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Abstract
Cardiac arrest complicating cancer chemotherapy is the most catastrophic endpoint of a broad spectrum of treatment-related cardiovascular injury. Although it is often the terminal expression of a mechanistically traceable pharmacological cascade, it is important to state at the outset that mechanistic traceability is not the same as individual clinical predictability: cardiac arrest in cancer patients is frequently multifactorial, compounded by sepsis, pulmonary embolism, electrolyte derangement, tumor-related inflammation, and pre-existing cardiovascular disease, and a substantial fraction of sudden cardiac deaths in this population has no single attributable drug cause. With that caveat, the principal mechanisms are increasingly well defined. Anthracyclines injure cardiomyocytes through topoisomerase IIβ poisoning and a constellation of iron-dependent oxidative pathways that now appears to include mitochondrial iron overload and ferroptosis alongside the classical reactive oxygen species paradigm. Fluoropyrimidines produce acute myocardial ischemia through mechanisms that probably combine coronary vasospasm with direct endothelial and mitochondrial toxicity, the relative contributions of which remain debated. HER2-targeted agents disrupt ErbB2/ErbB4 neuregulin-1 survival signaling, producing a typically reversible systolic dysfunction that becomes less reversible after anthracycline exposure. Tyrosine kinase inhibitors prolong repolarization through hERG channel blockade but, in practice, more commonly provoke atrial fibrillation and hypertension-mediated afterload stress than ventricular torsades. Immune checkpoint inhibitors trigger autoimmune myocarditis whose historical case-mortality of 25–50% has fallen substantially, to perhaps 10–15% in centers practicing systematic troponin surveillance with early corticosteroid treatment. High-dose alkylating agents cause direct hemorrhagic myocardial necrosis. Electrolyte dysregulation amplifies arrhythmic risk across all classes. This review maps each pathway from molecular target to arrest, provides comparative epidemiology of cardiac arrest and sudden cardiac death in oncology, and proposes a four-domain conceptual framework for risk-aligned surveillance, presented explicitly as a heuristic for organizing care rather than as a validated clinical risk model. We critically appraise the evidence for cardioprotective strategies, including the genuine clinical equipoise surrounding dexrazoxane, and address the practically important differential between treatment-related cardiogenic pulmonary edema and malignant lymphangitic disease.
Keywords: cardiac arrest; chemotherapy cardiotoxicity; anthracycline; topoisomerase II; immune checkpoint inhibitor myocarditis; QT prolongation; 5-fluorouracil; cardio-oncology; cardioprotection
Authors: Khalid Omer Alfarouk
Affiliation: Zamzam University College, Khartoum, Sudan
Vol. 1, Issue 1 · June 2026 · pp. 8–17