Fourteen quinolizidine derivatives, structurally related to the alkaloids lupinine and cytisine and previously studied for other pharmacological aims, were presently tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues, and to assess calcium antagonism in comparison to amiodarone, lidocaine, procainamide, and quinidine. All compounds, but two, compared favorably with the reference drugs. Potent antiarrhythmic activity was observed for compounds (in increasing order) 4, 1, 6 and 5. The last compound N-(3,4,5-trimethoxybenzoyl)aminohomolupinane) was outstanding, exhibiting a nanomolar potency (EC50 = 0.017 µM) for the increase of threshold of ac-arrhythmia, and being devoid of antihypertensive activity against spontaneously hypertensive rats.

Atrial fibrillation (AF), a complex cardiac arrhythmia, necessitates a shift in management paradigms, emphasizing an integrative approach that incorporates lifestyle modifications. Investigations into the role of interleukins and inflammatory mediators are underway, exploring their potential as diagnostic markers and predictors of cardiovascular events in AF. Despite the identification of biomarkers related to cardiac remodeling, their predictive ability for post-cardioversion outcomes remains controversial. Computational models are being developed to understand proarrhythmic contributions and identify anti-AF targets. Addressing the rising global incidence of AF, linked to stroke and heart failure, presents a critical health challenge. As risk factors like obesity prevail, AF becomes a pervasive public health concern, expected to double in prevalence over the next 50 years. The impact on mortality and morbidity, especially through hospitalizations, underscores the need for early detection and effective clinical management. Identifying individuals at increased AF risk becomes crucial for screening and prevention strategies. Lifestyle modifications, including weight management and physical activity, emerge as influential factors in AF management, offering the potential to alleviate symptoms and modify disease progression. The paper concludes by emphasizing the need for safer antiarrhythmic therapies based on AF mechanisms, promising improvement in global AF management. The multifaceted nature of AF etiology requires a broader perspective beyond traditional medical interventions, acknowledging the importance of integrated care to address this significant public health challenge.

Electrical remodelling as a result of the homeodomain transcription factor 2 (Pitx2)‐dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at chromosome 4q25 responded favorably to Class I antiarrhythmic drugs (AADs). The possible reasons behind this remain elusive. The purpose of this study was to assess the efficacy of AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue level, using drug binding models with multi-channel pharmacology. Experimentally calibrated populations of human atrial action potential (AP) models in both sinus rhythm (SR) and Pitx2-induced AF conditions were constructed by using two distinct models to represent morphological subtypes of AP. Multi-channel pharmacological effects of disopyramide, quinidine, and propafenone on ionic currents were considered. Simulated results showed that Pitx2-induced remodelling increased maximum upstroke velocity (dVdtmax) and conduction velocity (CV), and decreased AP duration (APD) and wavelength (WL). At the concentrations tested in this study, these AADs decreased dVdtmax and CV and prolonged APD in the setting of Pitx2-induced AF. Our findings of alterations in WL indicated that quinidine and disopyramide may be more effective against Pitx2-induced AF than propafenone by prolonging WL.

Electrical storm (ES) is defined as the presence of at least three episodes of sustained ventricular tachycardia or ventricular fibrillation within 24 hours. This patient had a previously known arterial hypertension, type II diabetes mellitus, and chronic kidney disease and has presented to the Emergency Department (ED) with symptoms of retrosternal chest pain lasting for several hours prior. The initial 12-lead electrocardiogram revealed ST segment elevation in the anterior leads (V1-V6). Emergent coronary angiography revealed an acute occlusion of the proximal left anterior descending artery (pLAD) and percutaneous coronary intervention was performed with successful implantation of one drug-eluting stent in the pLAD. On the day 8 of hospitalization, patient developed a refractory ES for which he received 50 DC shocks and did not respond to multiple lines of antiarrhythmic medications. Due to a failure of medical therapy, we decided to implant a temporary pacemaker and initiate ventricular overdrive pacing (VOP) that was successful in terminating ES. Following electrical stabilization, the patient underwent a successful ICD implantation. This case demonstrates that VOP can contribute to hemodynamic and electrical stabilization of a patient that suffers from refractory ES and this treatment modality might serve as a temporary bridge to ICD implantation.