Integrative Physiological Modelling of Cardiovascular-Renal Interaction in Heart Failure with Preserved Ejection Fraction: Data from a Multi-Site Nigerian Cohort

Background: Heart failure with preserved ejection fraction is characterised by diastolic dysfunction, neurohormonal activation, and impaired cardiorenal interaction. The cardiorenal syndrome in this heart failure phenotype, wherein renal impairment worsens cardiac function and vice versa, is governed by complex haemodynamic and neurohormonal feedback loops that have not been characterised in African populations. Nigerian cardiology data on heart failure with preserved ejection fraction remain sparse. Objectives: This study aims to characterise cardiorenal interaction physiology in Nigerian patients with heart failure with preserved ejection fraction across three sites using echocardiographic diastolic function grading, renal venous flow pattern by Doppler ultrasound, serum cystatin C-based estimated glomerular filtration rate, plasma renin activity, aldosterone, arginine vasopressin, and N-terminal pro-B-type natriuretic peptide, and to build an integrative physiological model using systems biology network analysis. Methods: Eighty patients with echocardiography-confirmed heart failure with preserved ejection fraction from Lagos, Enugu, and Maiduguri Teaching Hospitals alongside forty controls with preserved ejection fraction but no heart failure will be recruited. All physiological parameters will be assessed concurrently. Structural equation modelling and ordinary differential equation-based compartmental modelling will describe cardiorenal feedback dynamics. Sensitivity analysis will identify dominant physiological drivers. Expected Outcomes: Elevated central venous pressure, renin-angiotensin-aldosterone system activation, and arginine vasopressin excess are hypothesised to form a dominant cardiorenal feedback axis, with renal venous congestion mediating greater glomerular filtration rate decline than arterial underfilling. Conclusion: This systems physiology study will produce an original African cardiorenal interaction model for heart failure with preserved ejection fraction. Keywords: heart failure preserved ejection fraction, cardiorenal syndrome, systems physiology, neurohormonal, Nigeria multi-site.