Reddy, Vivek Y.

Background The PINNACLE FLX (Protection Against Embolism for Non‐valvular AF [Atrial Fibrillation] Patients: Investigational Device Evaluation of the Watchman FLX LAA [Left Atrial Appendage] Closure Technology) trial evaluated the safety and efficacy of a next‐generation left atrial appendage closure device (WATCHMAN FLX; Boston Scientific, Marlborough, MA). At 1 year, the study met the primary end points of safety and anatomical efficacy/appendage closure. This final report of the PINNACLE FLX trial includes the prespecified secondary end point of ischemic stroke or systemic embolism at 2 years, also making it the first report of 2‐year outcomes with this next‐generation left atrial appendage closure device. Methods and Results Patients with nonvalvular atrial fibrillation with CHA 2 DS 2 ‐VASc score ≥2 (men) or ≥3 (women), with an appropriate rationale for left atrial appendage closure, were enrolled to receive the left atrial appendage closure device at 29 US centers. Adverse events were assessed by an independent clinical events committee, and imaging was assessed by independent core laboratories. Among 395 implanted patients (36% women; mean age, 74 years; CHA 2 DS 2 ‐VASc, 4.2±1.5), the secondary efficacy end point of 2‐year ischemic stroke or systemic embolism was met, with an absolute rate of 3.4% (annualized rate, 1.7%) and an upper 1‐sided 95% confidence bound of 5.3%, which was superior to the 8.7% performance goal. Two‐year rates of adverse events were as follows: 9.3% all‐cause mortality, 5.5% cardiovascular death, 3.4% all stroke, and 10.1% major bleeding (Bleeding Academic Research Consortium 3 or 5). There were no additional systemic embolisms, device embolizations, pericardial effusions, or symptomatic device‐related thrombi after 1 year. Conclusions The secondary end point of 2‐year stroke or systemic embolism was met at 3.4%. In these final results of the PINNACLE FLX trial, the next‐generation WATCHMAN FLX device demonstrated favorable safety and efficacy outcomes.

Background: The Food and Drug Administration approved left atrial appendage occlusion with the Watchman device for patients who are at increased stroke risk and are suitable for oral anticoagulation but who have an appropriate reason to seek a nondrug alternative. These broad criteria raise the question of their interpretation in clinical practice. There is a lack of studies comprehensively evaluating the indications for Watchman implantation among a large series of patients from contemporary, real-world practice in the United States. Methods: We used the National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry to identify Watchman procedures performed between 2016 and 2018. We assessed procedural indications for Watchman implantation in the United States and evaluated the association between procedural indications and in-hospital adverse events. Results: A total of 38 314 procedures were included. The mean patient age was 76.1±8.1 years, and 58.9% were men. The mean CHA 2 DS 2 -VASc score was 4.8±1.5, whereas the mean hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol (HAS-BLED) score was 3.0±1.1. Prior stroke or transient ischemic attack was reported in 40.2% and prior bleeding in 70.1%, with gastrointestinal bleeding being most common (41.9%). The most common site-reported procedural indications for Watchman implantation were increased thromboembolic risk (64.8%) and history of major bleed (64.3%), followed by high fall risk (35.5%). Most (71.9%) had ≥2 procedural indications. Patients with high fall risk had increased risk of in-hospital adverse events (adjusted OR, 1.12; P =0.025), but no other differences were found in the risk of in-hospital adverse events by procedural indication. Conclusions: Among patients in the National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry, the most common procedural indications for Watchman implantation were increased thromboembolic risk, history of major bleed, and high fall risk. A majority of patients had multiple procedural indications. High fall risk conferred a modestly increased risk of in-hospital adverse events.

Aims In heart failure (HF) with preserved ejection fraction (HFpEF), excessive redistribution of blood volume into the central circulation leads to elevations of intracardiac pressures with exercise limitations. Splanchnic ablation for volume management (SAVM) has been proposed as a therapeutic intervention. Here we present preliminary safety and efficacy data from the initial roll‐in cohort of the REBALANCE‐HF trial. Methods and results The open‐label (roll‐in) arm of REBALANCE‐HF will enrol up to 30 patients, followed by the randomized, sham‐controlled portion of the trial (up to 80 additional patients). Patients with HF, left ventricular ejection fraction (LVEF) ≥50%, and invasive peak exercise pulmonary capillary wedge pressure (PCWP) ≥25 mmHg underwent SAVM. Baseline and follow‐up assessments included resting and exercise PCWP, New York Heart Association (NYHA) class, Kansas City Cardiomyopathy Questionnaire (KCCQ), 6‐min walk test, and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). Efficacy and safety were assessed at 1 and 3 months. Here we report on the first 18 patients with HFpEF that have been enrolled into the roll‐in, open‐label arm of the study across nine centres; 14 (78%) female; 16 (89%) in NYHA class III; and median (interquartile range) age 75.2 (68.4–81) years, LVEF 61.0 (56.0–63.2)%, and average (standard deviation) 20 W exercise PCWP 36.4 (±8.6) mmHg. All 18 patients were successfully treated. Three non‐serious moderate device/procedure‐related adverse events were reported. At 1‐month, the mean PCWP at 20 W exercise decreased from 36.4 (±8.6) to 28.9 (±7.8) mmHg ( p < 0.01), NYHA class improved by at least one class in 33% of patients ( p = 0.02) and KCCQ score improved by 22.1 points (95% confidence interval 9.4–34.2) ( p < 0.01). Conclusion The preliminary open‐label results from the multicentre REBALANCE‐HF roll‐in cohort support the safety and efficacy of SAVM in HFpEF. The findings require confirmation in the ongoing randomized, sham‐controlled portion of the trial.

Background: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. Methods: This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. Results: A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA 2 DS 2 -VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% ( P <0.0001). The incidence of the primary effectiveness end point was 100%, with a 1-sided 95% lower CI of 99.1%, again meeting the performance goal of 97.0% ( P <0.0001). Device-related thrombus was reported in 7 patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolizations. Conclusions: LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02702271.

AbstractAimsThe TactiCath Contact Force Ablation Catheter Study for Atrial Fibrillation (TOCCASTAR) clinical trial compared clinical outcomes using a contact force (CF) sensing ablation catheter (TactiCath) with a catheter that lacked CF measurement. This analysis links recorded events in the TOCCASTAR study and a large claims database, IBM MarketScan®, to determine the economic impact of using CF sensing during atrial fibrillation (AF) ablation.Methods and ResultsClinical events including repeat ablation, use of antiarrhythmic drugs, hospitalization, perforation, pericarditis, pneumothorax, pulmonary edema, pulmonary vein stenosis, tamponade, and vascular access complications were adjudicated in the year after ablation. CF was characterized as optimal if greater than or equal to 90% lesion was performed with greater than or equal to 10 g of CF. A probabilistic 1:1 linkage was created for subjects in MarketScan® with the same events in the year after ablation, and the cost was evaluated over 10 000 iterations. Of the 279 subjects in TOCCASTAR, 145 were ablated using CF (57% with optimal CF), and 134 were ablated without CF. In the MarketScan® cohort, 9811 subjects who underwent AF ablation were used to determine events and costs. For subjects ablated with optimal CF, total cost was $19 271 ± 3705 in the year after ablation. For ablation lacking CF measurement, cost was $22 673 ± 3079 (difference of $3402, P < .001). In 73% of simulations, optimal CF was associated with lower cost in the year after ablation.ConclusionCompared to ablation without CF, there was a decrease in healthcare cost of $3402 per subject in the first year after the procedure when optimal CF was used.

Background Recent publications reached conflicting conclusions about the cost‐effectiveness of left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, Marlborough, MA) for stroke risk reduction in nonvalvular atrial fibrillation (AF). This analysis sought to assess the cost‐effectiveness of LAAC relative to both warfarin and nonwarfarin oral anticoagulants (NOACs) using pooled, long‐term data from the randomized PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) and PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long‐Term Warfarin) trials. Methods and Results A Markov model was constructed from a US payer perspective with a lifetime (20‐year) horizon. LAAC clinical event rates and stroke outcomes were from pooled PROTECT AF and PREVAIL trial 5‐year data. Warfarin and NOAC inputs were derived from published meta‐analyses. The model was populated with a cohort of 10 000 patients, aged 70 years, at moderate stroke and bleeding risk. Sensitivity analyses were performed. LAAC was cost‐effective relative to warfarin by year 7 ($48 674/quality‐adjusted life‐year) and dominant (more effective and less costly) by year 10. LAAC became cost‐effective and dominant compared with NOACs by year 5. Over a lifetime, LAAC provided 0.60 more quality‐adjusted life‐years than warfarin and 0.29 more than NOACs. In sensitivity analyses, LAAC was cost‐effective relative to warfarin and NOACs in 98% and 95% of simulations, respectively. Conclusions Using pooled, 5‐year PROTECT AF and PREVAIL trial data, LAAC proved to be not only cost‐effective, but cost saving relative to warfarin and NOACs. LAAC with the Watchman device is an economically viable stroke risk reduction strategy for patients with AF seeking an alternative to lifelong anticoagulation.

Background: In patients with atrial fibrillation, left atrial appendage closure with the Watchman device prevents thromboembolism from the left atrial appendage; however, thrombus may form on the left atrial face of the device, and then potentially embolize. Herein, we studied the incidence, predictors, and clinical outcome of device-related thrombus (DRT) using a large series of clinical trial cohorts of patients undergoing Watchman implantation. Methods: We studied the device arms of 4 prospective Food and Drug Administration trials: PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) (n=463); PREVAIL (Evaluation of the Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) (n=269); CAP (Continued Access to PROTECT AF registry) (n=566); and CAP2 (Continued Access to PREVAIL registry) (n=578). Surveillance transesophageal echocardiographs were performed at 45 days and 12 months in all patients, and also at 6 months in the randomized control trials. We assessed both the incidence of DRT during these transesophageal echocardiographs (and other unscheduled transesophageal echocardiographs), and clinical outcomes of postprocedure stroke or systemic embolism (SSE) and adjusted for CHA 2 DS 2 -VASC and HAS-BLED scores. Results: Of 1739 patients who received an implant (7159 patient-years follow-up; CHA 2 DS 2 -VASc=4.0), DRT was seen in 65 patients (3.74%). The rates of SSE with and without DRT were 7.46 and 1.78 per 100 patient-years (adjusted rate ratio, 3.55; 95% confidence interval [CI], 2.18–5.79; P <0.001), and ischemic SSE rates were 6.28 and 1.65 per 100 patient-years (adjusted rate ratio, 3.22; 95% CI, 1.90–5.45, P <0.001). On multivariable modeling analysis, the predictors of DRT were as follows: history of transient ischemic attack or stroke (odds ratio [OR], 2.31; 95% CI, 1.26–4.25; P =0.007), permanent atrial fibrillation (OR, 2.24; 95% CI, 1.19–4.20; P =0.012); vascular disease (OR, 2.06; 95% CI, 1.08–3.91; P =0.028); left atrial appendage diameter (OR, 1.06 per mm increase; 95% CI, 1.01–1.12; P =0.019); left ventricular ejection fraction (OR, 0.96 per 1% increase; 95% CI, 0.94–0.99; P =0.009). DRT and SSE both occurred in 17 of 65 patients (26.2%). Of the 19 SSE events in these patients with DRT, 9 of 19 (47.4%) and 12 of 19 (63.2%) occurred within 1 and 6 months of DRT detection. Conversely, after left atrial appendage closure, most SSEs (123/142, 86.62%) occurred in patients without DRT. Conclusions: After left atrial appendage closure with Watchman, DRT (≈3.7%) is not frequent but, when present, is associated with a higher rate of stroke and systemic embolism.

Background and Purpose— Once a patient with atrial fibrillation experiences an embolic event, the risk of a recurrent event increases 2.6-fold. New treatments have emerged as viable treatment alternatives to warfarin for stroke risk reduction in secondary prevention populations. This analysis sought to assess the cost-effectiveness of left atrial appendage closure (LAAC) compared with warfarin and the non–vitamin K antagonist oral anticoagulants dabigatran 150 mg, apixaban and rivaroxaban in the prevention of stroke in nonvalvular atrial fibrillation patients with a prior stroke or transient ischemic attack. Methods— A Markov model was constructed using data from the secondary prevention subgroup analyses of the non–vitamin K antagonist oral anticoagulant and LAAC pivotal trials. Costs were from 2016 US Medicare reimbursement rates and the literature. The cost-effectiveness analysis was conducted from a US Medicare perspective over a lifetime (20 years) horizon. The model was populated with a cohort of 10 000 patients aged 70 years with a CHA 2 DS 2 -VASc score of 7 (annual stroke risk=9.60%) and HAS-BLED score of 3 (annual bleeding risk=3.74%). Results— LAAC achieved cost-effectiveness relative to dabigatran at year 5 and warfarin and apixaban at year 6. At 10 years, LAAC had more quality-adjusted life years (4.986 versus 4.769, 4.869, 4.888, and 4.810) and lower costs ($42 616 versus $53 770, $58 774, $55 656, and $58 655) than warfarin, dabigatran, apixaban, and rivaroxaban, respectively, making LAAC the dominant (more effective and less costly) stroke risk reduction strategy. LAAC remained the dominant strategy over the lifetime analysis. Conclusions— Upfront procedure costs initially make LAAC higher cost than warfarin and the non–vitamin K antagonist oral anticoagulants, but within 10 years, LAAC delivers more quality-adjusted life years and has lower total costs, making LAAC the most cost-effective treatment strategy for secondary prevention of stroke in atrial fibrillation.

Patients with nonvalvular atrial fibrillation have a 4- to 5-fold increase in strokes and that rhythm may be responsible for 15% to 20% of all strokes, particularly in the elderly. In this setting, thrombus in the left atrial appendage has been found to be the source of stroke in 90% of cases. Although oral anticoagulants have been found effective in reducing stroke rates, for a variety of issues, they may only be used in 40% to 50% of patients at increased risk for stroke. Given pathophysiology of stroke, site-specific therapy directed at left atrial appendage occlusion has been now studied for stroke prevention, and one device is FDA approved (Watchman). A meta-analysis of 2 randomized clinical trials and 2 registries with this device documented the following: (1) patients receiving the device had significantly fewer hemorrhagic strokes (hazard ratio 0.22, P =0.004); (2) a significant reduction in cardiovascular or unexplained death (hazard ratio 0.48, P =0.004); (3) more ischemic strokes in the device group; however, when periprocedural events were excluded, the difference was not significant; and (4) a significant reduction in nonprocedural bleeding with the device (hazard ratio 0.51, P =0.006) versus control. At present, the only device approved in the United States is indicated in patients with nonvalvular atrial fibrillation with acceptable anatomy who are at increased risk for stroke and would be candidates for anticoagulation in whom there is concern about the risk/benefit ratio for chronic anticoagulation. Unresolved issues include optimal patient selection criteria, the role of devices in patients in whom anticoagulation is contraindicated, and the relative role of novel oral anticoagulants versus the device which has not been tested in randomized trials.

Flex Tip Comparative AblationIntroductionNext‐generation catheters have been developed to reduce irrigation volume and preserve power delivery. A novel design uses a flexible tip (FlexAbility™ catheter) that directs flow to the contact surface. Because of recent safety issues with new catheters, we undertook a study in a canine heart with 3 irrigated catheters to compare efficacy and safety.MethodsEndocardial ablation was performed by 2 independent operators in 12 anesthetized canines with the FlexAbility (St. Jude Medical), ThermoCool™ (Biosense Webster), and ThermoCool™ SF (Biosense Webster) catheters. Endocardial RF lesions were delivered with each catheter in all 4 chambers of each animal for 52 ± 16 seconds. Each chamber was randomized to receive ablation from one catheter with recording of safety events. Cardiac pathology was performed with triphenyl tetrazolium chloride stain.ResultsAverage lesion dimensions were not significantly different between the 3 catheters. FlexAbility™ demonstrated a lower risk of steam pops relative to ThermoCool SF (P‐value = 0.013) despite equal mean power and radiofrequency time. High‐temperature generator shutdowns were observed with FlexAbility™ but not with either ThermoCool catheter. High‐temperature shutdowns were associated with larger average impedance drops (28.5 ohms vs. 19 ohms) without compromising lesion size.ConclusionsThe FlexAbility™ tip is safe and effective with no significant difference in lesion sizes compared to both standard ThermoCool and ThermoCool SF. FlexAbility™ has a significantly lower risk of steam pops compared to ThermoCool SF in a beating heart as defined predominantly by an abrupt rise of impedance.