Daniela Husser

Implant-based multiparameter telemonitoring of patients with heart failure (IN-TIME): a randomised controlled trial

BACKGROUND An increasing number of patients with heart failure receive implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation defibrillators (CRT-Ds) with telemonitoring function. Early detection of worsening heart failure, or upstream factors predisposing to worsening heart failure, by implant-based telemonitoring might enable pre-emptive intervention and improve outcomes, but the evidence is weak. We investigated this possibility in IN-TIME, a clinical trial. METHODS We did this randomised, controlled trial at 36 tertiary clinical centres and hospitals in Australia, Europe, and Israel. We enrolled patients with chronic heart failure, NYHA class II-III symptoms, ejection fraction of no more than 35%, optimal drug treatment, no permanent atrial fibrillation, and a recent dual-chamber ICD or CRT-D implantation. After a 1 month run-in phase, patients were randomly assigned (1:1) to either automatic, daily, implant-based, multiparameter telemonitoring in addition to standard care or standard care without telemonitoring. Investigators were not masked to treatment allocation. Patients were masked to allocation unless they were contacted because of telemonitoring findings. Follow-up was 1 year. The primary outcome measure was a composite clinical score combining all-cause death, overnight hospital admission for heart failure, change in NYHA class, and change in patient global self-assessment, for the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT00538356. FINDINGS We enrolled 716 patients, of whom 664 were randomly assigned (333 to telemonitoring, 331 to control). Mean age was 65·5 years and mean ejection fraction was 26%. 285 (43%) of patients had NYHA functional class II and 378 (57%) had NYHA class III. Most patients received CRT-Ds (390; 58·7%). At 1 year, 63 (18·9%) of 333 patients in the telemonitoring group versus 90 (27·2%) of 331 in the control group (p=0·013) had worsened composite score (odds ratio 0·63, 95% CI 0·43-0·90). Ten versus 27 patients died during follow-up. INTERPRETATION Automatic, daily, implant-based, multiparameter telemonitoring can significantly improve clinical outcomes for patients with heart failure. Such telemonitoring is feasible and should be used in clinical practice. FUNDING Biotronik SE & Co. KG.

Chromosome 4q25 Variants and Atrial Fibrillation Recurrence After Catheter Ablation

OBJECTIVES This study tested the hypothesis that chromosome 4q25 single-nucleotide polymorphisms (SNPs) associate with atrial fibrillation (AF) recurrence after catheter ablation. BACKGROUND Recent genome-wide association studies identified 2 SNPs on chromosome 4q25 associated with AF. Although the mechanisms underlying this increased risk are unknown, the closest gene, PITX2, is critical for myocardium development in the pulmonary veins. METHODS A total of 195 consecutive patients (mean age 56 +/- 12 years, 73% male) with drug-refractory paroxysmal (78%) or persistent (22%) AF who underwent AF catheter ablation were included. Two SNPs, rs2200733 and rs10033464, were genotyped using real-time polymerase chain reaction and fluorescence resonance energy transfer. Serial 7-day Holter electrocardiographic recordings were acquired to detect AF recurrences. RESULTS Early recurrence of atrial fibrillation (ERAF) (within the first 7 days) was observed in 37%, whereas late recurrence of atrial fibrillation (LRAF) (between 3 and 6 months) occurred in 21% of the patients. None of the clinical or echocardiographic baseline characteristics were associated with ERAF or LRAF. In contrast, the presence of any variant allele increased the risk for both ERAF (odds ratio [OR]: 1.994, 95% confidence interval [CI]: 1.036 to 3.837, p = 0.039) and LRAF (OR: 4.182, 95% CI: 1.318 to 12.664, p = 0.011). In patients with ERAF, 45% had LRAF, as opposed to 8% in patients without ERAF (OR: 9.274, 95% CI: 3.793 to 22.678, p < 0.001). CONCLUSIONS Polymorphisms on chromosome 4q25 modulate the risk for AF recurrence after catheter ablation. This finding points to a potential role for stratification of AF ablation therapy or peri-interventional management by genotype.

Thermal Esophageal Lesions After Radiofrequency Catheter Ablation of Left Atrial Arrhythmias

OBJECTIVES:Radiofrequency catheter ablation in patients with left atrial arrhythmias may cause esophageal damage because of the close proximity between the posterior wall of the left atrium and the esophagus. The aim of this prospective study was to determine the incidence, endoscopic characterization, and endoluminal temperature dependency of esophageal thermal lesions after catheter ablation.METHODS:In all, 185 consecutive patients with symptomatic atrial fibrillation or left atrial macro-re-entrant tachycardia who underwent left atrial radiofrequency catheter ablation were scheduled for upper gastrointestinal endoscopy. During the ablation procedure, a non-fluoroscopic three-dimensional system for catheter orientation, computed tomography (CT) image integration, and activation mapping was used. The esophagus was intubated with a temperature probe for visualization within the three-dimensional image and for real-time intraluminal temperature monitoring.RESULTS:A total of 27 (14.6%) asymptomatic ulcer-like or hemorrhagic esophageal thermal lesions with a diameter of 2–16 mm were observed. Esophageal lesions did not occur below an intraluminal esophageal temperature of 41 °C. The maximal temperature in the esophagus was significantly higher in patients with thermal lesions than in patients without lesions (42.6±1.7 °C vs. 41.4±1.7 °C, P=0.003). For every 1 °C increase in endoluminal temperature, the odds of an esophageal lesion increased by a factor of 1.36 (95% confidence interval (CI) 1.07–1.74, P=0.012). No progression of the lesions was observed during follow-up endoscopies.CONCLUSIONS:Localized esophageal ulcer-like lesion is a frequent event after left atrial catheter ablation and can be found in patients whose intraluminal temperature has reached at least 41 °C.

Steerable Versus Nonsteerable Sheath Technology in Atrial Fibrillation Ablation A Prospective, Randomized Study

Background— Steerable sheath technology is designed to facilitate catheter access, stability, and tissue contact in target sites of atrial fibrillation (AF) catheter ablation. We hypothesized that rhythm control after interventional AF treatment is more successful using a steerable as compared with a nonsteerable sheath access. Methods and Results— One hundred thirty patients with paroxysmal or persistent drug-refractory AF undergoing their first ablation procedure were prospectively included in a randomized fashion in 2 centers. Ablation was performed by 10 operators with different levels of clinical experience. Treatment outcome was measured with serial 7-day Holter ECGs and additional symptom-based arrhythmia documentation. Single procedure success (freedom from AF and/or atrial macroreentrant tachycardia) was significantly higher in patients ablated with a steerable sheath (78% versus 55% after 3 months, P=0.005; 76% versus 53% after 6 months, P=0.008). Rate of pulmonary vein isolation, procedure duration, and radiofrequency application time did not differ significantly, whereas fluoroscopy time was lower in the steerable sheath group (33±14 minutes versus 45±17 minutes, P<0.001). Complication rates showed no significant difference (3.2% versus 5%, P=0.608). On multivariable analysis, steerable sheath usage remained the only powerful predictor for rhythm outcome after 6 months of follow-up (hazard ratio, 2.837 [1.197 to 6.723]). Conclusions— AF catheter ablation using a manually controlled, steerable sheath for catheter navigation resulted in a significantly higher clinical success rate, with comparable complication rates and with a reduction in periprocedural fluoroscopy time. Clinical Trial Registration— URL: http://clinicaltrials.gov. Unique identifier: NCT00469638.

Echocardiographic and Electrocardiographic Predictors for Atrial Fibrillation Recurrence Following Cardioversion

Introduction: Identification of suitable candidates for cardioversion currently is not based on individual electrical and mechanical atrial remodeling. Therefore, this study analyzed the meaning of atrial fibrillatory rate obtained from the surface ECG (as a measure of electrical remodeling) and left atrial size (as measure of mechanical remodeling) for prediction of early atrial fibrillation (AF) recurrence following cardioversion.

Interatrial conduction can be accurately determined using standard 12-lead electrocardiography: validation of P-wave morphology using electroanatomic mapping in man.

BACKGROUND Different P-wave morphologies during sinus rhythm as displayed on standard ECGs have been postulated to correspond to differences in interatrial conduction. OBJECTIVE The purpose of this study was to evaluate the hypothesis by comparing P-wave morphologies using left atrial activation maps. METHODS Twenty-eight patients (mean age 49 +/- 9 years) admitted for ablation of paroxysmal atrial fibrillation were studied. Electroanatomic mapping of left atrial activation was performed at baseline during sinus rhythm with simultaneous recording of standard 12-lead ECG. Unfiltered signal-averaged P waves were analyzed to determine orthogonal P-wave morphology. The morphology was subsequently classified into one of three predefined types. All analyses were blinded. RESULTS The primary left atrial breakthrough site was the fossa ovalis in 8 patients, Bachmann bundle in 18, and coronary sinus in 2. Type 1 P-wave morphology was observed in 9 patients, type 2 in 17, and type 3 in 2. Seven of eight patients with fossa ovalis breakthrough had type 1 P-wave morphology, 16 of 18 patients with Bachmann bundle breakthrough had type 2 morphology, and both patients with coronary sinus breakthrough had type 3 P-wave morphology. Overall, P-wave morphology criteria correctly identified the site of left atrial breakthrough in 25 (89%) of 28 patients. CONCLUSION In the vast majority of patients, P-wave morphology derived from standard 12-lead ECG can be used to correctly identify the left atrial breakthrough site and the corresponding route of interatrial conduction.

Frequency Measures Obtained from the Surface Electrocardiogram in Atrial Fibrillation Research and Clinical Decision‐Making

Introduction: Frequency analysis of fibrillation (FAF) and time‐frequency analysis (TFA) were developed recently in order to quantify atrial electrical remodeling in atrial fibrillation (AF) from the surface ECG. This article describes the experience with these two different frequency analysis techniques in consecutive AF patients and discusses possible applications in AF research and clinical decision‐making.

Comparison of CHADS2, R2CHADS2 and CHA2DS2-VASc Scores for the Prediction of Rhythm Outcomes after Catheter Ablation of Atrial Fibrillation: The Leipzig Heart Center AF Ablation Registry

Background—Recurrences of atrial fibrillation (AF) occur in up to 30% within 1 year after catheter ablation. This study evaluated the value of CHADS2, R2CHADS2, and CHA2DS2-VASc scores for the prediction of rhythm outcomes after AF catheter ablation. Methods and Results—Using the Leipzig Heart Center AF Ablation Registry, we documented rhythm outcomes within the first 12 months in 2069 patients (67% men; 60±10 years; 35% persistent AF) undergoing AF catheter ablation. AF recurrences were defined as any atrial arrhythmia occurring within the first week (early recurrences, ERAF) and between 3 and 12 months (late recurrences, LRAF) after ablation. ERAF and LRAF occurred in 36% and 33%, respectively. On multivariable analysis, R2CHADS2 (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.02–1.21; P=0.016) and CHA2DS2-VASc (OR, 1.09; 95% CI, 1.017–1.17; P=0.015) scores as well as persistent AF and left atrial diameter were significant predictors for ERAF. Similarly, the same clinical variables remained significant predictors for LRAF even after adjustment for ERAF, which was the strongest predictor for LRAF (HR, 3.12; 95% CI, 2.62–3.71; P<0.001). However, using receiver operating characteristic curve analyses, both scores demonstrated relatively low predictive value for ERAF (area under the curve [AUC], 0.536 [0.510–0.563]; P=0.007; and AUC, 0.547 [0.521–0.573]; P<0.001 for R2CHADS2 and CHA2DS2-VASc, respectively) and LRAF (AUC, 0.548 [0.518–0.578]; P=0.002; and AUC, 0.550 [0.520–0.580]; P=0.001). Conclusions—R2CHADS2 and CHA2DS2-VASc were associated with rhythm outcomes after catheter ablation. However, AF type, left atrial diameter, and especially ERAF are also significant predictors for LRAF that should be included into new clinical scores for the prediction of rhythm outcomes after catheter ablation.

Common Genetic Variants and Response to Atrial Fibrillation Ablation

Background—Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near PITX2), 1q21 (rs13376333 in KCNN3), and 16q22 (rs7193343 in ZFHX3) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation. Methods and Results—Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio,1.3 [95% confidence intervals, 1.1–1.6]; P=0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence. Conclusions—Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF.

Catheter ablation of atrial fibrillation using remote magnetic catheter navigation: a case–control study

AIMS To compare the acute and the 6 month outcome of catheter ablation of atrial fibrillation (AF) using irrigated tip magnetic catheter and remote magnetic cathter navigation (RMN) with manual catheter navigation (MCN) in patients with paroxysmal and persistent AF. METHODS AND RESULTS In this retrospective analysis 356 patients (235 male, mean age: 57.9 ± 10.9 years) with AF (70.5%, paroxysmal) who underwent catheter ablation between August 2007 and May 2008 using either RMN (n = 70, 46 male, mean age: 57.9 ± 10.1 years, 50% paroxysmal) or MCN (n = 286, 189 male, mean age: 58.0 ± 13.9 years, 75.5% paroxysmal) were included. All patients completed an intensive follow-up strategy. Complete pulmonary vein isolation was achieved in 87.6 and 99.6% of patients in RMN and MCN groups, respectively (P < 0.05). The procedure, fluoroscopy, and radiofrequency application times were 223 ± 44 vs. 166 ± 52 min (P < 0.0001), 13.7 ± 7.8 vs. 34.5 ± 15.1 min (P < 0.0001), and 75.4 ± 20.9 vs. 53.2 ± 21.4 min (P < 0.0001) in RMN and MCN groups, respectively. Seven (10.0%) and 28 (9.8%) patients in RMN and MCN groups received antiarrhythmic medications during the follow-up (P = 0.96). All the patients completed the 6 month follow-up. Freedom from AF at 6 months was achieved in 57.8 and 66.4% of the patients in RMN and MCN groups, respectively (P = 0.196). In patients without previous AF catheter ablation procedure the freedom from AF at 6 months were 68.2 and 60.5% in the MCN and RMN groups, respectively (P = 0.36). CONCLUSION Catheter ablation using irrigated tip magnetic catheter and RMN is an effective and safe method for catheter ablation of AF. Compared to manual catheter navigation, the procedure and radiofrequency application times were longer and fluoroscopy time was shorter in the RMN group compared with the MCN group.