Temporal changes in the pattern of invasive angiography use and its outcome in suspected coronary artery disease: implications for patient management and healthcare resources utilization.

INTRODUCTION: Invasive coronary angiography (CAG), the 'gold standard' in coronary artery disease (CAD) diagnosis, requires hospitalization, is not risk-free, and engages considerable healthcare resources. AIM: To assess recent (throught out 10 years) evolution of 'significant' (≥ 50% stenosis(es)) CAD prevalence in subjects undergoing CAG for CAD diagnosis in a high-volume tertiary referral center. MATERIAL AND METHODS: Anonymized medical records were compared for the last vs. the first 2-years of the decade (June 2007 to May 2018). Referrals for suspected CAD were 2067 of 4522 hospitalizations (45.7%) and 1755 of 5196 (33.8%) respectively (p < 0.001). RESULTS: The median patient age (64 vs. 68 years) and the prevalence of heart failure (24.1% vs. 42.2%) increased significantly (p < 0.001). The CAG atherosclerotic lesions, for all stenosis categories (< 50%; ≥ 50%; ≥ 70%; occlusion(s)), were significantly more prevalent in men. The proportion of subjects with any atherosclerosis on CAG increased (80.7% vs. 77.6%, p = 0.015). However, in the absence of any gross change in, for instance, the fraction of women (40.4% vs. 41.8%), the proportion of CAGs with significant CAD (lesion(s) ≥ 50%) decreased from 55.2% in 2007/2008 to below 1 in every 2 angiograms (48.9%) in 2017/2018 (p < 0.001). This unexpected finding occurred consistently across nearly all CAG referral categories. CONCLUSIONS: Despite more advanced age and a higher proportion of subjects with 'any' coronary atherosclerosis on CAG, the likelihood of a 'negative' angiogram (lesion(s) < 50%; no further evaluation/intervention) has increased significantly over the last decade. The exact nature of this phenomenon requires further investigation, particularly as a reverse trend would be expected with the growing role (and current high penetration) of contemporary non-invasive diagnostic tools to rule out significant CAD.

Practice setting and secondary prevention of coronary artery disease.

INTRODUCTION: Patients with established coronary artery disease (CAD) are at high risk of recurrent cardiovascular events. The aim of the analysis was to compare time trends in the extent to which cardiovascular prevention guidelines have been implemented by primary care physicians and specialists. MATERIAL AND METHODS: Five hospitals with cardiology departments serving the city and surrounding districts in the southern part of Poland participated in the study. Consecutive patients hospitalized due to an acute coronary syndrome or for a myocardial revascularization procedure were recruited and interviewed 6-18 months after hospitalization. The surveys were carried out in 1997-1998, 1999-2000, 2006-2007 and 2011-2013. RESULTS: The proportion of smokers increased from 16.0% in 1997-1998 to 16.4% in 2011-2013 among those who declared that a cardiologist in a hospital outpatient clinic decided about the treatment, from 17.5% to 34.0% (p < 0.01) among those treated by a primary care physician, and from 7.0% to 19.7% (p = 0.06) among patients treated in private cardiology practices. The corresponding proportions were 44.6% and 42.4% (p < 0.01), 47.7% and 52.8% (p = 0.53), 44.2% and 42.2% (p = 0.75) for high blood pressure, and 42.5% and 71.2% (p < 0.001), 51.4% and 79.6% (p < 0.001), 52.4% and 72.4% (p < 0.01) for LDL cholesterol level not at recommended goal. The proportion of patients prescribed cardioprotective medications increased in every analyzed group. CONCLUSIONS: The control of cardiovascular risk in CAD patients has only slightly improved since 1997/98 in all health care settings. The greatest potential for further improvement was found among patients whose post-hospital care is provided by primary care physicians. It is associated with promotion of a no-smoking policy and enhanced prescription of guideline-recommended drugs.

Multimarker approach in discriminating patients with symptomatic and asymptomatic atherosclerotic carotid artery stenosis.

BACKGROUND AND PURPOSE: Several circulating biomarkers have been implicated in carotid atherosclerotic plaque rupture and thrombosis; however, their clinical utility remains unknown. The aim of this study was to determine the role of a large biomarker panel in the discrimination of symptomatic (S) vs. asymptomatic (A/S) subjects in a contemporary population with carotid artery stenosis (CS). METHODS: Prospective sampling of circulating cytokines and blood lipids was performed in 300 unselected, consecutive patients with ≥50% CS, as assessed by duplex ultrasound (age 47-83 years; 110 with A/S and 190 with S) who were referred for potential CS revascularization. RESULTS: CS severity and pharmacotherapy did not differ between the A/S and S patients. The median values of total cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) did not differ, but high-density lipoprotein (HDL) cholesterol was significantly higher (p<0.001) and triglycerides were lower (p=0.03) in the A/S-CS group than in the S-CS group. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were higher (p=0.04 and p=0.07, respectively) in the S-CS group. Circulating visfatin, soluble CD 40 receptor ligand, soluble vascular cell adhesion molecule, leptin, adiponectin, IL-1ß, IL-8, IL-18, monocyte chemoattractant protein-1, myeloperoxidase, matrix metalloproteinases-8, -9, and -10, and fibrinogen were similar, but tissue inhibitor of matrix metalloproteinases-1 (TIMP) was reduced in S-CS compared to A/S-CS (p=0.02). Nevertheless, incorporation of TIMP and IL-6 did not improve the HDL-cholesterol receiver operating characteristics for S-CS status prediction. S-CS status was unrelated to angiographic stenosis severity or plaque burden, as assessed by intravascular ultrasound (p=0.16 and p=0.67, respectively). Multivariate logistic regression analysis revealed low HDL-cholesterol to be the only independent predictor of CS symptoms, with an odds ratio of 1.81 (95% confidence interval=1.15-2.84, p=0.01) for HDL <1.00 mmol/L (first quartile) vs. >1.37 (third quartile). In S-CS, osteoprotegerin and lipoprotein-associated phospholipase A2 (Lp-PLA2) were elevated in those with recent vs. remote symptoms (p=0.01 and p=0.02, respectively). CONCLUSIONS: In an all-comer CS population on contemporary pharmacotherapy, low HDL-cholesterol (but not other previously implicated or several novel circulating biomarkers) is an independent predictor of S-CS status. In addition, an increase in circulating osteoprotegerin and Lp-PLA2 may transiently indicate S transformation of the carotid atherosclerotic plaque.

Infarct size determines myocardial uptake of CD34+ cells in the peri-infarct zone: results from a study of (99m)Tc-extametazime-labeled cell visualization integrated with cardiac magnetic resonance infarct imaging.

BACKGROUND: Effective progenitor cell recruitment to the ischemic injury zone is a prerequisite for any potential therapeutic effect. Cell uptake determinants in humans with recent myocardial infarction are not defined. We tested the hypothesis that myocardial uptake of autologous CD34(+) cells delivered via an intracoronary route after recent myocardial infarction is related to left ventricular (LV) ejection fraction (LVEF) and infarct size. METHODS AND RESULTS: Thirty-one subjects (age, 36-69 years; 28 men) with primary percutaneous coronary intervention-treated anterior ST-segment-elevation myocardial infarction and significant myocardial injury (median peak troponin I, 138 ng/dL [limits, 58-356 ng/dL]) and sustained LVEF depression at ≤45% were recruited. On day 10 (days 7-12), 4.3×10(6) (0.7-9.9×10(6)) (99m)Tc-extametazime-labeled autologous bone marrow CD34(+) cells (activity, 77 MBq [45.9-86.7 MBq]) were administered transcoronarily (left anterior descending coronary artery). (99m)Tc-methoxyisobutyl isonitrile (99(m)Tc-MIBI) single-photon emission computed tomography before cell delivery showed 7 (2-11) (of 17) segments with definitely abnormal/absent perfusion. Late gadolinium-enhanced infarct core mass was 21.7 g (4.4-45.9 g), and infarct border zone mass was 29.8 g (3.9-60.2 g) (full-width at half-maximum, signal intensity thresholding algorithm). One hour after administration, 5.2% (1.7%-9.9%) of labeled cell activity localized in the myocardium (whole-body planar γ scan). Image fusion of labeled cell single-photon emission computed tomography with LV perfusion single-photon emission computed tomography or with cardiac magnetic resonance infarct imaging indicated cell uptake in the peri-infarct zone. Myocardial uptake of labeled cells activity correlated in particular with late gadolinium-enhanced infarct border zone mass (r=0.84, P<0.0001) and with peak troponin I (r=0.76, P<0.001); it also correlated with severely abnormal/absent perfusion segment number (r=0.45, P=0.008) and late gadolinium-enhanced infarct core (r=0.58 and r=0.84, P<0.0001) but not with echocardiography LVEF (r=-0.07, P=0.68) or gated single-photon emission computed tomography LVEF (r=-0.28, P=0.16). The correlation with cardiac magnetic resonance imaging-LVEF was weak (r=-0.38; P=0.04). CONCLUSIONS: This largest human study with labeled bone marrow CD34(+) cell transcoronary transplantation after recent ST-segment-elevation myocardial infarction found that myocardial cell uptake is determined by infarct size rather than LVEF and occurs preferentially in the peri-infarct zone.

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.

Simvastatin administration reduces thromboxane production in subjects taking aspirin: links between aspirin resistance and thrombin generation.

BACKGROUND: Growing evidence indicates that statins may reduce thromboxane A(2) synthesis and thrombin generation. We investigated the relationships between thromboxane production, thrombin generation, and oxidative stress in patients receiving aspirin before and after statin administration. METHODS: An open-label study was conducted in 112 men, aged 54.4 ± 7.3 years, at an increased cardiovascular risk receiving aspirin (75 mg/d). Prior to and following a 3-month simvastatin treatment (40 mg/d), we evaluated circulating thromboxane B(2) (TXB(2)), inflammatory markers, 8-isoprostane, and prothrombin fragment 1.2 (F1.2), a marker of thrombin generation, which was also measured in blood collected every 60s at the site of standardized skin incisions. RESULTS: Subjects (n=28) with pretreatment TXB(2) concentrations in the highest quartile ("aspirin-resistant patients") were more frequently current smokers and had elevated C-reactive protein (CRP), interleukin-6, 8-isoprostane, shorter bleeding time, and increased F1.2 production in a model of microvascular injury, when compared with the 3 remaining quartiles (all, p<0.001). Simvastatin decreased serum TXB(2) in the whole group (by 20%, p=0.0008). Patients in the highest quartile of the baseline TXB(2) had still higher posttreatment TXB(2), CRP, interleukin-6, and F1.2 formation following injury (all, p<0.001). Simvastatin-induced change in TXB(2) correlated with the magnitude of changes in maximum levels and the velocity of F1.2 formation (all p<0.001) but not with changes in inflammatory markers or lipid profile. CONCLUSIONS: The study shows that statins significantly reduce platelet TXA(2) formation in patients taking low-dose aspirin and this effect is associated with attenuated thrombin formation in response to vascular injury.

Relationship between mitral leaflets angles, left ventricular geometry and mitral deformation indices in patients with ischemic mitral regurgitation: imaging by echocardiography and cardiac magnetic resonance.

UNLABELLED: Chronic ischemic mitral regurgitation (IMR) is associated with a markedly worse prognosis after myocardial infarction (MI).The study aimed to evaluate the relationship between anterior and posterior mitral leaflet angle (MLA) values, left ventricle remodeling and severity of ischaemic mitral regurgitation (IMR). METHODS: Forty-two patients (age 63.5 ± 9.7 years, 36 men) with chronic IMR (regurgitant volume, RV > 20 ml; >6 months after MI) underwent transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR) imaging. Anterior and posterior MLA, determined by echocardiography, were correlated with indices of LV remodeling, mitral apparatus deformation and IMR severity by CMR. The anterior and posterior MLA was 25.41 ± 4.28 and 38.37 ± 8.89° (mean ± SD). In 5 patients (11.9%) the posterior MLA was ≥45°. There was a significant correlation between anterior MLA and RV (r = 0.74, P = 0.01). For patients with RV > 30 ml this correlation was stronger (r = 0.97, P = 0.005) and, in addition, there was a correlation between the RV and posterior MLA (r = 0.90, P = 0.037), between tenting area and posterior MLA (r = 0.90, P = 0.04), and between tenting area and anterior MLA (r = 0.82, P = 0.08). With regard to LV remodeling parameters, there was weaker but significant correlation between posterior MLA and LV end-diastolic volume index (r = 0.35, P = 0.031), LV end-systolic volume index (r = 0.37, P = 0.021), stroke volume (r = 0.35, P = 0.03), sphericity index (r = 0.33, P = 0.041). Anterior MLA correlated with wall motion score index (r = 0.41, P = 0.019). Besides, there was a correlation between posterior MLA and left atrial volume (r = 0.41, P = 0.012). Measurement of anterior and posterior MLA may play an important role in evaluating patients with IMR.

Relationship between carotid intima-media thickness, cytokines, atherosclerosis extent and a two-year cardiovascular risk in patients with arteriosclerosis.

AIM: To investigate the relationship between carotid intima-media thickness (CIMT), biomarkers, atherosclerosis extent and a two-year cardiovascular (CV) event risk in patients with arteriosclerosis. METHODS: The CIMT, levels of high-sensitivity C-reactive protein (hs-CRP), tumour necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-ß), interleukin-6 (IL-6), interleukin-10 (IL-10), and NT-proBNP were measured in 279 subjects with atherosclerotic disease, mean age 64.1 ± 9.6 years. The patients were included when they had artery stenosis ≥ 50% in one, two, three or four arterial territories (coronary, supra-aortic, renal and/or lower limb arteries), and this was found in 97, 80, 69 and 33 patients, respectively. During a two-year follow-up, the incidences of CV death, myocardial infarction, ischaemic stroke and lesion progression were recorded. RESULTS: The identified independent predictors of ≥ 3-territorial stenoses ≥ 50% were CIMT > 1.3 mm (RR 1.72; p < 0.001), hs-CRP > 5 mg/dL (RR 1.28; p = 0.005), IL-6 > 6.5 pg/mL (RR 1.08; p = 0.089), IL-10 (RR 0.86; p = 0.002), diabetes (RR 1.11; p = 0.027), total-cholesterol (RR 1.21; p < 0.001), creatinine (RR 1.15; p = 0.004) and body mass index (RR 0.85; p = 0.001). During a two-year follow-up, CV events occurred in 52 (18.6%) patients. The CIMT > 1.3 mm (p < 0.001), diabetes (p = 0.018), TNF-α > 6 pg/mL (p = 0.018), LDL-cholesterol > 3.35 mmol/L (p = 0.012) and NT-proBNP (p = 0.074) were independent CV event risk factors associated with a 27%, 14%, 15%, 15% and 11% higher CV risk, respectively. However, after adjustment for a baseline location of artery stenosis ≥ 50%, CIMT became a non-significant predictor (p = 0.245). CONCLUSIONS: Levels of hs-CRP, IL-6, IL-10 are independently associated with atherosclerosis extent, while TNF-α and NT- -proBNP are mostly related to a two-year CV event risk. The CIMT > 1.3 mm seems to be a clinically relevant marker associated with atherosclerosis extent and CV risk, although CV event risk is primarily related to the baseline stenosis location.

Increased prevalence of cardiovascular risk factors in patients with acute coronary syndrome and indications for treatment with oral anticoagulation.

BACKGROUND: Antiplatelet drugs currently constitute the basic treatment of coronary artery disease (acute coronary syndrome [ACS], stable angina and patients treated with percutaneous coronary interventions [PCI]). The number of patients with indication for dual antiplatelet therapy with comorbidities with high thrombo-embolic risk (such as atrial fibrillation [AF], venous thrombotic disease, valvular diseases) is increasing. That is why the need for simultaneous administration of dual antiplatelet and oral anticoagulant therapy (triple therapy) has become more common recently. The AF is the most common indication for chronic anticoagulation. Because of the lack of large randomised trials regarding triple therapy, characteristics of this group has not been well established. AIM: To assess the presence of cardiovascular (CV) risk factors and concomitant diseases in patients with ACS requiring triple therapy. METHODS: Retrospective analysis included 2279 patients diagnosed with ACS who were admitted to the Departments of Cardiology in Cracow in 2008. In this group, 365 (16%) patients had indications for chronic anticoagulation. Demographic and clinical characteristics of these patients were compared with those of patients included in other published registries. RESULTS: Patients requiring triple therapy were aged 73.2 ± 9.5 years. Hypertension was diagnosed in 80%, hyperlipidaemia in 63%, smoking in 36%, prior myocardial infarction in 33%, prior stroke in 15%, previous treatment with PCI in 13%, coronary artery bypass grafting in 7%, diabetes in 36%, heart failure in 46%, anaemia in 33% and chronic ulcer disease or gastroesophageal reflux disease in 9%. The mean left ventricular ejection fraction was 46 ± 15%. Compared with other registries of patients without indications for triple therapy, our patients had significantly more frequently hypertension, diabetes and were older. CONCLUSIONS: Patients after an ACS requiring triple therapy have more often a history of comorbidities and CV risk factors when compared with the group of patients with ACS without indication for triple therapy.

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).

[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.

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.

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.

Carotid intima-media thickness, hs-CRP and TNF-α are independently associated with cardiovascular event risk in patients with atherosclerotic occlusive disease.

UNLABELLED: This prospective study aimed to determine whether carotid intima-media thickness (CIMT) and biomarkers can enhance the predictive value of classic atherosclerosis risk factors (RFs) for cardiovascular (CV) event risk in patients with confirmed atherosclerosis. METHODS: Baseline levels of hs-CRP, Tumor Necrosis Factor alpha (TNF-α), Transforming Growth Factor beta (TGF-ß), Interleukin-6 (IL-6), Interleukin-10 (IL-10) and Nt-proBNP were measured in 304 subjects (189 men) aged 64.2±9.4 years, with confirmed atherosclerotic occlusive disease. Maximum CIMT values of common, bulb and internal carotid arteries were measured and expressed as mean CIMT value. The incidences of CV death, myocardial infarction (MI), ischemic stroke (IS) and symptomatic lesion progression were recorded. RESULTS: During 44.7±12.1 months of follow-up, CV events occurred in 61 (20.1%) patients. Age (odds ratio: OR=1.04; p=0.013), diabetes (OR=2.01; p=0.007), LDL-cholesterol>3.35mmol/L (OR=2.03; p=0.007), previous MI (OR=2.14; p=0.003) and previous IS (OR=3.35; p<0.001) were found independent CV event RFs. Adding biomarkers or CIMT to classic RFs revealed that levels of TNF-α>6pg/mL (OR=1.77; p=0.024), hs-CRP>6mg/L (OR=1.69; p=0.009) or CIMT>1.25mm (OR=5.11; p<0.001) were independently associated with CV event risk. While Nt-proBNP was found RF of CV death (OR=1.19; p=0.003) and MI (OR=1.19; p=0.002). In patients with RFs plus TNF-α>6pg/mL and hs-CRP>6mg/L, a 2- and 5-year event-free survival was 8% and 4%, respectively, as compared to 42% and 33% in those with RFs but lower TNF-α and hs-CRP levels. While, CIMT<1.25mm increased a 2- and 5-year CV event-free survival probability to 79% and 73%, respectively, despite classic RFs presence. CONCLUSION: Additive value of TNF-α, hs-CRP and CIMT to classic RFs in CV risk stratification was found in patients with confirmed atherosclerosis. Nt-proBNP was found an independent risk factor of CV death and MI.

Fibrin presence within aortic valves in patients with aortic stenosis: association with in vivo thrombin generation and fibrin clot properties.

A role of coagulation in the pathogenesis of aortic stenosis (AS) is unknown. The aim of this study was to investigate the fibrin (Fn) presence and its determinants in calcified stenotic aortic valve leaflets. Twenty-one patients with dominant AS and 17 well-matched patients with dominant aortic insufficiency (AI) undergoing aortic valve replacement were studied. Immunofluorescence analysis was performed on decalcified leaflets using antibodies against human Fn and tissue factor (TF). Fn-positive (41.4%) and TF-positive (25.3%) areas were increased in AS valves compared with AI valves (7.9% and 5.9%, respectively, both p<0.001). Patients with AS had elevated plasma D-dimer (236.4 ± 28 ng/ml, p=0.002) and prothrombin fragment 1+2 (F1.2) (261.7 ± 27.1 pM, p=0.005) compared to AI subjects (142.8 ± 10 ng/ml and 131.2 ± 1.3 pM, respectively). In AS patients Fn-positive areas correlated with TF-positive areas (r=0.68, p=0.0005), D-dimer (r=0.45, p=0.018), F1.2 (r=0.64, p=0.002), the time required for plasma fibrin clot formation (r=0.44, p=0.015) and maximum absorbance of fibrin clots (r=-0.38, p<0.0001), but not with clot permeability or lysis time. Thickness of Fn layer within AS valves was associated with maximum transvalvular gradient (r =0.41, p=0.048). Patients with maximal gradient above 75 mmHg (n=11) showed significant associations between Fn-positive area and both maximal (r =0.63) and mean (r =0.67) transvalvular gradients. Large fibrin amounts, mostly co-localised with TF, are present within the valve leaflets of patients with advanced AS. In vivo thrombin generation and fibrin clot formation are associated with the extent of Fn presence within leaflets, which might contribute to the AS progression.

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.

Altered fibrin clot properties in patients with chronic heart failure and sinus rhythm: a novel prothrombotic mechanism.

BACKGROUND: Thromboembolic complications occur more frequently in patients with chronic heart failure (CHF) than in the general population. Formation of a compact fibrin clot resistant to lysis has been shown in arterial and venous thrombosis. OBJECTIVE: To investigate fibrin clot properties in patients with CHF. METHOD: Plasma clot permeability, compaction, turbidity and fibrinolysis were assessed in 36 consecutive patients with stable CHF (30M, 6F; aged 64+/-10 years, left ventricular ejection fraction (LVEF) 34.9+/-6.7%) and 36 controls matched for age, sex, cardiovascular risk factors and medication. Exclusion criteria were LVEF >40%, anticoagulant therapy, previous thromboembolic events, atrial fibrillation. RESULTS: Clots obtained from plasma of patients with CHF had 23% lower clot permeability (p<0.0001), 13% less clot compaction (p<0.001), 15% faster fibrin polymerisation (p<0.0001) and tended to have prolonged fibrinolysis time (p=0.1) compared with controls. C-reactive protein and fibrinogen were associated inversely with clot permeability (R(2)=0.84, p<0.0001 and R(2)=0.79, p<0.0001, respectively) and positively with fibrinolysis time (R(2)=0.88, p<0.0001 and R(2)=0.80, p<0.0001, respectively) in patients with CHF. Plasma thrombin-antithrombin complex concentrations were inversely correlated with clot permeability (R(2)=0.88, p<0.0001) and positively with fibrinolysis time (R(2)=0.91, p<0.0001). Left atrium diameter, but not LVEF, correlated with fibrinolysis time (R(2)=0.61, p=0.027). CONCLUSIONS: Patients with CHF with sinus rhythm are characterised by faster formation of compact plasma fibrin clots, which might predispose to thromboembolic complications.

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.

The dynamic assessment of right-ventricular function and its relation to exercise capacity in heart failure.

AIMS: To evaluate right-ventricular (RV) function during stress echocardiography (SE) and to assess its relationship with exercise capacity in heart failure (HF) patients. METHODS AND RESULTS: We included 88 patients aged 60.9 +/- 11.2 years with a mean LVEF of 27.2 +/- 9.5%. The following RV parameters were measured at baseline and peak exercise during semi-supine SE: velocity (IVV) and acceleration during isovolumic contraction (IVA), S', E', A', and ratio of early diastolic tricuspid velocity to E' (E/E') and longitudinal strain and strain rate. Patients were stratified into two groups according to their VO(2peak) values: group 1 (n = 35) with VO(2peak) <14 mL/kg/min and group 2 (n = 53) with VO(2peak) >or=14 mL/kg/min. At rest, all analysed variables were similar in the two groups, but during stress IVV, S', and E' were significantly higher and the E/E' ratio significantly lower in group 2. In broad terms, parameters measured at stress correlated much better with VO(2peak) than parameters assessed at baseline. However, results of multivariable analysis determined that the independent predictors of VO(2peak) were solely the left-ventricular (LV) parameters: E/E' and S'. CONCLUSIONS: Right-ventricular function (whether at rest or during stress tests) was not significantly associated with exercise capacity in our patients with HF. In contrast, systolic and, to a greater extent, diastolic LV parameters during the stress tests emerged as the most important indicators linked to exercise capacity in HF.