Troponin Levels Research Articles

Latent class analysis reveals a novel phenotype of heart failure that spans the left ventricular ejection fraction range

Abstract Background It is increasingly evident that heart failure (HF) represents a heterogenous syndrome rather than a single clinical entity. The elusiveness of effective therapies for heart failure with preserved ejection fraction (HFpEF) has led to a consensus that our current, unidimensional construct of HF using only left ventricular ejection fraction (LVEF) does not adequately capture the multiplicity of the disease states. The ability to harmonize echocardiographic data from multiple sources has enabled use of unsupervised cluster-based analysis to identify multidimensional cardiac structural phenotypes. Purpose To identify cardiac structural phenotypes of HF across the LVEF spectrum. Methods We harmonized echocardiographic data from eight randomized clinical HF trials (ESCAPE, EXACT-HF, FIGHT, I-PRESERVE, NEAT-HFpEF, RELAX, STICH and TOPCAT), which included both HFrEF and HFpEF populations (total n=4223 echocardiograms). These studies collectively spanned the years 2000 through 2015 and represent a balanced LVEF distribution. Latent class analysis (LCA) was performed iteratively to identify predominant structural phenotypes using LVEF, RV function, LV end diastolic volume, LV mass index, eccentricity, mitral valve deceleration time, and lateral E/e’ ratio. Results LCA identified 4 echocardiographic phenotypes. Three phenotypes skewed toward either high or low EF, but one phenotype demonstrated a relatively even distribution of patients with HFrEF, heart failure with mildly reduced ejection fraction (HFmrEF) and HFpEF (36.0%, 21.4% and 42.7%, respectively). Patients in this phenotype had preserved RV function and left ventricular hypertrophy (97%), of which 56.8% had concentric and 43.2% eccentric LVH. E/e’ was normal in 63% of subjects. A vast majority (91%) of patients had recent-onset HF (diagnosed within the past year). There were no remarkable distinguishing comorbidities. Notable differences in biomarker profile included higher levels of troponin I, cyclic GMP and lower levels of neurohormones (aldosterone, endothelin-1, dopamine, and norepinephrine) than the other phenotypes. Conclusions This is the first cluster-based analysis to identify a quantitative structural HF phenotype of HF that is not distinguished by LVEF. While the underlying pathophysiology is unclear, most patients have recent onset HF and biomarker profiles with relatively low neurohormone activity. These features may reflect a distinct pathophysiology that could indicate a specific, targeted intervention.

Increased index of microcirculatory resistance, capillary rarefaction, elevated troponin levels, and their association with transthyretin amyloidosis cardiomyopathy

Abstract Background The pathophysiology of coronary microvascular disease (CMD) in patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) remains unclear. Objective This study aims to functionally and pathologically assess coronary microvasculature to elucidate the underlying mechanisms of myocardial injury in patients with ATTR-CM. Methods Fifty patients (median age, 74 years; men, n=46, 92%) with echocardiographic evidence of left ventricular hypertrophy (≥12 mm) who underwent endomyocardial biopsy (EMB) and invasive coronary physiological assessments following coronary angiography were enrolled between October 2021 and September 2023 and divided into ATTR-CM (n=30) and non-cardiac amyloidosis (CA) (n=20) groups according to EMB results. All patients with ATTR-CM exhibited positive heart-to-contralateral (H/CL) ratios (>1.5) on technetium 99m pyrophosphate scintigraphy. Fractional flow reserve (FFR), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) were measured using the PressureWire X guidewire in the left anterior descending artery. Capillary density (/mm2) was determined with EMB tissues by counting the number of CD31 immunopositive luminal structures, whereas the amyloid deposition burden was assessed by measuring the transthyretin immunopositive areas. Circulating cardiac troponin T (hs-cTnT) and brain natriuretic peptide (BNP) were measured. Results Compared to the non-CA group, the ATTR-CM group exhibited lower CFR (2.4±0.3 vs. 3.6±0.4, p=0.01), higher IMR (35.4±3.0 vs. 18.7±3.7, p=0.0009), lower capillary density (255.3±24.9 /mm2 vs. 408.6±29.5 /mm2 , p=0.0002), and elevated hs-cTnT levels (0.056±0.006 ng/mL vs. 0.036±0.004 ng/mL, p=0.01), with similar FFR (0.87±0.015 vs. 0.84±0.013, p=0.1) and BNP levels (229.6±38.1 pg/mL vs. 210.2±46.7 pg/mL, p=0.75). In the overall and ATTR-CM groups, capillary density had no significant correlation with IMR (r=0.16, p=0.41 and r=0.04, p=0.84, respectively) and a significant inverse correlation with hs-cTnT (r=-0.47, p=0.001, and r=-0.48, p=0.009, respectively). In the ATTR-CM group, capillary density was not significantly correlated with the H/CL ratio (r=-0.23, p=0.09); nevertheless, transthyretin immunopositive areas were positively correlated with the H/CL ratio (r=0.47, p=0.01). Conclusion Capillary rarefaction correlates with elevated hs-cTnT levels but not with elevated IMR, and H/CL ratios, suggesting that CMD is involved at the capillary level in ATTR-CM-related myocardial injury independent of the amyloid deposition burden.

Clinical profile and prognosis of Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA) in patients with previous Acute Coronary Syndrome (ACS)

Abstract Introduction Myocardial infarction with non-obstructed coronary arteries (MINOCA) may occur in patients with a personal history of ischaemic heart disease, making diagnosis even more difficult. In addition, the role of cardiovascular risk factors, which are well known in patients with acute myocardial infarction with obstructed arteries (MICAD), is less well defined in MINOCA. The aim of this study is to define the clinical characteristics, risk factors and long-term prognosis in patients with MINOCA and previous acute coronary syndrome (ACS). Methods A prospective, analytical, observational study was designed. Included all patients admitted to our centre with ACS between 2016 and 2023 in which a coronary angiography was performed. Patients were classified as MINOCA according to the definition of the 2020 European ACS guidelines. MINOCA patients with and without a history of previous ischaemic heart disease were compared. At follow-up, MACE was defined as all-cause death, hospitalisation, reinfarction and stroke. The median follow-up was 43 [IQR 20-71]. Results A total of 136 patients were included, of whom 17 had a history of ACS. The proportion of men was significantly higher in the group with previous ACS (82% vs 48%; p=0.008). Patients with a history of ACS had higher rates of smoking (71% vs 51%, p=0.139), more night work (80% vs 39%, p=0.017) and less stress (33% vs 61%, p=0.152). They also had more peripheral vascular disease (24% vs 3%, p=0.005), diabetes (41% vs 19%, p=0.042), dyslipidaemia (71% vs 43%, p=0.04) and a higher rate of atrial fibrillation (29% vs 9%, p=0.032). However, despite a higher rate of previous ventricular dysfunction (24% vs 3%, p=0.005), they had lower troponin levels on admission (62 [IQR 37-368] vs 152 [IQR 49-424]). We found no differences in the other comorbidities analysed (Table 1). On admission, patients with previous ACS had significantly more non-ST-segment elevation (29% vs 10%, P=0.05) and received more beta-blocker treatment (82% vs 57%, p=0.046). When analysing the mechanism of infarction, patients without previous ACS were more likely to have vasospasm and coronary embolism. However, there was a significantly higher rate of type II AMI (41% vs 18%, p=0.044) in the group with previous ACS. During follow-up, patients with a history of ACS are more likely to have a new infarction (7% vs 3%, p=0.3) or stroke (14% vs 6%, p=0.2). There was also a trend towards a higher incidence of MACE in patients with prior ACS, although this did not reach statistical significance (HR 2.379, 95% IC 0,883-6,405) (Table 2). Conclusion MINOCA patients with a history of ACS have distinct and worse epidemiological features in which classic cardiovascular risk factors play a significant role, with more ventricular dysfunction and atrial fibrillation. In addition, they appear to have a worse prognosis with increased cardiovascular complications. That might suggest a more MICAD-like profile.

Ischemic Stroke Unveiling Takayasu Arteritis Complicated by Coronary Arteritis: A Case Study

Context: We present the case of a 38-year-old woman admitted for ischemic stroke. Etiological evaluation revealed halo signs on transesophageal echocardiography (TEE), suggestive of Takayasu arteritis. Case Presentation: During hospitalization, the patient developed chest pain, elevated troponin levels (300 ng/L), left ventricular hypokinesia on echocardiography, and T-wave inversions on electrocardiogram (ECG), indicating coronary arteritis. High-dose corticosteroid therapy led to rapid improvement in inflammatory markers. The diagnosis of Takayasu arteritis was confirmed based on the American College of Rheumatology (ACR) criteria. This case highlights the variable clinical presentation of Takayasu arteritis, including coronary involvement, and underscores the effectiveness of corticosteroid therapy in controlling inflammation. Conclusion: Takayasu arteritis, though rare, can manifest with ischemic stroke and coronary arteritis. Prompt recognition and corticosteroid treatment are essential in managing this potentially life-threatening condition.

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 < 0.001). Right ventricular / left ventricular ratio reduction was -0.48 ± 0.25 in the USAT group (p < 0.001) and -0.34 ± 0.14 in the MT group (p < 0.001) (between group difference p = 0.2). TAPSE increased by 8 mm ± 4.4 mm in the USAT group (p < 0.001) and by 8.7mm ± 3.8 mm in the MT group (p < 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.

How to predict myocardial injury in patients with large ischaemic burden identified during stress echocardiography?

Abstract Background/Introduction Stress echocardiography (SE) is well established diagnostic tool in coronary artery disease (CAD) with broadly agreed consensus for the indications and protocols. There is, however, no clear non-invasive SE parameter in identifying high risk features in patients with large burden of inducible regional wall motion abnormalities (RWMA) that would require prompt treatment or urgent admission. Purpose To identify high risk features during SE associated with myocardial injury following a positive SE with large amount of RWMA. Methods All consecutive patients referred for SE from June 2019 to November 2022 to diagnose coronary artery disease were assessed for inducible RWMAs using a hybrid protocol (low dose Dobutamine and exercise on supine bike with 3 min increments of workload of 25W). Those with ≥4/17 segments of inducible RWMAs underwent measurement of Troponin level 1 hour after the test termination. Somatometric characteristics, risks factors, symptoms, haemodynamic pre- and during SE and results of subsequent coronary angiography were recorded. Results 631 patients were referred for assessment of CAD. 87 patients had ≥4/17 inducible RWMAs out of 152 patients with positive SE. 61/87 who had Troponin measurements were included in the analysis. Mean age was 65 ± 13 yo, 61% were male. There was high prevalence of known CAD (77%) and cardiovascular risks factors as hypertension (59%) and hyperlipidaemia (61%). The median exercise time was 9 minutes, 46% developed chest pain (CP), 49% - ECG changes, 39% - left ventricular (LV) dilatation and 74% - reduction in LVEF. Troponin was positive in 25/61 patients. Invasive coronary angiography confirmed clinical CAD in 51/61 patients. 5 patients had either normal angiogram or non-obstructive CAD, 5 patients were awaiting diagnostic test. The severity of CAD appears to be associated with magnitude of Troponin release (1 vessel disease - 16.5 ng/L, 2 vessels disease - 39.9 ng/L, 3 vessels disease – 58.2 ng/L). All patients (6/61) with higher troponin values (>90ng/L) had multivessel disease involving the left anterior descending (LAD) artery. Interestingly, 2/5 patients without CAD had elevated Troponin suggesting possible ongoing myopathic process. The only non-invasive SE parameters that were significantly related to troponin increase were recovery time (P=0.001) and exercise time (P<0.05) whereas symptoms, BP response and LVEF reduction showed a trend which did not achieve significance. Conclusions In patient with positive SE with large burden of inducible RWMAs prolonged recovery time and low threshold for ischaemia appear to be the most reliable characteristic to identify patients with potential myocardial injury and should be used as a triaging tool for admission or early invasive assessment.

Explainable machine learning and multi-modal data for predicting readmission in patients with heart failure

Abstract Background Cardiovascular diseases (CVDs) are among the leading causes of mortality and morbidity globally, with an estimated 1 million hospital admissions for CVD in England in 2019/20, leading to 5.5 million bed days. In addition, patients with CVDs have a notably high rate of hospital readmission, with approximately one in four patients experiencing heart failure (HF) being readmitted within one month of discharge. We explored whether machine learning models trained on electrocardiogram (ECG) and patient electronic health records (EHRs) can support decision-making and risk management and ultimately improve health outcomes for HF patients. Purpose The project aims to develop a machine learning model to predict health outcomes for HF patients. To test the hypothesis, we trained and tested an explainable machine learning model to predict the risk of mortality and hospital readmission rate for HF patients. Methods We used EHR data and tabulated ECG records to train an XGBoost model to predict the risk of 30-day mortality and 30-day hospital readmission for HF patients. EHR data from a cohort of 2,868 patients with their ECG records were used for model development. We extracted a total of 78 features from the ECG data, such as heart rate variability (HRV), P-wave durations, and QT intervals. These ECG features were combined with coded and free-text EHR data (e.g., demographic information, diagnosis, medication history, and lab results) and used as tabular inputs to the XGBoost model. Of the 2,868 patients, an internal set of 574 patients stratified by age, sex, and health outcomes (30-day mortality and 30-day hospital readmission) were held out for testing. Results Among 2,868 HF patients with 10-year follow-up, 1065 patients were reported for mortality or hospital readmission within 30 days of discharge. When the machine learning model was trained on ECG data in addition to EHR data, the model was able to predict patient mortality and hospital readmission rate in the test set with an area under the curve (AUC) of 0.91 and 0.70, respectively. For mortality prediction, the model achieved a sensitivity and specificity of 0.81 and 0.82, respectively, when employing an operating point with minimum difference between the sensitivity and specificity. When the threshold was adjusted to favor sensitivity at 0.91, the model specificity decreased to 0.74. The machine learning model also identified high sensitive troponin levels, QT dispersion, and lactate dehydrogenase levels as features of high importance for predicting the outcomes for HF patients. Conclusions Our developed machine learning model was able to predict mortality and readmission risks in HF patients using multi-modal data. Upon further validation, the machine learning model has the potential to be tested for supporting clinical decision-making and risk management for HF patients.ROC CurveFeature Importance

Cardiac magnetic resonance in MINOCA patients: a non-tertiary hospital experience

Abstract Background Cardiac magnetic resonance (CMR) is a key tool in the diagnostic process of myocardial infarction with non-obstructive coronary arteries (MINOCA), impacting patient management and prognosis. Its use in non-tertiary hospitals is often constrained mainly by accessibility. Thus, the aim of this study was thoroughly evaluate CMR application in this context to optimize the process. Methods 136 MINOCA patients who were admitted to our hospital between 2016 and January 2024 were analyzed. Each MINOCA patient was reviewed by experts to align with the diagnosis criteria outlined in the 2020 ESC Guidelines and the American Heart Association position paper, which recommended CMR for MINOCA patient’s evaluation. To assess the factors associated with normal-CMR, a logistic regression analysis was performed. In a first step, some factors were detected, showing a trend in the association. In a second step, a backward elimination procedure was used, excluding factors with p>0.1. Results CMR was performed in 65 MINOCA patients (48% of the cohort), with a mean age of 59±15 years old, 35 of them were males (54% of total patients). During the follow-up, there were 4 deaths (6%) and 4 readmissions (6%). Out of the total 65 patients, the CMR diagnosis was myocardial infarction (MI) in 14 (21.5%) and myocarditis in 16 (24.6%), and was normal in 35 (53.9%). Therefore, CMR provided diagnostic information in 46% of the cases. It was noted that a normal CMR was associated with female gender, (OR 2.7, 95% CI 0.96-7.34, p=0.057), hypertension (OR 2.25, 95% CI 0.81-6.22, p=0.11), absence of segmental abnormalities in echocardiography (OR 0.14, 95% CI 0.035-0566, p=0.06) and lower high-sensitivity Troponin T (OR 0.79, 95% CI: 0.66-0.95, p=0.001). In the second step, only segmental abnormalities (OR 0.2, 95%CI 0.04-1.09, p=0.063) and troponin (OR 0.31, 95%CI 0.10-0.99, p=0.048) remained included. Additionally, the Youden Index was determined to obtain the threshold for troponin, resulting a value of 606 nG/mL, area under ROC curve (AUC) = 0.784 (figure). Conclusions - CMR was performed in 48% of the MINOCA patients, reflecting the limitation for its use in routine clinical practice. Furthermore, it was useful in 46% of those patients. - The main factors associated with normal CMR were absence of segmental echocardiography abnormalities and reduced troponin levels. - A troponin cutoff point of 606 ng/mL identified patients with a normal CMR (AUC=0.784).Figure 1.CMR in MINOCA patientsFigure 2.Area under ROC curve = 0.784

A systematic assessment of myocardial involvement and cardiovascular events up to six months in patients hospitalised with COVID-19

Abstract Background Retrospective cohort studies indicate that myocardial injury occurs in approximately 25% of patients hospitalised with COVID-19. However, prospective studies with a systematic assessment of myocardial involvement and major adverse cardiovascular events (MACE) after COVID-19 are scarce. Purpose The primary objective was to determine the incidence of MACE within six months of hospitalisation. MACE was defined as a composite of cardiac death, sudden death, life-threatening ventricular arrhythmia's, heart failure, non-fatal myocardial infarction, and/or non-fatal stroke. The main secondary objective was to determine the frequency of other cardiac complications not covered by this definition. Methods We conducted a prospective multicenter cohort study in 13 Dutch medical centers. Adult patients hospitalised with COVID-19 were consecutively recruited (May 2021-April 2023). Exclusion criteria were age ≥70 years, a history of new cardiac disease in the past six months, or dependency in the activities of daily living. Cardiac involvement was evaluated by a standardised healthcare pathway that was implemented in participating hospitals. All patients received an electrocardiogram, transthoracic echocardiogram, and troponin measurement at admission and at six months follow-up. Furthermore, a questionnaire was distributed at three and six months after admission to collect information on post-COVID symptomatology. Results In total 190 patients were included, median age of 57 years [IQR 48; 64], mostly male (n=110, 60%) and white (n=136, 72%). Cardiovascular risk factors were present in 116 (61.1%) patients and 33 (17.4%) had a history of cardiac disease. At admission, troponin was above the upper limit of normal in 68 (35.8%) patients. Seven (3.7%) patients died during follow-up. The cumulative incidence of MACE was 2.6% at discharge with no additional events during follow-up. Other cardiac complications were detected in 18 (9.5%) patients during admission with 3 (1.6%) additional events at six months follow-up. Supraventricular tachycardias (n=8, 4.2%) were the most common cardiac complication. Other complications were myocarditis (n=2, 1.1%), pericarditis (n=1, 0.5%), non-sustained ventricular tachycardia (n=1, 0.5%), and other arrhythmias or conduction disorders (n=5, 2.6%). At six months follow-up, three (2.3%) patients reported chest pain, with one requiring a percutaneous coronary intervention. Palpitations and dizziness were experienced by 88.9% and 83.3% of patients three months after admission but the prevalence of these symptoms decreased to 9.8% and 11.8% at six months. Conclusion With a systematic assessment, one in three patients hospitalized with COVID-19 have elevated troponin levels at admission. However, the overall incidence of MACE within six months is low. Palpitations and dizziness are commonly reported after discharge but these symptoms disappeared for most participants within six months.

Cangrelor use in ticagrelor-loaded ST-elevation myocardial infarction patients with high residual platelet reactivity: a randomized controlled trial

Abstract Background Despite the use of potent P2Y12 inhibitor, many patients still present with high platelet reactivity (HPR) at the time of primary percutaneous coronary intervention (PCI). HPR is associated with impaired myocardial reperfusion and the subsequent poor outcome. Purpose We sought to determine the impact of Cangrelor -a rapid and potent intravenous P2Y12 inhibitor- on myocardial reperfusion in patients with HPR admitted for primary PCI in a randomized trial. Methods Patients pre-treated with ticagrelor and aspirin with residual HPR (baseline platelet reactivity unit (PRU) > 208) were randomly assigned in a 1:1 ratio to receive cangrelor (experimental group) or not (control group) just before PCI. The primary endpoint was optimal myocardial reperfusion defined as a final myocardial blush grade (MBG) 3 assessed by an independent core laboratory. Results After screening of 128 patients, a total of 60 patients were with HPR were enrolled and randomized. The ticagrelor loading dose to PRU measurement times were 83 ± 32 and 90 ± 47 minutes in the experimental and control groups, respectively. Baseline PRU were 245 ± 30 and 252 ± 35 in the experimental and standard group, respectively. A final MBG 3 was observed in 21/30 (55%) and 17/30 (45%) the experimental and standard groups (p=0.29). A final TIMI flow grade 3 was observed in 30/30 (100%) and 27/30 (90%) the experimental and standard groups (p=0.24). Peak troponin levels after PCI were 51381 ± 50047 and 51078 ± 63960 ng/L (p=0.98) in the experimental and standard group, respectively. At the end of the PCI, control PRU were 36 ± 57 and 198 ± 107 (p<0.0001) in the experimental and standard group, respectively. One patient of the experimental group presented an in-hospital major bleeding (BARC 3). Conclusion In ticagrelor-loaded STEMI patients with residual HPR at the time of PCI, cangrelor use was associated with a more effective platelet inhibition but failed to significantly improve the rates of optimal final myocardial blush grades.

Serum potassium levels and in-hospital mortality in distinct phenotypes of myocardial infarction patients by machine learning clustering

Abstract Background Abnormal serum potassium levels are associated with an increased risk of mortality in patients with myocardial infarction (MI); however, it is unclear whether the impact of potassium levels on mortality risk varies depending on the characteristics of MI patients. Purpose We aimed to classify MI patients according to their clinical characteristics and explore the relationship between potassium levels and in-hospital mortality in distinct clusters of MI. Methods Using Medical Information Mart for Intensive Care (MIMIC) IV database, we identified 3,159 patients who admitted for the first time to the intensive care unit with a primary diagnosis of acute MI. Machine learning clustering was performed on this population based on available clinical and laboratory data. Results Three distinct clusters of MI patients were identified using clustering analysis: 1,455 (46%) in cluster 1, 587 (19%) in cluster 2, and 1,117 (35%) in cluster 3. Patients in cluster 2 were older, had the highest comorbidity burden, Sequential Organ Failure Assessment (SOFA) score, peak lactate, creatinine, peak troponin, N-terminal B-type natriuretic peptide (NT-proBNP) levels and the lowest hemoglobin levels among the 3 clusters. Patients in cluster 3 were younger, had the lowest comorbidity burden, SOFA score, peak lactate, creatinine, NT-proBNP levels. Patients belonging to cluster 1 had clinical characteristics intermediate to those of cluster 2 and 3, except for the lowest troponin level. In-hospital mortality was highest in cluster 2, followed by cluster 1 and then cluster 3. Patients in cluster 2 had the highest in-hospital mortality risk with hypokalemia (OR 3.71, 95% 1.81­­-7.63) and patients in cluster 3 had highest in-hospital mortality risk with hyperkalemia (OR 2.77, 95% CI 0.84-9.06). Patients in cluster 1 did not exhibit a linearly increasing mortality with hyperkalemia. Conclusions The use of clustering analysis in patients with acute MI could characterize baseline clinical data into clinically distinct clusters with different in-hospital mortality across the dyskalemia continuum. The results suggest that the optimal range of potassium levels in patients with MI may vary depending on patient characteristics.Figure - clusteringTable - K and In-hospital mortality

Trimethylamine N-oxide as a Novel Biomarker for Left Ventricular Diastolic Dysfunction and Functional Remodeling in ST-Elevation Myocardial Infarction Patients

Abstract Background Over the last three decades, the mortality from ST-elevation myocardial infarction (STEMI) has halved. However, the incidence of heart failure or persistent angina remains high after STEMI, and the post-STEMI left ventricular (LV) systolic and diastolic function remains unpredictable. Thus, there is an unmet need to identify patients at risk of LV diastolic dysfunction or adverse remodeling. Purpose This study aims to investigate the potential of Trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite associated with heart failure, and atherosclerosis, as a biomarker for adverse LV remodeling and diastolic dysfunction following STEMI. Methods In this prospective, observational cohort study, 210 STEMI patients with multivessel coronary artery disease (CAD) were enrolled after primary PCI. At 3 months follow-up, all patients underwent complete revascularization with FFR-guided PCI. Plasma TMAO, C-reactive protein (CRP), and brain natriuretic peptide (BNP) levels at 3 months follow-up and peak troponin level at primary PCI were collected. Echocardiographies were performed within 24 hours of STEMI and at 12-month follow-ups. Diastolic dysfunction was defined according to the ASE 2016 guidelines.(1) Functional LV remodeling (FLVR) was categorized into 4 categories according to Chimed et al.(2) Receiver operating characteristic (ROC) curve analysis, including the Delong test and Youden index, was performed to compare the biomarkers' diagnostic value and determine the optimal cutoffs for predicting diastolic dysfunction and FLVR, respectively. Results Of the 210 patients enrolled, 85 (40.48%) were female, with a median age of 65 years [interquartile range (IQR): 58.00, 76.00] and a median body mass index (BMI) of 27.39 kg/m² (IQR: [24.56, 30.69]). The area under the ROC curve for predicting post-PCI LV diastolic dysfunction ≥ grade II was 0.72 (95% CI 0.63–0.81; p<0.001) for TMAO (Figure 1). The optimal TMAO cutoff value of 3.80 yielded a sensitivity of 0.75 (95% CI 0.63–0.86) and a specificity of 0.82 (95% CI 0.76–0.88). For FLVR grade 3 or 4, the area under the ROC curve was 0.62 (95% CI 0.50–0.74) and 0.72 (95% CI 0.62 -0.83) for TMAO and BNP, respectively (Figure 2), but the AUC was not significantly different (p= 0.191). In multivariable logistic regression analysis, TMAO was independently associated with FLVR grade 3 or 4 (OR 1.18, 95% CI 1.00-1.38, p = 0.046) and diastolic dysfunction ≥grade 2 (OR 1.30, 95% CI 1.12-1.50, p < 0.001). Conclusion The novel parameter of TMAO is a useful predictor for LV diastolic dysfunction after STEMI. TMAO is independently associated with an increased risk of LV diastolic dysfunction and worse FLVR. These results suggest that monitoring plasma TMAO levels could be an effective and cost-efficient strategy for monitoring patients with an elevated risk of LV diastolic dysfunction or adverse LV remodeling.Figure 1Figure 2

Prevalence of transthyretin amyloid cardiomyopathy in patients hospitalised for heart failure with preserved ejection fraction in an LATAM center

Abstract Introduction Transthyretin Amyloid cardiomyopathy (ATTR-CM) usually presents as heart failure with preserved ejection fraction (HFpEF). Its diagnosis has a significant clinical impact, as specific treatment is currently available. Purpose To assess the prevalence of ATTR-CM in patients hospitalised for HFpEF and increased septal thickness in our institution of general community hospital in Latin America (LATAM). Methods Cross-sectional study. Patients hospitalised for HFpEF (>50%) and septal thickness ≥ 12 mm during the period from 8/2019 to 1/2023 were prospectively included. Patients with pacemaker, significant left valve disease and end-stage renal failure (creatinine clearance < 30 ml/min/BSA) were excluded. A pyrophosphate bone scintigraphy (PYP) was planned to be performed in order to assess ATTR-CM. The prevalence of ATTR-CM and its 95% confidence interval were calculated. Results A PYP was performed in 59/82 patients hospitalised for HFpEF. Median age was 85 [IQR 78-88] years, and 54% were women. At admission, 61% (n=36) had atrial fibrillation and the median NT Pro-Bnp was 3536 [1700-7748] pg/mL. The mean left ventricle ejection fraction was 57% (+/- 5%). The prevalence of ATTR-CM diagnosed by PYP was 19% (95% CI 9.7-30.1, n=11). There were no significant clinical differences between patients who performed a PYP and did not. Patients with ATTR-CM had lower blood pressure and higher septal thickness, NT Pro-Bnp and troponin levels compared to patients without ATTR-CM (TABLE). Conclusion In patients admitted for HFpEF and increased septal thickness, the diagnosis of ATTR-CM was relatively common (one of five had ATTR-CM) in our region (LATAM). We believe that systemic assessment with PYP should be performed in patients hospitalised with HFpEF and increased wall thickness.

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.

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).

A DIFFERENT VIEW OF MINOCA; A RARE CASE OF CORONARY CAMERAL FISTULA

Abstract Coronary cameral fistula (CCF) is defined as an abnormal connection between the coronary artery and the heart chambers. Although rare, most are asymptomatic, usually arising from the right coronary artery and terminating in the right ventricle or right atrium. Often detected incidentally, CCFs may present with symptoms of heart failure or rarely with anginal symptoms. Introduction A coronary cameral fistula is defined as an abnormal connection between the coronary artery and the heart chambers. CCFs are found in less than 1% of the population.[1] The most common coronary artery fistula is that arising from the right coronary artery and spilling into the right ventricle.[2] In particular, CCFs arising from all three epicardial coronary arteries are rare but can be clinically significant. These cases may present with acute coronary syndrome causing steal syndrome. Since there is usually no underlying obstructive lesion, these cases may be diagnosed as myocardial infarction without obstructive coronary arteries (MINOCA)[3] Case; A 51 years old male patient was admitted to the emergency room with a complaint of stabbing chest pain for the last one week. In his anamnesis, he described that the chest pain increased with exertion and radiated to the back. It was learned that he had no known disease and coronary history, was a 20 pack/year smoker, had no family history and was not taking any medication regularly. Vital signs in the emergency room revealed a blood pressure of 120/80 mmHg, pulse rate of 85 per minute and normal saturation. Electrocardiography (ECG) showed sinus rhythm V 1-6 with T negativity 85/min. (Figure 1) Echocardiography revealed no wall motion defect and no major valve pathology. Laboratory findings showed renal function tests within normal range, C-reactive protein within normal range, hemoglobulin level 17.6 gr/dl, HS Troponin-T level 12.9 ng/l (upper limit 14 ng/l). At 3 hours, the control HS Troponin-T level was 69.2 ng/l and the patient was hospitalized in the coronary intensive care unit with a prediagnosis of acute coronary syndrome. Coronary angiography was performed during follow-up. Angiography showed dilatation in the main coronary artery (LMCA), ectasia in the left anterior descending artery (LAD) and circumflex artery (CX), and diffuse tortuosity in the coronaries. CCF formed by the LAD, CX and right coronary artery (RCA) together and spilled into the left ventricle. Opaque filling was observed in the left ventricle. (Figure 2) Although the patient had a low body mass index, dilatation of the coronary arteries was thought to be the effect of steal syndrome caused by multiple fistulas. The patient was admitted to the coronary intensive care unit with medical follow-up. The patient's medical treatment was adjusted as acetylsalicylic acid (ASA) 100 mg pill 1*1, metaprolol 50 mg pill 1*1 and rosuvastatin 20 mg pill 1*1 due to an LDL cholesterol level of 149 mg/dl. In the patient who currently had no signs of heart failure, medical treatment was decided primarily in terms of CCF. The patient was discharged with the recommendation of outpatient follow-up. Discussion and Conclusion; CCFs are rare coronary anomalies.[1] When we look at the etiology, the most common cause of CCFs is abnormal embryogenesis.[4] While the diagnosis can be made at any age, the diagnosis is usually made in early childhood when a heart murmur occurs in an asymptomatic child or in a child with symptoms of heart failure. However, cases of CCF diagnosed at an advanced age with anginal complaints and signs of acute heart failure are seen in the literature. [5]Treatment depends on the anatomical features of the fistula and, of course, the patient's symptoms. While small fistulas may close spontaneously with age, large fistulas may require closure.It may cause anginal symptoms by causing heart failure symptoms and steal syndrome. [6]When we look at the literature, we can see that patients with CCF also present with acute coronary syndrome. [2, 4, 5,] As in the case reported by Alsancak Y et al., CCFs originating from all three coronary arteries cause steal syndrome and are often diagnosed with a prediagnosis of acute coronary syndrome.[7] The absence of an occlusive lesion after angiography in these patients with high troponin levels suggests atherosclerosis at the microvascular level and the diagnosis of MINOCA. [3]Angiography performed with suspicion of stenosis in the coronary arteries and finding a CHF instead of a stenosis may be considered lucky in these patients. The size of the fistula and the possibility that it may lead to heart failure in the follow-up will be the other side of the unlucky coin.

ELEVATED TROPONIN OF NON-CORONARY ETIOLOGY A REVIEW

Elevated troponin levels are traditionally associated with acute myocardial infarction (AMI) and are widely used as a specific marker for the diagnosis of ischemic myocardial injury. However, recent studies have shown that elevated troponin levels can occur in several non-coronary conditions, requiring a more careful diagnostic approach to avoid misinterpretations and inadequate management. This study aimed to perform a systematic review of the literature on the non-coronary causes of elevated troponin levels, seeking to identify the main associated clinical conditions and discuss their prognostic value in different contexts. To this end, a systematic review of articles published between 2014 and 2024 was conducted using the PubMed, Scopus and Web of Science databases. The results revealed that conditions such as sepsis, pulmonary embolism (PE), chronic renal failure (CRF), chronic obstructive pulmonary disease (COPD) and tachyarrhythmias are the main non-coronary causes of elevated troponin levels. It is concluded that elevated troponin levels of non-coronary etiology are an important marker of severity and poor prognosis in several systemic conditions. Troponin levels should be interpreted carefully, taking into account the clinical context and underlying conditions of each patient.

Cardiac Troponin Levels in Patients with Chronic Kidney Disease: "Markers of High Risk or Just Noise''?

Kidney disease is linked to the development of cardiovascular disorders, further increasing morbidity and mortality in this high-risk population. Thus, early detection of myocardial damage is imperative in order to prevent devastating cardiovascular complications within this patient group. Over the years, cardiac biomarkers have been identified and are now widely used in everyday clinical practice. More specifically, available data suggest that cardiac troponin and its regulatory subunits (TnT, TnI, and TnC) reflect the injury and necrosis of myocardial tissue. While cTnC is identical in cardiac and skeletal muscle, TnT and TnI constitute cardiac-specific forms of troponin, and, as such, they have been established by international societies as biomarkers of cardiac damage and diagnostic indicators for acute myocardial infarction. Elevations in the levels of both cardiac troponins (cTnT and cTnI) have been also reported in asymptomatic patients suffering from chronic kidney disease. Therefore, if abnormal, they often generate confusion among clinicians regarding the interpretation and clinical significance of their numerical values in emergency settings. The aim of this review is to explore the reasons behind elevated troponin levels in patients with chronic kidney disease and identify when these elevated levels of biomarkers indicate the need for urgent intervention, considering the high cardiovascular risk in this patient group.

Levels of high-sensitive troponin T and mid-regional pro-adrenomedullin after COVID-19 vaccination in vulnerable groups: monitoring cardiovascular safety of COVID-19 vaccination.

COVID-19 vaccines are well tolerated and effective but may have adverse effects on the cardiovascular system. Vaccine-associated myocardial injury was analysed by measuring high-sensitive troponin T (hsTnT); mid-regional pro-adrenomedullin (MR-proADM) levels were evaluated to assess endothelial dysfunction. This was a prospective study with a vulnerable population of healthcare workers (HCWs) and elderly patients (>70 years) who were vaccinated with either one dose of ChAdOx1 nCov-19 adenoviral vector vaccine (AZ) followed by one dose of the BNT162b2 messenger RNA vaccine (BNT), or with two doses of BNT (12th of January - 30th of November 2021). HsTnT and MR-proADM were measured in blood samples at three visits (V1: 1st immediately before vaccination; V2, 3: 3-4 weeks after 1st and 2nd vaccination). HsTnT of HCWs was compared to a healthy reference population. N = 162 volunteers were included (V1 = 161; V2, V3 = 162 each). N = 74 (45.7%) received AZ/BNT and n = 88 (54.3%) received BNT/BNT [elderly: n = 20 (12.3%), HCWs: n = 68 (42.0%)]. Median hsTnT levels were 4 ng/L, 5 ng/L and 4 ng/L (V1-V3) for AZ/BNT and at 5 ng/L, 6 ng/L and 6 ng/L (V1-V3) for BNT/BNT. Compared to the reference population (n = 300), hsTnT was significantly higher at all visits for both vaccination groups (p < 0.01), without differences between the AZ/BNT and BNT/BNT cohort. Median MR-proADM values were 0.43 nmol/L, 0.45 nmol/L, 0.44 nmol/L (V1-V3) in the AZ/BNT cohort and 0.49 nmol/L, 0.44 nmol/L, 0.47 nmol/L for BNT/BNT, respectively. Change of median hsTnT and MR-proADM between visits did not show significant increases. One HCW experienced a permanent and three a transient hsTnT increase ≥14 ng/L. No overall subtle, persistent cardiovascular involvement was observed after the 2nd COVID-19 vaccination. Elevated cardiovascular biomarkers in clinically asymptomatic individuals need further investigations.

Novel troponin fragmentation assay to discriminate between Takotsubo syndrome and acute myocardial infarction.

Cardiac troponin levels are elevated in Takotsubo syndrome (TTS) with significant overlap to acute myocardial infarction (MI). Long and intact cardiac troponin T (cTnT) forms are typical for MI. This study sought to assess whether the fragmentation composition of cTnT release in TTS differs from MI. The concentration of long molecular forms of cTnT (long cTnT) was measured with a novel upconversion luminescence immunoassay and total cTnT with a commercial high-sensitivity cTnT assay in 24 TTS patients and in 84 Type 1 MI patients. The ratio of long to total cTnT (troponin ratio) was determined as a measure of cTnT fragmentation. Troponin ratio was lower in TTS patients 0.13 [0.10-0.20] vs. 0.62 [0.29-0.96], p<0.001). In the ROC curve analyses, troponin ratio showed a better predictive power than total cTnT in discriminating TTS and MI patients (AUC 0.869 [CI95% 0.789-0.948)] vs. 0.766 [CI95% 0.677-0.855], p=0.047). When restricting the analysis to patients with total cTnT below 1200 ng/L (maximal value in TTS patients), the respective AUC values for total cTnT and troponin ratio were 0.599 (CI 95% 0.465-0.732) and 0.816 (CI95% 0.712-0.921), p =0.003). At a cutoff point of 0.12, troponin ratio correctly identified 95% of MI patients and 50% of TTS patients. In contrast to Type 1 MI, only a small fraction of circulating cTnT in TTS exists in intact or long molecular forms. This clear difference in troponin composition could be of diagnostic value when evaluating patients with cTnT elevations and suspicion of TTS. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04465591.