Vittoria Rizzello

Enhanced response of blood monocytes to in vitro lipopolysaccharide-challenge in patients with recurrent unstable angina.

BackgroundC-reactive protein (CRP) plasma levels have been associated with short- and long-term occurrence of coronary events. We investigated whether circulating inflammatory cell responsiveness to low-grade stimuli could contribute to the reported association between CRP and coronary events. Methods and ResultsWe studied 32 patients with unstable angina who were followed for 24 months and were free of symptoms for 6 months (group 1): 19 patients had persistently high CRP levels (>0.3 mg/dL) (group 1A); 13 patients had normal CRP levels (group 1B). During the follow-up, 12 (63%) group 1A but no group 1B patients developed an infarction or recurrence of unstable angina (P <0.001). Eighteen patients with chronic stable angina (group 2) and 18 healthy subjects (group 3) were studied as controls. Interleukin (IL)-6 production (median, range) by peripheral blood mononuclear cells after 4 hours of in vitro stimulation with 1 ng/mL lipopolysaccharide (LPS) was significantly higher in group 1A (4526 pg/mL, 3042 to 10 583 pg/mL) than in group 1B (1752 pg/mL, 75 to 3981 pg/mL), group 2 (707 pg/mL, 41 to 3275 pg/mL), and group 3 (488 pg/mL, 92 to 3503 pg/mL) (all P <0.001). No significant differences were observed among the other groups. IL-6 production after LPS-challenge was correlated with baseline CRP levels (r =0.42, P =0.005). ConclusionsMononuclear cells of patients with recurrent phases of instability exhibit an enhanced production of IL-6 in response to low-dose of LPS, correlated with baseline CRP levels, 6 months after the last acute event. This persisting enhanced acute-phase responsiveness may help explain the association between CRP and acute coronary events.

Modulation of CD4+CD28null T Lymphocytes by Tumor Necrosis Factor-α Blockade in Patients With Unstable Angina

Background— Tumor necrosis factor-&agr; (TNF-&agr;) is a proinflammatory cytokine that favors the expansion of CD4+CD28null T cells, an aggressive and unusual proinflammatory lymphocyte subset frequently observed in patients with unstable angina (UA). The purpose of the present ex vivo study was to evaluate whether inflammation in patients with UA may be modulated by selective blockade of TNF-&agr;. Methods and Results— Peripheral blood samples were collected from 17 patients with UA (Braunwald’s class IIIB). CD4+CD28null T cells were assessed by flow cytometry and expressed as a percentage of all CD4+ T cells after 24 hours of incubation of whole blood with and without increasing doses (0.1, 1, 10, and 100 &mgr;g/mL) of infliximab, an anti–TNF-&agr; monoclonal antibody. In addition, CD28 expression was assessed and expressed as mean fluorescence intensity (geometric mean of the CD28 fluorescence value on all CD4+ T cells). CD4+CD28null T-cell percentage decreased from a median of 6.2% (range, 1.2% to 23.9%) to 4.9% (range, 1.1% to 21.9%), 4.5% (range, 1.1% to 21.6%), and 4.1% (range, 0.4% to 21.4%) after incubation with 1, 10, and 100 &mgr;g/mL of infliximab (P for trend=0.043). Analysis of CD28 mean fluorescence intensity showed that the expression of CD28 on cell surface significantly increased after incubation with increasing doses of infliximab (P for trend=0.03). Conclusions— The findings of this ex vivo study show that CD4+CD28null T-cell expansion in patients with UA may be reduced by selective TNF-&agr; blockade. Further studies are warranted to evaluate the clinical benefit of CD4+CD28null T-cell modulation.

Assessment of resting perfusion defects in patients with acute myocardial infarction: comparison of myocardial contrast echocardiography, combined first-pass/delayed contrast-enhanced magnetic resonance imaging and 99mTC-sestamibi SPECT.

BackgroundInformation on the accuracy of both magnetic resonance imaging (MRI) and myocardial contrast echocardiography (MCE) for the identification of perfusion defects in patients with acute myocardial infarction is limited. We evaluated the accuracy of MRI and MCE, using Single Photon Emission Computed Tomography (SPECT) imaging as reference technique.MethodsFourteen consecutive patients underwent MCE, MRI and 99mTc-MIBI SPECT after acute myocardial infarction to assess myocardial perfusion. MCE was performed by Harmonic Power Angio Mode, with end-systolic triggering 1:4, using i.v. injection of Levovist®. First-pass and delayed enhancement MRI was obtained after i.v administration of Gadolinium-DTPA. At MCE, homogeneous perfusion was considered as normal and absent or “patchy” perfusion as abnormal. At MRI, homogenous contrast enhancement was defined as normal whereas hypoenhancement at first-pass followed by hyperenhancement or persisting hypoenhancement in delayed images was defined as abnormal.ResultsAt MCE 153 (68%) of segments were suitable for analysis compared to 220 (98%) segments at MRI (p<0.001). Sensitivity, specificity and accuracy of MCE for segmental perfusion defects in these 153 segments were 83, 73 and 77%, respectively. Sensitivity, specificity and accuracy of MRI were 63, 82, and 77%, respectively. MCE and MRI showed a moderate agreement with SPECT (k: 0.52 and 0.46, respectively). The agreement between MCE and MRI was better (k: 0.67) that the one of each technique with SPECT.ConclusionMCE and MRI may be clinically useful in the assessment of perfusion defects in patients with acute myocardial infarction, even thought MCE imaging may be difficult to obtain in a considerable proportion of segments when the Intermittent Harmonic Angio Mode is used.

Spontaneous Left Atrial Dissection and Hematoma Mimicking a Cardiac Tumor Findings From Echocardiography, Cardiac Computed Tomography, Magnetic Resonance Imaging, and Pathology

59-year-oldwomanwithnohistoryofcardiacsurgeryorthoracic trauma presented to the emergency departmentwith tachycardia and dyspnea. The ECG showed sinusrhythm (110 bpm). X-rays showed interstitial pulmonaryedema. Transthoracic echocardiography revealed a mild en-largement of the left atrium (LA), normal left ventricularfunction,andalargefixedmassoccupyingalmostentirelytheLA and arriving just near the posterior mitral annulus.Moderate mitral regurgitation was present. Transesophagealechocardiography confirmed the presence of an inhomoge-neous cyst-like mass with a thin hyperechogenic wall comingfrom the posterolateral wall of the LA and involving theinteratrial septum roof (Movie). Cardiac computed tomogra-phy and gadolinium-enhanced magnetic resonance imagingwere also performed (Figure).On the basis of the findings of the 3 techniques, apresumptive diagnosis of LA tumor was made and a cardiacoperation was performed with institution of cardiopulmonarybypass. A vertical extended transseptal incision was madeand an intramural mass was found in the posterior wall of theLA bulging into and occupying two thirds of the cavity.Macroscopically, no sign of infiltration was found in andoutside the LA wall, and no pericardial adhesions wereobserved. The endocardium was cut and a several clots werespread out from a non-capsulated cavity delimited by gray,fibrous, and atrophic tissue. The histopathological examina-tion showed that the mass consisted of fibrin, erythrocytes,and scattered leukocytes.The postoperative course was uneventful and the patientwas discharged on the seventh day. Repeat echocardiographyover the following months showed normal LA withoutresidual hematoma or dissection and residual mild mitralinsufficiency.SpontaneoushematomaisaveryrareA 59-year-old woman with no history of cardiac surgery or thoracic trauma presented to the emergency department with tachycardia and dyspnea. The ECG showed sinus rhythm (110 bpm). X-rays showed interstitial pulmonary edema. Transthoracic echocardiography revealed a mild enlargement of the left atrium (LA), normal left ventricular function, and a large fixed mass occupying almost entirely the LA and arriving just near the posterior mitral annulus. Moderate mitral regurgitation was present. Transesophageal echocardiography confirmed the presence of an inhomogeneous cyst-like mass with a thin hyperechogenic wall coming from …

C-reactive protein and primary prevention of ischemic heart disease

C-reactive protein (CRP) is the prototype acute phase reactant and therefore a marker of systemic inflammation. In the last decades, accumulating data have demonstrated the role of inflammation in the pathogenesis of ischemic heart disease. High CRP levels, measured by high-sensitivity methods, on admission have a short-term negative prognostic value and are associated with a worse outcome. In epidemiological studies, minor elevations of CRP are associated with future risk of myocardial infarction, stroke and peripheral vascular disease. This increased risk is independent of other biochemical and clinical risk factors, and the association between high CRP and an abnormal cholesterol ratio significantly increases the risk in the individual patient. Finally, the observation of an increased level of CRP may be of clinical utility in primary prevention, because these subjects favourably benefit from statin therapy.

Primary chylopericardium due to lymphangiectasias: the crucial role of lymphangiography

A 24-year-old woman was referred to our Cardiology Department because of cardiomegaly at a routine chest X-ray. She was asymptomatic except for some fatigability. Physical examination was unremarkable. Electrocardiogram showed only low QRS voltages. Echocardiography revealed large pericardial effusion with right atrial and ventricular collapse. Pericardiocentesis was performed and 1100 mL of milky fluid were removed, suggesting chylopericardium. The …

Benefits of coronary revascularisation in diabetic and non-diabetic patients with ischaemic cardiomyopathy: Role of myocardial viability

Diabetes mellitus in patients with coronary artery disease is associated with poor outcome. In this study, the relation between myocardial viability, diabetes, coronary revascularisation and outcome was evaluated.

673 Can resting 2D echocardiography identify patients with ischemic cardiomyopathy and low likelihood of functional improvement after revascularization

Background: To evaluate the potential of a simple and widely available technique such as 2-dimensional echocardiography to identify patients with ischemic cardiomyopathy and low likelihood of functional improvement after revascularization. Methods: Two-dimensional echocardiography was performed in 101 patients with left ventricular (LV) dysfunction due to chronic coronary artery disease, already scheduled for revascularization. Segmental wall motion abnormalities, wall motion score index (WMSI), end-diastolic wall thickness (EDWT), LV volumes and LV sphericity index (LVSI: DŁ) were evaluated. The LV ejection fraction (LVEF) was assessed by radionuclide ventriculography (RNV), before and 9 to 12 months after revascularization. An improvement in the LVEF > or = to 5% was considered clinically significant. Results: On the analysis 999 segments were severely dysfunctional (WMSI: 2.75±0.7); 149 (15%) had an EDWT or = to 140 ml had the best accuracy to identify patients that virtually never improve. LVEF improvement after revascularization was present only in 1 (4%) patient with ESV > or = to 140 ml as compared to 29 (41%) patients with ESV <140 ml (p<0.005). Conclusions: In patients with ischemic cardiomyopathy, the presence of severe LV enlargement significantly reduce the chance of functional improvement after revascularization. Hence, the assessment of LV volumes, by an extremely widespread diagnostic technique as 2-dimensional echocardiography at rest, can be an initial screening tool to identify patients in which further viability testing could be avoided.

543 Beneficial effects of coronary revascularization on left ventricular remodelling in patients with ischemic cardiomyopathy: the role of viable myocardium

Background: In patients (pts) with left ventricular (LV) dysfunction due to chronic coronary artery disease, preserved myocardial viability not always implies left ventricular function recovery after revascularization. However, additional benefits may be present. Aim: To test the hypothesis that myocardial viability may prevent LV remodeling after revascularization, independently of the effect on functional recovery. Methods: Dobutamine stress echocardiography (DSE) was performed in 88 pts with ischemic cardiomyophaty, already scheduled for revascularization, to detect the presence of viable myocardium. Resting 2D-echocardiography was performed at a mean of 4,5 months and 2,8 years after revascularization. LV volumes and the LV sphericity index (LVSI: D/L) were measured to evaluate LV remodeling (LV volumes and LVSI increase). Radionuclide ventriculography was performed before and at a mean of 4,5 months after revascularization to assess LV function. Results: After revascularization, progressive remodeling was observed in overall 35 pts (40%). In these pts, the end-diastolic volume increased from 173 ± 42 to 207 ± 56 (at 4,5 months, p<0.01) and to 242 ± 55 ml (at 2,8 years, p<0.05). The end-systolic volume increased from 109 ± 39 to 142 ± 24 (at 4,5 months, p<0.01) and to 169 ± 58 ml (at 2,8 years, p<0.05). The LVSI increased over the follow-up in 23 pts (66%) with LV volume increase. Clinical characteristics were similar in pts with and without remodeling, however, a substantial amount of viable myocardium (major or equal to 25%) was more often present in pts with no remodeling (81% vs 9%, p<0.0001). The number of viable segments was a strong predictor of no remodeling (OR 3, p<0.0001). The likelihood of no remodeling increased proportionally with the number of viable segments. The predictive value remained even after correction for LV function recovery after revascularization(OR 3.1, p<0.0001). After revascularization, LV ejection fraction increased significantly (major or equal to 5%) in 28 of 46 pts (61%) with substantial amount of viable myocardium. However, LV remodeling did not occur (preserved LV volumes and LVSI) in 17 of 18 pts (94%) with viable myocardium that did not recover in function. Conclusions: The presence of viable myocardium in pts with ischemic cardiomyopathy strongly prevents progressive LV remodeling. This benefit is independent of functional recovery after revascularization.