Aging is Associated With an Earlier Arrival of Reflected Waves Without a Distal Shift in Reflection Sites

Abstract

BackgroundDespite pronounced increases in central pulse wave velocity (PWV) with aging, reflected wave transit time (RWTT), traditionally defined as the timing of the inflection point (TINF) in the central pressure waveform, does not appreciably decrease, leading to the controversial proposition of a “distal‐shift” of reflection sites. TINF, however, is exceptionally prone to measurement error and is also affected by ejection pattern and not only by wave reflection. We assessed whether RWTT, assessed by advanced pressure‐flow analysis, demonstrates the expected decline with aging.Methods and ResultsWe studied a sample of unselected adults without cardiovascular disease (n=48; median age 48 years) and a clinical population of older adults with suspected/established cardiovascular disease (n=164; 61 years). We measured central pressure and flow with carotid tonometry and phase‐contrast MRI, respectively. We assessed RWTT using wave‐separation analysis (RWTTWSA) and partially distributed tube‐load (TL) modeling (RWTTTL). Consistent with previous reports, TINF did not appreciably decrease with age despite pronounced increases in PWV in both populations. However, aging was associated with pronounced decreases in RWTTWSA (general population −15.0 ms/decade, P<0.001; clinical population −9.07 ms/decade, P=0.003) and RWTTTL (general −15.8 ms/decade, P<0.001; clinical −11.8 ms/decade, P<0.001). There was no evidence of an increased effective reflecting distance by either method. TINF was shown to reliably represent RWTT only under highly unrealistic assumptions about input impedance.Conclusions RWTT declines with age in parallel with increased PWV, with earlier effects of wave reflections and without a distal shift in reflecting sites. These findings have important implications for our understanding of the role of wave reflections with aging.

Deep Phenotyping of Systemic Arterial Hemodynamics in HFpEF (Part 1): Physiologic and Technical Considerations

“…Furthermore, these analyses were based on use of the pressure waveform inflection as a surrogate for reflected wave transit time. More recent analyses by Phan et al 62 that utilized pressure and flow information, and more implicitly accounted for the complex nature of wave reflections, did not demonstrate such a distal shift and in fact suggested the opposite (a proximal shift of reflection sites with aging). These considerations have implications for our understanding of the role of wave reflections in microvascular disease, as discussed in more detail in the accompanying review.…”

“…30,46,61 Stiffer aortas thus conduct the forward and backward traveling waves at greater velocities and therefore promote shorter reflected wave transit times (i.e., earlier arrival of wave reflections to the LV). 11,62 …”

“…Due to the shorter wave transit time from the heart to reflection sites and back to the proximal aorta in the presence of increased pulse wave velocity among older adults, 11,62 wave reflections arrive back at heart while the LV is still ejecting blood, with predominant effects during mid-to-late systole. 30,63 Wave reflections thus increase the late systolic workload of the LV and profoundly impact its loading sequence (late relative to early systolic load).…”

“…The complex nature of wave reflections in the arterial tree is well recognized and is key to our understanding of the effects of arterial dysfunction on central hemodynamics. 11,62,71 First, due to the frequency-dependent complex nature of wave reflection, a reflected wave is not simply a “smaller” but otherwise identical “version” of the forward wave. Reflecting sites “reshape” the wave, partially because they shift its phase.…”

Deep Phenotyping of Systemic Arterial Hemodynamics in HFpEF (Part 2): Clinical and Therapeutic Considerations

“…The time of arrival of the reflected wave to the proximal aorta is strongly dependent on the pulse wave velocity (PWV) of conduit vessels, particularly the aorta, which transmits forward and backward traveling waves from and toward the LV, respectively [8–11]. Stiffer aortas, which exhibit greater PWV, conduct forward and backward traveling waves at greater velocities and therefore promote an earlier arrival of wave reflections to the LV [6, 8, 12–14]. As a consequence of the aortic stiffening that occurs with aging and various disease states, the hemodynamic effects of wave reflections shift from diastole to systole, with prominent effects during mid-to-late systole in older adults [8, 12], particularly in women [3, 6, 7, 12, 15–17] and in patients with HFpEF [18–20].…”