Part I ·  The Headline Data Five Years. 1,639 Patients. One Definitive Answer.

The RENOVATE-COMPLEX-PCI trial published its 5-year follow-up in the Journal of the American College of Cardiology earlier this year. The trial enrolled 1,639 patients with complex coronary artery lesions at 20 centers in South Korea, randomizing them 2:1 to intravascular imaging-guided PCI versus angiography-guided PCI. Median follow-up was 5.3 years, the longest randomized follow-up of its kind.

The primary endpoint was a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. The results:

32%  reduction in primary composite endpoint  HR 0.68 | 95% CI 0.51–0.91 | p=0.009

32%  reduction in cardiac death or target vessel-related MI  HR 0.68 | 95% CI 0.48–0.96 | p=0.029

83%  reduction in definite stent thrombosis  HR 0.17 | 95% CI 0.02–0.90 | p=0.036

2.4 months  additional event-free survival in imaging arm  RMST difference | 95% CI 0.6–4.1 | p=0.010

No late catch-up. The Kaplan-Meier curves separated in the first year and held that separation through 5+ years without convergence. The directional benefit beyond 2 years remained numerically intact (HR 0.72) even as the post-2-year period lost statistical power due to event density.

Based on this evidence, both ACC/AHA and ESC guidelines upgraded intravascular imaging guidance for complex PCI to a Class I recommendation. That is the highest guideline endorsement available. Adoption pressure is now institutional, not discretionary.

The trial doesn't just prove that imaging-guided PCI works. It tells us, with precision, where it works most and where current tools still leave patients at risk. That distinction is what builds the next product category.

Part II ·  The Mechanistic Architecture — Why Does Imaging Guidance Work? The Trial Tells You Exactly.

Figure 6 of the RENOVATE paper lays out the mechanistic cascade with unusual clarity for a clinical trial publication. It is worth reading carefully because it is effectively a product specification document for the next generation of intravascular imaging.

The mechanistic pathway runs through three phases:

Phase 1: Pre-Procedural Lesion Assessment

Intravascular imaging provides information that angiography cannot: true plaque burden, calcium arc and depth, vessel reference dimensions unobscured by foreshortening, and landing zone plaque characterization. Each of these inputs feeds a more accurate stent strategy.

Angiography gives you a luminogram. It shows you the shadow of a vessel. Intravascular imaging gives you the vessel wall. The difference between those two information sets is where stent underexpansion and geographic miss are born.

Phase 2: Stent Strategy and Sizing

Accurate reference vessel sizing is the single most consequential pre-deployment decision. Undersizing drives underexpansion. Oversizing risks dissection. Angiography-based sizing has well-documented systematic error, particularly in vessels with diffuse disease where the angiographic 'normal' reference segment is itself diseased.

The trial's stent length data reinforces this. Long coronary lesions (≥38mm intended stent length) showed an HR of 0.50. When a lesion requires a long stent, every millimeter of landing zone selection matters. Current IVUS and OCT provide this data in cross-section at discrete positions. The question is whether a tool can provide it more continuously, more quickly, and in anatomy currently inaccessible to a bulky catheter.

Phase 3: Post-Deployment Optimization

This is where the trial's optimization data becomes critical. Post-deployment assessment with intravascular imaging identifies underexpansion, malapposition, and edge dissection, then drives the additional post-dilatation or re-stenting that corrects them.

These corrections are the proximate cause of the clinical benefit.

The link between optimization and outcomes is quantified directly in the trial's exploratory Figure 5: patients with imaging-guided stent optimization achieved had a 9.1% primary endpoint rate at 5 years. Patients in the imaging arm without confirmed optimization: 11.7%. Angiography-guided arm: 14.9%. The optimization gradient is real and significant.

Key Inference:  The optimization gradient in the RENOVATE data — 9.1% TVF with optimized results versus 14.9% in the angiography arm — establishes the clinical value of every additional percentage point of procedural success. The challenge is that complex anatomy, lesion burden, and workflow constraints all limit how consistently that optimization ceiling can be reached.

Part III · The Optimization Gap — 45.4%. What That Number Actually Tells Us.

In the intravascular imaging-guided arm of RENOVATE, stent optimization criteria were met in 45.4% of patients. Not 75%. Not 60%. Fewer than half. This figure deserves careful interpretation.

It does not mean the imaging tools failed. It means that complex coronary artery disease is genuinely hard. The RENOVATE population was defined specifically by lesion complexity — CTOs, long lesions, calcified vessels, bifurcations, left main disease — and optimization in these settings is limited by anatomy, lesion biology, procedural time constraints, and operator workflow, not by imaging quality alone. The data breaks down further:

•       IVUS-guided optimization rate: 42.4% (339 of 800 patients)

•       OCT-guided optimization rate: 56.5% (157 of 278 patients)

•       At the lesion level: IVUS met all criteria in 55.5% of lesions, OCT in 65.9%

The OCT advantage over IVUS on optimization rates is a 14-point absolute difference at the patient level. OCT's higher resolution (approximately 10–15 microns versus IVUS at 100–150 microns) allows more reliable identification of stent strut apposition and edge dissection. But even the best-performing tool left a substantial proportion of cases without confirmed optimization — and the reasons are multi-factorial. Anatomy that limits catheter access, lesion length that challenges longitudinal assessment, and the cognitive demands of real-time image interpretation under procedural conditions all play a role.

What the optimization data does establish clearly is the clinical gradient: patients with confirmed imaging-guided optimization had a 9.1% primary endpoint rate at 5 years versus 11.7% in the imaging arm without confirmed optimization versus 14.9% in the angiography group. Every step up the optimization ladder has measurable clinical value.

The challenge is that fully capturing that value in the most complex cases requires tools and workflows that match the complexity of the anatomy.

The 45.4% optimization rate is not an indictment of IVUS or OCT. It is a measure of how demanding complex PCI truly is — and of how much clinical value remains to be captured as the field develops tools and workflows designed for the hardest anatomy.

What Optimization Failure Looks Like Over Time

Suboptimal stent deployment manifests through two primary failure modes on the long timeline:

• Underexpansion-driven restenosis: Stent underexpansion creates focal high-shear zones that drive neointimal hyperplasia. This typically manifests within 12 to 24 months and accounts for a significant proportion of early target lesion revascularization events. The imaging arm's superior early performance (HR 0.69 in the 0–2 year landmark period) reflects this mechanism being partially corrected.

• Malapposition and edge dissection-driven late thrombosis: Uncorrected malapposition leaves struts suspended in flowing blood, creating nidus for late stent thrombosis. Edge dissections, particularly those involving a lipid-rich plaque at the landing zone, can progress. The RENOVATE finding of 83% lower definite stent thrombosis risk in the imaging arm is the direct clinical consequence of catching these problems at the index procedure.

• Geographic miss-driven edge restenosis: This is the under-discussed failure mode. When stent edges land in diseased tissue, restenosis occurs at the margin rather than within the stent. The RENOVATE data makes this visible: edge restenosis accounted for 22.9% of target lesion revascularization events in the imaging arm versus 40.0% in the angiography arm. Imaging reduced but did not eliminate edge restenosis.

That last point is the one I want to sit with. Even with intravascular imaging guidance, nearly one in four TLR events in the imaging arm were caused by edge restenosis. The stent landed in diseased tissue that current imaging didn't fully characterize or flag.

That is a plaque characterization problem. It is solvable with better tissue characterization capability at the landing zone. It is one of the clearest technical gaps the trial exposes.

Part IV  ·  Subgroup Analysis  —  Where The Signal Is Strongest

The Lesion-Level Data Is the Roadmap.

The prespecified subgroup analysis is where the RENOVATE data becomes clinically granular and commercially instructive. Here is the full picture:

Reading this table as a product strategist tells a different story than reading it as a trialist. The gradient of benefit across lesion types is not random. It maps directly to the technical demands placed on current imaging tools.

Chronic Total Occlusion: HR 0.35

The most dramatic benefit in the entire trial. A 65% reduction in target vessel failure. CTO is also one of the most technically demanding settings for current intravascular imaging.

In CTO PCI, the fundamental challenge is that you cannot image inside the occlusion with current tools during wire crossing. IVUS and OCT require a lumen to traverse. They inform pre-crossing strategy (where to enter) and post-crossing optimization (did the wire go subintimal? is the stent properly expanded?), but they are silent during the actual crossing itself.

The benefit observed in the CTO subgroup almost certainly reflects the value of imaging in the pre- and post-deployment phases. Post-crossing, CTO vessels often have heavily diseased reference segments, calcified proximal caps, and distal vessel under-sizing risk from collapsed lumen in the chronic occlusion zone. Imaging catches these problems.

The SFE platform, with its miniaturized form factor, is designed to navigate complex tortuous anatomy. The clinical case for better imaging access during CTO crossing and post-crossing assessment in CTO PCI is established by this single data point. HR 0.35.

Unprotected Left Main: HR 0.37

Left main disease carries the highest per-event mortality risk of any coronary lesion. A 63% reduction in target vessel failure with imaging guidance in this subgroup is a powerful signal — and also reflects the demanding anatomy. Ostial left main lesions, distal bifurcation involvement, and the requirement for precise stent sizing in a large vessel with high flow all create conditions where the marginal value of accurate information is maximal.

Notably, left main PCI optimization with current tools requires careful imaging in both the left anterior descending and circumflex after stenting, creating a multi-vessel imaging workflow that adds procedural time. Better workflow efficiency in left main imaging — faster pullbacks, more automated measurement — is a design target with direct clinical relevance here.

Diffuse Long Lesion (≥38mm): HR 0.50

Long lesions expose the most significant limitation of current imaging workflow. IVUS and OCT provide cross-sectional information at one point in time. To assess a 50mm stented segment, a clinician pulls the catheter back through the stent and mentally integrates a sequence of cross-sections into a three-dimensional picture.

This cognitive assembly process introduces variability. Geographic miss — where a stent edge is placed in a diseased segment that 'looked' normal in a particular cross-section — is more likely across long stent lengths.

A platform capable of providing more continuous longitudinal vessel visualization, with automated edge assessment, would directly address the failure mode that the long lesion subgroup data implicates. The HR of 0.50 in this subset tells us the problem is real and large.

Severely Calcified Lesions: HR 0.48

Calcification creates two distinct imaging problems. First, heavy calcium attenuates ultrasound signal in IVUS and creates signal shadow in OCT, obscuring vessel wall anatomy behind calcium deposits. The true deep calcium arc, critical for deciding whether atherectomy or specialized balloon preparation is needed before stenting, can be underestimated.

Second, heavily calcified vessels often have complex calcium fracture patterns after high-pressure balloon dilatation. Imaging confirms whether calcium has cracked — a prerequisite for adequate stent expansion — but current tools have resolution limitations in characterizing fracture patterns within densely calcified plaques.

The imaging benefit in the severely calcified subgroup (HR 0.48) reflects the value of seeing calcium architecture that angiography completely misses. Better characterization of calcium before and after preparation remains a technical priority.

In-Stent Restenosis: A Note on Subgroup Interpretation

The RENOVATE subgroup data includes in-stent restenosis as a lesion category (HR 0.99, numerically the lowest benefit in the analysis). This finding warrants careful interpretation before drawing clinical conclusions.

First, the ISR subgroup was not a prespecified analysis endpoint — it was reported as part of the broader subgroup exploration. With approximately 240 patients in this category, the analysis was almost certainly underpowered to detect a meaningful difference even if one existed. Subgroup analyses of this size are hypothesis-generating at best, and should not be treated as definitive.

Second, and perhaps more importantly, the clinical picture for IVI in ISR is more nuanced than a single hazard ratio suggests. Intravascular imaging plays a well-established role in ISR management — characterizing the underlying mechanism (underexpansion, malapposition, neoatherosclerosis, or geographic miss), guiding preparation strategy, and sizing the new stent layer appropriately. The absence of a measurable outcome signal in a small subgroup does not negate that clinical utility. It is more likely a reflection of sample size than a true null effect.

Interpretive Caution:  Non-prespecified subgroup analyses with fewer than 300 patients are hypothesis-generating only. The ISR finding in RENOVATE should prompt further investigation, not clinical or strategic conclusions.

Part V ·  The Late Period Data — What Happens After Year Two Tells a Different Story.

The landmark analysis at 2 years provides a cleaner window into the biology of late benefit than the cumulative curves suggest. Between randomization and 2 years, the imaging arm benefit was strong and statistically significant (HR 0.69, p=0.013). Beyond 2 years, the primary endpoint trended toward imaging guidance but lost statistical significance (HR 0.72, p=0.267).

The conventional read is that early benefit is maintained without late catch-up. That is accurate. But the late-period secondary endpoint data contains something more interesting.

Repeat Revascularization Beyond 2 Years: HR 0.42, p=0.015

In the period beyond 2 years, overall repeat revascularization was 58% lower in the imaging group, and this was statistically significant. Late revascularization events beyond the stented segment — non-target vessel events — drove a striking result:

75%  reduction in non-target vessel revascularization beyond 2 years  HR 0.25 | 95% CI 0.09–0.68 | p=0.006

This result is not easily explained by index-procedure optimization. Non-target vessel revascularization beyond 2 years reflects disease progression in vessels that were not treated at the index procedure. The imaging group fared dramatically better on this metric.

Several explanations are plausible. Patients who receive comprehensive intravascular imaging at index procedure may have their total coronary disease burden better characterized, enabling more complete revascularization planning or better selection of medical therapy targets. Alternatively, the imaging group's lower rate of periprocedural myocardial infarction may reflect preserved coronary microvascular function that protects against ischemic progression in non-target territory.

The more intriguing possibility is that coronary imaging at the index procedure provides information about non-target vessel plaque burden that influences subsequent treatment decisions, even without a systematic protocol for doing so. This is the implicit argument for a platform that can assess the full coronary tree more efficiently — not just the culprit vessel.

Neoatherosclerosis: The Invisible Late Adversary

The RENOVATE trial does not directly address neoatherosclerosis, but Figure 6's mechanistic pathway explicitly names it as a driver of late stent failure. Neoatherosclerosis — the development of lipid-laden foam cells within neointimal tissue inside a deployed stent — is increasingly recognized as the mechanism behind very late stent thrombosis and late restenosis beyond 3 to 5 years.

Current intravascular imaging can suggest neoatherosclerosis through tissue characterization (lipid-laden neointima appears differently in OCT than fibrous neointima), but formal neoatherosclerosis assessment is not routine practice. It requires dedicated interpretation, and the current tools were not designed with this as a primary use case.

As the clinical community follows up stented patients beyond 5 years — as this trial encourages — the demand for imaging tools capable of characterizing neointimal tissue composition rather than just lumen geometry will grow. This is an application where the evolution of platform capability matters as much as procedural access.

Part VI ·  What SFE Is Designed to Address — Mapping the Gaps to the Platform.

VerAvanti is developing the Scanning Fiber Endoscope (SFE) platform. It is an investigational intravascular imaging system. It has not received FDA 510(k) clearance. Everything that follows is a description of the clinical rationale informing our development priorities — grounded in published evidence like the RENOVATE trial.

The SFE platform is built on a fundamentally different technology architecture than IVUS or OCT. Rather than a rotating transducer or interferometric backscatter, it uses a miniaturized scanning fiber that sweeps a focused light spot across tissue, enabling high-resolution forward and side visualization from an extremely small catheter profile. The result is a platform designed to reach anatomy that current tools cannot access and to provide imaging information that current tools do not deliver.

Here is how the RENOVATE data maps to our development priorities:

Priority 1: CTO and Complex Bifurcation PCI Access

Our first commercial target indications are CTO crossing and bifurcation PCI. This was not an arbitrary strategic choice. It reflects the clinical data.

The RENOVATE CTO subgroup showed HR 0.35 with current imaging tools. That means even the best available technology reduces but does not eliminate the CTO failure burden.

The remaining events include cases where imaging either could not access the anatomy or could not provide the information needed to avoid the failure mode.

The SFE platform's miniaturized profile is intended to enable imaging access in anatomy that excludes current IVUS and OCT catheters — smaller caliber vessels, complex curves, and potentially imaging in the context of microcatheter-assisted CTO crossing where there is no space for a conventional imaging catheter alongside the working wire.

In bifurcation PCI, the imaging requirement is three-dimensional: main vessel reference sizing, side branch ostial geometry, and post-stenting assessment of the carina and both limbs. Current imaging workflows address these sequentially with separate catheter passes. A platform with forward-looking visualization capability could transform bifurcation assessment from a series of pullbacks into a more continuous workflow.

Priority 2: Workflow Efficiency and Imaging Accessibility

One of the underappreciated constraints on optimization rates in complex PCI is procedural time. The RENOVATE imaging arm added approximately 15 minutes to procedure duration. That time cost is real — and in practice it creates pressure to abbreviate imaging protocols, particularly post-deployment assessment, in the most demanding cases.

A platform that reduces the time and complexity of comprehensive imaging assessment — without sacrificing coverage or resolution — makes the full imaging protocol more consistently executable across the operator spectrum. The goal is not to replace the clinical judgment of an experienced interventionalist, but to make rigorous imaging workflow accessible to every operator treating complex anatomy, not just those at high-volume centers with specialized imaging expertise.

The SFE platform's design intent includes rapid vessel assessment with integrated automated measurement support. The aim is to reduce the cognitive and time burden of complex imaging workflows, making thorough pre- and post-deployment assessment more consistently achievable in the hardest anatomical settings.

Priority 3: Landing Zone and Edge Assessment

Edge restenosis accounted for 22.9% of target lesion revascularization events even in the RENOVATE imaging arm. The mechanism is geographic miss — stent edges placed in diseased tissue that current imaging characterized as acceptable landing zones.

This is a plaque characterization problem. The landing zone plaque that drove future restenosis was visible to imaging but not flagged as a contraindication to stenting at that site. Better tissue characterization at landing zones — particularly identification of thin-cap fibroatheroma or heavily lipid-laden plaque that predisposes to geographic miss complications — is an unmet need that the RENOVATE edge restenosis data quantifies directly.

The SFE platform's optical approach is intended to enable tissue-level characterization beyond geometric lumen assessment. This is an area of active development, and the clinical case for it is now established in prospective randomized data.

Secondary Application: Long Lesion Automated Assessment

The long lesion subgroup (HR 0.50) represents the largest patient category in RENOVATE: 54.8% of the trial population had expected stent length ≥38mm. Providing comprehensive imaging assessment of a 50-60mm stented segment is cognitively demanding with current tools.

An SFE-based platform with automated longitudinal reconstruction and continuous edge-to-edge assessment is designed to reduce the cognitive integration burden. Rather than assembling a mental picture from sequential cross-sections, the operator receives a continuous rendering of the stented segment with automated flagging of underexpansion, malapposition, and edge dissection zones.

This is not a marginal workflow improvement. It is the difference between an imaging tool that requires an expert interpreter and one that can be deployed reliably across the full range of complex PCI operators. That scalability is what makes population-level outcome improvement possible.

Tertiary Application: Non-Coronary Vascular Indications

The SFE platform is designed as a head-to-toe intravascular imaging system. The clinical rationale extends meaningfully beyond coronary PCI.

In peripheral arterial disease, the RENOVATE data has an analogue: complex lesion types (long segment disease, heavily calcified vessels, in-stent restenosis) are the norm rather than the exception. Peripheral PCI optimization suffers from the same geometric miss and underexpansion problems as coronary PCI, with the additional challenge that current IVUS and OCT have limited adoption below the knee where vessel caliber shrinks. The SFE platform's small profile is particularly relevant in tibial and pedal vessel intervention.

In neurovascular intervention — an indication served by Dr. Luis Savastano, VerAvanti's clinical medical officer and a cerebrovascular and endovascular neurosurgeon at UCSF — the intracranial vessel environment presents imaging challenges that coronary-optimized tools are not designed to address. Intracranial vessel diameters, vessel tortuosity, and the blood-brain barrier environment all create a case for an imaging platform developed with neurovascular anatomy in mind from the outset rather than adapted from coronary tools.

Part VII  ·  The AI Layer — Imaging Plus Intelligence: The Platform Convergence Thesis.

The RENOVATE trial is a hardware story: imaging catheter guidance produces better outcomes than no imaging catheter guidance. But the underlying limitation that constrains the optimization rate is not purely hardware. It is also software.

The stent optimization criteria in RENOVATE were assessed by trained operators interpreting imaging data in real time. Meeting the criteria required recognizing underexpansion, malapposition, and edge dissection in cross-sectional images under procedural conditions. The 45.4% optimization rate reflects both the capability of the imaging tool and the reliability of human interpretation under those conditions.

AI-driven real-time interpretation of intravascular imaging changes the equation. If the imaging system automatically identifies optimization failures and alerts the operator — rather than requiring the operator to identify them — the optimization rate is no longer limited by interpretive variability. It becomes limited by the resolution and coverage of the imaging tool itself.

VerAvanti's development roadmap incorporates AI-assisted interpretation as a core SaMD layer on the SFE platform. The clinical rationale for this integration is now supported by the RENOVATE data in a specific, quantified way: every point of improvement in optimization rate has a measurable clinical value, and AI-driven consistency is the mechanism for capturing it.

The regulatory pathway for AI/SaMD in intravascular imaging is increasingly defined. The FDA has cleared multiple AI-assisted tools in adjacent imaging modalities. The SFE platform's development includes dedicated regulatory architecture for the AI layer, designed to support the FDA 510(k) pathway in parallel with the imaging hardware clearance process.

The SFE platform is not an imaging catheter with an app. It is an imaging-intelligence system where the miniaturized optics and the AI interpretation layer are co-designed to bring comprehensive intravascular imaging into the anatomical settings that current tools cannot consistently reach.

Part VIII ·  What This Means for the Field — The Guideline Upgrade Is the Starting Gun.

The ACC/AHA and ESC Class I guideline upgrade for intravascular imaging in complex PCI is a commercial inflection point. Hospital systems, cath lab directors, and value analysis committees will now evaluate whether they have adequate imaging infrastructure for complex PCI. The RENOVATE data gives them a five-year outcomes argument and a reimbursement narrative.

This creates a more favorable environment for VerAvanti's commercial launch than existed 18 months ago. The question is no longer whether to use intravascular imaging. The question is which imaging platform delivers the optimization capability that the guideline now mandates and the evidence now defines.

Current IVUS and OCT manufacturers will benefit from the guideline upgrade and will drive adoption. VerAvanti is not entering this market to displace those tools from their established indications. We are entering to serve the cases they cannot reach and the failure modes they have not eliminated.

The HR of 0.35 in CTOs — the anatomy where no current imaging tool has full access during crossing. The HR of 0.50 in long diffuse lesions — where longitudinal coverage and cognitive integration demand the most from operator and tool alike. The 22.9% edge restenosis rate even in the imaging arm — a signal that landing zone plaque characterization remains an unmet need. These are not arguments against IVUS and OCT.

They are the clinical rationale for what comes next.

The evidence is in — The work is not finished.

Five years of prospective randomized data tells us that intravascular imaging guidance saves lives in complex PCI. It also tells us, with a precision that only a long-follow-up trial can provide, exactly where the gaps remain. Those gaps are the clinical brief for the next generation of intravascular imaging.

That is what VerAvanti is building toward.

Disclosure: The VerAvanti SFE platform is investigational and has not received FDA 510(k) clearance. All clinical capabilities described are investigational.

Clinical reference: Lee JM, Kim O, Song YB, et al. Intravascular Imaging- vs Angiography-Guided Complex PCI: 5-Year Outcomes From a Randomized Trial. JACC. 2026. doi:10.1016/j.jacc.2026.01.035.