Cardiac End Research Articles

Prevalence of asymptomatic atrial fibrillation among multimorbid elderly patients: diagnostic implications.

Advancing age of the global population is one of the main reasons for the uprising trend in atrial fibrillation (AF) prevalence worldwide leading to a proper "AF epidemic". Strictly related to the increasing prevalence of AF in the elderly is the relevant burden of cardiac end extra-cardiac comorbidities that these patients show. Patients with AF are frequently asymptomatic (i.e., asymptomatic or silent AF) and thus the arrhythmia is generally underdiagnosed. Detainment of proper treatment in elderly and comorbid patients may potentially result in significant morbidity and mortality. Therefore, in recent years, several screening strategies (systematic vs opportunistic screening) for asymptomatic AF have been developed and early diagnosis of AF is an important treatment goal that can improve prognosis. This review will focus on the prevalence of asymptomatic AF in the elderly, frequently associated comorbidities, screening strategies, and implications for a correct AF diagnosis.

Transient receptor potential vanilloid 1-expressing cardiac afferent nerves may contribute to cardiac hypertrophy in accompany with an increased expression of brain-derived neurotrophic factor within nucleus tractus solitarius in a pressure overload model

ABSTRACT Introduction Increased sympathetic output contributes to cardiac hypertrophy. Sympathoexcitation is induced by activating the cardiac sympathetic afferent nerves through transient receptor potential vanilloid 1 (TRPV1) in cardiac afferent endings. Brainstem nucleus tractus solitarius (NTS) receives the sensory cardiac afferent inputs. Brain-derived neurotrophic factor (BDNF) is released within NTS from sensory neurons in an activity-dependent manner. Additionally, BDNF in NTS tonically regulates sympathetic activity. Therefore, we hypothesized that TRPV1-expressing cardiac afferent nerves contribute to cardiac hypertrophy in accompany with an increased BDNF expression in NTS. Methods and Results Abdominal aortic banding (AB) or sham operation was conducted in wild-type C57BL/6 J (WT-AB) and TRPV1 knockout mice (TRPV1 KO-AB). At 8 weeks post-operation, echocardiographic left ventricular wall thickness and heart weight/body weight ratio were significantly greater in WT-AB than WT-Sham mice, and these hypertrophic indexes were attenuated in TRPV1 KO-AB mice. Among the groups, left ventricular fractional shortening was not different. The protein levels of TRPV1 in heart and BDNF in NTS were significantly increased in WT-AB compared to WT-Sham mice, whereas BDNF expression in NTS was not increased by AB in TRPV1-KO mice. Chemical ablation of TRPV1-expressing cardiac afferents attenuated the AB-induced cardiac hypertrophy and increase in BDNF in NTS. Sympathetic activity analyzed using heart rate variability, and sympathoexcitatory responses to the stimulation of cardiac afferents were increased in WT-AB compared to WT-Sham mice. Conclusion TRPV1-expressing cardiac afferent nerves may contribute to pressure overload-induced cardiac hypertrophy in accompany with the increased BDNF within NTS.

Obesity and Over-Indexation of Right Ventricular Volumes—Potential Implications for Timing of Pulmonary Valve Replacement in Patients With Tetralogy of Fallot

In patients with pulmonary regurgitation (PR) after Tetralogy of Fallot (TOF) repair, cardiac MRI-derived right ventricular end diastolic volume index (RVEDVi)>150mL per m2 of body surface area (BSA) is sometimes considered an indication for pulmonary valve replacement. BSA however varies significantly with body habitus and RVEDVi can therefore under-represent right ventricular size in obese patients.

Abstract 12327: Intravenous Waveform Analysis Correlates With Volume Status in Resuscitation in In-Vivo Rat Model

Introduction: Current volume status markers under-perform. Dynamic markers demonstrate improved outcomes in goal directed fluid therapy but maintain validity in a narrow range of clinical parameters. In addition, they assess volume responsiveness over total volume status. Repeated echo assessments may be infeasible. Hypothesis: Intravenous waveform analysis-derived F1 more closely models volume status than current markers in a rat resuscitation model. Methods: Seven Sprague Dawley rats were anesthetized and mechanically ventilated. Pressure transductions occurred via cannulation of the right femoral vein, left femoral artery and right internal jugular vein. Hemorrhage and resuscitation occurred via the left femoral vein. Heparinized rats were bled to 80% of the estimated blood volume (EBV) then resuscitated with their own whole blood in increments of 2% of the EBV until euvolemia was reached. Cardiac output (CO) and left ventricular end diastolic area (LVEDA) were calculated with echocardiography. Fast Fourier transform was performed on venous waveforms to obtain the heart rate linked F1 amplitude. Pearson’s correlation coefficients were compared using Fisher’s Z transformation. Mixed effects modeling goodness-of-fit was assessed with Akaike information criterion (AIC). Significance was set at p=.05. Results: F1 had the strongest correlation with volume status, r= .70, followed by CO, r=.55, LVEDA, r=.55, mean arterial pressure (MAP), r=.50, central venous pressure r= -.02, and pulse pressure variation (PPV), r=.01. When compared, F1 rho was significantly greater than that of all variables except CO and LVEDA, p=.09 and p=.07, respectively. In mixed effects regression, F1 displayed the most significant AIC, -274, followed by CO at -239. Conclusions: The novel marker F1 is strongly correlated with volume status during whole blood resuscitation. F1 may be superior to current markers for directing volume resuscitation therapy.

A Randomized, double-blind, dose ranging clinical trial of intravenous FDY-5301 in acute STEMI patients undergoing primary PCI

BackgroundIschemia-reperfusion injury remains a major clinical problem in patients with ST-elevation myocardial infarction (STEMI), leading to myocardial damage despite early reperfusion by primary percutaneous coronary intervention (PPCI). There are no effective therapies to limit ischemia-reperfusion injury, which is caused by multiple pathways activated by rapid tissue reoxygenation and the generation of reactive oxygen species (ROS).FDY-5301 contains sodium iodide, a ubiquitous inorganic halide and elemental reducing agent that can act as a catalytic anti-peroxidant. We tested the feasibility, safety and potential utility of FDY-5301 as a treatment to limit ischemia-reperfusion injury, in patients with first-time STEMI undergoing emergency PPCI. MethodsSTEMI patients (n = 120, median 62 years) presenting within 12 h of chest pain onset were randomized at 20 PPCI centers, in a double blind Phase 2 clinical trial, to receive FDY-5301 (0.5, 1.0 or 2.0 mg/kg) or placebo prior to reperfusion, to evaluate the feasibility endpoints. Participants underwent continuous ECG monitoring for 14 days after PPCI to address pre-specified cardiac arrhythmia safety end points and cardiac magnetic resonance imaging (MRI) at 72 h and at 3 months to assess exploratory efficacy end points. ResultsIntravenous FDY-5301 was delivered before re-opening of the infarct-related artery in 97% participants and increased plasma iodide levels ~1000-fold within 2 min. There was no significant increase in the primary safety end point of incidence of cardiac arrhythmias of concern. MRI at 3 months revealed median final infarct sizes in placebo vs. 2.0 mg/kg FDY-5301-treated patients of 14.9% vs. 8.5%, and LV ejection fractions of 53.9% vs. 63.2%, respectively, although the study was not powered to detect statistical significance. In patients receiving FDY-5301, there was a significant reduction in the levels of MPO, MMP2 and NTproBNP after PPCI, but no reduction with placebo. ConclusionsIntravenous FDY-5301, delivered immediately prior to PPCI in acute STEMI, is feasible, safe, and shows potential efficacy. A larger trial is justified to test the effects of FDY-5301 on acute ischemia-reperfusion injury and clinical outcomes.Clinical Trial Registration: CT.govNCT03470441; EudraCT 2017-000047-41

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

English

BACKGROUND Thyroid eye disease is a relatively rare condition, with an incidence of 2.9 to 16.0 cases per 100 000 population per year. Approximately 50 % of patients with Graves’ disease (GD) develop clinically apparent thyroid eye disease. It may cause severe damage to vision and orbital architecture. It is the most frequent cause of unilateral or bilateral proptosis in adults. METHODS A cross sectional study of 80 patients with GD was carried out in association with thyroid clinic of Government Medical college Thiruvananthapuram for a period of 1 year from April 2017 to March 2018. Subjects who have a prior diagnosis of Graves’ disease including those who are on antithyroid drugs were included in the study. Patients who are sick due to other systemic diseases like cardiac failure and end stage renal disease were excluded. RESULTS Eighty patients with mean age of 45.31 years were studied. Out of them, 66% were females and 34% were males. Ophthalmopathy was present in 38.8%.Majority had mild and bilateral disease (61.2 %). Only a small percentage had sight threatening disease (6.4 %).The mean age of patients with ophthalmopathy was 47.93. Major population with ophthalmopathy was females. Majority of patients with ophthalmopathy (64.5 %) retained a good visual acuity better than 6 / 9. Lid retraction was the most common manifestation among patients with Graves’ ophthalmopathy that is 74.2% followed by exophthalmos (64.5 %) and eye movement restriction and soft tissue involvement (58.1 %). Diplopia, optic nerve dysfunction were rare (3.2 %). Only 19.3 % patients had active disease according to clinical activity score. Major clinical sign of activity was redness of conjunctiva. Maximum no. of patients with active disease had a clinical activity score of 4. Smoking showed a significant association with the severity of ophthalmopathy. (p value 0.001) There was a significant association between age and activity of disease. (p value 0.021). No association was found between duration of disease with presence or severity of ophthalmopathy. There was no association between co- morbidities with presence or severity of ophthalmopathy. No association was found between hormone status and presence or severity of ophthalmopathy. CONCLUSIONS Our results indicated that the prevalence of ophthalmopathy in our population with GD evaluated at our tertiary care centre was similar to that reported in the Caucasians of European origin. Clinically active and sight threatening ophthalmopathy was uncommon. KEYWORDS Graves’ Disease, Ophthalmopathy

Involvement of Sirtuins and Klotho in Cardioprotective Effects of Exercise Training Against Waterpipe Tobacco Smoking-Induced Heart Dysfunction.

Despite its negative effect on the cardiovascular system, waterpipe smoking (WPS) is currently popular worldwide, especially among youth. This study investigated the effects of moderate endurance exercise on heart function of rats exposed to WPS and its possible mechanism. The animals were randomly divided into four groups: control group (CTL), the exercise group (Ex) which trained for 8 weeks, the waterpipe tobacco smoking group (S) exposed to smoke inhalation (30 min per day, 5 days each week, for 8 weeks), and the group that did exercise training and received waterpipe tobacco smoke inhalation together (Ex + S). One day after the last session of Ex and WPS, cardiac pressures and functional indices were recorded and calculated. The levels of SIRT1, SIRT3, Klotho, Bax, and Bcl-2 in the serum and heart, the expression of phosphorylated GSK3β of heart tissue, and cardiac histopathological changes were assessed. WPS reduced systolic pressure, +dP/dt max, -dP/dt max, and heart contractility indices (P < 0.001 vs. CTL) and increased cardiac tissue lesions (P < 0.05 vs. CTL) and end diastolic pressure and Tau index (P < 0.001 vs. CTL) of the left ventricle. Exercise training normalized the left ventricular end diastolic pressure, +dP/dt max, and contractility index. Also, exercise improved the levels of SIRT1, SIRT3, Klotho, and Bcl-2 and reduced Bax level in the heart. The findings showed that WPS causes left ventricular dysfunction. Moderate exercise prevented WPS-induced heart dysfunction partly through its anti-apoptotic features and activation of the sirtuins and Klotho pathways.

Beating Versus Arrested Heart Isolated Tricuspid Valve Surgery: Long-term Outcomes

BackgroundIsolated tricuspid valve (TV) surgery is a rare procedure generally considered at high risk for perioperative mortality and poor long-term outcomes. Surgical treatment can be performed with either an arrested heart (AH) or beating heart (BH) technique. The aim of this study was to compare the outcomes of isolated tricuspid surgery with 2 different approaches. MethodsThe Surgical-Tricuspid Study is a multicenter international retrospective study enrolling adult patients who underwent isolated TV procedures (n = 406; age 56 ± 16 years; 56% female) at 13 international sites. The AH and BH strategies were performed in 253 and 153 patients, respectively. Propensity score-matched analysis was used to compare groups. ResultsAfter matching, 129 pairs were obtained and analyzed. The 30-day mortality rate was 6.2% versus 5.0% in the AH and BH groups, respectively (P = .9). The rates of acute renal failure requiring replacement therapy (10% versus 3%; P = .02) and stroke (1.6% versus 0%; P = .08) were numerically higher in the AH group. The 6-year survival rate was 67% ± 6% versus 78% ± 5% in the AH and BH groups, respectively (P = .18), whereas freedom from cardiac death was 75% ± 5% versus 84% ± 4% (P = .21). The 6-year composite cardiac end point of cardiac death and reoperation rate was 60% ± 9% versus 86% ± 5% (P = .024) comparing AH-TV replacement and BH-TV repair groups. ConclusionsIsolated TV surgery performed with a BH strategy is a safe option and resulted in a trend of increased long-term survival and freedom from reoperation compared with the standard AH technique. Patients undergoing BH valve repair had the best long-term outcome.

Агонисты рецепторов глюкагоноподобного пептида 1 типа и новые возможности первичной профилактики сердечно-сосудистых осложнений у больных сахарным диабетом 2 типа

Objective of the Review: To present mechanisms of system and cardioprotective action of glucagon-like peptide-1 receptor agonists (GLP-1 receptor agonists); to describe their efficiency and role in primary prevention of cardiovascular complications in patients with type 2 diabetes mellitus (DM2) following large randomised clinical cardiovascular safety trials from PubMed, Cochrane Library, Google Scholar. Key Points. Clinical trials showed that GLP-1 receptor agonists can have marked positive effect for glycated haemoglobin and low-density lipoprotein cholesterol levels, systolic blood pressure, body weight, and some drugs from this group can significantly reduce the rate of primary composite cardiac end point 3P-MACE, irrespective of history of cardiovascular diseases. Conclusion. GLP-1 receptor agonists exhibit proven advantages for cardiovascular outcomes. Therefore, they are drugs of choice in therapies of DM2 patients. GLP-1 receptor agonists can increase the efficiency of not only secondary, but also primary prevention of cardiovascular complications. Keywords: diabetes mellitus, glucagon-like peptide-1 receptor agonists, cardiovascular complications, primary and secondary prevention.

Deriving a parsimonious cardiac endpoint for use in epidemiological studies of Chagas disease: results from the Retrovirus Epidemiology Donor Study-II (REDS-II) cohort.

ABSTRACTChagas cardiomyopathy (ChCM) is a severe consequence of Trypanosoma cruzi infection and has a range of electrocardiographic (ECG) and echocardiographic (ECHO) manifestations. There is a need for a standard and parsimonious research cardiac end point that does not rely on expert panel adjudication, and it is not intended to change the ChCM definition. We use data from the REDS-II cohort to propose a simplified cardiac endpoint. A total of 499 T. cruzi-seropositive blood donors were included. All participants underwent a 12-lead ECG, echocardiogram and clinical examination, and those with abnormal findings were reviewed by a panel of cardiologists who classified cases as having Chagas cardiomyopathy or not. We created an exhaustive set of ECG and ECHO finding combinations and compared these with the panel’s classification. We selected the simplest combination that most accurately reproduced the panel’s results. Individual ECG and ECHO variables had low sensitivity for panel-defined cardiomyopathy. The best performing combination was right bundle branch block and/or ECHO evidence of left ventricular hypocontractility. This combination had 98% specificity and 85% sensitivity for panel-defined ChCM. It was not possible to improve the overall accuracy by addition of any other ECG or ECHO variable. Substituting right bundle branch block for the more inclusive finding of QRS interval > 120 ms produced similar results. The combination of prolonged QRS interval and/or left ventricular hypocontractility closely reproduced the REDS-II expert panel classification of Chagas ChCM. In conclusion, the simple and reproducible research endpoint proposed here captures most of the spectrum of cardiac abnormalities in Chagas disease.

Blood norepinephrine/epinephrine/dopamine measurements in 108 patients with takotsubo syndrome from the world literature: pathophysiological implications

Objectives Release of norepinephrine (NE) from neuronal cardiac nerve endings and/or blood-borne catecholamines (CATs), mainly epinephrine (EPI), may mediate TTS. The aim of this study was to document the levels of NE, EPI, and dopamine (DA) in patients with TTS. Materials and methods A qualitative/quantitative meta-analysis of CATs and their relationship to age, gender, and triggers, was carried out, employing the world literature on TTS, published in PubMed. Results NE/EPI/DA in108 patients with TTS, 65.2 ± 16.4 years old, 89 (82.4%) women, revealed that: NE was measured more frequently than EPI, and EPI than DA; the timing of the measurements was variable; CATs were reported variably (qualitatively/quantitatively/with/without upper limits of normal); NE/EPI or NE/EPI/DA rose to the same degree; CATs were normal, or mildly/moderately elevated, with only 6 patients showing markedly elevated NE/EP/DA; NE, EPI, and DA were similar in patients with physical triggers and NE was similar in patients with physical, emotional, or no triggers (p = 0.47); EPI was higher than NE in patients with emotional triggers and EPI was higher in patients with emotional than physical triggers (p = 0.012); NE, EPI, and DA rose to the same proportion in men and women; types of TTS triggers were distributed proportionally in men and women. Conclusion NE, EPI, and DA rise proportionally in patients with TTS; CATs are mildly/moderately, and rarely markedly elevated; measurements of CATs should become more systematised; although CATs may not be essential for TTS diagnosis, they may contribute to prognosis and elucidation of the pathophysiology of TTS.

Targeting the eCIRP/TREM-1 interaction with a small molecule inhibitor improves cardiac dysfunction in neonatal sepsis

BackgroundNeonatal sepsis and the associated myocardial dysfunction remain a leading cause of infant mortality. Extracellular cold-inducible RNA-binding protein (eCIRP) acts as a ligand of triggering receptor expressed on myeloid cells-1 (TREM-1). M3 is a small CIRP-derived peptide that inhibits the eCIRP/TREM-1 interaction. We hypothesize that the eCIRP/TREM-1 interaction in cardiomyocytes contributes to sepsis-induced cardiac dysfunction in neonatal sepsis, while M3 is cardioprotective.MethodsSerum was collected from neonates in the Neonatal Intensive Care Unit (NICU). 5–7-day old C57BL/6 mouse pups were used in this study. Primary murine neonatal cardiomyocytes were stimulated with recombinant murine (rm) CIRP with M3. TREM-1 mRNA and supernatant cytokine levels were assayed. Mitochondrial oxidative stress, ROS, and membrane potential were assayed. Neonatal mice were injected with rmCIRP and speckle-tracking echocardiography was conducted to measure cardiac strain. Sepsis was induced by i.p. cecal slurry. Mouse pups were treated with M3 or vehicle. After 16 h, echocardiography was performed followed by euthanasia for tissue analysis. A 7-day survival study was conducted.ResultsSerum eCIRP levels were elevated in septic human neonates. rmCIRP stimulation of cardiomyocytes increased TREM-1 gene expression. Stimulation of cardiomyocytes with rmCIRP upregulated TNF-α and IL-6 in the supernatants, while this upregulation was inhibited by M3. Stimulation of cardiomyocytes with rmCIRP resulted in a reduction in mitochondrial membrane potential (MMP) while M3 treatment returned MMP to near baseline. rmCIRP caused mitochondrial calcium overload; this was inhibited by M3. rmCIRP injection impaired longitudinal and radial cardiac strain. Sepsis resulted in cardiac dysfunction with a reduction in cardiac output and left ventricular end diastolic diameter. Both were improved by M3 treatment. Treatment with M3 attenuated serum, cardiac, and pulmonary levels of pro-inflammatory cytokines compared to vehicle-treated septic neonates. M3 dramatically increased sepsis survival.ConclusionsInhibition of eCIRP/TREM-1 interaction with M3 is cardioprotective, decreases inflammation, and improves survival in neonatal sepsis.Trial registration Retrospectively registered.

Low levels of fine particulate matter increase vascular damage and reduce pulmonary function in young healthy adults

BackgroundFine particulate matter (PM2.5) related mild inflammation, altered autonomic control of cardiovascular function, and changes to cell function have been observed in controlled human exposure studies.MethodsTo measure the systemic and cardiopulmonary impacts of low-level PM exposure, we exposed 20 healthy, young volunteers to PM2.5, in the form of concentrated ambient particles (mean: 37.8 μg/m3, SD 6.5), and filtered air (mean: 2.1 μg/m3, SD 2.6). In this double-blind, crossover study the exposure order was randomized. During the 4 h exposure, volunteers (7 females and 13 males) underwent light intensity exercise to regulate ventilation rate. We measured pulmonary, cardiac, and hematologic end points before exposure, 1 h after exposure, and again 20 h after exposure.ResultsLow-level PM2.5 resulted in both pulmonary and extra-pulmonary changes characterized by alterations in systematic inflammation markers, cardiac repolarization, and decreased pulmonary function. A mean increase in PM2.5 concentration (37.8 μg/m3) significantly increased serum amyloid A (SAA), C-reactive protein (CRP), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1), 1 h after exposure by 8.7, 9.1, 10.7, and 6.6%, respectively, relative to the filtered air control. SAA remained significantly elevated (34.6%) 20 h after PM2.5 exposure which was accompanied by a 5.7% decrease in percent neutrophils. Decreased pulmonary function was observed 1 h after exposure through a 0.8 and 1.2% decrease in forced expiratory volume in 1 s (FEV1) and FEV1/ forced vital capacity (FEV1/FVC) respectively. Additionally, sex specific changes were observed in repolarization outcomes following PM2.5 exposure. In males, P-wave and QRS complex were increased by 15.4 and 5.4% 1 h after exposure.ConclusionsThis study is the first controlled human exposure study to demonstrate biological effects in response to exposure to concentrated ambient air PM2.5 particles at levels near the PM2.5 US NAAQS standard.Clinical trial registration informationclinicaltrials.gov; Identifier: NCT03232086. The study was registered retrospectively on July 25, 2017, prior to final data collection on October 25, 2017 and data analysis.

Identification of Cardiac Expression Pattern of Transient Receptor Potential Vanilloid Type 1 (TRPV1) Receptor using a Transgenic Reporter Mouse Model

Transient receptor potential vanilloid type 1 (TRPV1) channels are structurally related, non-selective cation channels that exhibit a high permeability to calcium. Sensory nerve endings expressing TRPV1 channels play a prominent role in regulating the cardiac sympathetic afferent reflex and contribute to cardiac remodeling and dysfunction in chronic heart failure. However, the precise expression of TRPV1 channels in cardiomyocytes vs. non-cardiomyocytes remains debated. Here we utilized a tdTomato-GFP reporter mouse crossed with a mouse line expressing Cre recombinase under the control of the TRPV1 promoter to map the TRPV1 expression pattern in heart. In this model, TRPV1-negative cells express tdTomato protein (red), whereas TRPV1-positive cells express GFP protein (green). As we expected, substantial GFP expression was found in many small and medium diameter dorsal root ganglia neurons in heterozygous TRPV1-Cre +/-, tdTomato flox/flox +/- male mice, suggesting that this heterozygous model is sufficient for labeling TRPV1-positive cells. Furthermore, these results showed that GFP green staining was not detectable in cardiomyocytes. Instead, we found strong GFP green staining in cardiac blood vessels—thought to be arterioles—in the heart. We also observed strong GFP signals on PGP9.5-positive cardiac nerve endings in the epicardium. In summary, this study does not support the concept that TRPV1 channels are strongly expressed in mouse cardiomyocytes. We conclude that TRPV1 channels in mouse heart are mostly expressed on non-cardiomyocyte cells including cardiac nerve endings and vessels. These data have important implications for the modulations of cardiogenic reflexes.

Systems Toxicology Approach for Testing Chemical Cardiotoxicity in Larval Zebrafish.

Transcriptomic approaches can give insight into molecular mechanisms underlying chemical toxicity and are increasingly being used as part of toxicological assessments. To aid the interpretation of transcriptomic data, we have developed a systems toxicology method that relies on a computable biological network model. We created the first network model describing cardiotoxicity in zebrafish larvae-a valuable emerging model species in testing cardiotoxicity associated with drugs and chemicals. The network is based on scientific literature and represents hierarchical molecular pathways that lead from receptor activation to cardiac pathologies. To test the ability of our approach to detect cardiotoxic outcomes from transcriptomic data, we have selected three publicly available data sets that reported chemically induced heart pathologies in zebrafish larvae for five different chemicals. Network-based analysis detected cardiac perturbations for four out of five chemicals tested, for two of them using transcriptomic data collected up to 3 days before the onset of a visible phenotype. Additionally, we identified distinct molecular pathways that were activated by the different chemicals. The results demonstrate that the proposed integrational method can be used for evaluating the effects of chemicals on the zebrafish cardiac function and, together with observed cardiac apical end points, can provide a comprehensive method for connecting molecular events to organ toxicity. The computable network model is freely available and may be used to generate mechanistic hypotheses and quantifiable perturbation values from any zebrafish transcriptomic data.

Hollow Viscus Injuries Due To Trauma

Background: Hollow viscus injuries can be due to traffic accidents, fall from the height, and fall of heavy objects leading to trauma. Abdominal trauma is the most common with Injuries pertaining to Gastro-Intestinal tract from the cardiac end of the esophagus to the anus, gall bladder, and biliary tract and lower genitourinary tract. The aim of the study is to study the modes of trauma, clinical features of hollow viscus injuries, and the diagnosis and management of hollow viscus injuries. Subjects and Methods: This was a hospital-based cross-sectional study. conducted over a period of one year from June 2018 – May 2019. at Department of General Surgery on 90 patients with hollow viscus injury. After initial resuscitation of the trauma victims, a careful history was taken to document any associated medical problem. The collected data was analyzed with respect to the presentation by the patient’s age and sex incidence, etiologies, pathological features, morbidity, and mortality associated with causation and management. The ultrasound and CT- Scan were done to assess the injury and plan accordingly before taking up for the surgery. Results: The majority of the patients belonged to the age group of 21 – 30 years and the least pertaining to the age group of 41 – 50 years of age group. The Incidence in Males is much more than females. The males were 74% and females were 26%. The most common causative agent of hollow viscous injury was a Road traffic accident with 59%. Majority of the patients who were admitted more than 24 hours after the injury, the mortality rate was much higher compared to the patients who were admitted in less than 24 hours of the trauma. Conclusion: HVI is a dangerous condition. High mortality rates represent the seriousness of HVI and related injuries. Patients of HVI should be carefully monitored for associated injuries and complications.

Appropriate assessment method of 123I-MIBG myocardial scintigraphy for the diagnosis of Lewy body diseases and idiopathic REM sleep behavior disorder.

In 123I-metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy, the early heart-to-mediastinum (H/M) ratio is considered to reflect the density of the cardiac sympathetic nerve endings, washout rate (WR) is an indicator of the cardiac sympathetic tone, and the delayed H/M ratio reflects both. The Delayed H/M ratio is usually used to support the diagnosis of Lewy body diseases (LBDs) and idiopathic REM sleep behavior disorder (iRBD); however, which values should be used have not been specified. Here, we hypothesized that the combination of these values is appropriate for the diagnostic purpose. In this single-center retrospective cohort study, we recruited 106 patients with LBDs or iRBD and 33 patients without those diseases, of whom we reviewed the 123I-MIBG myocardial scintigraphy results. Sensitivity/specificity to diagnose LBDs and iRBD were 0.77/0.94 for the early H/M ratio (≤ 2.0), 0.82/0.94 for the delayed H/M ratio (≤ 2.0), and 0.89/0.91 for WR (≥ 23.0). When patients were considered positive if at least either the early H/M ratio or WR was abnormal, the sensitivity significantly increased to 0.97, whereas the specificity remained similar at 0.91. Furthermore, our subgroup analyses revealed that WR enhancement preceded H/M ratio reduction, but, in patients with a severely reduced early H/M ratio, paradoxically normal WR could be observed. We propose the highly sensitive, combined early H/M ratio and WR assessments for 123I-MIBG myocardial scintigraphy. The temporal precedence of cardiac sympathetic dysfunction over denervation and the floor effect in 123I-MIBG uptake may underlie the sensitivity improvement.

Cardiac-gated intracranial elastance in a swine model of raised intracranial pressure: a novel method to assess intracranial pressure-volume dynamics.

Previous studies have demonstrated the importance of intracranial elastance; however, methodological difficulties have limited widespread clinical use. Measuring elastance may offer potential benefit in helping to identify patients at risk for untoward intracranial pressure (ICP) elevation from small rises in intracranial volume. The authors sought to develop an easily used method that accounts for the changing ICP that occurs over a cardiac cycle and to assess this method in a large-animal model over a broad range of ICPs. The authors used their previously described cardiac-gated intracranial balloon pump and swine model of cerebral edema. In the present experiment they measured elastance at 4 points along the cardiac cycle-early systole, peak systole, mid-diastole, and end diastole-by using rapid balloon inflation to 1 ml over an ICP range of 10-30 mm Hg. The authors studied 7 swine with increasing cerebral edema. Intracranial elastance rose progressively with increasing ICP. Peak-systolic and end-diastolic elastance demonstrated the most consistent rise in elastance as ICP increased. Cardiac-gated elastance measurements had markedly lower variance within swine compared with non-cardiac-gated measures. The slope of the ICP-elastance curve differed between swine. At ICP between 20 and 25 mm Hg, elastance varied between 8.7 and 15.8 mm Hg/ml, indicating that ICP alone cannot accurately predict intracranial elastance. Measuring intracranial elastance in a cardiac-gated manner is feasible and may offer an improved precision of measure. The authors' preliminary data suggest that because elastance values may vary at similar ICP levels, ICP alone may not necessarily best reflect the state of intracranial volume reserve capacity. Paired ICP-elastance measurements may offer benefit as an adjunct "early warning monitor" alerting to the risk of untoward ICP elevation in brain-injured patients that is induced by small increases in intracranial volume.

SAT-496 Acute GI Bleed Associated with Myxedemic Coma: Yes It Still Exists!

Introduction: Myxedemic coma is a life-threatening medical emergency. It needs to be treated emergently & carries very high mortality. It involves multi-organ failure at cellular level due to severe thyroid hormone deficiency. Most common clinical presentation involves CVS. With advancement in health care it is now uncommon to see myxedemic coma especially associated with GI Bleed. Here in we present an interesting case of GI bleed associated with myxedemic coma. Case: 84 years old male was discovered in home, minimally responsive. EMS intubated & brought him to ED with agonal respirations, hypotensive & unresponsive, He was admitted to ICU. Past medical history was significant for smoking & hypertension. Physical Exam was significant for dryness of skin, obtundation, hypothermia, tachypnea & BMI >30. Initial Labs revealed anemia with Hemoglobin of 5.1mg/dL, Hematocrit 17.5%, Hyponatremia-134meq/L, Hyperkalemia-K+ levels 5.3meq/L, BUN-84mg/dL & creatinine-4.1mg/dL, His serum TSH levels were 352 mIU/ml with low free T4 and T3 levels at 0.15ng/dl and 1.99pg/ml, respectively. Stool was positive with Blood. IV fluids were given.GI was consulted. He underwent emergent upper GI endoscopy, which found the Dieulafoy’s lesion at cardiac end of stomach & treated with a combination of epinephrine injection, argon laser, & 3 hemo-clips. He had 6 PRBCs transfused. He was started on IV Thyroxine, Liothyronine and Hydrocortisone. His mental status improved, & hemoglobin remained relatively stable. Later on, he decided to move to palliative care & was discharged to hospice. Discussion: Myxedemic coma is a term generally used to denote most severe decompensated hypothyroidism. The typical progression is lethargy evolving into a stupor & eventually into a coma with respiratory failure and hypothermia. It can lead to volume depletion, hyponatremia, & AKI, which can worsen to ATN if prolonged ischemia remains.GI bleed is a rare manifestation of myxedemic coma. Pathophysiology of GI bleed in these patients involves mucosal edema & mucopolysaccharide infiltration. Also, myxedemic coma is associated with neurological changes resulting in slow peristalsis & GI atony. This coupled with coagulopathy associated with decompensated hypothyroidism results in increased risk of bleeding. Dieulfoy’s lesion are rare cause of GI bleed. Stress & ischemic changes are one of the inciting factors for these lesions. These lesions are more common in elderly males & are associated with severe systemic illness similar to our patient. Treatment is usually supportive with goal of identifying the lesions, stopping the bleed & aggressively managing myxedemic coma. We present an interesting case of GI bleed associated with myxedemic coma now relatively uncommon with advancement in healthcare. It provides an excellent learning opportunity for clinicians to consider while managing these patients.