Autonomic dysfunction is common in liver cirrhosis and is associated with cardiac dysfunction and mortality: prospective observational study

ABSTRACT BACKGROUND: Although autonomic dysfunction has been shown to be associated with liver cirrhosis, the prevalence and prognostic implications are unclear. Abnormal heart rate variability (HRV), a measure of autonomic function, has not been well investigated in cirrhosis. OBJECTIVE: To evaluate the prevalence of high-risk HRV parameters in a cohort of cirrhotic patients and their association with cardiac dysfunction and mortality. DESIGN AND SETTING: Prospective observational study conducted in the Federal University of São Paulo. METHOD: A cohort of 120 patients, comprising 17 healthy controls and 103 cirrhotic outpatients, was evaluated and followed for 10 months. HRV analysis was based on 24-hour Holter monitoring and defined using time-domain and frequency-domain parameters. RESULTS: The HRV parameters were statistically lower in cirrhotic patients than in healthy subjects. High-risk HRV parameters were prevalent, such that 64% had at least one high-risk parameter. Time-domain parameters correlated with Child scores (P < 0.0001). In regression models, HRV parameters were independent predictors of diastolic dysfunction and mortality. During 10 months of follow-up, there were 11 deaths, all of patients with at least one high-risk HRV parameter. Kaplan-Meier analysis estimated low survival rates among patients with standard deviation of normal-to-normal RR intervals (SDNN) < 100. CONCLUSION: Reduced HRV is prevalent in liver cirrhosis and is related to cardiac dysfunction, severity of liver disease and mortality. Abnormal high-risk HRV parameters are prevalent among cirrhotic patients and are also predictors of mortality. Our findings highlight the need for a more careful cardiac evaluation of cirrhotic patients.

Physiopathological and diagnostic aspects of cirrhotic cardiomyopathy / Aspectos fisiopatológicos y diagnósticos de la miocardiopatía cirrótica

Abstract Cirrhotic cardiomyopathy is characterized by the presence of structural and functional cardiac alterations in patients suffering from hepatic cirrhosis, without previously known cardiac causes that may explain it. Clinically, it is characterized by the presence of variable grades of diastolic and systolic dysfunction (SD), alterations in the electric conductance (elongation of corrected QT interval) and inadequate chronotropic response. This pathology has been related to substandard response in the management of patients with portal hypertension and poor outcome after transplant. Even when the first description of this pathology dates back from 1953, it remains a poorly studied and frequently underdiagnosed entity. Echocardiography prevails as a practical diagnostic tool for this pathology since simple measurements as the E/A index can show diastolic dysfunction. SD discloses as a diminished ejection fraction of the left ventricle and the latent forms are detected by echocardiography studies with pharmacological stress. In recent years, new techniques such as the longitudinal strain have been studied and they seem promising for the detection of early alterations.

Resumen La miocardiopatía cirrótica se caracteriza por la presencia de alteraciones cardiacas estructurales y funcionales en pacientes con cirrosis hepática, sin que existan otras causas de enfermedad cardiaca. Clínicamente se caracteriza por la presencia de grados variables de disfunción diastólica y sistólica, alteraciones de la conducción eléctrica (prolongación del intervalo QT) y respuesta cronotrópica inapropiada. Esta patología se ha relacionado con desenlaces clínicos adversos, mala respuesta en el manejo de la hipertensión portal y resultados desfavorables posterior a trasplante hepático ortotópico. A pesar de que las primeras descripciones datan de 1953, es una entidad poco estudiada y frecuentemente subdiagnosticada. El ecocardiograma es una herramienta de diagnóstico importante en esta entidad. Mediciones simples como el índice E/A pueden traducir disfunción diastólica. La disfunción sistólica se manifiesta con disminución de la fracción de eyección del ventrículo izquierdo y las formas latentes se detectan mediante estudios de ecocardiografía con estrés farmacológico; en los últimos años se han estudiado otras técnicas como el strain longitudinal, que parecen prometedoras en la detección de alteraciones tempranas.

Manifestaciones cardiovasculares de la cirrosis hepática según su gravedad evaluada por la clasificación de Child-Pugh / Cardiovascular manifestations of liver cirrhosis according to its severity evaluated through the Child-Pugh score

RESUMEN Introducción: La miocardiopatía cirrótica es una disfunción cardíaca que está presente en pacientes con cirrosis hepática, en ausencia de otra enfermedad cardíaca. Objetivos: Describir los hallazgos electrocardiográficos, ecocardiográficos y el estado de la oxigenación arterial en pacientes con cirrosis hepática. Método: Se realizó un estudio observacional, descriptivo, transversal, con 95 pacientes en protocolo de trasplante hepático en el CIMEQ, en el período establecido, para lo cual se tuvo en cuenta la clasificación de gravedad de Child-Pugh. Resultados: Se investigaron 95 pacientes (53 mujeres [55,7%]), a los cuales se les realizó electrocardiograma, ecocardiograma, determinación de la presión arterial de oxígeno y su saturación por oximetría. Se usó el SPSS (20), con medidas de resumen para variables cualitativas (razones y porcentajes) y cuantitativas (media y desviación estándar). Los resultados muestran mayor compromiso de las variables estudiadas en relación con la mayor gravedad de la cirrosis hepática, evaluada por Child-Pugh, en relación con la onda S' (p=0,03), onda A (p=0,03), presión sistólica del tronco de la arteria pulmonar (p=0,004) y presión parcial de oxígeno arterial (p=0,004). Conclusiones: Al tener en cuenta dicha clasificación, se evidenció acercamiento progresivo a valores anormales de las variables ecocardiográficas para el análisis de la función diastólica, presiones pulmonares y del estado de la oxigenación arterial expresado por la PaO2, en los estadios más avanzados de la cirrosis hepática.

ABSTRACT Introduction: Cirrhotic cardiomyopathy is a cardiac dysfunction that is present in patients with liver cirrhosis, in the absence of other heart disease. Objectives: To ascertain electrocardiographic and echocardiographic findings and arterial oxygenation state in patients with liver cirrhosis. Methods: An observational, descriptive, cross-sectional study was conducted with 95 liver transplant recipients at the CIMEQ over the established period. The Child-Pug severity classification was applied for this purpose. Results: We screened 95 patients (53 women [55.7%]) who underwent electrocardiography, echocardiography, and determination of blood oxygen pressure and oxygen saturation by oximetry. The SPSS (20), with summary measures for qualitative (ratios and percentages) and quantitative (mean and standard deviation) variables was used. Our results reveal greater compromise of the variables studied in correlation with a greater severity of liver cirrhosis, as assessed by Child-Pugh, in relation to S' wave (p=0.03), A wave (p=0.03), pulmonary artery trunk systolic pressure (p=0.004) and arterial oxygen partial pressure (p=0.004). Conclusions: Taking into account the Child-Pugh score, study showed a progressive approach to pathological values of echocardiographic variables for the analysis of diastolic function and pulmonary pressures, as well as oxygen content of arterial blood (PaO2), in the most advanced stages of liver cirrhosis.

Diastolic dysfunction in patients with liver cirrhosis: A short-term, observational study at a Malaysian hospital

@#Cirrhotic cardiomyopathy is a recognised complication of liver cirrhosis and predicts poor outcomes. Detection of diastolic dysfunction, an early indicator of left ventricular dysfunction can help identify those patients at risk of disease progression. In our study we showed that there was a high prevalence of diastolic dysfunction amongst patients with liver cirrhosis at our outpatient clinic, with the majority being Child-Pugh A/low MELD score. Multiple regression analysis indicated that age and sodium levels were significantly associated with the presence of diastolic dysfunction. This further reinforces the importance of dietary sodium restriction amongst patients with liver cirrhosis.

Cirrhotic cardiomyopathy: the liver affects the heart

Cirrhotic cardiomyopathy historically has been confused as alcoholic cardiomyopathy. The key points for diagnosis of cirrhotic cardiomyopathy have been well explained, however this entity was neglected for a long time. Nowadays the diagnosis of this entity has become important because it is a factor that contributes significantly to morbidity-mortality in cirrhotic patients. Characteristics of cirrhotic cardiomyopathy are a hyperdynamic circulatory state, altered diastolic relaxation, impaired contractility, and electrophysiological abnormalities, particularity QT interval prolongation. The pathogenesis includes impaired function of beta-receptors, altered transmembrane currents and overproduction of cardiodepressant factors, such as nitric oxide, cytokines and endogenous cannabinoids. In addition to physical signs of hyperdynamic state and heart failure under stress conditions, the diagnosis can be done with dosage of serum markers, electrocardiography, echocardiography and magnetic resonance. The treatment is mainly supportive, but orthotopic liver transplantation appears to improve this condition although the prognosis of liver transplantation in patients with cirrhotic cardiomyopathy is uncertain.

A study of cardiac dysfunction in cirrhotics.

Background: The heart and liver are organs that are closely related in both health and disease. Due to the limited number of human studies, the management of cirrhotic cardiomyopathy remains largely empirical. Material and methods: 30 Patients included in the study were recruited from the Department of Medical Gastroenterology, Narayana Medical College Hospital, Nellore. Consecutive patients diagnosed to have cirrhosis of nonalcoholic etiology formed the study group. The parameters that were assessed in echocardiography are E/A ratio, end diastolic volume (EDV), end systolic volume (ESV), ejection fraction. QTc interval more than 440 msec and E/A ratio less than 1 were considered diagnostic of cirrhotic cardiomyopathy in this study. Results: In 9 cases, cirrhosis was due to hepatic B viral infection, 4 due to due to hepatities C and in 17 patients it was cryptogenic. Of the 30 cases included in the study. Results: In 9 cases, cirrhosis was due to hepatic B viral infection, 4 due to hepatitis C and in 17 patients it was cryptogenic. Of the 30 cases included in the study, 7 cases (23.3%) had Class A CTP. 16 cases (53.3%) had Class B CTP, 7 cases had Class C CTP. Of the 30 patients included in this study, 21 patients had end diastolic volume above 90. 2 patients had end systolic volume above 38. 29 patients had ejection fraction above 60%. Out of the 30 cases, 23 showed features of cirrhotic cardiomyopathy. 7 patients had CTP Class A. 16 patients had CTP Class B.7 patients had CTP Class C. 12 patients with cirrhotic cardiomyopathy had CTP Class B. 7 patients with cirrhotic cardiomyopathy had CTP Class C. 3 patients with CTP Class A and 4 patients with CTP Class B did not have cirrhotic cardiomyopathy. The QTc was prolonged in 16 (53.3%) of patients in this study. 29 cases had ejection fraction above 60. Of the 23 cases that had cirrhotic cardiomyopathy 21 cases had ascites. 27 of the 30 cases had varices. 70.0% of the cases had end diastolic volume above 90. 76.2% of the cases with EDV above 90 had E/A ratio below 1. Conclusion: Cirrhotic patients with non alcoholic etiology do have evidence of cirrhotic cardiomyopathy. The presence of cirrhotic cardiomyopathy was independent of the etiology. Some degree of diastolic dysfunction is seen in most of the cirrhotics. Prolongation of QTc interval correlates with severity of cirrhosis. Ventricular end diastolic volume, end systolic volume and ejection fraction do not correlate with severity of cirrhosis.

Comparison of Doppler Echocardiographic Findings in Patients with Chronic Liver Disease with and without Intrapulmonary Shunt.

Aims: Doppler echocardiography is the gold standard for the diagnosis of intrapulmonary shunt (IPS) and screening for portopulmonary hypertension in chronic liver disease (CLD). Echocardiography has become fundamental to the diagnosis of cirrhotic cardiomyopathy in the last decade. The purpose of this article was to compare echocardiographic changes in patients with CLD, with and without IPS. Methodology: A total of 168 patients with CLD and portal hypertension underwent transthoracic contrast echocardiography and were allocated to two groups: Group 1 – 72 (42.9%) patients with IPS; and Group 2 – 96 (57.1 %) patients without IPS (control group). Echocardiographic variables and the presence/absence of IPS were evaluated in bilateral tests, with the level of statistical significance established at 5% (p < 0.05). Results: A higher prevalence of moderate diastolic dysfunction was found in patients with IPS (24 vs. 16 patients; p = 0.034). Patients with grade II IPS had a greater frequency of moderate diastolic dysfunction than those with grade I (16 vs. 8 patients; p = 0.028). No statistically significant differences between groups were found in left atrial volume (58 vs. 55 ml; p = 0.181) or the occurrence of pulmonary arterial hypertension (25 vs. 33 patients; p = 0.963). Conclusion: In the present study, IPS and grade II IPS were associated with moderate diastolic dysfunction determined by contrast-enhanced transthoracic Doppler echocardiography. Moderate diastolic dysfunction appeared to be a predictive factor for the onset of intrapulmonary shunt.

Disfunción cardiaca en la cirrosis hepática / Cardiac dysfunction in liver cirrhosis

Objetivo: determinar las alteraciones de la función cardiaca en las personas que padecen cirrosis hepática. Métodos: se desarrolló un estudio descriptivo transversal en el Instituto de Gastroenterología durante el período 2011-2012, en 33 cirróticos de causa viral y alcohólica, 57,6 por ciento del sexo masculino, con una edad promedio de 50 años, la mayoría (84,8 por ciento) tenía la enfermedad compensada. Resultados: la disfunción diastólica fue la alteración cardiaca más frecuente (39,3 por ciento) seguida de la prolongación del intervalo QT (12,1 por ciento), disfunción sistólica (6,1 por ciento) y miocardiopatía cirrótica (3 por ciento). No se identificaron rasgos distintivos epidemiológicos y/o clínicos que caracterizara a estos pacientes. La circulación hiperdinámica fue más evidente en los que presentaron disfunción diastólica y en la cirrosis de origen alcohólico; las dimensiones cardiacas fueron normales en todos los casos. Conclusiones: las personas que padecen cirrosis son susceptibles de presentar alteraciones de la función cardiaca, incluso, desde la etapa compensada de la enfermedad, lo que debe considerarse por las implicaciones terapéuticas que demanda este tipo de paciente...

Objective: to determine abnormalities of cardiac function in subjects with liver cirrhosis. Methods: a descriptive cross-sectional study was conducted at the Institute of Gastroenterology from 2011 to 2012, in 33 cirrhotic patients due to alcoholic and viral causes, 57.6 percent male, with an average age of 50 years, most (84,8 percent) had compensated disease. Results: diastolic dysfunction was the most common cardiac disorders (39.3 percent) followed by QT prolongation (12.1 percent), systolic dysfunction (6.1 percent) and cirrhotic (3 percent) cardiomyopathy interval. No distinctive epidemiological and/or clinical studies were identified to characterize these patients. The hyperdynamic circulation was more evident in those presenting diastolic dysfunction and alcohol-related cirrhosis. Cardiac dimensions were normal in all cases. Conclusions: people with cirrhosis are susceptible to alterations in cardiac function, even from the compensated stage of the disease, which should be considered by the therapeutic implications of this type of patient demand...

Dobutamine stress echocardiography for evaluating cirrhotic cardiomyopathy in liver cirrhosis / 대한간학회지

BACKGROUND/AIMS: The blunted ventricular systolic and diastolic contractile responses to physical and pharmacological stress in cirrhosis are termed cirrhotic cardiomyopathy (CCM). CCM has been known to involve multiple defects in the beta-adrenergic signaling pathway. The aim of this study was to determine whether cirrhotic patients have blunted cardiac responses to catecholamine stimulation through dobutamine stress echocardiography (DSE). METHODS: Seventy-one cirrhotic patients with normal left ventricular (LV) chamber size and ejection fraction were enrolled. The LV systolic and diastolic functions were evaluated by two-dimensional and Doppler echocardiography at rest and during peak dobutamine infusion (40 microg/kg/min). An abnormal response was defined as a decrease of less than 10% in LV end-diastolic volume, a decrease of less than 20% in end-systolic volume, and an increase of less than 10% in LV ejection fraction (EF) at peak dobutamine infusion, based on previously used criteria. The early/late diastolic flow (E/A) ratio and diastolic parameters were also measured. RESULTS: A blunted LV response to dobutamine was observed in 18 of 71 cirrhotic patients (25.4%). The baseline EF was significantly higher in 18 patients with a blunted DSE response than that of those with a normal DSE response (P<0.05). The baseline and peak E/A ratios, which are common diastolic dysfunction markers, were higher in the cirrhosis group than in the control group (P<0.001). No adverse events associated with DSE were observed. CONCLUSIONS: Blunted cardiac responses to dobutamine stimulation, which are implicated in defects in the beta-adrenergic signaling pathway, might contribute to the pathogenesis of CCM in patients with cirrhosis.