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The liver is a crucial metabolic organ that has a key role in maintaining immune and endocrine homeostasis. Accumulating evidence suggests that chronic liver disease might promote the development of various cardiac disorders (such as arrhythmias and cardiomyopathy) and circulatory complications (including systemic, splanchnic and pulmonary complications), which can eventually culminate in clinical conditions ranging from portal and pulmonary hypertension to pulmonary, cardiac and renal failure, ascites and encephalopathy. Liver diseases can affect cardiovascular function during the early stages of disease progression. The development of cardiovascular diseases in patients with chronic liver failure is associated with increased morbidity and mortality, and cardiovascular complications can in turn affect liver function and liver disease progression. Furthermore, numerous infectious, inflammatory, metabolic and genetic diseases, as well as alcohol abuse can also influence both hepatic and cardiovascular outcomes. In this Review, we highlight how chronic liver diseases and associated cardiovascular effects can influence different organ pathologies. Furthermore, we explore the potential roles of inflammation, oxidative stress, vasoactive mediator imbalance, dysregulated endocannabinoid and autonomic nervous systems and endothelial dysfunction in mediating the complex interplay between the liver and the systemic vasculature that results in the development of the extrahepatic complications of chronic liver disease. The roles of ageing, sex, the gut microbiome and organ transplantation in this complex interplay are also discussed.

Interplay of cardiovascular mediators, oxidative stress and inflammation in liver disease and its complications.

Patients with liver cirrhosis have autonomic dysfunction and complex cardiovascular changes. Increases risk for sudden cardiac death (SCD) was recently recognized in liver cirrhosis. This study analyzed risk predictors for SCD related to autonomic dysfunction in patients with alcoholic liver cirrhosis (ALC). Twenty five patients with ALC were examined and compared with healthy control group. Cardiovascular autonomic reflex tests, comprehensive ECG with QTc interval, late potentials, short-term heart rate variability (HRV) analysis (time domain, spectral and nonlinear-Poincare plot analysis) and 24-h Holter ECG with long-term HRV analysis were done. According to autonomic reflex tests patients with ALC had high incidence (56%) of severe autonomic dysfunction, manifested as pronounced damage of vagal function. Patients had significantly depressed HRV (SDNN, SDANN, triangular index, LF and HF) and more frequently had serious arrhythmias, prolonged QTc and Poincare plot in a shape of dot (p < 0.001). In patient group QTc significantly inversely correlated with spectral components from short-term HRV analysis (ln(LF): r = -0.53, ln(HF): r = -0.47; p < 0.05), and Lown class significantly correlated with total autonomic function score (r = 0.64, p = 0.04). This study indicates that in ALC autonomic neuropathy with vagal impairment and sympathetic predominance is related to SCD risk predictors and onset of serious ventricular arrhythmias.

/pdf/autonomic-dysfunction-in-alcoholic-cirrhosis-and-its-3bld7k4li8.pdf

Autonomic dysfunction in alcoholic cirrhosis and its relation to sudden cardiac death risk predictors.

Long-term, excessive consumption of alcoholic beverages produces a peripheral neuropathy with symptoms of decreased superficial sensation, hyperalgesia, and weakness. Alcoholic neuropathy is characterized by axonal degeneration with reduced density of both small and large fibers and axonal sprouting. Electrophysiologic studies reveal a marked reduction in the amplitude of sensory potentials and moderate slowing of nerve conduction, mainly in the lower extremities. Dietary deficiency of vitamins, which are often associated with chronic alcoholism, can contribute to the pathogenesis. Recent studies using animal models have identified several mechanisms by which ethanol impacts peripheral nerve function. Ethanol can exert direct neurotoxic effects on peripheral nerves via its metabolite acetaldehyde and by enhancing oxidative stress. Ethanol activation of protein kinase Ce signaling in primary afferent nociceptors plays an important role in lowering nociceptive threshold. Further, ethanol causes cytoskeletal dysfunction and inhibits both anterograde and retrograde axonal transport. Alcoholic neuropathy is potentially reversible and treatments include abstinence from alcoholic beverages and consumption of a nutritionally balanced diet supplemented with B vitamins. However, response to these treatment strategies can be variable, which underscores the need for novel therapeutic strategies. In this review, we provide an overview of the clinical findings and insights on molecular mechanisms from animal models.

Peripheral systems: neuropathy.

Reduced heart rate variability and baroreflex sensitivity in primary biliary cirrhosis

Introduction: There are different proofs about association of autonomic nervous system dysfunction, especially nonlinear parameters, with higher mortality after myocardial infarction. Objective The objective of the study was to determine predictive value of Poincare plot as nonlinear parameter and other significant standard risk predictors: ejection fraction of the left ventricle, late potentials, ventricular arrhythmias, and QT interval. Method The study included 1081 patients with mean follow up of 28 months (ranging fom 0-80 months). End-point of the study was cardiovascular mortality. The following diagnostic methods were used during the second week: ECG with commercial software Schiller AT-10: short time spectral analysis of RR variability with analysis of Poincare plot as nonlinear parameter and late potentials; 24-hour ambulatory ECG monitoring: QT interval, RR interval, QT/RR slope, ventricular arrhythmias (Lown >II); echocardiography examinations: systolic disorder (defined as EF 350 ms, positive late potentials, systolic dysfunction, Poincare plot as a point, ventricular arrhythmias (Lown > II). In multivariate analysis, the significant risk predictors were: Poincare plot as a point and mean RR interval lower than 800 ms. Conclusion Mean RR interval lower than 800 ms and nonlinear and space presentation of RR interval as a point Poincare plot were multivariate risk predictors.

/pdf/prognostic-value-of-poincare-plot-as-nonlinear-parameter-of-3i9ttvnbwc.pdf

Prognostic value of Poincare plot as nonlinear parameter of chaos theory in patients with myocardial infarction

Introduction: It has been shown that depolarization disorders, autonomic dysfunction, and systolic dysfunction of the left ventricle are associated with sudden cardiac death after myocardial infarction. Objective: The Objective of study was to examine the prognostic value of the most important predictors in the first week after myocardial infarction. Method: Study included 881 patients who were followed up from 1 to 60 months. During the first week after myocardial infarction, following examination were performed: ECG with standard leads and X, Y, Z orthogonal leads, vectorcardiogram, QT interval, late potentials, short-time spectral analysis of RR variability, nonlinear (Poincare plot) analysis and echocardiogram. Results: In univariate analysis, the following parameters measured on the first day were important predictors of sudden cardiac death: lower LF/HF ratio(<1.5) (p=0.000), T wave inversion in X lead (p=0.000), high P wave in D2 lead (p=0.030), and diminished systolic function (p=0.000). In multivariate analysis, the following parameters were significant risk predictors: T wave inversion in X lead, lower LF/HF ratio, positive late potentials and the left ventricle systolic dysfunction. Conclusion: The parameters of the left ventricle systolic dysfunction with sympathicovagal imbalance and electric instability are the key risk predictors in the first few days after myocardial infarction.

/pdf/early-risk-predictors-of-sudden-cardiac-death-after-48v247ffom.pdf

[Early risk predictors of sudden cardiac death after myocardial infarction: results of follow up of 881 patients].

Background The implantable loop recorder (ILR) is a small cardiac rhythm-monitoring device. Our aim was to determine ILR diagnostic value in patients with unexplained syncope, presyncope, or palpitations suggesting cardiac arrhythmias. Methods This has been a retrospective, observational, single-center study. We included 181 patients in whom ILR was implanted at the Clinical Center of Serbia between January 2006 and July 2019. An event was marked as diagnostic if it led to a diagnosis and ILR was considered diagnostic if it verified or excluded an arrhythmia as the cause of syncope or palpitations. Results The mean age was 51.8 ± 17.8 years and 94 (51.9%) were male. The mean follow-up period was 20.2 ± 15.8 months. ILR was diagnostic in 98 patients (54.1%). There was no significant difference in diagnostic value of ILR in regard to the baseline patients' characteristics. The mean time to occurrence of the diagnostic event was 11.1 ± 9.6 months. The time to occurrence of a diagnostic event did not differ significantly between patients who underwent basic as compared to extended diagnostics before ILR implantation. Conclusions ILR was able to achieve an etiological diagnosis in 54.1% of patients with unexplained syncope, presyncope, or palpitations suggesting cardiac arrhythmias. In a subgroup of patients with recurrent palpitations, ILR was significantly less diagnostic than in patients with syncope or presyncope. ILR should be implanted beforehand in syncope evaluation process.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/anec.12864

Diagnostic value of implantable loop recorders in patients with unexplained syncope or palpitations.


 
 
 Type of funding sources: None.
 
 
 
 Implantable cardiverter defibrillators (ICD) represent the only effective treatment in prevention of sudden cardiac death (SCD) in patients with Brugada syndrome (BrS). However, according to current ESC Guidelines, ICD implantation is recommended only in secondary prevention, while it should be considered in patients with a spontaneous diagnostic type I ECG pattern and history of syncope.
 
 
 
 We aimed to determine the frequency of ventricular tachyarrhythmias during the long-term follow-up among patients with BrS and ICDs implanted in primary or secondary prevention.
 
 
 
 This retrospective, observational study was conducted in a tertiary center among adult patients with BrS that underwent single or dual chamber ICD implantation from January 2008 to December 2017. The study group was devided into subgroups depending on weather the patients at the time of ICD implantation had documented sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) regardless of the ECG type of BrS (group I), had BrS type I and history of syncope (group II) or had BrS type I and were asymptomatic but assessed as in high risk of SCD due to non-sustained VT episodes, younger age or history of SCD in close family members (group III). We used patients medical records for collecting the data about VT and VF episodes during the follow-up period.
 
 
 
 In the course of ten-year period, ICDs were implanted in 21 adult patients with BrS (66.7% were male). Mean age at the ICD implantation time was 40.3 ± 14.9 years. We analyzed 8 patients from group I, 7 patients from group II, and 6 patients from group III. Mean follow-up period was 82.5 ± 33.3 months. During the obsereved period, VT/VF episodes were appropriately detected in 7 patients from group I (87.5%), in 3 patients from group II (42.86%) and in one patient from group III (16.67%). Kruskal-Wallis test showed that there was a statistically significant difference in the occurrence of ventricular tachyarrhythmias among at least one pair of observed groups (p = 0.031). Using Dunn-Bonferroni post hoc analysis we found statistically significant difference between the patients with malignant arrhythmias and asymptomatic patients (p = 0.03), but not between the other pairs.
 
 
 
 Although asymptomatic patients with BrS are at significantly lower risk of SCD, it is important to identify high-risk patients in the low-risk group. Therefore, creating a tool for calculating the risk of SCD among these patients might be helpfull in everyday clinical practice.


Vesna Bisenic

Papers

Autonomic dysfunction in alcoholic cirrhosis and its relation to sudden cardiac death risk predictors.

Prognostic value of Poincare plot as nonlinear parameter of chaos theory in patients with myocardial infarction

[Early risk predictors of sudden cardiac death after myocardial infarction: results of follow up of 881 patients].

Diagnostic value of implantable loop recorders in patients with unexplained syncope or palpitations.

Should we implant cardioverter defibrillators in asymptomatic patients with Brugada syndrome?