Serum Troponin Research Articles

Clinical significance of quantitative assessment of right ventricular amyloid burden with [99mTc]Tc-DPD SPECT/CT in transthyretin cardiac amyloidosis.

To evaluate right ventricular (RV) uptake measured by quantitative [99mTc]Tc-DPD SPECT/CT to investigate its role in predicting and evaluating prognosis and therapeutic outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CA). Patients with ATTR-CA were consecutively enrolled for quantitative [99mTc]Tc-DPD SPECT/CT. Ventricular amyloid burden was quantified by SUVmax and TBR. Differences in RV uptake (focal or diffuse) and associations with clinical characteristics and CMR data were evaluated. The primary endpoint was major adverse cardiac events (MACEs), including all-cause deaths, heart failure hospitalizations, complete atrioventricular block, sustained ventricular tachycardia, and atrial fibrillation/flutter. Prognostic associations were evaluated using Cox regression and Kaplan-Meier survival analysis. A secondary endpoint involved a longitudinal SPECT/CT analysis during Tafamidis therapy. The study included 76 patients, all showing both RV and LV uptake on SPECT imaging. Compared with patients with focal RV uptake, patients with diffuse RV uptake had higher serum troponin T levels (P < 0.05), septal thickness (P < 0.01), and external cardiac circulation volume (ECV) (P < 0.05). RV uptake was correlated with septal thickness, ECV, LV uptake, NT-proBNP and troponin-T (all P < 0.05). Among 53 patients, high LV and RV uptake significantly predicted MACEs (P < 0.001), with a median follow-up time of 16 months. A subgroup of 20 patients showed significant reductions in LV and RV uptake after Tafamidis treatment (P < 0.001). Increasing RV amyloid burden quantified by SPECT/CT is associated with advanced disease stage and predicts MACEs, serving as valuable markers for prognosis and treatment monitoring in ATTR-CA.

99mTc]-PentixaTec SPECT/CT for Imaging of Chemokine Receptor 4 Expression After Myocardial Infarction.

Accumulation of CXCR4 (C-X-C motif chemokine receptor 4)-positive immune cells after acute myocardial infarction (AMI) can be visualized by positron emission tomography. For a broader clinical application, there is a need for CXCR4-directed radiotracers labeled with isotopes that can be used with single-photon emission computed tomography (SPECT). We report on the detection of CXCR4 expression after AMI in humans using the novel tracer [99mTc]-PentixaTec. In this retrospective analysis, 9 patients with AMI after mechanical revascularization underwent myocardial inflammation imaging with [99mTc]-PentixaTec SPECT/computed tomography and rest perfusion SPECT imaging. Tracer uptake in the infarcted area, spleen, bone marrow, and blood pool were used for semiquantitative analysis and calculation of signal-to-background ratios. The extent and intensity of SPECT-derived inflammatory changes were compared with serological markers and perfusion defects. CXCR4-directed SPECT was positive in all patients. Increased CXCR4 expression was only detected in areas with diminished perfusion corresponding to the affected vessel in coronary angiography, with a signal-to-background ratio (infarcted area-to-blood pool) of 2.36±0.74. Uptake in bone marrow and spleen showed a significant correlation with CXCR4 expression in the infarcted areas (r=0.73 and P=0.03 for spleen and r=0.81 and P=0.008 for bone marrow, respectively). The extent and intensity of SPECT-derived inflammatory changes showed no significant association with serum troponin, CK (creatine kinase), leukocyte, or CRP (C-reactive protein) levels. This is the first report of in vivo CXCR4 imaging after AMI using a 99mTc-labeled tracer. Increased CXCR4 expression was observed locally in the infarcted region and was related to a systemic inflammatory response in the reticuloendothelial system. This proof-of-concept investigation demonstrates the general feasibility of evaluating the inflammation-related CXCR4 expression in the myocardium after AMI using conventional scintigraphy or SPECT and might, thus, broaden its worldwide application in clinical practice.

Abstract 4138310: Successful Endovascular Closure of Ascending Aortic Pseudoaneurysm Using Atrial Septal Defect Occluder

Introduction: Ascending aortic pseudoaneurysms are mostly related to either surgery or non-surgical trauma. Any pseudoaneurysm arising from graft anastomoses, regardless of size or location, must be repaired due to the potential for catastrophic rupture. Traditional surgical intervention has a high mortality rate, but percutaneous treatment has emerged as an alternative. We present such a case of pseudoaneurysm treated by percutaneous intervention using a 6-mm Amplatzer device. Case: A 77-year-old female with a history of type A aortic dissection s/p emergent repair with a 32 mm tube graft one year ago presented with chest pain radiating to her back. Initial vital signs showed a BP of 185/105, SaO2 98% on RA, 98.3 F, HR 98 bpm, and RR 24/min. A chest CT scan suggested a pseudoaneurysm at the proximal anastomotic site of the aortic graft (Figs. 1A and B). Serial troponin and EKGs were unremarkable for acute ischemia. Multiple quaternary centers declined intervention due to the high risk of redo sternotomy for open repair and patient frailty. After multidisciplinary discussions, it was felt that percutaneous closure with an Amplatzer device was possible without coronary obstruction. In the catheterization lab, a TEE probe was placed to visualize the pseudoaneurysm of the ascending aorta (Fig. 1C). Angiography showed the aneurysm coming off the posterior aorta just above the noncoronary cusp, with the neck measuring ~6 mm (Fig. 1D). The aneurysm was successfully engaged using an 8-French sheath and an 8-French AL1. Based on measurements from the TEE and the angiogram, a 6 mm ASO device was used. After device deployment and release, aortograms showed that the pseudoaneurysm was excluded (Fig. 1H). Assessment with TEE and CTA showed no residual flow in the pseudoaneurysm (Fig. 1 E–G). Conclusion: Using an atrial septal occluder, endovascular intervention may be a safe and effective alternative to surgery for treating the ascending aortic pseudoaneurysm, especially in patients with a high prohibitive surgical risk. Longitudinal follow-ups are needed to comment on long-term mortality benefits for these individuals.

Abstract 4115801: Assessing Prevalence of Cardiac Amyloidosis at the Time of Spinal Laminectomy for Spinal Stenosis

Introduction: Cardiac amyloidosis (CA) involves deposition of amyloid fibrils within cardiac myocardium, resulting in heart failure. Recent studies have shown an association between amyloid deposition in the ligamentum flavum (LF) and development of CA. Our study aims to investigate the prevalence of CA in patients identified with amyloid deposition in their LF at the time of spinal laminectomy for spinal stenosis, employing a comprehensive approach integrating multi-modality imaging and laboratory testing. Methods: This is a retrospective study of patients age &gt;50 years old who underwent spinal laminectomy for non-congenital spinal stenosis or spondyloarthropathy. LF tissue samples obtained during surgery were examined histologically for amyloid deposition. Patients with positive findings underwent testing, including serum markers, echocardiography, and 99mtechnetium pyrophosphate (99mTcPYP) scintigraphy. Additionally, cardiac magnetic resonance imaging (cMRI) was obtained when clinically appropriate to assess for CA. Results: Among the 197 enrolled patients, 39 (19.3%) exhibited amyloid deposition in LF tissue. Patient demographics and clinical characteristics did not significantly differ between the positive and negative groups (Table 1). Of the 39 amyloid positive specimens, subtyping using mass spectrometry identified 1 (3%) light-chain, 28 (72%) transthyretin (TTR), and 10 (25%) were unable to be subtyped. Of the 28 TTR positive patients, 8 were of the wild type genotype. Furthermore, 18 of the 28 TTR patients underwent 99mTcPYP scintigraphy, of which none had cardiac uptake consistent with TTR amyloidosis; the other 10 declined work up. Of the 10 untyped patients, 6 had 99mTcPYP scintigraphy with none of the patients having cardiac uptake. Adjunctive cMRI in select positive patients showed findings inconsistent with amyloid deposition. Serum NT-proBNP, Troponin T, and serum pre-albumin levels were similar between groups. Conclusion: Amyloid deposition in LF tissue did not correlate with cardiac manifestations of amyloidosis at the time of surgery. Longitudinal investigation is ongoing to better understand the relationship between amyloid deposition in LF tissue and the development of CA over time.

Abstract 4129440: Ventricular Stunning Following Direct Current Cardioversion: A Case Report

Background: Ventricular stunning refers to a transient mechanical dysfunction of the myocardium, typically manifesting in response to ischemic insults, reperfusion injury, inflammatory states, or neurohormonal overload. Here, we present an unusual case of ventricular stunning precipitated by direct current electrical cardioversion (DEC). Case Report: A 73-year-old man with a history of heart failure with reduced ejection fraction, paroxysmal atrial fibrillation (AF), coronary artery disease, and chronic kidney disease was admitted to a Veterans Affairs hospital for heart failure exacerbation. His hospitalization was complicated by recurrent episodes of symptomatic AF with ventricular rates in the 120-150’s. This was initially managed with intravenous amiodarone and eventually DEC. He continued to experience symptomatic episodes of AF. Later in the hospitalization a repeat DEC with a single 200 joule shock was performed with restoration of sinus rhythm. Several hours afterwards he was found to be unresponsive and hypotensive. Cool extremities and rising serum lactate raised suspicion for cardiogenic shock resulting in transfer to the intensive care unit where vasopressor and inotropic support were initiated. Echocardiogram revealed a precipitous decrease in left ventricular ejection fraction from 25% to 5%. Serum troponin concentrations were unchanged from prior and ECGs demonstrated rate-controlled AF. Clinical Decision Making: This case highlights an episode of unexpected decrease in cardiac output following an otherwise routine repeat DEC for recurrent AF requiring escalation to mechanical circulatory support. His decompensation worsened, necessitating transfer to the local university center for placement of catheter-based miniaturized ventricular assist device (Impella 5’5). Over the subsequent days, with supportive care, his left ventricular ejection fraction recovered to baseline, and mechanical and inotropic support were withdrawn. Conclusion: Ventricular stunning, leading to cardiogenic shock, is a rare and incompletely understood complication of DEC. It warrants consideration when monitoring patients after cardioversion. Implementing vigilant observation protocols post-DEC to detect ventricular stunning and predisposing risk factors could significantly enhance clinical management strategies.

Results of a German nationwide survey on perioperative cardiac management in vascular surgery

Because of the lack of specific recommendations concerning cardiac risk stratification before vascular surgery, appropriate decisions remain individual. The aim of the present study was to evaluate the perioperative cardiac management in vascular surgery in Germany.MethodsThis article is based on a survey from 2018 of heads of German vascular surgical departments or units regarding their experience with perioperative cardiac management. The questionnaire asked about the experience with preoperative cardiac evaluation and its extension, awareness of perioperative myocardial ischemia, the art of postoperative monitoring and the routine use of the best medical treatment.ResultsIn total, 62% of responders agreed that perioperative myocardial ischemia is a relevant postoperative problem in their clinic after open abdominal aortic surgery, while 47% stated the same after vascular surgery (VS) like carotid endarterectomy, peripheral arterial surgery or EVAR. Preoperative cardiological evaluations are performed routinely by 87% of responders before open abdominal aortic surgery and by 42% before VS. Preoperative cardiac evaluation included cardiac echography in 92% and stress diagnostics (stress echography, stress ECG) in 38%. Routine preoperative cardiac catheterisation is performed in 4% before OAS and only 0.5% before VS. In addition, 79% of participants initiate acetylsalicylic acid routinely and 68% use statins preoperatively. The serum troponin diagnostic test in asymptomatic patients was routinely applied by 19% of responders after OAS and by 6% after VS.ConclusionPerioperative myocardial ischemia is considered a relevant problem, primarily after aortic surgery. The preoperative cardiac stress diagnostics among vascular surgeons does not seem to be sufficiently widespread. The preoperative initiation of acetylsalicylic acid and statins is not routine in 30% of hospitals.

Abstract 4138376: A Machine Learning Approach to Predict Percutaneous Coronary Intervention in Patients with Critical Illness and Signs of Myocardial Injury

Background: Critically ill patients frequently experience multi-organ dysfunction and unstable vital signs, increasing their risk of myocardial injury and elevated serum troponin levels. Myocardial injury from oxygen supply-demand mismatch, whether due to systemic disease or obstructive coronary artery disease (CAD), often leads to patients undergoing an invasive coronary angiogram (ICA) and potentially percutaneous coronary intervention (PCI) if obstructive CAD is identified. However, this procedure carries significant risks for critically ill patients. To address this challenge, we aimed to develop a machine learning (ML) model to predict the need for PCI in critically ill patients with myocardial injury. Methods: The study cohort included critically ill patients with elevated serum troponin levels who underwent ICA during their hospitalization at a single institution from 2012 to 2022. We defined critical illness as a life-threatening condition requiring intensive support for vital sign instability. Patients with atherothrombosis identified during ICA were excluded from the study, focusing only on patients with type 2 MI. We utilized Matplotlib to analyze patient data, including demographics, lab results, vital signs, and comorbidities. We then used XGBoost, a supervised ML algorithm, for binary classification tasks. An ensemble of decision trees was employed, with gradient boosting to correct errors from previous trees. XGBoost iteratively adjusted predictions, creating a model to predict which patients required PCI. Results: Out of 765 patients, 173 (22.6%) underwent PCI. The cohort had a mean age of 60.5 ± 13.5 years, with 41.7% being female. The ML model accurately identified non-PCI candidates at 75% and PCI candidates at 64%, achieving an overall accuracy of 73%. The three most important features identified by the model were a history of diabetes, diastolic heart failure, and whether the patient received a blood transfusion during hospitalization. Conclusion: A ML approach using XGBoost demonstrated moderate accuracy in predicting the need for PCI in critically ill patients with signs of myocardial injury. This prediction holds clinical significance due to the heightened risks associated with ICA in these patients. Given that PCI occurred in only 22.6% of the cohort, future models should include a higher proportion of patients who underwent PCI to improve the robustness and true positive accuracy of the model.

The use of a point of care high sensitivity troponin in the investigation of patients presenting to the Emergency Department with undifferentiated chest pain

Abstract Background In 2012 in a hospital, New Zealand, a chest pain pathway was instituted for the use in patients presenting to the Emergency Department (ED) with undifferentiated chest pain. This reduced hospital admissions and ED length of stay (LOS) without adversely affecting outcomes. The pathway consists of risk stratification combined with ECG and troponin testing. The pathway suggests, but does not enforce, that low risk patients can be discharged after a single troponin, intermediate risk patients are for serial troponins (which can be done in ED or the next day in the community), with further testing if appropriate, and high risk patients are reviewed by Cardiology or General medicine. In August 2023, Siemens point of care high sensitivity troponin I (POC-hsTnI) was introduced for the use in ED, although Beckman laboratory troponin I (Lab–hsTnI) is still available. A POC test reduces result turnaround times but until recently there has been a lack of POC assays fulfilling criteria for "high sensitivity". Purpose To ascertain whether the availability of a POC-hsTnI in the ED is a viable option for use in the chest pain pathway Methods A 1 month "snap shot" of all consecutive patients presenting to the ED with chest pain was undertaken and the patients followed for adverse events using electronic notes review. October 2023 was selected for the post POC-hsTnI period and compared with April 2022. Results There were 688 patients presenting to ED with undifferentiated chest pain during October 2023 with a type 1 acute myocardial infarction (AMI) rate of 80 (11.6%), median age 58 (41-72), female 335 (48.7%). POC-hsTnI was used in isolation in 377 (54.8%), in conjunction with Lab-hsTnI in 218 (31.7%) and Lab-hsTnI was used alone in 93 (13.5%). The median turnaround time for POC-hsTnI was 11 minutes (10-11) compared with Lab-hsTnI 87 minutes (61-129). The POC-hsTnI was less sensitive for AMI than the Lab-hsTnI on presentation using the upper reference limit, 72.1% (60.6-81.6) versus 91.5% (83.0-96.4). However, when used with risk stratification, there were no excess adverse events (cardiac death or AMI) at 4 months in patients discharged with a diagnosis of non-cardiac chest pain – 7 (1.4%) (n=495) versus 5 (1.2%), (n=424) in 2022. Median LOS in the ED was 4.4 hours (2.9-6.2) versus 4.0h (3.0-5.9) in 2022. However, a higher proportion of patients had a second cTn: 414 (60.2%) versus 309 (48.4%) and a lower proportion had their second troponin the next day in the community, 28 (6.7%) versus 56 (18.1%). Conclusion The use of a POC-hsTnI is a practical solution to reduce turnaround times for troponin results and has the potential to reduce LOS or allow serial troponins to be measured in a timely manner during their ED visit, obviating the need for a next day community troponin. Whilst POC-hsTnI has a lower early sensitivity for AMI, the use of POC-hsTnI as part of a pathway does not adversely affect outcomes.

S-nitrosylation of aconitase-2 facilitates coronary microembolization-induced cardiac injury by suppressing iron-sulfur cluster assembly

Abstract Background Coronary microembolization (CME) is a common reason for periprocedural myocardial infarction after coronary interventions. S-nitrosylation (SNO), a prototypic redox-based posttranslational modification, is involved in the pathogenesis of several cardiovascular diseases. Purpose To explore the role of SNO of aconitase-2 (ACO2) in CME-induced cardiac injury, as well as the mechanism by which SNO-ACO2 modulates myocardial injury in response to CME. Methods CME models were established in C57BL/6J mice by injecting 300,000 polyethylene microspheres (diameter 9 µm) into the left ventricle chamber with the occlusion of the ascending aorta. Cardiac function was evaluated by echocardiography. Histological and serum analysis was performed to evaluate myocardial injury. Myocardial samples were scanned for S-nitrosylated proteins using biotin-switch procedures and liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. SNO sites of ACO2 were further identified through LC-MS/MS. De-nitrosylation of ACO2 was achieved by the mutation of SNO site or overexpression of the de-nitrosylation enzyme thioredoxin 1 (TRX1). Interacting effectors of SNO- ACO2 were screened through LC-MS/MS and confirmed by coimmunoprecipitation. Neonatal rat ventricular myocytes (NRVMs) were used for in vitro study. The cellular ACO2 activity was analysed using an ACO2 enzyme activity assay kit. Mitochondrial morphology and function were assessed by fluorescent staining and mitochondrial stress testing. Results Cardiac injury was exacerbated by CME as demonstrated by impaired cardiac contractile function, morphological changes, and increased fibrosis, microinfarct size and serum troponin I level. We identified 789 S-nitrosylated proteins in CME mouse hearts, and ACO2 is one of the highly S-nitrosylated proteins. The increased level of SNO-ACO2 was verified by immunoblot assay in CME mouse hearts and hypoxia-stimulated NRVMs. SNO site of ACO2 at cysteine 126 was identified by LC-MS/MS and confirmed in NRVMs. De-nitrosylation of ACO2 by the mutation of cysteine 126 or overexpression of TRX1 both greatly improved the activity of ACO2 by 39.7% and 31.4% respectively, furthermore restored the mitochondrial function, and attenuated CME-induced cardiac injury. Mechanistically, SNO-ACO2 at cysteine 126 suppressed the interaction between ACO2 and NFU1, an iron-sulfur (Fe-S) cluster scaffold protein. The dissociation from NFU1 deprived ACO2 of the Fe-S cluster and the enzyme activity, thereby promoting the disruption of the mitochondrial tricarboxylic acid cycle and cardiac injury. Conclusions Our data defined a previously unrecognized role of SNO-ACO2 in CME-induced cardiac injury. We demonstrated that SNO-ACO2 at cysteine 126 disrupted ACO2/NFU1 interaction to exacerbate myocardial injury after CME. Our results suggested that de-nitrosylation of ACO2 may provide a new therapeutic target for the treatment of CME.

Alterations of gut microbiome profiles as potential markers in patients developing acute coronary syndrome

Abstract Background Imbalanced gut microbiota or gut dysbiosis leads to systemic inflammation, one of key contributors to the development and progression of atherosclerosis. A recent study revealed the association of the gut microbiota and the severity of coronary artery lesions in patients with acute coronary syndrome (ACS). However, the gut microbiota profile in ACS patients in comparison with patients with high-risk cardiovascular disease (CVD) has not been thoroughly investigated. Purpose We aimed to compare the profiles of gut microbiome between patients with ACS and patients with high-risk CVD, as well as to determine the association between gut microbiota and CVD risk factors. Methods This cross-sectional study enrolled 24 stabilized ACS patients within 24 hrs of hospitalization and 59 outpatients in CVD clinics, as a control group. Echocardiography was done in those patients. Blood was collected for biochemical analysis, and fecal samples were collected for gut microbiome analysis via 16S RNA sequencing. Results The demographic data showed no significant differences between groups in CVD risk factors (age, levels of systolic and diastolic blood pressure, fasting glucose, high- and low-density cholesterol, and triglycerides). However, patients with ACS had greater cigarette use and alcohol consumption than the control group. For gut microbiome, both alpha and beta diversity levels of ACS group were significantly higher than those in a control group (Figure 1A-B). Differential abundance analysis by ANCOM-BC revealed significantly increased level of bacteria in the Atopobiaceae family in ACS patients, compared to controls (Figure 1C). Since Atopobiaceae was reported to be positively associated with percent atheroma volume (PAV), a marker of plaque deposit in the arteries, we found an increased number of Atopobiaceae which was positively associated with serum Troponin T level (Figure 1D), systemic inflammation (Figure 1E), and a trend to negatively correlated with LV ejection fraction. Conclusion Our findings suggested that alterations of gut microbiota occurred in ACS patients, and an increase in gut Atopobiaceae level could potentially be the predictive marker of the development of ACS in CVD patients.Figure 1

High-sensitivity troponin T and risk of stroke in persons with suspected acute coronary syndrome

Abstract Background Serial high-sensitivity troponin (hsTn) concentrations are associated with the risk of recurrent ischemic events and death from any cause. Higher hsTn levels may suggest greater infarct size and possibly, a more pronounced risk of non-coronary atherosclerotic events. Purpose To examine the association between single and serial hsTnT levels and the risk of incident stroke in individuals presenting with suspected acute coronary syndrome. Methods In this Danish nationwide registry-based study, we identified individuals without a history of stroke who presented for myocardial infarction, unstable angina, suspected myocardial infarction, or chest pain from 2013 through 2019, and who underwent serial hsTnT (Roche Diagnostics, Rotkreuz, Switzerland; 99th percentile upper reference limit: 13.5 ng/l) measurements 1-7 hours apart. Subjects were stratified according to their hsTnT level pattern from first to second measurement (main groups: normal, rising, persistently elevated, or falling) and the magnitude of hsTnT level change (secondary groups: &amp;lt;20%, &amp;gt;20 to 50%, or &amp;gt;50% in either direction). Additionally, they were grouped into quartiles based on the initial hsTnT measurement (&amp;lt;=9 ng/l, 10-16 ng/l, 17-68 ng/l, &amp;gt;=69 ng/l). The standardized risk of stroke was computed using multivariable logistic regression with average treatment effect modeling. Results The final study sample consisted of 26867 persons, of whom 10407 (38.7%) were diagnosed with myocardial infarction, 1404 (5.2%) with unstable angina, and 15056 (56.0%) with suspected myocardial infarction or chest pain. Median age was 64.3 years, and 40.1% were women. The prevalences of known cardiovascular disease were as follows: coronary artery disease, 20.2%; prior coronary revascularization, 8.4%; heart failure, 6.4%; and atrial fibrillation, 8.9%. At 30 days, 69 individuals had been diagnosed with a stroke, and an additional 185 individuals were diagnosed from days 31 through 365. The standardized risk of stroke at 30 days was &amp;lt;=0.31% in all main groups and did not meaningfully differ from each other. The risk remained low between days 31-365 (&amp;lt;=0,79%), with no significant between-group difference. The magnitude of hsTnT change within each group did not affect stroke risk, nor did hsTnT quartile based on the first measurement. Conclusions Persons with suspected acute coronary syndrome had a very low overall risk of incident stroke. Single or serial hsTnT levels at presentation did not seem helpful in identifying individuals at an increased risk of stroke.

The cardioprotective potential of soluble urokinase Plasminogen Activator Receptor (suPAR) in myocardial ischemia

Abstract Background and aims: Increased circulating soluble urokinase plasminogen activator receptor (suPAR) levels are associated with adverse cardiovascular outcomes, however, any cardiovascular-related functions remain unknown. This study aimed to (i) document haemodynamic profiles in isolated rat hearts under the influence of suPAR, and to (ii) explore any mechanisms triggered by suPAR following myocardial ischaemia-reperfusion. Methods We undertook a 4-pronged approach (Figure 1). A Langendorff isolated rat heart model was used to perfuse all hearts with Krebs-Henseleit solution flowing retrogradely through the aorta at 37°C. A balloon inserted into the left ventricle allowed measurements of ventricular pressure, and a pressure transducer placed above the aorta recorded perfusion pressure for coronary flow rates. The experimental protocol consisted an initial 30-minute stabilisation period, followed by 40 minutes of ischemia via buffer flow cessation. Hearts were subsequently recovered during 90 minutes of reperfusion, receiving either suPAR treatment or perfusion buffer as controls. An inhibitor arm comprising co-infusion of suPAR and a monoclonal antibody capable of binding to suPAR was also assessed. Troponin T was measured in outflow perfusates collected at specific intervals. Proteins from hearts in treatment groups were separated using gel electrophoresis, with Western blotting to visualise the phosphorylation status of kinases (Akt, STAT). High-flow respirometry and fluorometry were investigated in cardiac mitochondria to determine respiration rates and ATP production in ischaemia reperfusion under the influence of suPAR. Statistical analysis was conducted with ANOVA using SPSS. Results Hearts receiving suPAR infusion at reperfusion (n = 16) showed a significant increase in developed pressure (p = .017) and lower perfusion pressure (p = .02) compared to controls (n = 16), revealing that suPAR-treated hearts recovered with better contractility and vasodilatory properties post-ischaemia. suPAR’s haemodynamic profiles in the antibody group were similar to controls, attenuating suPAR-induced effects (n = 8). Outflow effluents in suPAR-treated hearts obtained &amp;gt;3 fold lower serial Troponin T values than controls (p &amp;lt; .001). Heart tissues receiving suPAR treatment revealed a 1.7-fold increase in Akt (p = .001) and a 3.8-fold increase in STAT3 phosphorylation compared to controls (p &amp;lt; .001) and the inhibitor group (p = .04). Finally, suPAR increased mitochondrial ATP production by 28% (p = .013) compared to controls after ischaemia. Conclusion This is a world-first demonstration of suPAR’s cardioprotective influences in isolated rat hearts recovering from ischaemia. suPAR’s ability to promote cardiac contractility and vasodilation was associated with lesser injury as shown by Troponin T reduction. Mechanistically, suPAR infusion upregulated two key cardioprotective pathways, which may also function to protect cardiac mitochondria.Figure 1 - Schematic of Methods

Serial troponin sampling over 60-minutes allows early distinction between myocardial infarction and chronic myocardial injury in patients presenting to emergency departments

Abstract Background High-sensitivity cardiac troponins (hs-cTn) are key clinical biomarkers in the assessment and diagnosis of patients with suspected acute coronary syndromes presenting to Emergency Departments (ED). These tests facilitate rapid triage through 0h/1h blood sampling regimens. Most patients will not have myocardial infarction (MI) diagnosed, having either hs-cTn levels below the upper reference limit (URL) or stable elevations. The latter group of complex, often multimorbid, patients is termed chronic myocardial injury (CMI) according to the 4th Universal Definition of MI (4thUDMI). These patients have long-term morbidity and mortality rates higher than those with type 1 MI. Early distinction of CMI from MI remains challenging with debate regarding optimal hs-cTnT delta cut-offs; both 3ng/L and 5ng/L over one-hour have been proposed. Methods and Results We prospectively collected 0-, 30- and 60-minutes (+/- 5 min) hs-cTnT samples from 185 patients presenting to Liverpool Hospital ED (Sydney, Australia) between March and August 2023. Diagnoses were adjudicated according to the 4thUDMI as follows: 16 (8.6%) MI ruled-in, 66 (35.7%) CMI and 103 (55.7%) MI ruled-out. Linear regression was used to calculate individual hs-cTnT slopes for each patient. Between CMI and MI, each 1 ng/L/hour increase in the slope of hs-cTnT resulted in a two-fold (95% CI: 1.5 to 2.9) greater likelihood of MI being diagnosed (P &amp;lt; 0.001). A stable hs-cTnT trajectory was observed in CMI, which ranged between 0 and 3 ng/L/hour in all patients with an initial hs-cTnT level ≤ 50 ng/L. Chronic myocardial injury patients with an initial hs-cTnT level &amp;gt; 50ng/L (n=12), exhibited more kinetic slopes ranging up to 8ng/L/hour (P &amp;lt;0.001). Unexpectedly, three MI patients had a non-linear slope, of whom two patients would not have displayed a significant rise had the additional 30-minute sample not been collected. These outlying patients presented at 9-12 hours and over 12 hours from symptom onset. Conclusion This study offers a novel characterisation of CMI, which has not previously been investigated in an unselected ED cohort using three serial samples over one hour. It validates a hs-cTnT delta of 3ng/L/hour in the recent ESC guidelines. However, there is a need for greater characterisation of short-term hs-cTn variability for more personalised MI risk stratification and to guide more targeted observation and further investigation of CMI patients.

Single spot albumin to creatinine ratio as an independent predictor of 12 years follow-up mortality in acute coronary syndromes without ST-segment elevation

Abstract Background To the best of our knowledge there is no evidence of the association between microalbuminuria, measured as single spot urine albumin to creatinine ratio (ACR), with very long-term mortality in patients with non-ST segment Elevation Acute Coronary Syndromes. Aim To evaluate the association between admission ACR and very long-term all-cause mortality in an unselected cohort of non-ST-segment elevation acute coronary syndromes patients. Methods A prospective cohort study was conducted, including patients with non-ST-segment elevation acute coronary syndromes admitted in the Intensive Care Unit. The ACR was determined in spontaneous urine samples during the first 24 hours after admission and analyzed by immunoturbidimetry. The primary endpoint was all-cause mortality during the follow-up. Actuarial survival curves were compared by log rank test and a logistical Cox regression analysis was performed to identify variables independently associated with mortality in the follow-up. Statistics were calculated using the IBM Statistics program SPSS version 26. Results 600 patients were analyzed. The overall average ACR value was 7 mg/gr (95% CI 4-26). 76% had normoalbuminuria (ACR 0-30 mg/gr), 22% had microalbuminuria (ACR 30-300 mg/gr), and 1.5% had macroalbuminuria (ACR &amp;gt; 300 mg/gr). The median and interquartile range of follow-up was 12 years (95% IC 11-14). The average ACR among those who met the primary endpoint was 59.15 mg/gr (95% CI 52-66) and among the survivors, 27.66 mg/gr (95 % CI 63-77), p &amp;gt; 0,003. ACR terciles were defined by 33th and 66th percentiles: tercile 1: patients with ACR of 0 to 4 mg/gr, tercile 2: ACR from 4 to 17 mg/g and tercile 3 values greater than 17mg/gr. Strong associations were observed between ACR with age, hypertension, stroke and history of COPD, previous use of angiotensin II converter/blocking enzyme inhibitors, systolic blood pressure at admission, ST segment deviation, left ventricle ejection fraction and elevation of serum Troponin T and CPK MB. All cause-mortality during the follow-up was 14% (CI 95% 11-17). Elevation of ACR was significantly associated with long term mortality risk: log rank test chi square: 133.936, p = 0.0001. By multivariate Cox regression analysis adjusted by age, gender, diabetes, hypertension, serum creatinine, troponin T elevation, ST segment deviation, previous AMI, prior use of aspirin, statins and percutaneous coronary intervention after hospitalization, the ACR was independently associated with a 12-year follow-up mortality: OR 13 (95% IC 5-35; p &amp;lt; 0.0001). Conclusion Single spot urine ACR at admission is a strong predictor of 12-year follow-up mortality in an unselected cohort of patients with non-ST-segment elevation acute coronary syndromes.Baselines characteristics of cohortsMultivariable COX regression analysis

Cardiac transthyretin amyloidosis in patients with conduction system disease

Abstract Background/Introduction Cardiac amyloidosis (CA) is characterized by extracellular deposition of misfolded proteins in the heart. The data suggest that cardiac amyloidosis is underappreciated as a cause of common cardiac diseases or syndromes. More than 98% of currently diagnosed cardiac amyloidosis result from fibrils consisting of monoclonal immunoglobulin light chains (AL) or transthyretin (ATTR). The natural history of ATTR cardiomyopathy commonly includes both the conduction system disease and arrhythmias, which may occur years before the onset of heart failure. Conduction abnormalities are commonly encountered among patients with CA and constitute an important cause of morbidity and mortality. Most reports agree that pacemakers are most common in wild type ATTR-CA, followed by hereditary ATTR-CA and, finally, AL-CA. Purpose As unexplained LV wall thickness ≥ 12 mm is a screening sign of possible cardiac ATTR, systematicscreening for CA in patients requiring permanent pacemakers with unexplained LV wall thickness of ≥ 12 mm seems to be rational and could possibly lead to early diagnosis of cardiac ATTR. To the best of our knowledge, the usefulness of such screening has not been investigated before. This project, therefore, aims to determine the prevalence of cardiac ATTR and its subtypes in this preselected group, and to propose the most suitable battery of diagnostic procedures for this purpose. Methods Population to be tested: Consecutive patients ≥50 years referred for permanent pacemaker implantation with unexplained LV wall thickness ≥12 mm determined by echocardiography. The research protocol was that of an open-label prospective study. Biochemistry samples including serum troponin I and NT-proBNP were collected before pacemaker implantation. All patients were screened for ATTR-CA according to the recommendations of the Position statement of the ESC Working group on myocardial and pericardial diseases. Tc-DPD scintigraphy scan served as a gold standard for determining the diagnosis of cardiac ATTR. Results Out of 100 consecutive patients meeting inclusion criteria, 15 % suffered from amyloidosis (12 patients were diagnosed with ATTR and 3 with AL cardiac amyloidosis). Table 1 shows a variety of parameters, many of which differed between patient groups with and without amyloidosis, confirming the wide range of parameters significantly associated with cardiac amyloidosis; our ongoing research in this field could lead to the development of a scoring system for detection of cardiac amyloidosis. Conclusions The prevalence of cardiac amyloidosis in the investigated group was 15 %. Systematic screening for ATTR in patients with unexplained LV wall thickness ≥ 12 mm requiring permanent pacemaker implantation seems to be rational and could possibly lead to an earlier diagnosis of cardiac amyloidosis, especially ATTR.

Early high-sensitivity troponin elevation in predicting short-term mortality in sepsis: A protocol for a systematic review with meta-analysis.

Sepsis is a common admission diagnosis in the intensive care unit (ICU). The Sepsis-3 consensus associates sepsis diagnosis with acute organ dysfunction. In these patients troponin elevation is a well-established phenomenon, but its clinical significance is not settled, as no systematic review has addressed the prognostic significance of the increasingly prevalent high-sensitivity troponin assays in acute organ dysfunction setting. This study aims to clarify the association between early serum troponin levels in high-sensitivity assays with short-term mortality risk in septic patients with acute organ dysfunction. We will systematically search PubMed, Scopus and Embase for original articles; additionally, a manual search will be carried out through relevant literature. Generally, studies will be deemed eligible for inclusion if they evaluate the association between high-sensitivity troponin in the first 24 hours of admission and ICU, 30-days, or In-hospital mortality; in patients with septic shock or sepsis related to acute organ dysfunction. Two reviewers will independently select studies and extract the data. A meta-analysis for mortality outcome will be performed for comparative data regarding two effect measures: Odd ratios and Standardized Mean differences. This study will provide further evidence about the role of high-sensitivity troponin assays in predicting mortality in septic patients; potentially helping to guide further research and yielding valuable information for patient assessment. Conclusion about the certainty of evidence will be presented in a ´Summary of findings´ table. PROSPERO registration: (CRD42024468883).

Microvascular obstruction in cardiac amyloidosis.

Cardiac amyloidosis (CA) is characterized by deposition of amyloid fibrils within the extracellular space, causing disarray of the myocardial structure and capillary architecture. This study aims to characterize the prevalence of microvascular obstruction (MVO) in patients with CA and to assess the association between MVO and prognosis. The study population comprised 800 patients, of which 400 had light-chain CA (AL-CA) and 400 had transthyretin CA (ATTR-CA). MVO was present in 221 (27.6%) patients, and more common in ATTR-CA than AL-CA (124 [56.1%] vs. 97 [43.9%], p = 0.033). Patients with MVO had a more severe cardiac phenotype evidenced by higher N-terminal pro-brain natriuretic peptide (3516 ng/L [1944-6247] vs. 2508 ng/L [1203-5752], p < 0.001), worse global longitudinal strain (-10.5% [-12.6; -7.9] vs. -12.0% [-16.0; -8.9], p < 0.001), and higher extracellular volume (56% [51-61] vs. 50% [45-57], p < 0.001). Patients with AL-CA and MVO had a higher serum troponin (86 ng/L [47-148] vs. 59 ng/L [44-78], p < 0.001), and higher T2 (53 ms [50-56] vs. 50 ms [48-52], p < 0.001), but lower extracellular volume (55% [50-60] vs. 58% [53-61], p = 0.008) and lower indexed myocyte cell volume (48.6 g/m2 [41.1-59.8] vs. 55.7 g/m2 [47.5-68.4], p < 0.001) than patients with ATTR-CA and MVO. MVO was associated with an increased risk of mortality in the overall population (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.03-1.59, p = 0.025), and the subgroup with AL-CA (HR 1.59, 95% CI 1.17-2.17, p = 0.003) but not ATTR-CA (HR 1.04, 95% CI 0.77-1.40, p = 0.814). Microvascular obstruction is common in CA and is related to markers of amyloid infiltration. MVO is associated with an increased risk of mortality in AL-CA, but not in ATTR-CA. This reflects the intrinsic differences in disease biology between these two forms of CA, with MVO likely related to multiple myocardial processes, amyloid infiltration, oedema and myocyte death.

Elevated Cardiac Troponin Levels as a Predictor of Increased Mortality Risk in Non-Cardiac Critically Ill Patients Admitted to a Medical Intensive Care Unit.

Background: Cardiac troponin I (TnI) is a specific marker of myocardial damage used in the diagnosis of acute coronary syndrome (ACS). TnI levels can also be elevated in patients without ACS, which is linked to a worse prognosis and mortality. We evaluated the clinical implications and prognostic significance of serum TnI levels in critically ill non-cardiac patients admitted to the intensive care unit (ICU) at a tertiary-level hospital. Materials and Methods: A three-year retrospective study including the years 2017-2020 was conducted to evaluate in-hospital mortality during ICU stay and mortality rates at 28 and 90 days, as well as one and two years after admission, in 557 patients admitted to the medical ICU for non-cardiac causes. Results: TnI levels were elevated in 206 (36.9%) patients. Patients with elevated TnI levels were significantly older and had higher rates of comorbidities, including chronic heart failure, coronary heart disease, and chronic kidney disease (p < 0.05 for all). Patients with elevated TnI levels required more invasive mechanical ventilation, vasopressor infusion, and dialysis in the ICU and experienced more shock within the first 72 h (p = 0.001 for all). High TnI levels were associated with higher Acute Physiological and Chronic Health Evaluation (APACHE) II (27.6 vs. 20.3, p = 0.001) and Sequential Organ Failure assessment (8.8 vs. 5.26, p = 0.001) scores. Elevated TnI levels were associated with higher mortality rates at 28 days (58.3% vs. 19.4%), 90 days (69.9% vs. 35.0%), one year (78.6% vs. 46.2%), and two years (82.5% vs. 55.6%) (p < 0.001 for all). Univariate logistic regression analysis revealed that high TnI levels were a strong independent predictor of mortality at all time points: 28 days (OR = 1.2, 95% CI: 1.108-1.3, p < 0.001), 90 days (OR = 1.207, 95% CI: 1.095-1.33, p = 0.001), one year (OR = 1.164, 95% CI: 1.059-1.28, p = 0.002), and two year (OR = 1.119, 95% CI: 1.026-1.22, p = 0.011). Multivariate analysis revealed that age, albumin level, APACHE II score, and requirements for dialysis and vasopressor use in the ICU were important predictors of mortality across all timeframes, but elevated TnI levels were not. Conclusions: Elevated TnI levels in critically ill non-cardiac patients are markers of disease severity. While elevated TnI levels were significant predictors of mortality in the univariate analysis, they lost significance in the multivariate model when adjusted for other factors. Patients with elevated TnI levels had higher mortality rates across all timeframes, from 28 days to two years.

Carbon monoxide-releasing molecule-3 ameliorates traumatic brain injury-induced cardiac dysfunctions via inhibition of pyroptosis and apoptosis.

Traumatic brain injury (TBI) frequently results in cardiac dysfunction and impacts the quality of survivors' life. It has been reported that carbon monoxide-releasing molecule-3 (CORM-3) administration immediately after hemorrhagic shock and resuscitation (HSR) ameliorated the HSR‑induced cardiac dysfunctions. The purpose of this study was to determine whether the application of CORM-3 on TBI exerted therapeutic effects against TBI-induced cardiac dysfunctions. Rats were randomly divided into four groups (n = 12) including Sham, TBI, TBI/CORM-3 and TBI/inactive CORM-3 (iCORM-3) groups. TBI was established by a weight-drop model. The rats in the TBI/CORM-3 group and TBI/iCORM-3 group were intravenously injected with CORM-3 and iCORM-3 (4mg/kg) following TBI, respectively. The time of death in the rats that did not survive within 24h was recorded. 24h post-trauma, the cardiac function, pathological change, serum troponin T and creatine kinase-MB (CK-MB) levels, pyroptosis, apoptosis and expressions of TUNEL staining, Gasdermin D (GSDMD), IL-1β, IL-18, ratio Bax/Bcl-2 were assessed by echocardiography, hematoxylin-eosin staining, chemiluminescence, immunofluorescence, and western blot assays, respectively. TBI-treated rats exhibited dramatically decreased ejection fraction and aggravated myocardial injury, increased mortality rate, elevated levels of serum troponin T and CK-MB, promoted cardiac pyroptosis and apoptosis, and upregulated expressions of cleaved caspase-3, GSDMD N-terminal fragments, IL-1β, IL-18, and ratio of Bax/Bcl-2, whereas CORM-3 partially reversed these changes. CORM-3 ameliorated TBI-induced cardiac injury and dysfunction. This mechanism may be responsible for the inhibition of pyroptosis and apoptosis in cardiomyocyte.

7087 An Unusual Movement Disorder, Case of Diabetic Striatopathy!

Abstract Disclosure: S. Azmat: None. O. Lodhi: None. R. Safi: None. H. harb: None. H. Ashok: None. M.F. Siddiqui: None. J.L. Gilden: None. Background: Non-ketotic Hyperglycemia Hemichorea-Hemiballismus Syndrome (NKH-CB) is rare complication of poorly controlled diabetes mellitus (DM) characterized by continuous, irregular jerky movements localized to one side of the body. It is commonly seen in type 2 DM and is often presented in females of East Asian descent. NKH-CB is often misdiagnosed due to its rarity and radiographic features easily mistaken for intracerebral hemorrhage.Case: A 70-year-old Latino male with type 2 diabetes mellitus, hypertension, bipolar disorder and past history of two cerebrovascular accidents presented to ED with non-radiating, midsternal chest pain. ACS was ruled out with negative serial troponins and normal EKG. Vital signs were significant for elevated blood pressure 151/64 mmHg. Labs showed blood glucose=447 mg/dL. Physical examination revealed large amplitude involuntary movements in left upper and lower extremities and facial region. He also veered to the left when ambulating. The patient reported that these abnormal movements were occurring for last three weeks although sensation was preserved bilaterally. Code stroke was called; non-contrast CT showed unilateral hyper density of the right caudate and putamen with no evidence of acute intracranial hemorrhage or large arterial territory infarction. CT Angiogram did not show any signs of stenosis or occlusion. He received intravenous fluids and 8 units lispro insulin in ED. Was admitted for further evaluation and received basal/bolus insulin therapy with target blood glucose of 140-160 mg%. He also received risperidone for his mental condition. Subsequent testing revealed hemoglobin A1C of 16.9% (reference range: &amp;lt; 5.7%). MRI Brian showed unilateral T1 hyperintensity involving right caudate and putamen corresponding to the hypodensity seen on CT. Neurology service was consulted. Based on clinical signs/symptoms coupled with neuroimaging, he was diagnosed with non-ketotic Hyperglycemia Hemichorea-Hemiballismus Syndrome. On day 2 with resolution of hyperglycemia, amplitude and frequency of involuntary arm movements were minimal. The patient was discharged with Lantus 7 and metformin 1000 mg for DM and risperidone for symptoms management. Conclusion: Diabetic neuropathy is commonly known to result in small and/or large fiber sensorimotor polyneuropathy, proximal motor, and acute mononeuropathies as well as entrapments, radiculopathies, autonomic neuropathies, and even cognitive disorders. This case describes rare case of simultaneous NKH-CB with history of CVA and antipsychotic medication use in a patient with poorly controlled DM which resolved with treatment of hyperglycemia. Thus offers valuable insights into the diagnostic challenges associated with this condition as well as potential links to other neurological complications. One should also remain vigilant of potential onset of seizures commonly seen with NKH. Presentation: 6/3/2024