High systemic inflammation as a novel cardiovascular risk factor and target for anti-cytokine therapy: comment regarding the triglyceride glucose index.

In the last century, there has been more than enough research that proved the association of high lipid and glucose levels with cardiovascular disease, thus establishing the current well-known traditional cardiovascular risk factors such as dyslipidemia, diabetes, and metabolic syndrome. Hence, these cardiovascular risk factors are target therapy for glucose and lipid-lowering agents to prevent adverse cardiovascular events. However, despite controlling the lipid and glucose levels, some studies demonstrated the subclinical atherosclerosis suggesting that these cardiovascular risk factors alone cannot account for the entire atherosclerosis burden. In the last years, large-scale clinical trials demonstrated the operation of the inflammatory pathway in atherosclerotic cardiovascular disease (ASCVD) by the immune system, both the innate (neutrophils, macrophages) and adaptive (T cell and other lymphocytes) limbs, contribute to atherosclerosis and atherothrombosis. In this regard, some studies that use antiinflammatory therapy targeting the immune system by modulating or blocking interleukins, also known as anti-cytokine therapy, have been shown to reduce the risk of adverse cardiovascular events in patients with previous coronary artery disease. In this regard, the U.S. Food and Drug Administration (FDA) approved the use of colchicine 0.5 mg once daily for reducing cardiovascular events in patients who have established ASCVD and high residual systemic inflammation. Therefore, measuring the systemic inflammation can improve the cardiovascular risk assessment and identify the subsets of patients that will benefit from anti-cytokine therapy after diagnosis of ASCVD or after myocardial revascularization.

Neutrophil-to-lymphocyte ratio an inflammatory biomarker, and prognostic marker in heart failure, cardiovascular disease and chronic inflammatory diseases: New insights for a potential predictor of anti-cytokine therapy responsiveness.

In the 20th century, research focused on cholesterol and lipoproteins as the key mechanism in establishing atherosclerotic cardiovascular disease (ASCVD). Given that some studies demonstrated subclinical atherosclerosis in subjects without conventional cardiovascular risk factors, the elevated low-density lipoprotein (LDL) levels alone cannot account for the entire burden of atherosclerosis. Hence, large-scale clinical trials demonstrated the operation of immune and inflammatory pathways in ASCVD. In this regard, the evidence establishes that cells of the immune system, both the innate (neutrophils, macrophages) and adaptive (T cell and other lymphocytes) limbs, contribute to atherosclerosis and atherothrombosis. Besides, basic science studies have identified proatherogenic cytokines such as interleukin (IL)-1, IL-12, and IL-18. In this regard, some studies showed that antiinflammatory therapy targeting the immune system by modulating or blocking interleukins, also known as anti-cytokine therapy, can reduce the risk of major cardiovascular adverse events. The neutrophils play a key role in the innate immune system, representing the acute phase of an inflammatory response. In contrast, lymphocytes represent the adaptive immune system and promote the induction of autoimmune inflammation, especially in the chronic inflammatory response. Through the literature review, we will highlight the inflammatory pathway for the physiopathology of ASCVD, HF, and COVID-19. In this regard, the neutrophil-to-lymphocyte ratio (NLR) integrates the innate immune and adaptive immune systems, making the NLR a biomarker of inflammation. In addition, we provided an update on the evidence showing that high NLR is associated with worse prognosis in heart failure (HF), ASCVD, and COVID-19, as well as their clinical applications showing that the normalization of NLR after anti-cytokine therapy is a potential predictor of therapy responsiveness and is associated with reduction of major adverse cardiovascular events.

Transcatheter aortic valve with a novel self-expandable device in patients with previous mechanical mitral valve prosthesis.

OBJECTIVES: The aim of this study was to describe the procedural and early outcomes of patients with mechanical mitral valve prosthesis (MVP) undergoing transcatheter aortic valve replacement (TAVR) with a novel self-expandable retrievable device. BACKGROUND: TAVR in patients with prior MVP may have an increased risk of complications related to device positioning and interference between both prosthetic valves. METHODS: An observational study was conducted, including eight patients with severe symptomatic aortic stenosis and prior mechanical MVP who underwent TAVR with the novel device AllegraTM (Biosensors). No transesophageal monitoring was used. RESULTS: The mean age of the study population was 75 years. The mean distance between MVP and aortic annulus was 3.8 mm. Procedural success was achieved in all patients with no major intraprocedural, in-hospital, or follow-up complications. CONCLUSIONS: TAVR with Allegra TAVI system in patients with prior MVP offers good procedural and clinical outcomes.

Pseudo-aortic dissection after sudden cardiac death in coronary angiography a case report: Pearls and pitfalls in false aortic dissection artifacts.

INTRODUCTION AND IMPORTANCE: Various artifacts mimicked aortic dissection, such as streak artifacts generated by high-attenuation material, high-contrast interfaces, cardiac motion, periaortic structures, aortic wall motion, and normal aortic sinuses, have been described in the literature. Most artifacts that simulate ascending aortic dissection occur frequently on conventional CT. Their position is predictable and is related to systolic aortic motion. However, so far, to the best of our knowledge, this is the first pseudo-aortic dissection reported during coronary angiography in cardiac arrest. CASE PRESENTATION: We report a case of a middle-aged man transferred to our hospital after an out-of-hospital cardiac arrest. The coronary angiography revealed non-obstructive coronary arteries and an image of probable aortic dissection was observed. Given the persistent asystole despite a prolonged advance cardiopulmonary resuscitation and the possibility of aortic dissection, a prompt in-room heart team discussion was performed. It was decided to stop and withdraw potentially life-sustaining treatment due to futility. The necropsy study revealed the aorta with some mild atherosclerotic plaques but without either aneurysm or thrombosis. The coronary arteries were reported as with patency, but in the proximal left anterior descending artery (LAD), the intima layer presented a thickness that decreased 50 % of the luminal area without signs of complicated acute plaques. CLINICAL DISCUSSION: In this case, the systolic aortic motion theory cannot explain the false-aortic dissection image in the coronary angiography because the patient was under cardiac arrest. Studies with arterial and venous pressures devices recording in cardiac arrest, demonstrated an abnormal hemodynamic flow, suggesting that the hemodynamic flow might be backward during cardiopulmonary resuscitation Therefore, in the setting of this abnormal hemodynamic flow, the injection of contrast may have an abnormal distribution and flow in the aorta creating an image of pseudo-aortic dissection. CONCLUSION: Although the exact mechanism of this false-positive aortic dissection in cardiac arrest remains unknown, operators should be aware of this entity during coronary angiography in the setting of cardiac arrest with mechanical chest compressions to avoid diagnostic errors in clinical practice.

Subtle QRS changes are associated with reduced ejection fraction, diastolic dysfunction, and heart failure development and therapy responsiveness: Applications for artificial intelligence to ECG.

BACKGROUND: Since the last century, the electrocardiogram (ECG) remains the non-invasive test, that is, most easily accessible, feasible, and inexpensive for cardiology assessment. In past years, many novel ECG indexes and patterns have been published that allow for a more advanced evaluation of what is currently being done, especially based on subtle QRS changes and patterns. OBJECTIVE: The objective of the study was to provide an update on the evidence and clinical applications of these ECG subtle QRS changes and patterns associated with heart disease. METHODS: Through the literature review, we will highlight the subtle QRS changes and patterns associated with heart disease, mainly focusing on QRS duration, voltage, morphology, axis, and QT interval. RESULTS: Small increases in QRS duration are associated with a reduction in left ventricular ejection fraction (EF), increased cardiac chamber dimensions, and risk for incident heart failure (HF). Moreover, fragmentation of the QRS complex is associated with myocardial fibrosis and is a substrate for developing arrhythmic events. Besides, low amplitude QRS voltage is associated with congestive HF, and an increase in the voltage of the QRS complexes is associated with the effectiveness of diuresis treatment. Furthermore, small increases in QT interval are associated with diastolic dysfunction due to impaired sarcoplasmic reticulum calcium handling as occurs in myocardial ischemia, hypertension, or diabetes. On the other hand, in patients with left ventricular dysfunction, the QRS area is associated with clinical and echocardiographic response to cardiac resynchronization therapy regardless of the type of bundle branch block. In addition, subtle ECG changes and patterns in the left bundle branch block are associated with concomitant right ventricular dilation, mostly based on the QRS axis and voltage. Notwithstanding, to identify these subtle changes in QRS require exact manual measurements that can take time. In this regard, applying artificial intelligence (AI) to the ECG can make a quicker and more complete assessment, as well as provide a low cost when applied to large populations. CONCLUSION: We provided an update on the evidence and clinical applications of these subtle QRS changes and patterns associated with diastolic dysfunction, reduced EF, and HF development and therapy responsiveness, as well as their applications for AI to ECG.

Calcium Signaling Pathway Is Involved in the Shedding of ACE2 Catalytic Ectodomain: New Insights for Clinical and Therapeutic Applications of ACE2 for COVID-19.

The angiotensin-converting enzyme 2 (ACE2) is a type I integral membrane that exists in two forms: the first is a transmembrane protein; the second is a soluble catalytic ectodomain of ACE2. The catalytic ectodomain of ACE2 undergoes shedding by a disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), in which calmodulin mediates the calcium signaling pathway that is involved in ACE2 release, resulting in a soluble catalytic ectodomain of ACE2 that can be measured as soluble ACE2 plasma activity. The shedding of the ACE2 catalytic ectodomain plays a role in cardiac remodeling and endothelial dysfunction and is a predictor of all-cause mortality, including cardiovascular mortality. Moreover, considerable evidence supports that the ACE2 catalytic ectodomain is an essential entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Additionally, endotoxins and the pro-inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor-alpha (TNFα) all enhanced soluble catalytic ectodomain ACE2 shedding from the airway epithelia, suggesting that the shedding of ACE2 may represent a mechanism by which viral entry and infection may be controlled such as some types of betacoronavirus. In this regard, ACE2 plays an important role in inflammation and thrombotic response, and its down-regulation may aggravate COVID-19 via the renin-angiotensin system, including by promoting pathological changes in lung injury. Soluble forms of ACE2 have recently been shown to inhibit SARS-CoV-2 infection. Furthermore, given that vitamin D enhanced the shedding of ACE2, some studies reported that vitamin D treatment is associated with prognosis improvement in COVID-19. This is an updated review on the evidence, clinical, and therapeutic applications of ACE2 for COVID-19.

The soluble catalytic ectodomain of ACE2 a biomarker of cardiac remodelling: new insights for heart failure and COVID19.

The angiotensin-converting enzyme 2 (ACE2) is a type I integral membrane that was discovered two decades ago. The ACE2 exists as a transmembrane protein and as a soluble catalytic ectodomain of ACE2, also known as the soluble ACE2 that can be found in plasma and other body fluids. ACE2 regulates the local actions of the renin-angiotensin system in cardiovascular tissues, and the ACE2/Angiotensin 1-7 axis exerts protective actions in cardiovascular disease. Increasing soluble ACE2 has been associated with heart failure, cardiovascular disease, and cardiac remodelling. This is a review of the molecular structure and biochemical functions of the ACE2, as well we provided an updated on the evidence, clinical applications, and emerging potential therapies with the ACE2 in heart failure, cardiovascular disease, lung injury, and COVID-19 infection.

Letter by Garcia A, et al. regarding article: Coronary artery disease risk reclassification by a new acoustic-based score.

The best cost-effective non-invasive test for the diagnosis of coronary artery disease (CAD) in patients with intermediate pre-test probability (PTP) is unknown. Nevertheless one of the most common non invasive test used is the exercise treadmill testing (ETT) that is the less expensive non-invasive test but with the lowest sensitivity for the diagnosis of CAD, therefore many patients with intermediate PTP will required another non-invasive test with a higher cost and some of them require exposure to radiation. Despite all these measures, an estimated $108.9 billion is spent annually on CAD treatment. Some studies had showed that diastolic dysfunction is associated to CAD. A novel signal-processed surface ECG (MyoVista hsECG) can detection the abnormal myocardial relaxation and therefore identified CAD. The non-invasive acoustic device CADScore V3 algorithm had lower cost compared with any noninvasive test, with a high negative predictive value but not good enough specificity to diagnose CAD, hence should be the first approach in patients with a low and intermediate probability of CAD, and if to this evaluation will added the Myovista hs ECG to detection of CAD, therefore some patients with intermediate PTP could be reclassified into high risk and a better cost-effective decisions could be taken as referring directly to coronary angiography.