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Open research questions in Coronary Interventions and Diagnostics

48 unresolved questions extracted from the limitations and future-work sections of 410 Coronary Interventions and Diagnostics papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • Whether DCB angioplasty combined with selective stent implantation compromises 1-year primary patency compared with DCB monotherapy remains uncertain.

    Contemporary outcomes of a DCB-based strategy with selective stent implantation for femoropopliteal artery lesions: results from the REAL-LEAD registry · 2026 · DOI

  • Although the reason for the association remains unknown, the lack of statistical power due to the small sample size and short duration of this observation study may have contributed to this finding, in addition to the favorable effect of antihypertensive drugs on endothelial function.

    Assessment of and Factors Contributing to Adequate Endothelization After Drug-Eluting Stent Implantation · 2026 · DOI

  • Clinical Significance of the Wire Bias Pattern The concept of a wire bias pattern has not been previously described as a predictor of complications during OA for CN.

    Longitudinal Wire Bias Pattern on Intravascular Ultrasound as an Independent Predictor of Coronary Artery Injury During Orbital Atherectomy for Calcified Nodules ― A Single-Center Retrospective Study ― · 2026 · DOI

  • Future research should focus on prospective validation of the wire bias pattern classification system and development of standardized assessment protocols. Investigation of wire repositioning techniques and alternative treatment strategies for high-risk patterns is warranted. Additionally, develop- ment of automated or semi-automated IVUS analysis tools to identify wire bias patterns could facilitate widespread Longitudinal Wire Bias Predicts Injury During OA for CNAdvance Publication 8 clinical adoption. Multicenter studies incorporating the extensive Japanese experience with atherectomy proce- dures would provide valuable validation of our findings.

    Longitudinal Wire Bias Pattern on Intravascular Ultrasound as an Independent Predictor of Coronary Artery Injury During Orbital Atherectomy for Calcified Nodules ― A Single-Center Retrospective Study ― · 2026 · DOI

  • Ultrasonic flow ratio (UFR), derived from intravascular ultrasound (IVUS), integrates intravascular imaging with computational physiological assessment; however, its prognostic performance relative to μQFR in patients undergoing IVUS-guided PCI remains insufficiently defined.

    Ultrasonic flow ratio versus Murray law-based quantitative flow ratio for predicting target vessel failure after IVUS-guided PCI · 2026 · DOI

  • 04), whereas BCB did not differ significantly from PCB in angiographic outcomes, although this finding is limited by the small number of BCB substantial studies heterogeneity. 10 mm for in-lesion MLD), and their clinical relevance remains uncertain given the absence of significant differences in clinical outcomes.

    A meta-analysis of the efficacy of limus-coated balloons vs. paclitaxel-coated balloons for coronary artery disease · 2026 · DOI

  • Very high-risk patients: Urgent coronary angiography and revascularization (<2 h) are recommended.

    CSC Guidelines for Percutaneous Coronary Intervention (2025) · 2026 · DOI

  • All previously men- tioned guidelines acknowledged that this topic represents a gap in evidence and encouraged future research on the tim- ing of revascularization of non-culprit lesions. The 2021 guidelines for coronary revascularization of the American College of Cardiology stated that evidence for immediate complete revascularization of non-culprit lesions in patients with STEMI is lacking [7]. ESC guide- lines for the management of STEMI and NSTEMI recom- mend complete revascularization of non-culprit lesions but a clear recommendation on the timing of revascularization of non-culprit lesions is lacking [8–10].

    Immediate versus staged revascularization in acute coronary syndrome and multivessel disease: a meta-analysis and meta-regression of RCTs · 2026 · DOI

  • Despite this there are limited data from studies comparing different types of DCB, particularly for a paclitaxel-coated balloon (PCB) using urea as the excipient.

    Real‐World Usage of a Paclitaxel‐Coated Balloon With Urea Compared With Other Contemporary Drug‐Coated Balloons: A 2‐Year Analysis From SCAAR in Over 6000 Patients · 2026 · DOI

  • While plaque morphology and composition are well recognized as critical determinants of vulnerability, their combined effects across clinically relevant stenosis severities (50%–80%) remain incompletely understood.

    Synergistic effects of plaque geometry and composition on coronary hemodynamics and mechanical stability: a multiscale computational study · 2026 · DOI

  • ABSTRACT Background The clinical impact of angiography‐based, computational pressure‐flow dynamics derived FFR (caFFR) after paclitaxel‑coated balloon (DCB) angioplasty remains unclear.

    Prognostic Value of Computational Pressure‐Flow Dynamics Derived FFR Measured Immediately After Successful Paclitaxel‑Coated Balloon Angioplasty for In‐Stent Restenosis Lesion · 2026 · DOI

  • The work is at the concept stage; the limitations below warrant explicit acknowledgment. (a) The two-regime plaque model is supported by the structural inhomogeneity observed in pathological specimens, but the quantitative partitioning between regimes (the 40%-60% weakly adhered estimate) is empirical and lesion-dependent. The actual partition across a clinical population is testable prediction 1. (b) The pointed balloon with pressure feedback approach assumes that gentle mechanical contact distinguishes weakly adhered material from structurally integrated material with adequate spatial resolution. This is a hypothesis based on the qualitative mechanics of layered atheroma; quantitative validation in real lesions across a representative population requires the porcine experiments. (c) The pressure feedback signal is an integrated measure of resistance over the full balloon-vessel contact area. Focal high-stress inclusions (small calcified spikes within otherwise soft material) may not raise the integrated signal above threshold despite producing dangerous local stress on intima or media. Conservative threshold calibration mitigates this; supplementary intra-chamber imaging recovers the missing channels for cases where focal inclusions matter. (d) The pressure feedback threshold calibration cycle has been specified but not validated. The asymmetric ratchet (initialize at population ceiling, adjust only downward) is a safety measure rather than a derivation; the appropriate population ceiling for each vessel class and indication is itself an empirical question. (e) The residual collagenase burden under the combined protocol is bounded above by the structurally integrated fraction of plaque (40%-60% of the chemistry-only specification) and may be lower if exposed-substrate kinetics provide an additional efficiency multiplier. The magnitude of any such kinetic enhancement is not derived in this work; the actual residual achievable while preserving cleaning efficacy is empirical and is testable prediction 3. (f) Direct percutaneous needle access to deep vessels has been described in the protocol, but the closure device performance for renal-artery-sized punctures (5-7 Fr) at this location has not been characterized at scale. Vascular closure device performance is itself one of the validation items. (g) The biodegradable coating concept is well supported by existing biomaterials research, but the specific deployment chemistry (in-situ polymerization in a saline-filled chamber, against a denuded vessel surface, with potential postcleaning chemical residue) requires preclinical material screening before in-vivo work. Coating adhesion to denuded vessel walls under returning pulsatile flow, dissolution kinetics tuned to expected reendothelialization windows, and cytotoxicity profiles are open questions. (h) The coronary ostial application requires a side-engaging asymmetric balloon that is not currently in the protocol's hardware set.

    Mechanical-Chemical Combined Atherectomy in a Topologically Isolated Arterial Segment · 2026 · DOI

  • Several directions extend the architecture beyond what is specified here. They are noted for future researchers, not developed as protocols ready for validation. Expanded mechanical methods within the chamber The pointed balloon with pressure feedback is recommended as the first-generation mechanical tool for reasons of regulatory shortness and clinician familiarity. The chamber, however, expands the operational envelope of every percutaneous mechanical method, and future operators may exploit this in several ways. Even cartilaginous or moderately cohesive atheroma can be reduced mechanically when the embolic constraint is removed, allowing methods more aggressive than balloon contact: rotational atherectomy burs, orbital atherectomy crowns, directional cutters, or scoring and cutting balloons can all be applied within the chamber to substrates they could not safely engage in flowing blood. A scoring balloon used early in the session to score the fibrous cap longitudinally can release softer underlying material into the next chemistry stage, potentially shortening that stage substantially; whether to do this depends on lesion characterization at the start of the session. Balloon surface modifications beyond the smooth or scoring profiles in current clinical use, including textured or abrasive surfaces with experimentally determined coarseness graded across balloon sizes, are open engineering directions. The role of these methods in the primary protocol depends on validation studies that have not been performed; the architecture supports their use if and when those studies establish appropriate safety and efficacy bounds.

    Mechanical-Chemical Combined Atherectomy in a Topologically Isolated Arterial Segment · 2026 · DOI

  • The increased cardiac death signal associated with paclitaxel-coated balloons, observed in exploratory post-hoc analyses, warrants further investigation and should be interpreted with caution given the limited event numbers and shorter follow-up in sirolimus-coated balloon lesion-driven trials.

    Drug-coated balloons vs. drug-eluting stents for coronary artery disease: an updated systematic review and meta-analysis of randomized controlled trials with lesion-specific insights · 2026 · DOI

  • in device-uncrossable lesions is the need to deliver the rotawire to the distal true lumen, which traditionally necessitates crossing the in-stent for rotational atherectomy CTO with an MC. This limitation makes rotational atherectomy less suited for overcoming device uncrossability, though it still remains an excellent bailout for undilatable lesions. On the other hand, laser atherectomy has the advantage of applicability over any 0.014 in. wire and can offer precise and effective tissue modification. Nevertheless, requiring specialized equipment and expertise that are not universally available may be the main limitation for its use. Balloon lithotripsy represents an emerging technology for modifying calcified plaques, though owing to its large, unfriendly profile, application in a CTO that cannot be crossed by low-profile balloons or MC is not impractical as a bailout strategy. Super high-pressure (OPN non-compliant) balloons and cutting/scoring balloons have proven effective in modifying the resistant neoatherosclerotic tissue in stent failure; however, their large profiles could limit their utility (20, 21). Similar to rotational atherectomy and balloon lithotripsy, these specialty balloons may better serve for undilatable lesions, but are less likely to overcome device uncrossability. low-cost In summary, in-stent Carlino probably can improve overall IS-CTO procedural success rates by providing a readily available catheterization standard, bailout option using laboratory equipment, potentially reducing the need for staged procedures or surgical revascularization. These two illustrative cases demonstrate that the in-stent Carlino technique can serve as an effective bailout strategy when conventional approaches to device uncrossability have been exhausted. The technique’s reliance on standard catheterization laboratory equipment and familiar procedural concepts enhances its practical applicability across diverse clinical settings. The improved safety profile— stemming from the tendency to confine injected contrast intra- plaque and reduce the risk of uncontrolled dissection— represents a significant advantage over conventional Carlino applications. Owing to its expected effectiveness, practicality, and safety, the in-stent Carlino technique can provide a valuable addition to the armamentarium for managing complex IS-CTOs. The presented cases provide a foundational concept for the technique and highlight its clinical utility as an innovative approach to overcome device uncrossability in IS-CTOs.

    In-stent Carlino—a novel bailout for device-uncrossable in-stent chronic total occlusions · 2026 · DOI

  • The in-stent Carlino technique represents an evolution in CTO intervention strategies, demonstrating how established concepts can be repurposed for novel applications. In-stent Carlino offers the advantage of utilizing standard catheterization to most laboratory equipment and interventional cardiologists. Future efforts should focus on defining selection, the appropriate patient and anatomy establishing standardized technical protocols, and conducting comparative studies with alternative bailout strategies. techniques familiar to this technique the role of fully establish Long-term angiographic and clinical outcomes data are needed in contemporary CTO practice. In addition, the role of adjunctive technologies, such as intravascular imaging guidance, should be investigated to further optimize technique performance and safety. The cases presented demonstrate that the in-stent Carlino technique offers a valuable addition to the armamentarium for managing challenging IS-CTOs, providing an effective bailout for device uncrossability while maintaining an solution improved conventional Carlino applications.

    In-stent Carlino—a novel bailout for device-uncrossable in-stent chronic total occlusions · 2026 · DOI

  • MLP performance degrades substantially with eccentric oval stenosis and dual-lesion configurations (R² = 0.0688 for single eccentric oval case); the paper identifies that MLP lacks geometric asymmetry handling but does not propose or test alternative fully-connected architectures, feature engineering strategies, or input preprocessing approaches that could improve MLP performance for eccentric stenosis prediction.

    Physics-informed graph neural networks for real-time prediction of wall shear stress in stenotic coronary arteries · 2026 · DOI

  • The Bland–Altman analysis for dual eccentric stenoses shows PI-GNN achieves the narrowest limits of agreement (−15.30 to 15.69 Pa), but the paper does not investigate whether this improvement scales consistently across varying Reynolds numbers, flow rates, or pulsatile flow conditions relevant to in vivo coronary hemodynamics.

    Physics-informed graph neural networks for real-time prediction of wall shear stress in stenotic coronary arteries · 2026 · DOI

  • Mixed-geometry scenarios combining upstream round and downstream oval eccentric stenoses (Fig. 17c) are tested only in single dual-lesion configurations; the generalizability of PI-GNN to complex clinical coronary artery geometries with three or more stenotic sites of varying shapes and eccentricities remains unvalidated.

    Physics-informed graph neural networks for real-time prediction of wall shear stress in stenotic coronary arteries · 2026 · DOI

  • The dual eccentric oval stenosis case (Fig. 17b) shows U-Net and PI-GNN both succeed in lesion localization, yet U-Net exhibits reduced wake prediction accuracy; a systematic comparison of feature extraction mechanisms between PI-GNN and U-Net for multi-lesion stenotic configurations is absent, preventing identification of which graph-based physics constraints enable superior wake pattern capture.

    Physics-informed graph neural networks for real-time prediction of wall shear stress in stenotic coronary arteries · 2026 · DOI

  • U-Net consistently underestimates peak wall shear stress and fails to fully resolve downstream wake patterns in eccentric oval stenosis configurations; the specific architectural modifications or training strategies needed to improve U-Net's handling of complex post-stenotic flow dynamics in coronary arteries are not addressed.

    Physics-informed graph neural networks for real-time prediction of wall shear stress in stenotic coronary arteries · 2026 · DOI

  • The PI-GNN model has been validated exclusively on severe stenosis cases (stenotic area ratio = 10%) with eccentric distances up to 0.6 mm; performance on mild-to-moderate stenosis severity levels (area ratios 30-70%) and larger eccentricities beyond 0.6 mm in eccentric coronary artery stenosis remains unexplored.

    Physics-informed graph neural networks for real-time prediction of wall shear stress in stenotic coronary arteries · 2026 · DOI

  • Chronic totally occluded (CTO) coronary artery often is problematic, with the majority of patients managed medically or referred for coronary artery bypass graft surgery (CABG), due to the lack of standardized indication criteria.

    Przezskórna rewaskularyzacja wieńcowa przewlekle zamkniętej tętnicy wieńcowej u pacjenta z ciężką dysfunkcja skurczową lewej komory. Mądre posunięcie? · 2020 · DOI

  • This is an important limitation because unmeasured variation in local practice, operator experience, imaging use, radiation practice, retrograde planning, and graft-route selection may have influenced both strategy selection and outcomes.

    Prior CABG and native-vessel CTO PCI: lesion complexity, strategy planning, procedural burden, and technical success in a multicenter registry · 2026 · DOI

  • To our knowledge, major atrioventricular (AV) conduction disturbances during CSR implantation have not been previously described.

    Case Report: Transient Complete Atrioventricular Block During Coronary Sinus Reducer Implantation: An Unexpected Complication · 2026 · DOI

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48 open questions have been extracted from the limitations and future-work passages of 410 Coronary Interventions and Diagnostics papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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