Assessment of anthracycline-induced cardiotoxicity with electrocardiography
Aim: Monitoring of anthracycline-induced cardiotoxicity with electrocardiography (ECG) and comparing ECG changes with findings on echocardiography (ECHO). Methods: A total of 26 adult acute leukemia patients (mean age 46.2 ± 12.4 years, 15 males) treated with 2–6 cycles of anthracycline-based chem...
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2009
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| Цитувати: | Assessment of anthracycline-induced cardiotoxicity with electrocardiography / J.M. Horacek, M. Jakl, J. Horackova, R. Pudil, L. Jebavy, J. Maly // Experimental Oncology. — 2009. — Т. 31, № 2. — С. 115–117. — Бібліогр.: 15 назв. — англ. |
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irk-123456789-1362132018-06-17T03:08:51Z Assessment of anthracycline-induced cardiotoxicity with electrocardiography Horacek, J.M. Jakl, M. Horackova, J. Pudil, R. Jebavy, L. Maly, J. Short communications Aim: Monitoring of anthracycline-induced cardiotoxicity with electrocardiography (ECG) and comparing ECG changes with findings on echocardiography (ECHO). Methods: A total of 26 adult acute leukemia patients (mean age 46.2 ± 12.4 years, 15 males) treated with 2–6 cycles of anthracycline-based chemotherapy (CT) were studied. Cardiac evaluation was performed at the baseline (before CT), after first CT, after last CT (cumulative anthracycline dose 464.3 ± 117.5 mg/m2 ) and circa 6 months after CT. Time ECG parameters, QRS voltage, presence of repolarization changes, arrhythmias and other abnormalities were evaluated. Results: During treatment and follow-up, we found a statistical significant QTc interval prolongation — 414.7 ± 16.0 ms (before CT), 419.6 ± 21.6 ms(after first CT), 428.0 ± 16.2 ms(after last CT) and 430.1 ± 18.4 ms(6 months after CT). Significant QTc interval prolongation (> 450 ms) occurred in 3 patients after first CT, in 4 patients after last CT and in 5 patients within 6 months after CT. Significant total QRS voltage lowering in the limb leads (> 1.0 mV versus before CT) occurred in 3 patients after first CT, in 5 patients after last CT and in 6 patients within 6 months after CT. We found a statistically significant correlation between decreased QRS voltage, QTc interval prolongation and left ventricular (LV) dysfunction on ECHO. Repolarization changes associated with oncology treatment were present in 9 patients within 6 months after CT. Conclusion: Anthracycline treatment is associated with changes in electrical activity of the myocardium. Prolonged QTc interval represents a risk for development of malignant ventricular arrhythmias. Decreased QRS voltage and prolonged QTc interval after anthracycline treatment could correlate with LV dysfunction on ECHO. Further studies will be needed to prove whether these ECG changes could serve as an accessible and non-invasive screening method indicating LV dysfunction after anthracycline treatment. 2009 Article Assessment of anthracycline-induced cardiotoxicity with electrocardiography / J.M. Horacek, M. Jakl, J. Horackova, R. Pudil, L. Jebavy, J. Maly // Experimental Oncology. — 2009. — Т. 31, № 2. — С. 115–117. — Бібліогр.: 15 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/136213 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| language |
English |
| topic |
Short communications Short communications |
| spellingShingle |
Short communications Short communications Horacek, J.M. Jakl, M. Horackova, J. Pudil, R. Jebavy, L. Maly, J. Assessment of anthracycline-induced cardiotoxicity with electrocardiography Experimental Oncology |
| description |
Aim: Monitoring of anthracycline-induced cardiotoxicity with electrocardiography (ECG) and comparing ECG changes with findings
on echocardiography (ECHO). Methods: A total of 26 adult acute leukemia patients (mean age 46.2 ± 12.4 years, 15 males)
treated with 2–6 cycles of anthracycline-based chemotherapy (CT) were studied. Cardiac evaluation was performed at the baseline
(before CT), after first CT, after last CT (cumulative anthracycline dose 464.3 ± 117.5 mg/m2
) and circa 6 months after CT.
Time ECG parameters, QRS voltage, presence of repolarization changes, arrhythmias and other abnormalities were evaluated.
Results: During treatment and follow-up, we found a statistical significant QTc interval prolongation — 414.7 ± 16.0 ms (before
CT), 419.6 ± 21.6 ms(after first CT), 428.0 ± 16.2 ms(after last CT) and 430.1 ± 18.4 ms(6 months after CT). Significant QTc
interval prolongation (> 450 ms) occurred in 3 patients after first CT, in 4 patients after last CT and in 5 patients within 6 months
after CT. Significant total QRS voltage lowering in the limb leads (> 1.0 mV versus before CT) occurred in 3 patients after first
CT, in 5 patients after last CT and in 6 patients within 6 months after CT. We found a statistically significant correlation between
decreased QRS voltage, QTc interval prolongation and left ventricular (LV) dysfunction on ECHO. Repolarization changes associated
with oncology treatment were present in 9 patients within 6 months after CT. Conclusion: Anthracycline treatment is associated
with changes in electrical activity of the myocardium. Prolonged QTc interval represents a risk for development of malignant
ventricular arrhythmias. Decreased QRS voltage and prolonged QTc interval after anthracycline treatment could correlate with
LV dysfunction on ECHO. Further studies will be needed to prove whether these ECG changes could serve as an accessible and
non-invasive screening method indicating LV dysfunction after anthracycline treatment. |
| format |
Article |
| author |
Horacek, J.M. Jakl, M. Horackova, J. Pudil, R. Jebavy, L. Maly, J. |
| author_facet |
Horacek, J.M. Jakl, M. Horackova, J. Pudil, R. Jebavy, L. Maly, J. |
| author_sort |
Horacek, J.M. |
| title |
Assessment of anthracycline-induced cardiotoxicity with electrocardiography |
| title_short |
Assessment of anthracycline-induced cardiotoxicity with electrocardiography |
| title_full |
Assessment of anthracycline-induced cardiotoxicity with electrocardiography |
| title_fullStr |
Assessment of anthracycline-induced cardiotoxicity with electrocardiography |
| title_full_unstemmed |
Assessment of anthracycline-induced cardiotoxicity with electrocardiography |
| title_sort |
assessment of anthracycline-induced cardiotoxicity with electrocardiography |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2009 |
| topic_facet |
Short communications |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/136213 |
| citation_txt |
Assessment of anthracycline-induced cardiotoxicity with electrocardiography / J.M. Horacek, M. Jakl, J. Horackova, R. Pudil, L. Jebavy, J. Maly // Experimental Oncology. — 2009. — Т. 31, № 2. — С. 115–117. — Бібліогр.: 15 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
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2025-07-10T00:52:21Z |
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2025-07-10T00:52:21Z |
| _version_ |
1837219179431723008 |
| fulltext |
Experimental Oncology 31, 115–117, 2009 (June) 115
Cardiotoxicity is a relatively frequent and potentially
serious complication of oncology treatment. Anthracy-
clines with their acute, chronic and late cardiotoxicity
represent the greatest risk [1]. Various methods have
been recommended for monitoring of cardiotoxicity
in oncology [2, 3]. In our conditions, echocardiography
(ECHO) and electrocardiography (ECG) are routinely
used [4, 5].
ECG is among recommended diagnostic methods
for detection of cardiotoxicity in oncology. It is a widely
available and low-cost examination. ECG changes
were registered in 11–29% patients during and shortly
after anthracycline administration, but the incidence
strongly depends on the frequency of monitoring.
In some studies, acute ECG changes and arrhythmias
were registered in up to 41% patients treated by anthra-
cyclines [2]. The ECG changes associated with anthra-
cyclines include non-specific changes in ST segment
and T wave, sinus tachycardia, supraventricular and
ventricular premature beats. These changes are usu-
ally transient and no relation to development of chronic
cardiotoxicity was proven. Continuous 24-hour moni-
toring of ECG (Holter) may reveal arrhythmias both
in early and late periods of anthracycline treatment [6].
Furthermore, QRS voltage lowering in the limb leads
was reported during progression of anthracycline-
induced cardiomyopathy with heart failure [7]. After
anthracycline-based treatment, QTc interval prolon-
gation and increased QTc dispersion were reported
[8–10] which generally represent a risk for malignant
ventricular arrhythmias and sudden cardiac death.
Some prior studies suggested that QTc interval pro-
longation after anthracycline administration could
be an early marker of left ventricular (LV) dysfunction
[9]. In other studies, however, QTc prolongation was
only transient and no correlation with LV dysfunction
on ECHO examination was found [11].
The aim of the presented study was to monitor ECG
changes during and after anthracycline treatment and
to compare these changes with findings on ECHO
examination.
A total of 26 patients with newly diagnosed acute
leukemia were included in the study. The cohort con-
sisted of 15 males and 11 females with the mean age
of 46.2 ± 12.4 years (range: 22–61, median 49). The
patients were treated with 2–6 cycles of chemotherapy
(CT) containing anthracycline agents (idarubicin,
daunorubicin or mitoxantrone) in combination with
cytarabine. The mean total cumulative dose of anthra-
cyclines reached 464.3 ± 117.5 mg/m2 (range 240–
ASSESSMENT OF ANTHRACYCLINE-INDUCED CARDIOTOXICITY
WITH ELECTROCARDIOGRAPHY
J.M. Horacek1, 4, *, M. Jakl2, 4, J. Horackova3, R. Pudil2, L. Jebavy1, 4, J. Maly1
1Department of Medicine II — Clinical Hematology
2Department of Medicine I — Cardiology
3Department of Gerontology and Metabolic Care, Faculty of Medicine, University Hospital and Charles
University, Hradec Kralove 500 05, Czech Republic
4Department of Internal Medicine, Faculty of Military Health Sciences, University of Defence, Hradec
Kralove 500 01, Czech Republic
Aim: Monitoring of anthracycline-induced cardiotoxicity with electrocardiography (ECG) and comparing ECG changes with fin-
dings on echocardiography (ECHO). Methods: A total of 26 adult acute leukemia patients (mean age 46.2 ± 12.4 years, 15 males)
treated with 2–6 cycles of anthracycline-based chemotherapy (CT) were studied. Cardiac evaluation was performed at the baseline
(before CT), after first CT, after last CT (cumulative anthracycline dose 464.3 ± 117.5 mg/m2) and circa 6 months after CT.
Time ECG parameters, QRS voltage, presence of repolarization changes, arrhythmias and other abnormalities were evaluated.
Results: During treatment and follow-up, we found a statistical significant QTc interval prolongation — 414.7 ± 16.0 ms (before
CT), 419.6 ± 21.6 ms (after first CT), 428.0 ± 16.2 ms (after last CT) and 430.1 ± 18.4 ms (6 months after CT). Significant QTc
interval prolongation (> 450 ms) occurred in 3 patients after first CT, in 4 patients after last CT and in 5 patients within 6 months
after CT. Significant total QRS voltage lowering in the limb leads (> 1.0 mV versus before CT) occurred in 3 patients after first
CT, in 5 patients after last CT and in 6 patients within 6 months after CT. We found a statistically significant correlation between
decreased QRS voltage, QTc interval prolongation and left ventricular (LV) dysfunction on ECHO. Repolarization changes associ-
ated with oncology treatment were present in 9 patients within 6 months after CT. Conclusion: Anthracycline treatment is associ-
ated with changes in electrical activity of the myocardium. Prolonged QTc interval represents a risk for development of malignant
ventricular arrhythmias. Decreased QRS voltage and prolonged QTc interval after anthracycline treatment could correlate with
LV dysfunction on ECHO. Further studies will be needed to prove whether these ECG changes could serve as an accessible and
non-invasive screening method indicating LV dysfunction after anthracycline treatment.
Key Words: cardiotoxicity, anthracyclines, electrocardiography, QTc interval, QRS voltage.
Received: January 25, 2009.
*Correspondence: E-mail: jan.hor@post.cz
Abbreviations used: CT — chemotherapy; CTCAE — Common
Terminology Criteria for Adverse Events v3.0; ECG — electrocar-
diography; ECHO — echocardiography; iRBBB — incomplete right
bundle branch block; LAH — left anterior hemiblock; LV — left ven-
tricular; NCI — National Cancer Institute; QTc interval — heart-rate
corrected QT interval.
Exp Oncol 2009
31, 2, 115–117
SHORT COMMUNICATIONS
116 Experimental Oncology 31, 115–117, 2009 (June)
715, median 429). Myeloablative preparative regimen
followed by hematopoietic cell transplantation was
subsequently administered in 16 patients. The study
was approved by the local ethical committee and all
patients gave a written consent before they were in-
cluded in the study.
In all patients, resting 12-lead ECG records with
a paper speed of 50 mm/s were performed at the base-
line (before CT), after the first CT with anthracyclines
(after first CT, mean cumulative anthracycline dose
136.3 ± 28.3 mg/m2), after the last CT with anthracyclines
(after last CT, mean 464.3 ± 117.5 mg/m2) and circa
6 months after completion of the treatment (6 months
after CT). Evaluated ECG parameters were as follows:
time parameters (heart rate, RR interval, PQ interval, QRS
duration, QT interval), voltage parameters (total QRS
voltage in the limb leads) and presence of repolarization
changes, arrhythmias or other abnormalities. The ECG
measurements were performed manually by 2 indepen-
dent physicians who were blinded to clinical data. A total
of 104 ECG records were evaluated.
To obtain heart-rate corrected values for QT in-
terval (QTc interval), we used the Bazett’s formula:
QTc = QT / √RR [12]. The upper limits of normal for
QTc interval duration using the Bazett’s formula were
suggested 420 ms for males and 430 ms for females.
According to the latest guidelines of the National Can-
cer Institute (NCI) — Common Terminology Criteria for
Adverse Events v3.0 (CTCAE), QTc interval prolonga-
tion above 450 ms in connection with oncology treat-
ment is regarded as cardiac adverse event [13]. In our
study, the QTc interval above 450 ms was considered
significantly prolonged and representing a risk factor
for development of ventricular arrhythmias. Decreases
in the total QRS voltage in the limb leads (measured
in leads I, II, III, aVR, aVL, aVF) by > 1.0 mV versus
baseline values were considered significant.
ECHO examinations were performed on Hewlett
Packard Image Point ultrasound at the same time
as ECG records. Parameters of systolic and diastolic left
ventricular (LV) function were assessed. Systolic LV dys-
function was defined as ejection fraction (LVEF) ≤ 55%.
Diastolic LV dysfunction was defined as E/A inversion
and E-wave deceleration time above 220 ms on the
transmitral Doppler curve (impaired relaxation).
Statistical analysis was performed with the “Sta-
tistica for Windows, Version 5.0” program. Analysis
of variance and McNemar tests were used. Correla-
tions were evaluated with normal and Spearman cor-
relation tests. The values are expressed as mean ± SD,
p < 0.01 was considered statistically significant.
ECG abnormalities in connection with anthracy-
cline treatment are shown in Table. During treatment
and follow-up, we found a statistical significant QTc
interval prolongation — 414.7 ± 16.0 ms (before CT),
419.6 ± 21.6 ms (after first CT), 428.0 ± 16.2 ms (after
last CT) and 430.1 ± 18.4 ms (6 months after CT). After
last CT and 6 months after CT, QTc interval prolonged
significantly in comparison with the baseline value
(p < 0.01). After first CT, no patient had QTc interval
prolongation above 450 ms. After first CT, QTc interval
prolonged above 450 ms in 3 (11.5%) patients, after
last CT in 4 (15.4%) patients, and 6 months after
CT in 5 (19.2%) patients.
Table. Occurrence of ECG abnormalities in connection with anthracycline
chemotherapy for acute leukemia (n = 26)
ECG abnormalities Before CT After first
CT
After last
CT
6 months
after CT
Tachycardia 4 3 0 3
Bradycardia 1 3 1 1
First degree AV block 0 1 5 2
iRBBB 1 2 3 3
LAH 0 1 2 3
Repolarization abnormalities 5 8 11 12
QTc prolongation 0 (6) 3 (8) 4 (16) 5 (15)
QRS voltage lowering – 3 5 6
Notes: tachycardia — heart rate above 100/min; bradycardia — heart rate
below 60/min; first degree AV block — PQ interval above 200 ms; iRBBB
(incomplete right bundle branch block) — RSR̓ pattern in V1 (V2), QRS
duration below 120 ms; LAH (left anterior hemiblock) — left axis deviation,
heart axis below –30°; nonspecific repolarization abnormalities — changes
in ST segment and T wave in 2 and more leads; QTc prolongation — QTc
interval above 450 ms regardless gender (above 420 ms in males, above
430 ms in females); QRS voltage lowering — decrease in the total QRS
voltage in the limb leads > 1.0 mV vs baseline values.
The total QRS voltage in the limb leads changed from
baseline 4.58 ± 1.31 mV (before CT) to 4.57 ± 1.55 mV
(after first CT), 4.42 ± 1.15mV (after last CT) and
4.22 ± 1.06 mV (6 months after CT). In comparison with
the baseline values, QRS voltage decreased signifi-
cantly in 3 (11.5%) patients after first CT, in 5 (19.2%)
patients after last CT and in 6 (23.1%) patients within
6 months after CT.
Repolarization abnormalities associated with on-
cology treatment (de novo changes or distinct progres-
sion of the baseline changes) were found in 9 (34.6%)
patients within 6 months after CT.
On ECHO examination, we found systolic LV dys-
function in 1 (3.8%) patients after first CT, in 3 (11.5%)
patients after last CT and in 5 (19.2%) patients within
6 months after CT. Diastolic LV dysfunction on ECHO
was detected in 5 (19.2%) patients after first CT,
in 6 (23.1%) patients after last CT and in 12 (46.2%)
patients within 6 months after CT.
We found significant correlations between QRS vol-
tage lowering and LV dysfunction on ECHO (r = 0.660,
p < 0.001 for systolic LV dysfunction; r = 0.592, p < 0.01
for diastolic LV dysfunction). Correlations between
prolonged QTc interval and LV dysfunction on ECHO
also reached statistical significance (r = 0.246, p < 0.01
for systolic LV dysfunction; r = 0.257, p < 0.01 for dia-
stolic LV dysfunction).
Our results show that anthracycline-based treat-
ment for acute leukemia causes changes in electrical
activity of the myocardium, both during the treat-
ment (acute cardiotoxicity) and during the follow-
up (chronic cardiotoxicity). QTc interval prolongation
above 450 ms, in our cohort in 5 (19.2%) patients
within 6 months after CT, represents a risk factor for
development of malignant ventricular arrhythmias (tor-
sade de pointes) and sudden cardiac death. In these
patients, regular monitoring of QTc interval is neces-
sary, complemented with searching for electrolyte dis-
orders (especially hypokalemia and hypomagnesemia,
e. g. in case of vomiting or diarrhea) with potential
Experimental Oncology 31, 115–117, 2009 (June) 117
correction, and rational prescription of QTc interval
prolonging drugs (many antiarrhythmics, tricyclic
antidepressants, antipsychotics, some antibiotics and
antifungal drugs etc.) [14, 15]. In our cohort, malignant
ventricular arrhythmias did not occur during the follow-
up in any of the patients with significantly prolonged
QTc interval.
In our study, decreased total QRS voltage in the
limb leads and prolonged QTc interval on ECG correla-
ted with systolic and diastolic LV dysfunction on ECHO.
Further studies on a larger number of patients will
be needed to prove whether these ECG changes could
serve as an accessible and non-invasive screening
method indicating LV dysfunction after anthracycline
treatment.
ACKNOWLEDGMENTS
The work was supported by research projects
MO 0FVZ 0000503 (Czech Ministry of Defence) and
MZO 00179906 (Czech Ministry of Health).
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