Does correction of carotid-femoral pulse wave velocity distance measurements improve disease discrimination? Jonathan R Weir-McCall, Arsh Thakur, Deirdre.

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Does correction of carotid-femoral pulse wave velocity distance measurements improve disease discrimination? Jonathan R Weir-McCall, Arsh Thakur, Deirdre Cassidy, Faisel Khan, Shona Z Matthew, Helen M Colhoun, J Graeme Houston Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, University of Dundee, DD1 9SY, UK. Background Pulse wave velocity is a well established marked of arterial stiffening with important prognostic implications.[1] Carotid femoral pulse wave velocity (cf-PWV) is the most commonly used technique for the measurement of PWV, however relies on the use of surface measures of distance to represent the convoluted path of the underlying arterial tree introducing potential errors in PWV calculation.[2] Whole body magnetic resonance angiography provides an accurate arterial map of the entire body, allowing measurement of the true pathlength travelled by the pulse wave. Use of this measurement to correct for the inaccuracies in surface measurement may in turn allow for an increased accuracy in the measurement of PWV and therefore better detection of those at high risk of disease. Aim The aim of the current study was to assess whether recalculation of cf-PWV using arterial centreline measurements derived from whole body MRA (MRA-PWV) improves the accuracy of PWV for identifying cardiovascular disease. Methods 109 participants were recruited and divided into 4 groups: Group 1 - T2DM & CVD (n=22) Group 2 - T2DM, No CVD (n=38) Group 3 – CVD (n=23) Group 4 - Healthy volunteers (n=26) All underwent whole body angiography, cardiac MR, and Carotid-femoral PWV Equipment 3T MRI unit (Siemens Tim Trio, Germany) Surface coils to cover whole body Dual pump injector (Medrad Spectris, US) Gadoterate meglumine (Dotarem, Villepont, France) Image Acquisition: 10ml contrast injection: First 2 stations angiogram acquired LV volumetric and mass quantification 15ml contrast injection: Second 2 stations of angiogram acquired Carotid-femoral PWV SphygmoCor device (Atcor Medical, West Ryde, Australia). Physical distance for PWV calculation was calculated using a proximal (carotid to sternal notch) and distal (sternal notch to umbilicus and umbilicus to femoral) measure with final distance being the proximal distance subtracted from the distal distance. MRA-PWV A curved MRP was generated from the carotid to the femoral arteries. From this, distances from the bifurcation of the common carotid to the aortic arch (proximal measurement), and from the aortic arch to the bifurcation of the common femoral artery (distal measurement) were measured. After subtracting the proximal from the distal measurement, this MRA derived distance was used to recalculate the cf-PWV to give an MRA-PWV. Figure 1: Curved MPR describing the central arterial pathlength between the carotid and femoral arteries. Results Significant differences were observed in the age, BMI, hypertensive status and rate of prescription of statins and antihypertensives between the 4 groups – see Table 1 below. PWV distance measurements were significantly lower using MRA arterial centrelines (mean diff = 94.0 ± 57.8 mm, p<0.001) resulting in cf-PWV being significantly higher than MRA-PWV (cf-PWV= 10.91 ± 2.67 vs. MRA-PWV= 9.0 ± 2.19ms-1, p<0.001). This is predominantly due to an underestimation of the carotid arteries to the arch distance measurement, and an over-estimation of the arch to femoral artery measurement (see Table 2 below). Group 1 T2DM+ CVD+ Group 2 T2DM+ CVD- Group 3 T2DM- CVD+ Group 4 T2DM- CVD- p-value Demographics N 22 38 23 26 Male (%) 17 (77%) 22 (58%) 16 (70%) 11 (42%) .15 Age (years) 64±7 61±9 69±9** 64±9 0.007 BMI (kg/m2) 31±4 29±3 28±4 0.03 Hypertension 16 (72%) 23 (61%) 20 (87%) 6 (24%) <0.001 Systolic BP 134 ± 13 136 ± 13 137 ± 14 131 ± 15 0.48 Diastolic BP 74 ± 8 79 ± 7 76 ± 8 77 ± 9 0.22 Antihypertensive therapy (%) 17 (81%) 21 (91%) 7 (28%) Statin 18 (82%) 27 (71%) 17 (74%) Current/previous smoker 19 (86%) 13 (57%) 16 (62%) 0.41 CAD 18 (81%) Cerebrovascular 3 (14%) 4 (17%) LEAD 2 (9%) 6 (26%) Cardiac MRI LVMI 57 ± 15 56 ± 10 59 ± 8 52 ± 8 0.10 LVEDVI 67 ± 18 67 ± 13 73 ± 13 68 ± 10 LVESVI 24 ± 12 23 ± 8 27 ± 12 24 ± 7 0.56 LVEF 62 ± 17 66 ± 13 0.55 Distance External MRA p-value Carotid-Arch (mm) 92 ± 15 156 ± 26 <0.001 Arch-Femoral (mm) 631 ± 44 600 ± 39 Subtracted measurement 538 ± 48 444 ± 40 Table 2: Comparison of the proximal and distal distance measurements obtained using tape measure and WB-MRA Despite this the PWV calculated using the two techniques for measuring the pulse wave travelled distance showed a high degree of correlation (R=0.89, p<0.001). Neither cf-PWV (F=1.86, p=0.14) nor MRA-PWV (F=1.73, p=0.17) differentiated between the four groups (See table 3 below). When the groups were combined into either having CVD (n=45) or no-CVD (n=64), a continued lack of difference between these groups was observed for both cf-PWV (t=1.17, p=0.25) and MRA-PWV (t=1.47, p=0.14). Neither cf-PWV (R=0.06, p=0.52) nor MRA-PWV (R=0.04, p=0.66) showed a significant correlation with indexed left ventricular mass. PWV technique Group 1 T2DM+ CVD+ Group 2 T2DM+ CVD- Group 3 T2DM- CVD+ Group 4 T2DM- CVD- p-value Cf-PWV 11.1 ± 2.7 11.2 ± 2.7 11.4 ± 2.6 9.9 ± 2.5 0.14 MRA-PWV 8.8 ± 2.1 9.9 ± 2.4 8.6 ± 2.0 0.17 Table 1: Comparison of demographic and CMR metrics between the 4 groups Table 3: Comparison of PWV calculated using tape measure and MRA arterial centre pathlength between the 4 groups. Conclusion While there are significant inaccuracies in the currently used external distance measuremed for the calculation of carotid-femoral pulse wave velocity, correction of this does not appear to improve discrimination between those with and without cardiovascular disease. This is due to a continued high correlation between the PWV calculated using both techniques. References Ben-Shlomo Y, Spears M, Boustred C, et al. Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. J Am Coll Cardiol 2014;63:636–46. doi:10.1016/j.jacc.2013.09.063 Huybrechts SAM, Devos DG, Vermeersch SJ, Mahieu D, Achten E, de Backer TLM, Segers P, van Bortel LM: Carotid to femoral pulse wave velocity: a comparison of real travelled aortic path lengths determined by MRI and superficial measurements. J Hypertens 2011, 29:1577–82.