Definition Of Myocardial Infarction Research Articles

Abstract 4136805: Type 2 Myocardial Infarction Patients Have Significantly More Days Not at Home

Background: A Type 2 (T2) myocardial infarction (MI) occurs “secondary to ischemia due to either increased oxygen demand or decreased supply,” while a Type 1 MI (T1) is atherothrombotic. Treatment includes correction of the underlying cause and not catheterization. The current study's aim is to assess the patient-centered outcome of days not at home (DNAH) within a year of discharge among older adults hospitalized with T1 and T2 MI, and to evaluate the distribution of non-home days. Methods: Data for this analysis came from a prospective cohort study of adults ≥75 years old hospitalized with MI at 94 U.S. hospitals and linked to Medicare claims and encounter data. MI type was adjudicated according to the Fourth Universal Definition of MI. Patient characteristics were identified via chart review or self-report. DNAH was defined as the number of days dead or in a hospital, skilled nursing facility (SNF), rehab facility, or hospice. Multivariable-adjusted negative binomial regression was used to evaluate the association between MI type and DNAH in the year after discharge. Results: Of the 375 participants evaluated in this interim analysis, 264 (70.4%) had T1 MI and 111 (29.6%) had T2 MI. There was no difference in distribution of age, gender, or race. T2 patients were more likely to have heart failure (HF), coronary artery disease (CAD), COPD, and arrythmias. Patients with T2 MI had a median [interquartile range] of 5 [0-71] DNAH in the year after discharge, compared with 2 [0-10] DNAH among patients with T1 MI (p = 0.008). After adjusting for age and comorbidities, T2 patients had 137% more DNAH (IRR = 2.37, 95% CI = 1.43, 3.94, p < 0.001) than T1 patients. The number of days dead or in SNF was significantly higher among patients with T2 MI compared with T1 MI, whereas the association between MI type and increase in days readmitted was borderline (p = 0.06). In the multivariable model, age, HF, and CAD were significantly associated with more DNAH, but COPD and arrhythmias were not. Conclusion: Our findings demonstrate that older patients with T2 MI have more days not at home, attributable to death, SNF stays, and to a lesser extent, rehospitalization. Interestingly, accounting for comorbidities did not significantly attenuate this association. Further studies are needed to develop guidelines for medical teams, including evaluating how receipt of cardiac interventions impacts home days in older patients with T1 and T2 MI.

Differential diagnosis of acute coronary syndrome without ST-segment elevation in a middle-aged patient

Acute Coronary Syndrome (ACS) is an initial diagnosis, which is transformed into the diagnosis of “myocardial infarction”, “unstable angina” or other diagnosis during the diagnostic process. If a patient meets the criteria for myocardial infarction (according to the Fourth Universal Definition of Myocardial Infarction), in the presence of atherothrombosis in the infarct-related coronary artery, Type 1 myocardial infarction is diagnosed. In most of the remaining cases Type 2 myocardial infarction is diagnosed. Acute myocardial injury due to various conditions is separately classified. In the presented case, a 54-year-old patient with a history of arterial hypertension and diabetes mellitus, not adherent to treatment and suffering from obesity, a smoker, was hospitalized with typical new-onset angina pectoris and ischemic changes on the ECG, by ambulance, with the initial diagnosis of “ACS without ST-segment elevation”. The diagnosis changed several times during the examination: “ACS without ST-segment elevation”, “CAD: myocardial infarction without ST-segment elevation”, “Myocardial infarction with non-obstructive coronary arteries (MINOCA)”, “Severe calcified aortic stenosis. Anemia. Type 2 myocardial infarction”. The peculiarity of this case is the debut of high-gradient aortic stenosis in a middle-aged man with clinical manifestations of ACS and high blood troponin level. Causes of severe aortic stenosis manifestation as myocardial infarction with elevation of cardiac-specific troponin in the blood, despite intact coronary vessels, are discussed in this article. The differential diagnosis of myocardial injury is discussed, as the correct diagnostic judgment directly determines the patient’s management strategy.

External validation of a stepwise 0/1/3h algorithm to triage patients with suspected myocardial infarction

Abstract Background In patients with suspected myocardial infarction (MI), application of 0/1h-algorithms is recommended by guidelines of the European Society of Cardiology. Depending on assay-specific changes of high-sensitivity troponin (hs-Tn), these algorithms allow for rule-in or rule-out of MI at presentation or after 1 hour (h). Yet, a relevant proportion of patients remain in the observe group at 1h in need for further diagnostic. Recently, specific cutoffs at 3h were suggested for hs-TnT, enabling an additional 3h triage option in conjunction with the 0/1h algorithm to further reduce the proportion of patients in the observe zone. Objective We aimed to externally validate the diagnostic performance of the 0/1/3h algorithm in patients with suspected MI. Methods We consecutively enrolled patients with symptoms suggestive of MI in the emergency department of a tertiary hospital in Germany. Patients with STEMI were excluded. Concentrations of hs-TnT were measured at presentation, after 1h and 3h. Final diagnoses were adjudicated by two cardiologists according to the 4th Universal Definition of MI. Applying the 0/1/3h algorithm, patients were triaged into rule-in, rule-out- and observe-group. We assessed the diagnostic performance parameters in the overall sample as well as for predefined subgroups including sex, age ≥65 vs. <65 years, glomerular filtration rate (GFR) ≥60ml/min/m² vs. <60ml/min/m², and symptom onset time <1h vs. 1-3h vs. >3h). Results In 2,514 patients (median age 64 years, 36.4% female), prevalence of NSTEMI was 14.4%. Application of the 0/1/3h algorithm ruled-out 1511 (60.1%) and ruled-in 587 (23.3%) patients. Only 416 (16.6%) remained in the observe group at 3h. Safety of rule-out was high with a sensitivity of 98.6% (95%CI 96.8%, 99.4%) and a corresponding negative predictive value of 99.7% (95%CI 99.2%, 99.9%). Rule-in performance was acceptable with a specificity of 89.3% (95%CI 87.9%, 90.5%) and positive predictive value (PPV) of 60.8% (95%CI 56.8, 64.7, Figure 1). Regarding subgroup analyses, sensitivity and NPV were marginally but statistically lower in patients with normal as compared with impaired renal function (p both <0.001). Further, specificity was substantially lower in older patients (84.8% vs. 93.3%, p<0.001), patients with GFR<60ml/min/m² (78.3% vs. 93.0%, p<0.001) as well as in male patients (88.1% vs. 91.2%, p=0.028) (Figure 2). A relevantly larger proportion of patients remained in the observe group after 3h in patients with impaired renal function (32.3% vs. 10.9%), as well as in patients aged ≥ 65 years (26.8% vs. 6.8%). Conclusion Application of the 0/1/3h algorithm in patients with suspected MI resulted in good diagnostic performance with excellent rule-out safety and moderate rule-in capacity. In patients with impaired renal function as well as elderly patients, specificity was significantly lower while observing a larger proportion of patients remaining in the observe zone at three hours.Figure 1:Diagnostic flowFigure 2:Forest Plots

Troponin/creatine kinase ratio for discrimination of type 1 and type 2 myocardial infarction

Abstract Background High-sensitivity cardiac troponin (hs-cTn) is the laboratory gold-standard to diagnose myocardial infarction (MI). Yet, discrimination between different entities of myocardial injury, i.e. acute and chronic myocardial injury, and Type 1 (T1MI) versus Type 2 MI (T2MI), is still most challenging. Since, management of these entities is substantially different, there is an unmet clinical need for better discrimination. In clinical practice creatine-kinase (CK) is often used to decide whether patients with elevated hs-cTn concentrations are referred to primary invasive coronary angiography. However, it is unclear if the combined evaluation of CK and hs-cTn improves the discrimination between different types of myocardial injury, and MI. Objective Our aim was to evaluate, if the combination hs-cTnI with CK improves discrimination of acute versus chronic myocardial injury, and T1MI versus T2MI. Methods We included patients presenting with suspected MI to the emergency department of a tertiary center. CK and hs-cTnI (Architect STAT) were determined at presentation, and after 1h and 3h. Final diagnoses were adjudicated according to the 4th Universal Definition of MI. STEMI patients were excluded from analyses. We calculated ratios of hs-cTnI and CK for each patient at each timepoint. Receiver-operator-curves with corresponding area under the curve (AUC) were used to assess the discriminative performance and compared with hs-cTnI alone. Logistic regression analysis was applied to calculate odds ratios (OR; 95% confidence intervals) for all ratios as well as hs-cTnI to distinguish T1MI vs T2MI, and chronic injury vs. any acute injury (acute myocardial injury, T1MI, T2MI). ORs are displayed using restricted cubic splines and values were entered log-transformed in the model. Results Of 3346 patients (median age 63 years, 36.4% women), 427 (12.8%) had MI, 103 (3.1%) had acute and 864 (25.8%) chronic injury. Log-transformed ratio of hs-cTnI/CK at presentation resulted in an AUC of 0.75 with an OR per SD for T1MI of 2.74 [2.14, 3.58], which was similar to hs-cTnI alone (AUC 0.76, p=0.75, OR per SD 3.07 [2.35, 4.09]). No significant differences were observed for measurements at 1h and 3h (Figure 1 A-C). Additionally, there was no improvement of discriminative performance regarding the discrimination of chronic and any acute myocardial injury by using hs-cTnI/CK ratios at any timepoint (AUCratio0h 0.77, AUChsTnI0h 0.8, p=0.17; ORratio0h per SD 3.44 [2.96, 4.02], ORhs-cTnI0h per SD 4.35 [3.66, 5.20]) (Fig. 1D-F). Restricted cubic splines show the overlapping correlation of increased propability for T1MI and any acute injury with higher hs-cTnI/CK ratios as well as hs-cTnI alone. (Figure 2). Conclusion The addition of CK to hs-cTnI does not improve discriminative capacity between patients with T1MI and T2MI, as well as between chronic and any acute myocardial injury compared to hs-cTnI alone.Figure 1:ROC curvesFigure 2:Natural cubic splines

Diagnosis of acute myocardial infarction in patients with renal failure using high-sensitivity cardiac troponin T

Abstract Background Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as these patients often have elevated baseline high-sensitivity cardiac troponin T (hs-cTnT) concentrations. Methods Observational U.S. cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with >1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2- and 6-hour hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (eGFR <60 ml/min/1.73m2). Results The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 701 (82%) patients with myocardial injury, 64 (7.5%) with type 1, and 91 (11%) with type 2 MI. In CKD patients with baseline hs-cTnT thresholds of >52, >100, >200 or >300 ng/L, PPVs for acute MI were 37% [95% CI 28-46], 53% (95% CI 39-67), 73% (95% CI 50-89) and 80% (95% CI 44-98), and in those without CKD, 64% (95% CI 50-77), 69% (95% CI 49-85), 59% (95% CI 33-82) and 54% (95% CI 25-81). In CKD patients with a 2-hour hs-cTnT delta of >10, >20 or >30 ng/L, the corresponding PPVs were 65% (95% CI 50-78), 86% (95% CI 68-96) and 88% (95% CI 68-97), and in those without CKD, 65% (95% CI 51-78), 73% (95% CI 57-86) and 75% (95% CI 58-88) (Figure). Conclusion Diagnostic performance of standard baseline and serial 2-hour hs-cTnT thresholds to rule-in MI is suboptimal in patients with CKD. It significantly improves when using higher baseline thresholds and delta values.

Comparison of multiple high sensitivity cardiac troponin assays for early low risk rule out of myocardial infarction: SCORECARD

Abstract Background/Introduction The use of a single low high-sensitivity cardiac troponin measurement to rule out myocardial infarction (MI) at presentation is advocated by international guidelines. Studies have not systematically compared high-sensitivity cardiac troponin (hs-cTn) I and T assays to determine which values should be used to rule out MI in patients with suspected acute coronary syndrome. Methods In a pooled analysis from three prospective observational cohort studies the lowest cTn concentration was determined that gave a negative predictive value (NPV) of ≥99.5% for MI or death at 30 days on presentation to the emergency department. EDTA or lithium heparin plasma or serum samples collected at presentation were measured using five hs-cTnI assays (Abbott ARCHITECT i2000, Beckman Coulter Access 2, Siemens Atellica IM, Ortho-Clinical Diagnostics VITROS 5600, LSI Medience PATHFAST) and one hs-cTnT assay (Roche Cobas e411). The diagnostic outcome of MI or death at 30 days was adjudicated according to the Fourth Universal Definition of MI. Optimal thresholds were determined to identify the highest proportion of patients that could be considered for discharge for a NPV of ≥99.5% for each assay. Results Among 941 patients, MI or death at 30 days occurred in 113 (12%). Optimized thresholds varied between assays ranging from <2 to <7 ng/L (Table) that identified between 22% and 60% of patients as low risk (0-1%) for MI or death at 30 days. Conclusions Our data identify differences in the effectiveness of thresholds between hs-cTnI and hs-cTnT assays for the same safety performance to rule out MI on presentation using a single measurement. In some cases, these thresholds differ from those used in clinical practice. Due to lack of assay standardization, optimal decision thresholds should be defined and validated for each high sensitivity cTn assay.

Impact of discordance in cardiac troponin T versus I on the performance of triage pathways for myocardial infarction

Abstract Background Biological, analytical, and regulatory differences between high-sensitivity cardiac troponin T (hs-cTnT) and hs-cTnI could lead to an underestimation of the performance of a hs-cTnT-based triage-algorithm if evaluated against a hs-cTnI-based reference standard, and vice versa. Unfortunately, the impact of hs-cTnT/hs-cTnI-discordance on diagnostic performance measures is largely unknown. Methods We quantified the impact of hs-cTnT/hs-cTnI-discordance on the diagnostic performance of the three most widely used and guideline recommended hs-cTnT/I-based triage algorithms for patients presenting with symptoms suggestive of myocardial infarction (MI): the ESC 0/1h-algorithm, the ESC 0/2h-algorithm and the High-STEACS pathway. For the central adjudication of the final diagnosis (reference standard), two independent cardiologists had access to all available clinical information and applied the 4th universal definition of MI, one time with serial hs-cTnT-Elecsys measurements (gold standard T) and a second time with serial hs-cTnI-Architect measurements (gold standard I). The primary diagnostic endpoint for the rule-out of NSTEMI was sensitivity, while for rule-in of NSTEMI specificity. Results Among 7728 eligible patients, the final diagnosis was NSTEMI in 1463 patients (18.9%). Of these, NSTEMI was diagnosed with only one of the two adjudication methods (either gold standard T or I) in 167 (11.4%) patients. When the three hs-cTnT-based early-triage algorithms were evaluated using gold standard T and gold standard I, sensitivity was very high and comparable. In contrast, when the three hs-cTnI-based early-triage algorithms were evaluated using gold standard T and gold standard I, sensitivity was again very high, but consistently lower when using gold standard T as compared to gold standard I. The difference in sensitivity was 1.1% (95%CI, 0.6–1.7) for ESC hs-cTnI-0/1h (Table 1A), 1.0% (95% CI, 0.5—1.6) for ESC hs-cTnI-0/2h (Table 1B), and 2.6% (95%CI, 1.7—3.5) for High-STEACS (Table 2). The differences observed in specificity mirrored those for sensitivity, i.e. always lower specificity when using the other hs-cTnT/I-assay for adjudication. Conclusion The impact of hs-cTnT/hs-cTnI-discordance on the diagnostic performance of hs-cTnT/I-based triage algorithms is modest, but large enough to result in a fallacious underestimation of the rule-out safety when evaluating hs-cTnI-based strategies using a hs-cTnT-based reference standard.

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

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

Frequency of periprocedural myocardial injury and infarction stratified by cardiac troponin I and T

Abstract Background There are different definitions of periprocedural myocardial infarction (PPMI) both in terms of thresholds for cardiac biomarkers and the ancillary criteria for myocardial ischemia. Cardiac Troponin I (cTnI) and cardiac Troponin T (cTnT) are used interchangeably to diagnose PPMI. Objectives This study evaluated the frequency of periprocedural myocardial injury and infarction as defined by the Society of Cardiovascular Angiography & Interventions (SCAI), the Academic Research Consortium-2 (ARC-2), and the 4th Universal definition of MI (4UDMI) stratified using cTnT versus cTnI, among patients with chronic coronary syndrome (CCS) and unstable angina. Results Among 830 patients, PPMI rates according to the SCAI, ARC2 and 4UDMI criteria were 4.34%, 2.05%, and 4.94% respectively, with higher rates seen for all definitions when using cTnI versus cTnT (SCAI: 9.84% vs. 1.91%, p<0.001; ARC 2: 3.15% vs. 1.56%, p=0.136; and 4UDMI 5.91% vs. 4.51%, p=0.391). Minor and major periprocedural myocardial injury was respectively observed in 58.31% and 27.10% of patients, with rates of both significantly higher when using cTnI versus cTnT (Minor: 69.29% vs. 53.47%, p<0.001, Major: 49.21% vs. 17.36%, p<0.001). Conclusions Among patients with CCS and unstable angina, PPMIs defined by SCAI occurred more frequently when using cTnI as opposed to cTnT, whereas the type of troponin had no impact on the incidence of PPMIs according to the ARC-2 and 4UDMI

Coronary Computed Tomographic Angiography (CCTA) in non-ST elevation acute coronary syndromes

Abstract Background In patients presenting with an acute coronary syndrome (ACS), a diverse range of coronary artery disease is observed from structurally normal vessels to non-obstructive atherosclerosis and severe/obstructive coronary artery disease (CAD). In current clinical practice guidelines, the main diagnostic route for optimal management of patients with non-ST segment elevation acute coronary syndrome is invasive coronary angiography. However, in 30-40% of cases, no significant coronary lesions are evident. The purpose of this study is to describe the role of coronary computed tomographic angiography (CCTA) in non-ST elevation acute coronary syndromes in low and intermediate risk patients. Methods We describe the results of 504 patients evaluated with a protocol that includes the use of CCTA in patients with ACS. Patients over 18 years of age with a diagnosis of ACS without ST elevation who did not meet high-risk criteria (hemodynamic instability, dynamic changes in the ST segment or T wave, ventricular arrhythmia, GRACE score >140, refractory angina, heart failure or cardiorespiratory arrest) were included. They underwent CCTA as the initial coronary evaluation. Data collection was carried out between May 11, 2022 and February 20, 2024. Results 504 patients were included, with a mean age of 58 years, of which 44% were women and 56% men. Among the admission diagnoses, 26% were NSTEMI and 74% were unstable angina according to the 4th universal definition of acute myocardial infarction (AMI). The median high-sensitivity cardiac troponin T value was 7 nanograms per liter (interquartile range, 7 to 15) for the first troponin measurement. CCTA was performed in 93% of the patients. It was observed that 28% did not have any coronary lesions or plaques. 36% had non-obstructive coronary artery disease (plaques <50%). The rest had significant lesions in at least one vessel (27%), predominantly in the left anterior descending artery, or were nondiagnostic (9%). 31% had myocardial bridges, while in 13% of the patients a high-risk plaque was found. 38% of the patients included underwent invasive coronary angiography and 23% required revascularisation. Conclusion This study shows that the prevalence of ACS with coronary arteries without significant lesions by CCTA was 28%, which suggests CCTA could have a predominant role in the diagnostic algorithm of acute coronary syndromes without high-risk criteria, implying a decrease in the need of invasive studies in these patients. Only 38% required invasive coronary angiography, while revascularisation was performed in 23% of the patients. Furthermore, CCTA allowed a better detection of non-obstructive coronary artery disease (NOCAD) in 36% of the patients, and a more complete characterization of the atherosclerotic plaque, which could prompt to an initiation of preventive therapies or the optimization of medical treatment in these patients.Table 1CCTA findings

Sex differences in clinical characteristics, phenotypes, management, and long-term outcomes of myocardial injury: an international cohort study

Abstract Background Several studies have demonstrated sex differences in patients presenting to the emergency department (ED) with myocardial infarction, heart failure or syncope. Whether sex-specific differences in chest pain patients with myocardial injury exist is unknown. Purpose To determine whether sex-specific differences in the clinical characteristics, phenotypes, management, and long-term outcomes of patients with myocardial injury exist. Methods Patients presenting to the ED with chest pain suggestive of MI were consecutively enrolled into a prospective multicenter international diagnostic study. Final diagnoses were centrally adjudicated by two independent cardiologists, applying the fourth universal definition of myocardial infarction, using all available medical records, including serial hs-cTn and cardiac imaging. Follow-ups were performed at 3 months, 1-, 2- and 5-years. The primary outcome was 5-year all-cause mortality. Secondary outcomes included 5-year cardiovascular mortality and non-cardiovascular mortality. Multivariable flexible parametric (Royston-Parmar) models assuming proportional hazards were fitted. Models were adjusted for age, history of coronary artery disease, history of malignancy, diabetes, hypertension, smoking status, history of liver disease, and renal function. Results Among 8046 chest pain patients presenting to the ED, 1158 (14.4%) had myocardial injury, of which 358 (31%) were females and 800 (69%) males. Women were older (79 years, vs. 73 years), had fewer cardiovascular risk factors and comparable non-cardiovascular comorbidities except for lung disease which was more commonly found in men. Myocardial injury phenotypes varied between sexes (Figure). The most common phenotype in both sexes was heart failure, yet it was more common in men (37.2%) than in women (22.3%). The second most common phenotype in women was hypertension (15.4%) and arrhythmia (15.4 %), while in men was myocarditis (17.8 %), followed by arrhythmia (15.8%). Women underwent less invasive coronary angiography (19.8% vs 26.9%) or stress testing (12% vs 21.5%). In the angiographic findings, women presented more often with normal findings (30.4% vs. 19.6%) or mild CAD (20.3% vs. 11.2%) whereas men displayed more frequently 3-vessel disease (14.5% vs. 36.4%), Table. After adjusting for known confounders, women were associated with a lower 5-years risk for all-cause mortality (HR 0.69; 95%CI: 0.56–0.83) and cardiovascular mortality (HR 0.61; 95%CI: 0.46–0.79). No statistically significant difference in non-cardiovascular mortality risk was found (HR 0.79; 95%CI: 0.59-1.04). Conclusions Women presenting with chest pain to the ED and having myocardial injury were less likely than men to undergo coronary angiography or non-invasive cardiac imaging. Long-term risk for all-cause or cardiovascular mortality was lower for women compared to men.Myocardial Injury phenotypesPatient management

Imprecision and real-time clinical performance of a whole blood high sensitivity point of care troponin i: ready for prime time?

Abstract Introduction High sensitivity troponin (hs-cTn) measurement is central to rapid diagnostic algorithms in acute coronary syndrome (ACS). Point of care (POC) testing reduces turnaround time when compared to central lab (CL) testing. Currently there is very little data on the performance of POC hs-cTn assays in a clinical environment with non-expert operators. Method In a nested sub-study of a randomised controlled trial (RCT), patients with suspected ACS were randomised to either the ESC 0/1 or 0/3 hour algorithm. They underwent whole blood (WB) sampling for Siemens Atellica VTLi hs-cTnI POC (VTLi POC), CL hs-cTnI and CL hs-cTnT assays. This was for both initial and repeat samples. Assay imprecision of the VTLi POC assay was assessed by 2 runs of 10 tests with whole blood at 9 different troponin levels. 4 devices were used with samples stored at room temperature.Final diagnosis was adjudicated based on all relevant clinical and imaging data together with CL hs-cTnT as the diagnostic biomarker in clinical use (10% coefficient of variation (CV) 3-5 ng/L, 99th percentile 14 ng/L) and using the 4th universal definition of myocardial infarction (MI). Clinical performance was assessed using Receiver Operator Characteristics (ROC) curves. Results 2144 patients consented and had WB VTLi POC, CL hs-cTnI and CL hs-cTnT available. The index adjudicated type 1 MI rate was 6.1%. Assay imprecision of the VTLi POC assay demonstrated a 10% Coefficient of Variation (CV) at 9.8ng/l. This was >50% lower than the 99th centile of 23ng/l (average for males and females) (Figure 1). Clinical performance of the VTLi POC assay was acceptable and equivalent to CL hs-cTnT: Area Under Curve (AUC) 0.92 (0.89-0.96), 0.98 (0.96-0.99) and 0.93 (0.87-0.98) at presentation (Figure 2), 1 and 3 hours respectively. However, clinical performance was inferior to CL hs-cTnI: AUC 0.96 (0.95-0.98) and 0.96 (0.93-0.98) at presentation (p=0.0007) and 3 hours (p<0.0001) respectively. Conclusion The Siemens Altellica VTLi hs-cTnI POC assay has imprecision levels consistent with a high sensitivity troponin assay. It has acceptable clinical performance though inferior to the equivalent CL hs-cTnI. Further validation of this assay, particularly with optimised single sample rule-out, could facilitate its use in routine clinical practice.

Elevated GDF-15 is associated with stroke severity, myocardial injury and poor clinical outcome in patients after acute ischemic stroke

Abstract Background GDF-15 is emerging as a biomarker of cardiometabolic risk and disease burden. Increased concentrations of circulating GDF-15 are associated with increased mortality in patients with acute coronary syndromes or heart failure. Purpose We aimed to describe relation between GDF-15 elevation with stroke severity, myocardial injury and poor clinical outcome in patients after acute ischemic stroke (AIS). Methods Patients after AIS were enrolled in our study. Blood samples were obtained from patients at the time of admission, 24 and 48 hours later to determine the plasma levels of GDF-15 and high-sensitive troponin I (hs-cTnI). Receiver-operating characteristic (ROC) curve analysis was used to determine the diagnostic accuracy and optimal elevation cut-off values of GDF-15 on day 1 for the severity of acute stroke defined by NIHSS score. The optimal cut off in our group was 1776 pg/ml (Sensitivity 0,8, Specificity 0,52). Myocardial injury was defined by fourth universal definition of myocardial infarction using hs-cTnI. Demographic characteristics, clinical data, functional outcome, and all-cause mortality at 1 year were compared between groups according to GDF-15 levels. National Institutes of Health Stroke Scale (NIHSS) at the time of admission and the modified Rankin Scale (mRS) 90 days following the patient’s discharge from the hospital were used to assess stroke severity and clinical outcome. All analyses were performed with SPSS 29.0 (SPSS Inc). Results Between August 2020 and August 2022, 177 patients after AIS were enrolled. Elevated GDF-15 was observed in 71 patients (40,1%). Most common comorbidities included arterial hypertension, dyslipidemia, type 2 DM and atrial fibrillation. In analysis, we observed a connection between elevated GDF-15 with unfavourable outcome evaluated by mRS at 90 days (HR 2.57, 95% CI 1,44 to 4,57, p=0.001) and with all-cause death at 1 year (HR 4.479, 95% CI 1,81 to 11,09, p=0.001). GDF-15 elevation was associated with myocardial injury (Figure 1C). Moreover, individuals with moderate to severe and severe strokes (NIHSS 16-42) displayed higher GDF-15 levels compared to those with minor to moderate stroke (Figure 1D). The Kaplan-Meier survival curve accentuated a significantly elevated all-cause mortality among patients with increased GDF-15 (p < 0.001) (Figure 2). In multivariate regression analysis elevated GDF-15 was associated with atrial fibrillation and high-sensitive troponin I elevation. Conclusion The conclusions drawn suggest that heightened GDF-15 is associated with increased stroke severity, myocardial injury and unfavourable outcome.

Predictors of periprocedural myocardial infarction following percutaneous coronary intervenction in NSTEMI

Abstract Background Percutaneous coronary intervention (PCI) has demonstrated a significant positive prognostic impact on outcomes in patients with Non-ST-elevation myocardial infarction (NSTEMI). However, PCI is associated with an increased risk of periprocedural complications, among which periprocedural myocardial infarction (PMI). Although risk factors of periprocedural events are only well established in patients undergoing PCI for chronic coronary syndrome with normal baseline cardiac troponin (cTn) levels, evidence on predictors of additional post-PCI myocardial infarction in patients with acute coronary syndrome who present elevated cTn levels at baseline (pre-PCI) is missing. Purpose To identify the predictors of PMI in patients affected by NSTEMI undergoing PCI. Methods We prospectively evaluated all NSTEMI patients admitted to our coronary care unit from 2017 to 2022 who underwent PCI. NSTEMI patients were managed according to the current European guidelines criteria. The diagnosis of PMI (type 4a myocardial infarction) was based on the Fourth Universal Definition of Myocardial Infarction. We only enrolled patients with stable (≤ 20% variation) or falling pre-procedure baseline cTn values. A multivariable logistic regression analysis was performed to investigate the factors independently associated with the occurrence of PMI after PCI. For the analysis, we selected the main known predictors of PMI after elective PCI, specifically age, serum creatinine, GRACE score > 140, multivessel disease, coronary bifurcation PCI, left main or proximal left anterior descending PCI, multivessel PCI and stent length ≥ 60 mm. Results The final court of the study included 1412 patients. PMI was recognized in 240 patients (17.0%). Although the patients who developed PMI had a higher risk profile as documented by a higher mean age, a higher complexity of atherosclerotic disease, and thus a significant technical difficulty of PCI compared to other patients, according to the multivariable model, only age [OR: 1.02 (95% CI: 1.01-1.04); p=0.006], coronary bifurcation PCI [OR: 3.71 (95% CI: 2.70-5.10); p<0.001], and stent length ≥ 60 mm [OR: 1.87 (95% CI: 1.30-2.68); p=0.001] were independent predictors of PMI. Interestingly, despite previous studies have demonstrated a predictive role of procedural complexity features, this was not completely confirmed by our analysis, in which left main or proximal left anterior descending PCI [OR: 0.92 (95% CI: 0.66-1.26); p=0.596] and multivessel PCI [OR: 0.83 (95% CI: 0.56-1.23); p=0.357] were not associated with an increased risk of periprocedural ischemic complications. Conclusions Among NSTEMI patients undergoing PCI, age, coronary bifurcation PCI and stent length ≥ 60 mm represent independent predictive factors of type 4a MI. This finding may have important clinical implications for clinical practice, providing valuable insights for the identification of higher-risk patients that can benefit from a more aggressive treatment.

Implications of a new clinical classification of acute myocardial infarction

Abstract Background The Universal Definition of Myocardial Infarction has provided standardisation of the diagnostic criteria for myocardial infarction. However, there remain significant challenges in adopting some of the current recommendations in practice. The diagnostic criteria for type 2 myocardial infarction identify a heterogenous group of patients with variable clinical outcomes and no clear treatment implications to date. Purpose To determine the implications of a new clinical classification for myocardial infarction with more objective diagnostic criteria using cardiac imaging.(1) Methods In a prospective cohort study,(2) patients with type 2 myocardial infarction underwent coronary angiography and cardiac magnetic resonance imaging or echocardiography. The new classification was applied to identify (a) spontaneous myocardial infarction due to acute coronary pathology, (b) secondary myocardial infarction precipitated by acute illness in the presence of obstructive coronary artery disease, a new regional wall motion abnormality or infarct pattern scarring, and (c) no myocardial infarction in the absence of obstructive disease or new myocardial abnormality. The diagnostic outcome was the proportion of patients with type 2 myocardial infarction reclassified as having spontaneous, secondary or no myocardial infarction by the new clinical classification. The prognostic outcome was a composite of all-cause death, any recurrent myocardial infarction, or heart failure hospitalisation during follow up. Results In 100 patients (65 years, 43% women) with type 2 myocardial infarction, the new classification identified 25 and 31 patients with spontaneous and secondary myocardial infarction, respectively, and 44 without myocardial infarction (Figure 1). Compared to patients without myocardial infarction, those with secondary myocardial infarction were older, had more risk factors, and higher troponin concentrations (P<0.05 for all). In patients who underwent cardiac magnetic resonance imaging, there was evidence of infarct-pattern late gadolinium enhancement in 95% (19/20) and 60% (15/25) of patients with spontaneous and secondary myocardial infarction, respectively, which was more likely to be transmural in the former. In patients reclassified as secondary myocardial infarction, just 45% and 58% were established on aspirin or a lipid lowering therapy. During a median follow up of 4.4 years, death, myocardial infarction or heart failure hospitalization was more common in secondary myocardial infarction compared to those without myocardial infarction (55% [17/31] versus 16% [7/44], P<0.001; Figure 2). Conclusions A new clinical classification of myocardial infarction informed by cardiac imaging would reduce the diagnosis of myocardial infarction in acute illness and identify those patients at highest risk who are most likely to benefit from treatment.Figure 1:Alluvial plotFigure 2:Kaplan Meier curve

Effect of nutritional guidance on mortality and composite endpoints in patients with acute myocardial infarction: a single center retrospective cohort study

Abstract Background/Introduction Acute myocardial infarction (AMI) stands as a major global cause of mortality. Various intervention strategies, such as pre-hospital care, reperfusion therapies, pharmacological interventions, dietary modifications, and exercise therapies, have been researched to improve patient prognosis (1,2). While reports suggest the efficacy of the Mediterranean diet, there remains a lack of evidence regarding the impact of nutritionist-led dietary guidance on the prognosis of AMI patients. Purpose This study aimed to elucidate whether nutritional guidance by nutritionists who have national qualifications would improve the mortality and the primary composite endpoint (including acute decompensated heart failure, stroke, and acute coronary syndrome) of patients following an acute myocardial infarction. Methods A retrospective cohort study was conducted, enrolling 446 consecutive AMI patients who underwent emergency coronary angiography and percutaneous coronary interventions between September 1, 2015, and October 31, 2023. Patients meeting the universal definition of myocardial infarction were included (3). After excluding 37 in-hospital deaths, evaluations for all-cause mortality, cardiovascular mortality, and composite endpoints were performed during follow-up in 409 patients. Nutritionists guided 223 patients (54.5%) during hospitalization in this study. The nutritional guidance used in our study was also based on the definition of adequate caloric intake of 25–30 kcal per ideal body weight (kg). Under an appropriate total energy intake, a fat energy ratio of 20–25% and a carbohydrate energy ratio of 50–60% are recommended, with protein and lipid restrictions depending on the disease state. Results During a median follow-up of 39 months, 24 cases of all-cause mortality (5.9%) and 6 cases of cardiovascular mortality (1.5%) were recorded. Additionally, 15 cases of nonfatal stroke (3.7%), 17 cases of nonfatal acute coronary syndrome (4.2%), and 20 cases of hospitalizations for acute decompensated heart failure (4.9%) were observed. Kaplan–Meier curves demonstrated significantly higher incidence rates of death and primary composite endpoints among patients without nutritional guidance. The multivariate Cox regression model incorporated all variables exhibiting statistically significant associations with long-term mortality, and the primary composite endpoints. The multivariate Cox regression model revealed nutritional guidance as a significant predictor for long-term mortality but not for primary composite endpoints. Conclusion Nutritional guidance for AMI patients may improve overall mortality. Further research is warranted to explore the physiological impacts of improved diets resulting from such guidance and their effects on enhancing prognosis.

Prognostic significance of type 4a myocardial infarction and periprocedural myocardial injury in NSTEMI patients

Abstract Background Type 4a myocardial infarction (MI) and periprocedural myocardial injury (PMI) might occur in patients with non-ST-elevation MI (NSTEMI) after percutaneous coronary intervention (PCI) procedures. Purpose This study investigated the incidence and prognostic relevance of type 4a MI and PMI, according to current definitions, in NSTEMI patients undergoing PCI. The best cardiac troponin (cTn) threshold of PMI for prognostic stratification is also identified. Methods In this observational cohort study, we enrolled consecutive NSTEMI patients undergoing PCI with stable or falling pre-PCI cTn levels. According to the 4th Universal Definition of Myocardial Infarction (UDMI), we stratified the study population into three subgroups: those experiencing 1) type 4a MI; 2) PMI; 3) no periprocedural ischemic events. The primary endpoint was 1-year all-cause mortality. The secondary endpoint consisted in a composite of major adverse cardiovascular events (MACE) at 1-year, including all-cause mortality, non-fatal reinfarction, urgent revascularization, non-fatal ischemic stroke and hospitalization for heart failure. Results Among 1412 NSTEMI patients undergoing PCI with stable or falling cTn levels at baseline, 240 (17.0%) experienced type 4a MI, 288 (20.4%) PMI, and 884 (62.6%) no periprocedural ischemic events. Patients with type 4a MI had the highest 1-year all-cause mortality and MACE rates. PMI defined by the 4th UDMI (post-PCI delta cTn >20%) did not show significant associations with primary and secondary endpoints. PMI redefined as post-PCI delta cTn >40% was significantly correlated with 1-year all-cause mortality and MACE. Conclusion Periprocedural ischemic events are common in NSTEMI patients undergoing PCI and influence patient outcomes. Type 4a MI and PMI redefined as post-PCI delta cTn >40% are strongly associated with 1-year death and MACE. This study highlights the importance of identifying periprocedural ischemic events to aid risk stratification and management of NSTEMI patients.PMI and type 4a MI: mortality 1-yearPMI and type 4a MI: MACE 1-year

Prognostic role of inflammatory status in type 2 myocardial infarction

Abstract Background there is a wealth of evidence on the importance of inflammatory status in destabilization of chronic artery plaques that led to acute myocardial infarction. However, its role in the setting of type 2 myocardial infarction (T2MI) is not yet specifically known. Purpose We investigated prognostic role of inflammatory parameters in T2MI. Methods We consecutively enrolled 461 T2MI patients from January 2017 to June 2021. T2MI was defined according to the fourth Universal Definition of Myocardial Infarction. We divided the overall population in patients who experience major cardiovascular events (MACE), n=166, and in those who do not (n=277). Receiver operating characteristic (ROC) curve analysis were used to assess the diagnostic accuracy of various inflammatory parameters for predict MACE occurrence during long term follow-up. We divided patients into two groups (high and low inflammatory burden) based on the value associated with the highest Youen index. Cox proportional hazards regression models were constructed to estimate the independent role of these parameters in predict MACE. Results We found that patients who experienced MACE had a higher level of inflammatory parameters, in particular hs-CRP (2.21±3.7 vs 1.48 ±3.5, p<0.001) and platelet-to-neutrophil ratio (3.72 ±1.52 vs 3.7±1.43, p=0.02). Using ROC analysis, the area under the curve (AUC) of hs-CRP was the largest among all inflammatory parameters and the optimal threshold, according to Youden’s index, was found to be 1.2 mg/dL. MACE-free survival curves, comparing groups with low hs-CRP (< 1.2 mg/dL) and high hs-CRP (≥ 1.2 mg/dL), showed that high hs-CRP was associated with a worse prognosis (p<0.001). At Cox regression models, hs-CRP value ≥1.2 mg/dL was independently associated with MACE (p=0.01) together with diabetes (p=0.006), chronic obstructive pulmonary disease (p=0.006), previous stroke (p=0.001) and older age (p<0.001). Conclusion T2MI patients who experienced MACE exhibited higher levels of inflammatory parameters. Patients with hs-CRP levels ≥1.2 mg/dL had a worse prognosis, independently predicting MACE. These findings underscore the potential utility of hs-CRP as a prognostic biomarker in risk-stratifying patients with T2MI and highlight the importance of addressing inflammatory status in optimizing patient management and improving outcomes.

Derivation and external validation of new ESC 0/1-h algorithm cut-offs for high-sensitivity troponin T and I in the cancer population

Abstract Background The diagnostic performance of high-sensitivity cardiac troponin T/I (hs-cTnT/I) and the efficacy of the European Society of Cardiology (ESC) 0/1h-hs-cTnT/I-algorithms for the early diagnosis of non-ST-elevation myocardial infarction (NSTEMI) is reduced in cancer patients presenting to the emergency department (ED) with chest pain.[1] Purpose This study aimed to derive and externally validate new cut-offs for the ESC 0/1h-hs-cTnT/I-algorithms in chest pain patients with active or past cancer. Methods Patients presenting with acute chest discomfort to the ED were prospectively enrolled in an international multicenter diagnostic study. Final diagnoses were centrally adjudicated by 2 independent cardiologists applying the fourth universal definition of myocardial infarction using all available medical records, cardiac imaging, and serial hs-cTnT/I. Hs-cTn concentrations were measured at presentation and after 1 hour. New assay-specific cutoffs for the ESC 0/1h-hs-cTnT/I-algorithm were derived and externally validated in two independent cohorts. Results Among 541 and 516 eligible patients with 0h and 1h hs-cTnT and hs-cTnI values, respectively, application of the current ESC 0/1h-hs-cTnT/I algorithm triaged 317 (58.6%) and 306 (59.3%) patients to either rule-out or rule-in, leaving 224 (41.4%) and 210 (40.7%) patients in the observe-zone of the ESC 0/1h-hs-cTnT/I algorithm, respectively. The novel ESC 0/1h-hs-cTnT cut-offs ruled out NSTEMI with a cut-off <8 ng/L at presentation (if chest pain onset >3 hours) or <14 ng/L together with a 0/1-hour delta <3 ng/L, ruling-out 241 patients (44.5%) with a sensitivity and negative predictive value (NPV) of 99.2% and 99.6%, respectively. The novel ESC 0/1h-hs-cTnI cutoffs ruled out NSTEMI with a cut-off <7 ng/L at presentation (if chest pain onset >3 hours) or <10 ng/L together with a 0/1-hour delta <3 ng/L, ruling-out 281 patients (54.5%) with a sensitivity and NPV of 99.1% and 99.6, respectively. Findings were confirmed in both internal and external validation (Figure 1). A total of 167 (32.8%) patients died at 5-years, of whom 61 died of cardiovascular causes, and 30 (5.9%) patients had an MI at 5 years. 5-year all-cause mortality for the rule-out group was similar for both the current and the novel ESC 0/1-h algorithm, although the novel one identified patients in the observe zone group as having the highest mortality (Figure 2). Incidence of 5-year cardiovascular mortality or AMI provided by the current ESC 0/1h-algorithm was similar for the rule-in and observe zone groups for both hs-cTnT and hs-cTnI. Conclusions In chest pain patients with a history of cancer, new derived assay-specific cutoffs for the ESC 0/1h-hs-cTnT/I-algorithm achieved a higher proportion of patients triaged to either rule-out or rule-in without decreasing safety. The low mortality rate of the rule-out group identified by the new algorithm further reassures on the safety of the new derived cut-offs.Sensitivity analysis in the APACE cohort5-year all-cause mortality

Influence of pathophysiological patterns of coronary artery disease on the safety and efficacy of percutaneous coronary intervention

Abstract Background Impaired blood flow after PCI, reflected by low FFR, portends a worse prognosis. Prior to intervention, pressure gradient distributions offer insights into the likelihood of subsequent PCI success. The pullback pressure gradient (PPG) serves as a quantifiable measure of CAD patterns: values approximating 1 signify focal disease, while values approaching 0 suggest diffuse disease. This study aimed to assess the impact of pathophysiological CAD patterns on the safety and efficacy of PCI. Methods PPG Global was a prospective, investigator-initiated, multicenter study, single-arm that enrolled patients with at least one lesion with an FFR ≤ 0.80 scheduled to be treated by PCI. The study enrolled 1004 patients (1057 vessels). A standardised physiological assessment was performed, including online PPG calculation from manual FFR pullbacks. CAD patterns were defined as predominantly focal or diffuse disease based on the median PPG value. The study was powered to ascertain the predictive capacity of PPG for optimal PCI results (defined as FFR≥0.88 after PCI) as assessed by the AUC. Immediate PCI outcomes were assessed using post-PCI FFR and CFR. Following PCI, biomarkers (troponin) were collected. An independent clinical events committee adjudicated periprocedural myocardial infarction. The assessment of peri-procedural myocardial infarction (MI) adhered to the criteria outlined in the 4th Universal Definition of Myocardial Infarction. Target vessel failure (TVF) was defined as cardiac death, myocardial infarction and target vessel revascularisation. Results One thousand and four patients with 1057 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, post-PCI FFR 0.87 ± 0.07, and post-PCI CFR was 3.19 ± 1.93. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI: 0.61-0.69, p<0.001) and showed an area under the curve of 0.82 (95% CI: 0.79-0.84) to predict optimal revascularisation. Suboptimal FFR (<0.88) after an angiographically successful PCI occurred in 471 vessels (53.5%) and was significantly higher in patients with diffuse disease (37.1% vs 74.0%, p<0.001). The change in CFR was sixfold higher in patients with high PPG (delta CFR focal 1.18 ± 1.94 and diffuse 0.19 ± 1.52, p<0.001). The rate of in-hospital TVF was similar between patients with focal vs diffuse disease (5.1% vs 8.5%, p=0.060). The incidence of periprocedural MI was significantly higher in patients with diffuse disease (5.9% vs 9.8%, p=0.050; OR 1.83, 95% CI 1.02 to 3.34). Conclusions Pathophysiological CAD patterns distinctly affect the safety and efficacy of PCI. PCI in focal disease was associated with improved physiological outcomes and a lower rate of periprocedural myocardial infarction compared to diffuse disease. Quantifying PPG before intervention reliably predicted post-PCI FFR. Further investigation through a randomised trial is warranted to explore the potential advantages of a PPG-guided PCI strategy.PPG and Revascularisation OutcomesPPG and FFR correlation Pre and Post-PCI