Attila Cziráki

A new oscillometric method for assessment of arterial stiffness: comparison with tonometric and piezo-electronic methods.

Introduction Pulse wave velocity (PWV) and augmentation index (AIx) are parameters of arterial stiffness and wave reflection. PWV and AIx are strong indicators for cardiovascular risk and are used increasingly in clinical practice. Previous systems for assessment of PWV and AIx are investigator dependent and time consuming. The aim of this study was to validate the new oscillometric method (Arteriograph) for determining PWV and AIx by comparing it to two clinically validated, broadly accepted tonometric and piezo-electronic systems (SphygmoCor and Complior). Design and method PWV and AIx were measured up to five times in 51 patients with the SphygmoCor, Complior and Arteriograph. In 35 patients, the measurements were repeated after 1 week in a second session using the same protocol. Results The correlations of the PWV as assessed with the Arteriograph with the values obtained using the SphygmoCor (r = 0.67, P < 0.001) and the Complior (r = 0.69, P < 0.001) were highly significant. Variability and reproducibility for PWV were best for the Arteriograph, followed by Complior and SphygmoCor. AIx (SphygmoCor versus Arteriograph) were very closely correlated (r = 0.92, P < 0.001). Perspectives The Arteriograph is a new, easy-to-use and time-effective method for assessing arterial stiffness and wave reflection.

Invasive validation of a new oscillometric device (Arteriograph) for measuring augmentation index, central blood pressure and aortic pulse wave velocity

Background The importance of measuring aortic pulse wave velocity (PWVao), aortic augmentation index (Aix) and central systolic blood pressure (SBPao) has been shown under different clinical conditions; however, information on these parameters is hard to obtain. The aim of this study was to evaluate the accuracy of a new, easily applicable oscillometric device (Arteriograph), determining these parameters simultaneously, against invasive measurements. Methods Aortic Aix, SBPao and PWVao were measured invasively during cardiac catheterization in 16, 55 and 22 cases, respectively, and compared with the values measured by the Arteriograph. Results We found strong correlation between the invasively measured aortic Aix and the oscillometrically measured brachial Aix on either beat-to-beat or mean value per patient basis (r = 0.9, P < 0.001; r = 0.94, P < 0.001), which allowed the noninvasive calculation of the aortic Aix without using generalized transfer function. Similarly strong correlation (r = 0.95, P < 0.001) was found between the invasively measured and the noninvasively calculated central SBPao; furthermore, the BHS assessment of the paired differences fulfilled the ‘B’ grading. The PWVao values measured invasively and by Arteriograph were 9.41 ± 1.8 m/s and 9.46 ± 1.8 m/s, respectively (mean ± SD); furthermore, the Pearsons correlation was 0.91 (P < 0.001). The limits of agreement were 11.4% for aortic Aix and 1.59 m/s for PWVao. Conclusion Aix, SBPao and PWVao, measured oscillometrically, showed strong correlation with the invasively obtained values. The observed limits of agreement are encouragingly low for accepting the method for clinical use. Our results suggest that the PWVao values, measured by Arteriograph, are close to the true aortic PWV, determined invasively.

Suppression of poly (ADP-ribose) polymerase activation by 3-aminobenzamide in a rat model of myocardial infarction: long-term morphological and functional consequences

Recent studies demonstrated that inhibition or genetic inactivation of the enzyme poly (ADP‐ribose) polymerase (PARP) is beneficial in myocardial reperfusion injury. PARP activation in the reperfused myocardium has been assumed, but not directly demonstrated. Furthermore, the issue whether pharmacological PARP inhibition affords long‐term functional benefit in the reperfused myocardium has not been explored. These questions were addressed in the present study. In a rat model of myocardial ischemia (1 h) and reperfusion (up to 24 h), there was a marked and significant activation of PARP in the ischemic borderzone, as determined by poly(ADP‐ribose) (PAR) immunohistochemistry. PAR localized to the nuclei of myocytes and infiltrating mononuclear cells. In the core of the infarction, necrotic tissues and diffuse PAR staining were observed. PARP activation remained markedly detectable 24 h after reperfusion. The PARP inhibitor 3‐aminobenzamide (20 mg kg−1 intraperitoneally 10 min before reperfusion, and every 2 h thereafter for 6 h) markedly reduced the activation of the enzyme in myocytes. 3‐aminobenzamide significantly protected against myocardial morphological and functional alterations at 24 h post‐reperfusion. Notably, infarct size was reduced, circulating creatine kinase activity was attenuated, and myocardial contractility (dP dt−1) was restored by 3‐aminobenzamide. Our results demonstrate a significant and prolonged activation of PARP in the reperfused myocardium, localizing to the necrotic area and the ischaemic borderzone. Furthermore, the studies demonstrate that PARP inhibition affords long‐term beneficial morphological and functional effects in the reperfused myocardium. These data strengthen the notion that pharmacological PARP inhibition is a viable novel experimental approach for protection against myocardial reperfusion injury.

Role of poly(ADP-ribose) polymerase activation in endotoxin-induced cardiac collapse in rodents

Reactive oxygen and nitrogen species are overproduced in the cardiovascular system during circulatory shock. Oxidant-induced cell injury involves the activation of poly(ADP-ribose) polymerase (PARP). Using a dual approach of PARP-1 suppression, by genetic deletion or pharmacological inhibition with the new potent phenanthridinone PARP inhibitor PJ34 [the hydrochloride salt of N-(oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide], we studied whether the impaired cardiac function in endotoxic shock is dependent upon the PARP pathway. Escherichia coli endotoxin (lipopolysaccharide, LPS) at 55 mg/kg, i.p., induced a severe depression of the systolic and diastolic contractile function, tachycardia, and a reduction in mean arterial blood pressure in both rats and mice. Treatment with PJ34 significantly improved cardiac function and increased the survival of rodents. In addition, LPS-induced depression of left ventricular performance was significantly less pronounced in PARP-1 knockout mice (PARP(-/-)) as compared with their wild-type littermates (PARP(+/+)). Thus, PARP activation in the cardiovascular system is an important contributory factor to the cardiac collapse and death associated with endotoxin shock.

Comparison of aortic and carotid arterial stiffness parameters in patients with verified coronary artery disease

Arterial stiffness parameters are commonly used to determine the development of atherosclerotic disease. The independent predictive value of aortic stiffness has been demonstrated for coronary events.

Effects of coronary revascularization with or without cardiopulmonary bypass on plasma levels of asymmetric dimethylarginine

ObjectivesWe measured and compared serum asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-arginine levels in patients undergoing coronary artery revascularization. MethodsTwo groups of patients with coronary artery disease were subjected to coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB; n=20) or with off-pump CABG surgery (OPCABG; n=21). Blood samples for measurements of ADMA, SDMA, and L-arginine were withdrawn and determined by liquid chromatography–tandem mass spectrometry from the coronary sinus (CS) and from the peripheral vein. ResultsOn the basis of the intraoperative (CS) samples, ADMA levels rose in the CPB group (F=0.416, P<0.685 and F=14.751, P<0.001 for OPCABG and CPB groups, respectively). A similar significant increase of ADMA was observed in the peripheral blood (F=30.738, P<0.001) during CPB, whereas ADMA levels remained unchanged during OPCABG. The time course of L-arginine levels was significantly different in the blood samples from CS (F=3.255, P<0.05), when compared with samples from the peripheral blood (F=3.255, P<0.05). The values of the L-arginine/ADMA ratio were significantly higher in the OPCABG group at baseline and on the first postoperative day compared with the results of the CPB group (178.29±11.56 vs. 136.28±13.72 and 129.43±7.08 vs. 106.8±6.9 for OPCABG and CPB groups, respectively). ConclusionPlasma levels of ADMA, SDMA, L-arginine, and L-arginine/ADMA ratio are reliable and feasible markers of an early ischemia-reperfusion injury. During CPB operation, the plasma concentration of ADMA increased significantly and remained elevated until the first postoperative day due to extensive ischemia-reperfusion injury caused by CPB.

Elevated levels of asymmetric dimethylarginine (ADMA) in the pericardial fluid of cardiac patients correlate with cardiac hypertrophy

Background Pericardial fluid (PF) contains several biologically active substances, which may provide information regarding the cardiac conditions. Nitric oxide (NO) has been implicated in cardiac remodeling. We hypothesized that L-arginine (L-Arg) precursor of NO-synthase (NOS) and asymmetric dimethylarginine (ADMA), an inhibitor of NOS, are present in PF of cardiac patients and their altered levels may contribute to altered cardiac morphology. Methods L-Arg and ADMA concentrations in plasma and PF, and echocardiographic parameters of patients undergoing coronary artery bypass graft (CABG, n = 28) or valve replacement (VR, n = 25) were determined. Results We have found LV hypertrophy in 35.7% of CABG, and 80% of VR patients. In all groups, plasma and PF L-Arg levels were higher than that of ADMA. Plasma L-Arg level was higher in CABG than VR (75.7±4.6 μmol/L vs. 58.1±4.9 μmol/L, p = 0.011), whereas PF ADMA level was higher in VR than CABG (0.9±0.0 μmol/L vs. 0.7±0.0 μmol/L, p = 0.009). L-Arg/ADMA ratio was lower in the VR than CABG (VRplasma: 76.1±6.6 vs. CABGplasma: 125.4±10.7, p = 0.004; VRPF: 81.7±4.8 vs. CABGPF: 110.4±7.2, p = 0.009). There was a positive correlation between plasma L-Arg and ADMA in CABG (r = 0.539, p = 0.015); and plasma and PF L-Arg in CABG (r = 0.357, p = 0.031); and plasma and PF ADMA in VR (r = 0.529, p = 0.003); and PF L-Arg and ADMA in both CABG and VR (CABG: r = 0.468, p = 0.006; VR: r = 0.371, p = 0.034). The following echocardiographic parameters were higher in VR compared to CABG: interventricular septum (14.7±0.5 mm vs. 11.9±0.4 mm, p = 0.000); posterior wall thickness (12.6±0.3 mm vs. 11.5±0.2 mm, p = 0.000); left ventricular (LV) mass (318.6±23.5 g vs. 234.6±12.3 g, p = 0.007); right ventricular (RV) (33.9±0.9 cm2 vs. 29.7±0.7 cm2, p = 0.004); right atrial (18.6±1.0 cm2 vs. 15.4±0.6 cm2, p = 0.020); left atrial (19.8±1.0 cm2 vs. 16.9±0.6 cm2, p = 0.033) areas. There was a positive correlation between plasma ADMA and RV area (r = 0.453, p = 0.011); PF ADMA and end-diastolic (r = 0.434, p = 0.015) and systolic diameter of LV (r = 0.487, p = 0.007); and negative correlation between PF ADMA and LV ejection fraction (r = -0.445, p = 0.013) in VR. Conclusion We suggest that elevated levels of ADMA in the PF of patients indicate upregulated RAS and reduced bioavailability of NO, which can contribute to the development of cardiac hypertrophy and remodeling.

Early post-operative thrombosis of the prosthetic mitral valve in patient with heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is one of the most common immune-mediated adverse drug reactions, with frequencies as high as 2-3% for certain groups of post-cardiac surgery patients. We report on an 50-year-old woman with early post-operative thrombosis of the prosthetic mitral valve due to heparin-induced thrombocytopenia. Non-invasive imaging (two-dimensional transesophageal echocardiography; 2D-TEE) allowed the exact localisation of thrombotic masses and revealed the increase of the mean diastolic mitral gradient. The HIT diagnosis was proved by the clinical scoring system, and with the identification of heparin platelet factor 4-induced antibodies. After the withdrawal of LMWH therapy and the start of intravenous lepirudin treatment, the patients medical condition improved continuously. Follow-up echocardiography showed a step-wise decrease in the severity of the mean diastolic mitral valve gradient and a complete resolution of thrombus formations. Perhaps we may remind ourselves that, whilst HIT is one of the most common immune-mediated adverse drug reactions for certain groups of post-cardiac surgery patients, it can be managed successfully. We would also stress the importance of serial 2D-TEE examinations in the early post-operative period.

P1-02: Aortic pulse wave velocity (PWVAO) but not augmentation index (AIX) is associated with asymptomatic carotid atherosclerosis (ACA)

BACKGROUND Association between ACA and aortic stiffness (PWVao) in healthy, normotensive population. METHODS 234 (51.0±11.1 years) normotensive subjects without cardiovascular disease or diabetes were studied. PWVao, Aix were measured with oscillometric, occlusive method (Arteriograph). ACA was defined as 1,0mm or larger echogen plaque and/or a focal increase of IMT 1,3mm or larger measured with ultrasound. Logistic regression analysis was used to define parameters related significantly and independently to ACA. RESULTS 60 patients (25.6%) had asymptomatic carotid atherosclerosis (ACA). Significant differences were found between patients with and without ACA in the stiffness parameters (PWVao 9.6±1,6m/s vs 8.2±v1.3, Aix 34.8±12.9 vs 25.7±14.5%), in age (58.9±8.7 vs 48.3±10.5 years) but no significant differences were seen in SBP (126.2±8.2 vs 124.1±9,2mmHg) and DBP (75.7±7.1 vs 75.2±7.6mmHg). Adding age, gender, smoking, BMI, SBP, HR, Aix and PWVao to the stepwise analysis PWVao was selected in the second step, and in the final model age, smoking and PWVao remained significant contributors to ACA. The optimal PWVao threshold for ACA proved to be 8.71m/s. The sensitivity of PWVao to reveal ACA turned to be 72%, the sensitivity 71%, the positive predictive value 45%, the negative predictive value 88%, the relative risk 3.77, the odds ratio 6.1. CONCLUSIONS In a middle age, apparently healthy, normotensive population PWVao measured with Arteriograph is independently related to ACA, while Aix did not, suggesting that PWVao is a more specific marker to macrovascular atherosclerosis. We hypothesize that Aix might be related to earlier stage of atherosclerosis that question has to be addressed for further studies.

DIURNAL RHYTHM OF CENTRAL HEMODYNAMICS DURING TWENTY-FOUR-HOUR AMBULATORY MONITORING

Objective: 24-hour ABPM is a better method for diagnosing hypertension and predicting BP-related complications than office-based measurements. In addition increasing amount of evidences supports that central (aortic) BP is stronger predictor of cardiovascular risk than the conventional brachial BP. Dipping status of subjects can be easily assessed according to night-to-day brachial BP ratio provided by ABPM. However there is no data in the literature whether the diurnal rhythm of central aortic systolic blood pressure (CASP) follows the same pattern as the brachial one (BrSP). The aim of our study was to compare the 24-hour pattern of peripherial and central blood pressure in the same individuals. Design and method: 24-hour monitoring of aortic and brachial blood pressure was performed with Arteriograph24, a newly developed upper-arm cuff oscillometric device in 55 hypertensive and normotensive subjects, 36 males and 19 females. The 24-hour systolic pressure amplification, the difference of brachial and aortic cystic pressures measured simultaneously was calculated. Augmentation index (AIx) which is one of the main determinants of central blood pressure was also assessed. Results: The nocturnal fall of CSP was significantly lower than the peripheral pressure fall in 47 subjects of 55. 24-hour systolic pressure amplification was significantly lower during the night than during the day. In contrast to the nighttime decrease of central-to-peripherial systolic pressure Augmentation index was increased during the night. Conclusions: Central hemodynamic parameters (AIx, cSBP) also have diurnal rhythm but in contrast to peripherial BP the circadian variation of central BP is not necessarily parallel with the corresponding peripherial values. Theoretically elevated peripherial vascular resistance (which is represented by the augmentation index) during nighttime helps to maintain the appropriate central systolic pressure which is mandatory for the perfusion of the brain, heart and kidneys.