Background/Objectives: Early circulating biomarkers capable of identifying patients at risk for impaired recovery of left ventricular (LV) systolic function after ST-segment elevation myocardial infarction (STEMI) remain limited. This exploratory study aims to determine whether serum follistatin measured within the first 24 h after coronary revascularization is associated with long-term LV systolic function, as assessed by cardiac magnetic resonance (CMR). Methods: In this prospective study, 31 patients with reperfused STEMI underwent serial CMR at 1 week and 6 months. Follistatin levels were measured within 24 h after revascularization. Associations between follistatin and CMR-derived LV systolic function were assessed using univariate and multivariable linear regression analyses. Results: Patients were stratified by median follistatin level (438 pg/mL) into below median (n = 15) and above median (n = 16). At 1 week, CMR-derived LV function, volumes, and structural indices were similar between groups. By 6 months, however, patients with follistatin above the median had higher LV ejection fraction (LVEF) [62 ± 9% vs. 54 ± 9%; p-value = 0.018] and lower LV end-systolic volume index (28 ± 12 vs. 41 ± 18 mL/m2; p-value = 0.037). In univariate analysis, follistatin was associated with 6-month LVEF (β = 0.027 per pg/mL; p-value = 0.004). After multivariable adjustment, follistatin remained independently associated with 6-month LVEF (β = 0.024 per pg/mL; p-value < 0.001) and with relative improvement in LVEF from 1 week to 6 months (β = 0.044 per pg/mL; p-value < 0.001). Conclusions: In reperfused STEMI patients, higher early follistatin levels were independently associated with more favorable LV systolic function at 6 months. These hypothesis-generating findings suggest that follistatin may represent a potential biomarker of subsequent systolic recovery after STEMI, warranting further validation in larger prospective studies.

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.

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.

Background/Objectives: Unlike post-mortem histopathology, cardiovascular magnetic resonance (CMR) and positron emission tomography (PET) enable longitudinal assessment of structural, functional, and metabolic alterations in preclinical myocardial infarction models. This study aims to describe the temporal evolution of infarct size and systolic function by CMR and glucose consumption via PET, explore their differences in non-reperfused and reperfusion infarction models, and assess their capacity to predict histology-derived infarct size and systolic function at chronic phase CMR. Methods: Two murine models of myocardial infarction were generated using permanent (non-reperfused, n = 8) or transient (reperfused, n = 9) coronary occlusion. CMR and fluorine-18 2-fluoro-2-deoxyglucose PET imaging were performed at baseline and at 1, 7, and 21 days post-infarction to quantify infarct size, systolic function, and myocardial glucose metabolism. Infarct size was also assessed using Masson’s trichrome staining. Results: At 24 h post-infarction, CMR-derived infarction together with significant reduction in systolic function and glucose metabolism were already noted in both models. At 21-day CMR, however, reperfused mice showed lower infarct size and more preserved systolic function compared to their non-reperfused counterparts, while no differences in glucose metabolism were reported. Infarct size and systolic function at 1-day CMR and the number of segments with reduced glucose consumption at 1-day PET independently predicted histology-derived infarct size and long-term systolic function. Conclusions: Combined PET/CMR imaging enables non-invasive, sequential evaluation of infarct size, systolic function, and glucose metabolism in experimental myocardial infarction. This multimodality approach is well suited for assessing the efficacy of emerging therapies in preclinical research.

Introduction and objectives The use of N-terminal pro-brain natriuretic peptide (NT-proBNP) after ST-segment elevation acute myocardial infarction (STEMI) is unclear. We evaluated its prognostic significance after post-STEMI cardiac rehabilitation. Methods The prognostic significance of NT-proBNP was tested upon completion of cardiac rehabilitation (median, 45 days post-STEMI) in an exploratory group (n = 105 patients with the researchers blinded to NT-proBNP values) and validated in the following 276 patients. Baseline and cardiac imaging variables including cardiovascular magnetic resonance (CMR) parameters were recorded. The primary endpoint was the occurrence of a first major adverse cardiac event (MACE: cardiac death, myocardial infarction, or re-admission for heart failure). Results In the exploratory group, a cut-off value of NT-proBNP >400 pg/mL emerged as a potent MACE predictor (37 % vs.17 %; hazard ratio [HR]: 6.8 [1.5-30.3], p = 0.01). In the study group, during a 203-week median follow-up, 88 (32 %) first MACEs were detected. NT-proBNP >400 pg/mL (n = 168, 61 %) associated with a higher MACE rate (46 % vs. 10 %, HR: 4.6 [2.3-8.9], p < 0.001) and, separately, with more cardiac deaths, myocardial infarctions, and re-admissions for heart failure (p < 0.05 for all comparisons). NT-proBNP improved the multivariate model for MACE prediction (area under the curve 0.81 vs. 0.72, p < 0.001). Conclusions Even after comprehensive adjustment, NT-proBNP emerges as a potent, accessible and inexpensive tool for risk stratification of STEMI patients after completion of rehabilitation programs.

Despite the improvement in prognosis in patients with acute myocardial infarction (AMI), a significant proportion of survivors still experience heart failure (HF)-related adverse outcomes. Adverse left ventricular remodeling (LVR), which refers to a progressive dilation of left ventricular (LV) end-diastolic and end-systolic volumes, usually accompanied by a deterioration in LV systolic function, occurs frequently and underlies most cases of HF development after AMI. In this review, we discuss the current definitions of post-AMI LVR, the most appropriate imaging modalities for its detection, and the pathophysiological mechanisms by which Cardiac Rehabilitation (CR) can improve LVR-including exercise interventions, cardiovascular risk factors control, and pharmacological therapy optimization. Finally, we provide up-to-date recommendations for the follow-up and management of LVR in post-AMI patients enrolled in CR and outline future prospects on this topic.

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.

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.

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 ± 0.7), abnormal stress CMR (mean ischemic burden: 5.8 ± 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, 1.5-9.2; 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.

We aimed to assess the correlation of cardiovascular magnetic resonance (CMR)-derived epicardial adipose tissue (EAT) with infarct size (IS) and residual systolic function in ST-segment elevation myocardial infarction (STEMI). We enrolled patients discharged for a first anterior reperfused STEMI submitted to undergo CMR. EAT, left ventricular (LV) ejection fraction (LVEF), and IS were quantified at the 1-week (n = 221) and at 6-month CMR (n = 167). At 1-week CMR, mean EAT was 31 ± 13 mL/m2. Patients with high EAT volume (n = 72) showed larger 1-week IS. After adjustment, EAT extent was independently related to 1-week IS. In patients with large IS at 1 week (>30% of LV mass, n = 88), those with high EAT showed more preserved 6-month LVEF. This association persisted after adjustment and in a 1:1 propensity score-matched patient subset. Overall, EAT decreased at 6 months. In patients with large IS, a greater reduction of EAT was associated with more preserved 6-month LVEF. In STEMI, a higher presence of EAT was associated with a larger IS. Nevertheless, in patients with large infarctions, high EAT and greater subsequent EAT reduction were linked to more preserved LVEF in the chronic phase. This dual and paradoxical effect of EAT fuels the need for further research in this field.

INTRODUCTION AND OBJECTIVES:Clinical and experimental studies have shown that, in patients with reperfused ST-segment elevation myocardial infarction (STEMI), abnormalities in the endothelial monolayer are initiated during ischemia but rapidly intensify upon restoration of blood perfusion to the ischemic area. We aimed to evaluate the effect of serum isolated after revascularization from STEMI patients on the degree of endothelial permeability in vitro, by promoting endothelial cell apoptosis and necrosis in vitro. We also investigated the association between the percentage of serum-induced endothelial cell apoptosis or necrosis in vitro and the extent of cardiovascular magnetic resonance (CMR)-derived parameters of reperfusion injury (edema, hemorrhage, and microvascular obstruction). METHODS:Human coronary artery endothelial cells were incubated with serum isolated 24hours after revascularization from 43 STEMI patients who underwent CMR and 14 control participants. We assessed the effect of STEMI serum on activation of apoptosis and necrosis, as well as on the permeability and structure of the endothelial monolayer. RESULTS:Serum from STEMI patients increased apoptosis (P <.01) and necrosis (P <.05) in human coronary artery endothelial cells and caused increased permeability of the endothelial monolayer in vitro (P <.01), due to enlarged intercellular spaces (P <.05 vs control in all cases). Higher serum-induced necrosis was associated with greater endothelial permeability in vitro (P <.05) and with more extensive CMR-derived indices of reperfusion injury and infarct size. CONCLUSIONS:Postreperfusion serum activates necrosis and apoptosis in endothelial cells and increases the degree of endothelial permeability in vitro. The more potent the necrosis-triggering effect of serum, the more deleterious the consequences in terms of the resulting cardiac structure.