Cardiac, neuroadrenergic, and portal hemodynamic effects of prolonged aldosterone blockade in postviral child A cirrhosis

Am J Gastroenterol. 2005 May;100(5):1110-6. doi: 10.1111/j.1572-0241.2005.41060.x.

Abstract

Objectives: The present study was designed to determine the effects of long-term antialdosterone treatment on cardiac structural and functional alterations, portal and systemic hemodynamic as well as adrenergic dysfunction characterizing Child A cirrhotic patients with F1 esophageal varices.

Methods: Twenty-two Child A postviral preascitic cirrhotic patients were randomly allocated to 200 mg/day K-Canrenoate (13 patients, age 59.6 +/- 2.2 yr, mean + SEM) or no-drug treatment (9 patients, age 61.8 +/- 2.3) for a 6-month-period. Measurements, which included hepatic venous pressure gradient (HVPG), left ventricular wall thickness, left ventricular end-diastolic volume and diastolic function (LVWT, LVEDV, and E/A ratio, echocardiography), and muscle sympathetic nerve activity (MSNA, microneurography, peroneal nerve), were obtained at baseline and following 6 months of drug or no-drug treatment. Ten healthy age-matched subjects served as controls.

Results: Cirrhotic patients were characterized by increased HVPG, LVWT, and MSNA values and by a depressed E/A ratio. K-Canrenoate treatment significantly reduced HVPG (from 15.3 +/- 1.0 to 13.8 +/- 0.8 mmHg, p < 0.05), LVWT (from 21.8 +/- 0.5 to 20.7 +/- 0.6 mm, p < 0.02), and LVEDV (from 99.2 +/- 7 to 86.4 +/- 6 ml, p < 0.01), leaving E/A ratio and MSNA almost unaltered. No significant change was observed in the untreated group of cirrhotic patients followed for 6 months without intervention.

Conclusions: These data provide evidence that aldosterone blockade by long-term K-Canrenoate administration improves hepatic hemodynamics by lowering HVPG and ameliorates cardiac structure and function by favoring a reduction in LVWT and LVEDV as well. They also show, however, that this therapeutic intervention neither improves left ventricular diastolic dysfunction nor exerts sympathoinhibitory effects.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adrenergic Fibers / drug effects*
  • Canrenoic Acid / therapeutic use*
  • Case-Control Studies
  • Diastole / drug effects
  • Esophageal and Gastric Varices / drug therapy
  • Female
  • Heart / drug effects*
  • Heart Ventricles / drug effects
  • Hemodynamics / drug effects
  • Hepatic Veins / drug effects
  • Hepatitis B / complications*
  • Hepatitis C / complications*
  • Humans
  • Liver Circulation / drug effects
  • Liver Cirrhosis / drug therapy*
  • Liver Cirrhosis / physiopathology
  • Liver Cirrhosis / virology
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mineralocorticoid Receptor Antagonists / therapeutic use*
  • Peroneal Nerve / drug effects
  • Portal System / drug effects*
  • Stroke Volume / drug effects
  • Venous Pressure / drug effects

Substances

  • Mineralocorticoid Receptor Antagonists
  • Canrenoic Acid