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British Journal of Pharmacology Mar 2022Ventricular cardiac arrhythmia is a life threating condition arising from abnormal functioning of many factors in concert. Animal models mirroring human... (Review)
Review
Ventricular cardiac arrhythmia is a life threating condition arising from abnormal functioning of many factors in concert. Animal models mirroring human electrophysiology are essential to predict and understand the rare pro- and anti-arrhythmic effects of drugs. This is very well accomplished by the canine chronic atrioventricular block (CAVB) model. Here we summarize canine models for cardiovascular research, and describe the development of the CAVB model from its beginning. Understanding of the structural, contractile and electrical remodelling processes following atrioventricular (AV) block provides insight in the many factors contributing to drug-induced arrhythmia. We also review all safety pharmacology studies, efficacy and mechanistic studies on anti-arrhythmic drugs in CAVB dogs. Finally, we compare pros and cons with other in vivo preclinical animal models. In view of the tremendous amount of data obtained over the last 100 years from the CAVB dog model, it can be considered as man's best friend in preclinical drug research. LINKED ARTICLES: This article is part of a themed issue on Preclinical Models for Cardiovascular disease research (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.5/issuetoc.
Topics: Animals; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Atrioventricular Block; Dogs; Heart; Humans
PubMed: 33684961
DOI: 10.1111/bph.15436 -
International Heart Journal Jan 2021Tricuspid valve (TV) surgery is associated with a high risk of postoperative pacemaker requirement. We set out to identify the incidence of atrioventricular block (AVB)...
Tricuspid valve (TV) surgery is associated with a high risk of postoperative pacemaker requirement. We set out to identify the incidence of atrioventricular block (AVB) after TV surgery and determine whether atrioventricular conduction recovers within time.We investigated pre/intra- and postoperative predictors of AVB in patients who underwent tricuspid valve surgery (not only isolated TV surgery) at our institution between 2004 and 2017. Patients who had pacemakers prior to surgery were excluded.One year after surgery, 5.8% of the surviving cohort had received a pacemaker due to AVB. In the complete follow-up time, 33 out of 505 patients required pacemaker implantation because of AVB. Of the 37 patients who presented to the intensive care unit postoperatively with AVB III, 14 (38%) underwent pacemaker implantation for AVB, and 20 (54%) did not require a pacemaker. AVB III at ICU admission was identified as a predictor of pacemaker implantation (OR: 9.7, CI: 3.8-24.5, P < 0.001). TV endocarditis was also identified as a predictor (OR: 12.4, CI: 3.3-46.3, P < 0.001). Eleven out of 32 patients (34%) with tricuspid endocarditis required a pacemaker for AVB. The mean ventricular pacing burden within the first 5 years after pacemaker implantation was 79%.The issue of AVB after TV surgery is significant. Both the initial rhythm after surgery and etiology of the tricuspid disease can help predict pacemaker requirement. Within the first 5 years after surgery, the ventricular pacing burden remains high without relevant rhythm recovery.
Topics: Adult; Aged; Aged, 80 and over; Atrioventricular Block; Disease-Free Survival; Endocarditis; Female; Follow-Up Studies; Heart Valve Diseases; Humans; Intensive Care Units; Male; Middle Aged; Pacemaker, Artificial; Postoperative Complications; Retrospective Studies; Risk Factors; Tricuspid Valve
PubMed: 33455981
DOI: 10.1536/ihj.20-278 -
Pacing and Clinical Electrophysiology :... Apr 2022COVID-19 has recently been associated with the development of bradyarrhythmias, although its mechanism is still unclear. We aim to summarize the existing evidence... (Review)
Review
COVID-19 has recently been associated with the development of bradyarrhythmias, although its mechanism is still unclear. We aim to summarize the existing evidence regarding bradyarrhythmia in COVID-19 and provide future directions for research. Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and EMBASE for all peer-reviewed articles using keywords including"Bradycardia," "atrioventricular block," and "COVID-19″ from their inception to October 13, 2021. Forty-three articles, including 11 observational studies and 59 cases from case reports and series, were included in the systematic review. Although some observational studies reported increased mortality in those with bradyarrhythmia and COVID-19, the lack of comparative groups and small sample sizes hinder the ability to draw definitive conclusions. Among 59 COVID-19 patients with bradycardia from case reports and series, bradycardia most often occurred in those with severe or critical COVID-19, and complete heart block occurred in the majority of cases despite preserved LVEF (55.9%). Pacemaker insertion was required in 76.3% of the patients, most of which were permanent implants (45.8%). This systematic review summarizes the current evidence and characteristics of bradyarrhythmia in patients with COVID-19. Further studies are critical to assess the reversibility of bradyarrhythmia in COVID-19 patients and to clarify potential therapeutic targets including the need for permanent pacing.
Topics: Atrioventricular Block; Bradycardia; COVID-19; Humans
PubMed: 35182433
DOI: 10.1111/pace.14466 -
JACC. Clinical Electrophysiology Jan 2020
Topics: Atrioventricular Block; Humans; Pacemaker, Artificial
PubMed: 31709983
DOI: 10.1016/j.jacep.2019.11.001 -
Journal of the American Heart... Jun 2024Advanced atrioventricular block (AVB), that is, higher than second-degree Mobitz-1, is an abnormal finding in athletes. Despite intensive investigation, in several cases...
BACKGROUND
Advanced atrioventricular block (AVB), that is, higher than second-degree Mobitz-1, is an abnormal finding in athletes. Despite intensive investigation, in several cases the pathogenesis remains unknown, but frequently pacemaker implantation is still indicated. Increasing evidence points to circulating anti-Ro/Sjögren syndrome-related antigen A (SSA) antibodies cross-reacting with L-type calcium channel and inhibiting the related current as an epidemiologically relevant and potentially reversible cause of isolated AVB in adults. The aim of the study was to determine the prevalence of anti-Ro/SSA-associated advanced AVBs in a large sample of young athletes.
METHODS AND RESULTS
A total of 2536 consecutive athletes aged <40 years without a history of cardiac diseases/interventions were enrolled in a cross-sectional study. Resting and exercise electrocardiography was performed, and those presenting any AVB were further evaluated by 24-hour Holter ECG. Athletes with second-degree AVBs and their mothers underwent anti-Ro/SSA testing. Moreover, purified immunoglobulin G from subjects with anti-Ro/SSA-positive and anti-Ro/SSA-negative advanced AVB were tested on L-type calcium current and L-type-calcium channel expression using tSA201 cells. The global prevalence of advanced AVB in the overall sample was ≈0.1%, but the risk considerably increased (2%) when intensely trained postpubertal male subjects were selectively considered. While none of the athletes with advanced AVB showed heart abnormalities, in 100% of cases anti-Ro/SSA antibodies were detected. Ex vivo experiments showed that immunoglobulin G from anti-Ro/SSA-positive but not -negative subjects with advanced AVB acutely inhibit L-type calcium current and chronically downregulate L-type-calcium channel expression.
CONCLUSIONS
Our study provides evidence that advanced AVB occurs in young athletes, in most cases associated with anti-Ro/SSA antibodies blocking L-type calcium channels. These findings may open new avenues for immunomodulating therapies to reduce the risk of life-threatening events in athletes, avoiding or delaying pacemaker implantation.
Topics: Humans; Male; Female; Adult; Cross-Sectional Studies; Atrioventricular Block; Prevalence; Young Adult; Calcium Channels, L-Type; Antibodies, Antinuclear; Athletes; Adolescent; Electrocardiography, Ambulatory; Ribonucleoproteins
PubMed: 38879447
DOI: 10.1161/JAHA.124.034893 -
Heart Rhythm Sep 2023
Topics: Humans; Atrioventricular Block
PubMed: 37648362
DOI: 10.1016/j.hrthm.2022.11.014 -
JAMA Network Open May 2019Pacemaker implantations as a treatment for atrioventricular (AV) block are increasing worldwide. Prevention strategies for AV block are lacking because modifiable risk...
IMPORTANCE
Pacemaker implantations as a treatment for atrioventricular (AV) block are increasing worldwide. Prevention strategies for AV block are lacking because modifiable risk factors have not yet been identified.
OBJECTIVE
To identify risk factors for AV block in community-dwelling individuals.
DESIGN, SETTING, AND PARTICIPANTS
In this population-based cohort study, data from the Mini-Finland Health Survey, conducted from January 1, 1978, to December 31, 1980, were used to examine demographics, comorbidities, habits, and laboratory and electrocardiographic (ECG) measurements as potential risk factors for incident AV block. Data were ascertained during follow-up from January 1, 1987, through December 31, 2011, using a nationwide registry. A total of 6146 community-dwelling individuals were included in the analysis performed from January 15 through April 3, 2018.
MAIN OUTCOMES AND MEASURES
Incidence of AV block (hospitalization for second- or third-degree AV block).
RESULTS
Among the 6146 participants (3449 [56.1%] women; mean [SD] age, 49.2 [12.9] years), 529 (8.6%) had ECG evidence of conduction disease and 58 (0.9%) experienced a hospitalization with AV block. Older age (hazard ratio [HR] per 5-year increment, 1.34; 95% CI, 1.16-1.54; P < .001), male sex (HR, 2.04; 95% CI, 1.19-3.45; P = .01), a history of myocardial infarction (HR, 3.54; 95% CI, 1.33-9.42; P = .01), and a history of congestive heart failure (HR, 3.33; 95% CI, 1.10-10.09; P = .03) were each independently associated with AV block. Two modifiable risk factors were also independently associated with AV block. Every 10-mm Hg increase in systolic blood pressure was associated with a 22% higher risk (HR, 1.22; 95% CI, 1.10-1.34; P = .005), and every 20-mg/dL increase in fasting glucose level was associated with a 22% higher risk (HR, 1.22; 95% CI, 1.08-1.35; P = .001). Both risk factors remained statistically significant (HR for systolic blood pressure, 1.26 [95% CI, 1.06-1.49; P = .007]; HR for glucose level, 1.22 [95% CI, 1.04-1.43; P = .01]) after adjustment for major adverse coronary events during the follow-up period. In population-attributable risk assessment, an estimated 47% (95% CI, 8%-67%) of AV blocks may have been avoided if all participants exhibited ideal blood pressure and 11% (95% CI, 2%-21%) may have been avoided if all had a normal fasting glucose level.
CONCLUSIONS AND RELEVANCE
In this analysis of data from a population-based cohort study, suboptimal blood pressure and fasting glucose level were associated with AV block. These results suggest that a large proportion of AV blocks are assocated with these risk factors, even after adjusting for other major adverse coronary events.
Topics: Adult; Age Factors; Atrioventricular Block; Blood Glucose; Blood Pressure; Cohort Studies; Cross-Sectional Studies; Female; Health Surveys; Humans; Independent Living; Male; Middle Aged; Registries; Risk Factors; Sex Factors
PubMed: 31125096
DOI: 10.1001/jamanetworkopen.2019.4176 -
Journal of the American Heart... Jun 2022
Topics: Atrioventricular Block; Cardiovascular System; Electrocardiography; Heart; Humans; Magnetic Resonance Imaging
PubMed: 35658512
DOI: 10.1161/JAHA.122.026199 -
Internal Medicine (Tokyo, Japan) Nov 2021
Topics: Atrial Fibrillation; Atrial Flutter; Atrioventricular Block; Electrocardiography; Humans
PubMed: 33994443
DOI: 10.2169/internalmedicine.7514-21 -
Journal of the American Heart... May 2021Background The temporal incidence of high-grade atrioventricular block (HAVB) after transcatheter aortic valve replacement (TAVR) is uncertain. As a result,...
Background The temporal incidence of high-grade atrioventricular block (HAVB) after transcatheter aortic valve replacement (TAVR) is uncertain. As a result, periprocedural monitoring and pacing strategies remain controversial. This study aimed to describe the temporal incidence of initial episode of HAVB stratified by pre- and post-TAVR conduction and identify predictors of delayed events. Methods and Results Consecutive patients undergoing TAVR at a single center between February 2012 and June 2019 were retrospectively assessed for HAVB within 30 days. Patients with prior aortic valve replacement, permanent pacemaker (PPM), or conversion to surgical replacement were excluded. Multivariable logistic regression was performed to assess predictors of delayed HAVB (initial event >24 hours post-TAVR). A total of 953 patients were included in this study. HAVB occurred in 153 (16.1%). After exclusion of those with prophylactic PPM placed post-TAVR, the incidence of delayed HAVB was 33/882 (3.7%). Variables independently associated with delayed HAVB included baseline first-degree atrioventricular block or right bundle-branch block, self-expanding valve, and new left bundle-branch block. Forty patients had intraprocedural transient HAVB, including 16 who developed HAVB recurrence and 6 who had PPM implantation without recurrence. PPM was placed for HAVB in 130 (13.6%) (self-expanding valve, 23.7% versus balloon-expandable valve, 11.9%; <0.001). Eight (0.8%) patients died by 30 days, including 1 unexplained without PPM present. Conclusions Delayed HAVB occurs with higher frequency in patients with baseline first-degree atrioventricular block or right bundle-branch block, new left bundle-branch block, and self-expanding valve. These findings provide insight into optimal monitoring and pacing strategies based on periprocedural ECG findings.
Topics: Aged, 80 and over; Aortic Valve Stenosis; Atrioventricular Block; Electrocardiography; Female; Follow-Up Studies; Heart Conduction System; Heart Rate; Humans; Incidence; Male; Minnesota; Postoperative Complications; Retrospective Studies; Risk Factors; Risk Management; Transcatheter Aortic Valve Replacement
PubMed: 33960210
DOI: 10.1161/JAHA.120.020033