Search Results (133)

The vein of Galen malformations (VoGMs) is mainly correlated with the retention of an embryonic pattern of vascularity, inducer of vein of Galen dilation, and formation of arteriovenous communications that give rise to the risk of systemic shunting, causing cardiac dysfunction, vascular steal, and venous hypertension. This is a rare cerebral vascular malformation in the newborn, accounting for 1% of all cerebral arteriovenous malformations and occurring in approximately 1 in 25,000–50,000 live births. We review nine cases of newborns diagnosed with vein of Galen malformations (VoGMs) to assess whether this pathology demonstrates a marked improvement over the past 13 years in diagnostic accuracy, treatment approaches, and patient survival rates within our clinic. Medical treatment was focused on providing inotropic support and tightly controlled peripheral and pulmonary vasodilation with the aim of overriding the effects of high output heart failure. Most of the patients underwent liver failure and flow-mediated pulmonary hypertension, while half of the newborns expressed anomalies of the nervous system due to impaired cerebral hemodynamics. Given the unavailability of endovascular treatment in our unit, which predisposes the newborns to a higher vital risk, we recognize the importance of delivering tailored intensive care aimed at maintaining cardiorespiratory and hemodynamic stability until a curative intervention can be performed in a specialized center. Full article

Endothelial dysfunction (characterized by reduced vasodilation or vasoconstriction, oxidative stress, inflammation, and pro-thrombotic condition) is a critical factor in the pathophysiology of various cardiovascular conditions, and the application of anesthetics can affect this dysfunction. Patients undergoing major surgery, especially cardiovascular surgery, are at increased risk of endothelial dysfunction. The impact of anesthetics on endothelial function can vary depending on the specific agent, dosage, duration of exposure, comorbidities, etc. Certain anesthetics, especially at higher doses, may increase the production of reactive oxygen species (ROS), leading to oxidative stress and endothelial dysfunction through reduced nitric oxid (NO) availability. Some anesthetics can modulate inflammatory responses, either by suppressing or exacerbating inflammation, or may affect the permeability of the endothelium, potentially leading to pulmonary edema and disruption of the blood-brain barrier. Anesthetics can influence endothelial glycocalyx. Understanding anesthetics effects is crucial for optimizing anesthetic management, particularly in patients with pre-existing cardiovascular issues. Therefore, the aim of this review is to critically evaluate the effects of different classes of anesthetics on endothelial function and oxidative stress. Specifically, we address how anesthetics influence NO bioavailability, endothelial glycocalyx integrity, inflammatory and oxidative pathways, and clinical outcomes in surgical patients. By summarizing current evidence, we aim to highlight mechanistic insights and identify potential perioperative strategies to minimize endothelial dysfunction. Full article

Persistent pulmonary hypertension of the newborn (PPHN) results from disrupted fetal–neonatal circulatory transition, characterized by elevated pulmonary vascular resistance (PVR), right-to-left shunting, and refractory hypoxemia. Despite improved perinatal care, PPHN remains a major source of neonatal morbidity and mortality. This review details PPHN phenotypes, pathophysiology, etiology, diagnostics including echocardiography and biomarkers like B-type Natriuretic Peptide (BNP) or N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), and current therapeutic modalities, from lung recruitment and surfactant to targeted vasodilator therapy (iNO, sildenafil, milrinone, bosentan) and extracorporeal membrane oxygenation (ECMO). We emphasize the role of endothelial and molecular mechanisms in precision therapy and outline guidelines for clinical decision-making in diverse care settings. Full article

Protein S-nitrosylation is a selective post-translational modification in which a nitrosyl group is covalently attached to the reactive thiol group of cysteine, forming S-nitrosothiol. This modification plays a pivotal role in modulating physiological and pathological cardiovascular processes by altering protein conformation, activity, stability, and other post-translational modifications. It is instrumental in regulating vascular and myocardial systolic and diastolic functions, vascular endothelial cell and cardiomyocyte apoptosis, and cardiac action potential and repolarization. Aberrant S-nitrosylation levels are implicated in the pathogenesis of various cardiovascular diseases, including systemic hypertension, pulmonary arterial hypertension, atherosclerosis, heart failure, myocardial infarction, arrhythmia, and diabetic cardiomyopathy. Insufficient S-nitrosylation leads to impaired vasodilation and increased vascular resistance, while excessive S-nitrosylation contributes to cardiac hypertrophy and myocardial fibrosis, thereby accelerating ventricular remodeling. This paper reviews the S-nitrosylated proteins in the above-mentioned diseases and their impact on these conditions through various signaling pathways, with the aim of providing a theoretical foundation for the development of novel therapeutic strategies or drugs targeting S-nitrosylated proteins. Full article

The common cause of porto-pulmonary hypertension and hepato-pulmonary syndrome is portal hypertension. Porto-pulmonary hypertension (PPHTN) is a form of pulmonary arterial hypertension, and hepato-pulmonary syndrome (HPS) occurs as a consequence of hepatic injury or vascular disorders. Demographic characteristics, pathophysiology, screening, differential diagnosis, and treatment of both disorders are treated in this review. Oxygen supply and other medical managements combined with vasodilator drugs are adopted for PPHTN and HPS treatment, but these two clinical conditions also represent an indication for liver transplantation. Despite poor evidence, PPHTN is treated as idiopathic pulmonary arterial hypertension. The latter is combined with improved pulmonary hemodynamics permitting lung transplant. Lung transplant improves PPHTN in one-half of patients and has been associated with longer survival in selected patients. However, the risk of the latter procedure can be relevant as it is closely related to PPHTN severity. Large clinical trials and international guidelines may have a predominant role in increasing our knowledge of both PPHNT and HPS and in improving their outcome by favoring an early diagnosis and more accurate treatment. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) can complicate the clinical course of patients with acute pulmonary embolism, with a variable prevalence of 0.5–4%. Beyond specific therapeutic strategies, including pulmonary endarterectomy, balloon pulmonary angioplasty and pulmonary vasodilators, lifelong anticoagulation still represents the mainstay of treatment for this condition. The main historical experience supports the use of vitamin K antagonists (VKAs) in CTEPH patients; conversely, the efficacy and safety of direct oral anticoagulants (DOACs) in this setting are unclear. Growing experience, mainly from small studies and registries, is improving our knowledge, showing that DOACs may represent a valid and promising alternative to warfarin in CTEPH patients. Therefore, in the management of cases with a newly diagnosed CTEPH, clinicians are very often in the difficult position of (a) having to choose which anticoagulant to initiate in anticoagulant-naïve patients or (b) having to evaluate whether it is necessary to switch to a VKA in patients already on DOACs. This article aims to critically summarize the current evidence comparing DOACs and VKAs in CTEPH, discussing their efficacy and safety profiles and exploring their clinical applicability. Full article

Pulmonary hypertension (PH) can develop from multiple etiologic mechanisms and disease states. Of all such conditions, left-sided heart disease (LHD) is commonly understood to be the most common etiology or mechanism. Given the widespread prevalence of left heart disease and the prognostic implications of PH, early diagnosis is imperative. More recently, the diagnostic cut-offs for mean pulmonary arterial pressure as well as peripheral vascular resistance have been lowered to achieve this objective. Despite these revised standards, the current indications for right heart catheterization are mostly aimed at identifying advanced disease. Proven vasodilator therapies for pulmonary arterial hypertension have so far not shown a meaningful role in the management of PH in LHD. This is largely related to the fact that multiple mechanisms and co-morbidities can independently lead to the development of PH in an individual patient. Understanding and identifying those phenotypes remain important in devising future treatment strategies. Molecular pathways that eventually lead to irreversibility of PH can provide another frontier in the pharmacologic management of PH in LHD. Full article

Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) and concomitant interstitial lung disease (ILD) are particularly challenging to manage due to concerns about ventilation–perfusion mismatch with systemic vasodilators. In this case series, we evaluated the effects of selexipag in eight prostacyclin-naïve CTD-PAH patients with concomitant ILD. Clinical, functional, and laboratory data were collected at baseline and after 16 weeks of treatment. After 16 weeks of treatment, the mean six-minute walk distance increased by 101.75 m (p < 0.05), and the mean estimated right ventricular systolic pressure decreased significantly (p < 0.05). Mean N-terminal pro b-type natriuretic peptide levels declined by 63%, though this reduction did not reach statistical significance. Importantly, supplemental oxygen requirements trended downward (p < 0.05) and pulmonary function tests remained stable. Pulmonary vasodilators have long been unsuccessfully studied in PH-ILD patients until the INCREASE trial. While other systemic agents used in PAH have not shown as much success as inhaled treprostinil in treating PH-ILD, our case series highlights the potential role of selexipag in patients with concomitant CTD-PAH and ILD. Further investigation of selexipag in pure Group 3 PH-ILD patients is warranted. Full article

Background: The aim of this study was to describe our centre experience in the use of pulmonary vasodilator therapy in Fontan patients. Methods: We retrospectively enrolled patients that underwent Fontan operation between 2000 and 2024, reporting demographic and operative data and noting complications and the use of pulmonary vasodilators. Results: A total of 117 patients were followed for a median time of 150 months (90–207). In total, 36.7% were female, and the median age during the intervention was 50 months (37–64), and 53% had a single left ventricle physiology. In 20 of these 117 patients (17.1%), at least one pulmonary vasodilator drug was used during their life for the following reasons: 6 elevated pressures in the circuit, 3 low oxygen saturation, 2 plastic bronchitis, 2 pleural effusion, 1 chylothorax, 1 persistent pericardial effusion, 1 haemoptysis, 1 protein losing enteropathy, 1 poor exercise tolerance, 1 pulmonary arterial hypertension present since birth and 1 diastolic dysfunction. They had a significantly higher prevalence of single right ventricle physiology (65% vs. 37%, p = 0.03), pulmonary hypertension (60% vs. 0, p = 0.0001), plastic bronchitis (10% vs. 0, p = 0.03) and declivous oedema in the follow-up period (10% vs. 0, p = 0.03), with a higher assumption of warfarin (35% vs. 6.2%, p = 0.001). Conclusions: We found that in the absence of a standardise protocol, we usually use pulmonary vasodilator therapy in Fontan patients, as it is guided by clinical aspects and hemodynamic conditions, which lead us to start and stop this therapy. Full article

Pulmonary arterial hypertension (PAH) is a lethal condition marked by the proliferation and remodeling of small pulmonary arteries, ultimately leading to right ventricular hypertrophy and right heart failure. PAH secondary to connective tissue diseases (CTDs) is a progressive complication with a complex pathogenesis that results in the reduced efficacy of vasodilation-based therapies and poor clinical outcomes. Systemic sclerosis is the most commonly associated CTD with PAH in Western countries and has been most extensively investigated. Systemic lupus erythematosus and other CTDs may also be associated with PAH; however, they are less studied. In this review, we explore the general pathobiology of PAH, with a particular emphasis on recent advances in the molecular pathogenesis of CTD-PAH, including endothelial cell dysfunction, dysregulated cell proliferation and vascular remodeling, extracellular matrix remodeling, in situ thrombosis, right ventricular dysfunction, genetic aberrations, and immune dysregulation. We also conduct a thorough investigation into the potential serum biomarkers and immune dysregulation associated with CTD-PAH, summarizing the associated autoantibodies, cytokines, and chemokines. Furthermore, relevant animal models that may help unravel the pathogenesis and contribute to the development of new treatments are also reviewed. Full article

Nitric oxide (NO), an endogenous vasodilator, has been proposed as a biomarker for pulmonary hypertension (PH) in humans. NO is synthesized by endothelial nitric oxide synthase (eNOS). Alterations in NO/eNOS have not been studied in dogs with PH. We assessed alterations in NO and eNOS in the blood of dogs with PH (n = 17) and healthy dogs (n = 10) and analyzed their correlations with echocardiographic parameters. The results showed significantly higher plasma NO and serum eNOS levels in dogs with PH compared with healthy dogs. Dogs with PH and ascites (n = 11) had significantly lower plasma NO levels than those without ascites (n = 6) and presented a decreasing eNOS trend. In dogs with PH, plasma NO was positively correlated with left ventricular hemodynamics, right ventricular compliance, and pulmonary distensibility, but was negatively correlated with pulmonary vascular resistance and right cardiac remodeling. Serum eNOS was positively correlated with the main pulmonary artery diameter. Increments in NO/eNOS reflected compensatory responses to cardiovascular changes in PH. These compensations were downward in the advanced stages. Other factors may also impact NO/eNOS compensation. Although the role of NO/eNOS as biomarkers for PH in dogs remains equivocal, they may indicate compensatory consequences of cardiovascular alterations. Full article

Background/Objectives: Pulmonary hypertension is a progressive disease leading to right heart failure. One treatment strategy is to induce vasodilation via the nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate (NO–sGC–cGMP) signaling pathway. There are currently two soluble guanylate cyclase stimulators on the market: Riociguat and vericiguat, with vericiguat having a longer half-life and needing to be taken only once a day. This study investigated whether the pharmacological differences between the drugs affect pulmonary vessels and airways. Methods: The effects of vericiguat and riociguat on pulmonary arteries, veins, and airways were studied using rat precision-cut lung slices (PCLS). Vessels were pretreated with endothelin-1 and airways with serotonin. In isolated perfused lungs (IPL), the effects of sGC stimulation on pulmonary artery pressure (PAP), airway resistance, inflammatory cytokine, and chemokine release were quantified. Results: Riociguat and vericiguat caused pulmonary artery dilation in PCLS. During IPL, riociguat was more effective than vericiguat in reducing PAP with a statistically significant reduction of 10%. Both drugs were potent bronchodilators in preconstricted airways (p < 0.001). Only vericiguat reduced airway resistance during IPL, as shown here for the first time. Both drugs significantly reduced IL-6 and IL-1ß levels, while riociguat also reduced VEGF-A and KC-GRO levels. Conclusions: Riociguat and vericiguat had three main effects in the two rat ex-vivo models: They dilated the pulmonary arteries, induced bronchodilation, and reduced inflammation. These properties could make sGC stimulators useful for treating diseases associated with endothelial dysfunction. In the future, vericiguat may provide an alternative treatment to induce bronchodilation in respiratory diseases. Full article

Pulmonary hypertension associated with interstitial lung disease (ILD-PH) frequently complicates the course of patients with fibrotic ILD. In this narrative review, the authors assess current diagnostic tools and management considerations in ILD-PH patients. ILD-PH is associated with increased morbidity and mortality and may be suggested by the presence of symptoms out of proportion to the extent of the ILD. There are other clues to the presence of PH in the context of ILD including the need for supplemental oxygen, a reduced DLCO especially if accompanied by a disproportionately higher forced vital capacity, imaging demonstrating an enlarged pulmonary artery or a dilated right ventricle, or objective evidence of a reduced exercise capacity. While echocardiography is one screening tool, right heart catheterization remains the gold standard for the diagnosis of PH. When appropriate, treatment with inhaled treprostinil, or possibly other pulmonary vasodilators, may be indicated. Full article

The gasotransmitter hydrogen sulfide (H₂S; also termed sulfide) generally acts as a vasodilator in the systemic vasculature but causes a paradoxical constriction of pulmonary arteries (PAs). In light of evidence that a fall in the partial pressure in oxygen (pO₂) increases cellular sulfide levels, it was proposed that a rise in sulfide in pulmonary artery smooth muscle cells (PASMCs) is responsible for hypoxic pulmonary vasoconstriction, the contraction of PAs which develops rapidly in lung regions undergoing alveolar hypoxia. In contrast, pulmonary hypertension (PH), a sustained elevation of pulmonary artery pressure (PAP) which can develop in the presence of a diverse array of pathological stimuli, including chronic hypoxia, is associated with a decrease in the expression of sulfide -producing enzymes in PASMCs and a corresponding fall in sulfide production by the lung. Evidence that PAP in animal models of PH can be lowered by administration of exogenous sulfide has led to an interest in using sulfide-donating agents for treating this condition in humans. Notably, intracellular H₂S exists in equilibrium with other sulfur-containing species such as polysulfides and persulfides, and it is these reactive sulfur species which are thought to mediate most of its effects on cells through persulfidation of cysteine thiols on proteins, leading to changes in function in a manner similar to thiol oxidation by reactive oxygen species. This review sets out what is currently known about the mechanisms by which H₂S and related sulfur species exert their actions on pulmonary vascular tone, both acutely and chronically, and discusses the potential of sulfide-releasing drugs as treatments for the different types of PH which arise in humans. Full article

Primary pulmonary hypertension (PPH), now known as pulmonary arterial hypertension (PAH), has induced significant treatment breakthroughs in the past decade. Treatment has focused on improving patient survival and quality of life, and delaying disease progression. Current therapies are categorized based on targeting different pathways known to contribute to PAH, including endothelin receptor antagonists (ERAs), phosphodiesterase-5 inhibitors (PDE-5 inhibitors), prostacyclin analogs, soluble guanylate cyclase stimulators, and activin signaling inhibitors such as Sotatercept. The latest addition to treatment options is soluble guanylate cyclase stimulators, such as Riociguat, which directly stimulates the nitric oxide pathway, facilitating vasodilation. Looking to the future, advancements in PAH treatment focus on precision medicine involving the sub-stratification of patients through a deep characterization of altered Transforming Growth Factor-β(TGF-β) signaling and molecular therapies. Gene therapy, targeting specific genetic mutations linked to PAH, and cell-based therapies, such as mesenchymal stem cells, are under investigation. Besides prevailing therapies, emerging PH treatments target growth factors and inflammation-modulating pathways, with ongoing trials assessing their long-term benefits and safety. Hence, this review explores current therapies that delay progression and improve survival, as well as future treatments with curative potential. Full article