Cardiovascular magnetic resonance imaging patterns of acute COVID-19 mRNA vaccine-associated myocarditis in young male patients: A first single-center experience.

Background: The risk of myocarditis after mRNA vaccination against COVID-19 has emerged recently. Current evidence suggests that young male patients are predominantly affected. In the majority of the cases, only mild symptoms were observed. However, little is known about cardiac magnetic resonance (CMR) imaging patterns in mRNA-related myocarditis and their differences when compared to classical viral myocarditis in the acute phase of inflammation. Methods and results: In total, 10 mRNA vaccination-associated patients with myocarditis were retrospectively enrolled in this study and compared to 10 patients suffering from viral myocarditis, who were matched for age, sex, comorbidities, and laboratory markers. All patients (n = 20) were hospitalized and underwent a standardized clinical examination, as well as an echocardiography and a CMR. Both, clinical and imaging findings and, in particular, functional and volumetric CMR assessments, as well as detailed tissue characterization using late gadolinium enhancement and T1 + T2-weighted sequences, were compared between both groups. The median age of the overall cohort was 26 years (group 1: 25.5; group 2: 27.5; p = 0.57). All patients described chest pain as the leading reason for their initial presentation. CMR volumetric and functional parameters did not differ significantly between both groups. In all cases, the lateral left ventricular wall showed late gadolinium enhancement without significant differences in terms of the localization or in-depth tissue characterization (late gadolinium enhancement [LGE] enlargement: group 1: 5.4%; group 2: 6.5%; p = 0.14; T2 global/maximum value: group 1: 38.9/52 ms; group 2: 37.8/54.5 ms; p = 0.79 and p = 0.80). Conclusion: This study yielded the first evidence that COVID-19 mRNA vaccine-associated myocarditis does not show specific CMR patterns during the very acute stage in the most affected patient group of young male patients. The observed imaging markers were closely related to regular viral myocarditis in our cohort. Additionally, we could not find any markers implying adverse outcomes in this relatively little number of patients; however, this has to be confirmed by future studies that will include larger sample sizes.

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

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

Generation and cardiac differentiation of an induced pluripotent stem cell line from a patient with arrhythmia-induced cardiomyopathy.

Arrhythmia-induced cardiomyopathy (AIC) is characterized by left-ventricular systolic dysfunction caused by persistent arrhythmia. To date, genetic or pathological drivers causing AIC remain unknown. Here, we generated induced pluripotent stem cells (iPSCs) from an AIC patient. The AIC-iPSCs exhibited full pluripotency and differentiation characteristics and maintained a normal karyotype after reprogramming. The AIC-iPSCs differentiated into functional beating AIC-iPSC-cardiomyocytes (CMs), which represents the cell-type of interest to study molecular, genetic and functional aspects of AIC.

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

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

Internal Versus External Electrical Cardioversion of Atrial Arrhythmia in Patients With Implantable Cardioverter-Defibrillator: A Randomized Clinical Trial.

BACKGROUND: Atrial arrhythmias are common in patients with implantable cardioverter-defibrillator (ICD). External shocks and internal cardioversion through commanded ICD shock for electrical cardioversion are used for rhythm-control. However, there is a paucity of data on efficacy of external versus internal cardioversion and on the risk of lead and device malfunction. We hypothesized that external cardioversion is noninferior to internal cardioversion for safety, and superior for successful restoration of sinus rhythm. METHODS: Consecutive patients with ICD undergoing elective cardioversion for atrial arrhythmias at 13 centers were randomized in 1:1 fashion to either internal or external cardioversion. The primary safety end point was a composite of surrogate events of lead or device malfunction. Conversion of atrial arrhythmia to sinus rhythm was the primary efficacy end point. Myocardial damage was studied by measuring troponin release in both groups. RESULTS: N=230 patients were randomized. Shock efficacy was 93% in the external cardioversion group and 65% in the internal cardioversion group (P<0.001). Clinically relevant adverse events caused by external or internal cardioversion were not observed. Three cases of pre-existing silent lead malfunction were unmasked by internal shock, resulting in lead failure. Troponin release did not differ between groups. CONCLUSIONS: This is the first randomized trial on external vs internal cardioversion in patients with ICDs. External cardioversion was superior for the restoration of sinus rhythm. The unmasking of silent lead malfunction in the internal cardioversion group suggests that an internal shock attempt may be reasonable in selected ICD patients presenting for electrical cardioversion. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03247738.

The detrimental potential of arrhythmia-induced cardiomyopathy.

Here we discuss a case of arrhythmia-induced cardiomyopathy (AIC) with consecutive severe multiple organ failure. In relation to this imposing case, we discuss the significance of this potentially underestimated cause of newly occurred left-ventricular systolic dysfunction and concomitant arrhythmia. We further delineate the diagnostic algorithm and differential diagnoses of AIC.

Arrhythmia-Induced Cardiomyopathy.

BACKGROUND: Heart failure affects 1­2% of the population and is associated with elevated morbidity and mortality. Cardiac arrhythmias are often a result of heart failure, but they can cause left-ventricular systolic dysfunction (LVSD) as an arrhythmia-induced cardiomyopathy (AIC). This causal relationship should be borne in mind by the physician treating a patient with systolic heart failure in association with cardiac arrhythmia. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed (1987­2017) and on the recommendations in current guidelines. RESULTS: The key criterion for the diagnosis of an AIC is the demonstration of a persistent arrhythmia (including pathological tachycardia) together with an LVSD whose origin cannot be explained on any other basis. Nearly any type of tachyarrhythmia or frequent ventricular extrasystoles can lead, if persistent, to a progressively severe LVSD. The underlying pathophysiologic mechanisms are incompletely understood; the increased ventricular rate, asynchronous cardiac contractions, and neurohumoral activation all seem to play a role. The most common precipitating factors are supraventricular tachycardias in children and atrial fibrillation in adults. Recent studies have shown that the causal significance of atrial fibrillation in otherwise unexplained LVSD is underappreciated. The treatment of AIC consists primarily of the treatment of the underlying arrhythmia, generally with drugs such as beta-blockers and amiodarone. Depending on the type of arrhythmia, catheter ablation for long-term treatment should also be considered where appropriate. The diagnosis of AIC is considered to be well established when the LVSD normalizes or improves within a few weeks or months of the start of targeted treatment of the arrhythmia. CONCLUSION: An AIC is potentially reversible. The timely recognition of this condition and the appropriate treatment of the underlying arrhythmia can substantially improve patient outcomes.

[Malignant bileaflet mitral valve prolapse syndrome in otherwise idiopathic ventricular fibrillation]. / Malignes Mitralklappenprolapssyndrom bei "idiopathischem" Kammerflimmern.

A 32-year-old, otherwise healthy woman was admitted after successful out-of-hospital resuscitation due to ventricular fibrillation. Established cardiac, pulmonary, metabolic, and toxicological causes were excluded. However, persisting (biphasic) negative T waves in the inferior ECG leads and premature ventricular contractions (PVC) were noted. PVC morphology indicated a focus alternating between the posterior papillary muscle/the left posterior fascicle and the left ventricular outflow tract region/anterior papillary muscle. Echocardiography revealed a bileaflet mitral prolapse with mild mitral valve regurgitation. This case is a typical presentation of the recently described malignant bileaflet mitral valve prolapse syndrome. The patient was discharged without overt neurological deficit after implantation of a cardioverter-defibrillator.

[Permanent junctional reciprocating tachycardia causing cardiomyopathy in an adult woman]. / Permanente junktionale Reentrytachykardie als Kardiomyopathie-Ursache bei einer erwachsenen Frau.

A 35-year-old female was referred with progressive dyspnoea and elevated heart rate. Surface electrocardiography (ECG) showed supraventricular tachycardia (SVT) with long RP interval and inverse P waves. ECG revealed left ventricular dilation and severe systolic dysfunction. An electrophysiological (EP) examination was performed due to incessant SVT despite betablocker medication. Permanent junctional reciprocating tachycardia (PJRT) was diagnosed and successfully ablated. During follow-up, the patient's symptoms abated and ECG parameters normalized. PJRT is usually found in infants and children, but should also be considered as a rare cause of incessant SVT and tachycardiomyopathy in adults.

Device malfunction caused by "auto-oversensing" of transthoracic impedance measurement test pulses in a modern minute ventilation dual-chamber pacemaker.

Oversensing of physiologic and non-physiologic electrical signals is a relevant cause of malfunctions in subjects with CIED. Physicians taking care of CIED patients must be aware of the potential causes of oversensing and their pattern in EGMs. The present case describes an uncommon source and unique underlying root cause for oversensing in a modern dual-chamber MV rate-adaptive pacemaker.

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

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

[Inappropriate sinus tachycardia]. / Die inadäquate Sinustachykardie.

Inappropriate sinus tachycardia is characterized by an unexplained increase of the resting sinus rate (> 100 bpm) with excess increase in response to moderate activity (mean heart rate > 90 bpm/24 h). Affected patients may suffer from heart race, palpitations, fatigue, weakness and dizziness. The mechanisms underlying inappropriate sinus tachycardia and its long term prognosis are poorly understood. Thus, diagnosis and treatment are empiric and require the initial exclusion of potential causes of secondary sinus tachycardia. Therapeutic approaches include physical training, beta blockers or ivabradine. Radiofrequency catheter ablation should be restricted to patients with refractory and longstanding symptoms.

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

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

Single-ring ablation compared with standard circumferential pulmonary vein isolation using remote magnetic catheter navigation.

PURPOSE: In ablation of atrial fibrillation, the single-ring method aims for isolation of the posterior wall of the left atrium (LA) including the pulmonary veins (PVs) but avoiding posterior LA lesions. The aim of this randomized prospective study was to evaluate safety and efficacy of remote magnetic navigation (RMN)-guided single-ring ablation strategy as compared to standard RMN-guided circumferential PV ablation (PVA). METHODS: Eighty consecutive patients undergoing PVA were enrolled prospectively and randomized equally into two study groups. RMN using the Stereotaxis system and open-irrigated 3.5-mm ablation catheters were used with a 3D mapping system in all procedures. Forty patients underwent RMN-guided single-ring ablation, and 40 patients received RMN-guided circumferential PVA. RESULTS: In the circumferential group, 3.3 ± 1.1 PVs were successfully isolated at the end of the procedure as compared to 3.1 ± 1.3 in the single-ring (box) group (p=0.38). All patients in the box group required additional posterior lesions in order to achieve electrical isolation of the PVs. Single-ring ablation was associated with longer procedure duration (p=0.01) and ablation time (p=0.001). After a single procedure, the proportion of patients free of any atrial tachycardia (AT)/atrial fibrillation (AF) episode at 12-month follow-up was 57 % in the box group and 58 % in the circ group. Using RMN, only minor complications have been observed. CONCLUSIONS: RMN-guided single-ring PVA provides comparable acute and long-term success rates as compared to RMN-guided circumferential PVA but requires additional posterior lesions to achieve PV isolation and increased procedure and ablation time. Procedural complication rates are low when using RMN.

Remote magnetic navigation for circumferential pulmonary vein ablation: single-catheter technique or additional use of a circular mapping catheter?

PURPOSE: Remote magnetic navigation (RMN) is utilized for catheter guidance during pulmonary vein ablation (PVA). We aimed to determine whether the additional use of a circular mapping catheter (CMC) influences efficacy and outcome of RMN-guided PVA. METHODS: A total of 80 consecutive subjects (65 % male, age 62 ± 9 years) underwent circumferential PVA with a 3D mapping system and an RMN-guided irrigated catheter. Procedural endpoint was complete PV isolation (PVI), total radiofrequency (RF) time >60 min, or procedure duration >5 h. PVI was defined as an entrance and/or exit block, diagnosed with a CMC within the PV ostium or by pacing via the roving RMN-guided catheter (single-catheter technique). Prolonged Holter monitoring after 3 and 6 months was used to detect atrial tachyarrhythmia (AT/AF) recurrences. RESULTS: Complete PVI was achieved in 56 % (45/80) of all subjects (isolated PVs per patient, 3.1 ± 1.2; RF time, 56.3 ± 17.2 min; procedure duration, 3.8 ± 0.8 h). Prospective validation of the single-catheter technique for diagnosing PVI demonstrated high concordance (94 %) with blinded CMC results. CMC use in first-time PVA was associated with similar total RF and procedure times but higher PV isolation rate. Upon multivariate analysis, CMC use, female gender, left PV, smaller PV ostium and repeat PVA predicted PVI during RMN-guided ablation. Persistent AF and mitral regurgitation at baseline and the number of non-isolated PVs predicted AT/AF recurrence during follow-up. CONCLUSIONS: Concomitant CMC use for first-time, RMN-guided PVA is associated with similar procedure duration but higher PV isolation rates as compared to a single-catheter approach. Since the number of isolated PVs predicts freedom from AT/AF, CMC utilization appears advisable for first-time, RMN-guided PVA.

Effects of ranolazine on torsades de pointes tachycardias in a healthy isolated rabbit heart model.

PURPOSE: Torsades de pointes (TdP) tachycardias are triggered, polymorphic ventricular arrhythmias arising from early afterdepolarizations (EADs) and increased dispersion of repolarization. Ranolazine is a new agent which reduces pathologically elevated late INa but also IKr . Aim of this study was to evaluate the effects of ranolazine in a validated isolated Langendorff-perfused rabbit heart model. METHODS: TdP was reproducibly induced with d-sotalol (10(-4)  mol/L) and low potassium (K) (1.0 mmol/L for 5 min, pacing at CL 1000 ms). In 10 hearts, ECG and 8 epi- and endocardial monophasic action potentials were recorded. Action potential duration (APD) was measured at 90% repolarization and dispersion defined as APD max-min. RESULTS: D-sotalol prolonged APD90 and increased dispersion of APD90 , simultaneously causing EADs and induction of TdP. The combination of d-sotalol and two concentrations of ranolazine did not increase dispersion of ventricular APD90 as compared to vehicle. Ranolazine at 5 µmol/L did not cause additional induction of EADs and/or TdP but also did not significantly suppress arrhythmogenic triggers. The higher concentration of ranolazine (10 µmol/L) in combination with d-sotalol caused further prolongation of APD90 , at the same time reduction in APD90 dispersion. In parallel, the incidence of EADs was reduced and an antitorsadogenic effect was seen. CONCLUSIONS: In the healthy isolated rabbit heart (where late INa is not elevated), ranolazine does not cause proarrhythmia but exerts antiarrhythmic effects in a dose-dependent manner against d-sotalol/low K-induced TdP. This finding-despite additional APD prolongation-supports the safety of a combined use of both drugs and merits clinical investigation.