Cardiac, neuroadrenergic, and portal hemodynamic effects of prolonged aldosterone blockade in postviral child A cirrhosis.
OBJECTIVE
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.
Pozzi
Massimo
M
Clinica Medica, Università Milano-Bicocca, Dipartimento di Radiologia, Ospedale San Gerardo, Monza, Italy.
Grassi
Guido
G
Ratti
Laura
L
Favini
Giorgio
G
Dell'Oro
Raffaella
R
Redaelli
Elena
E
Calchera
Ivan
I
Boari
Giuseppe
G
Mancia
Giuseppe
G
D000320:Adrenergic Fibers / Q000187:drug effects*; D002191:Canrenoic Acid / Q000627:therapeutic use*; D016022:Case-Control Studies; D003971:Diastole / Q000187:drug effects; D004932:Esophageal and Gastric Varices / Q000188:drug therapy; D005260:Female; D006321:Heart / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006503:Hepatic Veins / Q000187:drug effects; D006509:Hepatitis B / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008102:Liver Circulation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000627:therapeutic use*; D010543:Peroneal Nerve / Q000187:drug effects; D011168:Portal System / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects; D014690:Venous Pressure / Q000187:drug effects
D000451:Mineralocorticoid Receptor Antagonists; D002191:Canrenoic Acid