Relationship between right ventricular diastolic dysfunction, right atrial phasic function and ventricular filling in pulmonary arterial hypertension
Authors: Wessels J.N , Mouratoglou S.A , Van Wezenbeek J , Marcus J.T , Meijboom L.J , Strijkers G.J , Vonk Noordegraaf A , De Man F.S 
Published: November 2020

Abstract

Background
In pulmonary arterial hypertension (PAH) patients, the right ventricle (RV) stiffens due to hypertrophy, fibrosis and intrinsic (sarcomeric) stiffness. In these patients, end-diastolic elastance (stiffness, Eed) is associated with parameters of disease severity and predicts mortality. However, the effect of RV stiffness on RV filling and the effect of increased filling pressures on right atrial (RA) function remain elusive.

Purpose
To examine the relationship between RV diastolic stiffness and RA phasic function and the effect of diastolic dysfunction on ventricular filling in PAH patients.

Methods
Using single-beat pressure-volume analyses we determined Eed in controls (n=31) and baseline, treatment naive PAH patients (63 idiopathic, 9 hereditary and 25 connective tissue disease associated). We also measured RA reservoir, conduit and active strain by tissue tracking on cardiac magnetic resonance images. Furthermore, interventricular dyssynchrony was defined as a right to left difference in time to peak circumferential strain &gt;52ms (97.5th percentile in controls).

Results
End-diastolic pressure was higher in PAH patients (16±7 mmHg) than in controls (8±4 mmHg; p&lt;0.001). Median Eed in patients was 0.635 mmHg/mL (IQR: 0.40–0.99), while in controls it was 0.20 mmHg/mL (IQR: 0.15–0.24). In comparison with controls, patients had reduced RA reservoir (14.3±5.1% vs. 19.1±4.3%; p&lt;0.001) and conduit strain (−5.6±3.4% vs. −12.4±3.3%; p&lt;0.001), while RA active strain was enhanced (−9.0±4.0% vs. −7.5±2.8%; p=0.019). In patients with a stiff RV (Eed above median), RA conduit strain was worse than in patients with a more compliant RV as illustrated in figure A. However, no correlation between RA active strain and Eed was observed (Spearman rho 0.06; p=0.57).
Passive filling time of the RV (end-systole until start of atrial contraction) was shorter in patients than in controls (244±136ms vs. 365±103ms; p&lt;0.001). Higher heart rate and ventricular dyssynchrony are causes of a shorter passive filling time in patients as illustrated in figure B. When comparing patients with short vs. long passive filling time (cutoff median of 220ms), the RV passive filling volume was lower (24±15ml vs. 42±19ml; p&lt;0.001). The active filling volume was slightly higher, although not significantly (25±17ml vs. 19±15ml; p=0.12).

Conclusion
Stiffening of the RV in PAH patients is accompanied by increased filling pressures and decreased RA conduit strain, while there is no correlation between Eed and RA active strain. Higher heart rate and ventricular dyssynchrony lead to shorter passive filling time of the RV, which in turn leads to lower passive filling volume. In contrast, the active filling volume is preserved in these patients.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): The Netherlands Organization for Scientific Research