MF Širdies centras (04.45)

Background and Objectives: Guideline-directed medical therapy (GDMT) remains a challenge due to its low rates worldwide. Adherence to GDMT in patients with heart failure (HF) and reduced ejection fraction (rEF) in the Baltics (Estonia, Latvia, and Lithuania) has been unknown. This is the first study to describe the characteristics of patients with HFrEF and their treatment patterns in the Baltics. Materials and Methods: The EVOLUTION-HF study was a longitudinal, real-world evidence study that enrolled patients with HFrEF following newly initiated sodium–glucose cotransporter-2 inhibitor (SGLT2i) dapagliflozin therapy. In total, 12 study sites (four from each country) were included. Patients were followed up for 12 months. A pooled data set including adherence to GDMT, dapagliflozin’s usage, and patients’ profiles was evaluated. Results: Between April and December 2022, 178 patients with a median left ventricular ejection fraction of 32% were enrolled. At baseline, 155 (87%) patients received renin–angiotensin–aldosterone system inhibitors (RAASi), 168 (94%) received beta-blockers (BB), and 106 (60%) received mineralocorticoid receptor antagonists (MRA); however, only 47.8% of the study population were found to be treated with GDMT (including RAASi, BB, MRA, and dapagliflozin) at the beginning of the study. At the end of the follow-up, the percentage of GDMT users decreased to 42.3%. The number of dapagliflozin discontinuations per 100 patient-years was found to be 13.2 (95% CI 8.2–18.2). Conclusions: The findings indicate a low rate of dapagliflozin discontinuation (13%) and an overall suboptimal proportion of patients receiving GDMT for HFrEF (almost half of the patients). The low rate of GDMT use in the Baltics prompts great attention. Additional research and incremental joint efforts are needed to ensure an increase in GDMT use across diverse HF patient populations.

Background and objectives: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with endothelial glycocalyx injury and perioperative endothelial dysfunction. Syndecan-1 is commonly used as a biomarker of glycocalyx shedding, but data on its perioperative changes and their relationship with operative and patient-related factors remain limited. The aim of this study was to evaluate perioperative Syndecan-1 dynamics during coronary artery bypass grafting (CABG) with CPB and to assess associations with ischemia–reperfusion exposure and patient characteristics. Materials and methods: This prospective observational study included 147 patients undergoing elective CABG with CPB. Syndecan-1 concentrations were measured at five time points: before induction of anaesthesia, immediately after aortic cross-clamp application, immediately after aortic declamping, on arrival at the ICU and 24 h after surgery. Perioperative changes were analysed using non-parametric tests, Spearman’s rank correlation analysis and mixed-effects modelling. The study was registered at ClinicalTrials.gov (NCT03491163; registered on 29 March 2018). Results: Syndecan-1 concentrations changed significantly over time (p < 0.001), increasing from a baseline median of 49.74 ng/mL to a peak of 147.78 ng/mL at ICU admission, followed by a partial decline to 65.26 ng/mL at 24 h. Aortic cross-clamp duration was weakly but significantly associated with Syndecan-1 concentration at ICU admission (rs = 0.243, p = 0.003) and with perioperative increases from baseline to ICU admission (ΔS4-1: rs = 0.196, p = 0.017) and from aortic clamping to ICU admission (ΔS4-2: rs = 0.207, p = 0.012). No significant associations were observed between CPB duration and Syndecan-1 concentrations in univariable analyses. In the mixed-effects model, a significant non-linear temporal pattern of Syndecan-1 concentrations was observed (both linear and quadratic time terms, p < 0.001). Male sex (β = 0.247, p = 0.009) and aortic cross-clamp duration (β = 0.016, p = 0.005) were independently associated with higher Syndecan-1 concentrations, whereas smoking status, age, BMI, diabetes status, EuroSCORE II, and CPB duration were not independently associated. Conclusions: Syndecan-1 concentrations increase significantly during cardiac surgery with cardiopulmonary bypass, peaking at ICU admission and partially declining within 24 h. Aortic cross-clamping duration, but not total CPB duration, showed weak associations with glycocalyx shedding. Male sex was independently associated with higher Syndecan-1 concentrations. These findings support ischemia–reperfusion injury as an important contributor to endothelial glycocalyx shedding during cardiac surgery.

Background/Objectives: Dilated cardiomyopathy is a heterogeneous disorder with a substantial genetic contribution from a variety of pathogenic variants. Hereditary isolated DCM is often caused by variants in genes encoding sarcomere proteins, as well as proteins involved in desmosomes or other cardiac cell functions. Identifying genetic causes improves our understanding of DCM pathophysiology, facilitates prognostic assessment, and enables more personalized disease management. Methods: We retrospectively analyzed genetic data from adult patients with a clinical diagnosis of isolated DCM evaluated at a Lithuanian tertiary university hospital between 2019 and 2024. All patients were tested with a next-generation sequencing cardiovascular gene panel. Results: We gathered 169 patients and initially reached a 16.0% (n = 27) genetic testing diagnostic yield. We performed all genetic variant reanalyses with the most current classification guidelines, and we found an additional eight positive cases. Our final diagnostic yield was 20.7% (n = 35). TTN was the most frequently affected gene (n = 30), whereas variants in BAG3 (n = 2), DSP (n = 1), LMNA (n = 1), and FLNC (n = 1) were rare. In total, 15 variants were novel—not described in the literature or databases. We did not observe significant clinical differences between patients with pathogenic variants and those without pathogenic variants. We expected a different clinical course with variants in genes like BAG3 or LMNA, but there were only a few cases. Conclusions: Genetic testing remains an important tool for confirming complex DCM cases and allows earlier disease management for relatives at risk.

The formation of extracellular traps (ETs) through ETosis has emerged as a key mechanism in immunothrombosis. However, the temporal dynamics and clinical significance of ETosis in coronary thrombi of ST-elevation myocardial infarction (STEMI) patients remain incompletely understood. We investigated whether ETosis burden increases with thrombus age and is associated with DNASE1 and TREX1 genetic variants as well as impaired myocardial reperfusion. Thrombus aspirates from 81 STEMI patients undergoing primary percutaneous coronary intervention were histologically classified as fresh (n = 41) or lytic (n = 40). ETosis was quantified by citrullinated histone H3 (CitH3) immunohistochemistry and digital image analysis, complemented by multiplex staining for myeloperoxidase (MPO), CD68, caspase 3, and CD61. Plasma ET-related markers and genotyping of DNASE1 (rs1053874) and TREX1 (rs11797) were also performed. CitH3-positive cells were present in all thrombi but were more abundant in lytic (older) thrombi compared with fresh thrombi (1348 vs. 591 cells/mm2, p < 0.001). Increased ETosis was associated with neutrophil and macrophage infiltration, apoptosis, prolonged ischemia time, elevated systemic inflammation (neutrophil–lymphocyte ratio and C-reactive protein), and impaired myocardial reperfusion (lower TIMI flow grades). Moreover, the DNASE1 GG genotype was associated with higher densities of MPO- and CD68-positive cells, whereas the TREX1 CC genotype was associated with increased densities of CitH3-, MPO-, and CD68-positive cells. This study demonstrates that ETosis increases with coronary thrombus maturation and is associated with local inflammation and impaired reperfusion in STEMI. Genetic variants in DNASE1 and TREX1 may modulate inflammatory cell accumulation within thrombi. These findings suggest ETosis as a potential therapeutic target, particularly in patients with delayed presentation.

Background/Objectives: Cardiac magnetic resonance (CMR) imaging provides a comprehensive assessment of myocardial injury after ST-segment elevation myocardial infarction (STEMI), yet the relative prognostic value of segmental infarct zone parameters compared with global indices for predicting left ventricular (LV) functional recovery remains incompletely defined. This study aimed to determine whether segmental infarct zone functional and structural CMR parameters provide prognostic information for LV functional recovery after a first STEMI treated with primary percutaneous coronary intervention (PCI). Methods: In this prospective single-center study, 93 patients with a first STEMI (median age 61 years; 77% male) underwent CMR at baseline (median 3 days post-PCI) and at a 6-month follow-up. The comprehensive CMR assessment included cine imaging for volumetric and feature-tracking strain analysis, T1 and T2 mapping, and late gadolinium enhancement (LGE) for infarct size (IS) and microvascular obstruction (MVO) quantification. The myocardial segments were classified as infarcted, adjacent, or remote based on the LGE distribution. The primary outcome was unfavorable LV functional recovery, defined as failure to achieve an absolute increase of >10 percentage points in the LV ejection fraction (LVEF) or a follow-up LVEF ≤ 50%. Results: At the 6-month follow-up, significant reverse remodeling was observed: the LVEF improved from 49.0% [40.7–52.4] to 55.8% [47.9–59.9] (p < 0.001), the LV end-systolic volume decreased from 91.8 mL [75.1–113.8] to 80.8 mL [61.9–108.3] (p = 0.005), and the relative IS decreased from 30.9% [18.9–45.5] to 19.0% [11.1–31.3] of LV mass (p < 0.001). At the follow-up, MVO was no longer detectable in any patient. Unfavorable functional recovery occurred in 17 patients (18.3%). In the multivariable analysis, the infarct zone circumferential strain (CS) was the strongest independent predictor of unfavorable recovery (OR 8.81; 95% CI 1.98–39.28; p = 0.004), followed by the relative IS (OR 4.02; 95% CI 1.03–15.73; p = 0.045) and a lower infarct zone post-contrast T1 (OR 4.40; 95% CI 1.12–17.36; p = 0.034). Conclusions: Segmental infarct zone characteristics—particularly circumferential strain, post-contrast T1, and infarct size—provide clinically relevant prognostic information for LV functional recovery after STEMI. The infarct zone CS offers incremental predictive value beyond its structural parameters, reflecting the residual contractile reserve and myocardial viability.

Background: Chronic obstructive pulmonary disease (COPD) is associated with right ventricular (RV) dysfunction and subclinical myocardial injury. The effects of dual bronchodilation on RV function and cardiac injury biomarkers remain limited. Objectives: To evaluate 12-week changes in pulmonary function, RV function, and serum troponin-I in newly-diagnosed COPD patients receiving tiotropium/olodaterol as routine clinical care and to assess differences in RV function and troponin-I between COPD and non-COPD controls with comparable cardiovascular diseases (CVDs). Design: Prospective real-world observational study. Methods: Treatment-naïve patients with moderate-to-severe COPD were assessed at baseline and after 12 weeks of treatment. Evaluations included spirometry, plethysmography, two-dimensional and speckle-tracking transthoracic echocardiography, cardiac magnetic resonance imaging (MRI), and troponin-I. Baseline RV measurements and troponin-I were compared between COPD (n = 47) and controls (n = 23). Results: COPD patients had lower RV fractional area change and RV free-wall strain (FWS) than controls (p < 0.001 and p = 0.018, respectively). Troponin-I was above the limit of detection in 93.6% of COPD and in 56.5% of controls (p < 0.001). COPD treatment increased forced expiratory volume in 1 second (FEV1) and forced vital capacity while reducing residual volume-to-total lung capacity (TLC) and functional residual capacity (FRC)-to-TLC (p < 0.05). RV global longitudinal strain (GLS) improved from 21.7 ± 2.6% to 23.0 ± 2.8%, and RV-FWS from 24.2 ± 3.3% to 26.1 ± 3.6% (both p < 0.05) in echocardiography (n = 29). ΔRV-GLS correlated positively with ΔFEV1 and inversely with ΔFRC/TLC (p < 0.05). In the moderate COPD subgroup, RV-GLS in MRI changed from 22.6 ± 6.1% to 25.5 ± 7.5% (p = 0.037), and troponin-I decreased from 1.23 pg/mL (IQR 1.03–1.56) to 1.09 pg/mL (IQR 0.95–1.20; p = 0.049). Conclusion: COPD affects RV function and troponin-I regardless of concomitant CVDs. Initiation of dual bronchodilation is associated with beneficial effects on RV strain and troponin-I in patients with COPD. Because of the small sample size, these findings should be interpreted cautiously and confirmed in larger studies.

Background: Toxic epidermal necrolysis (TEN) is a rare but life-threatening complication that may occur in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in the context of extensive drug exposure. In this population, TEN can closely resemble severe acute graft-versus-host disease (GVHD), making diagnosis and management challenging. Case presentation: We report the clinical course of an allo-HSCT recipient who developed a rapidly progressive skin rash early after transplantation, and we analyzed the clinical features, histopathology, treatment and outcome. Results: The patient developed rapidly progressive epidermal detachment with severe oral, ocular, and genital mucosal involvement shortly after exposure to trimethoprim/sulfamethoxazole (TMP-SMX). Disease severity was reflected by a SCORTEN score of 5, corresponding to a very high predicted mortality risk. The clinical picture raised concern for both TEN and severe acute GVHD, while histopathological findings favored TEN but were not definitive. Management included systemic corticosteroids, intravenous immunoglobulin, ruxolitinib, and intensive supportive care. The patient gradually re-epithelialized and recovered without long-term sequelae. Conclusions: This case underscores the diagnostic difficulty of distinguishing TEN from severe acute GVHD in the early post-transplant period. Careful assessment of drug exposure, clinical evolution, and multidisciplinary evaluation are essential to guide timely and appropriate management.

Transthyretin amyloid cardiomyopathy (ATTR-CM) has undergone a shift towards noninvasive diagnostics using bone tracer scintigraphy with Perugini grading. While both grades 2 and 3 are considered diagnostic, potential phenotypic differences between these groups remain uncertain. We aimed to evaluate the diagnostic yield of technetium-99 m pyrophosphate (99mTc-PYP) scintigraphy and to compare clinical and multimodality imaging characteristics across scintigraphic grades in a single-center cohort.

To evaluate the safety and efficacy of Total Endovenous Laser Ablation (TEVLA) in a multicenter cohort.

Progression of ischemic heart disease to acute coronary syndrome (ACS) is fueled by endothelial dysfunction and disruptions in vascular signaling pathways. The relationship between the angiotensin-converting enzyme 2 (ACE2)/renin-angiotensin system (RAS) axis and eicosanoid metabolism is still not fully understood. This study aimed to investigate whether changes in circulating ACE2 and 20-hydroxyeicosatetraenoic acid (20-HETE) reflect dysregulation of a combined ACE2/RAS-eicosanoid axis in ACS and to evaluate the diagnostic and functional significance of 20-HETE. We studied 122 patients with ischemic heart disease (including stable coronary artery disease (SCAD) and ACS) and 54 controls. Levels of circulating ACE2 and 20-HETE were measured using ELISA. Additionally, in vitro experiments with cell culture models were conducted to evaluate how pharmacological modulation of the ACE2/RAS axis affects nitric oxide (NO) production, inflammatory signaling, and CYP4F2 expression. Both ACE2 and 20-HETE levels were significantly lower in ACS compared to SCAD and controls (p < 0.001). Circulating 20-HETE effectively distinguished ACS from SCAD with an AUC of 0.91. In endothelial cells, altering the ACE2/RAS axis impacted NO availability and inflammatory gene expression, correlating with changes in CYP4F2 levels. 20-HETE affected cellular metabolic activity and GPR75 signaling, indicating a functional connection between RAS signaling and eicosanoid pathways. Lower circulating 20-HETE levels are associated with disruption of the integrated ACE2/RAS-eicosanoid axis, which is linked to endothelial dysfunction in ACS. These results suggest that 20-HETE may serve not only as a biomarker but also as part of a broader vascular signaling network related to acute coronary instability.