Although cardiac metabolic adaptation has been observed in response to the ischemia-reperfusion, the specific temporal and spatial changes occurring in the main regulators of myocardial glucolipid metabolism in the infarcted heart have not been fully characterized. Myocardial infarction (MI) was induced in female swine by transient coronary occlusion. The study design consisted of one control and four MI groups (no reperfusion, 1 min, 1 week, and 1 month after reperfusion). Metabolites obtained from the coronary sinus were determined at baseline, during ischemia, and after coronary reperfusion. mRNA expression of genes related to beta-oxidation and glucose transport were quantified in the five experimental groups and in three myocardial regions (infarcted, adjacent, and remote). In the coronary sinus, reduced glucose and increased lactate levels were detected during ischemia and soon after reperfusion. However, non-esterified fatty acids increased during reperfusion. A general upregulation of genes implicated in glycolysis and beta-oxidation occurred during ischemia and few minutes after reperfusion. Contrarily, heightened mRNA expression of glucose transporters and decay in regulators of beta-oxidation were observed one week after coronary reperfusion. Glycolysis and beta-oxidation are activated during ischemia and few minutes after coronary reopening, while a shift from beta-oxidation to glycolysis is evidenced a few days afterwards.

IntroductionType 2 diabetes mellitus is associated with chronic inflammation and systemic complications, including ophthalmologic manifestations. While blood cytokines serve as inflammatory biomarkers, their expression in tears and correlation with systemic inflammation remain unclear. This study compared cytokine profiles in plasma and tears of well-controlled type 2 diabetes patients and controls, assessing their correlation and potential as biomarkers for disease monitoring.Materials and methodsThis cross-sectional study included 81 participants [40 with type 2 diabetes without retinopathy (T2DM group) and 41 controls (control group)] from primary care centers. Plasma and tear samples were analyzed using a multiplex immunoassay for 27 cytokines. Data were analyzed using ANCOVA (adjusted for age, hypertension, and dyslipidemia), and correlation analyses.ResultsPatients in the T2DM group exhibited distinct inflammatory profiles. Plasma levels of IL-2 (P < 0.05), IL-7 (P < 0.05), IL-9 (P = 0.001), and CCL4 (P < 0.01) were significantly lower, while tear levels of IL-6 (P < 0.01), CXCL8 (P = 0.001), IL-15 (P < 0.05), CCL5 (P < 0.001), and VEGF (P < 0.01) were elevated compared to controls. No significant correlations were observed between plasma and tear cytokines, suggesting independent regulation of systemic and ophthalmologic inflammation. Tear cytokines exhibited stronger intra-fluid correlations than plasma (98.4% vs. 66.5%), with minimal plasma-tear correlations (3.6%). Age influenced most tear cytokines (24/27 analytes) but had a weaker effect on plasma cytokines.ConclusionDespite glycemic control, patients with type 2 diabetes exhibited increased tear cytokines in the absence of diagnosed retinopathy, contrasting with reduced plasma cytokines. The lack of correlations suggests localized ophthalmologic inflammation independent of systemic inflammation, highlighting a persistent risk of retinal vascular damage in type 2 diabetes.

AIMS:The impact of sex on adverse left ventricular remodelling (LVR) after ST-elevation myocardial infarction (STEMI) is unclear due to conflicting results. This study sought to establish sex-based differences in adverse LVR using cardiovascular magnetic resonance (CMR) among STEMI patients and their impact on clinical outcomes. METHODS AND RESULTS:The study included patients with a first STEMI who underwent primary percutaneous coronary intervention (PCI). Cardiovascular magnetic resonance was performed at 6 days (interquartile range [IQR]: 4-9 days) and after 6 months (6.42 months; IQR: 5.98-7.47 months). Follow-up was 6.94 years (IQR: 4.48-9.32 years). The primary endpoint was the presence of adverse LVR (>15% of LV end-diastolic volume and a decrease of >3% in LV ejection fraction) at 6 months. The secondary endpoint was major adverse cardiac events (MACEs), defined as a combined variable: cardiovascular death, heart failure admission, or ventricular arrhythmias. One thousand sixty-seven patients were included (17.5% women; mean age: 58.71 ± 11.85 years). Women were older and had more cardiovascular risk factors (CVRF). There was no association between sex and adverse LVR [OR: 0.80; 95% confidence interval (CI), 0.39-1.64; P = 0.536]. Major adverse cardiac events occurred in 177 patients (16.7%) and was more frequent in women (22.6% vs. 15.4%; P = 0.017). However, after adjusting for baseline differences and CVRF, the female sex was not associated with MACE (hazard ratio: 1.21; 95% CI, 0.81-1.81; P = 0.343). CONCLUSION:The higher rate of MACE after STEMI in women compared to men appears to be associated with a higher prevalence of CVRF and comorbidities rather than a more significant occurrence of adverse LVR.

Anxiety and depression are common after a myocardial infarction (MI), so psychological and psychiatric mental health (MH) interventions are recommended during Cardiac Rehabilitation Programs (CRP). We aim to evaluate anxiety and depression symptoms and quality of life in MI sufferers followed in a CRP without dedicated MH resources. We prospectively included 164 MI patients in our CRP without dedicated MH resources. Patient Health Questionnaire 2-item (PHQ-2) and Generalized Anxiety Disorder 2-item (GAD-2) questionnaires for depression and anxiety screening (altered if ≥3 points) and the 36-Item Short Form Survey Instrument (SF-36) to analyze four MH components and Mental Component Summary (MCS) were assessed at the beginning and after CRP. The mean age was 61.35 ± 10.76 years, and most patients were male (86.6%). A significant improvement in SF-36 mental components (from +5.94 ± 27.98 to +8.31 ± 25 points, p < 0.001) and SF-36-MCS (+1.85 ± 10.23 points, p = 0.02) was noted, as well as a reduction in depression and anxiety symptoms in PHQ-2 and GAD-2 (p < 0.001). However, 33 (20.1%) patients showed a positive screening for depression and/or anxiety at the end of the program. These patients were younger (56.6 ± 8.05 vs. 62.55 ± 11.05 years, p = 0.004) and showed significantly worse initial scores of SF-36 mental components, PHQ-2, and GAD-2 (p < 0.001). We conclude that a Phase 2 CRP without dedicated MH resources can achieve significant improvements in MH well-being after MI. However, one-fifth of the population had substantial depression and/or anxiety symptoms at the end of the program. This subset, characterized by worse initial MH scores, may benefit from specific MH interventions during CRP.

Familial hypercholesterolemia (FH) is relatively prevalent in myocardial infarction (MI) sufferers, and its diagnosis could improve preventive treatment in family members. We aim to analyze the diagnosis of FH and the rate of genetic testing in a prospective cohort of 245 patients submitted to our Cardiac Rehabilitation Program (CRP) after MI. Baseline characteristics were registered, and basal low-density lipoprotein cholesterol (LDL-C) was calculated after correction for lipid-lowering therapies (LLT) before or during admission. Simplified Dutch Lipid Clinic Network Scores (sDLCNS) were retrospectively calculated based on personal and familial history of premature cardiovascular disease and basal LDL-C levels. Mean age was 62.19 ± 13.93 years, and most patients were male (81.6%). Mean LDL-C before admission and basal LDL-C corrected for LLT were 131.79 ± 45.34 mg/dL and 162.87 ± 44.17 mg/dL, respectively. Patients in the cohort were retrospectively categorized in the “unlikely” (<3 points; n = 162, 66.1%), “possible” (3–5 points; n = 72, 29.4%) and “probable” (6–8 points; n = 11, 4.5%) sDLCNS categories. Genetic testing for FH was requested in four (1.6%) patients, and no clinically significant genetic variants were detected. Patients who underwent genetic testing depicted significantly higher basal LDL-C (233 ± 49.09 vs. 161.71 ± 43.25 mg/dL, p = 0.001). However, the rate of individuals undergoing genetic testing was negligible even in the “possible” (n = 2, 2.8%) and “probable” (n = 1, 9.1%) sDLCNS categories. In conclusion, genetic testing for FH in our CRP after MI is largely underutilized, even in patients with a “possible” or “probable” diagnosis based on sDLCNS criteria, which represent about a third of the cohort. Strategies to improve screening for FH should be prospectively implemented.

Background: Exercise-based cardiac rehabilitation programs (CRP) are recommended for patients following acute coronary syndrome to potentially improve high-density lipoprotein cholesterol (HDL-C) levels and prognosis. However, not all patients reach target HDL-C levels. Here we analyze the dynamics and predictors of HDL-C increase during CRP in patients following ST-segment elevation myocardial infarction or occlusion myocardial infarction. Methods: We conducted a prospective study of myocardial infarction patients who completed exercise-based Phase 2 CRP. Data was collected on clinical variables, cardiovascular risk factors, treatment goals, pharmacological therapy, and health outcomes through questionnaires at the beginning and at the end of Phase 2 CRP. Lipid profile analysis was performed before discharge, 4 to 6 weeks after discharge, and at the end of Phase 2 CRP. Changes in lipid profiles were evaluated, and predictors of failure to increase HDL-C levels were identified by binary logistic regression analysis. Results: Our cohort comprised 121 patients (mean age 61.67 ± 10.97 years, 86.8% male, and 47.9% smokers before admission). A significant decrease in total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) were noted, along with an increase in HDL-C (43.87 ± 9.18 vs. 39.8 ± 10.03 mg/dL, p < 0.001). Patients achieving normal HDL-C levels (>40 mg/dL in men and >50 mg/dL in women) significantly increased from 34.7% at admission to 52.9% the end of Phase 2. Multivariable analysis revealed smoking history (hazard ratio [HR] = 0.35, 95% confidence interval [CI], 0.11–0.96, p = 0.04), increased reduction in total cholesterol (HR = 0.94, 95% CI, 0.89–0.98, p = 0.004), and increased reduction in LDL-C (HR = 0.94, 95% CI, 0.89–0.99, p = 0.01) were inversely associated with failure to increase HDL-C levels. Conversely, higher HDL-C before CRP (HR = 1.15, 95% CI, 1.07–1.23, p < 0.001) and increased lipoprotein (a) (HR = 1.01, 95% CI, 1–1.02, p = 0.04) predicted failure to increase HDL-C levels. No significant correlations were found with Mediterranean diet adherence, weekly physical activity, training modalities, or physical fitness parameters. Conclusions: Participation in an exercise-based Phase 2 CRP led to mild but significant increases in HDL-C. Smoking history and patients experiencing substantial reductions in total cholesterol and LDL-C were more likely to experience HDL-C increases, unlike those with higher HDL-C and lipoprotein (a) levels before CRP.

Background: A significant proportion of post-myocardial infarction (MI) patients do not reach target low-density lipoprotein cholesterol (LDL-C) levels. Suboptimal LDL-C reduction is often attributed to poor adherence to pharmacological therapy and lifestyle recommendations. Methods: In a prospective registry of 179 post-MI patients who completed a Phase 2 Cardiac Rehabilitation Program (CRP), we evaluated the characteristics and predictors of suboptimal LDL-C reduction. Key indicators were assessed before and after CRP: adherence to the Mediterranean diet (using the PREDIMED questionnaire), weekly physical activity (via the IPAQ questionnaire), therapeutic adherence (using the Morisky-Green questionnaire), and peak oxygen consumption (VO2) on exercise testing. Lipid-lowering therapy (LLT) and LDL-C were recorded prior to MI and both before and after Phase 2 CRP. At the end of Phase 2, we analyzed the difference between measured and theoretical LDL-C (basal LDL-C minus expected LDL-C reduction by LLT), which was defined as "residual difference in LDL-C" (RD-LDL-C). We analyzed the predictors of positive RD-LDL-C (lower than theoretically expected). Results: After CRP, 54 (30.2%) patients exhibited positive RD-LDL-C. Within this subgroup, LLT was uptitrated, and patients received more potent LLT at the conclusion of CRP (theoretical potency: 69.81 ± 7.07 vs. 66.41 ± 7.48%, p = 0.005). However, they were less likely to reach the target LDL-C level <55 mg/dL (66.7% vs. 93.6%, p < 0.001). Male sex (HR 17.96 [2.15, 149.92], p = 0.008) and higher lipoprotein (a) levels (HR 1.02 [1.01, 1.03] per mg/dL, p = 0.001) were associated with a positive RD-LDL-C. Conversely, diabetes mellitus (HR 0.17 [0.06, 0.51], p = 0.002), higher corrected basal LDL-C levels (HR 0.98 [0.97, 0.99] per mg/dL, p = 0.001), and supervised in-hospital training during CRP (HR 0.28 [0.09, 0.86], p = 0.03) were associated with a reduced probability of positive RD-LDL-C. No association was found with adherence to the Mediterranean diet (88.1%), therapeutic adherence (89.1%), reported weekly physical activity (median 3545 [1980, 6132] metabolic equivalents per week), or change in peak VO2. Conclusions: More than one-third of post-MI patients demonstrated lower than expected LDL-C reduction (positive RD-LDL-C) following CRP, a finding that could not be attributed to poor adherence to pharmacological therapy or lifestyle recommendations. These findings suggest that a personalized approach to prescribing and uptitrating LLT may help achieve LDL-C targets, particularly in MI patients with healthy lifestyle habits who exhibit a lower response to LLT.

Introduction: To evaluate [18F]Fluodeoxyglucose ([18F]FDG) distribution in a murine model of myocardial infarction (MI), using Positron Emission Tomography and Computed Tomography (PET/CT) to validate this approach for use in evaluating new therapies for MI treatment. Method: MI was induced by permanent ligation of the left anterior descending coronary artery. The study included a sham group, a group with 7 days infarction (acute infarction) and another with 21 days infarction (chronic infarction). Prior to euthanasia, each group was imaged by PET/CT approximately 60 minutes after injection of [18F]FDG. Total and maximal Region of Interest and Standard Uptake Value values were obtained using CT, which enables more precise delineation of the anatomy to assess between-group differences in [18F]FDG uptake in the heart, brain and bladder. Results: Following distribution of [18F]FDG throughout the body, at 60 minutes after injection homogeneous cardiac distribution of the radiopharmaceutical was observed in the healthy group, while in the infarcted groups there was an absence of uptake in the infarct area. Using ANOVA analysis and the Kruskal-Wallis test, statistically significant differences were detected between the healthy and acute infarction groups and the acute and chronic infarction groups. There were no significant differences between the three groups in brain uptake or radiopharmaceutical clearance. Conclusions: The microPET/CT technique has the sensitivity to detect infarcted areas in the murine model. Moreover, it allows us to quantify [18F]FDG uptake and thus assess uptake by the organs in the different groups studied.

We present the case of a 21-year-old male with chest pain, malaise, and fever, who was initially diagnosed with suspected acute myocarditis. The patient exhibited elevated cardiac troponin levels, occasional premature ventricular complexes, and right ventricular dilation, raising concerns about arrhythmogenic cardiomyopathy. Cardiac magnetic resonance (CMR) imaging showed myocardial edema and subepicardial enhancement in the basal anterolateral segment, confirming myocarditis, but also revealed severe dilation of the right chambers. Advanced imaging sequences identified a previously unrecognized inferior sinus venosus atrial septal defect (SVASD) with partial anomalous pulmonary venous return. This finding led to a significant left-to-right shunt and surgical correction was performed. SVASD, a rare congenital anomaly, often remains undiagnosed due to its subtle clinical presentation and limitations of standard imaging techniques. This case highlights the importance of tailored CMR acquisition protocols, which revealed a congenital heart defect in our patient despite an initial focus on myocarditis. The adjustment in diagnostic approach significantly altered the patient's management and may have improved his long-term prognosis.

Introduction and objectives: In patients with established chronic coronary syndrome (CCS), the significance of persistent angina is controversial. We aimed to evaluate the prognostic role of persistent angina in symptomatic CCS patients with abnormal stress cardiovascular magnetic resonance (CMR) and altered angiographic findings undergoing percutaneous revascularization. Methods: We analyzed 334 CCS patients with Canadian Cardiovascular Society angina class > 2, perfusion deficits on stress CMR and severe lesions in angiography who underwent medical therapy optimization plus CMR-guided percutaneous revascularization. We investigated the association of persistent angina at 6 months postintervention with subsequent cardiac death, myocardial infarction, and hospital admission. Results: All patients had angina class > 2 (mean: 2.8 f 0.7), abnormal stress CMR (mean ischemic burden: 5.8 f 2.7 segments), and severe angiographic lesions. The angina resolution rates were 81% at 6 months, and 81%, 81%, and 77% at 1, 2, and 5 years, respectively. During a median follow-up of 8.9 years, persistent angina was independently associated with higher rates of subsequent cardiac death (13% vs 4%; HR, 3.7; 95%CI, 1.59.2; P = .005), myocardial infarction (24% vs 6%; HR, 4.9; 95%CI, 2.4-9.9; P < .001), and hospital admission for heart failure (27% vs 13%; HR, 2.7; 95%CI, 1.5-5.2; P = .001). Conclusions: In CCS patients with robust diagnostic evidence from symptoms, stress CMR, and angiography, persistent angina after percutaneous revascularization is a strong predictor of subsequent cardiac death, myocardial infarction, and hospital admission for heart failure.

Aims:Recently, novel post-processing tools have become available that measure intraventricular pressure gradients (IVPGs) on routinely obtained long-axis cine cardiac magnetic resonance (CMR) images. IVPGs provide a comprehensive overview of both systolic and diastolic left ventricular (LV) functions. Whether IVPGs are associated with clinical outcome after ST-elevation myocardial infarction (STEMI) is currently unknown. Here, we investigated the association between CMR-derived LV-IVPGs and major adverse cardiovascular events (MACE) in a large reperfused STEMI cohort with long-term outcome. Methods and results:In this prospectively enrolled multi-centre cohort study, 307 patients underwent CMR within 14 days after the first STEMI. LV-IVPGs (from apex-to-base) were estimated on the long-axis cine images. During a median follow-up of 9.7 (5.9-12.5) years, MACE (i.e. composite of cardiovascular death and de novo heart failure hospitalisation) occurred in 49 patients (16.0%). These patients had larger infarcts, more often microvascular injury, and impaired LV-IVPGs. In univariable Cox regression, overall LV-IVPG was significantly associated with MACE and remained significantly associated after adjustment for common clinical risk factors (hazard ratio (HR) 0.873, 95% confidence interval (CI) 0.794-0.961, P = 0.005) and myocardial injury parameters (HR 0.906, 95% CI 0.825-0.995, P = 0.038). However, adjusted for LV ejection fraction and LV global longitudinal strain (GLS), overall LV-IVPG does not provide additional prognostic information (HR 0.959, 95% CI 0.866-1.063, P = 0.426). Conclusion:Early after STEMI, CMR-derived LV-IVPGs are univariably associated with MACE and this association remains significant after adjustment for common clinical risk factors and measures of infarct severity. However, LV-IVPGs do not add prognostic value to LV ejection fraction and LV GLS.

Following myocardial infarction (MI), adverse remodeling depends on the proper formation of fibrotic scars, composed of type I and III collagen. Our objective was to pinpoint the participation of previously unreported collagens in post-infarction cardiac fibrosis. Gene (qRT-PCR) and protein (immunohistochemistry followed by morphometric analysis) expression of fibrillar (types II and XI) and non-fibrillar (types VIII and XII) collagens were determined in RNA-sequencing data from 92 mice undergoing myocardial ischemia; mice submitted to permanent (non-reperfused MI, n = 8) or transient (reperfused MI, n = 8) coronary occlusion; and eight autopsies from chronic MI patients. In the RNA-sequencing analysis of mice undergoing myocardial ischemia, increased transcriptomic expression of collagen types II, VIII, XI, and XII was reported within the first week, a tendency that persisted 21 days afterwards. In reperfused and non-reperfused experimental MI models, their gene expression was heightened 21 days post-MI induction and positively correlated with infarct size. In chronic MI patients, immunohistochemistry analysis demonstrated their presence in fibrotic scars. Functional analysis indicated that these subunits probably confer tensile strength and ensure the cohesion of interstitial components. Our data reveal that novel collagens are present in the infarcted myocardium. These data could lay the groundwork for unraveling post-MI fibrotic scar composition, which could ultimately influence patient survivorship.

BACKGROUND:Left ventricular thrombus (LVTh) is a severe complication after ST-segment elevation myocardial infarction (STEMI). OBJECTIVES:We aim to predict LVTh occurrence by cardiac magnetic resonance (CMR) using clinical, echocardiographic, and electrocardiographic (ECG) variables readily available at admission. METHODS:We included 590 reperfused STEMI patients who underwent early (1-week) and/or late (6-month) CMR in our institution. Baseline clinical, echocardiographic (left ventricular ejection fraction -LVEF-) and ECG data (summatory of ST-segment elevation -sum-STE- and Q-wave and residual ST-elevation >1 mm -Q-STE-) during admission were registered. Multivariate binary logistic regression models and receiver operating characteristic curves were computed for LVTh prediction. RESULTS:LVTh was detected by CMR in 43 (7.3 %) patients and was predicted by previous chronic coronary syndrome (CCS, HR 4.74 [1.82-12.35], p = 0.001), anterior STEMI (HR 10.93 [2.47-48.31], p = 0.002), LVEF (HR 0.96 [0.93-0.99] per %, p = 0.008), maximum sum-STE (HR 1.04 [1.01-1.07] per mm, p = 0.04), and Q-STE (HR 1.31 [1.08-1.6] per lead, p = 0.008). High-risk patients with both major (anterior STEMI and Q-STE in ≥1 leads) and 1-3 minor (CCS, maximum sum-STE >10 mm, LVEF <50%) factors showed the highest LVTh risk (19.6 % within 6 months). The model showed excellent discrimination ability (area under the curve=0.85 [0.81-0.9], p < 0.001). Simplified 4-variable (excluding sum-STE) and 3-variable (also excluding CCS) risk scores showed similar discrimination ability and were externally validated. CONCLUSIONS:LVTh within 6 months post-STEMI can be predicted using pre-discharge clinical (anterior infarction and CCS), echocardiographic (LVEF), and ECG (sum-STE and Q-STE) data. Our results can help select patients who should undergo CMR after STEMI for LVTh detection.

Background/Objectives: Coronary artery disease (CAD) and type-2 diabetes mellitus (T2DM) are characterized by chronic low-grade inflammation. However, measuring cytokines typically involves invasive blood sampling, which can be problematic for CAD patients. This study aimed to assess ophthalmological parameters and tear cytokines in patients with CAD, comparing those with comorbid T2DM to those without to understand their inflammatory profiles. Methods: One hundred subjects with suspected chronic or acute CAD were initially included in this single-center cross-sectional study after clinical stabilization. Seventy-two patients with confirmed CAD were divided into two groups: 32 patients with T2DM and 40 patients without T2DM. A total of 144 eyes were examined, and tear fluid samples were collected to determine cytokine concentrations. Ophthalmological parameters and tear concentrations of cytokines were analyzed, controlling for age, sex, and other cardiovascular risk factors. Results: Patients with CAD and T2DM exhibited decreased ophthalmological parameters and increased cytokine concentrations in comparison to those without T2DM. Significant inverse correlations between ophthalmological parameters and cytokine concentrations were observed. Following adjustment, a full logistic regression model for distinguishing patients with CAD and comorbid T2DM included macular cube volume, mean macular thickness, interleukin (IL)-4, IL-5, IL-6, IL-8, IL-9, IL-13, granulocyte colony-stimulating factor (G-CSF), CCL3, CCL4, and CCL11/eotaxin-1, demonstrating excellent discriminatory power (Area Under the Curve = 0.95, 95% Confidence Interval = 0.91–0.99; p < 0.001). Subsequently, IL-5 (Odds Ratio = 1.68, 95% CI = 1.26–2.24; p < 0.001), G-CSF (OR = 1.06, 95% CI = 1.02–1.11; p < 0.01), and CCL11/eotaxin-1 (OR = 1.56, 95% CI = 1.19–2.05; p = 0.001) emerged as the most distinguishing variables in a reduced model (AUC = 0.89, 95% CI = 0.84–0.95; p < 0.001). Conclusions: Differences in ophthalmological variables, mainly in cytokine concentrations, suggest distinct pathophysiological mechanisms in patients with CAD based on the presence of T2DM. These findings demonstrate that the inflammatory profile can be readily detected through tear sample cytokines, proving valuable for establishing more accurate prognoses and monitoring in cardiometabolic disorders.