Sorafenib-Associated Heart Failure Complicated by Cardiogenic Shock after Treatment of Advanced Stage Hepatocellular Carcinoma: A Clinical Case Discussion

Abstract

Background. Sorafenib, an oral tyrosine kinase inhibitor (TKI), targets multiple tyrosine kinase receptors (TKRs) involved in angiogenesis and tumor growth. Studies suggest that inhibition of TKR impacts cardiomyocyte survival. Inhibition of VEGF signaling interrupts angiogenesis and is associated with the development of hypertension and compensatory hypertrophy. Compensated hypertrophy ultimately leads to heart failure. Case Description. A 76-year-old man with a past medical history of systolic heart failure due to ischemic cardiomyopathy and stage IIIC hepatocellular carcinoma (HCC) presented with symptoms of decompensated heart failure. Four months prior to admission, he was started on sorafenib. Results. Our patient was treated with intravenous furosemide and guideline directed therapy. Clinical status was complicated by the development of low cardiac output and shock requiring inotropic support. Careful titration of heart failure medication led to hemodynamic improvement and discontinuation of dobutamine. Conclusion. Greater awareness of sorafenib cardiotoxicity is essential. As TKI usage grows for treatment of cancers, heart failure-related complications will increase. In our patient, routine heart failure management and cessation of sorafenib led to clinical improvement. Future studies on the treatment of sorafenib cardiotoxicity should be explored further in this unique patient population.

The Hippo Signaling Pathway in Drug Resistance in Cancer

“…Dobutamine induces phosphorylation of YAP-Ser127 and subsequent suppression of YAP-dependent gene transcription [ 172 , 173 ] ( Figure 2 and Table 2 ). Dobutamine is guideline-recommended as one of the first-line medications for the treatment of acute heart failure [ 174 , 175 ], and is also used in cancer patients complicated with congestive heart failure [ 176 ] and cardiogenic shock [ 177 ]. Recently, its potential anti-cancer effect was examined in several cancer types.…”

Cardiotoxicity of sorafenib is mediated through elevation of ROS level and CaMKII activity and dysregulation of calcium homoeostasis

“…[9][10][11][12][13][14] A recent clinical report presented a patient with ischaemic cardiomyopathy and advanced HCC who was treated with Sor and subsequently developed heart failure complicated by cardiogenic shock. 15 Another case report described a patient with no history of heart diseases who developed a dilated cardiomyopathy with reduced left ventricular ejection fraction that was reversible after discontinuation of Sor therapy for 3 months. 16 The mechanisms underlying Sor-related cardiac toxicity remain unclear.…”

“…However, because of the importance of receptor tyrosine kinases in normal cellular homoeostasis, TKIs are also associated with a wide range of cardiovascular toxicities, including QT prolongation, hypertension, reduced ejection fraction, congestive heart failure, acute coronary syndromes and myocardial infarction . A recent clinical report presented a patient with ischaemic cardiomyopathy and advanced HCC who was treated with Sor and subsequently developed heart failure complicated by cardiogenic shock . Another case report described a patient with no history of heart diseases who developed a dilated cardiomyopathy with reduced left ventricular ejection fraction that was reversible after discontinuation of Sor therapy for 3 months …”

Management of Acute Complications of Targeted Therapy in Patients With Cancer: A Review of Cases Managed in ICU

“…It is not related to cumulative dose and is generally reversible. 19 Incidence of heart failure varies between 2.7% and 11% with sunitinib and sorafenib, 20,21,23,24,39 between 0.5% and 1.7% with imatinib, 21,22,24 between 2% and 4% with dasatinib, 24 between 0.2% and 2.2% with lapatinib, 21,24 and is found in up to 1.6% of cases with nilotinib. 24 Among the monoclonal antibodies, heart failure has been described with trastuzumab in 2% to 28% of cases 21,24,39 and bevacizumab between 2% and 4%.…”

“…24 Cardiogenic shock has been reported in association with sorafenib. 23 Management requires treatment discontinuation followed by diuretics, angiotensin-converting enzyme inhibitors, b-blockers, and dobutamine in case of cardiogenic shock. We did not find any study reporting restarting treatment after heart failure, but this should be avoided after >3 grade heart failure or cardiogenic shock.…”