End-organ Dysfunction Research Articles

Prognostic value of MELD-XI score and hemodynamic parameters in patients undergoing transcatheter tricuspid valve intervention

Abstract Background Hepatorenal dysfunction is a strong prognostic predictor in patients with tricuspid regurgitation. Patients are often hospitalized with acute heart failure due to volume overload and peripheral hypoperfusion. End-organ dysfunction is associated with the development of right ventricular failure related to hemodynamic changes such as low cardiac output and passive congestion from increased right ventricular filling pressures. Purpose This study aimed to investigate the prognostic value of hepatorenal dysfunction using the Model for End-stage Liver Disease (MELD) Score, the modified version of the score, MELD-XI, and of parameters determined during right-heart catheterization in patients undergoing transcatheter tricuspid valve intervention. Methods In this single-center prospective cohort study, data from patients undergoing edge-to-edge repair or heterotopic minimal invasive tricuspid valve repair were analyzed. Serum creatinine, INR and bilirubin were measured and the MELD score as well as the MELD XI score was calculated. All patients underwent right heart catheterization before the intervention. Receiver operator characteristics with calculation of the area under the curve (AUC) were performed to determine the predictive value of MELD (XI) score and hemodynamic parameters for the combined endpoint of rehospitalization due to decompensated heart failure and mortality within 3 months. Results Data from 36 consecutive patients were analyzed. 28 patients underwent edge-to-edge repair and 8 patients heterotopic minimal invasive tricuspid valve repair. Mean age of patients was 80.2 ± 5.9 years; 33.3% (12/36) were male. Baseline characteristics are shown in table 1. Rehospitalization due to decompensated heart failure occurred in 9/36 patients (25%). Mortality within the first 3 months was 11% (4/36). The predictive value for the composite endpoint of the modified MELD IX score was AUC 0.82 (95 % CI 0.63-0.99; p=0.009), while the conventional MELD score had an AUC of 0.77 (95 % CI 0.55-0.99; p = 0.059) (figure 1). RV pressure (AUC 0.84, 95% CI 0.66-1.00, p= 0.012) and RA pressure (AUC 0.83, 95% CI 0.67-0.98, p=0.016) showed a good predictive value for the composite endpoint (figure 2). The combination of MELD XI (at admission) and RV or PA pressure improved the AUC (MELD XI + RV: AUC 0.85; MELD XI + PA: AUC 0.84). Conclusion In this pilot-study, the modified MELD XI score, as indicator of hepatorenal dysfunction, was identified as a potential marker for short-term outcome after interventional tricuspid valve treatment.

Biomarkers of cardiohepatic syndrome in the cardiac intensive care unit

Abstract Introduction Non-cardiovascular end-organ dysfunction is an important determinant of outcomes in cardiac intensive care unit (CICU) patients. We examined the association between in-hospital mortality with the severity and extent of admission liver function test (LFT) abnormalities in a heterogeneous CICU population. Purpose We hypothesized that a greater severity or extent of LFT abnormalities would be associated with higher in-hospital mortality. Methods We included consecutive unique adult CICU patients with available data for one or more of the admission LFT values of interest. Admission laboratory values were defined as those closest to CICU admission. We used the NIH Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 to categorize the severity of each LFT abnormality from Grade 0 (normal) to Grade 4 (life-threatening). We defined the extent of LFT abnormality as the number of individual LFTs meeting criteria for CTCAE Grade 1 or greater. The primary outcome of interest was all-cause in-hospital mortality. Odds ratio (OR) and 95% confidence interval (CI) values for in-hospital mortality were estimated using logistic regression, before and after multivariable adjustment. Results Of 12,428 unique CICU patients, 5,144 were excluded due to a lack of available data for any admission LFT values. The remaining 7,284 patients comprised the final study population. Among patients with available data for each individual LFT, abnormal values were present in: AST, 2,743/5,733 (47.8%); ALT 1,576/5,512 (28.6%); ALK 611/3,684 (16.6%); and TB 898/5,155 (17.4%). A total of 864 (11.9%) patients died during hospitalization. In-hospital mortality was higher for patients with one or more LFTs meeting criteria for CTCAE Grade 1 or greater (17.9% vs. 6.4%, adjusted OR 1.54 [1.27-1.86], p <0.001). A stepwise increase in in-hospital mortality was observed with increasing CTCAE grade, both overall (adjusted OR 1.25 per each higher CTCAE grade [1.16-1.34], p <0.001); (Figure 1A), and for each individual LFT (Figure 1B). Conclusion Cardiohepatic syndrome is an important predictor of prognosis in CICU patients, as the extent and severity of LFT abnormalities are strongly associated with in-hospital mortality. This is the first large-scale study to examine the association between the magnitude of hepatic biomarker derangement with in-hospital mortality in unselected CICU patients. Patients with markedly elevated LFT values exhibited the highest risk of in-hospital mortality. This analysis advocates for the inclusion of commonly obtained LFTs in future risk-prediction tools for enhanced prognostication.

Adolescent and Young Adult Development in Transplant Recipients.

Solid organ transplantation (SOT) is the gold standard of therapy for individuals with end-organ dysfunction. Improved survival outcomes after SOT can help adolescent and young adult (AYA) recipients lead long and healthy life. However, successful SOT during adolescence and young adulthood is often complicated by the innate developmental challenges of this age group. The psychosocial tasks of adolescence include identity development, autonomous decision-making, establishing social networks, educational and vocational preparation, and navigating romantic relationships. These goals may be amplified or delayed for pediatric SOT recipients. Adolescence is also marked by rapid physical changes in linear growth and the development of secondary sexual characteristics. Yet AYA may experience physical and pubertal delays related to transplantation, as well as exaggerated body image dissatisfaction due to medication side effects. Strict adherence to medication and post-transplant regimens may interfere with adolescents' desire for normalcy and fitting in with peers. Healthcare providers should be aware that AYA value education and self-empowerment in transplant care. Transplant success needs to be defined by both medical and psychosocial outcomes, particularly when it relates to the vulnerable AYA population. Fortunately, investment from the patient, family, and care team can aid in transplant recovery and success. This article will identify the developmental challenges faced by AYA undergoing solid organ transplantation as well as strategies to engage positive outcomes.

7335 Myxedema Coma in an Adolescent Patient: A rare, lethal manifestation of profound hypothyroidism

Abstract Disclosure: C. Rodriguez: None. E.M. Mejias: None. L.R. Berrios: None. C. Currais: None. Myxedema coma is a rare, life-threatening condition that represents the most severe manifestation of profound hypothyroidism. It is characterized by extensive end-organ dysfunction. Therefore, it is crucial to have a high index of suspicion in order to identify it promptly and initiate treatment. We report a case of an adolescent patient with past medical history of Type 1 Diabetes Mellitus and hypothyroidism who was initially admitted to pediatric wards due to hypertension, constipation and acute kidney injury (AKI). The patient was transferred to the pediatric intensive care unit (PICU) after he developed multi-organ failure secondary to myxedema coma. His laboratory work up was remarkable for severe hypothyroidism with a thyroid-stimulating hormone (TSH) > 679, uncontrolled diabetes mellitus (Glycosylated Hemoglobin 13.1%) and chronic kidney disease (Creatinine 2.56). During his hospital course, he required long term hemodialysis, mechanical ventilation and underwent cardiorespiratory resuscitation multiple times. Since myxedema coma is an uncommon manifestation of pediatric hypothyroidism, pediatric guidelines are not available. We aim to reinforce the awareness of myxedema coma and encourage physicians to have a high index of suspicion as the widespread availability of TSH assays and its use can aid in the diagnosis and treatment of these patients. Furthermore, we emphasize an interdisciplinary approach to avoid mortality and long-term complications. Presentation: 6/1/2024

6423 The Storm in a Healthy 26-year-old Hispanic Female

Abstract Disclosure: P.M. Reyes-Torres: None. M. Hernandez-Hernandez: None. Uncontrolled hyperthyroidism can cause thyrotoxicosis and lead to end-organ dysfunction known as thyroid storm. The incidence is .20 and .76 per 100,000 persons per year, with an incidence of 4.8–5.6 per 100,000 hospitalized patients. Of those hospitalized with thyrotoxicosis in the U.S., thyroid storm is diagnosed in 16%. Most commonly affects females, middle-aged patients, and Caucasians. Can be precipitated by acute illnesses, surgery, or non-compliance with medications. Symptoms are characterized by fever, cardiac and gastrointestinal dysfunction, and altered mentation along with impaired thyroid function tests.A 26-year-old Hispanic female presented to our ER complaining of palpitations, general malaise, dysphagia, and fevers after attending a social event 3 days before. Physical examination revealed a fever of 101F, restless patient with pressured speech, and diffusely enlarged non-tender thyroid without discrete nodules. Labs were remarkable for WBC: 12 000, urinalysis, b-HCG, and CXR were all negative. Burch-Wartofsky Point Scale: 55 and biochemical tests (TSH: 0.005 ml/UL, free T4 >5 ng/dL, Total T3: 8.5 ng/mL, Total T4: 28.87 uG/DL, Thyroglobulin 34.81 ng/mL) for which diagnosis of thyroid storm was made. She was transferred to the ICU and treatment was initiated with fluids, Propranolol 60 mg PO q4hrs, PTU 250 mg PO q4hrs, and Hydrocortisone 300 mg IV as loading dose then 100mg IV q8hrs. TSI and TRAb were ordered. Thyroid US remarkable for bulky thyroid gland with heterogeneous, increased vascularity, no obvious cystic/solid lesions seen. Repeated tests showed a decreasing trend of free T4: 4.71 ng/dL and Total T3: 2.42ng/dL for which PTU was discontinued and Methimazole 15 mg PO BID was started. Five days after treatment started, the patient continued symptom-free and was discharged with Propranolol 60 mg PO q6hrs and Methimazole 15 mg PO BID. TSI and TRAb samples were obtained but results were pending before discharge. Follow-up was scheduled in 2 weeks with routine labs but the patient was lost to follow-up.This case highlights the importance of early recognition and treatment of thyroid storm in Hispanics, undiagnosed patients given the presenting nonspecific, life-threatening symptoms. We conclude that our patient's cause of thyrotoxicosis was an undiagnosed case of Graves Disease and the storm was most likely triggered by an upper viral respiratory tract infection. This case could potentially help physicians identify hyperthyroidism in an earlier phase, reducing incidence, mortality, and hospitalizations of thyroid storm since a variety of mimics make the diagnosis challenging. Furthermore, we could contribute to updated statistical knowledge regarding the risk of patients with thyrotoxicosis developing thyroid storm which despite advancements in technology, are currently lacking. Presentation: 6/1/2024

A-313 Use of the Preeclampsia Ratio in the Prognosis of Preterm Delivery and Adverse Outcomes

Abstract Background Preeclampsia (PE) is a hypertensive disorder of pregnancy that is characterized by high blood pressure and end-organ dysfunction with or without proteinuria after 20 weeks gestation. PE occurs in 6-8% of pregnancies and contributes to significant fetal, neonatal, and maternal morbidity and mortality. The ratio of two angiogenic placental proteins, soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF), are used in the management of PE. The purpose of this study was to evaluate use of the sFlt-1/PlGF ratio (PE ratio) generated using the ADVIA Centaur® and Atellica® IM sFlt-1 assay and the ADVIA Centaur and Atellica IM PlGF assays in the prognosis of preterm delivery and adverse outcomes in women presenting with signs and symptoms of PE. Methods A total of 654 females with singleton pregnancies between gestational weeks 20+0 days and 35+6 days and who had signs and symptoms of PE, but without severe features of PE were enrolled at 24 collection sites and followed prospectively for two weeks. Serum samples were collected at enrollment and adverse outcomes that included preterm delivery were prospectively collected within the two weeks after enrollment. Serum samples from approximately half of the population (n=316) were tested in singlicate using the sFlt-1 and PlGF assays on the ADVIA Centaur system in a derivation study that determined the optimal cutoff of the PE ratio in relation to adverse outcome. The remaining serum samples (n=338) were subsequently tested on the ADVIA Centaur system in a cut-off validation study that evaluated the clinical performance (sensitivity [SE], specificity [SP], positive predictive value [PPV], negative predictive value [NPV]) of the PE ratio at the derived cutoff in relation to adverse outcome. Method comparison studies were performed between the ADVIA Centaur versus the Roche Elecsys sFlt-1 and PlGF assays (n=255) and the ADVIA Centaur versus the Atellica IM sFlt-1 and PlGF assays (n=316). Results The rate of maternal adverse outcomes within two weeks was similar in the derivation study (32.3%) and validation study (28.1%). Using a receiver operating characteristic (ROC) curve analysis with the derivation cohort, a derived cutoff of 38 showed optimal clinical performance of the PE ratio in relation to adverse outcome (SE=72.5%, SP=94.7%, PPV=84.6%, NPV=89.5%). Similar clinical performance results of the PE ratio at the cutoff of 38 in relation to adverse outcome were found with the verification cohort (SE=88.42%, SP=87.65%, PPV=73.68%, NPV=95.09%). Weighted Deming regression analysis demonstrated equivalency between the Centaur, Roche, and Atellica PE ratios with correlation coefficients (r) of 0.9242 (Centaur vs Roche) and 0.995 (Centaur vs Atellica). Conclusions Measurement of sFlt-1 and PlGF to determine PE ratio can be performed on either the ADVIA Centaur or Atellica Analyzer and can be used to identify women presenting with PE or signs and symptoms of PE who are at high risk of experiencing an adverse event in the subsequent two weeks. Not available for sale in the U.S.A. The products/features mentioned herein are not commercially available in all countries. Their future availability cannot be guaranteed.

Ameliorative Review on Exploration of Spices in Aspects of Phytochemical Screening for their Antidiabetic Action

Diabetes is a diverse group of disorder characterized by hyperglycemia due to an deficiency in insulin production. Diabetes mellitus's chronic hyperglycemia is linked to end organ damage, dysfunction, and failure, including blood vessel, kidney, retina, and nervous system. With over 62 million cases of diabetes being identified in India, the disease is rapidly turning into a true epidemic. The majority of synthetic oral hypoglycemic medications available for the disease's treatment are costly, have significant adverse effects, and/or cannot be used while pregnant. As a result, a growing number of people worldwide are turning to traditional herbal remedies to prevent and treat diabetes. Spices having antioxidant, hypoglycemic, and hypolipidemic characteristics may be effective in the therapy of diabetes. As a result, these spices are growing in popularity due to their potential efficacy, little to nonexistent adverse effects, and synergistic effects. Spices are compounds used in food as coloring, flavoring, or preservation. They might be fresh or dried seeds, bark, roots, fruits, or even vegetables. This paper includes phytochemical screening of spices which have crucial role in the treatment of diabetis mellitus.

Clinical characteristics and outcomes in middle-aged Fontan patients

BackgroundMiddle-aged Fontan patients are underrepresented in contemporary studies. The purpose of this study was to describe the clinical characteristics and outcomes in middle-aged patients with Fontan palliation. MethodsAll adults with Fontan palliation were divided into ‘middle-aged’ group (>40 years of age at baseline encounter), and ‘young adult’ group. Clinical characteristics were assessed across multiple domains (atrial arrhythmias, heart failure, and hepatorenal function). Clinical outcomes were assessed as composite outcome of death/heart transplant. ResultsOf 455 adults (median age 26 years), 63 (14 %) were middle-aged adults while 392 (86 %) were young adults. Compared to the young adult group, the middle-aged group had a higher prevalence of atrial arrhythmias, greater neurohormonal activation, and worse hepatorenal function. Of 63 patients in the middle-aged group, 26 (41 %) patients died, and 4 (6 %) patients underwent heart transplant. The middle-aged group had a higher 5-year cumulative incidence of death/transplant (45 % versus 21 %, p < 0.001), and 10-year cumulative incidence of death/transplant (64 % versus 29 %, p < 0.001) compared to the young adult group. Higher pulmonary artery wedge pressure (hazard ratio 1.18 [1.09–1.27]), and higher model for end-stage liver disease excluding international normalized ratio score (hazard ratio 1.07, [1.03–1.14]), were associated with death/transplant. ConclusionsAbout 14 % of adults with Fontan palliation were middle-aged, and these patients had higher prevalence of cardiovascular comorbidities, hepatorenal dysfunction, and mortality. These data underscore the need for better risk stratification strategies to identify patients at risk for adverse outcomes and allow for early referral for transplant evaluation in this emerging subpopulation. Clinical summaryThe purpose of this study was to describe the clinical characteristics (comorbidities and end-organ dysfunction) and outcomes (death/transplant) in middle-aged patients with Fontan palliation. Of 455 patients (median age 26 years), 63 (14 %) were middle-aged adults while 392 (86 %) were young adults. Compared to the young adult group, the middle-aged group had a higher prevalence of atrial arrhythmias, greater neurohormonal activation, worse hepatorenal function, and higher risk of death/transplant. The correlates of death/transplant were higher pulmonary artery wedge pressure and hepatorenal dysfunction. These data underscore the need for better risk stratification in this emerging population.

REBOA in trauma: a life-saving intervention or a spectacular failure?

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a controversial haemorrhage control intervention often touted as the bridge to definitive haemorrhage control. This review summarizes the evolution of REBOA from its inception to the latest applications with an emphasis on clinical outcomes. This is a narrative review based on a selective review of the literature. REBOA remains a rarely utilized intervention in trauma patients. Complications have remained consistent over time despite purported improvements in catheter technology. Ischemia-reperfusion injuries, end-organ dysfunction, limb ischemia, and amputations have all been reported. Evidence-based guidelines are lacking, and appropriate indications and the ideal patient population for this intervention are yet to be defined. Despite the hype, purported technological advancements, and the mirage of high-quality studies over the last decade, REBOA has failed to keep up to its expectations. The quest to find the solution for uncontrolled NCTH remains unsolved.

Abstract MP28: Advanced Lipid Status Parameters in Women With Preeclampsia

Preeclampsia (PE) is a hypertensive disorder associated with pregnancy, usually occurring after the 20th week of gestation, followed by proteinuria or signs of end-organ dysfunction. Early-onset preeclampsia is associated with placental dysfunction, while late-onset preeclampsia is recognized as a maternal disorder, influenced by risk factors like maternal obesity, diabetes mellitus, or chronic hypertension. During physiological pregnancy, lipid metabolism changes to adequately supply the fetoplacental unit with nutrients and energy, consequently changing the composition of LDL and HDL particles. However, in preeclampsia, these changes become atherogenic. The study aimed to examine changes in advanced lipid status parameter concentrations and the dominant diameter of LDL and HDL particles during pregnancies affected by PE. In this study, 92 pregnant women at high risk for complication development were followed longitudinally throughout the first (T1), second (T2), and third (T3) trimesters. They were classified into high-risk (HR) (72 women) and PE (20 women) groups based on pregnancy outcomes. Total cholesterol (TC), HDL-C, triglycerides (TG), apoAI, and apoB concentrations were measured using commercial kits, while LDL-C concentrations and the atherogenic index of plasma (AIP) were calculated using established equations. Dominant LDL and HDL particle sizes were determined by gradient gel electrophoresis. TG levels were significantly higher in the PE group compared to the HR group across all trimesters (p&lt;0.05; p&lt;0.05; p&lt;0.01), while AIP was significantly elevated in T2 (p&lt;0.01) and T3 (p&lt;0.01). HDL-C levels were lower in the PE group than in the HR group in T2 (p&lt;0.05). In the HR group during pregnancy, concentrations of TC, TG, LDL-C, apoB, as well as HDL-C increased significantly (p&lt;0.05 for all parameters), while the dominant LDL diameter decreased markedly (p&lt;0.001) between all trimesters, without changes in the dominant HDL diameter. There were no changes in HDL-C concentration during pregnancy in the PE group. In contrast, TG concentrations increased significantly (p&lt;0.01), accompanied by a significant decrease in dominant LDL particle diameter (p&lt;0.05). In conclusion, pregnant women with PE exhibit atherogenic changes in lipid status parameters, including no increase in HDL-C concentration, potentially leading to a loss of HDL's protective effect.

Systemic inflammation following traumatic injury and its impact on neuroinflammatory gene expression in the rodent brain

BackgroundTrauma can result in systemic inflammation that leads to organ dysfunction, but the impact on the brain, particularly following extracranial insults, has been largely overlooked.MethodsBuilding upon our prior findings, we aimed to understand the impact of systemic inflammation on neuroinflammatory gene transcripts in eight brain regions in rats exposed to (1) blast overpressure exposure [BOP], (2) cutaneous thermal injury [BU], (3) complex extremity injury, 3 hours (h) of tourniquet-induced ischemia, and hind limb amputation [CEI+tI+HLA], (4) BOP+BU or (5) BOP+CEI and delayed HLA [BOP+CEI+dHLA] at 6, 24, and 168 h post-injury (hpi).ResultsGlobally, the number and magnitude of differentially expressed genes (DEGs) correlated with injury severity, systemic inflammation markers, and end-organ damage, driven by several chemokines/cytokines (Csf3, Cxcr2, Il16, and Tgfb2), neurosteroids/prostaglandins (Cyp19a1, Ptger2, and Ptger3), and markers of neurodegeneration (Gfap, Grin2b, and Homer1). Regional neuroinflammatory activity was least impacted following BOP. Non-blast trauma (in the BU and CEI+tI+HLA groups) contributed to an earlier, robust and diverse neuroinflammatory response across brain regions (up to 2–50-fold greater than that in the BOP group), while combined trauma (in the BOP+CEI+dHLA group) significantly advanced neuroinflammation in all regions except for the cerebellum. In contrast, BOP+BU resulted in differential activity of several critical neuroinflammatory-neurodegenerative markers compared to BU. t-SNE plots of DEGs demonstrated that the onset, extent, and duration of the inflammatory response are brain region dependent. Regardless of injury type, the thalamus and hypothalamus, which are critical for maintaining homeostasis, had the most DEGs. Our results indicate that neuroinflammation in all groups progressively increased or remained at peak levels over the study duration, while markers of end-organ dysfunction decreased or otherwise resolved.ConclusionsCollectively, these findings emphasize the brain's sensitivity to mediators of systemic inflammation and provide an example of immune-brain crosstalk. Follow-on molecular and behavioral investigations are warranted to understand the short- to long-term pathophysiological consequences on the brain, particularly the mechanism of blood–brain barrier breakdown, immune cell penetration–activation, and microglial activation.

Impact of Renal and Liver Function on Clinical Outcomes Following Tricuspid Valve Transcatheter Edge-to-Edge Repair

BackgroundThe TRILUMINATE Pivotal trial is a prospective, randomized, controlled study of patients with severe tricuspid regurgitation (TR). Venous congestion due to TR may lead to end-organ dysfunction and failure. The potential to reverse or stop further deterioration in end-organ function is an important goal of treatment. ObjectivesThis study sought to examine changes in end-organ function after tricuspid transcatheter edge-to-edge repair (TEER) and assess the association of baseline end-organ function with heart failure (HF) hospitalizations and mortality. MethodsSubjects were randomized 1:1 to either the TEER group (TriClip System + medical therapy) or control group (medical therapy alone). Laboratory assessments and TR grading were performed at baseline and at all follow-up visits (discharge, 30 days, 6 months, and 12 months). An independent echocardiography core laboratory assessed TR severity and an independent clinical events committee adjudicated adverse events. ResultsA total of 572 subjects were enrolled and randomized (285 TEER, 287 control patients). Patients with moderate-to-severe end-organ impairment (estimated glomerular ejection fraction [eGFR] <45 mL/min/1.73 m2 or Model for End-Stage Liver Disease excluding INR [MELD-XI] >15) at baseline had increased incidence of HF hospitalization and death through 12 months, regardless of treatment. There were no statistically significant differences between TEER and control patients in eGFR or MELD-XI at 12 months. In subgroup analyses examining only successful TEER patients (moderate or less TR at discharge) compared with control patients, as well as when censoring patients with normal baseline values, both eGFR (+3.55 ± 1.04 mL/min/1.73 m2 vs 0.07 ± 1.10 mL/min/1.73 m2; P = 0.022) and MELD-XI (−0.52 ± 0.18 vs 0.34 ± 0.18; P = 0.0007) improved. ConclusionsBaseline end-organ function was associated with HF hospitalization and death in patients with severe TR. At 12 months, eGFR and MELD-XI scores were not statistically significantly different between the overall TEER and control groups. In patients who had successful TEER, statistically significant, yet small, favorable changes occurred for both eGFR and MELD-XI. Further investigation is needed to assess whether these changes in end-organ function after successful TEER are clinically meaningful and reduce HF hospitalization or death. (Clinical Trial to Evaluate Cardiovascular Outcomes In Patients Treated With the Tricuspid Valve Repair System Pivotal [TRILUMINATE Pivotal]; NCT03904147)

Cardiogenic Shock: Focus on Non-Cardiac Biomarkers.

To examine the evolving multifaceted nature of cardiogenic shock (CS) in the context of non-cardiac biomarkers that may improve CS management and risk stratification. There are increasing data highlighting the role of lactate, glucose, and other markers of inflammation and end-organ dysfunction in CS. These biomarkers provide a more comprehensive understanding of the concurrent hemo-metabolic and cellular disturbances observed in CS and offer insights beyond standard structural and functional cardiac assessments. Non-cardiac biomarkers both refine the diagnostic accuracy and improve the prognostic assessments in CS. Further studies revolving around novel biomarkers are warranted to support more targeted and effective therapeutic and management interventions in these high-risk patients.

Increase of serum pancreatic enzymes during hospitalization for acute heart failure.

Acute heart failure (AHF) is associated with end-organ dysfunction. The effect of AHF on the pancreas has not been studied. We aim to evaluate serum markers of pancreatic damage during hospitalization for AHF. In data from the Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) study, amylase and lipase values were extracted from available serum samples at baseline, and at 24 and 72hafter hospitalization. The differences between pancreatic enzymes between timepoints were evaluated using the Friedman test. Associations with N-terminal pro-B-type natriuretic peptide (NT-proBNP) were tested using linear regression analysis. The study population consisted of 274 patients. Mean age was 73±11years, and 117 (43%) were women. Mean left ventricular ejection fraction (LVEF) was 38±14%; 53 (19%) patients had HF with a preserved LVEF (≥50%). At baseline, median amylase and lipase were within normal range (47 [33-63] U/L and 30 [21-44] U/L, respectively). Both enzymes significantly increased in the first 72h (P-value for trend <0.001); mean change was 9±22U/L for amylase, and 10±22U/L for lipase. Moreover, NT-proBNP at baseline showed a positive correlation with mean change in pancreatic enzymes in 72h (P=0.02 for amylase and P=0.006 for lipase). Patients admitted for AHF exhibited a significant increase in serum values of pancreatic enzymes in the first 72h, suggesting that an episode of AHF affects the pancreatic tissue. This rise in pancreatic enzymes was associated with HF severity, as reflected by NT-proBNP.

The Long-Term Survival of LVAD Patients-A TriNetX Database Analysis.

Background: Donor shortage limits the utilization of heart transplantation, making it available for only a fraction of the patients on the transplant waiting list. Therefore, continuous-flow left ventricular assist devices (CF-LVADs) have evolved as a standard of care for end-stage heart failure. It is imperative therefore to investigate long-term survival in this population. Methods: This study assesses the impact of demographics, infections, comorbidities, types of cardiomyopathies, arrhythmias, and end-organ dysfunction on the long-term survival of LVAD recipients. The TriNetX database comprises de-identified patient information across healthcare organizations. The log-rank test assessed post-implant survival effects, while Cox regression was used in the univariate analysis to obtain the Hazard Ratio (HR). All analyses were conducted using the Python programming language and the lifelines library. Results: This study identified CMV, hepatitis A exposure, atrial fibrillation, paroxysmal ventricular tachycardia, ischemic cardiomyopathy, renal dysfunction, diabetes, COPD, mitral valve disease, and essential hypertension as risk factors that impact long-term survival. Interestingly, hypokalemia seems to have a protective effect and gender does not affect survival significantly. Conclusions: This is the first report of a detailed long-term survival assessment of the LVAD population using a decoded database.

Cardiovascular risk reduction in type 2 diabetes: What the non-specialist needs to know about current guidelines.

In the US, approximately 11% of the population have diagnosed diabetes and nearly 40% have prediabetes. In addition, chronic kidney disease (CKD) affects 14% of the US population including up to 40% of those with diabetes. Cardiovascular disease (CVD) remains the leading cause of death worldwide where it affects approximately half of adults. The presence of CKD or diabetes doubles the risk of cardiovascular events. When both CKD and diabetes occur in the same patient the risks are further increased. The clinical problems of hypertension, hyperglycemia, and hyperlipidemia are all closely related with obesity, metabolic syndrome, Type 2 diabetes, CKD, atherosclerotic cardiovascular disease, heart failure and non-alcoholic fatty liver disease and metabolic dysfunction-associated steatohepatitis. The increasing frequency of obesity has driven increases in all of these medical comorbidities. These conditions frequently cluster together in the same patient exacerbating the risk of morbidity and mortality. They are also associated with cognitive dysfunction/dementia, pulmonary diseases, cancers, gastrointestinal diseases, immune system abnormalities, and inflammatory disorders. Only 6.8% of adults in US meet all targets for cardiovascular risk management with significant disparities based on race and ethnicity. Given the complexity of these multisystem problems in people with diabetes and obesity, it would seem reasonable to attempt to diagnose and treat many of the comorbidities earlier in the course of disease rather than wait for substantial end organ dysfunction to occur. The American Diabetes Association (ADA) has recently published a consensus statement recommending early screening for the diagnosis of heart failure, CKD and diabetes, recognizing both the frequency and gravity of this combination. Likewise, there are recommendations in the guidelines to facilitate screening for microalbuminuria, blood pressure, glycemic control and lipids earlier in patients at risk rather than wait and treat as a secondary prevention program. Thus, the general principle is to facilitate earlier recognition and diagnosis and provide treatment before downstream target organ complications occur. This review will focus on CVD and risk management based on newest recommendations and standards of care in people with diabetes by the ADA. The main considerations in the treatment of people with diabetes are glycemic control, blood pressure, lipids, and the use of medications with proven cardiorenal disease progression capability to prevent or delay.

Impact of minimal invasive extracorporeal circulation on systemic inflammatory response – a randomized trial

BackgroundExtracorporeal circulation causes a systemic inflammatory response, that may cause postoperative haemodynamic instability and end-organ dysfunction. This study aimed to investigate the impact of minimal invasive extracorporeal circulation (MiECC) on the systemic inflammatory response compared with conventional extracorporeal circulation (CECC).MethodsPatients undergoing coronary artery bypass grafting were randomized to MiECC (n = 30) and CECC (n = 30). Primary endpoint was tumor necrosis factor-α. Secondary endpoints were other biochemical markers of inflammation (IL1β, IL6 and IL8, C-reactive protein, leukocytes), and markers of inadequate tissue perfusion and tissue damage (lactate dehydrogenase, lactate and creatine kinase-MB). In addition, we registered signs of systemic inflammatory response syndrome, haemodynamic instability, atrial fibrillation, respiratory dysfunction, and infection.ResultsPatients treated with MiECC showed significantly lower levels of tumor necrosis factor-α than CECC during and early after extracorporeal circulation (median: MiECC 3.4 pg/mL; CI 2.2–4.5 vs. CECC 4.6 pg/mL; CI 3.4–5.6; p = 0.01). Lower levels of creatine kinase-MB and lactate dehydrogenase suggested less tissue damage. However, we detected no other significant differences in any other markers of inflammation, tissue damage or in any of the clinical outcomes.ConclusionsLower levels of TNF-α after MiECC compared with CECC may reflect reduced inflammatory response, although other biochemical markers of inflammation were comparable. Our results suggest better end-organ protection with MiECC compared with CECC. Clinical parameters related to systemic inflammatory response were comparable in this study.Clinical registration numberNCT03216720.

Neutrophil-to-Lymphocyte Ratio Predicts Sepsis in Adult Patients Meeting Two or More Systemic Inflammatory Response Syndrome Criteria.

Determining which patients who meet systemic inflammatory response syndrome (SIRS) criteria have bacterial sepsis is a difficult challenge for emergency physicians. We sought to determine whether the neutrophil-to-lymphocyte ratio (NLR) could be used to exclude bacterial sepsis in adult patients who meet ≥2 SIRS criteria and are being evaluated for sepsis. Consenting adult patients meeting ≥2 SIRS criteria and undergoing evaluation for sepsis were enrolled. We recorded patient age, gender, vital signs, and laboratory results. We then later reviewed health records for culture results, end organ dysfunction, survival to discharge, and final diagnoses. Patients were classified as having sepsis if they met ≥2 SIRS criteria and were ultimately diagnosed with a bacterial source. We analyzed data using descriptive statistics and sensitivity and specificity analyses. A receiver operating characteristic curve (ROC) was created to determine test characteristics. A total of 231 patients had complete datasets. Patients' median age was 69 (interquartile range [IQR] 54-81), and 49.6% were male. There were 154 patients (66.7%) ultimately diagnosed with sepsis with an identified bacterial source, while 77 patients with ≥2 SIRS criteria had non-infectious reasons for their presentations (33.3%). Septic patients had a median NLR 12.36 (IQR [interquartile range] 7.29-21.69), compared to those without sepsis (median NLR 5.62, IQR 3.89-9.11, P < 0.001). The NLR value of 3 applied as a cutoff for sepsis had a sensitivity of 96.8 (95% confidence interval [CI] 92.2-98.8), and a specificity of 18.2 (95% CI 10.6-29.0). The ROC for NLR had an area under the curve of 0.74. The neutrophil-to-lymphocyte ratio is a sensitive tool to help determine which patients with abnormal SIRS screens have bacterial sepsis.

An analysis of urodynamic parameters in diabetic and nondiabetic women.

Diabetes is highly prevalent worldwide, with an estimated 536 million living with diabetes in 2021, and that number projected to increase to 783 million by 2045. Diabetic bladder dysfunction is thought to affect up to 60%-90% of individuals with diabetes and can significantly impact quality of life. Despite the prevalence of diabetic bladder dysfunction, the exact pathophysiological mechanism, and resulting clinical presentation, remains debated. Our objective was to compare urodynamic parameters between diabetic and nondiabetic women, assessing the impact of various markers of diabetes severity on bladder function. A retrospective chart review was conducted on female patients aged 18 and above who underwent urodynamic studies at a single tertiary care university hospital system from 2014 to 2020. Patients were categorized based on diabetes status, and diabetes severity including duration of disease, hemoglobin A1c levels, insulin dependence, and markers of end-organ dysfunction. Urodynamic variables, including compliance, bladder voided efficiency, bladder contractility index, postvoid residual, maximum flow rate, capacity, voided volume, and detrusor overactivity, were assessed by two independent reviewers. Statistical analyses were performed to assess the impact of diabetes and diabetic severity on urodynamic parameters. A total of 652 female patients were included in the study, of which, 152 (23.3%) had diabetes, with an average duration of diagnosis of 82.3 months. Diabetic women were older and had higher body mass index compared to nondiabetic women. Diabetic retinopathy and neuropathy were present in 18% and 54.6% of diabetic patients, respectively. Significant differences in urodynamic parameters were observed between diabetic and nondiabetic women, with diabetic women showing higher rates of detrusor overactivity (p = 0.01), particularly associated with increasing BMI (p = 0.03). However, classic markers of diabetes severity including duration, as well as markers of end-organ damage, showed mixed associations with urodynamic changes. Despite the prevalence of diabetic bladder dysfunction and its impact on patient quality of life, the exact mechanisms and clinical presentation remain elusive. Our study highlights the significant differences in urodynamic parameters between diabetic and nondiabetic women, emphasizing the need for further research into the relationship between diabetes and diabetic bladder dysfunction.

Endothelial progenitor cells for diabetic cardiac and kidney disease.

The management of diabetes mellitus and its resultant end organ dysfunction represents a major challenge to global health-care systems. Diabetic cardiac and kidney disease commonly co-occur and are significant contributors to the morbidity and mortality of patients with diabetes, carrying a poor prognosis. The tight link of these parallel end organ manifestations suggests a deeper common underlying pathology. Here, we outline the mechanistic link between diabetic cardiac and kidney disease, providing evidence for the role of endothelial dysfunction in both processes and the potential for cellular therapy to correct these disorders. Specifically, we review the preclinical and clinical evidence for endothelial progenitor cell therapy in cardiac, kidney, and cardio-renal disease applications. Finally, we outline novel approaches to endothelial progenitor cell therapy through cell enhancement and the use of extracellular vesicles, discussing published and future work.