الفهرس 
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Abstract
One of the most pivotal issues on the United Nations’ 2030 Agenda is combatting viral hepatitis; the blood borne virus which comes in the seventh place on the list of leading causes of mortality globally.
The aim of this study is to review the adverse cardiac events and additional clinical findings noted in patients who were receiving DAAs for the treatment of HCV.
This study was carried out over a period of 24 months; from the 1st of May 2017 till the 30th of May 2019 on 100 subjects diagnosed as infected by hepatitis C virus (HCV) and treated with doses of SOF plus DCV only or in addition to weight-based RBV for 12 weeks. Their ages were between 42-59 years. They were 56 males and 44 females. The study included 69 (69%) subject was living in rural areas and 31 (31%) subjects was living in urban areas. Subjects were selected according to inclusion and exclusion criteria.
Subjects enrolled underwent clinical examination and investigations which involved 5 items; ECGs, TTEs, TN-I, CPK-MB, and BNP levels. All parameters were assessed before beginning of the treatment (week 0), sixth week of the treatment (week 6), and six weeks after DAAs termination.
Patients included into this study were divided into two groups according to their ejection fraction measurement to evaluate residual cardiac function. group 1: normal ejection fraction group (50% or above).group 2: affected ejection fraction group (less than 50%).
There was high significant difference between BNP, CPK-MB, TN-I levels at week 0, week 6 and six weeks after DAAs termination. There was high significant increase in frequency of abnormal BNP levels at week 6. There was high significant increase in frequency of abnormal CPK-MB and TN-I levels at week 6 and six weeks after DAAs termination. The interquartile ranges of BNP at week 6 and six weeks after DAAs termination were less than 125 Pg/ml (normal range), while that for CPK-MB at week 6 and six weeks after DAAs termination were between 5-25 IU/L (normal range). On the other hand, TN-I was at week 6 and six weeks after DAAs termination were less than 0.4 ng/ ml.
The current study showed that the abnormalities founded in ECG at 6 weeks’ review were: inverted T wave in (26) cases, sinus bradycardia in (20) cases, nonspecific inter-ventricular conduction defect in (18) cases, flat T wave in (15) cases, depressed ST segment in (7) cases, incomplete right bundle branch block in (5) cases, right bundle branch block in (4) cases, first degree heart block in (2) cases and borderline prolonged QTC in one case. Most of these abnormalities remained after DAAs termination check.
There was high significant difference between heart rates at week 0 and week 6 associated with significant difference between heart rates at week 0 and six weeks after DAAs termination; however there was no significant difference between heart rates at week 6 and six weeks after DAAs termination.
A high significant difference between P wave between week 0 and week 6 associated with significant difference between P wave at week 0 and six weeks after DAAs termination were described; however there was no significant difference between P wave at week 6 and six weeks after DAAs termination.
There was high significant difference between PR interval at week 0 and week 6 associated with significant difference between PR intervals at week 0 and six weeks after DAAs termination; however there was no significant difference between PR intervals at week 6 and six weeks after DAAs termination.
There was high significant difference between QRS widths at week 0, week6 and six weeks after DAAs termination as significant differences between each two times were proved. There was significant increase in frequency of abnormal QRS width at week 6 and six weeks after DAAs termination.
There was high significant difference between QT intervals at week 0, week 6 and six weeks after DAAs termination as significant difference between each two times were described. There was significant increase in frequency of abnormal QT interval at week 6 and six weeks after DAAs termination
High significant increases in frequency of bradycardia, abnormal QRS width and QT interval at week 6 and six weeks after DAAs termination were observed.
There was significant increase in frequency of abnormal P wave at week 6 and six weeks after DAAs termination.
The mean heart rate declined from 68.8 b/m at week 0 to 65.4 b/m at week 6 and was the same six weeks after DAAs termination.
The P wave duration mean was 87.7 ms at week 0, increased to 90.3 ms at week 6 and continued to increase to 90.8ms six weeks after DAAs termination.
The mean PR interval increased from 159 ms at week 0 to 164.2 ms at week 6 and continued to increase to 165 ms six weeks after DAAs termination.
The QRS width mean was 91.1 ms at week 0, increased to 100.1 ms at week 6 and continued to increase to 100.9 ms six weeks after DAAs termination.
The QT interval mean was 413 ms at week 0, increased to 418.9 ms at week 6 and continued to increase to 421.2 ms six weeks after DAAs termination.
There was high significant increase in frequency of reduced ejection fraction at week 6 and six weeks after DAAs termination. There were 6 cases with borderline ejection fraction and 15 cases with reduced ejection fraction at week 6. Six weeks after DAAs termination, there were 12 cases with borderline ejection fraction and 9 cases with reduced ejection fraction.
group 1 normal ejection fraction group (50% or above): 79 cases. group 2: affected ejection fraction group (less than 50%): 21 cases. Through statistical analysis this is the first clinical report to include factors that may increase or decrease the risk of cardiotoxicity in patients receiving new DAAs.
The optimal cutoff point of age is >51 years old with 100% sensitivity, 77.22% specifity and 82% accuracy. Every one year increase in age caused 55% increase in risk of developing affected cardiac function with (1.28-1.88) confidence interval and P value of <0.001 .
Sex correlation with ejection fraction groups revealed that (52.4%) of the affected group were females while (47.6%) of them were males. The difference wasn’t statistically significant.
Regarding residency, (81%) of the affected group were from rural area vs. (19%) were from urban area. The difference wasn’t statistically significant.
The optimal cutoff point of BNP level is >105.7 Pg /ml with 85.71% sensitivity, 96.2% specifity and 94% accuracy at week 6. Six weeks after DAAs termination, the optimal cutoff point of BNP level is >96.8Pg /ml with 57.14% sensitivity, 100% specifity and 91% accuracy. Every one Pg /ml increase in BNP level caused 8% increase in risk of developing affected cardiac function with (1.04-1.12) confidence interval and P value of <0.001 at week 6. Six weeks after DAAs termination, every one Pg /ml increase in BNP level caused 6% increase in risk of developing affected cardiac function with (1.03-1.09) confidence interval and P value of <0.001.
The optimal cutoff point of CPK-MB level is >25 IU/L with 100% sensitivity, 96.2% specifity and 97% accuracy at week 6. Six weeks after DAAs termination, the optimal cutoff point of CPK-mb level is >21.1 IU/L with 100% sensitivity, 92.41% specifity and 94% accuracy. Every one IU/L increase in CPK-mb level caused 38% increase in risk of developing affected cardiac function with (1.17-1.63) confidence interval and P value of <0.001 at week 6. Six weeks after DAAs termination, every one IU/L increase in CPK-mb level caused 44% increase in risk of developing affected cardiac function with (1.2-1.73)confidence interval and P value of <0.001.
The optimal cutoff point of TN-I level is >0.33 ng/ml with 100% sensitivity, 89.87% specifity and 92% accuracy at week 6. Six weeks after DAAs termination, the optimal cutoff point of TN-I level is >0.3 ng/ml with 85.71% sensitivity, 100% specifity and 97% accuracy. Regarding TN-I level, high OR was of no value due to very wide CI.
The optimal cutoff point of heart rate is ≤58 beat/min with 57.14% sensitivity, 89.87% specifity and 83% accuracy at week 6. Six weeks after DAAs termination, the optimal cutoff point of heart rate is ≤57beat/min with 47.62% sensitivity, 96.2% specifity and 86% accuracy. Every one beat /min increase in heart rate caused 14% decrease in risk of developing affected cardiac function with (0.78-0.93 ) confidence interval and P value of <0.001 at week 6. Six weeks after DAAs termination, every one beat/ min increase in heart rate level caused 15% decrease in risk of developing affected cardiac function with (0.77-0.93) confidence interval and P value of 0.001.
The optimal cutoff point of P wave is >97 ms with 52.38% sensitivity, 100% specifity and 90% accuracy six weeks after DAAs termination. Every one millisecond increase in P wave duration caused 27% increase in risk of developing affected cardiac function with (1.12-1.43) confidence interval and P value of <0.001 six weeks after DAAs termination .
The optimal cutoff point of PR interval is >171 ms with 52.38% sensitivity, 100% specifity and 90% accuracy at week 6. Six weeks after DAAs termination, the optimal cutoff point of PR interval is >175 ms with 38.1% sensitivity, 100% specifity and 87% accuracy. Every one millisecond increase in PR interval caused 8% increase in risk of developing affected cardiac function with (1.02-1.14) confidence interval and P value of 0.005 at week 6, six weeks after DAAs termination, and every one millisecond increase in PR interval caused 6% increase in risk of developing affected cardiac function with (1.02-1.11) confidence interval and P value of 0.007.
The optimal cutoff point of QRS width is >102 ms with 71.43% sensitivity, 84.81% specifity and 82% accuracy at week 6. Six weeks after DAAs termination, the optimal cutoff point of QRS width is >118 ms with 71.43% sensitivity, 96.2% specifity and 91% accuracy. Every one millisecond increase in QRS width caused 12% increase in risk of developing affected cardiac function with (1.06-1.17) confidence interval and P value of <0.001at week 6, six weeks after DAAs termination, every one millisecond increase in QRS width caused 13% increase in risk of developing affected cardiac function with (1.08-1.19) confidence interval and P value of <0.001.
The optimal cutoff point of QT interval is > 425 ms with 71.43% sensitivity, 83.54% specifity and 81% accuracy six weeks after DAAs termination. Every one millisecond increase in QT interval caused 13% increase in risk of developing affected cardiac function with (1.05-1.23) confidence interval and P value of 0.002 six weeks after DAAs termination.