Cardiac dysfunction in cirrhosis: a 2-yr longitudinal follow-up study using advanced cardiac imaging.

The temporal relationship between cirrhotic cardiomyopathy, progression of liver disease, and survival remains unknown. Our aim was to investigate the development of structural and functional cardiac changes over time with the progression of cirrhosis and outcome. Sixty-three cirrhotic outpatients (Child class: A = 9, B = 46, C = 8) and 14 healthy controls were included in this 2-yr longitudinal study. Advanced cardiac characteristics such as cardiac MRI with extracellular volume (ECV) quantification, speckle tracking echocardiography, and biomarkers were assessed at 0/6/12/18/24 mo. Patients were followed-up for a median of 30 mo with registration of acute decompensations (ADs), liver transplantations (LTs), and deaths. Patients who progressed, underwent LT or died had more pronounced cardiac dysfunction, structural myocardial changes, and left atrial enlargement. Conversely, limited cardiac deterioration was seen in patients who remained stable or improved in cirrhosis. During follow-up 25 patients developed AD, 4 underwent LT, and 20 died. Mean arterial pressure was the only cardiovascular parameter associated with death in a univariate analysis (P = 0.037), and the main predictors were model for end-stage liver disease and age. However, last-visit myocardial ECV was independently associated with the combined end point of LT/death (P = 0.001), and in patients with AD a low cardiac index was independently associated with death (P = 0.01). Cardiac function seems to deteriorate with the progression of cirrhosis and affects prognosis, especially in patients with AD. Conversely, patients with stable cirrhosis have limited progression in cardiac dysfunction over a 2-yr period with modest impact on survival. The results encourage careful cardiac monitoring in advanced cirrhosis.NEW & NOTEWORTHY For the first time, we have performed advanced cardiac imaging to investigate the development of cirrhotic cardiomyopathy over 2 years. We show that cardiac dysfunction deteriorates with progression of cirrhosis and may affect the prognosis in patients developing acute decompensation. Especially, structural myocardial abnormalities, left atrial enlargement, and a hypodynamic cardiac state seem of importance. Conversely, limited cardiac progression is seen in stable cirrhosis. These findings provide new insight into our understanding of cirrhotic cardiomyopathy.

Myocardial extracellular volume quantified by magnetic resonance is increased in cirrhosis and related to poor outcome.

BACKGROUND & AIMS: The underlying pathogenesis of cirrhotic cardiomyopathy remains unclear. Structural myocardial changes including diffuse fibrosis may be involved and can be accurately assessed by cardiac MRI (CMR) with quantification of the extracellular volume (ECV).This is the first application of this technique in patients with cirrhosis. We aimed to investigate the presence of diffuse myocardial fibrosis and to determine the relation to disease severity, cardiac function and outcome. METHODS: A prospective study including 52 cirrhotic patients and 10 healthy controls. All patients underwent CMR with ECV quantification, tissue Doppler echocardiography, and biochemical assessments. Patients were followed up for a median of 25 months with registration of death and liver transplantation (LT). RESULTS: Myocardial ECV was higher in the patients compared with healthy controls (31.2 ± 6 vs 27.4 ± 3%, P = .04). Furthermore, ECV increased across the Child Pugh A/B/C classes (26.9 ± 4/31.5 ± 5/34.4 ± 6%, P = .02). Four-teen patients experienced the composite end-point of death/LT during follow-up and these patients had higher ECV (33.2 ± 4 vs 30.4 ± 6%, P = .04). In a univariate Cox regression analysis ECV was associated with poor transplant-free survival (HR 3.6 [1.1-11.6]; P = .03). However, MELD and CRP remained the strongest predictors in a multivariate analysis. ECV correlated with cardiac index (r = 0.44, P = .001), CRP (r = 0.46, P = .001), proANP (r = 0.50, P < .001), and proBNP (r = 0.40, P = .005). CONCLUSIONS: Myocardial ECV is increased in patients with cirrhosis and seems related to disease severity and transplant-free survival. These changes most likely reflect subclinical diffuse myocardial fibrosis and may represent a structural element of cirrhotic cardiomyopathy.

Low ascitic fluid total protein levels is not associated to the development of spontaneous bacterial peritonitis in a cohort of 274 patients with cirrhosis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a complication to decompensated cirrhosis. Fluoroquinolones may prevent SBP. However, predictive markers for SBP are wanted. Guidelines suggest that patients with ascitic fluid protein below 15 g/l receive fluoroquinolones to prevent SBP. This study aimed to assess the clinical utility of low ascitic fluid protein in predicting SBP in patients with cirrhosis and ascites. METHODS: A total of 274 patients with cirrhosis and ascites underwent paracentesis between January 2010 and June 2015. Patients were followed until two years, development of SBP, initiation of ciprofloxacin, death or liver transplantation. Data were compared between groups of patients with 'high' or 'low' ascitic protein. RESULTS: SBP developed in 31 patients (11.3%). No difference in mean ascitic fluid protein levels were found (SBP, mean: 8.5 g/l and no SBP 8.2 g/l, p = .825). SBP developed at equal rates in patients with 'high' or 'low' ascitic protein (10.8% (≤15 g/l) and 14.0% (>15 g/l), p = .599). The same trend was observed when adjusting the threshold below 10 g/l (11.9% (≤10 g/l) and 10.2% (>10 g/l), p = .697). CONCLUSIONS: Low ascitic fluid protein does not predict SBP in patients with cirrhosis and ascites. Better markers are needed.

Left atrial volume changes assessed by real time 3-dimensional echocardiography in relation to liver function and prognosis in patients with cirrhosis.

Left atrial enlargement is a known marker of chronic diastolic dysfunction and was recently shown to be an independent predictor of mortality in cirrhosis. Real time 3-dimensional echocardiography (3DE) is an emerging modality that enables accurate measurements of the left atrial (LA) volume and function. Assessment of LA volumes with 3DE has never been applied in cases of cirrhosis. We therefore aimed to investigate LA volumes using the novel 3DE technique in relation to liver dysfunction and outcome in patients with cirrhosis. A prospective study of 47 cirrhotic patients without cardiovascular disease and ten healthy controls. The patients underwent clinical evaluation, blood sampling, liver vein catheterization, ECG and tissue Doppler echocardiography, including 3DE. Patients were followed up for a median of 25 months with registration of death and liver transplantation (LT). 3DE-derived maximal left atrial volume index (LAVImax) and minimal left atrial volume index (LAVImin) were higher in patients with a Child Pugh score of 8 or higher than in patients with a score lower than 8 (30.0 vs. 22.3 mL/m2, P=0.008 and 14.6 vs. 9.5 mL/m2, P=0.04, respectively). LA volumes correlated with model for end-stage liver disease (MELD) score (r=0.40, P=0.005), hepatic venous pressure gradient (r=0.34, P=0.04), and biochemical markers of advanced liver disease. Twelve patients experienced the composite end-point of death or LT during follow-up and these patients had increased LA volumes with a higher LAVImax (34.3±14.8 vs. 25.9±7.3 mL/m2, P=0.01) and a higher LAVImin (16.3±7.3 vs. 10.8±5.1 mL/m2, P=0.007). Patients with advanced cirrhosis have increased minimal and maximal left atrial volumes, which correlate with the degree of the liver dysfunction and poor prognosis.