Search Results (2,713)

Hypertension is a major risk factor for heart failure. Acetylation of p53 is known to regulate its activities. We have previously identified that p53 acetylation is required for cardiac remodeling in a mouse model of pressure overload-induced heart failure. Acetylation mutant p53 (p53aceKO) mice have been shown to have the ability to regulate SIRT3 KO-induced cardiac fibrosis. In the present study, we hypothesized that p53aceKO mice would exhibit cardiac protection and blunt cardiac fibrosis when subjected to Ang-II-induced hypertension. Control and p53aceKO mice received either a micro-osmotic pump implant administering Ang-II for 28 days or a sham procedure. Blood pressure was measured weekly, and echocardiography was performed every two weeks. Mice were euthanized and hearts were processed for histological analysis. While both control and p53aceKO mice receiving Ang-II exhibit increased systolic and diastolic blood pressures, control mice also demonstrate increases in ejection fraction and fractional shortening compared to the sham, while p53aceKO mice do not. Furthermore, control mice receiving Ang-II exhibit decreased left ventricular diameter and volume at end-systole and end-diastole, as well as thickening of both the anterior and posterior walls, while p53aceKO mice exhibit no significant changes in any of these parameters. Additionally, p53aceKO mice do not exhibit the Ang-II infusion-induced cardiac fibrosis seen in control mice treated with Ang-II. Mutation of p53 acetylation is protective against Ang-II infusion-induced cardiac fibrosis and dysfunction in mice. Acetylated p53 may, therefore, be a novel therapeutic target to address complications in the heart associated with hypertension. Full article

Cancer-induced cardiac dysfunction has become a major clinical challenge as advances in cancer therapies continue to extend patient survival. Once regarded as a secondary concern, cardiotoxicity is now recognized as a leading contributor to morbidity and mortality among cancer patients and survivors. Its pathophysiology is multifactorial, involving systemic inflammation (e.g., TNF-α, IL-6), oxidative stress driven by reactive oxygen species (ROS), neurohormonal imbalances (e.g., angiotensin II, endothelin-1), and metabolic disturbances. These mechanisms collectively promote cardiomyocyte apoptosis, atrophy, mitochondrial dysfunction, and impaired cardiac output. Cardiac complications may arise directly from cancer itself or as adverse effects of oncologic therapies such as anthracyclines, trastuzumab, and immune checkpoint inhibitors. These agents have been linked to heart failure (HF), systolic dysfunction, and cardiac atrophy, often progressing insidiously and underscoring the importance of early detection and careful monitoring. Current preventive and therapeutic strategies include pharmacological interventions such as ACE inhibitors, beta-blockers, statins, dexrazoxane, and endothelin receptor antagonists like atrasentan. Emerging compounds, particularly Withaferin A (WFA), have shown potential through their anti-inflammatory and cardiac protective properties. In addition, antioxidants and lifestyle modifications may provide supplementary cardioprotective benefits, while interventional cardiology procedures are increasingly considered in selected patients. Despite encouraging progress, standardized treatment protocols and robust long-term outcome data remain limited. Given the heterogeneity of cancer types and cardiovascular responses, a personalized and multidisciplinary approach is essential. Continued research and close collaboration between oncologists, cardiologists, and basic scientists will be the key to advancing care, reducing treatment-related morbidity, and ensuring that improvements in cancer survival are matched by preservation of cardiovascular health. Full article

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) are pathologies that impact mortality and morbidity worldwide. These chronic diseases have multiple causes, and they share some common clinical symptoms, such as diaphragm dysfunction (DD) and cognitive decline (CD), which, in turn, increase the mortality and morbidity rates in patients with COPD and CHF. One of the causes of CD is impaired glymphatic system function, with an accumulation of proteins and metabolites in the central nervous system. The glymphatic system is a structure that has not yet been widely considered by researchers and clinicians. Three key factors stimulate the ongoing physiological function of the glymphatic system: autonomic balance, heart rate, and, most importantly, the diaphragm. All these factors are altered in patients with COPD and CHF. This article reviews the relationship between the importance of the diaphragm, the glymphatic system, and CD, focusing on inspiratory rehabilitation training (IMT). Based on the data reported in this narrative review, we can strongly speculate that a consistent regimen of IMT in patients can improve cognitive status, reducing the cascade of symptoms that follow the diagnosis of CD. Further research is needed to understand whether targeting the glymphatic system with IMT is an effective option for helping patients delay the onset of CD. Full article

Background: Cardiotoxicity remains a concern across cancer therapies. To date, there is a lack of extensive studies evaluating the potential impact of radioligand therapy (RLT) on myocardial injury in patients with neuroendocrine tumors (NETs), particularly in subgroups with increased susceptibility to such injury. This study aimed to assess the potential cardiotoxic effects and myocardial dysfunction associated with RLT using both [¹⁷⁷Lu]Lu-DOTA-TATE and tandem therapy with [¹⁷⁷Lu]Lu-DOTA-TATE/[⁹⁰Y]Y-DOTA-TATE in patients with NETs, including specific high-risk subgroups such as patients with pre-existing heart failure, carcinoid heart disease or those previously treated with chemotherapy, by monitoring serum concentration of troponin I, CK-MB, and NT-proBNP before and after RLT. Methods: We conducted a retrospective observational analysis of 60 consecutive NET patients who underwent 228 RLT courses. A comprehensive cardiac assessment, including a detailed medical history, was performed. Additionally, serum troponin I, CKMB and NT-proBNP concentrations were measured prior to treatment and 48 h post-therapy. Fifty-two patients received [¹⁷⁷Lu]Lu-DOTA-TATE monotherapy, while eight patients were treated with tandem therapy. Results: No increase in cardiotoxicity markers was observed in the overall study population following RLT administration (ΔTroponin −0.2 [−1.4–0.3]ng/L, p = 0.007; ∆CKMB 0.0 [−4.0–3.0]U/L, p = 0.90; ΔNT-proBNP 4.0 [−45.6–33.6]pg/mL) as well as in the subgroup receiving tandem therapy (ΔTroponin 0.7 [−1.7–013]ng/L, p = 0.68; ΔCKMB −0.5 [−10.7–3.0]U/L, p = 0.21; ΔNT-proBNP −21.6 [−44.1–16.7]pg/mL). Furthermore, none of the predefined patient subgroups exhibited signs of cardiotoxicity or evidence of myocardial dysfunction. Conclusions: RLT is a safe anticancer treatment option for patients with NETs in terms of cardiotoxicity and cardiac dysfunction, including those at higher risk of cardiovascular complications. Full article

Introduction: Twelve-lead electrocardiography (ECG) remains an essential diagnostic tool for patients presenting with chest pain. Timely recognition of specific electrocardiographic patterns is critical for guiding reperfusion strategies and predicting adverse outcomes. Among these, Wellens’ pattern is a high-risk marker of critical left anterior descending (LAD) artery stenosis and an impending anterior myocardial infarction. Although typically described in clinically stable patients without heart failure, its occurrence in the setting of acute decompensation is rare. Case Report: We report the case of a 66-year-old male with hypertension, obesity, and active smoking who presented with exertional chest pain, dyspnea, and signs of acute heart failure. Initial ECG revealed biphasic T waves in V2–V4, consistent with type A Wellens’ pattern. Laboratory evaluation demonstrated elevated troponin I, while point-of-care ultrasound (POCUS) identified systolic and diastolic dysfunction, lateral wall hypokinesia, pericardial effusion, and cardiogenic pulmonary edema. The patient received acute management with antiplatelet therapy, statins, diuretics, and anticoagulation, followed by referral for coronary angiography. This revealed critical stenosis (>90%) of the proximal LAD, successfully treated with percutaneous coronary intervention and drug-eluting stent implantation. The in-hospital course was uneventful, and guideline-directed medical therapy was optimized at discharge, including dual antiplatelet therapy, beta-blocker, renin–angiotensin system inhibitor, and SGLT2 inhibitor. Conclusions: This case highlights the need for early recognition of Wellens’ pattern, even in atypical contexts such as acute heart failure. Integrating ECG interpretation with bedside POCUS facilitated diagnostic accuracy and guided an early invasive strategy, preventing extensive myocardial infarction. In resource-limited settings, strengthening frontline diagnostic capabilities and referral networks is crucial to improving patient outcomes. Full article

Background: Advanced heart failure (HF) carries high morbidity and mortality, and deterioration on the heart transplantation (HT) waiting list remains a major challenge. Intermittent outpatient levosimendan has been proposed as a bridge strategy, but the optimal regimen and its impact on peri-transplant outcomes remain uncertain. Within a personalized-medicine framework, we targeted a low-output/INTERMACS 3 phenotype and operationalized an adaptable, protocolized levosimendan pathway focused on perfusion/congestion stabilization to preserve transplant candidacy. Methods: We conducted a single-center, retrospective cohort study of 25 consecutive adults actively listed for HT between 2019 and 2024, treated with a standardized outpatient program of a 14-day interval of 6 h intravenous levosimendan infusions (target 0.2 μg/kg/min infusions) continued until transplant. Personalization in this program was operationalized through (i) phenotype-based eligibility (low CI and elevated filling pressures despite GDMT), (ii) predefined titration and safety rules for blood pressure, arrhythmias, and renal function, and (iii) individualized continuation until transplant with nurse-supervised monitoring and review of patient trajectories. Baseline characteristics, treatment exposure and safety, changes in hospitalizations and biomarkers, and peri-transplant outcomes were analyzed. Results: Patients were predominantly male (68%), with a mean age of 47.9 ± 17.5 years and severe LV dysfunction (LVEF 30.6 ± 9.8%). Median treatment duration was 131 days (IQR 60–241). No infusions required discontinuation for hypotension or arrhythmia, and no adverse events were directly attributed to levosimendan. Two patients (8%) died on the waiting list, both unrelated to therapy. During treatment, HF hospitalizations decreased significantly compared with the previous 6 months (48% vs. 20%, p = 0.033), renal function remained stable, and NT-proBNP trended downward. Of the 23 patients transplanted, two (9%) underwent urgent HT during decompensation. Post-transplant, vasoplegia occurred in 26% (n = 6 of 23), and 30-day mortality was 9% (n = 2 of 23). Conclusions: By defining the target phenotype, therapeutic goals, and adaptation rules, this study shows how a standardized but flexible outpatient levosimendan regimen can function as a personalized bridge strategy for low-output advanced HF. The approach was associated with fewer hospitalizations, stable renal function, and acceptable peri-transplant outcomes, and merits confirmation in multicenter cohorts with attention to patient heterogeneity and treatment effect refinement. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is strongly associated with cardiovascular morbidity, and depressive symptoms are common in affected individuals. Both OSA and depression have been linked to autonomic dysfunction, but the independent contribution of depressive symptoms to autonomic dysfunction in OSA remains unclear. We investigated whether depressive symptom severity is associated with autonomic function, indexed by heart-rate variability (HRV), in patients with OSA. Methods: We retrospectively analyzed 1713 adults with OSA at a university-affiliated sleep center from 2011 to 2024. HRV was derived from electrocardiography during polysomnography, and frequency-domain indices (natural log-transformed LF, HF, VLF, TP, and LF/HF) were computed. Depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II). Associations between BDI-II and HRV indices were evaluated using univariable and multivariable linear regressions. Results: In univariable regression analyses, higher BDI-II scores were significantly associated with lower HRV indices (ln LF, ln HF, ln VLF, ln TP; all p < 0.01). In multivariable analyses, higher BDI-II scores were independently associated with lower ln LF, ln HF, and ln TP (all p < 0.05), adjusting for age, sex, body mass index, hypertension, diabetes, apnea–hypopnea index, arousal index, and sleep quality. Conclusions: Greater depressive symptom burden is independently associated with reductions in multiple HRV indices, suggesting attenuated parasympathetic activity and autonomic dysregulation in patients with OSA. These findings support integrated management strategies that address both physiological and psychological domains in OSA and motivate longitudinal studies to test whether effective depression treatment improves HRV and mitigates long-term cardiovascular risk. Full article

Cardiorenal syndrome (CRS) reflects the intricate and bidirectional interplay between cardiac and renal dysfunction, commonly resulting in diagnostic uncertainty, therapeutic dilemmas and poor outcomes. While traditional biomarkers like serum creatinine (Cr) and natriuretic peptides remain widely used, their limitations in specificity, timing and contextual interpretation often hinder optimal management. This narrative review synthesizes the current evidence on established and emerging biomarkers in CRS, with emphasis on their clinical relevance, integration into real-world practice, and potential to inform precision therapy. Markers of glomerular filtration rate beyond creatinine—such as cystatin C—offer more accurate assessment in frail or sarcopenic patients, while tubular injury markers such as NGAL, KIM-1, and urinary L-FABP (uL-FABP) provide early signals of structural renal damage. The FDA-approved NephroCheck^® test—based on TIMP-2 and IGFBP7— enables risk stratification for imminent AKI up to 24 h before functional decline. Congestion-related markers such as CA125 and bio-adrenomedullin outperform natriuretic peptides in certain CRS phenotypes, particularly in right-sided heart failure or renally impaired patients. Fibrosis and inflammation markers (galectin-3, sST2, GDF-15) add prognostic insights, especially when combined with NT-proBNP or troponin. Rather than presenting biomarkers in isolation, this review proposes a framework that links them to specific clinical contexts—such as suspected decongestion-related renal worsening or persistent congestion despite therapy—to support actionable interpretation. A tailored, scenario-based, multi-marker strategy may enhance diagnostic precision and treatment safety in CRS. Future research should prioritize prospective biomarker-guided trials and standardized pathways for clinical integration. Full article

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

This study examined the expression of the renin-angiotensin system (RAS) and inflammatory markers in cardiovascular complications associated with long-term type 1 diabetes (T1D) using a rat model. After 24 weeks of streptozotocin-induced T1D, the animals exhibited metabolic alterations indicative of both cardiac and renal dysfunction. Tissue-specific dysregulation of RAS components and pro-inflammatory markers were observed in the heart, aorta, and perivascular adipose tissue (PVAT). In the heart, there was a significant upregulation of both classical (AT1R, 1.00 (0.22) vs. 1.70 (0.45) R.U.) and counter-regulatory RAS components (ACE2, 1.00 (0.43) vs. 1.96 (0.67) R.U.; p < 0.001) and MasR (1.00 (0.56) vs. 1.33 (0.29) R.U.; p = 0.004). The aorta displayed increased expression of classical RAS components alongside a significant reduction in ACE2 expression (1.00 (0.74) vs. 0.51 (0.48) R.U.; p < 0.032). Notably, PVAT showed a significant overexpression of classical RAS components (ACE 1.00 (0.22) vs. 4.08 (1.32) R.U.; p < 0.001, AT1R 1.00 (0.59) vs. 7.22 (4.14) R.U.; p < 0.001) and MasR (1.00 (0.70) vs. 4.52 (1.91) R.U.; p < 0.001), accompanied by increased expression of TNFα and ADAM17. These findings suggest that long-term T1D induces tissue-specific activation patterns of the RAS and inflammatory pathways within the cardiovascular system, which may contribute to the progression of diabetic cardiovascular complications. Therapeutic targeting of RAS components may represent a viable strategy for mitigating cardiovascular damage in T1D. Full article

Background and Clinical Significance: The pathology of the round ligament (RL) is rare and often remains in the shadow of common surgical emergencies. The preoperative diagnosis is challenging, leaving the surgeon perplexed as to whether and when to operate. The presented case deserves attention due to the difficult decision to operate based solely on the clinical picture, despite negative imaging diagnostic results. Case presentation: A 76-year-old woman was admitted to the Emergency Department with 6 h complaints of epigastric pain, nausea, and vomiting. She was afebrile with stable vital signs. The abdomen was slightly tender in the epigastrium, without rebound tenderness or guarding. The following blood variables were beyond the normal range: WBC—13.5 × 109/L; total bilirubin 26 mmol/L; amylase—594 U/L; CRP 11.4 mg/L; ASAT—158 U/L; and ALAT—95 U/L. The ultrasound (US) and multislice computed tomography (MSCT) of the abdomen were normal. A working diagnosis of acute pancreatitis was established, and intravenous infusions were initiated. The next day, the patient became hemodynamically unstable with blood pressure 80/60 mm Hg, heart rate 130/min, chills and fever of 39.5 °C, and oliguria. There was remarkable guarding and rebound tenderness in the epigastrium. The blood analysis revealed the following: WBC—9.9 × 109/L; total bilirubin—76 µmol/L; direct bilirubin—52 µmol/L; amylase—214 U/L; CRP 245 mg/L; ASAT—161 U/L; ALAT—132 U/L; GGT—272 U/L; urea—15.7 mmol/L; and creatinine—2.77 mg/dL. She was taken to the operating room for exploration, which revealed local peritonitis and phlegmon of the RL. Resection of the RL was performed. The microbiological analysis showed Klebsiella varicola. The patient had an uneventful recovery and was discharged on the 5th postoperative day. In the next months, the patients had several readmissions due to mild cholestasis and pancreatitis. The magnetic resonance demonstrated a duodenal diverticulum adjacent to the papilla, located near the junction of the common bile and pancreatic duct. This clinical manifestation and the location of the diverticulum were suggestive of Lemmel’s syndrome, but a papillary dysfunction attributed to the diverticulum or food stasis cannot be excluded. Conclusion: To our knowledge, we report the first association between RL gangrene and Lemmel’s syndrome. We speculate that duodenal diverticulitis with lymphatic spread of the infection or transient bacteriemia in the bile with bacterial translocation due to papillary dysfunction, as well as cholestasis resulting from the diverticulum, could be plausible and unreported causes of the RL infection. The preoperative diagnosis of RL gangrene is challenging because it resembles the most common emergency conditions in the upper abdomen. The present case warrants attention due to the difficult decision to operate based solely on the clinical picture, despite negative imaging results. A high index of suspicion should be maintained in a case of unexplained septic shock and epigastric tenderness, even in negative imaging findings. MSCT, however, is a valuable tool to avert unnecessary operations in conditions that must be managed conservatively, such as acute pancreatitis. Full article

Background: Mitral annular plane systolic excursion (MAPSE) is a simple and widely used M-mode echocardiographic marker of left-ventricular longitudinal function that correlates well with left ventricular ejection fraction (LVEF). Conventional chronic right ventricle (RV) pacing is associated with left ventricle (LV) dysfunction, inducing heart failure (HF) and leading to the development of pacing-induced cardiomyopathy (PiCM). The aim of this study is to ascertain the clinical usefulness of MAPSE in the assessment of LV function in patients with permanent RV pacing. Methods: We performed a cross-sectional association analysis, enrolling consecutive patients with pacemakers and chronic RV pacing burdens over 20% (Vp > 20%) from 2021 to 2024. All patients were assessed by standard transthoracic echocardiography (TTE) with LVEF and MAPSE among other parameters being assessed. We performed a correlation test using linear regression and plotted an ROC curve. Results: 409 patients (mean age = 68.7 year) were included, 225 men (55%) and 245 (59.9%) with dual-chamber pacemakers. The mean follow-up period was 18 ± 2 months, with HF incidence in the study group being 23.2%. The results showed that average, septal, and lateral MAPSE all correlate well with LVEF, but septal values seemed to provide the strongest correlation (r = 0.90, p < 0.001), and that a septal MAPSE cut off value of <10 mm (sensitivity 99.4, specificity 42.1, AUC = 0.89) was associated with impaired LVEF (<50%). Conclusions: MAPSE seems to corelate well with LVEF across the spectrum of HF in pts with chronic RV conventional pacing. Septal MAPSE shows the strongest correlation with LVEF, and a value of <10 mm is a cut-off for altered LVEF, making it a potentially useful marker of cardiac function in these pts. Full article

Tricuspid valve diseases are an increasing cause of cardiovascular mortality, peaking in the eighth decade of life. More than 75% of severe tricuspid regurgitations are recognized via functional mechanisms, often secondary to left heart disease and pulmonary hypertension. Surgical risk for isolated correction of tricuspid regurgitation, both repair or replacement, is associated with prohibitive risk mainly in elderly patients, with several comorbidities and right ventricular dysfunction. In the past decade, different percutaneous devices have been developed to treat a large group of high-surgical-risk patients. Early diagnosis and careful patient selection are essential to improving prognosis in severe TR. Potential treatment options may vary in different stages of disease. The current available results from present studies have proven the safety and effectiveness of these devices under proper clinical indications, although selection bias and non-randomization in most investigations at present do not allow for definite indications. Ideal anatomic and clinical parameters to predict interventional success are in continuous evolution and need definite standardization. We report three cases in which different percutaneous techniques were employed for treatment when surgery was not suitable. The literature is discussed for each condition. Despite promising results in terms of safety and success rate, further randomized studies are needed to better understand which patients may be subject to long-term effects on survival and quality of life. Full article

Right heart failure (RHF) remains an under-recognized yet devastating condition in critically ill and chronic patients, frequently complicating cardiac surgery, pulmonary embolism, advanced heart failure, sepsis and left ventricular assist device (LVAD) implantation. Despite growing awareness, clinical decision making is still hampered by the complex pathophysiology, limitations in diagnosis and a fragmented therapeutic landscape. In recent years, progress in hemodynamic phenotyping, advanced echocardiographic and biomarker-based assessment, and the development of mechanical circulatory support (MCS) systems, including percutaneous and surgical right ventricle assist devices (RVAD), veno-arterial extracorporeal membrane oxygenation (V-A ECMO), Impella RP (right percutaneous) or BiPella (Impella CP/5.0/5.5 + Impella RP) has expanded the armamentarium for managing RHF. This review synthetizes current evidences on the anatomical, physiological and molecular underpinnings of RHF, delineates the distinction and continuum between acute and chronic forms and provides a comparative analysis of diagnostic tools and MCS strategies. By integrating mechanistic insights with emerging clinical frameworks, the review aims to support earlier recognition, tailored management and innovative therapeutic approaches for this high-risk population. Full article

Chronic thromboembolic pulmonary hypertension (CTEPH) is a type of pulmonary hypertension due to unresolved thromboembolic disease that presents with signs of pulmonary artery obstruction and right heart dysfunction. Pulmonary thromboendoarterectomy (PTE) with deep hypothermic circulatory arrest remains the standard of care for the treatment of CTEPH, with significant improvements in symptoms and functional status after surgery. This review outlines the diagnostic workup, considerations during operative planning, surgical technique, and postoperative management of CTEPH patients. Full article