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Circulation Oct 2020Many widely used medications may cause or exacerbate a variety of arrhythmias. Numerous antiarrhythmic agents, antimicrobial drugs, psychotropic medications, and... (Review)
Review
Many widely used medications may cause or exacerbate a variety of arrhythmias. Numerous antiarrhythmic agents, antimicrobial drugs, psychotropic medications, and methadone, as well as a growing list of drugs from other therapeutic classes (neurological drugs, anticancer agents, and many others), can prolong the QT interval and provoke torsades de pointes. Perhaps less familiar to clinicians is the fact that drugs can also trigger other arrhythmias, including bradyarrhythmias, atrial fibrillation/atrial flutter, atrial tachycardia, atrioventricular nodal reentrant tachycardia, monomorphic ventricular tachycardia, and Brugada syndrome. Some drug-induced arrhythmias (bradyarrhythmias, atrial tachycardia, atrioventricular node reentrant tachycardia) are significant predominantly because of their symptoms; others (monomorphic ventricular tachycardia, Brugada syndrome, torsades de pointes) may result in serious consequences, including sudden cardiac death. Mechanisms of arrhythmias are well known for some medications but, in other instances, remain poorly understood. For some drug-induced arrhythmias, particularly torsades de pointes, risk factors are well defined. Modification of risk factors, when possible, is important for prevention and risk reduction. In patients with nonmodifiable risk factors who require a potentially arrhythmia-inducing drug, enhanced electrocardiographic and other monitoring strategies may be beneficial for early detection and treatment. Management of drug-induced arrhythmias includes discontinuation of the offending medication and following treatment guidelines for the specific arrhythmia. In overdose situations, targeted detoxification strategies may be needed. Awareness of drugs that may cause arrhythmias and knowledge of distinct arrhythmias that may be drug-induced are essential for clinicians. Consideration of the possibility that a patient's arrythmia could be drug-induced is important.
Topics: American Heart Association; Arrhythmias, Cardiac; Electrocardiography; Risk Factors; United States
PubMed: 32929996
DOI: 10.1161/CIR.0000000000000905 -
JAMA Internal Medicine Sep 2021The notion that caffeine increases the risk of cardiac arrhythmias is common. However, evidence that the consumption of caffeinated products increases the risk of...
IMPORTANCE
The notion that caffeine increases the risk of cardiac arrhythmias is common. However, evidence that the consumption of caffeinated products increases the risk of arrhythmias remains poorly substantiated.
OBJECTIVE
To assess the association between consumption of common caffeinated products and the risk of arrhythmias.
DESIGN, SETTING, AND PARTICIPANTS
This prospective cohort study analyzed longitudinal data from the UK Biobank between January 1, 2006, and December 31, 2018. After exclusion criteria were applied, 386 258 individuals were available for analyses.
EXPOSURES
Daily coffee intake and genetic polymorphisms that affect caffeine metabolism.
MAIN OUTCOMES AND MEASURES
Any cardiac arrhythmia, including atrial fibrillation or flutter, supraventricular tachycardia, ventricular tachycardia, premature atrial complexes, and premature ventricular complexes.
RESULTS
A total of 386 258 individuals (mean [SD] age, 56 [8] years; 52.3% female) were assessed. During a mean (SD) follow-up of 4.5 (3.1) years, 16 979 participants developed an incident arrhythmia. After adjustment for demographic characteristics, comorbid conditions, and lifestyle habits, each additional cup of habitual coffee consumed was associated with a 3% lower risk of incident arrhythmia (hazard ratio [HR], 0.97; 95% CI, 0.96-0.98; P < .001). In analyses of each arrhythmia alone, statistically significant associations exhibiting a similar magnitude were observed for atrial fibrillation and/or flutter (HR, 0.97; 95% CI, 0.96-0.98; P < .001) and supraventricular tachycardia (HR, 0.96; 95% CI, 0.94-0.99; P = .002). Two distinct interaction analyses, one using a caffeine metabolism-related polygenic score of 7 genetic polymorphisms and another restricted to CYP1A2 rs762551 alone, did not reveal any evidence of effect modification. A mendelian randomization study that used these same genetic variants revealed no significant association between underlying propensities to differing caffeine metabolism and the risk of incident arrhythmia.
CONCLUSIONS AND RELEVANCE
In this prospective cohort study, greater amounts of habitual coffee consumption were associated with a lower risk of arrhythmia, with no evidence that genetically mediated caffeine metabolism affected that association. Mendelian randomization failed to provide evidence that caffeine consumption was associated with arrhythmias.
Topics: Adult; Aged; Caffeine; Coffee; Cytochrome P-450 CYP1A2; Female; Follow-Up Studies; Humans; Incidence; Life Style; Male; Mendelian Randomization Analysis; Middle Aged; Polymorphism, Genetic; Prospective Studies; Risk Factors; Tachycardia; Time Factors; United States
PubMed: 34279564
DOI: 10.1001/jamainternmed.2021.3616 -
Academic Emergency Medicine : Official... Feb 2023The objective was to evaluate the comparative effectiveness and safety of pharmacological and nonpharmacological management options for atrial fibrillation/atrial... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The objective was to evaluate the comparative effectiveness and safety of pharmacological and nonpharmacological management options for atrial fibrillation/atrial flutter with rapid ventricular response (AFRVR) in patients with acute decompensated heart failure (ADHF) in the acute care setting.
METHODS
This study was a systematic review of observational studies or randomized clinical trials (RCT) of adult patients with AFRVR and concomitant ADHF in the emergency department (ED), intensive care unit, or step-down unit. The primary effectiveness outcome was successful rate or rhythm control. Safety outcomes were adverse events, such as symptomatic hypotension and venous thromboembolism.
RESULTS
A total of 6577 unique articles were identified. Five studies met inclusion criteria: one RCT in the inpatient setting and four retrospective studies, two in the ED and the other three in the inpatient setting. In the RCT of diltiazem versus placebo, 22 patients (100%) in the treatment group had a therapeutic response compared to 0/15 (0%) in the placebo group, with no significant safety differences between the two groups. For three of the observational studies, data were limited. One observation study showed no difference between metoprolol and diltiazem for successful rate control, but worsening heart failure symptoms occurred more frequently in those receiving diltiazem compared to metoprolol (19 patients [33%] vs. 10 patients [15%], p = 0.019). A single study included electrical cardioversion (one patient exposed with failure to convert to sinus rhythm) as nonpharmacological management. The overall risk of bias for included studies ranged from serious to critical. Missing data and heterogeneity of definitions for effectiveness and safety outcomes precluded the combination of results for quantitative meta-analysis.
CONCLUSIONS
High-level evidence to inform clinical decision making regarding effective and safe management of AFRVR in patients with ADHF in the acute care setting is lacking.
Topics: Adult; Humans; Atrial Fibrillation; Atrial Flutter; Diltiazem; Metoprolol; Anti-Arrhythmia Agents; Heart Failure; Randomized Controlled Trials as Topic; Observational Studies as Topic
PubMed: 36326565
DOI: 10.1111/acem.14618 -
Stroke May 2022The risk of major adverse cardiovascular events is substantially increased following a stroke. Although exercise-based cardiac rehabilitation has been shown to improve...
BACKGROUND
The risk of major adverse cardiovascular events is substantially increased following a stroke. Although exercise-based cardiac rehabilitation has been shown to improve prognosis following cardiac events, it is not part of routine care for people following a stroke. We, therefore, investigated the association between cardiac rehabilitation and major adverse cardiovascular events for people following a stroke. Following a stroke, individuals have an increased risk of new-onset cardiovascular complications. However, the incidence and long-term clinical consequence of newly diagnosed cardiovascular complications following a stroke is unclear. The aim of the present study was to investigate the incidence and long-term clinical outcomes of newly diagnosed cardiovascular complications following incident ischemic stroke.
METHODS
A retrospective cohort study was conducted using anonymized electronic medical records from 53 participating health care organizations. Patients with incident ischemic stroke aged ≥18 years with 5 years of follow-up were included. Patients who were diagnosed with new-onset cardiovascular complications (heart failure, severe ventricular arrhythmia, atrial fibrillation, ischemic heart disease, Takotsubo syndrome) within 4-weeks (exposure) of incident ischemic stroke were 1:1 propensity score-matched (age, sex, ethnicity, comorbidities, cardiovascular care) with ischemic stroke patients who were not diagnosed with a new-onset cardiovascular complication (control). Logistic regression models produced odds ratios (OR) with 95% CIs for 5-year incidence of all-cause mortality, recurrent stroke, hospitalization, and acute myocardial infarction.
RESULTS
Of 365 383 patients with stroke with 5-year follow-up: 11.1% developed acute coronary syndrome; 8.8% atrial fibrillation/flutter; 6.4% heart failure; 1.2% severe ventricular arrythmias; and 0.1% Takotsubo syndrome within 4 weeks of incident ischemic stroke. Following propensity score matching, odds of 5-year all-cause mortality were significantly higher in stroke patients with acute coronary syndrome (odds ratio, 1.49 [95% CI, 1.44-1.54]), atrial fibrillation/flutter (1.45 [1.40-1.50]), heart failure (1.83 [1.76-1.91]), and severe ventricular arrhythmias (2.08 [1.90-2.29]), compared with matched controls. Odds of 5-year rehospitalization and acute myocardial infarction were also significantly higher for patients with stroke diagnosed with new-onset cardiovascular complications. Takotsubo syndrome was associated with significantly higher odds of 5-year composite major adverse cardiovascular events (1.89 [1.29-2.77]). Atrial fibrillation/flutter was the only new-onset cardiac complication associated with significantly higher odds of recurrent ischemic stroke at 5 years (1.10 [1.07-1.14]).
CONCLUSIONS
New-onset cardiovascular complications diagnosed following an ischemic stroke are very common and associate with significantly worse 5-year prognosis in terms of major adverse cardiovascular events. People with stroke and newly diagnosed cardiovascular complications had >50% prevalence of recurrent stroke at 5 years.
Topics: Acute Coronary Syndrome; Adolescent; Adult; Atrial Fibrillation; Heart Failure; Humans; Incidence; Ischemic Stroke; Myocardial Infarction; Retrospective Studies; Risk Factors; Stroke; Takotsubo Cardiomyopathy
PubMed: 35354300
DOI: 10.1161/STROKEAHA.121.037316 -
Cell Cycle (Georgetown, Tex.) Nov 2019Preservation and development of life depend on the adequate segregation of sister chromatids during mitosis and meiosis. This process is ensured by the cohesin... (Review)
Review
Preservation and development of life depend on the adequate segregation of sister chromatids during mitosis and meiosis. This process is ensured by the cohesin multi-subunit complex. Mutations in this complex have been associated with an increasing number of diseases, termed cohesinopathies. The best characterized cohesinopathy is Cornelia de Lange syndrome (CdLS), in which intellectual and growth retardations are the main phenotypic manifestations. Despite some overlap, the clinical manifestations of cohesinopathies vary considerably. Novel roles of the cohesin complex have emerged during the past decades, suggesting that important cell cycle regulators exert important biological effects through non-cohesion-related functions and broadening the potential pathomechanisms involved in cohesinopathies. This review focuses on non-cohesion-related functions of the cohesin complex, gene dosage effect, epigenetic regulation and TGF-β in cohesinopathy context, especially in comparison to hronic trial and ntestinal ysrhythmia (CAID) syndrome, a very distinct cohesinopathy caused by a homozygous Shugoshin-1 (SGO1) mutation (K23E) and characterized by pacemaker failure in both heart (sick sinus syndrome followed by atrial flutter) and gut (chronic intestinal pseudo-obstruction) with no intellectual or growth delay. We discuss the possible impact of SGO1 alterations in human pathologies and the potential impact of the SGO1 K23E mutation in the sinus node and gut development and functions. We suggest that the human phenotypes observed in CdLS, CAID syndrome and other cohesinopathies can inform future studies into the less well-known non-cohesion-related functions of cohesin complex genes. : AD: Alzheimer Disease; AFF4: AF4/FMR2 Family Member 4; ANKRD11: Ankyrin Repeat Domain 11; APC: Anaphase Promoter Complex; ASD: Atrial Septal Defect; ATRX: ATRX Chromatin Remodeler; ATRX: Alpha Thalassemia X-linked intellectual disability syndrome; BIRC5: Baculoviral IAP Repeat Containing 5; BMP: Bone Morphogenetic Protein; BRD4: Bromodomain Containing 4; BUB1: BUB1 Mitotic Checkpoint Serine/Threonine Kinase; CAID: Chronic Atrial and Intestinal Dysrhythmia; CDK1: Cyclin Dependent Kinase 1; CdLS: Cornelia de Lange Syndrome; CHD: Congenital Heart Disease; CHOPS: Cognitive impairment, coarse facies, Heart defects, Obesity, Pulmonary involvement, Short stature, and skeletal dysplasia; CIPO: Chronic Intestinal Pseudo-Obstruction; c-kit: KIT Proto-Oncogene Receptor Tyrosine Kinase; CoATs: Cohesin Acetyltransferases; CTCF: CCCTC-Binding Factor; DDX11: DEAD/H-Box Helicase 11; ERG: Transcriptional Regulator ERG; ESCO2: Establishment of Sister Chromatid Cohesion N-Acetyltransferase 2; GJC1: Gap Junction Protein Gamma 1; H2A: Histone H2A; H3K4: Histone H3 Lysine 4; H3K9: Histone H3 Lysine 9; HCN4: Hyperpolarization Activated Cyclic Nucleotide Gated Potassium and Sodium Channel 4;p HDAC8: Histone deacetylases 8; HP1: Heterochromatin Protein 1; ICC: Interstitial Cells of Cajal; ICC-MP: Myenteric Plexus Interstitial cells of Cajal; ICC-DMP: Deep Muscular Plexus Interstitial cells of Cajal; I: Pacemaker Funny Current; IP3: Inositol trisphosphate; JNK: C-Jun N-Terminal Kinase; LDS: Loeys-Dietz Syndrome; LOAD: Late-Onset Alzheimer Disease; MAPK: Mitogen-Activated Protein Kinase; MAU: MAU Sister Chromatid Cohesion Factor; MFS: Marfan Syndrome; NIPBL: NIPBL, Cohesin Loading Factor; OCT4: Octamer-Binding Protein 4; P38: P38 MAP Kinase; PDA: Patent Ductus Arteriosus; PDS5: PDS5 Cohesin Associated Factor; P-H3: Phospho Histone H3; PLK1: Polo Like Kinase 1; POPDC1: Popeye Domain Containing 1; POPDC2: Popeye Domain Containing 2; PP2A: Protein Phosphatase 2; RAD21: RAD21 Cohesin Complex Component; RBS: Roberts Syndrome; REC8: REC8 Meiotic Recombination Protein; RNAP2: RNA polymerase II; SAN: Sinoatrial node; SCN5A: Sodium Voltage-Gated Channel Alpha Subunit 5; SEC: Super Elongation Complex; SGO1: Shogoshin-1; SMAD: SMAD Family Member; SMC1A: Structural Maintenance of Chromosomes 1A; SMC3: Structural Maintenance of Chromosomes 3; SNV: Single Nucleotide Variant; SOX2: SRY-Box 2; SOX17: SRY-Box 17; SSS: Sick Sinus Syndrome; STAG2: Cohesin Subunit SA-2; TADs: Topology Associated Domains; TBX: T-box transcription factors; TGF-β: Transforming Growth Factor β; TGFBR: Transforming Growth Factor β receptor; TOF: Tetralogy of Fallot; TREK1: TREK-1 K(+) Channel Subunit; VSD: Ventricular Septal Defect; WABS: Warsaw Breakage Syndrome; WAPL: WAPL Cohesin Release Factor.
Topics: Animals; Atrial Flutter; Cell Cycle Proteins; Chromatids; Chromosomal Proteins, Non-Histone; Chromosome Segregation; De Lange Syndrome; Humans; Intestinal Pseudo-Obstruction; Mice; Mice, Inbred C57BL; Proto-Oncogene Mas; Sick Sinus Syndrome; Cohesins
PubMed: 31516082
DOI: 10.1080/15384101.2019.1658476