Elevated Cardiac Troponin Research Articles

Endomyocardial biopsy in the diagnosis of cardiac sarcoidosis

Abstract Background Definite diagnosis of cardiac sarcoidosis (CS) requires proof of sarcoid granulomas in the heart. Endomyocardial biopsy (EMB) is considered a risky procedure with poor sensitivity (<25%) in CS (1), although comprehensive studies on its diagnostic performance are not available. Purpose We investigated the sensitivity, complications, and prognostic significance of EMB in a large cohort of patients with CS to help to choose diagnostic strategy when the disease is suspected. Methods We analysed the data of 260 consecutive patients diagnosed with CS in 1988-2022 at our institution. All met the diagnostic criteria of the Heart Rhythm Society (1). The use, findings, and complications of EMB were retrospectively noted in addition to patients’ demographics, presenting phenotype, diagnostic examinations, and future serious cardiac events. The data were retrieved from hospital records and an ongoing CS registry (2). Advanced imaging studies (cardiac magnetic resonance, positron emission tomography) were re-analysed and the follow-up information was updated until June 2023. EMB’s performance was assessed also in 30 cardiac transplant recipients having CS at the histopathologic study of the explanted heart. Results Of the 260 patients (mean age 49, 60% females), 216 (83%) underwent diagnostic EMB, 48 with repeat procedures. The sensitivity of EMB was 38%, rising to 49% after repeats. The predictors of positive EMB (Table 1) included the presenting phenotype and characteristics of the activity, extent, and location of myocardial involvement. Presentation with ventricular tachyarrhythmia, left ventricular (LV) ejection fraction ≤45%, elevation of cardiac troponins, and presence of middle or apical LV septal late gadolinium enhancement on magnetic resonance imaging were independent predictors (p<0.05) of positive biopsy. The sensitivity of EMB was directly related to the count of the predictors present (Figure 1). The rate of procedural complications was 9.7% overall and 0.7% for major events. One pericardial effusion needed drainage, but no deaths or long-term sequels followed the biopsies. Minor complications included 10 paroxysms of ventricular tachycardia and 6 small pericardial effusions. The 10-year rate (95% CI) of the composite of cardiac death, end-stage heart failure, or ventricular tachyarrhythmia was 55% (44-67%) with positive EMB vs 29% (17-44%) with negative EMB (p<0.001). When adjusted for the presenting phenotype and LV ejection fraction, EMB did not predict outcome events. In the 30 patients with CS in explanted hearts, the sensitivity of EMB, including the repeats, was 60%. Conclusion The sensitivity of EMB is better than usually presented in CS and the higher the more extensive myocardial involvement is. Risk of serious complications is <1%. In patients with suspect CS, the pre-test likelihood and value of positive EMB should be weighed against the procedural risks in shared decision-making when choosing the diagnostic pathway.

Cardiac troponin elevation in intracerebral hemorrhage patients may rather reflect acute myocardial damage than acute myocardial infarction

Abstract Background Patients with acute ischemic stroke (AIS) and elevated cardiac troponin (cTn) have worse functional and mortality-related outcome. While elevated cTn is also frequently observed in patients with intracerebral hemorrhage (ICH), routine invasive coronary angiography should not be performed on these patients. Existing data on correlation of cTn elevation with patient outcome and the underlying causes in this specific patient group are sparse and largely heterogeneous. Purpose To investigate the clinical variables that predict cTn elevation in patients with ICH and the impact of cTn elevation on intrahospital mortality and functional outcome. Methods Our long-term Stroke Database was screened for ICH patients with high-sensitivity (hs) cTn measurement on admission (from 2015 onwards). Baseline characteristics, intrahospital mortality and functional outcome at discharge were compared between the groups with and without cTn elevation (hs-cTnI > vs. ≤0.045 µg/L). In addition, clinical variables with suspected significance for cTn elevation were analyzed for their predictive value. Results A total of 93/498 patients with ICH (18.7%; mean age 73±15 years, 53.8% females) were found to have a cTn elevation. Regarding etiology, 38.7% had an ICH occurring after AIS and 31.2% had a hypertensive ICH (each p=NS between groups). Patients with cTn elevation did not have a more pronounced cardiovascular risk profile and had a comparably low prevalence of coronary artery disease (CAD; 18.5%, p=NS). However, they were significantly less likely to be on oral anticoagulation at the time of the bleeding event (7.5 vs. 18.0%, p=0.013). CTn elevation had no negative impact on intrahospital mortality (21.5 vs. 20.5%, p=NS) or functional outcome at discharge (NIHSS score 10 (2; 26) vs. 9 (2; 22) points, mRS 5 (3; 5) vs. 5 (3; 5) points, each p=NS). Increasing NIHSS score on admission (p=0.021, OR 1.084 [1.012-1.160]), mRS ≥4 on admission (p=0.005, OR 2.207 [1.180-2.826]), infratentorial bleeding localization (p=0.034, OR 4.899 [1.132-21.207]) and aortic valve stenosis ≥ intermediate (p<0.001, OR 8.435 [2.429-29.294]) predicted cTn elevation. In contrast, severely impaired left ventricular function, CAD, atrial fibrillation, intraventricular hemorrhage or ICH occurring after AIS had no predictive value. Conclusions Almost one fifth of patients with ICH had an elevated cTn. Unlike in AIS, in ICH cTn elevation was not associated with a worse functional or mortality-related intrahospital outcome. In particular, severe functional impairment on admission, reflecting severe ICH, or infratentorial hemorrhage localization, thought to affect the autonomic nervous system, was predictive of concomitant myocardial cell damage. CAD was rare overall. This could indicate that the cTn elevation in connection with ICH is primarily related to acute myocardial damage along the brain-heart axis and less to myocardial infarction.

Comprehensive echocardiographic and biomarker assessment of patients with diabetic ketoacidosis

BackgroundSystemic stress, inflammation, and hydroelectrolytic and acid‒base abnormalities observed during diabetic ketoacidosis (DKA) can cause changes in the heart and even induce cardiovascular damage. We aimed to evaluate the structure and function of the heart during and after a DKA episode via echocardiography and biomarker assessment.MethodsWe performed a transthoracic echocardiogram (TTE) in subjects with an episode of DKA in the first 4–6 h of treatment. We evaluated left ventricular wall thickness, diameters and volumes, as well as systolic and diastolic function using tissue Doppler imaging, pulsed wave Doppler and left ventricular ejection fraction (LVEF). Left ventricular function was also assessed with global longitudinal strain (GLS). We obtained cardiac troponin levels in the first 24 h after admission. A second TTE was performed following the same protocol 6–12 h after the resolution of the DKA episode.ResultsWe included a total of 20 subjects. The mean age was 33 ± 13.6 years; 70% were female, and 70% had type 1 DM. 75% of the patients experienced severe episodes, and the rest experienced moderate episodes. Left ventricular isovolumetric contraction and ejection time were significantly shorter during DKA and prolonged after the resolution of the episodes (47.6 ± 9.9 vs. 62.2 ± 14.1, p = < 0.001) and (218.6 ± 37.9 vs. 265.06 ± 34.7). The isovolumetric relaxation time was also shorter during DKA, (41.72 ± 8.29 vs. 59.32 ± 17.98, p = < 0.001). Volumes and diameters of the left ventricle increased significantly after DKA resolution. We found no difference between LVEF or GLS during and after DKA resolution. 20% of the participants had troponin elevations, half of whom had moderate episodes and half of whom had severe episodes. 35% had LV dysfunction, 28.5% both in GLS and LVEF. 28.5% occurred after DKA resolution, with alterations in GLS.ConclusionsDiabetic ketoacidosis induces changes in the structure and function of the heart, which are mostly transient, reflect the presence of a hyperdynamic state and resolve after the resolution of the episode. Some subjects present with evidence of myocardial injury with elevated cardiac troponin and left ventricular dysfunction.Graphical abstractIcons in the graphical abstract are made by Freepik from www.flaticon.com.

Cardiac troponin fragmentation in marathon runners. The MaraCat2 study

Abstract Background Cardiac troponins(cTn) are in a key role in the diagnosis of acute myocardial infarction (MI). Minor cardiac troponin elevations are also common after strenuous exercise, while limited evidence suggests this elevation consists mostly of smaller cTn fragments. Purpose We aimed to determine if our novel cardiac troponin assay, measuring long molecular forms of cardiac troponin (long cTnT) can differentiate cardiac troponin elevation associated with strenuous exercise from that seen in MI. Methods In a Proof-of-Principle study, we developed a simple time-resolved immunofluorometric assay based on europium chelate labels for the measurement of long cardiac troponin T molecules, which showed high accuracy in discriminating between cTn elevations in MI and end-stage renal failure. In the present study, we compared the characteristics of cTn release after a marathon race and Type 1 MI using an improved version of the long troponin test and a commercially available cTnT test. Troponin composition was analyzed in heparin plasma samples taken from 45 runners &amp;lt;1h after marathon race and from 45 patients with Type 1 MI. The concentration of long cTnT was measured with a novel immunofluorometric assay, total cTnT was measured with a commercial high-sensitivity cTnT assay, and the ratio of long to total cTnT (troponin ratio) was determined. Results Conventional cTnT exceeded the upper reference limit in 37 (82%) runners with a median concentration of 25.0 (IQR 16-36)ng/l. Median long cTnT concentration was 4.1 (IQR 2.4-5.8)ng/l. The median total and long cTnT concentration and the troponin ratio were higher in patients with MI than in marathon runners (p&amp;lt;0.001). Troponin ratio decreased (r=-0.497, p&amp;lt;0.001) in marathon runners and increased (r=0.466, p=0.001) in patients with MI with increasing troponin release (Figure 1). In the receiver operating characteristics curve analyses of all patients with cTnT release &amp;gt;14ng/l, long cTnT showed good predictive power with area under curve 0.969 (CI95% 0.939-1.000) in discriminating marathon runners from MI patients. Conclusions Our novel highly sensitive long cTnT immunoassay shows that the troponin release after strenuous exercise is composed mainly of smaller troponin fragments. Our test could be useful in separating benign cTnT elevations caused by exercise from those of acute MI.

Prevalence of elevated cardiac troponin in five non-cardiac diseases

Abstract Background Cardiac troponins (cTns) are regulatory proteins located in the cardiac muscle cells (cardiomyocytes). Since the 1990s, cTns have been the biochemical gold standard for detecting myocardial infarction. CTns are well studied among patients with cardiac illnesses and elevated concentrations are known to reflect myocardial injury. Still, high cTn concentrations are found in several non – cardiac conditions where signs of cardiac dysfunction are absent(1). This is especially found to be true for cardiac troponin T (cTnT) which is, more frequently than cardiac troponin I (cTnI), found to be elevated in patients with non – cardiac conditions(2,3). A study from 2016 of 1012 patients admitted to the emergency room, found troponin T elevations in 40.8% of patients without acute coronary syndrome vs. 7.4% with cTnI elevations(3). To our knowledge, no previous study has investigated cTn elevations across disease -groups where elevations of cTns are frequently detected. Purpose We aimed to investigate the prevalence of cTnT in five clinical non-cardiac disease-groups where frequent elevation of cTnT is previous described; Sepsis, rhabdomyolysis, end-stage renal disease (ESRD), stroke, and major non-cardiac surgery (MNCS). Methods Our study was a single-center prospective cross-sectional cohort study. Over a 6-month period, we included patients in the five above mentioned disease-groups. We excluded patients with any symptoms of cardiac disease or a prior history of cardiac diseases. All patients were included within 48 hours of admission and underwent clinical examination, vital signs, 12-lead electrocardiogram, echocardiography, and collections of blood samples. Cardiac troponin T was measured at patient’s bedside upon inclusion with the Cobas h232, cTnT point-of-care test. Results 89 patients were eligible for inclusion, 15 with sepsis, 18 with rhabdomyolysis, 11 with end-stage renal disease, 22 with stroke and 23 with major non-cardiac surgery. 53% were men. 17 patients (19%) had signs of cardiac disease confirmed on echocardiographic and/or electrocardiographic examinations and were excluded. Out of the 72 patients without signs of cardiac disease, elevated cTnT above the 99th percentile was found in 21 (29%) patients; 4 (36%) with sepsis, 6 (60%) with rhabdomyolysis, 4 (44%) with ESRD, 2 (9.5%) with stroke and 5 (24%) with MNCS. The median of cTnT in patients with elevated cTnT across all patient groups was 79.5 ng/L (IQR 52.5ng/L – 187.8 ng/L). Conclusions Cardiac troponin T elevations are frequent in the five non-cardiac diseases investigated. Elevations are most frequent in patients with rhabdomyolysis and end-stage renal disease. Further investigation is warranted to elucidate the underlying etiology contributing to the elevation of cardiac troponin in non-cardiac diseases.

Comparison of ultrasound-assisted thrombolysis and mechanical thrombectomy in patients with intermediate-high-risk pulmonary embolism

Abstract Background Pulmonary embolism (PE) can cause right heart failure and is associated with a high mortality. Early risk stratification is critical for individualized management. In patients with intermediate-high-risk PE, guidelines recommend to consider a percutaneous catheter-directed treatment (CDT). While different techniques are available, comparisons between treatments regarding right heart function and outcome are still scarce. Purpose To compare changes in right heart function as well as outcome in patients with intermediate-high-risk PE after catheter-directed treatment with ultrasound-assisted thrombolysis as compared to mechanical thrombectomy. Methods This is a retrospective, single-center study in intermediate-high-risk PE. According to the ESC guidelines, all patients had PESI class III-V, RV dysfunction and elevated cardiac troponin levels, but were hemodynamically stable. PE was confirmed by CT angiography. All patients underwent a catheter-directed treatment. One group received an ultrasound-assisted thrombolysis (USAT), while the other had a large-bore mechanical thrombectomy (MT). Right heart function (RV-Diameter, RV-/LV-Ratio, TAPSE) assessed via transthoracic echocardiography before and after CDT as well as interventional characteristics and postinterventional hospital stay were compared. Results From June 2022 to January 2024, 27 patients (43% female; aged 62 ± 14 years) were diagnosed with pulmonary embolism with intermediate-high-risk and underwent a catheter-directed treatment. Most patients (89%) had bilateral pulmonary embolisms. 15 patients (55%) received an ultrasound-assisted thrombolysis. 12 patients (45%) had a mechanical thrombectomy via a large-bore aspiration system. The mean procedural time was 41 ± 19 minutes for USAT and 106 ± 33 minutes for MT (p &amp;lt; 0.001). Right ventricular / left ventricular ratio reduction was -0.48 ± 0.25 in the USAT group (p &amp;lt; 0.001) and -0.34 ± 0.14 in the MT group (p &amp;lt; 0.001) (between group difference p = 0.2). TAPSE increased by 8 mm ± 4.4 mm in the USAT group (p &amp;lt; 0.001) and by 8.7mm ± 3.8 mm in the MT group (p &amp;lt; 0.001) (between group difference p = 0.7). The median postinterventional hospital stay was 7 days for the USAT patients and 7 days for the MT patients (between group difference p = 1). Conclusions In patients with intermediate-high-risk PE both ultrasound-assisted thrombolysis and large-bore mechanical thrombectomy lead to an improved right heart function with both interventions leading to a similar length of postprocedural hospital stay. Further randomized data have to discriminate differential impact of novel tools for the treatment of intermediate risk PE.

The Hidden Heart: Exploring Cardiac Damage Post-Stroke: A Narrative Review

Stroke–heart syndrome (SHS), a critical yet underrecognized condition, encompasses a range of cardiac complications that arise following an ischemic stroke. This narrative review explores the pathophysiology, clinical manifestations, and implications of SHS, focusing on the complex interplay between the brain and the heart. Acute ischemic stroke (AIS) triggers autonomic dysfunction, leading to a surge in catecholamines and subsequent myocardial injury. Our review highlights the five cardinal manifestations of SHS: elevated cardiac troponin (cTn) levels, acute myocardial infarction, left ventricular dysfunction, arrhythmias, and sudden cardiac death. Despite the significant impact of these complications on patient outcomes, there is a notable absence of specific guidelines for their management. Through a comprehensive literature search, we synthesized findings from recent studies to elucidate the mechanisms underlying SHS and identified gaps in the current understanding. Our findings underscore the importance of early detection and multidisciplinary management of cardiac complications post-stroke. Future research should focus on establishing evidence-based protocols to improve clinical outcomes for stroke patients with SHS. Addressing this unmet need will enhance the care of stroke survivors and reduce mortality rates associated with cardiac complications.

GIANT CELL MYOCARDITIS: AUTOPSY CONFIRMATION OF A DIAGNOSTIC DILEMMA - A RARE CASE REPORT

Abstract Introduction/Objective Giant cell myocarditis (GCM) is a rare and rapidly progressive form of myocarditis, commonly leading to fulminant heart failure (HF), refractory ventricular arrhythmias or conduction system abnormalities and carrying a high mortality rate without prompt treatment. Due to its rarity, there is limited data on its prevalence, although studies show an incidence of 0.007–0.053% among autopsied cases. This entity primarily affects the heart, exhibiting a rapid clinical course and a poor prognosis necessitating immunosuppressive therapy and, in most instances, heart transplantation to improve survival rates. Methods/Case Report We present a case of a 62-year-old male with a prior history of complete heart block status post permanent pacemaker placement, presenting with acute decompensated heart failure. Laboratory investigations revealed elevated cardiac troponin levels (&amp;gt;35000) with echocardiography showing a reduced ejection fraction of 25% and an initial diagnosis of non-ST elevation myocardial infarction (NSTEMI) was made. Endomyocardial biopsy revealed GCM. Despite aggressive management, including immunosuppressive therapy and mechanical circulatory support, his condition deteriorated rapidly, leading to multiorgan failure and eventual death. The diagnosis was confirmed on autopsy. The diagnostic challenge of GCM lies in its clinical or pathologic overlap with other myocardial disorders such as cardiac sarcoidosis, viral myocarditis, and cardiac amyloidosis. Endomyocardial biopsy (EMB) remains the gold standard for diagnosing this entity which is characterized by a widespread inflammatory cell infiltrate with multinucleated giant cells in association with myocyte damage. The etiology of GCM remains unclear, but it is believed to be immune-mediated, possibly triggered by an autoimmune response. Results (if a Case Study enter NA) NA Conclusion Pathologists should give importance to consider GCM in the differential diagnosis of patients presenting with acute heart failure refractory to standard therapy. Early recognition and prompt initiation of immunosuppressive therapy are crucial for improving outcomes in patients with GCM. Awareness of this entity is crucial to make a timely diagnosis.

Cardiac troponin elevation and mortality in takotsubo syndrome: New insights from the international takotsubo registry.

The clinical relevance of cardiac troponin (cTn) elevation in takotsubo syndrome (TTS) remains uncertain. The present study sought to investigate the role of cardiac troponin (cTn) elevations in mortality prediction of patients with Takotsubo syndrome (TTS). Patients enrolled in the International Takotsubo (InterTAK) Registry from January 2011 to February 2020 with available data on peak cTn levels were included in the analysis. Peak cTn levels during the index hospitalization were used to define clinically relevant myocardial injury. The threshold at which clinically relevant myocardial injury drives mortality at 1 year was identified using restricted cubic spline analysis. Out of 2'938 patients, 222 (7.6%) patients died during 1-year follow-up. A more than 28.8-fold increase of cTn above the upper reference limit was identified as threshold for clinically relevant myocardial injury. The presence of clinically relevant myocardial injury was significantly associated with an increased risk of mortality at 5 years (adjusted HR 1.58, 95% CI 1.18-2.12, p =.002). Clinically relevant myocardial injury was related to an increased 5-year mortality risk in patients with apical TTS (adjusted HR 1.57, 95% CI 1.21-2.03, p =.001), in presence of physical stressors (adjusted HR 1.60, 95% CI 1.22-2.11, p =.001), and in absence of emotional stressors (adjusted HR 1.49, 95% CI, 1.17-1.89, p =.001). This study for the first time determined a troponin threshold for the identification of TTS patients at excess risk of mortality. These findings advance risk stratification in TTS and assist in identifying patients in need for close monitoring and follow-up.

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.

Elevated high-sensitive cardiac troponin T in emergency department patients: insights from a retrospective descriptive cohort study

BackgroundHigh-sensitive cardiac troponin T (hs-cTnT) assessments are routinely conducted in German emergency departments (EDs). However, data describing a large number of ED patients with pathological hs-cTnT levels and subsequent clinical outcomes are limited.MethodsThis retrospective descriptive analysis included 141.892 patients who presented to the interdisciplinary ED at Klinikum rechts der Isar in Munich, Germany, between January 2019 and December 2021. Patients with trauma diagnoses were excluded, focusing on those with elevated hs-cTnT levels. These patients were categorized into three groups based on the International Classification of Procedures in Medicine (ICPM): those with elevated hs-cTnT who received no coronary angiography (NCA), those who underwent diagnostic coronary angiography (DCA), and those who received percutaneous coronary intervention (PCI). The objective of this study was to characterize a large emergency department patient cohort and assess their subsequent clinical outcomes.ResultsAfter initial Manchester Triage Sytem (MTS) categorization, 32.6% (46.307/141.892) of patients were identified as non-trauma cases. Of these, 9.9% (4.587/46.307) had hs-cTnT levels exceeding 14 ng/L. Within this subset, 70.4% (3.230/4.587) did not undergo coronary angiography, 15.4% (705/4.587) underwent DCA and 14.2% (652/4.587) received PCI. Chest pain occurred more frequently in the PCI group (28.0%, 160/652) compared to the DCA group (18.3%, 113/705) or NCA group (5.7%, 159/3230), p < 0.001. However, breathing problems occurred more frequently in the NCA group (23.2%, 647/3230) compared to the PCI group (17.7%, 101/652) or DCA group (21.8%, 135/705), p < 0.001. Also, collapse was more frequent in patients in the NCA group (4.0%, 112/3230) compared to the DCA group (3.4%, 21/705) or PCI group (3.5%, 20/652), p < 0.001. Overall, in-hospital mortality was significantly higher in the NCA group (7.9%, 256/3230) compared to the DCA group (2.3%, 16/705) or PCI group (4.1%, 27/652), p < 0.001.ConclusionEmergency patients with elevated hs-cTnT who did not undergo coronary angiography faced a higher risk of in-hospital mortality in our retrospective descriptive study. Given the heterogeneous nature of presenting complaints in emergency departments, identifying at-risk patients can pose challenges for treating physicians.

A-009 Analytical Characterization of a Novel NT-proBNP Assay on a Central Laboratory Platform

Abstract Background N-terminal pro-B-type Natriuretic Peptide (NT-proBNP) or B-type Natriuretic Peptide (BNP) assay(s) are widely measured with a Class 1, Level of Evidence A recommendation in professional heart failure (HF) guidelines for diagnosis and prognosis. We present the analytical characteristics of the first NT-proBNP assay on Beckman Coulter platforms. Methods Measurements were conducted with the Access NT-proBNP assay, a one-step sandwich immunoenzymatic assay using monoclonal capture and detection antibodies, on the DxI 9000 Immunoassay Analyzer with Lithium Heparin (LiHep) plasma samples. Performance was characterized according to CLSI guidelines for: Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ), linearity, imprecision (repeatability, reproducibility) and matrix comparison with LiHep, EDTA and serum. Reference intervals (RI) were evaluated in a healthy, adult U.S. population comprised of 675 subjects with 54.6% females, 79.1% White and 15.1% Black individuals. Exclusion criteria included elevated cardiac troponin, abnormal eGFR and cardiac medications. The 97.5th percentile RI upper limit was defined for age-stratified ranges of &amp;lt;50, 50-75, and &amp;gt;75 years old. Results Performance was LoB=1.1ng/L; LoD=4.8ng/L; LoQ=4.8ng/L; linearity=35,000ng/L. Repeatability ranged from 1.5%-3.5% and reproducibility from 2.3%-7.9% in seven samples ranging from 38ng/L to 23,848ng/L. Matrix measurement regression (n=68) yielded slopes of 1.00, 1.01; intercepts -0.03 to -2.63; r=0.98. Table 1 shows that NT-proBNP values increase with age and women generally have higher values than men. Conclusions The LoB, LoD and LoQ demonstrate highly sensitive low-end characteristics. Repeatability and reproducibility show excellent performance across a wide measurement range. NT-proBNP values are known to be age dependent, and the age-stratified 97.5th percentile RI upper limits were 162 ng/L for &amp;lt;50 years, 311 ng/L for 50-70 years, and 457 ng/L for &amp;gt;75 years. This novel Access NT-proBNP assay offers robust analytical performance as an aid to clinical HF management in acute settings.

Exploring strategies to rapidly identify false positives in high-sensitivity cardiac troponin I assay: A prospective study

BackgroundCardiac troponin is the pivotal biomarker of myocardial injury, playing a central role in the diagnosis of acute coronary syndrome and various clinical situations. Nevertheless, challenges arise when patients exhibit elevated cardiac troponin levels in the absence of evident cardiac origin, as evidenced by extensive cardiac exploration, which suggests the presence of an interfering factor. Despite the high performance of high-sensitive cardiac troponin immunoassays, these tests remain susceptible to interferences that may lead to false-positives. MethodsIn the period between July 2021 and July 2024, 8129 patients were hospitalized in the cardiology departments of Bordeaux University Hospital with positive results for high-sensitivity cardiac troponin I. Among them, 15 patients were suspected of having false-positive results, based on clinical and biological observations. ResultsIn this subpopulation, we evaluated prospectively various techniques, including serial dilutions, antibody-binding tubes, and alternative immunoassays (for cardiac troponin I and T) with the objective of identifying any potential analytical interference in their high-sensitive cardiac troponin I measurements. Our investigations revealed that 12 out of 15 suspected cases exhibited an interference on the high-sensitive cardiac troponin I assay. ConclusionIn conclusion, we propose an original algorithm designed to identify high-sensitive cardiac troponin I false-positives. This algorithm can help clinicians to make prompt and informed decisions about patient care, and to avoid erroneous clinical interventions that may result from such interferences.

S971 Nationwide Population-Based Study of the Outcomes of Cardiac Troponin Elevation in Patients With Acute GI Bleed

S971 Nationwide Population-Based Study of the Outcomes of Cardiac Troponin Elevation in Patients With Acute GI Bleed

Improved diagnostic performance of high-sensitivity cardiac troponins in muscle dystrophies using comprehensive definition criteria for cardiac involvement: A longitudinal study on 35 patients.

Sparse information is available on the correct interpretation of elevated high-sensitivity cardiac troponin (hs-cTn) in confirmed muscular dystrophies. Serum concentrations of hs-cTn T (hs-cTnT) and hs-cTn I (hs-cTnI) were determined in 35 stable outpatients with confirmed skeletal muscle dystrophies. We calculated sensitivities, specificities, and positive and negative predictive values of hs-cTnT and hs-cTnI for identification of cardiac involvement using a comprehensive definition that included diastolic left ventricular and right ventricular function, strain analysis using two-dimensional transthoracic echocardiogram and magnetic resonance imaging, myocardial biopsies, and consideration of a variety of triggers for cardiac injury, including arrhythmias, conduction disorders, and hypoxemia due to respiratory failure. Cardiac involvement was diagnosed in 34 of 35 cases. Specificities of hs-cTnT increased from 12.5% to 100% (p = 0.0006) applying the comprehensive definition compared to a definition based on electrocardiography and echocardiography alone. At the recommended 99th percentile upper limit of normal, sensitivities were significantly lower for hs-cTnI than for hs-cTnT (29.4% vs. 100%, p = 0.0164). Conversely, the specificities of hs-cTnT and hs-cTnI increased to 100% when using the comprehensive definition criteria for diagnosing cardiac involvement. Elevated hs-cTnT but not hs-cTnI discriminates cardiac involvement in cases with confirmed skeletal muscle dystrophies with very high sensitivity and 100% specificity. Prior reports on worse performance may be explained by the use of less sensitive imaging methods or incomplete assessment of cardiac involvement.

Functional cardiac consequences of β-adrenergic stress-induced injury in a model of Duchenne muscular dystrophy.

Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD); however, in the mdx mouse model of DMD, the cardiac phenotype differs from that seen in DMD-associated cardiomyopathy. Although some have used pharmacologic stress to stimulate injury and enhance cardiac pathology in the mdx model, many methods lead to high mortality with variable cardiac outcomes, and do not recapitulate the structural and functional cardiac changes seen in human disease. Here, we describe a simple and effective method to enhance the cardiac phenotype model in mdx mice using advanced 2D and 4D high-frequency ultrasound to monitor cardiac dysfunction progression in vivo. mdx and wild-type mice received daily low-dose (2 mg/kg/day) isoproterenol injections for 10 days. Histopathological assessment showed that isoproterenol treatment increased myocyte injury, elevated serum cardiac troponin I levels and enhanced fibrosis in mdx mice. Ultrasound revealed reduced ventricular function, decreased wall thickness, increased volumes and diminished cardiac reserve in mdx compared to wild-type mice. Our findings highlight the utility of challenging mdx mice with low-dose isoproterenol as a valuable model for exploring therapies targeting DMD-associated cardiac pathologies.

Significance of detecting cardiac troponin I and creatine kinase MB in critically Ill children without primary cardiac illness.

To investigate the incidence of myocardial injury in children with critically ill children without primary cardiac disease and the association between elevated cardiac troponin I (cTnl) and creatine kinase MB (CK-MB) concentrations and disease progression and prognosis to guide early treatment. The serum cTnI and CK-MB concentrations of 292 children with critically ill children without primary cardiac disease in Yantai Yuhuangding Hospital between January 2021 and January 2024 were retrospectively analyzed within 24 h after entering the Pediatric Intensive Care Unit (PICU). The children were divided into normal and abnormal groups according to the myocardial marker results. The abnormal group was further divided into the cTnI-elevated, CK-MB-elevated, single-elevated (cTnI- or CK-MB-elevated) and double-elevated (cTnI- and CK-MB-elevated) groups. The differences in the clinical indicators and their relationships with prognosis for the groups were compared. The incidence of myocardial injury among the critically ill children without primary cardiac disease was 55.1%. The incidence of myocardial injury in children with infectious diarrhea combined with moderate and severe dehydration reached 85.19%. The pediatric critical illness score; frequency of use of vasoactive drugs; hypotension, shock, heart failure, respiratory failure, and multiple organ dysfunction syndrome; and mortality indexes differed significantly for the normal and abnormal myocardial marker groups (P < 0.05). The single-elevated and normal groups only showed a difference in mortality (P < 0.017). The cTnI and CK-MB concentrations were negatively correlated with prognosis (P < 0.01). Myocardial injury, as evidenced by elevated cardiac biomarkers, is common in critically ill children without primary cardiac illness. cTnI and CK-MB are associated with outcomes. Shock, heart failure, and multiple organ dysfunction syndromes are independently associated with simultaneous elevations of CK-MB and cTnI concentrations. Further prospective studies are needed to elucidate the clinical utility of these biomarkers.

Exercise-Induced Cardiac Troponin I Elevation Is Associated With Regional Alterations in Left Ventricular Strain in High-Troponin Responders.

The implications of exercise-induced cardiac troponin elevation in healthy individuals are unclear. This study aimed to determine if individuals with a high exercise-induced cardiac troponin I (cTnI) response have alterations in myocardial function following high-intensity endurance exercise compared with normal-cTnI responders. Study individuals were recruited from previous participants in a 91-km mountain bike cycling race (the North Sea Race) and were classified as high- (n=34) or normal-cTnI responders (n=25) based on maximal cTnI values after the recruitment race. The present study exposed all participants to 2 prolonged high-intensity exercises: a combined lactate threshold and cardiopulmonary exercise test and repeated participation in the North Sea Race. Echocardiography was performed before, immediately after, and 24 hours following exercise. All study individuals (n=59) had normal coronary arteries, and were aged 51±10 years; 46 (74%) were men. There were no differences in baseline characteristics between the high- and normal-cTnI responders. Maximal cTnI levels 3 hours after exercise were significantly higher in the high- compared with normal-cTnI group (P<0.001-0.027). Following exercise, there were no differences in global ventricular function between the 2 groups. In contrast, high-cTnI responders had significantly lower regional strain in the anteroseptal segments following exercise, with more profound changes after the race. High-cTnI responders had lower anteroseptal segmental strain shortly after exercise than normal-cTnI responders. However, there were no permanent alterations in myocardial strain, indicating no short- or long-term adverse consequences of these exercise-induced alterations in myocardial function. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02166216.

The Predictive Role of Cardiac Troponin Elevation Ratio Combined With Heart Function Index Model in the Prognosis of Non-ST-Segment Elevation Myocardial Infarction Patients.

Non-ST-segment elevation myocardial infarction (NSTEMI) is a common form of coronary artery disease, and its prognosis is influenced by multiple factors. This study aimed to analyze the predictive role of the combined application of cardiac troponin and cardiac function indices in NSTEMI patients' prognosis. NSTEMI patients were screened and included in the study. Cardiac troponin elevation ratio (cardiac troponin I (cTnI)/upper limit of normal (ULN)) was measured upon admission, and cardiac function was assessed. General clinical data, laboratory parameters, Grace score, New York Heart Association (NYHA) functional class, complications, and mortality data were collected. The correlation between mortality in NSTEMI patients and clinical parameters was analyzed, and a nomogram prediction model for NSTEMI patient mortality was established. A total of 252 NSTEMI patients were included. Female gender, elevated high-sensitivity C-reactive protein (H-CRP), left ventricular ejection fraction (LVEF) < 50%, NYHA class III and IV, and cTnI/ULN elevation by 36.25-fold were significantly independently associated with mortality outcomes. Multifactorial logistic analysis indicated that these indices remained associated with mortality. A nomogram model predicting NSTEMI patient mortality was constructed using these indices, with an area under the curve (AUC) of 0.911, sensitivity of 97.5%, and specificity of 72.8%. This predictive model outperformed the Grace score (AUC = 0.840). In NSTEMI patients, a 36.25-fold increase in cTnI/ULN, coupled with NYHA class III and IV, independently predicted prognosis. We developed a nomogram model integrating cTnI/ULN and cardiac function indices, aiding clinicians in assessing risk and implementing early interventions for improved outcomes.

Role of Cardiac Biomarkers in Stroke and Cognitive Impairment.

This topical review assesses the growing role of cardiac biomarkers beyond cardiovascular health and focuses on their importance in stroke and dementia. The first part describes blood-based cardiac biomarkers in patients with stroke and highlights applications in the setting of early diagnosis, poststroke complications, outcome prediction as well as secondary prevention. Among other applications, natriuretic peptides can be helpful in differentiating stroke subtypes. They are also currently being investigated to guide prolonged ECG monitoring and secondary prevention in patients with stroke. Elevated cardiac troponin after ischemic stroke can provide information about various poststroke complications recently termed the stroke-heart syndrome. The second part focuses on the role of cardiac biomarkers in vascular cognitive impairment and dementia, emphasizing their association with structural brain lesions. These lesions such as silent brain infarcts and white matter hyperintensities often co-occur with cardiac disease and may be important mediators between cardiovascular disease and subsequent cognitive decline. ECG and echocardiogram measurements, in addition to blood-based biomarkers, show consistent associations with vascular brain changes and incident dementia, suggesting a role in indicating risk for cognitive decline. Together, the current evidence suggests that cardiac blood-based, electrophysiological, and imaging biomarkers can be used to better understand the heart and brain connection in the setting of not only stroke but also dementia.