[The healed plaque: tale of a story with good ending - with practical implications]. / La placca guarita: racconto di una storia a lieto fine, con implicazioni pratiche.

Acute coronary syndromes have heterogeneous clinical presentations, features and prognosis. They can also occur without angiographic evidence of significant coronary artery stenosis, based on multiple causes. We report on the diagnostic and therapeutic management of a 56-year-old man with an acute coronary syndrome and angiographic evidence of non-obstructive coronary artery disease. In addition to the basic angiographic evaluation, intracoronary imaging was here helpful to understand the underlying mechanism, prompting a tailored therapeutic strategy and avoiding inappropriate treatment with percutaneous coronary intervention and stenting. This clinical case here described offers the opportunity to briefly recapitulate the most meaningful milestones in the progress in the pathophysiology of acute coronary syndromes, also focusing on myocardial infarction non-obstructive coronary artery, and to appreciate the occurrence of rare cases and consequent lessons.

Isolated Exercise-Induced Pulmonary Hypertension Associates with Higher Cardiovascular Risk in Scleroderma Patients.

BACKGROUND AND AIM: Isolated exercise-induced pulmonary hypertension (ExPH) associates with cardiovascular (CV) events in patients with left heart disease. We investigated its prognostic significance in scleroderma patients at risk for pulmonary arterial hypertension (PAH). METHODS: In 26 consecutive scleroderma female patients with either low (n = 13) or intermediate probability (n = 13) of pulmonary hypertension (PH) at rest, we evaluated, both at time 0 and 1 year, prognostic determinants of CV risk: onset or progression of heart failure/syncope; worsening of functional class; functional performance at the 6-minute walking test and at cardiopulmonary exercise test; right atrial area; and pericardial effusion. We assigned a severity score 1-3 to each prognostic determinant, derived an overall CV risk score, and its 0-1 year change. Isolated ExPH during the cardiopulmonary exercise test (CPET) was defined as absence of PH at rest, reduced peak VO2, VE/VCO2 >30 at anaerobic threshold, reduced O2 pulse, and ΔVO2/ΔW <9 mL/min/W. We then correlated ExPH at time 0 with clinical worsening (risk score increase >20% after 1 year). RESULTS: ExPH was strongly associated with clinical worsening compared to patients without ExPH (p = 0.005). In patients without ExPH, none had > 20% increased CV risk score after 1 year. Conversely, about 50% of patients with ExPH had such an increase, suggesting a worsening of prognosis. CONCLUSIONS: Isolated ExPH associates with higher cardiovascular risk and thus clinical worsening in scleroderma patients. The assessment of ExPH by CPET can thus contribute to a better risk stratification and the planning of a more adequate follow-up.

[Management of acute coronary syndromes in the Abruzzi Region in Italy. Abruzzi Inter-societary Consensus Document.] / La gestione delle sindromi coronariche acute in Abruzzo 2016. Documento di Consenso Intersocietario Regione Abruzzo.

Consensus documents allow on the one hand the stardardization of therapeutic interventions to allow patients to receive the best possible treatments, but also imply practical choices, which reduce decision uncertainties and the often too many therapeutic options, possible source of errors. This standardization implies a necessary simplification of therapeutic options facing the complexity and multiplicity of clinical presentations. However, the risk of an over-simplification is smaller than to allow arbitrary treatments, which have dominated Medicine in the absence of evidences. With the publication of this document, the writing group of authors and the cardiologists who have agreed on it specifically intend to limit arbitrary therapeutic choices and to spread the culture of evidence-based medicine, operating choices to allow simplification of treatments and a trend towards cost containment. They also privilege "traditional" choices whenever more expensive and innovative strategies are not adequately supported by efficacy or safety evidences.

Association between prostaglandin E receptor subtype EP4 overexpression and unstable phenotype in atherosclerotic plaques in human.

OBJECTIVE: We recently demonstrated that inducible cyclooxygenase/PGE synthase-1 (COX-2/mPGES-1) are overexpressed in symptomatic plaques in association with PGE2-dependent metalloproteinase (matrix metalloproteinase [MMP]) biosynthesis and plaque rupture. However, it is not known which of the 4 PGE2 receptors (EP1-4) mediates macrophage metalloproteinase generation. The aim of this study was to characterize EP1-4 expression in plaques from symptomatic and asymptomatic patients undergoing carotid endarterectomy and correlate it with the extent of inflammatory infiltration, COX-2/mPGES-1 and MMP expression and clinical features of patients' presentation. METHODS AND RESULTS: Plaques were analyzed for COX-2, mPGES-1, EP1-4, MMP-2, and MMP-9 by immunohistochemistry, reverse-transcription polymerase chain reaction and Western blot; zymography was used to detect MMP activity. We observed strong EP4 immunoreactivity, only very weak staining for EP2, and no expression of EP1 and EP3 in atherosclerotic plaques. EP4 was more abundant in MMP-rich symptomatic lesions, whereas EP2 was no different between symptomatic and asymptomatic plaques. Finally, MMP induction by PGE2 in vitro was inhibited by the EP4 antagonist L-161 982, but not by its inactive analog L-161 983 or by the EP2 antagonist AH6809. CONCLUSIONS: This study shows that EP4 overexpression is associated with enhanced inflammatory reaction in atherosclerotic plaques. This effect might contribute to plaque destabilization by inducing culprit metalloproteinase expression.

Unexplained Cardiac Arrest After Near Drowning in a Young Experienced Swimmer: Insight from Cardiovascular Magnetic Resonance Imaging.

Cardiac magnetic resonance imaging (cMRI) is a well-established noninvasive imaging modality in clinical cardiology. Its ability to provide tissue characterization make it well suited for the study of patients with cardiac diseases. We describe a multi-modality imaging evaluation of a 45-year-old man who experienced a near drowning event during swimming. We underline the unique capability of tissue characterization provided by cMRI, which allowed detection of subtle, clinically unrecognizable myocardial damage for understanding the causes of sudden cardiac arrest and also showed the small damages caused by cardiopulmonary resuscitation.

Preprocedural level of soluble CD40L is predictive of enhanced inflammatory response and restenosis after coronary angioplasty.

BACKGROUND: Inflammation plays a pathogenic role in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). CD40-CD40L interaction is involved in the pathogenesis of atherosclerosis; however, its role in the pathophysiology of restenosis is still unclear. We tested the hypothesis that soluble CD40L (sCD40L) may be involved in the process of restenosis and that it exerts its effect by triggering a complex group of inflammatory reactions on endothelial and mononuclear cells. METHODS AND RESULTS: We studied 70 patients who underwent PTCA and who had repeated angiograms at 6-month follow-up. Plasma sCD40L was measured before and 1, 5, 15, and 180 days after PTCA, whereas plasma soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin, and monocyte chemoattractant protein (MCP)-1 were measured before and 24 hours after PTCA. Furthermore, the release of adhesion molecules and MCP-1 and the ability to repair an injury in endothelial cells, as well as the generation of O2- in monocytes, were analyzed in vitro after stimulation with serum from patients or healthy control subjects. Restenosis occurred in 18 patients (26%). Restenotic patients had preprocedural sCD40L significantly higher than patients with favorable outcomes (2.13+/-0.3 versus 0.87+/-0.12 ng/mL, P<0.0001). Elevated sCD40L at baseline was significantly correlated with adhesion molecules and MCP-1 generation after PTCA and with lumen loss at 6-month follow-up. Furthermore, high sCD40L was directly associated in vitro with adhesion molecules and MCP-1 generation and impaired migration in endothelial cells and with enhanced O2- generation in monocytes. CONCLUSIONS: We conclude that increased sCD40L is associated with late restenosis after PTCA. This may provide an important biochemical link between restenosis and aspirin-insensitive platelet activation. These results provide a rationale for studies with new antiplatelet treatments in patients who underwent PTCA.

Circulating myeloid-related protein-8/14 is related to thromboxane-dependent platelet activation in patients with acute coronary syndrome, with and without ongoing low-dose aspirin treatment.

BACKGROUND: Platelet activation is involved in acute coronary syndromes (ACS). Incomplete suppression by low-dose aspirin treatment of thromboxane (TX) metabolite excretion (urinary 11-dehydro-TXB2) is predictive of vascular events in high-risk patients. Myeloid-related protein (MRP)-8/14 is a heterodimer secreted on activation of platelets, monocytes, and neutrophils, regulating inflammation and predicting cardiovascular events. Among platelet transcripts, MRP-14 has emerged as a powerful predictor of ACS. METHODS AND RESULTS: We enrolled 68 stable ischemic heart disease (IHD) and 63 ACS patients, undergoing coronary angiography, to evaluate whether MRP-8/14 release in the circulation is related to TX-dependent platelet activation in ACS and IHD patients and to residual TX biosynthesis in low-dose aspirin-treated ACS patients. In ACS patients, plasma MRP-8/14 and urinary 11-dehydro-TXB2 levels were linearly correlated (r=0.651, P<0.001) but significantly higher than those in IHD patients (P=0.012, P=0.044) only among subjects not receiving aspirin. In aspirin-treated ACS patients, MRP-8/14 and 11-dehydro-TXB2 were lower versus those not receiving aspirin (P<0.001) and still significantly correlated (r=0.528, P<0.001). Higher 11-dehydro-TXB2 significantly predicted higher MRP-8/14 in both all ACS patients and ACS receiving aspirin (P<0.001, adj R(2)=0.463 and adj R(2)=0.497) after multivariable adjustment. Conversely, plasma MRP-8/14 (P<0.001) and higher urinary 8-iso-prostaglandin F2α (P=0.050) levels were significant predictors of residual, on-aspirin, TX biosynthesis in ACS (adjusted R(2)=0.384). CONCLUSIONS: Circulating MRP-8/14 is associated with TX-dependent platelet activation in ACS, even during low-dose aspirin treatment, suggesting a contribution of residual TX to MRP-8/14 shedding, which may further amplify platelet activation. Circulating MRP-8/14 may be a target to test different antiplatelet strategies in ACS.

[Unusual thrombus embolization during primary coronary angioplasty: a case report]. / Embolizzazione poco usuale del trombo durante angioplastica primaria: caso clinico.

Embolization of thrombotic material during primary angioplasty may occur even if the procedure is performed with appropriate medication as well as in hospital centers having a high volume of procedures. Over recent years the introduction of mechanical devices for thromboaspiration and/or distal protection have reduced the incidence of embolization thus improving myocardial reperfusion and survival. We report the case of a large thrombus migrated from the proximal left circumflex artery to the proximal left anterior descending artery during balloon inflation. In our opinion, the cause was retrograde expulsion of the thrombus by the deploying balloon.

An innocent bystander: a case of unstable angina.

We describe an usual case of unstable angina, with an unusual presentation, trying to demonstrate the importance to listen to our patients and their symptoms.

Feasibility and long-term safety of elective Impella-assisted high-risk percutaneous coronary intervention: a pilot two-centre study.

OBJECTIVE: We evaluated the acute and long-term results of the use of a new intracardiac microaxial pump, the Impella Recover LP 2.5, during elective high-risk percutaneous coronary interventions in a two-centre registry. METHODS: Ten consecutive patients with poor left ventricular function and multivessel or left main coronary artery disease were considered at high risk of haemodynamic compromise and underwent percutaneous coronary interventions with preintervention Impella implantation. Procedural complications, 30-day and 12-month clinical outcome were recorded. Left ventricular ejection fraction was assessed by echocardiography before procedure and after at least 6 months. RESULTS: The Impella was implanted before percutaneous coronary interventions by femoral approach and percutaneous coronary interventions were successfully performed (by contra lateral femoral or radial approach) in all cases. After percutaneous coronary intervention, Impella was removed in all patients, and haemostasis was obtained by prolonged manual compression or by double suture device preimplantation technique. No access-site complication was observed and no patient required transfusions. One patient died after Impella removal due to acute stent thrombosis. The other patients had an uncomplicated in-hospital course and were discharged within 5 days. At 1-year follow-up, no patient died nor suffered acute myocardial infarction, whereas two patients underwent re-percutaneous coronary intervention. Left ventricular ejection fraction at follow-up increased significantly in this study population (from 31 +/- 7% to 41% +/- 13%, P = 0.02). CONCLUSION: Our results support the feasibility and safety of Impella-assisted percutaneous coronary intervention in high-risk patients. Prospective randomized trials are needed to test the clinical impact of such an innovative approach.