Stres

Stress Hyperglycemia Ratio and Left Atrial Thrombus

Author Üns Hyperglycemia Ratio and Atrial Thrombus After Stroke: Thrombotic Signl Vural or Stress Response?

ÜDescriptionsal Vural

UIniversity of Health Sciences, Istanbul, Türkiye

Correacute ispondence: unsalvural@gmail.com

Critical narrative review

Abhemic stracoke, t

The stress hyperglycemia ratio (SHR) expresses acutelates admission glucose relative to estimated e to background glycemia. Its association with atrial thrombus after ischemic stroke raises a clinically relevant question. Does it identify a thrombogenic 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 at estimated from glycated hemoglobin. An association with thrombus found in the left atrium or its appendage has prompted interest in using SHR to select patients for transesophageal echocardiography. Atrial thrombus, although discrimination and adjustment vary. Experimental hypoglycemia studies demonstrate changes in platelet activity, fibrin structure 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 e arises from several rhythm, structural, hemodynamic and systemic conditions; glucose can also rise in response to the stroke itself. Existing evidence does not establishes a causal pathway or a safe imaging rule. Future studies should test whethe whether SHR adds 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 imagingreflects a thrombotic cause, an acute consequence or both, or whether it improves imaging decisions.

Keywords: stress hyperglycemia ratio; acute ischypoglycemia; emic stroke; left atrial thrombus; C-reactive protein; inflammationleft atrial appendage; transesophageal echocardiography; reverse causation; narrative reviewrisk stratification

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 identifyreveal a cardiac source missed by transthoracic echocardiography (TTE). Such findings can influence , with possible consequences for secondary stroke prevention. The clinical challenge is deciding who needs further imaging after an unrevealing initial assessment. [1,2]

SHR [2,12]. Yet TEE is not equally informative for has been proposed as an accessible marker of occult intracardiac thrombus very patient after ischemic stroke. [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 decisions or outcomes. Evidence for one does not automatically establish the others.

This The practical challenge is deciding whom to investigate further review 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 also considers how investigators define thrombus and how directly each study addresses atrial thrombosishen the first cardiac assessment is unrevealing.

2 Search approach and appraisal of evidence

A targeted 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, ecent report links higher SHR to left atrium, left atrialal or appendage, 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 thrombus found by TEE after ischemic stroke [1]. relevant primaryThe question is more demanding than whether two measurements are associated: studies.

Priorityoes was given to human studies with a defined exposure, sample size and ascertainable outcome. Anatomically detected glucose-derived signal reveal pre-existing atrial thrombus 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 inflammatoryogenicity, or does it largely register the physiological responses to glycemic change. Studies of s to a stroke prognosis alone were used for context. They were not treated as evidence that an atrial clot was present.

caused by that thrombus? Tablhes 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, 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 answer requires the established causes of atrial thrombus, the timing of the glucose measurement and the incremental value of SHR over information already available before TEE.

2 reAtrieval and publication bias.

ChatGPTal thrombus (OpenAI) assisted with literature-search planning, manuscript drafting, organization, and language revision.

3 Thas more than one catrial substratuse r

Lemainsft central

Aatrial thrombus develops where blood stasis, atrial tissue abnormalities and prothrombotic conditions intersect. Atrial fibrillation (AF) is a major contributor, but a sin because it disrupts effective atrial contraction and promotes slow flow in the appendage. However, a sinus-rhythm tracing does nat admission cannot exclude intermittent arrhythmia ortrial fibrillation or a pre-existing atrial cardiomyopathy. Esubstrate. Atrial enlargement, and fibrosis, impaired appendage emptying, mitral disease and ventricularstenosis or a prosthetic mitral valve, cardiac dysfunction can alter the local thrombotic environment. [4,5,6and systemic inflammatory or coagulation abnormalities may also affect risk [1,3–5].

These factors are related but are not interchangeable. AMitrial fibrosis can coexist with rhythm abnormalities. Mitral stenosis can promote atrial enlargement and slow flowal valve disease may promote atrial enlargement and flow stagnation; an atrial cardiomyopathy can coexist with or precede recognized atrial fibrillation. Reduced appendage emptying velocity and spontaneous echo contrast (SEC) provide information about stasis. However, these features are usuallevidence of sluggish flow, but they are commonly characterized during TEE [2,4,5]. They may help explain a thrombus after imaging, whereas they cannot ordinarily selectbe used to choose patients for the examinationTEE that first rreveals them.

Anatomy and rhythm should anchor interpretation before glucose. [1,5]

An metatomy and rhythmbolic marker should anchor interpretation before glucosebe judged against the atrial and valvular setting in which the clot develops. AAn association between glucose and thrombus is not evidence that glucose alone generated the thrombus.

In the circulating biomarker may reflect systemic stress withoutelevant stroke cohort, patients were in sinus rhythm on admission, but 24–72-hour monitoring subsequently identifying the anatomical locied paroxysmal atrial fibrillation of a clot. Conversely, a local thrombogenicin some of them; known persistent or permanent atrial fibrillation had been excluded [1]. Initial sinus rhythm therefore did not mean the atrial rhythm substrate may remain present when a blood marker is normal. Evaluation of a metabolic marker therefore requires comparison with the structural andwas absent. A short monitoring period can also leave uncertainty about an intermittent arrhythmia. This matters when an acute blood marker is evaluated alongside rhythm information already availablefindings obtained at different times.

43 What glycemicSHR can measurements can establish

4.1 Relative hyperglycemia and measurement context

SHR compares acute glucose with an estimated of usual glycemia derived from glycated hemoglobin (HbA1c). A common formulation divides admission glucose by estimated average glucose, using matchingexpressed in the same units. I; in mg/dL, estimated average glucose is= 28.7 × HbA1c (%) − 46.7. [7] SHR describes relative glycemic elevation. It does not directly measure catecholamines, endothelial injury or thrombogenicity.

T [6]. The thrombus study used the equivalent mmol/L formulatimiong matters. A: [admission glucose, 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 (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. [8,9]

An SHR below 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

Cis sensitive to when blood was drawn and to acute infection, treatment, nutrition and other stressors. It is less interpretable when HbA1c fails tont rolled experiments link acute hyperepresent earlier glycemia with endothelial and prothrombotic changes under specified insulin conditions. These findings provide biological plausibility for a relationship with thrombosis. [10]. Studies using other numerators or denominators do not produce interchangeable SHR cutoffs [6,7].

4 Biological plausibility, and however, does not establish the direction of creverse causation.

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

Strokce severity, infarct characteristics, sampling delay, infection and early treatment therefore deserve explicit consideration. Adjustment for diabetes alone does not capture these processessses offer plausible links between acute metabolic disturbance and thrombosis [7]. NorBiological plausibility, however, does not establish the direction of causation. doeObs adjustment for one inflammatory marker fully characterize the inflammatory response. Serial measurements would help separate persistent vulnerability from a transient conerving SHR after stroke leaves at least two time sequence of illnesss possible.

5 Hyperglycemia aInd imaging findings

5.1 Direct atrial evidence

Ci one sequencek, and colleagues studied 486 selected patients undergoing TEE after negative TTE. TEE identified atrial or appendage metabolic dysregulation contributes to a prothrombus 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 quantitativotic environment before the atrial thrombus and stroke. In another, an atrial thrombus embolizes to the brain; the results are summarized in Table 1. [3]

Subing injury and sympathequent correspondence discussedtic, endocrine and 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.

Aory responses raise glucose after the event. The latter sequence would make SHR a lmarger 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 ker of the stroke response rather than of prior thrombi, 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 attus formation. Shared factors such as inflammation or diabetes could also contributed to either biomarker or assumed to apply to discrete thrombus alone.

Comb to both finding SEC,s [3,7].

A singludge 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

Coe post-onset glucose result cannot distinguish these explanations. Stroke severity, infarct distribution, the interval fronarym studies provide 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 reportedymptom onset to blood sampling, infection and treatments must be considered. If the associations 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 weakens after accounting for these variables, SHR could remain prognobservations 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 atrial dysfunction. In the acute coronary and stroke cohorts discussed here, glucose was measured after the presenting eventtic while having limited value for identifying a pre-existing atrial source. Prognosis and diagnosis are separate questions [8,9].

This leaves temporal ambiguity.

Cutoffdis from acute 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 meaninginction has practical implications for research.

Studies ofA recurrent stroke 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 studiesstable metabolic association would have to remain inform prognosis. They do not verify an atrial source or validate a rule for excluding thrombus.

6 Inflammaative after considering stion as a comparator and shared pathway

CRP prooke sevides an important comparator because it can accompany acute tissue injury, infection and chronicrity and early inflammatory burden. 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.

Millness. A signal concentrated in severe strokes, later blood saehama and colleagues found 19 atrial thrombi among 190 ples or patients with non-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 pronounced systemic inflammation would be more compatible with a post-event stress responstenosis, 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.

Inflammatory ratios also r. Neither pattern alone would prove a causal pathway; both identify which explanation requires careful interpretation. Cicek and colleagues evaluated CRP-to-albumin ratio (CAR) in 303 selected stroke/TIA patientsfurther testing.

5 TWhirty-four had atrial thrombus. Admission glucose did not differ significantly between groups (p = 0.888). [21] This finding doeat the available clinical evidence shows

Inot test relative hyperglycemia. The CAR and SHR reports cover overlapping recruitment 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 colhe retrospective study by Cicek and colleagues, studied 623486 patients with nonvalvular 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.

Rischemic stroke underwent TEE after a TTE without visible thrombus. The study excluded isolated left ventriculatiosr can also 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 combineand right atrial thrombi and defined its outcome as a mass in the left atrium or append 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 consideredge. TEE detected thrombus in 64 patients (13.2%). Mean SHR was 0.99 ± 0.42 in the thrombus group and 0.84 ± 0.

Table 1.27 Human imaging studies of glycemic and inflammatory markers in relation ton the group without thrombus

Tabl; the 1. Hadjuman imaging studies of glycemic and inflammatory markers in relation to thrombus (continued)

Valuessted odds ratio for SHR in pwarentheses after odds ratios are s 2.39 (95% confidence intervals. Eff 1.11–5.17) [1].

Thect s retain each study’s exposure 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 presentedame cohort also demonstrates why a single metabolic explanation would be incomplete.

Evidence descPariptions are qualitative 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 usoxysmal atrial fibrillation was reported in 62.5% of thoses Cox/HR terminology in its methods but logistic/OR terminology in its results. Ratio units are not consistently specified. The reported OR is retainedwith thrombus and 6.9% of those without endorsing a transferable cutoff. Its recruitment period overlaps that of SHR2026; shared participants have not been confirmed.

ACS, ; mitral valve replacement in 23.4% and 8.3%, respectively. Ejection fracute 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, Cion was lower; admission glucose was 134 versus 118 mg/dL and C-reactive protein; 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- 63.4 versus 27.2 mg/L. HbA1c did not differ significantly between groups [1]. The glucose and inflammation index; STEMI, ST-elevation myocardial infarction; TEE/TTE, transesophageal/transthoracic echocardiography; TIA, transient ischemic attack; TIMI, Thrombolysis in Myocardial Infarction.

7 Hory differences raise the possibilitypoglycemia and experimental thrombogenicity

Hypoglycemiathat the is relevant because prothrombotic rcute responses 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.

Gogi contributes to the SHR signal, but they cannot determine its cause. The coexistidze Joy and colleagues compared euglycemic and hypoglycemic conditions in healthy volunteers and people with type 1 diabetes. Hypoglycemia increased several nce of rhythm, valvular, cardiac and inflammatory and prothrombotic markers. [23] A later experiment compared glycemic and insulin conditions in healthy adults. It showed why insulin exposure and glucose concentrsignals makes the biological interpretation must be interpreted together. [10] These studies support mechanisms, not estimates of clinical atrial thrombus riskof SHR less straightforward.

WrigThe reported area under the curve of 0.796 describes the multivariable model, not SHR used alone. Tht and colleagues used 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.

C analysis involved only patients selected for TEE, and its measurements cannot show and colleagues studied 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 preceding hypoglycemia. [25] The design strengthens temporal interpretation of laboratory changes but remains small and susceptible to order effects.

Ywhether elevated SHR preceded thrombus or followed cerebramamoto and colleagues assessed thrombus formation using a microchip flow chamber. One component examined ten injury [1]. Among patients with 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-chamberho were not referred for TEE, the proportion of missed atrial thrombogenic response is an ex vivo measurement, not a clot detected inside the left atrium.

Ti and the behe response is not uniform across 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 vior of the SHR signal remain unknown.

Prelative to baseline. Resting hypoglycemia increased fibrinolysis. [27] Exercise, insulin exposure and diabetes phenotype therefore matter when interpreting the net hemostatic responsegnostic findings answer another question.

Ta Roble 2 separates 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 rts and colleagues compared SHR, glucose and atrial thrombus. A controlled human study demonstrating hypogthe glycemia-induced, imaging-confirmed LA/LAA thrombosis was not identified in this targeted search.

Thc gap in 300 patients with ische mechanistic 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 1,151ic stroke [8]. In a separate analysis of 4,515 patients with acute ischemicmild stroke and hyperglycemia. Intensive control did not improve the primary functional outcome and caused severe hypoglycemia in the intensive group. [28] The trial did not teor high-risk transient ischemic attack, the highest SHR-guided treatment or atrial thrombus resolution.

T quartile habled 2. Human experimental studies of hypoglycemia, inflammation and thrombogenicity

Table 2. Ha greater adjuman experimental studies of hypoglycemia, inflammation and thrombogenicity (continued)

Noed 90-day recurrene of these experiments 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-stroke risk than the lowest quartile (hazard ratio 1.

For Hagelqvist et84; al., the 95% confidence intervals 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-se 1.30–2.61) [9]. These observations consitivity C-reactive protein; LY-30, clot lysis 30 minutesern outcome after maximum amplitude; PAI-1, plasminogen activator inhibitor-1; PL-T10, time to a 10-kPa pressure rise instroke, not the platelet microchip assay; T1D/T2D, type 1/type 2 diabetes; tPA, tissue plasminogen activator; vWF, von Willebrand factor.

8 Relresence of an atriability of the th thrombus endpoinat

TEE.

6 is Whighly useful, but an echodensity interpreted as thrombus is en could SHR change a TEE decisionot

The clidentnical to 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 denomest is incremental value. Before adding SHR, a TEE-selection model should use inatfor 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 andmation known at the decision point: atrial fibrillation history and rhythm monitoring, mitral valve disease or prosthesis, colleagues 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 vailable TTE findings including left atrial size and ventricular function, and stroke imaging characteristics [2,3,12]. Appendage flow velocity and spontaneous echo contrast, when known only fromuscles, anatomical ridges, reverberation and dense SEC can complicate interpretation. [1,31] When imaging and surgery are separated in timethe planned TEE, cannot enter this pre-TEE selection model.

SHR, interval dissolution or embolization can also explain disagreement. Non-confirmationdmission glucose and HbA1c should not automatically be equated with an initial diagnostic error.

For biomarker reseabe compared as alterch, blinded image adjudication and explicit definiative additions 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 Intto a credible clinical model. The question is whether SHR changes predictions beyond glucose or the egrated crxitical appraisal andsting clinical usefulnesass

9.1 Causal interpretation and the missing temporal sequence

The evidence contains 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 sment, particularly for patients whose need for TEE is uncertain. A significant odds ratio does not close the causal gap between a transient metabolic disturbance and formation of an atrial clot.

answer that question. Nor can an AnUC atrial 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, notfrom a combined model be attributed to its glucose-derived component [10].

A proof that the reported association is entirely noncausal. Future studies need measurements before the event or repeated measurements linked to serial imaging to distinguish these possibilities.

Infient with established atrial fibrillammation should 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

Theor a high-risk mitral valve condition may already warrant detailed cardiac assessment appropriaten clinical question is incremental value. A baseline model should usgrounds. SHR is more likely to be information 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 shove if it improves discrimination among patients whose need for TEE remains uld bnce compared 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 number of eventrtain after rhythm and structural assessment. Even in that group, any propos 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, featured SHR threshold must be tested in a population that includes patients not selection or resampling should remain within the training process.

9.3 Selection, treatment and transportability

Selectioed for imaging on for TEE is another important limitation. Clinicians may refer patients because of rhythm abnormalities, embolic patterns or other risk indicatorsthe basis of the marker.

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

Antic: how magulant exposure requires more detail than a yes/no variable. Timing, adherence andny examinations are avoided, how many treatment adequacy can affect the probability of detecting residual able thrombus. 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 imagii are missed and whether the added finding rule should state how many examinations it avoids and how many actionable thrombi it misses alter care. Decision-curve analysis can assesscompare the expected net benefit across clinicallyof using the rule with existing approaches across plausible thresholds. [33] [11]. UltAn association is not yet a TEE-selection policy.

7 Evimatdence needely, a pd and conclusion

Prospective impact studyies should test whether using the rule improves decisions or outcomes. An associdefine a population is not yet a TEE-selection policy.

A low SHR showith an uld not 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 withinrevealing initial evaluation, record why each patient received TEE and specify whether the target is left atrial or appendage thrombus or a broader diagnostic strategy.

10actionable Resecarch priorities and conclusions

Fdiac souture cohorts should recruit patients at the point when TEE is being considered. Sampling timesce. Glucose timing, HbA1c, stroke severity, infection, treatment and anticoagulant exposure should be documented prospectively. Glucose trajectories and HbA1c reliability should be assessed. Rhythm burden and atrialarct pattern, atrial rhythm monitoring, mitral disease, left atrial size, ventricular functional measures would help characterize the underlying substrate.

The pri and acute inflammatory imaging endpointconditions should be definite LA/LAA thrombus. SEC, sludge and uncertain findings should remain distinct secondary outcomes. Imaging adjudiccaptured before analysis. Internal and external validation should be blinded to biomarker results. Analyses shoulfollow a prespecified compare the same baselineison of clinical models with and without SHR, [10,11].

The glucose and inflammatory markers. External validation should precede implementation.

Theentral distinction remains current evidence supports an association between metabolic or inflammatory disturbance and nresolved: elevated SHR may reflect a thrombus-related findings in selected populations. It does not establish that an elevated SHR caused 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 author uogenic setting, the stress response to an embolic stroke, or both. Its association with TEE-detected atrial thrombus is a useful sed ChignatGPT (OpenAI) for assistance with literature-l for research 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, but the atrial substrate and the timing of stroke must applicable. This article is a literature-based review and does not report a new study involving human participants or animals.

Informed Consent Statement

Not apple addressed before it can guide imaging. The defensicable. This review doe question is not report new data from individual participants.

Data Availability Statement

Nwhether SHR co nrrew datasets were generated or analyzed for this review.

Funding

Nlates with thrombus, financial support was received for this work.

Author Contributions

Ünbut whether it addsal Vural: Conceptualization, critical interpretation of the literature, literature review, drafting, revision, and final approval of the manuscript.

Conflicts of Interest

reliable information that changes a patient’s TheEE author declares no conflict of interestdecision [1–3,10,11].

 References

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