Hematology
Contributions
Type: Publication Only
Background
Anthracyclines are used in induction treatment of acute myeloid leukemia. However, they cause dose-dependent cardiac dysfunction through generation of reactive oxygen species, mediated by topoisomerase -IIb in cardiomyocytes and forming complexes with intracellular iron, leading to lipid peroxidation and DNA damage. Due to low potential for regeneration in cardiac myocytes, these changes are likely irreversible. Early detection of cardiotoxicity is important before changes become clinically overt. Left ventricular ejection fraction (LVEF) has been the main indicator of cardiac dysfunction but impairment in LVEF is detected only after considerable myocyte loss has occurred. So, more sensitive tools to detect these alterations are warranted.
Aims
To study acute cardiac toxicity of anthracycline in acute myeloid leukemia (AML) patients by serial echocardiographic parameters during induction chemotherapy.
Methods
The prospective study included newly diagnosed AML patients. Patients with history of previous anthracycline exposure were excluded. AML induction therapy consisted of daunorubicin 60 mg/m2/day for 3 days and cytarabine 100 mg/m2/day for 7 days. All patients were assessed by echocardiography at start and end of induction chemotherapy and after 3 days of daunorubicin. Parameters on M mode, Doppler and tissue Dopper modes at mitral valve (lateral) and septum were recorded.
Results
A total of 32 patients of AML were enrolled with median age of 21 years (range 7-57 years) and 18 males (56.2%). Median leucocyte count was 6300/ul (range 300-380,000). 16 patients (50%) had fungal infection during induction and 14 patients expired (44%).
Cardiac chamber dimensions were not altered during induction.
Doppler parameters: E velocity decreased in AML patients (p value 0.023). A velocity did not changed significantly. E/A ratio showed overall decreasing trend (p value 0.09).
Tissue Doppler parameters: Em lateral decreased (p value 0.005) in AML patients. Em septal decreased from baseline to post chemotherapy echo (p value 0.04). Am lateral dropped from baseline to post chemotherapy echo in AML patients (p value 0.001). Sm lateral and septal were not altered significantly. Isovolumetric contraction time was significantly increased from baseline to post chemotherapy echo (p value 0.019). Ejection fraction did not show significant changes during induction.
|
| P value | ||||
Parameter | Baseline(B) | Mid (M) | Post (P) | B vs M | B vs P | M vs P |
E vel (cm/s) | 94.7+20.7 | 83.4+21.0 | 73.4+19.5 | 0.2 | 0.02 | 0.6 |
A vel (cm/s) | 63.5+19.2 | 57.1+20.1 | 67.1+17.6 | 0.09 | 0.9 | 0.5 |
E/A | 1.6+0.6 | 1.6+0.6 | 1.1+0.4 | 0.6 | 0.4 | 0.2 |
Sm (lateral)(cm/s) | 11.6+2.4 | 10.6+2.6 | 10.4+2.3 | 0.7 | 0.1 | 0.9 |
Sm (septal)(cm/s) | 8.9+1.4 | 8.6+1.6 | 8.3+1.5 | 0.9 | 0.9 | 0.9 |
Em (lateral)(cm/s) | 16.4+4.6 | 14.4+3.8 | 12.9+4.1 | 0.6 | 0.002 | 0.2 |
Em (septal)(cm/s) | 11.4+3.5 | 9.6+2.8 | 9.1+2.5 | 0.5 | 0.04 | 0.9 |
Am (lateral)(cm/s) | 8.9+2.6 | 7.7+2.2 | 6.7+2.0 | 0.4 | 0.001 | 0.2 |
Am (septal)(cm/s) | 8.5+2.4 | 8.0+1.9 | 7.8+2.1 | 0.9 | 0.4 | 0.9 |
LVEF (%) | 65.2+5.9 | 63.7+7.1 | 63.6+9.0 | 0.2 | 0.5 | 0.9 |
IVCT(ms) | 52.2+9.2 | 57.0+13.2 | 61.0+13.1 | 0.31 | 0.019 | 0.53 |
Summary
Significant changes occur in various Doppler and tissue doppler parameters during induction chemotherapy reflecting underlying diastolic dysfunction due to anthracycline induced cardiotoxicity. Ejection fraction is relatively insensitive tool to ascertain these early changes. It is suggested that these patients be followed up with repeated ECHO to find improvement or worsening of these changes before any overt clinical symptoms due to heart failure develop. Early interventions can be planned before overt heart failure in consultation with cardiologists especially while planning treatment for patients with relapsed disease or transplantation.
Keyword(s): Acute myeloid leukemia, Anthracycline, Toxicity
Type: Publication Only
Background
Anthracyclines are used in induction treatment of acute myeloid leukemia. However, they cause dose-dependent cardiac dysfunction through generation of reactive oxygen species, mediated by topoisomerase -IIb in cardiomyocytes and forming complexes with intracellular iron, leading to lipid peroxidation and DNA damage. Due to low potential for regeneration in cardiac myocytes, these changes are likely irreversible. Early detection of cardiotoxicity is important before changes become clinically overt. Left ventricular ejection fraction (LVEF) has been the main indicator of cardiac dysfunction but impairment in LVEF is detected only after considerable myocyte loss has occurred. So, more sensitive tools to detect these alterations are warranted.
Aims
To study acute cardiac toxicity of anthracycline in acute myeloid leukemia (AML) patients by serial echocardiographic parameters during induction chemotherapy.
Methods
The prospective study included newly diagnosed AML patients. Patients with history of previous anthracycline exposure were excluded. AML induction therapy consisted of daunorubicin 60 mg/m2/day for 3 days and cytarabine 100 mg/m2/day for 7 days. All patients were assessed by echocardiography at start and end of induction chemotherapy and after 3 days of daunorubicin. Parameters on M mode, Doppler and tissue Dopper modes at mitral valve (lateral) and septum were recorded.
Results
A total of 32 patients of AML were enrolled with median age of 21 years (range 7-57 years) and 18 males (56.2%). Median leucocyte count was 6300/ul (range 300-380,000). 16 patients (50%) had fungal infection during induction and 14 patients expired (44%).
Cardiac chamber dimensions were not altered during induction.
Doppler parameters: E velocity decreased in AML patients (p value 0.023). A velocity did not changed significantly. E/A ratio showed overall decreasing trend (p value 0.09).
Tissue Doppler parameters: Em lateral decreased (p value 0.005) in AML patients. Em septal decreased from baseline to post chemotherapy echo (p value 0.04). Am lateral dropped from baseline to post chemotherapy echo in AML patients (p value 0.001). Sm lateral and septal were not altered significantly. Isovolumetric contraction time was significantly increased from baseline to post chemotherapy echo (p value 0.019). Ejection fraction did not show significant changes during induction.
|
| P value | ||||
Parameter | Baseline(B) | Mid (M) | Post (P) | B vs M | B vs P | M vs P |
E vel (cm/s) | 94.7+20.7 | 83.4+21.0 | 73.4+19.5 | 0.2 | 0.02 | 0.6 |
A vel (cm/s) | 63.5+19.2 | 57.1+20.1 | 67.1+17.6 | 0.09 | 0.9 | 0.5 |
E/A | 1.6+0.6 | 1.6+0.6 | 1.1+0.4 | 0.6 | 0.4 | 0.2 |
Sm (lateral)(cm/s) | 11.6+2.4 | 10.6+2.6 | 10.4+2.3 | 0.7 | 0.1 | 0.9 |
Sm (septal)(cm/s) | 8.9+1.4 | 8.6+1.6 | 8.3+1.5 | 0.9 | 0.9 | 0.9 |
Em (lateral)(cm/s) | 16.4+4.6 | 14.4+3.8 | 12.9+4.1 | 0.6 | 0.002 | 0.2 |
Em (septal)(cm/s) | 11.4+3.5 | 9.6+2.8 | 9.1+2.5 | 0.5 | 0.04 | 0.9 |
Am (lateral)(cm/s) | 8.9+2.6 | 7.7+2.2 | 6.7+2.0 | 0.4 | 0.001 | 0.2 |
Am (septal)(cm/s) | 8.5+2.4 | 8.0+1.9 | 7.8+2.1 | 0.9 | 0.4 | 0.9 |
LVEF (%) | 65.2+5.9 | 63.7+7.1 | 63.6+9.0 | 0.2 | 0.5 | 0.9 |
IVCT(ms) | 52.2+9.2 | 57.0+13.2 | 61.0+13.1 | 0.31 | 0.019 | 0.53 |
Summary
Significant changes occur in various Doppler and tissue doppler parameters during induction chemotherapy reflecting underlying diastolic dysfunction due to anthracycline induced cardiotoxicity. Ejection fraction is relatively insensitive tool to ascertain these early changes. It is suggested that these patients be followed up with repeated ECHO to find improvement or worsening of these changes before any overt clinical symptoms due to heart failure develop. Early interventions can be planned before overt heart failure in consultation with cardiologists especially while planning treatment for patients with relapsed disease or transplantation.
Keyword(s): Acute myeloid leukemia, Anthracycline, Toxicity