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Year : 2015  |  Volume : 3  |  Issue : 2  |  Page : 35-38

Doxorubicin induced reversible cardiomyopathy: A Case report

1 Resident, Department of Cardiology, Dhiraj Hospital, Sumandeep Vidyapeeth, Vadodara, Gujarat, India
2 Associate Professor, Department of Cardiology, Dhiraj Hospital, Sumandeep Vidyapeeth, Vadodara, Gujarat, India
3 Professor & HOD, Department of Cardiology, Dhiraj Hospital, Sumandeep Vidyapeeth, Vadodara, Gujarat, India

Date of Web Publication24-Aug-2018

Correspondence Address:
K Tamakuwala
Resident, Department of Cardiology, Dhiraj Hospital, Sumandeep Vidyapeeth, Vadodara, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2347-6486.239795

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A middle aged male patient was diagnosed with B-cell non-Hodgkin's Lymphoma and treated with Rituximab, Doxorubicin, Vincristine, and Cyclophosphamide(R-CHOP) chemotherapy regimen for 6 months. Four months after the chemotherapy patient presented with symptoms of heart failure. There was no significant history of any cardiac disease in the past. Chest X-ray was done with showed enlarged cardiac silhouette. Echocardiography was done which revealed a dilated cardiomyopathy with severe left ventricular (LV) systolic dysfunction. Chest X ray before starting the chemotherapy had normal cardiac silhouette. Echocardiography reports before starting the chemotherapy were within normal limits with normal sized heart and normal ejection fraction. Patient was managed with optimal drugs and echocardiography was repeated after 1 year which showed an improved LV systolic function with ejection fraction of around 40%. This led to the diagnosis of Doxorubicin induced cardiomyopathy.

Keywords: Cardiomyopathy, doxorubicin, adverse effects, ejection fraction, echocardiography

How to cite this article:
Tamakuwala K, Panchani N, Gupta A, Rawal J. Doxorubicin induced reversible cardiomyopathy: A Case report. J Integr Health Sci 2015;3:35-8

How to cite this URL:
Tamakuwala K, Panchani N, Gupta A, Rawal J. Doxorubicin induced reversible cardiomyopathy: A Case report. J Integr Health Sci [serial online] 2015 [cited 2022 Dec 4];3:35-8. Available from: https://www.jihs.in/text.asp?2015/3/2/35/239795

  Introduction Top

A 56 year old male patient presented with breathlessness on exertion (NYHA Class II) for past 4 months which increased to NYHA Class III in last 2 weeks. There was no history of angina, palpitations, orthopnea, paroxysmal nocturnal dyspnea and cough with expectoration or fever. There was no history of any cardiac disease in the past. Patient was a known case of B-cell non-Hodgkin's Lymphoma and was treated with R-CHOP (Rituximab, Doxorubicin, Vincristine, and Cyclophosphamide) chemotherapy regimen for 6 months prior to these symptoms. General and systemic examination was unremarkable. Chest radiograph showed enlarged cardiac silhouette. The chest X-ray done prior to the initiation of chemotherapy had normal sized cardiac shadow. The ECG showed sinus tachycardia with frequent ventricular premature complexes (VPCs) and low voltage QRS complexes with no specific ST-T changes. The Brain Natri-uretic Peptide (BNP) levels were elevated (868 pg/ml, Normal levels: 0–99 pg/ml). An echocardiography was done which showed dilated LV of size 62 mm (Normal range– 42 to 59 mm) and dilated left atrium (LA) of size 42 mm (Normal range– 30 to 40 mm). There was severe global hypokinesia of LV with ejection fraction of 25%. There was mild mitral regurgitation (MR) and mild tricuspid regurgitation (TR). There was mild pulmonary artery hypertension (PAH) with pulmonary artery systolic pressure (PASP) by TR jet of 40 mm of Hg. The echocardiography which was done before starting chemotherapy ten months back was within normal limits with LV ejection fraction of 70%. Coronary angiography was performed which revealed normal coronary arteries. A cardiac MR (CMR) was done which showed dilated cardiomyopathy with ejection fraction of 27%. No other significant abnormality was found in myocardium on CMR. The patient was managed medically with a beta-blocker, an angiotensin converting enzyme inhibitor, digoxin and diuretics. Patients' symptoms improved subsequently. Echocardiography was repeated after one year on follow up. There was improvement in LV ejection fraction from 25% to 40%. There was mild LV global hypokinesia. There was regression in end diastolic LV size from 62 mm to 55 mm and end systolic LA size from 44 mm to 38 mm.[Figure 1][Figure 2]
Figure 1: Showing dilated left ventricle (6.2 cm) (left) and dilated left atrium (4.2 cm) (right)

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Figure 2: Showing regression in left ventricle size (5.5 cm) (left) and regression in left atrium size (3.8 cm) (right)

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The patient developed cardiomyopathy after receiving doxorubicin containing chemotherapy regimen. The cardiomyopathy regressed subsequently over the next one year after the chemotherapy was over. This led to a diagnosis of doxorubicin induced cardiomyopathy.

  Discussion Top

The anthracycline anticancer drug doxorubicin is an effective and frequently used chemotherapeutic agent for various malignancies.[1] Acute Doxorubicin cardiotoxicity can occur within 2–3 days of its administration. The incidence of acute cardiotoxicity is approximately 11%.[2] The manifestations are usually chest pain due to myopericarditis and/or palpitations due to sinus tachycardia, paroxysmal non-sustained supraventricular tachycardia and premature atrial and ventricular beats. The ECG may reveal nonspecific ST-T changes, left axis deviation and decreased amplitude of QRS complexes. The mechanisms for these acute changes are not clear but may be due to doxorubicin-induced myocardial edema, which is reversible.[3] Acute left-ventricular failure is rare, but it is also reversible with appropriate treatment. Chronic doxorubicin cardiotoxicity is reported in about 1.7% cases. It is usually evident within 30 days of administration of its last dose, but it may occur even after 6–10 years after its administration. The incidence of doxorubicin cardiomyopathy is primarily related to its dose. The incidence is about 4% when the dose of doxorubicin is 500–550 mg/m[2], 18% when the dose is 551–600 mg/m[2] and 36% when the dose exceeds 600 mg/m2.[4] Hypertensive individuals whether young or old are more prone to develop doxorubicin cardiotoxicity. Echocardiography may reveal all four cardiac chambers dilated. The ventricular ejection fraction and contractile function is reduced. There is concomitant diastolic dysfunction.[5] The proposed principal mechanisms of doxorubicin cardiotoxicity are increased oxidative stress. Decreased levels of antioxidants and sulfhydryl groups inhibition of nucleic acid and protein synthesis, release of vasoactive amines, altered adrenergic function and decreased expression of cardiac-specific genes are other proposed mechanisms. It is possible that more than one mechanism is operative.[5] Decreased expression of the contractile proteins is associated with myofibrillar loss and reduced myocardial contractile function.[6] Formation of hydrogen peroxide and superoxide has been implicated in doxorubicin-induced cardiomyocyte toxicity. When congestive heart failure develops, mortality is approximately 50%.The diagnosis of doxorubicin cardiomyopathy includes proper history taking, complete examination of the cardiovascular system to detect presence of signs of heart failure. An electrocardiogram should be done. A chest X-ray is also helpful to assess cardiomegaly and signs of pulmonary venous congestion. Echocardiography with doppler studies is used to detect early diastolic and systolic LV dysfunction. Radionuclide ventriculography and CMR can be used to assess LV systolic function. These tests however are not specific for doxorubicin cardiomyopathy. Antimyosin antibody study with the use of 111I-labelled monoclonal antimyosin antibody is used for the diagnosis of doxorubicin cardiomyopathy.[7] Plasma levels of B-type natriuretic peptide are elevated and correlate with the severity of congestive heart failure.[8] There is no specific treatment available for the management of patients with established heart failure. Diuretics, β-adrenergic blocking agents (e.g metoprolol), Angiotensin II inhibition therapy, low-dose hydralazine-isosorbide dinitrate combination treatment is often employed; however there is no information available to suggest that such treatment is effective in patients with doxorubicin cardiomyopathy.[9] Cardiac transplantation has been reported to improve long-term prognosis of the patients in whom the primary malignancy is cured following chemotherapy.[10]

  Conclusion Top

Dose of Doxorubicin can be reduced to < 450 mg/m2 to prevent Doxorubicin induced cardiomyopathy. The use of anthracycline analogues, alternative methods of drug delivery and continuous slow infusion instead of standard infusion protocols have also been employed to reduce the risk of dilated cardiomyopathy. As in our case, doxorubicin induced cardiomyopathy can be reversible. Proper follow up of the case with a yearly echocardiography and medical treatment with appropriate therapy for congestive heart failure is necessary. Extensive research has been done to understand the mechanism of doxorubicin cardiotoxicity and its prevention. However, further research regarding effective treatment of doxorubicin cardiotoxicity is required.

  References Top

Weiss RB. The anthracyclines: will we ever find a better doxorubicin?. InSeminars in oncology 1992 Dec;19 (6):670-86.  Back to cited text no. 1
Swain SM, Whaley FS, Ewer MS. Congestive heart failure in patients treated with doxorubicin. Cancer. 2003 Jun 1;97(11):2869-79.  Back to cited text no. 2
Singal PK, Deally CM, Weinberg LE. Subcellular effects of adriamycin in the heart: a concise review. Journal of molecular and cellular cardiology. 1987 Aug 31;19(8):817-28.  Back to cited text no. 3
Lefrak EA, Pit’ha J, Rosenheim S, Gottlieb JA. A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer. 1973 Aug 1;32(2):302-14.  Back to cited text no. 4
Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology. 2010;115(2):155-62.  Back to cited text no. 5
Kim Y, Ma AG, Kitta K, Fitch SN, Ikeda T, Ihara Y, Simon AR, Evans T, Suzuki YJ. Anthracycline-induced suppression of GATA-4 transcription factor: implication in the regulation of cardiac myocyte apoptosis. Molecular pharmacology. 2003 Feb 1;63(2):368-77.  Back to cited text no. 6
Hiroe M, Ohta Y, Fujita N, Nagata M, Toyozaki T, Kusakabe K, Sekiguchi M, Marumo F. Myocardial uptake of 111In monoclonal antimyosin Fab in detecting doxorubicin cardiotoxicity in rats. Morphological and hemodynamic findings. Circulation. 1992 Dec 1;86(6):1965-72.  Back to cited text no. 7
Suzuki T, Hayashi D, Yamazaki T, Mizuno T, Kanda Y, Komuro I, Kurabayashi M, Yamaoki K, Mitani K, Hirai H, Nagai R. Elevated B-type natriuretic peptide levels after anthracycline administration. American heart journal. 1998 Aug 31;136(2):362-3.  Back to cited text no. 8
Arnold JMO, Howlett JG, Ducharme A, et al. Canadian Cardiovascular Society Consensus Conference guidelines on heart failure – 2008 update: Best practices for the transition of care of heart failure patients, and the recognition, investigation and treatment of cardiomyopathies. The Canadian Journal of Cardiology. 2008;24(1):21-40.  Back to cited text no. 9
Shaddy RE, Olsen SL, Bristow MR, Taylor DO, Bullock EA, Tani LY, Renlund DG. Efficacy and safety of metoprolol in the treatment of doxorubicin-induced cardiomyopathy in pediatric patients. American heart journal. 1995 Jan 31;129(1):197-9  Back to cited text no. 10


  [Figure 1], [Figure 2]


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