Packer, Douglas L.

Background. ICD implantation for primary prevention of sudden death in patients with ischemic cardiomyopathy and left ventricular dysfunction is well established. However debate exists between the relationship between ischemia and the proarrhythmic state. Persistent ischemia may counter antiarrhythmic (AA) drug and/or device efficacy. Furthermore, the extent to which revascularization mitigates this influence of ischemia on efficacy is unknown. Methods . 704 patients enrolled in the MUSTT trial were studied. Ischemia was determined by the presence of angina within 6 weeks of enrollment and ≥ 2 reversible thallium defects. Revascularization was characterized as CABG or PTCA within 1 year of enrollment or the use of thrombolytics with the sentinal myocardial infarction (MI). We compared groups who were randomized to background medical treatment (BG Rx) verses those who were randomized to AA drug therapy in addition to EP testing (EP AARx). Results . 507 (81%) patients had ≤2 vessel CAD, whereas the remaining 19% had 3 vessel disease. 268 patients reported angina within 6 weeks of study enrollment. Thallium imaging revealed 0–1 defects in 458 (65%) and ≥2 in another 246 (35%). Those with ≥ 2 defects on Thallium and angina within 6 weeks of device implant had a significantly lower 5-year freedom from mortality in the EP AARx and BG Rx cohorts (Table ). Patients with EP AARx had an 8% lower mortality than those with BG Rx therapy alone if they received thrombolytics. However, if they did not receive thrombolytics, their mortality rate was 5% higher than the BG Rx group. Conclusion . Outcomes are worse in patients on antiarrhythmic therapy with ischemic factors compared to those on background therapy alone, particularly in the setting of recent angina. A proarrhythmic effect from antiarrhythmic drug therapy in patients with ischemia may underlie the higher mortality. ICD therapy mitigates the negative long-term effect of ischemia on mortality in those treated with AA therapy. Five Year Freedom from Mortality

Background : Lipid lowering therapy reduces mortality in patients with both ischemic and nonischemic cardiomyopathies and recently has been shown to decrease ICD shocks. Radiofrequency ablation (RFA) of recurrent VT in patients with an ICD also reduces shocks following intervention. It is unclear if statin therapy after VT RFA will further impact ICD shock rates. Methods : All patients from 1993–2005 who underwent a RFA procedure for recurrent VT at the Mayo Clinic with an ICD were included. Patient records were extracted for medical and procedural details and all ICD interrogations were reviewed for VT recurrence and therapies. Results: 63 patients (age 62±15 years) were followed over 3.9±3.6 years. Comorbid diseases included: coronary artery disease 37(58%, 34 prior myocardial infarction), ARVD/C 6(10%), nonischemic dilated cardiomyopathy 7(11%), moderate-severe valve disease 14(22%), hypertension 34(54%), and hyperlipidemia 35(56%). Ejection fraction was <0.35 in 34(56%). VT was induced in all patients (LV 55 (LVOT 1), RV 8 (RVOT 3) with multiple inducible VTs in 21(33%). VT was noninducible after RFA in 39(62%) patients. Dismissal medications included: statins 19(30%), beta blockers 40(66%), ACE/ARB 37(61%), diuretics 34(55%), and digoxin 23(37%). 5-year overall survival was 63%(95% CI 55–71). Age, diabetes, and renal insufficiency were associated with increased post ablation mortality, with no medication improving survival. 5-year survival free of ICD shocks was 31%(95% CI 24–38). Only statin therapy at discharge was associated with a decreased risk of ICD shocks [5(26%) versus 26(59%), p=0.020]. 7 additional patients received statins during follow-up, but not at discharge, of these 5(71%) had shocks. Conclusion : Statin use at discharge in patients with an ICD undergoing RFA for refractory VT significantly reduced recurrent ventricular arrhythmias and ICD shocks. Although the mechanism underlying the effects of statins on arrhythmic recurrence early after RFA requires further study, these data support aggressive therapy of the underlying substrate responsible for the VT.

Background: Although pulmonary vein (PV) isolation has been used to treat AF, complications create important limitations. New energy sources, including cryothermal, have been developed to minimize these complications. The purpose of this study was to evaluate the effect of PV cryoablation on esophageal (ESO) temperatures acutely and correlate them with chronic effects on the esophageal wall. Methods: A 23 mm cryoballoon was placed in the LA of 10 dogs through a 12 Fr deflectable sheath. PV and ESO temperatures (TEMP) were recorded using 7–9 thermocouples (TC) outside the PVs and on the external and internal ESO surfaces during 2 cryoablations of 4 min duration. Results : Cryoablation of 15 PV (10 RIPV and 5 LIPV) during 1.7±0.6 ablations yielded a total of 168 TC time-TEMP profiles (6.4±2.4/PV). Minimum tissue TEMP was inversely dependent on the distance of the TC from the balloon surface (Table 1 ). All PVs were isolated acutely and 14/15 (93%) chronically. Minimum TEMP achieved at the PV surface and external ESO were similar (−32±8 and −37±9 at targets within 2.5 mm from the balloon respectively [P=NS]). A TEMP decrease at the internal ESO was seen during 15 of 25 (60%) ablations, but was significantly less pronounced than the external TEMP (17.9°C±13.3 and 6.1°C±24.8 [p<0.05]) resulting in a minimum recorded internal TEMP of −6.2°C. The ESO histological examination in 5 dogs showed very limited external lesions in these dogs (depth= 2.2±1.1, width3 18.6±7.4 and length= 12±5.7 mm), but no transmural or internal ulceration, fibrosis or scarring seen. Conclusion: Although PV cryoablation decreases external ESO temperature and produces minor lesions, significant chronic disruptive tissue damage was not seen. Esophageal injury is an unlikely, but potential complication of cryoablation, with internal temperature proving unhelpful in predict negative outcome.

Determining whether retrograde ventriculoatrial (VA) conduction is through the AV node (AVN) or an accessory pathway (AP) is critical for successful ablation of supraventricular tachycardia (SVT). With introduction of ventricular extrastimuli (VEST), retrograde right bundle branch block (retro RBBB) may occur and result in abrupt VH interval prolongation. We hypothesized when retrograde conduction is via an AP, VA interval change is less than VH interval change, whereas with retrograde AVN conduction, VA interval change is equal to or greater than VH interval change. We retrospectively reviewed the electrophysiology (EP) studies of patients undergoing ablation for AVNRT (n=55) or AVRT (n=50). The intracardiac electrograms were reviewed for induction of retro RBBB and change in VH and VA intervals during VEST. Parahisian pacing, decremental pacing, arrhythmia diagnosis and ablation outcomes were reviewed. All results were found to be reproducible between two independent observers with inter and intra observer reliability scores of 1.00 for identification of retro RBBB and greater than 0.85 for measurement of VH and VA intervals. Of 105 patients, 84 (80%) had evidence of induced retro RBBB during VEST. The average VH interval increase with induction of retro RBBB was 53.7 ms for patients with retrograde AP conduction and 54.4 ms for patients with AVN conduction (p=ns). The average VA interval increase with induction of retro RBBB was 13.6 ms with AP conduction and 70.1 ms with AVN conduction (P < 0.001). All patients with a greater VH than VA interval change had a final diagnosis of AVRT and those with a VH change less than VA change had AVNRT, yielding sensitivity and specificity of 100%. Using a cutoff of 50 ms for change in VA interval with onset of retro RBBB to diagnose AVNRT accurately identified AVNRT in 100% and AVRT in 95%. Induction of retro RBBB during VEST is common during EP studies for SVT. The relative change in the VH and VA intervals during retro RBBB accurately differentiates retrograde AVN from retrograde AP conduction with strong predictive accuracy. The use of retro RBBB based intervals is a useful technique facilitating the diagnosis of SVT in the EP laboratory, even in the absence of inducible tachycardia.

Introduction: The spatial thermodynamics of very high power-short duration (vHPSD) radiofrequency (RF) application during pulmonary vein isolation (PVI) in in-vivo model has not been well characterized. This study was conducted to investigate the distance-temperature relationship during vHPSD-RF ablation. Methods: PVI was performed using the vHPSD catheter with the settings of 90W, RF time of 4 sec and 15mL/min irrigation in a canine model. Catheter contact force (CF) of 10-20g was defined as ‘normal’ and CF >20g as ‘firm’ CF. Tissue temperature was monitored using thermocouples implanted at the surface of the left atrial-pulmonary vein junction, left phrenic nerve, and the luminal esophagus. PVI using a standard contact-force sensing catheter (SCF) (settings of 35W, 30sec and 30mL/min irrigation) was performed for comparison. Results: A total of 334 TC profiles in 4 animals was investigated. Time to maximum tissue temperature (MTT) (6.0sec [vHPSD/normal CF] vs. 30.5 sec [SCF/normal CF], p<0.001; 8.0sec [vHPSD/firm CF] vs. 24.0sec [SCF/firm CF], p=0.022) was shorter with vHPSD than in SCF groups. MTT within 10mm from catheter-tip was lower in vHPSD ablation with normal CF than using SCF ablation (median 41.9°C [interquartile-range; 40.2-46.1] vs. 49.5°C [45.9-56.2], p=0.013). The distance margin to keep the MTT below 39ºC, 42ºC, and 50ºC were 4.9mm, 4.2mm, and 3.4mm, respectively in the vHPDS group. This margin was larger (8.0mm, 6.6mm, and 4.6mm) in the SCF group. Conclusion: Our study underscores that vHPSD creates greater resistive heating than conventional catheter ablation.

Abstract Aims With the implementation of saline-enhanced radiofrequency (SERF) needle-tip ablation, real-time validation of lesion formation is needed for the controllable creation of transmural lesions. The aim of the study was to analyse the ability of two-dimensional intracardiac echocardiography (2D-ICE) to guide and validate SERF ablation in real-time. Methods and results Fifty-six SERF energy deliveries at left ventricular sites of 11 dogs guided by 2D-ICE were analysed (power: 15–50 W; time: 25–120 s; irrigation saline: 60°C with 10 mL/min flow rate). Catheter tip/tissue orientation and lesion formation could be well detected by 2D-ICE in 49 (87.5%) energy deliveries. Gross pathology analysis confirmed excellent 2D-ICE lesion localization, the ability to detect transmural lesions (70% sensitivity, 47% specificity) and positive correlation between 2D-ICE and the corresponding gross pathology measurements of ‘maximal lesion depth’; (repeated measures correlation: rrm = 0.43, P = 0.012) and ‘depth at maximal lesion width’ (D@MW; rrm = 0.51, P = 0.003). The median angle between SERF catheter tip and endocardium was 76° [interquartile range (IQR) 58–83°]. The more perpendicular the catheter tip/tissue orientation was the deeper D@MW (rrm = 0.32, P = 0.045). Grade 3 microbubbles on 2D-ICE during ablation, indicating inadequate catheter tip/tissue contact, was associated with smaller lesion volumes than with Grade 1 microbubbles (284.8 mm3 [IQR 151.3–343.1] vs. 2114.1 mm3 [IQR 1437.0–3026.3], P &lt; 0.001). Conclusion With excellent lesion localization and a 70% detection rate of transmural lesions, 2D-ICE is well suited to validate SERF ablation lesion formation in real-time. The catheter tip/tissue angle impacts the lesion formation and through perpendicular catheter positioning, deeper intramural areas of the myocardium can be reached.

Background: The CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) was a randomized, prospective trial of left atrial catheter ablation versus drug therapy for treatment of atrial fibrillation (AF). As part of CABANA, a prospective imaging substudy was conducted. The main objectives were to describe the patterns of changes in the dimensions of the left atrium and pulmonary veins (PVs), and the relationship between these changes with treatment assignment and clinical outcomes. Methods: Computed tomography or magnetic resonance imaging was acquired at baseline and follow-up in 121 ablation (median follow-up 101 days) and 85 drug patients (median follow-up 97 days). Left atrial volume index, mean PV ostial diameter, and ostial diameters of each PV separately were computed. We examined the relationship between the change from baseline to follow-up with subsequent clinical outcomes (composite of death, disabling stroke, serious bleeding, or cardiac arrest [CABANA primary end point], total mortality or cardiovascular hospitalization, first AF recurrence after the 90-day blanking period, first AF/atrial flutter/atrial tachycardia after the 90-day blanking period) using Cox proportional-hazards models. Results: The median (25th to 75th) change from baseline for left atrial volume index was −7.8 mL/m 2 (−16.4 to 0.2), ablation arm and −3.5 mL/m 2 (−11.4 to 2.6), drug therapy arm. The left atrial volume index decreased in 52.9% of ablation patients versus 40.0% of drug therapy patients. Change for mean PV was −2.7 mm (−4.2 to −1.3) in the ablation arm versus −0.1 mm (−1.5 to 0.8) in the drug therapy arm. Changes in left atrium and PV dimensions had no consistent relationship with the risk of developing the study primary end point. Reductions in left atrial volume index, and in mean PV diameter were associated with decreased risk of AF recurrence. Conclusions: Ablation patients demonstrated more frequent and larger atrial structural changes compared with drug patients. These changes suggest a critical relationship between structural features and AF generation.

AbstractBackgroundPulmonary vein isolation (PVI) with autonomic modulation may be more successful than PVI alone for atrial fibrillation (AF) ablation and may be signaled by changes in sinus rhythm heart rate (HR) post ablation. We sought to determine if a change in sinus rhythm HR predicted AF recurrence post PVI.MethodsPatients who underwent AF ablation from 2000 to 2011 were included if sinus rhythm was noted on ECG within 90 days pre and 7 days post ablation. Basic ECG interval and HR changes were analyzed and outcomes determined.ResultsA total of 1152 patients were identified (74.3% male, mean age 57 ± 11 years). Mean AF duration was 5.2 ± 5.3 years. Paroxysmal AF was noted in 712 (61.8%) of the patients. Mean EF was 61% ± 6%. Sinus rhythm HR was 61 ± 11 pre‐ablation and 76 ± 13 bpm post‐ablation (27% ± 24% increase, p < .001). The ability of relative HR change post‐ablation to predict AF recurrence was borderline (hazard ratio 0.65 [0.41–1.01], p = .067). With patients separated into quartiles based on the relative HR change, the upper quartile with the largest relative increase in HR had a significantly lower rate of AF recurrence compared to the lowest quartile following multi variable modeling (p = .038). There were significant changes in PR (171 ± 28 to 167 ± 30 ms) and QTc (424 ± 25 to 434 ± 29 ms) intervals (both p < .001) but these were not predictive of outcome.ConclusionRelative changes in HR post AF ablation correlates with AF recurrence. Further prospective studies are needed to confirm this relationship.

Background: In patients with heart failure and atrial fibrillation (AF), several clinical trials have reported improved outcomes, including freedom from AF recurrence, quality of life, and survival, with catheter ablation. This article describes the treatment-related outcomes of the AF patients with heart failure enrolled in the CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation). Methods: The CABANA trial randomized 2204 patients with AF who were ≥65 years old or <65 years old with ≥1 risk factor for stroke at 126 sites to ablation with pulmonary vein isolation or drug therapy including rate or rhythm control drugs. Of these, 778 (35%) had New York Heart Association class >II at baseline and form the subject of this article. The CABANA trial’s primary end point was a composite of death, disabling stroke, serious bleeding, or cardiac arrest. Results: Of the 778 patients with heart failure enrolled in CABANA, 378 were assigned to ablation and 400 to drug therapy. Ejection fraction at baseline was available for 571 patients (73.0%), and 9.3% of these had an ejection fraction <40%, whereas 11.7% had ejection fractions between 40% and 50%. In the intention-to-treat analysis, the ablation arm had a 36% relative reduction in the primary composite end point (hazard ratio, 0.64 [95% CI, 0.41–0.99]) and a 43% relative reduction in all-cause mortality (hazard ratio, 0.57 [95% CI, 0.33–0.96]) compared with drug therapy alone over a median follow-up of 48.5 months. AF recurrence was decreased with ablation (hazard ratio, 0.56 [95% CI, 0.42–0.74]). The adjusted mean difference for the AFEQT (Atrial Fibrillation Effect on Quality of Life) summary score averaged over the entire 60-month follow-up was 5.0 points, favoring the ablation arm (95% CI, 2.5–7.4 points), and the MAFSI (Mayo Atrial Fibrillation-Specific Symptom Inventory) frequency score difference was –2.0 points, favoring ablation (95% CI, –2.9 to –1.2). Conclusions: In patients with AF enrolled in the CABANA trial who had clinically diagnosed stable heart failure at trial entry, catheter ablation produced clinically important improvements in survival, freedom from AF recurrence, and quality of life relative to drug therapy. These results, obtained in a cohort most of whom had preserved left ventricular function, require independent trial verification. Registration: URL: https://www.clinicaltrials.gov/ct2/show/NCT00911508 ; Unique identifier: NCT0091150.

Background: Among patients with atrial fibrillation (AF), women are less likely to receive catheter ablation and may have more complications and less durable results. Most information about sex-specific differences after ablation comes from observational data. We prespecified an examination of outcomes by sex in the 2204-patient CABANA trial (Catheter Ablation Versus Antiarrhythmic Drug Therapy for Atrial Fibrillation). Methods: CABANA randomized patients with AF age ≥65 years or <65 years with ≥1 risk factor for stroke to a strategy of catheter ablation with pulmonary vein isolation versus drug therapy with rate/rhythm control agents. The primary composite outcome was death, disabling stroke, serious bleeding, or cardiac arrest, and key secondary outcomes included AF recurrence. Results: CABANA randomized 819 (37%) women (ablation 413, drug 406) and 1385 men (ablation 695, drug 690). Compared with men, women were older (median age, 69 years versus 67 years for men), were more symptomatic (48% Canadian Cardiovascular Society AF Severity Class 3 or 4 versus 39% for men), had more symptomatic heart failure (42% with New York Heart Association Class ≥II versus 32% for men), and more often had a paroxysmal AF pattern at enrollment (50% versus 39% for men) ( P <0.0001 for all). Women were less likely to have ancillary (nonpulmonary vein) ablation procedures performed during the index procedure (55.7% versus 62.2% in men, P =0.043), and complications from treatment were infrequent in both sexes. For the primary outcome, the hazard ratio for those who underwent ablation versus drug therapy was 1.01 (95% CI, 0.62–1.65) in women and 0.73 (95% CI, 0.51–1.05) in men (interaction P value=0.299). The risk of recurrent AF was significantly reduced in patients undergoing ablation compared with those receiving drug therapy regardless of sex, but the effect was greater in men (hazard ratio, 0.64 [95% CI, 0.51–0.82] for women versus hazard ratio, 0.48 [95% CI, 0.40–0.58] for men; interaction P value=0.060). Conclusions: Clinically relevant treatment-related strategy differences in the primary and secondary clinical outcomes of CABANA were not seen between men and women, and there were no sex differences in adverse events. The CABANA trial results support catheter ablation as an effective treatment strategy for both women and men. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00911508.