Case Presentation: A 74-year old Hispanic male with comorbid conditions significant for renal cell carcinoma (RCC) status post left nephrectomy, hypertension, hyperlipidemia and hypothyroidism presented with one-month history of intermittent substernal chest pain, shortness of breath, paroxysmal nocturnal dyspnea and orthopnea. He had no prior cardiac history and his home medications included amlodipine, atorvastatin, levothyroxine, and Pazopanib. Patient was started on Pazopanib approximately fifty-four months ago for treatment of RCC and had normal thyroid-stimulating hormone and free thyroxine levels prior to initiation. On admission, labs were significant for elevated troponin 0.032 ng/mL (normal: 0.000-0.028 ng/mL), elevated B-natriuretic peptide (BNP) 116 pg/mL (normal: < 100 pg/mL), elevated thyroid-stimulating hormone of 85.81 UIU/mL (normal: 0.35-4.94 UIU/mL), and low free thyroxine 0.60 ng/dL (normal: 0.7-1.48 ng/dL).Electrocardiogram (EKG) showed a right bundle branch block and non-specific T-wave inversions in precordial leads without ST segment changes. Chest computed tomography was negative for acute pathology, including coronary calcification. Acute coronary syndrome was ruled out through serial EKG and troponins. Transthoracic echocardiogram was remarkable for reduced ejection fraction of 25-30% with severe global hypokinesis. His new-onset heart failure was attributed to under-treated hypothyroidism, poorly controlled hypertension, and cardiotoxic effects from Pazopanib. Patient was started on lisinopril, carvedilol and discharged with outpatient cardiology follow-up.
Discussion: Pazopanib is a tyrosine kinase inhibitor which primarily inhibits tumor proliferation through the inhibition of vascular endothelial growth factor and platelet derived growth factor receptors. It is commonly used for advanced RCC and soft tissue sarcomas (STS). Pazopanib has well-documented side-effects of severe hepatotoxicity in clinical trials. In the PALETTE phase III trials for Pazopanib treatment of STS, 369 were randomized to receive Pazopanib (n=246) vs placebo (n=123). Included participants were simultaneously on at least one regimen containing anthracycline chemotherapy. Approximately 6.5% of patients developed systolic heart failure in the Pazopanib group compared to 2.5% in the placebo group.
Conclusions: The patient had been tolerating Pazopanib for approximately fifty-four months without any signs or symptoms of systolic heart failure. The patient plans to complete an ischemic work-up outpatient and Oncology has stopped Pazopanib. This case study highlights the development of new-onset heart failure with Pazopanib without prior anthracycline use or cardiovascular history.