The relationship between the severity of coronary artery disease in angiography and the incidence of short-term major cardiovascular events of patients with Covid-19 and myocardial infarction: a cross-sectional study in Iran

doi:10.21203/rs.3.rs-2579378/v1

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The relationship between the severity of coronary artery disease in angiography and the incidence of short-term major cardiovascular events of patients with Covid-19 and myocardial infarction: a cross-sectional study in Iran

https://doi.org/10.21203/rs.3.rs-2579378/v1

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Background

Coronary artery disease (CAD) has been frequently recognized as a risk factor for poor prognosis in COVID-19 patients. Syntax score is an invasive coronary angiographic-based tool used to determine the severity of CAD. In this study, we aim to investigate the prognostic significance of syntax score for mortality and morbidity among COVID-19 patients.

Methods

In this cross-sectional study, we have included patients with confirmed COVID-19 diagnosis who underwent percutaneous coronary intervention (PCI). Based on angiographic records, the CAD complexity was measured by Syntax score, and echocardiographic variables were documented. The laboratory data were obtained from the HISS database of the hospital. All patients were followed up one month after discharge for new cardiovascular events, rehospitalization, heart failure (HF), stent thrombosis, cerebrovascular accidents, and death.

Results

In one month, 108 patients were included in the study. The mean age was 64.8 ± 11.6, and 74% were male. The Cox regression model found no association between the Syntax score and the composite outcomes. In the univariate cox proportional HR model, MPV, LDH, and ESR were found to have predictive significance for in-hospital death. AKI was resulted to be significantly associated with rehospitalization in multivariate analysis.

Conclusion

The present study did not find a significant association between adverse outcomes and syntax score in COVID-19 patients referred for PCI. Acute kidney injury and duration of ICU stay was found to be the main factor predicting rehospitalization and HF. Future studies are needed to confirm these findings.

Percutaneous coronary intervention

cardiovascular events

Covid-19

myocardial infarction

SARS-CoV2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has led to a global pandemic since 2019. This disease, also called coronavirus disease 2019 (COVID-19), initially emerged as an infectious disease, currently has been known to promote a multiorgan response (1). COVID-19 is associated with several cardiovascular complications (2). Coronary artery disease (CAD) is a significant cause of death worldwide (3). Inflammatory biomarkers play a crucial role in the pathogenesis of atherosclerotic plaque (4). Numerous studies have reported the paramount relationship between prior cardiac injury and myocardial infarction (MI) to higher mortality among COVID-19 patients (5). Invasive coronary angiography (CAG) is an essential diagnostic intervention to define underlying mechanisms and establish the proper treatment in patients with COVID-19 presenting with MI. The syntax score is an angiographic-based tool for grading the complexity of CAD (6). The relation between the extent of coronary lesions and the severity of SARS-CoV2 has been less argued; therefore, we aimed to explore the prognostic significance of angiographic characteristics measured by syntax score for mortality and morbidity.

Study Design And Participants:

This study was a single-center prospective cross-section study in Mousavi hospital for one month in Zanjan, Iran. The study was conducted under the principles of the Declaration of Helsinki and approved by the ethics committee of Zanjan University of medical sciences (IR.ZUMS.REC.1401.104). All the patients provided written informed consent. The study population included patients between 35 to 85 years old who presented with ST-elevation MI (STEMI) and were referred to our hospital for PCI. STEMI based on ECG, clinical symptoms, and troponin level who underwent successful primary angioplasty, and the COVID-19 disease was confirmed via PCR nasopharyngeal test. We used the Syntax score to quantify lesion complexity. Syntax score is an anatomic scoring system based on the coronary angiogram designed to anticipate better the risks of percutaneous or surgical revascularization (7). This tool classifies the patients based on the severity of CAD into three groups, i.e., mild (SS < 22), moderate (SS: 22–32), and severe (SS ≥ 33) CAD. A collaborative team of cardiologists assessed the angiographic films. A professional cardiologist performed echocardiography to obtain ejection fraction (EF) data.

The exclusion criteria included: 1) history of pulmonary parenchymal disease. 2) lack of PCR test 3) incomplete patient file data set.

Variables And Outcomes:

Patients' demographic data, in addition to the Syntax scores, were recorded in the checklist. Echocardiographic data were extracted from each patient's medical profile. The laboratory data were obtained from the HISS database of the hospital.

Patients were followed up through phone calls and clinic visits to be evaluated for new cardiovascular events, rehospitalization, heart failure, stent thrombosis, cerebrovascular accidents, and death.

Statistical analysis:

Data were analyzed using IBM SPSS Statistics software (version 24.0, SPSS, Chicago, Illinois) (8). Data normality was assessed using Kolmogorov-Smirnov Test. For descriptive analysis, Data normality was assessed using Kolmogorov-Smirnov Test. In the case of data normality, an independent t-test was used, and Mann-Whitney for non-normally distributed data. Cox proportional hazard regression models were used to identify the endpoints' predictive factors. A p-value < 0.05 was considered statistically significant.

This study was conducted on 108 COVID-19 patients with MI who underwent CAG. The baseline characteristics of the included patients are in Table 1. The mean age was 64.8 ± 11.6, and 74% were male. The most frequent underlying diseases were hypertension, followed by diabetes and dyslipidemia. Eighty-eight percent of patients complained of chest pain, 9.3% had dyspnea, and 2.8% presented with symptoms of syncope or impaired consciousness. The mean time of hospital stay was nine days. The total in-hospital death was 14.8%, and within 30 days after discharge, the death rate was 7.4% (Table 1). Overall, 22.2% of patients were re-hospitalized within one month, of which 12% were due to HF. Syntax score had a significant association with HDL and EF. The Cox regression model found no association between the Syntax score and the composite outcomes (Table 2). In the univariate Cox proportional HR model, MPV, LDH, and ESR were found to have predictive significance for in-hospital death (Table 3). For rehospitalization and 30-day mortality, no factors were found to be significantly associated (Table 4). AKI was resulted to be significantly associated with rehospitalization in multivariate analysis.

Table 1

Description of Study Cohort (n = 108).
	No. (%)	Mean ± SD
Male	74 (68.5)
Age (years)		64.8 ± 11.6
35–45	5 (4.6)
45–55	20 (18.5)
55–65	24 (22.2)
65–75	33 (30.6)
75–85	26 (24.1)
Body Mass Index		24.7 ± 2.7
Ejection Fraction (%)		43.0 ± 8.9
Syntax Score		22.6 ± 4.3
Underlying Comorbidities
Diabetes	35 (32.4)
Hypertension	43 (39.8)
Hyperlipidemia	23 (21.3)
Smoking	18 (16.7)
Cardiovascular disease	6 (5.6)
Prior CVA	1 (0.9)
Prior PCI	6 (5.6)
Adverse Outcomes
Atrial Fibrillation	3 (2.8)
Ventricular Tachycardia	1 (0.9)
Complete Heart Block	1 (0.9)
Acute Kidney injury	4 (3.7)
In-hospital Death	16 (14.8)
30-day Death	8 (7.4)
30-days Rehospitalization	24 (22.2)
30-days Heart Failure	13 (15.9)
Culprit Vessels in PCI
LAD	56 (51.9)
RCA	36 (33.3)
LCX	11 (10.2)
LCA	5 (4.6)
Stent Thrombosis	2 (1.9)

Table 2

Cox model of the association of Syntax score with adverse outcomes.
Outcomes	Hazard Ratio	P > z	95% Confidence interval
In Hospital death	1.18	0.25	(0.32; 4.25)
30-day death	0.91	0.43	(0.72; 1.14)
30-day heart failure	1.03	0.96	(0.21; 5.06)
Rehospitalization	3.31	0.06	(0.94; 11.6

Table 3

Factors Associate with In-hospital Death by Univariate Cox proportional Hazard Ratio Model.
Covariates	Coefficient	HR (95% CI)	P value
Age (median, years)	-0.70	0.98 (0.93, 1.03)	0.48
Sex (ref: Male)	-0.24	0.87 (0.29, 2.61)	0.81
BMI (≤ 25,>25kg/m2)	-1.32	0.86 (0.69, 1.07)	0.18
Diabetes Mellitus	-1.67	0.36 (0.11, 1.18)	0.09
Hypertension	-0.73	0.63 (0.19, 2.12)	0.46
Smoking	-0.68	0.63 (0.17, 2.31)	0.49
Fasting blood sugar mg/dl (75–110)	-1.21	0.99 (0.98, 1.00)	0.22
Triglyceride (< 150mg/dl)	0.76	1.00 (0.99, 1.01)	0.44
Total Cholesterol (< 200mg/dl)	0.33	1.00 (0.98, 1.02)	0.73
Hemoglobin g/L (11.5–15)	1.88	2.39 (0.96, 5.97)	0.06
White Blood count ×10E + 9/L (4.1–10)	-0.52	0.95 (0.78, 1.15)	0.60
Lymphocyte count ×10E + 9/L (1.1–3.2)	1.62	1.08 (0.98, 1.19)	0.10
Mean platelet volume ×10E + 9/L (135–350)	-2.82	0.17 (0.05, 0.58)	0.005
Lactate dehydrogenase, U/L (109–245)	-2.06	0.99 (0.98, 0.99)	0.04
ESR, mm/h (< 10- ≥10)	-2.69	0.93 (0.88, 0.98)	0.007
CPR mg/dL (< 4)	-0.92	0.98 (0.95, 1.01)	0.35
Ejection Fraction (≤ 50->50)	1.89	1.06 (0.99, 1.13)	0.058

Table 4

Factors Associate with Rehospitalization by Univariate Cox proportional Hazard Ratio Model.
Covariates	Coefficient	HR (95% CI)	P value
Age (median years)	0.64	1.01 (0.97, 1.04)	0.519
Sex (ref: Male)	-0.81	0.66 (0.24, 1.79)	0.41
BMI (≤ 25,>25kg/m2)	-0.31	0.97 (0.80, 1.16)	0.80
Diabetes Mellitus	-0.27	0.89 (0.39, 2.00)	0.78
Hypertension	0.85	1.46 (0.60, 3.51)	0.39
Smoking	0.12	1.06 (0.41, 2.72)	0.90
Fasting blood sugar mg/dl (75–110)	-0.62	0.99 (0.99, 1.00)	0.53
Triglyceride (< 150mg/dl)	1.07	1.00 (0.99, 1.00)	0.99
Total Cholesterol (< 200mg/dl)	0.80	1.00 (0.99, 1.01)	0.80
High-density lipoprotein (Men: ≥40mg/dl, Women ≥ 50)	-0.11	0.99 (0.91, 1.08)	0.91
Hemoglobin g/L (11.5–15)	-1.11	0.73 (0.42, 1.26)	0.26
White Blood Count ×10E + 9/L (4.1–10)	-0.02	0.99 (0.82, 1.21)	0.98
Lymphocyte count ×10E + 9/L (1.1–3.2)	-0.72	0.94 (0.82, 1.09)	0.47
Mean platelet volume ×10E + 9/L (135–350)	0.24	1.12 (0.43, 2.91)	0.81
Lactate dehydrogenase, U/L (109–245)	0.03	1.00 (0.99, 1.00)	0.97
ESR, mm/h (< 10- ≥10)	-0.44	0.99 (0.96, 1.02)	0.66
CPR, mg/dl (< 4)	0.77	1.01 (0.98, 1.04)	0.44
Ejection Fraction (≤ 50- >50)	-1.40	0.97 (0.93, 1.01)	0.16

The current literature on mortality among patients with concomitant COVID-19 and CAD acknowledges an elevated risk of adverse outcomes (9, 10). However, this contrasts our results which failed to achieve a significant level as a higher syntax score did not alter the composite endpoints. A study in Netherland found that the burden of coronary lesions and stent thrombosis was high among COVID-19 patients referred for CAG (11). CAD has been frequently recognized as a risk factor for poor prognosis in COVID-19 patients and is associated with the severity of COVID-19 disease (12). Nai Fovino et al. demonstrated that COVID-19 patients with higher coronary calcium score detected at HRCT had a higher risk of worse in-hospital complications, including death (13).

Moreover, both clinical and subclinical CAD was associated with major cardiovascular events independent of comorbidities and the severity of COVID-19 disease (14). Such findings highlight the interplay of SARS-Cov2 infection and the pathophysiology of atherosclerotic plaque formation. Chronic inflammation in the context of COVID-19 disease is a promoter for the activation of endothelium and platelets, facilitating atherosclerotic development. Therefore, the marked platelet-monocyte aggregation drives a state of thromboinflammation in COVID-19 (15).

In this study, the primary determinant marker of the rehospitalization rate was acute kidney injury (AKI). Similar to our results, the study of Barman et al. investigating the prognostic importance of cardiac injury measuring high sensitivity cardiac troponin I serum levels, acute kidney injury, and LDH were found to be associated with a lower rate of survival (16). The exacerbated previous chronic renal failure was one of the main pre-existing conditions that independently predicted rehospitalization after one year (17).

The detection of HF may have been underrated concerning the overlapping radiological presentations of COVID-19 and HF. The endothelial damage of SARS-Cov2 can activate thrombin and complement systems that would eventually contribute to the formation of thrombi within the vasculature; thus, the subsequent MI and HF can establish. Additionally, chronic hypoxia due to respiratory failure can induce right HF. Current evidence suggests a direct invasion of SARS-CoV-2 to the myocardium. The virus inclusions within the myocardium may promote restrictive infiltrative cardiomyopathy leading to HF (18). We have reported that length of stay in the intensive care unit (ICU) was an independent factor in predicting new-onset HF in hospitalized COVID-19 patients. Furthermore, Bin Saleh et al. reported that COVID-19 patients with HF, compared to their counterparts without HF, carried significantly higher mortality rates (19). In addition, atrial arrhythmias during admission had the highest odds ratio (OR) for predicting acute HF during follow-up in COVID-19 patients (20).

In this study, high BMI contributed to acute HF in the course of COVID-19 disease. Likewise, in a retrospective cohort study, obesity significantly predicted severe COVID-19 among young patients (21). Moreover, MPV was a significant parameter for in-hospital death, which is in line with the study of Aydinyilmaz et al., where MPV was associated with greater mortality with the area under the curve of 0.718 (22).

A lower syntax score was associated with decreased EF in our study population. Residual syntax score was a principal prognostic factor for in-hospital congestive HF (23). More recently, a new tool for the risk stratification of patients with complex CAD has been introduced that combined syntax score with age, creatinine, and EF (ACEF), and this combination has gained more ability to predict major adverse cardiovascular events (MACE) in patients undergoing PCI (24).

This study contains several limitations. A significant limitation of this study is the cross-sectional study design; therefore, the causal relationship between syntax score and the severity of COVID-19 needs to be clarified. The small sample size hinders the findings from being extrapolated to all COVID-19 patients with potential CAD.

The present study did not find a significant association between adverse outcomes and syntax score in COVID-19 patients referred for CAG. AKI and duration of ICU stay were found to be the main factor predicting rehospitalization and HF, respectively. Additionally, the syntax score was significantly associated with EF. Future large-scale studies are warranted to confirm such results.

AKI: Acute kidney injury

ICU: Intensive care unit

HF: Heart failure

EF: Ejection fraction

CAD: Coronary artery disease

LDH: Lactate dehydrogenase

CAG: Coronary artery angiography

PCI: Percutaneous coronary intervention

STEMI: ST elevation myocardial infarction

ECG: Electrocardiogram

PCR: Polymerase chain reaction

HRCT: High-resolution computed tomography

BMI: Body mass index

MPV: Mean platelet volume

ACEF: Age, creatinine, ejection fraction

MACE: Major adverse cardiovascular events

Ethics approval and consent to participate:

The study was conducted under the principles of the Declaration of Helsinki and approved by the ethics committee of Zanjan University of medical sciences (IR.ZUMS.REC.1401.104). All the patients provided written informed consent.

Consent for publication:

Not applicable.

Availability of data and materials:

The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.

Competing interests:

The authors contributing to the study have nothing relevant to disclose.

Funding:

None declared.

Authors' contributions:

Z.k, R.M, S.K and H.A collaborated in the design of the study and methodology. S.G, M.M, Z.k, R.M and S.K collaborated in the validation and data collection. K.M and R.H collaborated in data analysis. S.G, Z.K, M.M and S.K collaborated in writing, editing and designing the article. All authors read and approved the final manuscript.

Acknowledgment:

The authors would like to thank the Clinical Research Development Center of Ayatollah Mousavi Hospital, Zanjan University of Medical Sciences, Zanjan, Iran, for their cooperation and assistance throughout the study.

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No competing interests reported.

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The relationship between the severity of coronary artery disease in angiography and the incidence of short-term major cardiovascular events of patients with Covid-19 and myocardial infarction: a cross-sectional study in Iran

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Introduction

Methods

Study Design And Participants:

Variables And Outcomes:

Statistical analysis:

Results

Discussion

Conclusion

List Of Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1