The most frequent cause of cardiac failure globally is ischemic heart disease, with chemothera-py-related cardiovascular side effects emerging as the second most frequent cause. Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT pro-longation, torsades de pointes, pericardial effusion and hypotension, as well as chronic conditions, such as hypertension, systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovas-cular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovas-cular side effect continues even after the causative medication is stopped, it is referred to as cardi-otoxicity. A fibrotic response is the ultimate outcome of cardiac toxicity, which is defined as a dose-related cardiovascular adverse impact that lasts even after the causative treatment is stopped. Cardiotoxicity can occur after a single or brief exposure. On the other hand, the term cardiac or cardiovascular hypersensitivity describes an inflammatory reaction that is not dose-dependent, can occur at any point during therapy, even with very low medication dosages, and can show up as Kounis syndrome. It may also be accompanied by anti-drug antibodies and tryptase levels. In this comprehensive review, we present the current views on cardiac toxicity and cardiovascular hypersensitivity, together with the reviewed cardiac literature on the chemotherapeutic agents inducing hypersensitivity reactions. Cardiac hypersensitivity seems to be the pathophysiologic basis of coronary artery spasm, acute coronary syndromes such as Kounis syndrome and myocardi-tis caused by cancer therapy.

The impact of systemic vascular resistance (SVR) in hypertrophic (HCM) and amyloid cardio-myopathies has been seldom investigated. We studied pressure-strain loop derived myocardial work (MW) indices and SVR in patients with either sarcomere HCM or wild type transthyretin cardiac amyloidosis (ATTR), presented with heart failure and preserved left ventricular ejection fraction (HFpEF) at the outpatient cardiology units at Messina and Catania University Hospitals (Italy). Patients were in sinus rhythm and needed to have good transthoracic ultrasound imaging quality to undergo transthoracic strain-echocardiography. Other than conventional parameters, SVR and GWI (global work index) were measured. Based on cross-tabulation (a way to assess the ventricular-arterial coupling), the patients were then classified in 4 classes according to the cut-off values suggested by previous studies of 1,440 dyne/s/cm-5 for SVR (Stefadouros et al., 1973) and 1576 mm Hg% for GWI (Olsen et al., 2022). Sixty patients, 30 in each group, aged 61±16 years, 78% males, were studied. HCM were younger than ATTR patients and in a better clinical status (23% HCM vs 77% ATTR were NYHA class 3, p<0.001). Overall, 51 patients (85%) showed high SVR, of whom 21 were HCM (70%) and 30 ATTR (100%) (p<0.005). Both, SVR and GWI were impaired (the poorest class C) in 43% HCM patients (with greater left ventricular concentric hypertrophy) vs 93% of ATTR patients (in advanced NYHA class) (p<0.001). In conclusion, assessing SVR and GWI in HFpEF patients with HCM or ATTR can help clinicians to interpret the pathophysiological and clinical features of such complex diseases.

The novel severe acute respiratory coronavirus-2 (SARS-Cov-2) constitutes the causative agent of coronavirus disease-2019 (COVID-19). Several mechanisms have been proposed regarding the development of cardiovascular complications during and after acute COVID-19 infection. COVID-19, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. Several clinical and pathophysiologic mechanisms have been proposed for development of cardiovascular complications during and after acute COVID-19 infection. The myocardial injury in patients with COVID-19 has been attributed to coronary spasm, microthrombi formation, plaque rupture, hypoxic injury or cytokine storm disposing the same pathophysiology with the three clinical variants of Kounis syndrome. One of the main proposed mechanisms for development of cardiovascular complications is the angiotensin converting enzyme 2 (ACE2) and its interactions with the renin-aldosterone system (RAAS) and the kinin-kallikrein system (KKS). The ACE2 receptors are expressed throughout the human body located mainly in heart, blood vessels endothelium, lungs, intestines, testes and neurons. The SARS-CoV-2 directly invades the endothelial cells that contain ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This leads to downregulation of the ACE2 receptors and causes angiotensin II accumulation leading to prothrombotic effects such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. Indeed, angiotensin I exerts no direct biological function except that its high levels can stimulate catecholamine production. It is metabolized to its biologically active byproduct angiotensin II, a potent vasoconstrictor, by angiotensin converting enzyme (ACE) through cleavage of the two terminal amino acids. SARS-CoV-2 infection prevents the counterbalancing action of the KKS system that normally causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation. All this cascade leads to the following cardiovascular events: cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries and microvascular disease, Kounis syndrome, long COVID, myocardial fibrosis, myocarditis, new onset hypertension, pericarditis, postural orthostatic tachycardia syndrome (POTS), pulmonary hypertension, stroke, Takotsubo Syndrome, venous thromboembolism and thrombocytopenia. In this narrative review we describe and elucidate when and how the COVID-19 affects the human cardiovascular system, in various areas on the human body that are vulnerable in every category of patients including children and athletes.

Abstract Objective: To review the relevant literature on the use of atrioventricular node ablation and pacing in patients with heart failure and atrial fibrillation. Methods: A PubMed/MEDLINE and SCOPUS search was performed in order to assess the clinical outcomes of atrioventricular node ablation and pacemaker implantation, as well as the complications that may occur. Results: Several clinical trials, observational analyses and meta-analyses have shown that “pace and ablate” strategy not only improves symptoms but also can enhance cardiac performance in patients with heart failure and atrial fibrillation. Although this procedure is effective and safe, some complications may occur including worsening of heart failure, permanent fibrillation, arrhythmias and sudden death. Regarding the implantation of pacemaker, cardiac resynchronization therapy is shown to be the optimal choice compared to right ventricle apical pacing. His bundle pacing is a promising alternative to cardiac resynchronization therapy and has shown beneficial effects, while left bundle brunch pacing is an innovative modality. Conclusions: Atrioventricular node ablation and implantation of pacemaker is shown to have beneficial effects on clinical outcomes of patients with atrial fibrillation ± heart failure who do not respond or are intolerant to medical treatment. Cardiac resynchronization therapy is the treatment of choice and His bundle pacing seems to be an effective alternative way of pacing in these patients.