Electrocardiogram Features in Non-Cardiac Diseases: From Mechanisms to Practical Aspects.

Despite the noteworthy advancements and the introduction of new technologies in diagnostic tools for cardiovascular disorders, the electrocardiogram (ECG) remains a reliable, easily accessible, and affordable tool to use. In addition to its crucial role in cardiac emergencies, ECG can be considered a very useful ancillary tool for the diagnosis of many non-cardiac diseases as well. In this narrative review, we aimed to explore the potential contributions of ECG for the diagnosis of non-cardiac diseases such as stroke, migraine, pancreatitis, Kounis syndrome, hypothermia, esophageal disorders, pulmonary embolism, pulmonary diseases, electrolyte disturbances, anemia, coronavirus disease 2019, different intoxications and pregnancy.

Cardio-Oncoimmunology: Cardiac Toxicity, Cardiovascular Hypersensitivity, and Kounis Syndrome.

Cancer therapy can result in acute cardiac events, such as coronary artery spasm, acute myocardial infarction, thromboembolism, myocarditis, bradycardia, tachyarrhythmias, atrio-ventricular blocks, QT prolongation, torsades de pointes, pericardial effusion, and hypotension, as well as chronic conditions, such as hypertension, and systolic and diastolic left ventricular dysfunction presenting clinically as heart failure or cardiomyopathy. In cardio-oncology, when referring to cardiac toxicity and cardiovascular hypersensitivity, there is a great deal of misunderstanding. When a dose-related cardiovascular side effect continues even after the causative medication is stopped, it is referred to as a cardiotoxicity. 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 at very low medication dosages, and can present 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 myocarditis caused by cancer therapy.

Systemic Vascular Resistance and Myocardial Work Analysis in Hypertrophic Cardiomyopathy and Transthyretin Cardiac Amyloidosis with Preserved Left Ventricular Ejection Fraction.

Background: The pathophysiological impact of systemic vascular resistance (SVR) and pressure-strain loop-derived global myocardial work index (GWI) in hypertrophic cardiomyopathy (HCM) and transthyretin cardiac amyloidosis (ATTR) has been randomly investigated. Methods: Both SVR and GWI were assessed in outpatients consecutively referred at two Italian cardiology departments for heart failure with preserved left ventricular ejection fraction (LVEF), affected by either nonobstructive HCM or wild-type ATTR. Based on relevant cross-tabulations, the patients were gathered into 4 functional classes according to cut-off values of 1440 dyne/s/cm-5 for SVR, and 1576 mm Hg% for GWI, as suggested by previous studies. Results: A total of 60 patients, 30 in each group, aged 61 ± 16 years, with 78% males, were studied. HCM patients were younger than those with ATTR and in a better clinical condition (23% HCM vs. 77% ATTR were NYHA class II-III, p < 0.001). Overall, 51 patients (85%) showed a high SVR, 21/30 HCM (70%), and 30 ATTR (100%) (p < 0.005). Both SVR and GWI (expressions of ventricular-arterial coupling) were impaired in 43% of HCM patients (showing greater LV concentric hypertrophy) and 93% of ATTR patients (in advanced NYHA functional class) (p < 0.001). Conclusions: A substantial percentage of present study population showed impaired SVR and/or GWI, despite preserved LVEF. The proposed classification may shed further light on the pathophysiological and clinical characteristics of such hypertrophic phenotypes.

"When," "Where," and "How" of SARS-CoV-2 Infection Affects the Human Cardiovascular System: A Narrative Review.

Coronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory coronavirus-2 (SARS-CoV-2). Several explanations for the development of cardiovascular complications during and after acute COVID-19 infection have been hypothesized. The COVID-19 pandemic, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. The myocardial injury in COVID-19 patients has been associated with coronary spasm, microthrombi formation, plaque rupture, hypoxic injury, or cytokine storm, which have the same pathophysiology as the three clinical variants of Kounis syndrome. The angiotensin-converting enzyme 2 (ACE2), reninaldosterone system (RAAS), and kinin-kallikrein system are the main proposed mechanisms contributing to cardiovascular complications with the COVID-19 infection. ACE receptors can be found in the heart, blood vessels, endothelium, lungs, intestines, testes, neurons, and other human body parts. SARS-CoV-2 directly invades the endothelial cells with ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This causes angiotensin II accumulation downregulation of the ACE2 receptors, resulting in 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. The KKS system typically causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation, but SARS-CoV-2 infection impairs such counterbalancing effects. This cascade results in cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries, microvascular disease, Kounis syndrome, prolonged COVID, myocardial fibrosis, myocarditis, new-onset hypertension, pericarditis, postural orthostatic tachycardia syndrome, pulmonary hypertension, stroke, Takotsubo syndrome, venous thromboembolism, and thrombocytopenia. In this narrative review, we describe and elucidate when, where, and how COVID-19 affects the human cardiovascular system in various parts of the human body that are vulnerable in every patient category, including children and athletes.

Is Adrenaline Always the First Choice Therapy of Anaphylaxis? An Allergist-cardiologist Interdisciplinary Point of View.

Worldwide, adrenaline is considered the first choice therapy in the international guidelines for the management of anaphylaxis. However, the heart and cardiovascular apparatus are strongly involved in anaphylaxis; for that reason, there are some cardiac conditions and certain anaphylaxis patterns that make epinephrine use problematic without adequate heart monitoring. The onset of Kounis syndrome, takotsubo cardiopathy, or the paradoxical anaphylaxis require great attention in the management of anaphylaxis and adrenaline administration by clinicians, who should be aware of the undervalued evolution of anaphylaxis and the potential cardiologic complications of epinephrine administration. Numerous case reports and studies describe the unexpected onset of cardiac diseases following epinephrine treatment, despite the latter being the recommended therapy for anaphylaxis. Our review suggests that future anaphylaxis guidelines should incorporate cardiovascular specialists since the treatment of Kounis syndrome or takotsubo cardiopathy requires cardiologist skills.

[Ischemic heart scombroid syndrome: how to recognize what you know]. / La sindrome sgombroide ischemica miocardica: come riconoscere ciò che si conosce.

Mistreated fish products ingestion can lead to a histaminergic illness known as scombroid syndrome. The disease usually causes cutaneous rash, gastrointestinal, breathing disorders, hypotension with further histamine-related symptoms. Although cardiac complications are infrequent, some patients experienced chest pain consistent with an acute coronary syndrome on admission to hospital. The pathomechanism seems related to a transient coronary artery vasospasm. We performed a literature search for all cases published in the literature from 1997 to 2022 with suspected ischemic heart scombroid syndrome. Overall, 18 studies describing 25 patients were recognized and the main pathophysiological, clinical, diagnostic, therapeutic and prognostic features are discussed. A simplified diagnostic flowchart has also been proposed. Even though this syndrome can lead to hemodynamic instability in the acute phase, also in the young, prognosis is rather good.

Effects of COVID-19 Infection and Vaccination on the Female Reproductive System: A Narrative Review

Several studies and research papers have been published to elucidate and understand the mechanism of the coronavirus disease 2019 (COVID-19) pandemic and its long-term effects on the human body. COVID-19 affects a number of organs, including the female reproductive system. However, less attention has been given to the effects of COVID-19 on the female reproductive system due to their low morbidity. The results of studies investigating the relationship between COVID-19 infection and ovarian function in women of reproductive age have shown the harmless involvement of COVID-19 infection. Several studies have reported the involvement of COVID-19 infection in oocyte quality, ovarian function, and dysfunctions in the uterine endometrium and the menstrual cycle. The findings of these studies indicate that COVID-19 infection negatively affects the follicular microenvironment and dysregulate ovarian function. Although the COVID-19 pandemic and female reproductive health have been studied in humans and animals, very few studies have examined how COVID-19 affects the female reproductive system. The objective of this review is to summarize the current literature and categorize the effects of COVID-19 on the female reproductive system, including the ovaries, uterus, and hormonal profiles. The effects on oocyte maturation, oxidative stress, which causes chromosomal instability and apoptosis in ovaries, in vitro fertilization cycle, high-quality embryos, premature ovarian insufficiency, ovarian vein thrombosis, hypercoagulable state, women's menstrual cycle, the hypothalamus-pituitary-ovary axis, and sex hormones, including estrogen, progesterone, and the anti-Müllerian hormone, are discussed in particular.

Coronary Artery Spasm-Related Heart Failure Syndrome: Literature Review.

Although heart failure (HF) is a clinical syndrome that becomes worse over time, certain cases can be reversed with appropriate treatments. While coronary artery spasm (CAS) is still underappreciated and may be misdiagnosed, ischemia due to coronary artery disease and CAS is becoming the single most frequent cause of HF worldwide. CAS could lead to syncope, HF, arrhythmias, and myocardial ischemic syndromes such as asymptomatic ischemia, rest and/or effort angina, myocardial infarction, and sudden death. Albeit the clinical significance of asymptomatic CAS has been undervalued, affected individuals compared with those with classic Heberden's angina pectoris are at higher risk of syncope, life-threatening arrhythmias, and sudden death. As a result, a prompt diagnosis implements appropriate treatment strategies, which have significant life-changing consequences to prevent CAS-related complications, such as HF. Although an accurate diagnosis depends mainly on coronary angiography and provocative testing, clinical characteristics may help decision-making. Because the majority of CAS-related HF (CASHF) patients present with less severe phenotypes than overt HF, it underscores the importance of understanding risk factors correlated with CAS to prevent the future burden of HF. This narrative literature review summarises and discusses separately the epidemiology, clinical features, pathophysiology, and management of patients with CASHF.

Blood Transfusion Components Inducing Severe Allergic Reactions: The First Case of Kounis Syndrome Induced by Platelet Transfusion.

Kounis syndrome is a multisystem and multidisciplinary disease affecting the circulatory system that can be manifested as spasm and thrombosis. It can occur as allergic, hypersensitivity, anaphylactic, or anaphylactoid reactions associated with the release of inflammatory mediators from mast cells and from other interrelated and interacting inflammatory cells, including macrophages and lymphocytes. A platelet subset with high- and low-affinity IgE surface receptors is also involved in this process. Whereas the heart, and particularly the coronary arteries, constitute the primary targets of inflammatory mediators, the mesenteric, cerebral, and peripheral arteries are also vulnerable. Kounis syndrome is caused by a variety of factors, including drugs, foods, environmental exposure, clinical conditions, stent implantation, and vaccines. We report a unique case of a 60-year-old male with a past medical history of allergy to human albumin, alcoholic cirrhosis, and esophageal varices, who was admitted due to multiple episodes of hematemesis. Due to low hemoglobin levels, he was transfused with 3 units of red blood cells and fresh frozen plasma without any adverse reactions. On the third day of hospitalization, severe thrombocytopenia was observed and transfusion of platelets was initiated. Immediately following platelet infusion, the patient developed chest discomfort, skin signs of severe allergic reaction, and hemodynamic instability. The electrocardiogram revealed ST segment elevation in the inferior leads. Given the strong suspicion of Kounis syndrome/allergic coronary spasm, the patient was treated with anti-allergic treatment only, without any anti-platelet therapy. The clinical status of the patient gradually improved and the electrocardiographic changes reverted to normal. Based on these findings, Kounis hypersensitivity-associated acute coronary syndrome, specifically, type I Kounis syndrome, was diagnosed. Although platelet transfusion can be a life-saving therapy, each blood transfusion carries a substantial risk of adverse reactions. The aims of this report are to expand the existing knowledge of patient responses to blood transfusion and provide information on the incidence of various severe transfusion reactions to all blood components and especially to platelets. To the best of our knowledge, Kounis syndrome induced by platelet transfusionhas never been previously reported. Hypersensitivity to platelet external membrane glycoproteins in an atopic patient seems to be the possible etiology. Despite that Kounis syndrome remains an under-diagnosed clinical entity in everyday practice, it should always be considered in the differential diagnosis of acute coronary syndromes.

The Effect of Long COVID-19 Infection and Vaccination on Male Fertility; A Narrative Review.

Earlier research has suggested that the male reproductive system could be particularly vulnerable to SARS-CoV-2 (COVID-19) infection, and infections involving this novel disease not only pose serious health threats but could also cause male infertility. Data from multi-organ research during the recent outbreak indicate that male infertility might not be diagnosed as a possible consequence of COVID-19 infection. Several review papers have summarized the etiology factors on male fertility, but to date no review paper has been published defining the effect of COVID-19 infection on male fertility. Therefore, the aim of this study is to review the published scientific evidence regarding male fertility potential, the risk of infertility during the COVID-19 pandemic, and the impact of COVID-19 vaccination on the male reproductive system. The effects of COVID-19 infection and the subsequent vaccination on seminal fluid, sperm count, sperm motility, sperm morphology, sperm viability, testes and sex hormones are particularly reviewed.

Different types of Kounis syndrome caused by different episodes of bee sting anaphylaxis: Misfortunes never come singly.

We report our experience with a 69-year-old man who had different types of Kounis syndrome over a short time frame, caused by two episodes of bee sting anaphylaxis. After his first allergic reaction to a bee sting, he experienced a non-ST-segment elevation myocardial infarction; he was treated with percutaneous coronary intervention for near-occlusion of his right coronary artery. This episode was deemed type 2 Kounis syndrome. Four weeks later, we electively treated the nonculprit residual stenosis in his left anterior descending artery. Unfortunately, 2 weeks after this elective procedure, he experienced anaphylactic shock due to a second bee sting. Electrocardiography showed ST elevation in the anterior leads, and emergent coronary angiography showed thrombotic occlusion of the newly implanted stent in the left anterior descending artery. This second episode was deemed type 3 Kounis syndrome. Learning objectives: This is a rare example of different types of Kounis syndrome resulting from repeated exposures to an allergic source, an example that deepens our understanding of Kounis syndrome. This patient's experience illustrates the need for careful evaluation of the indications for revascularization of nonculprit lesions in patients with a history of Kounis syndrome.

Anti-Diabetic Therapy, Heart Failure and Oxidative Stress: An Update.

Diabetes mellitus (DM) and heart failure (HF) are two chronic disorders that affect millions worldwide. Hyperglycemia can induce excessive generation of highly reactive free radicals that promote oxidative stress and further exacerbate diabetes progression and its complications. Vascular dysfunction and damage to cellular proteins, membrane lipids and nucleic acids can stem from overproduction and/or insufficient removal of free radicals. The aim of this article is to review the literature regarding the use of antidiabetic drugs and their role in glycemic control in patients with heart failure and oxidative stress. Metformin exerts a minor benefit to these patients. Thiazolidinediones are not recommended in diabetic patients, as they increase the risk of HF. There is a lack of robust evidence on the use of meglinitides and acarbose. Insulin and dipeptidyl peptidase-4 (DPP-4) inhibitors may have a neutral cardiovascular effect on diabetic patients. The majority of current research focuses on sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. SGLT2 inhibitors induce positive cardiovascular effects in diabetic patients, leading to a reduction in cardiovascular mortality and HF hospitalization. GLP-1 receptor agonists may also be used in HF patients, but in the case of chronic kidney disease, SLGT2 inhibitors should be preferred.

The Chemokines CXC, CC and C in the Pathogenesis of COVID-19 Disease and as Surrogates of Vaccine-Induced Innate and Adaptive Protective Responses.

COVID-19 is one of the progressive viral pandemics that originated from East Asia. COVID-19 or SARS-CoV-2 has been shown to be associated with a chain of physio-pathological mechanisms that are basically immunological in nature. In addition, chemokines have been proposed as a subgroup of chemotactic cytokines with different activities ranging from leukocyte recruitment to injury sites, irritation, and inflammation to angiostasis and angiogenesis. Therefore, researchers have categorized the chemotactic elements into four classes, including CX3C, CXC, CC, and C, based on the location of the cysteine motifs in their structures. Considering the severe cases of COVID-19, the hyperproduction of particular chemokines occurring in lung tissue as well as pro-inflammatory cytokines significantly worsen the disease prognosis. According to the studies conducted in the field documenting the changing expression of CXC and CC chemokines in COVID-19 cases, the CC and CXC chemokines contribute to this pandemic, and their impact could reflect the development of reasonable strategies for COVID-19 management. The CC and the CXC families of chemokines are important in host immunity to viral infections and along with other biomarkers can serve as the surrogates of vaccine-induced innate and adaptive protective responses, facilitating the improvement of vaccine efficacy. Furthermore, the immunogenicity elicited by the chemokine response to adenovirus vector vaccines may constitute the basis of vaccine-induced immune thrombotic thrombocytopaenia.