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Although efficacious, catheter ablation (CA) of ventricular arrhythmias (VAs) originating from left ventricular (LV) papillary muscles (PAPs) has the potential to affect mitral valve (MV) function.The aim of this study was to determine whether lesions delivered during CA of VAs from LV PAPs affected MV function.Consecutive patients undergoing CA of LV PAP VAs from January 2015 to December 2020 in whom both preprocedural and postprocedural transthoracic echocardiography was performed were included. Radiofrequency ablation was performed with an irrigated-tip catheter with or without contact force sensing and intracardiac echocardiographic guidance. The PAPs were delineated into segments: tip, body, and base. Pre- and post-CA transthoracic echocardiograms were reviewed to assess MV regurgitation, which was graded 0 (none), 1 (mild), 2 (moderate), or 3 (severe). A change of ≥2 grades from baseline was considered significant.A total of 103 patients (mean age 63 ± 15 years, 78% men) were included. VAs were ablated from the anterolateral PAP in 35% (n = 36), posteromedial PAP in 55% (n = 57), and both PAPs in 10% (n = 10). Lesion distribution was as follows: PAP tip in 52 (50%), PAP base in 34 (33%), PAP body in 13 (13%), and entire PAP in 4 (4%). The mean number of lesions delivered was 16 ± 13 (median 14). Of 103 patients, 102 (99%) showed no change in MV function.Using intracardiac echocardiographic guidance, lesions can be safely delivered on various aspects of this structure without adverse impact on MV function.

The right ventricle (RV) is uncommonly implicated in postinfarction ventricular tachycardia (VT). The prevalence and features of the RV substrate participating in postinfarction VT are undefined.The purpose of this study was to characterize critical right ventricular substrate (CRVS) involvement in patients with postinfarction VT.We retrospectively reviewed 1279 patients with postinfarction VT undergoing catheter ablation at our center from January 2000 through May 2020. Cases with CRVS defined by conclusive demonstration of participation in VT with activation, entrainment, and/or pacemapping during sinus rhythm were identified.CRVS was identified in 27 of 1279 patients (2.1%): age 65 ± 13 years, 96% male, median left ventricular (LV) ejection fraction 25%, and 93% with left bundle branch block (LBBB) morphology VT. CRVS was identified by RV activation and/or entrainment mapping (n = 19) or by the presence of low-voltage abnormal electrograms with excellent pacemap for the targeted VT and noninducibility after ablation (n = 8). VT termination during RV ablation occurred in 15 patients. After median follow-up of 20 months (interquartile range 9-53 months) and median of 2 procedures (interquartile range 1-3), 22 of 27 patients (80%) had no VT recurrence and 11 (41%) died.The RV contains critical substrate elements of postinfarction VT in at least 2.1% of cases. RV mapping should be considered in cases in which LV mapping fails to demonstrate adequate targets, particularly in patients with LBBB morphology VT.

Background Interatrial septal tachycardias (IAS-ATs) following atrial fibrillation (AF) ablation or cardiac surgery are rare, and their management is challenging. Objective The purpose of this study was to investigate the electrophysiological features and outcomes associated with catheter ablation of IAS-AT. Methods We screened 338 patients undergoing catheter ablation of ATs following AF ablation or cardiac surgery. Diagnosis of IAS-AT was based on activation mapping and analysis of response to atrial overdrive pacing. Results Twenty-nine patients (9%) had IAS-AT (cycle length [CL] 311 ± 104 ms); 16 (55%) had prior AF ablation procedures (median 3; range 1–5), 3 (10%) had prior surgical maze, and 12 (41%) had prior cardiac surgery (including atrial septal defect surgical repair in 5 and left atrial myxoma resection in 1). IAS substrate abnormalities were documented in all patients. Activation mapping always demonstrated a diffuse early IAS breakout with centrifugal biatrial activation, and atrial overdrive pacing showed a good postpacing interval (equal or within 25 ms of the AT CL) only at 1 or 2 anatomically opposite IAS sites in all cases. Ablation was acutely successful in 27 patients (93%) (from only the right IAS in 2, only the left IAS in 9, both IAS sides with sequential ablation in 13, and both IAS sides with bipolar ablation in 3). After median follow-up of 15 (6–52) months, 17 patients (59%) remained free from recurrent arrhythmias. Conclusion IAS-ATs are rare and typically occur in patients with evidence of IAS substrate abnormalities and prior cardiac surgery. Catheter ablation can be challenging and may require sequential unipolar ablation or bipolar ablation.

Common genetic variants explain less variation in complex phenotypes than inferred from family-based studies, and there is a debate on the source of this 'missing heritability'. We investigated the contribution of rare genetic variants to tobacco use with whole-genome sequences from up to 26,257 unrelated individuals of European ancestries and 11,743 individuals of African ancestries. Across four smoking traits, single-nucleotide-polymorphism-based heritability ([Formula: see text]) was estimated from 0.13 to 0.28 (s.e., 0.10-0.13) in European ancestries, with 35-74% of it attributable to rare variants with minor allele frequencies between 0.01% and 1%. These heritability estimates are 1.5-4 times higher than past estimates based on common variants alone and accounted for 60% to 100% of our pedigree-based estimates of narrow-sense heritability ([Formula: see text], 0.18-0.34). In the African ancestry samples, [Formula: see text] was estimated from 0.03 to 0.33 (s.e., 0.09-0.14) across the four smoking traits. These results suggest that rare variants are important contributors to the heritability of smoking.

Objectives The goal of this study was to characterize the relationship between DF, the electroanatomic mapping (EAM) substrate, and outcomes of catheter ablation of VT in NICM. Background A substantial proportion of patients with nonischemic dilated cardiomyopathy (NICM) and ventricular tachycardia (VT) do not have scar detectable by cardiac magnetic resonance late gadolinium enhancement (LGE) imaging. In these patients, the significance of diffuse fibrosis (DF) detected with T1 mapping has not been previously investigated. Methods This study included 51 patients with NICM and VT undergoing catheter ablation (median age 55 years; 77% male subjects) who had no evidence of LGE on pre-procedural cardiac magnetic resonance. Post-contrast T1 relaxation time determined on the septum was assessed as a surrogate of DF burden. The extent of endocardial low-voltage areas (LVAs) at EAM was correlated with T1 mapping data. Results Bipolar LVAs were present in 22 (43%) patients (median extent 15 cm2 [8 to 29 cm2]) and unipolar LVA in all patients (median extent 48 cm2 [26 to 120 cm2]). A significant inverse correlation was found between T1 values and both unipolar-LVA (R2 = 0.64; β = –0.85; p Conclusions In patients with NICM and no evidence of LGE undergoing catheter ablation of VT, DF estimated by using post-contrast T1 mapping correlates with the voltage abnormality at EAM and seems to affect post-ablation outcomes.

The type 1 electrocardiographic (ECG) pattern diagnostic of Brugada syndrome (BrS) can be dynamic. Limited studies have rigorously evaluated the temporal stability of the Brugada ECG pattern.We sought to evaluate fluctuations of the Brugada pattern in serial resting ECGs from BrS patients managed within a large health care system.In our cohort of BrS patients with at least 2 standard, resting ECGs recorded on separate clinical encounters, we evaluated serial changes in the Brugada pattern and categorized patients into 1 of 3 groups: dynamic was defined as the presence of both type 1 and non-type 1 patterns in available ECGs; the provoked-only group was defined as having a non-type 1 Brugada pattern across resting ECGs; and the persistent group was defined as having a type 1 pattern on all ECGs. We also evaluated the clinical risk in this cohort according to the Shanghai risk score.In 72 patients with BrS (mean age 46 ± 15 years, 69% male), 828 standard, resting ECGs were recorded over a median duration of 30.2 (interquartile range 6.3-68.1) months. The dynamic group comprised 50 (69% of the cohort) patients, the provoked-only group consisted of 17 patients (24% of the cohort), and the persistent group included 5 patients. No significant differences were detected in the total number of ECGs evaluated during the follow-up period between any of the groups. Only sinus node dysfunction and a prior cardiac arrest were associated with the persistent type 1 group. The majority of patients had a low annualized risk of lethal arrhythmic events.Most BrS patients have a dynamic Brugada pattern noted on longitudinal, resting ECGs. Expert consensus statements should provide clarity on the frequency of obtaining resting ECGs in patients suspected of having BrS during follow-up.

Severe endoscopically detected esophageal thermal lesions (EDELs) have been associated with higher risk of progression to atrio-esophageal fistula (AEF) following radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). We sought to evaluate safety and feasibility of active esophageal cooling using the Attune Medical Esophageal Heat Transfer Device (EnsoETM) to limit frequency or severity of EDELs. We sought To evaluate safety and feasibility of active esophageal cooling using the Attune Medical Esophageal Heat Transfer Device (EnsoETM) to limit frequency or severity of EDELs Consecutive patients undergoing first-time RFCA were randomized in a 1:1 fashion to esophageal cooling (device group) or standard temperature monitoring (control group). Ablation on the posterior wall was performed with a maximum power of 30W for up to 20s. All patients underwent EGD within 48 h. Endoscopy findings were classified as 1, erythema–mild injury; 2, superficial ulceration–moderate injury; 3, deep ulceration–significant injury; and 4, fistula/perforation. Severe EDELs were defined as grade 3 or 4 lesions. Forty-four patients completed the study (22 device group, 22 control group). Adjunctive posterior wall isolation was performed more frequently in the device group (11/22, 50% vs. 4/22, 18%). EDELs were detected in 5/22 (23%) control group patients, with mild or moderate injury in 2/5 patients (40%) and severe thermal injury in 3/5 patients (60%). In the device group, EDELs were detected in 8/22 (36%) patients, with mild or moderate injury in 7/8 (87%) patients and severe thermal injury in 1/8 (12%) patients. There was no acute perforation or AEF during follow-up. Active esophageal cooling may reduce the occurrence of severe EDELs. A larger randomized study is warranted to further evaluate the benefit of this strategy.

ObjectiveTo evaluate the prognosis of patients with ischemic stroke according to the timing of an atrial fibrillation (AF) diagnosis, we created an inception cohort of incident stroke events and compared the risk of death between patients with stroke with (1) sinus rhythm, (2) known AF (KAF), and (3) AF diagnosed after stroke (AFDAS).MethodsWe used the Penn AF Free study to create an inception cohort of patients with incident stroke. Mortality events were identified after linkage with the National Death Index through June 30, 2017. We also evaluated initiation of anticoagulants and antiplatelets across the study duration. Cox proportional hazards models evaluated associations between stroke subtypes and death.ResultsWe identified 1,489 individuals who developed an incident ischemic stroke event: 985 did not develop AF at any point during the study period, 215 had KAF before stroke, 160 had AF detected ≤6 months after stroke, and 129 had AF detected >6 months after stroke. After a median follow-up of 4.9 years (interquartile range 1.9–6.8), 686 deaths occurred. The annualized mortality rate was 8.8% in the stroke, no AF group; 12.2% in the KAF group; 15.8% in the AFDAS ≤6 months group; and 12.7% in the AFDAS >6 months group. Patients in the AFDAS ≤6 months group had the highest independent risk of all-cause mortality even after multivariable adjustment for demographics, clinical risk factors, and the use of antithrombotic therapies (hazard ratio 1.62 [1.22–2.14]). Compared to the stroke, no AF group, those with KAF had a higher mortality risk that was rendered nonsignificant after adjustment.ConclusionsThe AFDAS group had the highest risk of death, which was not explained by comorbidities or use of antithrombotic therapies.

Guidelines recommend that initial trial of a "pill-in-the-pocket" (PIP) Class 1C antiarrhythmic drug (AAD) for cardioversion of atrial fibrillation (AF) be performed in a monitored setting because of the potential for adverse reactions.This study sought to characterize real-world, contemporary use of the PIP approach, including the setting of initiation and incidence of adverse events.This retrospective cohort study included all patients at the Hospital of the University of Pennsylvania treated with a PIP approach for AF between 2007 and 2020.A total of 273 patients (age 56 ± 13 years; 182 [67%] male; CHAOur data support the current recommendation to initiate PIP AAD in a monitored setting because of rare significant adverse reactions that can require urgent intervention.

Background Twelve-lead electrocardiogram (ECG) criteria have been developed to identify idiopathic ventricular arrhythmias (VAs) from the left ventricular (LV) papillary muscles (PAPs), but accurate localization remains a challenge. Objective The purpose of this study was to develop ECG criteria for accurate localization of LV PAP VAs using lead V1 exclusively. Methods Consecutive patients undergoing mapping and ablation of VAs from the LV PAPs guided by intracardiac echocardiography from 2007 to 2018 were reviewed (study group). The QRS morphology in lead V1 was compared to patients with VAs with a "right bundle branch block" morphology from other LV locations (reference group). Patients with structural heart disease were excluded. Results One hundred eleven patients with LV PAP VAs (mean age 54 ± 16 years; 65% men) were identified, including 64 (55%) from the posteromedial PAP and 47 (42%) from the anterolateral PAP. The reference group included patients with VAs from the following LV locations: fascicles (n = 21), outflow tract (n = 36), ostium (n = 37), inferobasal segment (n = 12), and apex (5). PAP VAs showed 3 distinct QRS morphologies in lead V1 93% of the time: Rr (53%), R with a slurred downslope (29%), and RR (11%). Sensitivity, specificity, positive predictive value, and negative predictive value for the 3 morphologies combined are 93%, 98%, 98%, and 93%, respectively. The intrinsicoid deflection of PAP VAs in lead V1 was shorter than that of the reference group (63 ± 13 ms vs 79 ± 24 ms; P Conclusion VAs originating from the LV PAPs manifest unique QRS morphologies in lead V1, which can aid in rapid and accurate localization.

Background Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. SARS-CoV-2 infection may cause injury to cardiac myocytes and increase arrhythmia risk. Objective To evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality. Methods We reviewed the characteristics of all COVID-19 patients admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias and in-patient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, kidney disease and ICU status as potential risk factors for each arrhythmia. Results Among 700 patients (mean age 50±18 years, 45% men, 71% African American, and 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred among patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (OR 4.68 [95% CI 1.66 – 13.18]) and NSVT (OR 8.92 [95% CI 1.73 – 46.06]) after multivariable adjustment. Also, age and incident AF (OR 1.05 [95% CI 1.02 – 1.09]); and prevalent heart failure and bradyarrhythmias (OR 9.75 [95% CI 1.95 – 48.65]) were independently associated. Only cardiac arrests were associated with acute, in-hospital mortality. Conclusion Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection., Graphical abstract

Objectives This study investigated the impact of the type of catheter irrigant used during delivery of radiofrequency ablation. Background The use of half-normal saline (HNS) as an irrigant has been suggested as a method for increasing ablation lesion size but has not been rigorously studied in the beating heart or the use of a low-flow irrigation catheter. Methods Sixteen swine underwent left ventricular mapping and ablation using either normal saline (NS) (group 1: n = 9) or half-normal saline (HNS) (group 2: n = 7). All lesions were delivered using identical parameters (40 W with 10-second ramp, 30-second duration, 15 ml/min flow, and 8- to14-g target contact force). An occurrence of steam pop, catheter char, or thrombus was assessed using intracardiac echocardiography and catheter inspection following each application. Lesion depth, width, and area were measured using electronic calibers. Results A total of 109 lesions were delivered in group 1 and 77 in group 2. There were significantly more steam pops in group 2 (32 of 77 [42%] vs. 24 of 109 [22%], respectively). The frequencies of catheter tip char were similar (group 1: 9 of 109 [8%] vs. group 2: 10 of 77 [13%]; p = 0.29). Lesion depths, widths, and areas also were similar in both groups. Conclusions The use of an HNS irrigant using a low-flow open irrigated ablation catheter platform results in more tissue heating due to higher radiofrequency current delivery directed to tissue, but this can lead to higher rate of steam pops. In this in vivo porcine beating-heart model, the use of HNS does not appear to significantly increase lesion size in normal myocardium despite evidence of increased radiofrequency heating.

Objectives This study sought to evaluate the prevalence, mapping features, and ablation outcomes of non–scar-related ventricular tachycardia (NonScar-VT) and Purkinje-related VT (Purkinje-VT) in patients with structural heart disease. Background VT in structural heart disease is typically associated with scar-related myocardial re-entry. NonScar-VTs arising from areas of normal myocardium or Purkinje-VTs originating from the conduction system are less common. Methods We retrospectively analyzed 690 patients with structural heart disease who underwent VT ablation between 2013 and 2017. Results A total of 37 (5.4%) patients (16 [43%] with ischemic cardiomyopathy, 16 [43%] with nonischemic dilated cardiomyopathy, and 5 [14%] others) demonstrated NonScar/Purkinje-VTs, which represented the clinical VT in 76% of cases. Among the 37 VTs, 31 (84%) were Purkinje-VTs (28 bundle branch re-entrant VT). The remaining 6 (16%) VTs were NonScar-VTs and included 4 idiopathic outflow tract VTs. A total of 16 patients had prior history of VT ablations: empirical scar substrate modification was performed in 6 (38%) patients and residual inducibility of VT had not been assessed in 7 (44%). In all 37 patients, the NonScar/Purkinje-VT was successfully ablated. After a median follow-up of 18 months, the targeted NonScar/Purkinje-VT did not recur in any patients, and 28 (76%) of patients were free from any recurrent VT episodes. Conclusions NonScar/Purkinje-VTs can be identified in 5.4% of patients undergoing VT ablation in the setting of structural heart disease. Careful effort to induce, characterize, and map these VTs is important because substrate-based ablation strategies would fail to eliminate these types of VT.

Objective: CD73 is an ectonucleotidase which catalyzes the conversion of AMP (adenosine monophosphate) to adenosine. Adenosine has been shown to be anti-inflammatory and vasorelaxant. The impact of ectonucleotidases on age-dependent atherosclerosis remains unclear. Our aim was to investigate the role of CD73 in age-dependent accumulation of atherosclerosis. Approach and results: Mice doubly deficient in CD73 and ApoE (apolipoprotein E; ( cd73 − /− /apoE −/− ) were generated, and the extent of aortic atherosclerotic plaque was compared with apoE −/− controls at 12, 20, 32, and 52 weeks. By 12 weeks of age, cd73 −/− /apoE −/− mice exhibited a significant increase in plaque (1.4±0.5% of the total vessel surface versus 0.4±0.1% in apoE −/− controls, P P P cd73 −/− /apoE −/− mice and apoE −/− controls. A reduction in lipolysis in CD73 competent mice was observed, even with similar plasma lipid levels ( cd73 −/− /apoE −/− versus apoE −/− at 12 weeks [16.2±0.7 versus 9.5±1.4 nmol glycerol/well], 32 weeks [24.1±1.5 versus 7.4±0.4 nmol/well], and 52 weeks [13.8±0.62 versus 12.7±2.0 nmol/well], P Conclusions: At early time points, CD73 exerts a subtle antiatherosclerotic influence, but with age, the pattern reverses, and the presence of CD73 promoted suppression of lipid catabolism.

Objective This study sought to investigate incidence of left atrial appendage (LAA) triggers of atrial fibrillation (AF) and/or organized atrial tachycardias (OAT) in patients undergoing AF ablation and to evaluate outcomes after ablation. Background Although LAA isolation is being increasingly performed during AF ablation, the true incidence of LAA triggers for AF remains unclear. Methods All patients with LAA triggers of AF and/or OAT during AF ablation from 2001 to 2017 were included. LAA triggers were defined as atrial premature depolarizations from the LAA, which initiated sustained AF and/or OAT. Results Out of 7,129 patients undergoing AF ablation over 16 years, LAA triggers were observed in 21 (0.3%) subjects (age 60 ± 9 years; 57% males; 52% persistent AF). Twenty (95%) patients were undergoing repeat ablation. The LAA was the only nonpulmonary vein trigger in 3 patients; the remaining 18 patients had both LAA and other nonpulmonary vein triggers. LAA triggers were eliminated in all patients (focal ablation in 19 patients; LAA isolation in 2 patients). Twelve months after ablation, 47.6% remained free from recurrent arrhythmia. After overall follow-up of 5.0 ± 3.6 years (median: 3.7 years; interquartile range: 1.4 to 8.9 years), 38.1% were arrhythmia-free. All 3 patients with triggers limited to the LAA remained free of AF recurrence. One patient undergoing LAA isolation developed LAA thrombus during follow-up. Conclusions The incidence of true LAA triggers is very low (0.3%). Most patients with LAA triggers have additional nonpulmonary vein triggers, and despite elimination of LAA triggers, long-term arrhythmia recurrence rates remain high. Potential risks of empiric LAA isolation during AF ablation (especially first-time AF ablation) may outweigh benefits.

Background: The substrate for ventricular tachycardia (VT) in left ventricular (LV) nonischemic cardiomyopathy may be epicardial. We assessed the prevalence, location, endocardial electrograms, and VT ablation outcomes in LV nonischemic cardiomyopathy with isolated epicardial substrate. Methods: Forty-seven of 531 (9%) patients with LV nonischemic cardiomyopathy and VT demonstrated normal endocardial (>1.5 mV)/abnormal epicardial bipolar low-voltage area (LVA, Results: Epicardial bipolar LVA (27.3 cm 2 [interquartile range, 15.8–50.0]) localized to basal (40), mid (8), and apical (3) LV with basal inferolateral LV most common (28/47, 60%). Of 44 endocardial maps available, 40 (91%) had endocardial unipolar LVA (24.5 cm 2 [interquartile range, 9.4–68.5]) and 29 (67%) had characteristic normal amplitude endocardial split electrograms opposite the epicardial LVA. At mean of 34 months, the VT-free survival was 55% after one and 72% after multiple procedures. Greater endocardial unipolar LVA than epicardial bipolar LVA (hazard ratio, 10.66 [CI, 2.63–43.12], P =0.001) and number of inducible VTs (hazard ratio, 1.96 [CI, 1.27–3.00], P =0.002) were associated with VT recurrence. Conclusions: In patients with LV nonischemic cardiomyopathy and VT, the substrate may be confined to epicardial and commonly basal inferolateral. LV endocardial unipolar LVA and normal amplitude bipolar split electrograms identify epicardial LVA. Ablation targeting epicardial VT and substrate achieves good long-term VT-free survival. Greater endocardial unipolar than epicardial bipolar LVA and more inducible VTs predict VT recurrence.

Background: Prescription opioids are a major contributor to the ongoing epidemic of persistent opioid use (POU). The incidence of POU among opioid-naïve patients after cardiac implantable electronic device (CIED) procedures is unknown. Methods: This retrospective cohort study used data from a national administrative claims database from 2004 to 2018 of patients undergoing CIED procedures. Adult patients were included if they were opioid-naïve during the 180-day period before the procedure and did not undergo another procedure with anesthesia in the next 180 days. POU was defined by filling an additional opioid prescription >30 days after the CIED procedure. Results: Of the 143 400 patients who met the inclusion criteria, 15 316 (11%) filled an opioid prescription within 14 days of surgery. Among these patients, POU occurred in 1901 (12.4%) patients 30 to 180 days after surgery. The likelihood of developing POU was increased for patients who had a history of drug abuse (odds ratio, 1.52; P =0.005), preoperative muscle relaxant (odds ratio, 1.52; P P =0.001) use, or opioid use in the previous 5 years (OR, 1.76; P P =0.5). In a sensitivity analysis excluding high-risk patients who were discharged to a facility or who had a history of drug abuse or previous opioid, benzodiazepine, or muscle relaxant use, 8.9% of the remaining cohort had POU. Patients prescribed >135 mg of oral morphine equivalents had a significantly increased risk of POU. Conclusions: POU is common after CIED procedures, and 12% of patients continued to use opioids >30 days after surgery. Higher initially prescribed oral morphine equivalent doses were associated with developing POU.

Background It remains unclear whether additional left atrial posterior wall isolation (LAPWI) beyond pulmonary vein reisolation (PVRI) is beneficial in atrial fibrillation (AF) patients undergoing repeat ablation. Objective We sought to assess impact of LAPWI on arrhythmia outcomes in patients undergoing repeat AF ablation. Methods All AF patients that underwent repeat ablation between January 2016 and December 2018 were included. Those undergoing PVRI only served as control, whereas those undergoing LAPWI (with or without PVRI) were the study group. Primary endpoint was freedom from atrial arrhythmias (AA) off antiarrhythmic drugs (AADs) at 1 year follow-up. Secondary endpoint was freedom from AA on/off AADs at 1 year follow-up. Results One hundred ninety-six patients (61% paroxysmal AF, 39% persistent AF) participated; 93 underwent PVRI and 103 underwent LAPWI±PVRI. Patients in the LAPWI group were older, had more hypertension and persistent AF, and had lower rates of PV reconnection (52.4% vs 100%, P < .001). LAPWI was performed empirically in 79.6% and to target triggers in 20.4%. It was accomplished by linear lesions across the LA floor and roof alone in 65% and additional LAPW lesions in 35%. The primary and secondary endpoints were similar between patients undergoing LAPWI and those undergoing PVRI (43.7% vs 69.9%, P = .50 and 66% vs 77.4%, P = .36, respectively). There was no difference in adverse events between the 2 groups. Conclusion LAPWI did not improve freedom from atrial arrhythmias on or off AADs at 1 year beyond PVRI in AF patients undergoing repeat ablation. Differences in patient demographics and AF type may underlie the observed lack of benefit of LAPWI, and further study is warranted., Graphical abstract Outcomes of left atrial posterior wall isolation during repeat atrial fibrillation ablation

This study sought to explore whether prolonged duration (PD) radiofrequency ablation (RFA) from adjacent endocardial locations can improve catheter ablation (CA) outcomes of left ventricular summit (LVS) ventricular arrhythmias (Vas).CA of VAs originating from the LVS region can be challenging.Patients undergoing CA of LVS VAs from January 1, 2015, to December 31, 2019, were included. Standard RFA approach involved incremental power titration (20-45 W) over 60-120 seconds with irrigated tip catheter to achieve 10%-12% impedance drop. Prolonged duration RFA involved similar power titration; however, lesion application was extended beyond 120 seconds (maximum 5 minutes). Lesions were confined to lowest aspect of aortic cusps and/or subvalvular LV outflow tract region (≤0.5 cm from the valve). Procedural success was defined as suppression of VA ≥30 minutes postablation and clinical success as no arrhythmia symptoms on follow-up and80% reduction of VA burden on postprocedure monitor.This study included 102 patients (60±14 years old, 62% male): standard RFA in 80 and PD RFA in 38. Procedural success was achieved in 54 patients with standard and 32 patients with PD RFA (68% vs 84%; P = 0.05). Short-term clinical success was achieved in 48 patients (60%) with standard and 30 patients (79%) with PD RFA (P = 0.04). Two pericardial effusions occurred (1 in each group) and no steam pops were noted. Patients in whom standard RFA was successful were more likely to have R/S ratio1 or absence of qS in lead I (odds ratio: 3.35; 95% CI: 1.20-9.35; P = 0.03).Prolonged duration RFA from adjacent endocardial locations is a safe and effective technique for successfully targeting challenging LVS VAs that fail standard RFA.

Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protective in models of heart failure (HF). How protection occurs remains unclear, although a causative block in cardiac BCAA oxidation is widely assumed. Here, we use in vivo isotope infusions to show that cardiac BCAA oxidation in fact increases, rather than decreases, in HF. Moreover, cardiac-specific activation of BCAA oxidation does not protect from HF even though systemic activation does. Lowering plasma and cardiac BCAAs also fails to confer significant protection, suggesting alternative mechanisms of protection. Surprisingly, activation of BCAA catabolism lowers blood pressure (BP), a known cardioprotective mechanism. BP lowering occurred independently of nitric oxide and reflected vascular resistance to adrenergic constriction. Mendelian randomization studies revealed that elevated plasma BCAAs portend higher BP in humans. Together, these data indicate that BCAA oxidation lowers vascular resistance, perhaps in part explaining cardioprotection in HF that is not mediated directly in cardiomyocytes.

BackgroundOlder patients are at risk of increased morbidity and mortality from COVID-19 disease due to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There are few effective treatments for outpatients with COVID-19.ObjectiveTo evaluate the efficacy of hydroxychloroquine to reduce time in quarantine for symptomatic ≥40 years-old COVID-19 patients.DesignA randomized, double-blind, placebo-controlled clinical trial.SettingOutpatients with polymerase chain reaction confirmed COVID-19 at a University of Pennsylvania affiliated testing center between April 15, 2020 and, July 14, 2020.ParticipantsOut of 5511 SARS-CoV-2 positive patients, 1072 met initial eligibility criteria for telephone-based recruitment, but only 34 subjects were able to be randomized.InterventionsHydroxychloroquine 400 mg per twice daily (n=17) or matching placebo (n=17), taken orally for up to 14 days.MeasurementsThe primary outcome was the time to release from quarantine. Secondary outcomes included the participant-reported secondary infection of co-inhabitants, hospitalization, treatment-related adverse events, time to symptom improvement, and incidence of cardiac arrhythmia.ResultsThe median time to release from quarantine for HCQ-treated vs. placebo-treated participants was 8 days (range 4-19 days) vs. 11 days (4-18 days); z-score +0.58, p=n.s. This did not meet the pre-specified criteria for early termination, however, this study was terminated early due to lack of feasibility. There was no mortality in either study arm.LimitationSince this study was terminated early due to a lack of feasibility, no conclusion can be made about the efficacy of hydroxychloroquine as a treatment for COVID-19 patients 40 years of age or older quarantined at home.ConclusionThe design of this remotely conducted study could guide testing of other more promising agents during the COVID-19 pandemic.Trial registrationClinicaltrials.gov identifier: NCT04329923

Background: We have previously shown that the presence of dual muscular coronary sinus (CS) to left atrial (LA) connections, coupled with rate-dependent unidirectional block in one limb, is associated with atrial fibrillation (AF) induction. This study sought to examine whether ablation of distal CS to LA connections at a first AF ablation reduces arrhythmia recurrence during follow-up. Methods: In this single-center, randomized, controlled trial, 35 consecutive patients with drug-refractory AF undergoing first-time ablation between August 2018 and August 2019, were randomly assigned to (1) standard ablation (pulmonary vein isolation and nonpulmonary vein trigger ablation) versus (2) standard ablation plus elimination of distal CS to LA connections targeting the earliest LA activation during distal CS pacing with a deca-polar catheter placed with its proximal electrode at the ostium. Change of the local CS atrial electrogram and LA activation sequence to early activation of the LA septum or roof during distal CS pacing were the end point for CS-LA connection elimination. Results: Thirty patients completed 6 months study follow-up (15 patients in each group). Demographic characteristics including age and AF persistence were similar in both groups. After a mean follow-up of 170±22 days, there were 7 atrial arrhythmia recurrences in the standard group and 1 recurrence in the CS-LA connection elimination group (46.7% versus 6.7%, hazard ratio, 0.12, P =0.047). Conclusions: Elimination of distal CS to LA connections reduced atrial arrhythmia recurrences compared with standard pulmonary vein isolation and nonpulmonary vein trigger ablation in patients undergoing a first AF ablation procedure in a small randomized study. This strategy warrants further evaluation in a multicenter randomized trial. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03646643.

Severe endoscopically detected esophageal thermal lesions (EDELs) have been associated with higher risk of progression to atrio-esophageal fistula (AEF) following radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF). We sought to evaluate safety and feasibility of active esophageal cooling using the Attune Medical Esophageal Heat Transfer Device (EnsoETM) to limit frequency or severity of EDELs.We sought To evaluate safety and feasibility of active esophageal cooling using the Attune Medical Esophageal Heat Transfer Device (EnsoETM) to limit frequency or severity of EDELs METHODS: Consecutive patients undergoing first-time RFCA were randomized in a 1:1 fashion to esophageal cooling (device group) or standard temperature monitoring (control group). Ablation on the posterior wall was performed with a maximum power of 30W for up to 20s. All patients underwent EGD within 48 h. Endoscopy findings were classified as 1, erythema-mild injury; 2, superficial ulceration-moderate injury; 3, deep ulceration-significant injury; and 4, fistula/perforation. Severe EDELs were defined as grade 3 or 4 lesions.Forty-four patients completed the study (22 device group, 22 control group). Adjunctive posterior wall isolation was performed more frequently in the device group (11/22, 50% vs. 4/22, 18%). EDELs were detected in 5/22 (23%) control group patients, with mild or moderate injury in 2/5 patients (40%) and severe thermal injury in 3/5 patients (60%). In the device group, EDELs were detected in 8/22 (36%) patients, with mild or moderate injury in 7/8 (87%) patients and severe thermal injury in 1/8 (12%) patients. There was no acute perforation or AEF during follow-up.Active esophageal cooling may reduce the occurrence of severe EDELs. A larger randomized study is warranted to further evaluate the benefit of this strategy.

ImportanceObservational studies have shown an association between hypertension and atrial fibrillation (AF). Aggressive blood pressure management in patients with known AF reduces overall arrhythmia burden, but it remains unclear whether hypertension is causative for AF.ObjectiveThe primary objective of this study was to investigate the relationship between blood pressure and risk of AF using genetic proxies for blood pressure within a Mendelian randomization (MR) framework. We secondarily explored the relationship between genetically proxied use of anti-hypertensive drugs and risk of AF.DesignTwo-sample MR was performed using an inverse-variance weighted meta-analysis with weighted median MR and Egger intercept tests performed as sensitivity analyses. Genetic proxies for the anti-hypertensive drug classes were used to investigate the impact of these therapies on the risk of AF.SettingInternational Consortium of Blood Pressure, UK Biobank and Atrial Fibrillation Genetics Consortium.ParticipantsSummary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure (PP) were obtained from the International Consortium of Blood Pressure and the UK Biobank discovery analysis (>750,000 individuals of European ancestry).Summary statistics for AF were obtained from the 2018 Atrial Fibrillation Genetics Consortium multi-ethnic GWAS (>65,000 AF cases and >522,000 referents).ExposureGenetically predicted SBP, DBP and PP as quantified by risk scores.Main OutcomeOdds ratio for AF per 10 mmHg increase in genetically proxied blood pressure.ResultsTen mmHg increases in genetically proxied SBP, DBP or PP were associated with increased odds of AF (SBP: OR 1.17, 95% CI 1.11-1.22, p=1⨯ 10−11; DBP: OR 1.25, 95% CI 1.16-1.35, p=3⨯ 10−8; PP: OR 1.1, 95% CI 1.0-1.2, p=0.05). Ten mmHg decreases in SBP estimated by genetic proxies of anti-hypertensive medications showed calcium channel blockers (OR 0.66, 95% CI 0.57-0.76, p=8⨯ 10−9) and beta-blockers (OR 0.61, 95% CI 0.46-0.81, p=6⨯ 10−4) decreased the risk of AF.Conclusions and RelevanceBlood pressure-increasing genetic variants were associated with increased risk of AF, consistent with a causal relationship between blood pressure and AF. These data support the concept that blood pressure reduction through pharmacologic intervention, and specifically calcium channel blockade or beta blockade could reduce the risk of AF.

The heart consumes circulating nutrients to fuel lifelong contraction, but a comprehensive mapping of human cardiac fuel use is lacking. We used metabolomics on blood from artery, coronary sinus, and femoral vein in 110 patients with or without heart failure to quantify the uptake and release of 277 metabolites, including all major nutrients, by the human heart and leg. The heart primarily consumed fatty acids and, unexpectedly, little glucose; secreted glutamine and other nitrogen-rich amino acids, indicating active protein breakdown, at a rate ~10 times that of the leg; and released intermediates of the tricarboxylic acid cycle, balancing anaplerosis from amino acid breakdown. Both heart and leg consumed ketones, glutamate, and acetate in direct proportionality to circulating levels, indicating that availability is a key driver for consumption of these substrates. The failing heart consumed more ketones and lactate and had higher rates of proteolysis. These data provide a comprehensive and quantitative picture of human cardiac fuel use.

Twelve-lead electrocardiogram (ECG) criteria have been developed to identify idiopathic ventricular arrhythmias (VAs) from the left ventricular (LV) papillary muscles (PAPs), but accurate localization remains a challenge.The purpose of this study was to develop ECG criteria for accurate localization of LV PAP VAs using lead VConsecutive patients undergoing mapping and ablation of VAs from the LV PAPs guided by intracardiac echocardiography from 2007 to 2018 were reviewed (study group). The QRS morphology in lead VOne hundred eleven patients with LV PAP VAs (mean age 54 ± 16 years; 65% men) were identified, including 64 (55%) from the posteromedial PAP and 47 (42%) from the anterolateral PAP. The reference group included patients with VAs from the following LV locations: fascicles (n = 21), outflow tract (n = 36), ostium (n = 37), inferobasal segment (n = 12), and apex (5). PAP VAs showed 3 distinct QRS morphologies in lead VVAs originating from the LV PAPs manifest unique QRS morphologies in lead V

Background Electrical posterior wall isolation (PWI) is increasingly being used for the treatment of patients with atrial fibrillation (AF). Few data exist on the durability of PWI using current technology. Objective The purpose of this study was to characterize the frequency and location of posterior wall reconnection at the time of repeat catheter ablation for AF. Methods We performed a single-center retrospective cohort study of 50 patients undergoing repeat AF ablation after previous PWI. Durability of PWI was assessed at the time of repeat ablation based on posterior wall entrance and exit block. Sites of posterior wall reconnection were characterized based on review of recorded electrical signals and electroanatomic maps. Results At the time of repeat ablation, mean age was 67 ± 10 years, 31 of 50 patients had persistent AF, and mean CHA2DS2-VASc score was 3.0 ± 1.8. Of the 50 patients, 30 had durable PWI at repeat ablation, 1.4 ± 1.6 years after the index procedure. Patients with posterior wall reconnection required repeat ablation earlier (0.9 ± 0.6 years vs1.8 ± 1.9 years from index PWI; P = .048) and were more likely to have atypical atrial flutter (55% vs 27%; P = .043). Among patients with posterior wall reconnection, the roof was the most common site of reconnection (14/20), and 12 patients had multiple regions of reconnection noted. Conclusion Posterior wall reconnection is noted in 40% of patients undergoing repeat ablation after an index PWI. The roof of the left atrium is the most common site of posterior wall reconnection.

This study sought to address whether technological innovations such as contact force sensing (CFS) can improve acute and long-term ablation outcomes of left ventricular papillary muscle (LV PAP) ventricular arrhythmias (VAs).Catheter ablation of LV PAP VAs has been less efficacious than another focal VAs. It remains unclear whether technological innovations such as CFS can improve acute and long-term ablation outcomes of LV PAP VA.From January 2015 to December 2019, a total of 137 patients underwent LV PAP VA ablation. VA site of origin (SOO) was identified using activation and pace-mapping guided by intracardiac echocardiography. Radiofrequency energy (20 to 50 W for 60 to 90 s) was delivered by irrigated catheter with or without CFS. We defined acute success as complete suppression of targeted VA ≥30 min post ablation and clinical success as ≥80% VA burden reduction at outpatient follow-up.VA manifested as premature ventricular complexes in 98 (71%), nonsustained ventricular tachycardia in 18 (13%), sustained ventricular tachycardia in 12 (9%) and premature ventricular complexes induced ventricular fibrillation in 9 (7%). VA SOO was anterolateral PAP in 51 (37%), posteromedial PAP in 73 (53%), and both PAPs in 13 (10%). VAs were targeted using CFS in 97 (71%) and non-CFS in 40 (29%). After a single procedure, acute success was achieved in 130 (95%) and clinical success was achieved in 112 (82%); neither was impacted by VA SOO and/or CFS. Complications occurred in 5 patients (3.6%).Independent of CFS technology, intracardiac echocardiography-guided catheter ablation is highly efficacious and may be considered as first-line therapy in the management of LV PAP VA.

This study sought to examine the impact of periprocedural acute kidney injury (AKI) in scar-related ventricular tachycardia (VT) patients undergoing radiofrequency catheter ablation (RFCA) on short- and long-term outcomes.The clinical significance of periprocedural AKI in patients with scar-related VT undergoing RFCA has not been previously investigated.This study included 317 consecutive patients with scar-related VT undergoing RFCA (age: 64 ± 13 years, mean left ventricular ejection fraction: 33 ± 13%, 55% ischemic cardiomyopathy). Periprocedural AKI was defined as an absolute increase in creatinine of ≥0.3 mg/dl over 48 h or an increase of1.5× the baseline values within 1 week post-procedure.Periprocedural AKI occurred in 31 patients (10%). Independent predictors of AKI included chronic kidney disease (odds ratio [OR]: 3.43; 95% confidence interval [CI]: 1.48 to 7.96; p = 0.004), atrial fibrillation (OR: 2.42; 95% CI: 1.01 to 5.78; p = 0.047), and peri-procedural acute hemodynamic decompensation (OR: 3.98; 95% CI: 1.17 to 13.52; p = 0.003). After a median follow-up of 39 months (interquartile range: 6 to 65 months), 95 patients (30%) died. Periprocedural AKI was associated with increased risk of early mortality (within 30 days; hazard ratio [HR]: 9.91; 95% CI: 2.87 to 34.22; p 0.001) and late mortality (within 1 year) (HR: 4.57; 95% CI: 2.08 to 10.05; p 0.001). After multivariable adjustment, AKI remained independently associated with increased risk of early and late mortality (HR: 4.49; 95% CI: 1.1 to 18.36; p = 0.04, and HR: 3.28; 95% CI: 1.43 to 7.49; p = 0.005, respectively).Periprocedural AKI occurs in 10% of patients undergoing RFCA of scar-related VT and is strongly associated with increased risk of early and late post-procedural mortality.

Randomized trials evaluating cardiac resynchronization therapy (CRT) have excluded patients with a pre-existing implantable cardioverter-defibrillator (ICD). The association of CRT upgrade with clinical outcomes in patients with a pre-existing ICD is unclear.The purpose of this study was to examine a CRT-eligible population to evaluate clinical outcomes associated with CRT upgrade compared to patients who did not undergo CRT.Using the National Cardiovascular Data Registry (NCDR) ICD Registry between April 2010 and December 2014, we created a hierarchical logistic regression model to identify predictors of CRT upgrade in a CRT-eligible ICD population. In the subpopulation of patients with Medicare-linked claims data, differential outcomes were determined with censoring at 3 years. The primary endpoint of this study was all-cause mortality, with secondary endpoints of rates of hospitalization and procedural complications.CRT upgrade was performed in 75.5% of CRT-eligible patients with pre-existing ICD (n = 15,803). Presence of left bundle branch block conduction was the strongest predictor of CRT upgrade (odds ratio [OR] 4.56; 95% confidence interval [CI] 4.08-5.11; P .0001). In both unadjusted and adjusted analyses, CRT upgrade was associated with a reduction in mortality at 3 years (unadjusted hazard ratio [HR] 0.80; 95% CI 0.70-0.92; P = .001; adjusted HR 0.84; 95% CI 0.72-0.98; P = .02, respectively). Compared to patients with ICD generator replacement only, patients who underwent CRT upgrade experienced no different 3-year rates of hospitalization (adjusted HR 1.01; 95% CI 0.91-1.12; P = .81) or 1-year periprocedural complication rates (adjusted HR 1.07; 95% CI 0.79-1.45; P = .66).In a national registry of CRT-eligible patients with pre-existing ICD, upgrade to CRT was associated with lower rates of mortality than continued medical management.

This study reports the long-term outcome of patients with bundle branch re-entrant tachycardia (BBRT) who underwent catheter ablation for ventricular tachycardia (VT).BBRT is an uncommon mechanism of VT. Data on long-term outcomes of patients with BBRT treated with catheter ablation are insufficient.Between 2005 and 2016, 32 patients had a sustained VT due to a bundle branch re-entrant mechanism. Diagnosis of BBRT was established per standard published criteria.The mode of presentation was syncope in 17 patients (53%) and palpitations in 15 (47%). BBRT was inducible in all subjects, and successful ablation of the right bundle branch in 19 patients (59%) or the left bundle branch in 13 patients (41%) was performed. During follow-up of 95 ± 36 months, 6 patients (19%) died, 3 of progressive heart failure and 3 of noncardiac causes. Recurrent VT due to BBRT did not occur in any patient. At baseline, 25 patients (78%) had a prolonged HV interval (55 ms) and 7 (22%) had a normal HV interval (≤55 ms). In patients with a normal HV interval, there was only 1 death (due to malignancy), and no one developed heart block during 90 ± 36 months of follow-up. Ten patients (31%) had normal left ventricular (LV) function (LV ejection fraction ≥50%), and 22 (69%) had depressed LV function (LV ejection fraction 50%). No deaths were recorded in patients with normal LV function (5 with no implantable cardioverter-defibrillator) compared with 6 deaths among patients with depressed LV function (n = 22; p = 0.07).Radiofrequency ablation of the bundle branch is an effective therapy for treatment of BBRT. Sustained BBRT can be seen in patients with normal LV systolic function and HV interval with excellent long-term outcomes after ablation.

Background: Conscious sedation is used during transcatheter aortic valve replacement (TAVR) with limited evidence as to the safety and efficacy of this practice. Methods: The National Cardiovascular Data Registry Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry was used to characterize the anesthesia choice and clinical outcomes of all US patients undergoing elective percutaneous transfemoral TAVR between April 1, 2014, and June 30, 2015. Raw and inverse probability of treatment-weighted analyses were performed to compare patients undergoing TAVR with general anesthesia with patients undergoing TAVR with conscious sedation on an intention-to-treat basis for the primary outcome of in-hospital mortality, and secondary outcomes including 30-day mortality, in-hospital and 30-day death/stroke, procedural success, intensive care unit and hospital length-of-stay, and rates of discharge to home. Post hoc falsification end point analyses were performed to evaluate for residual confounding. Results: Conscious sedation was used in 1737/10 997 (15.8%) cases with a significant trend of increasing usage over the time period studied ( P for trendP =0.31). The conscious sedation group was less likely to experience in-hospital (1.6% versus 2.5%, P =0.03) and 30-day death (2.9% versus 4.1%, P =0.03). Conversion from conscious sedation to general anesthesia was noted in 102 of 1737 (5.9%) of conscious sedation cases. After inverse probability of treatment-weighted adjustment for 51 covariates, conscious sedation was associated with lower procedural success (97.9% versus 98.6%, P P P P P Conclusions: In US practice, conscious sedation is associated with briefer length of stay and lower in-hospital and 30-day mortality in comparison with TAVR with general anesthesia in both unadjusted and adjusted analyses. These results suggest the safety of conscious sedation in this population, although comparative effectiveness analyses using observational data cannot definitively establish the superiority of one technique over another.

Key Clinical Message Adenosine is increasingly used to assess for dormant conduction following pulmonary vein isolation during atrial fibrillation ablation. While the half-life of adenosine is typically short and side effects transient, operators should be aware of more serious, lasting adverse reactions including anaphylaxis and bronchospasm.