[Show abstract][Hide abstract] ABSTRACT: Diseases of the heart and the cardiovascular system are the leading cause of death in developed countries. The heart rate variability is a promising marker for these diseases and shows a significant relationship to cardiovascular mortality, but is easily disrupted by ectopic heart beats. Numerous methods of ectopic beat correction exist to counteract this problem, but they need to be validated using comprehensive data sets with customizable features. Therefore, in this work an ectopic beat simulator based on physiologic data is presented. During its development, statistical properties of real heart rate variability data containing ectopic beats are evaluated and a model is built. This model is integrated in a simulator capable of mimicking numerous medical conditions. The results are inspected using qualitative and quantitative comparisons between the simulator and real heart rate variability data by visual inspection and analysis of covariance. They show a reasonable reproduction of ectopic beats, enabling comprehensive validation of ectopic beat correction methods.
[Show abstract][Hide abstract] ABSTRACT: Windkessel models are lumped-parameter models of the arterial system that describe the dynamic relation between blood flow and pressure in the aorta. Despite their simplicity, they are used in many applications including methods for the non-invasive stratification of cardiovascular risk. However, even though they have been studied extensively, there is still disunity regarding the question if pressure should be modelled as resulting solely from the ejection of the heart or if an asymptotic pressure level should be included which is independent from cardiac beating. The aim of this work is to mathematically analyse the influence of such a pressure level P∞ on the model behaviour of the four most widely used Windkessel models (two-, three- and four-element Windkessel, the latter in a series as well as a parallel configuration). Therefore, the model equations are introduced and Fourier analysis is performed to clarify the impact of P∞ on the other parameters. Then, a typical aortic flow wave is used as input to the models and simulation experiments with varying values of P∞ are performed. Theoretical considerations as well as numerical results show that, in all four models, including P∞ mainly affects the diastolic part of the modelled pressure wave and could potentially improve the fitting performance during diastolic decay. However, further research is needed to clarify the physiological interpretation of P∞ as well as its appropriate size.
[Show abstract][Hide abstract] ABSTRACT: Objectives:
Arterial stiffness and wave reflection parameters assessed from both invasive and non-invasive pressure and flow readings are used as surrogates for ventricular and vascular load. They have been reported to predict adverse cardiovascular events, but clinical assessment is laborious and may limit widespread use. This study aims to investigate measures of arterial stiffness and central hemodynamics provided by arterial tonometry alone and in combination with aortic root flows derived by echocardiography against surrogates derived by a mathematical pressure and flow model in a healthy middle-aged cohort.
Measurements of carotid artery tonometry and echocardiography were performed on 2226 ASKLEPIOS study participants and parameters of systemic hemodynamics, arterial stiffness and wave reflection based on pressure and flow were measured. In a second step, the analysis was repeated but echocardiography derived flows were substituted by flows provided by a novel mathematical model. This was followed by a quantitative method comparison.
All investigated parameters showed a significant association between the methods. Overall agreement was acceptable for all parameters (mean differences: -0.0102 (0.033 SD) mmHg*s/ml for characteristic impedance, 0.36 (4.21 SD) mmHg for forward pressure amplitude, 2.26 (3.51 SD) mmHg for backward pressure amplitude and 0.717 (1.25 SD) m/s for pulse wave velocity).
The results indicate that the use of model-based surrogates in a healthy middle aged cohort is feasible and deserves further attention.
PLoS ONE 10/2015; 10(10):e0141656. DOI:10.1371/journal.pone.0141656 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study is the prospective investigation of the association of brachial SBP (bSBP) and aortic SBP (aSBP) to all-cause mortality, with special emphasis on different calibration methods for central pressure estimates, in particular, brachial systolic and diastolic, as well as brachial mean and diastolic pressures.
One hundred and fifty-nine patients were enrolled in a longitudinal, prospective study of arterial stiffness and cardiovascular risk in a chronic kidney disease stages 2-4 cohort. Office measurements of bSBP and aSBP were assessed by a validated oscillometric device. Prognostic factors of survival were identified by use of Cox proportional-hazards regression models.
After a mean follow-up duration of 42 months (range 30-50 months), 13 patients died. In univariate Cox analysis, bSBP and aSBP calibrated using bSBP and bDBP did not significantly predict mortality, only aSBP assessed using measured mean and diastolic pressure calibration was significantly associated with mortality (hazard ratio 1.027, P = 0.008). This remained significant in multivariate analysis after adjustment for age, sex, and anthropometric measures. More important, adding bSBP to the multivariate model (hazard ratio 0.91, P = 0.003) lead to a significantly increased prognostic power of aortic systolic pressure (hazard ratio 1.097, P < 0.001) and indicated that differences between bSBP and aSBP are of potential interest.
Within our cohort, only aSBP assessed with measured mean and diastolic pressure independently predicted mortality and provided additional prognostic value on top of bSBP readings. Therefore, the method of calibration plays an important role for predictive power of aSBP.
Journal of Hypertension 06/2015; 33(9). DOI:10.1097/HJH.0000000000000633 · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Blood pressure measurements are associated with paradoxical effects in patients with systolic heart failure. Parameters, which have been associated with increased risk, lie within a normal range in patients with impaired systolic function. This implies that the noninvasive detection of reduced ejection fraction from blood pressure alone is difficult and additional biosignals are needed. A typical approach is the usage of arterial Doppler flow velocity measurements, which also facilitates more advanced techniques such as wave intensity analysis. In this method, distinct peaks in forward and backward traveling waves can be detected and quantified. However, aiming for simple noninvasive measurement techniques, blood flow models solely based on information from the pressure curve have been developed to replace ultrasound measurements. These models could be extended and controlled with features from the electrocardiogram (ECG), which have been related to impaired systolic function. This work presents wave intensity parameters as well as ECG intervals from a patient with normal (nEF) and a patient with severely reduced ejection fraction (rEF). The wave peak corresponding to the first forward compression wave is markedly reduced in the rEF patient. Moreover, ECG intervals are prolonged, especially when corrected for heart rate. These exemplary results strengthen the idea that it might be feasible to use a multisensor approach based on arterial pressure readings and electrocardiogram features to detect impaired systolic function and thus enhance cardiovascular risk stratification.
[Show abstract][Hide abstract] ABSTRACT: A number of operator-independent oscillometric devices to measure hemodynamics and arterial stiffness became available recently, but some and in particular VaSera VS-1500 do not provide estimates of aortic pressures and aortic pulse wave velocity (aPWV). The aim of this work was the retrospective application of the ARCSolver algorithm to pulse wave signals acquired with the VaSera VS-1500 device to estimate central systolic blood pressure (cSBP) and aPWV.
ARCSolver estimates of cSBP and aPWV, on the basis of brachial cuff measurements, were compared pair-wise with results from the tonometric SphygmoCor device in 68 individuals (mean age 51±18 years). We used variation estimates, correlation coefficients, age group-related t-tests, and the Bland-Altman method to analyze the reproducibility and agreement of the two methods.
cSBP reproducibility expressed as variability was 14.9% for ARCSolver and 11.6% for SphygmoCor. PWV reproducibility was better for ARCSolver, with a variation estimate of 6.5%, compared with 20.9% using SphygmoCor. The mean cSBP difference was 0.5 mmHg (SD 6.9 mmHg) and 0.32 m/s (SD 1.20 m/s) for PWV, respectively. The age-related differences between ARCSolver and SphygmoCor are in line with previous studies. Bland-Altman plots showed considerable agreement between the two methods without signs of systematic bias.
These results show that the combined application of the ARCSolver method with the VaSera VS-1500 device is feasible and the results are comparable with tonometric determination of cSBP and aPWV. This successful application of the ARCSolver may potentially help to improve cardiovascular risk stratification and prevention at an early stage in a community setting.
[Show abstract][Hide abstract] ABSTRACT: Arterial aging is one of the fundamental mechanisms underlying blood pressure (BP) increase, and may even precede BP rise. We hypothesized that the extent of arterial aging, quantified as aortic pulse wave velocity (aPWV) graded according to an age-specific reference group with normal BP, would be related to blood pressure classification, based on office and 24 hour ambulatory BP.
We measured BP and aPWV twice in the doctors office and performed 24 hour ambulatory BP monitoring with the oscillometric cuff-based mobilograph device (iem, Stolberg, Germany) in untreated and treated patients from a large group practice in internal medicine. APWV was estimated with the recently validated ARCSolver algorithm, based on age, systolic BP and waveform characteristics and was classified as < 50., 51.-95., and > 95 percentile of the age-specific reference group.
We included 839 patients (46.4% females, mean age 58.1 years, range 15-94 years). Mean office BP was 139/90 mm Hg, mean 24 hour BP was 128/80 mm Hg, mean aPWV was 9.6 m/sec. 247 patients were normotensive, 113 had white coat hypertension, 99 masked hypertension, and 380 were sustained hypertensive. 78.4% of the patients had aPWVs above the 95. percentile, 18.8% were between 50. and 95. percentile, and 2.7% were below the 50. percentile. There was a clear increase in the percentage of patients with sustained hypertension across the three categories of arterial aging (4.3%, 16.5%, and 53.6% in patients below the 50. percentile, between 50. and 95., and above the 95. percentile, respectively), and an inverse distribution related to normotension (Table). The differences were statistically highly significant (p < 0.0001). The relatively high percentage of patients with masked hypertension in the group < 50. percentile (30.4%) is of concern, but the absolute number is small (n = 7).
Arterial aging, based on age-specific percentiles, may be a useful screening tool for sustained hypertension, based on office and 24 hour ambulatory BP.(Figure is included in full-text article.).
[Show abstract][Hide abstract] ABSTRACT: We recently developed and validated a technique to separate the forward and backward components of the arterial pulse, based on pressure waves alone. While we found the results useful in the workup of heart failure with preserved ejection fraction, little is known about the diagnostic yield in patients with impaired systolic function.
Based on non-invasive radial waveforms from tonometry and a Windkessel model derived flow signal, we quantified the forward and backward waves in the aorta of 61 patients with severly reduced systolic function (rEF) and 122 controls with normal ejection fraction, matched for age, gender, and brachial blood pressures. Forward waves were quantified, using wave intensity analysis, resulting in systolic S-wave (increasing pressure and flow) and systolic D-wave (decreasing pressure and flow). Backward waves were quantified, using pulse wave analysis, resulting in Augmentation Index (AIx) and Pressure Augmentation (AP). Ejection duration was indexed to heart rate (LVETI). In addition, QRS duration from 12 lead ECGs was measured and normalized for heart rate, using the formula QRSc = QRS / sqrt(RR-interval).
For the same levels of brachial blood pressures, rEF was associated with shorter LVETI, lower S / D ratio, and lower AIx and AP. Based on ROC curve analysis, AUCs for the detection of rEF for LVETI, AIx, AP, and S/D ratio were 0.81, 0.73, 0.7, and 0.83, respectively (p < 0.0001 for all). Combining LVETI with AIx and S/D R increased AUC to 0.86 (CI 0.80-0.91). Adding QRSc significantly (p = 0.003) increased AUC to 0.94 (CI 0.89-0.97) and lead to a correct classification of 89.5% of the patients, see figure.
Characteristics of the pressure waveform, which potentially can be derived from oscillometric cuffs with automated algorithms, may help in the diagnosis of patients with impaired systolic function. Adding simple ECG characteristics significantly improves the prediction model. Ultimately, oscillometric blood pressure cuff-derived measures may indicate the need for further investigations, e.g. echocardiography.(Figure is included in full-text article.).
[Show abstract][Hide abstract] ABSTRACT: Williams-Beuren syndrome (WBS) is a genetic disorder that involves elastin gene causing cardiovascular abnormalities and increased risk. However, data on arterial function in these patients are only few and conflicting. Aim of this study was to evaluate dynamic behaviour of central and peripheral blood pressure (BP) and arterial stiffness parameters early in the course of WBS.
We enrolled 19 WBS paediatric patients (age 13 ± 4 years) and 23 age, height and BP-matched controls (10 ± 4 years). We evaluated 24-h ambulatory BP values via an ambulatory blood pressure monitoring (ABPM) system (Mobil-O-Graph) also capable to calculate 24-h central BP and 24-h arterial stiffness parameters. Carotid-femoral PWV (cf-PWV) was assessed in all WBS individuals (Complior).
BP values were similar in WBS and control, during the daytime and the night-time. The same behaviour applies to 24-h central BP. However, during the night, WBS showed heart rate values (HR; 78 ± 10 vs. 71 ± 9 bpm; P < 0.03), augmentation index (Aix; 24.6 ± 13.5% vs. 16.5 ± 8.9%; P = 0.03) and reflection magnitude (68 5.8 vs. 63.5 8.1; P = 0.02) higher than controls. The HR, Aix and reflection magnitude reduction in the day-night shift was lower in WBS than in controls. Cf-PWV in WBS children did not differ when compared with their normalized expected value.
In WBS children, the higher night-time HR, Aix and reflection magnitude and their impaired physiological reduction in the day-night shift suggests an abnormal sympathetic cardiovascular control, an augmented wave reflection and an increase in small arteries resistance. These alterations possibly due to a sympathetic overactivity can be regarded as earlier hallmarks of cardiovascular dysfunction in these patients.
Journal of Hypertension 04/2015; 33(4):804-809. DOI:10.1097/HJH.0000000000000454 · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare noninvasive methods to assess pulse wave velocity (PWV) with the invasive gold standard in terms of absolute values, age-related changes, and relationship with subclinical organ damage.
Invasive aortic PWV (aoPWVinv) was measured in 915 patients undergoing cardiac catheterization (mean age 61 years, range 27-87 years). Carotid-femoral PWV (cfPWV) was measured with tonometry, using subtracted distance (cfPWVsub), body height-based estimated distance (cfPWVbh), direct distance × 0.8 (cfPWVdir0.8), and caliper-based distance (cfPWVcalip) for travel distance calculation. Aortic PWV was estimated (aoPWVestim) from single-point radial waveforms, age, and SBP.
Invasive and noninvasive transit times were strikingly similar (median values 60.8 versus 61.7 ms). In the entire group, median value of aoPWVinv was 8.3 m/s, of cfPWVsub and cfPWVbh 8.1 m/s, and of aoPWVest 8.5 m/s. CfPWVsub overestimated aoPWVinv in younger patients by 0.7 m/s and underestimated aoPWVinv in older patients by 1.7 m/s, with good agreement from 50 to 70 years of age. AoPWVestim differed from aoPWVinv by no more than 0.4 m/s across all age groups. CfPWVdir0.8, measured in 632 patients, overestimated aoPWVinv by 1.7 m/s in younger patients, with good agreement in middle-aged and older patients. CfPWVcalip, measured in 336 patients, underestimated aoPWVinv in all ages. In 536 patients with preserved systolic function, aoPWVinv and aoPWVestim were superior to cfPWVs in predicting coronary atherosclerosis, renal function impairment, left atrial enlargement, and diastolic dysfunction.
CfPWVsub, cfPWVdir0.8, and aoPWVestim are reasonable surrogates for aoPWVinv. AoPWVinv predicts subclinical organ damage better than cfPWVs, and as good as aoPWVestim.
Journal of Hypertension 02/2015; 33(5). DOI:10.1097/HJH.0000000000000518 · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The non-invasive quantification of arterial wave reflection is an increasingly important concept in cardiovascular research. It is commonly based on pulse wave analysis (PWA) of aortic pressure. Alternatively, wave separation analysis (WSA) considering both aortic pressure and flow waveforms can be applied. Necessary estimates of aortic flow can be measured by Doppler ultrasound or provided by mathematical models. However, this approach has not been investigated intensively up to now in subjects developing systolic heart failure characterized by highly reduced ejection fraction (EF). We used non-invasively generated aortic pressure waveforms and Doppler flow measurements to derive wave reflection parameters in 61 patients with highly reduced and 122 patients with normal EF. Additionally we compared these readings with estimates from three different flow models known from literature (triangular, averaged, Windkessel). After correction for confounding factors, all parameters of wave reflection (PWA and WSA) were comparable for patients with reduced and normal EF. Wave separations assessed with the Windkessel based model were similar to those derived from Doppler flow in both groups. The averaged waveform performed poorer in reduced than in normal EF, whereas triangular flow represented a better approximation for reduced EF. Overall, the non-invasive assessment of WSA parameters based on mathematical models compared to ultrasound seems feasible in patients with reduced EF.