Comparison of electrical velocimetry and cardiac magnetic resonance imaging for the non-invasive determination of cardiac output.

A novel algorithm of impedance cardiography referred to as electrical velocimetry (EV) has been introduced for non-invasive determination of cardiac output (CO). Previous validation studies yielded diverging results and no comparison with the non-invasive gold standard cardiac magnetic resonance imaging (CMR) has been performed. We therefore aimed to prospectively assess the accuracy and reproducibility of EV compared to CMR. 152 consecutive stable patients undergoing CMR were enrolled. EV measurements were taken twice before or after CMR in supine position and averaged over 20 s (AESCULON(®), Osypka Medical, Berlin, Germany). Bland-Altman analysis showed insufficient agreement of EV and CMR with a mean bias of 1.2 ± 1.4 l/min (bias 23 ± 26 %, percentage error 51 %). Reproducibility was high with 0.0 ± 0.3 l/min (bias 0 ± 8 %, percentage error 15 %). Outlier analysis revealed gender, height, CO and stroke volume (SV) by CMR as independent predictors for larger variation. Stratification of COCMR in quintiles demonstrated a good agreement for low values (<4.4 l/min) with bias increasing significantly with quintile as high as 3.1 ± 1.1 l/min (p < 0.001). Reproducibility was not affected (p = 0.71). Subgroup analysis in patients with arrhythmias (p = 0.19), changes in thoracic fluid content (p = 0.51) or left heart failure (p = 0.47) could not detect significant differences in accuracy. EV showed insufficient agreement with CMR and good reproducibility. Gender, height and increasing CO and SV were associated with increased bias while not affecting reproducibility. Therefore, absolute values should not be used interchangeably in clinical routine. EV yet may find its place for clinical application with further investigation on its trending ability pending.

Influence of bag volume on reproducibility of inert gas rebreathing pulmonary blood flow measurements in patients with pulmonary diseases.

PURPOSE: Non-invasive inert gas rebreathing (IGR) has shown promising results in the determination of pulmonary blood flow. The volume of the rebreathing bag (V bag) is proposed by the system. However, elderly patients or those with severe pulmonary disease may be unable to rebreathe this volume entirely. We evaluated the effect of adapting V bag on the reproducibility of IGR. METHODS: A total of 270 valid measurements were obtained from 45 patients with obstruction (group A), restriction (group B), and in healthy controls (group C). Two measurements for each of three different V bag of 1,200, 1,700, and 2,200 ml were conducted in the supine position. RESULTS: We found no statistically significant difference of the repeated measurements neither between the different V bag in groups A to C nor between the three groups for identical V bag. There was a weak yet significantly worse coefficient of variation between a V bag of 2,200 ml in group A compared with group C with 2,200 and 1,200 ml, respectively. Intraclass correlation coefficient and repeatability coefficient yielded significantly worse values in group A for a V bag of 2,200 ml compared with healthy controls and lower bag volumes. No difference could be found intraclass nor interclass in groups B and C. CONCLUSIONS: V bag can be altered between 1,200 and 2,200 ml in most situations without affecting the reproducibility. Attention has to be paid to extreme volumes in obstructive patients. Nevertheless, V bag should be chosen as large as possible and therefore has to be carefully adapted, particularly in patients with obstruction or restriction.

Is arterial pulse contour analysis using Nexfin a new option in the noninvasive measurement of cardiac output?--A pilot study.

OBJECTIVES: A growing interest in monitoring cardiac output (CO) noninvasively has emerged; however, its determination has been difficult using the standard approaches. The aim of this study was to evaluate the accuracy and precision of pulse contour analysis (PCA) compared with cardiac magnetic resonance imaging (CMR). DESIGN: A single-center prospective study. SETTING: A university hospital. PARTICIPANTS: Thirty-nine consecutive stable patients undergoing CMR. INTERVENTIONS: CO was determined twice by PCA using the Nexfin monitoring system (BMEYE BV, Amsterdam, The Netherlands). Measurements were performed after 10 minutes of rest in a stable supine position immediately before or after the CMR examination. MEASUREMENTS AND MAIN RESULTS: There was a mean bias of 0.2 ± 1.9 L/min between CMR and PCA and a reproducibility of 0.2 ± 0.6 L/min for PCA. Between 4.8 and 6.3 L/min (second quartile of COCMR), there was a good agreement (mean bias = -0.2 ± 1.3 L/min). Comparing quartile 1 (-1.3 ± 2.0 L/min) overestimating and quartiles 3 (1.4 ± 0.9 L/min) and 4 (0.9 ± 2.0 L/min) underestimating CO, a statistically significant difference was found. The reproducibility was not affected by the quartile (p = 0.23, analysis of variance), whereas there was a significant difference between the nonoutlier and outlier group when using the Mann-Whitney U test (p = 0.02). CONCLUSIONS: Noninvasive PCA allows the safe and economic measurement of CO, yet it still has major limitations. Although the agreement with CMR was acceptable, there was a clinically unacceptable variation; absolute values should not be used interchangeably. These results suggest that therapeutic interventions and clinical decisions should not be based on noninvasive PCA measurements at the present time.

ESC Working Group on Valvular Heart Disease Position Paper: assessing the risk of interventions in patients with valvular heart disease.

AIMS: Risk scores provide an important contribution to clinical decision-making, but their validity has been questioned in patients with valvular heart disease (VHD), since current scores have been mainly derived and validated in adults undergoing coronary bypass surgery. The Working Group on Valvular Heart Disease of the European Society of Cardiology reviewed the performance of currently available scores when applied to VHD, in order to guide clinical practice and future development of new scores. METHODS AND RESULTS: The most widely used risk scores (EuroSCORE, STS, and Ambler score) were reviewed, analysing variables included and their predictive ability when applied to patients with VHD. These scores provide relatively good discrimination, i.e. a gross estimation of risk category, but cannot be used to estimate the exact operative mortality in an individual patient because of unsatisfactory calibration. CONCLUSION: Current risk scores do not provide a reliable estimate of exact operative mortality in an individual patient with VHD. They should therefore be interpreted with caution and only used as part of an integrated approach, which incorporates other patient characteristics, the clinical context, and local outcome data. Future risk scores should include additional variables, such as cognitive and functional capacity and be prospectively validated in high-risk patients. Specific risk models should also be developed for newer interventions, such as transcatheter aortic valve implantation.

How to: Success factors for the implementation and establishment of the "longitudinal curriculum" on communicative competencies at the Medical Faculty Mannheim.

Communicative competencies are of great importance to the medical profession, hence the teaching of them has been continuously expanded in recent years at many German medical schools. While individual courses on communicative competencies have already been established in the curricula, there remains, in part, a lack of longitudinal anchoring over the entire course of medical study. In 2008 the Medical Faculty Mannheim began implementing a longitudinal curriculum for communicative competencies. This paper outlines the general and phase-specific success factors in this process and gives practical recommendations and tips based on the personal experiences of the authors and the existing literature.

Authentic SP-based teaching in spite of COVID-19 - is that possible?

Objective: Medical conversation plays a central role in disease management and therapy. In teaching, standardized patients (SPs) are increasingly being used to present conversation situations with students and provide feedback afterwards. In order to maintain this teaching concept under pandemic conditions, a digital model was developed that should offer both high security and high authenticity. Methodology: A total of 176 teaching units of 45 minutes each were conducted digitally from May to August 2020. During the teaching units, medical students conducted interviews with SPs portraying various patients. The online conference software "HeiConf" was used for this purpose. During the teaching units, a total of 354 students were able to practice conversation techniques such as NURSE and SPIKES. After the teaching units, feedback was provided by students and SPs. Results: The digital lessons about medical conversation with SPs received positive feedback from SPs and students. The authenticity of the role portrayal of SPs seemed to be unaffected by the new format. Students were successful in training and observing conversation techniques. However, aspects of non-verbal communication, atmosphere and group dynamics as well as further discussions could not be carried out to the same extent as in the usual classroom teaching. Conclusion: The conversion of SP-based teaching to a digital format was successful in a short period of time and was able to prevent a cancellation of teaching units about medical conversation. Concrete conversation techniques could be tried out digitally by students. Due to the deficits of digital teaching in terms of non-verbal communication and atmosphere, a blended-learning format is planned for the future. In the first instance, concrete conversation techniques will be learned online in order to focus more on profound aspects of communication and discussions in a later physical teaching unit with SPs, thus enabling a learning experience that is as authentic as possible.

Automated Noninvasive Central Blood Pressure Measurements by Oscillometric Radial Pulse Wave Analysis: Results of the MEASURE-cBP Validation Studies.

BACKGROUND: Central blood pressure becomes increasingly accepted as an important diagnostic and therapeutic parameter. Accuracy of widespread applanation tonometry can be affected by calibration and operator training. To overcome this, we aimed to evaluate novel VascAssist 2 using automated oscillometric radial pulse wave analysis and a refined multi-compartment model of the arterial tree. METHODS: Two hundred and twenty-five patients were prospectively enrolled. Invasive aortic root measurements served as reference in MEASURE-cBP 1 (n = 106) whereas applanation tonometry (SphygmoCor) was used in MEASURE-cBP 2 (n = 119). RESULTS: In MEASURE-cBP 1, we found a mean overestimation for systolic values of 4 ± 12 mmHg (3 ± 10%) and 6 ± 10 mmHg (9 ± 14%) for diastolic values. Diabetes mellitus and low blood pressure were associated with larger variation. In MEASURE-cBP 2, mean overestimation of systolic values was 4 ± 4 mmHg (4 ± 4%) and 1 ± 4 mmHg (1 ± 7%) of diastolic values. Arrhythmia was significantly more frequent in invalid measurements (61 vs. 18%, P < 0.0001) which were most often due to a low quality index of SphygmoCor. CONCLUSIONS: Central blood pressure estimates using VascAssist 2 can be considered at least as accurate as available techniques, even including diabetic patients. In direct comparison, automated measurement considerably facilitates application not requiring operator training and can be reliably applied even in patients with arrhythmias.

The impact of pulmonary disease on noninvasive measurement of cardiac output by the inert gas rebreathing method.

Cardiac output (CO) is an important parameter for diagnosis and therapy of heart diseases, but it is still difficult to determine. Innocor, a novel noninvasive inert gas rebreathing (IGR) system, has shown promising results. However, the impact of pulmonary diseases on IGR remains unclear. The aim of the study therefore was to assess the accuracy and reliability of IGR in patients with distinct chronic lung disease. A total of 96 patients were enrolled, including 48 consecutive patients with variant lung diseases (group A) and 48 pair-matched pulmonary healthy patients (group B). CO was measured with cardiac magnetic resonance imaging (CMR) and IGR. Lung function testing was done by spirometry [FEV(1)/FVC (forced expiratory volume in one second/forced vital capacity), VC (vital capacity)] and determination of the diffusing capacity of the lung for carbon monoxide divided by alveolar volume (DLCO/VA). In group A we found a mean CO of 4.7 ± 1.3 L/min by IGR and 4.9 ± 1.2 L/min by CMR. Group B showed a mean CO of 4.8 ± 1.4 L/min by IGR and 5.0 ± 1.3 L/min by CMR. Bland-Altman analysis revealed good correspondence between CMR and IGR, with an average deviation of 0.1 ± 1.0 L/min in group A and 0.1 ± 1.0 L/min in group B (p = 0.99). Multiple regression analysis for the pulmonary parameters did not show a statistically significant impact on the mean bias of CO measurements (FEV(1)/FVC: r = 0.01, p = 0.91; VC: r = -0.2, p = 0.13; and DLCO/VA: r = 0.04, p = 0.82). IGR allows a feasible determination of CO even in patients with lung diseases. The accuracy of the IGR method is not influenced by either pulmonary obstructive and restrictive diseases or a reduced DLCO.

Noninvasive determination of cardiac output by the inert-gas-rebreathing method--comparison with cardiovascular magnetic resonance imaging.

BACKGROUND: An easy, noninvasive and accurate technique for measuring cardiac output (CO) would be desirable for the diagnosis and therapy of cardiac diseases. Innocor, a novel inert-gas-rebreathing (IGR) system, has shown promising results in smaller studies. An extensive evaluation in a larger, less homogeneous patient collective is lacking. METHODS: We prospectively assessed the accuracy and reproducibility of CO measurements obtained by IGR in 305 consecutive patients as compared to the noninvasive gold standard, cardiovascular magnetic resonance (CMR) imaging. RESULTS: Bland-Altman analysis showed a good correspondence of the two methods for CO measurement with an average deviation of 0.2 +/- 1.0 liters/min (mean +/- SD) and a good reproducibility with a mean bias of 0.2 +/- 0.5 liters/min. The accuracy of the present measurements at rest was significantly better in the physiological range than in higher or lower CO ranges. The error levels set forth by current recommendations were exceeded. CONCLUSION: The data show that IGR measurements are easy to perform and show good agreement with CMR; however, the technique appears to be less accurate in extreme CO ranges at rest. The clinical importance of the IGR method remains to be proven by further studies.

Percutaneous treatment of a coronary aneurysm by stent graft and drug-eluting stent implantation: a potential method to reduce stent graft restenosis.

Coronary artery aneurysms (CAAs) can occur congenitally or secondary to specific disorders such as Kawasaki disease or atherosclerosis. Apart from a surgical approach, CAA can be treated by coronary stent graft (CSG) implantation. However, restenosis is frequent after CSG placement, precluding a wider use of this technique. We hypothesized that implantation of a drug-eluting stent (DES) within a CSG could be of use to avoid CSG restenosis. We report the case of a patient with a large aneurysm of the right coronary artery who underwent CSG implantation followed by DES placement. The immediate angiographic result showed complete exclusion of the aneurysm. Intravascular ultrasound confirmed good apposition of both the CSG and DES. Follow-up angiography after 23 weeks demonstrated a good long-term result without restenosis. The patient has remained asymptomatic during 12 months of follow-up. In conclusion, the present case suggests that CSG placement followed by DES implantation is a safe and effective approach to treat coronary aneurysms interventionally.

Association of NT-proBNP with severity of heart valve disease in a medical patient population presenting with acute dyspnea or peripheral edema.

BACKGROUND AND AIM OF THE STUDY: The study aim was to perform a comprehensive evaluation of the association between N-terminal pro B-type natriuretic peptide (NT-proBNP) and the severity of heart valve diseases in a typical clinical population presenting with acute dyspnea or peripheral edema. METHODS: Among 401 eligible patients, 210 demonstrated evaluable complete echocardiographic examinations. Plasma levels of NT-proBNP were measured after the initial clinical evaluation. RESULTS: Patients with a prior valve replacement had higher plasma levels of NT-proBNP (median 3,366 pg/ml; n = 10) compared to all other patients (median 931 pg/ml; n = 200) (p < 0.05). In univariable analyses, NT-proBNP levels correlated with multiple valve diseases (r = 0.5; p < 0.001) and the severities of specific heart valve diseases, including aortic valve stenosis (AS) and regurgitation (AR), tricuspid (TR) and mitral valve regurgitation (MR) (p < 0.001). Within multivariable linear regression models, multiple heart valve diseases (Beta = 0.21; T = 3.56; p = 0.0001) and specifically valve regurgitations (AR (Beta = 0.16; T = 2.54; p = 0.012), MR (Beta = 0.36; T = 5.55; p = 0.0001), TR (Beta = 0.17; T = 2.55; p = 0.012)) were associated with increasing plasma levels of NT-proBNP. Patients with NT-proBNP plasma levels > 1,100 pg/ml showed the highest risk for future clinical events (odds ratio (OR) 4.86; p = 0.02), followed by patients with TR (OR 3.17; p = 0.03) and AS (OR 3.49; p = 0.06). CONCLUSION: In addition to clinical assessment and echocardiographic evaluation, the measurement of plasma NT-proBNP levels may serve as a valuable additional indicator of the severity of heart valve disease in individual patients.

Modification of the Harris-Benedict equation to predict the energy requirements of critically ill patients during mild therapeutic hypothermia.

UNLABELLED: The aim of the present study was the comparison of calculated and measured values of the energy expenditure of critically ill patients during the different phases of therapeutic mild hypothermia. PATIENTS AND METHODS: Five patients (mean age 40.6 years, range 23 to 68 years, 2 females) suffering from severe acute cerebral injuries who underwent mild hypothermia were prospectively included into the study. Indirect calorimetry measurements were made at intervals of 3-4 hours and subsequently, during the steady state, at least every 12 hours. The results were compared with the basal metabolic rate calculated by the Harris-Benedict equation. RESULTS: A close linear correlation between body temperature and basal metabolism could be observed across a wide range of temperatures from 30.5 degrees C to 38.3 degrees C (r=0.82, p<0.001). One degree drop in temperature led to a 5.9% reduction in energy. During mild hypothermia, oxygen consumption was reduced by 71 mL/min (95% confidence interval 57 to 86 mL/min; p<0.001) as compared to base line. The basal metabolism rate was decreased by 30.3% (95% confidence interval 24.7 to 35.9%, p<0.001). The average value recorded was 16.7% below the values calculated in accordance with the Harris-Benedict equation (95% confidence interval 12.8 to 20.6%). CONCLUSION: The immediate reduction in oxygen requirements achieved by hypothermia is linearly correlated with the reduction in temperature and the hypothermia induced reduction in oxygen requirement recorded by indirect calorimetry is considerably below that calculated in accordance with the Harris-Benedict equation. If indirect calorimetry should not be available and the Harris-Benedict equation is used, a corrective factor is therefore needed to avoid an inaccurate calorie administration.

Multiple coupled resonances in the human vascular tree: refining the Westerhof model of the arterial system.

The human arterial vascular tree can be described by multicompartment models using electrical components. First introduced in the 1960s by Noordergraaf and Westerhof, these hardware-based approaches required several simplifications. We were able to remove the restrictions using modern software simulation tools and improve overall model quality considerably. Whereas the original Westerhof model consisted of 121 Windkessel elements, the refined model has 711 elements and gives realistic pulse waveforms of the aorta and brachial and radial arteries with realistic blood pressures. Moreover, novel insights concerning the formation of the physiological aortic-to-radial transfer function were gained. Its being potentially due to the coupling of many small resonant elements gives new impetus to the discussion of arterial pressure wave reflection. The individualized transfer function derived from our improved model incorporates distinct patient characteristics and can potentially be used for estimation of central blood pressure values. NEW & NOTEWORTHY We were able to find an individualized transfer function giving realistic pulse waveforms and blood pressures using a multicompartment model of the arterial system. Based on the hardware-built Westerhof approach, several simplifications initially introduced in the 1960s could be reversed using software simulation. Overall model quality was improved considerably, and multiple coupled resonances were identified as potential explanation for the formation of the aortic-to-radial transfer function, giving new impetus to the discussion of arterial pressure wave reflection.

Systemic and local levels of fetuin-A in calcific aortic valve stenosis.

Calcific aortic valve stenosis, the most frequent heart valve disorder in developed countries, is an actively regulated process with similarities to bone formation. Fetuin-A has recently been identified as a potent circulating inhibitor of calcification. While several studies involving patients with end-stage renal disease have shown an association between low serum fetuin-A and cardiovascular calcification, nothing is known about fetuin-A serum levels in non-renal patients with calcific aortic valve stenosis. Furthermore, while fetuin-A has been localized in calcified areas of atherosclerotic arteries, data about fetuin-A deposition in stenotic aortic valves are unavailable at present. Serum fetuin-A levels were determined in patients with (n=31) and without (n=28) calcified aortic valve stenosis by ELISA. Creatinine and CRP levels were determined and glomerular filtration rate (GFR) was calculated by the MDRD formula. Immunohistochemistry for fetuin-A was performed on human calcified stenotic (n=14) and control (n=8) aortic valves using a monoclonal antibody. Serum fetuin-A levels were lower in patients with calcific aortic stenosis as compared to the control group (1.41+/-0.33 versus 1.57+/-0,27 mg/dl; p=0.046). This difference was particularly evident in individuals with a normal GFR >or=60 ml/min (1.36+/-0.24 versus 1.63+/-0.27 mg/dl; p=0.007). Furthermore, specific staining of fetuin-A was found in stenotic valves but not in healthy control valves. The data suggest a role of fetuin-A in the pathogenesis calcific aortic valve stenosis independently of the renal function and support the concept that mechanisms of calcium homeostasis are involved in the development of calcific aortic stenosis.

Impact of mitral E/A ratio on the accuracy of different echocardiographic indices to estimate left ventricular end-diastolic pressure.

The objective was to determine the influence of left ventricular (LV) inflow pattern on the accuracy of different echocardiographic indices for estimation of LV end-diastolic pressure (LVEDP). Echocardiography with color tissue Doppler imaging (TDI) and LVEDP measurements using fluid-filled catheters were performed in 176 consecutive patients on the same day. Mitral peak diastolic velocities (E, A) and the difference in duration between pulmonary venous retrograde velocity and mitral A-velocity (PV(R)-A) were recorded by pulsed Doppler. Propagation velocity of the early mitral inflow (V(P)) was assessed using color M-mode. Early diastolic longitudinal (E'(lat)) and radial (E'(radial)) velocities of mitral annulus were measured by TDI. Area under ROC curve (AUC) for prediction of elevated LVEDP (> or =15 mm Hg) was computed for each parameter. For E/A > or =1 (98 patients, 46 with elevated LVEDP), the AUC values were: PV(R)-A: 0.914; E/E'(lat): 0.780; E/E'(radial): 0.729; E/V(P): 0.712 (p < 0.001). When E/A <1 (78 patients, 26 with elevated LVEDP), only PV(R)-A reached statistical significance (AUC = 0.893, p < 0.001). The conclusions were: PV(R)-A enabled the most accurate noninvasive estimation of LVEDP irrespective of LV filling profile and combined indices E/V(P), E/E'(lat) and E/E'(radial) represent more feasible alternatives for patients with mitral E/A-1.

Prognostic value of plasma N-terminal pro-brain natriuretic peptide in patients with severe sepsis.

BACKGROUND: Increased plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) have been identified as predictors of cardiac dysfunction and prognosis in congestive heart failure and ischemic heart disease. In severe sepsis patients, however, no information is available yet about the prognostic value of natriuretic peptides. Therefore, the aim of the present study was to determine the role of the N-terminal prohormone forms of ANP (NT-proANP) and BNP (NT-proBNP) in the context of outcome of septic patients. Furthermore, the effect of treatment with recombinant human activated protein C [drotrecogin alfa (activated)] on plasma levels of natriuretic peptides in severe sepsis was evaluated. METHODS AND RESULTS: Fifty-seven patients with severe sepsis were included. Levels of NT-proANP and NT-proBNP were measured on the second day of sepsis by ELISA. Septic patients with NT-proBNP levels >1400 pmol/L were 3.9 times more likely (relative risk [RR], 3.9; 95% CI, 1.6 to 9.7) to die from sepsis than patients with lower NT-proBNP values (P<0.01). NT-proANP levels, however, were not predictive of survival in our patient population. A highly significant correlation was found between troponin I levels and plasma concentrations of NT-proBNP in septic patients (r=0.68, P<0.0001). In addition, troponin I significantly accounted for the variation in NT-proBNP levels (P<0.0001), suggesting an important role for NT-proBNP in the context of cardiac injury and dysfunction in septic patients. Twenty-three septic patients who received treatment with drotrecogin alfa (activated) presented with significantly lower concentrations of NT-proANP, NT-proBNP, and troponin I compared with patients not receiving drotrecogin alfa (activated). CONCLUSIONS: NT-proBNP may serve as useful laboratory marker to predict survival in patients presenting with severe sepsis.

Prevalence of atherosclerosis of the coronary and extracranial cerebral arteries in patients undergoing aortic valve replacement for calcified stenosis.

BACKGROUND AND AIM OF THE STUDY: The study aim was to investigate the coexistence of various atherosclerotic changes in patients with non-rheumatic calcific aortic valve stenosis (AS), since calcific AS shares various clinical risk factors with atherosclerosis. METHODS: In 282 consecutive patients with severe calcific stenosis of a tricuspid aortic valve scheduled for aortic valve replacement, the prevalence of atherosclerotic changes of the coronary and extracranial cerebral arteries were assessed using coronary angiography and Doppler sonography, respectively. RESULTS: The severities of coronary and extracranial cerebral artery atherosclerosis were significantly associated (p = 0.005). The prevalence and severity of both coronary and extracranial cerebral artery atherosclerosis were age-dependent. Coronary or extracranial cerebral artery stenosis was present in 59% and 16% of patients, respectively, while 91% of the study population and all patients aged > 80 years showed atherosclerosis of the coronary and/or extracranial cerebral arteries. CONCLUSION: The data obtained indicated a very high prevalence of atherosclerotic changes in patients with calcific AS, suggesting pathogenetic similarities of both disorders. Routine screening of the extracranial cerebral arteries is warranted in all patients with calcific AS and scheduled for valve replacement.

Lower serum calcium levels are associated with greater calcium hydroxyapatite deposition in native aortic valves of male patients with severe calcific aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the relationship between serum calcium levels and the degree of calcification found in stenotic aortic valves. METHODS: Using atomic absorption spectroscopy, the hydroxyapatite content of 228 excised human stenotic aortic valves was determined and expressed as a percentage of valve mass. Left heart catheterization preceded valve replacement. In addition, serum levels of calcium and creatinine were determined before native calcific aortic valve excision. RESULTS: Valves from male patients contained more hydroxyapatite than those of female patients (26 +/- 9 versus 22 +/- 9 mass%; p < 0.001). Patients presenting with lower serum calcium levels showed a slight trend towards higher levels of valve calcification (r = -0.15, p = 0.026), but this association appeared only within the subgroup of male patients. Male patients with lowest serum calcium levels displayed greatest valvular hydroxyapatite deposition (1st calcium tertiary: 29.5 +/- 8.9 mass% versus 2nd calcium tertiary 26.4 +/- 7.8 mass% versus 3rd calcium tertiary 21.4 +/- 8.9 mass%; n = 122; p = 0.001; r = -0.25; p = 0.006). This association was even more distinct in male patients with normal serum creatinine levels. Furthermore, serum calcium was inversely and significantly associated with serum C-reactive protein in male patients (r = - 0.34; p < 0.001). CONCLUSION: Serum calcium levels appear to be inversely related to valve calcification in patients with severe calcific aortic stenosis (AS). This finding indicates the importance of systemic calcium metabolism in calcific AS, independent of manifest disorders of calcium metabolism or renal function. Interestingly, this association was evident only in male patients, suggesting a gender-dependent pathogenesis.

Coagulation activation is associated with interleukin-6 plasma levels in patients with mechanical prosthetic heart valves.

BACKGROUND: The intensity of oral anticoagulant therapy in patients with mechanical heart valves is evaluated and controlled by the International Normalized Ratio (INR). However, intravascular coagulation activation can occur despite normal INR values and is related to clinical events. Here, anticoagulation efficiency was assessed by sensitive techniques and potential determinants of coagulation activation were identified. PATIENTS AND METHODS: Forty patients were enrolled after they had undergone mechanical aortic valve replacement. As markers of coagulation activation, plasma concentrations of the D-dimer antigen were prospectively measured. The patients were classified into quartiles according to the D-dimer plasma antigen level. Serum concentrations of the inflammatory markers C-reactive protein (CRP) and Interleukin (IL)-6 were also assessed. RESULTS: The D-dimer levels varied significantly despite therapeutic INR values. In patients with high D-dimer levels, the serum concentrations of IL-6 were significantly increased (top vs. bottom quartile, median, 1.35 versus 0.80 pg/ml; p<0.05), suggestive of subclinical inflammation. There was no association between the D-dimer levels and age, sex, cardiovascular risk factors or time since valve replacement. CONCLUSION: Coagulation activation and inflammation are associated with mechanical heart valves. The D-dimer antigen and IL-6 may be more sensitive than INR and CRP to detect these states and, therefore, could prove valuable additional markers, e.g., in determining the efficacy of new anticoagulant drugs.