Optimal allocation of defibrillator drones in mountainous regions

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

Thermic sealing in femoral catheterization: First experience with the Secure Device

Background: Devices currently used to achieve hemostasis of the femoral artery following percutaneous cardiac catheterization are associated with vascular complications and remnants of artificial materials are retained at the puncture site. The Secure arterial closure Device induces hemostasis by utilizing thermal energy, which causes collagen shrinking and swelling. In comparison to established devices, it has the advantage of leaving no foreign material in the body following closing. This study was designed to evaluate the efficacy and safety of the Secure Device to close the puncture site following percutaneous cardiac catheterization. Methods: The Secure Device was evaluated in a prospective non-randomized single-center trial with patients undergoing 6 F invasive cardiac procedures. A total of 67 patients were enrolled and the device was utilized in 63 patients. Fifty diagnostic and 13 interventional cases were evaluated. Femoral artery puncture closure was performed immediately after completion of the procedure. Time to hemostasis (TTH), time to ambulation (TTA) and data regarding short-term and 30-day clinical follow-up were recorded. Results: Mean TTH was 4:30 ± 2:15 min in the overall observational group. A subpopulation of patients receiving anticoagulants had a TTH of 4:53 ± 1:43 min. There were two access site complications (hematoma > 5 cm). No major adverse events were identified during hospitalization or at the 30 day follow-up. Conclusions: The new Secure Device demonstrates that it is feasible in diagnostic and interventional cardiac catheterization. With respect to safety, the Secure Device was non-inferior to other closure devices as tested in the ISAR closure trial

Left ventricular ejection fraction and cardiac biomarkers for dynamic prediction of cardiotoxicity in early breast cancer

BACKGROUND/PURPOSE: This study aims to quantify the utility of monitoring LVEF, hs-cTnT, and NT-proBNP for dynamic cardiotoxicity risk assessment in women with HER2+ early breast cancer undergoing neoadjuvant/adjuvant trastuzumab-based therapy. MATERIALS AND METHODS: We used joint models of longitudinal and time-to-event data to analyze 1,136 echocardiography reports and 326 hs-cTnT and NT-proBNP measurements from 185 women. Cardiotoxicity was defined as a 10% decline in LVEF below 50% and/or clinically overt heart failure. RESULTS: Median pre-treatment LVEF was 64%, and 19 patients (10%) experienced cardiotoxicity (asymptomatic n = 12, during treatment n = 19). The pre-treatment LVEF strongly predicted for cardiotoxicity (subdistribution hazard ratio per 5% increase in pre-treatment LVEF = 0.68, 95%CI: 0.48–0.95, p = 0.026). In contrast, pre-treatment hs-cTnT and NT-proBNP were not consistently associated with cardiotoxicity. During treatment, the longitudinal LVEF trajectory dynamically identified women at high risk of developing cardiotoxicity (hazard ratio per 5% LVEF increase at any time of follow-up = 0.36, 95% CI: 0.2–0.65, p = 0.005). Thirty-four patients (18%) developed an LVEF decline ≥ 5% from pre-treatment to first follow-up (“early LVEF decline”). One-year cardiotoxicity risk was 6.8% in those without early LVEF decline and pre-treatment LVEF ≥ 60% (n = 117), 15.9% in those with early LVEF decline or pre-treatment LVEF 5% during trastuzumab-based therapy. The longitudinal LVEF trajectory but not hs-cTnT or NT-proBNP allows for a dynamic assessment of cardiotoxicity risk in this setting

Transesophageal echocardiography-guided versus fluoroscopy-guided patent foramen ovale closure : A single center registry

Percutaneous closure of patent foramen ovale (PFO) is conventionally performed under continuous transesophageal echocardiographic (TEE) guidance. We aimed to evaluate whether a simplified procedural approach, including pure fluoroscopy-guidance and final TEE control, as well as an aimed 'next-day-discharge' is comparable with the conventional TEE-guided procedure in terms of periprocedural and intermediate-term outcomes.All patients who underwent a PFO closure at our center between 2010 and 2022 were retrospectively included. Prior to June 2019 cases were performed with continuous TEE guidance (TEE-guided group). Since June 2019, only pure fluoroscopy-guided PFO closures have been performed with TEE insertion and control just prior to device release (fluoroscopy-guided group). We analyzed procedural aspects, as well as long term clinical and echocardiographic outcomes.In total 291 patients were included in the analysis: 197 in the TEE-guided group and 94 in the fluoroscopy-guided group. Fluoroscopy-guided procedures were markedly shorter (48 ± 20 min vs. 25 ± 9 min; p < .01). There was no difference in procedural complications, including death, major bleeding, device dislodgement, stroke or clinically relevant peripheral embolization between the two groups (.5% vs. 0%; p = .99). Hospital stay was also shorter with the simplified approach (2.5 ± 1.6 vs. 3.5 ± 1.2 days; p < .01), allowing 85% same-day discharges during the last 12 months of observation period. At 6 ± 3 months echocardiographic follow-up a residual leakage was described in 8% of the TEE-guided cases and 2% of the fluoroscopy-guided cases (p = .08).While a complete TEE-free PFO closure might have potential procedural risks, our approach of pure fluoroscopy-guided with a brisk final TEE check seems to be advantageous in terms of procedural aspects with no sign of any acute or intermediate-term hazard and it could offer an equitable compromise between the two worlds: a complete TEE procedure and a procedure without any TEE

New Antihyperglycemic Drugs and Heart Failure: Synopsis of Basic and Clinical Data

The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors. LEADER, SUSTAIN-6, EMPA-REG OUTCOME, and CANVAS showed potential beneficial results, while the SAVOR-TIMI trial had an increased rate of hospitalization for heart failure. Meanwhile, the same drugs are investigated in preclinical experiments mainly using various animal models, which aim to find interactions and elucidate the underlying downstream mechanisms between the antihyperglycemic drugs and the cardiovascular system. Yet the direct link for observed effects, especially for DPP-4 and SGLT-2 inhibitors, is still unknown. Further inquiry into these mechanisms is crucial for the interpretation of the clinical trials’ outcome and, vice versa, the clinical trials provide hints for an involvement of the cardiovascular system. The synopsis of preclinical and clinical data is essential for a detailed understanding of benefits and risks of new antihyperglycemic drugs

Can sodium-glucose cotransporter 2 inhibitors be beneficial in patients with acute myocardial infarction?

The sodium-glucose cotransporter 2 inhibitors (SGLT2i), empagliflozin, dapagliflozin, and canagliflozin, have shown impressive beneficial effects in patients with type 2 diabetes mellitus in mandatory cardiovascular outcome trials. Retrospective data analysis revealed signals that pointed towards positive effects independent of the antidiabetic effects. This could be confirmed for empagliflozin and dapagliflozin in chronic heart failure with reduced ejection fraction alone, where rates of hospitalization for heart failure and cumulative major adverse cardiovascular events were reduced to a similar extent in patients with and without diabetes mellitus as in corresponding outcome trials. Cardiac remodeling following myocardial infarction leads to heart failure with reduced ejection fraction in many patients and aggravates morbidity and mortality. Clinical data of SGLT2i treatment after acute myocardial infarction is sparse. This review focuses on available experimental data on the effects of SGLT2i used before, during, and after myocardial infarction as well as already published and currently ongoing clinical trials

Automated external defibrillator delivery by drone in mountainous regions to support basic life support – A simulation study

Background: Out-of-hospital cardiac arrest (OHCA) is associated with poor survival rates. Factors that may enable survival include cardiopulmonary resuscitation (CPR) initiated by bystanders and early use of an automated external defibrillator (AED). This explorative simulation study was conceptualized to test the feasibility of a semi-autonomously operating drone that delivers an AED to a remote emergency location and its bystander-use. Methods: Ten paramedics and nineteen laypersons were confronted with a manikin simulating an OHCA as single bystanders within a field test located in a mountainous region between Austria and Slovenia. The scenario included a mock-call to the local emergency response center that dispatched a drone towards the caller’s GPS coordinates and supported the ongoing CPR. The outcomes were the successful delivery of the AED, the time to the first shock, hands-off times, and the overall performance of the CPR. Results: The AED was delivered by drone and used in all 29 scenarios without serious adverse events. The flight time of the drone was in median 5:20 (range: 1:35–8:19) minutes. The paramedics delivered the first shock after a mean of 12:15 ± 2:03 min and hands-off times were 50 ± 22 s. The laypersons delivered the first shock after 14:04 ± 2:10 min and hands-off times were 2:11 ± 0:39 min. All participants felt confident in the handling of the delivered AED. Conclusion: The delivery and usage of an AED via a semi-autonomously flying drone in a remote region is feasible. This approach can lead to early administration of shocks

The Anti-Cancer Multikinase Inhibitor Sorafenib Impairs Cardiac Contractility by Reducing Phospholamban Phosphorylation and Sarcoplasmic Calcium Transients

Abstract Tyrosine-kinase inhibitors (TKIs) have revolutionized cancer therapy in recent years. Although more targeted than conventional chemotherapy, TKIs exhibit substantial cardiotoxicity, often manifesting as hypertension or heart failure. Here, we assessed myocyte intrinsic cardiotoxic effects of the TKI sorafenib and investigated underlying alterations of myocyte calcium homeostasis. We found that sorafenib reversibly decreased developed force in auxotonically contracting human myocardia (3 µM: −25 ± 4%, 10 µM: −29 ± 7%, 30 µM: −43 ± 12%, p < 0.01), reduced peak cytosolic calcium concentrations in isolated cardiomyocytes (10 µM: 52 ± 8.1% of baseline, p < 0.001), and slowed cytosolic calcium removal kinetics (RT50, RT10, Tau, p < 0.05). Beta-adrenergic stimulation induced augmentation of calcium transient (CaT) amplitude was attenuated in sorafenib-treated cells (2.7 ± 0.3-fold vs. 3.6 ± 0.2-fold in controls, p < 0.001). Sarcoplasmic reticulum (SR) calcium content was reduced to 67 ± 4% (p < 0.01), and SR calcium re-uptake slowed (p < 0.05). Sorafenib significantly reduced serine 16 phosphorylation of phospholamban (PLN, p < 0.05), while PLN threonine 17 and CaMKII (T286) phosphorylation were not altered. Our data demonstrate that sorafenib acutely impairs cardiac contractility by reducing S16 PLN phosphorylation, leading to reduced SR calcium content, CaT amplitude, and slowed cytosolic calcium removal. These results indicate myocyte intrinsic cardiotoxicity irrespective of effects on the vasculature and chronic cardiac remodeling