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

Abstract

A better understanding of the pathophysiology of heart failure with a preserved left ventricular ejection fraction (HFpEF) is important. Detailed phenotyping of pulsatile hemodynamics has provided important insights into the pathophysiology of left ventricular remodeling and fibrosis, diastolic dysfunction, microvascular disease, and impaired oxygen delivery to peripheral skeletal muscle, all of which contribute to exercise intolerance, the cardinal feature of HFpEF. Furthermore, arterial pulsatile hemodynamic mechanisms likely contribute to the frequent presence of comorbidities, such as renal failure and dementia, in this population. Our therapeutic approach to HFpEF can be enhanced by clinical phenotyping tools with the potential to "segment" this population into relevant pathophysiologic categories or to identify individuals exhibiting prominent specific abnormalities that can be targeted by pharmacologic interventions. This review describes relevant technical and physiologic aspects regarding the deep phenotyping of arterial hemodynamics in HFpEF. In an accompanying review, the potential of this approach to enhance our clinical and therapeutic approach to HFpEF is discussed.

Keywords: Afterload; Arterial hemodynamics; Heart failure; Heart failure with preserved ejection fraction; Pulsatile load; Wave reflections.

Figure 1

Limitations of effective arterial elastance (EA) as an index of arterial load.

Figure 2

Primary measurements required for the assessment of arterial load via analyses of aortic pressure-flow relations. A pressure-flow pair can be acquired with a combination of arterial tonometry (which provides a pressure waveform) and either Doppler echocardiography or phase-contrast MRI of the ascending aorta (either of which can provide a flow waveform). Analyses of pressure-flow relations allow for a detailed assessment of arterial load, ventricular-arterial interactions and ventricular function.

Figure 3

Analysis of pulsatile pressure and flow in a reflection-less elastic conduit vessel. The effects of a compression wave are shown. This model illustrates the concept of characteristic impedance (Z_C) which governs the pulsatile pressure-flow relation in the absence of wave reflections.

Figure 4

Effect of forward, backward and rectified compression waves on pulsatile pressure and flow in the aortic root.

Figure 5

(A) Pressure and flow pair scaled by aortic root characteristic impedance. In early systole, Z_C governs the pulsatile pressure-flow relation. However, soon after ejection starts, the effects of wave reflection increase pressure relative to flow (red area): (B) Same signals, after flow has been multiplied by aortic root Z_C and the minimum of each signal has been subtracted, for a more intuitive graphic representation. The product of QZ_C has units of pressure and can therefore be directly related to the pressure waveform. The difference between QZ_C and measured pressure can be easily quantified in systole. It is an index of pressure that the LV needs to generate to overcome the effects of wave reflections, in order to eject the prevalent net flow. We hereby refer to this area as wasted LV effort, analogous to the concept was originally proposed using pressure-only approaches.^,

Figure 6

Wave separation analysis. Because net flow is the difference between forward and backward flow, whereas net pressure is the sum of forward and backward pressure, the red area in the pressure waveform (pressure - QZc) gets “partitioned” exactly in half between the forward (Pf) and the backward (Pb) waves. Consequently: (1) The systolic portion of the forward wave does not equal QZc, unless reflections are absent in systole; (2). The amplitude of Pf at any given time exceeds QZc by an amount equal to the amplitude of Pb, and is thus significantly influenced by wave reflections; (3) At any given time, the difference between QZc and measured pulsatile pressure equals twice the amplitude of Pb.

Figure 7

Time course of ejection-phase pressure (A), myocardial wall stress (MWS, B) and the pressure-stress relation. Normally, brisk force development and fiber shortening occur in early systole, resulting in an early peak in MWS and shortening rate, followed by continued LV ejection and a dynamic reconfiguration of LV geometry that results in a mid-systolic reduction in MWS relative to LV pressure, thus protecting the cardiomyocytes against excessive load in mid-to-late systole (a period of increased vulnerability). The mid-systolic reduction in MWS, relative to pressure, is impaired in the presence of a lower LV EF (even within the “normal” EF range), concentric LV remodeling or hypertrophy, and/or reduced early systolic ejection (despite a preserved overall EF).