Medicine and Pharmacology

Abstract: Chronic total coronary occlusion (CTO) occurs within advanced coronary artery disease (CAD), but its association with left ventricular (LV) deformation and pressure-strain-loop-derived myocardial work beyond LV ejection fraction (LVEF) is uncertain. We performed a retrospective cross-sectional analysis of 148 records with multivessel or left-main CAD, including 70 with and 78 without CTO. Absolute global longitudinal strain (GLS) was the principal endpoint; global work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were secondary endpoints. CTO coefficients were estimated using heteroscedasticity-consistent linear models. Prior myocardial infarction was more frequent with CTO (42.9% vs. 23.1%), with lower LVEF and larger LV volumes. Median GLS was 14.0% versus 15.5% (p = 0.021), and median GCW was 1723 versus 1997 mmHg% (p = 0.026). The CTO-minus-non-CTO GLS coefficient was −1.59 percentage points (95% CI, −2.98 to −0.20) unadjusted, −1.29 (95% CI, −2.75 to 0.18) after clinical adjustment, and −0.16 (95% CI, −1.24 to 0.92) after adding LVEF. CTO status marked a modest adverse global LV mechanical phenotype, but adjusted estimates were imprecise and markedly attenuated after accounting for LVEF. Prospective studies integrating ischemia, scar, viability, and longitudinal follow-up are needed.

Abstract: Background and Objectives: Hyponatremia and renal dysfunction can accompany cardiac tamponade and may improve after pericardial drainage. We quantified paired changes in serum sodium, hyponatremia status, and serum creatinine in an expanded cohort and tested whether sodium and creatinine responses were associated at the patient level. Materials and Methods: This single-center retrospective cohort included 48 adults who underwent percutaneous drainage for clinically diagnosed cardiac tamponade from 2010 to 2023. Sodium and creatinine were recorded within 2 days before and 5 days after drainage. Paired changes were assessed using Wilcoxon signed-rank tests and Hodges–Lehmann estimates, hyponatremia transitions using exact McNemar testing, and the association between continuous changes using Spearman correlation. Results: Thirty-four patients (70.8%) had malignant effusions. Median sodium rose from 136.0 to 138.5 mmol/L; the estimated paired shift was +3.5 mmol/L (95% CI +2.0 to +5.5; p < 0.001). Hyponatremia decreased from 18/48 (37.5%) to 6/48 (12.5%), an absolute paired reduction of 25.0 percentage points (95% CI 10.4–39.6; p = 0.004). Median creatinine fell from 76.0 to 70.5 µmol/L; the estimated paired shift was −9.0 µmol/L (95% CI −15.5 to −3.0; p = 0.004). Sodium and creatinine changes were not associated (Spearman ρ = 0.066, 95% CI −0.264 to +0.393; p = 0.656). Conclusions: Pericardial drainage was followed by a robust rise in serum sodium, fewer patients with hyponatremia, and a modest fall in serum creatinine. The two changes did not covary across patients and should be interpreted as parallel, heterogeneous postdrainage responses rather than evidence of a shared mechanism or reversal of formally defined acute kidney injury.

Abstract: Background: Bone marrow-derived CD133+ cells have been tested as autologous products in acute and chronic ischemic heart disease, but their mechanism and clinical value remain uncertain. Objective: To map the clinical, mechanistic, manufacturing, and regulatory evidence for bone marrow-derived immunoselected CD133+ products and identify gaps relevant to potency assessment. Methods: PubMed and Europe PMC were searched from inception through 13 August 2026, supplemented by backward citation searching and official regulatory sources. Records were organized in a single-reviewer PRISMA-ScR workflow and charted by evidence domain, cell source, design, delivery/manufacturing context, endpoints, and limitations. Results: The searches yielded 482 database records and 18 additional sources. After removal of 289 duplicates, 211 unique records were screened and 57 sources were included: 35 clinical reports, six direct preclinical/mechanistic studies, six manufacturing/quality studies, five contextual mechanistic studies, and five guidance/regulatory documents. Clinical studies support feasibility and limited-population safety but show no consistent improvement in global ventricular function or clinical outcomes. Direct adult bone marrow CD133+ mechanistic evidence remains sparse, while RECARDIO provides an associative product-to-perfusion bridge. Conclusions: A mechanism-linked potency strategy should prioritize source-specific endothelial rescue under hypoxia–reoxygenation, supported by migration, network formation, and a restricted directional secretome panel. Prospective product-to-perfusion validation is required before CD133+ therapy can be considered clinically established.

Abstract: Background: Anemia is a common comorbidity in patients with heart failure with reduced ejection fraction (HFrEF) and is associated with impaired functional capacity, poorer quality of life, increased hospitalization, and mortality. However, data from sub-Saharan Africa, particularly Ethiopia, remain limited. Objective: To determine the prevalence of anemia and identify factors associated with anemia among patients with HFrEF attending the cardiac clinic of Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia. Methods: We conducted a hospital-based cross-sectional study among adults with established HFrEF (left ventricular ejection fraction ≤40%) attending the TASH cardiac clinic between June 1 and October 30, 2020. Demographic, clinical, and laboratory data were collected through patient interviews and medical record review. Health-related quality of life was assessed using the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12). Anemia was defined according to World Health Organization criteria. Multivariable logistic regression was performed to identify factors independently associated with anemia. Results: A total of 138 patients were included, of whom 27 (19.6%) had anemia. Compared with patients without anemia, those with anemia had lower KCCQ-12 scores (33.7 vs 40.5, p=0.003), higher serum creatinine levels (1.6 vs 0.9 mg/dL, p=0.024), lower mean corpuscular volume (83.1 vs 88.9 fL, p=0.008), and more previous hospitalizations (44.4% vs 12.6%, p<0.001). In multivariable analysis, male sex (adjusted odds ratio [AOR] 5.34, 95% CI 1.33–21.50; p=0.018), higher serum creatinine (AOR 3.76, 95% CI 1.11–12.72; p=0.033), and lower KCCQ-12 score (AOR 0.91 per-point increase, 95% CI 0.84–0.98; p=0.008) were independently associated with anemia. Conclusions: Anemia affected approximately one in five patients with HFrEF in this Ethiopian cohort. Male sex, impaired renal function, and poorer health-related quality of life were independently associated with anemia. Routine assessment of hemoglobin status should be incorporated into the comprehensive management of patients with HFrEF.

Abstract: Objective: Heritable thoracic aortic disease (HTAD) is an important cause of thoracic aortic aneurysm and dissection, yet remains underdiagnosed. We aimed to summarize the prevalence of syndromic and non-syndromic HTAD, describe variants of uncertain significance (VUS), and evaluate the impact of family screening in a contemporary cardiothoracic surgical cohort. Methods: Between 2018 and 2026, 163 patients underwent genetic testing for suspected HTAD at our institution. A total of 139 patients with completed genetic testing were included in the analysis. Indications for testing included root aneurysm or acute aortic dissection before the age of 60 years with or without positive family history, aneurysms involving multiple vascular territories, or syndromic features suggestive of a heritable aortopathy. Results: The mean age at testing was 45.8 ± 15.1 years and 33% of patients were female. Aortic dissection represented the initial manifestation of disease in 40% of patients. Positive family history was present in 60% of patients. Genetic alterations were identified in 45% of patients, including pathogenic variants in 25%. Twenty-four patients were diagnosed with syndromic HTAD, most commonly Marfan syndrome, while 10 patients were found to have non-syndromic HTAD. Variants of uncertain significance were detected in 27 patients (20%), predominantly affecting MYLK and MYH11. Following diagnosis, 53 first-degree relatives underwent screening, resulting in 18 prophylactic aortic operations. Conclusion: Cardiac surgeons should be aware of the importance of genetic testing in patients with aortic disease. Beyond the individual patient, the broader goal is to identify at-risk family members and prevent acute aortic syndromes. Continued collection of genotype–phenotype data is essential to improve interpretation of variants of uncertain significance and optimize future patient care.

Abstract:

Background: Rubidium-82 (⁸²Rb) PET myocardial perfusion imaging (MPI) yields, in a single study, quantitative absolute myocardial blood flow (MBF, mL/min/g), myocardial flow reserve (MFR), and gated left ventricular (LV) function (LVEF, EDV, ESV, SV). These quantitative values depend on the tracer, scanner, kinetic model, software, and on the underlying population, and have been characterised almost exclusively in North American and European cohorts. The Arabian Gulf, where Kuwait has among the highest age-standardised diabetes prevalence worldwide (25.6%), is essentially unstudied, so the distribution and behaviour of these parameters in such a real-world cardiometabolic population are unknown. Objectives: To evaluate the distribution of the quantitative ⁸²Rb PET parameter set in a real-world Arabian Gulf cohort and, within a small strictly-defined normal subgroup, to describe sex- and age-related patterns in absolute MBF, MFR, and LV function. Given the limited size of the normal subgroup, these values are presented as exploratory, hypothesis-generating observations rather than definitive population reference norms. Methods: Retrospective single-centre study of 330 consecutive patients (mean age 63.5 ± 12.0 years) who underwent adenosine-stress ⁸²Rb PET/CT MPI. The truly-normal reference stratum, normal perfusion (C1), normal global MFR (≥ 2.0), normal resting LVEF, and no documented cardiac history, comprised 44 patients (25 female, 19 male). Reference values are reported as sex- and age-stratified centiles (5th, 25th, median, 95th percentiles), with the 5th percentile as the lower reference limit. Sex differences used Mann-Whitney U with rank-biserial r and Cohen's d (95% CI); age was examined across broad bands. All analyses followed APA 7 standards with Bonferroni correction. Results: In the truly-normal stratum, median global stress MBF was 2.94 mL/min/g (5th percentile 2.03) and median global MFR was 2.72 (5th percentile 2.06); every value satisfied the C1 definition (MFR ≥ 2.0). Consistent with published ⁸²Rb PET registries, women had higher global stress MBF (median 3.00 vs 2.91 mL/min/g) and lower MFR than men, and LV volumes were smaller in women with higher LVEF. The 5th-percentile lower reference limit for stress LVEF was 54% (women) and 53% (men). These absolute-flow reference values are lower than those reported for Western low-risk cohorts (stress MBF ~3.25 mL/min/g; MFR ~3.18), consistent with the higher cardiometabolic burden of this population. Conclusions: In this exploratory single-centre evaluation, quantitative ⁸²Rb PET flow values in a small strictly-normal Arabian Gulf subgroup were lower than Caucasian-derived values, while the expected sex and age patterns were preserved. Because the normal subgroup is small, these findings are hypothesis-generating and require confirmation in larger, prospectively screened cohorts before use as population reference values; they nonetheless indicate that population- and pipeline-specific calibration is needed when quantitative 82Rb thresholds derived elsewhere are applied locally.

Abstract: Hypertension remains the leading preventable cause of cardiovascular disease and premature death worldwide. In the hypertensive state, renal and cardiovascular dysfunctions become entrenched in a self-perpetuating feedback loop, with immune cells emerging as central coordinators of this pathological crosstalk. This review examines the mechanisms by which immune cells integrate signals from high salt, the renin-angiotensin-aldosterone system (RAAS), and the sympathetic nervous system (SNS) to drive chronic inflammation and end-organ damage. We highlight the salt-dendritic cell-isolevuglandin (IsoLG)-T cell axis as a critical pathway linking dietary sodium to immune activation and hypertension. We also explore bidirectional interactions between immune cells and RAAS components, as well as neuro-immune crosstalk that amplifies sympathetic outflow. Counter-regulatory mechanisms, including the ACE2/Ang-(1-7)/Mas axis, the kallikrein-kinin system, Urodilatin, Klotho, and renalase, provide endogenous braking signals that limit inflammation. Finally, we discuss emerging immunomodulatory therapeutic strategies and identify key unanswered questions for future research. Understanding immune cells as central coordinators of cardiorenal communication offers new opportunities for precision medicine approaches to hypertension.

Abstract: Аrterial hypertension (HTN) remains the leading modifiable cardiovascular risk factor worldwide, yet blood pressure (BP) control remains suboptimal in a substantial proportion of treated patients, including those with resistant HTN. This narrative literature review summarizes emerging pharmacological and device-based strategies that extend beyond conventional combination therapy. We critically review the current evidence regarding the clinical benefits of endothelin-receptor antagonists, selective aldosterone-synthase inhibitors, RNA interference targeting hepatic angiotensinogen, and the complementary BP-lowering effects of sacubitril/valsartan, sodium–glucose cotransporter 2 inhibitors, and non-steroidal mineralocorticoid receptor antagonists. We also discuss novel non-pharmacological approaches to the treatment of difficult-to-control HTN, including baroreflex activation therapy, endovascular baroreflex amplification, and other investigational neuromodulatory strategies. Several of these approaches achieve clinically meaningful BP reductions and may target distinct pathophysiological mechanisms or help overcome adherence-related barriers. However, the available evidence remains heterogeneous, and for most emerging antihypertensive therapies, adequately powered trials demonstrating reductions in major cardiovascular events and long-term comparative effectiveness are still lacking. Future management of HTN will likely combine guideline-directed single-pill regimens with phenotype-guided pharmacotherapy and carefully selected device-based interventions.

Abstract: Restenosis after drug-eluting stent (DES) implantation remains a major clinical challenge, with impaired endothelial repair contributing to recurrent narrowing. Circulating endothelial progenitor cells (EPCs) support vascular regeneration, but their functional capacity may be reduced in patients with restenosis. We conducted a cross-sectional study including 24 men categorized as restenosis (n=8), no restenosis post-DES (n=8), and no stenosis controls (n=8). Peripheral blood mononuclear cells were isolated and cultured on human fibronectin in endothelial basal medium. After seven days, EPC colony-forming units (EPC-CFUs) were enumerated following Giemsa staining, and endothelial nitric oxide synthase (eNOS) levels were quantified using ELISA. Kruskal–Wallis tests were used for group comparisons, and correlations were assessed with Spearman analysis. EPC-CFUs decreased progressively from no stenosis (15.3±3.1 colonies/well) to no restenosis (8.1±1.8) to restenosis (4.2±0.5) (H=20.1, p<0.001). eNOS levels mirrored this pattern: 13.7±2.5, 8.7±1.5, and 5.2±0.6 pg/mL, respectively (H=5.7, p<0.01), and correlated positively with EPC-CFUs (r=0.724, p<0.001). These results indicate a stepwise reduction in EPC-mediated endothelial reparative capacity in coronary artery disease, particularly in restenosis. EPC-CFU and eNOS measurements provide a pragmatic in vitro functional assessment and may serve as potential biomarkers for restenosis risk following DES implantation.

Abstract: Surgical mitral valve repair is the gold standard for severe primary mitral regurgitation (MR), yet when repairs fail, open reintervention carries substantial perioperative risk. Following band annuloplasty, minimally invasive options, such as transcatheter mitral valve replacement (TMVR), remain largely unexplored due to a hypothetical concern around the lack of circumferential radial support. We report the first transcatheter mitral valve-in-band (ViB) replacement in a large-animal model of failed mitral repair. A 68 kg, 20-month-old female Yucatan mini pig underwent placement of a 28 mm mitral annuloplasty band, oversized to create MR, via clamshell sternotomy under cardiopulmonary bypass; a simulated dilated left atrium enabled transcatheter access. A 23 mm Edwards Sapien Ultra valve was deployed within the band using the Commander delivery system under fluoroscopic guidance. The valve achieved stable fixation without embolization, paravalvular leak (PVL), or left ventricular outflow tract (LVOT) obstruction with resolution of MR on echocardiography. The native anterior leaflet and annulus contributed circumferential radial support, and the animal tolerated the procedure without complications. This first-in-animal study demonstrates the technical feasibility and acute safety of TMVR within a mitral annuloplasty band and supports further investigation of percutaneous band modification strategies to optimize ViB outcomes.

Abstract: Introduction: Scimitar syndrome is a rare congenital form of partial anomalous pulmonary venous return characterized by right pulmonary venous drainage into the inferior vena cava. This abnormal shunting leads to right sided volume overload and increased risk of supraventricular arrhythmias, particularly in adolescents and adults. However, existing studies do not clearly describe reported arrhythmia patterns or how heart rhythm changes over time. Objectives: This systematic review aims to describe how congenital cardiopulmonary abnormalities in patients with Scimitar syndrome contribute to atrial remodeling and the development of atrial and supraventricular arrhythmias. Methods A literature review search was conducted in PubMed. Relevant data were extracted after screening titles, 308 abstracts were assessed using inclusion and exclusion criteria. Full text screening was performed for 94 articles, Inclusion criteria consisted of patients with Scimitar syndrome. Exclusion criteria included literature review, animal studies and non-English articles. Results: Studies consistently showed that Scimitar syndrome is associated with right atrial enlargement and atrial remodeling due to chronic right-sided volume overload. These changes were linked to an increased burden of atrial and supraventricular arrhythmias, most commonly atrial fibrillation and atrial flutter. Arrhythmia risk was greater in patients with associated abnormalities such as atrial septal defects or pulmonary hypertension. Discussion and Conclusion: Scimitar syndrome often presents with atrial remodeling and cardiac abnormalities that increase the risk of arrhythmias, especially atrial fibrillation and atrial flutter. Given that scimitar syndrome can remain undiagnosed until adulthood, future studies should focus on the specific predictors for arrhythmia development to improve long-term electrophysiological outcomes.

Abstract: Background: Left ventricular thrombus (LVT) is a serious complication associated with cardiomyopathy and impaired left ventricular (LV) systolic function. Patients with LVT resolution remain at risk for recurrence and subsequent thromboembolism. However, the factors influencing the recurrence of LVT are not yet fully understood. This study aimed to identify the risk factors and clinical outcomes related to LVT recurrence and to improve follow-up strategies and treatment options. Methods and results: We retrospectively investigated patients diagnosed with LVT on transthoracic echocardiography from January 2018 to April 2021 in Zhongshan Hospital Fudan University. All patients received anticoagulant therapy for more than 6 months and underwent at least two follow-up transthoracic echocardiograms. No statistically significant differences were observed in baseline characteristics between the LVT recurrence and non-recurrence group, regarding gender, age, diabetes, hyperlipidemia, renal function, previous stroke history, other underlying medical conditions, ejection fraction, or left ventricular diameter. Patients in the recurrence group exhibited a higher prevalence of previous myocardial infarction and percutaneous coronary intervention compared to the non-recurrence group (84.6% vs 61.1%, p = 0.03; 76.9% vs 52.8%, p = 0.03). Additionally, patients in the recurrence group tended to have more ventricular aneurysms (50.0% vs 22.2%, p = 0.008) and larger previous thrombus sizes (27.7 ± 12.6 vs 21.4 ± 9.1 mm, p = 0.008) compared to those in the non-recurrence group. Multivariate logistic regression analysis indicated that the longitudinal diameter of the LVT was an independent risk factor for LVT recurrence (OR 1.058, 95% CI 1.003-1.115, p = 0.04). ROC curve analysis revealed an area under the curve of 0.647 for the longitudinal diameter of LVT, with an optimal cut-off value of 23.5mm, a sensitivity of 62%, and a specificity of 64%. After a follow-up of 3.0 ± 2.5 years, the incidence of non-fatal myocardial infarction and major adverse cardiovascular events (MACE) in the recurrence group was significantly higher than in the non-recurrence group [non-fatal myocardial infarction: 3 (11.5%) vs 1 (1.4%), p = 0.02; MACE: 7 (26.9%) vs 7 (9.7%), p = 0.01]. No statistically significant differences were found in bleeding events, systemic embolism, or all-cause death between the two groups. Conclusions: Our study indicates that a history of myocardial infarction, the presence of ventricular aneurysm, and larger thrombus diameter are significant factors influencing LVT recurrence. Furthermore, the longitudinal diameter of the thrombus is identified as an independent risk factor for recurrence following resolution. We recommend patients with a LVT diameter greater than 23.5 mm consider extending their anticoagulant therapy to mitigate the risk of recurrence.

Abstract: Background and Objectives: Drug-coated balloon (DCB) angioplasty is a brief-contact endovascular drug-delivery technology in which efficacy must be generated during a single balloon inflation. Unlike drug-eluting stents (DES), DCBs have no permanent scaffold or polymer reservoir; they must preserve coating integrity during delivery, release drug at balloon-vessel contact, transfer drug into the arterial wall, and sustain biologically meaningful mural exposure after device removal. This review examines coronary DCBs as engineered platforms in which drug physicochemistry, excipient function, coating morphology, mechanical stability, balloon-vessel contact, tissue pharmacokinetics, and lesion substrate jointly shape angiographic and imaging response. Materials and Methods: By integrating bench coating-stability studies, computational delivery models, porcine pharmacokinetic and downstream-response studies, intravascular imaging, randomized clinical trials, and meta-analyses, this review proposes a platform-focused mechanistic framework. Results: DCB performance should not be interpreted as a simple drug-class effect. Devices carrying the same antiproliferative agent may differ because of coating cohesion, particle loss, excipient chemistry, adhesion switching, carrier design, dose density, release trigger, and temporary tissue-reservoir formation. Paclitaxel has physicochemical features favorable for brief-contact delivery, whereas limus-based balloons generally require more explicit delivery engineering through crystalline, nanoparticle, phospholipid, porous-infusion, or micro-reservoir architectures. Coating survival during tracking, triggered release, wall apposition, tissue deposition, intramural distribution, retention kinetics, and lesion preparation are treated as upstream determinants of late lumen loss, binary restenosis, late lumen enlargement, remodeling, and repeat revascularization. Conclusions: However, performance remains platform-specific rather than drug-class determined. The aim is not to provide a clinical algorithm, but to clarify how device engineering and lesion context shape the angiographic and imaging phenotype of contemporary coronary DCB therapy.

Abstract: Background/Objectives: The mortality rate for acute high-risk and intermediate-high-risk pulmonary embolism (PE) was high despite treatment with heparin anticoagulation alone. Although adjunctive systemic thrombolysis can reduce mortality by more than 50%, these treatments significantly increase the incidence of major bleeding, particularly intracranial hemorrhage. Ultrasound-facilitated catheter-directed thrombolysis (USCDT) has been shown to reduce the incidence of major bleeding; however, the optimal treatment duration for further reducing mortality and major bleeding remains uncertain. Methods: This retrospective cohort study included 155 hospitalized patients with acute PE who underwent USCDT between January 2017 and June 2025 in the intensive care unit at China Medical University Hospital, Taichung, Taiwan. Patients were categorized into four groups based on average usage time: 12, 24, 36, and 48 hours. The primary endpoints were 30-day all-cause mortality rate and major bleeding. Covariates associated with 30-day all-cause mortality were estimated and adjusted using Cox regression modeling. Results: Across all treatment groups, USCDT significantly reduced pulmonary artery (PA) systolic pressure (26.9%), mean PA pressure (21.0%), fibrinogen levels (25.2%), and right ventricle-to-left ventricle diameter ratio (21.5%) (all p < 0.001). Standard-duration USCDT was associated with a lower odds ratio for 30-day all-cause mortality (OR: 0.35, 95% CI: 0.10–1.21) than extended-duration USCDT. Conclusions: Standard-duration USCDT (12–24 hours) may provide an optimal balance between efficacy and safety by reducing 30-day all-cause mortality and major bleeding in patients with acute PE.

Abstract: Kounis syndrome is an acute coronary syndrome occurring in the context of an allergic, hypersensitivity, or anaphylactic reaction. Its established classification includes coronary vasospasm, coronary atherosclerotic plaque thrombosis, and hypersensitivity-associated coronary stent thrombosis. Coronary artery bypass graft (CABG) involvement has recently emerged as a potential fourth (Type IV) variant but remains poorly characterized, with evidence limited to a few published case reports. We performed a focused literature review to identify all published cases of suspected or confirmed Kounis syndrome involving arterial or venous coronary bypass grafts. The available evidence encompasses anaphylaxis-associated myocardial infarction due to saphenous vein graft thrombosis, hypersensitivity-related thrombosis of a drug-eluting stent implanted within a saphenous vein graft, diffuse vasospasm involving arterial and venous bypass conduits, and probable transient graft vasomotor dysfunction. These observations support recognition of bypass graft spasm and thrombosis as distinct manifestations of allergic coronary disease. Saphenous vein grafts appear particularly vulnerable because accelerated atherosclerosis, endothelial dysfunction, disturbed shear stress, and a highly thrombogenic substrate may amplify the consequences of mast-cell activation. Early recognition requires simultaneous assessment of the allergic reaction, native coronary arteries, and all bypass conduits. Electrocardiography, coronary angiography, serum tryptase, and, when appropriate, intracoronary imaging and thrombus histology may improve diagnostic confidence. This is the first review specifically dedicated to Kounis syndrome involving coronary bypass grafts. Although current evidence remains limited, this review provides a comprehensive synthesis of the available literature and identifies the major diagnostic and therapeutic knowledge gaps that should guide future investigations.

Abstract: Introduction: The number of cancer survivors increases steadily over time because of improved cancer treatment. The number of survivors needing heart transplantation is also rising. This review addresses the post-transplant survival and cancer incidence of patients with a pretransplant malignancy. Methods: A literature search was performed for the last 10 years using the search terms: (heart OR cardiac) AND pretransplant* AND malignancy. Only full articles were included and assessed by the Newcastle-Ottawa Scale of their quality. Results: Nine manuscripts were identified, of which seven were of good quality. Only in four series, patients undergoing heart transplantation were analyzed separately from other solid organ transplants. The outcomes were survival, cancer specific survival, cancer recurrence and skin cancer specifically. Four series were single center based, the other five were region or nationwide surveys. Also, four series included only heart transplant patients. The outcome varied, but most series showed a significant increase in decreased survival and incidence of post-transplant malignancy if a pretransplant malignancy was present. Age, male gender and a fair skin were other risk factors, especially for post-transplant skin cancer. However, for patients with pretransplant malignancy, survival was acceptable. Conclusion: Pretransplant malignancy does not preclude heart transplantation. However, the time interval between pretransplant malignancy and heart transplantation, as well as the nature of malignancy should be considered. The research for the outcome after heart transplantation in these patients has serious limitations.

Abstract: Background: Colchicine has demonstrated anti-inflammatory and cardiovascular benefits in patients with coronary heart disease. However, evidence regarding its effects on postoperative inflammation and early clinical outcomes following coronary artery bypass grafting (CABG) remains limited. Objective: To evaluate the association between perioperative low-dose colchicine use and postoperative clinical outcomes, transfusion requirements, complications, and inflammatory markers in patients undergoing elective on-pump CABG. Methods: This retrospective study included 151 patients who underwent elective on-pump CABG: 81 received colchicine (0.5 mg once daily for 3 days preoperatively and 10 days postoperatively), and 70 did not receive colchicine. The primary clinical outcomes included ICU and total hospital length of stay, erythrocyte and fresh frozen plasma (FFP) transfusion requirements, wound infection, and surgical revision. Postoperative day 5 laboratory parameters included C-reactive protein, white blood cell (WBC) count, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and albumin. Between-group comparisons were performed using Student’s or Welch’s t test and Pearson’s chi-square or Fisher’s exact test, as appropriate. Results: Baseline age and sex distribution were similar between the groups. The colchicine group had a significantly shorter ICU stay than the control group (4.28±1.95 vs 5.83±3.04 days; mean difference, −1.54 days; 95% CI, −2.38 to −0.71; P< 0.001). FFP transfusion requirements were also significantly lower in the colchicine group (3.49±1.24 vs 8.13±3.97 units; mean difference, −4.63 units; 95% CI, −5.62 to −3.65; P< 0.001). Postoperative WBC counts were lower with colchicine (9.44±3.31 vs 10.78±4.04×10⁹/L; P=0.027). Total hospital stay, erythrocyte transfusion requirements, other inflammatory parameters, wound infection rates, and surgical revision rates did not differ significantly between the groups. Conclusion: Perioperative low-dose colchicine use was associated with shorter ICU stays, lower FFP transfusion requirements, and reduced postoperative WBC counts following elective on-pump CABG. Prospective randomized studies are required to confirm these findings and determine whether colchicine improves early postoperative outcomes.

Abstract: Background: Patients with coronary artery disease (CAD) receiving dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) remain at risk of early ad-verse outcomes, including in-hospital mortality. Simple risk stratification based on rou-tinely available variables may help identify higher-risk patients, but a limited number of outcome events constrains robust prediction-model development and validation. Aim: This exploratory study aimed to derive a preliminary, interpretable clinical score based on routinely available variables for risk stratification of all-cause in-hospital mor-tality in CAD patients receiving DAPT after PCI. In the clopidogrel-dominant practice set-ting of the participating centers, the score was conceived as a hypothesis-generating risk-enrichment framework rather than a validated treatment-selection tool or a surrogate measure of platelet reactivity. Methods: We analyzed a retrospective cohort of 1,600 adults with CAD admitted between 2022 and 2024; 36 in-hospital deaths occurred. Twenty demographic, clinical, laboratory, and instrumental variables were evaluated. The primary outcome was all-cause in-hospital mortality during the index hospitalization. For exploratory score derivation, the dataset was randomly divided into a derivation subset (75%; n = 1,200) and a hold-out assessment subset (25%; n = 400). Predictors were explored using univariable and multi-variable logistic regression with stepwise selection. Continuous variables were catego-rized using Weight of Evidence binning, and an integer point score was derived. Perfor-mance was summarized using ROC analysis, AUC, sensitivity, specificity, and accuracy. Given the small number of deaths and the data-driven modelling workflow, all perfor-mance estimates were considered preliminary rather than definitive internal validation. Results: The exploratory six-variable score included age ≥57 years, estimated glomerular filtration rate <45 mL/min/1.73 m², body mass index ≥25 kg/m², troponin I ≥100, prior myocardial infarction, and current smoking. In the derivation subset, each additional point was associated with higher odds of mortality (OR 1.39; 95% CI 1.29-1.51; p < 0.001), and the AUC was 0.654. A Youden-index threshold of approximately 6 points yielded sensitivity of 0.41, specificity of 0.80, and accuracy of 0.72. In the hold-out assessment subset, sensitivity was 0.53, specificity was 0.70, accuracy was 0.70, and AUC was 0.61. These estimates indicate modest discrimination and should be interpreted cautiously be-cause only 36 outcome events were available. Conclusions: This exploratory clinical score showed modest discrimination for all-cause in-hospital mortality and should be regarded as a preliminary, hypothesis-generating risk-stratification approach. It is not sufficiently validated for routine prognostic classifi-cation, platelet-reactivity triage, or antiplatelet treatment selection. Model redevelopment using event-efficient methods, resampling-based internal validation, and subsequent ex-ternal validation are required before clinical implementation.

Abstract: Background and Objectives: Coronary artery calcification impairs delivery and appli-cation of angioplasty equipment and is associated with worse outcomes following per-cutaneous coronary intervention (PCI). Although complex PCIs with the use of calci-um-modification techniques were historically concentrated in centers with on-site cardiac surgery, advances in PCI practice and percutaneous bailout strategies have expanded their use beyond surgical centers. Contemporary data regarding the safety and feasibility of the contemporary calcium-modification armamentarium at centers without on-site cardiac surgery remain limited. We aimed to evaluate the feasibility and safety of cal-cium-modification strategies at a single tertiary center without on-site cardiac surgery. Materials and Methods: In this single-center, retrospective, observational registry, 112 patients (83.0% male; mean age 71.9 ± 10.7 years) with 121 calcified lesions treated be-tween January 2019 and December 2024 were included; follow-up was available for 82 patients (median 34.2 months). The primary outcome was a composite of major adverse cardiac events (MACE: all-cause death, myocardial infarction, stroke, or clinically driven repeat revascularization). Exploratory analyses were performed to assess associations between clinical or procedural characteristics and adverse events. Results: Access was predominantly radial (90.7%). Calcium-modification strategies in-cluded intravascular lithotripsy (25.9%), rotational atherectomy (25.0%), non-compliant balloons (25.0%), cutting/scoring balloons (15.2%), and orbital atherectomy (8.9%). No patient required emergency coronary artery bypass grafting (CABG) or interhospital transfer for surgical management, and all procedural complications were managed percutaneously. MACE occurred in 18.3%, including all-cause mortality in 1.2%, major periprocedural myocardial injury in 2.4%, late myocardial infarction in 3.7%, no strokes, and clinically driven repeat revascularization in 13.4%. Observed event rates were within the range reported by contemporary calcium-modification trials conducted at centres with on-site cardiac surgery. Exploratory analyses were hypothesis-generating only; the as-sociations observed, for example with non-compliant balloon use and known coronary artery disease, are most consistent with confounding by indication rather than causal effects. Conclusions: In this retrospective single-center registry, contemporary calci-um-modification strategies, including atherectomy, intravascular lithotripsy, and spe-cialty balloon techniques, were feasible and safe at a center without on-site cardiac sur-gery. No patient required emergency CABG or surgical transfer, and observed rates of death, myocardial infarction, stroke, and procedural complications were low. These findings suggest that, in experienced hands and with percutaneous bailout capability, on-site cardiac surgery may not be a prerequisite for complex calcium-modification PCI in selected patients. Confirmation in larger, multicenter cohorts is required.

Abstract: Background and Purpose: Abnormality in the motion of the inferior papillary muscle was found, in the past, in Mitral Valve Prolapse (MVP). We visually observed an odd movement not only in the inferior wall but also in the anterolateral and inferolateral basal walls in several MVP patients as well. Therefore, the purpose of this work was to analyze this findings with the help of Strain (Speckle Tracking). Methods: 60 MVP patients, having a superior displacement of the posterior leaflet, the whole or part of, of at least 2 mm, and 20 normal controls were included. Longitudinal Strain was calculated in the 3 apical views (Philips iE 33 Matrix - implemented Strain software). The Strain in the 3 above mentioned basal segments was measured at 160 msec from the beginning of systole (mid-systole) and then averaged to form a “triad” that could be compared among the groups for statistical calculations. The Global Longitudinal Strain (GLS) was calculated for all as well. The Mann-Whitney U-test for comparisons was used. A “p” value ≤ 0.05 was considered significant. Results: According with the Strain patterns, we could identify two Groups of MVP patients: Group 1: having a “paradoxical” Strain at 160 msec (positive, that means “stretching”) in at least one of the three told basal segments (n = 35), and Group 2: not having a “paradoxical” Strain (n = 25) in any of the told three basal segments at the same mid-systolic point. Statistical significance was found between Groups 1 and 2 at 160 msec and at the peak (p < 0.0001 for both) and for GLS (p < 0.01) as well. Group 1 vs controls, of course, displayed significant difference in the Strain at160 msec (p < 0,0001) while Group 2 vs controls did not do and even not at the peak. Conclusions: According with our results, we found that there is a MVP population (more than half in our series) having a “paradoxical” Strain (= stretching) in at least one of the basal inferior-to-lateral segments in mid-systole. The passive continuous stretching of myocardial cells is known to lead, with time, to the replacement with fibrosis (and fibrosis is a condition that is well known to be a source of arrhythmias, and even malignant). Cardiac Magnetic Resonance (CMR) already demonstrated the presence of fibrosis just in the same basal wall segments in some MVP patients. Thus, considering our results in the Strain, in MVP patients with ventricular arrhythmias it is mandatory to analyze the Strain (not expensive tool), and then, if the Strain were to be found to be “paradoxical” even in only one segment of this previously called “triad”, a further evaluation with CMR (even if expensive) is highly recommended to look for the presence of fibrosis. The Strain is highly recommended because the topic is implicated in prognosis, in the further study of arrhythmias, and in the choice of a proper therapy a well.