Search Results (201)

Biventricular Takotsubo cardiomyopathy (TCM) is a rare variant characterized by involvement of both the left and right ventricles. This variant is associated with greater hemodynamic instability and longer hospital stays compared to the isolated left ventricular-only variant. We report the case of a 67-year-old female patient who underwent elective resection of a left adrenal adenoma. While her preoperative and intraoperative courses were uneventful, she developed cardiogenic shock postoperatively, necessitating prolonged intensive care unit (ICU) management and vasopressor support. Further evaluation revealed elevated high-sensitivity troponin levels and reduced ejection fraction on echocardiography (30–35%). Hypokinesis was noted in the apical and mid-ventricular segments of both ventricles. A coronary angiogram performed two months prior to admission showed no significant coronary artery disease. Based on these findings, a diagnosis of biventricular TCM was established. The patient was managed supportively and discharged in stable condition with ongoing therapy, including beta-blockers, renin–angiotensin–aldosterone system inhibitors (RAASis), and statins. Follow-up echocardiography showed resolution of regional wall motion abnormalities. Although rare, biventricular TCM is associated with increased severity and a higher risk of complications. Early recognition and timely management are essential to improve outcomes in affected patients. Full article

Background/Objectives: Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular dysplasia characterized by recurrent epistaxis, anemia, and visceral arteriovenous malformations. Epistaxis is the most frequent and disabling manifestation, with limited effective pharmacological options. Propranolol, a non-selective beta-blocker with vasoconstrictive and antiangiogenic properties, has shown benefit in other vascular anomalies but remains scarcely studied in HHT. This study aimed to evaluate the effect of oral propranolol on nasal bleeding in patients with HHT. Methods: A retrospective observational study including 151 adults with HHT (44 treated with propranolol, 107 untreated) was conducted using data from an Institutional HHT Registry from a referral center. Baseline demographic and clinical variables were recorded. Outcomes at 6 months included changes in hemoglobin, adherence to nasal hygiene, use of bleeding-related therapies, and improvement in epistaxis frequency and intensity according to the Sadick–Bergler scale. Logistic regression models were adjusted for confounders and indication bias using inverse probability of treatment weighting (IPTW). Results: After IPTW adjustment, propranolol was significantly associated with reduced frequency of epistaxis (adjusted OR: 3.8; 95% CI: 1.3–11.2; p = 0.016), while no effect was observed on intensity. Hemoglobin levels increased modestly in both groups without a significant difference. Patients without propranolol showed greater antifibrinolytic use, whereas adherence to nasal care remained stable among treated patients. Conclusions: Oral propranolol reduced nasal bleeding frequency in HHT, even among patients with greater baseline severity. Given its accessibility, safety, and potential to lessen treatment burden, it may represent a valuable adjunct therapy. This study represents the largest cohort of HHT patients treated with propranolol reported to date. Randomized trials including standardized bleeding scores and patient-reported outcomes are warranted to confirm clinical and quality-of-life benefits. Full article

The gut microbiota is crucial for metabolic homeostasis and cardiovascular health. Dysbiosis triggers a gut–brain–heart axis dysfunction: vagal signaling promotes neuroinflammation and cerebral damage, which in turn impairs cardiac function. This bidirectional cycle is further exacerbated by reduced cerebral perfusion. Trimethylamine-N-oxide (TMAO), a metabolite of dietary choline and L-carnitine, acts as a primary mediator in this network. Elevated TMAO levels—resulting from bacterial conversion and hepatic oxidation—are linked to atherosclerosis and heart failure. Mechanistically, TMAO activates the NLRP3 inflammasome, inhibits the SIRT3-SOD2 pathway, and promotes platelet hyperreactivity. Furthermore, it modulates the autonomic nervous system, enhancing sympathetic activity and cardiac arrhythmias. Clinical evidence suggests TMAO is a potent predictor of mortality in HF. While current HF therapies focus on end-organ response (beta-blockers) or humoral pathways (ACE inhibitors), directly targeting the microbiota and TMAO offers a novel therapeutic frontier. Integrating TMAO assessment into risk models and utilizing advanced in vitro gut–brain models will be essential for developing personalized, groundbreaking cardiovascular interventions. Within this framework, the main aim of the present review is to describe how cardiac autonomic control can be directly modulated by the microbiota and its byproducts like TMAO. This latter is a leading target candidate for novel HF prevention and therapy interventions. Full article

(1) Background: The systemic right ventricular (SRV) dysfunction and severe tricuspid regurgitation (TR) remain significant challenges in patients with congenitally corrected transposition of the great arteries (ccTGA) or following atrial switch procedures. Currently, there is no established, evidence-based medical therapy specifically designed for SRV failure, and treatment approaches are largely extrapolated from left ventricular heart failure (HF) guidelines. This therapeutic gap highlights the need for tailored pharmacologic strategies and optimized perioperative management in this unique population. The optimal timing of surgical intervention and the role of modern HF therapy are still under active investigation. (2) Methods: We present a case series of four patients (three adults and one child) with SRV dysfunction and severe TR, who underwent staged treatment consisting of optimized medical therapy followed by surgical tricuspid valve (TV) replacement. Medical therapy included positive inotropes, sacubitril/valsartan, sodium-glucose co-transporter 2 inhibitors (iSGLT2), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and loop diuretics. (3) Results: All patients demonstrated clinical and hemodynamic improvement prior to surgery, with an increase in systemic ventricular ejection fraction (SVEF > 40%) and cardiac index. TV replacement was performed with favorable early postoperative outcomes and preserved ventricular function at mid-term follow-up. No mortality or major adverse events occurred during follow-up. One case of acute cystitis was associated with dapagliflozin. In all patients, postoperative SVEF remained >40%, and no recurrence of significant TR was observed. (4) Conclusions: A stepwise approach combining modern heart failure therapy and elective TV replacement in patients with SRV dysfunction and TR is safe and effective. Preoperative optimization leads to improved ventricular function and may enhance surgical outcomes. These findings support the integration of contemporary pharmacotherapy in the management strategy for SRV failure. Full article

To better address the challenge of corneal ulcer healing, with already available standard agents, and those recently introduced, such as stable gastric pentadecapeptide BPC 157, we introduced a novel conceptual framework—the “triad” of corneal ulcer healing↔corneal neovascularization↔intraocular pressure—and extended it to avascular tissues such as tendon. Within this framework, cytoprotection serves as the unifying principle, underscoring that therapeutic effects are not isolated but interconnected. Preclinical studies with BPC 157 therapy, as a cytoprotection agent, illustrate this integration. BPC 157 rapidly normalizes elevated intraocular pressure in glaucomatous rats, preserves retinal integrity, restores pupil function, maintains corneal transparency during ulcer or abrasion healing, and counteracts both corneal neovascularization and dry eye. In parallel, its consistent efficacy in tendon injury models highlights a cytoprotective specificity across avascular tissues. The cornea’s “angiogenic privilege,” preserved during healing and tendon recovery together, provides strong proof of concept. Furthermore, mapping standard therapeutic agents used for corneal ulcers, neovascularization, or glaucoma onto this triad, and linking them with tendon healing, reveals both shared pathways and inconsistencies across existing drug classes. Analyzed were the ascorbate, fibronectin, hyaluronic acid, metalloproteinase inhibitors, EGF, FGF, NGF, insulin, and IGF-1 (corneal ulcer healing), the antiangiogenic agents (endostatin, PAI-1, PEDF, angiostatin, TSP-1, TSP-2, IFN-α), corticosteroids, NSAIDs, cyclosporine A, anti-VEGF drops (treatment of corneal neovascularization), and alpha 2-agonists, beta-blockers, carboanhydrase inhibitors, muscarinic agonists, Rho-kinase inhibitors, and prostaglandin analogs (glaucoma). Taken together, these findings advance cytoprotection as a unifying therapeutic paradigm, with BPC 157 emerging as its first exemplar, and encourage further translational research toward clinical application. Full article

Background/Objectives: Mavacamten is a first-in-class cardiac myosin inhibitor approved for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM). Long-term data regarding its real-world safety and effectiveness are limited. We aimed to describe the real-world experience of mavacamten in a large obstructive HCM cohort at a high-volume HCM center in the United States. Methods: Adult patients initiated on mavacamten between 29 April 2022 and 19 January 2025 at a single HCM center (n = 163) were retrospectively identified. Clinical effectiveness and safety data were collected through 108 weeks of treatment. Results: Rapid and sustained reductions in resting (baseline mean 53.0 ± 36.7 mm Hg to 10.0 ± 11.0 mm Hg) and Valsalva left ventricular outflow tract gradients (baseline mean 79.7 ± 33.2 mm Hg to 16.6 ± 15.4 mm Hg) were observed during treatment throughout the study period along with substantial improvements in New York Heart Association (NYHA) class (75% with >1 NYHA class improvement by Week 12). Mean maximal left ventricular wall thickness significantly decreased (β = 0.01 mm per week). Ten patients (6.1%) required temporary drug interruption due to decrement in left ventricular ejection fraction, and mavacamten was discontinued in six patients (3.7%). Doses of background beta blocker and nondihydropyridine calcium channel blocker were significantly reduced during the study period (p < 0.001). Conclusions: In this large single-center real-world experience of mavacamten therapy, mavacamten was highly effective and maintained an acceptable safety profile, comparable to the clinical trial long-term extension experience. Full article

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