Persistence of vitamin D deficiency among Italian patients with acute myocardial infarction.

BACKGROUND AND AIMS: Vitamin D deficiency is a common cardiovascular risk factor associated with the development of atherosclerosis. We evaluated changes in 25(OH)D concentrations in 1510 patients with acute myocardial infarction (AMI) over a long observation period, including the COVID-19 pandemic. METHODS AND RESULTS: Patients were separated into four groups according to the year of enrolment, group 1 (2009-2010), group 2 (2014-2016), group 3 (2017-2019), and group 4 (2020-2022). The median 25(OH)D concentration in the overall cohort was 17.15 (10.3-24.7) ng/mL. The median plasma concentrations of 25(OH)D for groups 1, 2, 3, and 4 were 14.45 (7.73-22.58) ng/mL, 17.3 ng/mL (10.33-24.2), 18.95 (11.6-26.73) ng/mL and 19.05 (12.5-27.3) ng/mL, respectively. Although 25(OH)D levels increased over the years, the prevalence of vitamin D deficiency remained high in each group (68.4%, 61.4%, 53.8%, and 52% respectively). Hypovitaminosis D was predicted by the season influence (OR:2.03, p < 0.0001), higher body mass index (OR:1.25; p = 0.001), diabetes mellitus (OR:1.54; p = 0.001), smoking (OR:1.47; p = 0.001), older age (OR:1.07; p = 0.008), higher triglycerides levels (OR:1.02; p = 0.01), and female gender (OR:1.3; p = 0.038). After multivariable adjustment, vitamin D ≤ 20 ng/mL was an independent predictor of mortality. CONCLUSION: Vitamin D deficiency is highly prevalent and persistent in patients with AMI despite a trend towards increasing 25(OH)D concentrations over the years. The frequent lockdowns did not reduce the levels of 25(OH)D in the fourth group. Low levels of 25(OH)D are an independent predictor of mortality.

Subcellular Effectors of Cocaine Cardiotoxicity: All Roads Lead to Mitochondria-A Systematic Review of the Literature.

Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine causes complex multiorgan toxicity, including in the heart where the blockade of the sodium channels causes increased catecholamine levels and alteration in calcium homeostasis, thus inducing an increased oxygen demand. Moreover, there is evidence to suggest that mitochondria alterations play a crucial role in the development of cocaine cardiotoxicity. We performed a systematic review according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) scheme to evaluate the mitochondrial mechanisms determining cocaine cardiotoxicity. Among the initial 106 articles from the Pubmed database and the 17 articles identified through citation searching, 14 final relevant studies were extensively reviewed. Thirteen articles included animal models and reported the alteration of specific mitochondria-dependent mechanisms such as reduced energy production, imbalance of membrane potential, increased oxidative stress, and promotion of apoptosis. However, only one study evaluated human cocaine overdose samples and observed the role of cocaine in oxidative stress and the induction of apoptosis though mitochondria. Understanding the complex processes mediated by mitochondria through forensic analysis and experimental models is crucial for identifying potential therapeutic targets to mitigate or reverse cocaine cardiotoxicity in humans.

Effect of prehospital treatment in STEMI patients undergoing primary PCI.

BACKGROUND: The appropriate timing to administer antithrombotic therapies in ST-elevation myocardial infarction (STEMI) remains uncertain. This study aims to evaluate the role of antithrombotic therapy administration at first medical contact (FMC) compared with the administration in the Cathlab. METHODS: We conducted a "before-after" observational study enrolling STEMI undergoing primary percutaneous coronary intervention (PCI). Outcomes were evaluated during two successive periods, before (control group: aspirin only at FMC) and after (pretreated intervention group: heparin, aspirin plus ticagrelor at FMC) the introduction of a new regional pretreatment protocol. RESULTS: A total of 537 consecutive patients (300 in control vs. 237 in intervention group) were enrolled. The pretreated compared with no pretreated population showed better basal reperfusion, expressed as basal Thrombolysis in Myocardial Infarction (TIMI)-flow (p for trend p < 0.001). Pretreated population showed lower frequency of TIMI 0 (56.5% vs. 73.7%, odds ratio [OR]: 0.46, 95% confidence interval [CI]: 0.32-0.67, p < 0.001) and higher frequency of TIMI 2-3 (33.3% vs. 19.3% OR: 2.0, 95% CI: 1.38-2.00, p < 0.001) and TIMI 3 (14.3% vs. 9.7%, OR: 1.56, 95% CI: (0.92-2.65), p = 0.094). Pretreated compared with no pretreated population showed reduced infarct size expressed as Troponin Peak (20,286 (8726-75,027) versus 48,676 (17,229-113,900), p = 0.001), and higher left ventricular ejection fraction at discharge (53% (44-59) vs. 50% (44-56), p = 0.027). In-hospital BARC ≥ 2 bleeding were similar (2.1% vs. 2.0%, p = 0.929, in pretreated versus no pretreated population, respectively). CONCLUSION: This study provides support for an early pretreatment strategy in STEMI patients and confirmed the importance of an efficient organization of STEMI networks which allow initiation of antithrombotic treatment at FMC.

Old and Novel Therapeutic Approaches in the Management of Hyperglycemia, an Important Risk Factor for Atherosclerosis.

Hyperglycemia is considered one of the main risk factors for atherosclerosis, since high glucose levels trigger multiple pathological processes, such as oxidative stress and hyperproduction of pro-inflammatory mediators, leading to endothelial dysfunction. In this context, recently approved drugs, such as glucagon-like-peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), could be considered a powerful tool for to reduce glucose concentration and cardiovascular risk. Interestingly, many patients with type 2 diabetes mellitus (T2DM) and insulin resistance have been found to be deficient in vitamin D. Recent studies pointed out the unfavorable prognostic values of T2DM and vitamin D deficiency in patients with cardiac dysfunction, either when considered individually or together, which shed light on the role of vitamin D in general health status. New evidence suggests that SGLT2i could adversely affect the production of vitamin D, thereby increasing the risk of fractures, which are common in patients with T2DM. Therefore, given the biological effects of vitamin D as an anti-inflammatory mediator and a regulator of endothelial function and calcium equilibrium, these new findings should be taken into consideration as well. The aim of this review is to gather the latest advancements regarding the use of antidiabetic and antiplatelet drugs coupled with vitamin D supplementation to control glucose levels, therefore reducing the risk of coronary artery disease (CAD).

Heart failure impairs the mechanotransduction properties of human cardiac pericytes.

The prominent impact that coronary microcirculation disease (CMD) exerts on heart failure symptoms and prognosis, even in the presence of macrovascular atherosclerosis, has been recently acknowledged. Experimental delivery of pericytes in non-revascularized myocardial infarction improves cardiac function by stimulating angiogenesis and myocardial perfusion. Aim of this work is to verify if pericytes (Pc) residing in ischemic failing human hearts display altered mechano-transduction properties and to assess which alterations of the mechano-sensing machinery are associated with the observed impaired response to mechanical cues. RESULTS: Microvascular rarefaction and defects of YAP/TAZ activation characterize failing human hearts. Although both donor (D-) and explanted (E-) heart derived cardiac Pc support angiogenesis, D-Pc exert this effect significantly better than E-Pc. The latter are characterized by reduced focal adhesion density, decreased activation of the focal adhesion kinase (FAK)/ Crk-associated substrate (CAS) pathway, low expression of caveolin-1, and defective transduction of extracellular stiffness into cytoskeletal stiffening, together with an impaired response to both fibronectin and lysophosphatidic acid. Importantly, Mitogen-activated protein kinase kinase inhibition restores YAP/TAZ nuclear translocation. CONCLUSION: Heart failure impairs Pc mechano-transduction properties, but this defect could be reversed pharmacologically.

Traditional and Emerging Biomarkers in Asymptomatic Left Ventricular Dysfunction-Promising Non-Coding RNAs and Exosomes as Biomarkers in Early Phases of Cardiac Damage.

Heart failure (HF) is one of the major causes of morbidity and mortality worldwide and represents an escalating problem for healthcare systems. The identification of asymptomatic patients with underlying cardiac subclinical disease would create an opportunity for early intervention and prevention of symptomatic HF. Traditional biomarkers are very useful as diagnostic and prognostic tools in the cardiovascular field; however, their application is usually limited to overt cardiac disease. On the other hand, a growing number of studies is investigating the diagnostic and prognostic potential of new biomarkers, such as micro-RNAs (miRNA), long non-coding RNAs, and exosome cargo, because of their involvement in the early phases of cardiac dysfunction. Unfortunately, their use in asymptomatic phases remains a distant goal. The aim of this review is to gather the current knowledge of old and novel biomarkers in the early diagnosis of cardiac dysfunction in asymptomatic individuals.

Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review.

Angiotensin-converting enzyme 2 (ACE2) is the entry receptor for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the cause of Coronavirus Disease-2019 (COVID-19) in humans. ACE-2 is a type I transmembrane metallocarboxypeptidase expressed in vascular endothelial cells, alveolar type 2 lung epithelial cells, renal tubular epithelium, Leydig cells in testes and gastrointestinal tract. ACE2 mediates the interaction between host cells and SARS-CoV-2 spike (S) protein. However, ACE2 is not only a SARS-CoV-2 receptor, but it has also an important homeostatic function regulating renin-angiotensin system (RAS), which is pivotal for both the cardiovascular and immune systems. Therefore, ACE2 is the key link between SARS-CoV-2 infection, cardiovascular diseases (CVDs) and immune response. Susceptibility to SARS-CoV-2 seems to be tightly associated with ACE2 availability, which in turn is determined by genetics, age, gender and comorbidities. Severe COVID-19 is due to an uncontrolled and excessive immune response, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. In spite of a lower ACE2 expression on cells surface, patients with CVDs have a higher COVID-19 mortality rate, which is likely driven by the imbalance between ADAM metallopeptidase domain 17 (ADAM17) protein (which is required for cleavage of ACE-2 ectodomain resulting in increased ACE2 shedding), and TMPRSS2 (which is required for spike glycoprotein priming). To date, ACE inhibitors and Angiotensin II Receptor Blockers (ARBs) treatment interruption in patients with chronic comorbidities appears unjustified. The rollout of COVID-19 vaccines provides opportunities to study the effects of different COVID-19 vaccines on ACE2 in patients on treatment with ACEi/ARB.

From Brain to Heart: Possible Role of Amyloid-ß in Ischemic Heart Disease and Ischemia-Reperfusion Injury.

Ischemic heart disease (IHD) is among the leading causes of death in developed countries. Its pathological origin is traced back to coronary atherosclerosis, a lipid-driven immuno-inflammatory disease of the arteries that leads to multifocal plaque development. The primary clinical manifestation of IHD is acute myocardial infarction (AMI),) whose prognosis is ameliorated with optimal timing of revascularization. Paradoxically, myocardium re-perfusion can be detrimental because of ischemia-reperfusion injury (IRI), an oxidative-driven process that damages other organs. Amyloid-ß (Aß) plays a physiological role in the central nervous system (CNS). Alterations in its synthesis, concentration and clearance have been connected to several pathologies, such as Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). Aß has been suggested to play a role in the pathogenesis of IHD and cerebral IRI. The purpose of this review is to summarize what is known about the pathological role of Aß in the CNS; starting from this evidence, we will illustrate the role played by Aß in the development of coronary atherosclerosis and its possible implications in the pathophysiology of IHD and myocardial IRI. Better elucidation of Aß's contribution to the molecular pathways underlying IHD and IRI could be of great help in developing new therapeutic strategies.

Cardiac stem cell aging and heart failure.

A side effect of the medical improvements of the last centuries is the progressive aging of the world population, which is estimated to reach the impressive number of 2 billion people with more than 65 years by 2050. As a consequence, age-related diseases, such as heart failure, will affect more and more patients in the next years. To understand the biological bases of these diseases will be a crucial task in order to find better treatments, and possibly slow age-related morbidity and mortality. Cardiac stem cells have been at the center of a heated debate and their potential involvement in cardiac homeostasis has been questioned. In this review, we summarize evidence obtained by independent groups, on different animal models and humans, that strongly support the important role played by immature, cardiac resident cells in the cardioprotection against heart failure.

Circulating cardiac biomarkers and postoperative atrial fibrillation in the OPERA trial.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery and predicts increased morbidity and mortality. Identification of patients at high risk of POAF with the help of circulating biomarkers may enable early preventive treatment but data are limited, especially in contemporary surgical patients. METHODS: Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured at enrollment, on the morning of cardiac surgery, at end surgery, and 2 days postsurgery in 562 patients undergoing cardiac surgery, randomized to perioperative supplementation with oral fish oil or placebo in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial (OPERA). The primary endpoint was incident POAF lasting ≥ 30 s, centrally adjudicated and confirmed electrocardiographically. RESULTS: Higher levels of NT-proBNP and hs-cTnT before surgery were associated with older age, renal or cardiac dysfunction and EuroSCORE. NT-proBNP peaked on postoperative day 2 (2172 [1238-3758] ng/L, median [Q1-Q3]), while hs-cTnT peaked at the end of surgery (373 [188-660] ng/L). Fish oil supplementation did not alter the time course of the cardiac biomarkers (P > 0.05). Concentrations of NT-proBNP or hs-cTnT, on the morning of surgery, or changes in their level between morning of surgery and postsurgery, were not significantly associated with POAF after adjustment for clinical and surgical characteristics. CONCLUSION: Among patients undergoing cardiac surgery, NT-proBNP and hs-cTnT are related to clinical and surgical characteristics, have different perioperative time courses but are not independently associated with risk of POAF.

Elevations of inflammatory markers PTX3 and sST2 after resuscitation from cardiac arrest are associated with multiple organ dysfunction syndrome and early death.

BACKGROUND: A systemic inflammatory response is observed after cardiopulmonary resuscitation. We investigated two novel inflammatory markers, pentraxin 3 (PTX3) and soluble suppression of tumorigenicity 2 (sST2), in comparison with the classic high-sensitivity C-reactive protein (hsCRP), for prediction of early multiple organ dysfunction syndrome (MODS), early death, and long-term outcome after out-of-hospital cardiac arrest. METHODS: PTX3, sST2, and hsCRP were assayed at ICU admission and 48 h later in 278 patients. MODS was defined as the 24 h non-neurological Sequential Organ Failure Assessment (SOFA) score ≥ 12. Intensive care unit (ICU) death and 12-month Cerebral Performance Category (CPC) were evaluated. RESULTS: In total, 82% of patients survived to ICU discharge and 48% had favorable neurological outcome at 1 year (CPC 1 or 2). At ICU admission, median plasma levels of hsCRP (2.8 mg/L) were normal, while levels of PTX3 (19.1 ng/mL) and sST2 (117 ng/mL) were markedly elevated. PTX3 and sST2 were higher in patients who developed MODS (p<0.0001). Admission levels of PTX3 and sST2 were also higher in patients who died in ICU and in those with an unfavorable 12-month neurological outcome (p<0.01). Admission levels of PTX3 and sST2 were independently associated with subsequent MODS [OR: 1.717 (1.221-2.414) and 1.340, (1.001-1.792), respectively] and with ICU death [OR: 1.536 (1.078-2.187) and 1.452 (1.064-1.981), respectively]. At 48 h, only sST2 and hsCRP were independently associated with ICU death. CONCLUSIONS: Higher plasma levels of PTX3 and sST2, but not of hsCRP, at ICU admission were associated with higher risk of MODS and early death.

Factor-V HR2 haplotype and thromboembolic disease.

OBJECTIVES: The objective of this study is to evaluate the prevalence of HR2 polymorphism among patients with pulmonary embolism (PE) and healthy subjects. BACKGROUND: Polymorphism in the factor V gene named HR2 has been described as a possible risk factor for venous thromboembolism (VTE) development. Contradictive results on this association have been reported. METHODS: Eighty-five patients admitted for PE and 72 healthy subjects were included in the study. Thrombophilia screening using genetic tests for factor V Leiden (G1691A/Leiden and HR2 haplotype) and other genetic mutations were investigated. RESULTS: Of 85 patients with PE, 20 (23.53%) carried the HR2 haplotype. Further, a majority of the patients with HR2 haplotype had recurrent venous thrombosis or PE (15 out of 20 patients). The HR2 haplotype was detected in 6 (8.3%) out of 72 healthy subjects. Patients had significantly higher HR2 haplotype frequency than healthy controls (P = 0.001). HR2 carriers had a three-fold increase in risk of developing PE (OR = 3.38, 95% CI = 1.27-8.96, P = 0.011). After adjustment for other tested defects for thrombophilia, HR2 haplotype was associated with increased risk of thromboembolic events (OR = 3.05, 95% CI = 1.11-8.35, P = 0.03). However, after adjustment for sex and age, HR2 polymorphism was no longer associated with the risk of thromboembolic event (OR = 1.22, 95% CI = 0.34-4.38, P = 0.76). CONCLUSIONS: Our study does not support the notion that factor V HR2 haplotype might be a risk factor for thrombosis despite its high prevalence among patients with PE.

Vitamin D Deficiency in Patients with Acute Myocardial Infarction: An Italian Single-Center Study.

BACKGROUND: Hypovitaminosis D is a vitamin deficiency that has been increasing in developed countries; it was also suggested as an emerging risk factor for developing of atherosclerosis and acute myocardial infarction. The primary source of vitamin D is its cutaneous synthesis under exposure to sunlight. It has been suggested that 30 min of sun exposure twice weekly leads to sufficient vitamin D synthesis. The residents of Trieste (Italy) are well-known for their high exposure to sunlight in all seasons. We aimed to investigate the vitamin D status in subjects with acute myocardial infarction living in this area. METHODS: Vitamin D status was identified in 478 subjects diagnosed with acute myocardial infarction. RESULTS: The median serum 25-hydroxyvitamin D concentration was 14.5 [7.8 - 22.7] ng/mL. Vitamin D deficiency and insufficiency were present in 324 (68 %) and 107 (22 %) subjects, respectively. Vitamin D deficiency was less frequent among subjects enrolled in the period from July to the end of September (p < 0.001). In a multivariate analysis vitamin D deficiency was predicted by older age (p = 0.02), female gender (p = 0.002), higher body mass index (p = 0.05), autumn/winter sampling (p < 0.001), increased parathyroid hormone (p = 0.03) and alkaline phosphatase (p = 0.003). CONCLUSIONS: We observed very high prevalence of vitamin D deficiency among subjects with myocardial infarction in all seasons of enrollment. However, it was lower in the summer when sun exposure is higher. The exposure to sunlight may be a cost-saving therapeutic strategy for the management of vitamin D deficiency.

New-onset left bundle branch block independently predicts long-term mortality in patients with idiopathic dilated cardiomyopathy: data from the Trieste Heart Muscle Disease Registry.

AIMS: Left bundle branch block (LBBB) is commonly associated with heart failure. We evaluated the prevalence, incidence, and impact of LBBB on long-term outcome in young patients with heart failure affected by idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: We included 608 patients with DCM from the Heart Muscle Disease Registry of Trieste in this retrospective analysis. At baseline electrocardiogram (ECG), 189 patients (31.1%) had LBBB. The patients with baseline LBBB had a significantly higher mortality rate than the patients without LBBB (38.6 vs. 27.9%, P = 0.002) at the univariate analysis. After a multiple covariate adjustment, the baseline LBBB was not associated with a significantly increased risk of death [hazard ratio (HR) 1.27, 95% confidence interval (CI): 0.88-1.81, P = 0.2]. Forty-seven (11.2%) patients without LBBB at baseline ECG developed LBBB during follow-up. Among these, the mortality rate was 49 vs. 25% in patients without new-onset LBBB (P = 0.001). New-onset LBBB was a strong and independent predictor of all-cause mortality (HR 3.18, 95% CI: 1.90-5.31, P < 0.001) at multivariate analysis. CONCLUSION: After correcting for potential confounders, new-onset LBBB was found to be associated with an increased risk of all-cause mortality. The management of patients with new-onset LBBB may need to be more aggressive, possibly including early cardiac resynchronization therapy/implantable cardioverter-defibrillator therapy.

Simulation-guided auscultatory training before graduation is associated with better auscultatory skills in residents.

INTRODUCTION: A growing body of scientific evidence shows that simulation-guided auscultatory training can significantly improve the skills of medical students. Nevertheless, it remains to be elucidated if this training has any long-term impact on auscultatory skills. We sought to ascertain whether there were differences in heart and lung auscultation among residents who received simulation-guided auscultatory training before graduation vs. those who did not. MATERIALS AND METHODS: A total of 43 residents were included in the study; 20 of them entered into Cardiology specialty school (C) and 23 of them entered into Internal and Occupational Medicine specialty schools (M) at the University of Trieste. Based on the history of simulation-guided auscultatory training before graduation (yes = Y; no = N), four groups were formed: CY, CN, MY, and MN. Residents were evaluated in terms of their ability to recognize six heart and five lung sounds, which were reproduced in a random order with the Kyoto-Kagaku patient simulator. Associations between history of simulation training, specialty choice and auscultatory skills were evaluated with Kruskal-Wallis test and logistic regression analysis. RESULTS: Auscultatory skills of residents were associated with simulation-guided training before graduation, regardless of the specialty chosen. Simulation-guided training had a higher impact on residents in Medicine. Overall, heart and lung sounds were correctly recognized in 41% of cases. Logistic regression analysis showed that simulation-guided training was associated with recognition of aortic stenosis, S2 wide split, fine crackles, and pleural rubs. Specialty choice was associated with recognition of aortic stenosis as well as aortic and mitral regurgitation. DISCUSSION: History of simulation-guided auscultatory training was associated with better auscultatory performance in residents, regardless of the medical specialty chosen. Choice of Cardiology was associated with better scores in aortic stenosis as well as aortic and mitral regurgitation. Nevertheless, overall auscultatory proficiency was quite poor, which suggests that simulation-guided training may help but is probably still too short.

HOMA-IR as a Predictor of PAI-1 Levels in Women with Severe Obesity.

BACKGROUND: Obesity is a chronic inflammatory disorder that increases the risk of cardiovascular diseases (CVDs). Given the high CVD mortality rate among individuals with obesity, early screening should be considered. Plasminogen activator inhibitor (PAI-1), a cytokine that links obesity and CVDs, represents a promising biomarker. However, PAI-1 is not part of the clinical routine due to its high cost. Therefore, it is necessary to find good predictors that would allow an indirect assessment of PAI-1. METHODS: This study enrolled 47 women with severe obesity (SO). The obtained anthropometric measurements included weight, height, neck (NC), waist (WC), and hip circumference (HC). Blood samples were collected to analyse glucose and lipid profiles, C-reactive protein, liver markers, adiponectin, and PAI-1 (determined by ELISA immunoassay). Homeostasis model assessment-adiponectin (HOMA-AD), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), triglyceride-glucose index (TyG), and atherogenic index of plasma (AIP) were calculated. The women were grouped according to PAI-1 levels. The data were analysed using IBM SPSS Statistics, version 21. The significance level for the analysis was set at 5%. RESULTS: Women with SO who have higher levels of PAI-1 have lower values of high-density lipoprotein cholesterol (HDL) (p = 0.037) and QUICKI (0.020) and higher values of HOMA-AD (0.046) and HOMA-IR (0.037). HOMA-IR was demonstrated to be a good predictor of PAI-1 in this sample (B = 0.2791; p = 0.017). CONCLUSIONS: HOMA-IR could be used as a predictor of PAI-1 levels, pointing out the relevance of assessing glycaemic parameters for the prevention of CVDs in women with SO.

Intra-hospital variation of gut microbiota product, trimethylamine N-oxide (TMAO), predicts future major adverse cardiovascular events after myocardial infarction.

OBJECTIVE: Trimethylamine N-oxide (TMAO) has been associated with atherosclerosis and poor outcome. We evaluated the prognostic impact of intra-hospital TMAO variation on patient outcome. METHODS AND RESULTS: Blood samples from 149 patients with acute myocardial infarction (AMI) were taken on admission and discharge. Plasma TMAO was determined by HPLC-MS. The endpoint was a composite three-point MACE (major adverse cardiovascular events), including all-cause mortality, re-infarction, or heart failure (HF) development. Median TMAO concentration on admission was significantly higher than on discharge (respectively, 7.81 [3.47-19.98] vs 3.45 [2.3-4.78] µM, p < 0.001). After estimating the 3.45 µM TMAO cut-off with the analysis of the continuous hazard ratio, we divided our cohort into two groups. The first group included 75 (50.3%) patients whose TMAO levels remained below or decreased under cut-off (low-low/high-low; LL/HL), while the second group included 74 (49.7%) patients whose TMAO levels remained high or increased above the cut-off during hospitalisation (high-high/low-high; HH/LH). During the median 30-month follow-up, 21.5% of patients experienced the composite endpoint. At Kaplan-Meier analysis, a trend of increasing MACE risk was observed in patients in the HH/LH group (p = 0.05). At multivariable Cox analysis, patients from the HH/LH group had more than two times higher risk of MACE during the follow-up than the LL/HL group (HR = 2.15 [95% CI, 1.03-4.5], p = 0.04). Other independent predictors of MACE were older age and worse left ventricular systolic function. CONCLUSION: In patients with AMI, permanently high or increasing TMAO levels during hospitalisation are associated with a higher risk of MACE during long-term follow-up.

Obesity and high waist circumference are associated with low circulating pentraxin-3 in acute coronary syndrome.

BACKGROUND: Long pentraxin 3 (PTX3) is a component of the pentraxin superfamily and a potential marker of vascular damage and inflammation, associated with negative outcome in patients with acute coronary syndromes (ACS). Obesity is a risk factor for cardiovascular disease and PTX3 production is reported in abdominal adipose tissue. Low PTX3 is however reported in the obese population, and obesity per se may be associated with less negative ACS outcome. METHODS: We investigated the potential impact of obesity and high waist circumference (reflecting abdominal fat accumulation) on plasma PTX3 concentration in ACS patients (n = 72, 20 obese) compared to age-, sex- and BMI-matched non-ACS individuals. RESULTS: Both obese and non-obese ACS patients had higher PTX3 than matched non-ACS counterparts, but PTX3 was lower in obese than non-obese individuals in both groups (all P < 0.05). PTX3 was also lower in ACS subjects with high than in those with normal waist circumference (WC). Plasma PTX3 was accordingly associated negatively with BMI and WC, independently of age and plasma creatinine. No associations were observed between PTX3 and plasma insulin, glucose or the short pentraxin and validated inflammation marker C-reactive protein, that was higher in ACS than in non-ACS individuals independently of BMI or WC. CONCLUSIONS: Obesity is associated with low circulating PTX3 in ACS. This association is also observed in the presence of abdominal fat accumulation as reflected by elevated waist circumference. Low PTX3 is a novel potential modulator of tissue damage and outcome in obese ACS patients.

COVID-19-Related Myocarditis: Are We There Yet? A Case Report of COVID-19-Related Fulminant Myocarditis.

There is increasing evidence of cardiac involvement in COVID-19 cases, with a broad range of clinical manifestations spanning from acute life-threatening conditions such as ventricular dysrhythmias, myocarditis, acute myocardial ischemia and pulmonary thromboembolism to long-term cardiovascular sequelae. In particular, acute myocarditis represents an uncommon but frightening complication of SARS-CoV-2 infection. Even if many reports of SARS CoV-2 myocarditis are present in the literature, the majority of them lacks histological confirmation of cardiac injury. Here, we report a case of a young lady, who died suddenly a few days after testing positive for SARS-CoV-2, whose microscopic and genetics features suggested a direct cardiac involvement compatible with fulminant myocarditis.

n-3 PUFA-Enriched Diet Preserves Skeletal Muscle Mitochondrial Function and Redox State and Prevents Muscle Mass Loss in Mice with Chronic Heart Failure.

Rationale and Methods: Skeletal muscle derangements, potentially including mitochondrial dysfunction with altered mitochondrial dynamics and high reactive oxygen species (ROS) generation, may lead to protein catabolism and muscle wasting, resulting in low exercise capacity and reduced survival in chronic heart failure (CHF). We hypothesized that 8-week n-3-PUFA isocaloric partial dietary replacement (Fat = 5.5% total cal; EPA + DHA = 27% total fat) normalizes gastrocnemius muscle (GM) mitochondrial dynamics regulators, mitochondrial and tissue pro-oxidative changes, and catabolic derangements, resulting in preserved GM mass in rodent CHF [Myocardial infarction (MI)-induced CHF by coronary artery ligation, left-ventricular ejection fraction <50%]. Results: Compared to control animals (Sham), CHF had a higher GM mitochondrial fission-fusion protein ratio, with low ATP and high ROS production, pro-inflammatory changes, and low insulin signalling. n-3-PUFA normalized all mitochondrial derangements and the pro-oxidative state (oxidized to total glutathione ratio), associated with normalized GM cytokine profile, and enhanced muscle-anabolic insulin signalling and prevention of CHF-induced GM weight loss (all p < 0.05 vs. CHF and p = NS vs. S). Conclusions:n-3-PUFA isocaloric partial dietary replacement for 8 weeks normalizes CHF-induced derangements of muscle mitochondrial dynamics regulators, ROS production and function. n-3-PUFA mitochondrial effects result in preserved skeletal muscle mass, with potential to improve major patient outcomes in clinical settings.