Quinidine for ventricular arrhythmias: a comprehensive review.

Quinidine, the first antiarrhythmic drug, was widely used during the 20th century. Multiple studies have been conducted to provide insights into the pharmacokinetics and pleiotropic effects of Class Ia antiarrhythmic drugs. However, safety concerns and the emergence of new drugs led to a decline in their use during the 1990s. Despite this, recent studies have reignited the interest in quinidine, particularly for ventricular arrhythmias, where other antiarrhythmics have failed. In conditions such as Brugada syndrome, idiopathic ventricular fibrillation, early repolarization syndrome, short QT syndrome, and electrical storms, quinidine remains a valuable asset. Starting from the European and American recommendations, this comprehensive review aimed to explore the various indications for quinidine and the studies that support its use. We also discuss the potential future of quinidine, including the necessary research to optimize its use and patient selection. Additionally, it addresses the imperative task of mitigating the iatrogenic burden associated with quinidine usage and confronts the challenge of ensuring drug accessibility.

Tinzaparin, an alternative to subcutaneous unfractionated heparin, in patients with severe and end-stage renal impairment: a retrospective observational single-center study.

BACKGROUND: Tinzaparin could be easier to manage than unfractionated heparin in patients with severe renal impairment. However, clinical and pharmacologic data regarding its use in such patients are lacking. OBJECTIVES: The aims of this study were to determine, in patients with estimated glomerular filtration rate (eGFR) of <30 mL.min⁻1, tinzaparin pharmacokinetics (PK) parameters using a population PK approach and bleeding and thrombotic complications. METHODS: We performed a retrospective observational single-center study, including in-patients with eGFR of <30 mL.min⁻1 receiving prophylactic (4500 IU.d⁻1) or therapeutic (175 IU.kg⁻1.d⁻1) tinzaparin. Measured anti-Xa levels were analyzed using a nonlinear mixed-effects modeling approach. Individual predicted tinzaparin exposure markers at steady state were calculated for each patient and dosing regimen. The PK was also evaluated through Monte Carlo simulations based on the final covariate model parameter estimates. RESULTS: Over a 22-month period, 802 tinzaparin treatment periods in 623 patients were analyzed: two-thirds received a prophylactic dose, 66% had an eGFR of <20 mL.min⁻1, and 25% were on renal replacement therapy. In patients for whom anti-Xa measurements were performed (n = 199; 746 values), PK parameters, profiles, and maximum plasma concentrations were comparable with those in patients without renal impairment or in healthy volunteers. In the whole population, major bleeding occurred in 2.4% and 3.5% of patients receiving prophylactic and therapeutic doses over a median 9- and 7-day treatment period, respectively. No patients had thrombotic complications. CONCLUSION: Tinzaparin PK parameters and profiles were not affected by renal impairment. This suggests that tinzaparin, at therapeutic or prophylactic dose, could be an alternative to unfractionated heparin in hospitalized patients with severe renal impairment.

Personalized screening before subcutaneous cardioverter-defibrillator implantation: Usefulness and outcomes in clinical practice-the S-ICD screening SIS prospective study.

BACKGROUND: Electrocardiographic screening before subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation is unsuccessful in around 10% of cases. A personalized screening method, by slightly moving the electrodes, to obtain a better R/T ratio has been described to overcome traditional screening failure. OBJECTIVE: The objectives of the SIS study were to assess to what extent a personalized screening method improves eligibility for S-ICD implantation and to evaluate the inappropriate shock rate after such screening success. METHODS: All consecutive patients eligible for an S-ICD implantation were prospectively recruited across 20 French centers between December 2019 and January 2022. In case of traditional screening failure, patients received a second personalized screening. If at least 1 vector was positive, the personalized screening was considered successful, and the patient was eligible for implantation. RESULTS: The study included 474 patients (mean age, 50.4 ± 14.1 years; 77.4% men). Traditional screening was successful in 456 (96.2%) cases. This figure rose to 98.3% (n = 466; P = .002) when personalized screening was performed. All patients implanted after successful personalized screening had correct signal detection on initial device interrogation. Nevertheless, after 1-year follow-up, 3 of the 7 patients (43%) implanted with personalized screening experienced inappropriate shock vs 18 of the 427 patients (4.2%) with traditional screening and S-ICD implantation (P = .003). CONCLUSION: Traditional S-ICD screening was successful in our study in a high proportion of patients. Considering the small improvement in success of screening and a higher rate of inappropriate shock, a strategy of personalized screening cannot be routinely recommended. CLINICALTRIALS: gov identifier: NCT04101253.