Leadless pacemaker implantation after lead extraction for cardiac implanted electronic device infection.

BACKGROUND: Cardiac implanted electronic device (CIED) pocket and systemic infection remain common complications with traditional CIEDs and are associated with high morbidity and mortality. Leadless pacemakers may be an attractive pacing alternative for many patients following complete hardware removal for a CIED infection by eliminating surgical pocket-related complications as well as lower risk of recurrent complications. OBJECTIVE: To describe use and outcomes associated with leadless pacemaker implantation following extraction of a CIED system due to infection. METHODS: Patient characteristics and postprocedural outcomes were described in patients who underwent leadless pacemaker implantation at Duke University Hospital between November 11, 2014 and November 18, 2019, following CIED infection and device extraction. Outcomes of interest included procedural complications, pacemaker syndrome, need for system revision, and recurrent infection. RESULTS: Among 39 patients, the mean age was 71 ± 17 years, 31% were women, and the most frequent primary pacing indication was complete heart block (64.1%) with 9 (23.1%) patients being pacemaker dependent at the time of Micra implantation. The primary organism implicated in the CIED infection was Staphylococcus aureus (43.6%). Nine of the 39 patients had a leadless pacemaker implanted before or on the same day as their extraction procedure, and the remaining 30 patients had a leadless pacemaker implanted after their extraction procedure. During follow-up (mean 24.8 ± 14.7 months) after leadless pacemaker implantation, there were a total of 3 major complications: 1 groin hematoma, 1 femoral arteriovenous fistula, and 1 case of pacemaker syndrome. No patients had evidence of recurrent CIED infection after leadless pacemaker implantation. CONCLUSIONS: Despite a prior CIED infection and an elevated risk of recurrent infection, there was no evidence of CIED infection with a mean follow up of over 2 years following leadless pacemaker implantation at or after CIED system removal. Larger studies with longer follow-up are required to determine if there is a long-term advantage to implanting a leadless pacemaker versus a traditional pacemaker following temporary pacing when needed during the periextraction period in patients with a prior CIED infection.

Acute echocardiographic and hemodynamic response to his-bundle pacing in patients with first-degree atrioventricular block.

BACKGROUND: Atrial pacing and right ventricular (RV) pacing are both associated with adverse outcomes among patients with first-degree atrioventricular block (1°AVB). His-bundle pacing (HBP) provides physiological activation of the ventricle and may be able to improve both atrioventricular (AV) and inter-ventricular synchrony in 1°AVB patients. This study evaluates the acute echocardiographic and hemodynamic effects of atrial, atrial-His-bundle sequential (AH), and atrial-ventricular (AV) sequential pacing in 1°AVB patients. METHODS: Patients with 1°AVB undergoing atrial fibrillation ablation were included. Following left atrial (LA) catheterization, patients underwent atrial, AH- and AV-sequential pacing. LA/left ventricular (LV) pressure and echocardiographic measurements during the pacing protocols were compared. RESULTS: Thirteen patients with 1°AVB (mean PR 221 ± 26 ms) were included. The PR interval was prolonged with atrial pacing compared to baseline (275 ± 73 ms, p = .005). LV ejection fraction (LVEF) was highest during atrial pacing (62 ± 11%), intermediate with AH-sequential pacing (59 ± 7%), and lowest with AV-sequential pacing (57 ± 12%) though these differences were not statistically significant. No significant differences were found in LA or LV mean pressures or LV dP/dT. LA and LV volumes, isovolumetric times, electromechanical delays, and global longitudinal strains were similar across pacing protocols. CONCLUSION: Despite pronounced PR prolongation, the acute effects of atrial pacing were not significantly different than AH- or AV-sequential pacing. Normalizing atrioventricular and/or inter-ventricular dyssynchrony did not result in acute improvements in cardiac output or loading conditions.

Safety and efficacy outcomes of left atrial posterior wall isolation compared to pulmonary vein isolation and pulmonary vein isolation with linear ablation for the treatment of persistent atrial fibrillation.

BACKGROUND: Pulmonary wall isolation (PWI) is increasingly used as an adjunctive lesion set to compliment pulmonary vein isolation (PVI), especially in patients with persistent atrial fibrillation (AF). The objective was to compare outcomes of catheter ablation in patients with persistent AF undergoing PVI with and without adjunctive PWI. METHODS: We performed a retrospective study of 558 patients who underwent de novo and repeat ablation for persistent AF. Subjects were matched using propensity score adjustments. Outcomes were freedom from recurrent atrial arrhythmia and adverse events. RESULTS: Among 558 patients who underwent ablation for persistent AF, 78 (14%) underwent PVI + PWI, 255 (46%) underwent PVI, and 225 (40%) underwent PVI + linear ablation. Stratified logistic regression analysis with propensity matching revealed higher odds of recurrent arrhythmia with PVI + PWI when compared to PVI (odds ratio [OR] 2.25, 95% CI 1.08-4.69, P = .030) and when compared to PVI + linear (OR 2.31, 95% CI 1.01-5.28, P = .048). Within the PVI + PWI group, 57.7% of subjects were in normal sinus rhythm at 6 months compared to 73.9% and 72.2% in PVI and PVI + linear groups, respectively. Adverse events were rare, with 19 events total identified across all groups. CONCLUSIONS: PVI + PWI does not appear to be as effective as PVI or PVI + linear ablation in reducing the recurrence of arrhythmia within 6 months of the index procedure in patients with persistent AF. A prospective, randomized controlled trial comparing these ablation techniques is needed to clarify the role of extensive substrate modification for treatment of persistent AF. CONDENSED ABSTRACT: PWI is increasingly used as an adjunctive lesion set to compliment PVI in patients with persistent AF. We performed a retrospective study of 558 patients who underwent de novo and repeat ablation for persistent AF to compare the outcomes between PVI with and without adjunctive PWI. We found an increased incidence in recurrence of AF and other atrial arrhythmias at 6 months in the PVI + PWI cohort compared to PVI with or without additional linear ablation. A prospective, randomized controlled trial comparing these ablation techniques is needed to clarify the role of extensive substrate modification for treatment of persistent AF.

Catheter ablation of atrial fibrillation in cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis is a progressive infiltrative disease involving deposition of amyloid fibrils in the myocardium and cardiac conduction system that frequently manifests with heart failure (HF) and arrhythmias, most frequently atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT). METHODS: We performed an observational retrospective study of patients with a diagnosis of cardiac amyloid who underwent catheter ablation at our institution between January 1, 2011 and December 1, 2018. Patient demographics, procedural characteristics, and outcomes were determined by manual chart review. RESULTS: A total of 13 catheter ablations were performed over the study period in patients with cardiac amyloidosis, including 10 AT/AF/AFL ablations and three atrioventricular nodal ablations. Left ventricular ejection fraction was lower at the time of AV node ablation than catheter ablation of AT/AF/AFL (23% vs 40%, P = .003). Cardiac amyloid was diagnosed based on the results of preablation cardiac MRI results in the majority of patients (n = 7, 70%). The HV interval was prolonged at 60 ± 15 ms and did not differ significantly between AV nodal ablation patients and AT/AF/AFL ablation patients (69 ± 18 ms vs 57 ± 14 ms, P = .36). The majority of patients undergoing AT/AF/AFL ablation had persistent AF (n = 7, 70%) and NYHA class II (n = 5, 50%) or III (n = 5, 50%) HF symptoms, whereas patients undergoing AV node ablation were more likely to have class IV HF (n = 2, 66%, P = .014). Arrhythmia-free survival in CA patients after catheter ablation of AT/AF/AFL was 40% at 1 year and 20% at 2 years. CONCLUSIONS: Catheter ablation of AT/AF/AFL may be a feasible strategy for appropriately selected patients with early to mid-stage CA, whereas AV node ablation may be more appropriate in patients with advanced-stage CA.

Death with an implantable cardioverter-defibrillator: a MADIT-II substudy.

AIMS: There are limited data regarding factors that identify implantable cardioverter-defibrillator (ICD) patients who will experience either ventricular tachyarrhythmic (VTA) or non-arrhythmic (NA) mortality, and the commonly used clinical classification of sudden cardiac death (SCD) vs. non-sudden cardiac death (NSCD) may not be accurate enough. We aimed to correlate clinical adjudication of mortality events to device interrogation data and to identify risk factors for VTA mortality in Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II). METHODS AND RESULTS: Of the 746 patients who received an ICD in MADIT-II, 44 died from cardiac causes and had available interrogation data at the time of death. Sudden cardiac death vs. NSCD was defined by an adjudication committee. Ventricular tachyarrhythmic and NA arrhythmic deaths were categorized by the presence or absence of ventricular tachycardia or fibrillation (VT/VF) during the terminal event. Mode of death was found to be inaccurate when validated by device interrogation for VTA events: 50% patients adjudicated as SCD did not have a VTA event at the time of death; and 25% of adjudicated NSCD were found to have VT/VF during the mortality event. Multivariate analysis showed that factors independently associated with VTA mortality included: VT/VF >72 h prior to the mortality event [hazard ratio (HR) 8.0; P < 0.001], hospitalization for heart failure (HR 6.7; P = 0.001), and a history of hypertension (HR 4; P = 0.04). CONCLUSION: Current classification of SCD vs. NSCD fails to identify VTA events at the time of death in a significant proportion of patients, and simple clinical parameters can be used to identify ICD recipients with increased risk for VTA mortality.

Predicting atrial fibrillation recurrence after ablation in patients with heart failure: Validity of the APPLE and CAAP-AF risk scoring systems.

BACKGROUND: Compared with medical therapy, catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) improves cardiovascular outcomes. Risk scores (CAAP-AF and APPLE) have been developed to predict the likelihood of AF recurrence after ablation, have not been validated specifically in patients with AF and HF. METHODS: We analyzed baseline characteristics, risk scores, and rates of AF recurrence 12 months postablation in a cohort of 230 consecutive patients with AF and HF undergoing PVI in the Duke Center for Atrial Fibrillation registry from 2009-2013. RESULTS: During a follow-up period of 12 months, 76 of 230 (33%) patients with HF experienced recurrent AF after ablation. The median APPLE and CAAP-AF scores were 1.5 ([Q1, Q3]: [1.0, 2.0]) and 4.0 ([Q1, Q3]: [3.0, 5.0]), respectively and were not different from those patients with and without recurrent AF. Freedom from AF was not different according to APPLE and CAAP-AF scores. Discrimination for recurrent AF with the CAAP-AF score was modest with a C-statistic of 0.60 (95% CI 0.52-0.67). Discrimination with the APPLE score was similarly modest, with a C-statistic of 0.54 (95% CI: 0.47-0.62). CONCLUSIONS: Validated predictive risk scores for recurrent AF after catheter ablation exhibit limited predictive ability in cohorts of AF and HF. Additional tools are needed to facilitate risk stratification and patient selection for AF ablation in patients with concomitant HF.

Effectiveness of high rate and delayed detection ICD programming by race: A MADIT-RIT substudy.

INTRODUCTION: Data on inappropriate and appropriate ICD therapy, and efficacy of ICD programing strategies by race are limited. METHODS: In MADIT-RIT, we evaluated the risk of ICD therapy by race, and the efficacy of high rate cut-off ventricular tachycardia (VT) zone ≥200 beats per minute (bpm) (Arm B), or 60 seconds delay in VT zone 170-199 bpm (Arm C), compared to 2.5 seconds delay at 170 bpm (Arm A) among black and white patients. RESULTS: MADIT-RIT enrolled 272 (20%) black and 1119 (80%) white patients. The risk of inappropriate therapy was similar among blacks and whites, HR 1.25, 95% CI (0.82-1.93), P  =  0.30. High rate cut-off or delayed VT therapy was associated with significant reductions in inappropriate therapy among whites, Arm B versus Arm A, HR 0.15, 95% CI (0.08-0.29), P < 0.0001, Arm C versus Arm A, HR 0.19, 95% CI (0.11-0.33), P < 0.001, and black individuals Arm B versus Arm A, HR 0.24, 95% CI (0.01-0.56), P  =  0.0001, Arm C versus Arm A, HR 0.30, 95% CI (0.13-0.68), P  =  0.004, P interaction > 0.10). However, delayed VT therapy was associated with a trend toward greater reduction in appropriate therapy in black individuals, HR 0.08, 95% CI (0.03-0.27), P < 0.0001 relative to white individuals, HR 0.27, 95% CI (0.16-0.43), P < 0.0001, P interaction  =  0.077. CONCLUSION: In MADIT-RIT, high rate and delayed detection ICD programming provided similar benefit with reductions in both inappropriate therapy and unnecessary appropriate therapy among black and white individuals. CLINICALTRIALS. GOV IDENTIFIER: NCT00947310.

Obstructive sleep apnea is associated with increased rotor burden in patients undergoing focal impulse and rotor modification guided atrial fibrillation ablation.

Aims: To assess whether obstructive sleep apnea (OSA) was associated with increased rotor burden among atrial fibrillation (AF) patients. Methods and results: We studied 33 consecutive patients who were scheduled for focal impulse and rotor modulation (FIRM) ablation at our institution to describe the mapping, ablation, and outcomes, among patients with and without OSA. Patients underwent biatrial FIRM mapping in AF with ablation of stable rotors in addition to conventional ablation lesion sets. Differences between groups were tested with student's t-tests and Fisher's exact tests, as appropriate. Survival analyses were performed using the Kaplan-Meier method. Twelve of the 33 (36%) patients had OSA and 8 (66%) used continuous positive airway pressure ventilation (CPAP). Obstructive sleep apnea patients had a higher body mass index (BMI) (33.6 vs. 28.8 kg/m2, P = 0.01) and were more commonly on beta blockers (67% vs. 29%, P = 0.03) but were otherwise similar regarding baseline characteristics, medication use, and prior AF treatments, including antiarrhythmic drugs and prior ablation. Focal impulse and rotor modulation mapping demonstrated increased rotor burden in the OSA patients (2.6 ± 0.9 vs. 2.0 ± 1.0, P =0.03). The increased rotor burden was more evident in the right atrium (RA) (1.0 ± 0.7 vs. 0.5 ± 0.7, P =0.04 compared with left atrium (1.7 ± 0.8 vs. 1.4 ± 0.7, P = 0.15). There was no correlation between BMI and total number of rotors (r = 0.0961, P = 0.59). Among the population of patients with OSA, CPAP therapy was associated with a lower number of RA rotors (0.8 ± 0.7 vs. 1.5 ± 0.6, P = 0.05) but no significant difference in overall rotors (P = 0.33). Conclusion: Obstructive sleep apnea patients demonstrate increased rotor prevalence, driven predominantly by an increase in RA rotors. CPAP therapy was associated with fewer RA rotors.

Postimplantation ventricular ectopic burden and clinical outcomes in cardiac resynchronization therapy-defibrillator patients: a MADIT-CRT substudy.

BACKGROUND: Frequent ventricular ectopy on preimplantation Holter has been associated with attenuated benefit from cardiac resynchronization therapy (CRT). However, it is unclear whether ectopic burden measured post-CRT implantation can be utilized to evaluate long-term prognosis. We aimed to describe the association between post-CRT implantation ectopic burden and subsequent risk of clinical outcomes. METHODS: At the 12-month follow-up visit, 24-hour Holter recordings were performed in 698 CRT-D patients from the MADIT-CRT study. The mean number of ventricular premature complexes (VPCs/hour) was calculated. High ectopic burden was defined as >10 VPCs/hour and low burden as ≤10 VPCs/hour. Multivariate Cox proportional hazards models were utilized to assess the association between 12-month ectopic burden and the risk of the end points of heart failure (HF) or death and ventricular tachyarrhythmias (VT/VF). RESULTS: At 12 months, 282 (40%) patients presented with low ectopic burden and 416 (60%) patients presented with high ectopic burden. The 3-year risk of HF/death and VT/VF was lower in patients with a low burden (7% and 8%) and significantly higher (25% and 24%) in patients with high burden. In multivariate analyses, patients with a high ectopic burden had approximately threefold increased risk of both HF/death (HR=2.76 [1.62-4.70], p < .001) and VT/VF (HR=2.79 [1.69-4.58], p < .001). CONCLUSION: In CRT-D patients with mild heart failure, high ectopic burden at 12-month follow-up was associated with a high 3-year risk of HF/death and VT/VF and threefold increased risk as compared to patients with low burden. Ectopic burden at 12 months may be a valuable approach for evaluating long-term prognosis.

Association Between a Prolonged PR Interval and Outcomes of Cardiac Resynchronization Therapy: A Report From the National Cardiovascular Data Registry.

BACKGROUND: A prolonged PR interval is common among cardiac resynchronization therapy (CRT) candidates; however, the association between PR interval and outcomes is unclear, and the data are conflicting. METHODS: We conducted inverse probability weighted analyses of 26 451 CRT-eligible (ejection fraction ≤35, QRS ≥120 ms) patients from the National Cardiovascular Data Registry ICD Registry to assess the association between a prolonged PR interval (≥230 ms), receipt of CRT with defibrillator (CRT-D) versus implantable cardioverter defibrillator (ICD), and outcomes. We first tested the association between a prolonged PR interval and outcomes among patients stratified by device type. Next, we performed a comparative effectiveness analysis of CRT-D versus ICD among patients when stratified by PR interval. Using Medicare claims data, we followed up with patients up to 5 years for incident heart failure hospitalization or death. RESULTS: Patients with a PR≥230 ms (15%; n=4035) were older and had more comorbidities, including coronary artery disease, atrial arrhythmias, diabetes mellitus, and chronic kidney disease. After risk adjustment, a PR≥230 ms (versus PR<230 ms) was associated with increased risk of heart failure hospitalization or death among CRT-D (hazard ratio, 1.23; 95% confidence interval, 1.14-1.31; P<0.001) but not ICD recipients (hazard ratio, 1.08; 95% confidence interval, 0.97-1.20; P=0.17) (Pinteraction=0.043). CRT-D (versus ICD) was associated with lower rates of heart failure hospitalization or death among patients with PR<230 ms (hazard ratio, 0.79; 95% confidence interval, 0.73-0.85; P<0.001) but not PR≥230 ms (hazard ratio, 1.01; 95% confidence interval, 0.87-1.17; P=0.90) (Pinteraction=0.0025). CONCLUSIONS: A PR≥230 ms is associated with increased rates of heart failure hospitalization or death among CRT-D patients. The real-world comparative effectiveness of CRT-D (versus ICD) is significantly less among patients with a PR≥230 ms in comparison with patients with a PR<230 ms.

Survival with cardiac-resynchronization therapy in mild heart failure.

BACKGROUND: The Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) showed that early intervention with cardiac-resynchronization therapy with a defibrillator (CRT-D) in patients with an electrocardiographic pattern showing left bundle-branch block was associated with a significant reduction in heart-failure events over a median follow-up of 2.4 years, as compared with defibrillator therapy alone. METHODS: We evaluated the effect of CRT-D on long-term survival in the MADIT-CRT population. Post-trial follow-up over a median period of 5.6 years was assessed among all 1691 surviving patients (phase 1) and subsequently among 854 patients who were enrolled in post-trial registries (phase 2). All reported analyses were performed on an intention-to-treat basis. RESULTS: At 7 years of follow-up after initial enrollment, the cumulative rate of death from any cause among patients with left bundle-branch block was 18% among patients randomly assigned to CRT-D, as compared with 29% among those randomly assigned to defibrillator therapy alone (adjusted hazard ratio in the CRT-D group, 0.59; 95% confidence interval [CI], 0.43 to 0.80; P<0.001). The long-term survival benefit of CRT-D in patients with left bundle-branch block did not differ significantly according to sex, cause of cardiomyopathy, or QRS duration. In contrast, CRT-D was not associated with any clinical benefit and possibly with harm in patients without left bundle-branch block (adjusted hazard ratio for death from any cause, 1.57; 95% CI, 1.03 to 2.39; P=0.04; P<0.001 for interaction of treatment with QRS morphologic findings). CONCLUSIONS: Our findings indicate that in patients with mild heart-failure symptoms, left ventricular dysfunction, and left bundle-branch block, early intervention with CRT-D was associated with a significant long-term survival benefit. (Funded by Boston Scientific; ClinicalTrials.gov numbers, NCT00180271, NCT01294449, and NCT02060110.).

Effects of implantable cardioverter/defibrillator shock and antitachycardia pacing on anxiety and quality of life: A MADIT-RIT substudy.

Effects of implantable cardioverter/defibrillator (ICD) shocks and antitachycardia pacing (ATP) on anxiety and quality of life (QoL) in ICD patients are poorly understood. METHODS: We evaluated changes in QoL from baseline to 9-month follow-up using the EQ-5D questionnaire in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Reduce Inappropriate Therapy (MADIT-RIT) (n=1,268). We assessed anxiety levels using the Florida Shock Anxiety Scale (1-10 score) in patients with appropriate or inappropriate shocks or ATP compared to those with no ICD therapy during the first 9 months postimplant. The analysis was stratified by number of ATP or shocks (0-1 vs ≥2) and adjusted for covariates. RESULTS: In MADIT-RIT, 15 patients (1%) had ≥2 appropriate shocks, 38 (3%) had ≥2 appropriate ATPs. Two or more inappropriate shocks were delivered in 16 patients (1%); ≥2 inappropriate ATPs, in 70. In multivariable analysis, patients with ≥2 appropriate shocks had higher levels of shock-related anxiety than those with ≤1 appropriate shock (P<.01). Furthermore, ≥2 inappropriate shocks produced more anxiety than ≤1 inappropriate shock (P=.005). Consistently, ≥2 appropriate ATPs resulted in more anxiety than ≤1 (P=.028), whereas the number of inappropriate ATPs showed no association with anxiety levels (P=.997). However, there was no association between QoL and appropriate or inappropriate ATP/shock (all P values > .05). CONCLUSIONS: In MADIT-RIT, ≥2 appropriate or inappropriate ICD shocks and ≥2 appropriate ATPs are associated with more anxiety at 9-month follow-up despite no significant changes in the assessment of global QoL by the EQ-5D questionnaire. Innovative ICD programming reducing inappropriate therapies may help deal with patient concerns about the device.

Sex Differences in Inappropriate ICD Device Therapies: MADIT-II and MADIT-CRT.

INTRODUCTION: Approximately 10-20% of ICD recipients receive inappropriate device therapies. The purpose of this study was to compare the frequency of inappropriate therapies (IT) between men and women enrolled in MADIT II and MADIT-CRT, and assess for potential adverse outcomes. METHODS: The electrograms for each ICD or CRT-D therapy, defined as either ATP or shock, were reviewed by adjudication committees for both studies. ICD therapy was considered inappropriate if it was delivered for reasons other than VT/VF. The rhythm triggering IT was categorized as atrial fibrillation/flutter, SVT, or inappropriate sensing when possible. RESULTS: One thousand nine hundred and fifty-four men and 556 women received ICD or CRT-D devices. The risk of IT was significantly lower in women than men (9.2% vs. 13.5%, P = 0.006). The most common cause of IT in men was atrial fibrillation (38%) and SVT in women (43%). Inappropriate shock was not associated with increased mortality in either women (HR 0.82 [95% CI 0.11-6.08]; P = NS) or men (HR 1.37 [95% CI 0.75-2.48]; P = NS) by multivariate analysis. Conversely, appropriate shock therapy strongly correlated with increased risk of death during subsequent post-shock follow-up in women (HR 5.99 [95% CI 2.75-13.02]; P < 0.0001) and men (HR 2.61 [95% CI 1.82-3.74]; P < 0.0001). CONCLUSIONS: Women experience significantly less IT than men, partially explained by the increased frequency of atrial fibrillation in men. IT was not associated with increased mortality in either sex. Appropriate shock therapy was a strong predictor of death in both, with women showing a 2-fold higher risk than men during post-shock long-term follow-up.

Adverse outcomes associated with postoperative atrial arrhythmias after lung transplantation: A meta-analysis and systematic review of the literature.

BACKGROUND: Postoperative atrial arrhythmias (AAs) are common after lung transplantation, but studies are mixed regarding their impact on outcomes. We therefore performed this systematic review and meta-analysis to determine whether AAs after lung transplantation impede postoperative recovery. METHODS: MEDLINE, EMBASE, CINAHL, and the Cochrane Register were searched to identify studies comparing outcomes in adult patients undergoing lung transplantation who experienced postoperative AAs in the immediate postoperative period vs those without postoperative AAs. Our primary outcome was perioperative mortality, and secondary outcomes were length of stay (LOS), postoperative complications, and mid-term (1-6 years) mortality. RESULTS: Nine studies including 2653 patients were included in this analysis. Of this group, 791 (29.8%) had postoperative AAs. Patients with postoperative AAs had significantly higher perioperative (OR 2.70 [95% CI: 1.73-4.19], P<.0001) mortality, longer hospital LOS (MD 8.29 [95% CI: 4.37-12.21] days, P<.0001), more frequent requirement for tracheostomy (OR 4.67 [95% CI: 2.59-8.44], P<.0001), and higher mid-term mortality (OR 1.71 [95% CI: 1.28-2.30], P=.0003). CONCLUSIONS: AAs after lung transplantation are frequent and associated with significantly higher mortality, longer hospital LOS, and requirement for tracheostomy. Given their impact on recovery, prophylactic strategies against AAs need to be developed.

Ranolazine reduces atrial fibrillatory wave frequency.

AIMS: Antiarrhythmic medications for the treatment of atrial fibrillation (AF) have limited efficacy and rare but potentially life-threatening side effects. Ranolazine is an antianginal agent that may have antiarrhythmic activity in AF. METHODS AND RESULTS: Using the Duke Enterprise Data Unified Content Explorer database, we analysed a cohort of AF patients on ranolazine. Patients served as their own historic control. Electrocardiograms (ECGs) were analysed before and after ranolazine initiation to determine the effect of ranolazine on dominant frequency (DF), f-wave amplitude, and organizational index (OI). We identified 15 patients with ECGs in AF before and after ranolazine. Ranolazine was associated with lower DF by an average of 10% (5.10 ± 0.74 vs. 5.79 ± 0.96 Hz, P = 0.04) but not with changes in OI (0.47 ± 0.11 vs. 0.50 ± 0.12, P = 0.71) or amplitude (0.47 ± 0.43 vs. 0.41 ± 0.40 mV, P = 0.82). Ranolazine was also associated with lower DF in patients (n = 10) not on concomitant antiarrhythmic therapy (5.25 ± 0.78 vs. 6.03 ± 0.79 Hz, P = 0.04). CONCLUSION: Ranolazine is associated with lower AF DF but no change in OI or fibrillatory wave amplitude. Prospective trials are needed to evaluate ranolazine's potential as a novel antiarrhythmic drug for AF.

Sinus Node Dysfunction and Atrial Fibrillation: A Reversible Phenomenon?

BACKGROUND: Symptomatic sinus node dysfunction (SND) consists of a variety of manifestations, including tachycardia-bradycardia syndrome. Atrial fibrillation (AF) is commonly associated with SND, which complicates the management of both conditions. This paper reviews the epidemiology, pathophysiology, and clinical trial data investigating therapeutic approaches for treatment of patients with both SND and AF. METHODS: The authors reviewed articles published in English describing the epidemiology, pathophysiology, and therapeutic approaches for patients with SND and AF. The search was conducted using PubMed. Keywords included: sick sinus syndrome, sinus node dysfunction, atrial fibrillation, pacing, and pulmonary vein isolation. RESULTS: SND affects up to one in five patients with AF. AF can lead to anatomical and electrophysiological remodeling in both atria, including the region of sinoatrial node. Changes including atrial fibrosis, altered calcium channel metabolism, and transformed gene expression have been demonstrated in patients with AF and SND. Nonrandomized clinical trial data have failed to demonstrate whether any pacing strategy can reduce the risk of AF. Pulmonary vein isolation appears to decrease episodes of tachybrady syndrome and sinus pauses. CONCLUSIONS: SND affects up to one in five patients with AF. The pathophysiological derangements in gene expression, ion channel metabolism, and alterations in myocardial architecture associated with AF may lead to anatomic and electrical changes in the region of the sinoatrial node. Ablation may improve symptoms associated with SND in patients with AF. Future randomized trials are needed to clarify the epidemiology and optimal management of patients with SND and AF.

Heart failure severity, inappropriate ICD therapy, and novel ICD programming: a MADIT-RIT substudy.

BACKGROUND: The effects of heart failure (HF) severity on risk of inappropriate implantable cardioverter-defibrillator (ICD) therapy have not been thoroughly investigated. We aimed to study the association between HF severity and inappropriate ICD therapy in MADIT-RIT. METHODS: MADIT-RIT randomized 1,500 patients to three ICD programming arms: conventional (Arm A), high-rate cut-off (Arm B: ≥200 beats/min), and delayed therapy (Arm C: 60-second delay for ≥170 beats/min). We evaluated the association between New York Heart Association (NYHA) class III (n = 256) versus class I-II (n = 251) and inappropriate ICD therapy in Arm A patients with ICD-only and cardiac resynchronization therapy with defibrillator (CRT-D). We additionally assessed benefit of novel ICD programming in Arms B and C versus Arm A by NYHA classification. RESULTS: In Arm A, the risk of inappropriate therapy was significantly higher in those with NYHA III versus NYHA I-II for both ICD (hazard ratio [HR] = 2.55, confidence interval [CI]: 1.51-4.30, P < 0.001) and CRT-D patients (HR = 3.73, CI: 1.14-12.23, P = 0.030). This was consistent for inappropriate ATP and inappropriate ICD therapy < 200 beats/min, but not for inappropriate shocks. Novel ICD programming significantly reduced inappropriate therapy in patients with both NYHA III (Arm B vs Arm A: HR = 0.08, P < 0.001; Arm C vs Arm A: HR = 0.17, P < 0.001) and NYHA I-II (Arm B vs Arm A: HR = 0.25, P < 0.001; Arm C vs Arm A: HR = 0.28, P < 0.001). CONCLUSION: Patients with more severe HF are at increased risk for inappropriate ICD therapy, particularly ATP due to arrhythmias < 200 beats/min. Novel programming with high-rate cut-off or delayed detection reduces inappropriate ICD therapies in both mild and moderate HF.

Why the Authors Use Cardiac Resynchronization Therapy with Defibrillators.

Cardiac resynchronization therapy (CRT) improves left ventricular function, especially in patients with left bundle branch block or those receiving chronic right ventricular pacing. CRT is typically accomplished by placing a right ventricular endocardial pacing lead and a left ventricular pacing lead via the coronary sinus to a coronary vein overlying the lateral or posterolateral left ventricle. CRT can be combined with an implantable defibrillator or with a pacemaker. Limited data are available to compare these two versions of CRT head to head. This review summarizes the relevant trials and meta-analyses regarding these two forms of CRT.

Interleukin-1ß gene variants are associated with QTc interval prolongation following cardiac surgery: a prospective observational study.

BACKGROUND: We characterized cardiac surgery-induced dynamic changes of the corrected QT (QTc) interval and tested the hypothesis that genetic factors are associated with perioperative QTc prolongation independent of clinical and procedural factors. METHODS: All study subjects were ascertained from a prospective study of patients who underwent elective cardiac surgery during August 1999 to April 2002. We defined a prolonged QTc interval as > 440 msec, measured from 24-hr pre- and postoperative 12-lead electrocardiograms. The association of 37 single nucleotide polymorphisms (SNPs) in 21 candidate genes -involved in modulating arrhythmia susceptibility pathways with postoperative QTc changes- was investigated in a two-stage design with a stage I cohort (n = 497) nested within a stage II cohort (n = 957). Empirical P values (Pemp) were obtained by permutation tests with 10,000 repeats. RESULTS: After adjusting for clinical and procedural risk factors, we selected four SNPs (P value range, 0.03-0.1) in stage I, which we then tested in the stage II cohort. Two functional SNPs in the pro-inflammatory cytokine interleukin-1ß (IL1ß), rs1143633 (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.53 to 0.95; Pemp = 0.02) and rs16944 (OR, 1.31; 95% CI, 1.01 to 1.70; Pemp = 0.04), remained independent predictors of postoperative QTc prolongation. The ability of a clinico-genetic model incorporating the two IL1B polymorphisms to classify patients at risk for developing prolonged postoperative QTc was superior to a clinical model alone, with a net reclassification improvement of 0.308 (P = 0.0003) and an integrated discrimination improvement of 0.02 (P = 0.000024). CONCLUSION: The results suggest a contribution of IL1ß in modulating susceptibility to postoperative QTc prolongation after cardiac surgery.

The association between biventricular pacing and cardiac resynchronization therapy-defibrillator efficacy when compared with implantable cardioverter defibrillator on outcomes and reverse remodelling.

AIMS: Previous studies on biventricular (BIV) pacing and cardiac resynchronization therapy-defibrillator (CRT-D) efficacy have used arbitrarily chosen BIV pacing percentages, and no study has employed implantable cardioverter defibrillator (ICD) patients as a control group. METHODS AND RESULTS: Using Kaplan-Meier plots, we estimated the threshold of BIV pacing percentage needed for CRT-D to be superior to ICD on the end-point of heart failure (HF) or death in 1219 left bundle branch block (LBBB) patients in the MADIT-CRT trial. Patients were censored at the time of crossover. In multivariable Cox analyses, no difference was seen in the risk of HF/death between ICD and CRT-D patients with BIV pacing ≤90% [HR = 0.78 (0.47-1.30), P = 0.344], and with increasing BIV pacing the risk of HF/death was decreased [CRT-D BIV 91-96% vs. ICD: HR = 0.63 (0.42-0.94), P = 0.024 and CRT-D BIV ≥97% vs. ICD: HR = 0.32 (0.23-0.44), P < 0.001]. The risk of death alone was reduced by 52% in CRT-D patients with BIV ≥97% (HR = 0.48, P < 0.016), when compared with ICD patients. Within the CRT-D group, for every 1 percentage point increase in BIV pacing, the risk of HF/death and death alone significantly decreased by 6 and 10%, respectively. Increasing BIV pacing percentage was associated with significant reductions in left ventricular volume. CONCLUSION: In patients with LBBB, who were in sinus rhythm at enrolment, BIV pacing exceeding 90% was associated with a benefit of CRT-D in HF/death when compared with ICD patients. Furthermore, BIV pacing ≥97% was associated with an even further reduction in HF/death, a significant 52% reduction in death alone, and increased reverse remodelling. Clinical trials.gov identifier: NCT00180271.