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Heart failure (HF) and liver disease often co-exist. This is because systemic disorders and diseases affect both organs (alcohol abuse, drugs, inflammation, autoimmunity, infections) and because of complex cardiohepatic interactions. The latter, which are the focus of this review, include the development of acute cardiogenic liver injury and conges...
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Context 1
... liver receives blood from the portal vein and hepatic artery (Figure 1) (5,6). Receiving blood from 2 vessels protects the liver: If 1 source fails, the liver continues to function as it is supplied by the other. ...
Context 2
... microbiota affect the heart-liver axis through a number of mechanisms including lipid and glucose metabolism, cholesterol, bile acids, and inflammation 4. Recent consensus recommendations (71) 5. Recent randomized study with b-blockers in cirrhotic cardiomyopathy and a brief discussion about the advantages and disadvantages of b-blocker use in cirrhotic cardiomyopathy (60) 6. The current review is accompanied by 5 figures and Online Figure 1, which depict important pathophysiological mechanisms and proposed management algorithms. Xanthopoulos et al. ...
Context 3
... liver receives blood from the portal vein and hepatic artery (Figure 1) (5,6). Receiving blood from 2 vessels protects the liver: If 1 source fails, the liver continues to function as it is supplied by the other. ...
Context 4
... microbiota affect the heart-liver axis through a number of mechanisms including lipid and glucose metabolism, cholesterol, bile acids, and inflammation 4. Recent consensus recommendations (71) 5. Recent randomized study with b-blockers in cirrhotic cardiomyopathy and a brief discussion about the advantages and disadvantages of b-blocker use in cirrhotic cardiomyopathy (60) 6. The current review is accompanied by 5 figures and Online Figure 1, which depict important pathophysiological mechanisms and proposed management algorithms. Xanthopoulos et al. ...
Citations
... The increased likelihood of cardiovascular disease is due to the increased life expectancy of oncology-treated patients as a result of the increasing efficacy of current therapies [39]. Cardiac abnormalities that occur many years after radiation therapy, such as arrhythmias, ischemia, inflammatory changes in the myocardium or pericardium, and sometimes acute heart failure, also adversely affect liver function [37,[40][41][42]. ...
The study aimed to investigate late radiation-induced changes in the histology, ultrastructure, and activity of lysosomal enzymes in mouse liver exposed to ionizing radiation. The experiment was conducted on C57BL/6J male mice whose distal part of the liver was exposed occasionally to single doses of radiation (6 MV photons) during targeted heart irradiation; estimated doses delivered to analyzed tissue were 0.025 Gy, 0.25 Gy, 1 Gy, and 2 Gy. Tissues were collected 40 weeks after irradiation. We have observed that late effects of radiation have an adaptive nature and their intensity was dose-dependent. Morphological changes in hepatocytes included an increased number of primary lysosomes and autophagic vacuoles, which were visible in tissues irradiated with 0.25 Gy and higher doses. On the other hand, a significant increase in the activity of lysosomal hydrolases was observed only in tissues exposed to 2 Gy. The etiology of these changes may be multifactorial and result, among others, from unintentional irradiation of the distal part of the liver and/or functional interaction of the liver with an irradiated heart. In conclusion, we confirmed the presence of late dose-dependent ultrastructural and biochemical changes in mouse hepatocytes after liver irradiation in vivo.
... In fact, HF and liver diseases commonly occur together [8]. Hepatic damages secondary to heart failure may be seen both as "congestive hepatopathy", due to elevated right-sided filling pressures [9], and ischaemia due to left ventricular failure (ischaemia-reperfusion injury) [10]. ...
... HF causes increased right-sided filling pressure, leading to LS increase and contributing to worsening liver function; on the other hand, HF is associated not only to hepatic congestion (right-sided HF), but also to reduced arterial flow to the liver, configuring "hypoxic hepatopathy" (left-sided HF) [29]. Conclusively, HF "per se" may lead to irreversible liver disease, and high LS values can result from congestion and liver disease (provided that concurrent etiologies of liver diseases are excluded) [8]. ...
Purpose
Heart failure (HF) is a major health problem affecting millions of people worldwide. In the latest years, many efforts have been made to identify predictors of poor prognosis in these patients. The aim of this systematic review and meta-analysis was to enlighten the correlation between liver stiffness (LS), assessed by Shear Wave Elastography techniques, and HF, particularly focusing on the prognostic value of LS on cardiovascular outcomes.
Methods
We searched the PUBMED databases (up to May 1st, 2023) for studies that enlightened the correlation between LS and cardiovascular outcomes in patients hospitalized for acute decompensated heart failure (ADHF). We performed a meta-analysis to estimate the efficacy of LS in predicting the prognosis of patients with ADHF.
Results
We analyzed data from 7 studies, comprising 677 patients, that assessed the prognostic value of LS in predicting cardiovascular outcomes in patients hospitalized for ADHF. The pooled analysis showed that increased liver stiffness was associated with higher risk of adverse cardiac events (hazard ratio 1.07 [1.03, 1.12], 95% CI).
Conclusion
Increased LS is associated with poor prognosis in patients hospitalized for HF and might help effectively identify those patients at high risk for worse outcomes.
... Regarding the prognostic impact of each individual "I Need Help" criterion, previous or ongoing need of inotropes, NYHA classes III and IV and persistently high natriuretic peptides, end-organ renal or liver dysfunction in the setting of HF, >1 HF hospitalization in the last year, persisting fluid overload and increasing diuretic requirement, and consistently low blood pressure were the 3 criteria independently associated with a higher risk of all-cause mortality or HF hospitalization. The prognostic role of these criteria underlines the profound relationship between cardiac-related hemodynamic parameters, persisting or worsening congestion, and noncardiac end-organ function in patients with advanced HF. Blood pressure is strongly related to stroke volume, peripheral hypoperfusion, and use of inotropes and represents a powerful prognostic marker in patients with HF. 11,12 Furthermore, hypoperfusion and the related need of intravenous inotropes are frequently accompanied by markers of end-organ injury that further worsen prognosis in the setting of HF. [13][14][15] In addition to these factors, NYHA classes III and IV and recurrent HF hospitalizations are relevant and well-known prognostic markers in HF, 1,14,16,17 and persisting edema or increasing diuretic requirement underlines the pivotal role of congestion in patients with worsening HF and advanced HF. 2,18,19 Data are presented as HR and 95% CI. eGFR indicates estimated glomerular filtration rate; HF, heart failure; HFA-ESC, Heart Failure Association of the European Society of Cardiology; HR, hazard ratio; and NYHA, New York Heart Association. ...
BACKGROUND
The “I Need Help” markers have been proposed to identify patients with advanced heart failure (HF). We evaluated the prognostic impact of these markers on clinical outcomes in a real-world, contemporary, multicenter HF population.
METHODS
We included consecutive patients with HF and at least 1 high-risk “I Need Help” marker from 4 centers. The impact of the cumulative number of “I Need Help” criteria and that of each individual “I Need Help” criterion was evaluated. The primary end point was the composite of all-cause mortality or first HF hospitalization.
RESULTS
Among 1149 patients enrolled, the majority had 2 (30.9%) or 3 (22.6%) “I Need Help” criteria. A higher cumulative number of “I Need Help” criteria was independently associated with a higher risk of the primary end point (adjusted hazard ratio for each criterion increase, 1.19 [95% CI, 1.11–1.27]; P <0.001), and patients with >5 criteria had the worst prognosis. Need of inotropes, persistently high New York Heart Association classes III and IV or natriuretic peptides, end-organ dysfunction, >1 HF hospitalization in the last year, persisting fluid overload or escalating diuretics, and low blood pressure were the individual criteria independently associated with a higher risk of the primary end point.
CONCLUSIONS
In our HF population, a higher number of “I Need Help” criteria was associated with a worse prognosis. The individual criteria with an independent impact on mortality or HF hospitalization were need of inotropes, New York Heart Association class or natriuretic peptides, end-organ dysfunction, multiple HF hospitalizations, persisting edema or escalating diuretics, and low blood pressure.
... The overall study population consisted mainly of overweight or obese (54.9% with BMI > 25) patients with a mean age of 63 ± 17 years and an ICU LOS of 19 days. Patients received 8 [5][6][7][8][9][10][11][12][13][14] days of PN, and in 12%, indirect calorimetry was performed with a median REE of 1834 kcal, corresponding to 25 [20][21][22][23][24][25][26][27][28][29] kcal/kg/day (mean weight patients with IC 73 kg). The overall study population consisted mainly of overweight or obese (54.9% with BMI > 25) patients with a mean age of 63 ± 17 years and an ICU LOS of 19 days. ...
... The overall study population consisted mainly of overweight or obese (54.9% with BMI > 25) patients with a mean age of 63 ± 17 years and an ICU LOS of 19 days. Patients received 8 [5][6][7][8][9][10][11][12][13][14] days of PN, and in 12%, indirect calorimetry was performed with a median REE of 1834 kcal, corresponding to 25 [20][21][22][23][24][25][26][27][28][29] kcal/kg/day (mean weight patients with IC 73 kg). ...
... A review from 2019 concluded that 20 to 30% of all patients show liver dysfunction due to acute heart failure (AHF). Patients often show few symptoms, but in laboratory tests, elevations up to 20× the ULN of aminotransferases can be observed [24]. Other studies [25][26][27] observed a predominant elevation in cholestatic enzymes or even a mixed pattern. ...
Background:
Parenteral nutrition (PN) is often associated with liver dysfunction in the ICU, although other factors such as sepsis, acute heart failure (AHF), and hepatotoxic drugs can be equally present. The relative impact of PN on liver dysfunction in critically ill patients is largely unknown.
Methods:
We recorded the presence of pre-existing liver disturbances, AHF, sepsis, daily PN volume, and commonly used hepatotoxic drugs in adult ICU patients, together with daily aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), alkalic phosphatase (AP), total bilirubin (TB), and INR values in patients with three or more PN treatment days. A linear mixed-effects model was used to assess the relative contribution of each liver parameter. Nutritional adequacy was defined as intake/needs.
Results:
We included 224 ICU patients with PN treatment lasting more than 3 days between 1 January 2017 and 31 December 2019. For AST, pre-existing liver disturbances (+180% ± 11%) and the presence of AHF (+75% ± 14%) were the main predictors of deterioration, whereas PN volume caused only a limited increase of 14% ± 1%/L. Similar results were observed for ALT. GGT, INR, and TB are mainly influenced by the presence of sepsis/septic shock and pre-existing liver disturbances, with no impact of PN or hepatotoxic drugs. Carbohydrate intake exceeded recommendations, and protein and lipid intake were insufficient in this study cohort.
Conclusions:
Liver test disturbances in ICU patients on PN are multifactorial, with sepsis and AHF having the highest influence, with only limited impact from PN and hepatotoxic drugs. Feeding adequacy can be improved.
... There is a vicious cycle between aortic stenosis (AS) and hepatorenal dysfunction. [1][2][3] Transcatheter aortic valve implantation (TAVI) is currently the guideline-recommended therapy for patients with severe AS, 4,5 and it has the potential to break this vicious cycle by relieving aortic valve obstruction. Prior studies showed that TAVI can bring about improvements in renal function 6 but may also be complicated by kidney injury which is a risk factor for prognosis. ...
Background:
Renal and liver dysfunctions are risk factors for mortality in patients with severe aortic stenosis (AS). Transcatheter aortic valve implantation (TAVI) has the potential to break the vicious cycle between AS and hepatorenal dysfunction by relieving aortic valve obstruction.
Hypothesis:
A part of patients can derive hepatorenal function improvement from TAVI, and this noncardiac benefit improves the intermediate-term outcomes.
Methods:
We developed this retrospective cohort study in 439 consecutive patients undergoing TAVI and described the dynamic hepatorenal function assessed by model for end-stage liver disease model for end-stage liver disease (MELD)-XI score in subgroups. The endpoint was 2-year all-cause mortality.
Results:
Receiver-operating characteristic analysis showed that the baseline MELD-XI score of 10.71 was the cutoff point. A high MELD-XI score (>10.71) at baseline was an independent predictor of the 2-year mortality hazard ratio (HR: 2.65 [1.29-5.47], p = .008). After TAVI, patients with irreversible high MELD-XI scores had a higher risk of 2-year mortality than patients who improved from high to low MELD-XI scores (HR: 2.50 [1.06-5.91], p = .03). Factors associated with reversible MELD-XI scores improvement were low baseline MELD-XI scores (≤12.00, odds ratio [OR]: 2.02 [1.04-3.94], p = .04), high aortic valve peak velocity (≥5 m/s, OR: 2.17 [1.11-4.24], p = .02), and low body mass index (≤25 kg/m2 , OR: 2.73 [1.25-5.98], p = .01).
Conclusion:
High MELD-XI score at baseline is an independent predictor for 2-year mortality. Patients with hepatorenal function improvement after TAVI have better outcomes. For patients with irreversible hepatorenal dysfunction after TAVI, further optimization of the subsequent treatment after TAVI is needed to improve the outcomes.
... Additionally, there is minimal data on liver disease in all of these studies (Table 1). This is particularly important given that HF and liver disease often co-exist due to cardio-hepatic interactions [110]. As such, a higher prevalence of liver disease among HF groups could lead to false positive findings. ...
Fibroblast growth factor 21 (FGF21) is a peptide hormone involved in energy homeostasis that protects against the development of obesity and diabetes in animal models. Its level is elevated in atherosclerotic cardiovascular diseases (CVD) in humans. However, little is known about the role of FGF21 in heart failure (HF). HF is a major global health problem with a prevalence that is predicted to rise, especially in ageing populations. Despite improved therapies, mortality due to HF remains high, and given its insidious onset, prediction of its development is challenging for physicians. The emergence of cardiac biomarkers to improve prediction, diagnosis, and prognosis of HF has received much attention over the past decade. Recent studies have suggested FGF21 is a promising biomarker candidate for HF. Preclinical research has shown that FGF21 is involved in the pathophysiology of HF through the prevention of oxidative stress, cardiac hypertrophy, and inflammation in cardiomyocytes. However, in the available clinical literature, FGF21 levels appear to be paradoxically raised in HF, potentially implying a FGF21 resistant state as occurs in obesity. Several potential confounding variables complicate the verdict on whether FGF21 is of clinical value as a biomarker. Further research is thus needed to evaluate whether FGF21 has a causal role in HF, and whether circulating FGF21 can be used as a biomarker to improve the prediction, diagnosis, and prognosis of HF. This review draws from preclinical and clinical studies to explore the role of FGF21 in HF.
... Over time, perisinusoidal and perivenular fibrosis progresses, forming bridging fibrosis between hepatic veins, which is considered to be a particular characteristic of end-stage CH (Wells et al. 2016). Recent epidemiological data have shown that the incidence of CH varies from 15% to 65% in patients with severe heart failure (Xanthopoulos et al. 2019). Moreover, CH is more frequent in male patients, and a positive correlation between patient's age and CH occurrence has been noted (Giallourakis et al. 2002), suggesting that older male patients are most likely to develop CH (Giallourakis et al. 2002). ...
Congestive hepatopathy (CH) is a chronic liver disease (CLD) caused by impaired hepatic venous blood outflow, most frequently resulting from congestive heart failure. Although it is known that heart failure and CLDs contribute to increased risk for age-related fractures, an assessment of CH-induced skeletal alterations has not been made to date. The aim of our study was to characterize changes in bone quality in adult male cadavers with pathohistologically confirmed CH compared with controls without liver disease. The anterior mid-transverse part of the fifth lumbar vertebral body was collected from 33 adult male cadavers (age range 43–89 years), divided into the CH group (n = 15) and the control group (n = 18). We evaluated trabecular and cortical micro-architecture and bone mineral content (using micro-computed tomography), bone mechanical competence (using Vickers micro-hardness tester), vertebral cellular indices (osteocyte lacunar network and bone marrow adiposity), and osteocytic sclerostin and connexin 43 expression levels (using immunohistochemistry staining and analysis). Deterioration in trabecular micro-architecture, reduced trabecular and cortical mineral content, and decreased Vickers microhardness were noted in the CH group (p < 0.05). Reduced total number of osteocytes and declined connexin 43 expression levels (p < 0.05) implied that harmed mechanotransduction throughout the osteocyte network might be present in CH. Moreover, elevated expression levels of sclerostin by osteocytes could indicate the role of sclerostin in mediating low bone formation in individuals with CH. Taken together, these micro-scale bone alterations suggest that vertebral strength could be compromised in men with CH, implying that vertebral fracture risk assessment and subsequent therapy may need to be considered in these patients. However, further research is required to confirm the clinical relevance of our findings.
... The occurrence of liver dysfunction was not rare in patients with heart failure and probably even more common in heart transplant candidates. Ischemic liver hypoperfusion and hepatic congestion were the two major pathogenic mechanisms in cardiogenic shock and congestive heart failure (21). Heart failure complicating with liver dysfunction adversely affected prognosis. ...
End stage renal disease (ESRD) is a contraindication to isolated heart transplantation (HT). However, heart candidates with cardiogenic shock may experience acute kidney injury and require renal replacement therapy (RRT) and isolated HT as a life-saving operation. The outcomes, including survival and renal function, are rarely reported. We enrolled 569 patients undergoing isolated HT from 1989 to 2018. Among them, 66 patients required RRT before HT (34 transient and 32 persistent). The survival was worse in patients with RRT than those without (65.2% vs 84.7%; 27.3% vs 51.1% at 1- and 10-year, p < 0.001 and p = 0.012, respectively). Multivariate Cox analysis identified pre-transplant hyperbilirubinemia (Hazard ratio (HR) 2.534, 95% confidence interval (CI) 1.098-5.853, p = 0.029), post-transplant RRT (HR 5.551, 95%CI 1.280-24.068, p = 0.022) and post-transplant early bloodstream infection (HR 3.014, 95%CI 1.270-7.152, p = 0.012) as independent risk factors of 1-year mortality. The majority of operative survivors (98%) displayed renal recovery after HT. Although patients with persistent or transient RRT before HT had a similar long-term survival, patients with persistent RRT developed a high incidence (49.2%) of dialysis-dependent ESRD at 10 years. In transplant candidates with pretransplant RRT, hyperbilirubinemia should be carefully re-evaluated for the eligibility of HT whereas prevention and management of bloodstream infection after HT improve survival.
... Multi-organ dysfunction, including hepatic and renal dysfunction, affects the prognosis and complicates the management of heart failure [13][14][15] . Cardiac dysfunction can lead to the renal or hepatic dysfunction and vice versa, the so-called cardiorenal and cardiohepatic syndromes. ...
... damage has not yet been identified. Since both renal and hepatic dysfunction are strong predictors of adverse clinical outcomes in patients with HF 13,15 , the combination of both can increase their ability for risk stratification. The MELD-XI score is one of the most established scoring systems for hepatorenal dysfunction, which is an alternative to the MELD scoring system that excludes the international normalized ratio from the calculation. ...
Hepatorenal dysfunction is a strong risk factor in patients with heart failure (HF). We investigated the prognostic significance of hepatorenal dysfunction in 172 consecutive patients undergoing transcatheter tricuspid valve repair (TTVR). The model for end-stage liver disease excluding international normalized ratio (MELD-XI) score was calculated as 5.11 × ln(serum total bilirubin [mg/dl]) + 11.76 × ln(serum creatinine [mg/dl]) + 9.44. Patients were stratified into two groups: high (≥ 14) or low (< 14) MELD-XI score, according to the best cut-off value to predict a one-year composite outcome consisting of all-cause mortality and HF hospitalization. Compared to patients with low MELD-XI score (n = 121), patients with high MELD-XI score (n = 51) had a higher incidence of the composite outcome (47.1% vs. 17.4%; p < 0.0001). In the multivariable analysis, the MELD-XI score was an independent predictor of the composite outcome (adjusted hazard ratio: 1.12; 95% confidence interval [CI] 1.05–1.19; p = 0.0003). In addition, post-procedural TR < 3 + after TTVR was independently associated with a reduction in MELD-XI score six months after TTVR (adjusted odds ratio: 3.37; 95% CI 1.09–10.40; p = 0.03). Thus, the MELD-XI score was associated with the risk of one-year composite outcome, consisting of mortality and HF hospitalization, after TTVR and may help the risk stratification in patients undergoing TTVR.
... Nevertheless, when interpreted in the context of the pre-existing literature on pathophysiological implications of chronic right heart failure, several potential explanations may account for the concept of different CO state phenotypes proposed in the present study. First, patients in a high CO state are characterized by more pronounced markers of congestive hepatopathy, such as a cholestatic laboratory profile[19][20][21] , and this cardio-hepatic interaction may contribute to alterations in the CO state. According to findings obtained on histopathological analysis, chronic venous congestion in right heart failure leads to sinusoidal dilatation, centrilobular and sinusoidal fibrosis, and hepatocyte atrophy. ...
Aims:
To investigate whether there is evidence for distinct cardiac output (CO) based phenotypes in patients with chronic right heart failure associated with severe tricuspid regurgitation (TR) and to characterize their impact on TR treatment and outcome.
Methods and results:
A total of 132 patients underwent isolated transcatheter tricuspid valve repair (TTVR) for functional TR at two centers. Patients were clustered according to k-means clustering into low (C-1: CI<1.7 l/min/m2 ), intermediate (C-2: CI=1.7-2.6 l/min/m2 ) and high CO (C-3: CI>2.6 l/min/m2 ) clusters. All-cause mortality and clinical characteristics during follow-up were compared among different CO-clusters. Mortality rates were highest for patients in a low - (24%) and high CO state (42%, log-rank p<0.001). High CO patients were characterized by larger vena cava inferior diameters (p=0.003), reduced liver function, higher incidence of ascites (p=0.006) and markedly reduced systemic vascular resistance (p<0.001) as compared to TTVR patients in other CO states. Despite comparable procedural success rates, the extent of changes in right atrial pressures (p=0.01) and right ventricular dimensions (p<0.001) per decrease in regurgitant volume following TTVR was less pronounced in high CO patients as compared to other CO states. Successful TTVR was associated with the smallest prognostic benefit among low- and high CO patients.
Conclusions:
Patients with chronic right heart failure and severe TR display distinct CO states. The high CO state is characterized by advanced congestive hepatopathy, a substantial decrease in peripheral vascular tone, a lack of response of central venous pressures to TR reduction, and worse prognosis. These data are relevant to the pathophysiological understanding and management of this important clinical syndrome.
