Benefits and limitations of implantable loop recorders in the very elderly.

BACKGROUND: Implantable loop recorder (ILR) allows rhythm-monitoring up to 3 years. They are recommended in patients with recurrent syncope and for the detection of atrial fibrillation (AF) in patients with cryptogenic thromboembolic events. AF and syncope occur more often in elderly patients. However, data in this cohort is limited. METHODS AND RESULTS: All patients ≥ 80 years undergoing ILR-implantation between 2011 and 2022 in our center were included. Permanent pacemaker implantation (PPI) and oral anticoagulation due AF were defined as primary endpoints. Forty-five patients ≥ 80 years were included, 33 because of recurrent syncope and 12 because of suspected AF. The average follow up (FU) was 17.6 months. Overall in 22 patients, ILR-implantation led to a therapeutic consequence (48.9%). In the 12 patients who underwent ILR-implantation for detection of AF, AF was detected in nine patients (75%). In the 33 elderly patients who received ILR-implantation after syncope, 11 underwent PPI during FU (33.3%). One patient accidentally removed the ILR himself via the implantation-wound, and no other ILR-related complications were observed. CONCLUSION: ILR are effective and safe in elderly patients. AF was often found in patients with suspected AF, especially in patients after catheter ablation of only documented atrial flutter (AFlu). PPI-rate was high in patients with recurrent syncope and ILR-implantation. Further investigations are necessary to determine whether PPI may be considered in elderly patients with syncope even in the absence of a bifascicular block.

Bradycardia in Patients with Subcutaneous Implantable Defibrillators-An Overestimated Problem? Experience from a Large Tertiary Centre and a Review of the Literature.

Background: The subcutaneous ICD (S-ICD) has developed as a valuable alternative to transvenous implantable cardioverter defibrillator (ICD) systems. However there are certain peculiarities which are immanent to the S-ICD and may limit its use. Besides oversensing the main issue is the missing option for antibradycardia pacing. To evaluate the actual need for pacing during follow-up and changes to transvenous ICD we analyzed our large tertiary centre registry and compared it with data from other large cohorts and trials. Methods and Results: We found out that in the 398 patients from our centre, there was a need for changing to a transvenous ICD in only 2 patients (0.5%) during a follow-up duration of almost 3 years. This rate was comparable to data obtained from other large data sets so that in the pooled analysis of almost 4000 patients the rate of bradycardia-associated complications was only 0.3%. Conclusions: The use of the S-ICD is safe in a variety of heart diseases and the need for antibradycardia stimulation is a very rare complication throughout many different large studies. Clinicians may take these results into account when opting for a certain ICD system and the S-ICD may be chosen more often also in elderly patients, in whom the risk for bradycardia is deemed higher.

[New developments in leadless pacing systems]. / Neue Entwicklungen bei kabellosen Schrittmachersystemen.

Leadless pacing systems, especially the Micra™ TPS system, deliver an effective and safe alternative to the previous conventional transvenous systems in patients with impossible transvenous access and seem to be compatible with other implantable devices (S-ICD, deep brain stimulators) with no limitations in efficacy or safety. Also, new outlooks on leadless resynchronization therapy seem promising and could prevent future patients from lead- or operation-associated complications. Current limits to the implementation in everyday clinical practice are mostly the unavailability of the devices or cost issues through lack of health insurance reimbursement. However, more promising data through further studies and rising implantation rates are expected based on the positive current clinical data.

Predicting inappropriate S-ICD® episodes by simple 12-lead surface ECG parameters.

AIMS: The present study aims at analyzing the role of a preimplantation 12-lead electrocardiogram (ECG) on the prediction of inappropriate S-ICD® episodes. METHODS: N=116 screened patients (pts) with an S-ICD® and a follow-up of at least 6 months were included. A preimplantation 12-lead ECG (50 mm/s, 10 mm/mV) was analyzed with regard to QRS and T-wave amplitude, T wave concordance or discordance and QRS/T wave ratio in all 12 leads. To ensure an exact determination of parameters Datinf® Measure software was used. Results were correlated to the occurrence of oversensing of cardiac signals during follow-up. RESULTS: N = 116 pts. (63,8% male, mean age 40,9 ± 15,5 years) were included (primary prevention in 47.4% of pts). The most frequent cardiac diseases were hypertrophic cardiomyopathy (HCM) in n = 25 (21,6%), electrical heart disease in n = 20 (17,2%), and dilated cardiomyopathy in n = 17 (14,7%). Mean follow-up was 740 ± 549 days. During follow- up n = 17 (14.7%) pts. experienced n = 27 inappropriate episodes due to T-wave oversensing. Besides HCM (OR 6.16, CI 1.79-21.15, p = 0.004) a discordance of QRS to T-wave in lead I (OR 6.5, CI 1.86-22.67, p = 0.003) was found to be a strong predictor for inappropriate shocks. In multivariate analysis the pts. with a combination of both had an 8.4-fold higher risk of misclassification of intracardiac signals (p = 0.003) with consecutive inappropriate therapy. CONCLUSION: A discordance of QRS to T-wave in lead I turned out to be a strong predictor for future inappropriate shocks in a typical S-ICD® cohort with special impact on HCM pts.

Clinical experience regarding safety and diagnostic value of cardiovascular magnetic resonance in patients with a subcutaneous implanted cardioverter/defibrillator (S-ICD) at 1.5 T.

BACKGROUND: Cardiovascular magnetic resonance (CMR) studies in patients with implanted cardioverter/defibrillators (ICD) are increasingly required in daily clinical practice. However, the clinical experience regarding the feasibility as well as clinical value of CMR studies in patients with subcutaneous ICD (S-ICD) is still limited. Besides safety issues, image quality and analysis can be impaired primarily due the presence of image artefacts associated with the generator. METHODS: Twenty-three patients with an implanted S-ICD (EMBLEM, Boston Scientific, Marlborough, Massachusetts, USA; MR-conditional) with suspected cardiomyopathy and/or myocarditis underwent multi-parametric CMR imaging. Studies were performed on a 1.5 T CMR scanner after device interrogation and comprised standard a) balanced steady state free precession cine, b) T2 weighted-edema, c) velocity-encoded cine flow, d) myocardial perfusion, e) late-gadolinium-enhancement (LGE)-imaging and f) 3D-CMR angiography of the aorta. In case of substantial artefacts, alternative CMR techniques such as spoiled gradient-echo cine-sequences and wide-band inversion-recovery LGE (wb-LGE) sequences were applied. RESULTS: Successful CMR studies could be performed in all patients without any case of unexpected early termination or relevant technical complication other than permanent loss of the S-ICD system beeper volume in 52% of our patients. Assessment of cine-CMR images was predominantly impaired in the left ventricular (LV) anterior, lateral and inferior wall segments and a switch to spoiled gradient echo-based cine-CMR allowed an accurate assessment of cine-images in N = 17 (74%) patients with only limited artefacts. Hyperintensity artefacts in conventional LGE-images were predominantly observed in the LV anterior, lateral and inferior wall segments and image optimisation by use of the wb-LGE was helpful in 15 (65%) cases. Aortic flow measurements and 3D-CMR angiography were assessable in all patients Perfusion imaging artefacts precluded a meaningful assessment in at least one half of the patients. A benefit in clinical-decision making was documented in 17 (74%) patients in the present study. CONCLUSION: Safe 1.5 T CMR imaging was possible in all patients with an S-ICD, though the majority had permanent loss of the S-ICD beeper volume. Achieving good image quality may be challenging in some patients - particularly for perfusion imaging. Using spoiled gradient echo-based cine-sequences and wb-LGE sequences may help to reduce the extent of artefacts, thereby allowing accurate cardiac assessment. Thus, 1.5 T CMR studies should not be withhold in patients with S-ICD for safety concerns and/or fear of extensive imaging artefacts precluding successful image analysis.

Long-term experience of atrioventricular node ablation in patients with refractory atrial arrhythmias.

Atrial fibrillation and other atrial tachyarrhythmias are increasing with age and concomitant morbidity. First options in symptomatic patients are drug treatment and catheter ablation. Nevertheless, a considerable number of patients suffer from refractory atrial tachyarrhythmias despite treatment. Atrioventricular node ablation (AVNA) may be helpful in many of these patients. Therefore, we investigated AVNA patients with a long-term follow-up. We enrolled 82 patients with a follow-up longer than 1 year receiving AVNA for drug- and ablation-resistant atrial tachyarrhythmias (AA) in a retrospective manner. Mean follow-up duration was 48 ± 24 months. 50% of the patients initially received AVNA to optimize biventricular pacing in cardiac resynchronization therapy, the other 50% because of refractory symptomatic tachyarrhythmias. Persistent AV block was achieved in every patient. Symptom relief and patient satisfaction were high during follow-up. Due to system upgrades there were 63% of patients with a biventricular system during follow-up. In these patients, left-ventricular ejection fraction (LV-EF) increased by 7% (42-49%) after ablation. AVNA is effective in increasing biventricular pacing as well as for symptom relief in patients with refractory atrial tachyarrhythmias. AVNA should be considered as a valuable option in patients with refractory atrial tachyarrhythmias lacking other treatment options.

The entirely subcutaneous ICDTM system in patients with congenital heart disease: experience from a large single-centre analysis.

AIMS: The subcutaneous implantable cardioverter-defibrillator (S-ICDTM) is an important advance in device therapy for the prevention of sudden cardiac death (SCD). Although current guidelines recommend S-ICDTM use, long-term data are still limited, especially in subgroups such as adult patients with congenital heart diseases. This cohort is of high interest because of the difficult anatomic conditions in these patients. METHODS AND RESULTS: All S-ICDTM patients with an underlying congenital heart disease (CHD) resulting in an indication for ICD implantation (n = 20 patients) in our large-scaled single-centre S-ICDTM registry (n = 249 patients) were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 36 months. Primary prevention of SCD was the indication for implantation of an S-ICDTM in six patients (30%). Of all 20 patients with an overall mean age of 40.5 ± 11.5 years, 12 were male (60%). The mean left ventricular ejection fraction was 46.5 ± 11.3%. Nine episodes of ventricular tachycardia (two monomorphic and seven polymorphic) were adequately terminated in three patients (15%). In two patients, T-Wave-Oversensing resulting in an inappropriate shock was observed, which could be managed by changing the sensing vector or activation of the SMART PASSTM filter. There were no S-ICDTM system-related infections. In one patient, surgical revision was necessary due to a persistent haematoma. CONCLUSION: The S-ICDTM seems to be a valuable option for the prevention of SCD in patients with various CHDs and complex anatomical anomalies. The S-ICDTM is safe and works effectively, also in these complex patients. Inadequate shock delivery was rare and could be managed by reprogramming.

Spotlight on S-ICD™ therapy: 10 years of clinical experience and innovation.

Subcutaneous ICD (S-ICD™) therapy has been established in initial clinical trials and current international guideline recommendations for patients without demand for pacing, cardiac resynchronization, or antitachycardia pacing. The promising experience in 'ideal' S-ICD™ candidates increasingly encourages physicians to provide the benefits of S-ICD™ therapy to patients in clinical constellations beyond 'classical' indications of S-ICD™ therapy, which has led to a broadening of S-ICD™ indications in many centres. However, the decision for S-ICD™ implantation is still not covered by controlled randomized trials but rather relies on patient series or observational studies. Thus, this review intends to give a contemporary update on available empirical evidence data and technical advancements of S-ICD™ technology and sheds a spotlight on S-ICD™ therapy in recently discovered fields of indication beyond ideal preconditions. We discuss the eligibility for S-ICD™ therapy in Brugada syndrome as an example for an adverse and dynamic electrocardiographic pattern that challenges the S-ICD™ sensing and detection algorithms. Besides, the S-ICD™ performance and defibrillation efficacy in conditions of adverse structural remodelling as exemplified for hypertrophic cardiomyopathy is discussed. In addition, we review recent data on potential device interactions between S-ICD™ systems and other implantable cardio-active systems (e.g. pacemakers) including specific recommendations, how these could be prevented. Finally, we evaluate limitations of S-ICD™ therapy in adverse patient constitutions, like distinct obesity, and present contemporary strategies to assure proper S-ICD™ performance in these patients. Overall, the S-ICD™ performance is promising even for many patients, who may not be 'classical' candidates for this technology.

Change of sensing vector in the subcutaneous ICD during follow-up and after device replacement.

BACKGROUND: The subcutaneous implantable cardioverter defibrillator (S-ICD) has been established as a valuable alternative to transvenous ICD for prevention of sudden cardiac death. The system automatically chooses the optimal sensing vector. However, during follow-up and especially after device replacement we observed a change of the suggested sensing vector in automatic setup. Therefore, we analyzed frequency and reasons of vector change and its impact on inappropriate shocks (IAS). MATERIAL AND METHODS: Between June 2010 and December 2017, a total of 216 patients with S-ICD® were included in this analysis. In all patients sensing vectors at the time of implantation, during follow-up, and after device replacement were investigated. Median follow-up time was 27.3 ± 25.3 months. RESULTS: A change of the initial vector was seen in 77 patients (35.7%). The most frequent reason for vector change was the postoperative setup in supine and erect position in 54 patients (70.1%). In 12 patients (15.5%), the vector was manually changed due to inappropriate sensing and/or therapies. Routine setup during follow-up led to automatic vector change in 10 cases (13.0%). In only 1 patient the vector was manually changed due to oversensing in an exercise treadmill test. In 27 patients, the device was replaced due to battery depletion and in 6 of these patients the sensing vector was changed by the automatic setup. Vector change did not have an impact for inappropriate therapies in the follow-up; only 1 patient received an IAS due to an inadvertent vector change after device replacement. CONCLUSION: In the present study, a significant number of S-ICD® patients had a manual or automatic vector change during follow-up and after device replacement. The study underlines the importance of a thoroughly performed screening and at least two valuable sensing vectors preimplant. Further studies are needed to evaluate the necessity of a routine automatic setup during follow-up.

Sensitive Detection of Atrial Fibrillation in Acute Stroke Patients by Short-Term Bedside Electrocardiography Monitoring Software Analysis.

BACKGROUND: Atrial fibrillation (AF) is an important cause of stroke. Continuous electrocardiography (ECG) monitoring with software-based analysis algorithms has been suggested to enhance the AF detection rate. We investigated the ability of stroke risk analysis (SRA) in the detection of AF in acute stroke patients. METHODS: Consecutive stroke patients numbering 1,153 were screened. Patients with cardioembolic stroke related to AF (n = 296, paroxysmal n = 63, persistent n = 233) and patients with cryptogenic stroke (n = 309) after standard diagnostic work-up (bedside ECG monitoring, ultrasound, transesophageal echocardiography, 24 h Holter ECG) received SRA during their stay at the Stroke Unit. Determination of AF risk by SRA in the patients with AF and in the patient group with cryptogenic stroke was assessed and compared. RESULTS: Median SRA monitoring analysis time was 16 h (range 2-206 h, interquartile range 10-36). In AF patients, SRA also detected a possible or definitive AF in 98%. The overall sensitivity of SRA to detect possible or definitive AF in patients with proven AF by standard diagnostic work up and cryptogenic stroke was 98%, specificity 27%, positive predictive value 56%, and the negative predictive value (NPV) was 92%. Area under ROC curve was 0.622. CONCLUSION: SRA was found to be highly sensitive to detect possible or definitive AF in clinical routine within a short monitoring time. However, low specificity and poor accuracy do not allow diagnosing AF by SRA alone, but with the high NPV compared to current diagnostic standard, it is a valid diagnostic tool to rule out AF. Thereby, SRA is a contribution to clarify stroke etiology.

Broad antiarrhythmic effect of mexiletine in different arrhythmia models.

Aims: Experimental studies and clinical reports suggest antiarrhythmic properties of mexiletine in different arrhythmias. We aimed at investigating mexiletine in experimental models of atrial fibrillation (AF) as well as in long-QT- (LQTS) and short-QT-syndrome (SQTS). Methods and results: In 15 isolated rabbit hearts, erythromycin (300 µM) was infused for simulation of long-QT-2-syndrome. In further 13 hearts, veratridine was administered to simulate long-QT-3-syndrome. Both drugs induced a significant QT-prolongation (erythromycin: +87 ms, P < 0.01; veratridine: +19 ms, P < 0.05) and increased dispersion of repolarization (erythromycin: +55 ms, P < 0.01; veratridine +31 ms, P < 0.01). Additional infusion of mexiletine (25 µM) resulted in a significant reduction of dispersion (erythromycin: -43 ms, P < 0.01; veratridine: -26 ms, P < 0.05). Reproducible induction of torsade de pointes was observed in 13 of 15 erythromycin-treated hearts (192 episodes) and 6 of 13 veratridine-treated hearts (36 episodes). Additional infusion of mexiletine significantly reduced ventricular tachycardia (VT) incidence. With mexiletine, only 3 of 15 erythromycin-treated hearts (27 episodes) and 1 of 13 veratridine-treated hearts (2 episodes) presented polymorphic VT. In additional 9 hearts, the IK-ATP-channel-opener pinacidil was employed to simulate SQTS and significantly abbreviated ventricular repolarization (QT-interval: -18 ms, P < 0.05) and enhanced induction of ventricular fibrillation (VF). Mexiletine reversed the effects of pinacidil, increase refractory period (+127 ms, P < 0.01) and significantly suppressed induction of VF. In further 13 hearts AF was induced by combined treatment with acetylcholine/isoproterenol. Mexiletine also increased atrial refractory period (+80 ms, P < 0.01) and thereby effectively suppressed atrial fibrillation. Conclusion: Acute infusion of mexiletine significantly reduced the occurrence of polymorphic VT in the presence of pharmacologically simulated LQTS. Furthermore, mexiletine demonstrated potent antiarrhythmic properties in a model of SQTS and in AF.

Postoperative ergometry-guided programming does not prevent T-wave oversensing and inappropriate shocks in S-ICD patients.

BACKGROUND: T-wave oversensing (TWOS) is a feared complication after subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation, potentially leading to inappropriate shocks (IS) with tremendous impact on quality of life. HYPOTHESIS: Postoperative ergometry facilitates primary and secondary prevention of TWOS or other potential causes of IS and optimizes S-ICD programming. METHODS: We analyze the impact of ergometry guided-programming (EMGP) on primary and secondary prevention of TWOS/IS in S-ICD patients, we screened 146 patients implanted in our center (2010-2016) for the incidence of TWOS/IS during postoperative ergometry. Furthermore, to evaluate the outcome in 123 eligible patients complete follow-up (FU) of at least 6 months up to 2 years was retrospectively analyzed. RESULTS: (1) Primary prevention: TWOS could only be provoked postoperatively in 3.7% of patients (n = 3/82). FU analyses did not reveal significant differences compared to our control group (Ctrl: n = 6/61, 9.8% vs EMGP: n = 5/62, 8.1%; P = 0.731). Further subgroup analyses of patients with postoperative ergometry in the close postoperative period (< 7 days; n = 3/45, 6.7%; P = 0.563) did not yield any significant difference. (2) Secondary prevention: We found various causes of TWOS/IS. In patients who underwent reprogramming due to previous TWOS/IS events we observed a 66.7% (n = 6/9) reduction of TWOS/IS using EMGP. CONCLUSION: TWOS/IS has various causes while not all cases are exercise-associated. Postoperative ergometry does not seem to be useful for primary prevention. Further trials need to investigate the potential benefit of EMGP for secondary prevention of TWOS/IS.

Ranolazine Prevents Levosimendan-Induced Atrial Fibrillation.

OBJECTIVES: Levosimendan is a calcium sensitizer that is used as positive inotropic drug in acute decompensated heart failure. An increased incidence of atrial fibrillation after levosimendan-treatment was observed in clinical and experimental studies. Due to the limited range of antiarrhythmic drugs, the aim of the present study was to assess potential antiarrhythmic effects of ranolazine in levosimendan-pretreated isolated rabbit hearts. METHODS: Twelve rabbit hearts were excised and retrogradely perfused employing the Langendorff setup. Left and right atrial catheters were used to record monophasic action potentials and to obtain cycle length-dependent atrial action potential durations (aAPD90) and effective refractory periods (aERP). After obtaining baseline data, 0.5 µmol/L levosimendan was infused. Subsequently, 10 µmol/L ranolazine was administered. RESULTS: Infusion of levosimendan led to a reduction of aAPD90 (-9 ms, p < 0.05) and aERP (-13 ms, p < 0.05). Additional treatment with ranolazine prolonged aAPD90 (+23 ms, p < 0.01) and aERP (+30 ms, p < 0.05). Under baseline conditions, a predefined pacing protocol induced 77 episodes of atrial fibrillation. Infusion of levosimendan enhanced the vulnerability to atrial fibrillation (132 episodes, p = 0.14). Further treatment with ranolazine had a significant antiarrhythmic effect (61 episodes, p < 0.05). CONCLUSIONS: In this study, ranolazine seems to prevent atrial fibrillation in levosimendan-pretreated hearts. Underlying mechanism is a prolongation of atrial repolarization and aERP.

Antiarrhythmic effect of vernakalant in an experimental model of Long-QT-syndrome.

AIMS: The antiarrhythmic drug vernakalant exerts antiarrhythmic effects in atrial fibrillation. Recent experimental data suggest interactions with the late sodium current and antiarrhythmic effects in ventricular arrhythmias. We aimed at investigating whether treatment with vernakalant reduces polymorphic ventricular tachycardia (VT) in an experimental model of Long-QT-syndrome (LQTS). METHODS AND RESULTS: Twenty-nine isolated rabbit hearts were assigned to two groups and treated with erythromycin (300 µM, n = 15) or veratridine (0.5 µM, n = 14) after obtaining baseline data. Thereafter, vernakalant (10 µM) was additionally infused. Infusion of erythromycin or veratridine significantly increased action potential duration (APD90) and QT interval. Erythromycin and veratridine also significantly augmented spatial dispersion of repolarization (erythromycin: +43 ms; veratridine: +55 ms, P < 0.01, respectively) and temporal dispersion of repolarization. After lowering extracellular [K+] in bradycardic hearts, 11 of 15 erythromycin-treated hearts and 4 of 14 veratridine-treated hearts showed early afterdepolarizations and subsequent polymorphic VT. Additional treatment with vernakalant resulted in a significant reduction of spatial dispersion of spatial dispersion in both groups (erythromycin: -32 ms; veratridine: -35 ms, P < 0.05 each) and a stabilization of temporal dispersion. After additional treatment with vernakalant, only 5 of 15 erythromycin-treated hearts (P = 0.07) and 1 of 14 veratridine-treated hearts (P = 0.32) presented polymorphic VT. CONCLUSION: Vernakalant has antiarrhythmic effects in this experimental model of acquired LQTS. A reduction of spatial dispersion of repolarization and a stabilization of temporal dispersion in hearts showing polymorphic VT represent the major underlying electrophysiological mechanisms.

Supraventricular premature beats and short atrial runs predict atrial fibrillation in continuously monitored patients with cryptogenic stroke.

BACKGROUND AND PURPOSE: Supraventricular premature beats (SPBs) may help to assess the risk of atrial fibrillation (AF) in patients with cryptogenic stroke and therefore guide therapy. METHODS: An internal loop recorder was implanted in consecutive patients with acute cryptogenic stroke. The occurrence and quantity of SPBs and short supraventricular runs (SVRs) in 24-hour ECG in patients with and without future AF were analyzed. We evaluated the relative risk of the upper quartile of SPB and SVR patients against the remainder and used binary logistic regression to evaluate a possible independent influence of SPBs and SVRs on AF occurrence. RESULTS: Twelve of 70 included patients (mean age, 59±13 years) experienced development of AF during a mean monitoring duration of 536±212 days. Patients with AF had a median of 22.8 SPBs/h versus 1.2 SPBs/h (P<0.0001) in patients without AF and a median of 0.7 SVRs/h (AF) versus 0 SVR/h (non-AF). Patients in the upper quartile of SPBs (>14.1/h) and SVRs (>0.2/h) demonstrated a relative risk of 4.0 (95% confidence interval, 1.1-14.6; P=0.04) and 6.9 (95% confidence interval, 1.8-26.7; P=0.005) for future AF, respectively. In binary logistic regression, SPBs (P=0.02) and SVRs (P=0.05) remained significant independent predictors for occurrence of AF. CONCLUSIONS: Numerous SPBs and SVRs demonstrated a high risk for future AF in patients with cryptogenic stroke.

Vernakalant in an experimental model of pacing-induced heart failure: lack of proarrhythmia despite prolongation of repolarization.

BACKGROUND: The present ESC guidelines on atrial fibrillation have introduced vernakalant (VER) for pharmacologic cardioversion of atrial fibrillation. The aim of the present study was to investigate possible proarrhythmic effects of vernakalant in an experimental model of heart failure (HF). METHODS AND RESULTS: In 12 female rabbits, HF was induced with the use of 4 weeks of rapid ventricular pacing. Twelve rabbits were sham operated. Isolated hearts demonstrated a significant prolongation of myocardial repolarization after induction of HF. Vernakalant caused a concentration-dependent (10 µmol/L and 30 µmol/L) increase of action potential duration (APD90) and QT interval without affecting spatial and temporal dispersion of repolarization. The increase in APD90 was accompanied by a greater increase in refractory period resulting in a significant increase in post-repolarization refractoriness. In control conditions, programmed ventricular stimulation and burst pacing led to ventricular fibrillation (VF) in 2 of the 12 sham (4 episodes) and in 3 of the 12 HF (24 episodes) subjects. In the presence of 30 µmol/L vernakalant, VF was no longer inducible in both groups (0 episodes). In the presence of low K+ concentration, neither sham nor HF vernakalant-treated subjects developed early after-depolarizations or ventricular tachyarrhythmias. CONCLUSION: In the present study, application of vernakalant led to a significant prolongation of myocardial repolarization and increased post-repolarization refractoriness but did not induce early after-depolarization and therefore did not cause proarrhythmia in failing hearts.

Mortality and rehospitalization in patients with pre-existing implantable pacemakers undergoing catheter ablation are related to increased comorbidity burden-data from the German Ablation Registry.

BACKGROUND: Catheter ablation of atrial fibrillation and atrial flutter is routinely performed in patients with implantable devices. The aim of the present study was to assess success rates and potential complications in a large registry cohort of patients with cardiac pacemakers. METHODS AND RESULTS: The German Ablation Registry is a nationwide, prospective registry with a 1-year follow-up investigating patients who underwent catheter ablation of supraventricular arrhythmias in 51 German centers. The present analysis focussed on the presence of cardiac pacemakers in 591 patients undergoing catheter ablation of atrial fibrillation or atrial flutter. These were compared to 7393 patients without a pacemaker. Patients with pacemakers were significantly older and presented more comorbidities like diabetes, renal failure, cardiovascular disease, or previous stroke. One-year mortality (2.4% vs. 1.3%, p = 0.022) and a combined endpoint of death, myocardial infarction, and stroke (3.6% vs. 2.1%, p = 0.014) were significantly elevated in patients with pacemakers. Re-hospitalization was also more common in patients with a pacemaker (53.3% vs. 45.0%, p < 0.01). After adjustment for important comorbidities, pre-existing pacemaker systems did not show any negative effect. Procedural success was reported in 98.8% vs. 98.4% (p = 0.93). Device-related complications were only observed in 0.4% of patients with pacemakers. CONCLUSION: Patients with pacemaker systems undergoing catheter ablation of atrial fibrillation or atrial flutter demonstrate an increased risk of death, cardiovascular events, and re-hospitalization. This observation can be largely attributed to an older patient population and an increased rate of comorbidities.

Use of class IC antiarrhythmic drugs in patients with structural heart disease and implantable cardioverter defibrillator.

BACKGROUND: Due to suspected pro-arrhythmic effects and increased mortality associated with class-IC antiarrhythmic drugs (AADs) in previous trials, AAD therapy in structural heart disease (SHD) is mainly restricted to amiodarone. In the presence of diagnostic and therapeutic advancements in cardiovascular medicine, it remains unclear if previous studies adequately reflect contemporary patients. In clinical practice, class-IC-AADs are occasionally used in individual cases, particularly in patients with an implantable cardioverter defibrillator (ICD). METHODS: This study retrospectively investigated outcome in ICD-carriers with SHD in whom class-IC-AADs were used as an individualized therapy due to failure, side effects, or unacceptable risk of alternative therapeutic options. RESULTS: Fifty patients from four tertiary centers were included (median age 48.5 years; 52% female). The most common underlying SHD were dilated (42%) or ischemic cardiomyopathy (26%) (median LVEF = 45%). Indications for AAD were sustained ventricular arrhythmias (VA) (58%), symptomatic premature ventricular contractions (26%), or atrial arrhythmias (16%). Median follow-up was 27.8 months. Freedom from sustained VA was 72%, and freedom from ICD therapy was 80%. In 19 patients (38%), AAD therapy was terminated. The most common reason was insufficient efficacy (n = 8). Pro-arrhythmia was suspected in three patients. Five patients died during follow-up (10.0%), two of cardiovascular cause (4.0%). CONCLUSION: In a multicenter cohort of ICD-carriers with SHD, class-IC-AADs were associated with a low rate of pro-arrhythmic effects or cardiovascular mortality. The majority of patients remained free from sustained VA during a follow-up of > 2 years. Further efforts should be made to evaluate the safety of class-IC-AADs in SHD patients receiving contemporary cardiovascular therapy.

Validation of the PRAETORIAN score in a large subcutaneous implantable cardioverter-defibrillator collective: Usefulness in clinical routine.

BACKGROUND: To assess the risk of unsuccessful conversion of ventricular fibrillation during defibrillation testing (DFT) with the subcutaneous implantable cardioverter-defibrillator (S-ICD), the PRAETORIAN score has been proposed. OBJECTIVE: The purpose of this study was to validate the PRAETORIAN score in a large S-ICD collective. METHODS: A retrospective single-center analysis of S-ICD patients receiving intraoperative DFT was performed. DFT was performed using a stepwise protocol with 65-J standard polarity, change of polarity, increase to 80 J, and repositioning if necessary. If all DFTs failed, we switched to a transvenous ICD. RESULTS: Overall, 398 patients were analyzed (268 male [67.3%]; mean age 42.4 ± 15.9 years; mean body mass index [BMI] 25.9 ± 4.8 kg/m2). Successful DFT with the first ICD shock was observed in 264 patients (66.3%). One hundred fourteen patients were defibrillated with the second (n = 104) or third (n = 10) DFT after changing shock polarity and/or shock energy. Overall, 20 patients needed at least 3 DFT (ie, 80 J and/or re-positioning). The majority (n = 88 [65.7%]) of DFT failures occurred before 2015 with the first-generation S-ICD. PRAETORIAN score was an independent predictor of DFT failure (odds ratio [OR] 1.007; 95% confidence interval [CI] 1.003-1.011 P ≤.001), while whereas BMI alone was not (P = .31). Presence of hypertrophic cardiomyopathy (HCM) (OR 2.6; 95% CI 1.3-4.4; P = .004) was predictive for at least 1 unsuccessful DFT in our multivariate regression analysis. CONCLUSION: PRAETORIAN score proved to be a useful and valid predictive tool for successful DFT, whereas BMI only had a limited role. Patients with HCM were at increased risk for DFT failure or needed higher DFT energy.

Relevance of mexiletine in the era of evolving antiarrhythmic therapy of ventricular arrhythmias.

Despite impressive developments in the field of ventricular arrhythmias, there is still a relevant number of patients with ventricular arrhythmias who require antiarrhythmic drug therapy and may, e.g., in otherwise drug and/or ablation refractory situations, benefit from agents known for decades, such as mexiletine. Through its capability of blocking fast sodium channels in cardiomyocytes, it has played a minor to moderate antiarrhythmic role throughout the recent decades. Nevertheless, certain patients with structural heart disease suffering from drug-refractory, i.e., mainly amiodarone refractory ventricular arrhythmias, as well as those with selected forms of congenital long QT syndrome (LQTS) may nowadays still benefit from mexiletine. Here, we outline mexiletine's cellular and clinical electrophysiological properties. In addition, the application of mexiletine may be accompanied by various potential side effects, e.g., nausea and tremor, and is limited by several drug-drug interactions. Thus, we shed light on the current therapeutic role of mexiletine for therapy of ventricular arrhythmias and discuss clinically relevant aspects of its indications based on current evidence.