Gregory E. Supple

Reverse Ventricular Remodeling Reduces Ischemic Mitral Regurgitation Echo-Guided Device Application in the Beating Heart

Background—In ischemic mitral regurgitation (MR), mitral leaflet closure is restricted by ventricular remodeling with displacement of the papillary muscles (PMs). Therapy is uncertain because ring annuloplasty does not alleviate PM displacement. We tested the hypothesis that echo-guided PM repositioning using an external device can reduce MR without compromising left ventricular (LV) function. Methods and Results—We studied 10 sheep with ischemic MR produced by circumflex ligation with inferior infarction, 6 acutely and 4 eight weeks after myocardial infarction (MI). A Dacron patch containing an inflatable balloon was placed over the PMs and adjusted under echo guidance to reverse LV remodeling and reposition the infarcted PM. 3D echo assessed mitral valve geometric changes. In 7 sheep, sonomicrometry and Millar catheters assessed changes in end-systolic and end-diastolic pressure-volume relationships, and microspheres were injected to assess coronary flow. Moderate MR after MI resolved with patch application alone (n=3) or echo-guided balloon inflation, which repositioned the infarcted PM, decreasing the PM tethering distance from 31.1±2.5 mm after MI to 26.8±1.8 with patch (P <0.01; baseline=25.5±1.5). LV contractility was unchanged (end-systolic slope=3.4±1.6 mm Hg/mL with patch versus 2.8±1.6 after MI). Although there was a nonsignificant trend for a mild increase in stiffness constant (0.07±0.05 mL−1 versus 0.05±0.03 after MI, P =0.06), LV end-diastolic pressure was unchanged as MR resolved. Coronary flow to noninfarcted regions was not reduced. Conclusions—An external device that repositions the PMs can reduce ischemic MR without compromising LV function. This relatively simple technique can be applied under echo guidance in the beating heart.

New Efficient Catheter-Based System for Myocardial Gene Delivery

Background—Manipulating gene expression in the failing heart has therapeutic promise, but until now efficient and homogeneous cardiac gene delivery has required an open-chest approach. This study examines the hypothesis that vector delivery promoted by echo contrast microbubbles will be maximized by injection of the vectors into the aortic root with brief balloon occlusion above the sinuses, while at the same time prolonging diastole and vasodilating with acetylcholine (ACh) to maximize coronary exposure. Methods and Results—After incubation with albumin-coated perfluorocarbon microbubbles, an adenovirus encoding a reporter gene was infused into the aortic root of rats. To maximize delivery, the aortic root was transiently occluded with a balloon catheter during a brief ACh-induced asystole. Ultrasound was used to image the delivery and disrupt the microbubbles. Aortic occlusion with concomitant ACh increased myocardial gene expression for virus + microbubbles by >2.5-fold, from 925±165 to 2358±376 relative units (RU;P <0.01). This delivery system also produced substantial expression with vector alone (1473±549 RU). All uptakes were significant compared with 433±332 RU without virus. Conclusions—An adenoviral delivery system combining echo contrast with a catheter-based technique to maximize coronary perfusion increases gene delivery compared with echo contrast alone. This novel method permits efficient percutaneous gene delivery in closed-chest animals.

Efforts to enhance catheter stability improve atrial fibrillation ablation outcome

BACKGROUND Contemporary techniques to enhance anatomical detail and catheter contact during atrial fibrillation (AF) ablation include (1) the integration of preacquired tomographic reconstructions with electroanatomical mapping (3-dimensional image integration [I-EAM]), (2) the use of steerable introducers (SIs), and (3) high-frequency jet ventilation (HFJV). OBJECTIVE To prove that using these stabilizing techniques during AF ablation improves 1-year procedural outcome. METHODS We studied 300 patients undergoing AF ablation at our institution. Patients were divided into 3 equal treatment groups (100 patients each) on the basis of the tools utilized: (1) group 1: AF ablation performed without I-EAM, SI, or HFJV; (2) group 2: AF ablation performed using I-EAM and SI, but without HFJV; and (3) group 3: AF ablation performed with I-EAM, SI, and HFJV. The primary outcome was freedom from AF 1 year after a single ablation procedure. The burden of both acute and chronic pulmonary vein reconnection was also assessed. RESULTS Patients from groups 2 and 3 had significantly more nonparoxysmal AF (17% vs 30% vs 39%; P = .002), larger left atria (4.2 ± 0.8 cm vs 4.4 ± 0.7 cm vs 4.5 ± 0.8 cm; P<.001), and higher body mass index (BMI; 28.5 ± 5.8 kg/m² vs 29.1 ± 4.8 kg/m² vs 31.2 ± 5.4 kg/m²; P<.001). Despite these differences, with adoption of I-EAM, SI, and HFJV we noted a significant improvement in 1-year freedom from AF (52% vs 66% vs 74%; P = .006) as well as fewer acute (1.1 ± 1.2 vs 0.9 ± 1.1 vs 0.6 ± 0.9; P = .03) and chronic (3.5 ± 0.9 vs 3.2 ± 0.9 vs 2.4 ± 1.0; P = .02) pulmonary vein reconnections. CONCLUSIONS The incorporation of contemporary tools to enhance anatomical detail and ablation catheter stability significantly improved 1-year freedom from AF after ablation.

Mobile Thrombus on Device Leads in Patients Undergoing Ablation Identification, Incidence, Location, and Association With Increased Pulmonary Artery Systolic Pressure

Background— Mobile thrombi, not routinely recognized on transthoracic echocardiography, are frequently identified on cardiovascular implantable electronic device leads with intracardiac echocardiography (ICE) during ablation procedures. Their incidence, characteristics, and consequences have not yet been defined. Methods and Results— We used ICE to examine leads for thrombi and to measure the pulmonary artery systolic pressure in patients with a cardiovascular implantable electronic device presenting for ablation. Patient clinical characteristics, device type, and lead characteristics were correlated with presence of thrombi. Most patients had congestive heart failure (84%), with an average left ventricular ejection fraction of 40%. Thrombi were seen with ICE in 26 of 86 patients (30%) but were seen on transthoracic echocardiography in only 1 of the 26 patients. Thrombi on ICE were mobile, averaged 18±5.9 mm long by 4.4±2.3 mm wide, and were more commonly identified in the right atrium (n=25) than in the right ventricle (n=5). Thrombi were associated with higher pulmonary artery systolic pressure: 39±9 mm Hg with thrombi versus 33±7 mm Hg without thrombi (odds ratio, 1.11; 95% confidence interval, 1.03 to 1.20; P=0.01). No other characteristic assessed was associated with a significant difference in the presence of lead thrombi. Conclusions— Mobile thrombi on cardiovascular implantable electronic device leads are present in 30% of patients undergoing ablation and are readily identified with ICE despite being underrecognized with transthoracic echocardiography. Further study is warranted to determine whether lead thrombi are a clinically relevant source of pulmonary emboli in some patients with cardiovascular implantable electronic devices.Background— Mobile thrombi, not routinely recognized on transthoracic echocardiography, are frequently identified on cardiovascular implantable electronic device leads with intracardiac echocardiography (ICE) during ablation procedures. Their incidence, characteristics, and consequences have not yet been defined. Methods and Results— We used ICE to examine leads for thrombi and to measure the pulmonary artery systolic pressure in patients with a cardiovascular implantable electronic device presenting for ablation. Patient clinical characteristics, device type, and lead characteristics were correlated with presence of thrombi. Most patients had congestive heart failure (84%), with an average left ventricular ejection fraction of 40%. Thrombi were seen with ICE in 26 of 86 patients (30%) but were seen on transthoracic echocardiography in only 1 of the 26 patients. Thrombi on ICE were mobile, averaged 18±5.9 mm long by 4.4±2.3 mm wide, and were more commonly identified in the right atrium (n=25) than in the right ventricle (n=5). Thrombi were associated with higher pulmonary artery systolic pressure: 39±9 mm Hg with thrombi versus 33±7 mm Hg without thrombi (odds ratio, 1.11; 95% confidence interval, 1.03 to 1.20; P =0.01). No other characteristic assessed was associated with a significant difference in the presence of lead thrombi. Conclusions— Mobile thrombi on cardiovascular implantable electronic device leads are present in 30% of patients undergoing ablation and are readily identified with ICE despite being underrecognized with transthoracic echocardiography. Further study is warranted to determine whether lead thrombi are a clinically relevant source of pulmonary emboli in some patients with cardiovascular implantable electronic devices. # Clinical Perspective {#article-title-24}

Idiopathic ventricular arrhythmias originating from the moderator band: Electrocardiographic characteristics and treatment by catheter ablation

BACKGROUND The moderator band (MB) can be a source of premature ventricular contractions (PVCs), monomorphic ventricular tachycardia (VT), and idiopathic ventricular fibrillation (IVF). OBJECTIVE The purpose of this study was to define the electrocardiographic (ECG) characteristics and procedural techniques to successfully identify and ablate MB PVCs/VT. METHODS In 10 patients with left bundle branch block morphology PVCs/VT, electroanatomic mapping in conjunction with intracardiac echocardiography (ICE) localized the site of origin of the PVCs to the MB. Clinical characteristics of the patients, ECG features, and procedural data were collected and analyzed. RESULTS Seven patients presented with IVF and 3 presented with monomorphic VT. In all patients, the ventricular arrhythmias (VAs) had a left bundle branch block QRS with a late precordial transition (>V4), a rapid downstroke of the QRS in the precordial leads, and a left superior frontal plane axis. Mean QRS duration was 152.7 ± 15.2 ms. Six patients required a repeat procedure. After mean follow-up of 21.5 ± 11.6 months, all patients were free of sustained VAs, with only 1 patient requiring antiarrhythmic drug therapy and 1 patient having isolated PVCs no longer inducing VF. There were no procedural complications. CONCLUSION VAs originating from the MB have a distinctive morphology and often are associated with PVC-induced ventricular fibrillation. Catheter ablation can be safely performed and is facilitated by ICE imaging.

Prevalence and distribution of focal triggers in persistent and long-standing persistent atrial fibrillation

BACKGROUND The relevance of focal triggers in persistent atrial fibrillation (PerAF) and long-standing persistent atrial fibrillation (LSPAF) has not been previously investigated. OBJECTIVE We prospectively evaluated the prevalence and distribution of AF triggers in patients referred for catheter ablation of PerAF and LSPAF. METHODS We analyzed consecutive patients undergoing first time AF ablation who underwent a standardized trigger protocol including cardioversion of induced or spontaneous AF and infusion of up to 20 μg of isoproterenol for 15-20 minutes either before or after pulmonary vein (PV) isolation accomplished. Triggers were defined as AF/sustained atrial tachyarrhythmia or repetitive atrial premature depolarizations. RESULTS A total of 2168 patients were included (mean age 57 ± 11 years; 1636 [75%] men), with 1531 patients having paroxysmal AF (PAF) (71%), 496 having PerAF (23%), and 141 having LSPAF (7%). PV triggers were found in 1398 patients with PAF (91%), 449 patients with PerAF (91%), and 129 patients with LSPAF (91%) (P = .856 for comparison across groups). Non-PV triggers were elicited in a total of 234 patients (11%), and the prevalence was similar across the different types of AF (PAF, 165 [11%]; PerAF, 54 [11%]; LSPAF, 15 [11%]; P = .996 for comparison across groups). CONCLUSION PVs are the main AF trigger site in patients with PerAF and LSPAF, with an overall prevalence similar to that found in patients with PAF. These results support the current recommendations for PV isolation as the cornerstone of catheter ablation to eliminate AF triggers in PerAF and LSPAF.

Core isolation of critical arrhythmia elements for treatment of multiple scar-based ventricular tachycardias.

Background—Radiofrequency ablation of multiple or unmappable ventricular tachycardias (VTs) remains a challenge with unclear end points. We present our experience with a new strategy isolating core elements of VT circuits. Methods and Results—Patients with structural heart disease presenting for VT radiofrequency ablation at 2 centers were included. Strategy involved entrainment/activation mapping if VT was hemodynamically stable, and voltage mapping with electrogram analysis and pacemapping. Core isolation (CI) was performed incorporating putative isthmus and early exit site(s) based on standard criteria. If VT was noninducible, the dense scar (<0.5 mV) region was isolated. Successful CI was defined by exit block (20 mA at 2 ms) within the isolated region. VT inducibility was also assessed. Forty-four patients were included (mean age, 63; 95% male; 73% ischemic cardiomyopathy; mean left ventricular ejection fraction, 31%; 68% with multiple unstable VTs [mean, 3+2]). CI area was 11+12 versus 55+40 cm2 total scar area. Additional substrate modification was performed in 27 (61%), and epicardial radiofrequency ablation was performed in 4 (9%) patients. CI was achieved in 37 (84%) and led to better VT-free survival (log rank P=0.013). Conclusions—CI is a novel strategy with a discrete and measurable end point beyond VT inducibility to treat patients with multiple or unmappable VTs. The CI region can be selected based on standard characterization of suspected VT isthmus surrogates thus limiting ablation target size. Exit block within the isolated area is achievable in most and may further improve long-term success.

Long-Term Outcome With Catheter Ablation of Ventricular Tachycardia in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy

Background—Catheter ablation of ventricular tachycardia (VT) in arrhythmogenic right ventricular cardiomyopathy improves short-term VT-free survival. We sought to determine the long-term outcomes of VT control and need for antiarrhythmic drug therapy after endocardial (ENDO) and adjuvant epicardial (EPI) substrate modification in patients with arrhythmogenic right ventricular cardiomyopathy. Methods and Results—We examined 62 consecutive patients with Task Force criteria for arrhythmogenic right ventricular cardiomyopathy referred for VT ablation with a minimum follow-up of 1 year. Catheter ablation was guided by activation/entrainment mapping for tolerated VT and pacemapping/targeting of abnormal substrate for unmappable VT. Adjuvant EPI ablation was performed when recurrent VT or persistent inducibility after ENDO-only ablation. Endocardial plus adjuvant EPI ablation was performed in 39 (63%) patients, including 13 who crossed over to ENDO–EPI after VT recurrence during follow-up, after ENDO-only ablation. Before ablation, 54 of 62 patients failed a mean of 2.4 antiarrhythmic drugs, including amiodarone in 29 (47%) patients. During follow-up of 56±44 months after the last ablation, VT-free survival was 71% with only a single VT episode in additional 9 patients (15%). At last follow-up, 39 (64%) patients were only on &bgr;-blockers or no treatment, 21 were on class 1 or 3 antiarrhythmic drugs (11 for atrial arrhythmias), and 2 were on amiodarone as a bridge to heart transplantation. Conclusions—The long-term outcome after ENDO and adjuvant EPI substrate ablation of VT in arrhythmogenic right ventricular cardiomyopathy is good. Most patients have complete VT control without amiodarone therapy and limited need for antiarrhythmic drugs.

Intracardiac Echocardiographic Diagnosis of Thrombus Formation in the Left Atrial Appendage: A Complementary Role to Transesophageal Echocardiography

We sought to develop and validate an intracardiac echocardiography (ICE) imaging strategy for evaluation of left atrial (LA) appendage (LAA) anatomy and function to clarify equivocal findings of LAA thrombus with transesophageal echocardiography (TEE).

Percutaneous Epicardial Ablation of Ventricular Arrhythmias Arising From the Left Ventricular Summit

Background—Percutaneous epicardial ablation of ventricular arrhythmias arising from the left ventricular summit is limited by the presence of major coronary vessels and epicardial fat. We report the outcomes of percutaneous epicardial mapping and ablation of ventricular arrhythmias arising from the left ventricular summit and the ECG features associated with successful ablation. Methods and Results—Between January 2003 and December 2012, a total of 23 consecutive patients (49±14 years; 39% men) with ventricular arrhythmias arising from the left ventricular summit underwent percutaneous epicardial instrumentation for mapping and ablation because of unsuccessful ablation from the coronary venous system and multiple endocardial LV/right ventricular sites. Successful epicardial ablation was achieved in 5 (22%) patients. In the remaining 18 (78%) cases, ablation was aborted for either close proximity to major coronary arteries or poor energy delivery over epicardial fat. The Q-wave amplitude ratio in aVL/aVR was higher in the successful group, with a ratio of >1.85 present in 4 (80%) patients in the successful group versus 2 (11%) in the unsuccessful group (P=0.008). The ratio of R/S wave in V1 was greater in the successful group, with 4 (80%) patients in the successful group having a R/S ratio of >2 in V1 versus 5 (28%) in the unsuccessful group (P=0.056). None of the patients in the successful group had an initial q wave in lead V1, as opposed to 6 (33%) in the unsuccessful group. The presence of at least 2 of the 3 ECG criteria above predicted successful ablation with 100% sensitivity and 72% specificity. Conclusions—Epicardial instrumentation for mapping and ablation of ventricular arrhythmias arising from the left ventricular summit is successful only in a minority of patients because of close proximity to major coronary arteries and epicardial fat. A Q-wave ratio of >1.85 in aVL/aVR, a R/S ratio of >2 in V1, and absence of q waves in lead V1 help identify appropriate candidates for epicardial ablation.