The Role of Left Atrial Function in the Continuum of Heart Failure with preserved Ejection Fraction

Sebastian Rosch (Leipzig)1, K.-P. Rommel (Leipzig)1, A. Schöber (Leipzig)1, F. Schlotter (Leipzig)1, K. Fengler (Leipzig)1, M. von Roeder (Leipzig)1, M. Gutberlet (Leipzig)2, H. Thiele (Leipzig)1, P. Lurz (Mainz)3, K.-P. Kresoja (Leipzig)1

1Herzzentrum Leipzig - Universität Leipzig Klinik für Innere Medizin/Kardiologie Leipzig, Deutschland; 2Herzzentrum Leipzig - Universität Leipzig Diagnostische und Interventionelle Radiologie Leipzig, Deutschland; 3Universitätsmedizin der Johannes Gutenberg-Universität Mainz Kardiologie 1, Zentrum für Kardiologie Mainz, Deutschland


AIMS: We aimed to investigate the role of atrial function over a wide range of stages of heart failure with preserved ejection fraction (HFpEF). Further, this study aimed to investigate the role of concomitant diastolic dysfunction induced by severe tricuspid regurgitation (TR), which has been shown to can be alleviated by tricuspid valve edge-to-edge repair (T-TEER) (NCT04782908). Whether this effect is solely driven by improved ventricular interdependence or also by increased forward flow and optimized left atrial (LA) function remains unclear.

METHODS: Aside from healthy control patients, HFpEF patients with (Afib+) and without (Afib-) atrial fibrillation and HFpEF patients with relevant TR undergoing T-TEER were included. All patients underwent cardiac magnetic resonance (CMR) imaging at baseline. The sub-cohort of HFpEF patients undergoing T-TEER additionally received CMR during follow-up. To assess load independent diastolic function, periprocedural pressure volume loop (PVL) analysis was performed using conductance catheters to detect immediate changes of left ventricular (LV) diastolic dysfunction as quantified by the LV end-diastolic pressure (EDP) by LV end-diastolic volume (EDV) ratio (LVEDP/EDV). LA strain was evaluated biplane using cardiovascular imaging version 42 software.

RESULTS: Overall, 10 healthy control, 10 HFpEF Afib-, 10 HFpEF Afib+ and 15 HFpEF TR patients were included. Follow-up CMR were archived after a median time to follow-up of 43 (IQR 32 to 62) days.
We identified a stepwise reduction of LA strain throughout the study cohorts with highest values in control (20.0% IQR 18.8 to 24.3) and lowest in HFpEF TR (4.6% IQR 4.0 to 6.6) (p<0.05, Figure 1A). 
To identify the role of atrial function in patients with HFpEF and TR, PVL analysis first confirmed a significant intraprocedural improvement of LV diastolic function (0.13 mmHg/ml IQR 0.10 to 0.17 vs. 0.10 mmHg/ml IQR 0.08 to 0.13, p<0.01) following T-TEER. During follow-up, CMR showed an optimized LV filling with an increased LV stroke volume (SV, p<0.01) compared to baseline. Despite increasing LVEDV (p<0.01) intraprocedural LVEDP (p=0.18) remained unchanged. In T-TEER patients LA strain improved significantly (6.3% IQR 5.1 to 8.4, p<0.01), but LA volume index remained unchanged (p=0.10). Interestingly, the change of LA strain (ΔLAstrain) showed an inverse correlation to the change of LVSV (ΔLVSV) (Figure 1B), while no significant correlation was found for ΔLAstrain and ΔLVEDP/EDV indicating that LA function was not coupled to diastolic function but rather to LV filling.

CONCLUSION: Patients with HFpEF have impaired LA function, which is worst among patients with Afib but is further aggravated in the presence of severe TR. Improvement in diastolic function by T-TEER in patients with severe TR and HFpEF does only lead to a minor improvement in LA function. This is likely attributable to the fact that, despite an improvement in LV diastolic function, LVEDP remains preserved as LV filling increases. This possibly explains why the change of LA function shows a paradox association with SV and not with changes in diastolic function. In patients with severe TR and HFpEF the role of LA function seems to be diminished to an extent that event improvement in diastolic function does not restore LA function. Improvement in diastolic function seem to be mainly mediated by ventricular interdependence.
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