Newly detected diabetes mellitus patients with acute coronary syndrome have an adverse cardiometabolic profile similar to patients with prior diabetes and a more extensive ischemic myocardial insult.

AIMS: The impact of newly detected diabetes mellitus (NDDM) on metabolic parameters and extent of myocardial necrosis in patients with acute coronary syndrome (ACS) is not fully explored. We examined the impact of NDDM on cardiometabolic characteristics and myocardial necrosis in ACS patients. METHODS: CALLINICUS-Hellas Registry is an ongoing prospective multicenter observational study evaluating the adherence to lipid-lowering therapy (LLT) among ACS patients in Greece. Three groups were created: a) patients with NDDM (abnormal fasting glucose, HbA1c ≥ 6.5 % and no previous history of DM), b) patients without known DM and HbA1c < 6.5 % (non-DM) and c) patients with prior DM. RESULTS: The prevalence of NDDM among 1084 patients was 6.9 %. NDDM patients had lower HDL-C [38 (32-45) vs 42 (36-50) mg/dL] and higher triglycerides levels [144 (104-231) vs 115 (87-152) mg/dL] compared to non-DM patients (p < 0.05). NDDM patients featured both higher body mass index [29.5 (26.4-34.3) vs 27.1 (24.9-29.9) kg/m2] and waist circumference [107 (100-114) vs 98 (91-106) cm] compared to non-DM patients (p < 0.05). In addition, NDDM patients had more extensive myocardial necrosis than patients with prior DM. CONCLUSIONS: ACS patients with NDDM have an adverse cardiometabolic profile similar to patients with prior DM and have more extensive myocardial insult.

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.

Intubation Time, Lung Mechanics and Outcome in COVID-19 Patients Suffering Acute Respiratory Distress Syndrome: A Single-Center Study.

Background: We examined the effect of intubation time and the lung mechanics on clinical outcomes in coronavirus disease 2019 (COVID-19) patients. Methods: Based on the patient's hospital admission, intubation time was defined as early (≤ 2 days) or late (> 2 days). Patients were further divided into three groups; early (≤ 3 days), late (4 - 6 days), and very late (> 6 days) intubated. Results: A total of 194 patients were included; 66.5% male, median age 65 years. Fifty-eight patients (29.9%) were intubated early and 136 (70.1%) late. Early intubated patients revealed lower mortality (44.8% vs. 72%, P < 0.001), were younger (60 vs. 67, P = 0.002), had lower sequential organ failure assessment (SOFA) scores (6 vs. 8, P = 0.002) and higher lung compliance on admission days 1, 6 and 12 (42 vs. 36, P = 0.006; 40 vs. 33, P < 0.001; and 37.5 vs. 32, P < 0.001, respectively). Older age (adjusted odds ratio (aOR) = 1.15, P < 0.001), intubation time (aOR = 1.15, P = 0.004), high SOFA scores (aOR = 1.81, P < 0.001), low partial pressure of oxygen (PaO2)/fractional inspired oxygen tension (FiO2) ratio (aOR = 0.96, P = 0.001), and low lung compliance on admission days 1 and 12 (aOR = 1.12, P = 0.012 and aOR = 1.14, P < 0.001, respectively) were associated with higher mortality. Very late and late intubated patients had higher mortality rates than patients intubated early (78.4% vs. 63.4% vs. 44.6%, respectively, P < 0.001). Conclusions: Among COVID-19 intubated patients, age, late intubation, high SOFA scores, low PaO2/FiO2 ratio, and low lung compliance are associated with higher intensive care unit (ICU) mortality.

"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.

Outcomes of Atrioventricular Node Ablation and Pacing in Patients with Heart Failure and Atrial Fibrillation: From Cardiac Resynchronization Therapy to His Bundle Pacing.

Objective: To review the relevant literature on the use of atrioventricular node ablation and pacing in patients with heart failure and atrial fibrillation. Methods: APubMed/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 the "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 pacemaker implantation, 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 branch pacing is an innovative modality. Conclusions: Atrioventricular node ablation and pacemaker implantation 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.

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.

Atrial fibrillation in heart failure patients: An update on renin-angiotensin-aldosterone system pathway blockade as a therapeutic and prevention target.

Heart failure (HF) and atrial fibrillation (AF) are two cardiovascular (CV) entities that affect millions of individuals worldwide and their prevalence is translated into a significant impact on health care systems. The common pathophysiological pathways that these two share have created an important clinical interrelation, as the coexistence of HF and AF is associated with worse prognosis and treatment challenges. Renin-angiotensin-aldosterone system (RAAS), a critical mechanism in blood pressure (BP) control, was proved to be involved in the pathogenesis of both conditions contributing to their further coexistence. Successful control of BP is of great importance to the management of HF, crucial for the prevention of arrhythmiogenic substrates, while RAAS antagonists may possibly affect the development of new-onset AF as well. There are numerous studies that evaluated the effectiveness of RAAS blockade in AF/HF population and despite comparable or modest results, there is a well-established suggestion that RAAS blockers may contribute to a reduction of HF, CV events and recurrence of AF, along with their potential effective role in the new-onset AF prophylaxis. Angiotensin receptor blockers, according to the evidence, are more effective in that direction, followed by angiotensin converting enzyme inhibitors, whereas the data on aldosterone antagonists are not encouraging, yet do have the potential of significant CV disease modificators regardless of their effects on BP.

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.

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.

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.

Ultrasound-guided femoral approach for coronary angiography and interventions in the porcine model.

Coronary angiography and percutaneous coronary intervention (PCI) procedural details in swine are similar to those performed to humans, since their heart and coronary anatomy closely resembles. However, only a few detailed descriptions of the procedure are available, containing notable differences. We present a feasible and reproducible protocol for percutaneous coronary interventions in porcine experimental models, utilizing ultrasound-guided femoral approach. Nine female pigs were studied to explore the feasibility of superficial femoral arterial (SFA) access for coronary angiography and provisional PCI, as well as the most suitable guiding coronary catheters and angiographic projections for the above interventions. Experiments were performed under general anesthesia, using ultrasound-guided puncture of the SFA to gain arterial access. The Amplatzer AR1® catheter, and the Right Coronary Bypass® catheter were used for the selective engagement of the right and the left coronary artery, respectively. Successful arterial access and subsequent cardiac catheterization were performed in all pigs. Only one animal required a second puncture for femoral artery access. None of the 9 animals presented any significant tachycardia or hypotensive episode. One animal developed an access site-related complication following the first catheterization procedure. During follow-up, 100% success of SFA catheterization was achieved using the same ultrasound-guided technique. The ultrasound-guided superficial femoral artery access for coronary angiography and provisional interventions in porcine models is a quick and safe alternative to the carotid artery approach. The RCB and AR1 catheters may be the best choice for the quick and easy selective coronary engagement of the right and left ostia, respectively.

Pharmacologic Rate versus Rhythm Control for Atrial Fibrillation in Heart Failure Patients.

Atrial fibrillation (AF) and Heart failure (HF) constitute two frequently coexisting cardiovascular diseases, with a great volume of the scientific research referring to strategies and guidelines associated with the best management of patients suffering from either of the two or both of these entities. The common pathophysiological paths, the adverse outcomes, the hospitalization rates, and the mortality rates that occur from various reports and trials indicate that a targeted therapy to the common background of these cardiovascular conditions may reverse the progression of their interrelating development. Among other optimal treatments concerning the prevalence of both AF and HF, the introduction of rhythm and rate control strategies in the guidelines has underlined the importance of sinus rhythm and heart rate control in the prevention of deleterious complications. The use of these strategies in the clinical practice has led to a debate about the superiority of rhythm versus rate control. The current guidelines as well as the published randomized trials and studies have not proved that rhythm control is more beneficial than the rate control treatments in the terms of survival, all-cause mortality, hospitalization rates, and quality of life. Therefore, the current therapeutic strategy is based on the therapy guidelines and the clinical judgment and experience. The aim of this review was to elucidate the endpoints of pharmacologic randomized clinical trials and the clinical data of each antiarrhythmic or rate-limiting medication, so as to promote their effective, individualized, evidence-based clinical use.