How non-alcoholic fatty liver disease and cirrhosis affect the heart

Møller, Søren; Wiese, Signe; Barløse, Mads; Hove, Jens D.

doi:10.1007/s12072-023-10590-1

Cited by 9 publications

(2 citation statements)

References 180 publications

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“…For example, MASLD has been linked to cardiac sympathetic/parasympathetic dysregulation [ 47 ], impaired heart rate variability [ 45 ], and also to QTc interval [ 48 – 50 ] and cardiac conduction abnormalities [ 48 , 51 ], and a higher risk of recurrent atrial fibrillation after ablation [ 52 ]. Furthermore, advanced liver disease at the stage of cirrhosis is known to considerably impair cardiac function via a hyperdynamic circulation and vasodilation, what has been termed “cirrhotic cardiomyopathy” [ 53 ]. In addition, MASLD represents a complex, multi-system disease, and it is still unclear whether MASLD represents a causal driver of cardiac arrhythmias, or whether it might simply reflect other, shared cardiometabolic risk factors.…”

Section: Discussionmentioning

confidence: 99%

Incident cardiac arrhythmias associated with metabolic dysfunction-associated steatotic liver disease: a nationwide histology cohort study

Simon,

Ebrahimi,

Roelstraete

et al. 2023

Cardiovasc Diabetol

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Background Prior studies suggest a link between metabolic dysfunction-associated steatotic liver disease (MASLD) and incident arrhythmias, including atrial fibrillation (AF). However, robust data are lacking from cohorts with liver histology, which remains the gold standard for staging MASLD severity. Methods This population-based cohort included all Swedish adults with histologically-confirmed MASLD and without prior cardiac arrhythmias (1966–2016; n = 11,206). MASLD was defined from prospectively-recorded histopathology, and characterized as simple steatosis, non-fibrotic steatohepatitis (MASH), non-cirrhotic fibrosis, or cirrhosis. MASLD patients were matched to ≤ 5 controls without MASLD or arrhythmias, by age, sex, calendar year and county (n = 51,856). Using Cox proportional hazards modeling, we calculated multivariable-adjusted hazard ratios (aHRs) for incident arrhythmias (including AF, bradyarrhythmias, other supraventricular arrhythmias, ventricular arrhythmias/cardiac arrest). Results Over a median follow-up of 10.8 years, incident arrhythmias were confirmed in 1351 MASLD patients (10.3/1000 person-years [PY]) and 6493 controls (8.7/1000PY; difference = 1.7/1000PY; aHR = 1.30, 95%CI 1.22–1.38), and MASLD patients had significantly higher rates of incident AF (difference = 0.9/1000PY; aHR = 1.26, 95%CI 1.18–1.35). Rates of both overall arrhythmias and AF were significantly elevated across all MASLD histological groups, particularly cirrhosis (differences, 8.5/1000PY and 5.3/1000PY, respectively). In secondary analyses, MASLD patients also had significantly higher rates of incident ventricular arrhythmias/cardiac arrest (aHR = 1.53, 95%CI 1.30–1.80), bradyarrhythmias (aHR = 1.26, 95%CI 1.06–1.48), and other supraventricular arrhythmias (aHR = 1.27, 95%CI 1.00–1.62), compared to controls. Conclusions Compared to matched controls, patients with biopsy-confirmed MASLD had modest but significantly higher incidence of cardiac arrhythmias, including AF, bradyarrhythmias, other supraventricular arrhythmias and ventricular arrhythmias/cardiac arrest. Excess risk was observed across all stages of MASLD and was highest with cirrhosis.

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Section: Discussionmentioning

confidence: 99%

Incident cardiac arrhythmias associated with metabolic dysfunction-associated steatotic liver disease: a nationwide histology cohort study

Simon,

Ebrahimi,

Roelstraete

et al. 2023

Cardiovasc Diabetol

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“…Recent studies have shown that CCM is associated with increased mortality and morbidity following major interventions such as liver transplantation and trans jugular intrahepatic portosystemic shunt (TIPS). Concurrently, CCM occurs in up to 50% of patients with cirrhosis ( 3 ). Therefore, the development of drugs to improve cardiovascular dysfunction related to the advanced liver disease is urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Protective role of the CD73-A2AR axis in cirrhotic cardiomyopathy through negative feedback regulation of the NF-κB pathway

Zhao,

Shao,

Xia

et al. 2024

Front. Immunol.

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BackgroundMyocardial inflammation and apoptosis induced by cirrhosis are among the primary mechanisms of cirrhotic cardiomyopathy. CD73, a common extracellular nucleotidase also known as 5’-nucleotidase, is associated with the progression of inflammation and immunity in multiple organs. However, the mechanism by which CD73 contributes to myocardial inflammation and apoptosis in cirrhosis remains unclear.MethodsIn this study, a cirrhotic cardiomyopathy model in mice was established by bile duct ligation. Myocardial-specific overexpression of CD73 was achieved by tail vein injection of AAV9 (adeno-associated virus)-cTNT-NT5E-mCherry, and cardiac function in mice was assessed using echocardiography. Myocardial inflammation infiltration and apoptosis were evaluated through pathological observation and ELISA assays. The expression of CD73, A2AR, apoptotic markers, and proteins related to the NF-κB pathway in myocardial tissue were measured.ResultsIn the myocardial tissue of the cirrhotic cardiomyopathy mouse model, the expression of CD73 and A2AR increased. Overexpression of CD73 in the myocardium via AAV9 injection and stimulation of A2AR with CGS 21680 inhibited myocardial inflammation and cardiomyocyte apoptosis induced by cirrhosis. Additionally, overexpression of CD73 suppressed the activation of the NF-κB pathway by upregulating the expression of the adenosine receptor A2A.ConclusionOur study reveals that the CD73/A2AR signaling axis mitigates myocardial inflammation and apoptosis induced by cirrhosis through negative feedback regulation of the NF-κB pathway.

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Evaluation of Aortic Hemodynamics Using Four‐Dimensional Flow of Magnetic Resonance Imaging in Rabbits with Liver Fibrosis

Li,

Lin

et al. 2024

Magnetic Resonance Imaging

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BackgroundLiver fibrosis (LF) precipitates systemic hemodynamic alterations, however, its impact on the aorta remaining undefined.PurposeTo assess aorta hemodynamics changes during LF development in a rabbit model.Study TypeProspective, experimental.Animal ModelThirty 7‐month‐old male rabbits underwent bile duct ligation (BDL) to induce LF.Field Strength/SequenceBiweekly four‐dimensional (4D) flow imaging incorporating a 3D gradient‐echo at 3.0 T scanner for 14 weeks post‐BDL.AssessmentHistopathological exams for 2–5 rabbits were performed at each time point, following each MRI scan. LF was graded using the Metavir scale by a pathologist. 4D flow was analyzed by two radiologists using dedicated postprocessing software. They recorded 4D flow parameters at four aorta sections (aortic sinus, before and after bifurcation of aortic arch, and descending aorta).Statistical TestsThe linear mixed model; Bonferroni correction; Pearson correlation coefficient (r); receiver operating characteristic (ROC) curve; Delong test. The level of significance was set at P < 0.05.ResultsFollowing BDL, the wall shear stress (WSS) (0.23–0.32 Pa), energy loss (EL) (0.27–1.55 mW) of aorta significantly increased at the second week for each plane, peaking at the sixth week (WSS: 0.35–0.49 Pa, EL: 0.57–2.0 mW). So did the relative pressure difference (RPD) (second week: 1.67 ± 1.63 mmHg, sixth week: 2.43 ± 0.63 mmHg) in plane 2. Notably, the RPD in plane 2 at the second week displayed the highest area under ROC curve of 0.998 (specificity: 1, sensitivity: 0.967). LF were found at the second, fourth, and sixth week after BDL, with grade F2, F3, and F4, respectively. The RPD in plane 2 was most strongly correlated with the severity of LF (r = 0.86).Data ConclusionsThe occurrence of LF could increase WSS, EL, and RPD of aorta as early as the second week following BDL.Level of Evidence1Technical EfficacyStage 2

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How non-alcoholic fatty liver disease and cirrhosis affect the heart

Cited by 9 publications

References 180 publications

Incident cardiac arrhythmias associated with metabolic dysfunction-associated steatotic liver disease: a nationwide histology cohort study

Incident cardiac arrhythmias associated with metabolic dysfunction-associated steatotic liver disease: a nationwide histology cohort study

Protective role of the CD73-A2AR axis in cirrhotic cardiomyopathy through negative feedback regulation of the NF-κB pathway

Evaluation of Aortic Hemodynamics Using Four‐Dimensional Flow of Magnetic Resonance Imaging in Rabbits with Liver Fibrosis

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