Safety of embolic protection device-assisted and unprotected intravascular ultrasound in evaluating carotid artery atherosclerotic lesions.

BACKGROUND: Significant atherosclerotic stenosis of internal carotid artery (ICA) origin is common (5-10% at ≥ 60 years). Intravascular ultrasound (IVUS) enables high-resolution (120 µm) plaque imaging, and IVUS-elucidated features of the coronary plaque were recently shown to be associated with its symptomatic rupture/thrombosis risk. Safety of the significant carotid plaque IVUS imaging in a large unselected population is unknown. MATERIAL/METHODS: We prospectively evaluated the safety of embolic protection device (EPD)-assisted vs. unprotected ICA-IVUS in a series of consecutive subjects with ≥ 50% ICA stenosis referred for carotid artery stenting (CAS), including 104 asymptomatic (aS) and 187 symptomatic (S) subjects (age 47-83 y, 187 men). EPD use was optional for IVUS, but mandatory for CAS. RESULTS: Evaluation was performed of 107 ICAs (36.8%) without EPD and 184 with EPD. Lesions imaged under EPD were overall more severe (peak-systolic velocity 2.97 ± 0.08 vs. 2.20 ± 0.08 m/s, end-diastolic velocity 1.0 ± 0.04 vs. 0.7 ± 0.03 m/s, stenosis severity of 85.7 ± 0.5% vs. 77.7 ± 0.6% by catheter angiography; mean ± SEM; p<0.01 for all comparisons) and more frequently S (50.0% vs. 34.6%, p=0.01). No ICA perforation or dissection, and no major stroke or death occurred. There was no IVUS-triggered cerebral embolization. In the procedures of (i) unprotected IVUS and no CAS, (ii) unprotected IVUS followed by CAS (filters - 39, flow reversal/blockade - 3), (iii) EPD-protected (filters - 135, flow reversal/blockade - 48) IVUS + CAS, TIA occurred in 1.5% vs. 4.8% vs. 2.7%, respectively, and minor stroke in 0% vs. 2.4% vs. 2.1%, respectively. EPD intolerance (on-filter ICA spasm or flow reversal/blockade intolerance) occurred in 9/225 (4.0%). IVUS increased the procedure duration by 7.27 ± 0.19 min. CONCLUSIONS: Carotid IVUS is safe and, for the less severe lesions in particular, it may not require mandatory EPD use. High-risk lesions can be safely evaluated with IVUS under flow reversal/blockade.

Systemic blood coagulation activation in acute coronary syndromes.

We evaluated systemic alterations to the blood coagulation system that occur during a coronary thrombotic event. Peripheral blood coagulation in patients with acute coronary thrombosis was compared with that in people with stable coronary artery disease (CAD). Blood coagulation and platelet activation at the microvascular injury site were assessed using immunochemistry in 28 non-anticoagulated patients with acute myocardial infarction (AMI) versus 28 stable CAD patients matched for age, sex, risk factors, and medications. AMI was associated with increased maximum rates of thrombin-antithrombin complex generation (by 93.8%; P< .001), thrombin B-chain formation (by 57.1%; P< .001), prothrombin consumption (by 27.9%; P= .012), fibrinogen consumption (by 27.0%; P= .02), factor (f) Va light chain generation (by 44.2%; P= .003), and accelerated fVa inactivation (by 76.1%; P< .001), and with enhanced release of platelet-derived soluble CD40 ligand (by 44.4%; P< .001). FVa heavy chain availability was similar in both groups because of enhanced formation and activated protein C (APC)-mediated destruction. The velocity of coagulant reactions in AMI patients showed positive correlations with interleukin-6. Heparin treatment led to dampening of coagulant reactions with profiles similar to those for stable CAD. AMI-induced systemic activation of blood coagulation markedly modifies the pattern of coagulant reactions at the site of injury in peripheral vessels compared with that in stable CAD patients.

Altered fibrin clot structure/function in patients with idiopathic venous thromboembolism and in their relatives.

We tested the hypothesis that fibrin structure/function is unfavorably altered in patients after idiopathic venous thromboembolism (VTE) and their relatives. Ex vivo plasma fibrin clot permeability, turbidimetry, and efficiency of fibrinolysis were investigated in 100 patients with first-ever VTE, including 34 with pulmonary embolism (PE), 100 first-degree relatives, and 100 asymptomatic controls with no history of thrombotic events. Known thrombophilia, cancer, trauma, and surgery were exclusion criteria. VTE patients and their relatives were characterized by lower clot permeability (P < .001), lower compaction (P < .001), higher maximum clot absorbancy (P < .001), and prolonged clot lysis time (P < .001) than controls, with more pronounced abnormalities, except maximum clot absorbance, in the patients versus relatives (all P < .01). Fibrin clots obtained for PE patients were more permeable, less compact, and were lysed more efficiently compared with deep-vein thrombosis patients (all P < .05) with no differences in their relatives. Being VTE relative, fibrinogen, and C-reactive protein were independent predictors of clot permeability and fibrinolysis time in combined analysis of controls and relatives. We conclude that altered fibrin clot features are associated with idiopathic VTE with a different profile of fibrin variables in PE. Similar features can be detected in VTE relatives. Fibrin properties might represent novel risk factors for thrombosis.

Effect of renal artery revascularization on left ventricular hypertrophy, diastolic function, blood pressure, and the one-year outcome.

OBJECTIVE: The study aimed to determine the potential interrelations between left ventricle mass (LVM), LV diastolic function, systolic blood pressure (SBP) and diastolic blood pressure (DBP) and cardiovascular events in patients undergoing renal artery stenting [corrected] (RAS). METHODS: Prior to RAS, 3 and 12 months afterward, the change in LVM, left ventricular mass index (LVMI), diastolic function (E/A ratio, E' wave velocity, isovolumetric relaxation time [IVRT], E/E' ratio) on echocardiography and change in SBP and DBP on 24-hour monitoring were assessed in 84 patients, aged 63.7 ± 10 years, who underwent RAS for renal artery stenosis > 60%. RESULTS: During 12 months, 12 (14.3%) cardiovascular (CV) events (five deaths) occurred. At 1 year, the mean LVM decreased from 179 ± 49 g to 141 ± 31 g (P < .001), LVMI in men decreased from 100 ± 20 g/m(2) to 79 ± 18 g/m(2) (P < .001), and the LVMI in women decreased from 96 ± 18 g/m(2) to 80 ± 17 g/m(2) (P < .001). No improvement in diastolic function parameters was seen. The mean SBP and DBP decreased from 133.5 ± 16.9 mm Hg to 127.9 ± 13.2 mm Hg (P = .007) and from 75.4 ± 10.2 mm Hg to 73.1 ± 8.8 mm Hg (P = .035), respectively. On multivariate logistic regression analysis, coronary artery disease (CAD) severity (relative risk [RR], 1.27; P = .023), smoking (RR, 1.29; P = .016), and baseline LVM (RR, 1.21; P = .07) were found as independent CV event risk factors. The independent factors associated with SBP and DBP improvement were grade of renal stenosis (RR, 1.28; P = .006), bilateral RAS procedure (RR, 1.17; P = .07), and baseline DBP value (RR, 1.74; P < .001). LVM reduction was associated with higher baseline ejection fraction (RR, 1.53; P < .001) and baseline LVM (RR, 1.7; P < 0.001). SBP and DBP value changes were independent of LVM change (r = 0.031; P = .796 and r = 0.098; P = .413, respectively). CONCLUSIONS: RAS induced LVM and LVMI reduction, which is independent of the change in blood pressure. Baseline LVM is associated with higher CV event risk following RAS.

Ezetimibe combined with simvastatin compared with simvastatin alone results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients after acute coronary events.

We compared the effect of simvastatin versus simvastatin combined with ezetimibe on hemostasis and inflammation after acute coronary events [acute coronary syndromes (ACS)]. In an investigator-initiated, double-blind, placebo-controlled, randomized study, patients with ACS were assigned to 40 mg/d of simvastatin + 10 mg/d of ezetimibe (n = 26) or 40 mg/d of simvastatin + placebo (n = 28) administered for 2 months. Markers of coagulation (prothrombin fragments 1.2, thrombin-antithrombin complexes, free tissue factor pathway inhibitor), fibrinolysis [plasminogen activator inhibitor-1, clot lysis time (CLT)], platelet activation (soluble CD40 ligand, ß-thromboglobulin, thromboxane B2), oxidative stress [8-iso-prostaglandin F2α (8-iso-PGF2α)], and inflammation (interleukin-6, interleukin-18, and interleukin-1ß) were measured within the first 12 hours of ACS and at 1 and 2 months of therapy. A final analysis comprised 20 patients in the simvastatin + ezetimibe group and 26 patients in the simvastatin + placebo group. Both groups were similar with regard to demographics, risk factors, medications, and routine laboratory results. Inflammatory, coagulation, and platelet markers did not differ between both treatment groups at all time points. Reductions in low-density lipoprotein cholesterol, CLT, plasminogen activator inhibitor-1, and 8-iso-PGF2α were significantly greater (by 10%, 8.7%, 17.5%, and 22.4%) in the simvastatin + ezetimibe group after 1 month, with further decreases in CLT and 8-iso-PGF2α at 2 months (all P < 0.05). These changes were not associated with lipid and inflammatory parameters. In conclusion, compared with simvastatin alone, simvastatin + ezetimibe results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients with ACS, indicating that ezetimibe might exert cholesterol-independent actions in humans (NCT00725829).

Randomized transcoronary delivery of CD34(+) cells with perfusion versus stop-flow method in patients with recent myocardial infarction: Early cardiac retention of 99(m)Tc-labeled cells activity.

BACKGROUND: For transcoronary progenitor cells' administration, injections under flow arrest (over-the-wire balloon technique, OTW) are used universally despite lack of evidence for being required for cell delivery or being effective in stimulating myocardial engraftment. Flow-mediated endothelial rolling is mandatory for subsequent cell adhesion and extravasation. METHODS: To optimize cell directing toward the coronary endothelium under maintained flow, the authors developed a cell-delivery side-holed perfusion catheter (PC). Thirty-four patients (36-69 years, 30 men) with primary stent-assisted angioplasty-treated anterior MI (peak TnI 151 [53-356]ng/dL, mean[range]) were randomly assigned to OTW or PC autologous 99Tc-extametazime-labeled bone marrow CD34(+) cells (4.34 [0.92-7.54] × 106) administration at 6-14 days after pPCI (LVEF 37.1 [24-44]%). Myocardial perfusion (99(m)Tc-MIBI) and labeled cells' activity were evaluated (SPECT) at, respectively, 36-48 h prior to and 60 min after delivery. RESULTS: In contrast to OTW coronary occlusions, no intolerance or ventricular arrhythmia occurred with PC cells' administration (P < .001). One hour after delivery, 4.86 [1.7-7.6]% and 5.05 [2.2-9.9]% activity was detected in the myocardium (OTW and PC, respectively, P = .84). Labeled cell activity was clearly limited to the (viable) peri-infarct zone in 88% patients, indicating that the infarct core zone may be largely inaccessible to transcoronary-administered cells. CONCLUSIONS: Irrespective of the transcoronary delivery method, only ≈ 5% of native (i.e., non-engineered) CD34(+) cells spontaneously home to the injured myocardium, and cell retention occurs preferentially in the viable peri-infarct zone. Although the efficacy of cell delivery is not increased with the perfusion method, by avoiding provoking ischemic episodes PC offers a rational alternative to the OTW delivery.

[Cardiovascular calcification and five-years mortality in patients on maintenance hemodialysis]. / Zwapnienia w ukladzie sercowo-naczyniowym a 5-letnia smiertelnosc pacjentów leczonych powtarzanymi hemodializami.

The very high cardiovascular mortality and morbidity in hemodialyzed patients (HD) is strongly associated with cardiovascular calcification. The aim of the study was to find the predictors of mortality in HD patients during 5-years observation period. The study group was composed of 64 patients (35 F, 29 M) aged 25-75 years (mean 48.9) hemodialyzed three times a week for 12-275 months (mean 77.8). The levels of hemoglobin, total protein, albumin, Ca, P, Ca x P, iPTH, cholesterol, triglycerides, fibrinogen, insulin, homocysteine, leptin, procalcitonin, CRP, IL-6, TGF-beta, PDGF were assessed and all patients underwent Calcium Score (CS) of coronary arteries (CACS) calculation using MSCT and B-mode ultrasound of carotid arteries for intima-media thickness (CCA-IMT), as well as echocardiographic assessment with LVMI calculation and heart valves evaluation at the start of observation. The self-elaborated Cumulative Calcification Index (CCl) was calculated as a sum of CACS Index according to Rumberger et al. (CS<10-0, 10400 - 3 points); number of calcified plaques in carotid arteries (0-0, 1 - 1, 2 - 2, 3 and more - 3 points) and the number of calcified heart valves. At the start of the study the median value of CCl was 4 and interquartile range 4. Only 2 (3%) patients were free of any type of cardiovascular calcification (CCl =0), 15 (23%) patients had minimal calcification (CCl 1 to 2 points), 33 (52%) average (2 - 6 points) and 14 (22%) patients had severe calcification (CCl>6). 21 (32,8%) patients died during observation period. Patients who died were older (56.9 vs. 45.3 yrs.) and had higher CS at the start (1275 vs. 356), higher CCA-IMT (0.948 vs. 0.687 mm) and CCl (6.15 vs. 3.63) values. Those patients had also higher CRP (0.645 vs. 0.245 mg/dl) and IL-6 (10.16 vs. 4.15 pg/ml) levels (p<0.05). LVMI and mean: hemoglobin, total protein, albumin, Ca, P, Ca x P, iPTH, cholesterol, triglycerides, fibrinogen, insulin, homocysteine, leptin, procalcitonin, TGF-beta as well as PDGF levels did not differ between the groups. In logistic regression model (p<0.00002), among tested parameters only CCl was an independent and statistically significant factor of mortality with OR=1.82 per every point of CCl (p<0.0003). Cardiovascular calcification expressed as CCl confirmed to be a strong predictor of mortality in HD patients.

Predictors of cerebral reperfusion injury after carotid stenting: the role of transcranial color-coded Doppler ultrasonography.

PURPOSE: To evaluate the possible role of transcranial color-coded Doppler ultrasonography (TCD) in predicting cerebral reperfusion injury (CRI) in patients undergoing carotid artery stenting (CAS) for internal carotid artery (ICA) stenosis. METHODS: TCD was obtained in 210 patients (149 men; mean age 64.2+/-8.4 years, range 44-83) who underwent CAS for ICA stenosis averaging 86.7%+/-8.4%. Contralateral ICA occlusion or near occlusion (stenosis >90%) was present in 67 (31.9%) patients. TCD was performed before and 24 hours after CAS with assessment of peak systolic velocities (PSVs) in the ipsilateral middle cerebral artery (iMCA) and contralateral middle cerebral artery (cMCA). PSV ratios (PSVR) in the iMCA and cMCA were calculated from the PSVs before and after CAS. RESULTS: CRI syndrome occurred in 3 (1.4%) patients (2 intracranial bleedings, 1 subarachnoid hemorrhage). The mean iMCA and cMCA PSVRs were 2.66+/-0.19 and 4.16+/-2.77, respectively, in CRI patients, while the PSVRs in CAS patients without neurological sequelae were 1.56+/-0.46 and 1.21+/-0.39, respectively (both p<0.001). The combination of iPSVR>2.4 and cPSVR>2.4 occurred in 4 patients with bilateral ICA disease; 3 (75%) of them developed CRI (100% sensitivity and 99% specificity for CRI prediction). The following independent CRI predictors were identified: combined iPSVR>2.4 and cPSVR>2.4 (RR 2.06, CI 1.89 to 2.24; p<0.001), high cMCA PSV after CAS (RR 1.23, CI 1.13 to 1.34; p<0.001), and contralateral ICA occlusion (RR 1.13, CI 1.03 to 1.23; p = 0.007). CONCLUSION: TCD is an important tool in CRI risk evaluation. The combination of iPSVR>2.4 and cPSVR>2.4 is an independent CRI risk factor, along with contralateral ICA occlusion and high cMCA PSVs after CAS.

Myocardial viability detected by myocardial contrast echocardiography--prognostic value in patients after myocardial infarction.

OBJECTIVE: This study aimed to assess the role of myocardial contrast echocardiography (MCE) as a predictor of cardiac events and death in patients with acute myocardial infarction (AMI). METHODS: Eighty-six patients underwent primary percutaneous coronary angioplasty for AMI. Segmental perfusion was estimated by MCE in real time at mean 5 days after PCI using low MI (0.3) after 0.3-0.5 ml bolus injection of intravenous Optison. MCE was scored semiquantitatively as: (1) normal perfusion (homogenous contrast effect), (2) partial perfusion (patchy myocardial contrast enhancement), (3) lack of perfusion (no visible contrast effect). A contrast score index (CSI) was calculated as the sum of MCE scores in each segment divided by the total number of segments. The patients were followed up for cardiac events and death. RESULTS: A CSI of >1.68 was taken to be a predictor of cardiac events and death. Death occurred only in patients with CSI >1.68. Patients with CSI >1.68 had a significantly (P = 0.03) higher incidence of cardiac death or cardiac events (75%) compared to those with CSI <1.68 (27%). The absence of residual perfusion within the infarct zone was an independent predictor of death and cardiac events (P = 0.02). CONCLUSIONS: The absence of residual myocardial viability in the infarct zone supplied by an infarct-related artery is a powerful predictor of cardiac events in patients after AMI.

Intracoronary infusion of bone marrow-derived selected CD34+CXCR4+ cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre Myocardial Regeneration by Intracoronary Infusion of Selected Population of Stem Cells in Acute Myocardial Infarction (REGENT) Trial.

AIMS: Comparison of intracoronary infusion of bone marrow (BM)-derived unselected mononuclear cells (UNSEL) and selected CD34(+)CXCR4(+) cells (SEL) in patients with acute myocardial infarction (AMI) and reduced <40% left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Two hundred patients were randomized to intracoronary infusion of UNSEL (n = 80) or SEL (n = 80) BM cells or to the control (CTRL) group without BM cell treatment. Primary endpoint: change of LVEF and volumes measured by magnetic resonance imaging before and 6 months after the procedure. After 6 months, LVEF increased by 3% (P = 0.01) in patients treated with UNSEL, 3% in patients receiving SEL (P = 0.04) and remained unchanged in CTRL group (P = 0.73). There were no significant differences in absolute changes of LVEF between the groups. Absolute changes of left ventricular end-systolic volume and left ventricular end-diastolic volume were not significantly different in all groups. Significant increase of LVEF was observed only in patients treated with BM cells who had baseline LVEF < median (37%). Baseline LVEF < median and time from the onset of symptoms to primary percutaneous coronary intervention > or = median were predictors of LVEF improvement in patients receiving BM cells. There were no differences in major cardiovascular event (death, re-infarction, stroke, target vessel revascularization) between groups. CONCLUSION: In patients with AMI and impaired LVEF, treatment with BM cells does not lead to a significant improvement of LVEF or volumes. There was however a trend in favour of cell therapy in patients with most severely impaired LVEF and longer delay between the symptoms and revascularization.

Altered fibrin clot structure/function in patients with cryptogenic ischemic stroke.

BACKGROUND AND PURPOSE: We tested the hypothesis that fibrin structure/function is unfavorably altered in patients with cryptogenic ischemic stroke. METHODS: Ex vivo plasma fibrin clot permeability, turbidimetry, and efficiency of fibrinolysis were determined in 89 patients with patent foramen ovale (PFO) and a history of first-ever stroke, 58 patients with first-ever stroke and no PFO, and 120 healthy controls. RESULTS: Stroke patients, evaluated 3 to 19 months after the event, and controls did not differ with regard to age, sex, smoking, and fibrinogen. Stroke patients with or without PFO had lower clot permeability (P<0.0001), faster fibrin polymerization (P<0.0001), prolonged clot lysis time (P<0.0001), higher maximum D-dimer levels released from clots (P<0.0001), and maximum rate of D-dimer release (P=0.02) than controls. Time from stroke occurrence showed no association with any clot variables. Scanning electron microscopy of fibrin clots showed increased fiber diameter and density in stroke patients. Clots from stroke patients with PFO were more permeable and showed shorter lysis time compared to those without PFO, and this was related to lower proportion of smokers in the former group. CONCLUSIONS: Altered fibrin clot structure and resistance to fibrinolysis are associated with cryptogenic stroke.

Flow reversal for proximal neuroprotection during endovascular management of critical symptomatic carotid artery stenosis coexisting with ipsilateral external carotid artery occlusion.

PURPOSE: To report the utility of proximal brain protection by flow reversal in endovascular management of critical internal carotid artery (ICA) stenosis coexisting with ipsilateral external carotid artery (iECA) occlusion. CASE REPORT: Four patients with a symptomatic, critical ICA stenosis (in-stent restenosis in one) and iECA occlusion were admitted for carotid artery stenting (CAS). In all cases, the stenosis severity and high-risk lesion morphology precluded the use of filter protection. The "tailored" CAS algorithm indicated that a proximal anti-embolism system should be used to maximize the potential for effective neuroprotection. The flow reversal system, which consists of an independent guiding sheath balloon positioned in the common carotid artery (CCA) and an iECA balloon-wire, was employed, using the CCA balloon only. The system was well-tolerated, and the CAS procedures were uneventful. CONCLUSION: Due to a unique design with separate CCA and iECA balloons, the flow reversal system can be used for proximal neuroprotection during CAS in severe, symptomatic ICA lesions coexisting with iECA occlusion.

Transcatheter closure as an alternative and equivalent method to the surgical treatment of atrial septal defect in adults: comparison of early and late results.

BACKGROUND: The clinical efficacy of transcatheter atrial septal defect (ASD) closure with the Amplatzer Septal Occluder (ASO) can only be judged against the results of contemporaneous surgery. The present study compared early and late results of ASD closure using ASO versus open-heart surgery. METHODS: Forty-eight adult patients were found eligible for transcatheter closure in transesophageal echocardiography. The surgical group consisted of 52 patients with isolated ostium secundum ASD. All patients underwent standard ECG, 24-hour ECG recording, and transthoracic echocardiography pre-procedure at 1-month and at 1-year follow-up. Physical fitness was assessed by cardiopulmonary exercise testing (CPX) prior to ASD closure and at 1-year follow-up. RESULTS: ASD closure was successful in all surgical patients and in 94% of the ASO group (0% mortality). The total complication rate for surgical vs. device closure was not significantly different (19.2% vs. 26.7%; p=0.383), despite more serious complications in the surgical group. Hospital stay was significantly shorter in the ASO group (5.4+/-2.2 vs. 9.1+/-1.2 days; p<0.001). Although echocardiographic parameters did not differ significantly between the respective groups at 1-year follow-up, CPX revealed a higher decrease in the VE/VCO2 slope in the ASO group (-3.7+/-3.4 vs.-1.2+/-4.8; p=0.003). CONCLUSIONS: As surgical and device closure appear similarly effective in adults with ASD, avoidance of thoracotomy and cardiopulmonary bypass, in conjunction with a shorter hospital stay, argues in favour of device closure in selected patients.

Usefulness of the evaluation of isovolumic and ejection phase myocardial signals during stress echocardiography in predicting exercise capacity in heart failure patients.

AIM: To assess changes of systolic function using tissue Doppler imaging (TDI) during stress echocardiography and its impact on exercise capacity in heart failure (HF) patients (pts). MATERIAL AND METHODS: 80 pts (65 male), mean age of 59.3 +/- 10.9 years, NYHA class 1.95 +/- 0.8, left ventricle ejection fraction (LVEF) 27.2 +/- 9.5 (10-45%). The etiology of HF was ischemic (ICM) in 50 pts and dilated cardiomyopathy (DCM) in 30 pts. Peak myocardial velocity (IVV) and acceleration (IVA) during isovolumic contraction and peak myocardial velocity during ejection phase (S') were measured at baseline and peak exercise during semi-supine stress-echo (20 Watts, 2-min increments). Concurrently peak oxygen uptake (VO(2) peak) was measured. RESULTS: Rest values of analyzed parameters were comparable in groups according to etiology of HF and physical capacity. However, peak stress parameters mainly S' were significantly higher in the DCM group and the group with better VO(2) peak. The best correlation with exercise capacity was S' at peak stress (r = 0.66; p < 0.0001). The most useful parameter for identifying severe exercise intolerance, VO(2) peak < 14 ml/kg/min, was S' with an area under ROC curve of 0.82 +/- 0.05 (95% CI 0.71-0.89). The cutoff of 5.75 cm/s for S' at peak stress showed a sensitivity of 61% with a specificity of 96%. CONCLUSIONS: The evaluation of systolic function by means of TDI instead of LVEF shows more clearly that systolic function is at least partly responsible for exercise tolerance in HF. Assessment of echocardiographic systolic parameters at peak stress provides more accurate information about exercise capacity in HF pts.

Enhanced oxidative stress in hypertrophic cardiomyopathy.

Elevated plasma levels of inflammation and endothelial dysfunction markers have been reported in patients with hypertrophic cardiomyopathy (HCM). The aim of the current study was to determine whether HCM is associated with enhanced oxidative stress. We enrolled 54 HCM patients with sinus rhythm, including 21 subjects with a left ventricular outflow tract (LVOT) obstruction (gradient >/= 30 mmHg), and 54 age- and sex-matched controls without cardiovascular diseases. Serum levels of 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)), a stable marker of oxidative stress, were determined. Serum 8-iso-PGF(2alpha) levels were elevated in HCM patients compared with controls (35.4 +/- 10.2 vs. 29.9 +/- 9.9 pg/ml, p < 0.001). Patients with obstructive HCM displayed higher 8-iso-PGF(2alpha) levels compared with the non-obstructive HCM subgroup (41.6 +/- 12.7 vs. 31.4 +/- 5.4 pg/ml, p < 0.0001). Both anatomic (mitral-septal distance) and hemodynamic (subaortic gradient) indexes of LVOT obstruction, but not other echocardiographic variables, correlated with 8-iso-PGF(2alpha) levels (r = -0.43; p < 0.05 and r = 0.39; p < 0.05, respectively). This study is the first to show that HCM is characterized by enhanced oxidative stress as evidenced by higher 8-iso-PGF(2alpha), which achieves its highest values in the presence of LVOT obstruction in HCM patients.

Chronic mitral regurgitation--significance of the echocardiographic determinants in predicting severity.

UNLABELLED: The aim of study was to determine the significance of the best echocardiographic parameters for assessing the severity of mitral regurgitation (MR). METHODS: The study population consisted of 107 patients, mean age 52 +/- 7 y with chronic isolated non-ischaemic MR. Quantification of the MR was performed using echocardiography through the proximal isovelocity surface area method (regurgitant volume (RV) and the effective regurgitant orifice (ERO) were calculated) and the assessment of vena contracta width (VCW). RESULTS: The ROC curve analysis and Peto odds used to differentiate between the significant (III-IV grade) and non-significant (I-II grade) MR groups of patients indicated thatVCW, RV and ERO were the most powerful predictors of MR.The area under the ROC curve was 0.931, 0.944, 0.927, respectively.The cut-off values defining significant MR were: VCW > or =7 mm, RV > or =45 ml, ERO > or = 0.33 cm2. CONCLUSIONS: The most powerful predictors of severe MR are VCW, ERO and RV.

Assessment of resting perfusion defect in patients with acute myocardial infarction: comparison of myocardial contrast echocardiography with contrast-enhanced magnetic resonance imaging.

BACKGROUND: Contrast-enhanced magnetic resonance imaging (CE-MRI) can identify myocardial scarring following acute myocardial infarction (AMI). AIM: To compare myocardial contrast echocardiography (MCE) and CE-MRI in detection of resting perfusion defect in patients with acute myocardial infarction. METHODS: Twenty four patients (21 men, 3 women, mean age 58.7 +/- 11.4 years) underwent primary percutaneous coronary angioplasty (PCI) for anterior AMI. All patients underwent MCE: segmental perfusion was estimated in real time before and immediately after PCI and on third day after PCI, using low mechanical index (0.3) after 0.3-0.5 ml bolus injections of intravenous OptisonTM. The MCE was scored semiquantitatively as: 1--homogenous contrast enhancement, 2--patchy contrast enhancement, 3--no contrast (non-viable myocardium). All patients underwent CE-MRI on a 1.5 T scanner (SONATA, Siemens) on the third day after PCI. Acquisition of short axis slices was performed before and 20 min after injection of Gd-DPTA (0.15 mmol/kg) with an inversion recovery TurboFLASH sequence (TE 1.1 ms, TR 700 ms, flip angle 300) in multiple breath-holds. The pattern of hyperenhancement representing MI (which intensity was more than 150% intensity of myocardium) was quantified by planimetry. The CE-MRI was scored according to the severity of myocardial scar as: 1--without scar, 2-- <50% of myocardial thickness, 3 - > 50% of myocardial thickness. RESULTS: Myocardial perfusion was analysed using MCE and contrast-enhanced MRI in 362 segments. Agreement between MCE and CE-MRI for identification of viable versus necrotic myocardium on third day after PCI was 86% (kappa = 0.73). Thirteen (54%) patients showed transmural necrosis at CE-MRI while 11 (46%) showed non-transmural necrosis. Patients from the transmural necrosis group showed a higher creatine kinase peak (p = 0.0001), higher CK-MB (p = 0.00002) and higher troponine level (p = 0.008), and more impaired baseline regional contractile function (p = 0.045). All angiographic parameters were less favourable in this group before as well as after PCI than in patients with non-transmural necrosis. CONCLUSIONS: Myocardial contrast echocardiography correlates very well with CE-MRI in the assessment of myocardial perfusion after PCI in AMI. Contrast-enhanced MRI is accurate technique for assessing the infarct zone. Identification by CE-MRI of transmural necrosis was associated with more impaired left ventricular function, non-reperfused MI, and presence of Q waves in ECG.

Thrombin formation and platelet activation at the site of vascular injury in patients with coronary artery disease treated with clopidogrel combined with aspirin.

BACKGROUND: Data on the effects of oral antiplatelet agents on blood coagulation in vivo are conflicting. The platelet glycoprotein (GP) IIIa PlA2 allele has been suggested to modulate antithrombotic actions of clopidogrel. AIM: We investigated whether clopidogrel combined with aspirin affects local thrombin formation and platelet activation triggered by vascular injury. METHOD: We studied patients with stable coronary artery disease on chronic aspirin therapy randomised to addition of clopidogrel 75 mg/d (n = 30) or continuation of aspirin 100 mg/d (n = 30) for 4 weeks. Markers of thrombin generation [thrombin-antithrombin complexes (TAT) and prothrombin 1.2 fragments (F1.2)] and markers of platelet activation [soluble CD40 ligand (sCD40L) and P-selectin] were determined in the supernatant of blood samples obtained from a microvascular injury site. RESULTS: Total amounts of thrombin markers produced at the site of injury were similar before and after addition of clopidogrel, whereas platelet release of sCD40L and P-selectin was lower during treatment with aspirin + clopidogrel by 33.8% and 27.8% (p < 0.001), respectively. Patients in the highest tertile of reduction in platelet activation had previous myocardial infarction and peripheral arterial disease and released the highest amounts of sCD40L and P-selectin at baseline. TAT and F1.2 generation as well as sCD40L or P-selectin release were not influenced by the presence of the PlA2 allele. CONCLUSION: Our study shows that clopidogrel combined with aspirin does not reduce thrombin formation following vascular injury, but attenuates platelet sCD40L and P-selectin release.

Supra-aortic extracranial artery atherosclerotic lesions in patients diagnosed for coronary artery disease: prevalence and predictors.

BACKGROUND: In patients with coronary artery disease (CAD), the presence of atherosclerotic lesions in other vascular beds is associated with a markedly worse prognosis. AIM: To determine the prevalence and predictors of extracranial supra-aortic artery atherosclerotic disease (SAD) in patients with suspected CAD. METHODS: Supra-aortic artery angiography was performed in 379 consecutive patients aged 64.2 +/- 8.8 years (231 male) referred for coronary angiography. Clinical and laboratory data (total cholesterol, LDL, HDL cholesterol, hs-CRP, creatinine level) and left ventricular ejection fraction were analysed. RESULTS: Significant stenosis (> or =50% by quantitative angiography) within at least one main branch of the coronary arteries was found in 314 (82.8%) patients, including 87 (27.7%), 96 (30.6%) and 131 (41.7%) with 1-vessel, 2-vessel, and 3-vessel CAD, respectively. Among all 379 patients, stenosis > or =50% of the carotid artery was documented in 9.5%, vertebral in 13.7%, and subclavian in 7.4% of patients. We found 130 stenoses > or =50% within the supra-aortic arteries in 90 patients (23.7% of the whole study group, and 28.7% of CAD patients), including 42 internal carotid artery stenoses in 36 patients, 58 vertebral artery stenoses in 52, and 30 subclavian stenoses in 28 patients. In 24 (6.3%) patients more than one SAD was present. The SAD > or =50% was found in 8 (12.3%) patients without significant CAD, in 22 (25.3%), 17 (17.7%) and 43 (32.8%) with 1-, 2- and 3-vessel CAD, respectively (p = 0.001). Independent predictors of SAD > or =50% identified by multivariate analysis were: previous neurological ischaemic event (p = 0.001), CAD (p = 0.015), creatinine level (p = 0.031), male gender (p = 0.001), claudication (p < 0.001) and low HDL cholesterol (p = 0.033). The following independent predictors of vertebral and/or subclavian artery stenosis > 50% were identified: CAD severity (p = 0.002), creatinine level (p = 0.024), male gender (p = 0.013), claudication (p < 0.001) and low HDL cholesterol level (p = 0.059). CONCLUSIONS: In a large patient sample, we have found that significant supra-aortic atherosclerosis is present in a quater of patients with suspected CAD. Importantly, SAD prevalence increases with CAD severity. Previous neurological ischaemic event, CAD, creatinine level, male gender, claudication and hyperlipidaemia were identified as independent predictors of SAD > or =50%.

Late gadolinium enhancement in cardiovascular magnetic resonance in patients with hypertrophic cardiomyopathy complicated by life-threatening ventricular tachyarrhythmia.

BACKGROUND: Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) has been shown to be associated with ventricular arrhythmias, however, its prognostic role in predicting sudden cardiac death has not yet been established. AIM: To explore a potential relationship between LGE visualised by CMR and life-threatening ventricular tachyarrhythmia in hypertrophic cardiomyopathy (HCM). METHODS: The LGE in CMR was assessed in 55 HCM patients. We compared the frequency and extent of LGE in HCM patients with sustained ventricular tachycardia (VT) or who survived ventricular fibrillation (VF) or sudden death [group VF (+)] versus HCM patients without these tachyarrhythmias [group VF (-)]. There were 14 patients in the VF (+) group and 41 patients in the VF (-) group, and they were followed for a mean period of 37 months. RESULTS: In group VF (+), adequate ICD intervention occurred in 9 patients (8 patients with VF and one patient with sustained VT), and VF arrest occurred in 5 patients (4 patients were resuscitated and one patient had a witnessed sudden death). In group VF (+) all patients had LGE whereas in group VF (-) 85% patients presented this abnormality (p = 0.13). Moreover, there were no statistical differences between groups in the following parameters: age, total left ventricular (LV) mass, maximal LV wall thickness, mass of hyperenhanced myocardium and percent of hyperenhanced myocardium. CONCLUSION: In HCM patients with life-threatening ventricular tachyarrhythmia LGE was both qualitatively and quantitatively comparable with patients without these tachyarrhythmias.