Prevalence of Periprocedural Complications and Associated Factors of Percutaneous Coronary Intervention in Patients with Ischemic Heart Disease at Coronary Care Units of Tikur Anbessa Specialized Hospital and Gesund Cardiac and Medical Center, Addis Ababa, Ethiopia: A Retrospective Cohort Study

Introduction

Cardiovascular disease (CVD) is a major contributor to early mortality and rising medical costs. Within three decades, the overall CVD prevalence nearly doubled.^1–3

According to the World Health Organization, over 30% of Ethiopians died from non-communicable diseases in 2014, with cardiovascular disease (CVD) accounting for 9% of these deaths. However, a comprehensive analysis found that the prevalence of CVD in Ethiopia ranged from 7.2 to 24%.^4,5

Ischemic heart disease (IHD) is caused by atherosclerotic changes in the coronary arteries.⁶ Clinically, coronary artery disease (CAD) presents as either an acute or chronic coronary syndrome.⁷ Growing rates of diabetes, obesity, hypertension, metabolic syndrome, and population aging are all contributing to an increase in the incidence of IHD.⁸ More than 126 million people worldwide are afflicted by this illness.⁹

The eighth-leading cause of mortality for both men and women in the area is IHD, which was long thought to be uncommon in sub-Saharan Africa. The incidence of IHD and related morbidity may also be rising due to unfavorable behavioral and lifestyle changes.¹⁰ Hospital-based research has established that CAD is a significant health concern, despite the fact that larger studies illustrating the magnitude of the problem in the population are scarce in Ethiopia.¹¹ From May 1, 2007, to December 30, 2011, 300 patients had diagnostic coronary angiography at the Addis Cardiac Centre in Addis Ababa, Ethiopia. 227 (75.7%) individuals with catheterization showed signs of CAD.¹²

Percutaneous coronary intervention (PCI) is a minimally invasive, wire- or catheter-based procedure used to dilate the lumen of coronary arteries to treat coronary artery stenosis or obstruction and enhance blood flow to ischemic tissue, which is often accomplished with ballooning the narrow segment or deploying a stent to keep the artery open, these being the most effective.¹³

Andreas Grüntzig performed the first percutaneous transluminal coronary angioplasty in 1977.^14,15 After Dr. Fikru Maru Wordofa, a cardiologist, established the nation’s first catheterization laboratory, Dr. Bekele Alemayehu Shashu, an interventional cardiologist, performed the first coronary angiography and PCI at Addis Cardiac Hospital in 2007.¹⁶

PCI is a frequent invasive cardiac procedure with a low likelihood of complications. PCI complications have a large impact on patient healthcare costs, as well as severe morbidity and mortality. Major PCI problems are rare but can have disastrous effects if not effectively controlled.¹⁷ PCI-related problems are getting less common compared with the early days of balloon angioplasty.^18–20 Adverse effects of PCI can include myocardial injury, hemodynamic or electrical instability, tamponade, peripheral vascular injury with bleeding, stroke, acute renal injury, or fatalities.^17,21–23 Acute problems are less common overall as a result of improvements in mechanical devices, pharmacotherapies, and PCI procedures.^24–29

As mentioned above, IHD is becoming more and more common. Currently, PCI is among the most commonly performed cardiac interventions and this procedure is well known to be associated with rare but life-threatening complications. There has yet to be a study that evaluated the incidence or prevalence of periprocedural complications and the factors that influence PCI in Ethiopia. With a particular focus on periprocedural bleeding, stroke, and CIN and the associated factors, this study offers information on the frequency of PCI-related complications and associated risk factors.

Research Methodology

A retrospective cohort study was conducted on the prevalence and associated factors of periprocedural complications of percutaneous coronary intervention in patients with IHD at Coronary Care Units of Gesund Cardiac and Medical Center and Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia from May 1, 2017 to June 30, 2022.

The cardiac unit provides treatment and follow up for both inpatient and outpatient clients. The coronary care unit which is under the cardiac unit was established May 2017 and the catheterization laboratory has run since then. Gesund Cardiac and Medical Center is one of the private cardiac facilities in Addis Ababa, Ethiopia.

Study Participants

Inclusion Criteria

We included patients with age 18 years and above who underwent PCI for diagnosis of both ACS and CCS from May 1, 2017 to June 30, 2022 at TASH and GCMC.

Exclusion Criteria

• Patients with estimated GFR less than 30 ml/min/1.73M² based on CKD-EPI calculator
• Patients on dialysis
• Patients with unilateral kidney
• Patients who have undergone renal transplantation
• Patients who have history of CIN
• Patients who have AKI
• Patients with sepsis
• Patients who survived cardiac arrest
• Patients with incomplete data or lost charts

All patients who underwent percutaneous coronary intervention at Coronary Care Units of Tikur Anbessa Specialized Hospital and Gesund Cardiac and Medical Center from 1 May, 2017 to 30 June, 2022 were included in the study. A total of 236 participants were included in the study.

Data Collection Procedure

A structured questionnaire and checklists were developed after review of relevant literatures. Data on socio-demographics, clinical and behavioral characteristics, co-morbid disease, and drugs relevant to this study was retrieved by chart and electronic record review using a structured questionnaire. Data on periprocedural complications were collected from procedure notes and patient charts.

Operational Definitions

• Adequate post procedural hydration: Patient received Intravenous fluid at a dose of 1 ml/kg/h for at least 6 hours.
• Contrast induced nephropathy: A rise in serum creatinine by ≥0.5 mg/dl or an increment by 25 or more percent from its baseline value within 24–72 hours after administration of contrast media.
• Major bleeding: Patients with intracranial hemorrhage or a ≥5 g/dl decrease in hemoglobin concentration or a ≥15% absolute decrease in hematocrit within 72 hours of procedure.
• Minor bleeding: Observed blood loss, ≥3 g/dl decrease in hemoglobin concentration or ≥10% decrease in hematocrit within 72 hours of procedure.
• Percutaneous coronary intervention: A procedure involving either balloon angioplasty or stent deployment of the coronary arteries.

Data Analysis

After checking the data for consistency, completeness, clarity, and accuracy, they were coded manually, then fed into a spreadsheet. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 26.0. Socio-demographic data were described by descriptive analysis. Mean and standard deviation were used to describe continuous variables and percentage and frequency were used to express categorical variables. The prevalence of periprocedural bleeding, stroke, and CIN were expressed using percentages. After assessing multicollinearity test, univariate and multivariate logistic regression analyses were performed to determine the association of independent variables with periprocedural bleeding and CIN. P-value less than 0.05 were considered to determine the statistical significance of the associations.

Ethical Clearance

The Institutional review board of AAU gave ethical clearance to conduct this study and permission was requested from the cardiology unit at TASH and GCMC prior to data collection. Since the data were collected retrospectively, no consent was required from study participants. Participants’ identity remained confidential. Individuals’ anonymity is protected. Ethical principles of the Declaration of Helsinki were respected during all processes of the study.

Results

Socio-Demographic Characteristics of the Study Participants

A total of 236 patients who underwent PCI were included in the study out of 317 retrieved charts (response rate 74.5%). The remaining patient charts were excluded due to: 46 patients with lost charts, 11 patients had acute kidney injury prior to PCI, 2 patients were post cardiac arrest, 7 patients had CKD with estimated GFR<30 ml/min/1.73m² and the remaining patients had sepsis.

The majority, 198 (83.9%), of the participants were males. The mean (SD) age of the study participants was 58.58±11.13 years with range between 29–89. One hundred and thirty-four (56.8%) of the participants were between 55–74 years of age. Only 35 (14.8%) of the study participants had a history of smoking with median (IQR) pack years of 12 (IQR = 7–20). More than half (20) of those with smoking history were active smokers.

The socio-demographic characteristics are shown in Table 1 below.

Table 1 Socio-Demographic and Behavioral Characteristics of the Study Participants at Coronary Care Units of Tikur Anbessa Specialized Hospital and Gesund Cardiac and Medical Center, Addis Ababa, Ethiopia, 2022

Clinical Characteristics of the Study Participants

Clinical Characteristics

The median systolic and diastolic blood pressure of the study participants during admission were 130 (IQR = 110, 140) and 80 (IQR = 70, 80), respectively, with median mean arterial pressure of 80 (IQR = 70, 80). Out of the 43 patients with documented BMI, 19 (44.2%) had normal BMI, 20 (46.5%) were overweight, and the remaining 4 (9.3%) of the patients were obese.

Acute coronary syndrome (ACS) was the most frequent clinical diagnosis in the participants, reported in two-thirds of the patients who underwent PCI. Among patients with ACS, STEMI was the most frequent diagnosis which was found in 123 (77.9%) of patients. The rest of the patients with ACS had NSTEMI, 31 (19.6%), and only 4 (2.5%) patients had unstable angina. Chronic coronary syndrome was found in 78 (33.1%) of the patients.

Among patients with ACS, 98 (63.6%), 47 (30.5%), 8 (5.3%), and only one (0.6%) of the patients had Killip class I, II, III, and IV ACS, respectively. All patients underwent echocardiographic assessment and determination of left ventricular systolic function before PCI. 121 (51.3%), 45 (19.1), and 70 (29.7%) of the patients had ejection fraction of ≥50%, 41–49%, and ≤40%, respectively.

Acute coronary syndrome presentation of patients with ischemic heart disease who underwent PCI is shown in Figure 1.

Figure 1 Acute coronary syndrome presentation of patients with ischemic heart disease who underwent PCI at Coronary Care Units of Tikur Anbessa Specialized Hospital and Gesund Cardiac and Medical Center, Addis Ababa, Ethiopia, 2022.

Co-morbidities

Half (118) of the study participants had hypertension and 89 (75.4%) of them were on treatment. The prevalence of diabetes mellitus and dyslipidemia among the study population were 121 (51.3%) and 51 (21.6%), respectively. Nearly 90% of those with diabetes mellitus and 47.1% of those with dyslipidemia were on medication. Furthermore, chronic kidney disease was reported in 11 (4.7%) of the patients; 6 (54.5%) of them had an estimated GFR of 30 ml/min/1.73M² to 44 ml/min/1.73M², while the remaining 5 had an estimated GFR of 45 ml/min/1.73M² to 59 ml/min/1.73M².

Co-morbidities among patients with ischemic heart disease who underwent PCI are shown in Figure 2.

Figure 2 Co-morbidities among patients with ischemic heart disease who underwent PCI at Coronary Care Units of Tikur Anbessa Specialized Hospital and Gesund Cardiac and Medical Center, Addis Ababa, Ethiopia, 2022.

Medications

Drug intakes of the study participants are shown in Figure 3. For diabetes mellitus, 90 (38.1%), 32 (13.6%), 17 (7.2%), 3 (1.3%), and 5 (2.1%) of the patients were taking metformin, insulin, sulfonylurea, SGLT2 inhibitors, and DPP4 inhibitors, respectively. The most commonly used medication for hypertensive patients were RAS inhibitors 50 (56.2%), beta blockers 41 (46.1%) and Diuretics 35 (39.3%). Beta blockers (17.8%), RAS inhibitors 25 (10.6%), MRA 15 (6.4%) and diuretics 43 (18.2%) were also given for patients with diagnosis other than hypertension after being diagnosed with IHD or heart failure. 88 (37.3%) of the patients were on statins. Double antiplatelet agents were used in 168 (71.2%) patients. All patients with ACS were taking dual antiplatelet agents (aspirin and clopidogrel) and anticoagulant, unfractionated heparin in 152 (64.4%) and enoxaparin in 6 (2.5%). Four patients received warfarin for concomitant left ventricular thrombus.

Figure 3 Medications given for patients with ischemic heart disease who underwent PCI at Coronary Care Units of Tikur Anbessa Specialized Hospital and Gesund Cardiac and Medical Center, Addis Ababa, Ethiopia, 2022.

Medications among patients with ischemic heart disease who underwent PCI are shown in Figure 3.

Clinical and treatment-related characteristics of the study participants are shown in Table 2.

Table 2 Clinical and Treatment-Related Characteristics of the Study Participants at Coronary Care Units of Tikur Anbessa Specialized Hospital and Gesund Cardiac and Medical Center, Addis Ababa, Ethiopia, 2022

Prevalence of Periprocedural Complications of PCI

Contrast Induced Nephropathy

During the study period, out of the 236 patients who underwent PCI, 201 of them had documented pre- and post-procedure creatinine determination. 201 participants were included for assessment of development of CIN. The mean baseline and post-procedural serum creatinine were 1.02±0.26 and 1.09±0.34, respectively. Out of the 201 patients, 18 (9%) developed CIN. Hydration with intravenous fluids was reported in 187 (79.2%) of the patients.

Among patients who developed CIN the mean pre- and post-PCI creatinine were 1.15±0.37 and 1.72±0.44, respectively. For pre- and post-procedure, the mean serum creatinine difference was −0.58±0.14, which was significantly higher post-PCI (P <0.001).

The mean serum creatinine differences of pre- and post-procedure are shown in Figure 4.

Figure 4 The mean serum creatinine difference of pre- and post-procedure which was significantly higher post-PCI (Left) and no mean difference in the group with no CIN (Right).

Bleeding

The study sample consisted of 217 (91.9%) patients who underwent PCI over the period under study who had documentation on the presence or absence of post-procedural bleeding as documented by the treating physician and 163 (69.1%) patients with both pre- and post-procedure hemoglobin level determination.

Out of the 163 patients with both pre- and post-procedure hemoglobin, hemoglobin drop was reported in 120 (73.6%). One hundred and four (63.8%) of the patients had hemoglobin drop <3 g/dl which does not fulfill the criteria for minor bleeding.

The prevalence of minor bleeding which was defined by hemoglobin drop of ≥3 g/dl to 5 g/dl, was 16 (9.8%) out of 163 patients with both pre- and post-procedure hemoglobin results. The mean pre- and post-procedural hemoglobin score among patients with hemoglobin drop between ≥3 g/dl to 5 g/dl were 16.04±2.36 g/dl and 12.25±2.46 g/dl, respectively. Among those with documented bleeding or minor bleeding as defined by hemoglobin drop of ≥3 g/dl to 5 g/dl, only two required transfusion. There was a statistically significant mean difference of 3.79±0.72 g/dl between pre- and post-PCI hemoglobin with the lower documented post-procedure (P <0.001).

Factors Associated with Complications Among Patients Who Underwent PCI

Contrast Induced Nephropathy

Independent variables were checked for the presence of association with CIN in bivariate logistic regression analysis. Smoking history, diuretics use, and CKD were found to be associated with CIN in bivariate analysis (P <0.05) and were entered for multi-variable logistic regression.

We carried out a multivariable logistic regression in which these factors were modeled against a dependent variable of presence of CIN. In this analysis (Table 2), the model explained only 7–16% of the variation (Cox and Snell R² = 0.073, Nagelkerke R² = 0.16) in outcome. All the three factors were found to have significant association with the occurrence of CIN.

On multivariate analysis, the likelihood of having CIN was 3.4 times higher among patients with smoking history as compared with those who do not have smoking history (AOR: 3.374, 95% CI (1.092,10.421)). Diuretic use increased by 3.9 times the chance of having CIN compared with patients who did not take diuretics (AOR: 3.858, 95% CI (1.357, 10.965)). Furthermore, the odds of having CIN are 6.2 times higher among patients with CKD than those without (AOR: 6.188, 95% CI (1.346, 28.458)).

Multivariable logistic regression to assess factors associated with CIN complications are shown in Table 3.

Table 3 Multivariable Logistic Regression to Assess Factors Associated with CIN Complications in Patients with Ischemic Heart Disease who Underwent PCI at Coronary Care Units of Tikur Anbessa Specialized Hospital and Gesund Cardiac and Medical Center, Addis Ababa, Ethiopia, 2022

Bleeding

Age, sex, smoking history, CKD, type of IHD, ACS type, Killip class and ejection fraction were the independent variables checked for the presence of association with post PCI bleeding in bivariate logistic regression analysis. No significant association was found with any of the independent variables and post-PCI bleeding in bivariate analysis.

Univariate logistic regression to assess factors associated with bleeding complications are shown in Table 4.

Table 4 Univariate Logistic Regression to Assess Factors Associated with Bleeding Complication on Patients with Ischemic Heart Disease That Underwent PCI in Addis Ababa, Ethiopia, 2022

Discussion

This study aimed to assess the prevalence and predictors of periprocedural complications of PCI in patients with ischemic heart disease at Coronary Care Units of Tikur Anbessa Specialized Hospital and Gesund Cardiac and Medical Center, Addis Ababa, Ethiopia.

The most common co-morbid condition found in the study was hypertension, while diabetes and dyslipidemia were the second and the third, respectively. The findings were higher than a study in Egypt and lower than a study in India.^30,31 This might be due to the differences in the study setting, patient population, and smaller sample size in ours compared with the Indian study. The reason behind these co-morbidities being most prevalent might be the fact that these illnesses are the most common causes for vascular injury and IHD.

The study revealed that the prevalence of CIN was found to be 9%. Our study showed a lower prevalence of CIN compared with studies from Egypt, China, and India.^30–32 The prevalence of CIN in these studies was 10.6% in the Egyptian study, 15.3% in a study in China, and 29% in the Indian study. This may be due to the retrospective nature of our study and high non-response rate due to data loss.

Patients with pre-existent CKD have a higher risk of developing CIN. This is in alignment with studies.^31,33 This can be explained by the fact that an already compromised kidney function can get worse with administration of contrast.

As was found in our study, a study conducted in India identified diuretic use as strong risk factor for CIN development.³¹ Diuretics put patients undergoing PCI at risk of dehydration from over-diuresis which subsequently results in increased concentration of the contrast media in the renal tubules. This subsequently results in decreased renal blood flow and medullary hypoxia. Central venous pressure measurement is advocated by some studies in patients with heart failure to guide diuretic therapy.³⁴

Many studies and meta-analysis showed a significant association between occurrence of CIN with diabetes and hypertension.^31,33 In contrast, despite a high prevalence of hypertension and diabetes mellitus found in our study, these co-morbidities were not found to be associated with the occurrence of CIN.³⁵ Furthermore, the meta-analysis has found age, Killip class ≥2 and having decreased left ejection fraction as independent determinants for the occurrence of CIN. These factors were not found to be associated with CIN in our study. The reason for not showing significant association might be due to the small sample size in our study.

The prevalence of minor bleeding was found to be 9.8% in our study and there was no reporting of major bleeding incidents following PCI. Contrary to this finding, major bleeding incidence was reported to be 3.1%, 3.9%, and 3% from Japan, Grace Data from USA and France studies.^33,36,37 This discrepancy might be due to information bias in our study that occurred because we conducted a retrospective study design by assessing secondary data. Also, the small sample size, population and study setting differences might be reasons for this finding.

In contrast to other studies,^35,36 age, sex, diabetes mellitus, history of smoking, and medications were not associated with post-PCI procedure in our study. The reason for not showing significant difference might be due to the smaller proportion of these subjects and smaller sample size of our study.

Strengths and Limitations of the Study

The study tried to look at the different variables related to PCI complications and determinants of complications in two centers with different setups. This study also tried to involve all patients who underwent PCI procedure over the study duration which will increase representativeness and decrease information loss. Additionally this is the first study in our setup that assessed the prevalence and predictors of periprocedural complications of PCI, which may lay a ground for further prospective study.

Limitations of this study include its retrospective nature and use of medical record reports which are secondary data sources with missing information and absence of important investigation results in a proportion of patients. Results from different laboratories may also result in measurement bias and affect the outcome of the study. The sample size is also small which possibly affects the results in both negative and positive directions.

Conclusion

Our study found, a low prevalence of contrast induced nephropathy and bleeding among cardiac patients who underwent PCI. Smoking, diuretics use and having chronic kidney disease were found to have a significant association with periprocedural CIN in this population. There is no case of stroke among all the study population and no association was identified between bleeding and the independent factors in this study.

Recommendations

Based on the findings of this study we have made the following recommendations.

For Care Providers

• As the study demonstrated there is an association between diuretic use and potential dehydration of patients that worsens the occurrence of CIN which mandates that care providers should assess fluid status of patients closely to balance between dehydration and fluid overload based on the proposed guidelines with particular attention in patients with underlying CKD.

For Health Institutions

• The findings from this study may be used by health institutions to enforce protocols and guidelines in a standard management of post-PCI CIN and bleeding patients.
• Advocate renal protection strategies for high-risk patients.

For Future Researchers

• Since this is a cross-sectional study with difficult retrieval of medical records and outcomes, it will be best to conduct a prospective cohort study with better determination cause and effect relationship and further follow up for adverse events.