💡 Research Hypothesis

Effect exists in one stratum only — an interaction, not a known main effect.

VCAM-1 reflects innate immune and endothelial activation. A change confined to No AF patients would suggest ongoing immune signalling that is dissociated from acute myocardial necrosis, a mechanism relevant to adverse remodeling.

• No AF: Baseline mean 664.95 → 6 Month Follow-up mean 539.59 ng/mL (n=173/169), p < 0.001
• AF: no significant change (p = 0.219)
• Effect size (Cohen's d) = -0.94
• Stratifying variable: Atrial Fibrillation vs None
• Candidate figures: Stratified trajectory plot (mean ± SEM per stratum); Forest plot of stratum-specific effects; Interaction term table
• Target journals: European Heart Journal – Acute Cardiovascular Care; Clinical Research in Cardiology

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Effect exists in one stratum only — an interaction, not a known main effect.

VCAM-1 reflects innate immune and endothelial activation. A change confined to No AF patients would suggest ongoing immune signalling that is dissociated from acute myocardial necrosis, a mechanism relevant to adverse remodeling.

• No AF: Baseline mean 664.95 → 6 Month Follow-up mean 539.59 ng/mL (n=173/169), p < 0.001
• AF: no significant change (p = 0.219)
• Effect size (Cohen's d) = -0.94
• Stratifying variable: Atrial Fibrillation vs None

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Effect exists in one stratum only — an interaction, not a known main effect.

A change confined to No AF patients may reflect a phenotype-specific biological pathway worth mechanistic investigation.

• No AF: Baseline mean 84.18 → 6 Month Follow-up mean 72.70 bpm (n=173/174), p < 0.001
• AF: no significant change (p = 0.234)
• Effect size (Cohen's d) = -0.91
• Stratifying variable: Atrial Fibrillation vs None

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Effect exists in one stratum only — an interaction, not a known main effect.

CK-MB indexes myocyte injury and wall stress. A change confined to No Anemia patients may reflect ongoing micro-injury or haemodynamic load rather than the index infarct.

• No Anemia: Baseline mean 22.90 → Day 5 mean 11.84 ng/mL (n=156/156), p < 0.001
• Anemia: no significant change (p = 0.276)
• Effect size (Cohen's d) = -0.87
• Stratifying variable: Anemia vs No Anemia

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Two coupled markers dissociate over time — a discordance, not an expected trend.

Two markers that share a baseline pathway but separate over time suggest distinct downstream biology — typically resolution of acute injury (Cardiac Output) versus a chronic, self-sustaining process (Stroke Volume).

• Baseline coupling: Pearson r = 0.94 (n = 180), p < 0.001
• Cardiac Output: significant decrease Baseline → 1 Year Follow-up
• Stroke Volume: no significant change over the same interval

• Model both trajectories jointly (bivariate mixed-effects model)
• Test whether the residual (discordance) predicts outcome
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Effect exists in one stratum only — an interaction, not a known main effect.

E/e' is a structural/functional remodeling measure; A change confined to No CKD patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• No CKD: Baseline mean 11.76 → 1 Year Follow-up mean 9.12 (n=161/155), p < 0.001
• CKD: no significant change (p = 0.227)
• Effect size (Cohen's d) = -0.83
• Stratifying variable: CKD vs No CKD

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Effect exists in one stratum only — an interaction, not a known main effect.

A change confined to High BNP patients may reflect a phenotype-specific biological pathway worth mechanistic investigation.

• High BNP: Baseline mean 115.10 → 6 Month Follow-up mean 97.80 ms (n=48/46), p < 0.001
• Low BNP: no significant change (p = 0.488)
• Effect size (Cohen's d) = -1.11
• Stratifying variable: High NT-proBNP vs Low NT-proBNP (median 540)

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Cross-domain association present in one stratum only (effect modification).

Native T1 is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.52, n = 145, p < 0.001
• Anterior: r = -0.05, n = 40, p = 0.765
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Cardiac biomarkers × MRI)
• Candidate figures: Scatter plot with separate regression lines per stratum; Correlation heat map by stratum
• Target journals: International Journal of Cardiology; Journal of Clinical Medicine

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Effect exists in one stratum only — an interaction, not a known main effect.

A change confined to Anterior patients may reflect a phenotype-specific biological pathway worth mechanistic investigation.

• Anterior: Baseline mean 112.72 → 6 Month Follow-up mean 95.37 ms (n=43/43), p < 0.001
• Non-Anterior: no significant change (p = 0.704)
• Effect size (Cohen's d) = -1.05
• Stratifying variable: Anterior MI vs Non-Anterior MI

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Effect exists in one stratum only — an interaction, not a known main effect.

TAPSE is a structural/functional remodeling measure; A change confined to High BNP patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• High BNP: Baseline mean 17.67 → 6 Month Follow-up mean 20.47 mm (n=49/49), p < 0.001
• Low BNP: no significant change (p = 0.818)
• Effect size (Cohen's d) = 0.96
• Stratifying variable: High NT-proBNP vs Low NT-proBNP (median 540)

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Cross-domain association present in one stratum only (effect modification).

Native T1 is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.52, n = 145, p < 0.001
• Anterior: r = -0.05, n = 40, p = 0.765
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Cardiac biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Cross-domain association present in one stratum only (effect modification).

T2 mapping is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.51, n = 142, p < 0.001
• Anterior: r = 0.08, n = 40, p = 0.639
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Cardiac biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Cross-domain association present in one stratum only (effect modification).

Native T1 is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.49, n = 144, p < 0.001
• Anterior: r = -0.12, n = 40, p = 0.477
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Inflammatory biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Cross-domain association present in one stratum only (effect modification).

Native T1 is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.49, n = 144, p < 0.001
• Anterior: r = -0.09, n = 43, p = 0.558
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Cardiac biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Cross-domain association present in one stratum only (effect modification).

Native T1 is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.49, n = 145, p < 0.001
• Anterior: r = -0.14, n = 41, p = 0.392
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Inflammatory biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Cross-domain association present in one stratum only (effect modification).

Native T1 is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.48, n = 140, p < 0.001
• Anterior: r = -0.14, n = 42, p = 0.369
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Cardiac biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Cross-domain association present in one stratum only (effect modification).

Infarct size is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.46, n = 144, p < 0.001
• Anterior: r = -0.04, n = 43, p = 0.818
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Cardiac biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Cross-domain association present in one stratum only (effect modification).

T2 mapping is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.46, n = 142, p < 0.001
• Anterior: r = 0.07, n = 39, p = 0.669
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Inflammatory biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Cross-domain association present in one stratum only (effect modification).

MVO extent is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.46, n = 138, p < 0.001
• Anterior: r = -0.11, n = 44, p = 0.481
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Cardiac biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Cross-domain association present in one stratum only (effect modification).

Native T1 is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.43, n = 146, p < 0.001
• Anterior: r = 0.08, n = 39, p = 0.612
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Inflammatory biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Cross-domain association present in one stratum only (effect modification).

T2 mapping is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.46, n = 137, p < 0.001
• Anterior: r = 0.15, n = 42, p = 0.340
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Cardiac biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Cross-domain association present in one stratum only (effect modification).

T2 mapping is a structural/functional remodeling measure; A biomarker–imaging coupling restricted to Non-Anterior patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Non-Anterior: r = 0.44, n = 142, p < 0.001
• Anterior: r = 0.14, n = 43, p = 0.375
• Effect modifier: Anterior MI vs Non-Anterior MI
• Cross-domain association (Cardiac biomarkers × MRI)

• Fit multivariable linear regression with the interaction term
• Perform mediation analysis to test the intermediate pathway
• Confirm with non-parametric (Spearman) and bootstrap confidence intervals

Prognostic separation emerges only during follow-up, not at presentation.

ECV is a structural/functional remodeling measure; Late divergence rather than an acute-phase difference may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Event group at 1 Year Follow-up: mean 28.75 % (n=36)
• Event-free group: mean 26.34 % (n=140)
• Welch t-test p = 0.002; Cohen's d = 0.65
• No baseline difference (p = 0.076) — the signal is temporal, not baseline risk
• Candidate figures: Trajectory plot by outcome group; Time-dependent ROC curves; Kaplan-Meier by follow-up tertile
• Target journals: American Journal of Cardiology; Open Heart

• Build a ROC / AUC model and identify an optimal threshold
• Fit a Cox model with time-dependent covariates
• Validate in an independent cohort before any clinical claim

Prognostic separation emerges only during follow-up, not at presentation.

ECV is a structural/functional remodeling measure; Late divergence rather than an acute-phase difference may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Event group at 1 Year Follow-up: mean 28.75 % (n=36)
• Event-free group: mean 26.34 % (n=140)
• Welch t-test p = 0.002; Cohen's d = 0.65
• No baseline difference (p = 0.076) — the signal is temporal, not baseline risk

• Build a ROC / AUC model and identify an optimal threshold
• Fit a Cox model with time-dependent covariates
• Validate in an independent cohort before any clinical claim

Effect exists in one stratum only — an interaction, not a known main effect.

LVESD is a structural/functional remodeling measure; A change confined to No Previous MI patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• No Previous MI: Baseline mean 39.56 → 6 Month Follow-up mean 35.75 mm (n=161/158), p < 0.001
• Previous MI: no significant change (p = 0.209)
• Effect size (Cohen's d) = -0.71
• Stratifying variable: Previous MI vs No Previous MI

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Effect exists in one stratum only — an interaction, not a known main effect.

LVESD is a structural/functional remodeling measure; A change confined to No AF patients may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• No AF: Baseline mean 39.56 → 6 Month Follow-up mean 35.90 mm (n=173/165), p < 0.001
• AF: no significant change (p = 0.277)
• Effect size (Cohen's d) = -0.69
• Stratifying variable: Atrial Fibrillation vs None

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Effect exists in one stratum only — an interaction, not a known main effect.

A change confined to No HF patients may reflect a phenotype-specific biological pathway worth mechanistic investigation.

• No HF: Baseline mean 11.64 → Day 1 mean 13.27 10³/µL (n=165/167), p < 0.001
• HF: no significant change (p = 0.886)
• Effect size (Cohen's d) = 0.68
• Stratifying variable: Heart Failure vs None

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Effect exists in one stratum only — an interaction, not a known main effect.

MCP-1 reflects innate immune and endothelial activation. A change confined to Low BNP patients would suggest ongoing immune signalling that is dissociated from acute myocardial necrosis, a mechanism relevant to adverse remodeling.

• Low BNP: Baseline mean 367.32 → Day 5 mean 306.02 pg/mL (n=145/142), p < 0.001
• High BNP: no significant change (p = 0.598)
• Effect size (Cohen's d) = -0.67
• Stratifying variable: High NT-proBNP vs Low NT-proBNP (median 540)

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Effect exists in one stratum only — an interaction, not a known main effect.

IL-1β reflects innate immune and endothelial activation. A change confined to No CKD patients would suggest ongoing immune signalling that is dissociated from acute myocardial necrosis, a mechanism relevant to adverse remodeling.

• No CKD: Baseline mean 5.95 → Day 5 mean 4.67 pg/mL (n=161/162), p < 0.001
• CKD: no significant change (p = 0.903)
• Effect size (Cohen's d) = -0.66
• Stratifying variable: CKD vs No CKD

• Test the formal interaction term in a mixed-effects model (variable × subgroup × time)
• Repeat as multivariable regression adjusted for age, sex and infarct size
• Pre-specify the subgroup and validate in an external cohort

Marker outperforms the conventional reference marker for remodeling.

IL-8 reflects innate immune and endothelial activation. An early marker tracking with late ventricular function would suggest ongoing immune signalling that is dissociated from acute myocardial necrosis, a mechanism relevant to adverse remodeling.

• Pearson r = -0.32 (n = 187), p < 0.001
• Rank 2 of 30 screened baseline variables
• Reference marker CRP: r = -0.25, p < 0.001
• Candidate figures: ROC curves (single markers vs combined score); Calibration plot; Variable-importance plot
• Target journals: Journal of the American Heart Association; Biomarkers in Medicine

• Multivariable model adjusted for infarct size, age and sex
• Combined biomarker score with cross-validated performance
• Build a ROC / AUC model and identify an optimal threshold
• Fit a Cox model with time-dependent covariates
• Validate in an independent cohort before any clinical claim

Prognostic separation emerges only during follow-up, not at presentation.

Echo LVEF is a structural/functional remodeling measure; Late divergence rather than an acute-phase difference may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Event group at 1 Year Follow-up: mean 54.98 % (n=39)
• Event-free group: mean 58.98 % (n=142)
• Welch t-test p = 0.019; Cohen's d = -0.48
• No baseline difference (p = 0.094) — the signal is temporal, not baseline risk

• Build a ROC / AUC model and identify an optimal threshold
• Fit a Cox model with time-dependent covariates
• Validate in an independent cohort before any clinical claim

Prognostic separation emerges only during follow-up, not at presentation.

Late divergence rather than an acute-phase difference may reflect a phenotype-specific biological pathway worth mechanistic investigation.

• Event group at 1 Year Follow-up: mean 7.97 10³/µL (n=35)
• Event-free group: mean 7.02 10³/µL (n=142)
• Welch t-test p = 0.024; Cohen's d = 0.43
• No baseline difference (p = 0.697) — the signal is temporal, not baseline risk

• Build a ROC / AUC model and identify an optimal threshold
• Fit a Cox model with time-dependent covariates
• Validate in an independent cohort before any clinical claim

Prognostic separation emerges only during follow-up, not at presentation.

LA volume is a structural/functional remodeling measure; Late divergence rather than an acute-phase difference may indicate a distinct healing phenotype (fibrosis, oedema resolution or microvascular obstruction).

• Event group at 1 Year Follow-up: mean 56.41 mL (n=37)
• Event-free group: mean 52.13 mL (n=141)
• Welch t-test p = 0.049; Cohen's d = 0.38
• No baseline difference (p = 0.865) — the signal is temporal, not baseline risk

• Build a ROC / AUC model and identify an optimal threshold
• Fit a Cox model with time-dependent covariates
• Validate in an independent cohort before any clinical claim

Marker outperforms the conventional reference marker for remodeling.

IL-8 reflects innate immune and endothelial activation. An early marker tracking with late ventricular function would suggest ongoing immune signalling that is dissociated from acute myocardial necrosis, a mechanism relevant to adverse remodeling.

• Pearson r = -0.32 (n = 187), p < 0.001
• Rank 2 of 30 screened baseline variables
• Reference marker CRP: r = -0.25, p < 0.001

• Multivariable model adjusted for infarct size, age and sex
• Combined biomarker score with cross-validated performance
• Build a ROC / AUC model and identify an optimal threshold
• Fit a Cox model with time-dependent covariates
• Validate in an independent cohort before any clinical claim

Marker outperforms the conventional reference marker for remodeling.

CD40 reflects innate immune and endothelial activation. An early marker tracking with late ventricular function would suggest ongoing immune signalling that is dissociated from acute myocardial necrosis, a mechanism relevant to adverse remodeling.

• Pearson r = -0.32 (n = 190), p < 0.001
• Rank 3 of 30 screened baseline variables
• Reference marker CRP: r = -0.25, p < 0.001

• Multivariable model adjusted for infarct size, age and sex
• Combined biomarker score with cross-validated performance
• Build a ROC / AUC model and identify an optimal threshold
• Fit a Cox model with time-dependent covariates
• Validate in an independent cohort before any clinical claim

Marker outperforms the conventional reference marker for remodeling.

Troponin indexes myocyte injury and wall stress. An early marker tracking with late ventricular function may reflect ongoing micro-injury or haemodynamic load rather than the index infarct.

• Pearson r = -0.25 (n = 188), p < 0.001
• Rank 4 of 30 screened baseline variables
• Reference marker CRP: r = -0.25, p < 0.001

• Multivariable model adjusted for infarct size, age and sex
• Combined biomarker score with cross-validated performance
• Build a ROC / AUC model and identify an optimal threshold
• Fit a Cox model with time-dependent covariates
• Validate in an independent cohort before any clinical claim

Data-driven phenotype not defined by any pre-specified clinical variable.

A profile combining opposite-direction markers does not follow a single severity axis and may represent a distinct biological phenotype (for example inflammation-dominant versus necrosis-dominant healing) rather than simply 'sicker' patients.

• Cluster size: 32 / 149 patients with complete baseline data
• Native T1: cluster mean z = -0.80
• LA volume: cluster mean z = 0.78
• CD40: cluster mean z = -0.75
• Infarct size: cluster mean z = -0.72
• CK: cluster mean z = -0.64
• Event rate 13% vs 21% (rest of cohort)
• Candidate figures: Cluster heat map of standardised variables; PCA/UMAP-style cluster projection; Kaplan-Meier by cluster
• Target journals: Frontiers in Cardiovascular Medicine; Scientific Reports

• Confirm cluster stability (hierarchical clustering, silhouette, bootstrap)
• Compare outcomes across clusters (Kaplan-Meier, log-rank)
• Characterise clusters in multivariable models and test a combined biomarker score

Data-driven phenotype not defined by any pre-specified clinical variable.

A profile combining opposite-direction markers does not follow a single severity axis and may represent a distinct biological phenotype (for example inflammation-dominant versus necrosis-dominant healing) rather than simply 'sicker' patients.

• Cluster size: 32 / 149 patients with complete baseline data
• Native T1: cluster mean z = -0.80
• LA volume: cluster mean z = 0.78
• CD40: cluster mean z = -0.75
• Infarct size: cluster mean z = -0.72
• CK: cluster mean z = -0.64
• Event rate 13% vs 21% (rest of cohort)

• Confirm cluster stability (hierarchical clustering, silhouette, bootstrap)
• Compare outcomes across clusters (Kaplan-Meier, log-rank)
• Characterise clusters in multivariable models and test a combined biomarker score

Data-driven phenotype not defined by any pre-specified clinical variable.

This cluster may capture a coherent severity or inflammatory phenotype that conventional single-variable cut-offs do not identify.

• Cluster size: 77 / 149 patients with complete baseline data
• CK: cluster mean z = 0.71
• Native T1: cluster mean z = 0.69
• Infarct size: cluster mean z = 0.68
• CD40: cluster mean z = 0.58
• Event rate 26% vs 13% (rest of cohort)

• Confirm cluster stability (hierarchical clustering, silhouette, bootstrap)
• Compare outcomes across clusters (Kaplan-Meier, log-rank)
• Characterise clusters in multivariable models and test a combined biomarker score

Data-driven phenotype not defined by any pre-specified clinical variable.

This cluster may capture a coherent severity or inflammatory phenotype that conventional single-variable cut-offs do not identify.

• Cluster size: 40 / 149 patients with complete baseline data
• LA volume: cluster mean z = -0.94
• Infarct size: cluster mean z = -0.70
• MVO extent: cluster mean z = -0.68
• CK: cluster mean z = -0.67
• Native T1: cluster mean z = -0.66
• Event rate 13% vs 22% (rest of cohort)

• Confirm cluster stability (hierarchical clustering, silhouette, bootstrap)
• Compare outcomes across clusters (Kaplan-Meier, log-rank)
• Characterise clusters in multivariable models and test a combined biomarker score