The cardiorenal link in advanced cirrhosis

doi:10.1016/j.mehy.2012.03.032

Medical Hypotheses

Volume 79, Issue 1, July 2012, Pages 53-55

https://doi.org/10.1016/j.mehy.2012.03.032 Get rights and content

Abstract

A considerable number of patients with advanced cirrhosis develop a hepatorenal syndrome. The pathogenesis involves liver dysfunction, splanchnic vasodilatation, and activation of vasoconstrictive systems. There are now several observations that indicate a relation between the renal failure and impaired cardiac function in patients with advanced cirrhosis. Cirrhotic cardiomyopathy has been described as a condition with impaired contractile responsiveness to stress and altered diastolic relaxation. We propose a cardiorenal interaction in patients with advanced cirrhosis and renal dysfunction that refers to a condition where cardiac dysfunction in cirrhosis is a major determinant of kidney function and survival. Thus, the relation between cardiac dysfunction and renal insufficiency should be target for future studies and development of new treatments should focus on ameliorating the cardiac dysfunction.

Section snippets

Background

Approximately 20% of patients with cirrhosis and refractory ascites develop a hepatorenal syndrome (HRS), which is a functional renal failure in patients with cirrhosis [1]. The major elements in the development of HRS are the diseased liver, the circulatory dysfunction, and an abnormal systemic and renal neuro-humoral regulation but the pathophysiology of the HRS is far from clear. Two types of HRS have been defined depending on the speed of onset and extent of renal failure [1]. Type 1 HRS is

Evaluation of the hypothesis

The development of bacterial infections is the most important precipitating risk factor for HRS [9]. Most patients have chronic elevation of proinflammatory cytokines such as IL-6 and TNF-alfa and endotoxins, which represent a chronic low-grade inflammatory state [10]. If infections or septicaemia occur, a compensatory cardiac reserve is important to protect the perfusion of vital organs such as the kidneys during vasodilatation. The activation of cytokines, vasoactive hormones, and alteration

The hypothesis

The evidence as outlined above strongly suggests that the combination of renal failure and decreased effective blood volume in cirrhosis, is not only a consequence of arterial vasodilatation but also of impaired cardiac contractility suggesting the existence of a cardiorenal syndrome in cirrhosis. We hypothesise that the cardiorenal relationship in decompensated cirrhosis is a result of an acute stress superimposed on an abnormal circulatory state. There may therefore be a link between the

Consequences of the hypothesis

Although the cardiac output is increased in patients with advanced cirrhosis, this increase is insufficient to maintain an adequate arterial blood pressure and renal perfusion and hence to prevent renal vasoconstriction and other counter-regulatory mechanisms. The recognition and understanding of a cardiac involvement would change the focus in prevention and treatment of renal dysfunction in cirrhosis and in the development of new treatments. The use of beta blockers, which is standard

Conflicts of interest

None declared.

Sources of funding

None.

Authors’ contributions

All authors contributed to concept and the writing and review of the paper.

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Cited by (53)

Mechanistic insights into the pathophysiology of cirrhotic cardiomyopathy
2022, Analytical Biochemistry
Myocardial dysfunction in end stage cirrhotic liver disease, termed cirrhotic cardiomyopathy, is a long known, but little understood comorbidity seen in ∼50% of adults and children who present for liver transplantation. Structural, functional, hemodynamic and electrocardiographic aberrations that occur in the heart as a direct consequence of a damaged liver, is associated with multi-organ failure and increased mortality and morbidity in patients undergoing surgical procedures such as porto-systemic shunt placement and liver transplantation. Despite its clinical significance and rapid advances in science and pharmacotherapy, there is yet no specific treatment for this disease. This may be due to a lack of understanding of the pathogenesis and mechanisms behind how a cirrhotic liver causes cardiac pathology. This review will focus specifically on insights into the molecular mechanisms that drive this liver-heart interaction. Deeper understanding of the etio-pathogenesis of cirrhotic cardiomyopathy will allow us to design and test treatments that can be targeted to prevent and/or reverse this co-morbid consequence of liver failure and improve health care delivery and outcomes in patients with cirrhosis.
Diagnosis and Management of Cirrhotic Cardiomyopathy
2022, Journal of Clinical and Experimental Hepatology
Cirrhotic cardiomyopathy refers to the structural and functional changes in the heart leading to either impaired systolic, diastolic, electrocardiographic, and neurohormonal changes associated with cirrhosis and portal hypertension. Cirrhotic cardiomyopathy is present in 50% of patients with cirrhosis and is clinically seen as impaired contractility, diastolic dysfunction, hyperdynamic circulation, and electromechanical desynchrony such as QT prolongation. In this review, we will discuss the cardiac physiology principles underlying cirrhotic cardiomyopathy, imaging techniques such as cardiac magnetic resonance imaging and scintigraphy, cardiac biomarkers, and newer echocardiographic techniques such as tissue Doppler imaging and speckle tracking, and emerging treatments to improve outcomes.
We reviewed available literature from MEDLINE for randomized controlled trials, cohort studies, cross-sectional studies, and real-world outcomes using the search terms “cirrhotic cardiomyopathy,” “left ventricular diastolic dysfunction,” “heart failure in cirrhosis,” “liver transplantation,” and “coronary artery disease”.
Cirrhotic cardiomyopathy is associated with increased risk of complications such as hepatorenal syndrome, refractory ascites, impaired response to stressors including sepsis, bleeding or transplantation, poor health-related quality of life and increased morbidity and mortality. The evaluation of cirrhotic cardiomyopathy should also guide the feasibility of procedures such as transjugular intrahepatic portosystemic shunt, dose titration protocol of betablockers, and liver transplantation. The use of targeted heart rate reduction is of interest to improve cardiac filling and improve the cardiac output using repurposed heart failure drugs such as ivabradine. Liver transplantation may also reverse the cirrhotic cardiomyopathy; however, careful cardiac evaluation is necessary to rule out coronary artery disease and improve cardiac outcomes in the perioperative period.
More data are needed on the new diagnostic criteria, molecular and biochemical changes, and repurposed drugs in cirrhotic cardiomyopathy. The use of advanced imaging techniques should be incorporated in clinical practice.
Evidence-based protocol for diagnosis and treatment of hepatorenal syndrome is independently associated with lower mortality
2022, Gastroenterologia y Hepatologia
Citation Excerpt :
Hepatorenal syndrome (HRS) is a severe complication of end-stage liver disease (ESLD), which occurs in cirrhotic patients with ascites.1 These patients generally have a marked circulatory dysfunction: the activation of cytokines and vasoactive hormones and the alteration in circulatory function in advanced cirrhosis and ascites without overt sepsis are similar to that seen in sepsis and septic shock without cirrhosis, which might cause renal hypoperfusion.2 Such circulatory dysfunction can also occur in patients with acute and acute-on-chronic liver failure (ACLF).3,4
Hepatorenal syndrome (HRS) is the deadliest complication of cirrhosis. The purpose of this study is to analyze if the use of a protocol for HRS is associated with higher survival in these patients.
An evidence-based protocol for the diagnosis and treatment of HRS was instituted in 2013. Data from medical records from 2010 to 2016 were obtained by searching the hospital database for patients who received terlipressin, in the three years before and after the institution of the protocol. Data were reviewed to confirm the diagnosis of HRS and multiple variables were collected. Liver-specific scores were calculated and a stepwise Cox regression approach was used for univariate and multivariate analysis.
The study included 46 patients, 20 from the pre-protocol period and 26 from the post-protocol period. Respectively, mortality at 30 days, 90 days and 365 days was 75%, 75% and 90% for the pre-protocol period, and 61%, 69% and 80% for the post-protocol period. In the multivariate analysis, an aspartate aminotransferase (AST) of <40 U/L, the pre-protocol period and higher Child-Turcotte-Pugh scores were associated with higher 30-day and 90-day mortality. The total mean dose of terlipressin and human albumin used per patient was reduced from 27 mg to 22 mg and from 236 g to 144 g, respectively, after the institution of the protocol. This was not associated with higher mortality.
The use of an evidence-based protocol for the treatment of HRS translated into a higher survival. The authors suggest that the use of evidence-based protocols for the diagnosis and treatment of HRS could reduce cost and mortality in tertiary hospitals.
El síndrome hepatorrenal (SHR) es la complicación más mortal de la cirrosis. El objetivo de este estudio es analizar si el uso de un protocolo para el SHR se asocia a una mayor supervivencia en estos pacientes.
En 2013 se instituyó un protocolo basado en la evidencia para el diagnóstico y tratamiento del SHR. Los datos de los registros médicos del 2010 al 2016 se obtuvieron mediante la búsqueda en la base de datos del hospital de pacientes que recibieron terlipresina, 3 años antes y después de la institución del protocolo. Se revisaron los datos para confirmar el diagnóstico de SHR y se recopilaron múltiples variables. Se calcularon las puntuaciones específicas del hígado y se utilizó un enfoque gradual de la regresión de Cox para el análisis univariado y multivariado.
Se incluyó a 46 pacientes, 20 del período preprotocolo y 26 posprotocolo. Respectivamente, la mortalidad a los 30, 90 y 365 días fue del 75, el 75 y el 90%, respectivamente, para el período previo al protocolo y del61, el 69 y el 80%, respectivamente, para el posterior al protocolo. En el análisis multivariado, aspartato aminotransferasa (AST) < 40 U/l, el período preprotocolo y las puntuaciones más altas de Child-Turcotte-Pugh se asociaron con una mayor mortalidad a los 30 y 90 días. Las dosis media total de terlipresina y albúmina humana utilizada por paciente se redujo de 27 a 22 mg de terlipresina y de 236 a 144 g de albúmina humana después de la institución del protocolo. Esto no se asoció con una mayor mortalidad.
El uso de un protocolo basado en la evidencia para el tratamiento del SHR se tradujo en una mayor supervivencia. Los autores sugieren que el uso de protocolos basados en la evidencia para el diagnóstico y tratamiento del SHR podría reducir el costo y la mortalidad en los hospitales de tercer nivel.
Ascites and Hepatorenal Syndrome
2019, Clinics in Liver Disease
Citation Excerpt :
However, as cirrhosis becomes more advanced, the degree of splanchnic arterial vasodilation becomes more severe and causes a marked reduction in SVR that cannot be compensated for by an increase in CO, thus resulting in effective arterial hypovolemia and systemic hypotension.2,9 Of note, evidence in the literature shows that patients with advanced cirrhosis also have cirrhotic cardiomyopathy, exacerbating the reduction in CO and worsening the arterial underfilling.10 The MAP reduction is sensed by arterial baroreceptors, triggering the activation of endogenous vasoconstrictor systems as a compensatory mechanism.4,11
Pathophysiology of the cardio-renal syndromes types 1–5: An uptodate
2017, Indian Heart Journal
According to the recent definition proposed by the Consensus conference on Acute Dialysis Quality Initiative Group, the term cardio-renal syndrome (CRS) has been used to define different clinical conditions in which heart and kidney dysfunction overlap.
Type 1 CRS (acute cardio- renal syndrome) is characterized by acute worsening of cardiac function leading to AKI (5, 6) in the setting of active cardiac disease such as ADHF, while type – 2 CRS occurs in a setting of chronic heart disease.
Type 3 CRS is closely link to acute kidney injury (AKI), while type 4 represent cardiovascular involvement in chronic kidney disese (CKD) patients.
Type 5 CRS represent cardiac and renal involvement in several diseases such as sepsis, hepato – renal syndrome and immune – mediated diseases.
Mechanisms of kidney dysfunction in the cirrhotic patient: Non-hepatorenal acute-on-chronic kidney damage considerations
2020, Annals of Hepatology
Citation Excerpt :
At rest, the intra-cardiac pressures are normal because the reduced afterload secondary to the systemic vasodilation compensates for both preload reduction and contractile dysfunction. This circulatory state, which resembles those of high cardiac output, results from increased blood flow and is defined as heart failure due to volume overload [43,44]. Although the cardiac output is increased in patients with advanced cirrhosis, this increase is insufficient to maintain an adequate arterial blood pressure and renal perfusion and hence to prevent renal vasoconstriction and other counter-regulatory mechanisms.
Renal dysfunction is a common finding in cirrhotic patients and has a great physiologic, and therefore, prognostic relevance. The combination of liver disease and renal dysfunction can occur as a result of systemic conditions that affect both the liver and the kidney, although primary disorders of the liver complicated by renal dysfunction are much more common. As most of the renal dysfunction scenarios in cirrhotic patients correspond to either prerenal azotemia or hepatorenal syndrome (HRS), physicians tend to conceive renal dysfunction in cirrhotic patients as mainly HRS. However, there are many systemic conditions that may cause both a “baseline” chronic kidney damage and a superimposed kidney dysfunction when this systemic condition worsens. The main aim of this article is to review some of the most important non prerenal non-HRS considerations regarding acute on chronic kidney dysfunction in cirrhotic patients, including renal manifestation of related to non-alcoholic steatohepatitis (NASH) viral hepatitis, the effect of cardiorenal syndrome in cirrhotics and corticosteroid-deficiency associated renal dysfunction.

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The cardiorenal link in advanced cirrhosis

Abstract

Section snippets

Background

Evaluation of the hypothesis

The hypothesis

Consequences of the hypothesis

Conflicts of interest

Sources of funding

Authors’ contributions

Hepatology

J Hepatol

J Am Coll Cardiol

Hepatology

Br J Anaesth

J Hepatol

J Hepatol

Gastroenterology

J Hepatol

J Hepatol

Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis

Gut

Cardiovascular complications of cirrhosis

Gut

Hyponatraemia during terlipressin therapy

Gut