Search

Cardiac amyloidosis (CA) is an infiltrative heart disease resulting from the deposition of amyloid fibrils in the interstitial spaces of the myocardium. The two main forms of CA are represented by light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) in the two forms familial or variant or wild-type or senile. Although considered a rare disease, CA is an underdiagnosed disease. Delay in diagnosis has a negative impact on the prognosis, delaying the initiation of specific therapy. The treatment of both forms of CA is based on: (i) prevention and slowing of the generation and deposition of amyloid fibrils and (ii) supportive care of complications. The main success of recent years has been the development of effective therapies that have been possible thanks to the understanding of the pathophysiology of amyloidosis. For the AL form, new therapeutic combinations between a proteasome inhibitor and a monoclonal antibody have been developed. For ATTR forms, the main strategies are transthyretin (TTR) production ‘silencers’ and TTR tetramer stabilizers. Supportive care of patients with CA involves various clinical aspects including treatment of heart failure, arrhythmias, conduction disturbances, thrombo-embolism, and the concomitant presence of aortic stenosis.

In patients with atherosclerotic disease, the occurrence of atherothrombotic events is the main determinant of morbidity and mortality. Growing evidence suggests the involvement of the coagulation pathway in the atherosclerotic process and the benefit of antithrombotic agents, such as direct oral anticoagulants, which interfere with both platelet aggregation and the coagulation cascade. The COMPASS trial has shown that in patients with stable coronary artery disease (CAD) or peripheral artery disease (PAD), low-dose rivaroxaban (2.5 mg twice daily) added to acetylsalicylic acid (ASA) 100 mg reduces major vascular events and mortality, with an increase in major bleeding but not in fatal bleeding or involving a critical organ. The reduction in major cardiovascular events has been confirmed in the overall population with CAD and in both patients with and without a previous percutaneous coronary revascularization, and also in patients with previous coronary bypass surgery. In patients with PAD, the combination of rivaroxaban 2.5 mg twice daily and ASA was found to reduce both major adverse cardiovascular events and major adverse limb events, including major limb amputations. In clinical practice, the use of rivaroxaban 2.5 mg co-administered with ASA has been approved in both patients with CAD and symptomatic PAD at high risk of ischemic events. However, in Italy, the national health system reimbursement is provided only for patients with PAD. In patients treated with rivaroxaban 2.5 mg, assessment and monitoring of bleeding risk is crucial to achieve the maximum clinical benefit.

The selection of patients eligible for implantable cardioverter defibrillator (ICD), in primary prevention, is a critical moment in the management of the patients with cardiomyopathies as it needs a right balance of the patients’ arrhythmic risk and the risks related to the implantation, as well as the device costs. Several data indicate that left ventricular ejection fraction alone is not a sufficient criterion for a proper identification of patients who could benefit most from ICD. Numerous findings show that genetic analysis and characterization of myocardial fibrosis with magnetic resonance imaging allow an important improvement of this process.

Aortic stenosis (AS) is defined as severe in the presence of: mean gradient ≥40 mmHg, peak aortic velocity ≥4 m/s, and aortic valve area (AVA) ≤1 cm2 (or an indexed AVA ≤0.6 cm2/m2). However, up to 40% of patients have a discrepancy between gradient and AVA, i.e. AVA ≤1 cm2 (indicating severe AS) and a moderate gradient: >20 and

The cardioprotective role that statin and aspirin has appears to be reduced in patients with chronic kidney disease (CKD). This analysis aims to evaluate the impact of statin and aspirin on the outcome of patients with CKD and acute coronary syndrome (ACS).All patients who were enrolled in the IN-ACS Outcome registry, diagnosed with CKD, were included in our analysis. We divided patients into four groups, according to previous chronic therapy: neither aspirin nor statin therapy (Group 1), aspirin only therapy (Group 2), statin only therapy (Group 3) and aspirin plus statin therapy (Group 4).Of the 5483 patients enrolled that had data on glomerular filtration rate available, 1484 had CKD: These segregated into 589 patients in Group 1, 477 in Group 2, 89 in Group 3 and 329 in Group 4. Despite having a higher baseline risk profile, groups 3 and 4, as compared to the other two groups, exhibited a significantly lower in-hospital mortality (1% in Group 3, 2% in Group 4; but 8% in Group 1 and 7% in Group 2, p = 0.0007); while at 30 days it remained so, as it was 1% in Group 3, 4% in Group 4 (and 10% in Group 1 and 10% in Group 2 p = 0.0002); and at 1 year it was 11% in Group 3 and 13% in Group 4 (compared to 20% in Group 1 and 23% in Group 2, p = 0.0012).In a large cohort of patients with CKD and ACS, chronic treatment with statin or the combination of aspirin and statin is associated with short-term and long-term better outcomes for in-hospital mortality, as compared to those receiving no therapy or aspirin therapy alone.

Background: The Italian network on acute coronary syndromes outcome (IN-ACS Outcome) study is a nationwide observational, multicenter study with the aim to describe clinical epidemiology, management, 30-days and one-year outcomes of ACS in Italy. Methods: All consecutive patients admitted for ACS to 38 hospitals, between December 2005 and February 2007, were enrolled in the study. Patient in-hospital details and follow-up data at 30-days and one-year were collected using a web-based CRF and stored in a central database. Results: A total of 6045 patients (age 68 13 years) were enrolled: 2313 patients (38.3%) had ST elevation myocardial infarction (STEMI) and 3732 (61.7%) patients had NSTE-ACS. Primary PCI was performed in 1085 (46.9%) STEMI patients, thrombolysis in 590 (25.5%) patients, whereas 638 (27.6%) patients were not reperfused. Among patients with NSTE-ACS, coronary angiography was performed in 2797 (75%) patients, PCI in 1797 (48.2%) patients and CABG in 213 (5.7%) patients. Thirty-days and one-year mortality rates were 5.8% and 9.8%, in STEMI patients and 3.1% and 8.6%, in NSTE-ACS patients. Conclusions: The IN-ACS Outcome study showed that the management of ACS is still suboptimal. Although 30-days mortality is low, the one-year mortality is still substantial.

The purpose of this study was to evaluate the prognostic significance of QRS duration in patients with suspected coronary artery disease (CAD) referred for noninvasive evaluation of myocardial ischemia by dobutamine stress echocardiography. QRS duration is a prognostic marker in patients with previous myocardial infarction and/or heart failure. The relation between QRS duration and outcome of patients without known heart disease has not been evaluated. A total of 1,227 patients (707 men, mean age 61 +/- 14 years) with suspected CAD underwent dobutamine stress echocardiography for evaluation of myocardial ischemia. Patients were followed to determine predictors of cardiac events and to assess the incremental significance of QRS duration compared to clinical and dobutamine stress echocardiographic data. During a mean follow-up of 4.2 +/- 2.4 years, 280 patients (23%) died (129 cardiac deaths), and 60 (5%) had a nonfatal infarction. Annualized cardiac death rates were 2.0% in patients with QRS duration = 120 ms, respectively (p = 120 ms (p = 0.0001). Multivariate models identified age, male gender, smoking, QRS duration >= 120 ms, and an abnormal dobutamine stress echocardiogram as independent predictors of cardiac death and the combined end point cardiac death/nonfatal infarction. In conclusion, QRS duration is an independent predictor of cardiac death and cardiac death/nonfatal infarction in patients with suspected CAD. This risk is persistent after adjustment for clinical variables, left ventricular function, and myocardial ischemia. (C) 2009 Elsevier Inc. All rights reserved. (Am J Cardiol 2009;104:1490-1493)

Background: In patients with ischaemic cardiomyopathy and viable myocardium, left ventricular ejection fraction (LVEF) does not always improve after revascularisation. Whether this may affect prognosis is unclear. Objective: To evaluate the prognosis of viable patients with and without improvement of LVEF after coronary revascularisation. Methods: Before revascularisation, radionuclide ventriculography (RNV) and dobutamine stress echocardiography were performed to assess LVEF and myocardial viability, respectively. Nine to 12 months after revascularisation, LVEF improvement was assessed by RNV. Patients were divided into three groups: group 1, viable patients with LVEF improvement (n = 27); group 2, viable patients without LVEF improvement (n = 15), group 3, non-viable patients (n = 48). Cardiac events were evaluated during a 4-year follow-up. Results: After revascularisation, the mean (SD) LVEF improved from 32 (9)% to 42 (10)% in group 1, but did not change significantly in group 2 and in group 3, p

To analyse osteoprotegerin (OPG), and B-type natriuretic peptide (BNP) levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion. OPG has been found in several tissues, including the cardiovascular system, BNP is selectively produced by myocardial cells.178 consecutive patients were classified in three groups: stable angina (SA), unstable angina/non-ST elevation myocardial infarction (NSTE-ACS) and control group, measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-, 2- , 3- or 4- vessels disease), and to the stenoses degree by Duke Jeopardy score.OPG levels were higher in patients respect to controls (p0.0001). Patients with SA showed more elevated levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p0.01). However patients with NSTE-ACS had higher OPG level with respect to SA patients (11.8+/-7.1 pmol/l p0.001). A positive relation was found between OPG levels and number of coronary plaques by Duke Jeopardy score (r=0.65). BNP levels were higher in patients with NSTE-ACS respect to controls and SA patients (p0.001). Besides, BNP was significantly higher in multivessels vs 1-vessel disease (p0.001).Patients with NSTE-ACS show high OPG levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the coronary disease progression. BNP is also increased during NSTE-ACS and more associated to coronary narrowing.

Objectives Our study investigated: 1) the contribution of nuclear factor kappa-B (NF-κB) signaling pathway to the enhanced inflammatory response observed in unstable angina (UA) patients with elevated levels of C-reactive protein (CRP); and 2) whether CRP may have direct proinflammatory effects via NF-κB activation. Background Unstable angina patients with elevated CRP have enhanced inflammatory response and increased risk of persistent instability, myocardial infarction, and death. Methods We studied 28 patients with history of UA and persistently elevated CRP (>3 mg/l) followed for 24 months and free of symptoms for at least 6 months (group 1), 14 patients with history of UA and low CRP (group 2), and 24 patients with chronic stable angina and low CRP (group 3). Peripheral blood monocytes were analyzed for spontaneous NF-κB activation and interleukin (IL)-6 and tumor necrosis factor (TNF)-α production. To assess the direct proinflammatory effects of CRP, monocytes from 8 healthy subjects were stimulated in vitro with increasing doses of CRP (5 to 10 to 25 μg/ml), lipopolysaccharide (LPS) (1 to 10 ng/ml), or both. Results Spontaneous NF-κB activation in vivo was demonstrated in 82% of group 1 versus 14% of group 2 and 21% of group 3 patients (p Conclusions Nuclear factor kappa-B activation might represent a mechanism by which CRP amplifies and perpetuates the inflammatory component of acute coronary syndromes and influences the clinical outcome.

Akinesis becoming dyskinesis (AKBD) at high-dose dobutamine stress echocardiography (DSE) has been disregarded as a marker of myocardial ischemia. However, its prognostic significance is unknown.We sought to assess the long-term outcome of patients with AKBD during DSE.A total of 731 patients (age 62 +/- 15 years, 628 men) with two or more akinetic left ventricular segments at rest underwent DSE and were followed up for a mean period of 5 +/- 2.7 years. The end points considered during follow-up were hard cardiac events (cardiac death and nonfatal myocardial infarction) and heart failure.Dyskinesis in two or more segments at peak stress developed in 60 patients (8%). Resting wall-motion score index was 2.6 +/- 0.56 in patients with AKBD versus 2.3 +/- 0.55 in patients without AKBD (P = .0002). Ischemia occurred in 197 patients (27%). During follow-up, 254 patients (35%) developed hard cardiac events and 204 patients (28%) developed heart failure. In all, 226 patients (31%) died of various causes (cardiac death in 172 patients). The annualized hard cardiac event rate was 11% in patients with AKBD and 6% in patients without (P = .03). The incidence of heart failure was significantly higher in patients with AKBD than without (47% vs 26%, P.001). Independent predictors of hard cardiac events were age (hazard ratio [HR] 1.03 [confidence interval {CI} = 1.01-1.04]), previous myocardial infarction (HR 1.4 [CI = 1.1-1.9]), diabetes mellitus (HR 1.8 [CI = 1.3-2.5]), resting wall-motion score index (HR 1.11 [CI = 1.01-1.04]), and AKBD (HR 1.6 [CI = 1.1-2.4]).AKBD at peak DSE is associated with increased risk of cardiac events in patients with akinetic segments at baseline echocardiogram.

Background: 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. Methods: 129 patients (31 diabetic, 98 non-diabetic) with ischaemic cardiomyopathy underwent dobutamine stress echocardiography to assess myocardial viability. Patients with ≥4 viable segments were defined as viable and patients with <

To evaluate the relative merits of viability and ischaemia for prognosis after revascularisation.Low-high dose dobutamine stress echocardiography (DSE) was performed before revascularisation in 128 consecutive patients with ischaemic cardiomyopathy (mean (SD) left ventricular ejection fraction (LVEF) 31 (8)%). Viability (defined as contractile reserve (CR)) and ischaemia were assessed during low and high dose dobutamine infusion, respectively. Cardiac death was evaluated during a five year follow up. Clinical, angiographic, and echocardiographic data were analysed to identify predictors of events.Univariable predictors of cardiac death were the presence of multivessel disease (hazard ratio (HR) 0.21, p0.001), baseline LVEF (HR 0.90, p0.0001), wall motion score index (WMSI) at rest (HR 4.02, p = 0.0006), low dose DSE (HR 7.01, p0.0001), peak dose DSE (HR 4.62, p0.0001), the extent of scar (HR 1.39, p0.0001), and the presence of CR inor = 25% of dysfunctional segments (HR 0.34, p = 0.02). The best multivariable model to predict cardiac death included the presence of multivessel disease, WMSI at low dose DSE, and the presence of CR inor = 25% of the severely dysfunctional segments (HR 9.62, p0.0001). Inclusion of ischaemia in the model did not provide additional predictive value.The findings of the present study illustrate that in patients with ischaemic cardiomyopathy, the extent of viability (CR) is a strong predictor of long term prognosis after revascularisation. Ischaemia did not add significantly in predicting outcome.

Previous studies have shown a good outcome for patients who present with normal findings on stress myocardial perfusion imaging. Currently, the prognostic implications of a normal study in patients who have a history of coronary artery disease (CAD) are not clear. This study investigated the long-term prognosis after a normal finding on stress technetium-99m (Tc-99m)-tetrofosmin single-photon emission computed tomography in patients with a history of CAD. The study included 147 consecutive patients with a history of CAD (previous myocardial infarction and/or myocardial revascularization), who underwent exercise bicycle or high-dose dobutamine-atropine stress Tc-99m-tetrofosmin single-photon emission computed tomography, and had normal perfusion results during stress and at rest. Follow-up was completed in all patients. During a follow-up of 6.5 +/- 1.9 years, 20 patients (14%) died, 10 (7%) of whom died due to cardiac causes, and 12 (8%) had a nonfatal myocardial infarction. Annual cardiac death rates were 0.5% during the first 3 years of follow-up and 1.3% in the subsequent 3 years. Independent predictors of cardiac death were male gender, rate-pressure product at rest, and rate-pressure product at peak stress. In conclusion, patients who have a history of CAD have a very low cardiac death rate during the 3 years after a normal finding on stress Tc-99m-tetrofosmin single-photon emission computed tomography. Repeated testing should be reconsidered 3 years after the initial evaluation and when a change in symptoms or clinical condition occurs.

Background There is experimental evidence that transplanting skeletal myoblasts (SM) into the post-infarction myocardial scar improves regional and global left ventricular (LV) function. Aims To evaluate short- and long-term regional and global LV functional effects of percutaneously transplanted SM in patients with ischaemic heart failure. Methods and results Ten patients (mean age 60 ± 10 years, 8 males) with dilated ischaemic cardiomyopathy underwent percutaneous injection of autologous myoblasts. Regional and global LV function was evaluated by 2-dimensional echocardiography and tissue Doppler imaging (TDI) at rest and during low-dose dobutamine infusion to assess contractile reserve. After a baseline examination, sequential follow-ups were performed at 1, 3, and 6 months and 1 year. NYHA functional class decreased from 2.7 ± 0.5 to 1.9 ± 0.5 (p < 0.01) at one year. LV function and volumes at rest remained unchanged while contractile reserve significantly improved during follow-up. At low-dose dobutamine infusion, the peak systolic velocity in the regions of myoblasts injection significantly increased at TDI examination (from 7.7 ± 2.1 to 8.6 ± 1.8 cm/s, p = 0.02); LV ejection fraction improved (from 40 ± 9% to 46 ± 8%, p < 0.0001) and end-systolic volumes decreased (from 56 ± 28 to 50 ± 25 ml/m2, p = 0.001) at 1 year. Conclusion In patients with ischaemic heart failure, percutaneous injection of autologous myoblasts may improve regional and global LV systolic function during dobutamine infusion, at 1-year follow-up.

This study was designed to assess the functional and prognostic significance of left anterior hemiblock (LAHB) in patients with no history of myocardial infarction referred for dobutamine stress echocardiography (DSE). BACKGROUND: The significance of isolated LAHB in patients with suspected coronary artery disease (CAD) is unclear. METHODS: We studied 1,187 patients with suspected CAD and no history of myocardial infarction who underwent DSE and were followed for occurrence of cardiac death. RESULTS: Left anterior hemiblock was detected on baseline electrocardiogram in 159 patients (13%). Ischemia occurred more frequently in patients with LAHB (43% vs. 33%, p = 0.02). During a mean follow-up of 5.0 +/- 2.5 years, 125 patients (11%) died of cardiac causes. The annual cardiac death rate was 4.9% in patients with LAHB and 1.9% for patients without (p < 0.0001). Patients with both LAHB and an abnormal DSE had the highest annual cardiac death rate (6.3%). In a Cox multivariable analysis, independent predictors of cardiac death were age, smoking, history of heart failure, diabetes, and ischemia. Left anterior hemiblock was independently associated with increased risk of cardiac death among patients with normal DSE (hazard ratio 1.8, 95% confidence interval 1.1 to 3.8) and in patients with abnormal DSE (hazard ratio 1.7, 95% confidence interval 1.1 to 2.7). CONCLUSIONS: In patients with suspected CAD referred for stress testing, LAHB is associated with increased risk of cardiac death. This risk is persistent after adjustment for major clinical data and abnormalities on the stress echocardiogram. Therefore, isolated LAHB should not be considered a benign electrocardiographic abnormality in these patients.

Objectives: To compare the long term prognosis of patients having silent versus symptomatic ischaemia during dobutamine stress echocardiography (DSE). Design: Observational study. Setting: Tertiary referral centre. Patients: 931 patients who experienced stress induced myocardial ischaemia during DSE. Results: Silent ischaemia was present in 643 of 931 patients (69%). The number of dysfunctional segments at rest (mean (SD) 9.6 (5.1) v 8.8 (5.0), p = 0.1) and of ischaemic segments (3.5 (2.2) v 3.8 (2.1), p = 0.2) was comparable in both groups. During a mean (SD) follow up of 5.5 (3.3) years, there were 169 (18%) cardiac deaths and 86 (9%) non-fatal infarctions. Multivariable Cox regression analysis showed age (hazard ratio (HR) 1.1, 95% confidence interval (CI) 1.02 to 1.05), previous myocardial infarction (HR 1.4, 95% CI 1.1 to 2.0), and number of ischaemic segments during the test (HR 2.0, 95% CI 1.0 to 3.7) as independent predictors of cardiac death and myocardial infarction. For every additional ischaemic segment there was a twofold increment in risk of late cardiac events. The annual cardiac death or myocardial infarction rate was 3.0% in patients with symptomatic ischaemia and 4.6% in patients with silent ischaemia (p < 0.01). Silent induced ischaemia was an independent predictor of cardiac death and myocardial infarction (HR 1.7, 95% CI 1.1 to 2.0). During follow up symptomatic patients were treated more often with cardioprotective therapy (p < 0.01) and coronary revascularisation (145 of 288 (50%) v 174 of 643 (27%), p < 0.001). Conclusions: Patients with silent ischaemia had a similar extent of myocardial ischaemia during DSE compared to patients with symptomatic ischaemia but received less cardioprotective treatment and coronary revascularisation and experienced a higher cardiac event rate.

The presence of myocardial ischemia during dobutamine stress echocardiography is independently associated with an increased risk of all-cause mortality in women after adjustment for clinical data. This association is observed in patients who have proved coronary artery disease and in patients who have no history of coronary artery disease.

Objectives The aim of this study was to investigate the effects of gender on long-term prognosis of patients undergoing dobutamine stress echocardiography (DSE). Background Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease undergoing DSE have not been adequately studied. Methods We studied 2,276 men and 1,105 women with known or suspected coronary artery disease who underwent DSE. Follow-up events were cardiac death and nonfatal myocardial infarction (MI). Results Dobutamine stress echocardiography was normal in 687 men (30%) and 483 women (44%) (p Conclusions Dobutamine stress echocardiography provides independent prognostic information in both men and women. In patients with normal DSE, gender is independently associated with cardiac events. The outcome of patients with abnormal DSE is not related to gender, after adjusting for stress echocardiographic abnormalities.

This study assessed the incidence, clinical correlates, and prognostic significance of angina during dobutamine stress echocardiography (DSE) in patients who did not have inducible wall motion abnormalities. We studied 2,117 patients (61 +/- 13 years of age; 1,149 men) who underwent large-dose DSE and had no new or worsening wall motion abnormalities during DSE. Follow-up events were hard cardiac events (cardiac death or nonfatal myocardial infarction) and myocardial revascularization. Angina was induced in 217 patients (10%) during stress. DSE was normal in 1,198 patients (57%), whereas 919 patients (43%) had fixed wall motion abnormalities. During a mean follow-up of 5.5 +/- 3.7 years, 143 patients (7%) died of cardiac causes and 78 (4%) had nonfatal myocardial infarction. Patients who developed angina during DSE were more likely to have a history of exertional angina (64% vs 16%, p0.001) and had a higher wall motion score index at rest (1.29 +/- 0.5 vs 1.17 +/- 0.4, p = 0.01) compared with patients who did not have angina. Annual hard cardiac event rates were 2.2% in patients who had dobutamine-induced angina (DIA) and 2.1% in patients who did not (p = NS). Myocardial revascularization was performed more frequently in patients who had DIA than in those who did not (39% vs 14%, p0.0001). In Cox's regression model, independent predictors of hard events were age (RR 1.03, 95% confidence interval [CI] 1.02 to 1.04), male gender (RR 1.6, 95% CI 1.1 to 2.2), smoking (RR 1.5, 95% CI 1.1 to 2.9), and wall motion score index at rest (RR 2.6, 95% CI 1.8 to 3.8). In conclusion, in patients who do not have ischemia by echocardiographic criteria during DSE, inducible angina pectoris is associated with a high incidence of revascularization during follow-up. However, the hard cardiac event rate does not differ in patients who develop DIA from those who do not.

OBJECTIVE: To evaluate prospectively the response of left ventricular ejection fraction (LVEF) to high dose dobutamine infusion in patients showing substantial viability, with and without improved resting LVEF after revascularisation. METHODS: Before and 9-12 months after revascularisation, 50 patients with ischaemic cardiomyopathy (LVEF 32 (8)%) and substantial myocardial viability (> or = 4 viable segments) underwent radionuclide ventriculography and dobutamine stress echocardiography. Patients were divided into group 1, patients with, and group 2, patients without significant improvement in resting LVEF (> or = 5% by radionuclide ventriculography) after revascularisation. The response of LVEF during dobutamine stress echocardiography was compared in these two groups. RESULTS: Groups 1 and 2 were comparable in baseline characteristics, resting LVEF, and number of viable segments (mean (SD) 7 (4) v 6 (2), not significant). After revascularisation, the LVEF response during dobutamine stress echocardiography improved significantly in both groups (group 1, 34 (10)% to 56 (8)%; group 2, 32 (10)% to 46 (11)%; both p < 0.001). Interestingly, although resting LVEF did not improve in group 2, peak stress LVEF after revascularisation did (p < 0.001). Group 1 patients had, however, a greater increase in peak stress LVEF (group 1, 22 (10)%; group 2, 13 (9)%; p < 0.01). New York Heart Association and Canadian Cardiovascular Society classes decreased in both groups. CONCLUSIONS: Although patients with viable myocardium did not always have improved rest LVEF after revascularisation, peak stress LVEF improved. Assessment of improvement of resting function may not be the ideal end point to evaluate successful revascularisation.

Objective: Dobutamine stress echocardiography (DSE), using subjective wall motion scoring, provides incremental prognostic information over clinical data. The aim of the study was to test the additional prognostic value of left ventriclar ejection fraction (LVEF) changes during DSE at different stages. Methods: The study population comprised 106 consecutive patients (mean age 60 ± 11 years, 73% men) with suspected or known coronary artery disease referred for DSE. Stress-induced ischemia was defined as new or worsening wall motion abnormalities. LVEF was measured at rest, peak stress and recovery. Follow-up was successful in 104 (98%) patients. Four patients who underwent revascularization within 60 days were excluded from the analysis. End-points during follow-up were cardiac death, non-fatal myocardial infarction and late revascularization. Results: During a mean follow-up of 5.3 ± 2.1 years, 26% of patients died: 13% due to cardiac death, 6% patients experienced non-fatal myocardial infarction and 38% underwent late revascularization. Rest-to-peak LVEF increase was lower in patients who experienced cardiac death or non-fatal myocardial infarction (4.9 ± 8.6 compared with 9.2 ± 7.5, P = 0.04) and any cardiac events (6.0 ± 8.5 compared with 10.5 ± 6.7, P = 0.004). An inverse correlation was found between left ventricular ejection increase and the number of ischemic segments (P < 0.0001). A multivariable Cox proportional hazard model demonstrated that, in addition to clinical data and new wall motion abnormalities, lower LVEF increase had an incremental prognostic value in predicting hard cardiac events (hazard ratio 1.1, 95% confidence interval 1.0-1.2). Conclusion: Failure of LVEF to significantly increase during DSE, denoting more extensive ischemia, identifies a higher-risk subgroup for late cardiac events.

Background Detection of myocardial viability is crucial for clinical treatment of patients with ischemic cardiomyopathy. Currently, quantitative information for the evaluation of systolic and diastolic function of viable tissue is limited. Our aim was to compare quantitatively systolic and diastolic function in viable and nonviable dysfunctional myocardium in patients with ischemic cardiomyopathy. Methods A total of 93 patients (mean age, 62 ± 10 years) underwent dobutamine stress echocardiography to assess myocardial viability. Pulsed-wave tissue Doppler imaging (TDI) was used to assess systolic ejection velocity (V S ) and early (V E ) and late (V A ) diastolic velocities at rest and at low-dose dobutamine infusion (10 μg/kg per minute) in viable and nonviable dysfunctional regions. Analysis was repeated after dividing study population in patients ≥65 years old (n = 40) and Results Pulsed-wave TDI demonstrated that V S was comparable in dysfunctional viable and nonviable regions at rest (V S , 6.3 ± 1.9 cm/s vs 6.3 ± 2.0 cm/s, respectively, P = .93). However, at low-dose dobutamine challenge, V S was significantly higher in viable regions (8.5 ± 2.7 cm/s vs 7.8 ± 2.4 cm/s, P = .002). Viable regions had higher V E at rest compared with nonviable regions (8.4 ± 2.5 cm/s vs 7.5 ± 2.8 cm/s, P = .003). Myocardial velocities were significantly higher in patients ≥65 years old, both in viable and nonviable regions. Conclusions Quantification of myocardial motion by pulsed-wave TDI demonstrates that at low-dose dobutamine stress, systolic velocity is markedly improved in viable myocardium, indicating the presence of contractile reserve in viable regions. A superior early diastolic filling at rest can also differentiate viable from nonviable myocardium.

Currently, there are no outcome data to suggest an incremental value of stress echocardiography in the risk stratification of patients who have hypertension after controlling for the left ventricular mass index (LVMI). This study assessed the incremental value of dobutamine stress echocardiography (DSE) for the prediction of mortality rate and cardiac events in patients who have hypertension. We studied 596 patients who had hypertension (mean age 62 ± 12 years; 382 men) and who underwent DSE for evaluation of known or suspected coronary artery disease. End points during follow-up were hard cardiac events (cardiac death and nonfatal myocardial infarction) and total mortality rate. Left ventricular hypertrophy was detected by echocardiography in 119 patients (20%). During a median follow-up of 3 years, 101 patients (17%) died (43 cardiac deaths) and 19 patients had nonfatal myocardial infarction. In an incremental multivariate analysis model, clinical predictors of hard cardiac events were age, history of congestive heart failure, and LVMI. The percentage of abnormal myocardial segments examined with DSE was incremental to the clinical model (chi square 41 vs 27, p

Background— Extensive left ventricular (LV) remodeling may not allow functional recovery after revascularization, despite the presence of viable myocardium. Methods and Results— Seventy-nine consecutive patients with ischemic cardiomyopathy (left ventricle ejection fraction [LVEF] 29±7%) underwent surgical revascularization. Before revascularization, viability was assessed by metabolic imaging with F18-fluorodeoxyglucose and SPECT. LV volumes and LVEF were assessed by resting echocardiography. LVEF was re-assessed by echocardiography 8 to 12 months after revascularization. Three-year clinical follow-up (events: cardiac death, infarction, and hospitalization for heart failure) was also obtained. Forty-nine patients had substantial viability; 5 died before re-assessment of LVEF. Of the remaining 44 patients, 24 improved ≥5% in LVEF after revascularization, whereas 20 did not improve in LVEF. LV end-systolic volume was the only parameter that was significantly different between the groups (109±46 mL for the improvers versus 141±31 mL for the nonimprovers; P Conclusion— Extensive LV remodeling prohibits improvement in LVEF after revascularization and affects long-term prognosis negatively, despite the presence of viability.

The presence of a right bundle branch block (RBBB) is associated with increased mortality. We studied the role of dobutamine stress echocardiography for the prognostic stratification of patients with RBBB. The presence of an abnormal dobutamine stress echocardiography was the strongest predictor of cardiac events and provided incremental prognostic information to clinical and stress test data.

Currently, the prediction of improvement of left ventricular (LV) ejection fraction (EF) after revascularization in patients with ischemic cardiomyopathy relies only on viable myocardium extent, whereas both the amount of viable and scar tissue may be important. A model was developed, based on the amount of viable and nonviable myocardium, to predict functional recovery. Viable and scarred myocardium was defined by dobutamine stress echocardiography (DSE) in 108 consecutive patients. LVEF before and 9 to 12 months after revascularization was assessed by radionuclide ventriculography; an improvement of ≥5% was considered significant. In the 1,089 dysfunctional segments (63%), DSE elicited biphasic response in 216 segments (20%), sustained improvement in 205 (19%), worsening in 43 (4%), and no change in 625 (57%). LVEF improved in 39 patients (36%). Only the numbers of biphasic and scar segments were predictors of improvement or no improvement of LVEF (odds ratio 1.5, 95% confidence interval 1.2 to 1.7, p

Technetium-99m (Tc-99m) tetrofosmin single-photon emission computed tomography (SPECT) is a useful alternative to thallium-201 scintigraphy for the assessment of myocardial perfusion. This study assessed the incremental value of exercise Tc-99m tetrofosmin SPECT for the prediction of cardiac events in patients with known or suspected coronary artery disease. Exercise Tc-99m tetrofosmin SPECT imaging was performed in 655 consecutive patients. Follow-up was successful in 648 patients (98.9%). Ten patients underwent early coronary revascularization and were excluded. End points were cardiac death, nonfatal infarction, and late (>60 days) coronary revascularization. An abnormal study was defined as the presence of fixed and/or reversible perfusion defects. A summed stress score (SSS) was derived to estimate the extent and severity of perfusion defects. An abnormal scan was detected in 344 patients (54%). During a mean follow-up period of 4 +/- 1.3 years, 56 patients (9%) died (22 cardiac deaths). Nonfatal myocardial infarction occurred in 19 patients (3%), and 89 patients (14%) underwent late coronary revascularization. An abnormal scan was an independent predictor of cardiac death (hazard ratio 3.5, confidence intervals [CI] 1.1 to 12.2) and provided incremental information over clinical and exercise test data (log-likelihood -133 to -125, p

Background: The hand-carried cardiac ultrasound (HCU) device is a recently introduced imaging device, which may be potentially useful in the primary care setting. Aim: To test the screening potential of a HCU for the detection of left ventricular (LV) dysfunction by evaluating LV ejection fraction (LVEF) and inferior vena cava (IVC) collapse. Standard echocardiographic system (SE) and plasma brain natriuretic peptide (BNP) measurements were used as a reference. Methods: Eighty-eight consecutive patients (56 male, aged 59±12 years) with suspected LV dysfunction were enrolled in the study. The HCU-LVEF was visually estimated and the SE-LVEF was derived by the Simpson's biplane method. A LVEF

Background —C-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 Results —We 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 P r =0.42, P =0.005). Conclusions —Mononuclear 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.

Widespread plaque inflammation has been demonstrated in acute coronary syndromes (ACS). We evaluated signs of plaque inflammation in carotid arteries of patients with ACS by contrast-enhanced magnetic resonance imaging (MRI). Carotid MRI was performed in 13 patients with ACS and in 9 controls having at least 1 carotid plaque with a stenosis ≥40%. MRI criteria of plaque inflammation were: increased T2 signal >50% of the plaque areas (tissue oedema) and/or enhancement after gadolinium injection (neo-vascularization). MRI signs of inflammation were found in 95% and in 33% of patients with ACS and controls, respectively ( p Carotid artery MRI may serve as a window to the entire cardiovascular system, to identify "vulnerable" patients.

Transient global amnesia (TGA) is a common paroxysmal disorder of episodic memory. The aetiology of TGA is still unknown. Brain ischaemia, migraine, epileptic seizure, venous congestion and psychological disturbances have been proposed as pathological mechanisms. Moreover, different precipitating events are recognised in most TGA patients including physical activity, severe emotional stress, painful experiences, immersion in cold water and sexual intercourse. We describe a 54-year-old woman who presented a TGA immediately after right-left shunt of saline contrast during the execution of transoesophageal echocardiography. Aetiopathological considerations for this uncommon presentation are discussed.

Technetium-99m-tetrofosmin single-photon emission computed tomography at rest is practical for routine assessment of viability in patients with ischemic cardiomyopathy. However, underestimation of viability may occur compared with 18F-fluorodeoxyglucose single-photon emission computed tomography, especially in the inferoposterior and septal regions.

Aims We conducted a population-based cross-sectional study to assess the prevalence of both preclinical and clinical heart failure (HF) in the elderly. Methods and results A sample of 2001 subjects, 65- to 84-year-old residents in the Lazio Region (Italy), underwent physical examination, biochemistry/N-terminal pro brain natriuretic peptide (NT-proBNP) assessment, electrocardiography, and echocardiography. Systolic left ventricular dysfunction (LVD) was defined as left ventricular ejection fraction (LVEF)

Two-dimensional and color-Doppler echocardiography is the most widely used imaging method in athletes. In these subjects, echocardiography is a valuable way to diagnose potentially lethal heart diseases. In fact, in the last few years episodes of sudden death associated with physical exercise in competitive athletes have become highly visible events fuelled by new media reports. Often the underlying cause of sudden death in such patients is represented by structural changes to the heart and/or great vessels that may be identified by echocardiography. The existence of heart disease may be an exclusion criterion in competitive sport in order to reduce the risk of sudden death and/or it may justify the implantation of an automatic defibrillator.

L’ecocardiografia bidimensionale e color-Doppler rappresenta la metodica di imaging di piu ampio utilizzo nella popolazione degli atleti. In questi soggetti l’ecocardiografia rappresenta un valido strumento per la diagnosi di cardiopatie potenzialmente letali. Infatti, negli ultimi anni hanno avuto molta risonanza mediatica degli episodi di morte improvvisa associata all’esercizio fisico in atleti a livello agonistico. Spesso la causa sottostante della morte improvvisa in tali pazienti e rappresentata da alterazioni strutturali cardiache e/o vascolari che possono essere identificate dall’ecocardiografia. La presenza di una cardiopatia puo rappresentare un criterio di esclusione da sport agonistici al fine di ridurre il rischio di morte improvvisa e/o puo giustificare l’impianto di un defibrillatore automatico. D’altro canto il cuore dell’atleta, e specificatamente il cuore di atleti molto allenati, praticanti sport di resistenza (maratona, nuoto) o misti (sci di fondo, ciclismo e canottaggio), va incontro a delle modificazioni strutturali e funzionali che vanno conosciute al fine di evitare diagnosi errate di cardiopatie. Il presente capitolo ha l’intento di fornire una guida strutturata allo studio ecocardiografico del cuore dell’atleta.

Obesity is associated with a high risk of coronary artery disease morbidity and mortality. Yet, postmortem studies have shown that severely obese subjects exhibit smooth coronary arteries, thus suggesting that they may be protected from atherosclerosis. We assessed vascular function and its possible determinants in a cohort of normal-weight to severely obese insulin-sensitive subjects (body mass index [BMI] 23.2-49 kg/m(2)).Seventy-one healthy, insulin-sensitive subjects (Homeostasis Model Assessment of Insulin Resistance index2.5), divided into normal-weight (n = 13; BMI = 23.2 +/- 1.6), obese (n = 35; BMI=32.6+/-2.5), and severely obese (n=23; BMI=49.0+/-7.9) groups, were enrolled. Vascular function was evaluated by flow-mediated dilation and carotid intima-media thickness. High-sensitivity C-reactive protein, leptin, adiponectin, vascular growth factors, and CD34+KDR+/CD133+ endothelial progenitor cells, known markers of vascular health/protection, also were measured.Flow-mediated dilation was higher in severely obese than in obese and normal-weight individuals (P=.019 and P=.011 respectively). Intima-media thickness was consistently lower in severely obese than in obese individuals (P=.040) and similar in severely obese and normal-weight individuals (P.99). Levels of high-sensitivity C-reactive protein and leptin were higher in severely obese than in obese and normal-weight individuals (high-sensitivity C-reactive protein: P=.018 and P=.05, respectively; leptin: P.001 for both comparisons). CD34+KDR+ endothelial progenitor cells were significantly higher in severely obese versus obese individuals (P=.039).Our study demonstrates that vascular function is paradoxically better in severely obese than in obese subjects and similar to that found in normal-weight subjects. Despite higher levels of high-sensitivity C-reactive protein and leptin, severely obese individuals may be partially protected from atherosclerosis, possibly by a greater mobilization of endothelial progenitor cells.

BACKGROUND: Acute coronary syndromes (ACS) and chronic stable angina represent extremes of the clinical spectrum of coronary artery disease (CAD). It is unknown whether genetic determinants affect the first clinical manifestation of CAD. We evaluated the role of the C(-260)T polymorphism in the promoter of the CD14-receptor gene, an important mediator of the inflammatory response to lipopolysaccharide. METHODS AND RESULTS: CD14 C(-260)T polymorphism was assessed in 100 patients with an acute presentation of CAD (group 1), 66 patients with stable presentation (group 2) and 88 healthy people (group 3); all patients were whites. In addition, baseline sCD14 plasma levels, and interleukin-6 production by circulating monocytes after in-vitro stimulation with lipopolysaccharide (1 ng/ml) were assessed. T/T homozygosis was more frequent in group 1 (36%, P < 0.001 versus others). Interleukin-6 production was higher in T/T homozygotes (median 4092.4; range 387-10 582 pg/ml) than in C/T heterozygotes (median 2442, range 40.5-9625 pg/ml, P < 0.001) and C/C homozygotes (median 3277.5; range 374.4-6250 pg/ml, P < 0.001). At multivariate analysis, T/T homozygosis and interleukin-6 production were independent predictors of acute presentation of CAD. CONCLUSION: The present study shows that genetic factors that influence the reactivity of inflammatory cells may play a role in determining the first clinical presentation of CAD.

Background: C-reactive protein (CRP) is an established prognostic marker in acute coronary syndromes (ACS); however, no study has specifically addressed its prognostic role in type 2 diabetes with ACS. We evaluated the prognostic role of CRP separately in diabetic and nondiabetic patients with ACS. Methods: We enrolled 251 patients with unstable angina and measured serum concentrations of high sensitivity (hs)CRP. Ninety-seven patients underwent coronary angiography with evaluation of atherosclerotic disease severity and extent by Bogaty score. Assessed endpoint was the combined occurrence of myocardial infarction (MI) and death at 1 year. Results: No significant differences were found in hs-CRP between patients with and without diabetes. By Cox regression, hsCRP was not associated with 1-year follow-up events in diabetic patients but was strongly associated with events in nondiabetic patients (P = 0.0012). Coronary angiography exhibited a higher extent index in patients with diabetes than in those without (P = 0.04). hsCRP concentrations were not associated with angiographic atherosclerotic burden. By Cox analysis, hsCRP and extent score were associated with events in patients who underwent coronary angiography (P < 0.001 and P = 0.034, respectively). In nondiabetic patients, hsCRP was the only predictor of events at 1-year follow-up (P < 0.001), whereas in diabetic patients, hsCRP was not associated with events and a weak association was observed for extent score (P = 0.06). Conclusions: Our study suggests that different pathophysiological mechanisms may be responsible for MI and death in unstable angina patients with or without diabetes and that severity of coronary artery disease plays a major role in diabetes (and inflammation in the absence of diabetes).

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 …

Objective Patients with unstable angina (UA) and high C-reactive protein (CRP) have increased cardiovascular risk. Whether genetic factors such as the synonymous 1059G/C polymorphism within the exon 2 of the human CRP gene determine CRP levels and outcome is unclear. Methods In 105 consecutive patients with UA, we assessed the CRP 1059G/C polymorphism, CRP plasma levels and interleukin-6 production after in-vitro stimulation of whole blood with lipopolysaccharide (1 ng/ml). Coronary events during a 24-month follow-up were recorded. Results CRP levels (median, range) were significantly lower among C-allele carriers (2.3 mg/l, 0.5-26.9) than among GG homozygotes (5.9 mg/l, 0.8-72.12, P=0.009). Interleukin-6 production was lower in C-allele carriers (1645 pg/ml, 832.0-9522) than in GG homozygotes (3929 pg/ml, 670.8-10 582), (P=0.085). At follow-up, 1059C-allele carriers experienced fewer coronary events than 1059GG homozygotes (13 vs. 47%, P=0.021). At multivariable analysis, a CRP level >3 mg/l, but not the 1059G/C polymorphism, was an independent predictor of coronary events (odds ratio 10.04, 95% confidence interval 2.84-35.44, P=0.0002). Conclusion This study shows that the CRP synonymous 1059G/C polymorphism affects CRP levels. No independent association was, however, observed between this polymorphism and clinical outcome in UA.

The prognostic significance of myocardial ischemia assessed by dobutamine stress echocardiography in asymptomatic patients with diabetes mellitus who have no previous coronary artery disease remains unclear. We assessed the value of dobutamine stress echocardiography for risk stratification in 161 asymptomatic patients with type 2 diabetes (mean 62 +/- 12 years of age; 96 men) who had no previous myocardial infarction or revascularization. End point during follow-up was hard cardiac events (cardiac death and nonfatal myocardial infarction). Ischemia was detected in 45 patients (28%). During a median follow-up of 5 years, 40 patients (25%) died (18 cardiac deaths) and 7 patients had nonfatal myocardial infarction (25 hard cardiac events). An abnormal dobutamine stress echocardiogram was associated with a higher mortality compared with a normal dobutamine stress echocardiogram (p = 0.03). In an incremental multivariate analysis model, clinical predictors of hard cardiac events were age and hypercholesterolemia. Ischemia was incremental to the clinical parameters. In conclusion, myocardial ischemia is an independent predictor of cardiac events in asymptomatic diabetic patients with no previous coronary artery disease.

A 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 …

Background— Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that favors the expansion of CD4 + CD28 null 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-α. Methods and Results— Peripheral blood samples were collected from 17 patients with UA (Braunwald’s class IIIB). CD4 + CD28 null 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 μg/mL) of infliximab, an anti–TNF-α 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 + CD28 null 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 μg/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 + CD28 null T-cell expansion in patients with UA may be reduced by selective TNF-α blockade. Further studies are warranted to evaluate the clinical benefit of CD4 + CD28 null T-cell modulation.

ObjectivesWe hypothesized that the expansion of unusual T lymphocytes, CD4+CD28nullT cells, might represent a key pathogenetic mechanism of recurrent instability.BackgroundClinical presentation of acute coronary syndromes (ACS) is variable. Some patients have recurrent episodes of instability, despite optimal treatment, whereas others have a single acute event in their life. The CD4+CD28nullT cells, with a functional profile that favors vascular injury, have recently been found both in peripheral blood and in unstable coronary plaques of patients with ACS.MethodsPeripheral blood T cells from 120 consecutive unstable angina (UA) patients were analyzed for the distribution of T-cell subsets by flow cytometry. Patients were subgrouped according to the occurrence of prior (during the 24 months before the study enrollment) and subsequent (during the 24 months of follow-up) acute coronary events. For 51 patients, the index event was the first ever (G1); 30 patients had prior events (G2); and 39 patients had further events at follow-up (death, myocardial infarction, or UA) or both before and after the index event (G3).ResultsThe CD4+CD28nullT-cell frequency was higher in G3 than in G2 and G1 (median 9.5% [range 2.4% to 48.0%] vs. 5.1% [range 0.4% to 27.8%] and 2.3% [range 0.2% to 22.8%], respectively; p < 0.001). The expansion of these unusual T lymphocytes was higher in patients with elevated C-reactive protein levels, and it was reduced by statin therapy. On multivariate logistic regression analysis, CD4+CD28nullT-cell frequency was an independent predictor of future acute coronary events (odds ratio 3.01, 95% confidence interval 1.1 to 8.25; p = 0.023).ConclusionsA perturbation of T-cell repertoire is strongly associated with the recurrence of acute coronary events, conceivably playing a key pathogenetic role.

Our study investigated: 1) the contribution of nuclear factor kappa-B (NF-kappaB) signaling pathway to the enhanced inflammatory response observed in unstable angina (UA) patients with elevated levels of C-reactive protein (CRP); and 2) whether CRP may have direct proinflammatory effects via NF-kappaB activation.Unstable angina patients with elevated CRP have enhanced inflammatory response and increased risk of persistent instability, myocardial infarction, and death.We studied 28 patients with history of UA and persistently elevated CRP (3 mg/l) followed for 24 months and free of symptoms for at least 6 months (group 1), 14 patients with history of UA and low CRP (group 2), and 24 patients with chronic stable angina and low CRP (group 3). Peripheral blood monocytes were analyzed for spontaneous NF-kappaB activation and interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha production. To assess the direct proinflammatory effects of CRP, monocytes from 8 healthy subjects were stimulated in vitro with increasing doses of CRP (5 to 10 to 25 microg/ml), lipopolysaccharide (LPS) (1 to 10 ng/ml), or both.Spontaneous NF-kappaB activation in vivo was demonstrated in 82% of group 1 versus 14% of group 2 and 21% of group 3 patients (p0.001). Interleukin-6 and TNF-alpha production was significantly correlated with the NF-kappaB activation status (r = 0.55, p0.001 and r = 0.53, p = 0.006, respectively). Patients with NF-kappaB activation had recurrence of acute coronary events (60% vs. 28%; p = 0.017). C-reactive protein induced a significant but modest in vitro NF-kappaB activation in human monocytes (p = 0.002). Coincubation with LPS produced a greater-than-additive response (p0.01 vs. CRP and LPS alone).Nuclear factor kappa-B activation might represent a mechanism by which CRP amplifies and perpetuates the inflammatory component of acute coronary syndromes and influences the clinical outcome.

Nuclear imaging using (18)F-FDG is an established method for the noninvasive assessment of myocardial viability. Data on the value of (18)F-FDG imaging in patients with diabetes mellitus are scarce. The aim of this study was to assess whether, in patients with diabetes mellitus and ischemic left ventricular (LV) dysfunction, (18)F-FDG imaging can predict improvement of LV function and heart failure symptoms after coronary revascularization.A total of 130 consecutive patients with ischemic LV dysfunction who were already scheduled for surgical revascularization were studied; 34 of the patients had diabetes mellitus. All patients underwent radionuclide ventriculography to assess left ventricular ejection fraction (LVEF), resting 2-dimensional echocardiography to identify dysfunctional myocardial tissue, and dual-isotope (18)F-FDG/(99m)Tc-tetrofosmin SPECT after oral administration of acipimox. Nine to 12 mo after coronary revascularization, radionuclide ventriculography and echocardiography were repeated. An improvement in LVEF by at least 5% was considered significant.(18)F-FDG SPECT demonstrated that 610 (50%) of 1,212 dysfunctional segments were viable. Patients with and without diabetes mellitus had a comparable number of dysfunctional but viable segments per patient. Also, the number of patients with a substantial amount of dysfunctional but viable myocardium (or=4 viable segments) was comparable between the groups with and without diabetes mellitus. The presence of substantial viability on (18)F-FDG SPECT was predictive of improvement in LVEF and heart failure symptoms postoperatively (sensitivity and specificity of 82% and 89%, respectively, in patients with diabetes and 83% and 93%, respectively, in patients without diabetes; not statistically significant).(18)F-FDG SPECT is practical for routine assessment of myocardial viability in patients with ischemic LV dysfunction with or without diabetes mellitus. Patients with substantial myocardial viability on (18)F-FDG SPECT have a high probability of improvement of LV function and symptoms after coronary revascularization, irrespective of the absence or presence of diabetes mellitus.

Non-invasive evaluation of coronary artery disease (CAD) in patients with left bundle branch block (LBBB) has limitations inherent to different tests, and the relative merits of these tests are unclear. This meta-analysis assessed the accuracy of the frequently used non-invasive techniques, including exercise electrocardiography (ECG), myocardial perfusion imaging (MPI) and stress echocardiography (SE), for detection of CAD and prediction of cardiac events in patients with LBBB. METHODS: A review was conducted of all reports on detection of CAD and prediction of cardiac events in patients with LBBB (published between January 1970 and December 2004), and revealed 55 diagnostic and nine prognostic reports with sufficient details to calculate test accuracy. Weighted (by sample size) sensitivity and specificity were calculated. Summary relative risk ratios (95% confidence intervals) were calculated. RESULTS: Overall sensitivity was higher for exercise ECG and (quantitatively analysed) MPI than for SE (83.4% and 88.5% versus 74.6% respectively, p

The relative merits of myocardial contrast echocardiography (MCE) and magnetic resonance imaging (MRI) to predict myocardial function improvement after percutaneous coronary intervention have not been evaluated until now. We studied 35 consecutive patients with acute myocardial infarction who underwent percutaneous coronary intervention using MCE and MRI and first-pass imaging for evaluation of myocardial perfusion. Delayed-enhanced MRI was included as another method to differentiate viable from infarcted tissue. MCE was performed by power modulation and intravenous Sonovue. A 16-segment model of the left ventricle was used to analyze all myocardial contrast echocardiograms and magnetic resonance images. At 60 days of follow-up, MCE showed improvement of function in 115 of 192 (60%) dysfunctional segments. The sensitivity, specificity, and accuracy for the prediction of functional improvement were comparable among MCE (87%, 90%, and 88%), first-pass MRI (87%, 60%, and 79%), and delayed-enhancement MRI (75%, 100%, and 82%, respectively, all p = NS). In conclusion, MCE and MRI allowed for prediction of myocardial function improvement after percutaneous coronary intervention. MCE had a comparable accuracy and, as a bedside technique, may be an alternative tool in the acute phase of acute myocardial infarction.