chronic myeloid leukemia ( cml ) is a myeloproliferative disorder caused by an acquired mutation of hematopoietic stem cells . this mutation results in a reciprocal translocation between chromosomes 9 and 22 termed the philadelphia chromosome ( t[9;22][q34;q11 ] ) and generates a novel fusion gene , bcr - abl , which encodes tyrosine kinase . imatinib mesylate ( gleevec , novartis ) , a small - molecule inhibitor of multiple tyrosine kinases , selectively prevents phosphorylation of bcr - abl and inhibits downstream signaling and growth of bcr - abl  positive cells . food and drug administration approved imatinib for treatment of cml , this drug has been a standard first - line therapy for cml , revolutionizing its treatment . both iris and target investigators have confirmed a good cardiac safety profile and efficacy in patients with cml receiving imatinib. imatinib has resulted in 90% of cml patients remaining in the chronic phase for at least five years . imatinib - induced cardiotoxicity , including lv dysfunction and heart failure , has received much attention in recent years . , however , van glabbeke et al . analyzed a eortc - isg - agitg study and found no instances of imatinib - related lv failure in patients with gastrointestinal stromal tumors patients . a recent prospective assessment of 59 cml patients found no clinically significant cardiotoxicity during 12 months follow - up ; the researchers concluded that specific consideration of imatinib - induced cardiotoxicity is not necessary when assessing candidates for imatinib treatment . ribeiro et al . studied 103 consecutive patients with cml receiving imatinib and found no evidence for systematic deterioration of cardiac function ; however , these researchers pointed out that there is a possibility of isolated cases of cardiotoxicity . here , we report an 88-year - old man with cml who developed decompensated heart failure four days after commencing imatinib treatment . an 88-year - old male with cml was admitted to our hospital on august 24 , 2010 because of significantly high white blood cell and platelet counts . he had been diagnosed with mds - u in september 2009 and cml in august 2010 . cytogenetic studies had shown positive results for the t(9;22 ) pdgfr fusion gene and bcr - abl ( 12.2% b2a2 ) . his medical history included hypertension ( well controlled ) , type 2 diabetes mellitus ( well controlled ) , and permanent atrial fibrillation with a satisfactory heart rate . on admission , b - type natriuretic peptide ( bnp ) concentrations were 2,467  pg / ml and a chest x - ray film was normal ( figure 1a ) . an ecg revealed t - wave inversion and st - segment depression in i , avl , v5 and v6 . an echocardiogram showed left and right atrial enlargement ( table 1 ) . on physical examination , the patient was in good general condition and his vital signs were within the normal range . there was no cardiac enlargement and the rhythm was irregular ( heart rate , 86 beats / min ) . the first heart sound at the apex was faint , no cardiac murmurs were heard . there was no hepatomegaly or edema of the lower limbs . on august 25 , 2010 , oral imatinib mesylate monotherapy ( gleevec , novartis , 400  mg once daily ) the patient complained of mild abdominal distension . on the 2 day after the initiation of therapy , he developed nausea and vomiting . his dose of imatinib was reduced to 200  mg daily and his gastrointestinal symptoms improved slightly . on day 4 of imatinib therapy , plasma tni , blood urea nitrogen and serum creatinine were in the normal range ( table 2 ) . an echocardiogram showed a slightly decreased lv ejection fraction ( ef ) and enlarged left atrial and ventricular chambers ( table 1 ) . a chest x - ray film revealed an enlarged cardiac profile and a pleural effusion ( figure 1b ) . he was prescribed comprehensive therapy including oxygen inhalation , diuretics and vasodilators according to the acc / aha 2009 guidelines for the diagnosis and management of heart failure in adults . by september 11 , 2010 , the patient 's symptoms and signs of heart failure had resolved and findings of biochemical tests , chest x - ray film and echocardiogram were all consistent with recovery . ( a ) : on admission and ( b ) when the patient had decompensated heart failure . an enlarged cardiac profile and pleural effusion are visible in figure 1b hf : heart failure ; la : left atrium ; lvedd : left ventricular end - diastolic dimension ; lvef : left ventricular ejection fraction ; lvesd : left ventricular end - systolic dimension ; ra : right atrium . bnp : b - type natriuretic peptide ; ck : creatine kinase ; ck - mb : mb isoenzyme of creatine kinase ; hf : heart failure ; ldh : lactate dehydrogenase ; tni : troponin i. we present here a case of an elderly patient with cml who developed decompensated heart failure after only four days of imatinib mesylate treatment . imatinib mesylate , a targeted drug for tyrosine kinases , has revolutionized the treatment of cml . in a phase iii , randomized , open - label iris trial , there were no instances of disease progression to an accelerated phase or blast crisis . the cumulative best complete cytogenetic response rate was 82% ; 63% of all patients randomized to receive imatinib and still on study treatment were still in best complete cytogenetic response at last assessment . the estimated event - free survival at 6 years was 83% and estimated rate of freedom from progression to accelerated phase and blast crisis 93% . although imatinib is less toxic and better tolerated than traditional chemotherapy drugs , it can cause serious cardiotoxicity . high - dose imatinib has a greater potential for severe cardiotoxicity than does standard - dose imatinib . , although imatinib 400  mg ( b.i.d . ) reportedly results in more rapid reduction in tumor burden than does imatinib 400  mg / d , cardiotoxicity related to high dosage must be considered . imatinib - induced cardiotoxicity , which ranges from asymptomatic mild lv dysfunction to congestive heart failure , may be facilitated by the presence of relevant comorbidities such as pre - existing cardiovascular disease or renal failure . bnp is a cardiac neurohormone that is secreted by membrane granules in the cardiac ventricles in response to ventricular volume expansion and pressure overload . bnp concentrations are reflective of lv diastolic filling pressures and are reportedly increased in patients with symptomatic lv dysfunction . in the present case , the concentration of bnp increased from 2467  pg / ml to 14,228  pg / ml after initiation of imatinib , reflecting deterioration in cardiac function and decompensated heart failure . after withdrawal of imatinib , not only were the symptoms relieved , but also the bnp concentration decreased significantly , which implied that decompensated heart failure in this patient was imatinib - related . similarly to the present patient , a patient with hypereosinophilic syndrome after receiving imatinib treatment for one week developed severe lv dysfunction that resolved after prompt drug withdrawal . however , the above - described relationships between bnp or left ventricle ef and imatinib treatment duration and dose are not supported by recent evidence . , a retrospective analysis of 219 consecutive patients treated with imatinib mesylate found that cardiotoxic adverse events occurred in 8.2% of them . these events were manageable with medical therapy and infrequently required dose reduction or discontinuation of imatinib mesylate . there was no statistical difference regarding cardiac symptoms and signs , bnp concentrations and echocardiographic measurements between imatinib and control groups . summarized all the available reported serious cardiac adverse events occurring in patients on clinical trials involving imatinib and reported that 22 ( 1.7% ) of 1276 patients developed systolic cardiac failure , 18 of whom had previous predisposing conditions such as cardiac failure , diabetes mellitus , hypertension , coronary artery disease , arrhythmia and cardiomyopathy . the eortc - isg - agitg study also failed to confirm previous suggestions of imatinib - induced cardiac toxicity . our patient had the predisposing conditions of hypertension , type 2 diabetes mellitus and permanent atrial fibrillation . however , although he had a relatively high concentration of bnp and abnormal cardiac chambers , his new york cardiac function classification was good . the significant increase in bnp concentration and corresponding changes in echocardiographic index following imatinib treatment indicated decompensated heart failure in this patient . in summary , imatinib therapy uncommonly causes heart failure and mainly occurs in elderly patients with preexisting cardiovascular conditions . we recommend that if such patients develop symptoms suggestive of heart failure , they be monitored closely and treated aggressively with standard medical therapy , including diuretics . in addition , imatinib mesylate should be discontinued or the dosage reduced . although imatinib - induced cardiotoxicity is uncommon in cml patients , even during long - term treatment , we strongly recommend standard cardiac monitoring of patients , especially the elderly , with a history of cardiovascular disease .
because it is safe and well tolerated , imatinib is a standard first - line therapy for chronic myeloid leukemia ( cml ) . 
 although there have been sporadic reports of imatinib - induced cardiotoxicity , including left ventricle ( lv ) dysfunction and heart failure , the evidence for it is contradictory . here , we reported a case of an 88-year - old male patient with cml developed decompensated heart failure following imatinib therapy . 
 four days after the initiation of imatinib , the patient developed orthopnea , edema and a pleural effusion accompanied by abdominal distension , nausea and vomiting . 
 the chest x - ray film showed an enlarged cardiac profile . 
 the echocardiogram demonstrated a decreased lv ejection fraction and enlarged left - side cardiac chambers . 
 b - type natriuretic peptide concentrations were markedly increased . 
 the patient recovered soon after the withdrawal of imatinib and introduction of comprehensive therapy for heart failure . 
 imatinib - induced cardiotoxicity in elderly patients is a potentially serious complication that merits further evaluation .