International Journal of Cardiovascular ResearchISSN: 2324-8602

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Research Article, Int J Cardiovasc Res Vol: 8 Issue: 3

Electrocardiogram Changes in Cancer Patients Taking 5-Flurouracil Chemotherapy at National Cancer Institute - University of Gezira (2018)

Abderrahman Ahmed Mohamed Ismail, Mawia Mohamed Ali Alhassan and Abdelmuniem Siddig Mohamed Ahmed*

University of Gezira, Sudan

*Corresponding Author: Abdelmuniem Siddig Mohamed Ahmed
University of Gezira, Khartoum, Sudan
Tel: +249912869216
E-mail: [email protected]

Received: May 03, 2019 Accepted: June 28, 2019 Published: July 05, 2019

Citation: Ismail AAM, Alhassan MMA, Ahmed ASM (2019) Electrocardiogram Changes in Cancer Patients Taking 5-Flurouracil Chemotherapy at National Cancer Institute - University of Gezira (2018). Int J Cardiovasc Res 8:3. doi: 10.4172/2324-8602.1000380

Abstract

Objective: To assess electrocardiogram changes in cancer patients taking 5-flurouracil chemotherapy at national Cancer institute- University of Gezira 2018.

Methods: This is a prospective, cross-section and analytical study, conducted to assess Electrocardiogram changes in cancer patients taking 5-flurouracil chemotherapy at national Cancer institute- university of Gezira in period between Septembers to December 2018. 100 patients diagnosed with cancer and on 5FU chemotherapy were included in the study.

Results: ECG records changed post 5 FU in 29% of patients. 4% have left axis deviation. 5% have right bundle branch block, 3% have inverted T wave, 5% have corrected QT interval between 0. 471-0.50 second and 3% more than 0.50 second, 2% developed left ventricular hypertrophy, 7% have a low voltage compared with ECG records before taking 5FU. No change in rhythm or ST segment. No relation between mode of administration and ECG changes. There was a relation between number of cycles and the heart rate after the treatment and between number of cycles and T wave inversion after the treatment.

Conclusions: 5-flurouracil chemotherapy cause electrocardiogram changes as an indicator of cardio toxicity effect of the drug.

Keywords: 5-flurouracil; Electrocardiogram; Cardio toxicity; Chemotherapy

Abbreviations

ECG: Electrocardiogram; 5-FU: 5-Flurouracil; CAD: Coronary Artery Disease; CTRCD: Cancer Therapeutic Related Cardiac Disease; CV: Cardiovascular; PET: Positron Emission Tomography; MRI: Magnetic Resonance Image; MI: Myocardial Infarction; FDUMP: Fluoro-Deoxy 5monophosphate Sodium; d-TMP: Deoxy Thymidine Triphosphate; d-UMP: Deoxyuridine Monophosphate; d-TTP: Deoxy Thymidine Triphosphate; TS: Thymdylate Synthase; DPD: Dihydropyrimidine Dehydrogenase; 5-F-du: 5-flouro-5-deoxyuridine; CCr: Creatinin Clearance Calculator; 5FU-CIV: Continuous Intravenous Infusion Fluorouracil; APC: Atrial Premature Complex; VPC: Ventricular Premature Complex

Introduction

Cardiovascular disease and cancer are the two most prevalent diseases around the world. As they coexist, it would be ideal to have an assessment of cardiovascular risk factors in every patient prior to initiation of cancer treatment. If not feasible in every patient, it is recommended in the patient who has known coronary artery disease (CAD) or equivalence (peripheral artery disease, cerebral vascular disease, aneurysmal dilatations, or end-stage renal disease), age .60 years old, or prior mediastina radiation. The objective of the assessment is to risk-stratify the patient and work on reducing modifiable risk factors prior to and during cancer treatment. This includes, but is not limited to, blood pressure control, cholesterol lowering, smoking cessation, and tight blood glucose control. This is particularly important when using chemotherapy agents that may affect the coronary vessels, or radiation therapy that may accelerate CAD [1].

Cardiovascular toxicity is a reality that impacts the quality of life and the overall survival of cancer patients. Careful analysis of the needs of these patients is mandatory to develop preventive strategies focused on the early detection and treatment of cardiovascular toxicities. Two major dilemmas are facing both the cardiologist and the hematologist/oncologist: the first is how to predict the risk of cancer therapeutics-related cardiac disease (CTRCD), and the second how to improve therapeutic strategies to reduce cardio toxicity without losing antitumor activity [1]

5-fluorouracil (5-FU) is a key chemotherapeutic agent in the treatment of many gastrointestinal tract adenocarcinomas. Despite its proven therapeutic efficacy, 5-FU also possesses several undesired cardiac toxicities, including coronary vasospasm, coronary thrombosis, cardiomyopathy, and sudden cardiac death [2].

Two major dilemmas are facing both the cardiologist and the hematologist/oncologist: the first is how to predict the risk of cancer therapeutics-related cardiac disease (CTRCD) [1,2] and the second how to improve therapeutic strategies to reduce cardio toxicity without losing antitumor activity [3]. The quality of cancer care requires a cultural transformation. We need cardio-oncology multidisciplinary teams to integrate skills and abilities and to standardize the care process [4]. All the diagnostic and therapeutic specialties involved in the multidisciplinary team must unify their clinical criteria in standardized protocols, to reduce the risk of cardiac diseases and the risk of discontinuation of cancer therapy. Multidisciplinary teams must agree quality standards and must also be involved in research and educational projects.

Much research needs to be done to identify the most appropriate protective strategies against the development of cancer therapeuticsrelated cardiac disease in cancer patients. We must focus on a tailored cancer therapy based on a cardio toxicity risk evaluation. Patients with a low cancer therapeutics-related cardiac disease risk profile need few clinical controls, whereas moderate- to high-risk patients will benefit from close follow-up or a primary cancer therapeutics-related cardiac disease prevention therapy. The most common CV toxicity, or at least the better recognized, is left ventricular dysfunction, mainly associated with the use of anthracyclines and trastuzumab. On the basis of observational studies, it appears that a number of agents may be effective in primary cancer therapeutics-related cardiac disease prevention. Statins, beta-blockers, and ACE inhibitors have been shown to reduce the risk of left ventricular dysfunction in high-risk populations treated with anthracyclines. However, there is limited evidence to support the use of a widespread intervention strategy. The development of new cancer treatments increases the number of open questions in this field. The most effective means of delivering protective strategies remains to be defined. Are new cancer treatments as cardio toxic as anthracyclines? Must we ask for a change in the preclinical development of new anticancer drugs, in terms of cardiovascular safety [1].

Materials and Methods

Study design

This is a prospective, cross-section and analytical hospital base study.

5.2. Study area: The study was conducted in republic of Sudan, Gezira state, Wad Medani district national Cancer institute -University of Gezira a governmental hospital and main Centre in Sudan, there are only three specialized oncology centers in Sudan and national Cancer institute -University of Gezira is one of them. It consists of oncology department, nuclear medicine, molecular biology, laboratories and blood bank, diagnostic radiology and medical physics and instrumentation. Also it consists of outpatient clinic, male and female admission word, psychologist, pharmacy and chemotherapy, radiotherapy and palliative therapy. The institute is attended by patients from various areas in Sudan that makes it a favorite place to meet cancer patients in different type of the disease.

Study population

The populations were Sudanese patients diagnosed as having cancer, who receive 5 fluorouracil regimens at the outpatient or admitted to the ward. The patients participate in appositive way in the study and welcomed answering the questions.

Study variables

The variables are age of the patients, gender, educational level, residency, personal habits, chronic illnesses, mode of drug administration, number of drug cycles, duration of chemotherapy, heart rate before the treatment, rhythm of the heart beats before the treatment, ST segments before the treatment, corrected QT interval before the treatment, heart voltage before the treatment, the axis before the treatment, bundle branches blockage, left ventricular hypertrophy before treatment, heart rate after the treatment, rhythm of the heart beats after the treatment, ST segments after the treatment, corrected QT interval after the treatment, heart voltage after the treatment, the axis after the treatment, bundle branches blockage, left ventricular hypertrophy after treatment, relation between mode of drug administration and ECG changes also relation between number of cycles had been received and ECG changes

Inclusion criteria

All cancer patients receive 5 fluorouracil chemotherapy irrespective to number of cycles of chemotherapy who attended to outpatient or admitted to national Cancer institute - University of Gezira.

Exclusion criteria

All Patients with previous history of heart disease

Sampling technique

It is a convenience non probability sampling technique because the total number of cancers patients coming or admitted to the cancer institute cannot be estimated, we used the non-probability sampling method and it is convenience because we go to the population and waiting for them in the place. The samples were collected during three months, from 1st of September to the end of November and it equal 100 sample (n=100).

Data collection tool

A structured questionnaire was designed with simple clear questions so as to be easily understood by the patients, the questionnaire includes the most personal data of the patient and other medically important points, the notes were taken and reviewed through which questionnaire was made. Questions were read to the patients and their answers were written in the questionnaire, so it is interview questionnaire. Then twelve-lead ECGs were recorded before, and 24 hours after the beginning of the administration of chemotherapy of 5fu. This regarding patients who received infusion dose then parameters such as heart rate and rhythm, presence of ST abnormalities, QT interval and total QRS voltage were analyzed. QT interval was corrected according to heart rate. Patients who took bolus dose of 5- fluorouracil the second electrocardiogram performed after two hours from the dose. Then ECG was interpreted by a cardiologist.

Data management and statistical analysis

Data was checked for completeness, consistency and ranges. SPSS version 20.0 was used to analyze data, descriptive frequency analysis was made for all variables, the relation between variables was analyzed according chi-square test (probability value=0.05) and result has been displayed in tables and figures constructed using Microsoft excel 2010 (Figures 1-28).

Figure 1: Demonstrate age group of the patients, n=100.

Figure 2: Demonstrate percentages of the gender of the patients, 67% were female and 33% were male, n=100.

Figure 3: Demonstrate percentage of the educational levels of the patients, 59% were illiterate, n=100.

Figure 4: Demonstrate occupation of the patients, n=100.

Figure 5: Demonstrate the residency of the patients, 79% were from rural area, n=100.

Figure 6: Demonstrate personal habits of the patients, 90% were neither smoker nor alcoholic, n=100.

Figure 7: Demonstrate the past medical history of the patients, n=100.

Figure 8: Percentage of mode of drug administration, 61% have been taken drug by infusion, n=100.

Figure 9: Percentage of the heart rate before beginning of the 5-flurouracil treatment, n=100.

Figure 10: Percentage of the heart rate after treatment with 5-flurouracil chemotherapy, n=100.

Figure 11: Percentage of heart rhythm before beginning of the 5-flurouracil treatment, n=10.

Figure 12: Percentage of the heart rhythm after treatment with 5-flurouracil chemotherapy, n=100.

Figure 13: Percentage of the T wave before beginning of the 5-flurouracil treatment, (n=100).

Figure 14: Percentage of the “T” wave after treatment with 5-flurouracil chemotherapy, n=100.

Figure 15: Percentage of the ST segment before treatment with 5-flurouracil chemotherapy, n=100.

Figure 16: Percentage of the ST segment after treatment with 5-flurouracil chemotherapy, n=100.

Figure 17: Percentage of Corrected QT interval before the treatment with 5-flurouracil chemotherapy, n=100.

Figure 18: Percentage of the Corrected QT interval after the treatment after treatment with 5-flurouracil chemotherapy, n=10.

Figure 19: Percentage of the duration of 5-flurouracil treatment, n=100.

Figure 20: Illustrated the number of cycles with 5-flurouracil chemotherapy, n=10.

Figure 21: Percentage of the axis before treatment with 5-flurouracil chemotherapy, n=100.

Figure 22: Percentage of the axis after treatment with 5-flurouracil chemotherapy, n=10.

Figure 23: Percentage of the Percentage of the bundle branch before treatment with 5-flurouracil chemotherapy, n=100.

Figure 24: Percentage of the bundle branches after treatment with 5-flurouracil chemotherapy, n=100.

Figure 25: Percentage of heart voltage before treatment with 5-flurouracil chemotherapy, n=100.

Figure 26: Percentage of the heart voltage after the treatment with 5-flurouracil chemotherapy, n=100.

Figure 27: Percentage of the left ventricular hypertrophy before treatment with 5-flurouracil chemotherapy, n=100.

Figure 28: Percentage of the left ventricular hypertrophy after the treatment after treatment with 5-flurouracil chemotherapy, n=100.

Results

This study was conducted in Republic of Sudan Gezira state, Wad Medani district in National cancer institute-university of Gezira, data collected from 100 patients have been diagnosed with cancer who receiving 5- fluorouracil. During the periods September and December 2018, mean age of the patients was 40 years (Table 1).

ECG changes after the treatment  Values Mode of administration Percentage P value
Bolus Infusion
Heart rate Less than 60 5 3 8% 0.2
60-90 33 53 86%
More than 90 1 5 6%
T wave Inverted 2 1 3% 0.31
Normal 37 16 97%
Corrected QT interval Less than 0.40 second 8 15 23% 0.5
0.40-0.470 second 29 40 69%
0.470-0.5 second 2 3 5%
Above 0.50 second 0 3 3%
Axis deviation Left axis deviation 1 3 4% 0.55
Normal axis 38 58 96%
Bundle branch block Right bundle branch block 3 2 5% 0.32
No bundle branch block 36 59 95%
Heart voltage Low voltage 2 5 7% 0.55
Normal voltage 37 56 93%
Left ventricular hypertrophy Present 1 1 2% 0.74
Absent 38 6 98%

Table 1: Correlation between Mode of drug administration and the heart rate, T wave, QTc interval, axis deviation, bundle branch block, heart voltage and left ventricular hypertrophy after the treatment.

Discussion

• Many studies suggest that treatment of various types of cancer with chemotherapy particularly 5-FU have a toxic effect on the heart (cardio toxicity), which is consider a very serious side effect. To investigate this we use the changes on ECG parameters as indicator of the toxicity.

• The mean age of the patients participate in the research was 40 years, (79%) are living in the rural areas, (59%) were illiterate, 61% are housewife, 7% are Employee and 23% are free worker.

• In this study patients who developed sinus bradycardia post 5- FU were 8%, this result is quite similar to the study done by Imran Hafeez, 2016 in which they found 8% of patients post 5FU developed sinus bradycardia [3].

• In our study all the patients had no rhythm abnormality, or ischemic ST segment changes in ECG records after 5FU. This result is similar to study done in 2007 which found that no ischemic ST changes or rhythm changes were observed after 5FU treatment [4].

• Small numbers of patients (4%) with left axis deviation changes in ECG records were observed after they received 5FU, comparable with normal axis on ECG records before receiving 5FU.

Small number of patients (5%) their ECG records were observed right bundle block changes after 5FU chemotherapy, comparable with normal ECG records before receive 5FU.

• In this study only (3%) of patient’s ECG records were observed T wave inversion after received 5FU . which is comparable with the study done by De Forni et al, 1992 in which 65% of patients T wave inversion were observed5.

• In this study (8%) of patient’s ECG records were observed significant prolongation of QT interval after received 5FU. as well as study showed significant prolongation of QTc after took 5FU [4].

• Small number of patients (2%) with left ventricular hypertrophy were observed in ECG records after they received 5FU. comparable with normal ECG records before of receive 5FU [5].

• Patients who developed low voltage after they received 5FU were only (7%), which is oppose to study done by De Forni et al., [4] in which 22% of patient’s developed low voltage after received 5FU.

• There were no relationship between mode of administration and The heart rate after the treatment (p value=0.2) or with T wave inversion after treatment (p value=0.31) or with prolongation of corrected QT interval after treatment (p value=0.5) or with left axis deviation after treatment (p value=0.32) or with low voltage after treatment (p value=0.55) or left ventricular hypertrophy after treatment (p value=0.74) (Table 2).

ECG changes after the treatment  Values More
than 5
Less than 3 Less than 5 Percentage P value
Heart rate Less than 60 3 2 2 8.00% 0.03
60-90 333 42 11 86.00%
More than 90 3 2 1 6.00%
T wave Inverted 1 1 0 3.00% 0.0001
Normal 38 45 14 97.00%
Corrected QT interval Less than 0.40 second 11 10 2 23.00% 0.92
0.40-0.470 second 25 31 12 69.00%
0.470-0.5 second 2 3 0 5.00%
Above 0.50 second 1 2 0 3.00%
Axis deviation Left axis deviation 2 1 1 4.00% 0.89
Normal axis 38 44 13 96.00%
Bundle branch block Right bundle branch block 2 2 1 5.00% 0.97
No bundle branch block 37 44 13 95.00%
Heart voltage Low voltage 1 6 0 7.00% 0.1
Normal voltage 38 40 14 93.00%
Left ventricular hypertrophy Present 1 1 0 2.00% 0.9
Absent 38 45 14 98.00%

Table 2: Correlation between number of cycles and the heart rate, T wave, QT interval, axis deviation, bundle branch block, heart voltage and left ventricular hypertrophy after the treatment.

• In our study there were, significant relationship between Number of 5FU cycles and The heart rate after the treatment (p value=0.03), however, the result showed there is no significant relation between number of cycles and Axis deviation after the treatment (p value=0.89. Also our result showed There was significant a relation between Number of cycles and T wave after the treatment (p value=0.0001 ), our results showed no relationship between Number of cycles and Corrected QT interval after the treatment(p value =0.92) also our results showed no relationship between number of cycles and Bundle branch after the treatment(p value=0.92) also our result showed no relationship between Number of cycles and Heart voltage after the treatment (p value=0.1) or between Number of cycles and Left ventricular hypertrophy after the treatment (p value=0.9) .

Conclusion

• The significant changes that appear on the ECG after the 5-FU treatment is the prolongation of corrected QT interval, developing sinus bradycardia, left axis deviation, right bundle branch block, inverted T wave low heart voltage and left ventricular hypertrophy.

• Regarding heart rhythm and ST segment there was no changes after 5FU treatment.

• There was significant relation between Number of cycles and (T wave, heart rate) after the 5-FU treatment.

• There was no relation between mode of drug administration and the ECG changes.

Acknowledgement

I am grateful to Allah, who gave me the strength, power and courage to finish this work.

Great thanks for Dr. Muawia deanship of cancer institute-University of Gezira for giving the approval to conduct this research. I would like to thank my supervisor Dr. Abderrahman Ahmed, for the patient guidance, and advice he has provided throughout my time. I have been extremely lucky to have a supervisor who cared so much about my work, and who responded to my questions and queries so promptly .Also thankfulness conducted for Dr. Mustafa Ibrahim the administrator of cardiac center for his useful guides and information. I would like to acknowledge my indebtedness and render my warmest thank to Dr. Mona and my friend Sundos who made this work possible. Also I would like to thank all the members of staff at national cancer institute who helped me in my research.

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