Abstract
Objectives
The objective of this research was to investigate the correlation between the SYNTAX score II (SS-II), a measure of the occurrence of coronary artery disease and mortality over a 4-year period, and factors that increase the susceptibility of individuals to atherosclerosis in coronavirus disease-2019 (COVID-19) patients diagnosed with non-ST-elevation myocardial infarction (NSTEMI).
Materials and Methods
We retrospectively examined 200 NSTEMI patients with COVID-19 who applied to Adıyaman Training and Research Hospital between 01.07.2021 and 01.11.2021. We recorded demographic data (age, gender), comorbid diseases, laboratory parameters (hemogram, biochemistry, serological test results), thorax computed tomography findings (COVID-19-compatible or not), angiography results, intervention needs, and mortality status. COVID-19 was confirmed by positive reverse transcription polymerase chain reaction. All patients had SS values and SS-II values calculated. Based on a median SS II value of 28.5, the patients were classified into the low and high SS-II groups.
Results
The high-SS-II group exhibited elevated total cholesterol, low-density lipoprotein, carotid intima-media thickness (CIMT), and left ventricular ejection fraction values (p<0.001). Logistic regression analysis revealed that CIMT (odds ratio: 3.124, 95% confidence interval: 1.744-5.628; p<0.001) was an independent predictor of SS-II.
Conclusion
In patients with NSTEMI and COVID-19, CIMT and SS-II might increase the risk of atherosclerosis. The combination of NSTEMI and COVID-19 increases mortality.
Introduction
Hubei Province’s Wuhan province announced a new coronavirus epidemic in December 2019. This sickness spreads uncontrollably. Coronavirus disease-2019 (COVID-19) most often affects the respiratory system, whereas cardiac dysfunction often draws attention to the cardiovascular (CV) system(¹). In an extensive case series, older patients with CV died the most and were most affected by the pandemic(²). A thorough COVID-19 case count of 72.314 was obtained from the Chinese Center for Disease Control and Prevention. Of 87% of 30-to 79-year-olds, 2.3% died. Mortality was 8% for patients aged 70-79 years and 14.8% for those aged 80+. Comorbidities increased diabetes CV mortality (10.5%)(1, 3).
COVID-19 causes myocardial infarction (MI), myocarditis, heart failure (HF), arrhythmia, and venous thromboembolism. Risk-averse patients with CV infection with COVID-19 postpone hospital admission, which worsens outcomes(4, 5). On myocardial cells, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can cause cardiac dysfunction. On angiotensin-converting enzyme 2 receptors, the virus strongly activates the innate immune system, producing proinflammatory cytokines and inducing systemic inflammation. A “cytokine storm” causes widespread endothelium and procoagulant activity(6). Local and systemic coagulation, platelet activation, and immunothrombosis increase with SARS-CoV-2 infection(7).
The severity of non-ST-elevated MI (NSTEMI) is dependent on clinical and laboratory findings(8). Coronary atherosclerosis causes NSTEMI. Clinical decision-making depends on risk categorization. Early risk, clinical syndrome, and therapy for NSTEMI determine mortality(9). Risk scoring is used by acute coronary syndrome (ACS) cardiologists to assess coronary artery disease (CAD) severity and complexity(9). The lack of clinical factors in the SYNTAX score (SS) has been recognized as a notable constraint when used for patients with intricate CAD in terms of classification ability. Recently, researchers have created SS-II as a new solution to overcome this constraints(10). Researchers have linked SS-II to both angiographic (anatomic SS) and clinical factors, including age, gender, left ventricular ejection fraction (LVEF), creatinine clearance, chronic obstructive pulmonary disease (COPD), and peripheral vascular disease(11). The application of this method allows for a more precise and personalized prediction of mortality, resulting in a clinically valuable tool for making decisions at the patient’s bedside and managing complex CAD(12).
To our knowledge, no study has examined the SS-II score for predicting lesion complexity in NSTEMI patients who survived COVID-19 without sequelae. Therefore, we believe our study will add to the literature. Therefore, we thought it appropriate to conduct a study on SS-II analysis in such patients.
Materials and Methods
Study Design
We retrospectively examined 200 NSTEMI patients with COVID-19 who applied to Adıyaman Training and Research Hospital between 01.07.2021 and 01.11.2021. The local ethics committees approved this Declaration of Helsinki-compliant study. Ethics committee approval was obtained from the Ethics Committee of Adıyaman University Non-Invasive Clinical Research (approval no.: 2021/04-15, date: 20.04.2021). All patients gave informed consent. We selected 213 patients with NSTEMI who underwent coronary angiography (CA) for the study. After determining the exclusion criteria, we admitted 200 consecutive eligible patients to our coronary care unit. At least 48 hours of cardiac troponin levels exceeding the 99th percentile upper reference limit and new or worsening chest discomfort at rest or with moderate effort defined NSTEMI. Abnormal chest discomfort occurred for more than 20 minutes, new-onset angina occurred, and its frequency, duration, and severity were increased. Heart troponin was detected at 0.04 ng/mL on the Alere Triage MeterPro [(Alere Inc., San Diego, California, United States of America (USA)]. The SS, which uses natural coronary arteries, has been found to exclude the recent coronary artery bypass graft patients(13). None had cardiogenic shock. Intrastent restenosis is also classified as de novo lesions. We recorded demographic data (age, gender), comorbid diseases, laboratory parameters (hemogram, biochemistry, serological test results), thorax computed tomography findings (COVID-19-compatible or not), angiography results, intervention needs, and mortality status. COVID-19 was confirmed by positive reverse transcription polymerase chain reaction (RT-PCR).
Study Protocol
Use of antihypertensive medication or arterial blood pressure >140/90 more than once defines hypertension (HT). Diabetes mellitus (DM) as ≥126 mg/dL fasting blood glucose or current antidiabetic medication use. Hyperlipidemia was diagnosed in patients with total cholesterol >200 mg/dL, triglycerides >150 mg/dL, and dyslipidemia or antilipidemic therapy. Active smoking was defined as 1 pack per year until 1 month before trial participation. Sudden cardiac death in male or female first-degree relatives under 55 or 65 was considered chronic HF. In the apical 4-chamber view, M-mode echocardiography measured the LVEF. Body mass index was calculated as weight in kg divided by height in meters squared.
In numerous angulated views, the Judkins method was used for femoral selective CA at 30 frames/s (Allura Xper FD10; Philips Healthcare, Best, The Netherlands). Separately, two invasive cardiologists evaluated coronary angiograms under clinical blinding. At least 50% luminal diameter stenosis in one major coronary artery is considered a significant vascular disease. For coronary lesions with a diameter stenosis ≥50% in arteries ≥1.5 mm, scores were required. In interventional cardiology, SS was determined using tertiles (<32, >32). We defined SS-II [percutaneous coronary intervention (PCI) and bypass] based on patient clinical characteristics(6). Based on a median SS-II value of 28.5, the patients were classified into the low and high SS-II groups.
Statistical Analysis
Statistic calculations were performed using IBM SPSS Statistics for Windows, Version 21.0 (IBM Corp., Armonk, New York, USA). Categorical variables were calculated using numbers and ratios. Mean ± standard deviation was used for regularly distributed data, whereas median (interquartile range) was used for non-normally distributed data. The Kolmogorov-Smirnov test confirmed data normality. Student’s t-test and Mann-Whitney U test were used to compare the two groups. Categorical variables were tested using the chi-square. The multivariate logistic regression analysis included possible risk factors identified by the univariate logistic regression analysis (p<0.25). Finally, forward logistic regression identified the most dissimilar factors between the groups. P<0.05 qualifies as statistically significant.
Results
The study included 200 patients with NSTEMI (mean age: 62.3±12.5 years, 65% male). Table 1 shows baseline demographic and clinical data according to SS-II for the research population. Smoking, HT, DM, COPD, peripheral arterial disease, previous PCI, stroke, and family history were significantly more frequent in the high SS-II group (p<0.001). The low SS group had a higher proportion of men, whereas the high SS-II group had a higher average age (p<0.001). The high SS-II group exhibited elevated total cholesterol, low-density lipoprotein (LDL), carotid intima-media thickness (CIMT), and LVEF values
(p< 0.001). The groups exhibited similar values for high-density lipoprotein (HDL) and triglyceride (TG) levels and medication rates (p>0.05).
Table 2 lists the parameters of the univariate linear regression analysis and the statistical evaluations. CIMT, HDL, LDL, and HT were independently associated with SS-II. Furthermore, logistic regression analysis revealed that CIMT (odds ratio: 3.124, 95% confidence interval: 1.744-5.628; p<0.001) was an independent predictor of SS-II.
Discussion
This study examined the correlation between SS-II and CIMT in patients with NSTEMI and COVID-19. The primary conclusions of this investigation were as follows: (i) There was a strong correlation between SS-II and CIMT, and (ii) CIMT is a reliable indicator of SS-II.
The COVID-19 pandemic has severely impacted healthcare services, limiting patient access, halting elective procedures, and causing patients to hesitate to visit hospitals due to infection transmission, particularly in NSTEMI(14, 15). Chronic illnesses COVID-19 increase risk and mortality. Ischemic heart disease, HT, HF, and atrial fibrillation are more common in COVID-19 deaths(16).
COVID-19 patients with elevated cardiac troponin levels, echocardiographic abnormalities, and electrocardiograms have reported acute myocarditis. Cardiac histopathological findings in deceased patients include inflammatory and prothrombotic features, damage from previous conditions, and myocardial hypertrophy. A significant proportion of patients with COVID-19 have increased high-sensitivity cardiac troponin (hs-cTn) levels, with over 50% of those who died having hs-cTnI levels above 28 mg/mL. We recommend searching for other clinical features because troponin elevation alone does not diagnose ACS. CA is recommended for patients with inflammatory marker values. Patients whose CT scan results were not compatible with COVID-19 and whose RT-PCR test was negative also required more intervention. Laboratory tests, RT-PCR test results, and thorax CT findings do not have a statistically significant effect on the requirement for CA(17-19).
A study by Majeed et al.(20) found that patients with NSTEMI and COVID-19 had a higher inpatient mortality rate, longer length of stay, and fewer invasive cardiac procedures. Despite lower underlying cardiac and pulmonary comorbidities, these patients have a five-fold mortality risk. COVID-19 can lead to various clinical symptoms, including MI, myocarditis, HF, arrhythmias, and venous thromboembolism. Cardiac damage in COVID-19 infections is attributed to mechanisms such as inflammation, cytokine storms, increased coagulation functions, and an imbalance between oxygen supply and demand(21).
The SS angiographic scoring instrument ranks coronary lesions by complexity. Patients with stable CAD, multivessel disease, or complicated coronary lesions were tested first. The SS-II grading system, which combines anatomical SS and clinical factors, may better predict clinical events(22). Song et al.(23) found SS-II better than SS for predicting 2-year death in patients with complicated CAD, and Salvatore et al.(24) showed it may predict unfavorable clinical outcomes in patients with severe CAD. Combined anatomical and clinical characteristics favored anatomical SYNTAX. Through cardiac bypass or PCI risk rating, SS-II was found to predict 4-year mortality. Age, creatinine, and ejection fraction enhanced SYNTAX adverse event prediction. Lower LVEF, creatinine clearance, anatomical SS, younger age, and female sex were favorable markers for coronary bypass in the SYNTAX research(25-27). CIMT, an atherosclerosis measure, was significantly correlated with SS-II in our research.
Hayiroglu et al.(28) observed that SS-II was associated with in-hospital mortality and major adverse cardiovascular events (MACE). To predict target lesion revascularization, stent thrombosis, or recurrent MI, SS-II is a poor predictor. We did not assess individuals with long-term MACE who tested positive for COVID-19 in cases of NSTEMI.
Study Limitations
The SS-II score in patients with COVID-19 and NSTEMI has several drawbacks. Hypercoagulability due to COVID-19 increases thrombosis risk. This may make CAD severity assessment and revascularization decisions more difficult, underestimating CAD’s complexity. Inflammation due to COVID-19 can worsen CV problems. This heightened inflammatory state can alter the presentation and prognosis of patients with NSTEMI, whereas the SYNTAX II score does not. In patients with severe COVID-19, hemodynamic instability may occur. This may cause SS-II score errors because it can complicate angiographic interpretation and coronary architecture assessment. COVID-19 can damage, inflame, and cause stress in the heart. The SS-II does not include these conditions, prioritizing anatomy over function. Catheterization laboratories and specialized staff may be scarce during the COVID-19 pandemic. Rapid or accurate patient assessment could potentially impact the SS-II.
SS-II predicts long-term results using anatomical and clinical characteristics. COVID-19 increases the risk of serious respiratory problems and longer hospital admissions, which can change the outcome. COVID-19’s symptoms and severity of COVID-19 affect NSTEMI’s clinical appearance. Due to this unpredictability, a standardized scoring system like SS-II may not adequately represent the clinical context of these patients.
Conclusion
The correlation between CIMT and SS-II in patients with COVID-19 diagnosed with NSTEMI might provide useful insights into their susceptibility to atherosclerosis. The correlation between NSTEMI and COVID-19 is a significant contributor to the increase in mortality rates.