 (25%) patients experienced sustained VT for the first time following the ablation procedure, requiring repeat ablation. No death or heart transplantation occurred. CONCLUSION: PVC ablation was not associated with a consistent reduction of the PVC burden in ARVC patients with symptomatic, frequent PVCs. PVC ablation may be reserved for highly symptomatic patients who failed AADs. Additional investigation is required to improve the efficacy of PVC ablation in ARVC patients.

Trans-nasal high-flow dehumidified air in acute migraine headaches: A randomized controlled trial.

BACKGROUND: Intranasal high flow of dehumidified (dry) air results in evaporative cooling of nasal passages. In this randomized clinical trial, we investigated the effect of dry gas induced nasal cooling on migraine headaches. METHODS: In this single-blind study, acute migraineurs were randomized to either nasal high-flow dry oxygen, dry air, humidified oxygen or humidified air (control) at 15 L/min for 15 min. All gases were delivered at 37°C. Severity of headache and other migraine associated symptoms (International Classification for Headache Disorders, 3rd edition criteria) were recorded before and after therapy. The primary endpoint was change in pain scores, while changes in nausea, photosensitivity and sound sensitivity scores served as secondary endpoints. A linear regression model was employed to estimate the impact of individual treatment components and their individual interactions. RESULTS: Fifty-one patients (48 ± 15 years of age, 82% women) were enrolled. When compared to the control arm (humidified air), all therapeutic arms showed a significantly greater reduction in pain scores (primary endpoint) at 2 h of therapy with dry oxygen (-1.6 [95% CI -2.3, -0.9]), dry air (-1.7 [95% CI -2.6, -0.7)]), and humidified oxygen (-2.3 [95% CI -3.5, -1.1]). A significantly greater reduction in 2-h photosensitivity scores was also noted in all therapeutic arms (-1.8 [95% CI -3.2, -0.4], dry oxygen; -1.7 [95% CI -2.9, -0.4], dry air; (-2.1 [95% CI -3.6, -0.6], humidified oxygen) as compared to controls. The presence of oxygen and dryness were independently associated with significant reductions in pain and photosensitivity scores. No adverse events were reported. CONCLUSION: Trans-nasal high-flow dry gas therapy may have a role in reducing migraine associated pain.Clinical Trial registration: NCT04129567.

Left ventricular fibro-fatty replacement in arrhythmogenic right ventricular dysplasia/cardiomyopathy: prevalence, patterns, and association with arrhythmias.

BACKGROUND: Left ventricular (LV) fibrofatty infiltration in arrhythmogenic right ventricular (RV) dysplasia/cardiomyopathy (ARVD/C) has been reported, however, detailed cardiovascular magnetic resonance (CMR) characteristics and association with outcomes are uncertain. We aim to describe LV findings on CMR in ARVD/C patients and their relationship with arrhythmic outcomes. METHODS: CMR of 73 subjects with ARVD/C according to the 2010 Task Force Criteria (TFC) were analyzed for LV involvement, defined as ≥ 1 of the following features: LV wall motion abnormality, LV late gadolinium enhancement (LGE), LV fat infiltration, or LV ejection fraction (LVEF) < 50%. Ventricular volumes and function, regional wall motion abnormalities, and the presence of ventricular fat or fibrosis were recorded. Findings on CMR were correlated with arrhythmic outcomes. RESULTS: Of the 73 subjects, 50.7% had CMR evidence for LV involvement. Proband status and advanced RV dysfunction were independently associated with LV abnormalities. The most common pattern of LV involvement was focal fatty infiltration in the sub-epicardium of the apicolateral LV with a "bite-like" pattern. LGE in the LV was found in the same distribution and most often had a linear appearance. LV involvement was more common with non-PKP2 genetic mutation variants, regardless of proband status. Only RV structural disease on CMR (HR 3.47, 95% CI 1.13-10.70) and prior arrhythmia (HR 2.85, 95% CI 1.33-6.10) were independently associated with arrhythmic events. CONCLUSION: Among patients with 2010 TFC for ARVD/C, CMR evidence for LV abnormalities are seen in half of patients and typically manifest as fibrofatty infiltration in the subepicardium of the apicolateral wall and are not associated with arrhythmic outcomes.

Feasibility study shows concordance between image-based virtual-heart ablation targets and predicted ECG-based arrhythmia exit-sites.

INTRODUCTION: We recently developed two noninvasive methodologies to help guide VT ablation: population-derived automated VT exit localization (PAVEL) and virtual-heart arrhythmia ablation targeting (VAAT). We hypothesized that while very different in their nature, limitations, and type of ablation targets (substrate-based vs. clinical VT), the image-based VAAT and the ECG-based PAVEL technologies would be spatially concordant in their predictions. OBJECTIVE: The objective is to test this hypothesis in ischemic cardiomyopathy patients in a retrospective feasibility study. METHODS: Four post-infarct patients who underwent LV VT ablation and had pre-procedural LGE-CMRs were enrolled. Virtual hearts with patient-specific scar and border zone identified potential VTs and ablation targets. Patient-specific PAVEL based on a population-derived statistical method localized VT exit sites onto a patient-specific 238-triangle LV endocardial surface. RESULTS: Ten induced VTs were analyzed and 9-exit sites were localized by PAVEL onto the patient-specific LV endocardial surface. All nine predicted VT exit sites were in the scar border zone defined by voltage mapping and spatially correlated with successful clinical lesions. There were 2.3 ± 1.9 VTs per patient in the models. All five VAAT lesions fell within regions ablated clinically. VAAT targets correlated well with 6 PAVEL-predicted VT exit sites. The distance between the center of the predicted VT-exit-site triangle and nearest corresponding VAAT ablation lesion was 10.7 ± 7.3 mm. CONCLUSIONS: VAAT targets are concordant with the patient-specific PAVEL-predicted VT exit sites. These findings support investigation into combining these two complementary technologies as a noninvasive, clinical tool for targeting clinically induced VTs and regions likely to harbor potential VTs.

Safety and Feasibility of a Novel Transnasal Cooling Device to Induce Normothermia in Febrile Cerebrovascular Patients.

BACKGROUND: Inducing normothermia with surface cooling temperature modulating devices (TMDs) is cumbersome and often associated with significant shivering. We tested the safety and feasibility of a novel transnasal evaporative cooling device to induce and maintain normothermia in febrile patients following ischemic and hemorrhagic stroke. METHODS: A single-center study utilizing the CoolStat® transnasal cooling device was used to achieve core temperature reduction in mechanically ventilated stroke patients with fever (T ≥ 38.3 C) refractory to acetaminophen by inducing an evaporative cooling energy exchange in the nasal turbinates thru a high flow of dehumidified air into the nasal cavity and out through the mouth. Continuous temperature measurements were obtained from tympanic and core (esophageal or bladder) temperature monitors. Safety assessments included continuous monitoring for hypertension, tachycardia, and raised intracranial pressure (when monitored). Otolaryngology (ENT) evaluations were monitored for any device-related nasal mucosal injury with a pre- and post-visual examination. Shivering was assessed every 30 min using the Bedside Shivering Assessment Scale (BSAS). Duration of device use was limited to 8 h, at which time patients were transitioned to routine care for temperature management. RESULTS: Ten subjects (median age: 54 years, BMI: 32.5 kg/m2, 60% men) were enrolled with normothermia achieved in 90% of subjects. One subject did not achieve normothermia and was later refractory to other TMDs. Median baseline temperature was 38.5 ± 0.1 C, with a reduction noted by 4 h (38.5 ± 0.1 vs 37.3 ± 0.8, P < 0.001) and sustained at 8 h (38.5 ± 0.1 vs 37.1 ± 0.7, P = 0.001). Time to normothermia was 2.6 ± 1.9 h. The median BSAS was 0 (range 0-1) with only 4 episodes necessitating meperidine across 76 h of study monitoring. No treatment was discontinued due to safety concerns. ENT evaluations noted no device-related adverse findings. CONCLUSIONS: Inducing normothermia with a novel transnasal TMD appears to be safe, feasible and not associated with significant shivering. A multicenter trial testing the ability of the CoolStat to maintain normothermia for 24 h is currently underway.

Esophageal injury associated with catheter ablation for atrial fibrillation: Determinants of risk and protective strategies.

Catheter ablation has become an important element in the management of atrial fibrillation. Several technical advances allowed for better safety profiles and lower recurrence rates, leading to an increasing number of ablations worldwide. Despite that, major complications are still reported, and esophageal thermal injury remains a significant concern as atrioesophageal fistula (AEF) is often fatal. Recognition of the mechanisms involved in the process of esophageal lesion formation and the identification of the main determinants of risk have set the grounds for the development and improvement of different esophageal protective strategies. More sensitive esophageal temperature monitoring, safer ablation parameters and catheters, and different energy sources appear to collectively reduce the risk of esophageal thermal injury. Adjunctive measures such as the prophylactic use of proton-pump inhibitors, as well as esophageal cooling or deviation devices, have emerged as complementary methods with variable but promising results. Nevertheless, as a multifactorial problem, no single esophageal protective measure has proven to be sufficiently effective to eliminate the risk, and further investigation is still warranted. Early screening in the patients at risk and prompt intervention in the cases of AEF are important risk modifiers and yield better outcomes.

Exercise restriction is protective for genotype-positive family members of arrhythmogenic right ventricular cardiomyopathy patients.

AIMS: In arrhythmogenic right ventricular cardiomyopathy (ARVC) patients, exercise worsens disease course, so exercise restriction is recommended. However, recommendations for genotype-positive ARVC family members is incompletely resolved. We aimed to provide evidence for exercise recommendations for genotype-positive ARVC family members. METHODS AND RESULTS: Arrhythmogenic right ventricular cardiomyopathy family members inheriting a pathogenic desmosomal variant were interviewed about exercise history from age 10. Exercise was characterized by duration, intensity, and dose (duration*intensity). Associations between exercise and (i) diagnosis by 2010 Task Force Criteria and (ii) development of sustained ventricular arrhythmias were examined. The study included 101 family members (age: 40.5 ± 19.3 years, male: 41%, Plakophilin-2 variant: 81%). Forty-four individuals (44%) met diagnostic criteria and 16 (16%) experienced sustained ventricular arrhythmia. Individuals who met diagnostic criteria had significantly higher average exercise duration and dose, but not peak intensity than those who did not. Only one individual who exercised below the American Heart Association recommended minimum (650 metabolic equivalent of task-hours/year) met diagnostic criteria or experienced sustained ventricular arrhythmia as opposed to 50% of individuals who exceeded it (adjusted odds ratio = 0.03, 95% confidence interval 0.003-0.26). The difference in exercise exposure between affected and unaffected individuals was more striking in females than in males. Females who had done high-dose exercise in adolescence had the worst survival free from diagnosis (P < 0.01). CONCLUSIONS: In phenotype-negative ARVC family members with a pathogenic desmosomal variant, athletic activities should be limited, particularly exercise dose. Exercise may play a greater role in promoting disease in female family members.

Diagnosing arrhythmogenic right ventricular cardiomyopathy by 2010 Task Force Criteria: clinical performance and simplified practical implementation.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is diagnosed by a complex set of clinical tests as per 2010 Task Force Criteria (TFC). Avoiding misdiagnosis is crucial to prevent sudden cardiac death as well as unnecessary implantable cardioverter-defibrillator implantations. This study aims to validate the overall performance of the TFC in a real-world cohort of patients referred for ARVC evaluation. METHODS AND RESULTS: We included patients consecutively referred to our centres for ARVC evaluation. Patients were diagnosed by consensus of three independent clinical experts. Using this as a reference standard, diagnostic performance was measured for each individual criterion as well as the overall TFC classification. Of 407 evaluated patients (age 38 ± 17 years, 51% male), the expert panel diagnosed 66 (16%) with ARVC. The clinically observed TFC was false negative in 7/66 (11%) patients and false positive in 10/69 (14%) patients. Idiopathic outflow tract ventricular tachycardia was the most common alternative diagnosis. While the TFC performed well overall (sensitivity and specificity 92%), signal-averaged electrocardiogram (SAECG, P = 0.43), and several family history criteria (P ≥ 0.17) failed to discriminate. Eliminating these criteria reduced false positives without increasing false negatives (net reclassification improvement 4.3%, P = 0.019). Furthermore, all ARVC patients met at least one electrocardiogram (ECG) or arrhythmia criterion (sensitivity 100%). CONCLUSION: The TFC perform well but are complex and can lead to misdiagnosis. Simplification by eliminating SAECG and several family history criteria improves diagnostic accuracy. Arrhythmogenic right ventricular cardiomyopathy can be ruled out using ECG and arrhythmia criteria alone, hence these tests may serve as a first-line screening strategy among at-risk individuals.

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).