{"id":"dccf321a-681f-4443-86f3-9fee33f2238c","arxiv_id":"2505.13536","paper_version":1,"verdict":"CONDITIONAL","confidence":"MODERATE","novelty_score":4.0,"correctness_risk":"medium","formal_verification":"none","parameter_count":2,"one_line_summary":"In reduced-order 1D-2D coronary CFD, irregular stenoses yield lower FFR and iFR and higher pressure drops than smooth stenoses at equal severity across all tested rheology models.","lead":"This study uses computer simulations of blood flow, combining a fast one-dimensional model of the full arterial tree with a detailed two-dimensional model of a narrowed coronary artery, to estimate the clinical scores FFR and iFR at 40 to 70 percent blockages. It finds that irregular blockages produce lower FFR and iFR values and higher pressure drops than smooth ones, suggesting wall roughness matters when assessing blockage severity.","discovery_kind":"extension","skeptic_critique":{"model":"deepseek-v4-flash","headline":"The irregularity model driving the headline claim is never specified: no shape equation, amplitude, or wavelength is given, so the FFR/iFR contrast cannot be reproduced or verified to compare equal severities.","rationale":"The reader's weakest assumption identifies the unverifiable periodic irregularity model as the load-bearing input, and that is exactly the concern that matters most here. The paper's novelty is the irregular-vs-smooth comparison; if the irregularity geometry is unspecified or unrepresentative, the central FFR/iFR contrast cannot be interpreted. I agree with the CONDITIONAL verdict: the direction of the result is physically reasonable, but the missing shape equation, absent reproducibility data, and unclear FFR/iFR definition mean the quantitative claim cannot be accepted as stated. The concrete sensitivity check would settle whether the finding is an artifact of the chosen amplitude or a genuine independent resistance effect. No change from the reader's verdict is needed, only a sharper statement of the condition: supply the geometry specification and the sensitivity analysis, and clarify the FFR/iFR computation protocol.","tokens_in":6611,"tokens_out":7821,"duration_ms":83272,"concrete_test":"Obtain from the authors the exact radial-coordinate function r(x) for both the smooth and irregular stenoses used in Section 2.1, and rerun the 2D axisymmetric simulations for irregularity amplitudes spanning 0.1x to 2x the calibrated value and wavelengths spanning 0.5x to 2x the nominal value. If the FFR/iFR difference between smooth and irregular lesions drops below 0.01 or changes sign for any amplitude within the physiological range, the headline claim is not robust. Also recompute the reported FFR using an explicitly hyperemic 1D boundary condition; if the irregularity effect changes by more than 0.01, the quantity should not be labeled FFR.","verdict_should_be":"UNCHANGED","load_bearing_attack":"The central comparison of Section 3 depends entirely on the generated irregular lesion geometry, but Section 2.1 does not actually specify that geometry. The paper reports only that the irregularity height is 'calibrated' to a left circumflex coronary arterial cast and that the shape is periodic; the wall-radius function, amplitude, wavelength, and number of undulations are absent, and the numerical height values are not reported, so the provenance cannot be checked. Without the shape equation, Figures 8-10 cannot be reproduced, and it is impossible to verify that the smooth and irregular cases share the same stenosis severity. If the periodic irregularities reduce the minimum lumen area beyond the nominal 40/50/70% severity, the observed lower FFR and iFR would reflect a severity mismatch rather than an independent irregularity effect. The manuscript also never defines how FFR and iFR are computed from the 1D-2D pressure/flow fields, including whether a hyperemic state is modeled for FFR, so the clinical interpretation is underspecified. The directional finding is physically plausible, but the quantitative contrast that the abstract presents as clinically meaningful rests on an unverifiable geometric and physiological protocol.","agreement_with_reader":"agree"},"referee_report":{"model":"deepseek-v4-flash","summary":"The paper presents a reduced-order CFD framework that couples a 1D model of the full arterial tree with a 2D axisymmetric model of a stenosed coronary artery, using patient-specific CT-based geometry described in the text. The authors compute FFR, iFR, and pressure drop for 40%, 50%, and 70% stenoses using Newtonian and non-Newtonian (power-law, Carreau-Yasuda, Casson) rheology models. The central reported finding is that irregularly stenosed arteries exhibit lower FFR and iFR values and higher pressure drops than smooth stenosed arteries at the same nominal severity. The paper also includes grid independence studies and validation against literature waveforms for the 1D and 2D solvers.","tokens_in":6814,"tokens_out":3272,"duration_ms":32722,"significance":"If the central irregular-versus-smooth contrast is robust, the finding that surface irregularity acts as an independent flow-resistance factor would be clinically relevant for non-invasive FFR/iFR estimation. The paper's strengths include an explicit 1D-to-2D boundary-condition pipeline, systematic comparison of four rheology models, grid independence checks, and validation against established numerical solutions. However, the significance is currently bounded by missing specification of the irregular lesion geometry and absent definitions of the clinical indices, which prevent reproduction and quantitative interpretation.","major_comments":[{"comment":"The analytic representation of the irregular stenosis is never specified. The paper states only that the irregularity height is 'calibrated' to a left circumflex coronary arterial cast and that the shape is assumed periodic, but it gives no wall-radius function, amplitude, wavelength, or number of undulations. Because the central irregular-versus-smooth contrast in Figures 8-10 depends entirely on this generated geometry, the authors must provide the exact formula and parameter values, and demonstrate that the minimal luminal area (and hence stenosis severity) is identical between the smooth and irregular cases.","section":"Section 2.1"},{"comment":"FFR and iFR are never defined. The manuscript does not state how these indices are computed from the 1D or 2D pressure/velocity fields, whether a hyperemic state is simulated for FFR, or which proximal and distal reference pressures are used. Without these definitions, the reported numerical values cannot be clinically interpreted or independently reproduced.","section":"Section 3"},{"comment":"The 2D validation is performed for a generic test case with diameter D = 1 m, viscosity μ = 1 Pa·s, and velocity U = 0.5 m/s. This demonstrates solver capability on idealized stenotic flows but does not validate the coronary-scale geometry, rheology, or the specific boundary-condition combination used in the clinical calculations. The authors should add a coronary-scale validation or explicitly qualify that the validation applies only to the underlying numerical scheme.","section":"Section 2.2.5"},{"comment":"Table 1 lists three single outlet pressure values (106.154, 104.296, and 93.303 mmHg) with no indication of whether these are mean, systolic, end-diastolic, or some time-averaged quantities. Since FFR is a ratio of distal to aortic pressure, the absolute FFR values reported in Figure 8 inherit the choice of these boundary conditions; the basis for these values and their relation to the 1D pressure waveforms must be clarified and justified.","section":"Table 1"},{"comment":"No comparison with measured FFR or iFR values is provided. The abstract claims a 'reliable, non-invasive diagnostic tool,' but without comparison to invasive or computed-tomography-derived FFR/iFR measurements from patients, the quantitative accuracy of the method is unverified. Add a validation against published clinical FFR/iFR data, or temper the clinical claim accordingly.","section":"Section 3"}],"minor_comments":[{"comment":"There are two subsections labeled '2.1.4' (Grid independence study and Validation study), and the later section heading '2 2D Numerical details' should be renumbered as 2.2. The subsection numbering throughout the methodology should be made consistent.","section":"Section 2.1"},{"comment":"The caption reads '1D boundary condition generated for different severity...', but the figure appears to show flow-rate waveforms. Make the caption consistent with the content, and clarify which variable is plotted.","section":"Figure 5"},{"comment":"The abstract and introduction emphasize patient-specific multi-slice CT scans, but the methodology does not describe how CT images are segmented or converted into the 1D arterial tree and the 2D stenosis model. A brief description of the imaging-to-model pipeline is needed.","section":"Introduction"},{"comment":"The sentence 'The severity of stenosis of patient-specific cases are 40, 50 and 70 which are of intermediate grade stenosis' has grammatical errors and does not state whether severity is a diameter reduction or area reduction. Please define severity and correct the phrasing.","section":"Section 2.1"},{"comment":"References [18] and [19] concern microfluidic particle sorting and appear unrelated to the stenosis validation context in which they are cited; please either integrate them into the text appropriately or remove them.","section":"References"}],"recommendation":"major_revision","confidential_remarks":"This manuscript is written in the style of a conference proceedings paper and appears to be submitted in that format. The missing geometrical specification and missing FFR/iFR definitions are load-bearing gaps, but they are fixable in a revision. I would advise the editor to request a clear revision that adds the analytic stenosis model, parameter values, index definitions, and a more nuanced validation statement. The claim of clinical reliability should be softened unless patient-data comparison is added."},"author_rebuttal":null,"desk_editor":{"model":"deepseek-v4-flash","letter":"Dear colleague,\n\nWhat you should know up front: this is a conference-scale in silico study. It computes FFR and iFR for 40/50/70% stenosed coronary arteries using a 1D arterial tree to feed boundary conditions into a 2D axisymmetric stenosis model, then compares smooth vs periodically irregular lesions across Newtonian and non-Newtonian rheology models. The directional finding—irregular lesions increase resistance, lowering FFR/iFR—is physically plausible and consistent with earlier irregular-artery studies. What is genuinely new is only the specific 1D-to-2D coupling workflow for this comparison; the building blocks are otherwise routine.\n\nThe paper does some things well. The 1D solver follows Sherwin and Mynard–Nithiarasu, the 2D solver is checked against published stenotic-flow benchmarks, and grid independence is shown for both. The matrix of three severities, three rheology models, and smooth/irregular geometries is cleanly presented.\n\nNow the soft spots, and they are significant. The central irregular-versus-smooth comparison depends on a periodic surface irregularity that is never specified: no shape equation, no amplitude, no wavelength—only a statement that the height was “calibrated” to a single left circumflex coronary cast. Figures 8–10 therefore cannot be reproduced, and one cannot verify that the smooth and irregular cases share the same minimum lumen area. If the undulations narrow the lumen beyond the nominal 40/50/70% severity, the “irregularity effect” is actually a severity mismatch. That is a load-bearing gap. Second, FFR and iFR are never defined. FFR normally presupposes maximal hyperemia; nothing in the paper models hyperemia, so the clinical interpretation of the numbers is underspecified. Third, the 2D validation uses a non-dimensional 1 m diameter setup, which is fine for code benchmarking but not evidence that the coronary-scale quantitative FFR values are accurate. Fourth, the abstract’s “reliable, non-invasive diagnostic tool” language far outruns what a preliminary in silico exercise without clinical validation can support. No code or data are shipped.\n\nWho is this for? Researchers exploring reduced-order coronary hemodynamics might take the workflow as a starting point, but clinicians should not rely on it in its current form. The central quantitative claim is not reproducible as submitted.\n\nMy recommendation: send it to peer review if the venue expects major revision. The missing geometry, undefined clinical indices, and absent clinical comparison are all fixable in principle. But the manuscript as it stands does not clear the bar for publication, and the irreproducibility is a real flaw rather than a cosmetic one.","headline":"A plausible reduced-order 1D–2D workflow for coronary stenosis FFR/iFR whose headline irregularity effect rests on an unspecified geometry, making the quantitative claim irreproducible as submitted.","tokens_in":7380,"tokens_out":2714,"would_cite":false,"duration_ms":28127,"reading_group":"maybe","serious_thinker":"yes","would_accept_peer_review":true},"rs_alignment":null,"lean_confirmation":null,"pith_extraction":{"msc":["76Z05","92C35"],"pacs":[],"model":"deepseek-v4-flash","headline":"Arterial wall irregularity independently lowers FFR and iFR and raises pressure drop in stenosed coronary arteries.","keywords":["coronary artery stenosis","fractional flow reserve","instantaneous wave-free ratio","surface irregularity","reduced-order CFD","non-Newtonian blood flow","one-dimensional arterial tree","2D axisymmetric model"],"falsifier":"A realistic three-dimensional reconstruction of an irregular human coronary plaque at the same percent stenosis as a smooth case would settle the claim: compute FFR and iFR and see whether the smooth–irregular gap persists with true roughness geometry rather than the analytic periodic pattern.","tokens_in":6393,"feed_emoji":"🫀","tokens_out":8737,"duration_ms":87878,"temperature":0.7,"pith_summary":"Coronary heart disease is assessed by indices such as Fractional Flow Reserve (FFR) and the instantaneous wave-free ratio (iFR), which measure whether a narrowed artery still delivers enough blood; lower values mean more severe functional blockage. This paper asks whether the roughness of the plaque, rather than just the percent narrowing, changes those indices. Using a reduced-order pipeline, a one-dimensional model of the full arterial tree that feeds boundary conditions into a two-dimensional axisymmetric model of the stenosed segment, it compares smooth and irregular blockages at 40, 50, and 70 percent severity under Newtonian and three non-Newtonian blood models. The paper reports that irregular lesions consistently yield lower FFR and iFR values and higher pressure drops than smooth lesions of the same severity. If this is right, surface irregularity acts as an independent resistance factor and should be included when interpreting non-invasive FFR and iFR estimates, because intervention decisions are often made on small differences around clinical thresholds.","feed_headline":"Rough plaque walls lower FFR and iFR at same stenosis","feed_subtitle":"Reduced-order flow models show irregular plaques restrict blood flow more than percent stenosis alone predicts.","key_machinery":"The load-bearing machinery is a coupled reduced-order hemodynamic pipeline. A one-dimensional model of a 61-segment arterial tree solves the mass and momentum conservation equations using forward and backward characteristic variables $W_1$ and $W_2$ (area and velocity are recovered from their sum and difference), with a pressure–area tube law $p = p_{\\mathrm{ext}} + \\beta(\\sqrt{A}-\\sqrt{A_0})$, inflow pressure from a sigmoid-shaped waveform, and an outflow resistance with zero reflection coefficient. The 1D results supply flow-rate and pressure boundary conditions for a 2D axisymmetric model of the stenosed segment, where blood is treated as Newtonian or as power-law, Carreau–Yasuda, or Casson fluid. The stenosis geometry itself is analytical, with a periodic surface irregularity whose amplitude is calibrated to height measurements from a left circumflex coronary arterial cast and whose effect is isolated by comparing with a smooth geometry of identical severity. This two-scale coupling is what lets the authors attribute changes in FFR, iFR, and pressure drop to irregularity rather than to whole-tree boundary-condition artifacts.","core_discovery":"The paper's central claim is that surface irregularity of a coronary stenosis is not a cosmetic detail: at the same percentage severity, an irregularly shaped plaque produces a consistently larger functional deficit than a smooth one. Across 40%, 50%, and 70% stenosis severities, the irregular arteries show lower Fractional Flow Reserve and lower instantaneous wave-free ratio, and higher pressure drop, than smooth arteries under the same rheological model. This ordering holds for Newtonian blood and for the power-law, Carreau–Yasuda, and Casson non-Newtonian models, although the magnitude of the irregularity effect varies with the model. The authors interpret the result as evidence that lesion irregularity contributes added resistance to blood flow, and therefore that non-invasive functional assessment of stenosis should not rely on severity alone. The accompanying contribution is a pipeline in which a one-dimensional model of the whole arterial tree supplies pressure and flow-rate boundary conditions to a two-dimensional axisymmetric model of the stenosed segment, so that both global and local hemodynamics are captured without full three-dimensional simulation.","pith_inferences":["The paper does not quantify it, but if the central claim is right, plaque roughness becomes a candidate imaging biomarker: texture features extracted from the same CT scan could sharpen non-invasive FFR and iFR prediction at no extra clinical cost.","A direct testable extension would vary the roughness amplitude and wavelength around the calibration point; the sensitivity of FFR and iFR to these parameters would show whether the reported irregularity effect is robust or tied to the chosen waviness.","Because iFR requires no hyperemic agent, the same 1D–2D pipeline could be applied to resting whole-cycle indices; the irregularity-induced resistance could interact differently with wave-free-period assumptions than with hyperemic conditions.","If confirmed in patient-specific three-dimensional reconstructions, the result implies that smooth-lumen idealizations in non-invasive functional assessment should be corrected for roughness, especially in diffuse mild disease where irregular surfaces are common."],"forward_implications":["A non-invasive FFR or iFR estimate computed on a smooth lumen will tend to overstate the functional capacity of an irregular lesion.","Identical percent stenosis does not imply identical functional severity when one lesion is irregular, so severity alone is an incomplete guide to intervention.","The rheological model changes the size of the irregularity effect but not its direction; quantitative thresholds therefore depend on model choice.","Because global boundary conditions come from the 1D tree and only the stenosed segment is resolved in 2D, irregularity-aware functional assessment remains computationally feasible for clinical use.","For intermediate stenoses (40–70%), where treatment decisions are hardest, irregularity shifts FFR and iFR values and can move a result across a decision threshold."],"supporting_citations":[{"why":"Supplies the one-dimensional mass and momentum conservation equations used to model flow in the arterial tree.","marker":"[3]"},{"why":"Provides the Locally Conservative Galerkin method and systemic–coronary coupling relationships used by the 1D solver.","marker":"[4]"},{"why":"Source of the left circumflex coronary arterial cast height data used to calibrate the periodic surface irregularity in the stenosis model.","marker":"[11]"},{"why":"Establishes prior evidence that arterial wall irregularities affect hemodynamic parameters, which the paper's FFR and iFR comparison extends.","marker":"[10]"},{"why":"Supplies the coefficient values for the power-law, Carreau–Yasuda, and Casson non-Newtonian blood models.","marker":"[12]"},{"why":"Demonstrates the 1D-versus-3D approach to FFR computation that motivates the reduced-order, patient-specific pipeline.","marker":"[5]"},{"why":"Provides the right carotid artery pressure-flow waveforms used to validate the 1D solver.","marker":"[15]"},{"why":"Provides the stenotic-flow benchmark results used to validate the 2D axisymmetric model.","marker":"[16]"}],"fun_headline_variants":["Irregular plaques lower FFR and iFR beyond stenosis severity","Stenosis roughness adds hidden resistance, cutting FFR and iFR","Plaque irregularity, not just severity, drives FFR and iFR drops","Rough stenoses cut FFR/iFR more than smooth ones at same severity","Irregular plaque geometry boosts flow resistance, worsening FFR"],"cache_read_input_tokens":3200,"weakest_assumption_plain":"The paper assumes that the periodic waviness imposed on the stenosis wall, with height calibrated from a single left circumflex coronary arterial cast, faithfully represents real lesion irregularity; if true plaque roughness differs, the reported FFR and iFR differences could shrink, grow, or reverse.","fun_headline_variants_meta":{"raw":{"variants":["Irregular plaques lower FFR and iFR beyond stenosis severity","Stenosis roughness adds hidden resistance, cutting FFR and iFR","Plaque irregularity, not just severity, drives FFR and iFR drops","Rough stenoses cut FFR/iFR more than smooth ones at same severity","Irregular plaque geometry boosts flow resistance, worsening FFR"]},"model":"deepseek-v4-flash","effort":"low","cost_usd":0.001052,"raw_usage":{"total_tokens":4446,"prompt_tokens":1003,"completion_tokens":3443,"prompt_tokens_details":{"cached_tokens":384},"prompt_cache_hit_tokens":384,"prompt_cache_miss_tokens":619,"completion_tokens_details":{"reasoning_tokens":3347}},"tokens_in":619,"tokens_out":3443,"duration_ms":25149,"temperature":1.0,"reasoning_tokens":3347,"cache_read_input_tokens":384,"cache_creation_input_tokens":0},"cache_creation_input_tokens":0},"created_at":"2026-08-15T20:32:59.638300+00:00","model_set":{"reader":"deepseek-v4-flash"},"falsifier":"A realistic three-dimensional reconstruction of an irregular human coronary plaque at the same percent stenosis as a smooth case would settle the claim: compute FFR and iFR and see whether the smooth–irregular gap persists with true roughness geometry rather than the analytic periodic pattern.","supporting_citations":[{"cited_title":null,"cited_arxiv_id":null,"evidence_quote":"Provides the stenotic-flow benchmark results used to validate the 2D axisymmetric model."},{"cited_title":null,"cited_arxiv_id":null,"evidence_quote":"Supplies the one-dimensional mass and momentum conservation equations used to model flow in the arterial tree."},{"cited_title":"Trends in coronary heart disease epidemiology in India","cited_arxiv_id":null,"evidence_quote":"Provides the Locally Conservative Galerkin method and systemic–coronary coupling relationships used by the 1D solver."},{"cited_title":"Effect of surface irregularities on unsteady pulsatile flow in a compliant artery","cited_arxiv_id":null,"evidence_quote":"Source of the left circumflex coronary arterial cast height data used to calibrate the periodic surface irregularity in the stenosis model."},{"cited_title":null,"cited_arxiv_id":null,"evidence_quote":"Establishes prior evidence that arterial wall irregularities affect hemodynamic parameters, which the paper's FFR and iFR comparison extends."},{"cited_title":null,"cited_arxiv_id":null,"evidence_quote":"Supplies the coefficient values for the power-law, Carreau–Yasuda, and Casson non-Newtonian blood models."},{"cited_title":null,"cited_arxiv_id":null,"evidence_quote":"Demonstrates the 1D-versus-3D approach to FFR computation that motivates the reduced-order, patient-specific pipeline."},{"cited_title":"The rheology of blood flow in a branched arterial system","cited_arxiv_id":null,"evidence_quote":"Provides the right carotid artery pressure-flow waveforms used to validate the 1D solver."}],"review_version":1}