The prognostic value of non-invasive pulse wave analysis in chronic heart failure

Richard Belciug (Graz)1, H. Riepl (Graz)1, D. Zach (Graz)1, V. Santner (Graz)1, V. Höller (Graz)1, S. Pilz (Graz)2, T. Weber (Wels)3, D. von Lewinski (Graz)1, M. Wallner (Graz)1, A. Zirlik (Graz)1, K. Ablasser (Graz)1, N. Verheyen (Graz)1, E. Kolesnik (Graz)1, N. Schwegel (Graz)1

1LKH-Univ. Klinikum Graz - Universitätsklinik für Innere Medizin Klinische Abteilung für Kardiologie Graz, Österreich; 2LKH-Univ. Klinikum Graz - Universitätsklinik für Innere Medizin Klinische Abteilung für Endokrinologie und Diabetologie Graz, Österreich; 3Klinikum Wels-Grieskirchen Kardiologie und Intensivmedizin Wels, Österreich


Chronic heart failure (CHF) is a major concern to public health, as it is one of the leading causes of mortality and hospitalization worldwide, with an ever-increasing prevalence. In patients with CHF, pulse waveforms are altered due to impaired ejection characteristics of the left ventricle. Yet, the prognostic value of these changes in patients with CHF remains unclear.
A total of 205 patients with stable CHF, a left ventricular ejection fraction (LVEF) <50% at inclusion, and a prior diagnosis of heart failure with reduced ejection fraction were enrolled in a prospective single-center cohort study. As part of the study protocol, all patients underwent a standardized examination of non-invasive pulse wave analysis (PWA) and pulse wave velocity (PWV) using the SphygmoCor Cardiovascular Management Suite (AtCor Medical, Sydney, Australia). We assessed the prognostic value of parameters derived from those analyses regarding a primary composite endpoint of unplanned hospitalization due to worsening heart failure (WHF) and all-cause mortality. Survival analyses were performed using univariate Cox-Regression as well as an adjusted, multivariable regression model.
PWA was feasible in 169 patients (82.4%), including 38 (22.5%) female patients. Median (interquartile range) age was 66.5 (58.1-73.2) years, median LVEF was 36 (31-43) %, median systolic blood pressure was 120 (108-135) mmHg, augmentation index (AIX) was 28.7 (22.5-36.2) %, and mean heart rate-corrected augmentation index (AIX@75) was 23.5 (17.4-30.8) %. 
At a median observation time of 5.0 (4.0-5.3) years, the composite endpoint occurred in 63 patients (37.3%). Lower AIX and AIX@75 were each significant predictors in univariate Cox-Regression regarding the composite endpoint (AIX HR 0.971 [95%CI 0.947-0.996], p = 0.023; AIX@75 HR 0.974 [95%CI 0.949-1.000], p = 0.049). 
These effects persisted in a multivariable model adjusted for age, gender, body mass index, systolic blood pressure, LVEF, and estimated glomerular filtration rate (AIX HR 0.958 [95%CI 0.924-0.994], p = 0.023; AIX@75 HR 0.962 [95%CI 0.926-1.000], p = 0.048).
PWV analysis was available in a subgroup of 79 patients. Of those, 52 (65.8%) patients had a history of arterial hypertension (aHT) and 22 (27.8%) had non-insulin dependent diabetes mellitus (NIDDM). Median PWV was 7.25 (5.9-8.7) m/s. Patients with NIDDM had significantly higher PWV (8.3[6.5-9.8] vs. 6.7 [5.3-8.1] m/s, p = 0.004). In patients with aHT PWV was higher but did not reach statistical significance (7.6 [6.0-9.1] vs. 6.6 [4.9-8.2] m/s, p=0.059). The composite endpoint occurred in 27 (34.2%) patients. PWV was not predictive of the primary endpoint (HR 0.932 [95%CI 0.762-1.141], p = 0.496).
Low augmentation index in PWA proofed to be an independent marker for poor prognosis in patients with CHF. This creates first evidence for the prognostic value of PWA in patients with CHF and impaired LVEF. PWV was overall lower than in historical studies in healthy individuals and associated with aHT and diabetes mellitus, but it was not significantly related with CHF outcomes.

Figure 1. Kaplan-Meier plots. Cumulative event-free time. (A) Augmentation index (AIX), (B) heart rate-corrected augmentation index (AIX@75), and (C) pulse wave velocity (PWV). Groups stratified by mean values.
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