COVID-19 may predispose patients to cardiac injuries but whether COVID-19 infection affects the morphological features of coronary plaques to potentially influence the outcome of patients with coronary artery disease (CAD) remains unknown. By using optical coherence tomography (OCT), this study compared the characteristics of coronary plaque in patients with CAD with/without COVID-19 infection. The 206 patients were divided into 2 groups. The COVID-19 group had 113 patients between December 7, 2022, and March 31, 2023, who received OCT assessment after China decided to lift the restriction on COVID-19 and had a history of COVID-19 infection. The non-COVID-19 group had 93 patients without COVID-19 infection who underwent OCT before December 7, 2022. The COVID-19 group demonstrated a higher incidence of plaque ruptures (53.1% vs 38.7%, p = 0.039), erosions (28.3% vs 11.8%, p = 0.004), fibrous (96.5% vs 89.2%, p = 0.041) and diffuse lesions (73.5% vs 50.5%, p <0.001) compared with the non-COVID-19 group, whereas non-COVID-19 group exhibited a higher frequency of cholesterol crystals (83.9% vs 70.8%, p = 0.027), deep calcifications (65.6% vs 51.3%, p = 0.039) and solitary lesions (57.0% vs 34.5%, p = 0.001). Kaplan-Meier survival analysis revealed a significantly lower major adverse cardiac events-free probability in the COVID-19 group (91.6% vs 95.5%, p = 0.006) than in the non-COVID-19 group. In conclusion, OCT demonstrated that COVID-19 infection is associated with coronary pathological changes such as more plaque ruptures, erosions, fibrosis, and diffuse lesions. Further, COVID-19 infection is associated with a higher propensity for acute coronary events and a higher risk of major adverse cardiac events in patients with CAD.
In 2019, the novel coronavirus rapidly spread to many countries, forming a global pandemic. Studies have shown that patients with COVID-19 are at risk for cardiac disease, and some of the patients develop cardiac injury, manifested as elevated high sensitivity-cardiac troponin I, cardiac arrhythmia, and heart failure, etc. , A study combined the results from 22 autopsy investigations found that 47.8% of 277 COVID-19 deaths had one pathological abnormalities such as macro or microvascular thrombi, inflammation or intraluminal megakaryocytes in the lumen. Post-acute sequelae of COVID-19-chronic cardiovascular disease encompasses a spectrum of cardiovascular conditions appearing in COVID-19 survivors at least 4 weeks after infection. This spectrum includes the onset or worsening of coronary artery disease (CAD) because of obstructive conditions, thromboembolism, etc. Recently, case reports have indicated that optical coherence tomography (OCT) in patients with CAD with COVID-19 shows thrombosis and honeycomb-like re-thrombosis, coronary spasm, plaque erosion, fibrous plaques, and macrophage accumulation among other lesions, which may be the cause or underlying basis for acute coronary events. On December 7, 2022, China decided to lift the restriction on COVID-19. The China restriction on COVID-19 was a policy that infected patients had to be isolated or quarantined. The general population had to stay at home with a nucleic acid test every day or once in 2 to 3 days. The impact of the novel coronavirus pneumonia epidemic on the characteristics of coronary heart disease and hospital deaths has been reported. Because there were only scare case reports on the OCT findings in patients with CAD after COVID-19 as mentioned previously, we systematically evaluated the characteristics of the coronary artery lesion by OCT in 113 patients with CAD after COVID-19 infection in comparison with 93 patients with CAD without COVID-19. The present study reports the important findings and the differences in the subsequent incidence of major adverse cardiac events (MACE).
Methods
Patients with CAD who accepted pre-interventional OCT assessment at TEDA International Cardiovascular Hospital, Tianjin, China between September 2022 and March 2023 were retrospectively reviewed. Exclusion criteria were: (1) presence of cardiogenic shock, severe lung, kidney, and/or liver dysfunction, allergy to contrast media, or contraindications for anti-thrombotic therapy; (2) incomplete or missing medical records; (3) patients who are unreachable for follow-up consultations or cannot revisit doctors; (4) extreme age (<18 or >80 years). The study protocol was approved by the Ethics Committee and Institutional Review Board of TEDA International Cardiovascular Hospital ([2023]-0518-2).
The diagnostic criteria for CAD were based on the current guidelines. Acute coronary syndrome (ACS) (including unstable angina, non-ST-segment elevation myocardial infarction [MI], and ST-segment elevation MI) was diagnosed according to “Chinese Guidelines for Emergency Rapid Diagnosis and Treatment of Acute Coronary Syndrome (2019).” COVID-19 infection was diagnosed according to “Diagnosis and Treatment Plan for Novel Coronavirus Infection (Tenth Edition for Trial Implementation)” issued by the Chinese Health Commission. OCT was performed when baseline angiogram showed no clear culprit lesion and the intravascular imaging (preferably OCT) in patients with ambiguous culprit lesions (class IIb) was indicated.
A total of 379 eligible patients with CAD were included in the present study. Of them, 173 patients were excluded from analysis for the following reasons: (1) percutaneous coronary intervention (PCI) before OCT examination (n = 172), (2) poor visualization of plaque characteristics because of massive thrombus or residual luminal blood (n = 1). The 206 patients with CAD analyzed were divided into 2 groups according to whether there was a history of COVID-19 infection and by the time point China lifted the restriction on COVID-19 on December 7, 2022.
The COVID-19 group comprised 113 patients who underwent OCT after December 7, 2022, and had a history of COVID-19 and had a positive nucleic acid test for COVID-19 (nucleic acid detection of COVID-19 [rapid reverse transcription-quantitative polymerase chain reaction (rRT-qPCR)]: SARS-CoV-2 ribonucleic acid [RNA] by nasopharyngeal swab). The non-COVID-19 group, consisting of 93 patients, underwent OCT before December 7, 2022, without a history of COVID-19 infection and was confirmed with negative nucleic acid test (nucleic acid detection of COVID-19 (rRT-qPCR): SARS-CoV-2 RNA by nasopharyngeal swab) for COVID-19 on admission and the detailed questionnaire about possible symptoms of COVID-19 before admission. The date (December 7, 2022) was the restriction policy for COVID-19 was lifted by the Government. After this date, almost the whole population was infected by COVID-19 including the authors. Further, there were no more nucleic acid tests performed after this date. Therefore, after this date, no patient could be confirmed without COVID-19 infection and no patient was suitable as the control because almost all the people were infected.
The flow chart ( Figure 1 ) illustrates patient selection and study design. Before interventional procedures, patients received a loading dose of dual antiplatelet therapy. Coronary angiography was conducted either through the radial or femoral route utilizing guiding catheters, after the intracoronary administration of 100 to 200 μg of nitroglycerin. Angiographic images were analyzed and evaluated for parameters such as maximal diameter stenosis and the number of diseased coronary arteries by 5 independent investigators (ZLX, CWQ, WYF, LFC, and LHP) who remained unaware of patient clinical data. Two experienced investigators analyzed each case. In the event of any discrepancy between the 2 investigators, a third investigator reviewed the case, and a consensus was reached through discussion.
OCT imaging of primary lesions was executed using the C7-XR/ILUMIEN OCT system (Abbott Vascular, Santa Clara, California). The OCT images were digitally stored in a database and assessed by 6 experienced investigators (ZLX, CWQ, WYF, LFC, LHP, and JSS) who were unaware of patient details and COVID-19 status. As previously mentioned, 2 experienced investigators analyzed each case, and in case of disagreement, a third investigator intervened, leading to a group discussion to achieve a unanimous conclusion.
OCT images were analyzed using previously established criteria. Plaques were identified as segments with luminal narrowing and a loss of the normal 3-layered structure of the vessel wall. , Lesions were categorized into 3 subtypes as follows: (1) diffuse lesions: the length of a single lesion >20 mm. Lesions with a ≥5-mm distance between were considered as separated plaques, otherwise, being considered as 1 long plaque; (2) segmental lesions: The length of a single lesion ranging from 10 to 20 mm; and (3) solitary lesions: the length of a single lesion <10 mm. Cross-sectional OCT images were analyzed at 1-mm intervals.
ACS culprit lesions were defined as follows: plaque rupture was identified by the presence of fibrous cap discontinuity with a cavity formed inside the plaque. Plaque erosion was defined by the integral fibrous cap and the presence of a thrombus. Spontaneous coronary artery dissection was defined as incomplete intima, tearing of the intima, and the formation of the intimal skin flaps. A calcified nodule was defined by fibrous cap disruption detected over a calcified plaque of protruding calcification and/or superficial calcium. Coronary spasm was defined when the middle membrane contracted and thickened, the intima aggregated and bulged, and the vascular lumen area decreased. When a sufficient dose of nitroglycerin was administered to the coronary artery, the phenomenon often disappeared.
Atherosclerotic plaques were classified as fibrous plaques (homogeneous, high backscattering region), lipid plaques (low signal region with a diffuse border), or calcified plaques (low backscattering heterogeneous region with a well-delineated border underlying the plaque). Lipid-rich plaque was identified as a lipid plaque. For lipid plaque, the maximal lipid length was recorded every 1-mm interval from the longitudinal view, and the lipid arc was measured in the cross-sectional view, with maximal lipid arc calculated. Minimal fibrous cap thickness was measured 3 times in the thinnest place to obtain a mean value. Calcification was recorded such as maximum calcium arc and calcium score that was analyzed by OCT-based calcium scoring system. Maximum calcium arc: >180° scores 2 points, ≤180° scores 0 points; Maximum calcium thickness: >0.5 mm scores 1 point, ≤0.5 mm scores 0 points; Calcium Length. >5 mm scores 1 point, ≤5 mm scores 0 points).
Calcification was described as (1) spotty calcification: calcification with maximum arc <90° and length<10 mm ; (2) superficial calcification: the distance between calcified plaque and the lumen was 65 to 100 μm ; (3) deep calcification: the distance between calcified plaque and the lumen was >100 μm ; (4) circular calcification: calcified plaque angle is >270° ; (5) severe calcification: is 4 points. Cholesterol crystals were identified as thin and linear regions of high signal intensity with high backscattering within a plaque.
Vulnerable plaques were diagnosed when the following 2 criteria were met :
(1) Thin-cap fibroatheroma was defined as a plaque with a maximal lipid arc ≥180° and thinnest fibrous cap thickness ≤65μm. (2) Macrophage accumulation was defined as the presence of radially highly backscattering regions within the fibrous cap. (3) Plaque erosion was defined by the integral fibrous cap and the presence of a thrombus. (4) Microchannels were defined as the presence of signal-poor structures with vesicular or tubular shapes. Microchannels were identified by OCT by the presence of a microchannel in ≥3 consecutively analyzed frames.
After the OCT assessment, patients received treatment tailored to their specific needs. The treatment options included PCI (such as stent placement and coronary artery balloon dilation) or medication (aiming at blood glucose and blood lipid control, along with antiplatelet drugs). The control targets were fasting blood glucose 4.4 to 7.0 mmol/L, total cholesterol <3.5 mmol/L, and low-density lipoprotein cholesterol <1.8 mmol/L.
Patients were followed up for MACE after being discharged, during a 1-month to 12-month period, either through outpatient service or telephonic consultation. The MACE encompassed cardiac death, new MI, refractory angina, and new heart failure.
Statistical analyses were performed using SPSS version 27.0 (IBM, Armonk, New York). The Kolmogorov-Smirnov normality test was performed to examine whether the data were normally distributed.
Continuous variables were denoted by mean ± SD if normally distributed, and the difference between groups was tested using an independent sample t test. Data of non-normal distribution were expressed as median and range, and comparisons were performed using the Mann-Whitney U test. Categorical data were presented as counts (proportions) and compared using the chi-square or Fisher’s exact test.
The Kaplan-Meier method was used to estimate the cumulative incidence of MACE-free and log-rank test was used to compare MACE-free probability. A p Value <0.05 was considered statistically significant.
Results
The 206 patients who were finally included in this study were aged from 24 to 79 years and the mean age was 60 years. The time interval from COVID-19 infection to undergoing OCT was 6.19 ± 3.26 weeks. The COVID-19 group (n = 113) and the non-COVID-19 group (n = 93) did not differ in age, gender ratio, body mass index, and proportions of hypertension, diabetes, hyperlipidemia, and smoking (p >0.05). None of the patients had previous coronary artery bypass grafting. Less patients had previous MI (7.1% vs 18.3%, p = 0.014), and previous PCI (24.8% vs 37.6%, p = 0.046) in the COVID-19 group than in the non-COVID-19 group. A higher triglyceride level was observed in the COVID-19 group compared with the non-COVID-19 group (1.75 ± 1.06 mmol/L vs 1.48 ± 0.91 mmol/L, p = 0.029). In addition, the COVID-19 group had a lower rate of angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker intake than the non-COVID-19 group upon discharge (25.7% vs 39.8%, p = 0.031). For other laboratory examination results and cardiovascular medications, no significant differences (p >0.05) were observed between the 2 groups ( Table 1 ).
| Overall Patients | Patients With COVID-19 | Patients Without COVID-19 | ||
|---|---|---|---|---|
| (n=206) | (n=113) | (n=93) | P Value | |
| Age, y | 60.00±10.68 | 59.77±11.15 | 60.28±10.12 | 0.838 |
| Male | 143 (69.4%) | 73 (64.6%) | 70 (75.3%) | 0.098 |
| BMI, kg/m 2 | 25.89±3.64 | 25.84±3.38 | 25.95±3.94 | 0.830 |
| Coronary risk factors | ||||
| Hypertension | 111 (53.9%) | 61 (54.0%) | 50 (53.8%) | 0.975 |
| Diabetes | 53 (25.7%) | 27 (23.9%) | 26 (28.0%) | 0.507 |
| Hyperlipidemia | 19 (9.2%) | 10 (8.8%) | 9 (9.7%) | 0.838 |
| Current smoker | 78 (37.9%) | 38 (33.6%) | 40 (43.0%) | 0.167 |
| Prior MI | 25 (12.1%) | 8 (7.1%) | 17 (18.3%) | 0.014 * |
| Prior PCI | 63 (30.6%) | 28 (24.8%) | 35 (37.6%) | 0.046 * |
| Prior CABG | 0(0.0%) | 0(0.0%) | 0(0.0%) | — |
| Clinical presentation | ||||
| STEMI | 8 (3.9%) | 6 (5.3%) | 2 (2.2%) | 0.420 |
| NSTEMI | 11 (5.3%) | 7 (6.2%) | 4 (4.3%) | 0.772 |
| Unstable angina | 146 (70.9%) | 76 (67.3%) | 70 (75.3%) | 0.208 |
| Laboratory data | ||||
| WBC, * 10 9 /L | 6.64±2.15 | 6.82±2.23 | 6.42±2.03 | 0.165 |
| Lymphocyte% | 27.95±8.87 | 27.92±8.74 | 27.99±9.06 | 0.956 |
| Lymphocyte, * 10 9 /L | 1.78±0.64 | 1.84±0.65 | 1.72±0.62 | 0.112 |
| Platelet, * 10 9 /L | 229.50±63.86 | 232.71±65.67 | 225.59±61.70 | 0.354 |
| Creatinine, umol/L | 66.34±17.69 | 65.73±19.33 | 67.10±15.53 | 0.581 |
| Uric Acid, umol/L | 328.57±92.56 | 321.73±93.19 | 336.89±91.60 | 0.242 |
| ALT, U/L | 26.47±21.57 | 25.09±24.68 | 28.15±17.03 | 0.063 |
| TC, mmol/L | 4.32±1.06 | 4.38±1.01 | 4.23±1.11 | 0.171 |
| Triglyceride, mmol/L | 1.63±1.00 | 1.75±1.06 | 1.48±0.91 | 0.029 * |
| LDL-C, mmol/L | 2.56±0.91 | 2.63±0.86 | 2.48±0.97 | 0.083 |
| HDL-C, mmol/L | 1.13±0.29 | 1.11±0.26 | 1.15±0.33 | 0.452 |
| Glucose, mmol/L | 6.42±2.66 | 6.37±2.39 | 6.48±2.96 | 0.871 |
| hs-CRP, mg/L | 6.92±19.02 | 8.38±22.54 | 5.04±13.23 | 0.240 |
| HbA1c, % | 6.66±1.23 | 6.73±1.45 | 6.57±0.90 | 0.872 |
| D-Dimer, mg/L | 0.28±0.31 | 0.30±0.34 | 0.25±0.27 | 0.344 |
| Cardiovascular medication | upon discharge | |||
| Aspirin | 203 (98.5%) | 111 (98.2%) | 92 (98.9%) | 1.000 |
| Clopidogrel | 92 (44.7%) | 52 (46.0%) | 40 (43.0%) | 0.666 |
| Ticagrelor | 72 (35.0%) | 37 (32.7%) | 35 (37.6%) | 0.464 |
| Nitrate ester | 136 (66.0%) | 79 (69.9%) | 57 (61.3%) | 0.194 |
| ACEI/ARB | 66 (32.0%) | 29 (25.7%) | 37 (39.8%) | 0.031 * |
| β-blockers | 125 (60.7%) | 67 (59.3%) | 58 (62.4%) | 0.653 |
| Statin | 202 (98.1%) | 111(98.2%) | 91 (97.8%) | 1.000 |
| Sacubitril Valsartan Sodium | 17 (8.3%) | 11 (9.7%) | 6 (6.5%) | 0.394 |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
