Abstract

Diastolic dysfunction (DD) is an early manifestation of cancer drugs cardiotoxicity. Anthracyclines are considered as more cardiotoxic than other chemotherapeutics but previous studies have shown that both anthracycline-based and nonanthracycline chemotherapy can cause an early DD, detected one week after the end of chemotherapy. Here we characterized if DD also occurred in a delayed form, detected six months after chemotherapy. Sixty-seven comorbidity-free patients were examined. DD was diagnosed by echocardiography and cardiac biomarkers. Early or delayed DD occurred in 26 or 13 patients, respectively, sharing a pattern of grade I DD (impaired relaxation at echocardiography) or elevated B-type natriuretic peptide. Binary logistic analysis showed that age, gender and type of chemotherapy (anthracycline-based versus nonanthracycline) did not independently increase the probability of early or delayed DD. Early DD was predicted by the patient's cardiovascular profile, and in particular by diastolic indices that were in ranges of normality but showed measurable discrepancies from mean control values. Delayed DD was not predicted by the patient's cardiovascular profile but was predicted by post-chemotherapy adjuvant treatments (e.g., chest radiation or hormone therapy). Early and delayed DD were accompanied my moderate LVEF decrements. These findings show that anthracycline-based and nonanthracycline chemotherapy can induce early or delayed DD, which are governed by different patient- or treatment- related factors. Pharmacologic interventions that prevent DD or mitigate its progression toward a more serious cardiac dysfunction should be considered.

Significance Statement Predictors of early or delayed diastolic dysfunction (DD) were investigated in cancer patients treated with anthracyline-based or nonanthracycline chemotherapy. The type of chemotherapy did not predict the risk of DD. Early DD was predicted by the patient’s cardiovascular profile. Delayed DD was predicted by the adjuvant treatments the patient received after chemotherapy. These findings show that any chemotherapeutic can cause DD; however, the trajectories of DD are differently influenced by patients’ characteristics or post-chemotherapy exposure to additional cardiotoxic hits.