Imatinib Fluid Retention Case: Heart Warning Signs With Preserved Pump Function

A 49-year-old woman treated for a gastrointestinal stromal tumor with imatinib developed shortness of breath, facial and lower-limb swelling, and elevated blood pressure roughly two months after starting therapy, despite echocardiography showing a fully preserved pumping function. Her case, published in the journal Pharmacia, offers a vivid illustration of a rare but clinically important cardiovascular side effect of one of modern oncology’s landmark drugs, and of the subtle biomarker patterns that can accompany it.

Imatinib has transformed the outlook for patients with advanced gastrointestinal stromal tumors, or GISTs. Before its clinical introduction in 2001, median survival in metastatic disease was only about 10 to 20 months. Early clinical studies reported complete remission in 4 percent of patients, partial remission in 67 percent, and stable disease in 18 percent, with only 11 percent progressing. With imatinib and later tyrosine kinase inhibitors such as sunitinib, regorafenib, and ripretinib, median survival in advanced disease now exceeds six years. GISTs themselves are rare, with an estimated 10 to 15 new diagnoses per million people each year, but they are the most common mesenchymal tumors of the digestive tract, arising most often from activating mutations in the KIT or PDGFRA genes.

The drug’s usual adverse effects, including anemia, periorbital edema, skin rash, fatigue, nausea, granulocytopenia, and diarrhea, are generally mild to moderate, and the fluid retention is often self-limiting. Imatinib-associated cardiotoxicity is considered uncommon and has been reported mainly in patients with pre-existing cardiovascular risk factors or underlying heart disease. Even so, new edema, dyspnea, hypertension, or heart failure-like symptoms shortly after treatment initiation should prompt cardiological assessment, particularly in patients receiving higher doses or requiring prolonged therapy.

In this case, the patient’s tumor journey began at a cardiology outpatient clinic, where she complained of easy fatigability and episodes of sweating. Initial electrocardiography and transthoracic echocardiography showed no abnormalities. Laboratory testing revealed iron-deficiency anemia, and abdominal ultrasonography demonstrated multiple rounded lesions in the small pelvis, confirmed by contrast-enhanced computed tomography. During laparoscopic surgery, an additional mass involving the small intestine was identified. Histopathological examination showed spindle-shaped cells with eosinophilic cytoplasm, moderate nuclear atypia, and a mitotic activity of 7 mitoses per 10 high-power fields. Immunohistochemical analysis showed diffuse positivity for CD117 and DOG1, supporting a spindle-cell variant GIST.

Molecular testing revealed a heterozygous six-nucleotide duplication in exon 9 of the c-KIT gene, with no mutations detected in c-KIT exon 11, PDGFRA exon 18, or BRAF exon 15. Because KIT exon 9-mutated GISTs are known to be less sensitive to standard-dose imatinib, treatment was initiated at 800 mg per day, administered in two divided doses. Approximately two months later, she developed shortness of breath, fluid retention, and elevated arterial blood pressure, with clinically evident edema predominantly involving the face and lower limbs.

Transthoracic echocardiography showed preserved left ventricular systolic function and preserved global longitudinal strain, measured at minus 21.2 percent. A small, hemodynamically insignificant pericardial effusion adjacent to the right atrium was detected during follow-up. Tissue Doppler velocities at the medial and lateral mitral annulus were preserved, and the E/e’ ratio remained below 8.8, arguing against elevated left ventricular filling pressures at the time of examination. Laboratory testing, in contrast, revealed elevated NT-proBNP levels, which fluctuated over time, while troponin values remained very low, suggesting no acute myocardial damage.

Treatment with torasemide 10 mg per day and candesartan 8 mg per day was initiated, with regular monitoring of electrolytes, particularly potassium and sodium. Imatinib was continued without dose reduction under close oncological and cardiological follow-up. One month later, the patient reported improvement in her general condition. Repeated echocardiographic examinations remained reassuring, showing preserved systolic function and strain, and the pericardial effusion resolved. NT-proBNP levels, however, remained above the reference range and continued to fluctuate, supporting ongoing cardiological follow-up.

The discussion surrounding imatinib cardiotoxicity dates to 2006, when Kerkelä and colleagues reported congestive heart failure in 10 patients treated with the drug and demonstrated left ventricular contractile dysfunction in imatinib-treated mice, suggesting a possible toxic myopathic mechanism based on mitochondrial abnormalities and membrane whorl accumulation. In response, Atallah and colleagues evaluated a large cohort of 1,276 patients and identified congestive heart failure in 22, corresponding to an incidence of 1.7 percent, occurring mainly in older patients with underlying cardiovascular risk factors or established disease. Further preclinical data published in 2010 reported that apoptosis and endoplasmic reticulum stress in cardiac myocytes and fibroblasts were observed only at cytotoxic concentrations of imatinib mesylate, whereas clinically relevant concentrations did not induce significant cardiac injury. The long-term results of the IRIS trial, following 1,106 patients with chronic myeloid leukemia for approximately 11 years, are consistent with this view, showing serious cardiac adverse events at a relatively low rate.

In this patient, the findings are most consistent with an imatinib-related fluid retention syndrome accompanied by mild cardiovascular involvement. Renal function was preserved, making renal impairment an unlikely explanation for the biomarker pattern. The patient had active malignancy, recent surgery, anemia, and repeatedly elevated D-dimer values, all of which may have influenced the clinical and laboratory picture, but no clinically overt thromboembolic event was documented during follow-up. In this context, the NT-proBNP elevation most probably reflected myocardial wall stress related to fluid retention and blood pressure elevation rather than direct myocardial damage. The authors emphasize that the findings should not be interpreted as overt systolic heart failure but as a possible early cardiovascular manifestation during imatinib therapy.

The case underlines the value of early cardiological assessment, echocardiographic follow-up with strain imaging, and cardiac biomarkers in patients who develop cardiovascular symptoms during imatinib therapy. Clinically significant cardiotoxicity during imatinib treatment remains uncommon, but new cardiovascular symptoms after treatment initiation deserve early assessment rather than routine observation alone. Serial echocardiography, including global longitudinal strain, together with cardiac biomarkers, may be useful for guiding supportive treatment in selected symptomatic patients.

Subject of Research: Imatinib-associated fluid retention with persistent NT-proBNP elevation during treatment of gastrointestinal stromal tumor: a case report

Article Title: Imatinib-associated fluid retention with persistent NT-proBNP elevation during treatment of gastrointestinal stromal tumor: a case report

Article References: Krastev, B., Megdanova-Chipeva, V., & Goudev, A. (2026). Imatinib-associated fluid retention with persistent NT-proBNP elevation during treatment of gastrointestinal stromal tumor: a case report. Pharmacia, 73, Article e204483. https://doi.org/10.3897/pharmacia.73.e204483

Image Credits: AI Generated

DOI: 10.3897/pharmacia.73.e204483

Keywords: Imatinib-associated, fluid, retention, persistent, NT-proBNP, elevation, during, treatment, gastrointestinal, stromal, tumor, case