Potential therapeutic targets in cirrhotic cardiomyopathy.
Cirrhotic cardiomyopathy is a recently identified pathological condition defined as "a chronic cardiac dysfunction in patients with cirrhosis characterized by blunted contractile responsiveness to stress and/or altered diastolic relaxation with electrophysiological abnormalities, in the absence of known cardiac disease". Overall there seems to be a link between the progression of liver function impairment, the development of portal hypertension and the degree of hyperdynamic circulation, the hallmark of the deranged cardiovascular function in advanced liver diseases. Although mechanical factors contribute to much of the increased resistance within the liver in portal hypertension, there is clearly a vasculogenic component to the development, perpetuation and progression of this syndrome as well. The vascular component of portal hypertension includes an increase in splanchnic blood flow, as well as an increase in intrahepatic vascular resistance. Dysregulation of the nitric oxide system appears to play a key role in both these processes with a paradoxical reduction of intrahepatic availability despite increased disposal in the splanchnic and other vascular districts with adverse effects on cardiac function and structure. Nevertheless, other putative mediators of cardiac damage in cirrhosis have been proposed and their role in the pathogenesis of cirrhotic cardiomyopathy investigated. This review involves a discussion of data achieved on pathogenesis and clinical features of cirrhotic cardiomyopathy but mainly focuses on considerations on potential therapeutic targets, in the light of the evidence that this mainly subclinical condition merges to clinical relevance when challenged with those therapeutic interventions and procedures currently employed to treat the major complications of cirrhosis that might produce a negative impact on the cardiovascular system.
Pozzi
Massimo
M
Cattedra di Medicina Interna, Università degli Studi di Milano-Bicocca, Clinica Medica, Ospedale San Gerardo dei Tintori, Via Pergolesi 33 - 20052 Monza (Milano), Italy. epa.monza@libero.it
Ratti
Laura
L
Guidi
Cristina
C
Milanese
Maria
M
Mancia
Giuseppe
G
D000818:Animals; D009202:Cardiomyopathies / Q000473:pathology / Q000628:therapy*; D002317:Cardiovascular Agents / Q000627:therapeutic use*; D005355:Fibrosis / Q000473:pathology / Q000628:therapy*; D006801:Humans
D002317:Cardiovascular Agents