Nailfold capillaroscopy findings after anthracycline-based chemotherapy and their association with subclinical...

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.

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%.

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).

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.