Background/Objectives: General cardio-oncology guidance describes cardiovascular toxicity from BRAF/MEK inhibitors and immune checkpoint inhibitors (ICIs), but it does not resolve how treatment decisions should change when heart failure (HF) is already present. This critical narrative review separates direct HF-specific evidence from indirect evidence and proposes an HF-centered framework for systemic melanoma.
Methods: MEDLINE/PubMed, Embase, and the Cochrane Library were searched for English-language sources published from January 2015 to April 2026, with targeted guideline, prescribing-information, interaction, and geriatric-oncology updates through July 2026. Sources were classified as direct, indirect, or extrapolated. This review follows SANRA principles but does not claim systematic-review conduct, pooled estimates, formal risk-of-bias assessment, or GRADE certainty.
Results: Only case-level evidence directly describes systemic melanoma treatment in established HF; most cardiotoxicity rates are derived from selected longitudinal and real-world cohorts. We therefore organize decisions across four domains: HF phenotype and current stability; oncological urgency and alternatives; treatment-specific toxicity phenotype; and detectability, reversibility, and patient priorities. Each domain is graded ordinally and generates its own decision output, and explicit precedence rules resolve situations in which several domains are simultaneously abnormal; the pathway from assessment to documented output is presented as a decision flowchart and applied to illustrative clinical cases. This approach modifies interpretation of symptoms, biomarkers, ventricular function, surveillance, drug interactions, treatment interruption, and rechallenge. Every actionable statement is labeled as guideline-supported or author-proposed, therapy-specific baseline and follow-up monitoring are tabulated separately for each treatment class, and heart failure with preserved ejection fraction is addressed as a phenotype in which clinical deterioration may occur without any change in ejection fraction. Patient-level priorities in older adults—survival, quality of life, avoidance of hospitalization, tolerance of frequent monitoring, oral versus infusion treatment, and functional expectation—are specified as items to be recorded rather than inferred.
Conclusions: Stable HF is not an automatic contraindication to effective melanoma therapy, whereas recent or active decompensation requires stabilization or monitored treatment when oncological delay is unsafe. The proposed framework operationalizes guideline principles for an understudied population while making the limits of the evidence explicit. It makes a procedural rather than an empirical claim: it is a transparent structure for documenting a decision that must be made anyway, not an algorithm derived from or validated against outcome data.
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