Sodium-glucose cotransporter 2 (SGLT2) inhibitors are gaining ground as standard therapy for heart failure with a class-I recommendation in the recently updated heart failure guidelines from the European Society of Cardiology. Different gliflozins have shown impressive beneficial effects in patients with and without diabetes mellitus type 2, especially in reducing the rates for hospitalization for heart failure, yet little is known on their antiarrhythmic properties. Atrial and ventricular arrhythmias were reported by clinical outcome trials with SGLT2 inhibitors as adverse events, and SGLT2 inhibitors seemed to reduce the rate of arrhythmias compared to placebo treatment in those trials. Mechanistical links are mainly unrevealed, since hardly any experiments investigated their impact on arrhythmias. Prospective trials are currently ongoing, but no results have been published so far. Arrhythmias are common in the heart failure population, therefore the understanding of possible interactions with SGLT2 inhibitors is crucial. This review summarizes evidence from clinical data as well as the sparse experimental data of SGLT2 inhibitors and their effects on arrhythmias.

Responding to emergencies in Alpine terrain is quite challenging as air ambulances and mountain rescue services are often confronted with logistics challenges and adverse weather conditions that extend the response times required to provide life-saving support. Among other medical emergencies, sudden cardiac arrest (SCA) is the most time-sensitive event that requires the quick provision of medical treatment including cardiopulmonary resuscitation and electric shocks by automated external defibrillators (AED). An emerging technology called unmanned aerial vehicles (or drones) is regarded to support mountain rescuers in overcoming the time criticality of these emergencies by reducing the time span between SCA and early defibrillation. A drone that is equipped with a portable AED can fly from a base station to the patient’s site where a bystander receives it and starts treatment. This paper considers such a response system and proposes an integer linear program to determine the optimal allocation of drone base stations in a given geographical region. In detail, the developed model follows the objectives to minimize the number of used drones and to minimize the average travel times of defibrillator drones responding to SCA patients. In an example of application, under consideration of historical helicopter response times, the authors test the developed model and demonstrate the capability of drones to speed up the delivery of AEDs to SCA patients. Results indicate that time spans between SCA and early defibrillation can be reduced by the optimal allocation of drone base stations in a given geographical region, thus increasing the survival rate of SCA patients.

Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed the effects of saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that the primary target of saxagliptin, dipeptidyl peptidase-4, is absent in cardiomyocytes, yet saxagliptin internalized into cardiomyocytes and impaired cardiac contractility via inhibition of the Ca2+/calmodulin-dependent protein kinase II-phospholamban-sarcoplasmic reticulum Ca2+-ATPase 2a axis and Na+-Ca2+ exchanger function in Ca2+ extrusion. This resulted in reduced sarcoplasmic reticulum Ca2+ content, diastolic Ca2+ overload, systolic dysfunction and impaired contractile force. Furthermore, saxagliptin reduced protein kinase C-mediated delayed rectifier K+ current that prolonged action potential duration and consequently QTc interval. Importantly, saxagliptin aggravated pre-existing cardiac dysfunction induced by ischemia/reperfusion injury. In conclusion, our novel results provide mechanisms for the off-target deleterious effects of saxagliptin on cardiac function and support the outcome of SAVOR-TIMI 53 trial that linked saxagliptin with the risk of heart failure.