Acute Preload Reduction as a Predictor of Cardiac Structural and Functional Changes Induced by Antihypertensive Therapy

Objective: In hypertension, treatment-induced cardiac structural and functional changes largely reflect the degree of blood pressure (BP) reduction. It remains unclear whether these effects are purely haemodynamic or involve interactions between pre-load, afterload, and contractility. We compared the effects of acute isolated preload reduction with antihypertensive therapy and assessed whether these responses are correlated. Design and method: Untreated hypertensive subjects underwent transthoracic echocardiography (TTE), including acute preload reduction via lower limb venous occlusion (LVO), achieved by inflating thigh cuffs above diastolic but below systolic pressure to limit venous return. TTE was repeated after eight weeks of randomised treatment with amlodipine (10 mg), chlorthalidone (25 mg), or lisinopril (20 mg). Diastolic function was assessed using left atrial volume (LAV) and E/E’ ratio. Ventricular volumes were measured using Simpson's biplane method, and stroke volume (SV) was calculated as the difference between end-diastolic and end-systolic volumes. Mixed-effects random-intercept linear regression models were fitted for each TTE variable, including fixed effects for baseline TTE values and the TTE LVO response. Nested models added fixed effects for treatment mean arterial pressure (MAP) change and treatment drug. Means and regression coefficients are presented with a 95% confidence interval or standard deviation. Results: 71 participants (mean age 43 [11] years, 60% male) were included; n=59, 50, and 52 completed follow-up after amlodipine, chlortalidone, and lisinopril, respectively. LVO produced minimal BP change compared with pharmacological treatment (mean change in MAP -0.3 [-1.7, 1.0] mmHg with LVO vs -8.7 [-10.5, -7.0] mmHg with antihypertensives). For multiple TTE measures (Fig.), treatment-induced changes were associated with LVO responses (regression coefficients: LAV 0.36 [0.14, 0.58], E/E’ 0.13 [-0.03, 0.29], and SV 0.27 [0.07, 0.47]). TTE treatment responses, and TTE LVO responses, were both not associated with MAP treatment responses. Associations between treatment and LVO responses were consistent across drug classes with no significant drug-LVO interaction. Conclusions: Preload reduction and antihypertensive therapy both influence cardiac volumes and diastolic function in hypertensive patients. Despite modest BP effects, LVO-induced TTE changes predict treatment responses, suggesting LVO may help anticipate therapeutic effects on echocardiographic parameters.