[The organisation of outpatient medical and nursing clinics for the follow-up of patients after hospitalization for a myocardial infarction or heart failure]. / L'organizzazione di ambulatori medico-infermieristici sul territorio per il follow-up dei pazienti dopo un ricovero per infarto miocardico o scompenso cardiaco.

. The organisation of outpatient medical and nursing clinics for the follow-up of patients after hospitalization for a myocardial infarction or heart failure. INTRODUCTION: Guidelines suggest careful monitoring of patients after acute heart failure (AHF) or acute myocardial infarction (AMI). OBJECTIVE: To describe the implementation of the 'accompanied discharge' (DIMACC) pathway for patients admitted for AHF or AMI in the Cardiology Department of the Pio XI hospital in Desio, and to evaluate its feasibility. METHODS: The DIMACC pathway was built following the recommendations of international guidelines and with the involvement of all the actors. RESULTS: At discharge, the health objectives to be achieved are defined, and outpatient visits during the first year after hospitalization in the District outpatient clinics with the cardiology doctor and family nurses are booked. The patient stays in the outpatient clinic about 1.5 hours to complete at first, in half an hour, questionnaires on measures, symptoms, adherence, quality of life; then, to receive the nursing visit lasting half an hour for the assessment of the questionnaires, measurement of clinical parameters and counseling; and finally, to be visited by the cardiologist. During the pilot phase (6 months of recruitment and 1 year of follow-up) 168 patients (129 AMI and 39 AHF) followed the pathway: 4 (2.4%) patients died during the follow-up, 14 (8.3%) abandoned the pathway and 150 (89.3%) completed it. CONCLUSIONS: The implementation of the DIMACC pathway required an investment of time (about a year) and resources but the follow-up is feasible. The next phase will be the evaluation of the patient outcomes.

Outcomes Related to Antiplatelet Therapy in a High-Risk ST-Segment Elevation Myocardial Infarction Population: A Retrospective Real-World Analysis of an Italian ECMO Center.

AIM: To evaluate outcomes related to antiplatelet therapy in patients with ST-elevation myocardial infarction (STEMI) admitted to the San Gerardo Hospital in Monza, an extracorporeal membrane oxygenation (ECMO) reference center in the Monza-Brianza area. METHODS: This retrospective study enrolled patients with STEMI hospitalized between 2013 and 2017. RESULTS: This study included 653 patients (mean age: 67.5 years, 71% male). Across the study period, ticagrelor use showed consistent increases, from 22% of patients during 2013 to 85% in 2017. Cardiac arrest prehospitalization occurred in 100 patients (15.3%), either at home (n = 85, 13.0%) or during transfer (n = 15, 2.3%); 46 patients underwent ECMO for refractory cardiac arrest. Rates of 90-day survival (hazard ratio [HR]: 2.4, 95% confidence interval [CI]: 1.3-4.4, P = .004) and ST resolution (odds ratio [OR]: 2.5, 95% CI: 1.6-4.1, P = .000) were higher with ticagrelor than with other antiplatelet agents. When analyzed by each agent, patients on ticagrelor had longer survival (HR: 0.4, 95% CI: 0.2-0.8, P = .008) than patients on clopidogrel and more frequent ST resolution than those on clopidogrel or prasugrel (OR: 0.4, 95% CI: 0.2-0.7, P = .002 and OR: 0.4, 95% CI: 0.2-0.7, P = .006). There was no difference in mortality between ticagrelor and prasugrel. CONCLUSIONS: Changes in the treatment of high-risk patients with STEMI over time are in line with changes in treatment guidelines. In these patients, ticagrelor is associated with significantly improved 90-day mortality compared with clopidogrel.

The hidden hypothesis: A disseminated tuberculosis case.

CASE PRESENTATION: 77-year-old former smoker admitted because of fatigue and abdominal distention. Past medical history positive for two previous hospitalizations for pericardial and pleural effusions (no diagnosis achieved). At admission erythrocyte sedimentation rate was 122mm per hour. Baseline investigations revealed ascitic, pleural and pericardial effusion. Effusions were tapped: neoplastic cells and acid-fast bacilli (AFB) were not identified, aerobic and mycobacterial culture resulted negative. QuantiFERON TB-Gold test was negative. Total body PET-CT and autoimmunity panel were negative. A neoplastic process was considered the most likely explanation. Before signing off the patient to comfort care, a reassessment was performed and an exposure to tuberculosis during childhood was documented. Because of constrictive pericarditis, pericardiectomy was performed: histologic examination showed chronic pericardial inflammation without granulomas, but Ziehl-Neelsen stain identified AFB and PCR was positive for Mycobacterium tuberculosis complex. Patient was started on anti-TB therapy with resolution of the effusions in the following months. Genes associated with defects in innate immunity were sequences and dentritic cells were studied, but no alterations were identified. DISCUSSION: A Bayesian approach to clinical decision making should be recommended. Interpretation of diagnostic tests should take into account the imperfect diagnostic performance of the majority of these tests. Further studies to investigate genetic susceptibility to tuberculosis are needed.

G-CSF for Extensive STEMI.

RATIONALE: In the exploratory Phase II STEM-AMI (Stem Cells Mobilization in Acute Myocardial Infarction) trial, we reported that early administration of G-CSF (granulocyte colony-stimulating factor), in patients with anterior ST-segment-elevation myocardial infarction and left ventricular (LV) dysfunction after successful percutaneous coronary intervention, had the potential to significantly attenuate LV adverse remodeling in the long-term. OBJECTIVE: The STEM-AMI OUTCOME CMR (Stem Cells Mobilization in Acute Myocardial Infarction Outcome Cardiac Magnetic Resonance) Substudy was adequately powered to evaluate, in a population showing LV ejection fraction ≤45% after percutaneous coronary intervention for extensive ST-segment-elevation myocardial infarction, the effects of early administration of G-CSF in terms of LV remodeling and function, infarct size assessed by late gadolinium enhancement, and myocardial strain. METHODS AND RESULTS: Within the Italian, multicenter, prospective, randomized, Phase III STEM-AMI OUTCOME trial, 161 ST-segment-elevation myocardial infarction patients were enrolled in the CMR Substudy and assigned to standard of care (SOC) plus G-CSF or SOC alone. In 119 patients (61 G-CSF and 58 SOC, respectively), CMR was available at baseline and 6-month follow-up. Paired imaging data were independently analyzed by 2 blinded experts in a core CMR lab. The 2 groups were similar for clinical characteristics, cardiovascular risk factors, and pharmacological treatment, except for a trend towards a larger infarct size and longer symptom-to-balloon time in G-CSF patients. ANCOVA showed that the improvement of LV ejection fraction from baseline to 6 months was 5.1% higher in G-CSF patients versus SOC (P=0.01); concurrently, there was a significant between-group difference of 6.7 mL/m2 in the change of indexed LV end-systolic volume in favor of G-CSF group (P=0.02). Indexed late gadolinium enhancement significantly decreased in G-CSF group only (P=0.04). Moreover, over time improvement of global longitudinal strain was 2.4% higher in G-CSF patients versus SOC (P=0.04). Global circumferential strain significantly improved in G-CSF group only (P=0.006). CONCLUSIONS: Early administration of G-CSF exerted a beneficial effect on top of SOC in patients with LV dysfunction after extensive ST-segment-elevation myocardial infarction in terms of global systolic function, adverse remodeling, scar size, and myocardial strain. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01969890.

Linking cell function with perfusion: insights from the transcatheter delivery of bone marrow-derived CD133+ cells in ischemic refractory cardiomyopathy trial (RECARDIO).

BACKGROUND: Cell therapy with bone marrow (BM)-derived progenitors has emerged as a promising therapeutic for refractory angina (RA) patients. In the present study, we evaluated the safety and preliminary efficacy of transcatheter delivery of autologous BM-derived advanced therapy medicinal product CD133+ cells (ATMP-CD133) in RA patients, correlating perfusion outcome with cell function. METHODS: In the phase I "Endocavitary Injection of Bone Marrow Derived CD133+ Cells in Ischemic Refractory Cardiomyopathy" (RECARDIO) trial, a total of 10 patients with left ventricular (LV) dysfunction (ejection fraction ≤ 45%) and evidence of reversible ischemia, as assessed by single-photon emission computed tomography (SPECT), underwent BM aspiration and fluoroscopy-based percutaneous endomyocardial delivery of ATMP-CD133. Patients were evaluated at 6 and 12 months for safety and preliminary efficacy endpoints. ATMP-CD133 samples were used for in vitro correlations. RESULTS: Patients were treated safely with a mean number of 6.57 ± 3.45 ×  106 ATMP-CD133. At 6-month follow-up, myocardial perfusion at SPECT was significantly ameliorated in terms of changes in summed stress (from 18.2 ± 8.6 to 13.8 ± 7.8, p = 0.05) and difference scores (from 12.0 ± 5.3 to 6.1 ± 4.0, p = 0.02) and number of segments with inducible ischemia (from 7.3 ± 2.2 to 4.0 ± 2.7, p = 0.003). Similarly, Canadian Cardiovascular Society and New York Heart Association classes significantly improved at follow-up vs baseline (p ≤ 0.001 and p = 0.007, respectively). Changes in summed stress score changes positively correlated with ATMP-CD133 release of proangiogenic cytokines HGF and PDGF-bb (r = 0.80, p = 0.009 and r = 0.77, p = 0.01, respectively) and negatively with the proinflammatory cytokines RANTES (r = - 0.79, p = 0.01) and IL-6 (r = - 0.76, p = 0.02). CONCLUSION: Results of the RECARDIO trial suggested safety and efficacy in terms of clinical and perfusion outcomes in patients with RA and LV dysfunction. The observed link between myocardial perfusion improvements and ATMP-CD133 secretome may represent a proof of concept for further mechanistic investigations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02059681 . Registered 11 February 2014.

Effects of extracorporeal cardiopulmonary resuscitation on neurological and cardiac outcome after ischaemic refractory cardiac arrest.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation is increasingly recognised as a rescue therapy for refractory cardiac arrest, nevertheless data are scanty about its effects on neurologic and cardiac outcome. The aim of this study is to compare clinical outcome in patients with cardiac arrest of ischaemic origin (i.e. critical coronary plaque during angiography) and return of spontaneous circulation during conventional cardiopulmonary resuscitation vs refractory cardiac arrest patients needing extracorporeal cardiopulmonary resuscitation. Moreover, we tried to identify predictors of survival after successful cardiopulmonary resuscitation. METHODS: We enrolled 148 patients with ischaemic cardiac arrest admitted to our hospital from 2011-2015. We compared clinical characteristics, cardiac arrest features, neurological and echocardiographic data obtained after return of spontaneous circulation (within 24 h, 15 days and six months). RESULTS: Patients in the extracorporeal cardiopulmonary resuscitation group ( n=63, 43%) were younger (59±9 vs 63±8 year-old, p=0.02) with lower incidence of atherosclerosis risk factors than those with conventional cardiopulmonary resuscitation. In the extracorporeal cardiopulmonary resuscitation group, left ventricular ejection fraction was lower than conventional cardiopulmonary resuscitation at early echocardiography (19±16% vs 37±11 p<0.01). Survivors in both groups showed similar left ventricular ejection fraction 15 days and 4-6 months after cardiac arrest (46±8% vs 49±10, 47±11% vs 45±13%, p not significant for both), despite a major extent and duration of cardiac ischaemia in extracorporeal cardiopulmonary resuscitation patients. At multivariate analysis, the total cardiac arrest time was the only independent predictor of survival. CONCLUSIONS: Extracorporeal cardiopulmonary resuscitation patients are younger and have less comorbidities than conventional cardiopulmonary resuscitation, but they have worse survival and lower early left ventricular ejection fraction. Survivors after extracorporeal cardiopulmonary resuscitation have a neurological outcome and recovery of heart function comparable to subjects with return of spontaneous circulation. Total cardiac arrest time is the only predictor of survival after cardiopulmonary resuscitation in both groups.

Role of microRNAs in doxorubicin-induced cardiotoxicity: an overview of preclinical models and cancer patients.

Cardiotoxicity is a well-known side effect of doxorubicin (DOX), but the mechanisms leading to this phenomenon are still not completely clear. Prediction of drug-induced dysfunction onset is difficult and is still largely based on detection of cardiac troponin (cTn), a circulating marker of heart damage. In the last years, several investigations focused on the possible involvement of microRNAs (miRNAs) in DOX-induced toxicity in vitro, with contrasting results. Recently, several groups employed animal models to mimic patient's condition, investigate the biological pathways perturbed by DOX, and identify diagnostic markers of cardiotoxicity. We reviewed the results from several studies investigating cardiac miRNAs expression in rodent models of DOX-treatment. We also discussed the data from two publications indicating the possible use of circulating miRNA as biomarkers of DOX-induced cardiotoxicity. Unfortunately, limited information was derived from these studies, as selection methods of candidate-miRNAs and heterogeneity in cardiotoxicity assessment greatly hampered the novelty and robustness of the findings. Nevertheless, at least one circulating miRNA, miR-1, showed a good potential as early biomarker of drug-mediated cardiac dysfunction onset. The use of animal models to investigate DOX-induced cardiotoxicity surely helps narrowing the gap between basic research and clinical practice. Despite this, several issues, including selection of relevant miRNAs and less-than-optimal assessment of cardiotoxicity, greatly limited the results obtained so far. Nonetheless, the association of patients-based studies with the use of preclinical models may be the key to address the many unanswered questions regarding the pathophysiology and early detection of cardiotoxicity.

Sacubitril/Valsartan in "Field Practice" Patients with Advanced Heart Failure: A Monocentric Italian Experience.

Patients with advanced heart failure (HF) experience a continuous decline in quality of life and have a very poor prognosis. Moreover, due to numerous comorbidities present in these patients, transplantation and left ventricular assist devices are usually impracticable in clinical practice. In this challenging setting, administration of inotropic agents may be the only possible therapy; however, this treatment requires frequent hospitalizations. Our hypothesis is that sacubitril/valsartan, given its marked efficacy and manageability, can be safely used in clinical practice in this setting, potentially reducing hospitalizations and the need for inotropic support. We report here our experience in a small series of patients with advanced HF treated with sacubitril/valsartan.

Cell Therapy for Refractory Angina: A Reappraisal.

Cardiac cell-based therapy has emerged as a novel therapeutic option for patients dealing with untreatable refractory angina (RA). However, after more than a decade of controlled studies, no definitive consensus has been reached regarding clinical efficacy. Although positive results in terms of surrogate endpoints have been suggested by early and phase II clinical studies as well as by meta-analyses, the more recent reports lacked the provision of definitive response in terms of hard clinical endpoints. Regrettably, pivotal trials designed to conclusively determine the efficacy of cell-based therapeutics in such a challenging clinical condition are therefore still missing. Considering this, a comprehensive reappraisal of cardiac cell-based therapy role in RA seems warranted and timely, since a number of crucial cell- and patient-related aspects need to be systematically analysed. As an example, the large variability in efficacy endpoint selection appears to be a limiting factor for the advancement of cardiac cell-based therapy in the field. This review will provide an overview of the key elements that may have influenced the results of cell-based trials in the context of RA, focusing in particular on the understanding at which the extent of angina-related endpoints may predict cell-based therapeutic efficacy.

Right ventricular reverse remodelling in Idiopathic Pulmonary Arterial Hypertension diagnosed during pregnancy: Is it possible?

We present a case of a 36-year-old woman who developed a severe form of Idiopathic Pulmonary Arterial Hypertension (IPAH) during pregnancy and after emergency delivery. The management of IPAH during or after pregnancy is complex. Due to the severity of her IPAH, an upfront triple combination therapy, including i.v. epoprostenol, was started. The rapid institution of this treatment regimen allowed a complete right ventricular reverse remodelling after 1 year of therapy, leading to a down-titration until complete suspension of epoprostenol from the treatment regimen.

BM ageing: Implication for cell therapy with EPCs.

The bone marrow (BM) is a well-recognized source of stem/progenitor cells for cell therapy in cardiovascular diseases (CVDs). Preclinical and clinical studies suggest that endothelial progenitor cells (EPCs) contribute to reparative process of vascular endothelium and participate in angiogenesis. As for all organs and cells across the lifespan, BM and EPCs are negatively impacted by ageing due to microenvironment modifications and EPC progressive dysfunctions. The encouraging results in terms of neovascularization observed in young animals after EPC administration were mitigated in aged patients treated for ischemic CVDs. The limited efficacy of EPC-based therapy in clinical setting might be ascribed at least partly to ageing. In this review, we comprehensively discussed the age-related changes of BM and EPCs and their implication for cardiovascular cell-therapies. Finally, we examined alternative approaches under investigation to enhance EPC potency.

Safety, Efficacy, and Complications of Pericardiocentesis by Real-Time Echo-Monitored Procedure.

Pericardiocentesis is useful in the diagnosis and treatment of pericardial effusive disease. To date, a number of methods have been developed to reduce complications and increase the success rate of the procedure. The aim of the present study was to evaluate the efficacy and the safety of echocardiography-guided pericardiocentesis under continuous echocardiographic monitoring in the management of pericardial effusion. We prospectively performed 161 pericardiocentesis procedures in 141 patients admitted from 1993 to 2015 in 3 centers. This procedure was performed for tamponade or large pericardial effusion in 157 cases and for diagnosis in 4 cases. A percutaneous puncture was performed where the largest amount of fluid was detected. To perform a real-time echo-guided procedure, a multi-angle bracket was mounted on the echocardiographic probe to support the needle and enable its continuous visualization during the puncture. The procedure was successful in 160 of 161 cases (99%). Two major complications occurred (1.2%): 1 mediastinal hematoma that required surgical drainage in a patient on anticoagulant therapy and 1 pleuropericardial shunt requiring thoracentesis. Seven minor complications occurred (4.3%): 1 pleuropericardial shunt, 1 case of transient AV type III block, 3 vasovagal reactions (1 with syncope), and 2 cases of acute pulmonary edema managed with medical therapy. No punctures of any cardiac chamber occurred, and emergency surgical drainage was not required in any case. In conclusion, echocardiography-guided pericardiocentesis under continuous visualization is effective, safe, and easy to perform, even in hospitals with low volumes of procedures with or without cardiac surgery.

Granulocyte-colony stimulating factor for large anterior ST-elevation myocardial infarction: rationale and design of the prospective randomized phase III STEM-AMI OUTCOME trial.

BACKGROUND: Granulocyte-colony stimulating factor (G-CSF) has been clinically tested in ST-elevation myocardial infarction (STEMI) with mixed results. Our 3-year follow-up data from STEM-AMI trial documented a sustained benefit of G-CSF on adverse ventricular remodeling after large anterior STEMI, when administered early and at a high-dose in patients with left ventricular (LV) dysfunction. The Aim of the present trial is to establish whether G-CSF improves hard clinical long-term outcomes. METHODS: The STEM-AMI OUTCOME is a prospective, multicenter, randomized, open-label, phase III trial. It will include 1,530 patients with anterior STEMI undergoing primary percutaneous coronary intervention 2 to 24 hours after symptoms onset and with LV ejection fraction ≤45% after successful reperfusion. Patients will be randomized 1:1 to G-CSF and/or standard treatment. The primary end point is a reduced occurrence of all-cause death, recurrence of myocardial infarction, or hospitalization due to heart failure in G-CSF-treated patients. Left ventricular remodeling will be assessed via cardiac ultrasound and a substudy with cardiac magnetic resonance will be carried out in 120 subjects. Accrual and follow-up periods will last 3 and 2 years, respectively. CONCLUSIONS: The STEM-AMI OUTCOME study is designed to be a rigorous controlled phase III trial with adequate statistical power to conclusively assess efficacy of G-CSF treatment in STEMI.

Myocardial metastasis from oesophageal cancer.

Three years after surgical resection of oesophageal tumour, during the regular instrumental oncologic follow-up performed by thoracic computed tomography scan in an otherwise asymptomatic 48-year-old man, a left ventricular mass was detected. It developed during a 6-month-period, and at the time of discovery it measured 63 × 61 mm. The mass was further evaluated with echocardiography and cardiac magnetic resonance imaging, and a histology specimen was obtained by myocardial biopsy, revealing it was a metastasis from the primitive tumour, in the absence of other organ involvement. The diagnostic process and possible therapeutic options for solitary intracardiac metastasis in the absence of involvement of other organs are briefly discussed.

The CD133+ cell as advanced medicinal product for myocardial and limb ischemia.

Ischemic diseases are the major cause of death and morbidity in Western countries. In the last decade, cell therapy has been suggested to be a promising treatment both in acute/chronic myocardial and peripheral ischemia. Different cell lineages have been tested, including endothelial progenitor cells. A subpopulation of bone marrow-derived immature ECPs, expressing the highly conserved stem cell glycoprotein antigen prominin-1 or CD133 marker, was shown to possess pro-angiogenic and antiapoptotic effects on ischemic tissues. The mechanisms implicated in CD133+ cells ability to contribute to neovascularization processes have been attributed to their ability to directly differentiate into newly forming vessels and to indirectly activate pro-angiogenic signaling by paracrine mechanisms. A large body of in vivo experimental evidences has demonstrated the potential of CD133+ cells to reverse ischemia. Moreover, several clinical trials have reported promising beneficial effects after infusion of autologous CD133+ into ischemic heart and limbs exploiting various delivery strategies. These trials have contributed to characterize the CD133+ manufacturing process as an advanced cell product (AMP). The aim of this review is to summarize available experimental and clinical data on CD133+ cells in the context of myocardial and peripheral ischemia, and to focus on the development of the CD133+ cell as an anti-ischemic AMP.

G-CSF treatment for STEMI: final 3-year follow-up of the randomised placebo-controlled STEM-AMI trial.

OBJECTIVE: To assess whether granulocyte colony-stimulating factor (G-CSF) treatment induces a sustained benefit on adverse remodelling in patients with large anterior ST-elevation myocardial infarction (STEMI) and left ventricular (LV) dysfunction after successful reperfusion. METHODS: The STEM-AMI Trial was a prospective, placebo-controlled, multicentre study. Sixty consecutive patients with a first anterior STEMI, who underwent primary percutaneous coronary intervention 2-12 h after symptom onset, with LV ejection fraction (LVEF) ≤45% measured by echocardiography within 12 h after successful revascularisation (TIMI flow score ≥2), were randomised 1:1 to G-CSF (5 µg/Kg body weight b.i.d.) or placebo. Clinical events and Major Adverse Cardiac and Cerebrovascular Event (MACCE) were monitored, and LVEF, LV end-diastolic (LVEDV) and end-systolic (LVESV) volumes, and infarct size were evaluated by MRI at the final 3-year follow-up. RESULTS: Fifty-four patients completed the study, of whom 35 with MRI. No significant differences were found in mortality and MACCE between G-CSF and placebo-treated groups. The 3-year infarct size was not different between groups, whereas LVEDV was significantly lower in G-CSF (n=20) than in placebo (n=15) patients (170.1±8.1 vs 197.2±8.9 mL, respectively; p=0.033 at analysis of covariance). A significant inverse correlation was detected in G-CSF patients between the number of circulating CD34 cells at 30 days after reperfusion and the 3-year absolute and indexed LVEDV (ρ=-0.71, 95% CI -0.90 to -0.30, and ρ=-0.62, -0.86 to -0.14, respectively), or their change over time (r=-0.59, -0.85 to -0.11, and r=-0.55, -0.83 to -0.06, respectively). CONCLUSIONS: G-CSF therapy may be beneficial in attenuating ventricular remodelling subsequent to a large anterior STEMI in the long term. No differences have been detected in clinical outcome.

Diagnostic potential of plasmatic MicroRNA signatures in stable and unstable angina.

PURPOSE: We examined circulating miRNA expression profiles in plasma of patients with coronary artery disease (CAD) vs. matched controls, with the aim of identifying novel discriminating biomarkers of Stable (SA) and Unstable (UA) angina. METHODS: An exploratory analysis of plasmatic expression profile of 367 miRNAs was conducted in a group of SA and UA patients and control donors, using TaqMan microRNA Arrays. Screening confirmation and expression analysis were performed by qRT-PCR: all miRNAs found dysregulated were examined in the plasma of troponin-negative UA (n=19) and SA (n=34) patients and control subjects (n=20), matched for sex, age, and cardiovascular risk factors. In addition, the expression of 14 known CAD-associated miRNAs was also investigated. RESULTS: Out of 178 miRNAs consistently detected in plasma samples, 3 showed positive modulation by CAD when compared to controls: miR-337-5p, miR-433, and miR-485-3p. Further, miR-1, -122, -126, -133a, -133b, and miR-199a were positively modulated in both UA and SA patients, while miR-337-5p and miR-145 showed a positive modulation only in SA or UA patients, respectively. ROC curve analyses showed a good diagnostic potential (AUC ≥ 0.85) for miR-1, -126, and -483-5p in SA and for miR-1, -126, and -133a in UA patients vs. controls, respectively. No discriminating AUC values were observed comparing SA vs. UA patients. Hierarchical cluster analysis showed that the combination of miR-1, -133a, and -126 in UA and of miR-1, -126, and -485-3p in SA correctly classified patients vs. controls with an efficiency ≥ 87%. No combination of miRNAs was able to reliably discriminate patients with UA from patients with SA. CONCLUSIONS: This work showed that specific plasmatic miRNA signatures have the potential to accurately discriminate patients with angiographically documented CAD from matched controls. We failed to identify a plasmatic miRNA expression pattern capable to differentiate SA from UA patients.

Added value of real time three-dimensional echocardiography in the diagnosis of an apical right ventricular metastasis from malignant melanoma.

In a man presenting to the emergency room with dyspnea and atypical chest pain irradiated among the scapulae, with new-onset diffuse negative T-waves on the ECG, the first clinical and diagnostic hypothesis was pulmonary embolism (PE). However, computed tomography (CT) performed in emergency was negative for PE, showing instead a marked defect in right ventricle (RV) filling. For this reason, echocardiography was performed to better investigate the nature of the space-occupying lesion, and several echocardiographic modalities were used (two-dimensional transthoracic and transesophageal echocardiography and three-dimensional [3D] transthoracic echocardiography). They revealed the presence of a mass attached to the apex of the RV, partially obstructing the inflow and outflow tracts. Cardiac magnetic resonance imaging was also performed, confirming the findings of 3D echocardiography. After that, several other diagnostic imaging techniques were used for disease staging, since the patient had a history of surgical excision of a malignant melanoma of the skin several years before. Whole-body CT, soft tissue echography and positron emission tomography revealed the widespread diffusion of the primary tumor to distant organs. For this reason, we suspected that the RV mass could also be an intracardiac metastasis from malignant melanoma, and did not perform biopsy given the bad clinical conditions and the worse prognosis of the patient. However, he was entered in an experimental therapeutic protocol with Vemurafenib because he showed B-RAF gene mutation at molecular gene analysis.