Levosimendan for acute right heart failure in COVID-19: another arrow in our quiver?

Objective: SARS-CoV-2 infection is associated with a higher risk of acute right heart failure (RHF) due to primary right ventricle (RV) dilation and systemic inflammatory response, which in turn lead to microvascular and cardiomyocytes dysfunction, local hypoxia and multi-organ failure. In this clinical setting, levosimendan could be a viable therapy thanks to its right-heart tropism and its additional pleiotropic properties.

Case Report: We present the case of a 72 years-old man with positive nasopharyngeal swab for SARS-CoV-2 infection, mild pulmonary involvement and clinical signs of new-onset RHF.

Advances and Challenges in Biomarkers Use for Coronary Microvascular Dysfunction: From Bench to Clinical Practice.

Coronary microvascular dysfunction (CMD) is related to a broad variety of clinical scenarios in which cardiac microvasculature is morphologically and functionally affected, and it is associated with impaired responses to vasoactive stimuli. Although the prevalence of CMD involves about half of all patients with chronic coronary syndromes and more than 20% of those with acute coronary syndrome, the diagnosis of CMD is often missed, leading to the underestimation of its clinical importance. The established and validated techniques for the measurement of coronary microvascular function are invasive and expensive.

Novel Biomarkers in Heart Failure: New Insight in Pathophysiology and Clinical Perspective.

Heart failure (HF) is a complex clinical syndrome with a huge social burden in terms of cost, morbidity, and mortality. Brain natriuretic peptide (BNP) appears to be the gold standard in supporting the daily clinical management of patients with HF. Novel biomarkers may supplement BNP to improve the understanding of this complex disease process and, possibly, to personalize care for the different phenotypes, in order to ameliorate prognosis.

Prevalence and characteristics of myocardial injury during COVID-19 pandemic: A new role for high-sensitive troponin.

Background: Coronavirus disease 2019 (COVID-19) is a pandemic disease that is causing a public health emergency. Characteristics and clinical significance of myocardial injury remain unclear.

Methods: This retrospective single-center study analyzed 189 patients who received a COVID-19 diagnosis out of all 758 subjects with a high sensitive troponin I (Hs-TnI) measurement within the first 24 h of admission at the Policlinico A.

Role of the central autonomic nervous system intrinsic functional organisation and psychosocial factors in primary microvascular angina and Takotsubo syndrome.

Introduction And Objective: Dysfunctional central autonomic nervous system network (CAN) at rest may result in aberrant autonomic responses to psychosocial stressors. We hypothesised that patients with primary microvascular angina (MVA) or Takotsubo syndrome (TTS) would exhibit a peculiar functional organisation of the CAN, potentially associated with psychological patterns.

Methods: Patients underwent a psychosocial evaluation: a clinical diagnostic interview, Millon Clinical Multiaxial Inventory III, State-Trait Anxiety Inventory form Y and Short Form 36 Health Survey (SF-36).

Healed Plaques in Patients With Stable Angina Pectoris.

Objective: Healed plaques, signs of previous plaque destabilization, are frequently found in the coronary arteries. Healed plaques can now be diagnosed in living patients. We investigated the prevalence, angiographic, and optical coherence tomography features of healed plaques in patients with stable angina pectoris.

High-sensitivity cardiac troponin assays and acute coronary syndrome: a matter of sex?

: Advances in technology have led to an improvement in the ability to detect and quantify acute cardiomyocyte injury with the measurement of high-sensitivity cardiac troponin as compared with conventional assays. The upper reference limit for the high-sensitivity cardiac troponin assays is defined as the 99th percentile cutoff value in a healthy reference population. Since sex-related threshold levels of high-sensitivity cardiac troponin assays have been proposed, this review will focus on the diagnostic and prognostic implications of adopting sex-specific threshold troponin values in patients with a suspected acute coronary syndrome.

Free light chains a novel biomarker of cardiovascular disease. A pilot study.

Objective: Atherosclerosis and ischemic heart disease (IHD) are the major cause of morbidity and mortality but their inflammatory pathogenesis is still unclear. In this scenario, the role of serum free light chains (sFLC) has never been fully evaluated. The aim of the present study is to assess the clinical and pathogenetic role of sFLC in patients with IHD and to propose their use as a new biomarker for cardiovascular disease.

Correlation between CD4CD28 T lymphocytes, regulatory T cells and plaque rupture: An Optical Coherence Tomography study in Acute Coronary Syndromes.

Background: A sizeable proportion of patients with Acute Coronary Syndromes (ACS) shows a unique adaptive immune system profile, associated to a worse outcome, characterized by higher CD4CD28 T-cells, lower regulatory T-cells (Treg) and increased CD4CD28/Treg ratio. We sought to investigate the correlation between CD4CD28 T-cells, Treg, CD4CD28/Treg ratio and plaque phenotype as assessed by Optical Coherence Tomography (OCT).

Methods: Peripheral blood mononuclear cells (PBMC) were collected from 30 Non-ST Elevation Myocardial Infarction (NSTEMI) patients, sub-grouped according to OCT analysis of culprit lesions into two cohorts: Ruptured Fibrous Cap (NSTEMI-RFC, n = 12) and Intact Fibrous Cap (NSTEMI-IFC, n = 18).

MiR-21 role in aspirin-dependent PPARα and multidrug resistance protein 4 upregulation.

Background: A mechanism involved in high on-aspirin treatment residual platelet reactivity is platelet multidrug resistance protein 4 (MRP4) overexpression. Aspirin enhances platelet MRP4 expression with a PPARα-dependent mechanism and reduces miR-21 expression that, in turn, downregulates PPARα expression.

Objective: The aim of our study was to verify the relationship between miR-21 and MRP4-PPARα levels induced by aspirin treatment.

Platelet miRNA-26b down-regulates multidrug resistance protein 4 in patients on chronic aspirin treatment.

Background: Multidrug resistance protein-4 (MRP4) is an ATP binding cassette membrane transporter, actively involved in the efflux of important pharmacological and physiological molecules. Recently, its over-expression has been associated with reduced aspirin (ASA) efficacy after by-pass surgery. MicroRNAs (miRNAs) are small molecules of non-coding RNA involved in the regulation of many physiological and pathophysiological pathways, are abundant in platelets, and can be modulated by several drugs.

Inflammasome, T Lymphocytes and Innate-Adaptive Immunity Crosstalk: Role in Cardiovascular Disease and Therapeutic Perspectives.

Over the past few decades, lot of evidences have shown atherosclerosis as a chronic progressive disease with an exquisite inflammatory feature. More recently, the role of innate immune response in the onset and progression of coronary artery disease (CAD) and an adaptive immunity imbalance, mostly involving T cell sub-sets, have been documented. Therefore, like in many other inflammatory and autoimmune disorders, an altered innate-adaptive immunity crosstalk could represent the key of the inflammatory burden leading to atherosclerotic plaque formation and progression and to the breakdown of plaque stability.

Indoleamine 2,3-Dioxygenase (IDO) Enzyme Links Innate Immunity and Altered T-Cell Differentiation in Non-ST Segment Elevation Acute Coronary Syndrome.

Atherosclerosis is a chronic inflammatory disease characterized by a complex interplay between innate and adaptive immunity. Dendritic cells (DCs) play a key role in T-cell activation and regulation by promoting a tolerogenic environment through the expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme involved in tryptophan catabolism. IDO expression and activity was analyzed in monocytes derived DCs (MDDCs) from non-ST segment elevation myocardial infarction (NSTEMI) patients, stable angina (SA) patients and healthy controls (HC) by real-time quantitative polymerase chain reaction (RT-qPCR) before and after in vitro maturation with lipopolysaccharide (LPS).

Matrix metalloproteinase-9 might affect adaptive immunity in non-ST segment elevation acute coronary syndromes by increasing CD31 cleavage on CD4+ T-cells.

Aims: In patients with acute coronary syndrome (ACS), the higher activity of effector T-cells suggests that mechanisms involving adaptive immunity dysregulation might play a role in coronary instability. The shedding of the functional CD31 domain 1-5 leads to uncontrolled lymphocyte activation. In experimental models, matrix metalloproteinase-9 (MMP-9) has been implicated in endothelial CD31 cleavage.

Cardiovascular safety of non-steroidal anti-inflammatory drugs revisited.

Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used to treat inflammatory pain for decades. More recently, newer NSAIDs were developed to target the inducible isoform of cyclooxygenase (COX), COX-2, with the aim of reducing gastrointestinal toxicity. While the COX-2 selective inhibitors were effective in reducing pain and gastrointestinal harm, they soon were associated with an increased risk of adverse cardiovascular events.

Where Does Inflammation Fit?

Purpose Of Review: This review focuses on the complex relationship between inflammation and the onset of acute coronary syndrome and heart failure.

Recent Findings: In the last few years, two important lines of research brought new and essential information to light in the pathogenesis of acute coronary syndrome: a) the understanding of the immune mediate mechanisms of inflammation in Ischemic Heart Disease (IHD) and b) evidence that the inflammatory mechanisms associated with atherosclerosis and its complications can be modulated by anti-inflammatory molecules. A large amount of data also suggests that inflammation is a major component in the development and exacerbation of heart failure (HF), in a symbiotic relationship.

Atorvastatin inhibits the immediate-early response gene EGR1 and improves the functional profile of CD4+T-lymphocytes in acute coronary syndromes.

Background- Adaptive immune-response is associated with a worse outcome in acute coronary syndromes. Statins have anti-inflammatory activity beyond lowering lipid levels. We investigated the effects of ex-vivo and in-vivo atorvastatin treatment in acute coronary syndromes on CD4+T-cells, and the underlying molecular mechanisms.

Epicardial adipose tissue microbial colonization and inflammasome activation in acute coronary syndrome.

Background: Epicardial adipose tissue (EAT) has a close functional and anatomic relationship with epicardial coronary arteries. Accumulating evidence suggests that host microbiome alterations may play a role in several inflammatory/immune disorders, triggering a robust proinflammatory response also involving interleukin-1β (IL-1β) and the NALP3 inflammasome. In the current study, we explore the hypothesis that in patients with non-ST elevation acute coronary syndrome (ACS), EAT contains potentially pro-atherosclerotic bacteria that might elicit inflammasome activation.

Prevalence and Predictors of Multiple Coronary Plaque Ruptures: In Vivo 3-Vessel Optical Coherence Tomography Imaging Study.

Objective: Plaque rupture may be the local expression of a widespread coronary instability. This study aimed to investigate: (1) the prevalence and characteristics of nonculprit plaque rupture; (2) the pancoronary atherosclerotic phenotype in patients with and without nonculprit plaque rupture; and (3) the prevalence and predictors of multiple plaque ruptures.

Approach And Results: Six hundred and seventy-five nonculprit plaques from 261 patients (34 acute myocardial infarction, 73 unstable angina pectoris, and 154 stable angina pectoris) were analyzed by 3-vessel optical coherence tomography.

Comparative safety and effectiveness of coronary computed tomography: Systematic review and meta-analysis including 11 randomized controlled trials and 19,957 patients.

Background/objectives: The clinical approach to suspected or established coronary artery disease (CAD) has been revolutionized in the last few decades by coronary computed tomography (coroCT). Yet, uncertainty persists on its comparative diagnostic and clinical effectiveness. We conducted a systematic review on randomized controlled trials (RCTs) of coroCT.

Associations between the Framingham Risk Score and coronary plaque characteristics as assessed by three-vessel optical coherence tomography.

Objectives: This study sought to explore the association between the Framingham Risk Score (FRS) and coronary plaque characteristics assessed by optical coherence tomography (OCT) imaging.

Background: Clinical prediction models are useful for identifying high-risk patients. However, coronary events often occur in individuals estimated to be at low risk.

Which Aspirin Dose and Preparation Is Best for the Long-Term Prevention of Cardiovascular Disease and Cancer? Evidence From a Systematic Review and Network Meta-Analysis.

The evidence base on aspirin in primary prevention suggests that it can reduce significantly the risk of cardiovascular disease (CVD) events and cancer, especially colorectal, albeit increasing bleeding. There is, however, uncertainty on the optimal aspirin dose and preparation for primary prevention. We thus aimed to review main sources of evidence informing on daily dosage and preparation of aspirin for primary prevention of CVD and cancer.