A 74-year-old woman was admitted to Fuwai Hospital, Chinese Academy of Medical Sciences, on February 18, 2025, for evaluation of worsening chest pain over the prior 10 days. She has had a cardiac history of more than one year, with intermittent retrosternal chest discomfort, such as a constricting feeling in a palm-sized area, mainly at rest and at night. The episodes radiated to the left shoulder and upper limb and lasted from a few to ten minutes before they went away on their own. She was admitted to a local hospital in April 2024, and coronary angiography (CAG) revealed the following findings (Fig. 1A-B): left main coronary artery (LM): no stenosis; mid-left anterior descending artery (LAD): 50% stenosis; left circumflex artery (LCX) ostium: 100% stenosis; and right coronary artery (RCA) ostium: 70% stenosis. Attempts to open the LCX were unsuccessful. Echocardiography revealed a normal left ventricular ejection fraction (LVEF). She was discharged after improvement following drug treatment with aspirin enteric-coated tablets, clopidogrel tablets, atorvastatin calcium tablets, etc. She was again admitted to an external hospital due to chest pain in December 2024. Repeated echocardiography revealed left ventricular enlargement. There was also slightly reduced left ventricular function, segmental wall motion abnormalities, mild to moderate mitral regurgitation, and mild aortic regurgitation. The CAGs showed the following (Fig. 1C): LM ostium and body: 90–95% stenosis; LAD ostium: 80% stenosis; LCX ostium: 100% stenosis; and RCA ostium: 70% stenosis. Two stents were implanted in the LM-LAD (Fig. 1D), and the patient was discharged after improvement. After being discharged on guideline-directed medical therapy (GDMT) and having her symptoms resolve, 10 days before the current admission, she developed chest pain that lasted for hours and radiated to the left upper limb again. Symptoms resolved with emergent medical management at a local hospital. She came to our hospital for further diagnosis and treatment.

Comorbidities: Hypertension (> 10 years; maximum BP 160/90 mmHg; managed with sacubitril/valsartan achieving 110–120/60–70 mmHg); Type 2 diabetes mellitus (2 years; treated with acarbose and dapagliflozin; no regular glucose monitoring); Hyperlipidemia (1 year; on atorvastatin); Cerebral infarction (6 months prior; no residual deficits).

Physical examination revealed the following: afebrile (36.1°C), normocardic (68 bpm), eupneic (19 breaths/min), and normotensive (105/63 mmHg). Height was 164 cm, weight 64 kg, and BMI 23.8 kg/m² (within the normal range). Lungs: Decreased breath sounds over bilateral lung bases without adventitious sounds. Cardiovascular: Regular rhythm with diminished intensity. Grade 3/6 holosystolic murmur in the mitral area. There was no murmur in the aortic valve region. Extremities: No peripheral edema.

Laboratory investigations: Cardiac biomarkers (Feb 18, 2025): Troponin I: 0.031 ng/mL at 16:37 (ref: 0–0.02 ng/mL); Troponin I: 0.028 ng/mL at 21:08; NT-proBNP: 2562.30 pg/mL (ref: 0–250 pg/mL). Platelet aggregation: Arachidonic acid-induced: 18.20%; ADP-induced: 36.30%; collagen-induced: 50.27%; and epinephrine-induced: 56.68%. Thrombophilia panel: antithrombin III: 74%; protein C activity: 69%; protein S activity: 117.3%. Lipid profile: Triglycerides: 0.92 mmol/L; total cholesterol: 3.32 mmol/L; HDL-C: 1.06 mmol/L; LDL-C: 1.92 mmol/L; non-HDL-C: 2.26 mmol/L. HbA1c: 6.9%. Urinalysis: Glucose 4+. Immunological studies: CD4/CD8 ratio: 3.24 (ref: 0.71–2.78); immunoglobulin M: 0.323 g/L (ref: 0.63–2.77); and IgG3: 0.963 g/L (ref: 0.11–0.85). The following normal parameters were used: thyroid function, complete blood count, coagulation studies, HIV/syphilis serology, inflammatory markers (CRP, PCT, ESR), autoantibodies (including ANA, antiphospholipid, ANCA), complement levels, and protein electrophoresis.

Imaging studies: Electrocardiogram (ECG): Sinus bradycardia, short PR interval, and significant ST-segment depression in leads V2-V5 during the episode of chest pain (Fig. 2).

Portable Chest Radiography (Adult): Bilateral lung markings are grossly normal without evidence of consolidation. Widened aortic knob. Straightened pulmonary artery segment. Echocardiography revealed regional wall motion abnormalities. Left heart enlargement (left atrial anteroposterior diameter: 39 mm; left ventricular end-diastolic diameter: 54 mm). Moderate-to-severe mitral regurgitation was noted. Moderate aortic regurgitation. Trends toward left ventricular apical and inferoposterior wall aneurysm formation were observed. Left ventricular systolic dysfunction (LVEF: 38%). Bilateral lower extremity arterial ultrasound revealed atherosclerosis with multiple small plaques in the bilateral lower extremity arteries. Severe stenosis, approaching occlusion, in the left anterior tibial artery. Bilateral carotid artery ultrasound revealed multiple plaques in the bilateral carotid arteries. The reduced flow velocity in the left internal carotid artery suggested near-occlusion. An elevated resistance index was detected in the left vertebral artery. Coronary CT angiography (CCTA) (Fig. 3A): Filling the defect within the proximal LM to the LAD artery metallic stent, suggestive of ISR. Increased perivascular density and soft tissue density shadows possibly indicate inflammation. Occlusion of the proximal LCX and intermediate arteries. 50%–70% stenosis at the origin of the RCA. Whole Aorta CT Angiography: Atherosclerotic changes in the aorta. There was no significant wall thickening or calcification in the ascending aorta. Severe stenosis (> 70%) at the origins of the bilateral vertebral arteries. Occlusion of the left internal iliac artery. Cardiac magnetic resonance imaging (MRI) with contrast agent: Old myocardial infarction, predominantly involving the LAD and LCX territories, which are mainly subendocardial. The late gadolinium enhancement (LGE) mass was 11.7 g (12.1% of the left ventricular mass). Associated regional left ventricular systolic dysfunction. Whole-body PET/CT (large vessels) (Fig. 3B) revealed increased glucose metabolism (SUVmax 5.9) in the LM and proximal LAD stents, suggesting inflammatory changes. Relatively uniform metabolic activity in large arteries, without significant evidence of active arteritis. Myocardial viability PET/CT (Fig. 3E): Quantitative blood flow analysis: Reduced resting blood flow in the LAD and LCX territories; normal resting blood flow in the RCA territory. Myocardial viability assessment: Predominantly viable myocardium in the left ventricular apex, apical and mid anterior wall, apical septum, and lateral wall (overall hibernating myocardium: 19% of the left ventricular mass). Normal metabolism in the remaining myocardial segments (81% of the left ventricular mass). Left Ventricular Function Assessment: Dilated left ventricular cavity. Hypokinesis of the left ventricular apex, anterior wall, and lateral wall. LVEF: 39%.

We diagnosed her condition as CAD, acute anterior wall myocardial infarction (Killip class II), and ISR. Following admission, guideline-directed medical therapy (GDMT) was initiated, including dual antiplatelet therapy (aspirin + clopidogrel), high-intensity statins (atorvastatin 20 mg daily), and guideline-directed heart failure medications (sacubitril/valsartan + beta-blockers) to attenuate ventricular remodelling.

Despite optimized medical therapy, the patient experienced recurrent angina episodes. Repeat CAG (February 28, 2025) revealed the following: proximal LM: 90% stenosis (ISR) (Fig. 1E); LCX ostium: 100% stenosis; and RCA ostium: 50% stenosis. The patient refused coronary artery bypass grafting (CABG). Percutaneous transluminal coronary angioplasty (PTCA) was performed on the left main lesion (Fig. 1F).

Following discharge, the patient adhered to the prescribed medication regimen. The dosage of prednisone acetate tablets was tapered by 5 mg every two weeks, whereas the other treatments remained unchanged. No further episodes of chest pain occurred. The patient was readmitted on May 13, 2025, for follow-up evaluation. Physical examination revealed no changes from the previous admission.

Laboratory studies (May 13, 2025): Hematology: neutrophil percentage: 77.5% (ref: 40–75%); absolute neutrophil count: 6.47×10⁹/L (ref: 1.80–6.30); lymphocyte percentage: 17.50% (ref: 20.0–50.0%); eosinophil percentage: 0.10% (ref: 0.4–8.0%); absolute eosinophil count: 0.010×10⁹/L (ref: 0.02–0.52). Cardiac biomarkers: troponin I: 0.017 ng/mL; NT-proBNP: 461 pg/mL. Lipid panel: Triglycerides: 0.81 mmol/L; total cholesterol: 4.96 mmol/L; HDL-C: 1.74 mmol/L; LDL-C: 3.09 mmol/L; non-HDL-C: 3.24 mmol/L. Immunoglobulins: IgM: 0.3 g/L (ref: 0.5–2.8); IgG3: 0.408 g/L (ref: 0.11–0.85). Inflammatory/autoimmune markers: Remaining negative.

Repeat echocardiography demonstrated a significant reduction in the left ventricular end-diastolic dimension (49 mm), which was a 9.26% reduction from the baseline value of 54 mm (February 2025). CAG revealed the following (Fig. 1G): proximal LM stenosis: 70% ISR; LCX ostium: 100% stenosis; and RCA ostium: 50% stenosis. The patient still refused CABG. Optical coherence tomography (OCT) (Fig. 1I-J)-guided drug-coated balloon angioplasty (Xun Niao, paclitaxel-coated, 3.0×25 mm) was successfully performed on the LM lesion (Fig. 1H).

Follow-up CCTA (Fig. 3C) revealed a patent stent in the proximal LM-LAD without significant stenosis at either end. Increased perivascular density and soft tissue density shadows were observed surrounding the stent and adjacent to the aortic root sinuses and proximal ascending aorta, suggesting perivascular inflammatory changes. Whole-body PET/CT (Vascular Assessment) (Fig. 3D): Stent-related metabolic activity: Persistent FDG uptake in the LM-LAD stent (SUVmax 4.6), 22.03% reduction from the baseline SUVmax of 5.9 (February 2025). Homogeneous tracer distribution without features of active vasculitis. Therapeutic Adjustments: Lipid management: evolocumab (140 mg) was added subcutaneously biweekly to address progressive hyperlipidemia (LDL-C: 3.09 mmol/L); immunosuppressive taper: prednisone acetate was reduced to 5 mg daily (50% dose reduction); and baseline GDMT was maintained. The resolution of inflammatory symptoms led to discharge with sustained clinical stability.

Chronic inflammation in the vascular wall following stent placement is a key underlying cause of ISR ^[1]. Even after standard treatments such as antiplatelet therapy and intensive lipid lowering, atherosclerotic cardiovascular events quickly recur after myocardial infarction, indicating that current treatments fail to adequately control residual inflammation. This patient experienced recurrent ISR despite regular blood loss, thinner use, aggressive cholesterol control, and multiple revascularizations, highlighting the limitations of traditional treatments. Gupta et al. ^[2] also noted the limitations of conventional risk factors in DES-related ISR. PET/CT scans allow visualization of vascular inflammation without surgery, providing important results for evaluating ISR inflammatory status ^[3]. Considering the patient's abnormal immune system results (e.g., low IgM and high CD4/CD8 ratios) and PET/CT findings (increased metabolic activity), understanding how immune inflammation contributes to ISR could aid in the development of personalized treatments.

First, the patient had multiple health issues, such as hypertension, type 2 diabetes, hyperlipidemia, and a history of stroke, and multiple heart catheterizations confirmed multivessel disease and repeated ISR episodes. Lab tests revealed unusual immune markers, such as low immunoglobulin M and a high CD4/CD8 ratio, while PET/CT revealed increased glucose metabolism around the stent, suggesting ongoing inflammation in that area. These findings provide key information about disease mechanisms. The ISR might be caused by immune system problems that damage blood vessel linings and trigger inflammatory cell buildup and cytokine release, accelerating atherosclerosis and ISR development ^[4]. Considering these immune abnormalities, inflammatory responses likely play a major role.

Therefore, in addition to standard treatments (blood thinners, cholesterol drugs, and heart function support), we added anti-inflammatory and immune-suppressing therapies. We used a combination of glucocorticoids (prednisone) and mycophenolate mofetil. Glucocorticoids have strong anti-inflammatory effects; they block the NF-κB pathway to reduce the effects of inflammatory chemicals, suppress T-cell activity, ease blood vessel inflammation, and stabilize plaques, lowering cardiovascular risk. However, long-term steroid use can cause metabolic side effects that actually increase heart risk, so we must be careful when the lowest effective dose for the shortest time needed is used ^[5]. Mycophenolate mofetil specifically stops lymphocyte growth, increasing immune suppression. It helps treat large-vessel inflammation and may indirectly benefit coronary disease by reducing vascular inflammation and protecting blood vessel cells. It is also used in tough cases of cardiac sarcoidosis alongside steroids to reduce steroid doses while maintaining effectiveness ^[6]. Notably, Munir et al. ^[7] described how immune checkpoint inhibitor-related heart inflammation involves immune cell interactions, noting that drugs such as glucocorticoids and mycophenolate mofetil can effectively regulate these processes, supporting our treatment approach. Similar cases have shown that such combinations significantly reduce ISR recurrence. Postintervention assessment revealed substantial clinical improvement, with resolution of angina symptoms (CCS class IV → I). Serial PET/CT scans confirmed reduced metabolic activity in the LM-LAD stents (SUVmax: 5.9 → 4.6; Δ = 22.03%), which was consistent with attenuated inflammatory burden. These findings corroborate the therapeutic rationale for targeting vascular inflammation in ISR management, aligning with recent evidence on anti-inflammatory strategies for stent-related complications.

Finally, this case provides valuable lessons for future research. These results suggest that we need to consider immune-inflammatory factors when studying coronary ISR mechanisms. We should also create more precise, personalized treatment plans based on each patient's situation to obtain better results and improve patient prognosis.

This study demonstrates the critical role of immune inflammatory responses in ISR by integrating immunological indicators with imaging features. Anti-inflammatory and immunosuppressive therapies provide novel therapeutic strategies for patients with such immune abnormalities, although treatment optimization still requires evidence-based validation. Future research should bridge cardiovascular and immunological disciplines to advance coronary disease management toward the era of precision medicine.