scholarly journals Acute cardiotoxicity after initiation of the novel tyrosine kinase inhibitor gilteritinib for acute myeloid leukemia

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Lisa Kim ◽  
Brian Fowler ◽  
Courtney M. Campbell ◽  
Jeremy Slivnick ◽  
Haseeb Nawaz ◽  
...  

Abstract Background Gilteritinib is a novel FMS-like tyrosine kinase 3 inhibitor recently approved by the United States Food and Drug Administration in 2018 for relapsed or refractory acute myeloid leukemia. However, gilteritinib may be associated with underrecognized cardiotoxicities. Case presentation This case describes a patient with a history significant for hyperlipidemia who was diagnosed with relapsed acute myeloid leukemia. After four doses of gilteritinib monotherapy, she abruptly developed acute systolic heart failure with global hypokinesis and septal wall motion abnormalities. Two days after discontinuation, cardiac magnetic resonance imaging showed partial recovery of her left ventricular ejection fraction as well as myocardial edema and non-ischemic fibrosis suggestive of inflammatory cardiomyopathy. She underwent intravenous diuresis and eventually started guideline-directed heart failure therapy. Follow-up cardiac magnetic resonance imaging five months later showed improved ejection fraction with mild non-ischemic fibrosis and resolution of myocardial edema and inflammation. She later received an allogeneic stem cell transplant from a matched unrelated donor. Conclusions Gilteritinib may be associated with early cardiotoxicities, including non-ischemic cardiomyopathy and myocarditis. Cardiac magnetic resonance imaging can be an important modality to help differentiate or diagnose early cardiotoxicities associated with novel targeted therapies.

2021 ◽  
Author(s):  
Lisa Kim ◽  
Brian Fowler ◽  
Courtney M. Campbell ◽  
Jeremy Slivnick ◽  
Haseeb Nawaz ◽  
...  

Abstract Background: Gilteritinib is a novel FMS-like tyrosine kinase 3 inhibitor recently approved by the United States Food and Drug Administration in 2018 for relapsed or refractory acute myeloid leukemia. However, gilteritinib may be associated with underrecognized cardiotoxicities.Case Presentation: This case describes a patient with a history significant for hyperlipidemia who was diagnosed with relapsed acute myeloid leukemia. After four doses of gilteritinib monotherapy, she abruptly developed acute systolic heart failure with global hypokinesis and septal wall motion abnormalities. Two days after discontinuation, cardiac magnetic resonance imaging showed partial recovery of her left ventricular ejection fraction as well as myocardial edema and non-ischemic fibrosis suggestive of inflammatory cardiomyopathy. She underwent intravenous diuresis and eventually started guideline-directed heart failure therapy. Follow-up cardiac magnetic resonance imaging five months later showed improved ejection fraction with mild non-ischemic fibrosis and resolution of myocardial edema and inflammation. She later received an allogeneic stem cell transplant from a matched unrelated donor. Conclusions: Gilteritinib may be associated with early cardiotoxicities, including non-ischemic cardiomyopathy and myocarditis. Cardiac magnetic resonance imaging can be an important modality to help differentiate or diagnose early cardiotoxicities associated with novel targeted therapies.


Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Abdullahi O Oseni ◽  
Waqas T Qureshi ◽  
Mohammed F Almahmoud ◽  
Alain Bertoni ◽  
David A Bluemke ◽  
...  

Background: Left ventricular hypertrophy (LVH) is an established risk factor for heart failure (HF). However, it is unknown whether LVH detected by electrocardiogram (ECG-LVH) is equivalent to LVH ascertained by cardiac magnetic resonance imaging (MRI-LVH) in terms of prediction of incident HF using risk prediction models like the Framingham Heart Failure Risk Score (FHFRS). Methods: This analysis included 4745 (mean age 61+10 years, 53.5% women, 61.7% non-whites) from the Multi-Ethnic Study of Atherosclerosis who were free of cardiovascular disease at the time of enrollment. ECG-LVH was defined using Cornell’s criteria while MRI-LVH was derived from left ventricular (LV) mass measured by cardiac MRI. Cox proportional hazard regression was used to examine the association between ECG-LVH and MRI-LVH with incident HF. Harrell’s concordance C-index was used to estimate the predictive ability of the FHFRS when either ECG-LVH or MRI-LVH were included as one of its components. The added predictive ability of ECG-LVH and MRI-LVH were investigated using integrated discrimination improvement (IDI) index and relative IDI. Results: ECG-LVH was present in 291(6.1%) while MRI-LVH was present in 499 (10.5%) of the participants. Over a median follow up of 10.4 years, 140 participants developed HF. Both ECG-LVH [HR (95% CI): 2.25(1.38-3.69)] and MRI-LVH [HR (95% CI): 3.80(1.56-5.63)] were associated with an increased risk of HF in multivariable adjusted models (Table 1). The ability of FHFRS to predict HF was improved with MRI-LVH (C-index 0.871, 95% CI: 0.842-0.899) when compared with ECG-LVH (C-index 0.860, 95% CI: 0.833-0.888) (p < 0.0001). To assess the potential clinical utility of using LVH-MRI instead of ECG-LVH, we calculated several measures of reclassification (Table 1), which were consistent with the statistically significantly improved C-statistic with MRI-LVH. Conclusion: Both ECG-LVH and MRI-LVH are predictive of HF when used in the FHFRS. Substituting MRI-LVH for ECG-LVH improves the predictive ability of the FHFRS.


Author(s):  
Carla Contaldi ◽  
Santo Dellegrottaglie ◽  
Ciro Mauro ◽  
Francesco Ferrara ◽  
Luigia Romano ◽  
...  

2019 ◽  
Vol 27 (6) ◽  
pp. 622-632 ◽  
Author(s):  
Carlos Crespo ◽  
Markus Linhart ◽  
Juan Acosta ◽  
David Soto-Iglesias ◽  
Mikel Martínez ◽  
...  

Background A recent study showed that the presence and characteristics of myocardial scar could independently predict appropriate implantable cardioverter-defibrillator therapies and the risk of sudden cardiac death in patients receiving a de novo cardiac resynchronisation device. Design The aim was to evaluate the cost-effectiveness of cardiac magnetic resonance imaging-based algorithms versus clinical practice in the decision-making process for the implantation of a cardiac resynchronisation device pacemaker versus cardiac resynchronisation device implantable cardioverter-defibrillator device in heart failure patients with indication for cardiac resynchronisation therapy. Methods An incidental Markov model was developed to simulate the lifetime progression of a heart failure patient cohort. Key health variables included in the model were New York Heart Association functional class, hospitalisations, sudden cardiac death and total mortality. The analysis was done from the healthcare system perspective. Costs (€2017), survival and quality-adjusted life years were assessed. Results At 5-year follow-up, algorithm I reduced mortality by 39% in patients with a cardiac resynchronisation device pacemaker who were underprotected due to misclassification by clinical protocol. This approach had the highest quality-adjusted life years (algorithm I 3.257 quality-adjusted life years; algorithm II 3.196 quality-adjusted life years; clinical protocol 3.167 quality-adjusted life years) and the lowest lifetime costs per patient (€20,960, €22,319 and €28,447, respectively). Algorithm I would improve results for three subgroups: non-ischaemic, New York Heart Association class III–IV and ≥65 years old. Furthermore, implementing this approach could generate an estimated €702 million in health system savings annually in European Society of Cardiology countries. Conclusion The application of cardiac magnetic resonance imaging-based algorithms could improve survival and quality-adjusted life years at a lower cost than current clinical practice (dominant strategy) used for assigning cardiac resynchronisation device pacemakers and cardiac resynchronisation device implantable cardioverter-defibrillators to heart failure patients.


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