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The relationship of hyperdynamic circulation and cardiodynamic states in cirrhosis

2018; Elsevier BV; Volume: 69; Issue: 3 Linguagem: Inglês

10.1016/j.jhep.2018.04.026

1600-0641

Edilmar Alvarado, Marta Garcia‐Guix, Sònia Mirabet, Cándid Villanueva,

Ultrasound in Clinical Applications

Cardiopulmonary hemodynamics and C-reactive protein as prognostic indicators in compensated and decompensated cirrhosisJournal of HepatologyVol. 68Issue 5PreviewCirrhosis represents the end-stage of chronic liver disease, with a course characterized by a transition from an asymptomatic compensated stage to a symptomatic decompensated stage.1 These stages have entirely different mortalities and should therefore be considered distinct entities. Decompensation is defined by the development of overt clinical complications of cirrhosis: ascites, variceal hemorrhage (VH), encephalopathy, and jaundice.1 Full-Text PDF Reply to: "Relationship of hyperdynamic circulation and cardiodynamic states in cirrhosis"Journal of HepatologyVol. 69Issue 3PreviewWe appreciate Dr. Alvarado and colleagues' comments regarding our study published in Journal of Hepatology describing that different cardiodynamic states (as determined by cardiac index at rest in a supine position) and systemic inflammation (as assessed by an elevated serum C reactive protein [CRP]) are independent predictors of disease outcomes in both compensated and decompensated patients with cirrhosis.1 Full-Text PDF In a recent issue of the Journal Turco et al. report a cohort study assessing systemic and cardiac hemodynamics across stages of cirrhosis from compensated patients with mild portal hypertension (PH) to patients with refractory ascites.[1]Turco L. et al.Cardiopulmonary hemodynamics and C-reactive protein as prognostic indicators in compensated and decompensated cirrhosis.J Hepatol. 2018; 68: 949-958Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar The authors defined three cardiodynamic states according to the cardiac index (CI): a hyperdynamic state defined by a CI above the upper normal limit (>4.2 L/min/m2), a ("relatively") hypodynamic state with a CI below the average for the general population (<3.2 L/min/m2) and a normodynamic state between both situations. However, these cardiodynamic states may be misleading. According to current knowledge, patients with cirrhosis have a hyperdynamic circulation characterized by an increase in CI and a decrease in peripheral vascular resistance, which may conceivably be driven by a progressive splanchnic (and systemic) vasodilatation.[2]Iwakiri Y. Groszmann R.J. The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule.Hepatology. 2006; 43: S121-S131Crossref PubMed Scopus (436) Google Scholar This hyperdynamic circulation develops progressively. In compensated patients, it is more developed in those with clinically significant PH (CSPH) than in those without CSPH and, among patients with CSPH it is less developed in those without varices than in those with varices (Table 1).[3]Villanueva C. Albillos A. Genescà J. Abraldes J.G. Calleja J.L. Aralic C. et al.Development of hyperdynamic circulation and response to b-blockers in compensated cirrhosis with portal hypertension.Hepatology. 2016; 63: 197-206Crossref PubMed Scopus (113) Google Scholar It is even more developed in patients with decompensated cirrhosis than in those compensated.[4]Alvarado E. Pavel O. Ardevol A. Graupera I. Huelin P. Colomo A. et al.Influence of previous decompensation of cirrhosis on hyperdynamic circulation and response to β-blockers in primary prophylaxis of variceal bleeding.J Hepatol. 2015; 62: S263-S864Abstract Full Text PDF Google Scholar The results reported by Turco et al. are in concordance with previous studies, showing a progressive development of hyperdynamic circulation from early stages of compensated cirrhosis to decompensated stages. Mean arterial pressure progressively decreased from PS1 to PS5 and CI progressively increased from PS1 to PS4, but not in those with advanced decompensation (PS5) compared with early decompensation (PS4). This is also in keeping with previous studies suggesting that cardiac dysfunction, with a reduction of CI, may be associated with the development of hepatorenal syndrome and has a negative impact on survival.5Ruiz-del-Arbol L. Monescillo A. Arocena C. Valer P. Ginès P. Moreira V. et al.Circulatory function and hepatorenal syndrome in cirrhosis.Hepatology. 2005; 42: 439-447Crossref PubMed Scopus (458) Google Scholar, 6Krag A. Bendtsen F. Henriksen J.H. Moller S. Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites.Gut. 2010; 59: 105-110Crossref PubMed Scopus (261) Google Scholar, 7Ruiz-del-Arbol L. Achecar L. Serradilla R. Rodriguez-Gandia M.A. Rivero M. et al.Diastolic dysfunction is a predictor of poor outcomes in patients with cirrhosis, portal hypertension and a normal creatinine.Hepatology. 2013; 58: 1732-1741Crossref PubMed Scopus (102) Google ScholarTable 1Progression of hyperdynamic circulation and portal hypertension across each evolutionary stage of cirrhosis, from patients compensated with mild PH to CSPH (with or without varices) and decompensation.Patients with compensated cirrhosis[3]Villanueva C. Albillos A. Genescà J. Abraldes J.G. Calleja J.L. Aralic C. et al.Development of hyperdynamic circulation and response to b-blockers in compensated cirrhosis with portal hypertension.Hepatology. 2016; 63: 197-206Crossref PubMed Scopus (113) Google ScholarMild PH (HVPG <10)CSPH & no varicesCSPH & varicesCardiac output (L/min)5.1 ± 1.15.4 ± 1.66.3 ± 1.7*p ≤0.01 for the comparison with the group in the left column.Cardiac index (L/min/m2)2.8 ± 0.43.1 ± 0.8*p ≤0.01 for the comparison with the group in the left column.3.4 ± 0.9*p ≤0.01 for the comparison with the group in the left column.Mean arterial pressure (mmHg)93 ± 1297 ± 1296 ± 12Heart rate (beats/min)70 ± 1072 ± 1072 ± 11Systemic vascular resistance (dyne.s.cm-5)1,469 ± 3351,408 ± 4511,235 ± 378*p ≤0.01 for the comparison with the group in the left column.Hepatic venous pressure gradient (mmHg)7.3 ± 1.313.8 ± 4.1*p ≤0.01 for the comparison with the group in the left column.15.4 ± 3.9*p ≤0.01 for the comparison with the group in the left column.Patients with compensated cirrhosis vs. patients decompensated[4]Alvarado E. Pavel O. Ardevol A. Graupera I. Huelin P. Colomo A. et al.Influence of previous decompensation of cirrhosis on hyperdynamic circulation and response to β-blockers in primary prophylaxis of variceal bleeding.J Hepatol. 2015; 62: S263-S864Abstract Full Text PDF Google ScholarCompensated & large varicesDecompensated & varicesCardiac output (L/min)6.9 ± 1.97.6 ± 2.3*p ≤0.01 for the comparison with the group in the left column.Cardiac index (L/min/m2)4.1 ± 1.34.5 ± 1.3*p ≤0.01 for the comparison with the group in the left column.Mean arterial pressure (mmHg)92 ± 1386 ± 12*p ≤0.01 for the comparison with the group in the left column.Heart rate (beats/min)76 ± 1280 ± 12*p ≤0.01 for the comparison with the group in the left column.Systemic vascular resistance (dyne.s.cm-5)1,042 ± 307858 ± 282*p ≤0.01 for the comparison with the group in the left column.Hepatic venous pressure gradient (mmHg)17.5 ± 419.3 ± 4*p ≤0.01 for the comparison with the group in the left column.Results expressed as mean ± SD. CSPH (defined by an HVPG ≥10 mmHg).CSPH, clinical significant portal hypertension; HVPG, hepatic venous pressure gradient; PH, portal hypertension.* p ≤0.01 for the comparison with the group in the left column. Open table in a new tab Results expressed as mean ± SD. CSPH (defined by an HVPG ≥10 mmHg). CSPH, clinical significant portal hypertension; HVPG, hepatic venous pressure gradient; PH, portal hypertension. Considering this background, what seems misleading in the present study is the proposed cardiodynamic classification. Since the "baseline" CI of patients is unknown, i.e. the CI when healthy or in an earlier state of the disease, it may cause confusion to define the observed value of CI as hypo or normodynamic when actually it can be much greater than a previous (unmeasured) value at an earlier stage and thus may actually reflect a relatively hyperdynamic state. Patients classified as hyperdynamic behave, as expected, with overt hyperdynamic circulation. However, it seems likely that a (great) proportion of those classified as normodynamics may be relatively hyperdynamic compared with their own earlier stages. Confusion grows when considering patients classified as "relatively" hypodynamic, since being below the average CI for normal patients may not mean being hypodynamic. More than 50% of patients with early compensated disease, still without CSPH (PS1), and more than 30% of those compensated with CSPH (PS2 and PS3) were relatively hypodynamic according to the classification proposed. It seems likely, however, that a large proportion of these patients are actually close to their baseline state, and thus may actually be normodynamic (PS1), or even may be relatively more hyperdynamic than earlier (PS2 and PS3). Furthermore, patients who are "relatively" hypodynamic at early stages (PS1/PS2) may not be the same as those hypodynamic at later, decompensated, stages (PS4/PS5). Some of those hypodynamic when decompensated may have been (more) hypodynamic at an earlier stage, but some may have been previously hyperdynamic and their final outcome may be different from that of those previously hypodynamic. In addition, some hypodynamic patients have pulmonary hypertension (as well as in the other cardiodynamic states) and these patients may be different from those without. Other issues in the study, such as the introduction of β-blockers after hemodynamic measurements in some patients (Table S1) or the performance of large volume paracentesis with albumin infusion hours before the hemodynamic measurements, introduce further confusion as they may bias the parameters measured. Stroke volume index decreased progressively from early to late stages in hypodynamic patients, but not in those normo or hyperdynamic in whom there was a trend towards an increase, which is in keeping with previous studies suggesting that left ventricular systolic function is enhanced in cirrhosis.[8]Yotti R. Ripoll C. Benito Y. Catalina M.V. Elizaga J. Rincon D. et al.Left ventricular systolic function is associated with sympathetic nervous activity and markers of inflammation in cirrhosis.Hepatology. 2017; 65: 2019-2030Crossref PubMed Scopus (39) Google Scholar This suggests that a proportion of hypodynamic patients may have cardiac dysfunction. This is a relevant issue considering that the results of this study indicate that hypodynamic patients are at risk of poor outcomes, as previously reported.5Ruiz-del-Arbol L. Monescillo A. Arocena C. Valer P. Ginès P. Moreira V. et al.Circulatory function and hepatorenal syndrome in cirrhosis.Hepatology. 2005; 42: 439-447Crossref PubMed Scopus (458) Google Scholar, 6Krag A. Bendtsen F. Henriksen J.H. Moller S. Low cardiac output predicts development of hepatorenal syndrome and survival in patients with cirrhosis and ascites.Gut. 2010; 59: 105-110Crossref PubMed Scopus (261) Google Scholar, 7Ruiz-del-Arbol L. Achecar L. Serradilla R. Rodriguez-Gandia M.A. Rivero M. et al.Diastolic dysfunction is a predictor of poor outcomes in patients with cirrhosis, portal hypertension and a normal creatinine.Hepatology. 2013; 58: 1732-1741Crossref PubMed Scopus (102) Google Scholar Nevertheless, no data is provided on how a potential cardiac dysfunction was evaluated and treated. The systematic assessment of cardiac function in these patients with pulse-wave tissue Doppler imaging to assess strain, or with new techniques such as ejection intraventricular pressure difference, and the assessment of cardiac biomarkers may help to adequately define different types of cardiac dysfunction.9Wiese S. Hove J.D. Bendtsen F. Møller S. Cirrhotic cardiomyopathy: pathogenesis and clinical relevance.Nat Rev Gastroenterol Hepatol. 2014; 11: 177-186Crossref PubMed Scopus (157) Google Scholar, 10Møller S. Hove J.D. Assessment of systolic function in the evaluation of patients with cirrhosis.Hepatology. 2017; 65: 1799-1802Crossref PubMed Scopus (7) Google Scholar Some relatively hypodynamic patients may have an associated cardiac disease, some may have cirrhotic cardiomyopathy (likely a greater proportion) with systolic and/or diastolic dysfunction and some may even have transient cardiac dysfunction due to concurrent circumstances. Future studies should properly define cardiac dysfunction in patients with cirrhosis, its different potential causes and the prognostic implications derived. The authors received no financial support to produce this manuscript. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. Download .pdf (.13 MB) Help with pdf files Supplementary data