The Hidden Time Bomb: Understanding Very Late Scaffold Thrombosis
A revolutionary medical device promises to disappear, but its legacy can be deadly.
Imagine a medical implant that does its job and then vanishes—no foreign material left behind, no permanent metallic cage in your arteries. This was the revolutionary promise of bioresorbable vascular scaffolds (BRS), the next great innovation in cardiac care. Unlike traditional metal stents that remain in the body permanently, these temporary scaffolds provide support to cleared arteries and then gradually dissolve over several years.
Yet this breakthrough came with an unexpected and dangerous trade-off: very late scaffold thrombosis (VLScT)—a sudden, potentially fatal blood clot that can form at the implantation site long after the procedure, even years later when the scaffold is supposedly safely dissolving. This phenomenon turned hope into concern, revealing complex challenges at the intersection of medical innovation and human biology.
The Revolution That Stumbled: From Metallic Stents to Disappearing Scaffolds
The evolution of coronary artery treatment has been marked by successive revolutions. First came balloon angioplasty, then bare-metal stents, followed by drug-eluting metal stents. Each solved previous limitations but introduced new complications, particularly the risk of late stent thrombosis with permanent metallic implants 8 .
Bioresorbable scaffolds emerged as the fourth revolution, designed to provide temporary support to arteries while releasing drugs to prevent restenosis (re-narrowing), then completely dissolve within 2-4 years. The theoretical advantages were compelling:
Advantages of BRS
- Restoration of natural vasomotion
- Elimination of permanent foreign material
- Potential for shorter antiplatelet therapy
- Facilitation of future surgical options
VLScT Concerns
- Blood clots forming >1 year after implantation
- Occurs during scaffold resorption phase
- Presents as sudden heart attacks
- Higher mortality rates
The most extensively studied BRS, the Absorb BVS, showed initial promise in clinical trials. But by 2016-2017, concerning signals emerged regarding VLScT—blood clots forming in the scaffold more than a year after implantation, often when the scaffold was well into its resorption phase 3 8 .
Why Very Late Thrombosis Matters
Unlike early complications, VLScT strikes unexpectedly in patients who have typically completed their standard course of antiplatelet therapy and resumed normal lives. The event is often dramatic—presenting as sudden heart attacks with high mortality rates. A meta-analysis of 24 studies revealed that the risk of VLScT between 1 and 2 years was significantly higher with bioresorbable scaffolds compared to conventional everolimus-eluting stents 3 .
Inside the INVEST Registry: A Forensic Investigation
To understand why VLScT occurs, the INVEST registry (Independent OCT Registry on Very Late Bioresorbable Scaffold Thrombosis) performed a detailed forensic analysis of this phenomenon. This international consortium brought together researchers from 19 centers to examine 36 patients with 38 documented VLScT cases using optical coherence tomography (OCT)—an advanced imaging technology that provides microscopic-level detail of coronary arteries 4 .
Methodology: Piecing Together the Puzzle
Case Identification
Between June 2013 and May 2017, they identified patients who experienced VLScT at a median of 20 months after Absorb BVS implantation.
Advanced Imaging
Each patient underwent OCT imaging during their thrombotic event, allowing researchers to see inside the arteries at ultra-high resolution (approximately 10-20 microns).
Thrombus Analysis
When possible, aspirated blood clots were examined using histopathological and spectroscopic methods to identify polymer fragments and cellular composition.
Mechanism Classification
Each case was analyzed to determine the primary mechanism leading to thrombosis, with particular attention to the relationship between scaffold struts, vessel wall, and thrombus material.
Revelations from the INVEST Registry
The INVEST registry identified several distinct mechanisms behind VLScT, with surprising findings that challenged initial assumptions about bioresorbable technology:
| Mechanism | Frequency | Description |
|---|---|---|
| Scaffold Discontinuity | 42.1% | Strut separation causing malapposition and flow disturbances |
| Malapposition | 18.4% | Struts not fully opposed to vessel wall, creating thrombogenic pockets |
| Neoatherosclerosis | 18.4% | New atherosclerotic plaque development within the scaffold |
| Underexpansion/Recoil | 10.5% | Insufficient initial expansion or late contraction of the scaffold |
| Uncovered Struts | 5.3% | Struts without endothelial coverage, exposing thrombogenic material |
| Edge Disease Progression | 2.6% | New disease developing at the edges of the scaffold |
The most surprising finding was that scaffold discontinuity—where the dissolving scaffold structure breaks apart—was the predominant mechanism, responsible for over 40% of cases 4 . This represented a failure mode unique to bioresorbable technology, not seen with permanent metallic stents.
| Characteristic | Finding in INVEST Registry | Significance |
|---|---|---|
| Timing | Median 20 months (IQR: 16-27) | Occurs during active scaffold resorption |
| Antiplatelet Therapy | 83% on aspirin alone, 17% on DAPT | Most events occurred after DAPT discontinuation |
| Strut Coverage | Significantly less in thrombosed areas | Incomplete healing increases thrombosis risk |
| Malapposed Struts | 17x higher odds in thrombosed areas | Improper strut-vessel contact enables clotting |
The Perfect Storm: Understanding Why Scaffolds Fail
The INVEST registry findings revealed that VLScT typically results from a combination of factors rather than a single cause.
Scaffold discontinuity occurs when the polymer structure fractures during the resorption process. Instead of harmonious, synchronized dissolution, portions of the scaffold break free, creating protruding fragments that disrupt blood flow and become nuclei for clot formation 4 .
Evidence suggests that first-generation bioresorbable scaffolds were particularly sensitive to implantation technique. The PSP approach (Proper vessel sizing, Slow expansion, High-pressure Post-dilation) emerged as crucial for optimal outcomes .
The very concept of "bioresorption" implies an inflammatory process as the body breaks down the polymer. In some cases, this process may become dysregulated, leading to delayed healing and inflammation.
Spectroscopic analysis of aspirated thrombi from some patients confirmed the presence of persistent intracoronary polymer fragments years after implantation—a finding that contradicted expectations of smooth, complete resorption 2 .
Spectroscopic Findings
Analysis confirmed persistent polymer fragments in aspirated thrombi, contradicting expectations of complete resorption 2 .
Clinical Case
A patient who discontinued antiplatelet therapy 10 months prior presented with VLScT at 28 months, suggesting healing abnormalities persist beyond standard DAPT duration 6 .
The Scientist's Toolkit: Investigating VLScT
Researchers studying VLScT rely on specialized tools and techniques to unravel this complex phenomenon:
| Tool/Technique | Primary Function | Research Application |
|---|---|---|
| Optical Coherence Tomography (OCT) | High-resolution intravascular imaging | Identifies malapposition, discontinuity, and tissue coverage |
| Histopathological Analysis | Microscopic tissue examination | Characterizes thrombus composition and inflammatory response |
| Spectroscopic Analysis | Material composition identification | Detects persistent polymer fragments in aspirated thrombi |
| Thrombus Aspiration | Physical clot removal | Provides material for analysis and restores blood flow |
| Serial Angiography | Visualizing arterial lumen | Assesses blood flow restoration and residual stenosis |
Lessons Learned and Future Directions
The VLScT story represents both a setback and a valuable learning opportunity for medical science. The higher rates of VLScT with first-generation BRS led to market withdrawal of the Absorb scaffold and prompted serious reevaluation of bioresorbable technology .
Silver Linings and Future Directions
Despite these challenges, the investigation of VLScT has yielded crucial insights:
Improved Device Design
Second-generation devices like the Magmaris resorbable magnesium scaffold show promise for better safety profiles 1 .
Technique Refinement
The importance of meticulous implantation technique is now widely recognized.
Patient Selection
Better understanding of which patients are—and aren't—suitable candidates for bioresorbable technology.
Therapy Individualization
Evidence suggests that prolonged dual antiplatelet therapy may be necessary for some patients 9 .
Case reports have emerged showing successful treatment of VLScT with newer technologies, including implantation of novel resorbable magnesium scaffolds within previously thrombosed segments, with excellent long-term results on follow-up imaging 1 .
Conclusion: The Path Forward
The story of very late scaffold thrombosis illustrates the complex, often unpredictable journey of medical innovation. What begins as a theoretically superior concept must withstand the rigorous test of human biology and real-world practice.
While first-generation bioresorbable scaffolds demonstrated higher than expected rates of VLScT, the investigation of this phenomenon has fundamentally advanced our understanding of vascular healing and device-body interactions. The knowledge gained continues to inform the development of safer, more effective bioresorbable technologies that may yet fulfill the original promise of temporary scaffolding that disappears without sequelae.
In interventional cardiology, as in all medicine, each setback contains valuable lessons that ultimately propel the field forward. The careful study of failure often illuminates the path to success.