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JAMA Network Open Oct 2023The combination of ceftriaxone and lansoprazole has been shown to prolong the corrected QT interval on electrocardiogram. However, it is unknown whether this translates...
IMPORTANCE
The combination of ceftriaxone and lansoprazole has been shown to prolong the corrected QT interval on electrocardiogram. However, it is unknown whether this translates to clinically important patient outcomes.
OBJECTIVE
To compare lansoprazole with another proton pump inhibitor (PPI) during ceftriaxone treatment in terms of risk for ventricular arrhythmia, cardiac arrest, and in-hospital mortality.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective cohort study including adult medical inpatients receiving ceftriaxone with lansoprazole or another PPI in 13 hospitals in Ontario, Canada, was conducted from January 1, 2015, to December 31, 2021.
EXPOSURE
Lansoprazole during ceftriaxone treatment vs other PPIs during ceftriaxone treatment.
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of ventricular arrhythmia or cardiac arrest that occurred after hospital admission. The secondary outcome was all-cause in-hospital mortality. Propensity-score weighting was used to adjust for covariates including hospital site, demographic characteristics, comorbidities, risk factors for ventricular arrhythmia, illness severity, admitting diagnoses, and concomitant medications.
RESULTS
Of the 31 152 patients hospitalized on internal medicine wards who were treated with ceftriaxone while receiving a PPI, 16 135 patients (51.8%) were male, and the mean (SD) age was 71.7 (16.0) years. The study included 3747 patients in the lansoprazole group and 27 405 patients in the other PPI group. Ventricular arrhythmia or cardiac arrest occurred in 126 patients (3.4%) within the lansoprazole group and 319 patients (1.2%) within the other PPI group. In-hospital mortality occurred in 746 patients (19.9%) within the lansoprazole group and 2762 patients (10.1%) in the other PPI group. After weighting using propensity scores, the adjusted risk difference for the lansoprazole group minus other PPI group was 1.7% (95% CI, 1.1%-2.3%) for ventricular arrhythmia or cardiac arrest and 7.4% (95% CI, 6.1%-8.8%) for in-hospital mortality.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that combination therapy with lansoprazole and ceftriaxone should be avoided. More studies are needed to determine whether these findings could be replicated in other populations and settings.
Topics: Adult; Humans; Male; Aged; Female; Lansoprazole; Ceftriaxone; Cohort Studies; Retrospective Studies; Arrhythmias, Cardiac; Heart Arrest; Proton Pump Inhibitors; Inpatients; Ontario
PubMed: 37883084
DOI: 10.1001/jamanetworkopen.2023.39893 -
Heart Rhythm Oct 2023This international multidisciplinary expert consensus statement is intended to provide comprehensive guidance that can be referenced at the point of care to cardiac...
This international multidisciplinary expert consensus statement is intended to provide comprehensive guidance that can be referenced at the point of care to cardiac electrophysiologists, cardiologists, and other health care professionals, on the management of cardiac arrhythmias in pregnant patients and in fetuses. This document covers general concepts related to arrhythmias, including both brady- and tachyarrhythmias, in both the patient and the fetus during pregnancy. Recommendations are provided for optimal approaches to diagnosis and evaluation of arrhythmias; selection of invasive and noninvasive options for treatment of arrhythmias; and disease- and patient-specific considerations when risk stratifying, diagnosing, and treating arrhythmias in pregnant patients and fetuses. Gaps in knowledge and new directions for future research are also identified.
Topics: Pregnancy; Female; Humans; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Tachycardia
PubMed: 37211147
DOI: 10.1016/j.hrthm.2023.05.017 -
European Heart Journal Sep 2023Mitral valve prolapse (MVP) is the most frequent valve condition but remains a conundrum in many aspects, particularly in regard to the existence and frequency of an... (Review)
Review
Mitral valve prolapse (MVP) is the most frequent valve condition but remains a conundrum in many aspects, particularly in regard to the existence and frequency of an arrhythmic form (AMVP) and its link to sudden cardiac death. Furthermore, the presence, frequency, and significance of the anatomic functional feature called mitral annular disjunction (MAD) have remained widely disputed. Recent case series and cohorts have shattered the concept that MVP is most generally benign and have emphasized the various phenotypes associated with clinically significant ventricular arrhythmias, including AMVP. The definition, evaluation, follow-up, and management of AMVP represent the focus of the present review, strengthened by recent coherent studies defining an arrhythmic MVP phenotypic that would affect a small subset of patients with MVP at concentrated high risk. The role of MAD in this context is of particular importance, and this review highlights the characteristics of AMVP phenotypes and MAD, their clinical, multimodality imaging, and rhythmic evaluation. These seminal facts lead to proposing a risk stratification clinical pathway with consideration of medical, rhythmologic, and surgical management and have been objects of recent expert consensus statements and of proposals for new research directions.
Topics: Humans; Mitral Valve Prolapse; Mitral Valve; Mitral Valve Insufficiency; Arrhythmias, Cardiac; Risk Assessment
PubMed: 37561995
DOI: 10.1093/eurheartj/ehad491 -
American Journal of Health-system... Aug 2023This is the second article in a 2-part series reviewing the pathophysiology and treatment considerations for arrhythmias. Part 1 of the series discussed aspects related... (Review)
Review
PURPOSE
This is the second article in a 2-part series reviewing the pathophysiology and treatment considerations for arrhythmias. Part 1 of the series discussed aspects related to treating atrial arrhythmias. Here in part 2, the pathophysiology of ventricular arrhythmias and bradyarrhythmias and current evidence on treatment approaches are reviewed.
SUMMARY
Ventricular arrhythmias can arise suddenly and are a common cause of sudden cardiac death. Several antiarrhythmics may be effective in management of ventricular arrhythmias, but there is robust evidence to support the use of only a few of these agents, and such evidence was largely derived from trials involving patients with out-of-hospital cardiac arrest. Bradyarrhythmias range from asymptomatic mild prolongation of nodal conduction to severe conduction delays and impending cardiac arrest. Vasopressors, chronotropes, and pacing strategies require careful attention and titration to minimize adverse effects and patient harm.
CONCLUSION
Ventricular arrhythmias and bradyarrhythmias can be consequential and require acute intervention. As experts in pharmacotherapy, acute care pharmacists can participate in providing high-level intervention by aiding in diagnostic workup and medication selection.
Topics: Adult; Humans; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Bradycardia; Emergency Service, Hospital; Heart Arrest
PubMed: 37235971
DOI: 10.1093/ajhp/zxad115 -
American Journal of Health-system... Aug 2023This article, the first in a 2-part review, aims to reinforce current literature on the pathophysiology of cardiac arrhythmias and various evidence-based treatment...
PURPOSE
This article, the first in a 2-part review, aims to reinforce current literature on the pathophysiology of cardiac arrhythmias and various evidence-based treatment approaches and clinical considerations in the acute care setting. Part 1 of this series focuses on atrial arrhythmias.
SUMMARY
Arrhythmias are prevalent throughout the world and a common presenting condition in the emergency department (ED) setting. Atrial fibrillation (AF) is the most common arrhythmia worldwide and expected to increase in prevalence. Treatment approaches have evolved over time with advances in catheter-directed ablation. Based on historic trials, heart rate control has been the long-standing accepted outpatient treatment modality for AF, but the use of antiarrhythmics is often still indicated for AF in the acute setting, and ED pharmacists should be prepared and poised to help in AF management. Other atrial arrhythmias include atrial flutter (AFL), atrioventricular nodal reentry tachycardia (AVNRT), and atrioventricular reentrant tachycardia (AVRT), which warrant distinction due to their unique pathophysiology and because each requires a different approach to utilization of antiarrhythmics. Atrial arrhythmias are typically associated with greater hemodynamic stability than ventricular arrhythmias but still require nuanced management according to patient subset and risk factors. Since antiarrhythmics can also be proarrhythmic, they may destabilize the patient due to adverse effects, many of which are the focus of black-box label warnings that can be overreaching and limit treatment options. Electrical cardioversion for atrial arrhythmias is generally successful and, depending on the setting and/or hemodynamics, often indicated.
CONCLUSION
Atrial arrhythmias arise from a variety of mechanisms, and appropriate treatment depends on various factors. A firm understanding of physiological and pharmacological concepts serves as a foundation for exploring evidence supporting agents, indications, and adverse effects in order to provide appropriate care for patients.
Topics: Humans; Adult; Atrial Fibrillation; Tachycardia, Supraventricular; Atrial Flutter; Tachycardia, Atrioventricular Nodal Reentry; Anti-Arrhythmia Agents
PubMed: 37227130
DOI: 10.1093/ajhp/zxad108 -
Journal of the American College of... Jun 2024Arrhythmias frequently accompany heart failure and left ventricular dysfunction. Tachycardias, atrial fibrillation, and premature ventricular contractions can induce a... (Review)
Review
Arrhythmias frequently accompany heart failure and left ventricular dysfunction. Tachycardias, atrial fibrillation, and premature ventricular contractions can induce a reversible form of dilated cardiomyopathy (CM) known as arrhythmia-induced CM (AiCM). The intriguing question is why certain individuals are more susceptible to AiCM, despite similar arrhythmia burdens. The primary challenge is determining the extent of arrhythmias' contribution to left ventricular systolic dysfunction. AiCM should be considered in patients with a mean heart rate of >100 beats/min, atrial fibrillation, or a PVC burden of >10%. Confirmation of AiCM occurs when CM reverses upon eliminating the responsible arrhythmia. Therapy choice depends on the specific arrhythmia, patient comorbidities, and preferences. After left ventricular function is restored, ongoing follow-up is essential if an abnormal myocardial substrate persists. Accurate diagnosis and treatment of AiCM have the potential to enhance patients' quality of life, improve clinical outcomes, and reduce hospital admissions and overall health care costs.
Topics: Humans; Arrhythmias, Cardiac; Cardiomyopathies; Cardiomyopathy, Dilated
PubMed: 38811098
DOI: 10.1016/j.jacc.2024.03.416 -
Current Cardiology Reports Jun 2024Fabry Disease (FD) is a rare lysosomal storage disorder characterised by multiorgan accumulation of glycosphingolipid due to deficiency in the enzyme α-galactosidase A.... (Review)
Review
PURPOSE OF REVIEW
Fabry Disease (FD) is a rare lysosomal storage disorder characterised by multiorgan accumulation of glycosphingolipid due to deficiency in the enzyme α-galactosidase A. Cardiac sphingolipid accumulation triggers various types of arrhythmias, predominantly ventricular arrhythmia, bradyarrhythmia, and atrial fibrillation. Arrhythmia is likely the primary contributor to FD mortality with sudden cardiac death, the most frequent cardiac mode of death. Traditionally FD was seen as a storage cardiomyopathy triggering left ventricular hypertrophy, diastolic dysfunction, and ultimately, systolic dysfunction in advanced disease. The purpose of this review is to outline the current evidence exploring novel mechanisms underlying the arrhythmia substrate.
RECENT FINDINGS
There is growing evidence that FD cardiomyopathy is a primary arrhythmic disease with each stage of cardiomyopathy (accumulation, hypertrophy, inflammation, and fibrosis) contributing to the arrhythmia substrate via various intracellular, extracellular, and environmental mechanisms. It is therefore important to understand how these mechanisms contribute to an individual's risk of arrhythmia in FD. In this review, we outline the epidemiology of arrhythmia, pathophysiology of arrhythmogenesis, risk stratification, and cardiac therapy in FD. We explore how advances in conventional cardiac investigations performed in FD patients including 12-lead electrocardiography, transthoracic echocardiography, and cardiac magnetic resonance imaging have enabled early detection of pro-arrhythmic substrate. This has allowed for appropriate risk stratification of FD patients. This paves the way for future work exploring the development of therapeutic initiatives and risk prediction models to reduce the burden of arrhythmia.
Topics: Fabry Disease; Humans; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Electrocardiography; alpha-Galactosidase; Risk Assessment
PubMed: 38607539
DOI: 10.1007/s11886-024-02053-2 -
Drugs Sep 2023Cardiac arrhythmias remain a common cause of death and disability. Antiarrhythmic drugs (AADs) and antiarrhythmic agents remain a cornerstone of current cardiac... (Review)
Review
Cardiac arrhythmias remain a common cause of death and disability. Antiarrhythmic drugs (AADs) and antiarrhythmic agents remain a cornerstone of current cardiac arrhythmia management, despite moderate efficacy and the potential for significant adverse proarrhythmic effects. Due to conceptual, regulatory and financial considerations, the number of novel antiarrhythmic targets and agents in the development pipeline has decreased substantially during the last few decades. However, several promising candidates remain and there are exciting developments in repurposing and reformulating already existing drugs for indications related to cardiac arrhythmias. This review discusses the key conceptual considerations for the development of new antiarrhythmic agents, summarizes new compounds and formulations currently in clinical development for rhythm control of atrial fibrillation, and highlights the potential for drug repurposing. Finally, future directions in AAD development are discussed. Together with an ever-increasing understanding of the molecular mechanisms underlying cardiac arrhythmias, these components support a cautiously optimistic outlook towards improved pharmacological treatment opportunities for patients suffering from cardiac arrhythmias.
Topics: Humans; Anti-Arrhythmia Agents; Atrial Fibrillation
PubMed: 37540446
DOI: 10.1007/s40265-023-01923-3 -
Heart (British Cardiac Society) Jan 2024Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease characterised by fibrofatty replacement of the ventricular myocardium due to specific mutations,... (Review)
Review
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease characterised by fibrofatty replacement of the ventricular myocardium due to specific mutations, leading to ventricular arrhythmias and sudden cardiac death. Treating this condition can be challenging due to progressive fibrosis, phenotypic variations and small patient cohorts limiting the feasibility of conducting meaningful clinical trials. Although widely used, the evidence base for anti-arrhythmic drugs is limited. Beta-blockers are theoretically sound, yet their efficacy in reducing arrhythmic risk is not robust. Additionally, the impact of sotalol and amiodarone is inconsistent with studies reporting contradictory results. Emerging evidence suggests that combining flecainide and bisoprolol may be efficacious.Radiofrequency ablation has shown some potential in disrupting ventricular tachycardia circuits, with combined endo and epicardial ablation yielding better results which could be considered at the index procedure. In addition, stereotactic radiotherapy may be a future option that can decrease arrhythmias beyond simple scar formation by altering levels of Nav1.5 channels, Connexin 43 and Wnt signalling, potentially modifying myocardial fibrosis.Future therapies, such as adenoviruses and GSk3b modulation, are still in early-stage research. While implantable cardioverter-defibrillator implantation is a key intervention for reducing arrhythmic death, the risks of inappropriate shocks and device complications must be carefully considered.
Topics: Humans; Arrhythmogenic Right Ventricular Dysplasia; Arrhythmias, Cardiac; Anti-Arrhythmia Agents; Death, Sudden, Cardiac; Sotalol; Tachycardia, Ventricular; Defibrillators, Implantable
PubMed: 37433658
DOI: 10.1136/heartjnl-2023-322612 -
Herzschrittmachertherapie &... Jun 2024
Topics: Humans; Cardiology; Electrophysiologic Techniques, Cardiac; Arrhythmias, Cardiac; Cardiac Electrophysiology
PubMed: 38755469
DOI: 10.1007/s00399-024-01024-y