Aims Interatrial shunting (IAS) reduces left atrial pressure in patients with heart failure. Several clinical trials reported that IAS improved the New York Heart Association score and exercise capacity. However, its effects on haemodynamics vary depending on shunt size, cardiovascular properties, and stressed blood volume. To maximize the benefit of IAS, quantitative prediction of haemodynamics under IAS in individual patients is essential. The generalized circulatory equilibrium framework determines circulatory equilibrium as the intersection of the cardiac output curve and the venous return surface. By incorporating IAS into the framework, we predict the impact of IAS on haemodynamics. Methods and results In seven mongrel dogs, we ligated the left anterior descending artery and created impaired cardiac function with elevated left atrial pressure (baseline: 7.8 ± 1.0 vs. impaired: 11.9 ± 3.2 mmHg). We established extracorporeal left-to-right atrial shunting with a centrifugal pump. After recording pre-IAS haemodynamics, we changed IAS flow stepwise to various levels and measured haemodynamics under IAS. To predict the impact of IAS on haemodynamics, we modelled the fluid mechanics of IAS by Newton's second law and incorporated IAS into the generalized circulatory equilibrium framework. Using pre-IAS haemodynamic data obtained from the dogs, we predicted the impact of IAS flow on haemodynamics under IAS condition using a set of equations. We compared the predicted haemodynamic data with those measured. The predicted pulmonary flow [r 2 = 0.88, root mean squared error (RMSE) 11.4 mL/min/kg, P < 0.001), systemic flow (r 2 = 0.92, RMSE 11.2 mL/ min/kg, P < 0.001), right atrial pressure (r 2 = 0.92, RMSE 0.71 mmHg, P < 0.001), and left atrial pressure (r 2 = 0.83, RMSE 0.95 mmHg, P < 0.001) matched well with those measured under normal and impaired cardiac function. Using this framework, we further performed a simulation study to examine the haemodynamic benefit of IAS in heart failure with preserved ejection fraction. We simulated the IAS haemodynamics under volume loading and exercise conditions. Volume loading and exercise markedly increased left atrial pressure. IAS size-dependently attenuated the increase in left atrial pressure in both volume loading and exercise. These results indicate that IAS improves volume and exercise intolerance. Conclusions The framework developed in this study quantitatively predicts the haemodynamic impact of IAS. Simulation study elucidates how IAS improve haemodynamics under volume loading and exercise conditions. Quantitative prediction of IAS haemodynamics would contribute to maximizing the benefit of IAS in patients with heart failure.