Sotatercept in pulmonary hypertension and beyond.

Sotatercept binds free activins by mimicking the extracellular domain of the activin receptor type IIA (ACTRIIA). Additional ligands are BMP/TGF-beta, GDF8, GDF11 and BMP10. The binding with activins leads to the inhibition of the signalling pathway and the deactivation of the bone morphogenic protein (BMP) receptor type 2.

A Personalized Approach to Vitamin D Supplementation in Cardiovascular Health Beyond the Bone: An Expert Consensus by the Italian National Institute for Cardiovascular Research.

Vitamin D is increasingly recognized for its role in cardiovascular health beyond its well-established effects on bone metabolism. This review synthesizes findings from observational studies, interventional trials, and meta-analyses to clarify the mechanisms through which vitamin D impacts cardiovascular health, including its influence on vascular function, inflammation, and metabolic pathways. Additionally, this review emphasizes the importance of a personalized approach to vitamin D supplementation, integrating individual cardiovascular risk profiles, baseline vitamin D levels, and comorbid conditions, such as hypertension and diabetes.

Sotatercept: New drug on the horizon of pulmonary hypertension.

Sotatercept (brand name WINREVAIR, developed by Merck) is an activin receptor type IIA-Fc (ActRIIA-Fc), working by sequestering free activins. Sotatercept restores the balance between the activin proliferative pathway and the bone morphogenic protein (BMP) antiproliferative pathway in the pulmonary arterial cirulation. Sotatercept recently received approval in the USA and in Europe for the treatment of adults with pulmonary arterial hypertension (PAH) Group 1, on top of background PAH therapy to increase exercise capacity, improve WHO functional class and reduce the risk of clinical worsening events.

Perspectives on Sotatercept in Pulmonary Arterial Hypertension.

Sotatercept acts as a type IIA-Fc activin receptor, thereby scavenging free activin from its physiological membrane receptor. Through this type of action, sotaterpect leads to a rebalancing of the proliferation and antiproliferation pathways of pulmonary smooth muscle cells in response to bone morphogenic protein (BMP). Although sotatercept has been approved as the fourth pillar of therapy for group 1 pulmonary arterial hypertension (PAH) in the United States and Europe, several studies are ongoing to broaden the application of the drug to non-Group 1 PAH.

Not Just CTEPH: A Narrative Review on the Spectrum Approach to Postpulmonary Embolism Conditions.

Three mutually exclusive entities can underlie a postpulmonary embolism syndrome (PPES): not obstructed postpulmonary embolism syndrome (post-PE dyspnea), chronic thromboembolic pulmonary disease (CTEPD), and chronic thromboembolic pulmonary hypertension (CTEPH). Cardiorespiratory impairment in CTEPH and CTEPD underlies respiratory and hemodynamic mechanisms, either at rest or at exercise. Gas exchange is affected by the space effect, the increased blood velocity, and, possibly, intracardiac right to left shunts.

Right ventricular phenotyping in incident patients with idiopathic pulmonary arterial hypertension.

Background: Right ventricular (RV) imaging has not a definite role in risk stratification of pulmonary arterial hypertension (PAH) patients. We tested the hypothesis that echocardiography-derived phenotypes, depicting different degrees of RV remodeling and dysfunction, may provide additional prognostic information to current risk stratification tools.

Methods: Consecutive incident PAH patients aged ≥18 years, diagnosed between January 2005 and December 2021, underwent clinical assessment, right heart catheterization, standard echocardiography.

Omega-3 polyunsaturated fatty acids and pulmonary arterial hypertension: Insights and perspectives.

Pulmonary arterial hypertension (PAH) is a rare and progressive disorder that affects the pulmonary vasculature. Although recent developments in pharmacotherapy have extended the life expectancy of PAH patients, their 5-year survival remains unacceptably low, underscoring the need for multitarget and more comprehensive approaches to managing the disease. This should incorporate not only medical, but also lifestyle interventions, including dietary changes and the use of nutraceutical support.

Cardiovascular outcomes and molecular targets for the cardiac effects of Sodium-Glucose Cotransporter 2 Inhibitors: A systematic review.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new class of glucose-lowering drugs traditionally used to control blood glucose levels in patients with type 2 diabetes mellitus, have been proven to reduce major adverse cardiovascular events, including cardiovascular death, in patients with heart failure irrespective of ejection fraction and independently of the hypoglycemic effect. Because of their favorable effects on the kidney and cardiovascular outcomes, their use has been expanded in all patients with any combination of diabetes mellitus type 2, chronic kidney disease and heart failure. Although mechanisms explaining the effects of these drugs on the cardiovascular system are not well understood, their effectiveness in all these conditions suggests that they act at the intersection of the metabolic, renal and cardiac axes, thus disrupting maladaptive vicious cycles while contrasting direct organ damage.

Inferior vena cava filters: Concept review and summary of current guidelines.

Anticoagulation is the first-line approach in the prevention and treatment of pulmonary embolism. In some instances, however, anticoagulation fails, or cannot be administered due to a high risk of bleeding. Inferior vena cava filters are metal alloy devices that mechanically trap emboli from the deep leg veins halting their transit to the pulmonary circulation, thus providing a mechanical alternative to anticoagulation in such conditions.

Vasostatins: new molecular targets for atherosclerosis, post-ischaemic angiogenesis, and arteriogenesis.

The chromogranin-secretogranin secretory proteins-granins-are acidic proteins localized in granules of endocrine cells and neurons. The chromogranin family includes chromogranins A (CgA) and B, as well as secretogranin II (once called chromogranin C). Members of this family undergo catalytic proteolysis to produce active peptides.

Chronic thromboembolic pulmonary disease: Association with exercise-induced pulmonary hypertension and right ventricle adaptation over time.

Background And Aim: Chronic thromboembolic pulmonary disease (CTEPD) is a progressive condition caused by fibrotic thrombi and vascular remodeling in the pulmonary circulation despite prolonged anticoagulation. We evaluated clinical factors associated with CTEPD, as well as its impact on functional capacity, pulmonary haemodynamics at rest and after exercise, and right ventricle (RV) morphology and function.

Methods: We compared 33 consecutive patients with a history of acute pulmonary embolism and either normal pulmonary vascular imaging (negative Q-scan, group 1, n = 16) or persistent defects on lung perfusion scan (positive Q-scan) despite oral anticoagulation at 4 months (group 2, n = 17).

Atrial Strain Assessment for the Early Detection of Cancer Therapy-Related Cardiac Dysfunction in Breast Cancer Women (The STRANO STUDY: Atrial Strain in Cardio-Oncology).

Left ventricular global longitudinal strain (GLS) has an important role in the diagnosis of cancer therapy-related cardiac dysfunction (CTRCD). Little is known about the role of atrial function in diagnosing CTRCD. The aim of our study was to assess the impact of anti-cancer drugs on atrial function measured by speckle-tracking echocardiography in breast cancer women.

Endothelial heterogeneity and their relevance in cardiac development and coronary artery disease.

Micro- and macrovascular endothelial cells (ECs) are characterized by structural and functional heterogeneity, which is also reflected in their secretory activity. The root of this heterogeneity and related regulatory mechanisms are still poorly understood. During embryogenesis, microvascular ECs participate in organogenesis prior to the development of the fetal circulation, suggesting that ECs are capable of releasing paracrine trophogens, termed angiocrine factors (AFs).

Antineoplastic drugs inducing cardiac and vascular toxicity - An update.

With the improvement in cancer prognosis due to advances in antitumor therapeutic protocols and new targeted and immunotherapies, we are witnessing a growing increase in survival, however, at the same timeincrease in morbidity among cancer survivors as a consequences of the increased cardiovascular adverse effects of antineoplastic drugs. Common cardiovascular complications of antineoplastic therapies may include cardiac complications such as arrhythmias, myocardial ischemia, left ventricular dysfunction culminating in heart failure as well as vascular complications including arterial hypertension, thromboembolic events, and accelerated atherosclerosis. The toxicity results from the fact that these drugs not only target cancer cells but also affect normal cells within the cardiovascular system.

Exploring the significance of epicardial adipose tissue in aortic valve stenosis and left ventricular remodeling: Unveiling novel therapeutic and prognostic markers of disease.

Aortic stenosis (AS) is a dynamic degenerative process that shares many pathophysiological features with atherogenesis, from initial proinflammatory calcification and focal thickening of the valve leaflets to obstruction of left ventricular outflow due to superimposed of severe calcification and immobilization of the valve leaflets. As the prevalence increases with age, AS is expected to become one of the most common heart diseases worldwide. In both obese and nonobese patients, persistent thickening of epicardial adipose tissue (EAT) is associated with a shift in its normal metabolic functions toward a dysmetabolic and proatherogenic phenotype that may impair the physiology of adjacent coronary arteries and promote the occurrence of coronary atherosclerosis.

Autophagy, innate immunity, and cardiac disease.

Autophagy is an evolutionarily conserved mechanism of cell adaptation to metabolic and environmental stress. It mediates the disposal of protein aggregates and dysfunctional organelles, although non-conventional features have recently emerged to broadly extend the pathophysiological relevance of autophagy. In baseline conditions, basal autophagy critically regulates cardiac homeostasis to preserve structural and functional integrity and protect against cell damage and genomic instability occurring with aging.

Biobanks: The unmet need in heart failure management.

Heart failure (HF) represents a major health and economic issue, with increasing morbidity and mortality in spite of novel therapeutic weapons. The disappointing results of HF management may be due to the current therapeutic approach based on the paradigm "one fits all", that cannot apply to a complex and multifaceted syndrome as HF. At this regard, the European Union is developing policies to move from reductionism to precision medicine, in order to identify specific disease biomarkers and develop targeted therapeutic strategies.

Vascular Progenitor Cells: From Cancer to Tissue Repair.

Vascular progenitor cells are activated to repair and form a neointima following vascular damage such as hypertension, atherosclerosis, diabetes, trauma, hypoxia, primary cancerous lesions and metastases as well as catheter interventions. They play a key role not only in the resolution of the vascular lesion but also in the adult neovascularization and angiogenesis sprouting (i.e.

Empagliflozin inhibits excessive autophagy through the AMPK/GSK3β signalling pathway in diabetic cardiomyopathy.

Aims: Sodium-glucose cotransporter 2 inhibitors have beneficial effects on heart failure and cardiovascular mortality in diabetic and non-diabetic patients, with unclear mechanisms. Autophagy is a cardioprotective mechanism under acute stress conditions, but excessive autophagy accelerates myocardial cell death leading to autosis. We evaluated the protective role of empagliflozin (EMPA) against cardiac injury in murine diabetic cardiomyopathy.