Hemodynamic Derangements Research Articles

Computational Assessment of Valvular Dysfunction in Discrete Subaortic Stenosis: A Parametric Study.

Discrete subaortic stenosis (DSS) is a left-ventricular outflow tract (LVOT) obstruction caused by a membranous lesion. DSS is associated with steep aortoseptal angles (AoSAs) and is a risk factor for aortic regurgitation (AR). However, the etiology of AR secondary to DSS remains unknown. This study aimed at quantifying computationally the impact of AoSA steepening and DSS on aortic valve (AV) hemodynamics and AR. An LV geometry reconstructed from cine-MRI data was connected to an AV geometry to generate a unified 2D LV-AV model. Six geometrical variants were considered: unobstructed (CTRL) and DSS-obstructed LVOT (DSS), each reflecting three AoSA variations (110°, 120°, 130°). Fluid-structure interaction simulations were run to compute LVOT flow, AV leaflet dynamics, and regurgitant fraction (RF). AoSA steepening and DSS generated vortex dynamics alterations and stenotic flow conditions. While the CTRL-110° model generated the highest degree of leaflet opening asymmetry, DSS preferentially altered superior leaflet kinematics, and caused leaflet-dependent alterations in systolic fluttering. LVOT steepening and DSS subjected the leaflets to increasing WSS overloads (up to 94% increase in temporal shear magnitude), while DSS also increased WSS bidirectionality on the inferior leaflet belly (+ 0.30-point in oscillatory shear index). Although AoSA steepening and DSS increased diastolic transvalvular backflow, regurgitant fractions (RF < 7%) remained below the threshold defining clinical mild AR. The mechanical interactions between AV leaflets and LVOT steepening/DSS hemodynamic derangements do not cause AR. However, the leaflet WSS abnormalities predicted in those anatomies provide new support to a mechanobiological etiology of AR secondary to DSS.

Upregulation of Inflammatory Cytokines in Pulmonary Embolism Using Biochip-Array Profiling.

The complex pathophysiology of pulmonary embolism (PE) involves hemostatic activation, inflammatory processes, cellular dysfunction, and hemodynamic derangements. Due to the heterogeneity of this disease, risk stratification and diagnosis remains challenging. Biochip-array technology provides an integrated high throughput method for analyzing blood plasma samples for the simultaneous measurement of multiple biomarkers for potential risk stratification. Using biochip-array method, this study aimed to quantify the inflammatory biomarkers such as interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and epidermal growth factor (EGF) in 109 clinically confirmed PE patients in comparison to the control group comprised of plasma samples collected from 48 healthy subjects. Cytokines IL-4, IL-6, IL-8, IL-10, IL-1β, and MCP-1 demonstrated varying level of significant increase (P < 0.05) in massive-risk PE patients compared to submassive- and low-risk PE patients. The upregulation of inflammatory cytokines in PE patients observed in this study suggest that inflammation plays an important role in the overall pathophysiology of this disease. The application of biochip-array technology may provide a useful approach to evaluate these biomarkers to understand the pathogenesis and risk stratification of PE patients.

Effect of different doses of topical ketamine on hemodynamics in patients undergoing modified radical mastectomy

BackgroundKetamine has been administered by many routes with different adverse effects according to the selected route of administration and the given doses.ObjectivesWe investigated the effect of three different doses of topical ketamine on hemodynamics and adverse effects. We aimed to find the most effective dose with the least hemodynamic derangements and minimal adverse effects.Study designA prospective, double-blind randomized dose finding study was conducted.SettingThe study was done at the Cancer Institute.Patients and methodsPatients scheduled for modified radical mastectomy were enrolled into three groups (n=30) to receive ketamine hydrochloride topical instillation. The study drug was diluted by 20-ml normal saline (0.9%) and instilled before wound closure by anesthesia assistant as follows: groups A, B, and C: in which patients received 1 mg, 2 mg, and 3 mg/kg ketamine, respectively. Hemodynamic assessments included the mean arterial blood pressure, heart rate, and respiratory rate recorded at baseline and 2, 4, 6, 12, 24, 36, and 48 h postoperatively.ResultsIntergroup comparison showed that the three doses of ketamine instillation (1, 2, and 3 mg/kg), showed no difference in the mean arterial blood pressure, either in the heart rate or respiratory rate at any time point during the study (P>0.05). Five patients versus 2 and 4 experienced postoperative nausea and two patients versus 6 and 6 vomited in groups A, B, and C, respectively.LimitationsSmall sample size was a limitation.ConclusionTopical instillation of ketamine in patients undergoing modified radical mastectomy is a safe technique. The three doses investigated were comparable regarding the hemodynamics with no significant adverse effects.

Artificial hyperventilation normalizes haemodynamics and arterial oxygen content in hypoxic rats.

Although humans are capable of enduring critically low levels of oxygen, many hypoxaemic patients die despite aggressive therapies. Mimicking the physiological hyperventilation necessary to survive extreme hypoxic conditions could minimize the derangements caused by acute hypoxic-hypoxia. The objective of this study was to measure the haemodynamic-biochemical response to artificially induced hyperventilation in hypoxic rats. Twenty-four deeply anaesthetized and mechanically ventilated rats were allocated to 3 groups: control (n = 5, FiO2 = 1); hypoxic spontaneously hyperventilating (n = 10, FiO2 = 0.08); and hypoxic artificially induced hyperventilation (n = 9, targeting PaCO2 = 10 mm Hg, FiO2 = 0.08). We compared the spontaneously and artificially hyperventilating groups. P-values < 0.01 were considered statistically significant. Mean arterial pressure (MAP) and serum chemistry were measured for 180 minutes. The control group remained stable throughout the experiment. The hypoxic groups developed profound hypotension after the decrease in FiO2. However, the artificially induced hyperventilated rats recovered their MAP to levels higher than the spontaneously hyperventilating group (117.1 ± 17.2 vs. 68.1 ± 16.0, P = 0.0048). In regard to the biochemical derangements, even though the serum lactate and PaO2 were not different among the hypoxic groups, the artificially hyperventilated group achieved significantly higher SaO2 (94.3 ± 3.6 vs. 58.6 ± 9.6, P = 0.005), pH (7.87 ± 0.04 vs. 7.50 ± 0.13, P = 0.005), and CaO2 (17.7 ± 2.6 vs. 10.2 ± 1.3, P = 0.005) at 180 minutes. Artificially induced hyperventilation led to the correction of arterial oxygen content, severe serum chemistry, and haemodynamic derangements. These findings may represent anovel rescue manoeuvre and serve as abridge to apermanent form of support, but should be further studied before being translated to the clinical setting.

Short Duration Catheter-directed Thrombolysis for Acute Pulmonary Embolism Rapidly Improves Acute Cardiac Function

Treatment of massive and submassive pulmonary embolism (PE) has been shown to be a valuable therapeutic modality. However, a paucity of data exists, regarding length and guidelines for treatment and typically these patients are treated by other than vascular surgery specialists. The aim of this study is to evaluate the effectiveness and safety of short duration treatment of massive and submassive PE, exclusively by vascular surgeons, without routine follow-up pulmonary angiography. Retrospective analysis of prospectively collected data at a single-institution treating massive and submassive PE with catheter-directed thrombolysis (CDT). Internal review board approval was obtained. Descriptive statistical analysis was performed from the data set. Continuous covariates were presented in mean (SD) or median (IQR) and categorical covariates as number (percentage). For continuous variables, a paired t test was used to measure results against the baseline. P value less than 0.05 was defined as statistically significant. STATA® statistical software was used for analysis. From January of 2013 to December of 2016, 28 consecutive patients were treated for massive and submassive PE with CDT. All patients had evidence of right heart strain on echocardiogram, as evidence by a right ventricular to left ventricular (RV/LV) diameter ratio of >0.9. Of the 28 patients, 19 (68%) had hemodynamic derangement with either systolic blood pressure (SBP) less then 90 or tachycardia (HR>100). The mean RV/LV ratio before CDT was 1.18. After therapy, RV/LV ratio was reduced to 0.86 at 48hr (P<0.0001). In addition, mean right ventricular systolic pressure (RVSP) before CDT treatment was 53mm Hg, and after treatment, RVSP was reduced to 40mm Hg at 48-hr (P value=0.0001). There was complete resolution of hypotension in hemodynamically unstable patients (i.e., SBP <90) after CDT. Mean HR before therapy was 102. After 24hr of CDT, mean HR reduced to 84 (P<0.0001). From 2013 to 2016, there was a significant decrease in mean hospital length of stay from 8days to 4days (P=0.05). Mean t-PA dose used decreased, as well, from 2014 (21.7mg) to 2016 (14.9mg), but this was not statistically significant (P=0.13). There was no major bleeding complications or CDT-related death in any of the patients treated during the study period. CDT treatment of massive and submassive PE is safe and highly efficacious at reducing right heart strain acutely. Significant hemodynamic improvement was shown in our cohort throughout the study period. Improvement in tachycardia and resolution of hypotension were seen within 24hr of CDT. Tissue plasminogen activator dosage decreased throughout the study period as a more restrictive approach to follow-up angiography was used without adverse safety or patient outcomes.

Evaluation of a hospital-wide vancomycin-dosing nomogram in patients with continuous-flow left ventricular assist devices

Hemodynamic derangements due to heart failure are associated with alterations in pharmacokinetics. Although use of mechanical circulatory support mitigates such derangements, little evidence is available regarding pharmacokinetics in patients with LVADs. A previous pharmacokinetic analysis of vancomycin among patients with LVADs observed a reduced volume of distribution and clearance compared with estimates based on population kinetics. A total of 28 adult patients with LVADs hospitalized between January 2014 and May 2018 who received vancomycin through a pharmacist dosing consult were included. Internal medicine patients without heart failure receiving vancomycin were enrolled in a 2:1 fashion to make a control group. Exclusion criteria were unstable renal function, ESRD, acute decompensation, cardiac surgery within the preceding 5 days, or weight >110 kg. No difference was observed in the proportion achieving goal trough (64% of LVAD patients vs 71% control patients, p = 0.50). However, mean trough was significantly higher among LVAD patients (23.4 mg/L vs 17.7 mg/L, p = 0.017). Furthermore, there was a significant difference in the distribution of trough levels (p = 0.025) with LVAD patients being more likely to attain levels >25 mg/L (32% vs 14%) and less likely to have troughs <10 mg/L (4% vs 14%). A numerically greater number of LVAD patients experienced nephrotoxicity but this did not reach statistical significance (32% vs 18%, p = 0.14). The use of vancomycin in LVAD patients may result in higher trough levels when compared to internal medicine patients. Increased monitoring or conservative dosing may be warranted to improve safety and efficacy.

Abstract 339: Relationship Between Post-arrest Care Hemodynamics and Cerebral Oxygen Saturation in Comatose Survivors of Out-of-hospital Cardiac Arrest: Insights From the CAPITAL-RETURN Trial

Introduction: Comatose survivors of OHCA develop a post cardiac arrest syndrome (PCAS) characterized by myocardial dysfunction and cerebrovascular dysregulation. Hemodynamic derangements related to PCAS can jeopardize cerebral oxygen delivery and therefore impair neurologic recovery. However, optimal hemodynamic targets to ensure adequate cerebral oxygen delivery following OHCA remain undefined. Accordingly, we examined the relationship between cardiac index (CI), mean arterial pressure (MAP), and regional cerebral oxygen saturation (rO 2 %) following OHCA. Methods: CAPITAL-RETURN was a prospective, single-center observational study examining hemodynamics in comatose survivors of OHCA undergoing targeted temperature management after an initial shockable rhythm. Between August 2016 and December 2017, comatose survivors of OHCA underwent continuous, blinded, non-invasive monitoring of CI and rO 2 % using bioimpedance (Cheetah Medical, Portland, OR, USA) and near-infrared spectroscopy (Covidien, Boulder, CO, USA), respectively, for 96 hours after intensive care unit admission. In the present study, we examined the relationship between CI, MAP, and rO 2 % using multivariable linear regression. Results: In 56 patients in this analysis, the mean CI and MAP during the first 96 hours of intensive care unit admission were 3.2±0.5 L/min/m 2 and 76±6 mmHg, respectively (Figure). The mean rO 2 % was 63±9% and increased over time (+0.1% per hour; p&lt;0.001). Higher CI was associated with improved rO 2 % (+3.2% per L/min/m2 increase in CI; p&lt;0.0001). There was no association between MAP and rO 2 % (p=0.42). After adjustment for MAP, the association between CI and rO 2 % remained significant (+3.1% per L/min/m2 increase in CI; p&lt;0.0001). Conclusion: In comatose survivors of OHCA with an initial shockable rhythm, a higher CI is associated with improved rO 2 %. Further studies are needed to determine whether CI targets improve rO2% and neurologic outcomes following OHCA.

INNOVATIVE USE OF HYDROXOCOBALAMIN WITH THIAMINE, ASCORBIC ACID, AND HYDROCORTISONE IN THE TREATMENT OF A SEPTIC SHOCK PATIENT WITH FULMINANT LEPTOSPIROSIS: A CASE REPORT

SESSION TITLE: Medical Student/Resident Critical Care Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Leptospirosis can escalate to septic shock and multi-organ failure. Despite consistent compliance to sepsis bundle, mortality rate remains high. In 2016, a retrospective study suggested the addition of thiamine, ascorbic acid and hydrocortisone to standard sepsis therapy can improve organ injury, shock time reversal, and mortality rate (1). Adjunctive high dose hydroxocobalamin has also been recently reported to reverse septic shock (2). We are reporting the first innovative use of hydroxocobalamin, thiamine, ascorbic acid, and hydrocortisone to standard sepsis protocol in rapid and successful reversal of septic shock in a case of fulminant leptospirosis. CASE PRESENTATION: A 59-year-old Pacific Islander presented with two days of recurrent headache, vomiting, abdominal pain, and myalgia. He was discharged after receiving antiemetics and fluids. Patient returned two days later with worsening abdominal discomfort, persistent headaches, coughing, and black tarry stool. He was admitted with acute respiratory distress syndrome, septic shock, acute liver and renal failure. Patient was placed on mechanical ventilation; he developed cardiac arrest for a brief period but had return of spontaneous circulation. Initial Sequential Organ Failure Assessment score was 16. With his history of working barefooted in a taro farm, it prompted an order for Leptospira Immunoglobulin M antibody test, which was positive. Along with intravenous fluid and broad-spectrum antibiotics, he required continuous norepinephrine, phenylephrine, vasopressin drips, and hydrocortisone. On day 3, hydroxocobalamin, thiamine, and ascorbic acid were added as adjunctive therapies due to continued hemodynamic compromise. Within 24 hours, he was successfully liberated off all vasopressors. Despite being in the intensive care unit for 16 days and a prolonged hospitalization, he was discharged home and continued to be functional and ambulatory one year later. DISCUSSION: Even with aggressive adherence to sepsis bundle in septic shock, mortality remains high. Despite numerous clinical trials, they have been unsuccessful in reversing this trend. Addition of thiamine, ascorbic acid, and hydrocortisone to multiple vasopressors have been reported to potentially address the hemodynamic derangement. More recently, there has been suggestion that hydroxocobalamin could further contribute to reversing these processes. CONCLUSIONS: This is the first known successfully rapid reversal of septic shock due to fulminant leptospirosis treated with combination of hydroxocobalamin, thiamine, ascorbic acid, and hydrocortisone, added to standard sepsis protocol. The combination of these vitamins and hydrocortisone resulted in synergistic and lasting effect of hemodynamic parameters that can potentially improve quality of health for septic shock survivors. Well-designed prospective studies are warranted to further evaluate their true efficacy. Reference #1: Marik, P. E., Khangoora, V., Rivera, R., Hooper, M. H., & Catravas, J. (2017). Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest, 151(6): 1229-1238. Reference #2: Lin, Y., & Vu, T. Q. (2019). Use of High-Dose Hydroxocobalamin for Septic Shock: A Case Report. A&A Practice, 12(9): 332-335. DISCLOSURES: No relevant relationships by Angelica Guzman Paz, source=Web Response No relevant relationships by Takkin Lo, source=Web Response

CLINICAL CHARACTERISTICS, TREATMENT RESPONSE, AND SURVIVAL OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOSITIS AND PULMONARY ARTERIAL HYPERTENSION

CLINICAL CHARACTERISTICS, TREATMENT RESPONSE, AND SURVIVAL OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOSITIS AND PULMONARY ARTERIAL HYPERTENSION

Pulmonary Hypertension and its Association with Cardiac Transplant Outcomes: Does PA Systolic Matter?

Background Pulmonary hypertension (PH) is a common in patients with chronic heart failure (HF). For patients who progress to end stage HF and require orthotropic heart transplant (OHT), irreversible PH is a relative contraindication as it may lead to post-operative right HF. The International Society of Heart and Lung Transplant (ISHLT) recommends that transplantation be pursued in patients with a pulmonary vascular resistance (PVR) Methods This was an analysis of OHT recipients captured in the United Network for Organ Sharing (UNOS) transplant registry. We included OHT recipients with a PVR ≤ 3 Woods Units for analysis. The cohort was further categorized by PASP (PASP > 50 mmHg and PASP ≤ 50 mmHg). Primary outcome was survival. We classified survival as short term (0-5 years), Intermediate (6-10 years) and long-term (>15 years). Secondary outcome was graft failure. Baseline characteristics were compared between the two groups using the chi-squared analysis. Unadjusted associations between PASP and patient survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models. Results Our study included 62,793 OHT recipients (7,187 PASP>50 mmHg, 55,606 PASP ≤50 mmHg) from 1999-2019. The PASP >50 mmHg group had a mean PASP of 60 ±8 mmHg, were older (50.9 vs 44.9 years, p= Conclusions In this large multicenter study of OHT recipients, patients with PASP>50 mmHg have similar outcomes to patients with lower PASP. OHT should be considered an option for patients with this hemodynamic derangement. Studies into factors that affect long-term outcomes is warranted.

Increased Risk of Supratherapeutic Vancomycin Exposure Among Lvad Recipients

Introduction Hemodynamic derangements due to heart failure are associated with alterations in pharmacokinetics. Although use of mechanical circulatory support mitigates such derangements, little evidence is available regarding pharmacokinetics in patients with LVADs. This is particularly concerning for medications with narrow therapeutic indices for which changes in drug disposition could lead to increased toxicity or a lack of efficacy. A previous pharmacokinetic analysis of vancomycin in LVAD patients observed a reduced volume of distribution and clearance compared with estimates based on population kinetics. Hypothesis The use of a hospital-wide vancomycin dosing nomogram would result in supratherapeutic vancomycin levels in patients with LVADs. Methods A retrospective cohort study was conducted in patients with LVADs who received vancomycin along with a pharmacist dosing consult. Internal medicine patients without heart failure were the control group (1:2) since the dosing nomogram was validated in this population. Patients aged 18-75 years were included if they received nomogram-dosed vancomycin with an appropriately drawn steady-state trough. Patients with unstable renal function, ESRD, acute decompensation, cardiac surgery within the preceding 5 days, or weight >110 kg were excluded. The primary outcome was attainment of goal trough (10-25 mg/L). Secondary outcomes included mean trough level and change in renal function. Results A total of 28 LVAD patients (53% Heartmate II, 43% HVAD, 4% Heartmate 3) were included. They were similar in age, BMI, CrCl, and number of concomitant nephrotoxic medications when compared to the control group (n=56). However, they were more often men (82% vs. 50%), had a greater mean weight (86 kg vs. 77 kg) and baseline SCr (1.12 mg/dL vs 0.91 mg/dL), and were more likely to receive loop diuretics (54% vs. 18%). The most common indication was skin and soft tissue infections in both groups. No difference was observed in goal trough achievement (64% of LVAD patients vs. 71% control patients, p=0.50). However, mean trough was higher in LVAD patients (23.4 mg/L vs. 17.7 mg/L, p=0.017). Furthermore, the distribution of trough levels differed (p=0.025), with troughs in LVAD patients more likely to be >25 mg/L (32% vs. 14%) and less likely to be Conclusions The use of vancomycin in LVAD patients may result in higher trough levels when compared to a control group of medicine patients receiving equivalent doses. Increased monitoring frequency or conservative dosing may result in fewer supratherapeutic levels in these patients, which has implications in preventing nephrotoxicity in this high-risk population.

Altered Hemodynamics and End-Organ Damage in Heart Failure: Impact on the Lung and Kidney.

Heart failure is characterized by pathologic hemodynamic derangements, including elevated cardiac filling pressures ("backward" failure), which may or may not coexist with reduced cardiac output ("forward" failure). Even when normal during unstressed conditions such as rest, hemodynamics classically become abnormal during stressors such as exercise in patients with heart failure. This has important upstream and downstream effects on multiple organ systems, particularly with respect to the lungs and kidneys. Hemodynamic abnormalities in heart failure are affected by processes that extend well beyond the cardiac myocyte, including important roles for pericardial constraint, ventricular interaction, and altered venous capacity. Hemodynamic perturbations have widespread effects across multiple heart failure phenotypes, ranging from reduced to preserved ejection fraction, acute to chronic disease, and cardiogenic shock to preserved perfusion states. In the lung, hemodynamic derangements lead to the development of abnormalities in ventilatory control and efficiency, pulmonary congestion, capillary stress failure, and eventually pulmonary vascular disease. In the kidney, hemodynamic perturbations lead to sodium and water retention and worsening renal function. Improved understanding of the mechanisms by which altered hemodynamics in heart failure affect the lungs and kidneys is needed in order to design novel strategies to improve clinical outcomes.

Implication of Hemodynamic Assessment during Durable Left Ventricular Assist Device Support.

Durable left ventricular assist device therapy has improved survival in patients with advanced heart failure refractory to conventional medical therapy, although the readmission rates due to device-related comorbidities remain high. Left ventricular assist devices are designed to support a failing left ventricle through relief of congestion and improvement of cardiac output. However, many patients still have abnormal hemodynamics even though they may appear to be clinically stable. Furthermore, such abnormal hemodynamics are associated with an increased risk of future adverse events including recurrent heart failure, gastrointestinal bleeding, stroke, and pump thrombosis. Correction of residual hemodynamic derangements post-implantation may be a target in improving longitudinal clinical outcomes during left ventricular assist device support. Automatic and timely device speed adjustments considering a patients’ hemodynamic status (i.e., with a smart pump) are potential improvements in forthcoming devices.

Management of cardiovascular insufficiency in ICU: the BEAT approach.

A large number of patients admitted to ICU display hemodynamic deterioration at some time during their stay. The management of acute hemodynamic derangement of any cause can be difficult and has to be accomplished quickly and correctly as delayed and inappropriate resuscitation treatments carry increased mortality. Cardiovascular insufficiency shows end-organ hypoperfusion-associated dysfunction, thus decreasing level of consciousness, falling urine output, ileus, new onset tachypnea and the presence of skin mottling are important clinical clues to cardiovascular deterioration and should be promptly looked for and if detected alert the bedside clinician that further assessment and potentially treatment is necessary. Although measures of serum lactate are useful to document the presence of tissue hypoperfusion, they are non-specific in defining its etiology. In a patient with acute hemodynamic instability, we propose a step-by-step approach as follows: 1) rapid initial ultrasound assessment of heart function; 2) pathophysiological understanding of heart and circulation interaction; 3) functional hemodynamic monitoring; and 4) treatment. We named such approach BEAT, which stands for: browse the heart, measure the elastances, assess volume status, and treat. Combining bedside echocardiography, including the evaluation of the interaction between the heart and the circulation, with FHM offers the opportunity to personalize the hemodynamic management to the specific requirements.

Paracentesis-Induced Circulatory Dysfunction With Modest-Volume Paracentesis Is Partly Ameliorated by Albumin Infusion in Acute-on-Chronic Liver Failure.

Paracentesis-induced circulatory dysfunction (PICD) is a serious complication of large-volume (>5L) paracentesis in cirrhosis and is reduced with albumin infusion. There is a lack of data on PICD in acute-on-chronic liver failure (ACLF). Because ACLF patients have greater hemodynamic derangements than patients with decompensated cirrhosis, we investigated whether PICD could develop with modest-volume paracentesis (MVP) and the role of albumin infusion. A total of 80 ACLF patients undergoing <5L paracentesis were randomized to receive albumin (8 g/dL of ascitic fluid; n=40) or no albumin (n=40) and serially followed to detect PICD. Baseline characteristics were comparable between groups, including volume of ascitic tap (4.16±0.23 versus 4.14±0.27 L; P=0.72) and plasma renin activity (PRA; 20.5±7.03 versus 23.2±8.24ng/mL/hour; P=0.12). PICD was more frequent in the no-albumin group than the albumin group (70% versus 30%; P=0.001), with higher incidence of hepatic encephalopathy (50% versus 27.5%; P=0.04), hyponatremia (67.5% versus 22.5%; P<0.001), acute kidney injury (62.5% versus 30%; P=0.001), and in-house mortality (62.5% versus 27.5%; P=0.003). PRA of 25.15ng/mL at day 3 had sensitivity and specificity of 71% and 68%, respectively, for development of PICD at day 6. Albumin infusion decreased the incidence of PICD at day 6 (odds ratio, 0.068; 95% confidence interval, 0.011-0.43; P=0.005). PICD is common and develops even with MVP in ACLF patients. Albumin infusion decreases the incidence of PICD and mortality in patients with ACLF. Clinical trial identifier: NCT02467348.

Hemodynamic and Functional Impact of Epicardial Adipose Tissue in Heart Failure With Preserved Ejection Fraction

ObjectivesThis study determined the impact of excess epicardial adipose tissue (EAT) in patients with the obese phenotype of heart failure with preserved ejection fraction (HFpEF). BackgroundPatients with HFpEF and an elevated body mass index differ from nonobese patients, but beyond generalized obesity, fat distribution may be more important. Increases in EAT are associated with excess visceral adiposity, inflammation, and cardiac fibrosis, and EAT has been speculated to play an important role in the pathophysiology of HFpEF, but no study has directly evaluated this question. MethodsPatients with HFpEF and obesity (n = 169) underwent invasive hemodynamic exercise testing with expired gas analysis and echocardiography. Increased EAT was defined by echocardiography (EAT thickness ≥9 mm). ResultsCompared with obese patients without increased EAT (HFpEFEAT−, n = 92), obese patients with HFpEF with increased EAT (HFpEFEAT+; n = 77) displayed a higher left ventricular eccentricity index, indicating increased pericardial restraint, but similar resting biventricular structure and function. In contrast, hemodynamics were more abnormal in patients with HFpEFEAT+, with higher right atrial, pulmonary artery, and pulmonary capillary wedge pressures at rest and during exercise compared with those of patients with HFpEFEAT−. Peak oxygen consumption (VO2) was reduced in both groups but was 20% lower in patients with HFpEFEAT+ (p < 0.01). ConclusionsAmong patients with the obese phenotype of HFpEF, the presence of increased EAT is associated with more profound hemodynamic derangements at rest and exercise, including greater elevation in cardiac filling pressures, more severe pulmonary hypertension, and greater pericardial restraint, culminating in poorer exercise capacity. Further study is needed to understand the biology and treatment of excessive EAT in patients with HFpEF.

Non-selective Beta-Blockers in Decompensated Cirrhosis

The safety of non-selective beta-blockers (NSBB) in decompensated cirrhosis, particularly in patients with refractory ascites, has recently been called int question. This review summarizes recent evidence on the role of NSBBs in decompensated cirrhosis and provides recommendations for their appropriate use. Current evidence on the use of NSBBs in decompensated cirrhosis is mixed and is based on observational data. An initial study in 2010 demonstrated decreased survival in patients with refractory ascites who received propranolol compared to those who did not. Since then, multiple subsequent studies have not demonstrated a harmful effect of NSBBs in this setting. The safety of NSBB use is mediated by its dose, the type of NSBB, and the presence of underlying hemodynamic derangements related to end-stage cirrhosis. Refractory ascites per se is not a contraindication to NSBB use. NSBBs can be safely used in decompensated cirrhosis, though the decision to do so requires careful decision making on the risk and benefit profile of NSBBs for each individual patient.

The Majority of Major Amputations After Resuscitative Endovascular Balloon Occlusion of the Aorta Are Associated With Preadmission Trauma

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potentially lifesaving intervention. However, recent reports of associations with limb loss and mortality have called its safety into question. We aimed to evaluate patient and hospital characteristics associated with major amputation and inpatient mortality in patients undergoing REBOA for major trauma. The National Trauma Data Bank (2015-2017) was queried for patients who presented to trauma centers and were treated with REBOA. We included REBOAs performed on hospital day 1 in patients who survived at least 6 hours from presentation. Univariable and multivariable analyses were performed to evaluate associations with major amputation and in-hospital mortality. A total of 316 patients underwent REBOA and survived in the acute period after presentation. Overall, mean age was 45 ± 20 years, and the majority were men (73%) and white (56%). Most patients presented to level I trauma centers (72%) after blunt injuries (79%) with an average Injury Severity Score of 31 ± 15. In 15 patients (5%), there were 18 major amputations, 7 above knee (39%) and 11 below knee (61%). Eleven of the amputations (61%) were either traumatic amputations (73%) or mangled limbs requiring amputation within 24 hours (27%). Of the remaining amputations, 71% were associated with ipsilateral vascular or orthopedic lower extremity (LE) injuries of serious to severe Abbreviated Injury Scale. Comparison of patients with and without major amputations revealed no significant differences in patients’ demographics or chronic comorbidities or hospital characteristics. Patients undergoing major amputation were more likely to present with LE vascular injuries (33% vs 9%; P = .01) and LE Abbreviated Injury Scale severe vascular injuries (6.7% vs 1.3%; P = .01). They more frequently received open peripheral vascular interventions (40% vs 10%; P = .002) and developed compartment syndrome (13% vs 2%; P = .04) during hospitalization. There were 110 deaths (35%). On multivariable analysis, prehospital cardiac arrest (odds ratio [OR], 8.47; 95% confidence interval [CI], 1.47-48.66; P = .02), penetrating vs blunt trauma (OR, 5.5; 95% CI, 1.05-28.82; P = .04), increased age (OR, 1.06; 95% CI, 1.03-1.1; P < .001), increased Injury Severity Score (OR, 1.05; 95% CI, 1-1.1; P = .03), and decreased total Glasgow Coma Scale score (OR, 0.85; 95% CI, 0.76-0.95; P = .005) were associated with increased mortality. The majority of major amputations in patients undergoing REBOA are trauma related from injuries sustained before admission. Injury type and severity as well as initial hemodynamic derangements are associated with mortality after REBOA. Despite concerns about limb complications of REBOAs, baseline injuries appear to be the primary cause of limb loss, but further prospective analysis is needed.

Genetic and Biological Effects of ICAM-1 E469K Polymorphism in Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a complex disease, in which local inflammatory stress results from both metabolic and hemodynamic derangements. Intercellular adhesion molecule 1 (ICAM-1) is an acute-phase protein marker of inflammation. In the recent years, clinical observations have reported that increased serum/plasma ICAM-1 levels are positively correlated with albuminuria in the patients with type 1 (T1D) and type 2 diabetes (T2D). Genetic association studies have demonstrated that genetic polymorphisms, including SNP rs5498 (E469K, G/A), in the ICAM1 gene is associated with DKD. rs5498 is a nonsynonymous SNP and caused by substitution between E (Glu) and K (Lys) for ICAM-1 protein. In this review, we first summarized the genetic effects of ICAM1 E469K polymorphism in DKD and then demonstrated the possible changes of ICAM-1 protein crystal structures according to the genotypes of this polymorphism. Finally, we discussed the genetic effects of the ICAM1 E469K polymorphism and the biological role of increased circulating ICAM-1 protein and its formation changes in DKD.

Roflumilast counteracts DMH-induced preneoplastic colon damage in albino Wistar rats.

The study explored the chemoprophylactic potential of roflumilast against 1,2-dimethylhydrazine (DMH) actuated preneoplastic colon damage in albino Wistar rats. Animals were arbitrarily divided into five groups of six animals each. DMH was used to induce preneoplastic colon damage (20 mg/kg/7 days, subcutaneously, for 42 days). Roflumilast was administered subcutaneously at two doses (1 and 5 mg/kg/day, from day 28 to 42). At the end of the study, the animals were recorded for the electrocardiographic changes and heart rate variability (HRV) paradigms on 42nd day, using PowerLab system. Blood samples were collected from all the animals to measure hydrogen sulfide (H2S) and nitric acid. The colon tissue was dissected out and analyzed for inflammatory markers, biochemical parameters including, superoxide dismutase, thiobarbituric acid reactive substances, catalase, and glutathione reductase and histopathology. DMH caused derangement of HRV factors, abnormal antioxidant markers, and elevated levels of inflammatory markers. H2S and nitric oxide levels upsurge in DMH-treated rats and promoted preneoplastic damage. Histopathologically, loss of crypts, goblet cells, and distorted lamina propria were observed in toxic group. Treatment with roflumilast was able to curtail down oxidative stress and inflammatory markers and stabilitate the hemodynamic derangements as well as was able to restore the normal architecture of colonic mucosa. The findings from the present study conclude that treatment with roflumilast positively modulates the preneoplastic colon damage.