PH-DyPred: A Multimodal Dynamic Risk Prediction Study in Pulmonary Hypertension

Defined as any of the following: hospitalization for PH, escalation of therapy, 6MWD decrease >15%, WHO-FC worsening, or death. Measured from baseline.

Death from any cause during follow-up, as confirmed by medical records or death registry.

Area under the ROC curve for the multimodal model predicting adverse outcomes.

Evaluate biomarker dynamics and predictive value.

Frequency of hospital admissions due to PH complications.

TAPSE (mm) will be measured via transthoracic echocardiography to evaluate longitudinal right ventricular systolic function over time.

Right ventricular internal diameter (mm) will be assessed by echocardiography as an indicator of RV structural remodeling.

RVFAC (%) will be calculated as the percentage change in RV area between end-diastole and end-systole to assess systolic function.

RVEF (%) will be quantified using cardiac magnetic resonance imaging to evaluate global systolic function.

Right ventricular end-diastolic volume (mL) will be measured by CMR to assess structural remodeling over time.

Right ventricular mass (grams) will be measured by CMR as an index of ventricular hypertrophy and remodeling.

tandardized uptake value mean (SUVmean) of FAPI in the right ventricular free wall will be quantified using PET-MR imaging to assess fibroblast activation and myocardial fibrotic activity over time in patients with pulmonary hypertension.

Maximum standardized uptake value (SUVmax) of FAPI in the right ventricle will be measured via PET-MR as an indicator of peak regional fibroblast activation.

The ratio of right ventricular to left ventricular myocardial FAPI uptake (SUVmean RV/SUVmean LV) will be calculated as a normalized index of right ventricular fibrotic remodeling.

Health-related quality of life (HRQoL) will be assessed using validated instruments such as the EQ-5D-3L and/or the emPHasis-10 questionnaire, both commonly used in pulmonary hypertension research. The emPHasis-10 is a disease-specific, patient-reported outcome measure developed for individuals with pulmonary hypertension, covering domains such as breathlessness, fatigue, social limitation, and psychological burden. Changes in HRQoL scores will be evaluated over time and correlated with clinical events (e.g., hospitalization, WHO functional class deterioration), imaging parameters (e.g., RV function), biomarkers (e.g., NT-proBNP), and model-predicted risk strata. Analyses will include repeated measures ANOVA or mixed-effects modeling to examine within-subject longitudinal chan

The area under the receiver operating characteristic curve (AUC) will be calculated to evaluate the discrimination performance of the multimodal dynamic risk prediction model for adverse outcomes.

The concordance index (C-index) will be computed to assess the predictive accuracy of the multimodal risk prediction model.

Calibration slope will be estimated to measure agreement between predicted and observed risks in the dynamic risk prediction model.

Net benefit will be calculated using decision curve analysis to evaluate the clinical usefulness of the multimodal risk prediction model in guiding clinical decision-making.

NT-proBNP concentration will be measured in plasma using a standardized immunoassay (pg/mL). Pearson correlation coefficients (r) will be calculated between NT-proBNP levels and right ventricular ejection fraction (RVEF, %) measured by cardiac MRI.

Unit of Measure: Correlation coefficient (r)

NT-proBNP concentration measured by immunoassay (pg/mL) will be correlated with right ventricular end-diastolic volume (mL) assessed by cardiac MRI. Pearson correlation coefficients (r) will be calculated at each follow-up time point.

Unit of Measure: Correlation coefficient (r)

NT-proBNP levels (pg/mL) obtained by immunoassay will be correlated with tricuspid annular plane systolic excursion (TAPSE, mm) measured on transthoracic echocardiography using Pearson correlation.

Unit of Measure: Correlation coefficient (r)

NT-proBNP values (pg/mL) will be correlated with right ventricular longitudinal strain (%) measured by speckle-tracking echocardiography. Pearson correlation coefficients (r) will be reported.

Unit of Measure: Correlation coefficient (r)

Plasma NT-proBNP level (pg/mL) will be correlated with right ventricular fractional area change (RVFAC, %) measured using echocardiography, and correlation coefficients (r) will be calculated over time.

Unit of Measure: Correlation coefficient (r)

Baseline plasma NT-proBNP levels (pg/mL), measured using a standardized immunoassay, will be analyzed using Cox proportional hazards models to assess their association with time to clinical worsening, defined as hospitalization for pulmonary hypertension, WHO functional class deterioration, or death.

Unit of Measure: Hazard ratio (HR)

Baseline NT-proBNP concentration (pg/mL), measured using a standardized immunoassay, will be analyzed using multinomial or logistic regression models to evaluate its association with model-predicted risk categories (e.g., low-, intermediate-, and high-risk strata) generated by the multimodal dynamic risk prediction model.

Unit of Measure: Odds ratio (OR)