Search Results (332)

Background and Clinical Significance: Obstructive sleep apnea (OSA) is a common comorbidity in patients with cardiac and metabolic disorders. The coexistence of central sleep apnea with Cheyne–Stokes breathing (CSA-CSB) in heart failure patients, especially those with preserved ejection fraction (HFpEF), represents a diagnostic and therapeutic challenge. Data on continuous positive airway pressure (CPAP) failure and successful adaptation to servo-ventilation (ASV) in the context of complex comorbidities remain limited. Case Presentation: We present the case of a 74-year-old male with a history of type 2 diabetes mellitus, paroxysmal atrial fibrillation, HFpEF, essential hypertension, and bladder carcinoma. He was referred for pre-operative OSA screening, reporting excessive daytime sleepiness, insomnia, and witnessed apneas. Initial respiratory polygraphy revealed severe sleep-disordered breathing with dominant CSA-CSB and moderate OSA. Laboratory investigations also revealed severe iron-deficiency anemia, which was managed with parenteral iron supplementation. The patient underwent CPAP titration, which led to modest improvement and residual high apnea–hypopnea index (AHI). After persistent symptoms and an inadequate CPAP response, an ASV device was initiated with significant clinical and respiratory improvement, demonstrating normalization of hypoxic burden and optimal adherence. Conclusions: CSA-CSB in HFpEF patients with anemia poses unique therapeutic difficulties. This case highlights the importance of individualized diagnostic and therapeutic strategies, including transitioning to ASV in CPAP-refractory cases, which can lead to improved adherence, reduced hypoxia, and better overall outcomes in high-risk patients. Full article

Background/Objectives: Pulmonary vein isolation (PVI) via cryoballoon ablation (CBA) is a recommended therapeutic strategy for patients with symptomatic paroxysmal and persistent atrial fibrillation (AF) who are refractory to antiarrhythmic drugs. Although PVI has demonstrated efficacy in reducing AF recurrence and improving patients’ quality of life, its impact on respiratory function is not well understood, particularly in patients with comorbid conditions. The aim of the study was to search for functional predictors of the respiratory system in the process of evaluating the efficiency of clinical assessment of CBA in patients with AF. Methods: We conducted a prospective study on 42 patients with symptomatic AF who underwent CBA, assessing their respiratory function through spirometry before and 30 days after the procedure. Exclusion criteria included pre-existing lung disease and cardiac insufficiency. The impact of variables such as body mass index (BMI), coronary artery disease (CAD) and heart failure (HF) on spirometry parameters was analyzed using statistical tests. Results: No significant changes were observed in overall post-PVI spirometry parameters for the full cohort. However, post hoc analyses revealed a significant decline in ΔMEF₇₅ in patients with CAD and BMI ≥ 30 kg/m², whereas ΔFEV₁/FVCex was significantly increased in patients with HF, as well as in patients with ejection fraction (EF) < 50%. Conclusions: CBA for AF does not universally affect respiratory function in the short term, but specific subgroups, including patients with CAD and a higher BMI, may require post-procedure respiratory monitoring. In addition, PVI may improve lung function in patients with HF and reduced EF. Full article

Background/Objectives: Heart transplantation is a life-saving procedure for patients with end-stage heart failure, yet it involves significant psychological and emotional challenges throughout its various stages. International guidelines recommend a multi-professional approach to the care of these patients and a psycho-social assessment for listing. The recommendations focus on content aspects, but not on the psychometric measure to be administered to patients as part of the assessment. Therefore, the purpose of this study is to provide the preliminary results of administering the protocol used by our center, measuring coping strategies, cognitive functioning, quality of life, and psychological distress in a sample of patients who are candidates for and undergo cardiac transplantation, and to observe any variations after the procedure. Methods: We conducted a comprehensive psychological-clinical assessment involving 40 patients, focusing on psychosocial functioning, cognitive reserves, mental health, and coping strategies. Tools such as the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT), Beck Depression Inventory-II (BDI-II), Montreal Cognitive Assessment (MoCA), General Anxiety Disorder 7 (GAD-7), and Medical Outcomes Survey Short Form 36 (SF-36) were employed to evaluate readiness for transplantation and post-transplant adaptation. Results: Results showed high levels of clinical anxiety (52.5%) and low perceived physical health (98%) before the transplant, while post-operative evaluations indicated reduced anxiety (13.51%) and depressive symptoms (10.81%), along with improved psychological well-being and reintegration into daily life. Conclusions: These results show improvement in physical and cognitive levels, accompanied by a state of enhanced psychological well-being after transplantation. A longitudinal psychological approach, from pre-transplant screening to post-discharge follow-up, is needed to address distress, improve coping mechanisms, and promote treatment adherence. This integrative strategy is critical to improving the quality of life and long-term outcomes for heart transplant recipients. Full article

Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective of this review is to elucidate how seizures disrupt critical physiological systems, especially the brainstem, heart, and lungs, contributing to SUDEP, with emphasis on respiratory control failure and autonomic instability. Methods: The literature from experimental models, clinical observations, neuroimaging studies, and genetic analyses was systematically examined. Results: SUDEP is frequently preceded by generalized tonic–clonic seizures, which trigger central and obstructive apnea, hypoventilation, and cardiac arrhythmias. Brainstem dysfunction, particularly in areas such as the pre-Bötzinger complex and nucleus tractus solitarius, plays a central role. Genetic mutations affecting ion channels (e.g., SCN1A, KCNQ1) and neurotransmitter imbalances (notably serotonin and GABA) exacerbate autonomic dysregulation. Risk is compounded by a prone sleeping position, reduced arousal capacity, and impaired ventilatory responses. Conclusions: SUDEP arises from a cascade of interrelated failures in respiratory and cardiac regulation initiated by seizure activity. The recognition of modifiable risk factors, implementation of monitoring technologies, and targeted therapies such as serotonergic agents may reduce mortality. Multidisciplinary approaches integrating neurology, cardiology, and respiratory medicine are essential for effective prevention strategies. Full article

Objectives: To evaluate the long-term prognostic value of left ventricular ejection fraction (LVEF) in consecutive patients undergoing invasive coronary angiography (CA). Background: LVEF is a key prognostic marker in cardiovascular disease, but its value across different clinical indications for CA remains insufficiently characterized. Methods: Consecutive patients undergoing CA between January 2016 and August 2022 were retrospectively included at one institution. Patients were stratified into four LVEF groups: ≥ 55%, 45–54%, 35–44%, and <35%. The primary endpoint was rehospitalization for heart failure (HF) at 36 months. Secondary endpoints were acute myocardial infarction (AMI) and coronary revascularization. Kaplan–Meier and multivariable Cox regression analyses were conducted within the entire study cohort and pre-defined subgroups. Results: A total of 6888 patients were included (median age: 71 years; 65.2% males). LVEF < 35% was associated with a higher comorbidity burden and more extensive coronary artery disease (e.g., three-vessel CAD: 38.6% vs. 20.7%, p < 0.001). Event rates for HF rehospitalization and AMI increased progressively with declining LVEF, while revascularization rates varied across categories. Statistically significant differences across LVEF groups were observed for all three endpoints in unadjusted analyses (log-rank p < 0.001). In multivariable models, LVEF < 35% independently predicted HF rehospitalization (HR = 3.731, p < 0.001) and AMI (HR = 4.184, p < 0.001), but not revascularization (HR = 0.867, p = 0.378). The prognostic association was demonstrated across all subgroups stratified by age, sex, subtype of acute coronary syndrome, and CAD severity. Conclusions: Reduced LVEF is an independent predictor of HF rehospitalization and AMI in patients undergoing coronary angiography, irrespective of its indication, whereas no independent association was observed with coronary revascularization. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive form of pre-capillary pulmonary hypertension characterized by persistent, organized thromboemboli in the pulmonary vasculature, leading to vascular remodeling, elevated pulmonary artery pressures, right heart failure, and significant morbidity and mortality if untreated. Despite advances, CTEPH remains underdiagnosed due to nonspecific symptoms and overlapping features with other forms of pulmonary hypertension. Basic Methodology: This review synthesizes data from large international registries, epidemiologic studies, translational research, and multicenter clinical trials. Key methodologies include analysis of registry data to assess incidence and risk factors, histopathological examination of lung specimens, and molecular studies investigating endothelial dysfunction and inflammatory pathways. Diagnostic modalities and treatment outcomes are evaluated through observational studies and randomized controlled trials. Recent Advances and Affected Population: Research has elucidated that CTEPH arises from incomplete resolution of pulmonary emboli, with subsequent fibrotic transformation mediated by dysregulated TGF-β/TGFBI signaling, endothelial dysfunction, and chronic inflammation. Affected populations are typically older adults, often with prior venous thromboembolism, splenectomy, or prothrombotic conditions, though up to 25% have no history of acute PE. The disease burden is substantial, with delayed diagnosis contributing to worse outcomes and higher societal costs. Microvascular arteriopathy and PAH-like lesions in non-occluded vessels further complicate the clinical picture. Conclusions: CTEPH is now recognized as a treatable disease, with multimodal therapies—surgical endarterectomy, balloon pulmonary angioplasty, and targeted pharmacotherapy—significantly improving survival and quality of life. Ongoing research into molecular mechanisms and biomarker-driven diagnostics promises earlier identification and more personalized management. Multidisciplinary care and continued translational investigation are essential to further reduce mortality and optimize outcomes for this complex patient population. Full article

Pulmonary hypertension (PH) is broadly defined as a mean pulmonary arterial pressure (mPAP) exceeding 20 mm Hg at rest. Pulmonary arterial hypertension (PAH) is a specific subset of PH characterized by a normal pulmonary arterial wedge pressure (PAWP), combined with elevated mPAP and increased pulmonary vascular resistance (PVR), without other causes of pre-capillary hypertension such as lung diseases or chronic thromboembolic pulmonary hypertension. The majority of PAH cases are idiopathic; other common etiologies include connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. To a lesser extent, genetic and familial forms of PAH can also occur. The pathophysiology of PAH involves the following four primary pathways: nitric oxide, endothelin-1, prostacyclin, and activin/bone morphogenetic protein (BMP). Dysregulation of these pathways leads to a progressive vasculopathy marked by vasoconstriction, vascular proliferation, elevated right heart afterload, and ultimately right-sided heart failure. Diagnosing PAH is challenging and often occurs at advanced stages. The gold standard for diagnosis remains invasive right heart catheterization. Along with invasive hemodynamic measurements, several noninvasive imaging modalities such as echocardiography and ventilation-perfusion scanning are key adjunct techniques. Also, recent advancements in cardiac magnetic resonance (CMR) have opened a new era for PAH management. Additionally, CMR and echocardiography not only enable diagnosis but also aid in evaluating disease severity and monitoring treatment responses. Current PAH treatments focus on targeting molecular pathways, reducing inflammation, and inhibiting right-sided heart failure. Integrating imaging with basic science techniques is crucial for enhanced patient diagnosis, and precision medicine is emerging as a key strategy in PAH management. Additionally, the incorporation of artificial intelligence into both molecular and imaging approaches holds significant potential. There is a growing need to integrate new imaging modalities with high resolution and reduced radiation exposure into clinical practice. In this review, we discuss the molecular pathways involved in PAH, the imaging modalities utilized for diagnosis and monitoring, and current targeted therapies. Advances in molecular understanding and imaging technologies, coupled with precision medicine, could hold promise in improving patient outcomes and revolutionizing the management of PAH patients. Full article

Background/Objectives: Organ transplantation is a life-saving intervention for patients with terminal organ failure, but long-term success is hindered by graft rejection and dependence on lifelong immunosuppressants. These drugs pose risks such as opportunistic infections and malignancies. Chimeric antigen receptor (CAR) technology, originally developed for cancer immunotherapy, has been adapted to regulatory T cells (Tregs) to enhance their antigen-specific immunosuppressive function. This systematic review evaluates the preclinical development of CAR-Tregs in promoting graft tolerance and suppressing graft-versus-host disease (GvHD). Methods: A systematic review following PROSPERO guidelines (CRD420251073207) was conducted across PubMed, Scopus, and Web of Science for studies published from 2015 to 2024. After screening 105 articles, 17 studies involving CAR-Tregs in preclinical or in vivo transplant or GvHD models were included. Results: CAR-Tregs exhibited superior graft-protective properties compared to unmodified or polyclonal Tregs. HLA-A2-specific CAR-Tregs consistently improved graft survival, reduced inflammatory cytokines, and suppressed immune cell infiltration across skin, heart, and pancreatic islet transplant models. The inclusion of CD28 as a co-stimulatory domain enhanced Treg function and FOXP3 expression. However, challenges such as Treg exhaustion, tonic signaling, and reduced in vivo persistence were noted. Some studies reported synergistic effects when CAR-Tregs were combined with immunosuppressants like rapamycin or tacrolimus. Conclusions: CAR-Tregs offer a promising strategy for inducing targeted immunosuppression in allogeneic transplantation. While preclinical findings are encouraging, further work is needed to optimize CAR design, ensure in vivo stability, and establish clinical-scale manufacturing before translation to human trials. Full article

Acute heart failure (AHF) is a clinical syndrome characterized by the sudden onset or rapid worsening of heart failure signs and symptoms, frequently triggered by myocardial ischemia, pressure overload, or cardiotoxic injury. A central component of its pathophysiology is the activation of intracellular signal transduction cascades that translate extracellular stress into cellular responses. Among these, the mitogen-activated protein kinase (MAPK) pathways have received considerable attention due to their roles in mediating inflammation, apoptosis, hypertrophy, and adverse cardiac remodeling. The canonical MAPK cascades—including extracellular signal-regulated kinases (ERK1/2), p38 MAPK, and c-Jun N-terminal kinases (JNK)—are activated by upstream stimuli such as angiotensin II (Ang II), aldosterone, endothelin-1 (ET-1), and sustained catecholamine release. Additionally, emerging evidence highlights the role of receptor-mediated signaling, cellular stress, and myeloid cell-driven coagulation events in linking MAPK activation to fibrotic remodeling following myocardial infarction. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade plays a central role in regulating cardiomyocyte survival, hypertrophy, energy metabolism, and inflammation. Activation of the PI3K/Akt pathway has been shown to confer cardioprotective effects by enhancing anti-apoptotic and pro-survival signaling; however, aberrant or sustained activation may contribute to maladaptive remodeling and progressive cardiac dysfunction. In the context of AHF, understanding the dual role of this pathway is crucial, as it functions both as a marker of compensatory adaptation and as a potential therapeutic target. Recent reviews and preclinical studies have linked PI3K/Akt activation with reduced myocardial apoptosis and attenuation of pro-inflammatory cascades that exacerbate heart failure. Among the multiple signaling pathways involved, glycogen synthase kinase-3β (GSK-3β) has emerged as a key regulator of apoptosis, inflammation, metabolic homeostasis, and cardiac remodeling. Recent studies underscore its dual function as both a negative regulator of pathological hypertrophy and a modulator of cell survival, making it a compelling therapeutic candidate in acute cardiac settings. While earlier investigations focused primarily on chronic heart failure and long-term remodeling, growing evidence now supports a critical role for GSK-3β dysregulation in acute myocardial stress and injury. This comprehensive review discusses recent advances in our understanding of the MAPK signaling pathway, the PI3K/Akt cascade, and GSK-3β activity in AHF, with a particular emphasis on mechanistic insights, preclinical models, and emerging therapeutic targets. Full article

Targeting fibrosis in Duchenne muscular dystrophy (DMD)-associated cardiomyopathy is a critical outstanding clinical issue, as cardiac failure remains a leading cause of death despite advances in supportive care. This study evaluates the therapeutic efficacy of CSPG4-targeted chimeric antigen receptor (CAR) T cells in reducing cardiac fibrosis and improving heart function in a preclinical model of the disease. DMD is a progressive genetic disorder characterized by degeneration of skeletal and cardiac muscle. Cardiomyopathy, driven by fibrosis and chronic inflammation, is a leading contributor to mortality in affected patients. Proteoglycans such as CSPG4, critical regulators of extracellular matrix dynamics, are markedly overexpressed in dystrophic hearts and promote pathological remodeling. Current treatments do not adequately target the fibrotic and inflammatory processes underlying cardiac dysfunction. CSPG4-specific CAR-T cells were engineered and administered to dystrophic mice. Therapeutic efficacy was assessed through histological, molecular, and echocardiographic analyses evaluating cardiac fibrosis, inflammation, innervation, and overall function. Treatment with CSPG4 CAR-T cells preserved myocardial integrity, improved cardiac performance, and reduced both fibrosis and inflammatory markers. The therapy also restored cardiac innervation, indicating a reversal of neural remodeling commonly seen in muscular dystrophy-related cardiomyopathy. CSPG4-targeted CAR-T therapy offers a novel, cell-based strategy to mitigate cardiac remodeling in dystrophic hearts. By addressing core fibrotic and inflammatory drivers of disease, this approach represents a significant advancement in the development of precision immune therapies for muscular dystrophies and cardiovascular conditions. Full article

Right heart failure (RHF) is a major cause of morbidity and mortality, often resulting from pulmonary arterial hypertension and characterized by impaired calcium (Ca²⁺) handling and maladaptive remodeling. Phosphodiesterase 9A (PDE9A), a cGMP-specific phosphodiesterase, has been proposed as a potential contributor to RHF pathogenesis by suppressing the cardioprotective cGMP–PKG signaling pathway—a conclusion largely extrapolated from left-sided heart failure models. This review examines existing evidence regarding PDE9A’s role in RHF, focusing on its effects on intracellular calcium cycling, fibrosis, hypertrophy, and contractile dysfunction. Data from preclinical models demonstrate that pathological stress upregulates PDE9A expression in cardiomyocytes, leading to diminished PKG activation, impaired SERCA2a function, RyR2 instability, and increased arrhythmogenic Ca²⁺ leak. Pharmacological or genetic inhibition of PDE9A restores cGMP signaling, improves calcium handling, attenuates hypertrophic and fibrotic remodeling, and enhances ventricular compliance. Early-phase clinical studies in heart failure populations suggest that PDE9A inhibitors are well tolerated and effectively augment cGMP levels, although dedicated trials in RHF are still needed. Overall, these findings indicate that targeting PDE9A may represent a promising therapeutic strategy to improve outcomes in RHF by directly addressing the molecular mechanisms underlying calcium mishandling and myocardial remodeling. Full article

One of the most common malignant tumors worldwide is lung cancer, and it is associated with the highest death rate among all cancers. Traditional treatment options for lung cancer include radiation, chemotherapy, targeted therapy, and surgical resection. However, the survival rate is low, and the outlook is still dreadfully dire. The pursuit of a paradigm change in treatment approaches is, therefore, imperative. Tyrosine kinases (TKs), a subclass of protein kinases, regulate vital cellular function by phosphorylating tyrosine residues in proteins. Mutations, overexpression, and autocrine paracrine stimulation can transform TKs into oncogenic drivers, causing cancer pathogenesis. Tyrosine kinase inhibitors (TKIs) have emerged as an attractive targeted therapy option, especially for non-small cell lung cancer (NSCLC). However, resistance to TKIs, and adverse cardiovascular effects such as heart failure, atrial fibrillation, hypertension, and sudden death, are among the most common adverse effects of TKIs. There is increasing interest in plant-derived natural products in the hunt for powerful chemosensitizer and pathway modulators for enhancing TKI activity and/or overcoming resistance mechanisms. This highlights the mechanism of TKs’ activation in cancer, the role of TKIs in NSCLC mechanisms, and the challenges posed by TKI-acquired resistance. Additionally, we explored various plant-derived natural products’ bioactive compounds with the chemosensitizer and pathway-modulating potential with TKs’ inhibitory and anticancer effects. Our review suggests that a combination of natural products with TKIs may provide a novel and promising strategy for overcoming resistance in lung cancer. In future, further preclinical and clinical studies are advised. Full article

Background and Clinical Significance: Fulminant pulmonary embolism (PE) leading to an out-of-hospital cardiac arrest (OHCA) is associated with a high mortality rate and cardiopulmonary resuscitation (CPR) frequently failing to achieve return of spontaneous circulation (ROSC). Extracorporeal CPR (eCPR) has emerged as a potential life-saving intervention. Case Presentation: A 66-year-old woman suffered an OHCA due to massive PE, presenting with pulseless electrical activity (PEA). After 90 min of pre- and in-hospital CPR without sustained ROSC, venoarterial extracorporeal membrane oxygenation (va-ECMO) was initiated as eCPR upon arrival at the hospital. Even after implantation of the va-ECMO, there was initially a pronounced acidosis (pH 6.9) with a high elevated lactate level (>30 mmol/L); these factors, together with the prolonged low-flow period, indicated a poor prognosis. Further diagnostic tests revealed intracranial hemorrhage (subdural hematoma), and systemic lysis was not possible. With persistent right heart failure, surgical thrombectomy was performed during hospitalization. Intensive multidisciplinary management finally led to successful therapy and weaning from mechanical ventilation, as well as to complete neurological recovery (CPC-Score 1-2). Conclusions: This case illustrates that eCPR can facilitate survival with good favorable neurological outcomes despite initially poor prognostic predictors. It underscores the importance of refining patient selection criteria and optimizing management strategies for eCPR in refractory cardiac arrest secondary to PE. Full article

Right heart failure is a condition where the right ventricle fails to pump blood into the pulmonary artery, and, in turn, the lungs. This condition frequently presents after the implantation of a left ventricular assist device (LVAD). Ventricular assist candidates who have LVADs implanted possess various pathophysiological and cardiovascular features that contribute to the later development of RHF. With LVADs serving as bridge-to-transplantation, bridge-to-candidacy, and destination therapies, it is imperative that the pre-operative indicators of RHF are identified and assessed. Multiple predictive models and parameters have been developed to quantify the risk of post-LVAD right heart failure. Clinical, laboratory, hemodynamic, and echocardiographic parameters have all been used to develop these predictive approaches. RHF remains a major cause of morbidity and mortality after LVAD implantation. Predicting RHF helps clinicians assess treatment options, including biventricular support or avoiding high-risk surgery. In our review, we noted the varying definitions for RHF in recent models, which affected respective predictive accuracies. The pulmonary arterial pulsatile index (PAPi) and right ventricular longitudinal strain parameters were noted for their potential to enhance current models incrementally. Meanwhile, mechanistic and machine learning approaches present a more fundamental shift in the approach to making progress in this field. Full article

Heart failure with preserved ejection fraction (HFpEF) is a complex and heterogeneous clinical syndrome characterized by signs and symptoms of heart failure despite normal or near-normal ejection fraction. It is a debilitating chronic disease that affects millions of people worldwide, and due to the paucity of evidence-based pharmacological treatments for HFpEF, nonpharmacological approaches as potential therapeutic alternatives are of growing interest. As a result, renal denervation (RDN), initially developed as a therapeutic tool for resistant hypertension, has become an area of active clinical interest. RDN is a catheter-based procedure that targets the renal sympathetic pathways, aiming to reduce neurohormonal activation and mitigate maladaptive cardiac remodeling. Preclinical studies in animal models have demonstrated that RDN can improve cardiac and vascular fibrosis, reduce renal inflammation, control hypertension, and alleviate endothelial dysfunction. Recent clinical studies have further highlighted the potential benefits of RDN in patients with HFpEF and uncontrolled hypertension. In this review, we aim to outline the pathophysiology of HFpEF and demonstrate the complex clinical interplay involved in how RDN impacts the heart. Moreover, we discuss the present status of clinical studies on RDN and explore its therapeutic potential as a viable treatment for HFpEF. Full article