Markus Zabel

Chronic vagus nerve stimulation: a new and promising therapeutic approach for chronic heart failure

AIMS In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy. METHODS AND RESULTS This multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class II-IV patients [age 56 ± 11 years, LV ejection fraction (LVEF) 23 ± 8%]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 2-4 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6%), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 ± 76 to 471 ± 111 m), LVEF (from 22 ± 7 to 29 ± 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. CONCLUSIONS This open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted.

Automatic home monitoring of implantable cardioverter defibrillators

AIMS With the expanding indications for implantable cardioverter defibrillator (ICD) and reports of unexpected ICD failures, home monitoring (HM) was proposed to decrease follow-up workload and increase patient safety. Home monitoring implantable cardioverter defibrillators offer wireless, everyday transfer of ICD status and therapy data to a central HM Service Center, which notifies the attending physician of relevant HM events. We evaluated functionality and safety of HM ICDs. METHODS AND RESULTS A total of 260 patients with HM ICDs were monitored for a mean of 10 +/- 5 months. Time to HM events [medical (ventricular tachycardia/ventricular fibrillation) and technical (ICD system integrity)] since ICD implantation and since the latest in-clinic follow-up was analysed. Mean number of HM events per 100 patients per day was calculated, without and with a 2-day blanking period for re-notifying the same type of event. About 41.2% of the patients had HM events (38.1% medical, 0.8% technical, and 2.3% both types). Probability of any HM event after 1.5 years was 0.50 (95% confidence interval: 0.42-0.58). More than 60% of new HM event types occurred within the first month after follow-up. A mean of 0.86 event notifications was received per 100 patients per day or 0.45 with the 2-day blanking period. CONCLUSION Home monitoring is feasible and associated with an early detection of medical and technical events.

Assessment of repolarization heterogeneity for prediction of mortality in cardiovascular disease: peak to the end of the T wave interval and nondipolar repolarization components.

BACKGROUND In the canine wedge preparation, the interval from the peak to the end of the T wave (TpTe) reflects transwedge heterogeneities. Increase of ventricular dispersion of action potential durations has been repeatedly shown to be arrhythmogenic; thus, prolonged TpTe intervals were assumed to reflect increased risk. However, despite attempted extrapolation to clinical electrocardiograms, the appropriateness of this assumption has not been investigated in a large population. In another animal model, nondipolar components of the descending T-wave limb (TWRd) have been shown to correlate with TpTe interval. Although total T-wave nondipolar components (TWRt), believed to reflect heterogeneities during total repolarization, were shown associated with worse outcome of cardiac patients, this has not been investigated for TWRd. METHODS AND RESULTS Male cardiovascular patients (n = 813) had digital 12-lead electrocardiograms recorded between 1984 and 1991 and were followed until 2000. Using commercial and previously validated technology, QT intervals, TpTe intervals, TWRd, and TWRt were calculated, heart rate corrected, and compared between survivors and nonsurvivors. Their predictive power was also compared with established markers of mortality risk. In contrast to former reports, TpTe(c) intervals were significantly shorter in nonsurvivors (98.76 ± 20.63 milliseconds vs 103.14 ± 20.87 milliseconds, P = .016) and not predictive of outcome. Although TWRd(c) was significantly higher in nonsurvivors (0.007% ± 0.02% vs 0.005% ± 0.08%, P = .03), it was also not predictive of outcome. Only increased TWRt(c), increased heart rate, and increased age were predictive of death. CONCLUSIONS The findings challenge the concept that prolongation of TpTe corresponds to higher risk of death from any cause in every population. Further investigations are needed to confirm that clinically measured TpTe reflects transmural repolarization heterogeneity in all clinical populations and indeed is a useful risk marker.

Remote magnetic catheter navigation for cavotricuspid isthmus ablation in patients with common-type atrial flutter

Background—Conventional catheter ablation of cavotricuspid isthmus (CTI)-dependent atrial flutter is a widely applied standard therapy. Remote magnetic catheter navigation (RMN) may provide benefits for different ablation procedures, but its efficacy for CTI ablation has not been evaluated in a randomized, controlled trial. Methods and Results—Ninety patients undergoing de novo ablation of atrial flutter were randomly assigned to conventional manual (n=45) or RMN-guided (n=45) CTI ablation with an 8-mm-tip catheter. Complete bidirectional isthmus block was achieved in 84% (RMN) and 91% (conventional catheter ablation) of the cases (P=0.52). RMN was associated with shorter fluoroscopy time (median, 10.6 minutes; interquartile range [IQR], 7.6 to 19.9, versus 15.0 minutes; IQR, 11.5 to 23.1; P=0.043) but longer total radiofrequency application (17.1 minutes; IQR, 8.6 to 25, versus 7.5 minutes; IQR, 3.6 to 10.9; P<0.0001), ablation time (55 minutes; IQR, 28 to 76, versus 17 minutes; IQR, 7 to 31; P<0.0001), and procedure duration (114±35 versus 77±24 minutes, P<0.0001). Procedure duration in the RMN group did not decrease significantly with case experience. Long-term procedure success, defined as achievement of complete CTI block and freedom from atrial flutter recurrence during 6 months of follow-up, was lower in the RMN group (73% versus 89%, P=0.063). Right atrial angiography after ablation revealed no significant differences between groups in terms of right atrial diameter or CTI length, morphology, and angulation. Furthermore, none of these parameters was predictive for difficult (ablation time >20 minutes) or unsuccessful ablation. Conclusions—RMN-guided CTI ablation is associated with reduced radiation exposure but prolonged ablation and procedure times as compared with conventional catheter navigation. Our findings suggest that ablation lesions produced with an RMN-guided 8-mm catheter are less effective irrespective of CTI anatomy. Trial Registration—clinicaltrials.gov Identifier: NCT00560872

Detection of left atrial thrombus during routine diagnostic work-up prior to pulmonary vein isolation for atrial fibrillation: Role of transesophageal echocardiography and multidetector computed tomography☆

BACKGROUND Transesophageal echocardiography (TEE) and multidetector computed tomography (MDCT) are frequently used imaging modalities prior to pulmonary vein isolation (PVI) in order to exclude left atrial (LA) and left atrial appendage (LAA) thrombus and to visualize the anatomy of LA and pulmonary veins. This study aimed to identify predictors of LA/LAA thrombus and to analyze the diagnostic yield of routine pre-procedural TEE and MDCT. METHODS 329 patients with drug-refractory atrial fibrillation (AF) (age 62 ± 10 years; 65% males; 247 paroxysmal AF) referred for pulmonary PVI were included. Prior to the procedure, all patients underwent 64-slice MDCT and TEE, which was used as the gold standard. Risk parameters for thrombus formation were determined, including the CHADS(2) and CHA(2)DS(2)-VASc scores. RESULTS MDCT identified 10 LA/LAA thrombi (3.0%) (8 false positive, 2 true positive), whereas 7 actual thrombi (2.1%) were detected by TEE (5 false negative by MDCT). Sensitivity and specificity of MDCT was 29% and 98%, respectively, with a negative predictive value of 98% and a positive predictive value of 20%. All patients with thrombus were on effective anticoagulation. In multivariate analysis, diabetes mellitus, CHADS(2) score ≥3, and CHA(2)DS(2)-VASc score ≥4 were significantly associated with LA/LAA thrombus. No thrombus was seen in patients without risk factors. CONCLUSIONS In patients presenting for PVI, MDCT does not reliably exclude LA/LAA thrombus. Our study revealed a small but significant prevalence of thrombus despite effective anticoagulation. Diabetes mellitus, CHADS(2) score ≥3, and CHA(2)DS(2)-VASc score ≥4 were independent risk predictors of LA/LAA thrombus.

Cardiac resynchronization therapy and atrial overdrive pacing for the treatment of central sleep apnoea

The combined therapeutic impact of atrial overdrive pacing (AOP) and cardiac resynchronization therapy (CRT) on central sleep apnoea (CSA) in chronic heart failure (CHF) so far has not been investigated. We aimed to evaluate the effect of CRT alone and CRT + AOP on CSA in CHF patients and to compare the influence of CRT on CHF between CSA positive and CSA negative patients.

Left atrial volumetry from routine diagnostic work up prior to pulmonary vein ablation is a good predictor of freedom from atrial fibrillation

AIMS This study aimed to identify whether left atrial (LA) volume assessed by multidetector computed tomography (MDCT) is related to the long-term success of pulmonary vein ablation (PVA). MDCT is used to guide PVA for the treatment of atrial fibrillation (AF). MDCT permits accurate sizing of LA dimensions. METHODS AND RESULTS We analysed data from 368 ablation procedures of 279 consecutive patients referred for PVA due to drug-refractory symptomatic AF (age 62 ± 10; 58% men; 71% paroxysmal AF). Prior to the procedure, all patients underwent ECG-gated 64-MDCT scan for assessment of LA and PV anatomy, LA thrombus evaluation, LA volume estimation, and electroanatomical mapping integration. Within a mean follow-up of 356 ± 128 days, 64% of the patients maintained sinus rhythm after the initial ablation, and 84% when including repeat PVA. LA diameter (P = 0.004), LA volume (P = 0.002), and type of AF (P = 0.001) were independent predictors of AF recurrence in univariate analysis. There was a relatively low correlation between the echocardiographic LA diameter and LA volume from MDCT (P = 0.01, r = 0.5). In multivariate analysis, paroxysmal AF (P < 0.006) and LA volume below the median value of 106 mL (P = 0.042) were significantly associated with the success of PVA, whereas LA diameter was not (P = 0.245). Analysing receiver-operator characteristics, the area under the curve for LA volume was 0.73 (P = 0.001) compared with 0.60 (P = 0.09) for LA diameter from echocardiography. CONCLUSION LA volume assessed by MDCT is a better predictor of AF recurrence after PVA than echocardiograpic LA diameter and can be derived from the pre-procedural imaging data set.

Misleading Long Post-Pacing Interval After Entrainment of Typical Atrial Flutter From the Cavotricuspid Isthmus

OBJECTIVES The purpose of this study was to evaluate the prevalence and mechanism of a misleading long post-pacing interval (PPI) upon entrainment of typical atrial flutter (AFL) from the cavotricuspid isthmus (CTI). BACKGROUND In typical AFL, the PPI from entrainment at the CTI is expected to closely match the tachycardia cycle-length (TCL). METHODS Sixty patients with confirmed CTI-dependent AFL were retrospectively analyzed and grouped into short (≤30 ms) or long (>30 ms) PPI-TCL. Thereafter, we prospectively studied 16 patients to acquire the PPI-TCL at 4 CTI sites with entrainment at pacing cycle-lengths (PCLs) 10 to 40 ms shorter than the TCL. Conduction times during AFL and entrainment were compared in 5 segments of the AFL circuit. RESULTS Eleven patients (18%) in the retrospective analysis had a long PPI-TCL after entrainment from the CTI. Subjects with long PPI-TCL had similar baseline characteristics but greater beat-to-beat TCL variability. In the prospective cohort, PPI-TCL was influenced by the difference between PCL and TCL and site of entrainment. Conduction delays associated with a long PPI-TCL were located predominantly in the segment activated first by the paced orthodromic wave front, and were mainly due to local pacing latency, as confirmed by the use of monophasic action potential catheters. CONCLUSIONS A long PPI upon entrainment of typical AFL from the CTI is common and due to delayed conduction with entrainment. Whether these findings apply to other macro-re-entrant tachycardias warrants further investigation.

Gold vs. platinum-iridium tip catheter for cavotricuspid isthmus ablation: the AURUM 8 study.

AIMS Gold electrodes have the theoretical advantage of creating bigger lesions than platinum-iridium (Pt-Ir) electrodes. We performed a prospective randomized study to compare the clinical efficacy of standard 8 mm Pt-Ir tip catheter (control) and 8 mm gold-tip catheters in the ablation of the cavotricuspid isthmus (CTI)-dependent atrial flutter. METHODS AND RESULTS A total of 463 patients undergoing CTI ablation in 19 clinical centres were randomized to receive the treatment by gold-tip or control catheter. The primary endpoint was cumulative radiofrequency (RF) application duration until achieving bidirectional CTI block. It did not differ significantly for the two catheters. The gold-tip catheter was, however, associated with a higher ablation success rate (94.3 vs. 89.0%, P = 0.042) and a substantially lower incidence of char and coagulum formation (4.8 vs. 37.9%, P < 0.001), which required exchange of 1 gold-tip (0.4%) and 10 control catheters (4.6%, P = 0.005). The gold-tip catheter delivered more mean power (52 ± 12 W) than the control catheter (48 ± 13 W, P < 0.001). Both mean and maximum temperatures measured by the thermocouple integrated in the catheter tip were statistically significantly lower in the gold (mean: 53.2 ± 4.7°C, max: 68.7 ± 6.6°C) than in the control catheter (54.3 ± 5.2 and 70.2 ± 7.0°C, respectively, P < 0.05). Fluoroscopy time, procedure duration, procedural-related complications, and arrhythmia recurrence during 6 months of follow-up did not differ between the two catheters. CONCLUSION Owing to a higher primary ablation success rate and reduced incidence of char/coagulum formation, gold may be preferred over Pt-Ir as electrode material for 8 mm tip catheters for CTI ablation. ClinicalTrials.gov: NCT00326001 (http://clinicaltrials.gov/ct2/show/NCT00326001).

Ventricular oversensing due to manufacturer-related differences in implantable cardioverter-defibrillator signal processing and sensing lead properties

AIMS Ventricular oversensing remains a significant problem in modern implantable cardioverter-defibrillator (ICD) systems. The role of manufacturer-related differences in device-based signal processing on the one hand and sensing lead properties on the other is largely unknown. This retrospective study aimed to evaluate and compare the incidence and mechanisms of ventricular oversensing in single- or dual-chamber ICD systems from Biotronik (BTK), Guidant (GDT), and Medtronic (MDT). METHODS AND RESULTS In 245 consecutive patients, device function, stored episodes, and lead parameters were evaluated at implant and during 243 ± 18 days of follow-up. Oversensing occurred in 3.3% of the patients [four T-wave oversensing (TWO), three R-wave double-sensing, and one diaphragmatic myopotentials]. The incidence of ventricular oversensing was generally low if an ICD device and an ICD lead were from one identical manufacturer (BTK: 2/68, GDT: 1/80, and MDT: 1/69; P = 0.67). In the subgroup of ICDs connected to leads from other manufacturers, however, ventricular oversensing was observed in none of 19 GDT and MDT ICDs but in 4 of 9 BTK devices (44.4%, P = 0.012). These four cases of oversensing (three R-wave double-sensing and one TWO) all occurred in BTK ICDs connected to integrated bipolar ICD leads from other manufacturers. CONCLUSION Significant manufacturer-related differences exist in the incidence of ventricular oversensing in single- and dual-chamber ICD systems. Biotronik devices connected to integrated bipolar ICD leads from other manufacturers have an increased risk for R-wave double-sensing.