[Pulmonary hypertension clinical pathway: ANMCO Tuscany Board model]. / Clinical pathway per l'ipertensione polmonare: la proposta di ANMCO Toscana.

Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure >20 mmHg at rest during right heart catheterization. PH prevalence is about 1% of the global population. The PH clinical classification includes five groups: pulmonary arterial hypertension, PH associated with left heart disease, PH associated with lung disease, PH associated with pulmonary artery obstructions, PH with unclear and/or multifactorial mechanisms. In case of clinical suspicion, echocardiography is the first-line tool to start the diagnostic process. Right heart catheterization is the gold standard for diagnosis of PH, requires great experience and should be performed in expert centers. The classification of the PH patient in a specific subgroup requires multidisciplinary clinical and instrumental skills that only a reference center can provide. This document proposes a clinical pathway for the management of PH patients in the Tuscany region in order to standardize access to specialized care.

[Arrhythmias in adult congenital heart disease at the emergency department: ANMCO Tuscany clinical pathway]. / I clinical pathways dell'ANMCO Toscana: la gestione in urgenza delle aritmie nel cardiopatico congenito adulto.

Arrhythmias are a common complication in the adult population with congenital heart disease (ACHD). Arrhythmias often lead to hemodynamic instability and, on the other hand, may be a marker of hemodynamic impairment in ACHD patients, both in natural history and after cardiac surgery. Treatment requires knowledge of basic anatomy and any previous cardiac surgery; the availability of patient's health records, if possible, is therefore crucial for therapeutic choices. In the emergency setting, the first target is represented by the patient's hemodynamic stabilization; mainly in moderate or high complexity ACHD, the connection with the referral center is recommended, to which patients should be entrusted for follow-up. A regional epidemiological observatory, aiming to assess the number, type and outcomes of emergency admissions of ACHD patients could be a useful tool for analyzing the effectiveness of the collaboration network between the different structures involved and for implementing organizational pathways.

[A clinical cardio-oncology pathway for the cardiology management of cancer outpatients: a joint proposal by ANMCO and AIOM Tuscany]. / Modello organizzativo e di un percorso clinico per la gestione cardiologica ambulatoriale del paziente oncologico: una proposta congiunta ANMCO e AIOM Toscana.

Cardio-oncology is now part of the standard clinical approach for patients with cancer and cannot be overlooked anymore. While its scientific background is solid and its clinical relevance is well known, its application in daily practice varies greatly among hospitals. To provide the best cardio-oncology care to cancer patients and to make cardio-oncology's clinical use uniform, we developed a shared multidisciplinary proposal for a dedicated clinical pathway. Our proposition presents the minimum requirements needed to which this path caters for, identifies patient categories to be entered into the path, highlights the role of a specific inter-hospital clinical and imaging network and indicates follow-up strategies during and after oncological treatments. The proposed pathway is based on some key elements and is easily adaptable to different hospitals with minimal changes.

Left atrial thrombus and smoke resolution in patients with atrial fibrillation under chronic oral anticoagulation.

BACKGROUND: The study aimed to explore the resolution of left atrial and left atrial appendage (LAA) spontaneous echo-contrast or thrombus in patients with nonvalvular atrial fibrillation/flutter (AF/AFL) under chronic oral anticoagulation (OAC). METHODS: A single-center retrospective analysis of patients who underwent a transesophageal echocardiography (TOE) for an electrical cardioversion was conducted. RESULTS: Among 277 TOE performed, 73 cases (26%) of LAA echo-contrast or thrombus were detected, 53 patients with LAA/LA echo-contrast (19%) and 20 (7%) with a thrombus. All patients were under chronic anticoagulation with a VKA (65%) or with a NOAC (35%). The Echo-contrast Group maintained the same OAC strategy in 49 patients (93%). The Thrombus Group kept the same OAC strategy with a NOAC in 6 cases (30%) and changed the strategy in 14 patients (70%), titrating NOAC dose in 1 (5%) and the VKA dose in 4 (20%) and switching from NOAC to VKA in 5 (25%), from VKA to NOAC in 3 (15%), and from NOAC to NOAC in 1 (5%). Smoke resolution was observed in 4/40 cases (10%) of the smoke group and thrombus resolution in 8/15 (53%) of the thrombus group. Patients with thrombus resolution had a lower CHA2DS2-Vasc score (3.5 ± 2 vs 4 ± 1, p = 0.05), were more often under NOAC (37.5 vs 28%, p = 0.07), and had a longer anticoagulation time (7.5 vs 4 months, p = 0.08). CONCLUSION (S): Changing OAC strategy is associated with thrombus resolution in more than 50% of chronically anticoagulated patients.

The C242T polymorphism of the p22phox component of NAD(P)H oxidase and vascular risk. Two case-control studies and a meta-analysis.

NAD(P)H oxidase is a prominent source of reactive oxygen species in the vasculature. Vascular NAD(P)H oxidase is comprised of several subunits, one of which, p22phox, is encoded by a gene exhibiting several allelic variants. Here the C(242)T nucleotide transition has been found to alter superoxide anion production and associated with an altered risk of coronary artery disease (CAD). We assessed the role of this variant in two case-control studies, and performed a meta-analysis of previously reported investigations relating it to vascular risk. Population I was comprised of 492 subjects with type 2 diabetes, with or without macrovascular disease, matched for age, sex, and duration of diabetes. Population II was comprised of 158 subjects with or without either CAD or cerebro-vascular disease, and matched for age, sex, smoking status, weight category and the presence of hypertension, dyslipidemia, and diabetes. Our findings were meta-analyzed together with additional studies retrieved from the literature. The C(242)T polymorphism distribution did not differ between cases and controls in populations I and II both at univariate and multivariate analyses, and this was confirmed in a meta-analysis with 11 previously published populations. The meta-analysis, however, suggested a protective role of the T allele on CAD as an end point in Asian populations. In conclusion, these data suggest a significant heterogeneity for a modulating role of the T allele in the C(242)T polymorphism of p22-phox for the occurrence of CAD across ethnicities, with the absence of a significant effect in Caucasians.

[Coronary angiography in stable angina: friends and foes]. / Quando fare (e quando non fare) la coronarografia nel paziente con angina stabile.

Preventive intervention presupposes a threat that can be averted at an acceptable cost; in patients with stable coronary artery disease, the threat of subsequent myocardial infarction and death is generally low, and proper management can usually control symptoms and improve prognosis substantially. In general, patients who have indications for coronary angiography are also potential candidates for revascularization. The relation of typical angina to prognosis is mediated by its relation to the extent of coronary disease; since the risk of coronary occlusion is not proportional to stenosis severity, it is not surprising that treating one or more stable tight lesions does not reduce the rates of subsequent major cardiac events. Clinical evaluation, ventricular function, response to stress testing, and the extent of coronary artery disease are the key pieces of information to stratify patient risk. In subjects without a markedly positive stress test, the ischemic burden is helpful in decision-making with respect to selecting initial therapy, and contributes to risk assessment. An initial invasive strategy without prior functional testing is rarely indicated, and may only be considered for patients with severe valve disease, serious arrhythmias or when therapy has failed to control symptoms satisfactorily, with a view to revascularization. In the absence of uncontrolled symptoms, patients are potentially eligible for coronary angiography if noninvasive tests reveal a substantial area of myocardium at risk. Coronary angiography should also be undertaken in patients with moderate to severe ischemia who do not have a significant reduction of the ischemic burden with therapy, given their worse prognosis. Because the treatment of asymptomatic patients cannot improve their symptoms, recommendations for coronary angiography in this subset are weaker and limited to risk stratification in subjects with high-risk criteria. Invasive procedures require a high likelihood of success and acceptable risk of morbidity and mortality and patients should be fully informed of the risks of the therapeutic modality individually. Regardless of the treatment modality used (early invasive vs selectively invasive), noninvasive imaging of the ischemic burden may assist in both decision-making for initial therapy and determining therapeutic efficacy related to long-term outcome.

Homocysteine induces VCAM-1 gene expression through NF-kappaB and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants.

Hyperhomocysteinemia is a recognized risk factor for vascular disease, but pathogenetic mechanisms involved in its vascular actions are largely unknown. Because VCAM-1 expression is crucial in monocyte adhesion and early atherogenesis, we evaluated the NF-kappaB-related induction of VCAM-1 by homocysteine (Hcy) and the possible inhibitory effect of dietary polyphenolic antioxidants, such as trans-resveratrol (RSV) and hydroxytyrosol (HT), which are known inhibitors of NF-kappaB-mediated VCAM-1 induction. In human umbilical vein endothelial cells (HUVEC), Hcy, at 100 micromol/l, but not cysteine, induced VCAM-1 expression at the protein and mRNA levels, as shown by enzyme immunoassay and Northern analysis, respectively. Transfection studies with deletional VCAM-1 promoter constructs demonstrated that the two tandem NF-kappaB motifs in the VCAM-1 promoter are necessary for Hcy-induced VCAM-1 gene expression. Hcy-induced NF-kappaB activation was confirmed by EMSA, as shown by the nuclear translocation of its p65 (RelA) subunit and the degradation of the inhibitors IkappaB-alpha and IkappaB-beta by Western analysis. Hcy also increased intracellular reactive oxygen species by NAD(P)H oxidase activation, as shown by the membrane translocation of its p47(phox) subunit. NF-kappaB inhibitors decreased Hcy-induced intracellular reactive oxygen species and VCAM-1 expression. Finally, we found that nutritionally relevant concentrations of RSV and HT, but not folate and vitamin B6, reduce (by >60% at 10(-6) mol/l) Hcy-induced VCAM-1 expression and monocytoid cell adhesion to the endothelium. These data indicate that pathophysiologically relevant Hcy concentrations induce VCAM-1 expression through a prooxidant mechanism involving NF-kappaB. Natural Mediterranean diet antioxidants can inhibit such activation, suggesting their possible therapeutic role in Hcy-induced vascular damage.

Both vitamin B6 and total homocysteine plasma levels predict long-term atherothrombotic events in healthy subjects.

AIMS: The contribution of homocysteine and group B vitamins in determining cardiovascular risk is debated. We assessed the predictive value of total homocysteine (tHcy), vitamin B12, folate, and vitamin B6 on the long-term occurrence of coronary and cerebral atherothrombotic events in a nested case-control study. METHODS AND RESULTS: Within a cohort of 1021 healthy subjects (490 men and 531 women) recruited in 1987, 66 first-ever coronary and 43 first-ever cerebrovascular events were recorded at a 12-year follow-up (cases, n=109). A total of 109 control subjects (remaining free from events) were matched with cases according to age, sex, smoking, hypertension, dyslipidaemia, and body mass index. Serum samples obtained in 1987 at baseline were used to measure tHcy, folate, and vitamins B12 and B6, as well as C-reactive protein plasma concentrations. We found a significant graded association between tHcy levels and the risk of coronary and cerebrovascular events [odds ratio (OR) for uppermost vs. lowermost quartile=1.34, 95% CI 1.01-1.76)]. Folate and vitamin B12 did not significantly differ between cases and controls, but were negatively (P<0.01) correlated with tHcy. Vitamin B6 did not correlate with tHcy levels, but differed significantly between cases and controls: for subjects in the uppermost quartile vs. the lowermost quartile of vitamin B6, OR=0.69 (95% CI 0.49-0.98). For subjects in the lowermost quartile of vitamin B6 and the uppermost quartile of tHcy, OR=17.50 (95% CI 1.97, 155.59). Cases and controls were not different as to C-reactive protein. CONCLUSION: tHcy and plasma vitamin B6 are long-term independent risk factors for coronary and cerebrovascular events.

Heart involvement in T cell lymphoma through hypereosinophilic syndrome: a common complication of a rare condition.

This case describes a 42-year-old male affected by hypereosinophilic syndrome associated with angioimmunoblastic lymphoma. Heart involvement was suspected at ECG mimicking left ventricular hypertrophy. MRI clarified the extensive endomyocardial fibrosis, confirming the role of this technique in in-vivo tissue characterization. Finally, the study investigates the association of T cell lymphoma, hypereosinophilic syndrome, and Loeffler endomyocardial disease.