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Stress Hyperglycemia Ratio and Atrial Thrombus After Stroke: Thrombotic Signal or Stress Response?

Ünss Hypergalycemia Ratio and Left Atri Vural Thrombus

Author ÜUniversal Vural

Description Iity of Health Sciences, acute iIstanbul, Türkiye

Correspondenchemic e: unsalvural@gmail.com

Critical narrative review

Abstroke, act

The stress hyperglycemia ratio (SHR) exprelates admissionsses acute glucose to e relative to estimated background glycemia estimated from glycated hemoglobin. An association with. Its association with atrial thrombus after ischemic stroke raises a clinically relevant question. Does it identify a thrombus found in the left atrium or its appendage has prompted interest in using SHR to select patients for transesophageal echocardiography. Aogenic atrial substrate, reflect the response to cerebral injury, or capture both? This critical narrative review compares human studies of glycemic disturbance, inflammatory biomarkers and thrombus-related outcomes. Anatomically detected thrombus, composite echocardiographic findings, coronary thrombus burden and laboratory thrombogenicity are evaluated separately. The identified atrial SHR evidence is observational. Coronary studies provide supporting context but examine a different vascular process. C-reactive protein (CRP) and related inflammatory indices also show associations with atrial thrombus arises from several rhythm, , although discrimination and adjustment vary. Experimental hypoglycemia studies demonstrate changes in platelet activity, fibrin structural, hemodynamic and systemic conditions; glucose can also rise in response to the stroke itself. Existing evidence does not establishe and ex vivo thrombus formation. They do not establish hypoglycemia-induced atrial thrombosis. Interpretation is further limited by measurement timing, selected imaging populations, possible cohort overlap and imperfect thrombus classification. Neither an adjusted association nor a high multivariable-model area under the curve establishes a causal pathway or a safe imaging rule. Future studies should test whether SHR reflects a thrombotic cause, an acute consequence or both, or whether it improves imaging decisionsadds clinically useful information beyond atrial structure, rhythm, inflammation and stroke severity. Current evidence supports mechanistic investigation and prospective validation rather than biomarker-directed anticoagulation or omission of indicated imaging.

Keywords: stress hyperglycemia ratio; ahypoglycute ischemic stroke; left emia; atrial thrombus; left atrial appendageC-reactive protein; inflammation; transesophageal echocardiography; reverse causation; risk stratificationnarrative review

1 Introduction and the clinical question

A negative transthoracic echocardiogram does not exclude a left atrial (LA) or left atrial appendage (LAA) thrombus. Transesophageal echocardiography (TEE) can revealidentify a cardiac source missed by transthoracic echocardiography (TTE), with possible consequences for . Such findings can influence secondary stroke prevention [2,12]. Yet TEE is not equally inform. The clinical challenge is deciding who needs further imaging after an unrevealing initial assessment. [1,2]

SHR hativs bee for every patient n proposed as an accessible marker of occult intracardiac thrombus after ischemic stroke. The practical challenge i [3] This proposal requires three separate judgments. The first concerns biological plausibility. The second concerns diagnostic information beyond existing clinical assessment. The third concerns whether using the marker improves deciding whom tosions or outcomes. Evidence for one does not automatically establish the others.

This revinvestigate further when the first cardiac ew examines those distinctions across hyperglycemia, hypoglycemia and inflammation. The central question is whether an acute metabolic measurement identifies a pre-existing atrial source or mainly reflects the consequences of an embolic event. The assessment is unrevalso considers how investigators define thrombus and how directly each study addresses atrial thrombosis.

2 Search approach aling.nd appraisal of evidence

A tarecent report links higher SHR to geted narrative literature search was completed on 25 September 2026. Web-based searches were used to locate PubMed-indexed records, primary journal reports and accessible author manuscripts. Search combinations linked stress hyperglycemia ratio, hyperglycemia, HbA1c or hypoglycemia with thrombus, thrombosis, left atrial orum, left atrial appendage thrombus found by TEE after ischemic stroke [1]., platelet activation and fibrinolysis. Additional searches combined C-reactive protein, CRP, CRP-to-albumin ratio, neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio with atrial thrombus. Reference lists and related correspondence were checked for relevant The question is more demanding than whether two measurements are associated:primary studoesies.

Priority wa glucose-derived signal reveal pre-existings given to human studies with a defined exposure, sample size and ascertainable outcome. Anatomically detected atrial thrombogenicity, or does it largely register the physiologicalus was considered the most directly relevant endpoint. Coronary thrombus studies were retained as evidence from another vascular setting. Controlled experiments were included when they measured hemostatic or inflammatory response to a ss to glycemic change. Studies of stroke caused by that thrombus? prognosis alone were used for context. They were not treated as evidence that an atrial clot was present.

Thable answer requires the established causes of atrial thrombus, ths 1 and 2 present selected studies rather than an exhaustive systematic inventory. Data were checked against primary full texts where accessible and indexed primary abstracts otherwise. Study design, participant and event counts, exposure timing of the glucose measurement and the incremental value of SHR over information already available before TEE, outcome definition, adjustment and validation informed the appraisal. Causal confidence and directness were assessed separately. The evidence descriptions are qualitative judgments, not formal GRADE ratings. No pooled estimate was calculated because populations, exposures and endpoints were not sufficiently comparable. This approach remains vulnerable to incomplete retrieval and publication bias.

2ChatGPT Atrial thrombus has more than on(OpenAI) assisted with literature-search planning, manuscript drafting, organization, and language revision.

3 The catriausl substrate

L remains cefnt aral

Atrial thrombus develops where blood stasis, atrial tissue abnormalities and prothrombotic conditions intersect. Atrial fibrillation (AF) is a major contributor because it disrupts effective atrial contraction and promotes slow flow in the appendage. However, a sin, but a sinus-rhythm tracing at admission canndoes not exclude intermittent atrial fibrillation or a pre-existing arrhythmia or atrial substrate. Atrial ecardiomyopathy. Enlargement and , fibrosis, impaired appendage emptying, mitral stenosis or a prosthetic mitral valve, cardiacdisease and ventricular dysfunction and systemic inflammatory or coagulation abnormalities may also affect risk [1,3–5can alter the local thrombotic environment. [4,5,6].

These factors are related but are not interchangeable. MiAtral valve disease mayial fibrosis can coexist with rhythm abnormalities. Mitral stenosis can promote atrial enlargement and flow stagnation; an atrial cardiomyopathy can coexist with or precede recognized atrial fibrillationslow flow. Reduced appendage emptying velocity and spontaneous echo contrast (SEC) provide evidence of sluggish flow, but they are commoninformation about stasis. However, these features are usually characterized during TEE [2,4,5]. They may help explain a thrombus after imaging, whereas they cannot ordinarily be used to choose select patients for the TEEexamination that rfirst reveals them. [1,5]

Anatomy and rhythm should anchor interpretation before glucose. A menatabolic markeromy and rhythm should be judged against the atrial and valvular setting in which the clot developsanchor interpretation before glucose. An association between glucose and thrombus is not evidence that glucose alone generated the thrombus.

InA the cirelevant stroke cohort, patients were in sinus rhythm on admission, but 24–72-hour monitoring subsequentlyculating biomarker may reflect systemic stress without identified paroxysmal atrial fibrillying the anatomical location in some of them; known persistent or permanent atrial fibrillation had been excluded [1]. Initial sinus rhythm therefore did not mean the atrial rhythm of a clot. Conversely, a local thrombogenic substrate was absent. A short monitoring period can also leave uncertainty about an intermittent arrhythmia. This matters when an acute blood marker is evaluated alongsidemay remain present when a blood marker is normal. Evaluation of a metabolic marker therefore requires comparison with the structural and rhythm findings obtained at different timesinformation already available.

34 What SHR canglycemic measurements can establish

4.1 Relative hyperglycemia and measurement context

SHR compares acute glucose with an estimate ofd usual glycemia derived from glycated hemoglobin (HbA1c). A common formulation divides admission glucose by estimated average glucose, expressed in the same units; iusing matching units. In mg/dL, estimated average glucose =is 28.7 × HbA1c (%) − 46.7 [6]. The thrombus study used the equivalent mmol/L formulat. [7] SHR describes relative glycemic elevation. It does not directly measure catecholamines, endothelial injury or thrombogenicity.

Tiomin: [ag matters. Admission glucose (mg/dL) / 18] / [1.59 × HbA1c (%) − 2.59] [1]. Higher SHR describes a greater acute glucose elevation relative to background glycemia, rather than directly measuring catecholamines or thrombogenicity, fasting glucose and later inpatient measurements are different exposures. Infection, nutrition, insulin and other treatments can alter the numerator. Hemolysis, blood loss, transfusion or altered erythrocyte turnover can distort HbA1c and therefore the denominator. A falsely low HbA1c can increase SHR without a corresponding rise in acute glucose. These limitations are particularly relevant in surgical and critically ill patients. [8,9]

An SHR is sensitive to when blood was drawn and to acute infection, treatment, nutrition and other stressors. It is less interpretable when HbA1c fails tbelow 1 does not itself diagnose hypoglycemia. It indicates glucose below the estimated average used in the denominator. Likewise, a higher mean SHR in one group does not establish absolute hyperglycemia in every participant. Both components should be reported. Thresholds derived from different sampling schedules or formulations should not be assumed equivalent.

4.2 Biological plausibility and temporal direction

Controlled represent earlier experiments link acute hyperglycemia. Studies using other numerators or denominators do not produce interchangeable SHR cutoffs [6,7].

4 with endothelial and prothrombotic changes under specified insulin conditions. These findings provide biological plausibility for a relationship with thrombosis. [10] Biological plausibility, however, and reverse does not establish the direction of causation.

HypMerglycemia can be accompanied by endothelial dysfunction, oxidative stress, platelet activationtabolic disturbance might contribute to a prothrombotic environment before clot formation. Alternatively, an atrial thrombus might embolize first. Cerebral injury and its neuroendocrine and impaired fibrinolysis. Tnflammatory responses could then raise glucose. Shared factors could also influence both measurements. A single blood sample after stroke cannot distinguish these pathways.

Strockesses offer plausible links between acute metabolic disturbance and thrombosis [7]. severity, infarct characteristics, sampling delay, infection and early treatment therefore deserve explicit consideration. Adjustment for diabetes alone does not capture these processes. Nor Biological plausibility, however, does not establish the direction of causation.does Obadjuserving SHR after stroke leaves at least two time tment for one inflammatory marker fully characterize the inflammatory response. Serial measurements would help separate persistent vulnerability from a transient consequences possible of illness.

I5 Hyperglycemia an one d imaging findings

5.1 Direct atrial evidence

Cicequek ance, metabolic dysregulation contributes to a prod colleagues studied 486 selected patients undergoing TEE after negative TTE. TEE identified atrial or appendage thrombotic environment before the atrial thrombus and stroke. In another, an atrial thrombus embolizes to the brain; thus in 64 patients. The adjusted association with SHR persisted, but the study was retrospective and excluded previous anticoagulant use. Its area under the receiver-operating-characteristic curve (AUC) of 0.796 described the combined model, not SHR alone. The main quantitative resulting injs are summarized in Table 1. [3]

Subsequent corry and sympathetic, endocrine and inflammatory responses raise glucose after the event. The latter sequence would make SHR aespondence discussed inflammation and the atrial substrate. [11] In their reply, the authors emphasized that SHR and CRP retained associations in the same model. They also acknowledged unavailable detailed measures of atrial cardiomyopathy and the need for external validation. [12] Mutual adjustment supports conditional statistical associations. It does not prove separate causal mechanisms or eliminate reverse causation.

A mlarker of the stroke response rather than of priorger sample does not necessarily provide more direct evidence. Song and colleagues analyzed 1,217 patients with nonvalvular atrial fibrillation. Their 112 positive outcomes comprised 28 thrombus formation. Shared factors such as inflammation or diabetes could also coni, four sludge findings and 80 SEC findings. HbA1c and CRP were important model features. The reported AUC of 0.97 belonged to a multivariable machine-learning model. A thrombus-only sensitivity analysis was described, but separate discrimination estimates were not given in that section. [13] The overall AUC cannot be attribute to both fd to either biomarker or assumed to apply to discrete thrombus alone.

Combindings [3,7].

A SEC, sinludgle post-onset glucose result cannot distinguish these explanations. Stroke severity, infarct distribution, the intee and thrombus increases the number of positive outcomes but changes the research question. Such a model identifies an echocardiographic risk milieu. It does not necessarily identify an established clot. Feature importance also describes the behavior of a fitted model; it is not a causal effect estimate.

5.2 Coronary evidence and limits of transfer

Coronary studies proval from symptom onset to blood sampling, infection and treatments must be considered. If theide a broader test of metabolic associations with thrombosis. Chu and colleagues examined 227 patients with diabetes and ST-elevation myocardial infarction. Algül and colleagues studied 1,222 patients with acute coronary syndrome. Both reported association weakens after accounting for these variables, SHR could remain progns between SHR and angiographic thrombus burden. [14,15] A post hoc analysis of the prospective CorLipid cohort also linked stress-induced hyperglycemia with large coronary thrombus burden. [16]

These obstic while having limited value for identifying a pre-existing atrial source. Prognoservations support a thrombotic context for acute dysglycemia. They do not establish a common mechanism across coronary and atrial disease. Coronary thrombosis involves plaque-related injury and arterial flow. Atrial thrombosis often develops in a setting of stasis and diagnosis are separate questions [8,9]atrial dysfunction. In the acute coronary and stroke cohorts discussed here, glucose was measured after the presenting event.

This leaves temporal diambiguity.

Cutoffs from acutinction has practical implications for researche coronary cohorts should therefore not be transferred to stroke-related TEE selection. Odds ratios based on categorical SHR, continuous SHR or absolute fasting glucose also represent different contrasts. Pooling them without a prespecified harmonization strategy would obscure their meaning.

Studies Aof recurrent stable metabolic association would have to remainroke or functional outcome address another question. Roberts and colleagues evaluated glycemic measures in 300 stroke patients. An INSPIRES analysis studied 4,515 patients with mild stroke or high-risk transient ischemic attack. [17,18] These studies informative after considering s prognosis. They do not verify an atrial source or validate a rule for excluding thrombus.

6 Inflammation as a comparoke seator and shared pathway

CRP providerity and earlys an important comparator because it can accompany acute tissue injury, infection and chronic inflammatory illness. A signal concentrated in severe strokes, later blood sburden. Its association with thrombus may represent a shared disease process, a response to injury or residual confounding. The same temporal questions raised for SHR therefore apply to CRP.

Maehampa and colles or agues found 19 atrial thrombi among 190 patients with pronounced systemic inflammation would be more compatible with a post-event stress responnon-rheumatic atrial fibrillation. CRP was independently associated with thrombus. Nevertheless, the proposed cutoff had a positive predictive value of only 19%, despite a negative predictive value of 97%. [19] A high negative predictive value in a selected, relatively low-prevalence cohort is not sufficient to establish a safe replacement for imaging.

In rheumatic mitral ste. Neither pattern alone would prove a causal pathway; both identify which explanatinosis, Belen and colleagues linked CRP and the platelet-to-lymphocyte ratio with atrial thrombus. Glucose did not differ significantly between groups. [20] This is a useful negative comparator, but it does not refute SHR in stroke. The exposure, anatomical substrate and clinical setting differ.

Inflammatonry ratios also requires further testing careful interpretation. Cicek and colleagues evaluated CRP-to-albumin ratio (CAR) in 303 selected stroke/TIA patients.

5 WThat the available clinical evidence showirty-four had atrial thrombus. Admission glucose did not differ significantly between groups (p = 0.888). [21] This finding does not test relative hyperglycemia. The CAR and SHR reports

I cover overlapping the retrospective study by Cicekrecruitment periods and cite the same ethics approval. Patient overlap is possible but unconfirmed. They should not be counted as independent replication without clarification. [3]

Zhou and colleagues, studied 486623 patients with ischemic stroke underwent TEE after a TTE without visible thrombus. The study excluded isolatednonvalvular atrial fibrillation, including 59 with atrial thrombus. The neutrophil-to-lymphocyte ratio (NLR) retained an adjusted association, but discrimination was modest. Other indices did not consistently retain significance after fuller adjustment. [22] These results illustrate why a collection of significant univariable markers is not equivalent to a useful diagnostic panel.

Ratios can aleft ventricular and right atrial thrombi and defined itsso obscure the source of an association. A high CAR may reflect higher CRP, lower albumin, or both. The same principle applies to SHR. An informative analysis should compare the ratio with its individual components. This would clarify whether the ratio adds information or mainly repackages an existing signal.

A coutcome as a mass in the left atrium or appendage. TEE detected thrombus imbined metabolic and inflammatory model is plausible. Its value must be demonstrated by direct comparison with a clinical model, followed by validation. Entering SHR and CRP into one regression does not establish complementary clinical usefulness. Correlation, measurement error and shared responses to acute illness must also be considered.

Table 1. Human 64imaging patients (13.2%). Mean SHR was 0.99 ± 0.42 in thestudies of glycemic and inflammatory markers in relation to thrombus

Table gro1. Hup and 0.84 ± 0.27 in the group withoutman imaging studies of glycemic and inflammatory markers in relation to thrombus; (continued)

Values in parenthe adjustedses after odds ratio for SHR was 2.39 (9s are 95% confidence interval 1.11–5.17) [1].

Ts. Effects retain each study’s e same cohort also demonstrates why a single metabolic exxposure scale; their magnitudes are not directly comparable. Counts are participants with the stated outcome, not necessarily new incident thrombi. No pooled sample size or effect is presented.

Evidence descriptions are qualanation would be incomplete. Paroxysmal atrial fibrillation was reportitative appraisals of design and endpoint directness, not formal GRADE ratings. All studies in this table are observational. Prospective collection does not by itself establish temporal causation.

CAR2024 useds Cox/HR in 62.5% of those with thrombus and 6.9% of thoseterminology in its methods but logistic/OR terminology in its results. Ratio units are not consistently specified. The reported OR is retained without; mitral valve replacement in 23.4% and 8.3%, respectively. Ejection fr endorsing a transferable cutoff. Its recruitment period overlaps that of SHR2026; shared participants have not been confirmed.

ACS, acution was lower; admission glucose was 134 versus 118 mg/dL ande coronary syndrome; AF, atrial fibrillation; aOR, adjusted odds ratio; AUC, area under the receiver-operating-characteristic curve; CAR, CRP-to-albumin ratio; CBC, complete blood count; CRP, C-reactive protein 63.4 versus 27.2 mg/L. HbA1c did not differ significantly between groups [1]. The glucose and ; HbA1c, glycated hemoglobin; LA/LAA, left atrium/left atrial appendage; NLR, neutrophil-to-lymphocyte ratio; NPV/PPV, negative/positive predictive value; NVAF, nonvalvular AF; PLR, platelet-to-lymphocyte ratio; SEC, spontaneous echo contrast; SHAP, Shapley additive explanations; SHR, stress hyperglycemia ratio; SII, systemic immune-inflammatory differences raise the possibilition index; STEMI, ST-elevation myocardial infarction; TEE/TTE, transesophageal/transthoracic echocardiography; TIA, transient ischemic attack; TIMI, Thrombolysis in Myocardial Infarction.

7 Hypoglycemia that theand experimental thrombogenicity

Hypoglycemia is relevacutent because prothrombotic response contributes to the SHR signal, but they cannot determine its cause. The coexiss are not confined to high glucose. Human clamp experiments can establish the timing of a physiological response more clearly than a post-event observational sample. However, their outcomes usually concern platelets, coagulation proteins or clot properties. They do not directly demonstrate an atrial thrombus.

Gogitidzence of rhythm, valvular, cardiac and Joy and colleagues compared euglycemic and hypoglycemic conditions in healthy volunteers and people with type 1 diabetes. Hypoglycemia increased several inflammatory signals makes the biological interpretand prothrombotic markers. [23] A later experiment compared glycemic and insulin conditions in healthy adults. It showed why insulin exposure and glucose concentration of SHR less straightforwardmust be interpreted together. [10] These studies support mechanisms, not estimates of clinical atrial thrombus risk.

The reported area under the curve of 0.796 describes the multivariable model, not SHR used alone.Wright and colleagues Thuse analysis involved only patients selected for TEE, and its md a randomized, counterbalanced design in 32 adults. They observed inflammatory and platelet–monocyte responses, with a rise in high-sensitivity CRP in the nondiabetic group. [24] This links hypoglycemia to inflammatory signaling. It does not show that CRP mediates subsequent atrial thrombosis.

Chow and colleagues surements cannot show whether elevated SHRtudied 12 participants with type 2 diabetes and 11 controls. Platelet responses occurred acutely, while adverse fibrin properties in diabetes persisted after recovery. Their paired clamp studies used a fixed sequence, with euglycemia preceded thrombus or fing hypoglycemia. [25] The design strengthens temporal interpretation of laboratory changes but remains small and susceptible to order effects.

Yamamoto and collowed cerebral injury [1]. Amongeagues assessed thrombus formation using a microchip flow chamber. One component examined ten patients who were not referred for TEE, the proportion of missed atrialith diabetes before and after comprehensive care. Another examined ten patients undergoing an insulin tolerance test without a concurrent euglycemic control. [26] The terminology requires care: a flow-chamber thrombi and the beogenic response is an ex vivo measurement, not a clot detected inside the left atrium.

The response is not uniform avior of the SHR signal remain unknowncross settings. Hagelqvist and colleagues randomized the order of exercise-related and resting hypoglycemia in 15 men with type 1 diabetes. Exercise-related hypoglycemia increased clot strength and reduced fibrinolysis relative to baseline.

Pr Resting hypoglycemia inostic findings answer another questioncreased fibrinolysis. [27] Exercise, insulin exposure and diabetes phenotype therefore matter when interpreting the net hemostatic response.

Table 2 Robserts and colleagues compared SHR,parates these experiments from the clinical imaging studies. Their findings argue against treating glucose as a simple one-directional surrogate for thrombosis. They do not establish a U-shaped relationship between glucose and the gatrial thrombus. A controlled human study demonstrating hypoglycemic gap in 300 patients with ischa-induced, imaging-confirmed LA/LAA thrombosis was not identified in this targeted search.

The mic stroke [8]. In a separate analysis of 4,515echanistic evidence also limits therapeutic inference. If elevated SHR accompanies thrombus, it does not follow that aggressively lowering glucose will remove the clot or improve stroke recovery. SHINE randomized 1,151 patients with mildacute ischemic stroke or high-risk transient ischemic attack, the higheand hyperglycemia. Intensive control did not improve the primary functional outcome and caused severe hypoglycemia in the intensive group. [28] The trial did not test SHR quartile h-guided treatment or atrial thrombus resolution.

Tadble 2. a greater adjHuman experimental studies of hypoglycemia, inflammation and thrombogenicity

Table 2. Human experimental sted 90-day recuudies of hypoglycemia, inflammation and thrombogenicity (continued)

None of these experriment-stroke risk than the lowest quartile (hazard rats used imaging-confirmed atrial thrombus as its outcome. Randomization strengthens interpretation of the measured physiological response; it does not convert a surrogate endpoint into direct evidence of clinical thrombosis. Participant totals are not pooled because overlap across laboratory reports has not been excluded.

For Hagelqviost et 1.84;al., the 95% confidence interval 1.30–2.61) [9]. These obs were 2.04–3.51 mm for the change in clot strength and −0.60 to −0.29 percentage point for LY-30. The randomized experimental sample was 15, not 30.

hsCRP, high-sensitivity C-rvations concern outcome after stroke, not the presence of an atreactive protein; LY-30, clot lysis 30 minutes after maximum amplitude; PAI-1, plasminogen activator inhibitor-1; PL-T10, time to a 10-kPa pressure rise in the platelet microchip assay; T1D/T2D, type 1/type 2 diabetes; tPA, tissue plasminogen activator; vWF, von Willebrand factor.

8 Reliabil thity of the thrombus aendpoint

TEE.

6 is Whighen could SHR change a TEE decision

Thely useful, but an echodensity interpreted as thrombus is not clindentical test is incremental value. Before adding SHR, a TEE-selection model so surgical confirmation. In Manning and colleagues’ prospective intraoperative study, surgery confirmed 12 of 14 TEE-positive findings among 231 patients. Two positive findings were not confirmed. Both had been reported by only one observer. [29]

The denould use information known at the decision point: atrial fibrillation history and rhythm monitoring, mitral valve disease or prosthesis,minator matters. The unconfirmed proportion among positive TEE findings was 2/14, or 14.3%. The conventional false-positive rate among surgically thrombus-negative patients was 2/219, or 0.9%. These are different quantities. Neither is a universal estimate for contemporary stroke investigations.

Kaymaz and colleavailable TTE findings including left atrial size and ventricular function, and stroke imaging characteristics [2,3,12]. Appendage flow velocity and spontaneous echo contrast, when knowgues evaluated 474 surgical patients with rheumatic mitral disease. TEE sensitivity and specificity for appendage thrombi were both 98%; performance differed for thrombi in the main atrial cavity. [30] A recent case report also documents an apparent appendage thrombus that was not found during surgery. [31] A case report establishes possibility, not frequency.

Pectinate only from the planned TEE, cannot enter this pre-TEE selection model.

SHRmuscles, anatomical ridges, reverberation and dense SEC can complicate interpretation. [1,31] When imaging and surgery are separated in time, intervadmission glucose and HbA1cl dissolution or embolization can also explain disagreement. Non-confirmation should be compared as altenot automatically be equated with an initial diagnostic error.

For biomarker research, blinative addided image adjudication and explicit definitions to a credible clinical model. The question is whether SHR changes predictions beyond glucose or the are therefore essential. Definite thrombus, sludge, SEC and an equivocal mass should be recorded separately. Historical surgical percentages should not be applied as correction factors to a different cohort. The concern is outcome reliability, not an assumption that misclassification occurred in the SHR study.

9 Intexgrated cristingtical appraisal and clinical ausefulness

9.1 Causal interpretation and the missing temporal sequence

The evidence containssment, particularly for patients whose need for TEE is uncertain. A significant odds ratio a consistent gap. Imaging cohorts identify thrombus but usually cannot establish whether dysglycemia preceded it. Clamp studies establish exposure timing but do not demonstrate clinical atrial thrombosis. Combining these designs improves biological interpretation. It does not answer that question. Nor can a close the causal gap between a transient metabolic disturbance and formation of an atrial clot.

An AUCatrial from a combined model be attributed to its glucose-derived component [10]thrombus detected after stroke may be residual evidence of the embolic source. A glucose measurement obtained later may instead reflect injury severity. This is a plausible competing explanation, not proof that the reported association is entirely noncausal.

A Future pastient with established atrial fibriludies need measurements before the event or repeated measurements linked to serial imaging to distinguish these possibilities.

Inflammation or a high-risk mitral valve condition may already warrant detailed cardiac assessmentshould not be treated as a competing explanation that automatically displaces glucose. It could precede both dysglycemia and thrombosis, accompany the same stress response, or lie on a causal pathway. Each possibility changes the meaning of statistical adjustment. A prespecified causal model is therefore preferable to selecting adjustment variables solely because their univariable p values are significant.

9.2 Prediction requires more than statistical association

The appronpriate clinical grounds. SHR is more likely to bquestion is incremental value. A baseline model should use informative if it improves discrimination among patients whose need for TEE remains on available when the imaging decision is made. This includes rhythm history and monitoring, mitral disease or prosthesis, available TTE findings, ventricular function and stroke characteristics. Variables first obtained from the proposed TEE cannot legitimately justify selecting patients for that same test.

SHR shounld be certain after rhythm and structural assessment. Even in that group, anyompared with admission glucose, HbA1c and inflammatory markers as alternative additions to the same clinical model. Model discrimination, calibration and uncertainty should be reported. A combined-model AUC cannot be assigned to one component. Internal validation also does not establish performance in a new institution or a different stroke population. [32]

The pnumberoposed SHR threshold must be tested in a population that includes patients not s of events matters as much as the total sample. Sixty-four thrombi provide less modeling information than 486 participants might suggest. Composite outcomes may increase statistical precision while reducing clinical specificity. Models with many candidate predictors require protection against overfitting. Any imputation, feature selection or resampling should remain within the training process.

9.3 Selection, treatment and transportability

Selection for TEE is anothed for imaging on the basis of the markerr important limitation. Clinicians may refer patients because of rhythm abnormalities, embolic patterns or other risk indicators.

Analyses proposed rule should report calibration and demonstrate what its threshold means inrestricted to those patients may not generalize to all stroke presentations. Exclusion of anticoagulated patients creates a further limitation when applying results to routine clinical practice:.

Anticoagulant hexpow many examinations are avoided, how many treatablesure requires more detail than a yes/no variable. Timing, adherence and treatment adequacy can affect the probability of detecting residual thrombi are missed and whether the addeus. Short rhythm monitoring can also miss intermittent AF. Residual confounding by atrial disease may persist even after adjustment for recorded AF and atrial diameter.

9.4 Clinical decisions and the limits of intervention

A proposed findings alter caremaging rule should state how many examinations it avoids and how many actionable thrombi it misses. Decision-curve analysis can compare the eassess expected net benefit of using the rule with existing approaches acrossacross clinically plausible thresholds [11].. [33] An association is not yet a TEE-selection policy.

7 EvUltidmatence needed and conclusion

Ply, a prospective impact studiesy should define a popultest whether using the rule improves decisions or outcomes. An association with an is not yet a TEE-selection policy.

A low SHR should nrevealing initial evaluation, record why each patient received TEE and specify whether the target is left atrial or appendage thrombus or ot override an established indication for imaging. A high SHR or CRP alone does not establish an atrial source or justify anticoagulation. Equivocal imaging requires assessment of anatomy and clinical context. These biomarkers remain candidates for evaluation within a broader actdiagnostic strategy.

10 Research priorities anabld conclusions

Future caohordiac source. Glucose timing, HbA1cts should recruit patients at the point when TEE is being considered. Sampling times, stroke severity, infarct pattern, atrial rhythm monitoring, mitral disease, left atrial size, ventricularection, treatment and anticoagulant exposure should be documented prospectively. Glucose trajectories and HbA1c reliability should be assessed. Rhythm burden and atrial function and acute inflamal measures would help characterize the underlying substrate.

The primatory conditionsimaging endpoint should be captured before analysis. Internal and external validdefinite LA/LAA thrombus. SEC, sludge and uncertain findings should remain distinct secondary outcomes. Imaging adjudication should follow a prespecifie be blinded to biomarker results. Analyses should comparison of clinicale the same baseline models with and without SHR [10,11], glucose and inflammatory markers. External validation should precede implementation.

The currentral distinction remains unresolved: evidence supports an association between metabolic or inflammatory disturbance and thrombus-related findings in selected populations. It does not establish that an elevated SHR may reflect a thrombogenic setting, the stress response to an embolic stroke, or both. Its association with TEE-detected atrial thrombus is a usefcaused an atrial clot. Hypoglycemia experiments strengthen the biological link between glycemic disturbance and hemostasis, but remain indirect for atrial thrombosis. The decisive question is whether a marker adds reliable information that improves an individual patient’s imaging decision and subsequent care.

Acknowledgments

The aulthor signal for reused ChatGPT (OpenAI) for assistance with literature-search, but the atrial substrate and the timing of stroke must planning, manuscript drafting, organization, and language revision. The author reviewed and edited the content and takes full responsibility for the manuscript.

Institutional Review Board Statement

Not applicabe addressed before it can guide imaging. The defensle. This article is a literature-based review and does not report a new study involving human participants or animals.

Informed Consent Statement

Not applicable question i. This review does not whether SHR creport new data from individual participants.

Data Availability Statement

Norr nelates with thrw datasets were generated or analyzed for this review.

Funding

Nombu financial s, but whether it upport was received for this work.

Author Contributions

Ünsaddsl reliable information that changes a patient’sVural: Conceptualization, critical interpretation of the literature, literature review, drafting, revision, and final approval of the manuscript.

Conflicts of Interest

The TEEauthor decision [1–3,10,11]lares no conflict of interest.

References 

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