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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 -
Clinical Medicine (London, England) Sep 2023Ventricular tachycardia (VT) describes rapid heart rhythms originating from the ventricles. Accurate diagnosis of VT is important to allow prompt referral to specialist... (Review)
Review
Ventricular tachycardia (VT) describes rapid heart rhythms originating from the ventricles. Accurate diagnosis of VT is important to allow prompt referral to specialist services for ongoing management. The diagnosis of VT is usually made based on electrocardiographic data, most commonly 12-lead echocardiography (ECG), as well as supportive cardiac telemetric monitoring. Distinguishing between VT and supraventricular arrhythmias on ECG can be difficult. However, the VT diagnosis frequently needs to be made rapidly in the acute setting. In this review, we discuss the definition of VT, review features of wide-complex tachycardia (WCT) on ECG that might be helpful in diagnosing VT, discuss the different substrates in which VT can occur and offer brief comments on management considerations for patients found to have VT.
Topics: Humans; Tachycardia, Supraventricular; Diagnosis, Differential; Tachycardia, Ventricular; Heart Ventricles; Electrocardiography
PubMed: 37775174
DOI: 10.7861/clinmed.2023-23.5.Cardio3 -
Science (New York, N.Y.) Sep 2023After heart injury, dead heart muscle is replaced by scar tissue. Fibroblasts can electrically couple with myocytes, and changes in fibroblast membrane potential can...
After heart injury, dead heart muscle is replaced by scar tissue. Fibroblasts can electrically couple with myocytes, and changes in fibroblast membrane potential can lead to myocyte excitability, which suggests that fibroblast-myocyte coupling in scar tissue may be responsible for arrhythmogenesis. However, the physiologic relevance of electrical coupling of myocytes and fibroblasts and its impact on cardiac excitability in vivo have never been demonstrated. We genetically engineered a mouse that expresses the optogenetic cationic channel ChR2 (H134R) exclusively in cardiac fibroblasts. After myocardial infarction, optical stimulation of scar tissue elicited organ-wide cardiac excitation and induced arrhythmias in these animals. Complementing computational modeling with experimental approaches, we showed that gap junctional and ephaptic coupling, in a synergistic yet functionally redundant manner, excited myocytes coupled to fibroblasts.
Topics: Animals; Mice; Arrhythmias, Cardiac; Cicatrix; Fibroblasts; Myocytes, Cardiac; Channelrhodopsins; Optogenetics; Connexin 43; Gene Knockout Techniques
PubMed: 37769108
DOI: 10.1126/science.adh9925 -
JACC. Clinical Electrophysiology Oct 2023Of the monomorphic ventricular tachycardias, there are 4 specific tachycardias related to the Purkinje system: 1) idiopathic verapamil-sensitive fascicular ventricular... (Review)
Review
Of the monomorphic ventricular tachycardias, there are 4 specific tachycardias related to the Purkinje system: 1) idiopathic verapamil-sensitive fascicular ventricular tachycardia (FVT); 2) non-re-entrant FVT; 3) bundle branch re-entry and interfascicular re-entry; and 4) Purkinje-mediated VT in structural heart disease. Verapamil-sensitive FVT is classified into 4 types according to the location of the circuit: 1) left posterior type; 2) left anterior type; 3) left upper septal type;and 4) reverse type. And, in the left anterior and posterior types, there are septal and papillary muscle subtypes. Although macro-re-entry has been reported to be the mechanism underlying verapamil-sensitive FVT, recording the entire circuit is challenging. One possible reason is that the Purkinje-muscle junction may penetrate the myocardial layer as a part of the circuit. The Purkinje network may thus play an important role in the initiation and maintenance of ventricular fibrillation. Further, it has been reported that the development and the abnormalities of the Purkinje system are associated with the arrhythmogenesis of ventricular fibrillation. Furthermore, it has been reported that catheter ablation of trigger ventricular premature complexes, and/or "de-networking" of the Purkinje system, can be used as electrical bailout therapy. There is a hypothesis that the intramural Purkinje system is involved in the generation of J waves. Nevertheless, as there are still unresolved issues that must be debated and accurately analyzed, this review aims to discuss the solved and unsolved questions related to Purkinje-related arrhythmias.
Topics: Humans; Ventricular Fibrillation; Purkinje Fibers; Tachycardia, Ventricular; Verapamil; Ventricular Premature Complexes
PubMed: 37498247
DOI: 10.1016/j.jacep.2023.05.040 -
Deutsches Arzteblatt International Aug 2023Perioperative arrhythmias are common depending on the type of the operation and can increase morbidity and mortality. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Perioperative arrhythmias are common depending on the type of the operation and can increase morbidity and mortality.
METHODS
This review is based on pertinent publications retrieved by a selective search in PubMed, as well as the relevant European guidelines.
RESULTS
Arrhythmias are seen in more than 90% of cardiac operations; they are usually transient and often asymptomatic. The risk factors for arrhythmia include ion channel diseases, old age, structural heart disease, cardiac surgery, noncardiac surgery with major fluid shifts, and pulmonary resection. The full spectrum of supraventricular and ventricular arrhythmias can arise perioperatively. Correct ECG interpretation, consideration of the arrhythmia in the overall clinical context, and an understanding of its causes, pathophysiology, and options for effective treatment are critically important. According to a meta-analysis, betablockers lower the risk of perioperative atrial fibrillation (OR = 0.56; 95% confidence interval: [0.35; 0.91]). If anticoagulant treatment is not interrupted for surgery, there is less bleeding with direct oral anticoagulants than with vitamin K antagonists (relative risk: 0.62 [0.47; 0.82]). Moreover, clinical follow-up is important, especially for patients with new-onset atrial fibrillation or heart failure.
CONCLUSION
The identification of high-risk patients and the provision of individualized perioperative monitoring are essential aspects of patient safety. Outpatient cardiological follow-up can improve outcomes.
Topics: Humans; Atrial Fibrillation; Heart Diseases; Hemorrhage
PubMed: 37097070
DOI: 10.3238/arztebl.m2023.0052 -
International Journal of Cardiology Jan 2024Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent "non-ischemic" myocardial scarring predisposing to ventricular electrical...
Arrhythmogenic cardiomyopathy (ACM) is a heart muscle disease characterized by prominent "non-ischemic" myocardial scarring predisposing to ventricular electrical instability. Diagnostic criteria for the original phenotype, arrhythmogenic right ventricular cardiomyopathy (ARVC), were first proposed in 1994 and revised in 2010 by an international Task Force (TF). A 2019 International Expert report appraised these previous criteria, finding good accuracy for diagnosis of ARVC but a lack of sensitivity for identification of the expanding phenotypic disease spectrum, which includes left-sided variants, i.e., biventricular (ABVC) and arrhythmogenic left ventricular cardiomyopathy (ALVC). The ARVC phenotype together with these left-sided variants are now more appropriately named ACM. The lack of diagnostic criteria for the left ventricular (LV) phenotype has resulted in clinical under-recognition of ACM patients over the 4 decades since the disease discovery. In 2020, the "Padua criteria" were proposed for both right- and left-sided ACM phenotypes. The presently proposed criteria represent a refinement of the 2020 Padua criteria and have been developed by an expert European TF to improve the diagnosis of ACM with upgraded and internationally recognized criteria. The growing recognition of the diagnostic role of CMR has led to the incorporation of myocardial tissue characterization findings for detection of myocardial scar using the late‑gadolinium enhancement (LGE) technique to more fully characterize right, biventricular and left disease variants, whether genetic or acquired (phenocopies), and to exclude other "non-scarring" myocardial disease. The "ring-like' pattern of myocardial LGE/scar is now a recognized diagnostic hallmark of ALVC. Additional diagnostic criteria regarding LV depolarization and repolarization ECG abnormalities and ventricular arrhythmias of LV origin are also provided. These proposed upgrading of diagnostic criteria represents a working framework to improve management of ACM patients.
Topics: Humans; Cicatrix; Consensus; Contrast Media; Gadolinium; Arrhythmogenic Right Ventricular Dysplasia; Cardiomyopathies; Arrhythmias, Cardiac
PubMed: 37844667
DOI: 10.1016/j.ijcard.2023.131447 -
Circulation Sep 2023Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date.
METHODS
Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies.
RESULTS
Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82-1.30]; =0.80). There was no between-group difference in the occurrence of any of the secondary outcomes.
CONCLUSIONS
PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT01920048.
Topics: Humans; Male; Aged; Female; Stroke Volume; Death, Sudden, Cardiac; Ventricular Function, Left; Arrhythmias, Cardiac; Ventricular Dysfunction, Left; Defibrillators, Implantable; Treatment Outcome
PubMed: 37555345
DOI: 10.1161/CIRCULATIONAHA.123.065300 -
Annual Review of Medicine Jan 2024Dilated cardiomyopathy (DCM) is defined as dilation and/or reduced function of one or both ventricles and remains a common disease worldwide. An estimated 40% of cases... (Review)
Review
Dilated cardiomyopathy (DCM) is defined as dilation and/or reduced function of one or both ventricles and remains a common disease worldwide. An estimated 40% of cases of familial DCM have an identifiable genetic cause. Accordingly, there is a fast-growing interest in the field of molecular genetics as it pertains to DCM. Many gene mutations have been identified that contribute to phenotypically significant cardiomyopathy. DCM genes can affect a variety of cardiomyocyte functions, and particular genes whose function affects the cell-cell junction and cytoskeleton are associated with increased risk of arrhythmias and sudden cardiac death. Through advancements in next-generation sequencing and cardiac imaging, identification of genetic DCM has improved over the past couple decades, and precision medicine is now at the forefront of treatment for these patients and their families. In addition to standard treatment of heart failure and prevention of arrhythmias and sudden cardiac death, patients with genetic cardiomyopathy stand to benefit from gene mechanism-specific therapies.
Topics: Humans; Cardiomyopathy, Dilated; Arrhythmias, Cardiac; Death, Sudden, Cardiac; Mutation; Heart Failure
PubMed: 37788487
DOI: 10.1146/annurev-med-052422-020535 -
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 -
BMJ (Clinical Research Ed.) Apr 2024To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia.
OBJECTIVE
To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia.
DESIGN
Population based matched cohort study.
SETTING
Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England.
POPULATION
Adults (≥50 years) with a diagnosis of dementia between 1 January 1998 and 31 May 2018 (n=173 910, 63.0% women). Each new antipsychotic user (n=35 339, 62.5% women) was matched with up to 15 non-users using incidence density sampling.
MAIN OUTCOME MEASURES
The main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators. An unrelated (negative control) outcome of appendicitis and cholecystitis combined was also investigated to detect potential unmeasured confounding.
RESULTS
Compared with non-use, any antipsychotic use was associated with increased risks of all outcomes, except ventricular arrhythmia. Current use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio 2.19, 95% confidence interval (CI) 2.10 to 2.28), acute kidney injury (1.72, 1.61 to 1.84), venous thromboembolism (1.62, 1.46 to 1.80), stroke (1.61, 1.52 to 1.71), fracture (1.43, 1.35 to 1.52), myocardial infarction (1.28, 1.15 to 1.42), and heart failure (1.27, 1.18 to 1.37). No increased risks were observed for the negative control outcome (appendicitis and cholecystitis). In the 90 days after drug initiation, the cumulative incidence of pneumonia among antipsychotic users was 4.48% (4.26% to 4.71%) versus 1.49% (1.45% to 1.53%) in the matched cohort of non-users (difference 2.99%, 95% CI 2.77% to 3.22%).
CONCLUSIONS
Antipsychotic use compared with non-use in adults with dementia was associated with increased risks of stroke, venous thromboembolism, myocardial infarction, heart failure, fracture, pneumonia, and acute kidney injury, but not ventricular arrhythmia. The range of adverse outcomes was wider than previously highlighted in regulatory alerts, with the highest risks soon after initiation of treatment.
Topics: Adult; Humans; Female; Male; Antipsychotic Agents; Cohort Studies; Venous Thromboembolism; Appendicitis; Stroke; Myocardial Infarction; Arrhythmias, Cardiac; Heart Failure; Dementia; Pneumonia; Acute Kidney Injury; Cholecystitis
PubMed: 38631737
DOI: 10.1136/bmj-2023-076268