Prior research has conducted a limited number of studies on the efficacy of atenolol in preventing atrial fibrillation following cardiac surgery (CS). Consequently, a comprehensive evaluation and meta-analysis were undertaken to assess the effectiveness and safety of atenolol in patients undergoing CS for the prevention of postoperative atrial fibrillation (POAF). A meta-analysis of randomized controlled trials was performed. Searches were conducted across multiple databases up to December 1, 2024. The primary focus was the incidence of POAF. Risk ratios (RRs) for treatment effects on dichotomous variables were calculated. The data analysis encompassed 6 randomized controlled trials involving a total of 870 patients. The meta-analysis revealed that atenolol significantly reduces the incidence of POAF in adult patients undergoing CS (RR, 0.55; 95% confidence interval [CI]: 0.32-0.93; P = .03) with moderate heterogeneity (I2 = 57%; P = .10). Atenolol did not demonstrate superiority over sotalol in reducing POAF (RR, 2.39; 95% CI: 1.41-4.04; P = .001) with moderate heterogeneity (I2 = 40%; P = .19). Furthermore, no significant difference was observed between atenolol and the control group (comprising propafenone, metoprolol, nebivolol, and digoxin) in the prevention of POAF (RR, 1.28; 95% CI: 0.76-2.16; P = .35) with moderate heterogeneity (I2 = 43%; P = .15). Recent studies suggest that atenolol could be a safe and effective intervention for the prevention of POAF in adult patients undergoing CS.

Metoprolol is a beta-blocker indicated for the treatment of various cardiovascular diseases, including hypertension, arrhythmias, angina, myocardial infarction, and heart failure (HF). Metoprolol selectively blocks beta1-adrenoreceptors, which are expressed predominantly in cardiac tissue. The primary therapeutic effect resulting from the blockade of these receptors is a reduction in heart rate and a decrease in the force of heart contractions. Metoprolol is metabolized extensively by the hepatic CYP2D6 enzyme. Approximately 8% of Caucasians and 2% of most other populations have absent CYP2D6 activity and are known as “CYP2D6 poor metabolizers (PM).” In addition, several drugs inhibit CYP2D6 activity, such as bupropion, quinidine, fluoxetine, paroxetine, and propafenone. The FDA-approved drug label for metoprolol states that CYP2D6 PM and normal metabolizers (NM) who concomitantly take drugs that inhibit CYP2D6 will have increased metoprolol blood levels, decreasing metoprolol’s cardioselectivity; co-medication with CYP2D6 inhibitors warrants close monitoring (1). (Table 1) Beta-blockers, such as metoprolol, have been demonstrated in several large clinical trials to be safe and effective for the treatment of individuals with cardiovascular disease. As a mainstay of therapy associated with improvements in quality of life, hospitalization rates, and survival (2, 3), clinical care pathways that might lead to the underutilization of beta-blockers require scrutiny. It is common clinical practice to adjust the dose of metoprolol according to individual heart rate until either the target or maximum tolerated dose is reached. The FDA does not specifically comment on the role of genetic testing for initiating therapy. The Clinical Pharmacogenetics Implementation Consortium (CPIC) recommends that CYP2D6 PM should initiate metoprolol therapy at the lowest recommended starting dose, and titration should be performed with care and close monitoring for bradycardia. (Table 2) Standard dosing and care are recommended for intermediate metabolizers (IM) and NM of CYP2D6, but no recommendation is made for ultrarapid metabolizers (UM) given the limited data on this phenotype and beta-blocker response. (4) The Dutch Pharmacogenetics Working Group (DPWG) of the Royal Dutch Pharmacists Association (KNMP) has also published metoprolol dosing recommendations based on CYP2D6 genotype. For individuals who have a CYP2D6 gene variation that reduces the conversion of metoprolol to inactive metabolites (namely, the IM and PM phenotype), DPWG states that the clinical consequences are limited mainly to the occurrence of asymptomatic bradycardia. For CYP2D6 PM or IM, if a gradual reduction in heart rate is desired, or in the event of symptomatic bradycardia, DPWG recommends increasing the dose of metoprolol in smaller steps, prescribing no more than 25% (PM) or 50% (IM) of the standard dose, or both. For CYP2D6 UM, DPWG indicates that clinical response is hardly decreased at a dose of 200 mg/day. However, if efficacy is insufficient at this maximum dose, the DPWG recommends increasing the dose based on effectiveness and side effects up to a maximum of 2.5 times the normal dose, or selecting an alternative. (Table 3) (5).

Propafenone is a class IC anti-arrhythmic agent with potent fast sodium channel blockade whose overdose may result in profound intraventricular conduction delay and malignant ventricular arrhythmias. Management strategies are largely derived from isolated case reports, and consensus guidelines are lacking. We describe a case of a young man with a history of supraventricular tachycardia who presented following intentional polysubstance ingestion, including at least 600 mg of propafenone. On presentation, he was hypoxemic, acidotic, and minimally responsive. Electrocardiography revealed sustained wide complex tachycardia with marked QRS widening. Initial laboratory testing demonstrated normal electrolyte levels with a modestly elevated troponin, along with severe anion-gap metabolic acidosis, elevated lactate levels, acute kidney injury, and toxic acetaminophen concentrations. Intravenous sodium bicarbonate was initiated to achieve mild alkalemia, along with aggressive electrolyte correction and supportive intensive care. Within 1 h of bicarbonate therapy, the ventricular tachycardia resolved with rapid narrowing of the QRS complex and restoration of sinus rhythm. Serial electrocardiograms over the ensuing 24 h showed continued normalization of conduction. This case highlights the electrophysiologic manifestations of propafenone toxicity and underscores the value of QRS duration as a dynamic marker of toxicity severity and treatment response. Early alkalinization with intravenous sodium bicarbonate may rapidly correct conduction disturbances and stabilize malignant arrhythmias in severe class IC anti-arrhythmic overdose.

Premature ventricular contractions (PVCs) are a common arrhythmia. Long-term frequent PVCs may contribute to tachycardia-induced cardiomyopathy, exacerbate angina, or trigger more severe ventricular arrhythmias, increasing cardiovascular risk. Current Western guidelines recommend pharmacotherapy or catheter ablation, with conservative drug therapy (e.g., lidocaine, propafenone, metoprolol, amiodarone, verapamil) remaining the mainstay. Metoprolol tartrate, a first-line drug, is effective for PVCs but has single targets, limited efficacy, and potential long-term cardiovascular adverse effects. Traditional Chinese Medicine (TCM) offers high efficacy and low toxicity. Guipi Mixture, a Chinese patent medicine for heart-spleen deficiency syndrome, combined with Western medicine may overcome these limitations. This study evaluates the efficacy and safety of Guipi Mixture plus metoprolol for PVCs (heart-spleen deficiency syndrome).

Therapeutic drug monitoring (TDM) of antiarrhythmic drugs (AADs) remains underutilized in clinical practice despite the narrow therapeutic windows and marked inter-individual pharmacokinetic variability of these agents. Here, we developed and validated a simple, high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantification of four commonly prescribed AADs-amiodarone, dronedarone, flecainide, and propafenone-and two metabolites, noramiodarone and debutyldronedarone, in human serum, and applied it to routine clinical samples. Sample preparation consisted of simple protein precipitation using only 10 μL of serum, with a 2 μL injection volume and a total run time of 5.7 min. The method showed excellent linearity for all analytes (R[2] > 0.99), acceptable precision (%CV 0.9-5.9%) and accuracy (%bias -6.5-10.5%), minimal matrix effects (88.1-106.6%), satisfactory extraction recoveries (93.9-104.1%), and no significant carryover. No exogenous interference was observed from 25 commonly co-administered cardiovascular drugs, or from 45 neuropsychiatric drugs. The validated assay was successfully applied to 622 serum samples from 524 Korean patients with various arrhythmias. AAD concentrations showed substantial inter-individual variability at identical daily doses, and high proportions of samples were below the therapeutic ranges, supporting the potential utility of routine AAD TDM. This LC-MS/MS method provides a rapid, robust, and clinically practical platform for routine individualized AAD TDM in real-world serum samples with complex matrices.

Supraventricular arrhythmias, especially new-onset atrial fibrillation, occur in approximately 8-46% of critically ill patients with sepsis, depending on the population and monitoring intensity. New-onset atrial fibrillation is independently associated with increased mortality, prolonged intensive care unit stay, and elevated thromboembolic risk. Sepsis-associated atrial fibrillation arises from the interplay of pre-existing patient risk factors, systemic inflammation, sepsis-induced atrial and ventricular remodeling, catecholamine exposure, mechanical ventilation, and electrolyte disturbances. Fluid loading further augments arrhythmia risk in the context of diastolic dysfunction and increased right-ventricular afterload in acute respiratory distress syndrome. Evidence regarding antiarrhythmic drug choice remains limited. The Propafenone vs. Amiodarone for Supraventricular Arrhythmias in Septic Shock trial, the only double-blind randomized comparison of these agents, showed similar 24-hour cardioversion rates but faster cardioversion and fewer recurrences with propafenone, with treatment effects strongly modified by left atrial volume index. Trials of ultra-short acting beta-blockers demonstrated reliable heart-rate control but heterogeneous and fragile mortality signals, with the suggested benefit largely driven by single-center esmolol data and not consistently reproduced in multicenter landiolol studies. Evidence for digoxin and magnesium supports primarily adjunctive roles rather than first-line rate- or rhythm-control strategies. No study has evaluated vernakalant specifically in sepsis, limiting the evidence for its use in hemodynamically unstable patients. Anticoagulation decisions in sepsis-associated new-onset atrial fibrillation are complicated by high bleeding risk, potential changes in stroke risk over time, and limited data on long-term thromboembolic outcomes, underscoring the need for individualized assessment. Overall, current evidence supports prioritizing correction of triggers and individualized selection of a rate- vs. rhythm-control strategy based on hemodynamic status, ventricular function, left atrial size, and arrhythmia characteristics. Future multicenter randomized trials are required to refine antiarrhythmic and anticoagulation strategies in this high-risk population.

The saga of antiarrhythmic drug (AAD) therapy reflects a field shaped by empiricism and burdened by challenges related to safety. The Singh-Vaughan-Williams classification was a timely necessity that eventually slowed pharmacological innovation by prioritizing electrophysiologic properties over arrhythmogenic mechanisms. The present, limited pharmacological armamentarium demands efforts to reassess legacy antiarrhythmics, repurpose non-antiarrhythmic agents as upstream or downstream therapy, and develop novel compounds. Flecainide, propafenone, and dronedarone have demonstrated their reliable efficacy and safety, even in patients with structural heart disease, which should allow clinicians to reduce their reliance on amiodarone. Previous concerns regarding the proarrhythmic risk of dofetilide and ibutilide are currently managed through careful patient selection and adequate QT interval monitoring. Novel targeted AADs are advancing through the development pipeline, of which etripamil and landiolol have already been approved. Other emerging drugs, such as SK channel blockers (AP30663 and AP31969), RyR2 blockers, CaMKII inhibitors, and TASK-1 blockers (doxapram), are aligned with the new paradigm of atrial fibrillation that focuses on triggers and re-entry. Once triggered, arrhythmias are perpetuated by the underlying substrate, which could be directly targeted by antifibrotic therapy. Developing concepts such as atrial cardiomyopathy allows clinicians to characterize substrate objectively, in order to assess disease severity and individualize antiarrhythmic treatment. The future of antiarrhythmic therapy will be reshaped by artificial intelligence and digital twinning, which allow precise phenotyping and a tailored approach based on individual patient profiles, complemented by rhythm monitoring through wearables.