Persistent Opioid Use After Cardiac Implantable Electronic Device Procedures.

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<0.001) or benzodiazepine (odds ratio, 1.23; P=0.001) use, or opioid use in the previous 5 years (OR, 1.76; P<0.0001). POU did not differ after subcutaneous implantable cardioverter defibrillator or other CIED procedures (11.1 versus 12.4%; 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.

Prognostic Value of Nonischemic Ringlike Left Ventricular Scar in Patients With Apparently Idiopathic Nonsustained Ventricular Arrhythmias.

BACKGROUND: Left ventricular (LV) scar on late gadolinium enhancement (LGE) cardiac magnetic resonance has been correlated with life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). We investigated the prognostic significance of a specific LV-LGE phenotype characterized by a ringlike pattern of fibrosis. METHODS: A total of 686 patients with apparently idiopathic nonsustained VA underwent contrast-enhanced cardiac magnetic resonance. A ringlike pattern of LV scar was defined as LV subepicardial/midmyocardial LGE involving at least 3 contiguous segments in the same short-axis slice. The end point of the study was time to the composite outcome of all-cause death, resuscitated cardiac arrest because of ventricular fibrillation or hemodynamically unstable ventricular tachycardia and appropriate implantable cardioverter defibrillator therapy. RESULTS: A total of 28 patients (4%) had a ringlike pattern of scar (group A), 78 (11%) had a non-ringlike pattern (group B), and 580 (85%) had normal cardiac magnetic resonance with no LGE (group C). Group A patients were younger compared with groups B and C (median age, 40 vs 52 vs 45 years; P<0.01), more frequently men (96% vs 82% vs 55%; P<0.01), with a higher prevalence of family history of sudden cardiac death or cardiomyopathy (39% vs 14% vs 6%; P<0.01) and more frequent history of unexplained syncope (18% vs 9% vs 3%; P<0.01). All patients in group A showed VA with a right bundle-branch block morphology versus 69% in group B and 21% in group C (P<0.01). Multifocal VAs were observed in 46% of group A patients compared with 26% of group B and 4% of group C (P<0.01). After a median follow-up of 61 months (range, 34-84 months), the composite outcome occurred in 14 patients (50.0%) in group A versus 15 (19.0%) in group B and 2 (0.3%) in group C (P<0.01). After multivariable adjustment, the presence of LGE with ringlike pattern remained independently associated with increased risk of the composite end point (hazard ratio, 68.98 [95% CI, 14.67-324.39], P<0.01). CONCLUSIONS: In patients with apparently idiopathic nonsustained VA, nonischemic LV scar with a ringlike pattern is associated with malignant arrhythmic events.

Transdermal oestradiol for androgen suppression in prostate cancer: long-term cardiovascular outcomes from the randomised Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme.

BACKGROUND: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme. METHODS: PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 µg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive. FINDINGS: Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4-7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80-1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86-1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001). INTERPRETATION: Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer. FUNDING: Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London.

Evaluation of Potential Cumulative Risk of Multiple 1.5-T MRI Examinations in Patients With Cardiac Implanted Electronic Devices.

Although professional societies now support MRI in patients with nonconditional (legacy) cardiac implanted electronic devices (CIEDs), concern remains regarding potential cumulative effects of serial examinations. We evaluated 481 patients with CIEDs who underwent 599 1.5-T MRI examinations (44.6% cardiac examinations), including 68 patients who underwent multiple examinations (maximum, seven examinations). No major events occurred. The minor adverse event rate was 5.7%. Multiple statistical evaluations showed no increase in adverse event rate with increasing number of previous examinations.

Continuous rhythm monitoring-guided anticoagulation after atrial fibrillation ablation.

INTRODUCTION: Oral anticoagulation (OAC) based on estimated stroke risk is recommended following catheter ablation (CA) of atrial fibrillation (AF), regardless of the extent of arrhythmia control. However, discontinuing OAC in selected patients may be safe. We sought to evaluate a strategy of OAC discontinuation following AF ablation guided by continuous rhythm monitoring. METHODS AND RESULTS: We prospectively studied AF ablations performed at our institution from June 2015 to December 2019. Patients that had pre-existing cardiac implantable electronic devices (CIEDs) or underwent insertable cardiac monitor (ICM) implantation immediately following AF ablation were included. OAC was continued for 6 weeks following CA in all patients, following which OAC management was guided by CHA2 DS2 -VASc score and continuous rhythm monitoring results, according to a prespecified protocol. AF recurrence was defined as ≥30 s (CIEDs) or ≥2 min (ICM). We studied 196 patients (mean age 64.7 ± 11.3 years, 66.8% male, 85.7% ICM, 14.3% CIEDs). Mean CHA2 DS2- VASc score was 2.2 ± 1.5. One-year AF-free survival following CA was 83% for paroxysmal AF and 63% for persistent AF patients. Over 3 year follow-up, OAC was discontinued in 57 (33.7%) patients, mean 7.4 ± 7.1 months following ablation. Following discontinuation, OAC was restarted for AF recurrence in 9 (15.8%) patients, mean 11.7 ± 6.8 months after stopping. This discontinuation protocol led to a 21.9% reduction in overall time exposed to OAC. There were no thromboembolic or major bleeding events. CONCLUSION: OAC can be discontinued in a significant percentage of patients following CA of AF. When guided by continuous rhythm monitoring, this practice does not unacceptably increase the risk of thromboembolic events.

Catheter ablation of atrial arrhythmias following lung transplant: Electrophysiological findings and outcomes.

INTRODUCTION: Data on the mechanisms of atrial arrhythmias (AAs) and outcomes of catheter ablation (CA) in lung transplantation (LT) patients are insufficient. We evaluated the electrophysiologic features and outcomes of CA of AAs in LT patients. METHODS AND RESULTS: We conducted a retrospective study of all the LT patients who underwent CA for AAs at our institution between 2004 and 2019. A total of 15 patients (43% males, age: 61 ± 10 years) with a history of LT (60% bilateral and 40% unilateral) were identified. All patients had documented organized AA on surface electrocardiogram and seven patients also had atrial fibrillation (AF; 47% with >1 clinical arrhythmia). At electrophysiological study, 19 organized AAs were documented (48% focal and 52% macro-re-entrant). Focal atrial tachycardias/flutters were targeted along the pulmonary vein (PV) anastomotic site at the left inferior PV (n = 2), ridge and carina of the left superior PV (n = 2), left atrium (LA) posterior wall (n = 3), LA roof (n = 1), and tricuspid annulus (n = 1). Macro-re-entrant AAs included cavotricuspid isthmus-dependent flutter (n = 2), incisional LA flutter (n = 4), LA roof-dependent flutter (n = 1), and mitral annular flutter (n = 3). In patients with LA mapping (n = 13), PV reconnection on the side of the LT was found in six patients (40%, all with clinically documented AF), with a mean of 2.1 ± 0.9 PVs reconnected per patient. Patients with AF underwent successful PV isolation. After a median follow-up of 19 months (range: 6-86 months), 75% of patients remained free from recurrent AAs. No procedural major complications occurred. CONCLUSION: In patients with prior LT, recurrent AAs are typically associated with substrate surrounding the surgical anastomotic lines and/or chronically reconnected PVs. CA of AAs in this population is safe and effective to achieve long-term arrhythmia control.

Collateral injury of the conduction system during catheter ablation of septal substrate in nonischemic cardiomyopathy.

INTRODUCTION: In patients with nonischemic cardiomyopathy (NICM) little is known about the clinical impact of catheter ablation (CA) of septal ventricular tachycardia (VT) resulting in the collateral injury of the conduction system (CICS). METHODS AND RESULTS: Ninety-five consecutive patients with NICM underwent CA of septal VT. Outcomes in patients with no baseline conduction abnormalities who developed CICS (group 1, n = 28 [29%]) were compared to patients with no CICS (group 2, n = 17 [18%]) and to patients with preexisting conduction abnormalities or biventricular pacing (group 3, n = 50 [53%]). Group-1 patients were younger, had a higher left ventricular ejection fraction and a lower prevalence of New York Heart Association III/IV class compared to group 3 while no significant differences were observed with group 2. After a median follow-up of 15 months, VT recurred in 14% of patients in group 1, 12% in group 2 (P = .94) and 32% in group 3 (P = .08) while death/transplant occurred in 14% of patients in group 1, 18% in group 2 (P = .69) and 28% in group 3 (P = .15). A worsening of left ventricular ejection fraction (LVEF) (median LVEF variation, -5%) was observed in group 1 compared to group 2 (median LVEF variation, 0%; P < .01) but not group-3 patients (median LVEF variation, -4%; P = .08) with a consequent higher need for new biventricular pacing in group 1 (43%) compared to group 2 (12%; P = .03) and group 3 (16%; P < .01). CONCLUSIONS: In patients with NICM and septal substrate, sparing the abnormal substrate harboring the conduction system provides acceptable VT control while preventing a worsening of the systolic function.

Impact of a nurse-led limited risk factor modification program on arrhythmia outcomes in patients with atrial fibrillation undergoing catheter ablation.

BACKGROUND: We have previously demonstrated the feasibility of a nurse-led risk factor modification (RFM) program for improving weight loss and obstructive sleep apnea (OSA) care among patients with atrial fibrillation (AF). OBJECTIVE: We now report its impact on arrhythmia outcomes in a subgroup of patients undergoing catheter ablation. METHODS: Participating patients with obesity and/or need for OSA management (high risk per Berlin Questionnaire or untreated OSA) underwent in-person consultation and monthly telephone calls with the nurse for up to 1 year. Arrhythmias were assessed by office ECGs and ≥2 wearable monitors. Outcomes, defined as Arrhythmia control (0-6 self-terminating recurrences, with ≤1 cardioversion for nonparoxysmal AF) and Freedom from arrhythmias (no recurrences on or off antiarrhythmic drugs), were compared at 1 year between patients undergoing catheter ablation who enrolled and declined RFM. RESULTS: Between 1 November 2016 and 1 April 2018, 195 patients enrolled and 196 declined RFM (body mass index, 35.1 ± 6.7 vs 34.3 ± 6.3 kg/m2 ; 50% vs 50% paroxysmal AF; P = NS). At 1 year, enrolled patients demonstrated significant weight loss (4.7% ± 5.3% vs 0.3% ± 4.4% in declined patients; P < .0001) and improved OSA care (78% [n = 43] of patients diagnosed with OSA began treatment). However, outcomes were similar between enrolled and declined patients undergoing ablation (arrhythmia control in 80% [n = 48] vs 79% [n = 38]; freedom from arrhythmia in 58% [n = 35] vs 71% [n = 34]; P = NS). CONCLUSION: Despite improving weight loss and OSA care, our nurse-led RFM program did not impact 1-year arrhythmia outcomes in patients with AF undergoing catheter ablation.

Cardiac Pacing and Defibrillation Devices: Cost and Effectiveness.

Implantable cardiac pacing and defibrillation devices are effective and commonly used therapies for patients with cardiac rhythm disorders. Because device implantation is not easily reversible, as well as the high healthcare costs inherent in device use, a clear understanding of the clinical benefits relative to costs is essential for both appropriate clinical use and rational policy making. Cardiac implantable electronic devices (CIEDs) have been among the best-investigated therapies in medicine; these devices have been the topic of numerous clinical and economic evaluations during the past 30 years. However, many important questions remain unclarified. We review the evidence supporting the clinical benefits of CIEDs, including effectiveness in extending survival as well as improving quality of life. We also summarize the economic studies that have investigated costs associated with these devices and their overall cost effectiveness, and we highlight important potential areas for future research.

"As Needed" nonvitamin K antagonist oral anticoagulants for infrequent atrial fibrillation episodes following atrial fibrillation ablation guided by diligent pulse monitoring: A feasibility study.

INTRODUCTION: After atrial fibrillation (AF) ablation, oral anticoagulation (OAC) is recommended if stroke risk as assessed by CHA2 DS 2 -VASc score is high. However, patients without AF are often reluctant to take daily OAC. We describe outcome using as needed nonvitamin K antagonist (NOACs) guided by pulse monitoring to detect AF following successful ablation. METHODS AND RESULTS: We identified 99 patients (84% male, age 64 ± 8 years), CHA2 DS 2 -VASc score greater than or equal to 1 in men and greater than or equal to 2 in women (median 2, range 1-6), capable of pulse assessment twice daily and no AF on extended monitoring after AF ablation. All patients were instructed to start NOAC if AF >1 hour or recurrent shorter episodes. Duration of NOAC use after restart was typically 2 to 4 weeks. After 30 ± 14 months (total 244 patient-years), 22 patients (22%) transitioned to daily NOAC because of noncompliance with pulse assessment or patient preference (six patients) or because of suspected or documented AF episode(s) in 16 (16%) patients. Of the remaining 77 (78%), 14 (14%) used NOACs but did not transition back to daily use, most (10 patients) with single use (seven patients) or non-AF rhythm (three patients) documented. There was only one thromboembolic event (0.4%/yr of follow-up) in patient without AF and one mild bleeding event (epistaxis). CONCLUSION: The use of as needed NOACs when AF is suspected with pulse monitoring is effective and safe to maintain low risk of stroke and bleeding after successful ablation. Transition back to daily NOAC use should be anticipated in about one quarter of patients.

Catheter ablation of premature ventricular complexes with low intraprocedural burden guided exclusively by pace-mapping.

BACKGROUND: Catheter ablation (CA) of idiopathic premature ventricular complexes (PVCs) is typically guided by both activation and pace-mapping, with ablation ideally delivered at the site of the earliest local activation. However, activation mapping requires sufficient intraprocedural quantity of PVCs. This study aimed to investigate the outcome of CA of infrequent PVCs guided exclusively by pace-mapping. METHODS: We retrospectively analyzed all patients undergoing CA of idiopathic PVCs between 2014 and 2017. RESULTS: Among 327 patients, 24 (7.3%) had low intraprocedural PVC burden despite isoproterenol, including two patients with zero PVCs, rendering activation mapping impractical/impossible. All 24 had a history of symptomatic PVCs. During ablation, a median of 27 (17-55) pace-maps were performed, with best median PASO score of 97 (96-98)%. A median of 12 (8.75-18.75) radiofrequency (RF) lesions were delivered with 11.4 (8.5-17.6) minutes of total RF time. Clinical success, defined as more than 80% reduction in the burden of previously frequent PVCs and/or absence of symptoms as well as any documented clinical PVCs among those with infrequent or exercise-induced PVCs, was achieved in 19 (79%) patients over 9.2 (2.0-15.0) months of follow-up. CONCLUSIONS: When activation mapping cannot be performed due to inadequate intraprocedural PVC burden, detailed pace-mapping can frequently identify the precise arrhythmia site of origin, thereby guiding successful CA.

P-wave morphology and multipolar intracardiac atrial activation to facilitate nonpulmonary vein trigger localization.

INTRODUCTION: Nonpulmonary vein (non-PV) triggers of atrial fibrillation (AF) are targets for ablation but their localization remains challenging. The aim of this study was to describe P-wave (PW) morphologic characteristics and intra-atrial activation patterns and timing from multipolar coronary sinus (CS) and crista terminalis (CT) catheters that localize non-PV triggers. METHODS AND RESULTS: Selective pacing from six right and nine left atrial common non-PV trigger sites was performed in 30 consecutive patients. We analyzed 12 lead ECG features based on PW duration, amplitude and morphology, and patterns and timing of multipolar activation for all 15 sites. Regionalization and then precise localization required criteria present in at least 70% of assessments at each pacing site. The algorithm was then prospectively evaluated by four blinded observers in a validation cohort of 18 consecutive patients undergoing the same pacing protocol and 60 consecutive patients who underwent successful non-PV trigger ablation. The algorithm for site regionalization included 1) negative PW in V1, ≥30 µV change in PW amplitude across the leads V1-V3, and PW duration ≤100 milliseconds in lead 2 and 2) unique intra-atrial activation patterns and timing noted in the multipolar catheters. Specific ECG and intra-atrial activation timing characteristics included in the algorithm allowed for more precise site localization after regionalization. In the prospective evaluation, the algorithm identified the site of origin for 72% of paced and 70% of spontaneous non-PV trigger sites. CONCLUSION: An algorithm based on PW morphology and intra-atrial multipolar activation pattern and timing can help identify non-PV trigger sites of origin.

Anatomical proximity dictates successful ablation from adjacent sites for outflow tract ventricular arrhythmias linked to the coronary venous system.

AIMS: Catheter ablation of outflow tract ventricular arrhythmias (OTVAs) with the earliest activation within the coronary venous system (CVS) can be challenging. When ablation from the CVS is not feasible or ineffective, an approach from anatomically adjacent site(s) can be considered. We report the outcomes of an anatomical approach for OTVAs linked to the CVS. METHODS AND RESULTS: We retrospectively analysed 665 OTVA patients. Of these, 65 (9.8%) had the earliest activation within the CVS. In 53 (82%) cases, an anatomical approach was attempted. The targeted adjacent anatomical structure was the endocardial left ventricular outflow tract (LVOT) in 24 (45%), the left coronary cusp or the left/right cusp junction in 17 (32%) patients, and the right ventricular outflow tract (RVOT) in 12 (23%). The anatomical approach was successful in 26 (49%) patients (27% from the coronary cusps, 65% from the LVOT, and 8% from the RVOT). The difference in activation times between the earliest activation site within the CVS and the targeted site was not significantly different between the successful and unsuccessful groups (14.2 ± 11.2 ms vs. 13.2 ± 9.3 ms; P = 0.89). The anatomical distance from the earliest activation site to the targeted site was shorter for the successful group (9.7 ± 2.4 mm vs. 13.1 ± 6.5 mm; P < 0.05). In particular, when the anatomical distance was >12.8 mm, anatomical approach was successful in only 1/13 (8%). CONCLUSION: In patients with OTVAs linked to the CVS, an anatomical approach targeting an adjacent site can be effective, particularly when the distance between the sites is <12.8 mm.

Long-term outcome and mode of recurrence following noninducibility during noninvasive programmed stimulation after ventricular tachycardia ablation.

BACKGROUND: Noninducibility of ventricular tachycardia (VT) at noninvasive programmed stimulation performed shortly following ablation (negative NIPS) predicts low risk of the medium-term recurrence. This study aimed to evaluate long-term rate and mode of recurrence following negative NIPS. METHODS: We extended follow-up on patients in whom no VT could be induced at NIPS following ablation between 2008 and 2010. Recurrent VTs were categorized as "Original clinical" if they matched VT that had occurred spontaneously prior to the index ablation; "Original nonclinical" if they matched VT that was induced during the index ablation but had not occurred spontaneously; or "New." Among those undergoing repeat ablation, the area ablated to treat the recurrent VT was categorized as "Targeted initial scar" if it was targeted during the index procedure; "Untargeted initial scar" if it was present but not targeted during the index procedure; or "New scar" if it was not present during the index procedure. RESULTS: Of 60 patients with negative NIPS, 18 (30%) had recurrent VT and nine underwent repeat ablation over (4.1 ± 3.2) years follow-up. Of 23 recurrent VTs, 18 (78%) were "New." During repeat ablations, six (46%) of the 13 recurrent VTs were ablated in "untargeted initial scar" and four (31%) in "new scar." CONCLUSIONS: When spontaneous or inducible VTs are eliminated with ablation and no longer inducible during NIPS, these VTs are unlikely to recur during long-term follow-up. More commonly, new VTs occur, which are either associated with areas of scar not present or not targeted during the initial ablation.

Effect of Single-Fraction vs Multifraction Radiotherapy on Ambulatory Status Among Patients With Spinal Canal Compression From Metastatic Cancer: The SCORAD Randomized Clinical Trial.

Importance: Malignant spinal canal compression, a major complication of metastatic cancer, is managed with radiotherapy to maintain mobility and relieve pain, although there is no standard radiotherapy regimen. Objective: To evaluate whether single-fraction radiotherapy is noninferior to 5 fractions of radiotherapy. Design, Setting, and Participants: Multicenter noninferiority randomized clinical trial conducted in 42 UK and 5 Australian radiotherapy centers. Eligible patients (n = 686) had metastatic cancer with spinal cord or cauda equina compression, life expectancy greater than 8 weeks, and no previous radiotherapy to the same area. Patients were recruited between February 2008 and April 2016, with final follow-up in September 2017. Interventions: Patients were randomized to receive external beam single-fraction 8-Gy radiotherapy (n = 345) or 20 Gy of radiotherapy in 5 fractions over 5 consecutive days (n = 341). Main Outcomes and Measures: The primary end point was ambulatory status at week 8, based on a 4-point scale and classified as grade 1 (ambulatory without the use of aids and grade 5 of 5 muscle power) or grade 2 (ambulatory using aids or grade 4 of 5 muscle power). The noninferiority margin for the difference in ambulatory status was -11%. Secondary end points included ambulatory status at weeks 1, 4, and 12 and overall survival. Results: Among 686 randomized patients (median [interquartile range] age, 70 [64-77] years; 503 (73%) men; 44% had prostate cancer, 19% had lung cancer, and 12% had breast cancer), 342 (49.8%) were analyzed for the primary end point (255 patients died before the 8-week assessment). Ambulatory status grade 1 or 2 at week 8 was achieved by 115 of 166 (69.3%) patients in the single-fraction group vs 128 of 176 (72.7%) in the multifraction group (difference, -3.5% [1-sided 95% CI, -11.5% to ∞]; P value for noninferiority = .06). The difference in ambulatory status grade 1 or 2 in the single-fraction vs multifraction group was -0.4% (63.9% vs 64.3%; [1-sided 95% CI, -6.9 to ∞]; P value for noninferiority = .004) at week 1, -0.7% (66.8% vs 67.6%; [1-sided 95% CI, -8.1 to ∞]; P value for noninferiority = .01) at week 4, and 4.1% (71.8% vs 67.7%; [1-sided 95% CI, -4.6 to ∞]; P value for noninferiority = .002) at week 12. Overall survival rates at 12 weeks were 50% in the single-fraction group vs 55% in the multifraction group (stratified hazard ratio, 1.02 [95% CI, 0.74-1.41]). Of the 11 other secondary end points that were analyzed, the between-group differences were not statistically significant or did not meet noninferiority criterion. Conclusions and Relevance: Among patients with malignant metastatic solid tumors and spinal canal compression, a single radiotherapy dose, compared with a multifraction dose delivered over 5 days, did not meet the criterion for noninferiority for the primary outcome (ambulatory at 8 weeks). However, the extent to which the lower bound of the CI overlapped with the noninferiority margin should be considered when interpreting the clinical importance of this finding. Trial Registration: ISRCTN Identifiers: ISRCTN97555949 and ISRCTN97108008.

Lead I R-wave amplitude to differentiate idiopathic ventricular arrhythmias with left bundle branch block right inferior axis originating from the left versus right ventricular outflow tract.

INTRODUCTION: Differentiation of right versus left ventricular outflow tract (RVOT vs. LVOT) arrhythmia origin with left bundle branch block right inferior axis (LBRI) morphology is relevant to ablation planning and risk discussion. Our aim was to determine if lead I R-wave amplitude is useful for differentiation of RVOT from LVOT arrhythmias with LBRI morphology. METHODS: The R-wave amplitude in lead I was measured in a retrospective cohort of 75 consecutive patients with LBRI pattern ventricular arrhythmias (VAs) successfully ablated from the RVOT (n = 54), LVOT (n = 16), or the anterior interventricular vein (AIV; n = 5). The optimal R-wave threshold was identified and diagnostic indices were compared with the previously reported transitional zone (TZ) index and V2S/V3R index. RESULTS: An R-wave amplitude greater than or equal to 0.1 mV predicted LVOT origin with 75% sensitivity and 98.2% specificity. In comparison, the TZ and V2S/V3R indices had 50% and 68.8% sensitivity, and 75.9% and 88.9% specificity, respectively, for predicting LVOT origin. The area under the curve (AUC) was 0.85 for lead I R-wave amplitude, 0.87 for V2S/V3R, and 0.72 for the TZ index. Of 36 cases with QS in lead I, 30 (83.3%) were from the anterior RVOT, three (8.3%) from the LVOT, and three (8.3%) from the AIV. CONCLUSION: The presence of R-wave amplitude in lead I (≥0.1 mV) is a simple and useful criterion to identify LVOT cusp or endocardium focus in LBRI arrhythmias. A QS pattern in lead I suggests an origin in the anterior RVOT, or less commonly the adjacent LV summit.

Epicardial ventricular tachycardia in ischemic cardiomyopathy: Prevalence, electrophysiological characteristics, and long-term ablation outcomes.

INTRODUCTION: The characteristics of the epicardial (EPI) substrate responsible for ventricular tachycardia (VT) in ischemic cardiomyopathy (ICM) are undefined, and data on the long-term outcomes of EPI catheter ablation limited. We evaluated the prevalence, electrophysiologic features, and outcomes of catheter ablation of EPI VT in ICM. METHODS AND RESULTS: From December 2010 to June 2013, a total of 13 of 93 (14%) patients with ICM underwent catheter ablation at our institution and had conclusive evidence of critical EPI substrate demonstrated to participate in VT with activation, entrainment and/or pace mapping during sinus rhythm (two other patients underwent EPI mapping but had no optimal ablation targets). The electrophysiologic substrate characteristics and activation/entrainment mapping data were compared with a reference group of ICM patients without evidence of critical EPI substrate (N = 44), defined as a complete procedural success (noninducibility of any VT at programmed stimulation) after endocardial (ENDO)-only ablation. Patients with failed EPI access (N = 2) or history of cardiac surgery (N = 92) were excluded from the study. All 13 patients had evidence of abnormal EPI substrate with fractionated/late/split electrograms and low-bipolar voltage areas. The critical VT ablation sites were all located within the EPI bipolar "dense" scar (<1.0 mV) opposite the ENDO bipolar scar in 77% of cases and extending beyond the ENDO bipolar scar (within the ENDO unipolar low-voltage area) in the remaining patients. Compared with the reference ENDO-only group, patients with EPI VT had a smaller ENDO bipolar scar area, 54.0 (37.1-84) vs 86.7 (55.6-112) cm2 ; P = 0.0159, with a similar extent of ENDO unipolar low voltage. No other substrate characteristics or location differed between the two groups. After 35.2 ± 24.2 months of follow-up, VT-free survival was 73% in patients with EPI VT compared with 66% in the ENDO-only group (log-rank P = 0.56). CONCLUSIONS: The presence of the critical EPI substrate responsible for VT can be demonstrated in at least 14% of patients with ICM. The majority of EPI critical ablation sites are distributed opposite the ENDO bipolar scar area and catheter ablation is effective in achieving long-term arrhythmia control.

Imaging characteristics of papillary muscle site of origin of ventricular arrhythmias in patients with mitral valve prolapse.

BACKGROUND: Mitral valve prolapse has been associated with increased risk of ventricular arrhythmias. We aimed to examine whether certain cardiac imaging characteristics are associated with papillary muscle origin of ventricular arrhythmias in these patients. METHODS AND RESULTS: We screened electronic medical records of all patients documented to have mitral valve prolapse on either transthoracic echocardiogram (TTE) or cardiac magnetic resonance imaging (CMR) in our center, who also underwent an electrophysiologic study (EPS) between 2007 and 2016. Anterior and posterior mitral leaflet thickness and prolapsed distance were measured on TTE and late gadolinium enhancement (LGE) was assessed on CMR. Patients were categorized as papillary muscle positive (pap (+)) or negative (pap (-)) using EPS. Eighteen patients were included in this study. Of the 15 patients who underwent TTE, a significantly higher proportion of patients in the pap (+) group had an anterior to posterior leaflet prolapse ratio of >0.45 indicating more symmetric leaflet prolapse. There were no differences in anterior or posterior leaflet thickness or prolapse distance between the groups. Patients in the pap (+) group were more likely to be women. Of the 7 patients who underwent CMR, those who were pap (+) were more likely to have LGE in the region of the papillary muscles than those who were pap (-). CONCLUSION: Female gender, more symmetric bileaflet prolapse on TTE, and the presence of papillary muscle LGE on CMR may be associated with papillary muscle origin of ventricular arrhythmias in patients with mitral valve prolapse.

Anticoagulation use and clinical outcomes after catheter ablation in patients with persistent and longstanding persistent atrial fibrillation.

INTRODUCTION: Whether successful catheter ablation for atrial fibrillation (AF) reduces risk of cerebrovascular events (CVEs) remains controversial and whether oral anticoagulation therapy (OAT) can be safely discontinued in patients rendered free of AF recurrences remains unknown. We evaluated OAT use patterns and examined long-term rates of CVEs (stroke/TIA) and major bleeding episodes (MBEs) in patients with nonparoxysmal AF treated with catheter ablation. METHODS AND RESULTS: Four hundred patients with nonparoxysmal AF (200 persistent, 200 longstanding persistent; mean age 60.3 ± 9.7 years, 82% male) undergoing first AF ablation were followed for 3.6 ± 2.4 years. OAT discontinuation during follow-up was permitted in selected patients per physician discretion. At last follow-up, allowing for multiple ablations, 172 (43.0%) patients were free of AF recurrence. Two hundred and seven (51.8%) discontinued OAT at some point; 174 (43.5%) were off OAT at last follow-up. Patients without AF recurrence were more likely to remain off OAT (HR 0.23 [95% CI 0.17-0.33]). Patients with persistent (versus longstanding persistent) AF type prior to ablation (HR 0.6 [CI 0.44-0.83]) and those with CHA2 DS2 -VASc score <2 (HR 0.56 [0.39-0.80]) were less likely to continue OAT. Seven patients had CVEs (incidence: 0.49/100 patient years) and 14 experienced MBE during follow-up (incidence: 0.98/100 patient years). Older age (P  =  0.001) and coronary artery disease (P  =  0.028) were associated with CVE. CONCLUSION: Anticoagulation discontinuation in well selected, closely monitored patients following successful ablation of nonparoxysmal AF was associated with a low rate of clinical embolic CVEs. Prospective studies are required to confirm safety of OAT discontinuation after successful AF ablation.