• Heart rate complexity
• Heart rate multiscale entropy
• Heart rate variability
• Liver transplantation
• Model for end-stage liver disease

• Adult
• Humans
• Heart Rate/physiology
• Liver Transplantation/adverse effects
• Entropy
• Living Donors
• Heart
• Autonomic Nervous System Diseases

• 99-2627-B-008-003 National Science and Technology Council

• Child-Pugh stage
• Corrected QT interval
• Liver cirrhosis
• Liver transplantation
• Meta-analysis
• Model for end-stage liver disease score

• cirrhotic cardiomyopathy diastolic dysfunction liver cirrhosis portal hypertension prolonged QTc

• genome-wide association studies
• genetic markers

• Arrhythmias, Cardiac/genetics
• Death, Sudden, Cardiac
• Electrocardiography/methods
• Genetic Testing
• Humans
• Male

• MR/N025083/1 Medical Research Council
• R01 HL128914 NHLBI NIH HHS
• R01 HL105756 NHLBI NIH HHS
• K24 HL148521 NHLBI NIH HHS
• U24 AG051129 NIA NIH HHS
• R01 DK124097 NIDDK NIH HHS
• MR/S019669/1 Medical Research Council
• R01 HL141989 NHLBI NIH HHS
• R01 HL139731 NHLBI NIH HHS
• U01 AG068221 NIA NIH HHS
• K24 HL105780 NHLBI NIH HHS
• K23 HL127704 NHLBI NIH HHS
• R01 HL092577 NHLBI NIH HHS
• R01 HL143070 NHLBI NIH HHS
• U01 HG007416 NHGRI NIH HHS
• MR/R017468/1 Medical Research Council
• Department of Health
• R01 HL142302 NHLBI NIH HHS
• R01 DK110113 NIDDK NIH HHS
• R01 HL138737 NHLBI NIH HHS
• MC_UU_00007/10 Medical Research Council
• R01 DK107786 NIDDK NIH HHS
• T32 HL139439 NHLBI NIH HHS
• MR/R010676/1 Medical Research Council
• 19SFRN34830063 American Heart Association-American Stroke Association
• R01 HL142825 NHLBI NIH HHS
• U54 GM115428 NIGMS NIH HHS
• T32 HL007604 NHLBI NIH HHS
• Individual author funding is supplied in the acknowledgements section. Study funding is supplied in detail, in Supplementary Note 6 - Study funding.

• Non-alcoholic fatty liver disease (NAFLD)
• cardiac risk assessment
• cirrhosis
• end-stage liver disease
• liver transplantation (LT)
• non-alcoholic steatohepatitis (NASH)
• transplant evaluation

• Biopsy/adverse effects
• Elasticity Imaging Techniques/adverse effects
• Elasticity Imaging Techniques/methods
• Heart Failure/complications
• Humans
• Liver/diagnostic imaging
• Liver/pathology
• Liver Cirrhosis/complications
• Non-alcoholic Fatty Liver Disease/complications
• Non-alcoholic Fatty Liver Disease/pathology

Here, we aimed to compare the effects of two anesthetic methods (desflurane inhalation anesthesia vs. propofol-based total intravenous anesthesia (TIVA)] on corrected QT interval (QTc) values during living donor liver transplantation. Altogether, 120 patients who underwent living donor liver transplantation were randomized to either the desflurane or TIVA group. The primary outcome was intraoperative QTc change. Other electrocardiogram, hemodynamic findings and postoperative outcomes were examined as secondary outcomes. QTc values were prolonged intraoperatively in both groups; however, the change was smaller in the TIVA group than in the desflurane group (P_{Group × Time} < 0.001). More patients had QTc values of > 500 ms in the desflurane group than in the TIVA group (63.3% vs. 28.3%, P < 0.001). In patients with preoperative QTc prolongation, QTc was further prolonged in the desflurane group, but not in the TIVA group (P_{Group × Time} < 0.001). Intraoperative norepinephrine and vasopressin use were higher in the desflurane group than in the TIVA group. Propofol-based TIVA may reduce QTc prolongation during living donor liver transplantation compared to that observed with desflurane inhalational anesthesia, particularly in patients with preoperative QTc prolongation. Additionally, patients managed with propofol-based TIVA required less vasopressor during the procedure as compared with those managed with desflurane inhalational anesthesia.

• cardiovascular disease
• cirrhosis
• clinical research/practice
• complication: medical/metabolic
• diagnostic techniques and imaging: echocardiography
• liver transplantation/hepatology
• translational research/science

It is widely known that liver cirrhosis, regardless of the etiologies is accompanied by severe hemodynamic changes. The principal pathophysiological mechanisms are the hyperdynamic circulation with increased cardiac output, heart rate along with reduced systemic vascular resistance. Thus, counteractive mechanisms may develop that eventually lead to systolic as well as diastolic dysfunction and rhythm disturbances, in order to keep a steady homeostasis in the human body.

Literally, blunted contractile responsiveness to physical or pharmacological stress, impaired diastolic relaxation and electrophysiological changes, primarily QT interval prolongation, do occur progressively in a cirrhotic patient with no known preexisting cardiac disease. This condition is identified as cirrhotic cardiomyopathy (CCM), an entity different from that seen in alcoholic cardiac muscle disease.

For the past decades, clinicians did study and attempt to understand the pathophysiology and clinical significance of this process. Indeed, various factors have been identified acting at the molecular and cellular level.

Electrocardiography, echocardiography and various serum biomarkers are the main tools that help healthcare practitioners to point to the correct diagnosis.

Noteworthy, the subjects that suffer from cirrhotic cardiomyopathy may progress to heart failure during invasive procedures such as surgery, insertion of a transjugular intrahepatic portosystemic shunting (TIPS) and liver transplantation. Besides, several studies have illustrated that CCM is a contributing factor, or even a precipitant, of hepatorenal syndrome (HRS), a conceivable reversible kidney failure in patients with liver cirrhosis and ascites.

The treatment is the same as it is in the patients with liver cirrhosis and heart failure and there is no particular treatment for cirrhotic cardiomyopathy. Hence, it is of utmost importance to clearly comprehend the pathophysiology of this disease in order to design more accurate diagnostic tools and definitive treatments in a way to prevent the complications of cirrhosis and overt heart failure.

The objective of this review is to describe in a comprehensive way the pathological alterations that occur in the cardiovascular system of cirrhotic patients. It will also point the limitations that remain in the diagnosis and treatment strategies and more importantly, this review will alert the clinicians in the modern era to further observe and record additional pathological changes in this subset of patients.

• Cirrhosis
• TIPS
• cirrhotic cardiomyopathy
• diastolic dysfunction
• heart failure
• homeostasis
• systolic dysfunction

• anesthesia/pain management
• cardiovascular disease
• cirrhosis
• clinical research/practice
• heart disease
• liver disease
• liver transplantation/hepatology
• liver transplantation: split

• Adrenergic beta-antagonists
• Dysautonomia
• Heart rate
• Liver cirrhosis

Impairment of cardiac function and arrhythmias often coexist in patients with liver diseases. Many studies have proved this coexistence and put forward various theories toward its pathophysiology. This narrative review tries to find the answers with supporting evidence on five main questions:

Clinical evidence was obtained by using search engines, namely, Cochrane Library, PubMed, and Google Scholar. Studies published in journals in the English language, between January 1969 and December 2019, which mentioned the relationship between cardiac arrhythmia and liver disease, were included. We used the keywords: jaundice, bilirubin, arrhythmia, ECG, QTc interval, QT dispersion, liver, and cirrhosis. Relevant animal or human studies answering the five main questions were extracted and reviewed.

The evidence included in our review sheds light on the fact that approximately 50% of liver cirrhosis cases develop cirrhotic cardiomyopathy (CC) and there has been an association between liver abnormalities and cardiac pathology. The present review also supports that there exists a strong association between high levels of serum bilirubin levels and cardiac arrhythmias, QTc value can be relied upon as a risk factor for predicting imminent arrhythmias, and that it is associated with mortality. Its basic pathophysiology can be explained by the potential action of bile acids in prolonging the QT interval. It also causes cardiac hypertrophy and apoptosis of cardiomyocytes leading to cardiac dysfunction.

Arya S, Kumar P, Tiwari B, Belwal S, Saxena S, Abbas H. What Every Intensivist should Know about Impairment of Cardiac Function and Arrhythmias in Liver Disease Patients: A Review. Indian J Crit Care Med 2020;24(12):1251–1255.

• Arrhythmia
• Bilirubin
• Bradycardia
• Cirrhosis
• Corrected QT interval
• Dysrhythmias
• ECG
• Jaundice
• Levels
• Liver
• QT dispersion
• QT interval
• Serum

The severity of fatty liver at ultrasound has been associated with QT length, a finding invoked to explain the excess cardiovascular risk of patients with fatty liver. However, the ability of ultrasound to stage accurately the severity of fatty liver is limited, with fibrosis a major confounder. Here, we aimed to verify the alleged relationship between fat liver content and QT length using a technique apt at discriminating steatosis from fibrosis noninvasively, i.e., transient elastography (TE) with measure of liver stiffness (LS) and controlled attenuation parameter (CAP). A prospectively collected derivation cohort of 349 patients with chronic liver disease (CLD) of any etiology (N = 105 with nonalcoholic fatty liver) was studied to identify clinical, laboratory, and instrumental predictors of the corrected QT interval (QTc) and QTc prolongation, including LS and CAP. The results were validated on a subgroup of patients belonging to the derivation cohort (out of sample validation), as well as on a completely different group of N = 149 subjects with CLD (out of time validation). QTc values were directly related to liver stiffness (LS; ρ = 0.137; p = 0.011), heart rate (HR; ρ = 0.307; p < 0.001), and age (ρ = 0.265; p < 0.001) and were significantly longer in females (p < 0.001). In contrast, QTc was not associated with the value of controlled attenuation parameter (ρ = 0.019; p = 0.718); moreover, no discernible differences in QTc length were noted based on CLD etiology. QTc was prolonged in 24/349 patients (6.9%); age, HR, and LS were independent predictors of QTc prolongation (χ² = 23.7, p < 0.001). Furthermore, QTc values (after logarithmic transformation) were predicted by a model including age, gender, HR, and LS (F = 14.1, R² = 0.198, p < 0.001). These latter results were validated by both out-of-sample and out-of-time methods. In conclusion, TE findings strongly suggest that among patients with CLD, fibrosis, not steatosis, is a major determinant of QTc length.

• Direct-acting antivirals
• FIB-4 score
• Hepatitis C virus
• QT prolongation

• Arrhythmias, Cardiac/physiopathology
• Biomarkers/metabolism
• Death, Sudden, Cardiac/etiology
• Electrocardiography/methods
• Female
• Humans
• Liver Cirrhosis/surgery
• Liver Transplantation/adverse effects
• Long QT Syndrome/metabolism
• Long QT Syndrome/physiopathology
• Male
• Middle Aged
• Multivariate Analysis
• Retrospective Studies
• Risk Factors

• cardiomyopathies
• electrocardiography
• end stage liver disease
• liver transplantation
• mortality

• Adult
• Electrocardiography
• End Stage Liver Disease/diagnosis
• End Stage Liver Disease/etiology
• End Stage Liver Disease/physiopathology
• End Stage Liver Disease/surgery
• Female
• Humans
• Liver Transplantation
• Long QT Syndrome/diagnosis
• Long QT Syndrome/physiopathology
• Male
• Middle Aged
• Prognosis
• Severity of Illness Index
• Treatment Outcome

• Cardiac autonomic neuropathy
• Child-Pugh score
• Cirrhotic cardiomyopathy
• Liver cirrhosis
• Model for end-stage liver disease score
• QT interval

• Cardiovascular disease
• Liver disease
• Review

• Cardiovascular Agents/therapeutic use
• Chemical and Drug Induced Liver Injury
• Heart/physiopathology
• Heart Failure/complications
• Heart Failure/therapy
• Humans
• Liver/physiopathology
• Liver Diseases/complications
• Liver Diseases/therapy

• Bile acids
• Cirrhotic cardiomyopathy
• Intrahepatic cholestasis of pregnancy
• Primary biliary cholangitis
• Primary sclerosing cholangitis
• Ursodeoxycholic acid

• cardiovascular disease
• clinical research/practice
• heart disease
• liver disease
• liver transplantation/hepatology
• risk assessment/risk stratification

• Cardiovascular Diseases/diagnosis
• Cardiovascular Diseases/etiology
• Consensus
• Humans
• Liver Transplantation/adverse effects
• Lung Diseases/diagnosis
• Lung Diseases/etiology
• Practice Guidelines as Topic/standards
• Risk Assessment/methods
• Vascular Resistance

• K23 HL136891 NHLBI NIH HHS
• KL2 TR001424 NCATS NIH HHS
• L30 HL129581 NHLBI NIH HHS

Prolongation of the corrected QT (QTc) interval is well known for many drugs, some of which are an integral part of the therapeutic regimen after lung transplantation (LTX). Therefore, we investigated the QTc interval after LTX in the present study.

The medical records of patients after LTX were studied for demographic data, indication of LTX, medication, and baseline and follow-up ECGs. The QT interval was corrected for the patient's heart rate using the different formulae of Bazett, Fridericia, Hodges, and Framingham.

Fifty-nine patients were included. The mean age ± SD was 55.6 ± 7.8 years (median 58 years). After LTX, QTc intervals showed no (relevant) changes during follow-up, even though all patients were treated with drugs (in combination) known to bear a risk of prolonged QTc interval and cortisone. The longest QTc intervals were obtained using Bazett's formula.

The QTc interval did not increase under immunosuppressive medication after LTX in our cohort of patients. We speculate that the concurrent use of cortisone may shorten the QT(c) intervals or cancel out drug-induced prolongation of the QTc interval.

Heart failure (HF) following liver transplant (LT) surgery is a distinct clinical entity with high mortality. It is known to occur in absence of obvious risk factors. No preoperative workup including electrocardiogram, echocardiography at rest and on stress, reasonably prognosticates the risk. In patients of chronic liver disease, cirrhotic cardiomyopathy, alcoholic cardiomyopathy, and stress induced cardiomyopathy have each been implicated as a cause for HF after LT. However distinguishing one etiology from another not only is difficult, several etiologies may possibly coexist in a given patient. Diagnostic dilemma is further compounded by the fact that presentation and management of HF irrespective of the possible underlying cause, remains the same. In this case series, 6 cases are presented and in the light of existing literature modification in the preoperative workup are suggested.

• Liver transplant
• Heart failure
• Cirrhotic cardiomyopathy
• Stress cardiomyopathy
• Alcohol cardiomyopathy

• MELD
• QT prolongation
• electrocardiogram
• liver transplantation
• prescription medications

• Circulation
• Cirrhosis
• Liver disease
• Vascular resistance

To determine the prevalence of QT prolongation in a large series of end stage liver disease (ESLD) patients and its association to clinical variables and mortality.

The QT interval was measured and corrected for heart rate for each patient, with a prolonged QT cutoff defined as QT > 450 ms for males and QT > 470 ms for females. Multiple clinical variables were evaluated including sex, age, serum sodium, international normalized ratio, creatinine, total bilirubin, beta-blocker use, Model for End-Stage Liver Disease (MELD), MELD-Na, and etiology of liver disease.

Among 406 ESLD patients analyzed, 207 (51.0%) had QT prolongation. The only clinical variable associated with QT prolongation was male gender (OR = 3.04, 95%CI: 2.01-4.60, P < 0.001). During the study period, 187 patients (46.1%) died. QT prolongation was a significant independent predictor of mortality (OR = 1.69, 95%CI: 1.03-2.77, P = 0.039). In addition, mortality was also associated with viral etiology of ESLD, elevated MELD score and its components (P < 0.05 for all). No significant reversibility in the QT interval was seen after liver transplantation.

QT prolongation was commonly encountered in an ESLD population, especially in males, and served as a strong independent marker for increased mortality in ESLD patients.

• Cirrhosis
• Electrophysiology
• Arrhythmias
• QT prolongation
• Mortality
• Liver transplantation

• autonomic dysfunction
• cirrhosis
• liver transplantation

• Adult
• Arrhythmias, Cardiac/complications
• Arrhythmias, Cardiac/diagnosis
• Arrhythmias, Cardiac/physiopathology
• Autonomic Nervous System Diseases/complications
• Autonomic Nervous System Diseases/diagnosis
• Autonomic Nervous System Diseases/physiopathology
• Female
• Humans
• Male
• Migraine Disorders/complications
• Migraine Disorders/diagnosis
• Migraine Disorders/physiopathology

• Alcoholic cardiomyopathy
• Alcoholic liver cirrhosis
• Alcoholic liver disease
• Cirrhotic cardiomyopathy
• Hemodynamics

• Cardiac function
• Cirrhosis
• Liver transplantation

• Diastole
• Echocardiography/methods
• Female
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/surgery
• Liver Transplantation
• Male
• Middle Aged
• Systole
• Ventricular Dysfunction, Left/diagnostic imaging
• Ventricular Dysfunction, Left/etiology
• Ventricular Dysfunction, Left/physiopathology
• Ventricular Function, Left
• Ventricular Function, Right