Search Results (195)

Background/Objectives: Vitamin D deficiency is highly prevalent worldwide and is associated with multiple comorbidities and pharmacological treatments that may interfere with its metabolism. Evidence on the effect of supplementation across different drug user groups remains limited. Methods: A prospective study was conducted across community pharmacies over twelve months. Baseline socio-demographic, serum 25(OH)D concentration, quality of life (QoL), lifestyle habits, and medication use were collected. Participants received vitamin D supplementation for 12 months. Changes in vitamin D status and QoL were analyzed according to medication use. Logistic regression identified predictors of achieving adequate serum vitamin D levels (>30 ng/mL). Statistical significance was set at p < 0.05. Results: At baseline, 87.2% of 210 participants had insufficient or deficient vitamin D levels. After supplementation, mean serum vitamin D increased significantly from 21.3 ± 8.2 to 32.1 ± 12.6 ng/mL (p < 0.001), and QoL scores improved from 68.6 ± 18.7 to 77.8 ± 18.5 (p < 0.001). Dietary intake of vitamin D–rich foods and outdoor activity also increased. Supplementation improved vitamin D status among users of benzodiazepines, proton pump inhibitors, beta-blockers, statins, levothyroxine, metformin, and angiotensin-converting enzyme inhibitors, but not among corticosteroid, nonsteroidal anti-inflammatory drugs, or vitamin K antagonist. Multivariate analysis confirmed adherence as a strongest predictor of vitamin D adequacy (OR = 15.31, 95% CI = 2.90–80.75), while corticosteroid therapy, diabetes, and hypercholesterolemia were negatively associated. Conclusions: Vitamin D supplementation effectively corrected deficiency and improved QoL, but its efficacy varied according to comorbidities and medication use. Personalized supplementation strategies, emphasizing adherence and considering pharmacological profiles, may optimize outcomes. Further studies should explore mechanistic drug–nutrient interactions and long-term clinical implications. Full article

Background/Objectives: Urgent hospitalization due to acutely decompensated heart failure (ADHF) is an unfavorable event in the trajectory of this disease. Patient condition during decompensation frequently limits opportunities to implement and optimize guideline-directed medical therapy (GDMT). To define the tasks of post-hospital care, it is essential to gain knowledge regarding the extent of GDMT implementation on the day of discharge after ADHF episodes. The purpose of this analisis was to evaluate GDMT changes during hospitalization due to ADHF, with a particular emphasis on patients with reduced ejection fraction. Methods: The analysis was conducted in a group of 262 patients hospitalized due to ADHF and with known left ventricular ejection fraction (LVEF). The HEROES study was a prospective, multi-center, observational study. Results: The mean age in the study group (196 men and 66 women) was 67.6 ± 14.6 years, with a mean LVEF of 33.9 ± 14.8%. Six patients died during hospitalization. In the analysis for the whole group (regardless of ejection fraction [EF]), ARNI (angiotensin receptor-neprilysin inhibitor)/ACEI (angiotensin-converting enzyme inhibitor)/ARB (angiotensin receptor blocker) use increased from 63.3% of the subjects at admission to 81.3% at discharge, beta-blocker use increased from 70.6% to 92.6%, MRA (mineralocorticoid receptor antagonist) use increased from 43.1% to 75.8%, and SGLT2i (sodium-glucose co-transporter 2 inhibitor) use increased from 30.1% to 75.0%. ARNI/ACEI/ARB therapy was optimized in 48.4% of the subjects, with optimization rates of 37.9%, 40.2%, and 44.1% for beta-blockers, MRAs, and SGLT2is, respectively. However, only 38 (22.0%) patients reached the level of treatment corresponding to “SGLT2i and ARNI/ACEI/ARB and betablocker and MRA in doses ≥ 50%”. Conclusions: In patients hospitalized due to ADHF in the HEROES study, the use of GDMT at discharge was significantly higher than at admission. In patients with reduced ejection fraction, GDMTs from all drug classes were prescribed to over 80% of patients. However, an insufficient number of patients attained high doses of GDMT, which emphasizes the need for effective dose up-titration in outpatient settings. Full article

Chronic liver disease (CLD) imposes a major global health burden, with portal hypertension (PH) and its complications driven by complex pathophysiological mechanisms. Understanding these processes is essential for effective therapy. The hepatic venous pressure gradient (HVPG) is the gold standard for assessing portal hypertension, providing key diagnostic, prognostic, and therapeutic guidance—particularly in distinguishing its type and monitoring response to treatments such as non-selective beta-blockers. While non-invasive tests like elastography and serum biomarkers are valuable for screening and follow-up, they cannot fully replace HVPG when precise measurement is needed. HVPG contains not only prognostic information but also helps to decide if pharmacological therapy is indicated and to monitor therapeutic effects with reductions correlating with improved outcomes. In this review, we highlight the comprehensive management of patients with PH and the indications for measurement of HVPG. Full article

In the context of multi-organ involvement in sepsis, cardiac toxicity is manifested as sepsis-induced cardiomyopathy (SICM). To date, no unified SICM definition exists, though a left ventricular ejection fraction ≤ 50% and/or an absolute drop ≥ 10% from baseline are the most widely accepted components. Several molecular pathways have been associated with SICM, including (i) pro-inflammatory mediator-induced cardiac depression; (ii) sarcolemmal membrane dysfunction; (iii) autonomic nervous system (ANS) imbalance; (iv) blunted cardiovascular response to catecholamines; (v) dysfunctional intracellular calcium handling; (vi) mitochondrial dysfunction; (vii) metabolic reprogramming; and (viii) disturbed endothelial and microcirculatory function. Atrial and ventricular arrhythmias—particularly atrial fibrillation—commonly complicate disease management and are associated with adverse outcomes. Key mechanisms outlining sepsis-induced arrhythmogenesis are (i) inflammation; (ii) electrolyte imbalances; (iii) myocardial ischemia; (iv) QT prolongation/dispersion; (v) adrenergic overactivation; (vi) calcium mishandling; and (vii) fever-induced arrhythmogenesis in Brugada. Established therapeutic approaches include prompt treatment with antibiotics, hemodynamic optimization, and/or selective use of beta-blockers. Furthermore, several molecules are currently being investigated targeting numerous pathways activated in sepsis. Vitamin C, ginsenoside Rc, Schistosoma Japonicum cystatin, and gasmerdin-D inhibitor Y2 exert anti-inflammatory actions, while melatonin and α-ketoglutarate regulate mitochondrial homeostasis. Triiodothyronine targets microcirculatory optimization and regulates protective pathways against stress-related cell death. Engineered exosomes may facilitate targeted drug delivery, inflammatory response modulation, and activation of pathways related to cell survival, while sodium octanoate exhibits anti-inflammatory actions coupled with improved energy metabolism. Finally, gene-regulating therapies aiming at inflammatory response optimization have also been proposed and are currently under development. Future research should aim to standardize the SICM definition, translate emerging therapeutics into clinical practice, identify novel molecular targets, and implement personalized treatment strategies for SICM. Full article

Background: Pharmacologic therapy guided by invasive coronary function tests (CFTs) may improve symptomatic outcomes in patients with angina and non-obstructive coronary artery disease (ANOCA). In this study, we specifically aimed to investigate whether the induction of coronary microvascular spasm (CMVS) by the acetylcholine (Ach) test predicts a better therapeutic effect of calcium-channel blocker therapy compared to beta-blocker therapy. Methods: We enrolled 31 ANOCA patients, who were divided into two groups according to the result of Ach testing: 16 patients with CMVS (CMVS group) and 15 patients with a negative test (NEG group). Patients with Ach-induced epicardial spasm were excluded. In an open-label crossover trial, patients were randomly assigned to each receive, for a period of 4 weeks, either metoprolol (50 mg twice daily) or diltiazem (120 mg twice daily). At the end of each 4-week period, patients underwent an ECG–exercise stress test (EST) and were invited to fill out the Seattle Angina Questionnaire (SAQ). Results: No significant differences were found between metoprolol and diltiazem in terms of SAQ scores, and ECG-EST results were also largely comparable with the two drug treatments, both in the CMVS group and the NEG group. In particular, the SAQ summary score was 63.1 ± 24 and 66.0 ± 25 (p = 0.59) for metoprolol and diltiazem, respectively, in the CMVS group, and 70.9 ± 17 and 74.3 ± 16 (p = 0.37) with the two drugs, respectively, in the NEG group. Conclusions: Our small open-label study shows that patients with ANOCA with negative Ach test or Ach-induced CMVS show largely comparable short-term symptomatic outcomes and ECG-EST results when treated with either metoprolol or diltiazem. Full article

Background: Patient-reported outcomes are integral to chronic coronary syndrome (CCS) care. The Seattle Angina Questionnaire (SAQ) is validated and prognostic, yet its clinical integration in Bulgaria is undefined. Aim: The aim of this study was to provide a structured, clinically oriented framework for integrating the SAQ into the full CCS care pathway—from screening and phenotyping (obstructive vs. ANOCA/INOCA endotypes) to diagnostics, mechanism-tailored therapy, and follow-up—while outlining a pragmatic roadmap for Bulgarian implementation. Methods: We conducted a semi-structured narrative review (1995–2024) of SAQ’s validation, prognostic utility, and implementation in the literature, augmented with guideline-based frameworks for CCS/ANOCA care. Results: The SAQ (and SAQ-7) shows strong reliability and responsiveness and independently predicts health status and clinical outcomes. Embedding the SAQ at baseline, at 4–12 weeks after therapy changes, and after 6–12 months enables symptom-guided decision-making. A phenotype-guided pathway is proposed that couples the SAQ with CAD burden assessment and—where indicated—ANOCA diagnostics (CFR/IMR, vasoreactivity testing). Mechanism-tailored therapy maps to endotypes (e.g., VSA → CCB ± nitrates; MVA → beta-blocker/ACEi/statin ± ranolazine; obstructive CADGDMT ± PCI/CABG). A minimum dataset, metrics, and registry fields are specified for Bulgarian deployment. Conclusions: A clinically structured framework clarifies how the SAQ adds value beyond description—by informing triage, treatment selection, and follow-up across CCS phenotypes. This approach provides educational guidance and a practical blueprint for pilot implementation in Bulgaria. Full article

The growing overlap between cardiovascular disease and cancer has made cardio-oncology a key subspecialty in modern oncology care. Improved cancer survival has increased the burden of therapy-related cardiovascular complications, including heart failure, arrhythmias, ischemic events, and vascular toxicity, driven by oxidative stress, endothelial dysfunction, immune-mediated injury, and metabolic vulnerability. Effective management requires a continuum-of-care approach, integrating baseline risk assessment, biomarker- and imaging-guided surveillance, and timely cardioprotective therapy without compromising cancer treatment. Key strategies include validated risk scores (HFA/ICOS, Mayo), early detection of subclinical dysfunction via troponin, natriuretic peptides, and strain imaging, and proactive cardioprotective agents such as ACE inhibitors, beta-blockers, SGLT2 inhibitors, and statins in high-risk patients. This narrative review summarizes risk-stratification models, structured care pathways, and multidisciplinary hub-and-spoke networks linking specialized centers with community oncology services. It emphasizes modifiable cardiometabolic factors, obesity, insulin resistance, NAFLD, sarcopenia, and chronic inflammation, which heighten cardiotoxicity risk and should guide precision prevention and survivorship care. We also address emerging challenges, including the integration of digital health, tele-monitoring, and AI-based decision support, and the shift toward value-based reimbursement models, highlighting persistent barriers such as data privacy, infrastructure gaps, and inequitable access to specialized care. Full article

Background and Objectives: Erlotinib, a tyrosine kinase inhibitor (TKI), is an established therapy for patients with metastatic non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. Preclinical and clinical evidence suggests that chronic stress, mediated through β-adrenergic signaling, promotes tumor progression, angiogenesis, and therapy resistance. Furthermore, interactions between β-adrenergic signaling and EGFR pathways have been hypothesized to negatively influence treatment responses. Based on this rationale, we investigated whether concomitant beta-blocker use may improve survival outcomes in EGFR-mutant NSCLC patients treated with erlotinib. Materials and Methods: This retrospective analysis included 103 patients with metastatic EGFR-mutant NSCLC who received erlotinib. Patients were classified according to concurrent beta-blocker use, defined as continuous therapy for at least six months prior to erlotinib initiation, prescribed for cardiovascular indications. Progression-free survival (PFS) and overall survival (OS) were compared between beta-blocker users and non-users. Results: Patients receiving erlotinib with concomitant beta-blocker therapy achieved a median PFS (mPFS) of 21.4 months (95% CI, 13.1–29.7), compared with 9.7 months (95% CI, 6.7–12.7) in non-users (p = 0.003). Median OS (mOS) was 32.4 months (95% CI, 14.8–50.0) in the beta-blocker group versus 19.9 months (95% CI, 14.8–25.0) in the non-beta-blocker group (p = 0.010). Multivariate Cox regression confirmed beta-blocker use as an independent prognostic factor for both PFS (p = 0.004) and OS (p = 0.014). Conclusions: Concomitant beta-blocker use was associated with significantly prolonged survival in patients with EGFR-mutant metastatic NSCLC receiving erlotinib. These findings support the hypothesis that β-adrenergic inhibition enhances the efficacy of EGFR-targeted therapy. Prospective studies are warranted to validate these results and to further elucidate the underlying biological mechanisms. Full article

Background: Conventional HF treatment in transthyretin cardiac amyloidosis (ATTR-CA) resulting in restrictive cardiomyopathy is debated due to absent trial evidence in this specific sub-population of heart failure (HF) patients. Current European Society of Cardiology guidelines recommend the use of diuretics and mineralocorticoid receptor antagonists (MRAs). However, beta-blockers (BBs) and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) are often discontinued due to hypotension or bradycardia. This study assesses real-world HF treatment patterns and their impact on survival in a multinational ATTR-CA cohort. Methods: A retrospective analysis of 794 ATTR-CA patients examined baseline BB, ACEi/ARB, and MRA prescriptions. The cohort was divided based on guideline publication dates. Results: Patients were predominantly male (73.2%) with a median age of 78 years. Prescription of diuretics (52.8%) and disease-modifying therapy (44.9%), mostly tafamidis, was common. BBs (43.7%) and ACEi/ARBs (41.2%) were prescribed more often in patients with higher NYHA class, elevated NT-proBNP, and more comorbidities. Blood pressure and heart rate were similar regardless of BB or ACEi/ARB use. BB prescription and combination therapy with BB and ACEi/ARB increased over time. Neither BB nor ACEi/ARB use significantly impacted mortality when analyzed in a multivariate Cox proportional hazard regression. Conclusions: Use of BBs and ACEi/ARBs has increased over time, particularly in advanced-stage ATTR-CA patients, and although these therapies appear to be reasonably tolerated, survival was not significantly altered. Full article

Ischemic heart disease remains the leading cause of death despite substantial advances in diagnosis, revascularization therapies, and risk-factor control. Beta-adrenergic receptor blockers (Beta-Blockers, BBs), long used to control heart rate, blood pressure, and reduce arrhythmic risk, may also confer cardioprotection through mechanisms beyond hemodynamic unloading. This review integrates an extensive range of preclinical, translational, and clinical studies to present a comprehensive overview of the cardioprotective effects of BBs in the context of myocardial ischemia and reperfusion injury. Mechanistic domains include modulation of redox homeostasis, attenuation of inflammation and neutrophil activation, preservation of mitochondrial integrity and anti-apoptotic signaling, improvement of endothelial function, and stabilization of calcium handling. Third-generation compounds, carvedilol and nebivolol, demonstrate additional antioxidant and vasodilatory benefits compared with first- and second-generation agents; however, no consistent class-wide effect exists across most pathways. The evidence base remains fragmented, often derived from agent- or context-specific studies in heterogeneous populations, with uncertainty surrounding optimal timing of intervention. By bridging mechanistic understanding with clinical outcomes, this review highlights the importance of standardized assessment of BB effects, the development of personalized treatment approaches, and the pursuit of future research to address ongoing translational gaps. 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

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: Familial Mediterranean Fever (FMF) is a chronic autoinflammatory disorder that is characterized by increased arterial stiffness and subtle cardiovascular dysfunction. Colchicine remains the mainstay of treatment and may provide vascular benefits that extend beyond its anti-inflammatory effects. However, the association between colchicine therapy and ventriculoarterial coupling (VAC), a hemodynamic marker of cardiovascular efficiency, has not been previously studied. Methods: In this cross-sectional study, 97 patients with FMF receiving colchicine therapy for at least one year and 81 colchicine-naive individuals without FMF were consecutively enrolled from a tertiary rheumatology outpatient clinic. The VAC was evaluated using the Chen method, calculated as the ratio of arterial elastance (Ea) to end-systolic elastance (Es), based on echocardiographic measurements and noninvasive brachial blood pressure. Correlation analyses and stepwise multivariate linear regression analyses were performed to identify independent predictors of VAC. Results: Patients with FMF demonstrated significantly lower VAC values compared to controls (1.23 ± 0.34 vs. 1.40 ± 0.57; p = 0.001). The colchicine dose was inversely correlated with VAC (r = −0.243; p = 0.001) and remained an independent predictor in multivariate analysis (β = −0.186, p = 0.018). Beta-blocker use was positively associated with VAC (β = 0.194, p = 0.014), whereas female sex showed a borderline inverse association. Conclusions: Colchicine use in patients with FMF was associated with more favorable VAC in a dose-dependent manner. These findings suggest that colchicine may exert cardiovascular effects beyond the control of inflammation. VAC may be a useful noninvasive marker for assessing vascular–ventricular interactions in FMF. Full article

Breast cancer (BC) is associated with multiple molecular factors such as overexpression of the beta-2 adrenergic receptor (ADRB2) and the overproduction of its agonists (norepinephrine and epinephrine). The role of adrenergic signaling in BC highlights the therapeutic potential of non-selective beta-blockers (nsBBs) as inhibitors of well-established protumor signaling pathways related to ADRB2 and their possible affinity for other important protumoral receptors. Our aim was to identify how nsBBs currently prescribed may also interact with receptors other than ADRB2, which are related to the pathophysiology of BC, using bioinformatic intracellular pathway analysis (BIPA). Subsequently, the affinity of nsBBs for both ADRB2 and the targets identified by BIPA was evaluated. We found that, beyond ADRB2, both receptor tyrosine kinase 2 (ERBB2) and neuropeptide Y receptor (NPYR) are promising targets for nsBBs in the adjuvant treatment of BC, according to BIPA. Docking studies showed that the nsBB with the highest binding affinity (ΔG) was carvedilol (−10.5 kcal/mol), followed by propranolol (−8.5 kcal/mol). These in silico findings suggest previously unrecognized pharmacological mechanisms for nsBBs in the possible treatment for BC. Notably, differences in receptor affinity were observed among the nsBBs, with carvedilol exhibiting the strongest binding affinity values on ADRB2, ERBB2, and NPYR as biological targets against BC cells. These promising results require future experimental validation. Full article

Background and Objectives: Atrial fibrillation (AF) in critically ill patients (CIP) is associated with worse outcomes and increased mortality in the intensive care unit (ICU). Rhythm control strategies are often unfeasible due to underlying comorbidities, making rate control the preferred initial approach. However, conventional beta-blockers may worsen hemodynamics through negative inotropic effects and peripheral vasodilation. Landiolol, an ultra-short-acting adrenoreceptor antagonist, may offer an alternative due to its high β₁-cardioselectivity and minimal blood pressure (BP) impact. This study evaluated the efficacy and feasibility of landiolol in hemodynamically unstable CIP with tachyarrhythmia, used as add-on therapy after failure of standard treatments. Materials and Methods: Ten CIP, admitted for non-postoperative reasons, were prospectively enrolled for landiolol treatment (L-group) in the ICU of Ulm University Heart Center between July and December 2017. The control group contained 41 patients who had received standard therapy without landiolol (NL-group). The primary composite endpoint was defined as heart rate (HR) reduction while maintaining mean arterial pressure (MAP) above 65 mmHg. Results: The most frequent reason for ICU admission was hemodynamic instability related to tachyarrhythmia in patients with cardiogenic or septic shock. At therapy initiation, all patients exhibited a compromised hemodynamic status, with a median MAP of 68.0 (IQR 60.0–80.0) mmHg and a median HR of 160.0 (IQR 144.0–176.0) bpm. After a three-hour observation period, no significant differences in BP values were observed between the groups. The primary composite endpoint was achieved at comparable rates in both groups (p = 0.525). However, patients in the L-group achieved a greater reduction in HR compared to those in the NL-group (25.3% vs. 21.9%, p < 0.001). Conclusions: Landiolol achieved more effective HR control than standard therapy without adversely affecting BP stability. These findings suggest that landiolol may be a feasible and effective option for HR control in ICU CIP. Full article