Cardio-Hepatic Interaction in Cardiac Amyloidosis

Sandra Michaela Ihne-Schubert; Oliver Goetze; Felix Gerstendörfer; Floran Sahiti; Ina Schade; Aikaterini Papagianni; Caroline Morbach; Stefan Frantz; Hermann Einsele; Stefan Knop; Claudia Sommer; Beat Müllhaupt; Torben Schubert; Stefan Störk; Andreas Geier

doi:10.3390/jcm13051440

Cardio-Hepatic Interaction in Cardiac Amyloidosis

J Clin Med. 2024 Mar 1;13(5):1440. doi: 10.3390/jcm13051440.

Authors

Sandra Michaela Ihne-Schubert^{1

2

3

4}, Oliver Goetze^{1

5

6}, Felix Gerstendörfer^{1

2}, Floran Sahiti^{1

7

8}, Ina Schade⁹, Aikaterini Papagianni^{1

10}, Caroline Morbach^{1

7

8}, Stefan Frantz^{1

7

8}, Hermann Einsele^{1

2}, Stefan Knop^{1

2

11}, Claudia Sommer^{1

10}, Beat Müllhaupt¹², Torben Schubert^{3

13}, Stefan Störk^{1

7

8}, Andreas Geier^{1

5}

Affiliations

¹ Interdisciplinary Amyloidosis Center of Northern Bavaria, University Hospital Würzburg, 97080 Würzburg, Germany.
² Department of Internal Medicine II, Hematology, University Hospital Würzburg, 97080 Würzburg, Germany.
³ CIRCLE-Centre for Innovation Research, Lund University, 22100 Lund, Sweden.
⁴ Department of Internal Medicine IV, University Hospital Gießen and Marburg, 35392 Gießen, Germany.
⁵ Department of Internal Medicine II, Hepatology, University Hospital Würzburg, 97080 Würzburg, Germany.
⁶ Department of Medicine, Universitätsklinikum Knappschaftskrankenhaus Bochum, 44892 Bochum, Germany.
⁷ Comprehensive Heart Failure Center, University Hospital Würzburg, 97080 Würzburg, Germany.
⁸ Department of Internal Medicine I, Cardiology, University Hospital Würzburg, 97080 Würzburg, Germany.
⁹ Department of Thoracic Surgery and Thoracic Endoscopy, Helios Klinikum Erfurt, 99089 Erfurt, Germany.
¹⁰ Department of Neurology, University Hospital Würzburg, 97080 Würzburg, Germany.
¹¹ Department of Internal Medicine V, Hospital Nürnberg Nord, 90419 Nürnberg, Germany.
¹² Department of Gastroenterology and Hepatology, University Hospital Zurich, 8091 Zurich, Switzerland.
¹³ Fraunhofer Institute for Systems and Innovation Research ISI, 76139 Karlsruhe, Germany.

Abstract

Background: Congestion is associated with poor prognosis in cardiac amyloidosis (CA). The cardio-hepatic interaction and the prognostic impact of secondary liver affection by cardiac congestion in CA are poorly understood and require further characterisation. Methods: Participants of the amyloidosis cohort study AmyKoS at the Interdisciplinary Amyloidosis Centre of Northern Bavaria with proven transthyretin (ATTR-CA) and light chain CA (AL-CA) underwent serial work-up including laboratory tests, echocardiography, and in-depth hepatic assessment by vibration-controlled transient elastography (VCTE) and ¹³C-methacetin breath test. Results: In total, 74 patients with AL-CA (n = 17), ATTR-CA (n = 26) and the controls (n = 31) were analysed. ATTR-CA patients showed decreased microsomal liver function expressed by maximal percentage of dose rate (PDR_peak) related to hepatic congestion. Reduced PDR_peak in AL-CA could result from altered pharmacokinetics due to changed hepatic blood flow. Liver stiffness as a combined surrogate of chronic liver damage and congestion was identified as a predictor of all-cause mortality. Statistical modelling of the cardio-hepatic interaction revealed septum thickness, NT-proBNP and PDR_peak as predictors of liver stiffness in both CA subtypes; dilatation of liver veins and the fibrosis score FIB-4 were only significant for ATTR-CA. Conclusions: Non-invasive methods allow us to characterise CA-associated hepatic pathophysiology. Liver stiffness might be promising for risk stratification in CA.

Keywords: 13C-methacetin breath test (MBT); PDRpeak; cardiac amyloidosis; congestion; liver stiffness; vibration-controlled transient elastography (VTCE).

Grants and funding

Sandra Ihne-Schubert was a fellow of the local Clinician Scientist program of the Interdisciplinary Center of Clinical Research—IZKF, Würzburg (2018–2021, Z-2_CSP-08).