Lidia Tomkiewicz-Pajak

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.

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.

Heart structure and function in patients with generalized autoimmune diseases: echocardiography with tissue Doppler study.

Objective Heart pathology strongly infl uences the course and prognosis of patients with generalized autoimmune diseases. In spite of autoimmunity being a common denominator of these diseases, systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and dermato/polymyositis (DPM) diff er signifi cantly in the pathogenesis of organ damage. The aim of the study was to compare pathologic changes in heart structure and function in these diseases by means of standard echocardiography and tissue Doppler (TDE). Material and methods Four groups were examined: 60 SSc, 60 SLE and 15 DPM patients in stable clinical conditions and 30 healthy control subjects. Echocardiography with TDE was performed with the assessment of systolic (S) and diastolic (E) velocities of mitral and tricuspid annuli. Results Heart in SSc was characterized by signifi cant diastolic left ventricular dysfunction (mitral E 8.61 ± 2.3 cm/s vs. 12.4 ± 3.5 cm/s in the control group; P < 0.01) with preserved systolic function (mitral S 7.85 ± 1.5 cm/s vs. 7.95 ± 0.9 cm/s in control group; ns). SLE and DPM resulted mainly in pathologic thickening of valvular leafl ets and/or pericardium [mitral or aortic leafl ets thickened in 38 (63.3%) of SLE patients, 7 (46.7%) of DPM patients; pericardium thickened in 36 (60%) of SLE patients]. Pulmonary capillary wedge pressure was elevated in SSc (13.8 ± 3.5 mmHg) and DPM (13.2 ± 2.5 mmHg) patients, as compared to the control group (9.2 ± 3.7 mmHg, P < 0.01). Right ventricular systolic and diastolic dysfunction was frequent irrespective of the presence or absence of pulmonary hypertension. Conclusions Echocardiography with TDE reveals characteristic pathology in diff erent forms of generalized autoimmune diseases refl ecting their diff erent pathogenetic mechanisms. Overproduction of collagen in SSc results in diastolic left ventricular dysfunction, while generalized infl ammation in SLE and DPM leads mainly to pathologic changes on valvular leafl ets and/or pericardium. Interestingly, right ventricular dysfunction is common in all diseases analyzed, regardless of the presence of pulmonary hypertension. Echocardiography, preferably with TDE, could add valuable information about usually asymptomatic heart pathology in an individual patient with generalized autoimmune disease.

Iron deficiency and hematological changes in adult patients after Fontan operation

BACKGROUND Growing evidence indicates that iron-deficiency anemia is common in patients with congenital heart diseases. The aim of this study was to characterize hematologic changes and iron metabolism in adult Fontan patients. We also searched for the associations between these parameters and physical performance in the study group. METHODS AND RESULTS Thirty-two white Fontan patients with a mean age of 25 ± 4.5 years and 30 healthy control subjects matched for age and sex were studied. Complete blood count together with iron-related parameters was determined in plasma of peripheral venous blood. The cardiopulmonary exercise test was performed. The Fontan patients had higher red blood cell counts (6.0 ± 2.1 × 10(9)/μl vs. 4.8 ± 0.4 × 10(9)/μl, p<0.001), hemoglobin (16.7 ± 1.4 g/dl vs. 14.2 ± 1.3g/dl, p<0.001), hematocrit (49 ± 3.4% vs. 42.1 ± 3.1%, p<0.001), red cell distribution width (RDW) (14.3 ± 2.4% vs. 12.8 ± 0.5%, p<0.001), while mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were similar in both the groups. Compared to the controls, the Fontan patients had higher unsaturated iron binding capacity (46.1 ± 12.6 μmol/l vs. 38.4 ± 11.9 μmol/l, p=0.02), total iron-binding capacity (62.8 ± 9.8 μmol/l vs. 57.8 ± 8.5 μmol/l, p=0.04), lower transferrin saturation (27.4 ± 11.4% vs. 34.6 ± 13.4%, p=0.03), and oxygen uptake, while iron and ferritin levels were comparable in both the groups. The multivariate model showed that SatO2 and cystatin C were independent predictors of RDW, and alanine aminotransferase was an independent predictor of ferritin level. Interestingly RDW was an independent predictor of oxygen uptake. CONCLUSION Adult patients after Fontan operation despite having increased hemoglobin, hematocrit, and red blood cells have insufficient iron stores. Red cell distribution width is an indicator of iron deficiency in adult Fontan patients and it correlates with lower exercise capacity. Elevated ferritin levels in adult patients after Fontan surgery are associated with liver failure.

Aspirin resistance in adult patients after Fontan surgery

BACKGROUND Thrombotic complications are common in adult patients who have had a Fontan operation early in life for treatment of congenital heart disease. OBJECTIVE To characterize platelet function and responsiveness to aspirin in relation to thrombogenesis, systemic inflammation, and markers of endothelial function in adults with Fontan circulation (FC). METHODS Thirty-four FC patients (age 18-40years; 62% taking aspirin chronically and 38% not taking aspirin) and 32 age- and sex-matched healthy controls were studied. Platelet function was evaluated by measurement of basal concentrations of thromboxane B2 (TXB2) and sCD40L and ex-vivo generation of TXB2 and sCD40L. Plasma concentrations of thrombin-antithrombin, endothelin-1, vWF, IL-6, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 also were measured. RESULTS Platelet numbers were significantly lower in FC patients than in controls, but the patients had significantly higher platelet activity, as evidenced by higher TXB2 and sCD40L concentrations and higher ex vivo generation of TXB2. Chronic aspirin treatment had no effect on plasma concentrations of TXB2 and sCD40L in FC, but in 52% of aspirin-treated FC subjects, TXB2 concentrations remained elevated at 60min of TXB2 generation, indicating aspirin resistance. In addition, FC patients had increased levels of thrombin-antithrombin, endothelin-1, vWF, IL-8, MCP-1, MIP-1β, TNFα, sVCAM-1, and syndecan-1 but not of IL-6. CONCLUSION Adults with FC had lower platelet numbers but increased platelet activity, increased thrombogenesis, systemic inflammation, and endothelial dysfunction. A significant proportion of aspirin-treated FC adults had aspirin resistance, which may be at least in part responsible for their increased incidence of thrombotic complications.

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 (VO2 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 VO2 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, VO2 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.