Present criteria for prophylactic ICD implantation: Insights from the EU-CERT-ICD (Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators in EUrope) project.

BACKGROUND: The clinical effectiveness of primary prevention implantable cardioverter defibrillator (ICD) therapy is under debate. It is urgently needed to better identify patients who benefit from prophylactic ICD therapy. The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter Defibrillators (EU-CERT-ICD) completed in 2019 will assess this issue. SUMMARY: The EU-CERT-ICD is a prospective investigator-initiated non-randomized, controlled, multicenter observational cohort study done in 44 centers across 15 European countries. A total of 2327 patients with heart failure due to ischemic heart disease or dilated cardiomyopathy indicated for primary prophylactic ICD implantation were recruited between 2014 and 2018 (>1500 patients at first ICD implantation, >750 patients non-randomized non-ICD control group). The primary endpoint was all-cause mortality, and first appropriate shock was co-primary endpoint. At baseline, all patients underwent 12­lead ECG and Holter-ECG analysis using multiple advanced methods for risk stratification as well as documentation of clinical characteristics and laboratory values. The EU-CERT-ICD data will provide much needed information on the survival benefit of preventive ICD therapy and expand on previous prospective risk stratification studies which showed very good applicability of clinical parameters and advanced risk stratifiers in order to define patient subgroups with above or below average ICD benefit. CONCLUSION: The EU-CERT-ICD study will provide new and current data about effectiveness of primary prophylactic ICD implantation. The study also aims for improved risk stratification and patient selection using clinical risk markers in general, and advanced ECG risk markers in particular.

Sex difference in appropriate shocks but not mortality during long-term follow-up in patients with implantable cardioverter-defibrillators.

AIMS: Implantable cardioverter-defibrillators (ICDs) have been shown to improve survival, although a considerable number of patients never receive therapy. Implantable cardioverter-defibrillators are routinely implanted regardless of sex. There is continuing controversy whether major outcomes differ between men and women. METHODS AND RESULTS: In this retrospective single-centre study, 1151 consecutive patients (19% women) undergoing ICD implantation between 1998 and 2010 were followed for mortality and first appropriate ICD shock over 4.9 ± 2.7 years. Sex-related differences were investigated using multivariable Cox models adjusting for potential confounders. During follow-up, 318 patients died, a rate of 5.9% per year among men and 4.6% among women (uncorrected P = 0.08); 266 patients received a first appropriate ICD shock (6.3% per year among men vs. 3.6% among women, P = 0.002). After multivariate correction, independent predictors of all-cause mortality were age (hazard ratio, HR = 1.04 per year of age, 95% confidence interval (CI) [1.03-1.06], P < 0.001), left ventricular ejection fraction (HR = 0.98 per %, 95% CI [0.97-1.00], P = 0.025), renal function (HR = 0.99 per mL/min/1.73 m(2), 95% CI [0.99-1.00], P = 0.009), use of diuretics (HR = 1.81, 95% CI [1.29-2.54], P = 0.0023), peripheral arterial disease (HR = 2.21, 95% CI [1.62-3.00], P < 0.001), and chronic obstructive pulmonary disease (HR = 1.48, 95% CI [1.13-1.94], P = 0.029), but not sex. Female sex (HR = 0.51, 95% CI [0.33-0.81], P = 0.013), older age (HR = 0.98, 95% CI [0.97-0.99], P < 0.001), and primary prophylactic ICD indication (HR = 0.69, 95% CI [0.52-0.93], P = 0.043) were independent predictors for less appropriate shocks. CONCLUSION: Women receive 50% less appropriate shocks than men having similar mortality in this large single-centre population. These data may pertain to individually improved selection of defibrillator candidates using risk factors, e.g. sex as demonstrated in this study.

A randomized study of remote monitoring and fluid monitoring for the management of patients with implanted cardiac arrhythmia devices.

AIMS: Only limited comparative data exist on the benefits of fluid monitoring (FM) combined with remote monitoring (RM) regarding morbidity and mortality of heart failure (HF) patients. This prospective single-centre randomized pilot study aimed to estimate the influence of RM in combination with FM on HF hospitalizations as well as ventricular tachyarrhythmias and mortality. METHODS AND RESULTS: Patients with standard indication for implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy and defibrillator were implanted with devices capable of RM and FM, and were followed for 15 months. Subjects were randomly allocated to RM including OptiVol and predefined management of alerts (remote group), or standard in-office visits every 3 months (control group). A total of 176 patients (77% male; 66 ± 12 years; left ventricular ejection fraction (LVEF) 32 ± 11%; ischemic cardiomyopathy 50%; CRT device 50%; primary prevention 85%) were analysed. Cox proportional hazard analysis on the time to first HF-related hospitalization showed a hazard ratio of 1.23 [0.62-2.44] (P = 0.551) favouring the control group. In the remote group, 13 patients (15%) experienced ICD shocks vs. 10 patients (11%) in the control group (P = 0.512). The average time to first ICD shock was 212 ± 173 days in the remote arm and 212 ± 143 days in the control arm (P = 0.994). The Kaplan-Meier estimate of mortality after 1 year was 8.6% (eight deaths) in the remote group vs. 4.6% in the control group (six deaths; P = 0.502). CONCLUSION: In a single-centre randomized pilot study of RM in combination with FM, no significant influence on HF-related hospitalizations, ICD shocks, or mortality was found.

Rationale and design of the MONITOR-ICD study: a randomized comparison of economic and clinical effects of automatic remote MONITORing versus control in patients with Implantable Cardioverter Defibrillators.

BACKGROUND AND AIMS: Implantable cardioverter defibrillator (ICD) remote follow-up and ICD remote monitoring (RM) are established means of ICD follow-up. The reduction of the number of in-office visits and the time to decision is proven, but the true clinical benefit is still unknown. Cost and cost-effectiveness of RM remain leading issues for its dissemination. The MONITOR-ICD study has been designed to assess costs, cost-effectiveness, and clinical benefits of RM versus standard-care follow-up in a prospective multicenter randomized controlled trial. METHODS AND RESULTS: Patients indicated for single- or dual-chamber ICD are eligible for the study and are implanted an RM-capable Biotronik ICD (Lumax VR-T or Lumax DR-T; Biotronik SE & Co KG, Berlin, Germany). Implantable cardioverter defibrillator programming and alert-based clinical responses in the RM group are highly standardized by protocol. As of December 2011, recruitment has been completed, and 416 patients have been enrolled. Subjects are followed-up for a minimum of 12months and a maximum of 24months, ending in January 2013. Disease-specific costs from a societal perspective have been defined as primary end point and will be compared between RM and standard-care groups. Secondary end points include ICD shocks (including appropriate and inappropriate shocks), cardiovascular hospitalizations and cardiovascular mortality, and additional health economic end points. CONCLUSIONS: The MONITOR-ICD study will be an important randomized RM study to report data on a primary economic end point in 2014. Its results on ICD shocks will add to the currently available evidence on clinical benefit of RM.

Passive-fixation lead failure rates and long-term patient mortality in subjects implanted with Sprint Fidelis electrodes.

AIMS: To evaluate passive-fixation lead failure rates and long-term patient survival in subjects implanted with Sprint Fidelis electrodes. METHODS AND RESULTS: We identified 748 subjects who received a Sprint Fidelis (n = 429; Medtronic models 6948: 94.8%, 6949: 2.6%, 6930: 1.9%, 6931: 0.7%) or a Sprint 'non-Fidelis' implantable cardioverter defibrillator lead (n = 319, Medtronic models 6944: 68.6%, 6947: 17.9%, 6942: 7.8%, 6943: 3.4%, 6945: 2.2%) at our centre between 1998 and 2008. Kaplan-Meier patient survival was lower in the Fidelis group than in the Control cohort (68.4 vs. 77.0% at 5 years, P = 0.0061), but multivariate analyses revealed no significant association between mortality and implanted lead type. Passive-fixation lead failure rate at 5 years was 14.4% (95% confidence interval (CI) [9.2, 19.3]) in the Fidelis (n = 414) group and 1.8% (95% CI [0.0-3.8]) in the Control (n = 241) cohort (P < 0.001 upon multivariate comparison). CONCLUSION: Failure rates of passive-fixation Sprint Fidelis leads are increased and similar to those previously reported for active-fixation Fidelis electrodes. Despite the elevated risk for lead failure and its potential sequelae, the Sprint Fidelis has no obvious impact on long-term mortality.

Measurement of Left Atrial Pressure is a Good Predictor of Freedom From Atrial Fibrillation.

BACKGROUND: It is suggested that an elevated left atrial pressure (LAP) promotes ectopic beats emanating in the pulmonary veins (PVs) and that LAP might be a marker for structural remodeling. This study aimed to identify if the quantification of LAP correlates with structural changes of the LA and may therefore be associated with outcomes following pulmonary vein isolation (PVI). METHODS: We analysed data from 120 patients, referred to PVI due to drug-refractory atrial fibrillation (AF) (age 63±8; 57% men). The maximum (mLAP) and mean LAP (meLAP) were measured after transseptal puncture. RESULTS AND CONCLUSIONS: Within a mean follow-up of 303±95 days, 60% of the patients maintained in sinus rhythm after the initial procedure and 78% after repeated PVI. Performing univariate Cox-regression analysis, type of AF, LA-volume (LAV), mLAP and the meLAP were significant predictors of recurrence after PVI (p=0.03; p=0.001; p=0.01). In multivariate analysis mLAP>18mmHg, LAV>100 ml and the presence of persistent AF were significant predictors (p=0.001; p=0.019; p=0.017). The mLAP >18 mmHg was associated with a hazard ratio of 3.8. Analyzing receiver-operator characteristics, the area under the curve for mLAP was 0.75 (p<0.01). mLAP >18 mmHg predicts recurrence with a sensitivity of 77 % and specificity of 60 %. There was a linear correlation between the LAV from MDCT and mLAP (p = 0.01, R2 = 0.61). The mLAP measured invasively displays a significant predictor for AF recurrence after PVI. There is a good correlation between LAP and LAV and both factors may be useful to quantify LA remodeling.

Impact of obstructive sleep apnoea on diastolic function.

We investigated whether obstructive sleep apnoea (OSA) independently affects diastolic function in a primary care cohort of patients with cardiovascular risk factors. 378 study participants with risk factors for diastolic dysfunction were prospectively included and a polygraphy was performed in all patients. Diastolic dysfunction was assessed by comprehensive echocardiography including tissue Doppler. Sleep apnoea was classified according to apnoea/hypopnoea index (AHI) as none (AHI <5 events·h(-1)), mild (AHI ≤5 to <15 events·h(-1)) or moderate-to-severe (AHI ≥15 events·h(-1)). Patients with central sleep apnoea (n=14) and patients with previously diagnosed sleep apnoea (n=12) were excluded. In the remaining 352 subjects, 21.6% had an AHI ≥15 events·h(-1). The prevalence of diastolic dysfunction increased with the severity of sleep apnoea from 44.8% (none) to 56.8% (mild) to 69.7% (moderate-to-severe sleep apnoea) (p=0.002). The degree of diastolic dysfunction also increased with sleep apnoea severity (p=0.004). In univariate regression analysis, age, desaturation index, AHI, cardiac frequency, angiotensin receptor 1 antagonist therapy, body mass index (BMI) and left ventricular mass were associated with diastolic dysfunction. In multivariate regression analysis, only age, BMI, AHI and cardiac frequency were independently associated with diastolic dysfunction. Moderate-to-severe OSA is independently associated with diastolic dysfunction in patients with classical risk factors for diastolic dysfunction.

Pulmonary vein anatomy predicts freedom from atrial fibrillation using remote magnetic navigation for circumferential pulmonary vein ablation.

AIMS: Multidetector computed tomography (MDCT) is frequently used to guide circumferential pulmonary vein ablation (PVA) for treatment of atrial fibrillation (AF) as it offers accurate visualization of the left atrial (LA) and pulmonary vein (PV) anatomy. This study aimed to identify if PV anatomy is associated with outcomes following PVA using remote magnetic navigation (RMN). METHODS AND RESULTS: We analysed data from 138 consecutive patients and 146 ablation procedures referred for PVA due to drug-refractory symptomatic AF (age 63 ± 11 years; 57% men; 69% paroxysmal AF). The RMN using the stereotaxis system and open-irrigated 3.5 mm ablation catheters was used in all procedures. Prior to PVA, all patients underwent electrocardiogram-gated 64-MDCT for assessment of LA dimensions, PV anatomy, and electro-anatomical image integration during the procedure. Regular PV anatomy was found in 68%, a common left PV ostium was detected in 26%, and variant anatomy of the right PVs was detected in 6%. After a mean follow-up of 337 ± 102 days, 63% of the patients maintained sinus rhythm after the initial ablation, and 83% when including repeat PVA. Although acutely successful PV isolation did not differ between anatomical subgroups (regular 3.5 ± 0.8 vs. variant 3.2 ± 1.3; P = 0.31), AF recurrence was significantly higher in patients with non-regular PV anatomy (P = 0.04, hazard ratio 1.72). Pulmonary vein anatomy did not influence complication rates. CONCLUSION: Pulmonary vein anatomy assessed by MDCT is a good predictor of AF recurrence after PVA using RMN.

Sleep-disordered breathing in deep vein thrombosis and acute pulmonary embolism.

Sleep-disordered breathing (SDB) may trigger thromboembolic events by enhancing intravascular clot formation. The primary objective of the present nested case-control study was to investigate whether the prevalence of SDB is increased in patients with deep vein thrombosis (DVT) and/or acute pulmonary embolism (PE). 82 consecutive patients with DVT and/or PE (cases) were prospectively enrolled irrespective of SDB-related symptoms and formed matched pairs with patients without DVT and/or PE (controls) according to sex and pre-defined categories of age and body mass index. The prevalence of SDB (respiratory disturbance index assessed by polygraphy ≥ 15 events·h(-1)) was significantly greater in the cases with DVT and/or PE than in controls (40 versus 26%, p=0.046) and was predominantly obstructive in nature. Multiple regression analysis revealed that SDB was significantly associated with DVT and/or PE (OR 2.28, 95% CI 1.08-4.85; p=0.032) independent of established risk factors for thrombosis. In the sex-specific analyses this association was significant in females (OR 4.14, 95% CI 1.05-16.36; p=0.042), but not in males (OR 1.55, 95% CI 0.57-4.21; p=0.391). SDB occurs more frequently in females with DVT and/or PE than in controls matched for anthropometric variables, and is independently associated with the occurrence of these thromboembolic events.

Rationale, objectives, and design of the EUTrigTreat clinical study: a prospective observational study for arrhythmia risk stratification and assessment of interrelationships among repolarization markers and genotype.

AIMS: The EUTrigTreat clinical study has been designed as a prospective multicentre observational study and aims to (i) risk stratify patients with an implantable cardioverter defibrillator (ICD) for mortality and shock risk using multiple novel and established risk markers, (ii) explore a link between repolarization biomarkers and genetics of ion (Ca(2+), Na(+), K(+)) metabolism, (iii) compare the results of invasive and non-invasive electrophysiological (EP) testing, (iv) assess changes of non-invasive risk stratification tests over time, and (v) associate arrythmogenomic risk through 19 candidate genes. METHODS AND RESULTS: Patients with clinical ICD indication are eligible for the trial. Upon inclusion, patients will undergo non-invasive risk stratification, including beat-to-beat variability of repolarization (BVR), T-wave alternans, T-wave morphology variables, ambient arrhythmias from Holter, heart rate variability, and heart rate turbulence. Non-invasive or invasive programmed electrical stimulation will assess inducibility of ventricular arrhythmias, with the latter including recordings of monophasic action potentials and assessment of restitution properties. Established candidate genes are screened for variants. The primary endpoint is all-cause mortality, while one of the secondary endpoints is ICD shock risk. A mean follow-up of 3.3 years is anticipated. Non-invasive testing will be repeated annually during follow-up. It has been calculated that 700 patients are required to identify risk predictors of the primary endpoint, with a possible increase to 1000 patients based on interim risk analysis. CONCLUSION: The EUTrigTreat clinical study aims to overcome current shortcomings in sudden cardiac death risk stratification and to answer several related research questions. The initial patient recruitment is expected to be completed in July 2012, and follow-up is expected to end in September 2014. Clinicaltrials.gov identifier: NCT01209494.

Local and systemic effects of angiotensin receptor blockade in an emphysema mouse model.

OBJECTIVES: COPD with emphysema causes marked neurohumoral activation. Angiotensin II receptors are highly expressed within the lung and interfere with mechanisms involved in the progression of emphysema. This study examined the effects of an angiotensin II receptor blocker (ARB) on pulmonary and systemic manifestations of emphysema in a mouse model. METHODS: Female NMRI mice received five intratracheal instillations of porcine pancreatic elastase (emphysema; n = 11) or phosphate-buffered saline (PBS; n = 4). Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, and lung biomechanics by compliance. Following emphysema induction, 6 mice were treated with the ARB irbesartan for 8 weeks, while 5 mice receiving standard food served as controls. RESULTS: Following emphysema induction, mean linear intercept was higher in elastase-treated than in PBS-treated lungs (103.0 ± 6.2 µm vs. 35.0 ± 0.6 µm; p = 0.043) while running distance was shorter in emphysema mice (418.6 ± 83.5 m vs. 906.6 ± 244.6 m, p = 0.028). Irbesartan-treated emphysema mice showed a lower mean linear intercept (90.8 ± 3.8 µm vs. 121.5 ± 8.1 µm; p = 0.005), improved compliance (163.6 ± 55.9 µl/cmH(2)O vs. 354.4 ± 72.5 µl/cmH(2)O; p = 0.063) and greater running distance (p ANOVA = 0.015) compared to emphysema mice receiving standard food. CONCLUSIONS: The ARB irbesartan elicits encouraging beneficial effects on emphysema severity, lung biomechanics and exercise capacity in an emphysema mouse model. These findings might help to understand the corresponding positive effects of angiotensin II receptor blockade noticed in patients with COPD.

Acute and long-term feasibility of contralateral transvenous lead placement with subcutaneous, pre-sternal tunnelling in patients with chronically implanted rhythm devices.

AIMS: A growing number of patients with implanted rhythm devices require new or additional leads, e.g. in cases of electrode defect or planned device upgrade. If the ipsilateral subclavian vein is occluded, transvenous electrode placement from the contralateral side with subcutaneous, pre-sternal lead tunnelling (TUN) is one potential option that has been described in anecdotal reports. The aim of this retrospective study was to determine the acute and long-term feasibility of this approach. METHODS AND RESULTS: We identified 18 subjects (67% male, 66±14 years) who underwent TUN at our institution between the years 1995 and 2009. Implantation protocols and patient files were reviewed for peri-operative complications and long-term lead performance. Furthermore, patients were interviewed for symptoms related to the tunnelled lead. Twenty transvenous leads (seven implantable cardioverter defibrillator leads; five left ventricular, four right ventricular, four right atrial pace/sense electrodes) were successfully tunnelled without significant peri-operative complications. The follow-up duration was 29±36 (3-162) months. Electrical parameters remained stable in 95% (19/20) of the tunnelled leads. In one right ventricle pace/sense lead, ventricular oversensing was documented 10 months after TUN, and the lead was replaced because a structural defect could not be excluded. Five patients died without causal relationship to the procedure 4-48 months after TUN. One patient reported discomfort related to the tunnelled lead. CONCLUSION: Contralateral transvenous lead implantation with subcutaneous, pre-sternal TUN appears to be a feasible option in selected patients with an implanted rhythm device and ipsilateral subclavian vein occlusion.

Sudden cardiac death after implantation of a cardiac resynchronization therapy pacemaker: a case report illustrating that not always less is more.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves symptoms and survival in selected patients with systolic heart failure and ventricular conduction delay. In subjects without prior life-threatening ventricular arrhythmia, clinicians have to select between implanting a CRT pacemaker (CRT-P) or a more complex device with additional defibrillator capability (CRT-D). This individual decision can be challenging in light of the available evidence and the potential risks and benefits. CASE SUMMARY: A 76-year-old male with non-ischaemic cardiomyopathy, heart failure New York Heart Association Class III, left bundle branch block (QRS duration 185 ms) and a left ventricular ejection fraction of 30% despite optimal medical therapy was indicated for CRT. In light of the patient characteristics and clinical condition, a CRT-P device was implanted. No complication occurred, and the patient was discharged after an appropriate device function was confirmed. Despite the clinical improvement, he died suddenly without prior symptoms approximately 2 months thereafter. Post-mortem device interrogation provided no evidence for device malfunction and confirmed sudden cardiac death (SCD) due to spontaneous ventricular fibrillation. DISCUSSION: Patients indicated for CRT often have overlapping internal cardioverter defibrillator indication for the primary prevention of SCD. By weighing individual risks and potential benefits, clinicians have to decide whether to implant a CRT-P (less is more) or a more complex and costly CRT-D device. Despite careful consideration of patient characteristics and clinical conditions, however, SCD can occur in subjects categorized as low risk and implanted with a CRT-P. More data from randomized clinical trials are needed to better support physicians in the often challenging process of selecting the most appropriate device for CRT.

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.

Interference of remote magnetic catheter navigation and ablation with implanted devices for pacing and defibrillation.

AIMS: Remote magnetic catheter navigation (RMN) may facilitate catheter ablation. However, as the system uses permanent magnets, interference (INF) with devices for pacing [pacemaker (PM)], defibrillation [implantable cardioverter defibrillators (ICD)], or cardiac resynchronisation [cardiac resynchronization therapy (CRT)] may occur. We investigated the effects of the RMN system on implanted arrhythmia devices in a prospective series. METHODS AND RESULTS: Prior to RMN-guided electrophysiological procedures, devices were fully interrogated and programmed to VVI 40/min with tachycardia detection off (if applicable). Periprocedural device performance was monitored by 12-lead electrocardiogram, and duration and effect of asynchronous stimulation resulting from INF were evaluated. Following the procedure, devices were again interrogated and system integrity verified. A total of 21 procedures in 18 patients with implanted devices [PM n = 12, ICD n = 3, CRT-pacemaker (P) n = 1, CRT-defibrillation (D) n = 2] were evaluated. No relevant changes in lead parameters or device programming were observed after the procedure. No INF was noted in ICD/CRT-D devices (tachycardia detection off) and in 2 PMs, whereas 10 PMs and 1 CRT-P switched to asynchronous stimulation for 1.8 ± 0.3 h (63 ± 13% of RMN duration) without clinical adverse effects. In one patient, ventricular tachycardia (VT) degenerating in ventricular fibrillation occurred, but no causal relation between INF and VT initiation could be ascertained. CONCLUSION: This prospective data provide no evidence that using RMN in patients with implanted arrhythmia devices may cause persistent device dysfunction. Asynchronous PM stimulation is common without negative clinical consequences. Although a causal role of INF for the VT observed seems unlikely, risks and benefits of RMN utilization should carefully be weighed for each patient with an implanted arrhythmia device.

[Safety and efficiency of interventional electrophysiology utilizing the German "Belegarztsystem"]. / Effizienz und Sicherheit einer interventionellen Elektrophysiologie im kooperativen Belegarztsystem.

INTRODUCTION: Electrophysiology study (EPS) and catheter ablation (abl.), in particular for atrial fibrillation, are increasingly performed in Germany. Therefore, measures and steps to ensure quality assurance are indicated. Most of the procedures are performed by physicians employed by hospitals; however, some are also carried out by attending cardiologists on contract in private practice, applying the so-called Belegarztsystem. The aim of this study was to determine the safety and efficiency of an interventional electrophysiology performed in a German Belegarztsystem. METHODS: Based on a prospective registry, we analyzed procedure-related data from 1400 consecutive EPS/abl. performed at our center between 2014 and 2018. One-year follow-up data (arrhythmia recurrences, complications, deaths) were collected for all procedures carried out during the first 2 years. RESULTS: In the total study cohort, no periprocedural death occurred, and there was a low cumulative incidence of groin complications (0.9%). The most common procedure (n = 772) was complex ablation for atrial fibrillation/flutter (55%). In this group, the success rate was 98% (acute) and 65% (1 year), and the cumulative rate of complications was 5.0% (transient ischemic attack/stroke 0.1%, pericardial tamponade 0.4%, relevant pericarditis/pericardial effusion 1.1%, groin complication 1.5%, other 1.9%). For the other procedures, rates for success and complications were comparable, and procedure times and x­ray doses tended to be lower in our analysis as compared to prior reports. CONCLUSION: Interventional electrophysiology, carried out by experienced operators and qualified staff, can be performed safely and effectively by attending physicians in a Belegarztsystem.

Exercise intolerance and systemic manifestations of pulmonary emphysema in a mouse model.

BACKGROUND: Systemic effects of chronic obstructive pulmonary disease (COPD) significantly contribute to severity and mortality of the disease. We aimed to develop a COPD/emphysema model exhibiting systemic manifestations of the disease. METHODS: Female NMRI mice were treated 5 times intratracheally with porcine pancreatic elastase (emphysema) or phosphate-buffered saline (control). Emphysema severity was quantified histologically by mean linear intercept, exercise tolerance by treadmill running distance, diaphragm dysfunction using isolated muscle strips, pulmonary hypertension by measuring right ventricular pressure, and neurohumoral activation by determining urinary norepinephrine concentration. RESULTS: Mean linear intercept was higher in emphysema (260.7 +/- 26.8 microm) than in control lungs (24.7 +/- 1.7 microm). Emphysema mice lost body weight, controls gained weight. Running distance was shorter in emphysema than in controls. Diaphragm muscle length was shorter in controls compared to emphysema. Fatigue tests of muscle strips revealed impaired relaxation in emphysema diaphragms. Maximum right ventricular pressure and norepinephrine were elevated in emphysema compared to controls. Linear correlations were observed between running distance changes and intercept, right ventricular weight, norepinephrine, and diaphragm length. CONCLUSION: The elastase mouse model exhibited severe emphysema with consecutive exercise limitation, and neurohumoral activation. The model may deepen our understanding of systemic aspects of COPD.

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

AIMS: 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. METHODS AND RESULTS: Thirty patients with CRT indication underwent full night polysomnography, echocardiography, exercise testing, and neurohumoral evaluation before and 3 months after CRT implantation. In CSA positive patients (60%), two additional sleep studies were conducted after 3 months of CRT, with CRT alone or CRT + AOP, in random order. Cardiac resynchronization therapy resulted in significant improvements of NYHA class, left ventricular ejection fraction, N-terminal pro-brain natriuretic peptide, VO(2)max, and quality of life irrespective of the presence of CSA. Cardiac resynchronization therapy also reduced the central apnoea-hypopnoea index (AHI) (33.6 +/- 14.3 vs. 23.8 +/- 16.9 h(-1); P < 0.01) and central apnoea index (17.3 +/- 14.1 vs. 10.9 +/- 13.9 h(-1); P < 0.01) without altering sleep stages. Cardiac resynchronization therapy with atrial overdrive pacing resulted in a small but significant additional decrease of the central AHI (23.8 +/- 16.9 vs. 21.5 +/- 16.9 h(-1); P < 0.01). CONCLUSION: In this study, CRT significantly improved CSA without altering sleep stages. Cardiac resynchronization therapy with atrial overdrive pacing resulted in a significant but minor additional improvement of CSA. Positive effects of CRT were irrespective of the presence of CSA.

Reverse left ventricular structural remodeling after catheter ablation of atrial fibrillation in patients with preserved left ventricular function: Insights from cardiovascular magnetic resonance native T1 mapping.

BACKGROUND: Catheter ablation of atrial fibrillation (AF) improves left ventricular (LV) function in patients with LV systolic dysfunction, suggestive of underlying arrhythmia-induced adverse remodeling. OBJECTIVES: The objectives of this study were to evaluate whether arrhythmia-induced LV remodeling occurs in patients with AF and preserved LV systolic function and to assess whether this remodeling is reversible after restoration of sinus rhythm by catheter ablation. METHODS: Forty-three patients with AF and preserved LV systolic function (LV ejection fraction 62% ± 7%) underwent cardiovascular magnetic resonance (CMR) imaging before catheter ablation including native T1 mapping using a modified Look-Locker inversion recovery sequence. Twenty-five patients underwent follow-up CMR 3 months after catheter ablation. Twenty-two matched controls without AF underwent the same CMR protocol. RESULTS: Patients with AF had higher baseline LV native T1 values than did controls (1296 ± 55 ms vs 1243 ± 55 ms; P < .01). During a median follow-up of 9 months (interquartile range 4-14 months), 17 patients (40%) experienced AF recurrence. No differences in baseline T1 values were observed between patients with and without AF recurrence. There was a significant decrease in native T1 values in patients with successful restoration of sinus rhythm after catheter ablation at 3 months of follow-up CMR (1300 ± 45 ms vs 1270 ± 55 ms; P < .01), while they remain unchanged in patients with AF recurrence (1303 ± 51 ms vs 1309 ± 31 ms; P = .64). CONCLUSION: These preliminary results suggest that subclinical arrhythmia-induced LV structural remodeling occurs in patients with AF and preserved LV systolic function. This remodeling might be reversible after catheter ablation with successful restoration of sinus rhythm as quantified noninvasively and gadolinium-free by CMR native T1 mapping.