Pentraxin 3 (PTX3) plays cardioprotective and anti-atherogenic roles in murine models. PTX3 blood levels raise during early acute myocardial infarction (AMI). Neutrophils from healthy subjects physiologically contain PTX3 in secondary (also called specific) granules. In this study, we report that circulating neutrophils release preformed PTX3 in the early phase of AMI (within 6 h from the onset of clinical symptoms). Depletion of intracellular PTX3 correlates with increased plasma levels and with platelet–neutrophil heterotypic aggregates. Neutrophil PTX3 returns to normal values 48 h after the onset of symptoms; concentration does not vary in matched healthy controls or in patients with chronic stable angina. In vitro, recognition of activated P-selectin+ platelets causes the formation of neutrophil–platelet heteroaggregates and the release of neutrophil PTX3. Purified or membrane-bound P-selectin triggers PTX3 release from resting neutrophils. Released PTX3 binds to activated platelets in vitro. Moreover, PTX3 binds to a substantial fraction of platelets from patients in the circulating blood. PTX3-bound activated platelets have a reduced ability to 1) form heterotypic aggregates with neutrophils and monocytes; 2) activate neutrophils, as evaluated assessing the upregulation of leukocyte β2 integrins; 3) aggregate with other platelets; and 4) bind to fibrinogen. Our results suggest that neutrophils early release prestored PTX3 in patients undergoing AMI. PTX3 binds to activated circulating platelets and dampens their proinflammatory and prothrombotic action, thus possibly contributing to its cardioprotective effects.

BackgroundNeutrophils are involved in thrombus formation. We investigated whether specific features of neutrophil activation characterize patients with acute coronary syndromes (ACS) compared to stable angina and to systemic inflammatory diseases.Methods and FindingsThe myeloperoxidase (MPO) content of circulating neutrophils was determined by flow cytometry in 330 subjects: 69 consecutive patients with acute coronary syndromes (ACS), 69 with chronic stable angina (CSA), 50 with inflammation due to either non-infectious (acute bone fracture), infectious (sepsis) or autoimmune diseases (small and large vessel systemic vasculitis, rheumatoid arthritis). Four patients have also been studied before and after sterile acute injury of the myocardium (septal alcoholization). One hundred thirty-eight healthy donors were studied in parallel. Neutrophils with normal MPO content were 96% in controls, >92% in patients undergoing septal alcoholization, 91% in CSA patients, but only 35 and 30% in unstable angina and AMI (STEMI and NSTEMI) patients, compared to 80%, 75% and 2% of patients with giant cell arteritis, acute bone fracture and severe sepsis. In addition, in 32/33 STEMI and 9/21 NSTEMI patients respectively, 20% and 12% of neutrophils had complete MPO depletion during the first 4 hours after the onset of symptoms, a feature not observed in any other group of patients. MPO depletion was associated with platelet activation, indicated by P-selectin expression, activation and transactivation of leukocyte β2-integrins and formation of platelet neutrophil and -monocyte aggregates. The injection of activated platelets in mice produced transient, P-selectin dependent, complete MPO depletion in about 50% of neutrophils.ConclusionsACS are characterized by intense neutrophil activation, like other systemic inflammatory syndromes. In the very early phase of acute myocardial infarction only a subpopulation of neutrophils is massively activated, possibly via platelet-P selectin interactions. This paroxysmal activation could contribute to occlusive thrombosis.

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Myocardial ischaemia results from a direct mismatch between oxygen supply and demand, commonly arising as a result of coronary atherosclerosis, microvascular dysfunction or acute thrombosis and luminal obstruction. However, transient ischaemia may also occur due to coronary spasm leading to acute and unexpected myocardial ischaemia without obvious visible coronary pathology. Aside from symptoms of chest pain, coronary spasm can cause infarction, LV impairment, promote life threatening arrhythmias and ultimately sudden cardiac death. While therapeutic options are available, controversies exist around diagnosis, pathology, management and prognosis. This review summarises some of the common questions in this area. In particular we explore and discuss the available evidence for the pharmacological treatment of coronary spasm, and strategies for identification and management of very high risk patients to try and reduce the incidence of sudden premature death.

AimsThe prognostic role of tricuspid regurgitation (TR) associated with organic left-sided valvular heart disease is well known. However, no data are available regarding the prognostic value of functional TR (FTR) in patients with functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction. The purpose of this study was to evaluate the prognostic role of FTR for occurrence of heart failure (HF) and mortality in patients with FMR. Methods and resultsWe enrolled 373 consecutive patients (mean age 68 + 11 years) with LV dysfunction and at least mild FMR and with or without FTR, both quantitated by echocardiography. The median follow-up was 32 months (range 1-120 months); 132 (35.4%) and 97 patients developed HF or died, respectively. The incidence of HF at 3 and 6 years was 36 + 2% and 55 + 4%, respectively. Moderate to severe FTR [hazard ratio (HR) 1.4, 95% confidence interval (CI) 1.1-2.1, P ¼ 0.01) was an independent determinant of HF. The incidence of HF was 41 + 5, 46 + 7, 57 + 7, and 65 + 8% for patients without, and with mild, moderate, and severe FTR respectively (P ¼ 0.03). At 3 and 6 years the survival free of all-cause mortality was 77.5 + 2% and 60 + 3%, respectively. Moderate to severe FTR (HR 1.6, 95% CI 1.2-2.1, P ¼ 0.01) was an independent determinant of overall mortality. At 6 years, survival free of all-cause mortality was 69 + 2.5, 67 + 2.1, 51 + 2.5, and 40 + 4.8% for patients without, and with mild, moderate, and severe FTR, respectively (P ¼ 0.004). ConclusionsModerate or more FTR is independently associated with worse survival and a high incidence of HF episodes in patients with FMR.--

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cute chest pain or anginal equivalents associated with mild troponin rise remain a diagnostic challenge, particularly in patients at low to intermediate risk for acute coronary syndrome. Coronary CT angiography can be used to safely triage these patients (1,2). In previous large multicenter trials with participants with acute chest pain at low to intermediate pretest risk of acute coronary syndrome, coronary CT angiography was associated with higher detection of coronary artery disease (CAD) (3), shorter length of stay (3,4), and higher rate of discharge (3,4) compared with the standard of care, without an increase in major adverse events at 28 days (4) and at a longer follow-up (5). Acute aortic syndrome, pulmonary embolism, and CAD can be simultaneously ruled out with use of a triple-rule-out (TRO) CT protocol (6,7). However, a TRO CT study cannot help identify nonvascular causes of acute myocardial injury (8). In patients with troponin-positive acute chest pain and unobstructed coronary arteries, cardiac MRI was found to provide a diagnosis in 74%-95% (9-12), identifying myocarditis, takotsubo cardiomyopathy, and myocardial infarction with nonobstructed coronary arteries as the most frequent causes of symptoms and alteration in cardiac biologic markers (10-12). Cardiac MRI was found to change the Background: Acute chest pain with mild troponin rise and inconclusive diagnosis after clinical evaluation represents a diagnostic challenge. Triple-rule-out (TRO) CT may exclude coronary artery disease (CAD), as well as acute aortic syndrome and pulmonary embolism, but cannot help identify other causes of myocardial injury.Purpose: To investigate the diagnostic value of a comprehensive CT protocol including both an angiographic and a late contrast enhancement (LCE) scan in participants with troponin-positive acute chest pain. Materials and Methods:In this prospective study, consecutive patients with troponin-positive acute chest pain or anginal equivalent and inconclusive diagnosis after clinical evaluation (symptoms, markers, electrocardiography, and echocardiography) who underwent TRO CT between June 2018 and September 2020 were enrolled. TRO CT was performed to evaluate the presence of obstructive CAD (stenosis 50%), acute aortic syndrome, and pulmonary embolism. If the findings on the TRO CT scan were negative, an LCE CT scan was acquired after 10 minutes to assess the presence and pattern of scar and quantify the myocardial extracellular volume fraction. CT-based diagnoses were compared with diagnoses obtained with reference standard methods, including invasive coronary angiography, cardiac MRI, and endomyocardial biopsy.Results: Eighty-four patients (median age, 69 years [interquartile range, 50-77 years]; 45 men) were enrolled. TRO CT helped identify obstructive CAD in 35 participants (42%), acute aortic syndrome in one (1.2%), and pulmonary embolism in six (7.1%). LCE CT scans were acquired in the remaining 42 participants. The following diagnoses were reached with use of LCE CT: myocarditis (22 of 42 partici...

BACKGROUND Left main coronary artery (LMCA) disease treatment is traditionally surgical in most cases. Continuous improvement of devices and the emergence of drug-eluting stents (DES) has increased indications of percutaneous treatment in these high-risk lesions. The main objective of this study was to evaluate the efficacy and safety of percutaneous coronary intervention (PCI) with DES on LMCA at a 10 year follow-up. METHODSWe prospectively included 324 patients (69.53 AE 12.60 years, 73.4% male) with severe LMCA disease undergoing PCI from June 2006 to April 2015. We evaluated major cardiovascular events defined as cardiac death, nonfatal myocardial infarction, target lesion revascularization (RLT) and stent thrombosis after long-term clinical follow-up (median 41.5 months).