Nailfold capillaroscopy findings after anthracycline-based chemotherapy and their association with subclinical changes in left ventricular ejection fraction

BACKGROUND: Anthracyclines can induce endothelial and microvascular injury that precedes measurable myocardial dysfunction. However, reliable early markers of such injury are lacking. Nailfold capillaroscopy (NFC) is a noninvasive imaging technique that visualizes microcirculatory alterations. This pilot prospective study aimed to explore post-treatment NFC findings after anthracycline-based chemotherapy and their association with subclinical changes in left ventricular ejection fraction (LVEF) in patients with breast cancer. METHODS: Twenty-six patients with breast cancer scheduled for four cycles of neoadjuvant doxorubicin/cyclophosphamide (AC) were prospectively enrolled. All patients underwent baseline and post-chemotherapy echocardiography and post-treatment NFC assessment. Capillaroscopic abnormalities (tortuosity, crossing capillaries, extravasation, hemorrhage, dilated capillaries, giant capillaries, and neoangiogenesis) were recorded to generate a composite NFC score (0-7). Early cardiotoxicity was defined as ≥ 10% reduction in LVEF or LVEF < 53%. Correlations between change in ejection fraction (ΔEF) and NFC score were analyzed using Spearman's test. Exploratory ROC analysis was performed using any EF decline as a sensitive pilot endpoint, and an additional sensitivity analysis was performed using a more conservative threshold of ΔEF ≥ 3%. RESULTS: The mean age was 51.8 ± 11.2 years. Baseline and post-AC LVEF were 60.1 ± 2.2% and 58.4 ± 2.6%, respectively (ΔEF = -1.73 ± 2.15%). No clinical cardiotoxicity was observed. The mean composite NFC score was 3.15 ± 0.73. Higher NFC scores showed a negative correlation with ΔEF that did not reach statistical significance (Spearman ρ = -0.36, 95% CI: -0.67 to 0.00, p = 0.072). Exploratory ROC analysis using any EF decline as a sensitive pilot outcome yielded an AUC of 0.78 (95% CI: 0.57-0.95), with an optimal cutoff of NFC ≥ 4. In a sensitivity analysis using ΔEF ≥ 3%, the findings remained directionally consistent (AUC 0.79; optimal cutoff NFC ≥ 4). CONCLUSIONS: Post-treatment NFC abnormalities were frequently observed after anthracycline-based chemotherapy and showed an exploratory association with modest subclinical declines in left ventricular ejection fraction. As a prospective pilot study integrating NFC with paired echocardiographic assessment in a homogeneous anthracycline-treated breast cancer cohort, this work provides early hypothesis-generating evidence for a potential microvascular imaging approach in cardio-oncology. Given the absence of baseline NFC assessment and the non-significant primary correlation, these findings should be interpreted cautiously rather than as evidence of anthracycline-induced microvascular injury. Larger longitudinal studies are warranted to clarify the potential role of NFC in cardio-oncology.