Computational assessment of model-based wave separation using a database of virtual subjects.

The quantification of arterial wave reflection is an important area of interest in arterial pulse wave analysis. It can be achieved by wave separation analysis (WSA) if both the aortic pressure waveform and the aortic flow waveform are known. For better applicability, several mathematical models have been established to estimate aortic flow solely based on pressure waveforms. The aim of this study is to investigate and verify the model-based wave separation of the ARCSolver method on virtual pulse wave measurements. The study is based on an open access virtual database generated via simulations. Seven cardiac and arterial parameters were varied within physiological healthy ranges, leading to a total of 3325 virtual healthy subjects. For assessing the model-based ARCSolver method computationally, this method was used to perform WSA based on the aortic root pressure waveforms of the virtual patients. Asa reference, the values of WSA using both the pressure and flow waveforms provided by the virtual database were taken. The investigated parameters showed a good overall agreement between the model-based method and the reference. Mean differences and standard deviations were -0.05±0.02AU for characteristic impedance, -3.93±1.79mmHg for forward pressure amplitude, 1.37±1.56mmHg for backward pressure amplitude and 12.42±4.88% for reflection magnitude. The results indicate that the mathematical blood flow model of the ARCSolver method is a feasible surrogate for a measured flow waveform and provides a reasonable way to assess arterial wave reflection non-invasively in healthy subjects.

Wave intensity of aortic root pressure as diagnostic marker of left ventricular systolic dysfunction.

BACKGROUND: Systolic left ventricular function strongly influences the blood pressure waveform. Therefore, pressure-derived parameters might potentially be used as non-invasive, diagnostic markers of left ventricular impairment. The aim of this study was to investigate the performance of pressure-based parameters in combination with electrocardiography (ECG) for the detection of left ventricular systolic dysfunction defined as severely reduced ejection fraction (EF). METHODS AND RESULTS: Two populations, each comprising patients with reduced EF and pressure-matched controls, were included for the main analysis (51/102 patients) and model testing (44/88 patients). Central pressure was derived from radial readings and used to compute blood flow. Subsequently, pulse wave analysis and wave intensity analysis were performed and the ratio of the two peaks of forward intensity (SDR) was calculated as a novel index of ventricular function. SDR was significantly decreased in the reduced EF group (2.5 vs. 4.4, P<0.001), as was central pulse pressure, augmentation index and ejection duration (ED), while the QRS-duration was prolonged. SDR and ED were independent predictors of ventricular impairment and when combined with QRS in a simple decision tree, a reduced EF could be detected with a sensitivity of 92% and a specificity of 80%. The independent power of ED, SDR and QRS to predict reduced EF was furthermore confirmed in the test population. CONCLUSION: The detection or indication of reduced ejection fraction from pressure-derived parameters seems feasible. These parameters could help to improve the quality of cardiovascular risk stratification or might be used in screening strategies in the general population.

Ambulatory (24 h) blood pressure and arterial stiffness measurement in Marfan syndrome patients: a case control feasibility and pilot study.

BACKGROUND: The aim of this work is the investigation of measures of ambulatory brachial and aortic blood pressure and indices of arterial stiffness and aortic wave reflection in Marfan patients. METHODS: A case-control study was conducted including patients with diagnosed Marfan syndrome following Ghent2 nosology and healthy controls matched for sex, age and daytime brachial systolic blood pressure. For each subject a 24 h ambulatory blood pressure and 24 h pulse wave analysis measurement was performed. RESULTS: All parameters showed a circadian pattern whereby pressure dipping was more pronounced in Marfan patients. During daytime only Marfan patients with aortic root surgery showed increased pulse wave velocity. In contrast, various nighttime measurements, wave reflection determinants and circadian patterns showed a significant difference. CONCLUSIONS: The findings of our study provide evidence that ambulatory measurement of arterial stiffness parameters is feasible and that these determinants are significantly different in Marfan syndrome patients compared to controls in particular at nighttime. Further investigation is therefore indicated.

Assessment of Model Based (Input) Impedance, Pulse Wave Velocity, and Wave Reflection in the Asklepios Cohort.

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. METHODS: 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. RESULTS: 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). CONCLUSION: The results indicate that the use of model-based surrogates in a healthy middle aged cohort is feasible and deserves further attention.

Determinants and covariates of central pressures and wave reflections in systolic heart failure.

BACKGROUND: In general, higher blood pressure levels and increased central pulsatility are indicators for increased cardiovascular risk. However, in systolic heart failure (SHF), this relationship is reversed. Therefore, the aim of this work is to compare pulsatile hemodynamics between patients with SHF and controls and to clarify the relationships between measures of cardiac and arterial function in the two groups. METHODS: We used parameters derived from angiography, echocardiography, as well as from pulse wave analysis (PWA) and wave separation analysis (WSA) based on non-invasively assessed pressure and flow waves to quantify cardiac function, aortic stiffness and arterial wave reflection in 61 patients with highly reduced (rEF) and 122 matched control-patients with normal ejection fraction (nEF). RESULTS: Invasively measured pulse wave velocity was comparable between the groups (8.6/8.05 m/s rEF/nEF, P = 0.24), whereas all measures derived by PWA and WSA were significantly decreased (augmentation index: 18.1/24.8 rEF/nEF, P < 0.01; reflection magnitude: 56.3/62.1 rEF/nEF, P < 0.01). However, these differences could be explained by the shortened ejection duration (ED) in rEF (ED: 269/308 ms rEF/nEF, P < 0.01; AIx: 22.2/22.8 rEF/nEF, P = 0.7; RM: 59.3/60.6 rEF/nEF, P = 0.47 after adjustment for ED). Ventricular function was positively associated with central pulse pressures in SHF in contrast to no or even a slightly negative association in controls. CONCLUSIONS: The results suggest that the decreased measures of pulsatile function may be caused by impaired systolic function and altered interplay of left ventricle and vascular system rather than by a real reduction of wave reflections or aortic stiffness in SHF.

Noninvasive methods to assess pulse wave velocity: comparison with the invasive gold standard and relationship with organ damage.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: CfPWVsub, cfPWVdir0.8, and aoPWVestim are reasonable surrogates for aoPWVinv. AoPWVinv predicts subclinical organ damage better than cfPWVs, and as good as aoPWVestim.

Non-invasive wave reflection quantification in patients with reduced ejection fraction.

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.