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Cardiac amyloidosis—interdisciplinary approach to diagnosis and therapy

Kardiale Amyloidose – interdisziplinärer Ansatz bei Diagnose und Therapie

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Abstract

The vast majority of cardiac amyloidosis (CA) cases are caused by light chain (AL) or transthyretin (ATTR) amyloidosis. The latter is divided into hereditary (ATTRv) and wild-type forms (ATTRwt). The incidence of ATTRwt amyloidosis has significantly increased, particularly due to the improved diagnosis of cardiac manifestations, with relevant proportions in patient populations with heart failure (HF) and preserved ejection fraction (HFpEF). Cardiac amyloidosis should be suspected in HF with indicative clinical scenarios/“red flags” with typical signs of CA in echocardiography. Further noninvasive imaging (cardiovascular magnetic resonance imaging, scintigraphy) and specific laboratory diagnostics are important for the diagnosis and typing of CA into the underlying main forms of ATTR and AL amyloidosis. The histopathologic analysis of an endomyocardial biopsy is necessary if noninvasive diagnostic methods do not enable reliable typing of CA. This is crucial for initiating specific therapy. Therapy of HF in CA is largely limited to the use of diuretics in the absence of evidence on the benefit of classic HF therapy with neurohormonal modulators. Innovative therapies have been developed for amyloidosis with improvement in organ protection, prognosis, and quality of life. These include specific cytoreductive therapies for monoclonal light-chain disease in AL amyloidosis and pharmacologic stabilization or inhibition of transthyretin expression in ATTR amyloidosis. Since the CA underlying amyloidosis is a systemic disease also affecting other organ systems, close interdisciplinary cooperation is crucial for rapid and effective diagnosis and therapy.

Zusammenfassung

Die große Mehrheit der kardialen Amyloidosen (CA) wird durch eine Leichtketten(AL)- oder Transthyretin(ATTR)-Amyloidose verursacht. Letztere wird in hereditäre (ATTRv) und Wildtypformen (ATTRwt) unterteilt. Die Inzidenz der ATTRwt-Amyloidose hat v. a. aufgrund verbesserter Diagnostik der kardialen Manifestation deutlich zugenommen – mit relevanten Anteilen bei Patientenkollektiven mit Herzinsuffizienz (HI) und erhaltener Pumpfunktion. Eine CA muss bei HI und wegweisenden klinischen Szenarien/„red flags“ mit typischen Zeichen einer CA in der Echokardiographie vermutet werden. Für die Diagnose und Typisierung der CA in die Hauptformen ATTR- und AL-Amyloidose ist eine weiterführende nichtinvasive Bildgebung (kardiovaskulare Magnetresonanztomographie, Szintigraphie) und spezifische Labordiagnostik wichtig. Die histopathologische Analyse einer endomyokardialen Biopsie ist notwendig, wenn die nichtinvasive Diagnostik keine sichere Typisierung der CA ermöglicht. Dies ist entscheidend für die Einleitung einer spezifischen Therapie. Die Therapie der HI bei CA beschränkt sich bei fehlender Evidenz für den Nutzen der klassischen HI-Therapie mit neurohormonellen Modulatoren weitgehend auf den Einsatz von Diuretika. Für die Amyloidose wurden innovative Therapien entwickelt mit Verbesserung der Organprotektion, Prognose und Lebensqualität. Dazu gehören spezielle zytoreduktive Therapien der monoklonalen Leichtkettenerkrankung bei AL-Amyloidose und die pharmakologische Stabilisierung oder Hemmung der Expression von Transthyretin bei ATTR-Amyloidose. Da die zur CA führende Amyloidose als Systemerkrankung auch andere Organsysteme betrifft, ist für eine zügige und effektive Diagnostik und Therapie eine enge interdisziplinäre Zusammenarbeit entscheidend.

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Authors and Affiliations

  1. Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany

    A. Hänselmann, D. Berliner, J. Bauersachs &  U. Bavendiek MD

  2. Amyloidosezentrum Niedersachsen, Hannover Medical School, Hannover, Germany

    U. Bavendiek MD

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  1. A. Hänselmann
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  2. D. Berliner
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  3. J. Bauersachs
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  4. U. Bavendiek MD
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Correspondence to U. Bavendiek MD.

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Conflict of interest

A. Hänselmann received honoraria and/or travel support from Novartis, Bayer, Boehringer Ingelheim, Abiomed, Alnylam, Pfizer.

D. Berliner received honoraria and/or travel support from Abbott, Bayer, Biotronik, Boehringer Ingelheim, Daiichi Sankyo, Novartis, Orion Pharma, and Pfizer, and research support from CVRx, Novartis, and Zoll.

J. Bauersachs received honoraria for lectures/consulting from Novartis, Vifor, Bayer, Pfizer, Boehringer Ingelheim, AstraZeneca, Cardior, CVRx, BMS, Amgen, Corvia, not related to this article; and research support for the department from Zoll, CVRx, Abiomed, not related to this article.

U. Bavendiek received honoraria and/or travel support from Astra Zeneca, Alnylam, Amgen, Bayer, Pfizer, and research support from Alnylam.

For this article no studies with human participants or animals were performed by any of the authors. All studies mentioned were in accordance with the ethical standards indicated in each case.

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Hänselmann, A., Berliner, D., Bauersachs, J. et al. Cardiac amyloidosis—interdisciplinary approach to diagnosis and therapy. Herz 47, 324–331 (2022). https://doi.org/10.1007/s00059-022-05122-w

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