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Abstract Normothermic regional perfusion (NRP) allows assessment of therapeutic interventions prior to donation after circulatory death transplantation. Sodium-3-hydroxybutyrate (3-OHB) increases cardiac output in heart failure patients and diminishes ischemia–reperfusion injury, presumably by improving mitochondrial metabolism. We investigated effects of 3-OHB on cardiac and mitochondrial function in transplanted hearts and in cardiac organoids. Donor pigs (n = 14) underwent circulatory death followed by NRP. Following static cold storage, hearts were transplanted into recipient pigs. 3-OHB or Ringer’s acetate infusions were initiated during NRP and after transplantation. We evaluated hemodynamics and mitochondrial function. 3-OHB mediated effects on contractility, relaxation, calcium, and conduction were tested in cardiac organoids from human pluripotent stem cells. Following NRP, 3-OHB increased cardiac output (P

Recent advances in cancer therapy have led to increased survival rates for cancer patients, but also allowed cardiovascular complications to become increasingly evident, with more than 40% of cancer deaths now being attributed to cardiovascular diseases. Cardiotoxicity is the most concerning cardiovascular complication, one caused mainly due to anti-cancer drugs. Among the harmful mechanisms of these drugs are DNA damage, endothelial dysfunction, and oxidative stress. Cancer patients can suffer reduced cardiorespiratory fitness as a secondary effect of anti-cancer therapies, tumor burden, and deconditioning. In the general population, regular exercise can reduce the risk of cardiovascular morbidity, mortality, and cancer. Exercise-induced modifications of gene expression result in improvements of cardiovascular parameters and an increased general fitness, influencing telomere shortening, oxidative stress, vascular function, and DNA repair mechanisms. In cancer patients, exercise training is generally safe and well-tolerated; it is associated with a 10–15% improvement in cardiorespiratory fitness and can potentially counteract the adverse effects of anti-cancer therapy. It is well known that exercise programs can benefit patients with heart disease and cancer, but little research has been conducted with cardio-oncology patients. To date, there are a limited number of effective protective treatments for preventing or reversing cardiotoxicity caused by cancer therapy. Cardiac rehabilitation has the potential to mitigate cardiotoxicity based on the benefits already proven in populations suffering from either cancer or heart diseases. Additionally, the fact that cardiotoxic harm mechanisms coincide with similar mechanisms positively affected by cardiac rehabilitation makes cardiac rehabilitation an even more plausible option for cardio-oncology patients. Due to unstable functional capacity and fluctuating immunocompetence, these patients require specially tailored exercise programs designed collaboratively by cardiologists and oncologists. As the digital era is here, with the digital world and the medical world continuously intertwining, a remote, home-based cardio-oncology rehabilitation program may be a solution for this population.

The coronavirus disease 2019 (COVID-19) pandemic has remarkably challenged health care organizations and societies. A key strategy for confronting the disease implications on individuals and communities was based on harnessing multidisciplinary efforts to develop technologies for mitigating the disease spread and its deleterious clinical implications. One of the main challenging characteristics of COVID-19 is the provision of medical care to patients with a highly infective disease mandating the use of isolation measures. Such care is complicated by the need for complex critical care, dynamic treatment guidelines, and a vague knowledge regarding the disease’s pathophysiology. A second key component of this challenge was the overwhelming surge in patient burden and the relative lack of trained staff and medical equipment which required rapid re-organization of large systems and augmenting health care efficiencies to unprecedented levels. In contrast to the risk management strategies employed to mitigate other serious threats and the billions of dollars that are invested in reducing these risks annually by governments around the world, no such preparation has been shown to be of effect during the current COVID-19 pandemic. Unmet needs were identified within the newly opened COVID-19 departments together with the urgent need for reliable information for effective decision-making at the state level. This review article describes the early research and development response in Israel under the scope of in-hospital patient care, such as non-contact sensing of patients’ vital signs, and how it could potentially be weaved into a practical big picture at the hospital or national level using a strategic management system. At this stage, some of the described technologies are still in developmental or clinical evidence generation phases with respect to COVID-19 settings. While waiting for future publications describing the results of the ongoing evidence generation efforts, one should be aware of this trend as these emerging tools have the potential to further benefit patients as well as caregivers and health care systems beyond the scope of the current pandemic as well as confronting future surges in the number of cases.

The use of opioids in acute pulmonary oedema is considered standard therapy by many physicians. The immediate relieving effect of morphine on the key symptomatic discomfort associated with acute heart failure, dyspnoea, facilitated the categorisation of morphine as a beneficial treatment in this setting. During the last decade, several retrospective studies raised concerns regarding the safety and efficacy of morphine in the setting of acute heart failure. In this article, the physiological effects of morphine on the cardiovascular and respiratory systems are summarised, as well as the potential clinical benefits and risks associated with morphine therapy. Finally, the reported clinical outcomes and adverse event profiles from recent observational studies are discussed, as well as future perspectives and potential alternatives to morphine in the setting of acute heart failure.

Chemotherapy-associated myocardial toxicity is increasingly recognized with the expanding armamentarium of novel chemotherapeutic agents. The onset of cardiotoxicity during cancer therapy represents a major concern and often involves clinical uncertainties and complex therapeutic decisions, reflecting a compromise between potential benefits and harm. Furthermore, the improved cancer survival has led to cardiovascular complications becoming clinically relevant, potentially contributing to premature morbidity and mortality among cancer survivors. Specific higher-risk populations of cancer patients can benefit from prevention and screening measures during the course of cancer therapies. The pathobiology of chemotherapy-induced myocardial dysfunction is complex, and the individual patient risk for heart failure entails a multifactorial interaction between the selected chemotherapeutic regimen, traditional cardiovascular risk factors, and individual susceptibility. Treatment with several specific chemotherapeutic agents, including anthracyclines, proteasome inhibitors, epidermal growth factor receptor inhibitors, vascular endothelial growth factor inhibitors, and immune checkpoint inhibitors imparts increased risk for cardiotoxicity that results from specific therapy-related mechanisms. We review the pathophysiology, risk factors, and imaging considerations as well as patient surveillance, prevention, and treatment approaches to mitigate cardiotoxicity prior, during, and after chemotherapy. The complexity of decision-making in these patients requires viable discussion and partnership between cardiologists and oncologists aiming together to eradicate cancer while preventing cardiotoxic sequelae.

BackgroundAcute kidney injury (AKI) following primary percutaneous coronary intervention (pPCI) is frequently interpreted as contrast‐induced AKI but may result from other insults. We aimed to determine the causal association of contrast material exposure and the incidence of AKI following pPCI using a control group of propensity score–matched patients with ST‐segment–elevation myocardial infarction who were not exposed to contrast material. Methods and ResultsWe studied 2025 patients with ST‐segment–elevation myocardial infarction who underwent pPCI and 1025 patients receiving fibrinolysis or no reperfusion who were not exposed to contrast material during the first 72 hours of hospital stay (control group). AKI was defined as creatinine of ≥0.5 mg/dL or >25% rise within 72 hours. AKI rates were similar in the pPCI and control groups (10.3% versus 12.1%, respectively; P=0.38). Propensity score matching resulted in 931 matched pairs with PCI and no PCI, with balanced baseline covariates (standardized difference

Pro-arrhythmia (development of cardiac arrhythmias as a pharmacological side effect) has become the single most common cause of the withdrawal or restrictions of previously marketed drugs. The development of new medications, free from these side effects, is hampered by the lack of an in vitro assay for human cardiac tissue. We hypothesized that human embryonic stem cell–derived cardiomyocytes (hESC-CMs) assessed with a combination of single cell electrophysiology and microelectrode array (MEA) mapping can serve as a novel model for electrophysiological drug screening. Current-clamp studies revealed that E-4031 and Sotalol (IKr blockers) significantly increased hESC-CM’s action potential duration and also induced after-depolarizations (the in vitro correlates of increased arrhythmogenic potential). Multicellular aggregates of hESC-CMs were then analyzed with the MEA technique. Application of class I (Quinidine, Procaineamide) and class III (Sotalol) antiarrhythmic agents, E-4031, and Cisapride (a noncardiogenic agent known to lengthen QT) resulted in dose-dependent prolongation of the corrected field potential duration (cFPD). We next utilized the MEA technique to also assess pharmacological effects on conduction. Activation maps demonstrated significant conduction slowing following administration of Na channel blockers (Quinidine and Propafenone) and of the gap junction blocker (1-heptanol). While most attention has been focused on the prospects of using hESC-derived cardiomyocytes for regenerative medicine, this study highlights the possible utilization of these unique cells also for cardiac electrophysiological studies, drug screening, and target validation. [ABSTRACT FROM AUTHOR]