Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide [...].

The severity of viral myocarditis in humans and mice is variable between individuals. Numerous observations demonstrate the influence of host genetics on disease course, but few genes have actually been identified to have such properties. In past work, mouse strains that are sensitive or resistant to severe disease were used to map the viral myocarditis susceptibility locus Vms1. Here, we demonstrate that Tnni3k, one of the genes within the Vms1 locus, influences the severity of disease following inoculation with coxsackievirus CVB3. Compared to disease-resistant C57BL/6J wild-type mice, strain-matched Tnni3k knockout mice showed higher cardiac inflammation and, in particular, a greater infiltration of macrophages into the heart. Long-term damage associated with viral infection was comparable in mice of both genotypes. Use of a second mouse line engineered with a point mutation to encode a kinase-dead version of Tnni3k showed the same elevated inflammation as the full null. These results identify Tnni3k and its kinase activity as being protective in modulating the acute phase of inflammatory response to CVB3 infection in the heart.

Endothelial dysfunction is a key player in stroke pathophysiology. The Endothelial Activation and Stress Index (EASIX) is a biomarker of endothelial injury validated in hematology, sepsis, and cardiovascular cohorts; however, its prognostic role in stroke remains unclear. This retrospective cohort study aims to provide preliminary evidence on the potential utility of EASIX levels as a biomarker for assessing stroke severity and predicting outcomes. We retrospectively studied 100 patients aged ≥ 18 years admitted with acute ischemic stroke (AIS) or transient ischemic attack (TIA) between January 2020 and July 2024. EASIX was calculated on admission as LDH × creatinine/platelets. Outcomes included in-hospital and 12-month mortality, stroke severity assessed by the NIHSS score, and disability assessed as a modified Rankin score (mRS). Median age was 82 years; 56% were female. The in-hospital and 12-month mortality rates were 47.9% in patients with AIS and 17.2% in patients with TIA, respectively. Overall, EASIX was not associated with NIHSS, mRS, or mortality in the total cohort. Ιn the subgroup of patients with small vessel disease (n = 10), higher EASIX was associated with worse mRS at 12 months (β = 2.383, p = 0.02) and increased mortality (β = 0.653, p = 0.02). EASIX correlated positively with WBC (p < 0.001) and CRP (p = 0.01). Female sex was associated with lower EASIX values. EASIX was not associated with outcomes in the overall AIS/TIA cohort, but it demonstrated potential prognostic relevance in small vessel disease (SVD), which has not been reported previously in the literature. Further prospective research is warranted to validate the potential association between systemic endothelial stress and small vessel disease before the implementation of EASIX as a prognostic tool in patients with stroke due to SVD.

We greatly appreciate the thoughtful and detailed comments provided by Bruno Marino and his colleagues [...].

Neurodegeneration and dementia are key factors in Alzheimer's disease (AD). The deposition of amyloid-ß into senile plaques in the brain parenchyma and in cerebral vessels known as cerebral amyloid angiopathy (CAA) are the main clinical parameters of AD. Acute myocardial infarction (AMI) and AD share a comparable pathophysiology. However, the underlying mechanisms and the consequences of AMI in AD patients are unclear to date. AD transgenic APP23 mice were analyzed in experimental AMI using the closed-chest model. APP23 mice displayed significantly decreased left ventricular function as detected by FS/MPI (fractional shortening/myocardial performance index) after 24 h and 3 weeks after ligation of the LAD compared to WT controls. No differences have been observed in infarct and scar size. The analysis of cardiac remodeling after 3 weeks showed an altered composition of the collagen tissue of the scar with elevated tight but reduced fine collagen in APP23 mice. Altered scar formation was accompanied by elevated degranulation of platelets following activation of the collagen receptor GPVI. These results suggest that AD patients are at higher risk for cardiac damage after AMI. This implies the need for a personalized therapy of AMI in AD patients.

The pharmacologic management of patent ductus arteriosus (PDA) presents a challenge to clinicians due to the interindividual variability in drug response to available medications. There is evidence that CYP2C9 is associated with the response to PDA treatment; however, no data from the Middle East is available. This study aimed to investigate the association between CYP2C8 and CYP2C9 genetic polymorphisms and response to ibuprofen or indomethacin in neonates with PDA. We conducted a retrospective cohort study of neonates with a gestational age < 32 weeks and birthweight < 1500 g with PDA between 2019 and 2023. Eligible neonates were those diagnosed with PDA and treated with at least one course of ibuprofen or indomethacin. Genotyping was performed to identify four single-nucleotide polymorphisms (SNPs), namely CYP2C8*3 rs10509681, CYP2C9*2 rs1799853, CYP2C9 rs2153628, and CYP2C9*3 rs1057910. Allele frequencies were compared between responders and non-responders, and non-genetic predictors were assessed using logistic regression. A total of 146 infants were identified. Of these, 86 were enrolled. Genetic analysis showed that the heterozygote genotype (TC) for the CYP2C8 gene was the most common (45%), while wild-type alleles were predominant for CYP2C9 variants. No significant differences in allele frequencies were found between responders and non-responders to the treatment (p > 0.05). In a secondary analysis, the need for multiple surfactant doses independently predicted poor response (aOR 0.244, 95% CI 0.086–0.693, p = 0.008), while extremely low birth weight showed a borderline association (aOR 0.281, 95% CI 0.062–1.268, p = 0.099). Carriers of CYP2C8*3 rs10509681, CYP2C9*2 rs1799853, CYP2C9 rs2153628, and CYP2C9*3 rs1057910 were not associated with variations in response to NSAIDs.

We appreciate the careful and critical reading of our work by Eltawil et al [...].

Stage B heart failure (SBHF) increases the risk of symptomatic HF. Current guideline criteria for SBHF lack sex and ethnic thresholding and cardiac magnetic resonance (CMR) imaging cut-offs. We aimed to assess the prevalence of SBHF in a large cohort of people with type 2 diabetes (T2D) and healthy controls and propose a refined CMR definition for SBHF. Sex- and ethnic-specific thresholds for imaging criteria were derived from 373 healthy controls, who underwent CMR cine imaging. The current definition for SBHF and refined criteria was applied to our prospectively recruited and intensively phenotyped cohort of asymptomatic people with T2D and no evidence of cardiovascular disease. The prevalence of SBHF by different definitions was calculated and patient characteristics, including exercise capacity, were compared between those classified as Stage A vs. B HF. Finally, the refined criteria were also applied to the following two historical cohorts with symptomatic cardiovascular disease: severe aortic stenosis (AS n = 70) and HF with preserved ejection fraction (HFpEF n = 136). A total of 423 people with T2D and a subset of 102 healthy controls who underwent echocardiography were prospectively recruited. Current guideline criteria classified 91% of those with T2D and 69% of the healthy controls as SBHF, suggesting a lack of specificity. Applying derived sex- and ethnicity-specific thresholds, combining echo and CMR measures, the prevalence of SBHF was reduced to 30% in those with T2D. Using the refined definition, those with Stage B HF had lower exercise capacity than those with Stage A HF (percentage predicted maximal oxygen consumption 81 ± 16% vs. 91 ± 20%, p < 0.001). Applying the refined definition to symptomatic AS and HFpEF participants classified 89% and 85% with abnormal cardiac remodelling. Current guideline criteria for SBHF are non-specific and likely of limited value in clinical practice. Refining these criteria with sex- and ethnic-specific thresholds may improve identification of those at risk of developing symptomatic disease. Further research is required to validate these criteria.

Intravascular imaging (IVI) was introduced 35 years ago to assess coronary artery pathology and plaque vulnerability. However, from its first applications it became apparent that it can also be useful in percutaneous coronary intervention (PCI) planning and optimizing PCI results. In the early days of PCI, IVI was used to examine the efficacy of emerging endovascular devices and the vessel wall response to therapy, while in the drug-eluting stent (DES) era, IVI was used to guide DES implantation and assess final results post-intervention. The first studies assessing the role of IVI in guiding PCI with DES have failed to demonstrate a prognostic benefit for the use of IVI; however, more recent large-scale randomized trials have underscored its value in this setting. IVI, with its high resolution, allows optimal stent sizing, prompt identification and correction of common causes of stent failure, and it has been shown that it improves outcomes in complex procedures. This review summarizes the evidence supporting the role of IVI in PCI planning in DES era, synopsizes the studies that have highlighted the value of IVI in predicting stent failure, discusses the limitations of the first randomized trials that failed to demonstrate a prognostic benefit from its use, and presents the results of the more recent large-scale outcome studies that underscored its role in complex PCI planning.

Background: Coronary artery bypass grafting (CABG) is a well-established revascularization strategy for patients with multivessel coronary artery disease. The effectiveness of CABG is significantly influenced by antiplatelet therapy aimed at maintaining graft patency and reducing thrombotic complications. However, substantial inter-individual variability exists in platelet function responses to standard therapies such as aspirin and clopidogrel, leading to antiplatelet resistance. This variability has been linked to increased risks of myocardial infarction, stroke, and early graft failure. Platelet function testing (PFT) offers a potential strategy to identify resistance and guide more personalized antiplatelet therapy. This study aims to evaluate the association between perioperative platelet function test results and clinical outcomes following CABG. By assessing platelet responsiveness at multiple timepoints and correlating findings with postoperative events, the study seeks to determine whether PFT can stratify risk and improve patient management. Methods: This is a prospective, single-centre, observational cohort study conducted at a tertiary NHS cardiac surgery centre. Patients having elective or urgent isolated CABG will be enrolled and undergo perioperative PFT using the TEG6s system. Clinical outcomes will be monitored for 12 months postoperatively, with primary endpoints assessing the correlation between platelet function results and major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints will include the prevalence of antiplatelet resistance, demographic predictors, and the feasibility of integrating PFT into clinical workflows. Results: This study will report the prevalence of aspirin and clopidogrel resistance in CABG patients based on TEG6s PFT, as well as the correlation between platelet function results and MACCE, postoperative bleeding, and the need for surgical re-exploration. Additionally, it will examine the associations between demographic and clinical factors—such as diabetes status, renal function, BMI, and surgical technique—and variability in platelet responsiveness. The feasibility of incorporating PFT into perioperative workflows will also be evaluated, assessing whether results could support personalized antiplatelet management in future clinical trials. Conclusions: Findings from this study will provide real-world evidence regarding platelet function variability in CABG patients and suggest that PFT may identify those at increased risk of thrombotic complications. This exploratory analysis supports the need for larger interventional trials aimed at optimizing individualized postoperative antiplatelet therapy to improve surgical outcomes.