Piotr Podolec

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.

Left ventricular geometry and function in patients with aortic stenosis: gender differences

BACKGROUND Gender differences in cardiac size have been described in normal and pathological conditions in human and animals. Sex determination of a pattern of hypertrophy as a response to pressure overload has not been extensively evaluated and is still poorly understood in humans. METHODS AND RESULTS To investigate the influence of gender in the left ventricle remodelling and preservation of the left ventricle function 195 adults (140 men and 55 women) with isolated aortic stenosis were evaluated. The mean age was 52 +/- 11 years for men and 53 +/- 13 years for women. All the patients had similar degree of aortic stenosis finally treated with valve replacement, similar clinical status and no signs of coronary artery disease in coronary angiograms. On echocardiography the left ventricle of women had a smaller the end systolic (30.5 +/- 7.8 vs. 39.4 +/- 11.2, P<0.001) and the end diastolic (49.4 +/- 9 vs. 57.3 +/- 11, P<0.001) chamber size. The female left ventricle generated a higher relative wall thickness (0.65 +/- 0.21 vs. 0.52 +/- 0.12, P<0.01), a greater fractional shortening (35.3 +/- 8.5 vs. 32.0 +/- 9.0, P<0.01) and a higher ejection fraction (64.4 +/- 12.7 vs. 57.5 +/- 14.6, P<0.001). The left ventricle posterior wall thickness and the septal thickness indexes were similar in both groups. There were also significant differences between the two groups in the left ventricle mass index. CONCLUSIONS Gender has an important influence on the left ventricle adaptation pattern to pressure overload due to aortic stenosis. Women developed a greater degree of left ventricle hypertrophy documented as changes in left ventricle geometry (increased relative wall thickness, left ventricular mass) and left ventricle function (fractional shortening and ejection fraction).

Influence of atorvastatin on coronary calcifications and myocardial perfusion defects in systemic lupus erythematosus patients: a prospective, randomized, double-masked, placebo-controlled study

IntroductionMortality in systemic lupus erythematosus (SLE) patients is influenced by an increased occurrence of severe cardiovascular complications. Statins have been proven to protect a wide spectrum of SLE patients from these complications. This study was conducted to determine the possible efficacy of atorvastatin in SLE patients as assessed by multi-detector computed tomography (MDCT)-based coronary calcium scoring and single photon emission computed tomography (SPECT) of the myocardium.MethodsSixty SLE patients in stable clinical conditions were randomized to receive either atorvastatin (40 mg daily; n = 28) or placebo (n = 32). Clinical and biochemical evaluation together with MDCT-based coronary calcium scoring and SPECT studies (Tc-99 m sestamibi) were performed at the time of randomization and after 1 year of treatment.ResultsAt randomization, SPECT revealed perfusion defects at rest in 22 (36.7%) patients and exercise-induced defects in 8 (13.3%), whereas MDCT revealed coronary calcifications in 15 subjects (25%). Coronary calcium deposits increased after 1 year in the placebo group (plaque volume change from 35.2 ± 44.9 to 62.9 ± 72.4, P < 0.05; calcium score from 32.1 ± 39.1 to 59.5 ± 64.4; P < 0.05), but not in the atorvastatin group (plaque volume 54.5 ± 62.4 vs. 51.0 ± 47.6, P not significant; calcium score 44.8 ± 50.6 vs. 54.9 ± 62.5, P not significant). The atorvastatin group showed a decrease in total serum cholesterol (from 5.1 ± 1.2 to 4.4 ± 0.7 mmol/L, P < 0.05), LDL cholesterol (2.9 ± 1.0 to 2.3 ± 0.6 mmol/L, P < 0.05), triglycerides (1.6 ± 0.6 to 1.2 ± 0.5 mmol/L, P < 0.05), and C-reactive protein (CRP) (4.4 ± 4.1 to 2.7 ± 1.7 mg/L, P < 0.05). There was no change in the mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score in patients from both groups. Perfusion defects observed at randomization showed no change after one year treatment with atorvastatin.ConclusionsIn SLE patients 40 mg of atorvastatin daily for 1 year led to a decrease in serum lipids and CRP levels. Additionally the progression of atherosclerosis, as assessed by MDCT-based coronary calcium scoring, is restrained by atorvastatin treatment. The value of statin treatment in patients with SLE free from cardiovascular disease clinical symptoms should be addressed in large, prospective clinical trials.

Reoperation after fresh homograft replacement: 23 years’ experience with 655 patients

OBJECTIVE Through a retrospective study on the use of fresh homografts in 655 aortic valve replacement patients over a period of 23 years, we aimed to assess the reasons for eventual reoperation and causes of valve dysfunction. METHODS Between January 1980 and December 2002, 655 patients received fresh homografts. All homografts were antibiotic sterilized and stored at 4 degrees C. During this time, 139 patients (116 male and 23 female) with a mean age of 46.7 years (range 18-72) required reoperation. RESULTS The 30-day hospital overall mortality was 2.87%. The mean durability for all homografts was 12.4+/-4.54 years (1 month to 23 years). The cumulative rates for freedom from reoperation for any cause were 94.09+/-2% at 5 years and 87.9%+/-4% at 10 years, 76.6 at 15 years, 49.55 at 20 years. The major cause of valve dysfunction and indication for reoperation was degeneration in 111 patients (79.8%). Predominant aortic valve insufficiency in 87 patients (62.5%) and predominant stenosis in 24 patients (17.26%). Endocarditis occurred in 21 patients (15.1%). Early endocarditis was diagnosed in five patients (3.59%), late endocarditis in 16 patients (11.5%). Additional causes for reoperation included ascending aortic aneurysm, mitral valve insufficiency and congestive cardiomyopathy. Seventeen patients (12.2%) required concomitant procedures. Coronary artery bypass grafting was performed in six cases (4.3%), mitral valve replacement in five cases (3.59%), mitral valve annuloplasty in six (4.3%). The primary reoperative procedure was artificial/mechanical aortic valve implantation. In five cases, St. Jude Medical conduit grafts were implanted due to ascending aortic aneurysms. Homograft reimplantation was performed in four cases. One patient underwent mitral valve replacement and one patient received a heart transplant. CONCLUSION The results of the study suggest that reoperation in patients with aortic homografts is a low-risk procedure as compared to alternative therapies. Primary allograft aortic valve replacement can give acceptable results for up to 23 years. The major cause of valve dysfunction and indication for reoperation was degeneration. Cumulative rates for freedom from reoperation for any cause in age groups suggest careful selection and indications in homograft implantation in the younger patients. Young age is a risk factor for an early homograft structural deterioration (degeneration).

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-β), 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.

Abnormalities in blood coagulation, fibrinolysis, and platelet activation in adult patients after the Fontan procedure

BACKGROUND Thrombosis occurs in up to 30% of patients with various forms of congenital single ventricle after the Fontan procedure. We investigated hemostatic abnormalities in adult Fontan patients. METHODS Forty-eight Fontan patients between ages 18 and 40 years, including 10 (21%) patients with previous thromboembolism 5 to 15 years after surgery, and 35 control subjects matched for age and sex were studied. Coagulation factors and inhibitors, together with markers of fibrinolysis, platelets, and endothelial activation, were determined in peripheral venous blood plasma. RESULTS Compared with control subjects, Fontan patients showed lower, although mostly within normal ranges, values of all coagulation factors, as well as reduced free protein S, in association with higher antithrombin and free tissue factor pathway inhibitor levels. Thrombin generation, reflected by prothrombin fragment 1.2, and platelet activation markers were increased in Fontan patients. The plasma clot lysis time was prolonged in Fontan patients, which was associated with an increased activity of thrombin-activatable fibrinolysis inhibitor. Fontan patients with previous thromboembolism had lower oxygen saturation, coagulation factors V and VIII, and free protein S, and increased von Willebrand factor, soluble CD40 ligand, and P-selectin. Other laboratory or clinical parameters were not associated with prior thrombotic episodes. CONCLUSIONS Adult Fontan patients are characterized by enhanced platelet activation and endothelial injury, heightened thrombin formation, and impaired fibrinolysis. Patients showed reduced free protein S levels, increased platelet activation, and endothelial damage after thromboembolic events observed late after Fontan surgery. Our findings indicate novel prothrombotic mechanisms in adult Fontan patients, which might help to optimize thromboprophylaxis.

Aortic Pulse Wave Velocity and Carotid-Femoral Pulse Wave Velocity : Similarities and Discrepancies

The objectives of this study were to determine the relationship between carotid-femoral (cfPWV) and aortic pulse wave velocity (aPWV) and to compare their modulators and association with coronary artery disease (CAD). We studied 107 consecutive patients (68 men) with a mean age of 60.49±8.31 years who had stable angina and had been referred for coronary angiography. cfPWV and aPWV were measured simultaneously during cardiac catheterization using the Complior® device and aortic pressure waveform recordings, respectively. Based on the presence or absence of significant coronary artery stenosis (CAS) patients were subdivided into a CAS+ or CAS− group. The mean values of cfPWV and aPWV were 10.65±2.29 m/s and 8.78±2.24 m/s, respectively. They were significantly higher in the CAS+ (n=71) compared with the CAS− (n=36) group and predicted significant CAS independently of cardiovascular risk factors and mean or systolic aortic blood pressure. aPWV and cfPWV were significantly correlated (r=0.70; p<0.001) but the degree of correlation differed significantly (p<0.03) between the CAS+ (r=0.74, p<0.001) and CAS− group (r=0.46, p=0.003). Age and mean aortic blood pressure were independent predictors for aPWV as well as cfPWV. In the receiver operating characteristic (ROC) analysis, aPWV and cfPWV had similar accuracy in identification of significant CAS (AUC [area under the ROC curve]=0.76 and 0.69, respectively; p=0.13). However, neither cfPWV nor aPWV was effective at differentiating the extent of CAD. In conclusion, aPWV and cfPWV are highly correlated parameters with similar determinants and comparable accuracy in predicting significant CAS. The strength of correlation between these two indices differed significantly between subjects with and those without CAS.

Cardiorespiratory Response to Exercise in Children after Modified Fontan Operation

Objective : Examination of exercise function of Fontan patients and comparison with healthy control subjects. Design : Fourteen patients (6 males, 8 females; age: 5.7-17 years, mean 8.1 years) after Fontan repair in New York Heart Association (NYHA) class I with rest O 2 sat > 85% requiring no cardiovascular medications performed graded exercises on a treadmill 0.5-3.2 years postoperatively (mean 1.8 years). During the tests the heart and respiratory rate, blood pressure, oxygen uptake, carbon dioxide production, minute ventilation, tidal volume and O 2 sat were recorded. Spirometry was performed before and during exercise. Results : The peak VO 2 max in Fontan patients was significantly reduced compared with controls ( p = 0.0002). Other parameters: anaerobic threshold ( p = 0.0001); pulsO 2 ( p = 0.00005); peak minute ventilation ( p = 0.0014); physiological dead space to tidal volume ratio at peak exercise ( p = 0.0004); maximal work rate ( p = 0.00008); exercise time ( p = 0.00003) were significantly reduced in univentricular patients. The heart rate at peak exercise was lower in the patients ( p = 0.0003) and O 2 sat dropped significantly ( p = 0.003). Conclusion : The aerobic capacity, work and ventilatory parameters in Fontan patients are markedly reduced compared with controls. The anaerobic threshold was significantly lower. The decreased O 2 sat at peak exercise may suggest intrapulmonary shunting.

Atherosclerosis progression affects the relationship between endothelial function and aortic stiffness

Aortic stiffening is the most important determinant of elevated systolic blood pressure which in turn is the main contributor to the burden of disease attributable to hypertension. Endothelial function may affect arterial stiffening as has been shown for carotid-aorto-femoral segments in healthy humans or subjects with cardiovascular risk factors. We investigated whether this association is present selectively for aorta and whether it extends to patients with advanced atherosclerosis. Direct measurements of aortic pulse wave velocity (aPWV) to assess aortic stiffness and brachial artery flow-mediated dilatation (bFMD) tests to assess endothelial function were performed in 111 consecutive patients suspected of coronary artery disease. Progression of atherosclerosis was determined on the basis of the presence or absence of significant coronary artery stenosis, CAS (>or=50%) in angiography. bFMD was lower (P<0.001) and aPWV was higher (P<0.001) in a group of 72 patients with advanced atherosclerosis when compared with a group of 39 patients without significant CAS. bFMD was inversely associated with aPWV but only in patients without advanced atherosclerosis (r=-0.37, P=0.02), even after adjustment of confounding factors in a multivariate analysis model (R(2)=0.37, P<0.001). We concluded that endothelial function may influence aortic stiffness which is limited however by the progression of atherosclerosis.

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/mL [limits, 58–356 ng/mL]) and sustained LVEF depression at ⩽45% were recruited. On day 10 (days 7–12), 4.3×106 (0.7–9.9×106) 99mTc-extametazime–labeled autologous bone marrow CD34+ cells (activity, 77 MBq [45.9–86.7 MBq]) were administered transcoronarily (left anterior descending coronary artery). 99mTc-methoxyisobutyl isonitrile (99mTc-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 &ggr; 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); it also correlated with peak TnI (r=0.76, P<0.001), severely-abnormal/absent perfusion segment number (r=0.45, P=0.008), and late gadolinium-enhanced infarct core (r=0.58, P=0.0003) 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.