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Gut microbiota is an emerging editable cardiovascular risk factor. We aim to investigate gut and coronary plaque microbiota, using fecal samples and angioplasty balloons from patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS) and control subjects. We examined bacterial communities in gut and coronary plaques by 16S rRNA sequencing and we performed droplet digital PCR analysis to investigate the gut relative abundance of the bacterial genes CutC/CntA involved in trimethylamine N-oxide synthesis. Linear discriminant analysis effect size (LEfSe) at the genus and species levels displayed gut enrichment in Streptococcus, Granulicatella and P. distasonis in ACS compared with CCS and controls; Roseburia, C. aerofaciens and F. prausnitzii were more abundant in controls than in patients. Principal component analysis (PCA) of 41 differentially abundant gut taxa showed a clustering of the three groups. In coronary plaque, LEfSe at the genus level revealed an enrichment of Staphylococcus and Streptococcus in ACS, and Paracoccus in CCS, whereas PCA of 15 differentially abundant plaque taxa exhibited clustering of ACS and CCS patients. CutC and CntA genes were more abundant in ACS and CCS than in controls while no significant difference emerged between ACS and CCS. Our results indicate that ACS and CCS exhibit a different gut and plaque microbial signature, suggesting a possible role of these microbiotas in coronary plaque instability.

Aims The functional capacity of the immune cells is strongly dependent on their metabolic state and inflammatory responses are characterized by a greater use of glucose in immune cells. This study is aimed to establish the role of glucose metabolism and its players [glucose transporter 1 (GLUT-1) and pyruvate kinase isozyme M2 (PKM2)] in the dysregulation of adaptive immunity and inflammation observed in patients with non-ST-segment elevation myocardial infarction (NSTEMI). Methods and results We enrolled 248 patients allocated to three groups: NSTEMI patients, chronic coronary syndromes (CCS) patients, healthy subjects (HSs). NSTEMI patients showed higher expression of GLUT-1 and an enhanced glucose uptake in T cells when compared with CCS patients (P < 0.0001; P = 0.0101, respectively) and HSs (P = 0.0071; P = 0.0122, respectively). PKM2 had a prevalent nuclear localization in T lymphocytes in NSTEMI (P = 0.0005 for nuclear vs. cytoplasm localization), while in CCS and HS, it was equally distributed in both compartments. In addition, the nuclear fraction of PKM2 was significantly higher in NSTEMI compared with HS (P = 0.0023). In NSTEMI patients, treatment with Shikonin and Fasentin, which inhibits PKM2 enzyme activity and GLUT-1-mediated glucose internalization, respectively, led to a significant reduction in GLUT-1 expression along with the down-regulation of pro-inflammatory cytokine expression. Conclusion NSTEMI patients exhibit dysregulation of the GLUT-1/PKM2 metabolic loop characterized by nuclear translocation of PKM2, where it acts as a transcription regulator of pro-inflammatory genes. This detrimental loop might represent a new therapeutic target for personalized medicine.

Myocardial bridging (MB) is the most frequent congenital coronary anomaly in which a segment of an epicardial coronary artery takes a tunneled course under a bridge of the myocardium. This segment is compressed during systole, resulting in the so-called "milking effect" at coronary angiography. As coronary blood flow occurs primarily during diastole, the clinical relevance of MB is heterogeneous, being usually considered an asymptomatic bystander. However, many studies have suggested its association with myocardial ischemia, anginal symptoms, and adverse cardiac events. The advent of contemporary non-invasive and invasive imaging modalities and the standardization of intracoronary functional assessment tools have remarkably improved our understanding of MB-related ischemia, suggesting the role of atherosclerotic lesions proximal to MB, vasomotor disorders and microvascular dysfunction as possible pathophysiological substrates. The aim of this review is to provide a contemporary overview of the pathophysiology and of the non-invasive and invasive assessment of MB, in the attempt to implement a case-by-case therapeutic approach according to the specific endotype of MB-related ischemia.

Myocardial bridge (MB) is the most frequent inborn coronary artery variant in which a portion of the myocardium overlies an epicardial coronary artery segment. Although MB has long been considered a benign entity, a growing body of evidence has suggested its association with angina and adverse cardiac events. However, to date, no data on long-term prognosis are available, nor on therapies improving cardiovascular outcomes. We are currently conducting an ambispective, observational, multicentre, study in which we enrol patients with a clinical indication to undergo coronary angiography (CA) and evidence of MB, aiming to describe the incidence of symptoms and cardiovascular events at baseline and at long-term follow-up (FUP). The role of invasive full-physiology assessment in modifying the discharge therapy and eventually the perceived quality of life and the incidence of major cardiovascular events will be analysed. Basal clinical-instrumental data of eligible and consenting patients have been acquired after CA; FUP was performed 6, 12, and 24 months after the angiographic diagnosis of MB. The primary endpoint of the study is the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, cardiac hospitalization, and target vessel revascularization; the secondary endpoints are the rate of patients with Seattle Angina Questionnaire (SAQ) summary score <70 and the incidence of MACE in patients undergoing invasive intracoronary assessment. Among patients undergone FUP visits, we recorded 31 MACE at 6 months (11.6%), 16 MACE at 12 months (6.5%), and 26 MACE at 24 months (13.5%). The rate of patients with SAQ <70 is 18.8% at 6 months, 20.6% at 12 months, and 21.8% at 24 months. To evaluate the prognostic role of invasive intracoronary assessment, we compared MB patients who underwent only angiographic evaluation (Angio group) to those who underwent acetylcholine (ACH) provocative test with indication to

Aims Coronary microvascular obstruction (MVO) occurs frequently in patients with ST-elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). However, mechanisms are multiple and not yet fully understood. Perilipin 2 (PLIN2) is involved in lipid metabolism of macrophages resident in atherosclerotic plaques, along with a role in enhancing plaque inflammation. We studied the association between PLIN2 and MVO in STEMI patients undergoing primary PCI, and we assessed the role of PLIN2 to predict major adverse cardiovascular events (MACEs).Methods and results STEMI patients undergoing primary PCI were enrolled. PLIN2 was evaluated in peripheral blood monocytes; MVO was assessed using coronary angiogram. MACEs, as a composite of cardiac death, non-fatal myocardial infarction, re-admission for heart failure, and target vessel revascularization were investigated at follow-up. Among 100 STEMI patients, 33 (33.0%) had MVO. Patients with MVO had higher levels of PLIN2 (1.030.28 vs. 0.90 +/- 0.16, P = 0.019). Age [odds ratio (OR) (95% confidence interval, CI), 1.045 (1.005-1.087), P=0.026] and PLIN2 [OR (95% CI), 16.606 (2.027-136.030), P = 0.009] were associated with MVO at univariate analysis, although only PLIN2 [OR (95% CI), 12.325 (1.446-105.039), P = 0.022] was associated with MVO at multivariate analysis. After a mean follow-up of 182.2 +/- 126.6 days, 13 MACEs occurred. MVO [hazard ratio (HR) (95% CI), 6.791 (2.053-22.462), P = 0.002], hypercholesterolaemia [HR (95% CI), 3.563 (1.094-11.599), P = 0.035], and PLIN2 [HR (95% CI), 82.991 (9.857-698.746), P < 0.001] were predictors of MACEs at univariate analysis, although only PLIN2 [HR (95% CI), 26.904 (2.461-294.100), P = 0.007] predicted MACEs at multivariate analysis.Conclusions In STEMI patients undergoing primary PCI, PLIN2 was independently associated with MVO and was an independent predictor of MACEs at follow-up, suggesting to further explore PLIN2 as a target for future cardioprot

AIMS: Coronary microvascular obstruction (MVO) occurs frequently in patients with ST-elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). However, mechanisms are multiple and not yet fully understood. Perilipin 2 (PLIN2) is involved in lipid metabolism of macrophages resident in atherosclerotic plaques, along with a role in enhancing plaque inflammation. We studied the association between PLIN2 and MVO in STEMI patients undergoing primary PCI, and we assessed the role of PLIN2 to predict major adverse cardiovascular events (MACEs).METHODS AND RESULTS: STEMI patients undergoing primary PCI were enrolled. PLIN2 was evaluated in peripheral blood monocytes; MVO was assessed using coronary angiogram. MACEs, as a composite of cardiac death, non-fatal myocardial infarction, re-admission for heart failure, and target vessel revascularization were investigated at follow-up. Among 100 STEMI patients, 33 (33.0%) had MVO. Patients with MVO had higher levels of PLIN2 (1.03±0.28 vs. 0.90±0.16, P=0.019). Age [odds ratio (OR) (95% confidence interval, CI), 1.045 (1.005-1.087), P=0.026] and PLIN2 [OR (95% CI), 16.606 (2.027-136.030), P=0.009] were associated with MVO at univariate analysis, although only PLIN2 [OR (95% CI), 12.325 (1.446-105.039), P=0.022] was associated with MVO at multivariate analysis. After a mean follow-up of 182.2±126.6 days, 13 MACEs occurred. MVO [hazard ratio (HR) (95% CI), 6.791 (2.053-22.462), P=0.002], hypercholesterolaemia [HR (95% CI), 3.563 (1.094-11.599), P=0.035], and PLIN2 [HR (95% CI), 82.991 (9.857-698.746), P<0.001] were predictors of MACEs at univariate analysis, although only PLIN2 [HR (95% CI), 26.904 (2.461-294.100), P=0.007] predicted MACEs at multivariate analysis.CONCLUSIONS: In STEMI patients undergoing primary PCI, PLIN2 was independently associated with MVO and was an independent predictor of MACEs at follow-up, suggesting to further explore PLIN2 as a target for future cardioprotection therapies.

Background: the RIGENERA trial assessed the efficacy of granulocyte-colony stimulating factor (G-CSF) in the improvement of clinical outcomes in patients with severe acute myocardial infarction. However, there is no evidence available regarding the long-term safety and efficacy of this treatment. Methods: in order to evaluate the long-term effects on the incidence of major adverse events, on the symptom burden, on the quality of life and the mean life expectancy and on the left ventricular (LV) function, we performed a clinical and echocardiographic evaluation together with an assessment using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Heart Failure Model (SHFM) at 10-years follow-up, in the patients cohorts enrolled in the RIGENERA trial. Results: thirty-two patients were eligible for the prospective clinical and echocardiography analyses. A significant reduction in adverse LV remodeling was observed in G-CSF group compared to controls, 9% vs. 48% (p = 0.030). The New York Heart Association (NYHA) functional class was lower in G-CSF group vs. controls (p = 0.040), with lower burden of symptoms and higher quality of life (p = 0.049). The mean life expectancy was significantly higher in G-CSF group compared to controls (15 ± 4 years vs. 12 ± 4 years, p = 0.046. No difference was found in the incidence of major adverse events. Conclusions: this longest available follow-up on G-CSF treatment in patients with severe acute myocardial infarction (AMI) showed that this treatment was safe and associated with a reduction of adverse LV remodeling and higher quality of life, in comparison with standard-of-care treatment.

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Duchenne's muscular dystrophy is an X-linked neuromuscular disease that manifests as muscle atrophy and cardiomyopathy in young boys. However, a considerable percentage of carrier females are often diagnosed with cardiomyopathy at an advanced stage. Existing therapy is not disease-specific and has limited effect, thus many patients and symptomatic carrier females prematurely die due to heart failure. Early detection is one of the major challenges that muscular dystrophy patients, carrier females, family members and, research and medical teams face in the complex course of dystrophic cardiomyopathy management. Despite the widespread adoption of advanced imaging modalities such as cardiac magnetic resonance, there is much scope for refining the diagnosis and treatment of dystrophic cardiomyopathy. This comprehensive review will focus on the pertinent clinical aspects of cardiac disease in muscular dystrophy while also providing a detailed consideration of the known and developing concepts in the pathophysiology of muscular dystrophy and forthcoming therapeutic options.