The left ventricular end-diastolic pressure (LVEDP), a marker of diastolic function, is strongly influenced by cardiac preload. In vitro experiments have demonstrated that LVEDP is also affected by intracardiac hydrostatic pressure gradients, which depend on heart's orientation. Though lacking clinical validation, the relationship between intracardiac hydrostatic pressure gradient and cardiac filling could significantly impact the symptomatology of heart failure patients and the interpretation of cardiac function in clinical imaging.

The aim was to isolate the intracardiac pressure gradient's effect independently of preload, exploring the orientation dependency of cardiac function in healthy and diabetic individuals.

This prospective study aimed to recruit 32 subjects (16 healthy and 16 with diabetes), sequentially exposed to acute alterations of cardiac preload in various heart orientations: supine position via Lower Body Negative Pressure (LBNP) and upright position via Head-Up Tilt (HUT) test. Using a standardized protocol, all subjects underwent gradual preload variations during HUT (22°, 42°, 58°, and 80°) and LBNP (−10, −20, −35, −50 torr). Arterial blood pressure was continuously monitored non-invasively, while thoracic fluid shifts were assessed using bioelectrical impedance. Cardiac dimensions and left ventricular systolic and diastolic functions were evaluated at each stage via transthoracic echocardiography.

Hemodynamic and fluid shift responses were collected from 20 subjects to date (7 healthy and 13 with diabetes). The current sample size per group precludes intergroup comparisons. Both LBNP and HUT induced comparable fluid shifts in the thoracic region, resulting in similar preload modifications (Fig. 1A). Blood pressure regulation was appropriate in both conditions, maintaining mean arterial blood pressure stable, except during HUT at 80° (Fig. 1B). A significant difference in stroke volume was observed between HUT at 80° and LBNP at −50 torr, with the latter associated with an uncompensated drop in stroke volume (Fig. 1C).

Cardiac adaptation to upright posture effectively compensates for preload reduction, unlike in the supine position. Despite similar preload variations, intracardiac hydrostatic pressure in an upright posture sustains cardiac stroke volume, potentially due to gravitational effects. Confirmation through echocardiographic analysis, especially in diabetic subjects prone to early myocardial impairments, could significantly impact cardiac function interpretation in clinical practice and have important implications in aerospace medicine.