Long-term risk of cardiovascular implantable electronic device reinterventions following external cardioversion of atrial fibrillation and flutter: A nationwide cohort study.

BACKGROUND: External cardioversion (ECV) is an essential part of rhythm control of atrial fibrillation and flutter in patients with and without cardiovascular implantable electronic devices (CIEDs). Long-term follow-up data on ECV-related CIED dysfunctions are limited. OBJECTIVE: The purpose of this study was to investigate the risk of CIED reintervention following ECV in a nationwide cohort. METHODS: We identified CIED implants and surgical reinterventions from 2005 to 2021 in the Danish Pacemaker and ICD Register. We included CIED patients undergoing ECV from 2010 to 2019 from the Danish National Patient Registry. For each ECV-exposed generator, 5 matched generators without ECV were identified, and for each ECV-exposed lead, 3 matched leads were identified. The primary endpoints were generator replacement and lead reintervention. RESULTS: We compared 2582 ECV-exposed patients with 12,910 matched patients with a pacemaker (47%), implantable cardioverter-defibrillator (ICD) (29%), cardiac resynchronization therapy-pacemaker (6%), or cardiac resynchronization therapy-defibrillator (18%). During 2 years of follow-up, 210 ECV-exposed generators (8.1%) vs 670 matched generators (5.2%) underwent replacements, and 247 ECV-exposed leads (5.6%) vs 306 matched leads (2.3%) underwent reintervention. Unadjusted hazard ratios were 1.61 (95% confidence interval [CI] 1.37-1.91; P <.001) for generator replacement and 2.39 (95% CI 2.01-2.85; P <.001) for lead reintervention. One-year relative risks were 1.73 (95% CI 1.41-2.12; P <.001) for generator replacement and 2.85 (95% CI 2.32-3.51; P <.001) for lead reintervention, and 2-year relative risks were 1.39 (95% CI 1.19-1.63; P <.001) and 2.18 (95% CI 1.84-2.57; P <.001), respectively. CONCLUSION: ECV in patients with a CIED is associated with a higher risk of generator replacement and lead reintervention. The risks of reinterventions were more pronounced within the first year after cardioversion.

External cardioversion of atrial fibrillation and flutter in patients with cardiac implantable electrical devices.

BACKGROUND: Atrial fibrillation and flutter are often treated with external electrical cardioversion (ECV) in patients with potentially electrically sensitive cardiovascular implantable electronic devices (CIED). Long-term follow-up data on contemporary CIED undergoing ECV is sparse. The aim is to investigate shock-related complications and impact on CIEDs. METHODS: All ECV procedures from 2010 to 2020 in patients with CIED performed at a tertiary university hospital were identified in the Danish National Patient Registry. Changes in device measurements after ECV were retrospectively studied and procedure-related complications were identified by review of medical records. RESULTS: We analyzed 763 ECV procedures in 372 patients, median device implant time 1.9 years. The mean age of patients was 69.9 ± 9.9 years of which 73.4% were men. We identified two cases of device programming changes and four cases of premature battery depletion (≤3 years after device implant). Minor changes in device measurements were found for impedances, sensing, and pacing thresholds. No patients died due to ECV-related device dysfunctions within the first 12 months after cardioversions. CONCLUSION: External cardioversion in patients with contemporary pacemakers and implantable cardioverter-defibrillators seems safe in the majority of patients. Clinically important changes in device function following cardioversion were rarely observed but may be critical for device function. In an observational study, causality between cardioversion and device dysfunction cannot be established. For patient safety, we suggest that routine device interrogation after cardioversion still should be part of standard care.

Duration of resuscitation and long-term outcome after in-hospital cardiac arrest: A nationwide observational study.

BACKGROUND: Prior studies have investigated the association between duration of resuscitation and short-term outcomes following in-hospital cardiac arrest (IHCA). However, it remains unknown whether there is an association between duration of resuscitation and long-term survival and functional outcomes. METHOD: We linked data from the Danish in-hospital cardiac arrest registry with nationwide registries and identified 8,727 patients between 2013 and 2019. Patients were stratified into four groups (A-D) according to quartiles of duration of resuscitation. Standardized average probability of outcomes was estimated using logistic regression. RESULTS: Of 8,727 patients, 53.1% (n = 4,604) achieved return of spontaneous circulation. Median age was 74 (1st-3rd quartile [Q1-Q3] 65-81 years) and 63.1% were men. Among all IHCA patients the standardized 30-day survival was 62.0% (95% CI 59.8-64.2%) for group A (<5 minutes), 32.7% (30.8-34.6%) for group B (5-11 minutes), 14.4% (12.9-15.9%) for group C (12-20 minutes) and 8.1% (7.0-9.1%) for group D (21 minutes or more). Similarly, 1-year survival was also highest for group A (50.4%; 48.2-52.6%) gradually decreasing to 6.6% (5.6-7.6%) in group D. Among 30-day survivors, survival without anoxic brain damage or nursing home admission within one-year post-arrest was highest for group A (80.4%; 78.2-82.6%), decreasing to 73.3% (70.0-76.6%) in group B, 67.2% (61.7-72.6%) in group C and 73.3% (66.9-79.7%) in group D. CONCLUSION: Shorter duration of resuscitation attempt during an IHCA is associated with higher 30-day and 1-year survival. Furthermore, we found that the majority of 30-day survivors were still alive 1-year post-arrest without anoxic brain damage or nursing home admission despite prolonged resuscitation.

Diagnostic Yield of Genetic Testing in Young Patients With Atrioventricular Block of Unknown Cause.

Background The cause of atrioventricular block (AVB) remains unknown in approximately half of young patients with the diagnosis. Although variants in several genes associated with cardiac conduction diseases have been identified, the contribution of genetic variants in younger patients with AVB is unknown. Methods and Results Using the Danish Pacemaker and Implantable Cardioverter Defibrillator (ICD) Registry, we identified all patients younger than 50 years receiving a pacemaker because of AVB in Denmark in the period from January 1, 1996 to December 31, 2015. From medical records, we identified patients with unknown cause of AVB at time of pacemaker implantation. These patients were invited to a genetic screening using a panel of 102 genes associated with inherited cardiac diseases. We identified 471 living patients with AVB of unknown cause, of whom 226 (48%) accepted participation. Median age at the time of pacemaker implantation was 39 years (interquartile range, 32-45 years), and 123 (54%) were men. We found pathogenic or likely pathogenic variants in genes associated with or possibly associated with AVB in 12 patients (5%). Most variants were found in the LMNA gene (n=5). LMNA variant carriers all had a family history of either AVB and/or sudden cardiac death. Conclusions In young patients with AVB of unknown cause, we found a possible genetic cause in 1 out of 20 participating patients. Variants in the LMNA gene were most common and associated with a family history of AVB and/or sudden cardiac death, suggesting that genetic testing should be a part of the diagnostic workup in these patients to stratify risk and screen family members.

The clinical utility of procainamide-induced late potentials on the signal averaged ECG.

BACKGROUND: Late potentials (LPs) identified on the signal averaged electrocardiogram (SAECG) are a marker for an increased risk of arrhythmias in Brugada syndrome (BrS). Procainamide is a sodium channel blocker used to diagnose BrS. The effects of Procainamide on the SAECG in those with BrS and the significance of Procainamide-induced LPs are unknown. METHODS: Procainamide provocation was performed for suspected BrS with 12-lead and SAECG pre- and post-infusion. Filtered QRS duration (fQRSd), duration of low amplitude signals <40 µV (LAS40) and root-mean-square voltage in the terminal 40 ms (RMS40) were determined. RESULTS: Data from 150 patients were included in the analysis (mean age 44.5 years, 109 males). Procainamide increased fQRSd (Pre 118.8 ± 10.5 ms, post 121.2 ± 10.2 ms, p < 0.001) and LAS40 (Pre 38.7 ± 9.8 ms, post 40.2 ± 10.5 ms, p = 0.005) and decreased RMS40 (Pre 24.6 ± 12 ms, post 22.8 ± 12 ms, p = 0.002). LPs were present in 68/150 (45%) at baseline. Fifteen patients with negative baseline SAECGs had LPs unmasked by Procainamide, but six patients had LPs at baseline that were no longer present following Procainamide. Comparing those with normal hearts (n = 48) to those with a final diagnosis of BrS (n = 38), Procainamide prolonged fQRSd to a greater extent in those with BrS. Comparing those with Procainamide-induced LPs to those with no LPs at any time did not highlight any aspect of phenotype and did not correlate with a history of ventricular arrhythmias. CONCLUSIONS: Procainamide influences the SAECG, provoking LPs in a small proportion of patients. However, there is no evidence that Procainamide-induced LPs provide additional diagnostic information or aid risk stratification.

Vasopressin and methylprednisolone for in-hospital cardiac arrest - Protocol for a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To describe the clinical trial "Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest" (VAM-IHCA). METHODS: The VAM-IHCA trial is an investigator-initiated, multicenter, randomized, placebo-controlled, parallel group, double-blind, superiority trial of vasopressin and methylprednisolone during adult in-hospital cardiac arrest. The study drugs consist of 40 mg methylprednisolone and 20 IU of vasopressin given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU).The primary outcome is return of spontaneous circulation and key secondary outcomes include survival and survival with a favorable neurological outcome at 30 days. 492 patients will be enrolled. The trial was registered at the EU Clinical Trials Register (EudraCT Number: 2017-004773-13) on Jan. 25, 2018 and ClinicalTrials.gov (Identifier: NCT03640949) on Aug. 21, 2018. RESULTS: The trial started in October 2018 and the last patient is anticipated to be included in January 2021. The primary results will be reported after 3-months follow-up and are, therefore, anticipated in mid-2021. CONCLUSION: The current article describes the design of the VAM-IHCA trial. The results from this trial will help clarify whether the combination of vasopressin and methylprednisolone when administered during in-hospital cardiac arrest improves outcomes.

Regression models for interval censored data using parametric pseudo-observations.

BACKGROUND: Time-to-event data that is subject to interval censoring is common in the practice of medical research and versatile statistical methods for estimating associations in such settings have been limited. For right censored data, non-parametric pseudo-observations have been proposed as a basis for regression modeling with the possibility to use different association measures. In this article, we propose a method for calculating pseudo-observations for interval censored data. METHODS: We develop an extension of a recently developed set of parametric pseudo-observations based on a spline-based flexible parametric estimator. The inherent competing risk issue with an interval censored event of interest necessitates the use of an illness-death model, and we formulate our method within this framework. To evaluate the empirical properties of the proposed method, we perform a simulation study and calculate pseudo-observations based on our method as well as alternative approaches. We also present an analysis of a real dataset on patients with implantable cardioverter-defibrillators who are monitored for the occurrence of a particular type of device failures by routine follow-up examinations. In this dataset, we have information on exact event times as well as the interval censored data, so we can compare analyses of pseudo-observations based on the interval censored data to those obtained using the non-parametric pseudo-observations for right censored data. RESULTS: Our simulations show that the proposed method for calculating pseudo-observations provides unbiased estimates of the cumulative incidence function as well as associations with exposure variables with appropriate coverage probabilities. The analysis of the real dataset also suggests that our method provides estimates which are in agreement with estimates obtained from the right censored data. CONCLUSIONS: The proposed method for calculating pseudo-observations based on the flexible parametric approach provides a versatile solution to the specific challenges that arise with interval censored data. This solution allows regression modeling using a range of different association measures.

Long-term follow-up of abandoned transvenous defibrillator leads: a nationwide cohort study.

AIMS: Commonly, a dysfunctional defibrillator lead is abandoned and a new lead is implanted. Long-term follow-up data on abandoned leads are sparse. We aimed to investigate the incidence and reasons for extraction of abandoned defibrillator leads in a nationwide cohort and to describe extraction procedure-related complications. METHODS AND RESULTS: All abandoned transvenous defibrillator leads were identified in the Danish Pacemaker and ICD Register from 1991 to 2019. The event-free survival of abandoned defibrillator leads was studied, and medical records of patients with interventions on abandoned defibrillator leads were audited for procedure-related data. We identified 740 abandoned defibrillator leads. Meantime from implantation to abandonment was 7.2 ± 3.8 years with mean patient age at abandonment of 66.5 ± 13.7 years. During a mean follow-up after abandonment of 4.4 ± 3.1 years, 65 (8.8%) abandoned defibrillator leads were extracted. Most frequent reason for extraction was infection (pocket and systemic) in 41 (63%) patients. Procedural outcome after lead extraction was clinical success in 63 (97%) patients. Minor complications occurred in 3 (5%) patients, and major complications in 1 (2%) patient. No patient died from complication to the procedure during 30-day follow-up after extraction. CONCLUSION: More than 90% of abandoned defibrillator leads do not need to be extracted during long-term follow-up. The most common indication for extraction is infection. Abandoned defibrillator leads can be extracted with high clinical success rate and low risk of major complications at high-volume centres.

Fracture of an epicardial left ventricular lead implanted at open-heart surgery in anticipation of future need for cardiac resynchronization therapy.

Epicardial left ventricular leads can be implanted at open-heart surgery for cardiac resynchronization therapy. We report a 2-year-old fractured epicardial left ventricular lead detected at generator implant. It highlights the importance of good surgical implant technique and of rigorous lead evaluation for signs of impending failure at generator implant.

Single and dual coil shock efficacy and predictors of shock failure in patients with modern implantable cardioverter defibrillators-a single-center paired randomized study.

PURPOSE: Implantable cardioverter defibrillators (ICDs) can treat life-threatening tachyarrhythmia with high-voltage shocks. The aims were to compare the efficacy of single and dual coil shock vectors in modern ICDs and to identify predictors of shock failure. METHODS: This is a single-center paired randomized study including 216 patients with mixed indications and ICDs from four manufacturers. All patients underwent two implant defibrillation tests using single and dual coil vectors with the test order randomized. Tested shock energy differed slightly between manufacturers because of differences in device programmability: first shock approximately 15 J below maximal output-if failed, second shock approximately 10 J below maximal output-if failed, third shock at maximal output. RESULTS: First shock success rate was 399/432 (92.4%). Comparing single and dual coil vectors, no differences were seen in first shock efficacy (91.7% vs. 93.1%, P = 0.629) or lowest tested succesfully stored energy (27.2 J vs. 27.1 J, P = 0.620). All successive internal shocks failed in 4/432 (0.9%) of inductions requiring external rescue shocks to restore circulation. Multivariate predictors of first shock failure were QRS duration (relative risk 0.81 per 10 ms, P = 0.001), amiodarone treatment (relative risk 3.30, P = 0.003), and body height (relative risk 1.70 per 10 cm, P = 0.019). CONCLUSIONS: Implant defibrillation testing of modern intravenous ICD systems demonstrates high shock efficacy with no difference between single and dual coil vectors.

Vectorcardiographic QRS area is associated with long-term outcome after cardiac resynchronization therapy.

BACKGROUND: Recent studies have suggested that vectorcardiographic measures predict left ventricular (LV) reverse remodeling and clinical outcome in patients receiving cardiac resynchronization therapy (CRT). OBJECTIVES: The objectives of this study were to compare predictive abilities of different vectorcardiographic measures (QRS area and sum absolute QRS-T integral) and transformation methods (Kors and inverse Dower) and to assess the independent association between the best predictor and outcomes in CRT recipients. METHODS: This retrospective study included CRT recipients with a digital baseline electrocardiogram, QRS duration ≥120 ms, and ejection fraction ≤35%. The end point was a composite of heart transplantation, LV assist device implantation, or all-cause death. Analyses were performed for the overall cohort and for a prespecified subgroup of patients with left bundle branch block (LBBB). RESULTS: Of 705 included patients with a mean age of 66.6 ± 11.5 years, 492 (70%) were men, 374 (53%) had ischemic heart disease, and 465 (66%) had LBBB. QRS area from vectorcardiograms derived via the Kors transformation demonstrated the best predictive value. In multivariable Cox regression, patients with a smaller QRS area (≤ 95 µVs) had an increased hazard in the overall cohort (adjusted hazard ratio 1.65; 95% CI 1.25-2.18 P < .001) and in the LBBB subgroup (adjusted hazard ratio 1.95; 95% CI 1.38-2.76 P < .001). QRS area was associated with outcome in patients with QRS duration <150 ms (unadjusted hazard ratio 3.85; 95% CI 2.02-7.37 P < .001) and in patients with QRS duration ≥150 ms (unadjusted hazard ratio 1.76; 95% CI 1.32-2.34 P < .001). CONCLUSION: Vectorcardiographic QRS area is associated with survival free from heart transplantation and LV assist device implantation in CRT recipients.

Fatal cardiac arrhythmia caused by tumor lysis in a patient with diffuse large B-cell lymphoma upon start of R-CHOP.

Tumor lysis syndrome is rare in diffuse large cell lymphoma, but it is important to recognize the risk in patients with massive tumor burden and reduced kidney function. Very intense vigilance can be necessary despite adequate prophylactic measures and certain drugs may exacerbate electrolyte derangements.

Failure to Treat Life-Threatening Ventricular Tachyarrhythmias in Contemporary Implantable Cardioverter-Defibrillators: Implications for Strategic Programming.

BACKGROUND: In clinical trials, manufacturer-specific, strategic programming of implantable cardioverter-defibrillators (ICDs), including faster detection rates, reduces unnecessary therapy but permits therapy for ventricular tachycardia/ventricular fibrillation (VF). Present consensus recommends a generic rate threshold between 185 and 200 beats per minute, which exceeds the rate tested in clinical trials for some manufacturers. In a case series, we sought to determine the relationship between programmed parameters and failure of modern ICDs to treat VF. METHODS AND RESULTS: We reviewed cases in which normally functioning ICDs failed to deliver timely therapy for VF from April 2015 to January 2017 at 4 institutions. Of 10 ambulatory patients, 5 died from untreated VF, 4 had cardiac arrests requiring external shocks, and 1 was rescued by a delayed ICD shock. VF did not satisfy programmed detection criteria in 9 patients (90%). Seven of these patients had slowest detection rates that were consistent with generic recommendations but not tested in a peer-reviewed trial for their manufacturer's ICDs. Manufacturer-specific factors interacted with fast detection rates to withhold therapy, including strict VF episode termination rules, enhancements to minimize T-wave oversensing, and features that restrict therapy to regular rhythms in ventricular tachycardia zones. Untreated VF despite recommended programming accounted for 56% of sudden deaths and 11% of all deaths during the study period. CONCLUSIONS: Complex and unanticipated interactions between manufacturer-specific features and generic programming can prevent therapy for VF. More data are needed to assess the risks and benefits of translating evidence-based detection parameters from one manufacturer to another.

Validation of defibrillator lead performance registry data: insight from the Danish Pacemaker and ICD Register.

AIMS: The validity of registry data on defibrillator lead performance is described only sparsely, despite its clinical importance. This study investigated the validity of defibrillator lead performance registry data in a nationwide and population-based registry. METHODS AND RESULTS: We identified all reported surgical interventions due to defibrillator lead events in the Danish Pacemaker and ICD Register (DPIR) from 2000 to 2013. Medical records of all patients (n = 753) were examined blinded for 5 predefined intervention types and 18 reasons for lead intervention. The overall level of agreement for the types of lead intervention had a positive predictive value (PPV) of 89.4% [95% confidence interval (CI): 87.0-91.5%] and an adjusted agreement (κ value) of 0.81 (95% CI: 0.77-0.85) representing an almost perfect match. Regarding the reasons for lead intervention, the overall PPV was 63.0% (95% CI: 54.8-61.7%) with a κ value of 0.60 (95% CI: 0.55-0.64) representing a moderate match with only few subcategories having low PPV. By redistribution of the specific reasons for lead interventions into three categories commonly used to report lead performance, the overall PPV improved to 87.9% (95% CI: 85.2-90.2%) with a κ value of 0.82 (95% CI:0.78-0.86) representing an almost perfect match. CONCLUSION: The validity of data on defibrillator lead performance recorded in the DPIR is excellent for the specific types of lead intervention and good for the specific reasons for defibrillator lead intervention. The validity of the less detailed overall reasons for lead interventions commonly used to report lead performance is also excellent. These findings indicate high registry data quality appropriate for scientific analysis and industry-independent post-marketing surveillance.

Acute coronary angiography in patients resuscitated from out-of-hospital cardiac arrest--a systematic review and meta-analysis.

INTRODUCTION: Out-of-hospital cardiac arrest has a poor prognosis. The main aetiology is ischaemic heart disease. AIM: To make a systematic review addressing the question: "In patients with return of spontaneous circulation following out-of-hospital cardiac arrest, does acute coronary angiography with coronary intervention improve survival compared to conventional treatment?" METHODS: Peer reviewed articles written in English with relevant prognostic data were included. Comparison studies on patients with and without acute coronary angiography were pooled in a meta-analysis. RESULTS: Thirty-two non-randomised studies were included of which 22 were case-series without patients with conservative treatment. Seven studies with specific efforts to control confounding had statistical evidence to support the use of acute coronary angiography following resuscitation from out-of-hospital cardiac arrest. The remaining 25 studies were considered neutral. Following acute coronary angiography, the survival to hospital discharge, 30 days or six months ranged from 23% to 86%. In patients without an obvious non-cardiac aetiology, the prevalence of significant coronary artery disease ranged from 59% to 71%. Electrocardiographic findings were unreliable for identifying angiographic findings of acute coronary syndrome. Ten comparison studies demonstrated a pooled unadjusted odds ratio for survival of 2.78 (1.89; 4.10) favouring acute coronary angiography. CONCLUSION: No randomised studies exist on acute coronary angiography following out-of-hospital cardiac arrest. An increasing number of observational studies support feasibility and a possible survival benefit of an early invasive approach. In patients without an obvious non-cardiac aetiology, acute coronary angiography should be strongly considered irrespective of electrocardiographic findings due to a high prevalence of coronary artery disease.

[Coronary angiography should be considered after out-of-hospital cardiac arrest]. / Koronarangiografi bør overvejes efter hjertestop uden for hospital.

Cardiac arrest has a poor prognosis. Ischaemic heart disease is the main cause of out-of-hospital cardiac arrest. This paper is a review of the essential studies on acute coronary angiography and angioplasty in post resuscitation care. No randomised studies were found. Observational studies support the use of acute angiography in ST-segment elevation myocardial infarction. The negative predictive value of ST-segment elevation can be low after out-of-hospital cardiac arrest, and acute angiography should be considered regardless of electrocardiographic findings.