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Herzinsuffizienz mit erhaltener Ejektionsfraktion als Modellerkrankung für das kardio-pulmo-renale Syndrom

Bedeutung der viszeralen Fettexpansion als zentraler Pathomechanismus

Heart failure with preserved ejection fraction as a model disease for the cardio-pulmonary-renal syndrome

Importance of visceral fat expansion as central pathomechanism

  • Schwerpunkt: Kardio-pulmo-renale Medizin
  • Published:
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Zusammenfassung

Die Herzinsuffizienz mit erhaltener Ejektionsfraktion („heart failure with preserved ejection fraction“ [HFpEF]) stellt ein heterogenes Syndrom mit unterschiedlichen Ätiologien und pathophysiologischen Faktoren dar. Adipositas und Diabetes mellitus Typ 2 (T2DM), die überzufällig häufig koexistieren, induzieren eine Vielfalt von metabolischen und nichtmetabolischen Signalstörungen, die Entzündung, Fibrose und Myozytensteifigkeit – alles Kennzeichen der HFpEF – begünstigen. Dabei sind im Gegensatz zu anderen HFpEF-Risikofaktoren die Adipositas und der T2DM häufig mit der vermehrten Bildung von viszeralem Fettgewebe assoziiert, das einen hochaktiven endokrinen Gewebeverbund darstellt, der Inflammation und Fibrose über verschiedene para- und vasokrine Signale verstärken und so die Funktion von Herz, Niere und pulmonalem Gefäßbett nachhaltig beeinflussen kann. Ein abnorm ausgedehntes epikardiales Fettgewebe („epicardial adipose tissue“ [EAT]) bedingt hierbei nicht nur eine mechanische Einengung des diastolischen Füllungsvorgangs des Herzens, sondern ist aufgrund der hohen Konzentrationen freigesetzter proinflammatorischer Adipokine insbesondere auch mit einer erhöhten Inzidenz von Vorhofflimmern und eingeschränkten linksventrikulären Kontraktionsparametern vergesellschaftet. Adipöse Patienten mit HFpEF gehören daher zu einem HFpEF-Phänotyp mit besonders schlechter Prognose und könnten von einer EAT-ausgerichteten phänotypspezifischen Intervention profitieren. Dabei könnte neben Statinen und Antidiabetika wie Metformin gerade Glucagon-like-peptide-1(GLP-1)-Rezeptor-Agonisten oder Natrium-Glukose-Kotransporter-2(SGLT-2)-Inhibitoren eine besondere Rolle zukommen.

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with diverse underlying etiologies and pathophysiological factors. Obesity and type 2 diabetes mellitus (T2DM), diseases which frequently coexist, induce a cluster of metabolic and nonmetabolic signaling derangements, which promote induction of inflammation, fibrosis and myocyte stiffness, all representing hallmarks of HFpEF. In contrast to other HFpEF risk factors, obesity and T2DM are often associated with the formation of an enlarged visceral adipose tissue (VAT), which is a highly active endocrine organ that can sustainably exacerbate inflammation and fibrotic remodeling of myocardial, renal, and vascular tissues via various paracrine and vasocrine signals. An abnormally large epicardial adipose tissue (EAT) thus not only causes a mechanical constriction of the diastolic filling procedure of the heart but is also associated with an increased release of proinflammatory adipokines that trigger atrial fibrillation and impaired left ventricular contraction parameters. Obese patients with HFpEF therefore belong to a unique HFpEF phenotype with a particularly poor prognosis that could benefit from an EAT-oriented phenotype-specific intervention. In addition to statins and antidiabetic drugs such as metformin, glucagon-like peptide‑1 (GLP-1) receptor agonists and sodium-glucose transporter 2 (SGLT-2) inhibitors could also play an important role.

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Authors and Affiliations

  1. Berlin Institute of Health at Charite (BIH), Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Deutschland

    Carsten Tschöpe, Ahmed Elsanhoury & Sophie Van Linthout

  2. Partner site Berlin, German Center for Cardiovascular Research (DZHK), Berlin, Deutschland

    Carsten Tschöpe, Ahmed Elsanhoury, Sophie Van Linthout & Sebastian Kelle

  3. Abteilung für Innere Medizin/Kardiologie, Campus Virchow (CVK), Charité Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Deutschland

    Carsten Tschöpe, Vivian Nelki & Sebastian Kelle

  4. Klinik für Innere Medizin/Kardiologie, Deutsches Herzzentrum Berlin, Berlin, Deutschland

    Sebastian Kelle

  5. Klinik für Kardiologie, Herz- und Gefäßzentrum Bad Bevensen, Bad Bevensen, Deutschland

    Andrew Remppis

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  1. Carsten Tschöpe
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Correspondence to Carsten Tschöpe.

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Interessenkonflikt

C. Tschöpe hat Referentenhonorare und/oder Beiträge zu Kongressen von Abbott, Abiomed, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Pfizer und Servier erhalten; alle außerhalb der eingereichten Arbeit. S. Kelle erhielt Referentenhonorare von Bayer, Berlin-Chemie und Philips, alle ohne Bezug zu dieser Publikation. A. Remppis erhielt Referentenhonorare von Novartis, Bayer, Vifor, AstraZeneca und Impulse Dynamic, alle ohne Bezug zu dieser Publikation. A. Elsanhoury, V. Nelki und S. Van Linthout geben an, dass kein Interessenkonflikt besteht.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

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B. Andrew Remppis, Bad Bevensen

Vedat Schwenger, Stuttgart

Claus F. Vogelmeier, Marburg

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Tschöpe, C., Elsanhoury, A., Nelki, V. et al. Herzinsuffizienz mit erhaltener Ejektionsfraktion als Modellerkrankung für das kardio-pulmo-renale Syndrom. Internist 62, 1141–1152 (2021). https://doi.org/10.1007/s00108-021-01182-y

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