Appraising Cardiac Dysfunction in Liver Transplantation
Cirrhosis-associated cardiac dysfunction can gravely and viciously aggravate other organ systems in patients with ESLD. This vicious cycle of adverse consequences adds to the baseline pathological circulatory state encountered in ESLD.
The circulatory state in ESLD is described as; hyperkinetic, centrally under-filled, peripherally vasodilated and mal-distributive. The release of nitric oxide together with failure of the liver to clear circulating vasodilators such as glucagon result in severe splanchnic vasodilation leading to renal and gut under-perfusion.
As a result, sympathetic nervous system, renin–angiotensin system and argenine–vasopressin systems get stimulated. This results in tachycardia and increase in cardiac output, in renal and brain vasoconstriction, and in sodium and water retention, as an attempt to restore mean perfusion pressure to these organs. Because of a surplus of splanchnic vasodilators, the splanchnic circulation becomes more resistant to circulating vasoconstrictors (angiotensin, catecholamines) resulting in vicious release of this vasoconstrictors leading to renal and brain vasoconstriction and the development of ascites (relative hypovolaemia).
As time progresses, the increase in cardiac output becomes insufficient to meet the increased demands in ESLD leading to a relative reduction in effective circulatory volume and perfusion pressures leading to kidney injury. It is thus conceivable that cirrhosis-associated (or -aggravated) cardiac dysfunction can hasten the development of kidney injury and ascites formation. Patients with ESLD who are on beta-blockers are particularly at risk of the negative consequences of cardiac output reduction. In fact beta- blockers (propranolol) were shown to be independently associated with reduced survival in a cohort of cirrhotics with ascites. Similar considerations are applicable for angiotensin-converting enzyme inhibitors which can worsen the underlying severe vasodilatory state in patients with ESLD leading to decreased renal perfusion pressure.
Both systolic and diastolic dysfunctions are associated with kidney injury in ESLD. Right or left ventricular systolic dysfunction may lead to a reduction in the stroke volume and renal blood flow. Backward failure resulting from uni- or biventricular systolic or diastolic dysfunction may result in renal congestion that may add to the renal insult.
Based on the above, it is not surprising what recent literature suggests of a prognostic cardio-renal relationship in ESLD. In a small prospective study, Krag et al. demonstrated that the reduction in cardiac index to below 1.5 L/m/m – as measured by myocardial perfusion scan – was associated with the development of type-1 hepatorenal syndrome and that their combination was associated with a significant reduction in survival. Interestingly, cardiac index performed superiorly to MELD score in predicting survival. An earlier study on patients with ESLD and a diagnosis of spontaneous bacterial peritonitis demonstrated a significant inverse correlation between cardiac output and the development of renal failure. It remains to be determined, though, whether cardiac dysfunction is a risk factor vs. a risk marker for hepatorenal syndrome. Also, it remains to be determined whether more sensitive markers of ventricular mechanical dysfunction and renal dysfunction retain a similar relationship compared with their less sensitive counterparts.
Consequences of Cardiac Dysfunction on Other Organ Systems in End-stage Liver Disease
Cirrhosis-associated cardiac dysfunction can gravely and viciously aggravate other organ systems in patients with ESLD. This vicious cycle of adverse consequences adds to the baseline pathological circulatory state encountered in ESLD.
The circulatory state in ESLD is described as; hyperkinetic, centrally under-filled, peripherally vasodilated and mal-distributive. The release of nitric oxide together with failure of the liver to clear circulating vasodilators such as glucagon result in severe splanchnic vasodilation leading to renal and gut under-perfusion.
As a result, sympathetic nervous system, renin–angiotensin system and argenine–vasopressin systems get stimulated. This results in tachycardia and increase in cardiac output, in renal and brain vasoconstriction, and in sodium and water retention, as an attempt to restore mean perfusion pressure to these organs. Because of a surplus of splanchnic vasodilators, the splanchnic circulation becomes more resistant to circulating vasoconstrictors (angiotensin, catecholamines) resulting in vicious release of this vasoconstrictors leading to renal and brain vasoconstriction and the development of ascites (relative hypovolaemia).
As time progresses, the increase in cardiac output becomes insufficient to meet the increased demands in ESLD leading to a relative reduction in effective circulatory volume and perfusion pressures leading to kidney injury. It is thus conceivable that cirrhosis-associated (or -aggravated) cardiac dysfunction can hasten the development of kidney injury and ascites formation. Patients with ESLD who are on beta-blockers are particularly at risk of the negative consequences of cardiac output reduction. In fact beta- blockers (propranolol) were shown to be independently associated with reduced survival in a cohort of cirrhotics with ascites. Similar considerations are applicable for angiotensin-converting enzyme inhibitors which can worsen the underlying severe vasodilatory state in patients with ESLD leading to decreased renal perfusion pressure.
Both systolic and diastolic dysfunctions are associated with kidney injury in ESLD. Right or left ventricular systolic dysfunction may lead to a reduction in the stroke volume and renal blood flow. Backward failure resulting from uni- or biventricular systolic or diastolic dysfunction may result in renal congestion that may add to the renal insult.
Based on the above, it is not surprising what recent literature suggests of a prognostic cardio-renal relationship in ESLD. In a small prospective study, Krag et al. demonstrated that the reduction in cardiac index to below 1.5 L/m/m – as measured by myocardial perfusion scan – was associated with the development of type-1 hepatorenal syndrome and that their combination was associated with a significant reduction in survival. Interestingly, cardiac index performed superiorly to MELD score in predicting survival. An earlier study on patients with ESLD and a diagnosis of spontaneous bacterial peritonitis demonstrated a significant inverse correlation between cardiac output and the development of renal failure. It remains to be determined, though, whether cardiac dysfunction is a risk factor vs. a risk marker for hepatorenal syndrome. Also, it remains to be determined whether more sensitive markers of ventricular mechanical dysfunction and renal dysfunction retain a similar relationship compared with their less sensitive counterparts.
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