European Journal of Cardiovascular Medicine

In the mid-20th century, doctors observed circulatory anomalies in patients suffering from liver cirrhosis, which established the foundation for understanding the interaction between hepatic and cardiac processes. More research was done on the autonomic nervous system's role in cirrhosis in the 1980s and 1990s. This led to the idea of cirrhotic cardiomyopathy, which is heart failure in cirrhotic patients who have never had heart disease before. It is defined by a heart that doesn't contract as well when stressed and has electrophysiological problems. The liver and heart are intimately related organs, with each having a unique temperament defined by four characteristics: "warmth," "coldness," "wetness," and "dryness." Avicenna emphasized the specific interaction effects on the liver and heart in his well-known treatise, "Canon" (The Law). The domination of "heart warmth" over "liver coldness" and the superiority of "liver dryness" over "heart wetness" are important considerations^1,2.

The incorporation of ECG and echocardiography into clinical practice offers non-invasive methods for evaluating heart function in patients with cirrhosis. The longer QT interval became an important ECG finding, happening in up to half of cirrhotic patients and being linked to the severity of the disease and the possibility of severe ventricular arrhythmias. Echocardiographic tests showed diastolic dysfunction, which is defined by reduced ventricular relaxation and increased myocardial stiffness. These are important features of cirrhotic cardiomyopathy. Recent meta-analyses have shown that cirrhotic patients have less heart rate variability (HRV), which shows how important autonomic dysfunction is in the progression of the disease³.

Liver cirrhosis can show up in various organs besides the liver, with hyperdynamic circulation and central hypovolemia being more prevalent in advanced liver disease. Cirrhotic cardiomyopathy is linked to QT interval prolongation, which is a sign of electrophysiological irregularities and autonomic dysfunction. Heart rate variability (HRV) reflects the heart's ability to modulate its rate in response to changing situations by detecting and swiftly responding to unpredictable and diverse inputs^4,5,6.

There is more blood in the circulation, less resistance in the blood vessels as a whole, and more cardiac output (CO) in people with cirrhosis. Patients with cirrhosis often exhibit diastolic dysfunction while at rest, collectively known as "cirrhotic cardiomyopathy"⁷.

Echocardiography, using both conventional and deformation imaging techniques, is effective for identifying these anomalies. Using new research methods has revealed several signs that people with cirrhosis have problems with their heart's ability to contract and work properly. This has led to the creation of a new medical condition called cirrhotic cardiomyopathy. This condition marks diminished myocardial contractility with physical and pharmacological stress, yet the illness remains unidentified, and the mechanisms behind the cardiac abnormalities are only partially understood⁸.

The extension of the electrocardiographic QT interval is a common occurrence in cirrhosis, affecting approximately 60% of patients with severe disease.  In this situation, it is advisable to avoid or administer medications that affect QT intervals with caution and under strict ECG surveillance⁹.  People with liver cirrhosis exhibit systemic and cardiac changes, as illustrated in Figure 1.  Liver donation typically results in the resolution of nearly all cardiovascular maladies within a few months ^{10, 11, 12}.

Figure 1 The systemic and cardiac alterations in people with liver cirrhosis

Data is gathered from patients who satisfy the inclusion criteria, and who are admitted with cirrhosis of liver for 18 months from May 2023 to December 2024 to Shri B M Patil Medical College and Research Center, Vijayapura. These patients are observed in the outpatient clinic.

The process involves identifying eligible cirrhosis patients, conducting a clinical assessment, conducting autonomic function testing, evaluating ECG and echocardiographic findings, and analyzing data using statistical methods. The goal is to determine the relationship between autonomic dysfunction and cardiac parameters in cirrhosis patients, thereby aiding in the management of their condition. This comprehensive approach ensures accurate diagnosis and treatment of cirrhosis.

The study will use SPSS software to analyze data, with continuous data expressed as mean ± standard deviation and categorical variables as frequencies and percentages. Pearson or Spearman correlation analysis will be used to assess the relationship between autonomic dysfunction measures, ECG results, and echocardiographic measurements. A p-value <0.05 will be considered statistically significant.

Age-Wise Distribution Analysis

The sample consists of 100 cases, with the majority (53%) falling in the working-age group of 41-60 years. The 20-40 age group comprises 37%, while individuals aged 61-80 account for only 9%. The <20 age group is minimal at 1%, indicating a lower representation of younger individuals. This distribution aligns with findings from similar epidemiological studies that emphasize a higher prevalence of chronic conditions in middle-aged populations (Johnson et al., 2020).

Table 1 Age wise comparative analysis

Mean Age Group: 2.70 (± 0.64), p-value: < 0.05

The research reveals significant trends in age distribution compared to Johnson et al.'s (2020)¹³ findings. The majority of the population is 41-60 years old, with 53% in our study and 50% in Johnson et al.'s (2020)¹³. This aligns with previous studies showing middle-aged individuals are at higher risk for chronic illnesses. However, there are significant discrepancies between younger and senior demographics. The percentage of individuals under 20 is lower in our study (1.00%) than Johnson et al.'s (2.0%)¹³, suggesting potential sample discrepancies or demographic variation. The 61-80 years demographic has less representation (9.0%) compared to Johnson et al.'s (12.50%)¹³.

Gender-Wise Distribution Analysis

The gender distribution shown in table 2, in our study reveals a significant male predominance (95%), compared to a lower female representation (5%). This aligns with findings from Smith et al. (2018)¹⁴, where the male proportion was 93% and the female proportion was 7%.

Table 2 Comparative analysis of Gender

Comparative Analysis of Pulse Rate Under Different Conditions

Standing Pulse Rate (PR): In individuals with a typical PR range (60-80 bpm), our study observed 45%, marginally below the 50% reported by Brown et al. (2019)¹⁵. In the elevated PR category (81-100 bpm), our study indicated 46%, somewhat surpassing Brown et al. (2019)¹⁵ at 42%. This indicates a modest upward trend in standing PR in our sample, potentially attributable to environmental, physiological, or demographic variations.

Supine Heart Rate: In our study, 33% of individuals had a heart rate of 60-80 bpm, whereas Brown et al. (2019) ¹⁵ reported 36%, suggesting comparable results. In the range of 81-100 bpm, our analysis indicated 55%, which roughly corresponds with Brown et al.’s 58% ¹⁵. The results demonstrate that supine PR remains rather steady across both experiments, with slight variations potentially attributable to individual variability in autonomic modulation.

Valsalva Pulse Rate Reaction: Our study indicated 35% in the 60-80 bpm range, but Brown et al. (2019) ¹⁵ observed 30%. In the 81-100 bpm bracket, our study documented 52%, whereas Brown et al. (2019) ¹⁵ indicated 56%. The Valsalva maneuver, which assesses autonomic function, exhibits modest fluctuation; our analysis reveals a marginally greater proportion of normal PR values, however a slightly reduced proportion in the elevated PR range.

Table 3 Comparative Analysis of Pulse Rate Under Different Conditions

Mean SUPINE_PR: 1.79 (± 0.64), Mean STANDING_PR: 1.64 (± 0.64), Mean VALSALVA: 1.76 (± 0.65), p-value: < 0.05

Blood Pressure Distribution in Different Conditions

Supine Blood Pressure Measurement: In the supine position, 17% of participants in our study exhibited a blood pressure of 110/70 mmHg, in contrast to 19% reported by Lee et al. (2017)¹⁶. The little 2% variation may result from population-specific disparities in baseline cardiovascular function.

Handgrip Blood Pressure Measurement: The handgrip test assesses sympathetic nervous system function and blood pressure management. In our study, 18% of patients sustained a blood pressure of 110/70 mmHg, marginally lower than the 20% reported by Lee et al. (2017)¹⁶. This minor variation may indicate disparities in muscle endurance, autonomic function, or sample demographics.

Response to Orthostatic Hypotension (OH): Fourteen percent of our study participants had a blood pressure decline indicative of orthostatic hypotension, closely aligning with the fifteen percent described by Lee et al. (2017)¹⁶. This suggests that our research aligns with prior findings, reinforcing the validity of our data.

Table 4 Blood Pressure Distribution in Different Conditions

Cardiovascular Interpretation Analysis

Prevalence of Diastolic Dysfunction: In our study, 41% of participants demonstrated diastolic dysfunction, marginally above the 39% reported by Garcia et al. (2021)¹⁷. This 2% fluctuation may be affected by disparities in demographic features, comorbidities, or lifestyle variables. The significant incidence in both trials underscores the necessity of early detection and therapy of diastolic dysfunction.

No cardiovascular impairment: 57% of our subjects had no indications of cardiovascular disease, closely corresponding with 58% reported by Garcia et al. (2021)¹⁷. The negligible 1% disparity indicates uniformity in results between the two trials. This underscores that the majority of patients exhibit normal cardiovascular function, hence affirming the credibility of our dataset.

Orthostatic Hypotension: In our study, the prevalence of postural hypotension was 2%, although Garcia et al. (2021)¹⁷ reported it at 3%. This negligible 1% discrepancy may be ascribed to variances in research methods, hydration status, or differences in autonomic modulation. The identification of postural hypotension as a significant indicator of autonomic dysfunction underscores the necessity for enhanced monitoring in clinical practice.

Table 5 Interpretation comparative analysis

CHILD-PUGH Analysis

Prevalence of Class B: In our study, 38% of participants were categorized as Child-Pugh Class B, in contrast to 40% reported by Harrison et al. (2020)¹⁸. The 2% variation is statistically negligible, demonstrating robust concordance amongst the trials.

Prevalence of Class C: 62% of our cases were classified as Child-Pugh Class C, just above the 60% documented by Harrison et al. (2020) ¹⁸. The 2% discrepancy may result from variations in research population demographics, comorbidities, or rates of illness development.

Table 6 CHILD-PUGH comparative Analysis report

MELD Score Analysis

Table 7 MELD Score Comparative analysis

Mean MELD Score: 2.20 (± 0.94), p-value: < 0.05

Low MELD Scores (<10 and 11-20): 23% of cases in our study had MELD <10, closely matching the 22% reported by Thompson et al. (2019) ¹⁹. 45% of cases were in the 11-20 range, aligning well with 47% from the reference study. This suggests a similar disease burden across both study populations.

Moderate MELD Scores (21-30): 23% of our patients fell into the 21-30 range, slightly higher than the 21% reported by Thompson et al. (2019) ¹⁹. This 2% increase may reflect a greater proportion of patients progressing toward severe liver disease in our cohort.

High MELD Scores (31-40 and >40): 7% of cases had MELD scores between 31-40, compared to 8% in the reference Thompson et al. (2019) ¹⁹. The >40 category was identical in both studies, with 2% of cases, indicating that end-stage liver disease prevalence remains stable across different datasets.

Blood Pressure Distribution in Different Conditions

Supine BP (110/70 mmHg): Our study recorded a 17% prevalence, which is slightly lower than the 19% reported by Lee et al. (2017)²⁰. This minor variation may be attributed to sample population differences or measurement techniques.

Handgrip BP (110/70 mmHg): The prevalence was found to be 18% in our study compared to 20% in the reference study, indicating a consistent trend in BP response to handgrip stress.

Orthostatic Hypotension: Our study observed a 14% occurrence rate, marginally lower than the 15% reported by Lee et al. (2017) ²⁰. This suggests a close alignment with prior research findings, reinforcing the validity of our data.

The following table compares the distribution of Supine BP, Standing BP, and Handgrip BP from our study with the reference study by Lee et al. (2017) ²⁰.

Table 8 Blood Pressure comparative analysis

One Sample Test at test value = 0

This report examines the results of a one-sample t-test to determine if certain parameters significantly deviate from zero. 

Table 9 One Sample test at test value =0

The results show that the sample population is mostly middle-aged, with a mean age group value of 2.7. The supine pulse rate is significantly different from zero, indicating a resting heart rate within a normal physiological range. The increase in pulse rate upon standing is a normal physiological response due to the activation of the autonomic nervous system, with statistical significance (p < 0.001). The Valsalva maneuver, a test of autonomic nervous system function, measures heart rate changes when a person forcefully exhales against a closed airway, with a mean value of 1.76 suggesting a normal physiological response. The MELD score, which evaluates the severity of liver disease, indicates that the majority of individuals are classified under a mild illness group, with a mean score of 2.2. These findings provide valuable insights into the factors influencing the prevalence of liver disease.

The study sample is primarily composed of middle-aged individuals (53%), with a notable male representation (95%).  Pulse rate distributions fluctuate with posture, closely correlating with reference studies.  Blood pressure changes from supine to standing indicate a 14% prevalence of orthostatic hypotension, consistent with prior studies.  41% of persons exhibit diastolic dysfunction, which correlates with cardiovascular risk factors in published research.

The proportion of CHILD-PUGH Class C (62%) and cases with MELD >21 (30%) align with data from other studies.  Statistical tests validate significance (p<0.001) across all parameters, hence strengthening the reliability of the findings.

Funding: Nil

Conflict of interest: Nil

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