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BACKGROUND Previous studies have raised serious concerns on cardiovascular safety of widely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, the aim of this study was to characterize the electrophysiological effects of certain NSAIDs in an established whole heart model of proarrhythmia. METHODS AND RESULTS Thirty-eight hearts of New Zealand White rabbits were harvested and retrogradely perfused employing a Langendorff setup, and electrophysiology studies were performed to investigate action potential duration at 90% of repolarization (APD90 ), QT intervals, and effective refractory period (ERP). After generating baseline data, hearts were perfused with ibuprofen (Group 1, n = 12; 10 and 30 μM), indomethacin (Group 2, n = 13; 10 and 20 μM) and diclofenac (Group 3, n = 13; 10 and 20 μM), respectively, and the pacing protocols were repeated for each concentration. In all groups, perfusion with the NSAIDs resulted in a significant and reproducible shortening of APD90 and QT interval. In all groups, the arrhythmia susceptibility was significantly raised as occurrence of monomorphic ventricular tachycardia under programmed ventricular stimulation was significantly increased under perfusion with ibuprofen, indomethacin and diclofenac in all concentrations. CONCLUSION The perfusion with ibuprofen, indomethacin and diclofenac in commonly used doses raised the arrhythmia susceptibility in an established rabbit whole-heart model while APD shortening and shortened ERP seem to be crucial for arrhythmogenesis.

The aim of this study is to evaluate retinal and optic nerve head (ONH) perfusion in patients with systolic chronic heart failure (CHF) compared to healthy control subjects. Twenty-seven eyes of 27 patients with CHF (study group) and 31 eyes of 31 healthy subjects (control group) were prospectively included in this study. CHF Patients had a left ventricular ejection fraction (LVEF)

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.

Introduction Supraventricular tachycardias (SVT) are often difficult to document due to their intermittent, short-lasting nature. Smartphone-based one-lead ECG monitors (sECG) were initially developed for the diagnosis of atrial fibrillation. No data have been published regarding their potential role in differentiating inappropiate sinus tachycardia (IST) from regular SVT. If cardiologists could distinguish IST from SVT in sECG, economic health care burden might be significantly reduced. Methods We prospectively recruited 75 consecutive patients with known SVT undergoing an EP study. In all patients, four ECG were recorded: a sECG during SVT and during sinus tachycardia and respective 12-lead ECG. Two experienced electrophysiologists were blinded to the diagnoses and separately evaluated all ECG. Results Three hundred individual ECG were recorded in 75 patients (47 female, age 50 ± 18 years, BMI 26 ± 5 kg/m2, 60 AVNRT, 15 AVRT). The electrophysiologists’ blinded interpretation of sECG recordings showed a sensitivity of 89% and a specificity of 91% for the detection of SVT (interobserver agreement κ = 0.76). In high-quality sECG recordings (68%), sensitivity rose to 95% with a specificity of 92% (interobserver agreement of κ = 0.91). Specificity increased to 96% when both electrophysiologists agreed on the diagnosis. Respective 12-lead ECG had a sensitivity of 100% and specificity of 98% for the detection of SVT. Conclusion A smartphone-based one-lead ECG monitor allows for differentiation of SVT from IST in about 90% of cases. These results should encourage cardiologists to integrate wearables into clinical practice, possibly reducing time to definitive diagnosis of an arrhythmia and unnecessary EP procedures. Graphical abstract A smartphone-based one lead ECG device (panel A) can be used reliably to differentiate supraventricular tachycardia (panel B) from inappropriate sinus tachycardia when compared to a simultaneously conducted gold-standard electrophysiology study (panels C, D).

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by noncaseating granulomas. Cardiac involvement is often limiting patients' prognosis. Cardiac sarcoidosis can manifest with variant cardiac arrhythmias, of which atrioventricular (AV)-block-related bradycardia and ventricular tachycardias are the most common. Although cardiac sarcoidosis remains a histopathological diagnosis, the significance of imaging modalities, especially cardiac magnetic resonance imaging is increasing rapidly but mainly remains reserved for patients with a high suspicion due to a previous arrhythmia or unknown cardiomyopathy. Thus, there is a need for screening in daily clinical practice so that possible characteristic electrocardiographic (ECG) findings may guide the way to detect the disease. We therefore evaluated the ECG as a potential tool for screening of cardiac sarcoidosis and present different electrophysiological manifestations of cardiac sarcoidosis based on a literature review. The ECG is a valuable tool for screening of cardiac involvement in patients with sarcoidosis. Several parameters have been shown to be associated with cardiac involvement in sarcoidosis such as higher-degree AV-block, QRS complex fragmentation and widening, as well as certain T wave abnormalities that may indicate cardiac involvement, of which the latter two are most promising and specific. However, prospective studies examining a large number of trials are desirable.

Atrioventricular nodal reentry tachycardia (AVNRT) is the most common regular supraventricular tachycardia (SVT). Slow pathway modification (SPM) is the accepted first line treatment with reported success rates around 95%. Information regarding possible predictors of AVNRT recurrence is scarce.Out of 4170 consecutive patients with SPM in our department from 1993-2018, we identified 78 patients (1.9%) receiving > 1 SPM (69% female, median age 50 years) with a recurrence of AVNRT after a successful SPM. We matched these patients for age, gender and number of radiofrequency applications during first SPM with 78 patients who received one successful SPM in our center without AVNRT recurrence. Both groups were analyzed for possible predictors of a recurrence of AVNRT during long-term follow-up. The recurrence group contained a significantly lower proportion of patients with an occurrence of junctional beats during SPM (69% versus 89%, P = 0.006). Moreover, significantly more cases of previously diagnosed atrial fibrillation/tachycardia (AF/AT; 21% versus 5%, P = 0.007) and inducible AF/AT during electrophysiology study (23% versus 6%, P = 0.006) were present in the recurrence group. While more than half of patients had a recurrence within the first year, in 20% symptoms reappeared ≥ 4 years after ablation.In a small percentage of patients, AVNRT recurs after an initially successful ablation. Interestingly, these patients had significantly fewer junctional beats during ablation and a higher rate of other (inducible) arrhythmias. AVNRT recurrence spanned a considerable timeframe and should remain a differential diagnosis, even years after ablation.

Background The benefits of de novo cardiac resynchronization therapy (CRT) in patients with QRS-prolongation and impaired left-ventricular function (LVEF) are well established. Current guidelines also recommend CRT-upgrade in patients requiring permanent or frequent right ventricular pacing (RVP) with symptomatic heart failure and reduced LVEF. Whereas several predictors of response to de novo CRT-implantation such as female gender, QRS-duration, non-ischemic cardiomyopathy (NICM) are known due to large prospective trials, similar factors regarding CRT-upgrade are currently lacking. Methods and results We examine 114 patients 3–6 months after CRT-upgrade due to frequent RVP (> 50%) and symptomatic heart failure. Response to CRT was evaluated by improvement in NYHA class referring to the Minnesota Living With Heart Failure Questionnaire. Only cardiomyopathy type and use of Angiotensin-converting-enzyme (ACE) inhibitor had an impact on response to CRT-upgrade in a linear regression model. Patients with NICM presented a greater responder rate than patients with ischemic cardiomyopathy (ICM) (80.4 vs. 60.3%, p Conclusion Only underlying heart disease (NICM vs. ICM) and the use of ACE inhibitor were significant predictors of response to CRT-upgrade. In contrast to de novo CRT-recipients, where pre-implant QRS-duration is a key predictor, QRS-duration during RV-pacing has no significant impact on CRT-response in this cohort. Graphic abstract

Aim The subcutaneous ICD (S-ICD) has evolved to a potential first option for many patients who have to be protected from sudden cardiac death. Many trials have underlined a similar performance regarding its effectiveness in relation to transvenous ICDs and have shown the expected benefits concerning infective endocarditis and lead failure. However, there have also been problems due to the peculiarities of the device, such as oversensing and myopotentials. In this study, we present patients from a large tertiary centre suffering from complications with an S-ICD and propose possible solutions. Methods and results All S-ICD patients who experienced complications related to the device (n = 40) of our large-scale single-centre S-ICD registry (n = 351 patients) were included in this study. Baseline characteristics, complications occurring and solutions to these problems were documented over a mean follow-up of 50 months. In most cases (n = 23), patients suffered from oversensing (18 cases with T wave or P wave oversensing, 5 due to myopotentials). Re-programming successfully prevented further oversensing episode in 13/23 patients. In 9 patients, generator or lead-related complications, mostly due to infectious reasons (5/9), occurred. Further problems consisted of ineffective shocks in one patient and need for antibradycardia stimulation in 2 patients and indication for CRT in 2 other patients. In total, the S-ICD had to be extracted in 10 patients. 7 of them received a tv-ICD subsequently, 3 patients refused re-implantation of any ICD. One other patient kept the ICD but had antitachycardic therapy deactivated due to inappropriate shocks for myopotential oversensing. Conclusion The S-ICD is a valuable option for many patients for the prevention of sudden cardiac death. Nonetheless, certain problems are immanent to the S-ICD (limited re-programming options, size of the generator) and should be addressed in future generations of the S-ICD. Graphic abstract

Several case reports suggest QT prolongation leading to ventricular arrhythmias with fatal outcome after intoxication with the μ-opioid receptor agonist and anti-diarrheal agent loperamide. The number of cases of loperamide misuse are growing due to its potential stimulating effects. Loperamide intoxications can be treated by naloxone. However, previous reports described a further QT prolongation associated with naloxone administration. Therefore, the aim of this study was to investigate the effects of loperamide and naloxone on the cardiac electrophysiology in a sensitive whole-heart model. Twenty-six hearts of New Zealand White rabbits were retrogradely perfused in a modified Langendorff apparatus. Monophasic action potentials were recorded by endo- and epicardially positioned catheters. Hearts were stimulated at different cycle lengths, thereby obtaining action potential duration at 90% of repolarization (APD90) and QT intervals. Programmed ventricular stimulation was used to assess ventricular vulnerability. Fourteen hearts were perfused with ascending concentrations of loperamide (0.2 μM, 0.35 μM, and 0.5 μM) after obtaining baseline data. Another 12 hearts were treated with naloxone (0.1 μM, 0.5 μM, 2 μM). Loperamide led to a significant increase in QT interval, APD90, and ventricular tachycardia (VT) episodes. In contrast, naloxone led to a decrease in QT interval and APD90. Accordingly, the number of VT episodes was unaltered. To the best of our knowledge, this is the first experimental study that investigated the effects of loperamide and naloxone in a whole-heart model. Loperamide led to a significant increase in action potential duration and QT interval. Simultaneously, the number of ventricular tachycardias was significantly increased. In contrast, naloxone led to a shortening of the action potential duration without altering arrhythmia susceptibility.

Background The right bundle branch block (RBBB) and the bifascicular blocks affect QRS duration in the right precordial leads, which are usually used for QT interval determination. Up to now, there is no clear recommendation how to determine QT interval in patients with RBBB or bifascicular block. Hypothesis The hypothesis of the present study was to evaluate the feasibility of a simple formula for RBBB and bifascicular block correction, thereby making it easier to determine the QTc interval. Methods In patients with intrinsic QRS duration

Background The subcutaneous implantable-cardioverter defibrillator (S-ICD™, Boston Scientific, Natick, MA, USA) is an important advance in device therapy for the prevention of sudden cardiac death (SCD). Although current guidelines recommend S-ICD™ use, long-term data are still limited, especially in subgroups. Dilated cardiomyopathy (DCM) is a common reason for the implantation of an ICD. However, there are no sufficient data on the performance of the S-ICD™ in this patient cohort. Materials and methods All S-ICD™ patients with DCM as the main indication for ICD implantation (n = 47 patients) in our large-scaled single-center S-ICD™ registry (n = 294 patients) were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 22.9 ± 18.5 months. Results A total of 47 patients with DCM as the underlying structural heart disease received an S-ICD™ in our institution. Mean left ventricular ejection fraction was 37 ± 12% and a 28% had a history of ventricular tachyarrhythmia. During follow-up eight ventricular tachyarrhythmias were adequately terminated in three patients. In four patients, oversensing resulting in an inappropriate shock was observed, which could be managed by changing the sensing vector. There was no need for a change to a cardiac resynchronization (CRT) system while one system was changed to a VVI-ICD due to S-ICD™ wound infection. Conclusion The S-ICD™ seems to be a valuable option for the prevention of SCD in patients with DCM and no indication for CRT. As clinically relevant ventricular arrhythmias consisted of ventricular fibrillation or fast ventricular tachycardia in all patients in our cohort, no change to transvenous ICDs for anti-tachycardia pacing delivery was necessary.

In patients with high risk for sudden cardiac death the implantation of a defibrillator is an established treatment. However the benefits and risks for patients in accordance to the number of the leads are not clear. Even in the current guidelines a recommendation to this question is missing. We analyzed advantage and disadvantages of single-chamber implantable cardioverter defibrillators (VVI-ICD) versus dual-chamber implantable cardioverter defibrillators (DDD-ICD) in the prospective German Device Registry. The data of 2240 patients who underwent ICD implantation in 45 German Centers between January 2007 and March 2011 were included in a prospective device registry (VVI: n = 1629, male = 1358, EF = 34% ± 13%; DDD: n = 611, male = 491, EF = 35% ± 14%). The in-hospital complications were significantly higher in the DDD-ICD group with higher revision/device complication rates (3.0% vs. 1.2%; p = 0.003) but also higher mortality rate (1.0% vs. 0.1%; p

Aims: Thromboembolic events, including stroke, are typical complications of COVID-19. Whether arrhythmias, frequently described in severe COVID-19, are disease-specific and thus promote strokes is unclear. We investigated the occurrence of arrhythmias and stroke during rhythm monitoring in critically ill patients with COVID-19, compared with severe pneumonia of other origins.Methods and Results: This retrospective study included 120 critically ill patients requiring mechanical ventilation in three European tertiary hospitals, including n =60 COVID-19, matched according to risk factors for the occurrence of arrhythmias in n = 60 patients from a retrospective consecutive cohort of severe pneumonia of other origins. Arrhythmias, mainly atrial fibrillation (AF), were frequent in COVID-19. However, when compared with non-COVID-19, no difference was observed with respect to ventricular tachycardias (VT) and relevant bradyarrhythmias (VT 10.0 vs. 8.4 %, p = ns and asystole 5.0 vs. 3.3%, p = ns) with consequent similar rates of cardiopulmonary resuscitation (6.7 vs. 10.0%, p = ns). AF was even more common in non-COVID-19 (AF 18.3 vs. 43.3%, p = 0.003; newly onset AF 10.0 vs. 30.0%, p = 0.006), which resulted in a higher need for electrical cardioversion (6.7 vs. 20.0%, p = 0.029). Despite these findings and comparable rates of therapeutic anticoagulation (TAC), the incidence of stroke was higher in COVID-19 (6.7.% vs. 0.0, p = 0.042). These events also happened in the absence of AF (50%) and with TAC (50%).Conclusions: Arrhythmias were common in severe COVID-19, consisting mainly of AF, yet less frequent than in matched pneumonia of other origins. A contrasting higher incidence of stroke independent of arrhythmias also observed with TAC, seems to be an arrhythmia-unrelated disease-specific feature of COVID-19.

Background: Different electrocardiogram (ECG) findings are known to be independent predictors of clinical response to cardiac resynchronization therapy (CRT). It remains unknown how these findings influence very long-term prognosis. Methods and Results: A total of 102 consecutive patients (75 males, mean age 65 ± 10 years) referred to our center for CRT implantation had previously been included in this prospective observational study. The same patient group was now re-evaluated for death from all causes over a prolonged median follow-up of 10.3 years (interquartile range 9.4–12.5 years). During follow-up, 55 patients died, and 82% of the clinical non-responders (n = 23) and 44% of the responders (n = 79) were deceased. We screened for univariate associations and found QRS width during biventricular (BIV) pacing (p = 0.02), left ventricular (LV) pacing (p &lt, 0.01), Δ LV paced–right ventricular (RV) paced (p = 0.03), age (p = 0.03), New York Heart Association (NYHA) class (p &lt, 0.01), CHA2DS2-Vasc score (p &lt, 0.01), glomerular filtration rate (p &lt, 0.01), coronary artery disease (p &lt, 0.01), non-ischemic cardiomyopathy (NICM) (p = 0.01), arterial hypertension (p &lt, 0.01), NT-proBNP (p &lt, 0.01), and clinical response to CRT (p &lt, 0.01) to be significantly associated with mortality. In the multivariate analysis, NICM, the lower NYHA class, and smaller QRS width during BIV pacing were independent predictors of better outcomes. Conclusion: Our data show that QRS width duration during biventricular pacing, an ECG parameter easily obtainable during LV lead placement, is an independent predictor of mortality in a long-term follow-up. Our data add further evidence that NICM and lower NYHA class are independent predictors for better outcome after CRT implantation.

Background: The subcutaneous ICD (S-ICD) is used in an increasing number of patients for primary and secondary prevention of sudden cardiac death. Decision-making in primary prevention is not always trivial and many clinical scenarios are not reflected in current ICD guidelines. To help evaluating the patient’s individual risk, a new score trying to predict the benefit of an ICD implantation for primary prevention, the MADIT-ICD benefit score, which tries to predict occurrence of ventricular arrhythmias and non-arrhythmic death, has been proposed. We therefore aimed at examining its usefulness in a large single centre register of S-ICD patients Methods and results: All S-ICD patients with a primary preventive indication for ICD implantation from our large single centre database were included in the analysis (n=173). During a follow-up of 1227±978 days 27 patients developed sustained ventricular arrhythmias, while 6 patients died for non-arrhythmic reasons. Occurrence of ventricular arrhythmias could not sufficiently be predicted by the MADIT-ICD VT/VF score (p=0.3) in patients with (n=142, p=0.19) as well as patients without structural heart disease (n=31, p=0.88). However, there was a significant correlation for patients with ischemic cardiomyopathy (ICM) (n=29, p=0.04). Only one parameter (non-sustained ventricular tachycardia) was significantly associated with sustained ventricular arrhythmias (p=0.02). Of note, non-arrhythmic death could effectively be predicted by the proposed non-arrhythmic mortality score as part of the benefit score (p=0.001, r=0.3) also mainly driven by ICM patients. Age, diabetes mellitus, and a BMI 2 were key predictors of non-arrhythmic death implemented in the score.Conclusion: The MADIT-ICD benefit score adds a new option to evaluate expected benefit of ICD implantation for primary prevention. However, in our S-ICD cohort, the only group in which the score worked properly for prediction of sudden and non-sudden death were ICM patients, so that a larger validation in more heterogeneous cohorts in mandatory to claim general validity for this score in risk stratification for primary preventive ICD implantation.

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 subcutaneous ICD (S-ICD™) is an important advance in device therapy for the prevention of sudden cardiac death (SCD). Although current guidelines recommend S-ICD™ use, long-term data are still limited, especially in subgroups. Among several cardiac diseases that prone to SCD, coronary artery disease (CAD) carries several peculiarities that may hamper S-ICD™ therapy in this cohort. CAD can lead to an ischemic cardiomyopathy (ICM) with a reduced left-ventricular ejection fraction (LVEF) and bundle branch blocks, which can be difficult for ICD sensing and discrimination of arrhythmia. CAD is mainly driven by risk factors such as diabetes mellitus, which put these patients at an elevated risk for infectious complications of cardiac devices. Furthermore, in ICM myocardial scars are frequent and are a potential substrate for ventricular tachycardia, which may be accessible for antitachycardia pacing. At the moment, it remains unclear if there is a value of S-ICD™ therapy in this subgroup. Therefore, this study analysed patients with CAD. All S-ICD™ patients with CAD as the main indication for ICD implantation (n = 45 patients) in our large-scaled single-center S-ICD™ 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 22.5 ± 8.3 months. Primary prevention of SCD was the indication for implantation of an S-ICD™ in 28 patients (62%). Of all 45 patients with an overall mean age of 58.1 ± 11.4 years, 40 were male (88%). The mean LVEF was 37.7 ± 12.6%. Three episodes of ventricular arrhythmia (one monomorphic, one polymorphic, one ventricular fibrillation) were adequately terminated in three patients (7%). In only one patient, oversensing resulting in an inappropriate shock was observed, which could be managed by changing the sensing vector. 15 of the examined 45 patients previously had a transvenous ICD, which was explanted due to system-related infections. In only two patients, S-ICD™ was changed to transvenous ICD because of the need of antibradycardia stimulation. There were no S-ICD™ system-related infections. The S-ICD™ seems to be a valuable option for the prevention of SCD in CAD patients. Patients with systemic infections of a transvenous ICD and, therefore, a need for an alternative might benefit from the absence of intracardiac leads as the S-ICD™ is safe and works flawlessly in these patients. Inadequate shock delivery was very rare, while every episode of ventricular arrhythmia was terminated by the first shock.

A post hoc analysis of the PALLAS trial suggested life-threatening interactions of digitalis and dronedarone. Thus, there is concern about an interplay between digitalis and other drugs that influence cardiac electrophysiology. We therefore investigated the interaction between digitalis and flecainide or ranolazine. Twenty-five rabbit hearts were Langendorff-perfused and treated with flecainide (2 µM, 12 hearts) or ranolazine (10 µM, 13 hearts). Infusion of flecainide prolonged mean action potential duration [APD90, from 153 ms (interquartile range (IQR): 29.7 ms) to 159 ms (IQR: 24.9 ms, p = 0.04)] and effective refractory period [ERP, 170 ms (IQR: 40 ms) vs. 200 ms (IQR: 32.5 ms, p

Background Metoclopramide (MCP) is a dopamine D2 -receptor antagonist, mainly used to treat post-operative or chemotherapy-induced nausea. While it is very effective in the cure of gastric symptoms, MCP can cause severe neurologic side effects. Furthermore, there is growing evidence for severe arrhythmic side effects resulting from inhibitory effects on cardiac sodium and potassium channels. Methods and results Thirteen hearts of New Zealand white rabbits were retrogradely perfused, and electrophysiology studies were performed to obtain action potential duration (APD90 ) and effective refractory period (ERP). After generating baseline data, the hearts were perfused with increasing concentrations of metoclopramide (MCP 10 µM, MCP 50 µM, MCP 100 µM) and the standardized protocol was repeated for each concentration. Perfusion with MCP resulted in a significant prolongation of APD90 and QT interval. In parallel, the incidence of ventricular tachycardias was significantly increased by high doses of MCP. Conclusion This is the first experimental study that investigated the effect of increasing doses of metoclopramide on a sensitive whole-heart model of proarrhythmia. MCP led to a significant increase in action potential duration and QT interval; meanwhile, the number of ventricular tachycardias was significantly increased.

Background Previous studies report conflicting data regarding anti- or proarrhythmic effects of sacubitril. The aim of the presents study was to assess the impact of sacubitril in different arrhythmia models. Methods and results In 12 isolated rabbit hearts, sacubitril was infused in rising concentrations (3, 5, 10μM) after obtaining baseline data. In 12 further hearts, erythromycin was administered to simulate long QT syndrome-2 (LQT2). Other 12 hearts were perfused with veratridine to mimic long QT syndrome-3 (LQT3). Both LQT groups were treated with sacubitril (5μM). Ventricular vulnerability was assessed by a pacing protocol. AV-blocked bradycardic hearts were perfused with a hypokalemic solution to trigger torsade de pointes (TdP). In further 13 hearts, AF was induced by a combination of acetylcholine and isoproterenol (ACH/ISO) and sacubitril (5μM) was added afterwards. With sacubitril, action potential duration (APD) was abbreviated whereas spatial dispersion of repolarization (SDR) remained stable. In both LQT groups, APD and SDR were increased. Infusion of sacubitril reduced APD and SDR in the LQT2-group (APD: −21 ms, p Conclusion Sacubitril abbreviated APD and was not proarrhythmic. SDR is a major pathomechanism of TdP and was reduced by sacubitril in both LQT groups. Thereby, sacubitril exhibits antiarrhythmic effects in LQT2 and may be beneficial in LQT3. Furthermore, sacubitril suppressed AF by prolonging aERP. Our results indicate beneficial effects of sacubitril on cardiac electrophysiology. Funding Acknowledgement Type of funding source: None

Background Dexmedetomidine is increasingly employed for conscious sedation during electrophysiological procedures. Recent experimental data have suggested direct effects of dexmedetomidine on cardiac electrophysiology. The aim of the present study was to assess the effects of dexmedetomidin on drug-induced QT-prolongation. Methods and results In 12 isolated rabbit hearts the macrolide antibiotic erythromycin (300μM) was infused as a potent Ikr blocker after obtaining baseline data. Eight endo- and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG showed a significant prolongation of QT-interval (+25ms, p Lowering of potassium concentration in bradycardic AV-blocked hearts resulted in the occurrence of early afterdepolarizations (EAD) and drug induced proarrhythmia with torsade de pointes in 6 of 12 erythromycin-treated hearts (40 episodes). Additional infusion of dexmedetomidine reduced the occurrence of torsade de pointes (4 of 12 hearts, 9 episodes). Conclusion Infusion of dexmedetomidine resulted in a reduction of spatial dispersion of repolarization in the presence of a prolonged repolarization period. This resulted in a reduction of torsade de pointes with dexmedetomidine. Furthermore, an increase of ventricular refractory periods reduced inducibility of ventricular arrhythmias. Thus, in an experimental setting dexmedetomidine shows significant antiarrhythmic effects, which may influence electrophysiologic findings during clinical electrophysiologic studies. This needs to be studied in the clinical setting. Funding Acknowledgement Type of funding source: None

Proper measurement of the QT interval on the 12-lead body-surface ECG is challenging in daily practice. Even more difficult is its correct estimation in the presence of repolarization abnormalities, arrhythmias or bundle-branch blocks (BBB). The QT interval results from two parts of the ECG: (1) the QRS complex, describing the excitation of the ventricles and (2) the JT interval, describing the repolarisation of the ventricles. Prolongation of the QRS width - like in the presence of BBB - entails prolongation of the QT interval, making the estimation of the true repolarisation time challenging. The US recommendations for the standardization and interpretation of the ECG suggest focusing on the JT interval in presence of BBB. However, in clinical practice physicians have become more familiar with the interpretation of QT-interval measurements than with the interpretation of the JT Interval. In the last decade, a simple formula for the estimation of the "modified QT interval" in the presence of left or right BBB has been developed and evaluated. In this formula, the modified QT interval is calculated by subtracting 50% of the length of the BBB-QRS from the measured QT interval (QT(m) = QT(BBB) - 50% QRS(BBB)). Subsequently, rate-correction formula should be applied as usual. In this review, we discuss the determination of the QT-interval in the presence of BBB and summarize the origin and application of the modified QT-interval formula. (C) 2020 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

The aim of this study was to investigate the effects of a combination of ranolazine with different selective inhibitors of the Na+/Ca2+-exchanger (NCX) in an established experimental model of atrial fibrillation (AF). Eighteen hearts of New Zealand white rabbits were retrogradely perfused. Atrial catheters were used to record monophasic action potentials (aPRR). Hearts were paced at three different cycle lengths. Thereby, atrial action potential durations (aAPD90), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness were obtained. Isoproterenol and acetylcholine were employed to increase the occurrence of AF. Thereafter, the hearts were assigned to two groups (n = 9 each group) and additionally perfused with a combination of 10 &micro, M ranolazine and 1 &micro, M of the selective NCX-inhibitor ORM-10103 (group A: Rano-ORM) or 10 &micro, M of another NCX-inhibitor, SEA0400 (group B: Rano-SEA). The infusion of Iso/ACh led to a shortening of aAPD90, aERP, aPRR and the occurrence of AF episodes was significantly increased. Additional perfusion with ranolazine and ORM-10103 (group A) significantly prolonged the refractory periods and aPRR and AF episodes were effectively reduced. In group B, Rano-SEA led to a slight decrease in aAPD90 while aERP and aPRR were prolonged. The occurrence of AF episodes was consecutively reduced. To our knowledge, this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Both combinations prolonged aERP and aPRR and thereby suppressed the induction of AF.

Plenty of non-cardiovascular drugs alter cardiac electrophysiology and may ultimately lead to life-threatening arrhythmias. In clinical practice, measuring the QT interval as a marker for the repolarization period is the most common tool to assess the electrophysiologic safety of drugs. However, the sole measurement of the QT interval may be insufficient to determine the proarrhythmic risk of non-cardiovascular agents. Several other markers are considered in pre-clinical safety testing to determine potential harm on cardiac electrophysiology. Besides measuring typical electrophysiologic parameters such as repolarization duration, whole-heart models allow the determination of potential predictors for proarrhythmia. Spatial and temporal heterogeneity as well as changes of shape of the action potential can be easily assessed. In addition, provocation manoeuvers (either by electrolyte imbalances or programmed pacing protocols) may induce sustained arrhythmias and thereby determine ventricular vulnerability to arrhythmias. Compared with the human heart, the rabbit heart possesses a similar distribution of ion currents that govern cardiac repolarization, resulting in a rectangular action potential configuration in both species. In addition, similar biophysical properties of rabbit and human cardiac ion channels lead to a comparable pharmacologic response in human and rabbit hearts. Of note, arrhythmia patterns resemble in both species due to the similar effective size of human and rabbit hearts. Thus, the rabbit heart is particularly suitable for testing the electrophysiologic safety of drugs. Several experimental setups have been developed for studying cardiac electrophysiology in rabbits, ranging from single cell to tissue preparations, whole-heart setups, and in vivo models.

Background In patients with repaired Tetralogy of Fallot (ToF), implantable cardioverter defibrillators (ICD) are considered reasonable in selected adults with multiple risk factors for sudden cardiac death. Patients and methods We performed a retrospective cohort study of all 174 patients with repaired ToF who are followed at the University Hospital of Muenster. We analyzed data according to the risk score previously proposed by Khairy and coworkers and patient outcome. We analyzed data separately for patients without previous sustained ventricular tachycardia (VT) (risk stratification group, n = 157) and patients with VT/secondary prevention ICD (n = 17). Results In the risk stratification group, a mean of 4 ± 1 risk score parameters were available. All six risk parameters were known in 10%, five in 14%. Risk score increased with availability of parameters. 15 patients with secondary prevention ICD had a mean risk score of 6.3 ± 2.2 (range 2–10). 11 patients of the risk stratification group with primary prevention ICD had a mean risk score 5.8 ± 2.4 (range 3–8). During follow-up of up to 14 years, five patients died (3%): at age 58, two at 69 and two at 76 years. Conclusion In the majority of patients risk score variables were incomplete, severely limiting its applicability because the true score cannot be calculated. Risk scores were not different between patients with secondary prevention ICD and patients with ICD for primary prevention based on current guidelines. Standardization of follow-up and prospective evaluation of these standards in large prospective patient cohorts is desirable to improve risk stratification in patients with ToF.

Ivabradine has recently been demonstrated to have antiarrhythmic properties in atrial fibrillation. The aim of the present study was to assess the electrophysiologic profile of ivabradine in an experimental whole-heart model of long-QT-syndrome. In 12 isolated rabbit hearts long-QT-2-syndrome (LQT2) was simulated by infusion of d,l-sotalol (100 µM). 12 rabbit hearts were treated with veratridine (0.5 µM) to mimic long-QT-3-syndrome (LQT3). Sotalol induced a significant prolongation of QT-interval (+ 40 ms, p

A limited number of case reports of coronary sinus (CS) diverticula complicating catheter ablation have been published. We retrospectively analysed 2245 patients who underwent ablation of an accessory pathway (AP) at our institution between 1/11/1993 and 31/10/2016. Eight patients (0.36%) were found to have a CS diverticulum in venography. APs showed a mean antegrade conduction time of 276 ± 23 ms (range 220–310 ms) and a mean retrograde conduction of 301 ± 45 ms (230–350 ms). Four patients had 1 (n = 2), 2 (n = 1), or 3 (n = 1) previously failed ablation attempts. Pathways could not be ablated with a conventional 4 mm tip catheter in 7 of 8 cases. In seven patients, ablation was successful, in two using an 8-mm ablation catheter, in two using cryoablation, and in the remaining three with an irrigated tip ablation catheter. After failed femoral approach, one 9-year-old female was successfully ablated via the right jugular vein. In one 75-year-old female, ablation was not successful. During a mean follow-up of 8.9 ± 6.4 years, all patients remained free of recurrences. In inferoseptal pathways, especially with previous failed ablation attempts, venographies of the CS should be performed. After successful ablation long-term prognosis is excellent.

Administration of digitalis in heart failure (HF) increases quality of life but does not carry a prognostic benefit. Digitalis is an indirect inhibitor of the Na+ /Ca2+ exchanger (NCX), which is overexpressed in HF. We therefore used the cardiac glycoside ouabain in Ca2+ imaging experiments and patch-clamp experiments in isolated ventricular myocytes from nonfailing transgenic NCX overexpressor mice (OE). In field-stimulated myocytes, ouabain (1-100 μm) increased the amplitude of the Ca2+ transient in OE and wild-type (WT) similarly. Ouabain-mediated spontaneous Ca2+ -activity was significantly more pronounced in OE compared to WT myocytes at higher concentrations (100 μm). Also, at very high concentrations (1000 μm) of ouabain, the number of cells with hypercontraction leading to cell death was higher in OE. Ouabain (10 μm) shortened the action potential duration in both genotypes. Our findings suggest that the proarrhythmic but not the inotropic effects of cardiac glycosides are enhanced by increased NCX expression. This may offer an explanation for the observed lack of prognostic benefit but increased quality of life in HF, which is accompanied by NCX upregulation.

Background The subcutaneous implantable cardioverter–defibrillator (S-ICD) has evolved as a valuable alternative to the transvenous ICD, especially in young patients. Unfortunately, some of these patients are ineligible for S-ICD implantation due to specific electrocardiographic features. So far, these patients were identified by mandatory pre-implantation screening using the manual screening tool (MST), which lacks objective value. Therefore, a novel automated screening tool (AST) has been introduced recently for objective screening, which has not been evaluated yet. Methods/results We here first investigate the novel AST, in direct comparison to MST, in 33 consecutive patients with already implanted S-ICD system to compare predicted eligibility by screening tools with true sensing of the S-ICD system. Both screening tools reliably predicted true ineligible single vectors, but also suggested overall ineligibility in a similar fraction of patients (MST: 3.0%; AST: 6.1%), albeit the implanted S-ICD worked flawlessly in these patients. AST did not predict the finally selected sensing vector better than MST. There was a surprising mismatch between AST and MST for the predicted eligibility of single vectors; only in 49% of patients did both screening tools predict eligibility for the same vectors. Conclusions The novel AST predicted overall eligibility approximately similar to MST. Both tools predicted ineligibility in a few patients, who were actually eligible. There was a striking mismatch between both screening tools when eligibility of single vectors was predicted. Thus, the AST seems to be a valuable advance, due to its standardized and objective process, but it still lacks specificity.

The subcutaneous ICD is a promising treatment option in patients at risk for sudden cardiac death. Approved in 2009, the first S-ICD® in Germany was implanted in June 2010. Although large prospective registry studies have shown safety and efficacy of the system, there is a lack of long-term data with regard to battery longevity of the S-ICD®. Therefore, we report follow-up of our first initial S-ICD® cases from implantation till battery depletion. All S-ICD® patients with device replacement for battery depletion in our large single-center S-ICD® registry were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a median follow-up of 75.9 ± 6.8 months. Twenty-eight patients with S-ICD® systems were included in this study. Of these patients, 21 were male and 7 were female, with an overall mean age of 41.9 ± 12.6 years. Primary prevention of sudden cardiac death was the indication in 19 patients (67.9%). Ventricular tachycardia was adequately terminated in two patients (7.1%). In 7 patients, non-sustained ventricular arrhythmias were not treated. A total of three inappropriate shocks occurred in three patients (10.7%). Mean time from implantation till battery depletion was 65.8 ± 8.1 months. Only one patient presented premature elective replacement criteria because of rapid battery depletion. No lead-related complication occurred during follow-up and no complications were seen regarding device replacement. In one patient (3.6%), the system was explanted without replacement due to patient’s preference. The estimated battery longevity of S-ICD® of about 5 years was reached in all but one patient. Compared to larger S-ICD® registry studies, frequency of inappropriate shocks was relatively high in the initial S-ICD® cases. Both technological improvement as well as programming and operators’ experience have led to a reduction of complications. Replacement of the S-ICD® seems to be a safe and effective procedure.

The presence of left bundle branch block (LBBB) represents a particular challenge in properly measuring the QT interval. Here we demonstrate the applicability of the “Bogossian formula” in pacemaker patients with LBBB due to apical or nonapical right ventricular (RV) pacing and preserved left ventricular function. A total of 163 patients with a cardiac one- or two-chamber pacemaker were included in this prospective, multicentre observational study. Twelve-lead ECG recordings were obtained during both intrinsic rhythm and RV pacing with induced LBBB. The QT interval measured during LBBB was corrected using the Bogossian formula to obtain the “modified QT” (QTm). The QTmc interval was calculated with the Bazett formula, and this was compared with the QTc interval during intrinsic rhythm. Eighty-three patients (78 ± 9 years; male n = 83) with apical and eighty patients (71 ± 13 years; male n = 80) with non-apical RV pacing were included in this study. In the apical group the QTmc was determined to be 444 ± 39 ms in paced rhythm and the QTc interval 413 ± 36 ms in intrinsic rhythm. In the non-apical group these values were 430 ± 34 ms in paced and 416 ± 32 ms in intrinsic rhythm. The Bogossian formula is a reliable tool for QTc interval evaluation in pacemaker patients with LBBB due to apical or non-apical RV pacing. However, an overestimation of 30 ms should be included in the calculation.

Slow pathway modulation is the treatment of choice in patients with atrioventricular nodal reentrant tachycardia (AVNRT). No comparative data on ablation strategies exist. Therefore, we sought to compare two common ablation approaches. We analyzed prospective ablation databases of two high-volume tertiary centers (> 1000 ablations/year) using either 30 or 50 W for slow pathway modulation from 2012 to 2013. We analyzed procedural characteristics as well as short- and long-term outcomes. Mean follow-up was 36 ± 9 months. Six hundred thirty-four patients (50 W center: n = 342, 30 W center: n = 292) were ablated. Slow pathway modulation was successful in 99% in both groups (p = ns). Periprocedural AV block occurred in nine patients (2.6%) in the 50 W and five patients (1.7%) in the 30 W group (p = 0.59), respectively. We documented no permanent higher-degree AV block. The number of RF lesions and seconds of RF delivery was significantly less in the 50 W group (p = 0.04 for number of lesions; p

Background: Pulmonary vein isolation (PVI) and antiarrhythmic drug therapy are established treatment strategies to preserve sinus rhythm in atrial fibrillation (AF). However, the efficacy of both interventional and pharmaceutical therapy is still limited. Solid evidence suggests an important role of the cardiac sympathetic nervous system in AF. In this blinded, prospective observational study, we studied left ventricular cardiac sympathetic activity in patients treated with PVI and with antiarrhythmic drugs. Prospectively, Iodine-123-benzyl-guanidine single photon emission computer tomography (123I-mIBG-SPECT) was performed in a total of 23 patients with paroxysmal AF, who underwent PVI (n = 20) or received antiarrhythmic drug therapy only (n = 3), respectively. 123I-mIBG planar and SPECT/CT scans were performed before and 4 to 8 weeks after PVI (or initiation of drug therapy, respectively). For semiquantitative SPECT image analysis, attenuation-corrected early/late images were analyzed. Quantitative SPECT analysis was performed using the AHA 17-segment model of the left ventricle. Results: PVI with point-by-point radiofrequency ablation led to a significantly (p &lt, 0.05) higher visual sympathetic innervation defect score when comparing pre-and post PVI. Newly emerging innervation deficits post PVI were localized predominantly in the inferior lateral wall. These findings were corroborated by semiquantitative SPECT analysis identifying inferolateral segments with a reduced tracer uptake in comparison to SPECT before PVI. Following PVI, patients with an AF relapse showed a different sympathetic innervation pattern compared to patients with sufficient rhythm control. Conclusions: PVI results in novel defects of cardiac sympathetic innervation. Differences in cardiac sympathetic innervation remodelling following PVI suggest an important role of the cardiac autonomous nervous system in the maintenance of sinus rhythm following PVI.

The If channel inhibitor ivabradine is recommended for treatment of chronic heart failure. However, ivabradine also inhibits human ether-a-go-go (hERG) mediated potassium currents. The aim of the present study was to assess the electrophysiologic effects of ivabradine in an experimental model of short-QT-syndrome. 12 rabbit hearts were isolated and Langendorff-perfused. After obtaining baseline data, pinacidil, an IK-ATP channel opener, was infused (1μM). Eight endo- and epicardial monophasic action potentials and a 12-lead ECG showed a significant abbreviation of QT interval (-32ms,p

Recent experimental studies suggested direct effects of the anti-influenza drug oseltamivir on cardiac electrophysiology. We therefore aimed at analyzing potential antiarrhythmic effects of oseltamivir on atrial fibrillation (AF) in an experimental whole-heart model. Twelve rabbit hearts were isolated and Langendorff perfused. Thereafter, hearts were paced at cycle lengths of 350, 250, and 200 ms in the atrium. A standardized protocol employing atrial burst pacing induced AF in 4 of 12 hearts under baseline conditions (33%, 11 episodes). Subsequently, a combination of acetylcholine (1 μM) and isoproterenol (1 μM) was administered to increase AF occurrence. Two monophasic action potential recordings on the left and two on the right atrial epicardium displayed a decrease of atrial action potential duration (aAPD, −38 ms, p

The calcium sensitizer levosimendan is clinically employed in decompensated heart failure. The aim of the present study was to assess effects of levosimendan on atrial electrophysiology in an experimental whole-heart model.13 rabbit hearts were isolated and Langendorff-perfused. Thereafter, hearts were paced at cycle lengths of 350ms, 250ms and 200ms in the atrium. A standardized protocol employing atrial burst pacing induced atrial fibrillation (AF) in 4 of 13 hearts under baseline conditions (mean: 3.3±2.1 episodes). Subsequently, levosimendan was administered in two concentrations (0.25μM, 0.5μM). Two monophasic action potential recordings on the left- and two on the right atrial epicardium displayed a decrease of atrial action potential duration (aAPD, -27ms, p0.05) and atrial effective refractory period (aERP; -29ms, p0.05) under the influence of 0.5μM levosimendan. The described alterations of atrial electrophysiology led to and increased inducibility of AF. Of note, treatment with 0.25μM levosimendan resulted in induction of AF in 11 of 13 hearts (mean: 8.9±3.5 episodes). Under the influence of 0.5μM levosimendan 12 of 13 hearts were inducible (mean: 9.8±3.8 episodes).In the present study acute infusion of levosimendan in isolated rabbit hearts resulted in an abbreviation of atrial action potential duration and a reduction of aERP. This led to a significantly elevated inducibility of atrial fibrillation. These results suggest a proarrhythmic effect of levosimendan regarding atrial fibrillation. This aspect should be further investigated in the clinical setting.

Ivabradine is an inhibitor of mixed NaIn 12 isolated rabbit hearts AF was induced in 7 of 12 hearts (13 episodes) under baseline conditions by a standardized protocol employing atrial burst pacing. Thereafter, a combination of acetylcholine and isoproterenol was employed to enhance AF occurrence. Monophasic action potential recordings showed a decrease of atrial action potential duration (aAPD,-37ms, p0.05) and atrial effective refractory period (aERP;-39ms, p0.05) after infusion of both acetycholine (1μM) and isoproterenol (1μM) as compared with baseline. This led to induction of AF in 11 of 12 hearts (124 episodes). Simultaneous infusion of ivabradine (3μM) led to a significant reduction of AF (6 of 11 hearts, 63 episodes). Ivabradine induced an increase of aAPD (+9ms) and aERP (+30ms, p0.05) leading to a marked increase of atrial post-repolarization refractoriness (aPRR), defined as the difference of aERP and aAPD (+21ms, p0.05). Results were compared to 10 rabbits treated with flecainide. Flecainide treatment also induced a significant increase of aPRR and resulted in induction of AF in 6 of 10 hearts (58 episodes) while 9 of 10 hearts were inducible during sole treatment with acetylcholine and isoproterenol (129 episodes).In the present experimental study, administration of ivabradine reduced inducibility of AF and therefore may represent a supplemental therapeutic option in AF. Of note, its antiarrhythmic efficacy was comparable to the established agent flecainide.

BACKGROUND: The present European guidelines suggest a diagnostic electrophysiological (EP) study to determine indication for cardiac pacing in patients with bundle branch block and unexplained syncope. We evaluated the prognostic relevance of an EP study for mortality and the development of permanent complete atrioventricular (AV) block in patients with symptomatic bifascicular block and first‐degree AV block. HYPOTHESIS: The HV interval is a poor prognostic marker to predict the development of permanent AV block in patients with symptomatic bifascicular block (BFB) and AV block I°. METHODS: Thirty consecutive patients (mean age, 74.8 ± 8.6 years; 25 males) with symptomatic BFB and first‐degree AV block underwent an EP study before device implantation, according to current guidelines. For 53 ± 31 months, patients underwent yearly follow‐up screening for syncope or higher‐degree AV block. RESULTS: Thirty patients presented with prolonged HV interval during the EP study (mean, 82.2 ± 20.1 ms; range, 57–142 ms), classified into 3 groups: group 1, 70 to ≤100 ms (mean, 80 ± 8 ms; range, 70–97 ms; n = 18), and group 3, >100 ms (mean, 119 ± 14 ms; range, 107–142 ms; n = 5). According to the guidelines, patients in groups 2 and 3 received a pacemaker. The length of the HV interval was not associated with the later development of third‐degree AV block or with increased mortality. CONCLUSIONS: Our present study suggests that an indication for pacemaker implantation based solely on a diagnostic EP study with prolongation of the HV interval is not justified.

BACKGROUND The presence of left bundle branch block (LBBB) due to right ventricular pacing represents a particular challenge in properly measuring the QTc interval. In 2014, a new formula for the evaluation of QT interval in patients with LBBB was reported. METHODS 145 patients with implantable cardioverter defibrillator were included in this prospective multicenter observational study. Inclusion criteria were: no permanent right ventricular stimulation, an intrinsic QRS interval of

Increasing evidence supports a role of inflammation in the development of atrial fibrillation (AF). However, direct evidence of persistent inflammatory activity in the atria of AF patients is scarce. In this study, we used 18-Fluor-Deoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT) to determine atrial inflammation in patients with and without AF. Retrospectively, 18F-FDG PET/CT scans were analyzed. 37 patients with a history of AF were compared to an age and sex matched control group with no history of AF. Standardized uptake values were obtained in the atrial walls, in the left ventricular wall, and in the right ventricular blood pool, respectively. Target to background ratios (TBR) were determined in the atrial and left ventricular walls and compared between the two groups. TBR values of the left atrial wall were slightly but not significantly higher in patients with AF (1.21 ± 0.27) compared to those without AF (1.14 ± 0.29; p = 0.85). Likewise, a weak but not significant difference was observed in signal intensities in the right atrial wall between patients in the AF (1.14 ± 0.45) and the control group (0.96 ± 0.2; p = 0.41). TBR values of the left ventricular myocardium did not differ between the groups; no significant correlation was found between the TBR in the left and right atrial wall and blood glucose levels. 18F-FDG PET/CT performed under routine conditions did not detect a significant difference in inflammatory activity in the left or right atrium between patients with and without AF. Contrary to previous reports, these results therefore do not clearly support a role for ongoing atrial inflammation in patients with AF. Prospective clinical studies using myocardial glucose uptake suppression strategies may be helpful to clarify these issues.

Aims In atrial fibrillation, increased function of the Na+/Ca2 +-exchanger (NCX) is one among several electrical remodeling mechanisms. Methods/results Using the patch-clamp- and Ca2 + imaging-methods, we investigated atrial myocytes from NCX-homozygous-overexpressor (OE)- and heterozygous-knockout (KO)-mice and their corresponding wildtypes (WTOE; WTKO). NCX mediated Ca2 + extrusion capacity was reduced in KO and increased in OE. There was no evidence for structural or molecular remodeling. During a proarrhythmic pacing-protocol, the number of low amplitude delayed afterdepolarizations (DADs) was unaltered in OE vs. WTOE and KO vs. WTKO. However, DADs triggered full spontaneous action potentials (sAP) significantly more often in OE vs. WTOE (ratio sAP/DAD: OE:0.18 ± 0.05; WTOE:0.02 ± 0.02; p

Background Many clinical studies suggest an impact of propofol on the occurrence of atrial arrhythmias. Purpose Since experimental data is sparse, purpose of this study was to investigate the influence of propofol on atrial electrophysiology and the vulnerability to atrial fibrillation in a sensitive whole-heart model of atrial fibrillation. Methods 11 hearts of New Zealand white rabbits were isolated and Langendorff-perfused. Two catheters were placed on both atria to record atrial monophasic action potentials. Hearts were stimulated at three different cycle lengths (350ms, 250ms, 150ms), thereby obtaining cycle-length dependent atrial action potential durations (aAPD90) and effective refractory periods (aERP). Atrial post-repolarization (aPRR) refractoriness was defined as the difference between aERP and aAPD90. To increase the occurrence of atrial fibrillation, hearts were perfused with a combination of acetylcholine (ACh, 1μM) and isoproterenol (Iso, 1μM) after obtaining baseline data. Vulnerability to atrial fibrillation was tested by a standardized protocol consisting of several trains of burst pacing. Results Acetylcholine/isoproterenol infusion reduced aAPD90 (−3ms), aERP (−16ms) and aPRR (−14ms). Additional treatment with propofol prolonged aAPD90 (+5ms), aERP (+24ms) and aPRR (+20ms). Under baseline conditions, 13 episodes of atrial fibrillation lasting longer than 1s occurred. Additional treatment with acetylcholine/isoproterenol provoked more episodes of atrial fibrillation (33 episodes, p Conclusion In this study, propofol prolonged aAPD90 and significantly reduced the occurrence of atrial fibrillation. Prolongation of effective refractory periods and especially of post-repolarization refractoriness protects the atrial myocardium against premature excitation and thereby prevents arrhythmias.

Background Implantable cardioverter- defibrillator (ICD) therapy is established for prevention of sudden cardiac death (SCD) in different entities. However, data from large patient cohorts on patients with electrical heart disease of hypertrophic cardiomyopathy (HCM) is rare. Therefore, we investigated these patients by analysing registry data from a multi-center “real-life” registry. Methods The German Device Registry (DEVICE) is a nationwide, prospective registry with one-year follow-up investigating 5450 patients receiving device implantations in 50 German centres. The present analysis of DEVICE focussed on patients with electrical heart disease or HCM who received an ICD for primary or secondary prevention. Results 174 patients with HCM and 112 patients with electrical heart disease were compared with 5164 other ICD patients. Median follow-up was 17.0 months. Patients in the control group were significantly older. Of note, overall mortality after one year was 1.8% in HCM patients, 6.6% in patients with electrical heart disease and 7.3% in the control group. Patients in the control group presented significantly more severe comorbidities. In contrast to HCM patients and the control group where primary prevention was the major indication for ICD implantation 77.5% of patients with electrical heart disease received an ICD for secondary prevention. The number of surgical revisions was higher in patients with electrical heart disease. Conclusion Data from the present registry display a surprisingly high mortality in patients with electrical heart disease equivalent to the control group. A high proportion of patients who received an ICD for secondary prevention may be regarded as a major determinant for these results while severe comorbidities such as diabetes, hypertension and renal failure are major determinants for mortality in the control cohort.

The performance of the subcutaneous ICD (S-ICD™) has been described in different kinds of heart disease and has been proven to be an important advance in prevention of sudden cardiac death (SCD). While positive experiences with the S-ICD™ initially came from collectives of patients without structural heart diseases, positive results have also been collected from cohorts with structural heart disease. All S-ICD™ patients with either ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) as the main indication for ICD implantation (n = 144 patients) or electrical heart disease/idiopathic ventricular fibrillation (n = 83 patients) in our large-scaled single-center S-ICD™ registry were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 18 ± 15 months. Baseline characteristics were significantly different between the two groups in most categories. In contrast, there was no difference concerning neither appropriate nor inappropriate shock delivery between the two groups. Also other outcome parameters such as need for surgical revisions and all-cause mortality did not differ. There was a significant difference between the first- and second-generation S-ICDs™ in inadequate shocks mainly driven by patients with HCM. In our study, S-ICD™ performance was similar in patients with and without structural heart disease. Decision pro- or contra-S-ICD™ should be made rather on the basis of expected shock rate and probability of the need for future anti-tachycardia or anti-bradycardia pacing than in dependence of the underlying heart disease.

Several studies suggest QT prolongation and torsade de pointes with acetylcholine-esterase inhibitors. We therefore examined the electrophysiologic profile of donepezil, rivastigmine, and galantamine in a sensitive whole-heart model of proarrhythmia. 34 rabbit hearts were isolated and retrogradely perfused employing the Langendorff setup. Hearts were treated either with donepezil, rivastigmine, or galantamine in rising concentrations and electrophysiologic studies were performed. In the presence of donepezil and galantamine, spatial dispersion of repolarization was amplified. Cardiac repolarization (QT interval and action potential duration) was prolonged with donepezil but not with galantamine. Remarkably, both drugs induced triggered activity (early afterdepolarizations and torsade de pointes tachycardia). Despite a pronounced prolongation of repolarization with rivastigmine, no increase in spatial dispersion of repolarization and thus no triggered activity was observed. In the present study, donepezil and galantamine provoked triggered activity, whereas rivastigmine did not have proarrhythmic effects. Spatial dispersion of repolarization but not duration of cardiac repolarization was associated with increased risk of drug-induced proarrhythmia with acetylcholine-esterase inhibitors. Consequently, QT interval duration might be insufficient to estimate the risk of proarrhythmia with acetylcholine-esterase inhibitors. Our findings emphasize the need for further electrocardiographic risk predictors.

Introduction The AliveCor Kardia ECG monitor (ACK) offers a smartphone-based one-lead ECG recording for the detection of atrial fibrillation. We compared ACK lead I recordings with the 12-lead ECG and introduce a novel parasternal lead (NPL). Methods Consecutive cardiac inpatients were recruited. In all patients a 12-lead ECG, ACK lead I and NPL were obtained. Two experienced electrophysiologists were blinded and separately evaluated all ECG. We calculated sensitivity, specificity, and predictive values of the ACK ECG compared to the 12-lead ECG. Results 296 ECG from 99 patients (38 female, age 64 ± 15 years, BMI 27.8 ± 5.1 kg/m2) were analyzed. 20% of ACK lead I recordings contained a critical amount of artifact. The electrophysiologists’ interpretation of the ACK recordings yielded a sensitivity of 100% and specificity of 94% for atrial fibrillation or flutter in lead I (κ = 0.90) and a sensitivity of 96% and specificity of 97% in the NPL (κ = 0.92). The ACK diagnostic algorithm displayed a significantly lower sensitivity (55–70%), specificity (60–69%), and accuracy (κ = 0.4–0.53) but a high negative predictive value (100%). Patients with atrial flutter (n = 5) and with ventricular stimulation (n = 12) had a high likelihood of being misclassified by the algorithm. Conclusion The AliveCor Kardia ECG monitor allows a highly accurate detection of atrial fibrillation by an interpreting electrophysiologist both in the standard lead I and a novel parasternal lead. The diagnostic algorithm offered by the system may be useful in screening recordings for further review. Diagnostic challenges present in atrial flutter and ventricular pacemaker stimulation.

Recent experimental studies showed a protective effect of the renin inhibitor aliskiren regarding atrial structural remodeling. Purpose of this study was to assess acute electrophysiologic effects of aliskiren in a whole-heart model of atrial fibrillation (AF) and to investigate its impact on the ventricle. Twelve rabbit hearts were excised, retrogradely perfused, and paced at different cycle lengths. To enhance atrial vulnerability, a combination of acetylcholine (ACh) and isoproterenol (Iso) was infused and significantly reduced atrial action potential duration (aAPD90) and atrial effective refractory period (aERP). Additional infusion of aliskiren prolonged aAPD90 but did not alter aERP. A triangulation of action potential with ACh/Iso and a further triangulation after treatment with aliskiren were noted. Vulnerability to AF was tested by employing trains of burst pacing. Administration of ACh/Iso provoked more episodes of AF (baseline: 26 episodes, Iso/Ach: 48 episodes). Additional treatment with aliskiren induced AF significantly more often (108 episodes). Another nine hearts were perfused with aliskiren to examine its ventricular effects. Infusion with aliskiren abbreviated ventricular APD90 and ERP. Utilizing programmed ventricular stimulation, a trend towards more ventricular arrhythmias in aliskiren-treated hearts was observed. Though aliskiren did not reduce aAPD90 or aERP, acute treatment with aliskiren promoted AF. Triangulation of atrial action potentials, which is an established risk factor for ventricular proarrhythmia, may contribute to the increased atrial vulnerability. This effect may interfere with its recently demonstrated beneficial properties in atrial remodeling. Of note, aliskiren might have a proarrhythmic effect on the ventricular level.

Background Outcome of ischemic VT ablation may differ between patients with previous myocardial infarction (MI) in relation to infarct localization. Methods We analyzed procedural data, acute and long-term outcomes of 152 consecutive patients (139 men, mean age 67 ± 9 years) with previous anterior or inferior MI who underwent ischemic VT ablation at our institution between January 2010 and October 2015. Results More patients had a history of inferior MI (58%). Mean ejection fraction was significantly lower in anterior MI patients (28 ± 10% vs. 34 ± 10%, p p = 0.18). Procedural parameters and acute success did not differ between the groups. During a mean follow-up of 3 ± 2 years, more anterior MI patients had undergone a re-ablation (49% vs. 33%, p = 0.09, Chi-square test). There was a trend towards more ICD shocks in patients with previous anterior MI (46% vs. 34%). After adjusting for risk factors and ejection fraction, multivariable Cox regression analyses showed no significant difference in mortality (p = 0.78) and cardiovascular mortality between infarct localizations (p = 0.6). Conclusion Clinical characteristics of patients with anterior and inferior MI are similar except for ejection fraction. Patients with inferior MI appear to have better outcome regarding survival, ICD shocks and re-ablation, but this appears to be related to better ejection fraction when compared with anterior MI.