"Slow kill" treatment protocol in naturally infected dogs with Dirofilaria immitis and assessment of serum NT-proBNP and plasma D-dimer as biomarkers of this infection

This study assessed the efficacy of the "slow kill" protocol (ivermectin and doxycycline) on Dirofilaria immitis infection in dogs and the biomarker value of NT-proBNP and D-dimer in these cases. Dogs were tested for heartworm presence using a rapid antigen test, and blood samples were collected on days: 0 (T₀), 90 (T₉₀), and 180 (T₁₈₀). Dogs were divided into three groups based on clinical symptoms: asymptomatic (G_ASX), moderate (G_MODERATE), and severe (G_SEVERE). At T₀, NT-proBNP levels were within the reference values in G_ASX and G_MODERATE groups but elevated in G_SEVERE and significantly (p < 0.05) higher than in G_ASX. D-dimer levels were within the reference range in all groups without significant (p > 0.05) differences among them. At T₉₀, NT-proBNP remained within the reference values only in G_ASX and was not significantly different (p > 0.05) among groups. However, D-dimer levels increased in G_MODERATE and G_SEVERE, being significantly (p < 0.05) higher than in G_ASX group. At T₁₈₀, NT-proBNP was elevated in all groups, being significantly higher in G_MODERATE (p < 0.05) and G_SEVERE (p < 0.01) compared to G_ASX. D-dimer decreased across all groups but remained above the reference values, being significantly higher in G_MODERATE (p < 0.05) and G_SEVERE (p < 0.001) than in G_ASX. The "slow kill" treatment did not reduce NT-proBNP and D-dimer levels, having in mind long retention of adults, suggesting that cardiac and antithrombotic therapies may be necessary. Considering the relationship between the severity of clinical pictures and the levels of NT-proBNP and D-dimer, they have potential as prognostic markers in veterinary practice for heartworm-infected dogs.