Intravascular ultrasound-guided percutaneous coronary intervention for syphilitic coronary ostial lesions: a single-center case series

Abstract

Objectives

This study aims to preliminarily explore the feasibility and safety of intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) for syphilitic coronary artery ostial lesions (SCAOL), providing hypothesis-generating insights for optimal stenting strategies in this distinct pathological entity.

Background

Cardiovascular syphilis, a severe manifestation of tertiary syphilis, frequently leads to coronary ostial stenosis. While coronary artery bypass grafting (CABG) is the traditional revascularization modality, PCI has emerged as a minimally invasive alternative. Given the “borderless” inflammatory nature of syphilitic aortitis, the efficacy of the conventional “flush-alignment” stenting strategy lacks specific evidence.

Methods

We retrospectively analyzed seven consecutive patients with confirmed SCAOL who underwent PCI at our center between January 2019 and February 2026 (follow-up through March 2026). All cases were diagnosed via syphilis serology, and IVUS was utilized for pre-procedural assessment and post-stenting optimization. The IVUS characteristics of SCAOL and PCI-related outcomes were analyzed to explore the potential impact of stent positioning strategies. The study received institutional ethical approval and written informed consent from all patients.

Results

The cohort included four males and three females (mean age: 54.3 ± 3.4 years). Pre-procedural IVUS consistently revealed concentric fibrous hyperplasia and significant negative remodeling, lacking typical atherosclerotic plaque features. Second-generation drug-eluting stents (DES) were successfully implanted in all seven patients. Six patients, whose stents protruded variably into the aortic sinus (ranging from approximately 2–4 mm in most cases), remained free of major adverse cardiovascular events (MACE) over a median follow-up of 4 years (IQR: 3–6 years). Conversely, one patient (Case 6), who received a “flush-alignment” LM stent (protrusion <1 mm) and lacked standardized anti-syphilitic therapy, developed NSTEMI due to severe in-stent restenosis (ISR) 8 months post-procedure. A bailout PCI utilizing a protrusion of approximately 4–5 mm was performed, and the stent remained patent at the 13-month follow-up.

Conclusions

IVUS-guided PCI was technically feasible in this small retrospective series of patients with suspected syphilitic coronary ostial lesions. Moderate aortic protrusion may help ensure ostial coverage, but the optimal protrusion length and its effect on restenosis require confirmation in larger multicenter studies. Furthermore, mechanical revascularization must be coupled with standardized systemic anti-syphilitic therapy and careful control of residual inflammatory activity to optimize long-term prognosis.

Introduction

Syphilis is a systemic infection caused by Treponema pallidum. Despite the long-term application of penicillin effectively curbing its epidemic, a striking global resurgence has been observed in recent years. Cardiovascular syphilis, a fatal manifestation of tertiary syphilis, frequently involves the coronary ostia, leading to syphilitic coronary artery ostial lesions (SCAOL)— a rare but life-threatening cardiovascular manifestation of late tertiary syphilis. Although the abbreviation SCAOL is utilized herein for concise reporting of this specific cohort, it refers explicitly to isolated or bilateral ostial stenosis driven by syphilitic patch-like aortic endarteritis, distinct from conventional atherosclerotic ostial disease. These lesions often affect relatively young populations and are prone to inducing acute myocardial infarction or sudden cardiac death, posing a substantial clinical hazard (1).

The pathological characteristics of SCAOL are distinctly different from typical coronary atherosclerosis. The disease originates from obliterative endarteritis of the vasa vasorum in the aortic adventitia, leading to significant fibrosis and elastic recoil of the involved vessel wall. These lesions often extend diffusely without clear boundaries (‘borderless’) (1, 2). Historically, coronary artery bypass grafting (CABG) was the primary revascularization modality. However, with the evolution of interventional techniques, percutaneous coronary intervention (PCI), leveraging its minimally invasive advantages, has emerged as a crucial alternative for patients who are elderly or surgically ineligible (3, 4).

Despite significant advancements, a critical clinical gap remains: the optimal stent positioning strategy for SCAOL has not yet been established. Unlike focal atherosclerotic plaques, the ‘borderless’ nature of syphilitic inflammation raises a clinical concern: is the traditional ‘flush-alignment’ technique sufficient to cover the inflamed ostial margins, or does it increase the risk of early postoperative restenosis?.

This study retrospectively analyzed seven SCAOL patients who underwent IVUS-guided PCI. By evaluating clinical outcomes and long-term imaging follow-up, particularly the clinical course of Case 6, we sought to describe procedural experience and generate hypotheses regarding stent positioning strategies in this rare disease entity.

Materials and methods

Study design and participants

This retrospective, single-center case series included seven consecutive patients diagnosed with syphilitic coronary artery ostial lesions (SCAOL) who underwent PCI at the Department of Cardiology, China-Japan Union Hospital of Jilin University, between January 2019 and February 2026 (follow-up cutoff: March 2026). All cases were discussed collectively by the Heart Team. To ensure diagnostic and procedural rigor, a standardized matrix of core evaluation metrics was applied throughout the study period (Table 1), with granular interventional and procedural parameters meticulously tracked across all treated segments (detailed in Supplementary Table S1). Exclusion criteria consisted of concomitant severe aortic regurgitation requiring surgical valve replacement, acute ST-segment elevation myocardial infarction (STEMI) necessitating emergency surgery, or clinical suspicion of other vasculitides, such as Takayasu arteritis (2).

Table 1.

Core evaluation metrics and corresponding assessment tools for patients with syphilitic coronary artery ostial lesions (SCAOL).

Category	Specific Parameters	Assessment Tool
Baseline Diagnosis	TPPA, RPR, Treponema-specific antibodies	Serological assay
Morphological Assessment	Lumen area, plaque burden, vessel wall thickness	IVUS
Procedural Success	TIMI flow grade 3, residual stenosis <10%	Coronary angiography
Follow-up Endpoints	Cardiac death, NSTEMI, TLR	Clinical follow-up/Angiography

IVUS, intravascular ultrasound; NSTEMI, non-ST-elevation myocardial infarction; RPR, rapid plasma reagin; SCAOL, syphilitic coronary artery ostial lesions; TIMI, thrombolysis in myocardial infarction; TLR, target lesion revascularization; TPPA, treponema pallidum particle agglutination.

Diagnostic criteria for enrollment were defined as follows: (1) positive syphilis serology, confirmed by reactive results on both the Treponema pallidum particle agglutination (TPPA) assay and the rapid plasma reagin (RPR) test; (2) coronary angiography demonstrating >70% stenosis in at least one coronary ostium, with intervention extended to the contralateral ostium when bilateral involvement was angiographically confirmed; and (3) IVUS-confirmed non-atherosclerotic features isolated to the coronary ostium, consistent with syphilitic involvement.

Diagnostic definition of suspected syphilitic coronary ostial lesions

The diagnosis of suspected syphilitic coronary ostial lesions was established through integration of clinical history, serological testing, coronary angiography, and IVUS findings. All included patients demonstrated positive treponemal and non-treponemal serological tests together with isolated coronary ostial stenosis and IVUS characteristics suggestive of non-atherosclerotic fibroproliferative disease.

Whenever available, echocardiography and aortic imaging were reviewed to assess associated cardiovascular syphilis manifestations. Comprehensive CTA, MRI, or PET-CT was not routinely available in all patients because of the retrospective design. All suspected cases were multi-disciplinarily confirmed by both senior interventional cardiologists and infectious disease specialists. Alternative causes of ostial coronary stenosis, including Takayasu arteritis, Behçet disease, IgG4-related disease, radiation-associated vasculopathy, and congenital coronary ostial abnormalities, were excluded based on clinical history, laboratory findings, and imaging evaluation.

Given the retrospective nature of this study and the absence of histopathological confirmation, diagnostic certainty should be interpreted with appropriate caution.

IVUS analysis

All available IVUS studies were retrospectively reviewed. Quantitative measurements included minimum lumen area, lesion length, reference vessel dimensions, and minimum stent area after implantation whenever image quality permitted reliable assessment.

Measurements were performed by experienced interventional cardiologists using standard IVUS analysis software. Due to the retrospective nature of the study, certain parameters were unavailable in some cases.

Assessment of aortic protrusion length

Aortic protrusion length was retrospectively estimated using a combination of angiographic orthogonal projections, stent-enhancement imaging, IVUS pullback assessment, and procedural records.

The aorto-coronary junction served as the anatomical reference point for estimation of stent protrusion. Because precise determination of the true ostial plane remains technically challenging, particularly in retrospective analysis, protrusion measurements should be regarded as semi-quantitative estimates rather than exact anatomical measurements.

All measurements were reviewed by experienced operators familiar with the index procedures.

Interventional procedure

Procedural details, including vascular access, guide catheter selection, lesion preparation strategy, stent implantation technique, post-dilation parameters, and final angiographic outcomes, were retrospectively collected from procedural reports and imaging archives. All patients received standard dual antiplatelet therapy (DAPT; aspirin 100 mg/d plus clopidogrel 75 mg/d or ticagrelor 90 mg twice daily) prior to the procedure. Access was obtained via the radial or femoral artery. For cases of critical ostial stenosis, operators specifically selected guide catheters with side holes or lower backup support to prevent transient myocardial ischemia or ventricular fibrillation induced by complete hemodynamic occlusion of the stenotic ostium.

Intravascular ultrasound (IVUS; Boston Scientific iLab or Volcano) was utilized for procedural guidance throughout. The standardized interventional strategy comprised the following phases:

1. Pre-treatment: Robust pre-dilation of the ostial fibrous annulus was performed using cutting balloons and high-pressure non-compliant (NC) balloons.

2. Stent Implantation: Second-generation drug-eluting stents (DES) were utilized in all cases. Stents were initially deployed flush with the coronary ostium under tangential angiographic projection, followed by IVUS-guided positioning optimization.

3. Post-dilation and Optimization: High-pressure post-dilation was performed under IVUS guidance to ensure optimal stent expansion, complete coverage of the coronary ostium, and full strut apposition.

Clinical management, follow-Up, and clinical endpoints

Post-procedural management followed a multidisciplinary collaboration model:

1. Anti-syphilitic Therapy: Adhering to CDC guidelines, regimens were formulated by infectious disease specialists, typically consisting of benzathine penicillin G (2.4 million units, intramuscularly, once weekly for three consecutive weeks) (5).

2. Anti-inflammatory and Lipid-lowering Therapy: Long-term moderate-intensity statins were administered to achieve a target low-density lipoprotein cholesterol (LDL-C) level <1.4 mmol/L. While routine anti-inflammatory therapy was not generally prescribed, adjunctive low-dose colchicine (0.5 mg/d) was administered in Case 6 following bailout stenting to suppress the localized inflammatory milieu.

3. Imaging Follow-up: Routine coronary angiography and IVUS were scheduled at 1-year post-procedure. In cases of recurrent angina or suspected ischemia within the follow-up period, repeat imaging was performed promptly. The primary endpoint was major adverse cardiovascular events (MACE), strictly defined as a standard 3-point composite of cardiac death, myocardial infarction (MI, specifically NSTEMI), and clinically driven target lesion revascularization (TLR). To ensure diagnostic precision, all-cause death, target vessel revascularization (TVR), stent thrombosis, and hospitalizations for unstable angina were tracked independently as secondary outcomes and explicitly excluded from the primary MACE composite.

Results

Clinical and baseline characteristics

The study cohort comprised seven consecutive patients with a mean age of 54.3 ± 3.4 years, notably younger than the typical population with atherosclerotic coronary artery disease (Table 2). The group included four males and three females. Remarkably, traditional cardiovascular risk factors were largely absent: only two patients had hypertension, and none had diabetes mellitus or pathological dyslipidemia.

Table 2.

Baseline characteristics, stent positioning, clinical outcomes, and follow-up assessment of 7 patients with SCAOL.

Case	Age/Sex	Clinical Presentation	Vessel(s)	RPR (Baseline)	RPR (Follow-up)	Antibiotic Regimen	Antiplatelet Regimen	Protrusion	Result	Outcome	Clinical FU	Angio FUd	MACE	ISR
1	50F	Intermittent precordial pain (2 months); syncope (×2)	LM, RCA	1:32	N/A	Benzathine penicillin G 2.4 MU IM q.w. × 3	Aspirin 100 mg/d + Clopidogrel 75 mg/d	≈4.0 mm (LM); ≈4.0 mm (RCA)	Success	Event-free (6 years)	6 years	Yes (4.5 years; patent)	None	None
2	56M	Intermittent precordial pain (1 month), worsening ×3 days	LM (treated); RCA (involved, not intervened)e	1:64	N/A	Benzathine penicillin G 2.4 MU IM q.w. × 3	Aspirin 100 mg/d + Clopidogrel 75 mg/d	3.5 mm (LM)	Success	Event-free (6 years)	6 years	Yes (6 years; patent)	None	None
3	48F	Epigastric pain (3 h)	LM, RCA	1:16	1:16b	Benzathine penicillin G 2.4 MU IM q.w. × 3	Aspirin 100 mg/d + Clopidogrel 75 mg/d	2.5 mm (LM); 2.0 mm (RCA)	Success	Event-free (5 years)	5 years	Clinical only	None	None
4	52M	Intermittent precordial pain (10 days), worsening ×1 day	LM, RCA	1:32	N/A	Benzathine penicillin G 2.4 MU IM q.w. × 3	Aspirin 100 mg/d + Clopidogrel 75 mg/d	4.0 mm (LM); <1 mm (RCA)	Success	Event-free (4 years)	4 years	Clinical only	None	None
5	59M	Precordial pain (1 day)	LM, RCA	1:64	N/A	Benzathine penicillin G 2.4 MU IM q.w. × 3	Aspirin 100 mg/d + Ticagrelor 90 mg b.i.d.	3.4 mm (LM); 2.0 mm (RCA)	Success	Event-free (3 years)	3 years	Clinical only	None	None
6 (Index)	53M	Intermittent precordial chest tightness (6 months)	LM, RCA	1:128	1:128c	Not completedc	Aspirin 100 mg/d + Clopidogrel 75 mg/d	<1 mm (LM); 4.0 mm (RCA)	Success	ISR/NSTEMI (8 months)	8 months	Yes (8 months; LM ISR 80%, RCA ISR 80%)	Yes	Yes
6 (Bailout)	53M	Anterior chest and back pain (3 days); recurrent bilateral ostial stenosis	LM, RCAa	1:128	—	Benzathine penicillin G 2.4 MU IM q.w. × 3 + Colchicine 0.5 mg/d	Aspirin 100 mg/d + Ticagrelor 90 mg b.i.d.	4–5 mm (intentional)	Success	Event-free (13 months)	13 months	Yes (13 months; patent)	None	None
7	57F	Intermittent precordial pain (6 months), worsening ×1 week	LM, RCA	1:16	1:16b	Benzathine penicillin G 2.4 MU IM q.w. × 3	Aspirin 100 mg/d + Clopidogrel 75 mg/d	2.0 mm (LM); 2.1 mm (RCA)	Success	Event-free (6 months)	6 months	Clinical only	None	None

Protrusion length was estimated semi-quantitatively using a combination of angiographic projections, stent-enhancement imaging, and IVUS pullback findings; detailed baseline metrics are provided in Supplementary Table 2. The bailout protrusion (4–5 mm) represents an intentional mechanical salvage strategy.

^aCase 6 (Bailout): Surveillance angiography revealed recurrent severe bilateral ostial stenosis (80% at both LM and RCA). Mechanistically, the LM lesion represented true in-stent restenosis (ISR) driven by inadequate initial ostial coverage (<1 mm protrusion) combined with uncontrolled syphilitic aortitis, whereas the RCA lesion manifested as de novo atherosclerotic plaque progression. Both ostia were successfully treated during the bailout procedure.

^bFull regimen completed; serofast response (defined as a failure to achieve a ≥ 4-fold reduction in RPR titer despite completing the CDC-recommended regimen; a recognized phenomenon in late cardiovascular syphilis that does not necessarily indicate treatment failure).

^cStandardized anti-syphilitic therapy was not completed after the index procedure; persistent systemic serological activity likely contributed to the subsequent development of ISR.

^dRoutine follow-up IVUS was clinically recommended for all subjects but was not performed due to the retrospective, real-world nature of this cohort; follow-up surveillance relied on coronary angiography and clinical event adjudication.

^eCase 2: RCA demonstrated mild-to-moderate area stenosis (45%) by IVUS; intervention was not performed given the absence of hemodynamically significant stenosis at this site. b.i.d., twice daily; FU, follow-up; IM, intramuscularly; ISR, in-stent restenosis; LM, left main; MU, million units; N/A, not available; q.w., once weekly; RCA, right coronary artery; RPR, rapid plasma reagin; TLR, target lesion revascularization.

Laboratory investigations revealed that all patients had reactive syphilis serology with RPR titers ≥1:16, reaching a maximum of 1:128 in Case 6, indicating active Treponema pallidum infection. Echocardiographic assessment demonstrated mild-to-moderate ascending aortic dilation in all patients and mild aortic regurgitation in two cases, neither of which met the criteria for surgical valve replacement (1).

Angiographic and intravascular imaging (IVUS) characteristics

Distinct from typical atherosclerosis, coronary angiography in SCAOL patients consistently revealed lesions isolated to the coronary ostia, while the mid-to-distal segments remained remarkably smooth. Furthermore, a high prevalence of bilateral involvement (LM and RCA) was observed. IVUS analysis identified several hallmark features across all cases (Figure 1):

1. Concentric Fibrous Hyperplasia: The vessel wall exhibited uniform, high-echoic, and circular fibrotic changes rather than eccentric plaques.

2. Absence of Lipid and Calcification: No lipid pools, necrotic cores, or significant calcifications were observed throughout the lesion segments, aligning perfectly with the fibroproliferative pathology of syphilitic endarteritis.

3. Negative Remodeling: Manifested as a reduced vessel area at the coronary ostial segments, leading to severe luminal restriction.

Figure 1.

Representative coronary angiography and IVUS images of SCAOL. (a) Coronary angiography shows severe stenosis at the opening of the left main coronary artery (arrow indicated). (b) IVUS shows fibrous plaque at the opening of the left main trunk, uniformly thickened, without calcification or lipid pool (as indicated by the arrow). (c) Severe stenosis at the opening of the right coronary artery (indicated by the arrow). (d) IVUS shows concentric and uniform fibrous thickening in the proximal segment of the right coronary artery, without calcification or lipid pools (as indicated by the arrow).

Clinical comparison of stent positioning strategies

In our cohort, all initial procedures followed the conventional ostial stenting technique, aiming for a “flush-alignment” with the inferior margin of the coronary ostium under a tangential angiographic view. However, IVUS revealed subtle variations in the final stent position relative to the aortic wall. Six patients, whose stents were intentionally or incidentally protruded ≥1 mm into the aortic sinus, remained free of ischemic symptoms or major adverse cardiovascular events (MACE) over a median follow-up of 4 years (IQR: 3–6 years). Follow-up angiography in these cases confirmed persistent stent patency with favorable endothelialization.

Mechanistic analysis of a clinical failure: case 6

Conversely, Case 6 followed a distinct clinical course that provided critical observations relevant to both procedural and systemic disease management. During the index procedure, the left main (LM) stent was deployed flush with the ostial margin, exhibiting only minimal protrusion (<1 mm) beyond the ostial edge (Figure 2), whereas the right coronary artery (RCA) stent was deployed with a secure 4.0-mm aortic protrusion. Notably, the patient was non-compliant with standardized anti-syphilitic therapy post-procedure.

Figure 2.

Post-procedural IVUS imaging of the left main ostium (case 6). (a) Baseline IVUS image of left main trunk opening in Case 6; (b) After the first PCI, IVUS showed that the stent completely covered the left main opening lesion, and the stent trabeculae had covered the aortic sinus (indicated by the arrow icon).

Eight months later, the patient was readmitted urgently with NSTEMI. Repeat angiography revealed severe, bilateral ostial in-stent restenosis (ISR) at both the LM (80%) and RCA (80%). Remarkably, pre-intervention IVUS during the bailout procedure demonstrated two distinctly different restenotic phenotypes between the two vessels, providing a unique intra-patient comparison:

1. Periaortic Fibrous Proliferation at the LM Ostium: At the initial “flush” site (<1 mm protrusion), significant concentric fibrous tissue hyperplasia was observed at the proximal stent edge, appearing to propagate directly from the adjacent inflamed aortic wall. This underscored a mechanical failure to shield the ostium from active syphilitic aortitis.

2. Neoatherosclerosis at the RCA Ostium: In contrast, the RCA ostium (protected by the initial 4.0-mm protrusion) was structurally isolated from periaortic syphilitic extension. However, it exhibited advanced in-stent neoatherosclerosis (ISNA) characterized by lipid-rich plaque accumulation within the stent, likely driven by uncontrolled systemic inflammation and traditional mechanisms (6).

Bailout strategy and long-term management for case 6

A comprehensive, bilateral bailout strategy was successfully executed. The primary therapeutic focus was directed at the LM ostium, where a new drug-eluting stent (DES) was deployed overlapping the original stent, with an intentional protrusion (4–5 mm) into the aortic sinus to ensure complete mechanical scaling across the affected aorto-coronary junction. Concurrently, the atherosclerotic RCA ISR was systematically treated with an additional overlapping DES as an adjunctive intervention (detailed in Supplementary Table S1).

Following revascularization, a multidisciplinary consultation initiated a standardized course of benzathine penicillin G combined with adjunctive low-dose colchicine to stabilize the localized inflammatory milieu. During the subsequent 13-month follow-up, the patient remained completely asymptomatic, and repeat angiography confirmed optimal stent patency in both vessels (Figure 3).

Figure 3.

Treatment of restenosis within the stent (case 6). (a) The first imaging showed severe stenosis of the left main trunk opening (indicated by the arrow icon). (b) The imaging after the first PCI showed that the stent was placed flush with the left main trunk opening. (c) After 8 months, the imaging showed a restenosis of the left main portal opening and the proximal segment of the stent (indicated by the yellow circle icon). (d) Stent boost shows that the 5.0 × 10 mm stent protrudes into the aortic sinus after being connected to the original stent by about 1/2 (indicated by the red circle icon), indicating that the stent protrudes into the aortic sinus by about 4-5 mm. (e) The final imaging result after salvage PCI. (f) One year later, a follow-up angiography showed that the left main stent was unobstructed.

Discussion

This case series describes the procedural feasibility of IVUS-guided PCI in patients with suspected syphilitic coronary ostial lesions and generates hypotheses regarding lesion coverage strategies in this unique clinical setting. The heterogeneous duration of follow-up reflects the retrospective nature of the study. Nevertheless, complete follow-up was achieved in all patients, thereby reducing uncertainty regarding major clinical outcomes.

Diagnostic considerations

We acknowledge that definitive attribution of coronary ostial disease to syphilis remains challenging in the absence of histopathological confirmation. Therefore, the diagnosis in the present study was based on a combination of serological evidence, characteristic lesion morphology, IVUS findings, and exclusion of alternative etiologies. Future multicenter studies incorporating advanced multimodality imaging and pathological correlation may further improve diagnostic certainty.

Imaging guidance: the indispensability of IVUS

Coronary angiography has significant limitations in managing SCAOL due to vessel overlap, rapid contrast dilution at the aortic root, and negative remodeling of inflammatory lesions, which often lead to underestimation of stenosis or anatomical misjudgment.

IVUS provides real-time tomographic imaging that not only quantifies stenosis but, more importantly, identifies the axial extent of the lesion. In selected cases, IVUS suggested that angiographically flush stent deployment might not fully cover the thickened aorto-coronary transition zone. IVUS-guided post-dilation and repositioning ensure that the proximal stent edge truly bridges the active inflammatory zone while achieving an optimal Minimum Stent Area (MSA) (7). This aligns with expert consensus recommending that adequate MSA and complete lesion coverage are paramount for improving long-term outcomes in complex ostial lesions (8). Although OCT provides higher resolution for detecting syphilis-specific vasa vasorum depletion and elastic fiber fragmentation, its procedural complexity in ostial positioning—driven by the need for voluminous contrast displacement and susceptibility to aortic wall interference—limits its utility in this context (9). The addition of quantitative IVUS measurements may facilitate future comparisons with larger studies and improve characterization of this uncommon lesion subtype.

Mechanical versus biological contributors to failure

The clinical course of Case 6 warrants cautious interpretation. Although minimal stent protrusion (<1 mm) may have resulted in incomplete coverage of the aorto-coronary transition zone, the patient simultaneously exhibited the highest RPR titer within the cohort and did not receive standardized anti-syphilitic therapy following the index procedure.

Notably, the RCA stent, which had a secure 4.0-mm aortic protrusion, also developed severe ISR, manifesting as in-stent neoatherosclerosis rather than periaortic fibrous proliferation. This indicates that adequate mechanical protrusion alone does not guarantee protection against restenosis when systemic inflammatory and lipid-related processes remain uncontrolled, and reinforces that protrusion length addresses only the mechanical dimension of this multifactorial disease.

Accordingly, two non-mutually exclusive mechanisms may have contributed to the subsequent development of ISR: (1) incomplete lesion coverage at the ostial margin and (2) persistent inflammatory or infectious activity associated with inadequately controlled cardiovascular syphilis.

Because of the small sample size and observational design of this study, the relative contribution of these factors cannot be determined in this study. Therefore, Case 6 should not be interpreted as evidence of a causal relationship between stent protrusion length and restenosis. It should be regarded solely as an observational case illustrating the coexistence of procedural and systemic factors.

Pathological dimension: From vasa vasorum to “borderless” lesions

The essence of syphilitic aortitis is the involvement of the vasa vasorum in the aortic adventitia (1). Treponema pallidum invades the perivascular lymphatics, triggering lymphoplasmacytic infiltration and subsequent obliterative endarteritis. This process is most severe at the aortic root due to the high density of vasa vasorum. Destruction of medial elastic fibers and subsequent fibrosis (the “bark-like” appearance) lead to diminished mechanical support and compensatory intimal thickening (4).

Two key features of this inflammatory process are critical: first, it involves the entire vessel wall rather than being limited to the intima; second, it is “borderless” (1). In treating SCAOL, the angiographic ostial margin often does not represent the inflammatory terminus. Histologically, collagen disarray and endarteritis have been reported to frequently extend into the seemingly ‘normal’ aortic sinus wall, based on autopsy and surgical pathology series (1). Consequently, a conventional “flush-alignment” strategy may not fully account for the histological extent of inflammatory involvement described in prior pathological studies. Residual inflammatory tissue at the stent margin may theoretically contribute to neointimal proliferation and adverse vascular remodeling. However, the present study cannot determine whether this mechanism played a dominant role in the development of ISR observed in Case 6.

PCI versus CABG in syphilitic coronary ostial disease

Although PCI offers a less invasive revascularization strategy and may be particularly attractive for isolated ostial lesions, CABG remains an important therapeutic option in selected patients,with prior comparative data suggesting lower restenosis rates and better mid-term outcomes with surgical revascularization in SCAOL (10).

Surgical treatment may be preferred in the presence of significant aortic regurgitation, ascending aortic aneurysm, diffuse aortitis requiring root reconstruction, complex multivessel disease, or when concomitant valvular surgery is anticipated.

Conversely, PCI may represent a reasonable alternative in patients with isolated ostial disease, elevated surgical risk, or anatomy suitable for percutaneous treatment.

Because excessive stent protrusion could theoretically complicate future coronary re-engagement or surgical manipulation of the aortic root — particularly in patients who may subsequently require aortic valve surgery or root reconstruction — individualized procedural planning and consideration of stent protrusion length are recommended in clinical decision-making (11). In such cases, early multidisciplinary discussion between interventional cardiologists and cardiac surgeons is strongly recommended before committing to a percutaneous strategy.

Systemic management: the bedrock of success

The restenosis observed in Case 6 involved both procedural and systemic factors and cannot be attributed to a single mechanism. The persistently elevated RPR titer (1:128), together with the absence of standardized anti-syphilitic treatment, was present in this case; however, its direct contribution to ISR cannot be determined (12). The severe restenosis in Case 6 may suggest that incomplete pathological coverage at the stent margin, combined with uncontrolled inflammation, deteriorates the mechanical environment and accelerates ISNA, which is consistent with observations reported in previous IVUS studies describing residual edge-related restenosis patterns, where residual lesions at the stent margins led to procedural failure (13).

Therefore, successful management of SCAOL must integrate:

1. Standardized Antibiotic Therapy: Essential for eradicating spirochetes and halting aortitis progression (5).

2. Anti-inflammatory Intervention: The potential role of colchicine in syphilitic coronary ostial disease remains speculative. Although anti-inflammatory benefits have been demonstrated in atherosclerotic coronary disease, direct evidence supporting its use in syphilitic aortitis or syphilitic coronary ostial lesions is currently lacking (14, 15). Accordingly, colchicine remains investigational, and no recommendation for routine use can be made based on the present evidence.

3. Stringent LDL-C Targets: In patients with cardiovascular syphilis, achieving a lower LDL-C threshold (e.g., <1.4 mmol/L) is paramount. This target aligns with the 2019 ESC/EAS guidelines for very-high-risk populations and has been proven effective and achievable in clinical practice (14). From a mechanistic perspective, such intensive lipid-lowering therapy may help reduce the risk of inflammation-associated neoatherosclerosis, as suggested in prior studies (12), thereby mitigating the risk of late stent failure.

4. Prevention of Jarisch-Herxheimer Reaction (JHR): The Jarisch–Herxheimer reaction may occur following the initiation of anti-syphilitic therapy, potentially inducing transient hemodynamic instability (5, 16). To prevent acute coronary vasospasm or ostial occlusion triggered by the massive release of toxins from dying spirochetes, prophylactic low-dose corticosteroids may be considered prior to initiating antibiotic treatment in selected high-risk patients, in close collaboration with infectious disease specialists, although supporting evidence remains limited to case reports and expert opinion.

Hemodynamic dimension: mechanical rationale for protrusion vs. Flush-Alignment

The coronary ostium resides in a complex hemodynamic environment characterized by high shear stress and flow instability. Computational fluid dynamics simulations in ostial lesions suggest that conventional flush-alignment stenting may induce localized flow disturbances at the aortic root. In the context of SCAOL, a modest protrusion (∼2–4 mm) has been hypothesized to potentially influence local flow patterns at the coronary ostium by exposing the stent inlet to more stable aortic flow, thereby minimizing localized low wall shear stress that drives neointimal hyperplasia. In this study, six patients with favorable clinical outcomes had stents protruding 2–4 mm into the aortic sinus. This observation may be useful for hypothesis generation but should not be interpreted as evidence supporting a specific protrusion target. However, as computational modeling was not performed in our specific cohort, this mechanical rationale remains hypothesis-generating. Conversely, excessive protrusion (>5 mm) must be strictly avoided, as it has been associated with aortic valvular injury, future thrombotic complications, and potential impedance to future surgical or percutaneous aortic root intervention (17, 18).

Practical considerations for PCI in SCAOL

Synthesizing our experience with seven SCAOL cases, we propose the following practical procedural considerations (Table 3):

Table 3.

Proposed procedural considerations and potential mechanistic rationale for PCI in patients with SCAOL.

Procedural Step	Technical Essentials	Mechanistic Rationale
Pre-procedural Imaging	IVUS assessment of fibrotic severity	To exclude calcification and define the true anatomical ostium
Lesion Preparation	Robust pre-dilation with cutting balloons and high-pressure NC balloons	SCAOL is highly resilient and fibrotic; requires aggressive mechanical expansion
Stent Selection	Second- or third-generation DES (EES/SES)	Potent inhibition of exuberant neointimal hyperplasia
Stent Positioning	Aortic Sinus Protrusion (≥1 mm, commonly 2–4 mm)	May facilitate complete ostial coverage; requires further validation
Post-stenting Optimization	Maximize MSA under IVUS guidance	May help reduce flow disturbances that are associated with ISR in prior studies
Systemic Therapy	Penicillin + Investigational Colchicine (selected cases) + Statins	To eradicate the infectious source and suppress inflammation-driven progression

DES, drug-eluting stent; EES, everolimus-eluting stent; ISR, in-stent restenosis; IVUS, intravascular ultrasound; MSA, minimum stent area; NC, non-compliant; PCI, percutaneous coronary intervention; SCAOL, syphilitic coronary artery ostial lesions; SES, sirolimus-eluting stent.

Conclusion

This case series suggests that IVUS-guided PCI is technically feasible in selected patients with suspected syphilitic coronary ostial lesions. Moderate aortic protrusion was observed in this case series and may help ensure ostial coverage in the setting of inflammatory ostial disease, although its clinical significance for restenosis prevention remains uncertain. However, the present study cannot determine the optimal protrusion length or establish its impact on restenosis risk. These observations should be considered hypothesis-generating and require confirmation in larger multicenter studies.

Mechanical intervention remains only one component of comprehensive management; clinicians must ensure that mechanical revascularization is synergistically coupled with standardized systemic anti-syphilitic therapy. Future large-scale, multicenter prospective studies and computational fluid dynamics (CFD) simulations are warranted to further refine the optimal aortic protrusion depth and evaluate long-term safety and efficacy in this unique patient population.

Funding Statement

The authors declare that financial support was received for the research and/or publication of this article. This work was supported by the project of Prof. Xiangdong Li (No. 3R2210188430).

Data availability statement

The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.

Ethics statement

The studies involving human participants were reviewed and approved by the Ethics Committee of China-Japan Union Hospital of Jilin University. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

Author contributions

YQ: Writing – original draft, Formal analysis, Visualization, Software, Conceptualization, Validation, Investigation, Writing – review & editing, Data curation. ZW: Methodology, Validation, Formal analysis, Writing – original draft, Data curation, Project administration, Investigation, Visualization. JL: Methodology, Writing – review & editing, Software, Investigation, Supervision, Data curation, Visualization, Funding acquisition, Resources, Formal analysis, Conceptualization, Validation, Project administration. XL: Supervision, Writing – review & editing, Validation, Conceptualization, Investigation, Data curation, Project administration, Funding acquisition, Formal analysis, Methodology, Software, Resources, Visualization.

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

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Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fcvm.2026.1849354/full#supplementary-material