Virtual Twin-Matched Design Reveals the Prognostic Role of Myocardial T1 Mapping in Chronic Kidney Disease: a prospective from the UK Biobank

Background: Diffuse myocardial fibrosis increases progressively with advancing chronic kidney disease (CKD). Cardiovascular magnetic resonance (CMR) T1-mapping enables non-invasive quantification of myocardial fibrosis, but its prognostic significance in CKD and its relationship to adverse cardiovascular outcomes remain uncertain.

Methods: As an approach in precision medicine, we conducted a 1:1 virtual twin-matched cohort study within the UK Biobank imaging cohort, tailoring individualized comparisons within patient-specific contexts. Each CKD participant was matched to a phenotypically near-identical non-CKD control, using multidimensional Euclidean distance matching on standardized continuous variables with a 1-SD caliper, balancing demographics, comorbidities, socioeconomic status, and cardiovascular risk factors. Myocardial T1 differences were assessed using paired statistical tests. Stratified Cox proportional hazards models evaluated linear associations between a 1-SD increase in T1 and incident cardiovascular death, heart failure (HF), atrial fibrillation (AF), myocardial infarction (MI), and all-cause mortality over a median follow-up of 4.9 years.

Results: A total of 193 matched pairs (median age 68 years, 57.5% women) were included. After matching, demographic and clinical characteristics were balanced (all p > 0.05 and SMD < 0.001), (Table 1). CKD participants had trend-level higher myocardial T1 vs. controls (p = 0.063). Paired analyses revealed greater T1 differences in participants with adverse events (Figure 1). Over the period of follow-up, CKD participants had higher incidence rates of HF: 12.7 vs. 3.9 events/1,000 person-years (p=0.021) and all-cause mortality: 11.3 vs. 3.8 events/1,000 person-years (p=0.049). In Cox models, each 1-SD increase in T1 was independently associated with CV death (HR 2.20; 95% CI 1.14–4.24), HF (HR 1.89; 95% CI 1.22–2.92), AF (HR 2.22; 95% CI 1.17–4.19), but not MI or all-cause mortality. No significant associations were seen in matched controls (Figure 2).

Conclusion:
Conclusion: In this virtual twin–matched study using large-scale population data, elevated myocardial T1 predicted CV death, HF, and AF in CKD but not in matched controls. This approach represents a methodological shift in cardiovascular epidemiology. By enhancing phenotypic comparability and integrating both linear and non-linear analyses within a digital twin framework, this approach strengthens interpretability and supports T1-mapping as a promising imaging biomarker for cardiovascular risk stratification in CKD.

Table 1. Baseline characteristics of the study population stratified by the presence of Chronic Kidney Disease (CKD)

Table 1. Baseline characteristics of the study population stratified by the presence of Chronic Kidney Disease (CKD)

Covariates	Non-CKD group (N= 193)	CKD group (N= 193)	P-value	SMD
Sex, %	111 (57.5%)	111 (57.5)	1.000	< 0.001
Age	68.0 (62.0, 73.0)	68.0 (62.0, 73.0)	0.961	< 0.001
BMI, kg/m2	27.5 (25, 31)	28 (25, 31)	0.964	0.06
Smoking, %	4 (2.1)	4 (2.1)	1.00	< 0.001
Ethnic Qrisk imp %
1	184 (95.3)	184 (95.3)	1.00	< 0.001
2	1 (0.5)	1 (0.5)	1.00	< 0.001
9	8 (4.1)	8 (4.1)	1.00	< 0.001
Deprivation Townsend	-2.3 (-3.6, -0.2)	-2.1 (-3.7, 0.1)	0.775	0.1
Diabetes, %	34 (17.6)	34 (17.6)	1.00	< 0.001
Hyperlipidemia, %	111 (57.5)	111 (57.5)	1.00	< 0.001
Hypertension, %	136 (70.5)	136 (70.5)	1.00	< 0.001
Any baseline Cardiac disease, %	62 (32.1)	62 (32.1)	1.00	< 0.001
Stroke, %	13 (6.7)	13 (6.7)	1.00	< 0.001
Global LV T1, ms	919 (889, 952)	929 (893, 958)	0.097	0.2

CKD: Chronic Kidney Disease; BMI: Body Mass Index; IQR: Interquartile Range; LV: Left Ventricle; SMD: Standardized mean difference