When right ventricular pressure meets volume: The impact of arrival time of reflected waves on right ventricle load in pulmonary arterial hypertension

Abstract

Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. A larger volume at a given pressure generates more wall tension. Return of reflected waves early after the onset of contraction, when RV volume is larger, may augment RV load. We aimed to elucidate: (1) the distribution of arrival times of peak reflected waves in treatment-naïve PAH patients; (2) the relationship between time of arrival of reflected waves and RV morphology; and (3) the effect of PAH treatment on the arrival time of reflected waves. Wave separation analysis was conducted in 68 treatment-naïve PAH patients. In the treatment-naïve condition, 54% of patients had mid-systolic return of reflected waves (defined as 34-66% of systole). Despite similar pulmonary vascular resistance (PVR), patients with mid-systolic return had more pronounced RV hypertrophy compared to those with late-systolic or diastolic return (RV mass/body surface area; mid-systolic return 54.6 ± 12.6 g m^-2 , late-systolic return 44.4 ± 10.1 g m^-2 , diastolic return 42.8 ± 13.1 g m^-2 ). Out of 68 patients, 43 patients were further examined after initial treatment. At follow-up, the stiffness of the proximal arteries, given as characteristic impedance, decreased from 0.12 to 0.08 mmHg s mL^-1 . Wave speed was attenuated from 13.3 to 9.1 m s^-1 , and the return of reflected waves was delayed from 64% to 71% of systole. In conclusion, reflected waves arrive at variable times in PAH. Early return of reflected waves was associated with more RV hypertrophy. PAH treatment not only decreased PVR, but also delayed the timing of reflected waves. KEY POINTS: Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. Larger volume at a given pressure causes larger RV wall tension. Early return of reflected waves adds RV pressure in early systole, when RV volume is relatively large. Thus, early return of reflected waves may increase RV wall tension. Wave reflection can provide a description of RV load. In PAH, reflected waves arrive back at variable times. In over half of PAH patients, the RV is exposed to mid-systolic return of reflected waves. Mid-systolic return of reflected waves is related to RV hypertrophy. PAH treatment acts favourably on the RV not only by reducing resistance, but also by delaying the return of reflected waves. Arrival timing of reflected waves is an important parameter for understanding the relationship between RV load and its function in PAH.

Keywords: pulmonary artery-right ventricle coupling; pulmonary hypertension; right ventricle failure; ventricular afterload; wave reflection.

Figure 1. Study scheme

Scheme of study population and study aims. RV, right ventricle; PAH, pulmonary arterial hypertension.

Figure 2. Cardiac magnetic resonance velocity quantification

Cardiac magnetic resonance velocity quantification in the main pulmonary artery (PA) A, magnitude (top) and velocity (bottom) images of the main PA at two time‐points. B, curves of PA flow (red) and the area of the main PA (green) during a whole cardiac cycle. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 3. The distribution of reflected wave arrival times (A) and representative examples (B)

A, distribution of arrival time of peak reflected waves over total study population in the treatment‐naive condition (n = 68). B, representative flow (top) and pressure (bottom) waveforms with peak reflected waves at mid‐systolic phase (left), late‐systolic phase (middle) and diastolic phase (right). Solid curves present the measured flow or pressure waveform. Dotted curves present forward flow or pressure waveform. Difference between forward and measured waveform present the reflected waveform. The x‐axis is given by the time of peak reflected wave (% of systole). [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 4. Right ventricular load and mass in treatment‐naïve conditions

Right ventricular load and mass in treatment‐naïve conditions (n = 68). Pulmonary vascular resistance (PVR), total arterial compliance and characteristic impedance of the proximal arteries (Zc) are represented by a box plot, and RV mass/BSA is represented by a bar chart (mean ± SD). PVR and total arterial compliance were compared using one‐way ANOVA after log‐transformation. Zc was compared using a Kruskal–Wallis test with Dunn's multiple comparison as a result of the non‐normal distribution of log‐transformed Zc. Numbers of patients: 37 in mid‐systolic returners, 20 in late‐systolic returners and 11 in diastolic returners.

Figure 5. Characteristic impedance, total arterial compliance and pulse pressure

Correlations of characteristic impedance with total arterial compliance and pulse pressure. A, all PAH patients in the treatment naïve‐condition (n = 68). B, mid‐systolic returners (n = 37). C, late‐systolic returners (n = 20). D, diastolic returners (n = 11). Correlations was analysed by a Spearman’ rank correlation test. Zc, characteristic impedance.

Figure 6. Linear regression analysis

Linear regression analysis with logarithm of time of peak reflected waves as the indicator of RV mass/BSA. RV, right ventricle. The x‐axis is represented by a linear scale. RV mass/BSA = −15 × ln (time% of reflected waves) + 114. The number of analysed patients was 63 for diastolic returners. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 7. Wave separation analysis and stiffness of proximal arteries

Wave separation analysis (A) and stiffness of proximal arteries (B) at baseline and 1 year of follow‐up (n = 43). A, changes in time of reflected waves (left) and time% of reflected waves (right). B, changes in characteristic impedance (Zc) (left) and estimated wave speed (right panels). For each, both individual changes and box plot are provided. [Colour figure can be viewed at wileyonlinelibrary.com]

Figure 8. Change in RV mass after PAH treatment

Change in RV mass in patients with delayed waves (n = 29) and not‐delayed waves (n = 10) after PAH treatment. Change in RV mass (%) was determined as: (RV mass/BSA_follow‐up − RV mass/BSA_baseline)/RV mass/BSA_baseline ×100. One patient with delayed waves was excluded as a result of the unavailability of RV mass/BSA at follow‐up. [Colour figure can be viewed at wileyonlinelibrary.com]