Search Results (426)

Cardiac transplantation remains an important therapy for end-stage heart failure, although allograft rejection continues to pose significant clinical challenges. This review evaluates both established and emerging blood-based biomarkers for noninvasive monitoring of rejection in heart transplant recipients. Donor-derived cell-free DNA (ddcfDNA) and gene expression profiling (GEP) represent well-validated, commercially available molecular tools that demonstrate strong discriminative capacity for acute rejection episodes. Additionally, microRNAs (miRs) and extracellular vesicles (EVs) show considerable potential as novel biomarkers, although further validation is required. In contrast, conventional biomarkers such as B-type natriuretic peptide (BNP), cardiac troponins, and creatine kinase-MB (CK-MB) offer limited specificity in the context of rejection. This review synthesizes current evidence on the clinical utility, methodological challenges, and integration strategies of these biomarkers, highlighting a shift toward molecular-based approaches for improving post-transplant surveillance and patient outcomes. Full article

Background: recently, regenerative medicine has introduced a new branch of science that facilitates the repair of damaged tissues and organs in acute myocardial infarction. This study explores the role of the C-type natriuretic peptide (CNP) system in myocardial infarction (MI) and its modulation by Apelin-13 functionalized patches (A-13p). Methods: using an experimental rat model of ischemia/reperfusion, the rats were divided into four groups: Sham, Infarct, Sham with A-13p, and Infarct with A-13p. Cardiac tissue from the infarct, border, and remote zones was analyzed for CNP and its receptors’ mRNA expression via Real-Time PCR. Results: histological analysis, 4 weeks post A-13p implantation, showed no damage from A-13p implantation in either MI or Sham groups, with reduced left ventricle wall thinning in the Infarct group treated with A-13p. CNP mRNA expression was higher in the infarcted groups (p = ns), especially in the border/infarct zone (BZ + IZ), compared to the Sham group (p = 0.05). NPR-B receptor expression was higher in the RZ than in (BZ + IZ), both in the absence (p = 0.02) and presence of patches (p = 0.01), while NPR-C expression was lower. No significant differences were observed in VEGF mRNA levels across the groups. Conclusions: the findings suggest that the CNP system is involved in MI and that A-13p modulates CNP expression, highlighting CNP as a potential target for therapeutic strategies aimed at regulating vascular remodeling and angiogenesis in MI treatment. Full article

Understanding thrombosis in acute coronary syndromes (ACSs) has evolved through advances in biomarkers, intracoronary imaging, and emerging analytical tools, improving diagnostic accuracy and risk stratification in high-risk patients. This narrative review provides an integrative overview of contemporary evidence from clinical trials, meta-analyses, and international guidelines addressing circulating biomarkers, intracoronary imaging modalities—including optical coherence tomography (OCT), intravascular ultrasound (IVUS), and near-infrared spectroscopy (NIRS)—artificial intelligence–based analytical approaches, and emerging antithrombotic therapies. High-sensitivity cardiac troponins and natriuretic peptides remain the most robust and guideline-supported biomarkers for diagnosis and prognostic assessment in ACS, whereas inflammatory markers and multimarker strategies offer incremental prognostic information but lack definitive validation for routine therapeutic guidance. Intracoronary imaging with IVUS or OCT is supported by current guidelines to guide percutaneous coronary intervention in selected patients with ACS and complex coronary lesions, leading to improved procedural optimization and clinical outcomes compared with angiography-guided strategies. Beyond procedural guidance, OCT enables detailed plaque characterization and mechanistic insights into ACS, while NIRS provides complementary information on lipid-rich plaque burden, primarily for risk stratification based on observational evidence. Artificial intelligence represents a rapidly evolving tool for integrating clinical, laboratory, and imaging data, with promising results in retrospective and observational studies; however, its clinical application in thrombosis management remains investigational due to the lack of outcome-driven randomized trials. In the therapeutic domain, factor XI inhibitors have demonstrated favorable safety profiles with reduced bleeding and preserved antithrombotic efficacy in phase II and early phase III studies, but their definitive role in ACS management awaits confirmation in large, outcome-driven randomized trials. Overall, the integration of biomarkers, intracoronary imaging, and emerging analytical and pharmacological strategies highlights the potential for more individualized cardiovascular care. Nevertheless, careful interpretation of existing evidence, rigorous validation, and alignment with guideline-directed practice remain essential before widespread clinical adoption. Full article

Background: Atrial dilated cardiomyopathy (ADCM) related to homozygous Natriuretic Peptide Precursor A (NPPA) pathogenic variants is an exceptionally rare inherited atrial cardiomyopathy characterized by progressive atrial enlargement, supraventricular arrhythmias, and eventual atrial standstill. Case summary: We report the case of a 9-year-old girl identified through population genetic screening as a homozygous carrier of the NPPA c.449G>A (p.Arg150Gln) variant who subsequently developed symptomatic paroxysmal atrial fibrillation (AF) at the age of 18. Although baseline cardiac investigations were normal, her current evaluation shows biatrial enlargement with preserved ventricular function. She underwent radiofrequency pulmonary vein isolation; however, recurrent symptomatic AF persists, requiring ongoing antiarrhythmic therapy and long-term oral anticoagulation (CHA₂DS₂-VA: 0; HAS-BLED: 0). Notably, patients with NPPA-related ADCM have a markedly increased thromboembolic risk due to progressive atrial mechanical failure, and anticoagulation should therefore be considered irrespective of conventional clinical risk scores. Discussion and conclusions: This case highlights the importance of genetic testing in young patients with atrial fibrillation and no underlying structural heart disease. The early identification of NPPA-related atrial dilated cardiomyopathy may aid in risk stratification and guide rhythm and anticoagulation management. Expanding genetic screening in select individuals with isolated atrial fibrillation may facilitate earlier diagnosis in this exceptionally rare condition. Full article

Biomarker-based prevention is rapidly expanding, driven by advances in molecular diagnostics, genetic profiling, and commercial direct-to-consumer (DTC) testing. General practitioners (GPs) increasingly encounter biomarker results of uncertain relevance, often introduced outside the guideline frameworks. This creates new challenges in interpretation, communication, and equitable resource use in primary care. This narrative review synthesizes evidence from population-based studies, guideline frameworks, consensus statements, and communication research to evaluate the predictive value, limitations, and real-world implications of biomarkers in asymptomatic adults. Attention is given to polygenic risk scores, DTC genetic tests, neurodegenerative and cardiovascular biomarkers, and emerging multi-omics and aging markers. Several biomarkers, including high-sensitivity cardiac troponins, N-terminal pro–B-type natriuretic peptide, lipoprotein(a), coronary artery calcium scoring, and plasma p-tau species, showed robust predictive validity. However, many widely marketed biomarkers lack evidence of clinical utility, offer limited actionable benefits, or perform poorly in primary care populations. Unintended consequences, such as overdiagnosis, false positives, psychological distress, diagnostic cascades, and widening inequities, are well documented. Patients often misinterpret unvalidated biomarker results, whereas DTC testing amplifies demand without providing adequate counseling or follow-up. Only a minority of biomarkers currently meet the thresholds of analytical validity, clinical validity, and clinical utility required for preventive use in general practices. GPs play a critical role in contextualizing biomarker results, guiding shared decision-making, and mitigating potential harm. The responsible integration of biomarkers into preventive medicine requires clear communication, strong ethical safeguards, robust evidence, and system-level support for equitable, patient-centered care. Full article

Background/Objectives: Transthyretin cardiomyopathy (ATTR-CM) is frequently associated with conduction disease requiring pacing. Conventional right ventricular pacing may worsen cardiac function, whereas left bundle branch area pacing (LBBAP) aims to preserve physiological activation. Evidence for LBBAP in ATTR-CM remains limited. Methods: A structured narrative review of PubMed and Google Scholar was performed through November 2025 using predefined terms related to LBBAP and ATTR-CM. Peer-reviewed articles, case reports, case series, and relevant abstracts were included. Studies exclusively on light-chain cardiac amyloidosis were excluded. Results: Ten publications met inclusion criteria, comprising three case reports, five case series, one retrospective cohort without a comparator, and one cohort comparing LBBAP with cardiac resynchronization therapy (CRT). In total, 56 patients with ATTR-CM underwent LBBAP. Implantation success was high, with stable acute and mid-term electrical parameters. Follow-up (typically 3–12 months) showed stable electrical parameters with narrow paced QRS complexes and preserved or improved left ventricular ejection fraction in most reports. Symptomatic improvement and reductions in natriuretic peptides were variably described. No major lead-related complications were reported. Comparative data remain sparse and inconclusive. Conclusions: This review suggests that LBBAP is a feasible and safe pacing approach in patients with ATTR-CM and may help to stabilize or improve heart failure symptoms. Further prospective studies are needed to confirm its clinical effectiveness. Full article

Background: In common clinical practice, cardiac overload is still often overlooked in patients with chronic obstructive pulmonary disease (COPD) despite its substantial impact on clinical outcomes and mortality. This study aimed to assess the prevalence of cardiac overload and heart failure (HF) risk, using N-terminal pro-B-type natriuretic peptide (NT-proBNP), in older COPD patients eligible for single-inhaler triple therapy (SITT) and without history of overt HF. We also evaluated changes in NT-proBNP after 3 months of SITT. Methods: This multicenter observational study included 165 older outpatients with a recent moderate-to-severe acute exacerbation of COPD (AECOPD), categorized as ‘Group E’ according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Patients were stratified for the presence of cardiac overload and HF risk using age- and comorbidity-adjusted NT-proBNP thresholds, as recommended by the 2023 Clinical Consensus Statement of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). NT-proBNP was measured at baseline and after three months of SITT (116 patients with available test at three months). Results: Mean age was 80.7 ± 9.7 years. Patients with NT-proBNP levels indicative of “HF likely” and “HF very high-risk” were 43.0% and 24.2%, respectively. After 3 months of SITT, NT-proBNP significantly decreased by 7.2% (95%CI 9.0–5.4%, p < 0.001), with the largest reductions observed in younger patients [11.0% (95% CI 14.1–7.2%) ≤ 76 years old, 8.4% (95% CI −11.3–5.5%) in 77–87 years old, −3.0% (95% CI −6.1–0.0%) in ≥88 years old, p for interaction = 0.007]. Conclusions: In real-life clinical practice, a substantial proportion of older patients with GOLD Group E COPD had elevated NT-proBNP, suggestive of cardiac overload and high risk of HF. The early identification of these patients may prompt further cardiologic evaluation and management. After SITT and before cardiology evaluation, a significant NT-proBNP reduction has been observed, suggesting potential cardiovascular benefit of SITT. Full article

Background and aims: Vericiguat lowers cardiovascular death or heart-failure hospitalization in recently worsened heart failure with reduced ejection fraction (HFrEF), but its effects on cardiac remodeling are less well characterized. Our aim was to evaluate whether the addition of vericiguat to guideline-directed medical therapy (GDMT) promotes reverse myocardial remodeling in patients with HFrEF and recent worsening. Methods: We conducted a prospective, non-randomized, single-center study enrolling 34 consecutive patients with HFrEF who had experienced recent worsening and were on stable GDMT for at least 3 months prior to decompensation. Clinical, biochemical, and echocardiographic assessments were performed at baseline and at 6 months. Results: A total of 24 patients completed the 6-month follow-up (mean age 63 ± 9 years; 92% male), 96% of whom were in New York Heart Association (NYHA) class III or IV. After 6 months of vericiguat therapy, right ventricular systolic function improved significantly, with an increase in tricuspid annular plane systolic excursion (TAPSE) from 18.5 ± 4.3 mm to 21.4 ± 4.8 mm (p = 0.003). Left ventricular systolic function improved, with a numerical increase in left ventricular ejection fraction (LVEF) (30.1 ± 5.9% to 32.2 ± 10.5%; p = 0.122) and a significant increase in left ventricular outflow tract velocity-time integral (LVOT VTI) (14.8 ± 3.7 cm to 16.1 ± 3.8 cm; p = 0.011). Functional improvements were accompanied by structural remodeling, including reductions in right ventricular internal diameter in diastole (RVIDd) (40.5 ± 5.8 mm to 37.9 ± 6.9 mm; p = 0.002) and left ventricular end-systolic volume (LVESV) (144.0 ± 40.3 mL to 132.4 ± 61.0 mL; p = 0.031). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels also decreased significantly (median 1829.0 ng/mL to 1241.0 ng/mL; p = 0.03). Conclusions: In patients with HFrEF and recent worsening, the addition of vericiguat to GDMT may be associated with reverse myocardial remodeling. Full article

Cirrhotic cardiomyopathy encompasses structural and functional cardiac abnormalities occurring in patients with liver cirrhosis despite the absence of pre-existing heart disease, yet its diagnosis remains challenging. Although echocardiography is the standard diagnostic tool, circulating biomarkers may provide complementary value when imaging findings are inconclusive. This study evaluated the association between N-terminal pro-B-type natriuretic Peptide (NT-proBNP), soluble Suppression of Tumorigenicity 2 (sST2), and diastolic dysfunction in cirrhotic patients without known cardiac disease. We conducted a prospective case–control study including 83 participants (43 patients with non-alcoholic cirrhosis and 40 healthy controls), assessed clinically, biochemically, and echocardiographically between June 2020 and July 2021. Cirrhotic patients showed significantly higher NT-proBNP (94.17 ± 151.36 pg/mL vs. 19.2 ± 5.47 pg/mL, p < 0.001) and sST2 levels (5.4 ± 2.31 ng/mL vs. 2.4 ± 0.99 ng/mL, p < 0.001). NT-proBNP demonstrated limited diagnostic accuracy for diastolic dysfunction (accuracy 52.6%, sensitivity 50%, specificity 60%, AUC 0.51), but it correlated modestly with congestion markers such as left atrial volume and pulmonary artery systolic pressure. A multimarker model combining age, NT-proBNP, and sST2 substantially improved diagnostic performance for diastolic dysfunction (accuracy 75%, sensitivity 77.1%, specificity 71.4%, AUC 0.925). In conclusion, NT-proBNP is associated with diastolic dysfunction but is influenced by cirrhosis congestion status. A combined NT-proBNP and sST2 assessment enhances diagnostic precision and may aid therapeutic decision-making, particularly regarding congestion and diuretic management in cirrhotic patients. Full article

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, with heart failure (HF) representing a major contributor to hospitalizations, healthcare costs, and death. Effective management of HF is hindered by the limitations of current biomarkers and diagnostic tools. Conventional biomarkers, such as natriuretic peptides, primarily reflect downstream hemodynamic stress and often lack specificity, particularly in HF with preserved ejection fraction or multiple comorbidities. While imaging provides valuable structural and functional information, it is resource-intensive, costly, and unsuitable for frequent longitudinal monitoring. As a result, these conventional approaches are inadequate to capture the dynamic and heterogeneous nature of HF pathophysiology. Circulating cell-free nucleic acids (cfNAs), including cell-free DNA (cfDNA) and RNA (cfRNA), have emerged as promising noninvasive liquid biopsy biomarkers capable of providing real-time insight into upstream pathological events, such as cardiomyocyte injury, immune activation, inflammation, and maladaptive remodeling. Importantly, cfNAs also act as active mediators of CVD pathology. When released under stress or injury, cfNAs interact with pattern recognition receptors (PRRs) that trigger sterile inflammation, cardiovascular cell dysfunction, and adverse cardiac remodeling. This review summarizes the origins, mechanistic roles, and clinical significance of cfNAs in HF and related CVD, highlighting their dual roles as diagnostic biomarkers and mechanistic effectors of disease. Finally, we discuss emerging cfNA-targeted therapeutic strategies, challenges, and future opportunities for precision medicine in HF and HF-associated CVD. Full article

Transient receptor potential melastatin 2 (TRPM2) channel is a Ca²⁺-permeable, redox-activated cardiac ion channel protective in ischemia–reperfusion, but whether it regulates atrial endocrine output under stress is unclear. Here, we investigated whether TRPM2 contributes to the atrial natriuretic peptide (ANP) response during β-adrenergic stimulation. We compared how male C57BL/6J wild-type (WT) and TRPM2 knockout (TRPM2^−/−) mice (8–12 weeks old) respond to β-adrenergic stress induced by isoproterenol (ISO) using echocardiography, histology, RT-PCR, electrophysiology, Ca²⁺ imaging, ELISA, and atrial RNA-seq. We detected abundant Trpm2 transcripts in WT atria and measured ADP-ribose (ADPr)-evoked currents and hydrogen peroxide (H₂O₂)-induced Ca²⁺ influx characteristic of TRPM2; these were absent in TRPM2^−/− cells. Under the ISO-induced hypertrophic model, TRPM2^−/− mice developed greater cardiac hypertrophy, fibrosis, and systolic dysfunction compared with WT mice. Atrial bulk RNA-seq showed significant induction of Nppa (ANP precursor gene) in WT + ISO, accompanied by higher circulating ANP; TRPM2^−/− + ISO showed blunted Nppa and ANP responses. ISO-treated TRPM2^−/− mice exhibited more blunt responses, in both Nppa transcripts and circulating ANP levels. Exogenous ANP attenuated ISO-induced dysfunction, hypertrophy, and fibrosis in TRPM2^−/− mice, suggesting that TRPM2 is needed for the cardioprotective endocrine response via ANP to control stress-induced β-adrenergic remodeling. Full article

Background. Gestational diabetes mellitus (GDM) induces maternal hyperglycemia, which may alter fetal cardiac structure and function, increasing short- and long-term cardiovascular risks. Purpose. To systematically review the evidence on the fetal cardiac structural and functional effects of GDM, to explore the diagnostic role of novel imaging and biochemical biomarkers, and to summarize the long-term cardiovascular complications associated with GDM. Materials and Methods. A systematic search of PubMed, Scopus, and Cochrane Library was conducted according to the PRISMA guidelines. All studies comparing cardiac outcomes in GDM and non-GDM pregnancies were included. Data on myocardial hypertrophy, diastolic and systolic function, imaging modalities, and biomarkers were extracted and qualitatively synthesized. Results. A total of twelve eligible studies were identified. Fetal cardiac hypertrophy and diastolic and early systolic dysfunction are common among GDM pregnancies and can be detected by dual-gate Doppler and speckle-tracking echocardiography. Abnormalities are observed in indices such as the myocardial performance index, E/A, E/e′ ratios, and global longitudinal and circumferential strain in fetuses and may persist in the neonatal period. Alterations may be more pronounced for the right ventricle compared to the left. Septal hypertrophy is associated with elevated umbilical cord pro-brain natriuretic peptide. The risk of early-onset cardiovascular disease in the progeny of diabetic mothers is 29% higher, as evidenced by population-based cohort data. Conclusions. GDM is linked to fetal cardiac remodeling and an increased long-term cardiovascular risk. Early detection and customized interventions to reduce adverse outcomes may be achieved by integrating advanced echocardiographic techniques and biomarkers into prenatal surveillance. Full article

Background and Clinical Significance: Intermediate-high-risk pulmonary embolism is characterized by right-ventricular dysfunction and positive cardiac biomarkers in the absence of hemodynamic instability. Current guidelines recommend anticoagulation with vigilant monitoring, and reserve systemic fibrinolysis for patients who deteriorate hemodynamically. However, some patients may experience physiologic decompensation manifested by refractory hypoxemia rather than hypotension, despite preserved systemic perfusion and normal lung parenchyma. In such cases, oxygenation failure reflects the severity of perfusion impairment and incipient right-ventricular-circulatory collapse. Whether this scenario justifies systemic fibrinolysis remains uncertain. Case Presentation: We present a 75-year-old man, five days after arthroscopic meniscus repair, presenting with acute dyspnea, tachycardia, and severe respiratory failure despite normal chest radiography. Laboratory findings revealed elevated troponin-I and brain natriuretic peptide, and echocardiography demonstrated marked right-ventricular dilation. Computed tomographic pulmonary angiography confirmed extensive bilateral central emboli with preserved lung parenchyma. Despite high-flow nasal oxygen at 100% fraction of inspired oxygen, respiratory failure worsened, necessitating intubation under lung-protective settings. With catheter-directed therapy unavailable and transfer unsafe, a multidisciplinary team administered staged systemic fibrinolysis with alteplase, pausing heparin during infusion. No bleeding or surgical complications occurred. Oxygenation and right-ventricular indices improved promptly. The patient was extubated on day 2, discharged from intensive care unit on day 7, and remained asymptomatic with normal echocardiography at 3 months. Conclusions: Refractory hypoxemia in intermediate-high-risk, normotensive pulmonary embolism, particularly when parenchymal disease and ventilator confounding are excluded, may represent an early form of circulatory decompensation warranting rescue reperfusion. In the absence of catheter-directed options and with acceptable bleeding risk, staged full-dose systemic fibrinolysis can be life-saving and physiologically justified. This case supports expanding the concept of “clinical deterioration” in intermediate-risk pulmonary embolism to include isolated, unexplained respiratory failure, highlighting the need for future trials to refine individualized reperfusion thresholds. Full article

Background and Objectives: Cardiovascular–kidney–metabolic (CKM) syndrome reflects the interconnection between metabolic risk factors, chronic kidney disease (CKD), and cardiovascular disease (CVD). Despite increasing awareness, population-based data on CKM syndrome are limited, particularly in Europe. This study assessed the prevalence of CKM syndrome and the use of renal and cardiac biomarkers in Lithuania. Materials and Methods: Health records of 923,329 adults aged ≥40 years from the national Electronic Health Services and Cooperation Infrastructure Information System were analyzed. CKM-associated conditions (prediabetes/type 2 diabetes, obesity, CKD) and cardiovascular outcomes (atherosclerotic CVD, peripheral vascular disease, stroke, heart failure, atrial fibrillation) were identified. CKM stages were defined as stage 0 (no CKM conditions), stages 1–3 (at least one CKM condition), and stage 4 (at least one CVD diagnosis). The use of estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR) and N-terminal pro–B-type natriuretic peptide (NT-proBNP) testing was evaluated. Results: Overall, 34.8% of adults met criteria for stage 4 CKM syndrome, and 23.4% were classified as stage 1–3. Obesity (21.2%) and type 2 diabetes (17.2%) were the most common CKM-associated conditions. Heart failure (25.4%) and atrial fibrillation (14.0%) were the most common cardiovascular outcomes, with ≥2 CVD diagnoses present in 15.4% of patients. Among stage 1–3 patients, eGFR, ACR, and NT-proBNP were measured in 53.5%, 9.0%, and 4.9%, respectively. Conclusions: A third of Lithuanian adults aged ≥40 years had stage 4 CKM syndrome. The underuse of biomarker testing highlights missed opportunities for early detection. Broader implementation of biomarker testing and integrated care is warranted to slow progression of CKM syndrome and reduce cardiovascular risk. Full article

The utility of physical exercise in congestive heart failure is not yet well known in the field of veterinary cardiology, despite many studies already published, unlike in human medicine where the benefits and safety of exercise training have been widely proven and included in recommendations and consensus. Several studies have been conducted since the end of the 20th century, evaluating the usefulness of physical exercise in the diagnosis, prognosis, as well as the treatment of congestive heart failure in dogs. The information from these studies has been compiled in this work to conduct a literature review and propose a work base, information, and protocols to develop knowledge about the effect of exercise training on congestive heart failure for future clinical research in dogs. Two major types of exercise tests have been published: the 6 min walk test, easy to implement and seemingly better at reflecting the daily physical capacities of cardiac dogs, and treadmill tests, such as the ergometric test or incremental tests, which, combined with the measurement of plasma concentration of NT-proBNP (N-terminal pro B-type natriuretic peptide), are promising for prognostic evaluation and monitoring of conventional drug therapy. An exercise training program does not reverse the damage caused by congestive heart failure but can help delay and slow the progression of the disease, essentially having effects on heart rate and sympathetic modulation of cardiac activity and preserving cardiac function. Additionally, an improvement in the functional class of heart failure and quality of life due to physical exercise has been observed, a key point for owners. Even though there are risks associated with this complementary therapy (syncope or risk of exacerbating symptoms of cardiac pathologies), the risk–benefit balance seems to clearly favor the use of exercise when used in a controlled manner in stable patients. Evidence of the utility of physical exercise as a testing method or as a complementary treatment has been gathered in this review. However, to further develop the clinical practice of exercise, additional studies need to be conducted to develop standardized testing methods, clarify the impact of exercise training programs on all classes of heart failure, assess the risks, and analyze the long-term effects on canine species. Full article