Marc A. Miller

Left Atrial Appendage Closure With the Watchman Device in Patients With a Contraindication for Oral Anticoagulation: The ASAP Study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology)

OBJECTIVES The purpose of this study was to assess the safety and efficacy of left atrial appendage (LAA) closure in nonvalvular atrial fibrillation (AF) patients ineligible for warfarin therapy. BACKGROUND The PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that LAA closure with the Watchman device (Boston Scientific, Natick, Massachusetts) was noninferior to warfarin therapy. However, the PROTECT AF trial only included patients who were candidates for warfarin, and even patients randomly assigned to the LAA closure arm received concomitant warfarin for 6 weeks after Watchman implantation. METHODS A multicenter, prospective, nonrandomized study was conducted of LAA closure with the Watchman device in 150 patients with nonvalvular AF and CHADS₂ (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score ≥1, who were considered ineligible for warfarin. The primary efficacy endpoint was the combined events of ischemic stroke, hemorrhagic stroke, systemic embolism, and cardiovascular/unexplained death. RESULTS The mean CHADS₂ score and CHA₂DS₂-VASc (CHADS₂ score plus 2 points for age ≥75 years and 1 point for vascular disease, age 65 to 74 years, or female sex) score were 2.8 ± 1.2 and 4.4 ± 1.7, respectively. History of hemorrhagic/bleeding tendencies (93%) was the most common reason for warfarin ineligibility. Mean duration of follow-up was 14.4 ± 8.6 months. Serious procedure- or device-related safety events occurred in 8.7% of patients (13 of 150 patients). All-cause stroke or systemic embolism occurred in 4 patients (2.3% per year): ischemic stroke in 3 patients (1.7% per year) and hemorrhagic stroke in 1 patient (0.6% per year). This ischemic stroke rate was less than that expected (7.3% per year) based on the CHADS₂ scores of the patient cohort. CONCLUSIONS LAA closure with the Watchman device can be safely performed without a warfarin transition, and is a reasonable alternative to consider for patients at high risk for stroke but with contraindications to systemic oral anticoagulation. (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology [ASAP]; NCT00851578).

Clinical ResearchAtrial FibrillationLeft Atrial Appendage Closure With the Watchman Device in Patients With a Contraindication for Oral Anticoagulation: The ASAP Study (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology)

OBJECTIVES The purpose of this study was to assess the safety and efficacy of left atrial appendage (LAA) closure in nonvalvular atrial fibrillation (AF) patients ineligible for warfarin therapy. BACKGROUND The PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that LAA closure with the Watchman device (Boston Scientific, Natick, Massachusetts) was noninferior to warfarin therapy. However, the PROTECT AF trial only included patients who were candidates for warfarin, and even patients randomly assigned to the LAA closure arm received concomitant warfarin for 6 weeks after Watchman implantation. METHODS A multicenter, prospective, nonrandomized study was conducted of LAA closure with the Watchman device in 150 patients with nonvalvular AF and CHADS₂ (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score ≥1, who were considered ineligible for warfarin. The primary efficacy endpoint was the combined events of ischemic stroke, hemorrhagic stroke, systemic embolism, and cardiovascular/unexplained death. RESULTS The mean CHADS₂ score and CHA₂DS₂-VASc (CHADS₂ score plus 2 points for age ≥75 years and 1 point for vascular disease, age 65 to 74 years, or female sex) score were 2.8 ± 1.2 and 4.4 ± 1.7, respectively. History of hemorrhagic/bleeding tendencies (93%) was the most common reason for warfarin ineligibility. Mean duration of follow-up was 14.4 ± 8.6 months. Serious procedure- or device-related safety events occurred in 8.7% of patients (13 of 150 patients). All-cause stroke or systemic embolism occurred in 4 patients (2.3% per year): ischemic stroke in 3 patients (1.7% per year) and hemorrhagic stroke in 1 patient (0.6% per year). This ischemic stroke rate was less than that expected (7.3% per year) based on the CHADS₂ scores of the patient cohort. CONCLUSIONS LAA closure with the Watchman device can be safely performed without a warfarin transition, and is a reasonable alternative to consider for patients at high risk for stroke but with contraindications to systemic oral anticoagulation. (ASA Plavix Feasibility Study With Watchman Left Atrial Appendage Closure Technology [ASAP]; NCT00851578).

Permanent Leadless Cardiac Pacing: Results of the LEADLESS Trial

Background— Conventional cardiac pacemakers are associated with several potential short- and long-term complications related to either the transvenous lead or subcutaneous pulse generator. We tested the safety and clinical performance of a novel, completely self-contained leadless cardiac pacemaker. Methods and Results— The primary safety end point was freedom from complications at 90 days. Secondary performance end points included implant success rate, implant time, and measures of device performance (pacing/sensing thresholds and rate-responsive performance). The mean age of the patient cohort (n=33) was 77±8 years, and 67% of the patients were male (n=22/33). The most common indication for cardiac pacing was permanent atrial fibrillation with atrioventricular block (n=22, 67%). The implant success rate was 97% (n=32). Five patients (15%) required the use of >1 leadless cardiac pacemaker during the procedure. One patient developed right ventricular perforation and cardiac tamponade during the implant procedure, and eventually died as the result of a stroke. The overall complication-free rate was 94% (31/33). After 3 months of follow-up, the measures of pacing performance (sensing, impedance, and pacing threshold) either improved or were stable within the accepted range. Conclusions— In a prospective nonrandomized study, a completely self-contained, single-chamber leadless cardiac pacemaker has shown to be safe and feasible. The absence of a transvenous lead and subcutaneous pulse generator could represent a paradigm shift in cardiac pacing. Clinical Trial Registration— URL: . Unique identifier: [NCT01700244][1]. # CLINICAL PERSPECTIVE {#article-title-26} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01700244&atom=%2Fcirculationaha%2F129%2F14%2F1466.atomBackground— Conventional cardiac pacemakers are associated with several potential short- and long-term complications related to either the transvenous lead or subcutaneous pulse generator. We tested the safety and clinical performance of a novel, completely self-contained leadless cardiac pacemaker. Methods and Results— The primary safety end point was freedom from complications at 90 days. Secondary performance end points included implant success rate, implant time, and measures of device performance (pacing/sensing thresholds and rate-responsive performance). The mean age of the patient cohort (n=33) was 77±8 years, and 67% of the patients were male (n=22/33). The most common indication for cardiac pacing was permanent atrial fibrillation with atrioventricular block (n=22, 67%). The implant success rate was 97% (n=32). Five patients (15%) required the use of >1 leadless cardiac pacemaker during the procedure. One patient developed right ventricular perforation and cardiac tamponade during the implant procedure, and eventually died as the result of a stroke. The overall complication-free rate was 94% (31/33). After 3 months of follow-up, the measures of pacing performance (sensing, impedance, and pacing threshold) either improved or were stable within the accepted range. Conclusions— In a prospective nonrandomized study, a completely self-contained, single-chamber leadless cardiac pacemaker has shown to be safe and feasible. The absence of a transvenous lead and subcutaneous pulse generator could represent a paradigm shift in cardiac pacing. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT01700244.

Activation and Entrainment Mapping of Hemodynamically Unstable Ventricular Tachycardia Using a Percutaneous Left Ventricular Assist Device

OBJECTIVES Our goal was to investigate the effects of percutaneous left ventricular assist device (pLVAD) support during catheter ablation of unstable ventricular tachycardia (VT). BACKGROUND Mechanical cardiac support during ablation of unstable VT is being increasingly used, but there is little available information on the potential hemodynamic benefits. METHODS Twenty-three consecutive procedures in 22 patients (ischemic, n = 11) with structural heart disease and hemodynamically unstable VT were performed with either pLVAD support (n = 10) or no pLVAD support (intra-aortic balloon pump counterpulsation, n = 6; no support, n = 7). Procedural monitoring included vital signs, left atrial pressure, arterial blood pressure, cerebral perfusion/oximetry, VT characteristics, and ablation outcomes. RESULTS The pLVAD group was maintained in VT significantly longer than the non-pLVAD group (66.7 min vs. 27.5 min; p = 0.03) and required fewer early terminations of sustained VT for hemodynamic instability (1.0 vs. 4.0; p = 0.001). More patients in the pLVAD group had at least 1 VT termination during ablation than non-pLVAD patients (9 of 10 [90%] vs. 5 of 13 [38%]; p = 0.03). There were no differences between groups in duration of cerebral deoxygenation, hypotension or perioperative changes in left atrial pressure, brain natriuretic peptide levels, lactic acid, or renal function. CONCLUSIONS In patients with scar-related VT undergoing catheter ablation, pLVAD support was able to safely maintain end-organ perfusion despite extended periods of hemodynamically unstable VT. Randomized studies are necessary to determine whether this enhanced ability to perform entrainment and activation mapping will translate into a higher rate of clinical success.

New classification scheme of left ventricular noncompaction and correlation with ventricular performance.

Isolated left ventricular noncompaction (LVNC) is an increasingly-recognized cardiomyopathy, and the possibility that it exists as a spectrum of disease has yet to be explored. We sought to determine the prevalence, spectrum, and functional consequences of LVNC; 2 blinded reviewers assessed 500 transthoracic echocardiograms for LVNC for adequate study quality, absence of co-existing cardiomyopathy, and LVNC. If present, the ratio of the maximum linear length of noncompacted to compacted myocardium (NC/C) and the planimetered area of LVNC on apical 4-chamber view were measured. Patients were classified by degree of noncompaction measured by either the NC/C ratio or LVNC area as controls, mild, moderate, and severe; 380 patients were included in the analysis and 60 (15.8%) had evidence of noncompaction. Patients with increasing severity of noncompaction had significantly decreased ejection fractions. In conclusion, these findings indicate that LVNC may be more common than previously recognized and may exist as a spectrum, which can be classified using the NC/C ratio or LVNC area classification schemes.

Bipolar irrigated radiofrequency ablation: A therapeutic option for refractory intramural atrial and ventricular tachycardia circuits

BACKGROUND Irrigated radiofrequency (RF) ablation can be insufficient to eliminate intramurally located septal atrial flutter (AFL) and ventricular tachycardia (VT) circuits. Bipolar ablation between 2 ablation catheters may be considered for such circuits. OBJECTIVE To evaluate the utility of bipolar irrigated ablation to terminate arrhythmias resistant to unipolar ablation. METHODS In vitro: Bipolar and sequential unipolar RF ablation lesions were placed on porcine ventricular tissue in a saline bath to assess for lesion transmurality. Clinical: 3 patients with atypical septal flutter (AFL), 4 patients with septal VT, and 2 with left ventricle free-wall VT, all of whom failed sequential unipolar RF ablation, underwent bipolar RF ablation using irrigated catheters placed on either surface of the interatria/interventricular septum and left ventricle free-wall, respectively. RESULTS In vitro: Bipolar RF was found to be more likely to achieve transmural lesions (82% vs 33%; P = .001) and could do so in tissues with thicknesses of up to 25 mm. Clinical: All 5 AFLs (3 patients) were successfully terminated with bipolar RF. In follow-up, AFL recurred in 2 of the 3 patients and atrial fibrillation and AFL recurred in 1 of the 3. All 3 thereafter underwent repeat procedures with successful maintenance of sinus rhythm in 2 of the 3 patients (6-month follow-up). In the VT subgroup, 5 of 6 septal VTs and 2 of 3 free-wall VTs were terminated successfully during ablation. In follow-up (12 months), 2 of the 4 patients in the septal bipolar group and 1 of the 2 patients in the free-wall group remained free of VT. CONCLUSIONS Bipolar RF can be used to terminate arrhythmias in select patients with tachyarrhythmias.

The Role of Implantable Cardioverter-Defibrillators in Patients With Continuous Flow Left Ventricular Assist Devices

Background—The prognosis for patients experiencing ventricular arrhythmias (VAs) while on continuous flow left ventricular assist device (LVAD) support has not been well elucidated. Accordingly, the role of implantable cardioverter-defibrillators (ICDs) in this patient population remains undefined. Methods and Results—Records of 106 consecutive patients undergoing implantation of the HeartMate II LVAD at a single center were reviewed. For patients surviving >30 days postimplant (98 patients), the impact of VAs and ICDs on survival was analyzed. Mean age was 56.6±11.4 years, 82.1% were male, 42.5% had an ischemic cardiomyopathy, 87.7% were bridge to transplantation, and median length of support was 217 days. Twenty-one (19.8%) patients died, 60 (56.6%) survived to transplantation, and 25 patients (23.6%) reached the end of study, had the LVAD explanted, or were lost to follow-up. Post-LVAD VAs occurred in 37 patients (34.9%) but were not associated with increased mortality (hazard ratio, 0.58 [0.18–1.90]). Sixty-two (63.3%) patients had an active ICD, and 36 (36.7%) patients had no ICD or an inactivated ICD post-LVAD. Patients with an ICD were more likely to be INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) level 3 or 4 at the time of implant (54.8% versus 33.3%; P=0.04). An appropriate shock was delivered in 27.3% of patients, but the presence of an active ICD was not associated with improved survival (hazard ratio, 1.12 [0.37–3.35]). Conclusions—VAs are common in patients with continuous flow LVADs. Although some episodes may be clinically significant, VAs are not associated with a worse prognosis, and concomitant ICDs in these patients may not reduce mortality.

Multicenter study on acute and long-term safety and efficacy of percutaneous left atrial appendage closure using an epicardial suture snaring device

BACKGROUND Pericardial suture ligation of the left atrial appendage (LAA) may be an alternative to endoluminal devices for stroke prevention in patients with atrial fibrillation, but multicenter safety and efficacy data in high-risk patients with contraindications to oral anticoagulation are lacking. OBJECTIVE The purpose of this study was to report the outcomes of consecutive cases of pericardial suture ligation of the LAA in high-risk patients performed at 4 centers. METHODS The cohort included 41 consecutive patients who underwent LAA closure with the LARIAT system. Epicardial and transeptal access was obtained, and the epicardial snare was advanced over an endo-epicardial magnetic-tipped guidewire to close the LAA. Transesophageal echocardiography was used to confirm LAA exclusion. RESULTS Mean age was 75 ± 10 years, mean CHADS2 score was 3.0 ± 1.3, and mean HAS-BLED score was 4.4 ± 1.4. These patients accumulated 24.6 person-years of follow-up. Acute LAA closure was achieved in 38 patients (93%). Transesophageal echocardiography or computerized tomographic angiography performed up to 3.3 ± 0.8 months after the procedure demonstrated LAA leakage in 24% of patients. One patient (2%) had a transient ischemic attack, and 8 (20%) developed pericardial effusions requiring pericardiocentesis. Four cases (9%) were complicated by perforation of the LAA, with 2 of these patients requiring open surgical correction. CONCLUSION This multicenter experience revealed that pericardial suture ligation with the LARIAT system is technically feasible and acutely efficacious. However, additional improvements are required to minimize the rate of pericardial complications. A randomized study is warranted to accurately define the long-term efficacy and safety profile of percutaneous epicardial suture ligation.

Percutaneous hemodynamic support with Impella 2.5 during scar-related ventricular tachycardia ablation (PERMIT 1).

Background—Percutaneous left ventricular assist devices (pLVADs) are increasingly being used to facilitate ablation of unstable ventricular tachycardia (VT), but the safety profile and hemodynamic benefits of these devices have not been described in a systematic, prospective manner. Methods and Results—Twenty patients with scar VT underwent ablation with a pLVAD. Neuromonitoring using cerebral oximetry was performed to evaluate a cerebral desaturation threshold to guide the duration of activation/entrainment mapping. The efficacy of pLVAD support was tested in a controlled manner with simulated VT. Complete procedural success was achieved in 50% (n=8) of patients, who were initially inducible for sustained VT, and partial procedural success in 37% (n=6). Using a cerebral desaturation level of 55% as a lower safety limit to guide the duration of sustained VT, 3 patients (15%) developed mild acute kidney injury (all resolved), and 1 (5%) patient developed mild cognitive dysfunction. During fast simulated VT (300 ms), cerebral desaturation to ⩽55% occurred in more than half (53%) of patients tested without pLVAD support, compared with only 5% with full pLVAD support (P=0.003). Conclusions—In a consecutive series of patients with severe left ventricular dysfunction, pLVAD-supported scar VT ablation was safe and feasible. During fast simulated VT, a miniaturized axial flow pump imparted a more favorable hemodynamic profile compared with pharmacological agents alone. Cerebral oximetry is a complimentary monitoring modality during scar VT ablation, and avoidance of cerebral desaturations below a threshold of 55% may safely guide the duration of mapping during unstable VT.

Leadless Cardiac Pacemakers: Back to the Future

Despite significant advances in battery longevity, lead performance, and programming features since the first implanted permanent pacemaker was developed, the basic design of cardiac pacemakers has remained relatively unchanged over the past 50 years. Because of inherent limitations in their design, conventional (transvenous) pacemakers are prone to multiple potential short- and long-term complications. Accordingly, there has been intense interest in a system able to provide the symptomatic and potentially lifesaving therapies of cardiac pacemakers while mitigating many of the risks associated with their weakest link-the transvenous lead. Leadless cardiac pacing represents the future of cardiac pacing systems, similar to the transition that occurred from the use of epicardial pacing systems to the familiar transvenous systems of today. This review summarizes the current evidence and potential benefits of leadless pacing systems, which are either commercially available (in Europe) or under clinical investigation.