Spironolactone Improves Right Atrial Function in Patients with Resistant Hypertension (RF_SA_478)

Background: Right atrial (RA) strain impairment is associated with pulmonary arterial hypertension and heart failure. Previous investigations have reported that the mineralocorticoid receptor antagonist spironolactone can reduce aortic stiffness and improve left atrial size and function in patients with resistant hypertension (RHTN). Other studies have demonstrated that spironolactone can reduce fibrotic remodeling in atrial myocardium in animal models. Based on these findings, we hypothesize that spironolactone will improve RA function in patients with RHTN.

Methods: Patients with RHTN (n=33, 55±7 yrs., 64% male, with normal left and right ventricular ejection fraction) were recruited and spironolactone was initiated at 25 mg/day and increased to 50 mg/day after 4 weeks. Other antihypertensives were discontinued in a step-wise manner to maintain constant blood pressure. Patients underwent cardiac magnetic resonance imaging at baseline and after 6 months. RA endocardial contour data were downloaded from the imaging analysis software (CAAS-MRV, Pie Medical Imaging, The Netherlands) into MATLAB (MathWorks, Natick, MA), and a custom-made program was used to calculate RA volume indexed to body surface area (RAVI) and global RA longitudinal strain (RALS). RAVI was calculated using biplane area-length method at all cardiac phases from standard 4-chamber images, and total, passive, and active RA emptying fractions (RAEF) were then calculated (Figure 1 and Figure 2). Reservoir, passive, and active RALS were calculated in accordance with guideline recommendations. Right ventricular (RV) volume was measured from short-axis images using CAAS-MRV software. Healthy volunteers (n=11, 56±7 yrs., 46% male) without known cardiovascular disease were recruited as a normal control group.

Results: In RHTN patients, baseline RV stroke volume was increased (P< 0.05 vs. control), and became comparable to control values, following spironolactone treatment, along with a reduction of RV end-diastolic volume (Table). Spironolactone increased plasma renin activity and decreased plasma concentration of brain natriuretic peptide while changes in plasma creatinine and potassium levels were moderate (Table). Baseline RAVI values were significantly increased (P< 0.01 vs. control) and incompletely recovered with treatment (P< 0.05 vs. control, Table). Despite high RA volumes in those with RHTN, baseline values of RAEF and RALS were comparable to control and improved with spironolactone. Interestingly, the degree of improvement of RA properties was similar in patients with high (n=16) and normal (n=17) aldosterone status (data not shown).

Conclusion: Spironolactone treatment in patients with RHTN is associated with improvements in RA size and function. These findings should be further tested in a larger study group.