The diagnostic yield of transesophageal echocardiography in patients with cryptogenic cerebral ischaemia: a meta-analysis.

BACKGROUND AND PURPOSE: The diagnostic utility of transesophageal echocardiography (TEE) in patients with cryptogenic ischaemic stroke (IS) or transient ischaemic attack (TIA) remains controversial. METHODS: A systematic review and meta-analysis was performed according to PRISMA guidelines to estimate the pooled prevalence of potential cardioembolic causes detected by TEE in prospective observational studies of cryptogenic IS/TIA. Cardiac conditions causally associated with cerebral ischaemia were considered to be intramural thrombi and intracardiac tumors according to ASCO phenotyping of IS. RESULTS: Thirty-five eligible studies, comprising 5772 patients (mean age 53.6 years, 56.9% men) were identified. The most common TEE finding was ascending aorta and/or aortic arch atheroma [51.2% (27.4%-74.5%)], followed by patent foramen ovale (PFO) [43.2% (36.3%-50.4%)]. Complex aortic plaques and large PFOs were reported in 14% (10.2%-18.9%) and 19.5% (16.6%-22.8%) of TEE evaluations. The prevalence of atrial septal aneurysm was 12.3% (7.9%-18.7%) and was significantly higher in conjunction with PFO presence (risk ratio 2.04, 95% confidence interval 1.63-2.54, P < 0.001). The prevalence of left atrial thrombus [3.0% (1.1%-8.3%)] and spontaneous echo contrast [3.8% (2.3%-6.2%)] was low. The prevalence of intracardiac tumors was extremely uncommon [0.2% (0%-0.7%)]. Significant heterogeneity was identified (I(2) > 60%) in the majority of analyses. Heterogeneity was not affected by cryptogenic stroke definition (TOAST versus alternative criteria). After dichotomizing available studies using a cut-off of 50 years, PFO was significantly (P = 0.001) more prevalent in younger than in older patients. CONCLUSION: Routine TEE in patients with cryptogenic IS/TIA commonly identifies abnormal findings. However, the prevalence of cardiac conditions considered to be causally associated with cerebral ischaemia (intracardiac thrombi and tumors) is low.

Effects of adiponectin in TNF-α, IL-6, and IL-10 cytokine production from coronary artery disease macrophages.

Adiponectin, an adipose tissue secreted protein, exhibits anti-inflammatory and antiatherogenic properties. We examined the effects of the globular and full-length adiponectin on cytokine production in macrophages derived from Coronary Artery Disease (CAD) patients and control individuals. Adiponectin's effects in human macrophages upon lipopolysaccharide (LPS) treatment were also examined. Full length adiponectin acted differently on TNF-α and IL-6 production by upregulating TNF-α and IL-6 protein production, but not their mRNA expression. Additionally, full length adiponectin was unable to abrogate LPS proinflammatory effect in TNF-α and IL-6 mRNA expression in CAD and NON-CAD macrophages. In contrast, globular adiponectin appeared to have proinflammatory properties by potently upregulating TNF-α and IL-6 mRNA and protein secretion in human macrophages while subsequently rendered cells resistant to further proinflammatory stimuli. Moreover, both forms of adiponectin powerfully suppressed scavenger MSR-AI mRNA expression and augmented IL-10 protein release, both occurring independently of the presence of LPS or CAD. These data indicate that adiponectin could potentially protect human macrophages via the elevated IL-10 secretion and the suppression of MSR-AI expression. It can also be protective in CAD patients since the reduced adiponectin-induced IL-6 release in CAD macrophages compared to controls, could be beneficial in the development of inflammation related atherosclerosis.

Incremental value of arterial wave reflections in the determination of left ventricular diastolic dysfunction in untreated patients with essential hypertension.

Systemic arterial stiffness is an indicator of cardiovascular disease and an independent marker of morbidity and cardiovascular mortality. We investigated the association of arterial wave reflections with left ventricular (LV) diastolic dysfunction and their incremental value to other determinants of LV diastolic dysfunction in patients with essential hypertension. In total 143 patients and 20 controls with similar atherosclerotic risk factors were examined by applanation tonometry of the radial artery (Sphygmocor) and echocardiography. Central augmentation index (CAI%) of reflected arterial waves as well as aortic strain (AoS) assessed by echocardiography were estimated. Doppler diastolic abnormalities were defined as proposed by the European Study Group on diastolic heart failure by measurement of E/A ratio (the ratio of the mitral inflow velocities), isovolumic relaxation time, deceleration time and flow propagation velocity. AoS and CAI were impaired in patients compared with controls (4.67 +/- 2.94 vs 6.06 +/- 4.91% and 145.8 +/- 22.7 vs. 135.7 +/- 20.3%, P < 0.01) as well as in patients with LV diastolic dysfunction compared to patients without, (5.52 +/- 4.29 vs. 10.73 +/- 5.77% and 139.5 +/- 21.7 vs. 124.5 +/- 17.0%, P < 0.05). The odds ratio (OR) of AoS and CAI for diastolic dysfunction was OR:0.918, 95% confidence interval (CI):0.837-0.99, P = 0.04 and OR:1.023, 95% CI: 1.023-1.040 P = 0.010, respectively. The addition of CAI to the multivariable model including age, LV mass index, AoS and mean arterial pressure increased the power of the model for determination of LV diastolic dysfunction (-2 log likelihood = 139.368, change of chi2 = 4.2, P-value for change=0.04). In untreated patients with newly diagnosed essential hypertension, wave reflections are independent and additive determinants of LV diastolic dysfunction.

The combined effect of augmentation index and carotid intima-media thickness on cardiovascular risk in young and middle-aged men without cardiovascular disease.

Carotid artery intima-media thickness (IMT) has been used as a surrogate marker of atherosclerosis and is related to cardiovascular risk. Indices of arterial stiffness are also associated with cardiovascular risk and atherosclerosis. The aim of this study was to assess the prognostic value of the combination of surrogate markers of cardiovascular disease measured non-invasively in subjects without cardiovascular disease. In this cross-sectional study, 81 young and middle aged males (39.2+/-6.3 years) without evidence of overt cardiovascular disease or diabetes mellitus were enrolled. High-resolution B-mode ultrasonography and pulse wave analysis were used to measure carotid artery IMT and augmentation index (AI), a measure of arterial stiffness. Framingham risk score (FRS) was used as an estimate of the risk for development of cardiovascular disease. Regional differences were observed in the carotid arteries' IMT regarding their relationship with FRS: combined (average from all sites) IMT and IMT in the carotid bulb (CB), but not in the common (CC) and internal carotid artery (IC), and AI showed significant increases of FRS by their tertiles. However, subjects with both AI and IMT at any site in the highest tertile (AI>15%, CC>0.65 mm, CB>0.8 mm, IC>0.65 mm) had an increased FRS compared to subjects with one or none of these parameters in the highest tertile. In conclusion, young and middle-aged men without overt cardiovascular disease with both high IMT and AI are in high cardiovascular risk, as assessed by FRS. Epidemiological studies are needed to further validate this combination.

P673Improvement of arterial stiffness and myocardial deformation in patients with poorly controlled diabetes mellitus type 2 after optimization of antidiabetic medication.

BACKGROUND: Arterial stiffness is associated with increased risk for cardiovascular disease. The purpose of this study is to investigate the arterial stiffness and myocardial deformation in patients with poorly controlled diabetes mellitus type 2 before and after glycemic control by optimal medication. METHODS: In 50 patients with uncontrolled type 2 diabetes(age:52±10years)and 25 controls of similar age and sex and no atherosclerotic risk factors we measured at baseline and 6 months after glycemic control a) carotid-femoral pulse wave velocity(PWVc m/sec-Complior SP ALAM),central systolic blood pressure(cSBP -mmHg),augmentation index(AI%), of the aortic pulse wave(ArteriographTensioMed) b)S',E'(m/sec)andE'/A'of mitral annulus by Tissue Doppler c)LV longitudinal strain(GLS-%),systolic(LongSr-l/sec)and diastolic(LongSrE-l/sec)strain rate, twisting(Tw-deg),peak twisting(Tw)and untwisting(unTw-deg/sec)velocity using speckle tracking echocardiography.The degree of LV untwisting was calculated as the percentage difference between peak twisting and untwisting at MVO(%dp PeakTw-UntwMVO)and between peak twisting and untwisting at peak and end of the mitral inflow E wave d)perfusion boundary region(PBR- micrometers)of the sublingual arterial microvessels(ranged from 5-25 micrometers)using Sideview,Darkfield imaging(Microscan,Glycocheck).Increased PBR is considered an accurate index of reduced endothelial glucocalyx thickness because of a deeper RBC penetration in the glucocalyx e) Flow mediated dilatation(FMD) of the brachial artery and percentage difference of FMD (FMD%). RESULTS: Compared to controls,diabetics had higher PWVa(10.3±2.2 vs. 8.1±1.9), AI(27.9±15 vs. 19.4±14.7), PWVc(11.8±3.2 vs. 8.8±1.3),cSBP(136±20 vs. 119±18),PBR (2.1±0.2 vs 1.89±0.1)and lower GLS(-15±3 vs. -18±3),LongSr(-0.78±0.1 vs. -0.96±0.2),LongSrE(0.77±0.29 vs. 1.2±0.3),S',E' and E/A(p<0.05 for all comparisons). Baseline FMD was related with Untw at peak E%(r=0,65, p<0.05). Six months after the modification of antidiabetic medication all patients achieved glycaemic control and there was a reduction of PWVc(12.3±2.9 vs. 11.3±3.2,p<0.05) in parallel with a increase of Untw velocity (-73±27 vs. -98±43,p<0.05),Untw MVO%(20±9 vs. 30±2),Untw peak E% (40±14 vs. 50±16)and FMD%(7.8±3 vs. 13.6±11,p<0.01).Reduced PWVc was related with reduced SBP(r=0.62),cSBP(r=0.55)and increased LongsrE(r=-0.50), Untw at end E(r=-0.56)respectively(p<0.05 for all associations). CONCLUSION: Glycaemic control after optimizing medical treatment improves arterial stiffness, LV myocardial strain, twisting and untwisting velocity in diabetics.

Increased proinflammatory cytokines in patients with chronic stable angina and their reduction by aspirin.

BACKGROUND: Proinflammatory cytokines released by injured endothelium facilitate interaction of endothelial cells with circulating leukocytes and thus may contribute to development and progression of atherosclerosis. We investigated whether cytokines and C-reactive protein (CRP) are indicative of myocardial ischemia or of diseased vessels and whether they are influenced by aspirin treatment in patients with chronic stable angina. METHODS AND RESULTS: Plasma macrophage colony stimulating factor (MCSF), IL-1b, IL-6, and CRP were measured in 60 stable patients after 48-hour Holter monitoring and in 24 matched controls. All patients had angiographic documentation of disease and positive exercise ECGs. Patients with ischemia on Holter monitoring (n=40) received aspirin or placebo in a 6-week, randomized, double blind, crossover trial. Blood sampling was repeated at the end of each treatment phase (3 weeks). Compared to controls, patients had more than twice median MCSF (800 versus 372 pg/mL), IL-6 (3.9 versus 1.7 pg/mL), and CRP (1.25 versus 0.23 mg/L) levels (P<0.01 for all comparisons). MCSF was related to ischemia on Holter monitoring (P<0.01), to low ischemic threshold during exercise (P<0.01), and together with IL-1b to number of diseased vessels (P<0.05). MCSF, IL-6, and CRP were all reduced after 6 weeks of aspirin treatment (P<0.05). CONCLUSIONS: These findings suggest that cytokines are associated with both ischemia and anatomic extent of disease in patients with stable angina. Reduced cytokine and CRP levels by aspirin may explain part of aspirin's therapeutic action.

Significance of persistent left ventricular dysfunction during recovery after dobutamine stress echocardiography.

OBJECTIVES: This study sought to determine the duration of new or worsening left ventricular regional wall motion abnormalities (RWMAs) after dobutamine stress echocardiography (DSE) and their relation to the extent of coronary artery disease (CAD). BACKGROUND: Despite extensive reports on DSE, little is known about the duration of new or worsening RWMAs during recovery. We hypothesized that the persistence of RWMAs during recovery may be associated with the extent of CAD and therefore ischemia. METHODS: Sixty-five consecutive patients with positive results on DSE and angiographically documented CAD were studied. Each patient underwent 12-lead electrocardiography and two-dimensional echocardiography at rest, during dobutamine infusion and continuously during recovery to assess the recovery time of ischemic myocardial regions. RESULTS: All patients had at least one ischemic region during DSE. Complete resolution of RWMAs occurred within 25 min in patients with multivessel CAD, within 20 min in those with two-vessel disease and within 15 min in those with single-vessel disease (p < 0.001). The greater the wall motion score index at peak stress, the longer the duration of RWMAs into the recovery phase (p < 0.01). RWMAs persisted long after normalization of each patient's symptoms, electrocardiographic (ECG) changes, heart rate and rate-pressure product during recovery. CONCLUSIONS: We demonstrated that normalization of left ventricular RWMAs occurs after resolution of symptoms and ECG changes during recovery. The time to recovery is related to the extent of CAD and myocardial ischemia as well as to the presence or absence of collateral circulation. These findings may represent stunned myocardium after brief period of ischemia.

Assessment of left ventricular wall motion and delineation of the endocardial border after intravenous injection of Infoson during dobutamine stress echocardiography.

OBJECTIVES: To investigate whether intravenous injection of Infoson facilitates the assessment of left ventricular wall motion and definition of endocardial border and thereby reduces inter- and intra-observer variability during dobutamine stress echocardiography. BACKGROUND: Clear detection of the endocardial border is essential during dobutamine stress echocardiography. Although several contrast agents have been tested for their efficacy in enhancing definition of left ventricular endocardium, their usefulness during dobutamine stress echocardiography has not been evaluated. METHODS: Thirty coronary artery disease patients underwent dobutamine stress echocardiography. Infoson was injected at 0.2 ml/kg in both apical four- and two-chamber views. Detection of the left ventricular endocardial borders was scored from 0 (undetectable) to 10 (best) and expressed as a percentage of image quality at rest and peak stress by two independent observers. Regional wall motion was also evaluated and the total wall motion score index calculated each time. RESULTS: Delineation of the left ventricular endocardium improved from 76 +/- 4% to 84 +/- 2% at rest (P < 0.01) and from 75 +/- 4% to 89 +/- 1% at peak stress (P < 0.01) after administration of Infoson. The greatest improvement was seen in the basal and middle regions of the lateral and anterior walls. Inter- and intra-observer variability was reduced after administration of Infoson. At rest, the probability of concordance between two observers increased from 0.86 (0.82-0.89) to 0.91 (0.88-0.94) (P < 0.05) and at peak stress from 0.86 (0.82-0.9) to 0.90 (0.86-0.92) after administration of Infoson (P < 0.05). The probability of concordance between on- and off-line assessment by one observer also increased from 0.84 (0.8-0.88) to 0.90 (0.86-0.93) (P < 0.01) at rest and from 0.90 to 0.92 (NS) at peak stress. Overall, a change in wall motion score index occurred in 16 of 30 (53%) patients after administration of Infoson, thus improving the accuracy of the stress test compared with coronary angiography. The wall motion score index was overestimated in 11 of 16 (37%) patients without Infoson while the detection of new wall motion abnormalities increased in 5 of 16 (17%) (P < 0.01). CONCLUSIONS: Intravenous administration of Infoson facilitates the assessment of wall motion, particularly of the basal lateral and anterior walls where endocardial border drop-out frequently occurs during dobutamine stress echocardiography; it thus reduces the inter- and intra-observer variability.

Incidence of ventricular arrhythmias during silent myocardial ischaemia in coronary artery disease.

This study investigated the relationship between silent myocardial ischaemia during daily life and ventricular ectopic activity in patients with angiographically confirmed coronary artery disease and preserved left ventricular function. We studied 45 patients (37 men, 8 women, aged 42-70 years) who satisfied the above criteria. All underwent 72-h continuous electrocardiographic monitoring for the detection of silent ischaemic episodes and ventricular arrhythmias. A total of 225 ischaemic episodes were recorded, of which 198 (88%) were silent. Fourteen of the silent episodes (7.1%) were associated with ventricular arrhythmias. There was no statistically significant relationship between the association of silent ischaemia with arrhythmias and the patients' exercise test or angiography findings. However, the ventricular arrhythmias tended to be associated with ischaemic episodes of longer duration and with greater maximum ST-segment depression. Silent myocardial ischaemia during everyday activity is accompanied by ventricular ectopic activity in only a small percentage of cases. The association between ischaemia and ventricular arrhythmias seems to have more to do with the duration of the ischaemic episode and the degree of ST segment depression than with the severity of the underlying coronary artery disease.

Routine arterial oxygen saturation monitoring is not necessary during transesophageal echocardiography.

BACKGROUND: Transesophageal echocardiography (TEE) is now an established adjunct to routine echocardiography, its diagnostic impact making it an invaluable first-line diagnostic procedure in many cardiac conditions. However, there is no unanimity in the way the transesophageal procedure is carried out, especially with regard to the need for antibiotic prophylaxis, sedation, and the monitoring of oxygen saturation. HYPOTHESIS: This study was prospectively undertaken (1) to determine the presence and magnitude of oxygen desaturation and (2) the changes in heart rate and blood pressure following sedation for routine TEE in an unselected and consecutive group of patients to identify those at high risk. METHODS: Arterial oxygen saturation, heart rate, and systolic, diastolic, and mean blood pressure were monitored in 106 consecutive patients undergoing routine transesophageal echocardiography. Ninety-four (89%) patients received intravenous sedation with midazolam. RESULTS: Three min after midazolam administration there was a drop in oxygen saturation from 97 +/- 2.5 to 95 +/- 2.9 (p < 0.001), in systolic blood pressure from 139 +/- 19.5 to 124.8 +/- 22.2 mmHg (p < 0.001), in diastolic blood pressure from 86.6 +/- 19.9 to 77.5 +/- 17.7 mmHg (p < 0.001), and in mean blood pressure from 108.3 +/- 18 to 95.6 +/- 28.8 mmHg (p < 0.001). After introduction of the transesophageal probe and during the examination, there was a further drop in oxygen saturation with a maximum drop at the 15th min of the examination (93.7 +/- 3.7 vs. 97 +/- 2.5, p < 0.001). The maximum blood pressure drop occurred at the 12th min into recovery: systolic blood pressure dropped from 139 +/- 19.5 to 118 +/- 20.8 mmHg (p < 0.001), diastolic blood pressure from 86.6 +/- 16.9 to 75.8 +/- 17.9 mmHg (p < 0.005), and mean blood pressure from 108.3 +/- 18 to 92.5 +/- 19.4 mmHg (p < 0.01). Patients with congestive heart failure had a greater drop in oxygen saturation compared with patients who were not in heart failure (p < 0.01). Twelve patients did not receive any sedation; however, they all showed a drop in oxygen saturation from 97.8 +/- 2.3 to 94.6 +/- 3.4 (p < 0.001), with a maximum drop at the 15th min during the transesophageal examination. CONCLUSION: In patients with no chronic obstructive airway disease who are not in congestive heart failure, routine oxygen saturation monitoring is not deemed necessary during transesophageal examination. The cause of hypoxemia during the procedure is not only related to sedation but also to esophageal intubation.

Association of soluble apoptotic markers with impaired left ventricular deformation in patients with rheumatoid arthritis. Effects of inhibition of interleukin-1 activity by anakinra.

Myocardial function is impaired in rheumatoid arthritis (RA). Inhibition of interleukin (IL)-1 activity reduces experimental myocardial infarction by limiting apoptosis. We investigated whether a) soluble apoptotic markers are related with impaired left ventricular (LV) performance and b) treatment with anakinra, an IL-1 receptor antagonist, reduces apoptotic markers leading to improved LV performance in RA. We studied 46 RA patients. In an acute, double-blind cross-over trial, 23 patients were randomised to a single injection of anakinra or placebo and after 48 hours (h) to the alternative treatment. In a chronic trial, 23 patients who received anakinra for 30 days were compared with 23 patients who received prednisolone. At baseline, 3 h and 30 days after treatment, we measured circulating IL-1ß, tumour necrosis factor (TNF)-α, Fas, Fas-ligand and caspase-9 to assess apoptosis. At baseline and 30 days after treatment, we assessed LV longitudinal strain, strain rate and E/Em ratio using 2D-speckle tracking and tissue Doppler echocardiography. At baseline, increased apoptotic markers were related with reduced LongSRS and increased E/Em (p<0.05). After 3 h and 30 days of anakinra, there was a reduction in Fas (median 481 vs. 364 vs. 301 pg/ml), Fas-ligand (median 289 vs. 221 vs. 190 pg/ml), caspase-9 (median 1.90 vs. 1.40 vs. 1.07 ng/ml), TNF-α and IL-1ß (p<0.05 for all comparisons). E/Em, LongS and LongSRS were improved after anakinra (p<0.01) and their percent changes were related with the corresponding changes of Fas and caspase-9 (p<0.05). No changes of the examined parameters were observed after prednisolone. In conclusion, inhibition of IL-1 activity by anakinra reduces apoptotic markers leading to improved LV performance in RA.

Paclitaxel chemotherapy and vascular toxicity as assessed by flow-mediated and nitrate-mediated vasodilatation.

BACKGROUND: Antitumor activity of paclitaxel is based on promotion of abnormal microtubule (MT) assembly but it is also considered to have significant pro-inflammatory and anti-angiogenic effects in vivo and thus may cause vascular dysfunction. METHODS: We studied 27 women treated with paclitaxel-containing combinations for breast or ovarian cancer. The control group was represented by 10 women with carcinoma of the uterine cervix who received low doses of weekly cisplatin as radiation sensitizer. We measured endothelial-dependent flow-mediated dilatation (FMD) and nitrate-mediated dilatation (NMD) of the right brachial artery by ultrasonography, as well as levels of the inflammatory cytokines TNF-alpha and IL-6 before and after chemotherapy. RESULTS: Patients who received paclitaxel and an anthracycline had the most marked reduction in both FMD (p=0.005) and NMD (p=0.027). A significant reduction in FMD was also observed in patients treated with weekly paclitaxel (p=0.045), whereas NMD was not affected (p=0.421). Although TNF-alpha and IL-6 levels were different among chemotherapy groups after treatment, no significant differences were observed between levels of both markers before and after chemotherapy. CONCLUSION: Treatment with paclitaxel-containing combinations impairs endothelial function in vivo but endothelial function deterioration is not related to the serum levels of inflammation markers.

Evaluation of left atrial longitudinal function in patients with hypertrophic cardiomyopathy: a tissue Doppler imaging and two-dimensional strain study.

OBJECTIVE: We sought to quantify left atrial longitudinal function by tissue Doppler (TDI) and two-dimensional (2D) strain in patients with hypertrophic cardiomyopathy (HCM). DESIGN: Case-control study. SETTING: Tertiary university hospital. PATIENTS: 43 consecutive patients with familial HCM, aged 49 (SD 18) years, along with 21 patients with non-HCM left ventricular hypertrophy (LVH, aged 52 (12) years) and 27 healthy volunteers (aged 42 (13) years). INTERVENTIONS: Subjects were studied by both TDI and 2D left atrial strain during all three atrial phases (reservoir, conduit, contractile), as well as by left ventricular systolic strain; total atrial deformation (TAD) was defined as the sum of maximum positive and maximum negative strain during a cardiac cycle. MAIN OUTCOME MEASURES: Left atrial longitudinal function. RESULTS: Both TDI and 2D atrial strain and TAD were significantly reduced in HCM, compared to the other two groups in all atrial phases (p<0.001 in most cases); left ventricular systolic strain was also significantly reduced in HCM (p<0.001). Adding 2D contractile atrial strain to a model of conventional echo measurements (including left atrial diameter and volume index, interventricular septal thickness and E/A ratio and E/e' ratios) increased its prognostic value in differentiating HCM from non-HCM LVH (p value of the change <0.001), while addition of TDI atrial strain or left ventricular strain did not. A cut-off for 2D contractile strain of -10.82% discriminated HCM from non-HCM LVH with a sensitivity of 82% and a specificity of 81%. Intra-observer and inter-observer variabilities for atrial strain in HCM were 16% and 17.5% for TDI and 8% and 9.5% for 2D, respectively. Processing time per case in HCM was 12.5 (2.6) minutes for TDI versus 3.8 (1.2) minutes for 2D strain (p<0.001). CONCLUSION: Left atrial longitudinal function is reduced in HCM compared to non-HCM LVH and healthy controls. In addition, 2D atrial strain has an additive value in differentiating HCM from non-HCM LVH and it is more reproducible and less time consuming than TDI strain.

Lowering interleukin-1 activity with anakinra improves myocardial deformation in rheumatoid arthritis.

OBJECTIVE: Inhibition of interleukin-1 activity improves nitro-oxidative stress, endothelial and coronary function. The authors investigated (a) the association of nitro-oxidative stress and endothelial function with myocardial deformation, (b) the effects of anakinra, an interleukin-1a receptor antagonist on myocardial deformation in patients with rheumatoid arthritis (RA). METHODS: The authors compared 46 RA patients to 23 normal controls. 23 patients received anakinra (150 mg subcutaneously once daily) and 23 patients a 5-mg increase of prednisolone dose for 30 days. At baseline and post-treatment this study assessed (a) the left ventricular (LV) longitudinal, circumferential and radial strain and strain rate, using speckle tracking echocardiography, (b) the coronary flow reserve (CFR), (c) the flow-mediated endothelial-dependent dilation of the brachial artery (FMD) and (d) nitrotyrosine (NT) and malondialdehyde blood levels. RESULTS: Patients had impaired baseline myocardial deformation indices compared to controls (p<0.05). CFR and NT levels were related to longitudinal strain, systolic and diastolic strain rate, circumferential strain and systolic strain rate (p<0.05). FMD was related to longitudinal and circumferential diastolic strain rate (p<0.01). Compared to baseline, anakinra-treated patients increased the longitudinal strain (-17.8% (3.7%) vs -22.1% (3.5%)), systolic (-1.02 (0.23) l/s vs -1.25 (0.23) l/s) and diastolic (0.96 (0.37) l/s vs 1.20 (0.39) l/s) longitudinal strain rate, circumferential strain and strain rate (p<0.05 for all comparisons). No significant changes were observed among prednisolone-treated patients CONCLUSIONS: Myocardial deformation is impaired in RA patients and is related to nitro-oxidative stress and endothelial dysfunction. Chronic inhibition of IL-1 improves LV deformation in parallel with endothelial function and nitro-oxidative stress.

Aspirin reduces anticardiolipin antibodies in patients with coronary artery disease.

BACKGROUND: Anticardiolipin antibodies (aCL) have been found to be elevated in patients with coronary artery disease (CAD) and have been associated with an adverse outcome owing to their prothrombotic activity. The aim of this study was to investigate the effect of aspirin treatment on aCL levels in patients with chronic CAD. MATERIALS AND METHODS: Forty patients with chronic CAD scheduled for elective coronary artery bypass graft surgery (CABG) and 40 healthy controls participated in the study. Patients were treated with 300 mg of aspirin once daily (o.d.) for the first 12 days and placebo for the following 12 days before CABG in a double-blind, cross-over trial. Immunoglobulin (Ig) G-, IgM-, IgA-aCL and C-reactive protein (CRP) levels were measured in the controls and at the end of each treatment period in the patients with CAD. RESULTS: The IgA- and IgG-aCL levels were greater in patients with CAD than in the controls. Compared with the placebo, IgA, IgG subtypes and CRP levels were reduced after aspirin treatment (P = 0.001, P = 0.02, P = 0.04, respectively). The percentage reduction of IgA- and IgG-aCL was related to the percentage reduction of CRP after aspirin (P < 0.05). CONCLUSION: Aspirin treatment with 300 mg o.d. reduced the serum levels of IgA and IgG subtypes in patients with chronic CAD in parallel to a reduction in CRP. These findings offer an additional pathophysiological mechanism of the beneficial effects of aspirin in patients with chronic CAD.

Reduction of daily life ischaemia by aspirin in patients with angina: underlying link between thromboxane A2 and macrophage colony stimulating factor.

OBJECTIVES: To evaluate whether aspirin reduces the incidence and frequency of daily life myocardial ischaemia in a cohort of patients with chronic stable coronary artery disease. SETTING: Tertiary referral centre. METHODS: 60 patients with chronic stable coronary artery disease underwent 48 hour Holter monitoring to assess the incidence and frequency of daily life myocardial ischaemia. Those with myocardial ischaemia (40/60) entered a double blind, crossover trial of aspirin (300 mg/day for three weeks) versus placebo. After each treatment arm, 48 hour Holter monitoring was repeated and urinary thromboxane (Tx) B2, 11-dehydro-TxB2, plasma prothrombin fragment F1+2, macrophage colony stimulating factor (MCSF), and interleukin (IL)-6 were measured. RESULTS: Aspirin reduced the total number and duration of ischaemic episodes from 339 to 251 and from 1765 to 1365 minutes, respectively (p < 0.01 for both). TxB2 was also reduced from 0.2 to 0.1 ng/mg creatinine, 11-dehydro-TxB2 from 3.3 to 1.3 ng/mg creatinine, F1+2 from 1.5 to 1.2 nmol/l, MCSF from 991 to 843 pg/ml, and IL-6 from 3.5 to 2.9 pg/ml (p < 0.05 for all). 11-dehydro-TxB2 excretion with and without aspirin was related to MCSF concentrations (p < 0.01), and the percentage reduction of MCSF by aspirin was related to the reduction of 11-dehydro-TxB2 (p < 0.05) and the reduction of the ischaemic burden compared with placebo (p < 0.05). CONCLUSIONS: In patients with daily life ischaemia, aspirin reduces the incidence and frequency of ischaemic episodes as well as the systemic concentrations of haemostatic/inflammatory markers. Aspirin may prevent transient coronary flow reductions through platelet, thrombin, and cytokine inhibition.

Natural history of early aortic paraprosthetic regurgitation: a five-year follow-up.

OBJECTIVES: To assess the incidence and natural course of paravalvular leaks detected early after aortic valve replacement. BACKGROUND: Although the use of echocardiography has simplified the postoperative assessment of patients with aortic valve replacement, there are no data regarding the natural history of early detected paravalvular aortic leaks. METHODS: Eighty-four consecutive patients with aortic valve replacement were prospectively followed clinically every 6 months and by echocardiography early (11 +/- 7 days), at midterm (27 +/- 3 months), and late (63 +/- 4 months) after aortic valve replacement. The competence of artificial valves was assessed by Doppler color flow mapping. RESULTS: Paraprosthetic leaks were detected in 40 (47.6%) aortic prostheses during the early study; the majority (90%) were small. All leaks remained unchanged during the follow-up period. Left ventricular dimensions and function did not differ between patients with or without paravalvular leak during the follow-up. Left ventricular fractional shortening, however, increased during the intermediate study in both subgroups, indicating improved left ventricular function overall. Three patients had severe paravalvular regurgitation suddenly develop from late infective endocarditis, and 1 patient had a degenerative tissue valve failure 4 years after implantation. CONCLUSIONS: Paraprosthetic aortic leaks detected early after surgery, in the absence of valve infection, are common, are usually small, and have a benign course. However, the development of new, usually severe, regurgitation should raise the suspicion of prosthetic valve endocarditis or bioprosthetic valve failure.