Implications of Elevated Fibrosis-4 Index in Patients Receiving Trans-Catheter Aortic Valve Replacement

Background: The prognostic implication of the fibrosis-4 index, which represents the degree of hepatic injury, on patients receiving trans-catheter aortic valve replacement (TAVR) remains unknown. Methods: Patients who underwent TAVR to treat severe aortic stenosis at our institute between 2015 and 2020 were included in this retrospective study and followed for 2 years from the index discharge. The impact of the fibrosis-4 index, which was calculated using age, hepatic enzymes, and platelet count, on 2-year heart failure readmissions was investigated. Results: A total of 272 patients (median age 85 (82, 88) years old, 76 (28%) men) were included. The median baseline fibrosis-4 index was 2.8 (2.2, 3.7). A high fibrosis-4 index (>3.79) was associated with higher cumulative incidence of the primary endpoint (18% versus 4%, p < 0.001) and higher event rates (0.1041 versus 0.0222 events/year, p < 0.001), with an adjusted hazard ratio of 1.27 (95% confidence interval 1.04–1.54, p = 0.019). Conclusion: an elevated fibrosis-4 index at baseline, indicating the existence of persistent hepatic congestion, was associated with incidences of heart failure following TAVR. Calculating the fibrosis-4 index before TAVR is highly encouraged for risk stratification and shared decision making.

Overview on Cardiac Cirrhosis and Congestive Hepatopathy - A Review

Cardiac cirrhosis (congestive hepatopathy) refers to a group of hepatic abnormalities that develop as a result of right-sided heart failure. Cirrhosis of the liver can be induced by any right-sided pathology that leads to right-sided heart failure, which leads to increased venous congestion and pressure in the hepatic sinusoids. Because cardiac cirrhosis might be asymptomatic or diagnosed incorrectly due to other types of liver disease, determining its prevalence is difficult. The underlying heart disease, rather than the hepatic congestion and damage, is usually the cause of death in cardiac cirrhosis. The control of the underlying cardiac disease, as well as the optimization of cardiac output, are the mainstays of congestive hepatopathy treatment. Diuresis can help with hepatic congestion, but it must be used with caution to avoid causing hepatic ischemia. Hemodynamic therapy may be able to reverse the early stages of congestive hepatitis. The widespread use of heart transplantation (HT) and considerable breakthroughs in medical and surgical treatments have drastically altered the profile of CH patients. In this overview we will be looking at the disease cause, epidemiology, diagnosis, and treatment.

Susceptibility of Goldfish to Cyprinid Herpesvirus 2 (CyHV-2) SH01 Isolated from Cultured Crucian Carp

Cyprinid herpesvirus 2 (CyHV-2), a member of the Alloherpesviridae family belonging to the genus Cyprinivirus, is a fatal contagious aquatic pathogen that affects goldfish (Carassius auratus) and crucian carp (Carassius carassius). Although crucian carp and goldfish belong to the genus Carassius, it is unclear whether they are susceptible to the same CyHV-2 isolate. In addition, the origin of the crucian carp-derived CyHV-2 virus isolate remains unclear. CyHV-2 SH01 was isolated during herpesviral hematopoietic necrosis disease (HVHN) outbreaks in crucian carp at a local fish farm near Shanghai. CyHV-2 SH01 was confirmed by PCR and Western blot analysis of kidney, spleen, muscle, and blood tissue from the diseased crucian carp. Moreover, histopathological and ultra-pathological analyses revealed pathological changes characteristic of CyHV-2 SH01 infection in the tissues of the diseased crucian carp. In the present study, goldfish and crucian carp were challenged with CyHV-2 SH01 to elucidate viral virulence. We found that CyHV-2 SH01 could cause rapid and fatal disease progression in goldfish and crucian carp 24 h post-injection at 28 °C. Experimental infection of goldfish by injection indicated that the average virus titer in the kidney of the goldfish was 103.47 to 103.59 copies/mg. In addition, tissues exhibited the most prominent histopathological changes (cellular wrinkling and shrinkage, cytoplasmic vacuolation, fusion of the gill lamellae, and hepatic congestion) in CyHV-2 SH01-infected goldfish and crucian carp. Thus, crucian carp and goldfish showed a high sensitivity, with typical symptoms, to HVHN disease caused by CyHV-2 SH01.

991 Managing Recurrent Bleeding from Varicose Veins of The Scrotum: A Case Report

Introduction Spontaneous recurrent bleeding scrotal varicosity is a rare clinical presentation. The management is undefined and is usually anecdotal from previous case reports. The anatomy and pathophysiology of these presentations are usually complex hence resulting in atypical and challenging management options. To highlight this, we present a case of a patient with recurrent scrotal bleeding secondary to scrotal varicosities. Care report A 39-year-old gentleman with heart failure, 4 previous episodes of transient ischemic attacks and atrial fibrillation who was anticoagulated, presented with recurrent left sided scrotal bleeding from dilated superficial scrotal veins. In total, he had 11 presentations over 4 years requiring blood transfusion on 4 occasions. On one occasion the patient required 7 units of packed red blood cells transfused. He had a background of heart failure with hepatic congestion and ascites which failed medical management. Compression, adrenaline and tranexamic acid-soaked gauze, as well as over-sewing feeder vessels offered only short-term relief. His heart failure was difficult to optimise and stopping anticoagulation was not possible, even for a short period of time, due to the high risk of stroke in this patient. Venography revealed a prominent left testicular vein that extensively fed the scrotal veins with bilateral varicoceles. After discussion with the Vascular team, percutaneous coil embolization of the left testicular vein was performed with good results. He has had no significant scrotal bleeding since. Conclusions Managing bleeding scrotal varicose veins can be challenging. A multidisciplinary approach may be the most appropriate in managing these patients.

296 Case Report: Pacemaker Lead-Induced Fibrosis Resulting in Right Atrial and Tricuspid Stenosis Managed with An Open Surgical Approach

Pacemaker leads can result in localised inflammation and, over time, fibrosis. Rarely, this can significantly alter the anatomy of the heart and impair cardiac function. In this case, a fifty-year-old female had undergone pacemaker placement in her teens having experienced symptomatic bradycardia. Due to pacemaker pocket erosion, she had undergone a lead extraction where lead fragments had been left in-situ. Years after a new generator and leads were placed, she presented with symptoms of proximal venous congestion and superior vena cava (SVC) syndrome. A venogram demonstrated completely occluded brachiocephalic and innominate veins with significant adjacent venous collateralization. Computed tomography showed partial obstruction of the SVC and tricuspid stenosis. Initially, a decision was made not to intervene. After developing abdominal distension, she was diagnosed with hepatic congestion and cirrhosis secondary to elevated right sided pressures and right atrial congestion due to tricuspid stenosis. It was concluded that the patient’s symptoms were the result of occluded proximal veins, SVC syndrome, and functional tricuspid stenosis, all of which were likely the result of fibrotic tissue secondary to pacemaker lead-induced inflammation. Due to the severity of her symptoms, the patient accepted the risks associated with surgical management. Intra-operatively, electrocautery was used to debride the fibrotic tissue inhibiting the leaflets of the tricuspid valve. This worked to great effect and additional valve repair/replacement was not necessary. Whilst the patient has been left with SVC syndrome, her tricuspid stenosis symptoms are greatly improved. To our knowledge, such a case has not been previously described.

MicroRNA-29b/c-3p Indicate Advanced Liver Fibrosis/Cirrhosis in Univentricular Heart Patients With and Without Fontan Palliation

Aim: The present study aims to identify those microRNAs (miRNAs) in patients with univentricular heart (UVH) disease with and without Fontan palliation that may be associated with advanced liver fibrosis/cirrhosis.Materials and Methods: SurePrint™ 8 × 60K Human v21 miRNA arrays were used to determine the miRNA abundance profiles in the blood of 48 UVH patients with and without Fontan palliation and 32 matched healthy controls. The abundance levels of selected miRNAs have been validated by quantitative reverse transcription-polymerase chain reaction (RT-qPCR).Results: According to microarray analysis, 50 miRNAs were found to be significantly abundant in UVH patients of which miR-29b-3p and miR-29c-3p were significantly related to the model of end-stage liver disease (MELD)-Albumin and albumin-bilirubin (ALBI) score representing advanced liver fibrosis/cirrhosis. Relative expression levels of both miRNAs were significantly higher in patients with a higher collapsibility index representing venous hepatic congestion, a higher MELD-Albumin or ALBI score and incomplete or no Fontan palliation. In the logistic regression analysis, a MELD-Albumin score ≥ 11 or ALBI score &gt; −2.6 were best predicted by total bilirubin (OR 6.630, P = 0.016), albumin (OR 0.424, P = 0.026), and miR-29c-3p (OR 33.060, P = 0.047). After adjustment to the status of Fontan palliation, however, no statistical significance of these parameters was found thus underlining the importance of palliation status on progression of liver fibrosis/ cirrhosis in UVH patients.Conclusions: In UVH patients with and without Fontan palliation, miR-29b-3p and miR-29c-3p seem to be markers of advanced liver fibrosis/cirrhosis and thus may be used in the risk assessment of these patients.

SOFTWARE-ASSISTED IMAGE ANALYSIS FOR IDENTIFICATION AND QUANTIFICATION OF HEPATIC SINUSOIDAL DILATATION AND CENTRILOBULAR FIBROSIS

ABSTRACT Background: Heart dysfunction and liver disease often coexist because of systemic disorders. Any cause of right ventricular failure may precipitate hepatic congestion and fibrosis. Digital image technologies have been introduced to pathology diagnosis, allowing an objective quantitative assessment. The quantification of fibrous tissue in liver biopsy sections is extremely important in the classification, diagnosis and grading of chronic liver disease. Aim: To create a semi-automatic computerized protocol to quantify any amount of centrilobular fibrosis and sinusoidal dilatation in liver Masson’s Trichrome-stained specimen. Method: Once fibrosis had been established, liver samples were collected, histologically processed, stained with Masson’s trichrome, and whole-slide images were captured with an appropriated digital pathology slide scanner. After, a random selection of the regions of interest (ROI’s) was conducted. The data were subjected to software-assisted image analysis (ImageJ®). Results: The analysis of 250 ROI’s allowed to empirically obtain the best application settings to identify the centrilobular fibrosis (CF) and sinusoidal lumen (SL). After the establishment of the colour threshold application settings, an in-house Macro was recorded to set the measurements (fraction area and total area) and calculate the CF and SL ratios by an automatic batch processing. Conclusion: Was possible to create a more detailed method that identifies and quantifies the area occupied by fibrous tissue and sinusoidal lumen in Masson’s trichrome-stained livers specimens.

Deportalization, Venous Congestion, Venous Deprivation: Serial Measurements of Volumes and Functions on Morphofunctional 99mTc-Mebrofenin SPECT-CT

The objective was to assess the changes in regional volumes and functions under venous-impaired vascular conditions following liver preparation. Twelve patients underwent right portal vein embolization (PVE) (n = 5) or extended liver venous deprivation (eLVD, i.e., portal and right and middle hepatic veins embolization) (n = 7). Volume and function measurements of deportalized liver, venous-deprived liver and congestive liver were performed before and after PVE/eLVD at days 7, 14 and 21 using 99mTc-mebrofenin hepatobiliary scintigraphy with single-photon emission computed tomography and computed tomography (99mTc-mebrofenin SPECT-CT). Volume and function progressed independently in the deportalized liver (p = 0.47) with an early decrease in function (median −18.2% (IQR, −19.4–−14.5) at day 7) followed by a decrease in volume (−19.3% (−22.6–−14.4) at day 21). Volume and function progressed independently in the venous deprived liver (p = 0.80) with a marked and early decrease in function (−41.1% (−52.0–−12.9) at day 7) but minimal changes in volume (−4.7% (−10.4–+3.9) at day 21). Volume and function progressed independently in the congestive liver (p = 0.21) with a gradual increase in volume (+43.2% (+38.3–+51.2) at day 21) that preceded a late and moderate increase in function at day 21 (+34.8% (−8.3–+46.6)), concomitantly to the disappearance of hypoattenuated congestive areas in segment IV (S4) on CT, initially observed in 6/7 patients after eLVD and represented 35.3% (22.2–46.4) of whole S4 volume. Liver volume and function progress independently whatever the vascular condition. Hepatic congestion from outflow obstruction drives volume increase but results in early impaired function.

Abstract 13678: Serum Hepatokine Selenoprotein P is Upregulated by Hepatic Hypoperfusion and Predicts Adverse Prognosis in Heart Failure Patients

Introduction: Cardiac and multiple organ network is involved in the pathophysiology of heart failure (HF). Hepatokines, which are produced and secreted from the liver, have regulatory functions in the peripheral tissues. However, the interaction between the heart and liver or clinical relevance of hepakokines in HF remains poorly understood. The present study aimed to elucidate the clinical significance of hepatokine selenoprotein P in HF. Methods and Results: We enrolled 250 participants including 171 hospitalized patients with HF and 79 control subjects. The serum concentration of selenoprotein P was measured by an enzyme-linked immunosorbent assay. We found that the serum selenoprotein P levels in HF patients were significantly higher than those in controls (14.8 ± 7.5 vs. 8.4 ± 4.6 mg/L, P<0.01). Next, the HF patients were categorized into 4 groups based on the hepatic hemodynamics assessed by abdominal-ultrasonography, which determined liver congestion by shear wave elastography (liver-SWE, >1.33 m/s) and liver hypoperfusion by peak systolic velocity of the celiac artery (celiac-PSV, <62.4 cm/s). Selenoprotein P levels were significantly upregulated in patients with liver hypoperfusion compared to patients with liver congestion ( Figure A ). Selenoprotein P was negatively correlated with celiac-PSV (P<0.01), cardiac output (P<0.01), and left ventricular stroke volume (P=0.03), whereas no correlations were observed between selenoprotein P and indices of congestion such as liver-SWE and right atrial pressure. Kaplan-Meier analysis demonstrated that a higher selenoprotein P group showed a lower event-free rate from re-hospitalization due to worsening HF ( Figure B ). Conclusion: Upregulation of liver-derived selenoprotein P was associated with hepatic hypoperfusion, not hepatic congestion, and related to the adverse prognosis in HF. Selenoprotein P may be a novel molecule involved in the cardio-hepatic interaction.