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Emerging role of immune checkpoint inhibitors and their relevance for the cardiovascular system

Zunehmende Relevanz von Immuncheckpoint-Inhibitoren und deren Bedeutung für das kardiovaskuläre System

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Abstract

Immune checkpoint inhibitor (ICI) therapy induces an immune response against cancer cells. Immune checkpoint inhibitor therapy has tremendously improved the prognosis for a large number of cancers, but is associated with considerable immune-related adverse events (irAEs). Cardiovascular complications from ICI therapy occur in a modest proportion of patients, but show the highest lethality rates of all ICI-related complications. While ICI-related myocarditis is the most dangerous complication, its clinical manifestation varies, e.g., asymptomatic reduction of left ventricular function, isolated increase in cardiac troponins, and arrhythmias. This review delineates current data on cardiovascular complications of ICI therapy. The effects of ICI therapy on the cardiovascular system are classified in the context of preclinical data on the biochemical and immunological function of the immune checkpoint signaling pathways in the heart and the vascular system. Incidence, suspected pathomechanisms, typical symptoms, as well as recommended diagnostics are summarized. Current therapy recommendations for ICI-related cardiotoxicity are outlined and innovative new approaches with high potential for improving outcome in ICI-related myocarditis are delineated. A better understanding of cardiovascular complications is essential for the best possible oncocardiology care of the growing number of patients undergoing ICI therapy.

Zusammenfassung

Das Ziel der Immuncheckpoint-Inhibitor(ICI)-Therapie ist die Induktion einer Immunreaktion gegen Krebszellen. Die ICI-Therapie hat bei einer Vielzahl von Tumorerkrankungen zu einer deutlich verbesserten Prognose geführt, ist jedoch mit erheblichen immunvermittelten Nebenwirkungen assoziiert. Kardiovaskuläre Komplikationen der ICI-Therapie treten bei einem geringen Anteil von Patienten auf, zeigen jedoch die höchste Letalität aller immunvermittelten Nebenwirkungen. Während die fulminante ICI-assoziierte Myokarditis die gefährlichste Komplikation darstellt, zeigen aktuelle Daten auch eine relevante Prävalenz von weiteren Nebenwirkungen, wie einer asymptomatischen Einschränkung der linksventrikulären Funktion, einer isolierten Erhöhung des kardialen Troponins oder einer bradykarden und tachykarden Herzrhythmusstörung. Diese Übersichtsarbeit behandelt die aktuelle Datenlage zu kardiovaskulären Komplikationen der ICI-Therapie. Es erfolgt eine Zusammenfassung von Inzidenz, vermutetem Pathomechanismus, typischen Symptomen sowie empfohlener Diagnostik und Therapieoptionen. Darüber hinaus werden die Effekte einer ICI-Therapie auf das kardiovaskuläre System im Kontext der verfügbaren präklinischen Daten zur biochemischen und immunologischen Funktion der Immuncheckpoint-Signalwege im Herzen und in Gefäßen eingeordnet. Aktuelle Therapieempfehlungen zur ICI-bedingten Kardiotoxizität werden dargestellt und innovative neue Ansätze mit hohem Potenzial für eine Verbesserung der Behandlung zusammengefasst. Das bessere Verständnis von kardiovaskulären Komplikationen ist essenziell für die bestmögliche onkokardiologische Betreuung des wachsenden Kollektivs von Patienten unter ICI-Therapie.

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Authors and Affiliations

  1. Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, Medical Faculty, University Hospital Essen, Hufelandstr. 55, 45147, Essen, Germany

    Lars Michel MD & Matthias Totzeck MD

  2. Cardio-oncology Unit, Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    Lorenz Lehmann MD & Daniel Finke MD

  3. DZHK (German Centre for Cardiovascular Research), partner site Heidelberg/Mannheim, Heidelberg, Germany

    Lorenz Lehmann MD & Daniel Finke MD

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Correspondence to Lars Michel MD.

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L. Michel, M. Totzeck, L. Lehmann, and D. Finke declare that they have no competing interests.

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

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Michel, L., Totzeck, M., Lehmann, L. et al. Emerging role of immune checkpoint inhibitors and their relevance for the cardiovascular system. Herz 45, 645–651 (2020). https://doi.org/10.1007/s00059-020-04954-8

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