Management and outcomes with 5-year mortality of patients with mildly elevated high-sensitivity troponin T levels not meeting criteria for myocardial infarction.

OBJECTIVES: To examine management and outcomes of patients presenting to EDs with symptoms suggestive of acute coronary syndrome, who have mild non-dynamically elevated high-sensitivity troponin T (HsTnT) levels, not meeting the fourth universal definition of myocardial infarction (MI) criteria (observation group). METHODS: Consecutive patients presenting to the ED with symptoms suggestive of acute coronary syndrome at Liverpool Hospital, Sydney, Australia, those having ≥2 HsTnT levels after initial assessment were adjudicated according to the fourth universal definition of MI, as MI ruled-in, MI ruled-out, or myocardial injury in whom MI is neither ruled-in nor ruled-out (>1 level ≥15 ng/L, called observation group); follow-up was 5 years. RESULTS: Of 2738 patients, 547 were in the observation group, of whom 62% were admitted to hospital, 52% to cardiac services, whereas 97% of MI ruled-in patients and 21% of MI ruled-out patients were admitted; P < 0.001. Non-invasive testing occurred in 42% of observation group patients (36% had echo-cardiography), and 16% had coronary angiography. Of observation group patients, MI rates were 1.5% during hospitalisation and 4% during the following year, similar to that in those with MI ruled-in, among those with MI ruled-out, the MI rate was 0.2%. The 1-year death rate was 13% among observation group patients and 11% MI ruled-in patients (P = 0.624), whereas at 5 years among observation group patients, type 1 MI and type 2 MI were 48%, 26% and 58%, respectively (P = 0.001). CONCLUSION: Very few unselected consecutive patients attending ED, with minor stable HsTnT elevation, had MI, although most had chronic myocardial injury. Late mortality rates among observation group patients were higher than those with confirmed type 1 MI but lower than those with type 2 MI.

Impacts of high sensitivity troponin T reporting on care and outcomes in clinical practice: Interactions between low troponin concentrations and participant sex within two randomized clinical trials.

BACKGROUND: The impacts of high sensitivity cardiac troponin (hs-cTn) reporting on downstream interventions amongst suspected acute coronary syndrome (ACS) in the emergency department (ED), especially amongst those with newly identified hs-cTn elevations and in consideration of well-established sex-related disparities, has not been critically evaluated to date. This investigation explores the impact of hs-cTnT reporting on care and outcomes, particularly by participant sex. METHODS: Two similarly ED-based randomized controlled trials conducted between July 2011 to March 2013 (n = 1988) and August 2015 to April 2019 (n = 3378) were comparatively evaluated. Clinical outcomes were adjudicated to the Fourth Universal Definition of MI. Changes in practice were assessed at 30 days, and death or MI were explored to 12 months. RESULTS: The HS-Troponin study demonstrated no difference in death or MI with unmasking amongst those with hs-cTnT <30 ng/L, whereas the RAPID TnT study demonstrated a significantly higher rate. In RAPID TnT, there was significant increase in death or MI associated with unmasking for females with hs-cTnT <30 ng/L (masked: 11[1.5%], unmasked: 25[3.4%],HR: 2.27,95%C.I.:1.87-2.77,P < 0.001). Less cardiac stress testing with unmasking amongst those <30 ng/L was observed in males in both studies, which was significant in RAPID TnT (masked: 92[12.0%], unmasked: 55[7.0%], P = 0.008). In RAPID TnT, significantly higher rates of angiography in males were observed with unmasking, with no such changes amongst females <30 ng/L (masked: 28[3.7%], unmasked: 51[6.5%],P = 0.01). CONCLUSION: Compared with males, there were no evident impacts on downstream practices for females with unmasking in RAPID TnT, likely representing missed opportunities to reduce late death or MI.

Rapid access chest pain clinics in Australia and New Zealand.

Chest pain is the second most common reason for adult emergency department presentations. Most patients have low or intermediate risk chest pain, which historically has led to inpatient admission for further evaluation. Rapid access chest pain clinics represent an innovative outpatient pathway for these low and intermediate risk patients, and have been shown to be safe and reduce hospital costs. Despite variations in rapid access chest pain clinic models, there are limited data to determine the most effective approach. Developing a national framework could be beneficial to provide sites with evidence, possible models, and business cases. Multicentre data analysis could enhance understanding and monitoring of the service.

STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) guidelines recommend pharmaco-invasive treatment if timely primary percutaneous coronary intervention (PCI) is unavailable. Full-dose tenecteplase is associated with an increased risk of intracranial hemorrhage in older patients. Whether pharmaco-invasive treatment with half-dose tenecteplase is effective and safe in older patients with STEMI is unknown. METHODS: STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) was an investigator-initiated, open-label, randomized, multicenter study. Patients ≥60 years of age with ≥2 mm ST-segment elevation in 2 contiguous leads, unable to undergo primary PCI within 1 hour, were randomly assigned (2:1) to half-dose tenecteplase followed by coronary angiography and PCI (if indicated) 6 to 24 hours after randomization, or to primary PCI. Efficacy end points of primary interest were ST resolution and the 30-day composite of death, shock, heart failure, or reinfarction. Safety assessments included stroke and nonintracranial bleeding. RESULTS: Patients were assigned to pharmaco-invasive treatment (n=401) or primary PCI (n=203). Median times from randomization to tenecteplase or sheath insertion were 10 and 81 minutes, respectively. After last angiography, 85.2% of patients undergoing pharmaco-invasive treatment and 78.4% of patients undergoing primary PCI had ≥50% resolution of ST-segment elevation; their residual median sums of ST deviations were 4.5 versus 5.5 mm, respectively. Thrombolysis In Myocardial Infarction flow grade 3 at last angiography was ≈87% in both groups. The composite clinical end point occurred in 12.8% (51/400) of patients undergoing pharmaco-invasive treatment and 13.3% (27/203) of patients undergoing primary PCI (relative risk, 0.96 [95% CI, 0.62-1.48]). Six intracranial hemorrhages occurred in the pharmaco-invasive arm (1.5%): 3 were protocol violations (excess anticoagulation in 2 and uncontrolled hypertension in 1). No intracranial bleeding occurred in the primary PCI arm. The incidence of major nonintracranial bleeding was low in both groups (<1.5%). CONCLUSIONS: Halving the dose of tenecteplase in a pharmaco-invasive strategy in this early-presenting, older STEMI population was associated with electrocardiographic changes that were at least comparable to those after primary PCI. Similar clinical efficacy and angiographic end points occurred in both treatment groups. The risk of intracranial hemorrhage was higher with half-dose tenecteplase than with primary PCI. If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02777580.

Early Effects of Ticagrelor Versus Clopidogrel on Peripheral Endothelial Function After Non-ST-Elevation Acute Coronary Syndrome and Assessment of Its Relationship With Coronary Microvascular Function.

Peripheral endothelial dysfunction is an independent predictor of adverse long-term prognosis after acute coronary syndrome. Data are lacking on the effects of oral P2Y12-inhibitors on peripheral endothelial function in non-ST-elevation acute coronary syndrome (NSTEACS). Furthermore, the relation between peripheral endothelial function and invasive indexes of coronary microvascular function in NSTEACS is unclear. Between March 2018 and July 2020, hospitalized patients with NSTEACS were randomized (1:1) to ticagrelor or clopidogrel. Peripheral endothelial function was assessed with brachial artery flow-mediated vasodilation (FMD). Invasive indexes of coronary microvascular function were obtained using an intracoronary pressure-temperature sensor-tipped wire. In 70 patients included, mean age was 58.6 years, 78.6% (n = 55) were male and 20% (n = 14) had diabetes mellitus. Compared with clopidogrel, ticagrelor significantly improved FMD (14.2 ± 5.4% vs 8.9 ± 5.3%, p <0.001) after a median treatment time of 41.2 hours. The FMD was significantly correlated with the index of microcirculatory resistance (IMR) measured in the infarct-related artery (r = -0.38, p = 0.001), with a stronger correlation found in those who did not have percutaneous coronary intervention (r = -0.52, p = 0.03). Using receiver operating characteristic curve analysis, an FMD of 8.2% identified an IMR of >34 as the threshold, with 77.6% sensitivity and 52.4% specificity. In patients who did not have a percutaneous coronary intervention, an FMD of 11.49% identified an IMR of >34 with 84.6% sensitivity and 80% specificity. In conclusion, ticagrelor significantly improved peripheral endothelial function compared with clopidogrel in patients with NSTEACS. There was a significant correlation between brachial artery FMD and IMR of the infarct-related artery.

Late Outcomes of Patients With Prehospital ST-Segment Elevation and Appropriate Cardiac Catheterization Laboratory Nonactivation.

Background Patients with suspected ST-segment-elevation myocardial infarction (STEMI) and cardiac catheterization laboratory nonactivation (CCL-NA) or cancellation have reportedly similar crude and higher adjusted risks of death compared with those with CCL activation, though reasons for these poor outcomes are not clear. We determined late clinical outcomes among patients with prehospital ECG STEMI criteria who had CCL-NA compared with those who had CCL activation. Methods and Results We identified consecutive prehospital ECG transmissions between June 2, 2010 to October 6, 2016. Diagnoses according to the Fourth Universal Definition of myocardial infarction (MI), particularly rates of myocardial injury, were adjudicated. The primary outcome was all-cause death. Secondary outcomes included cardiovascular death/MI/stroke and noncardiovascular death. To explore competing risks, cause-specific hazard ratios (HRs) were obtained. Among 1033 included ECG transmissions, there were 569 (55%) CCL activations and 464 (45%) CCL-NAs (1.8% were inappropriate CCL-NAs). In the CCL activation group, adjudicated index diagnoses included MI (n=534, 94%, of which 99.6% were STEMI and 0.4% non-STEMI), acute myocardial injury (n=15, 2.6%), and chronic myocardial injury (n=6, 1.1%). In the CCL-NA group, diagnoses included MI (n=173, 37%, of which 61% were non-STEMI and 39% STEMI), chronic myocardial injury (n=107, 23%), and acute myocardial injury (n=47, 10%). At 2 years, the risk of all-cause death was higher in patients who had CCL-NA compared with CCL activation (23% versus 7.9%, adjusted risk ratio, 1.58, 95% CI, 1.24-2.00), primarily because of an excess in noncardiovascular deaths (adjusted HR, 3.56, 95% CI, 2.07-6.13). There was no significant difference in the adjusted risk for cardiovascular death/MI/stroke between the 2 groups (HR, 1.23, 95% CI, 0.87-1.73). Conclusions CCL-NA was not primarily attributable to missed STEMI, but attributable to "masquerading" with high rates of non-STEMI and myocardial injury. These patients had worse late outcomes than patients who had CCL activation, mainly because of higher rates of noncardiovascular deaths.

Utility of prehospital electrocardiogram interpretation in ST-segment elevation myocardial infarction utilizing computer interpretation and transmission for interventional cardiologist consultation.

OBJECTIVES: We examined the appropriateness of prehospital cardiac catheter laboratory activation (CCL-A) in ST-segment elevation myocardial infarction (STEMI) utilizing the University of Glasgow algorithm (UGA) and remote interventional cardiologist consultation. BACKGROUND: The incremental benefit of prehospital electrocardiogram (PH-ECG) transmission on the diagnostic accuracy and appropriateness of CCL-A has been examined in a small number of studies with conflicting results. METHODS: We identified consecutive PH-ECG transmissions between June 2, 2010 and October 6, 2016. Blinded adjudication of ECGs, appropriateness of CCL-A, and index diagnoses were performed using the fourth universal definition of MI. The primary outcome was the appropriate CCL-A rate. Secondary outcomes included rates of false-positive CCL-A, inappropriate CCL-A, and inappropriate CCL nonactivation. RESULTS: Among 1088 PH-ECG transmissions, there were 565 (52%) CCL-As and 523 (48%) CCL nonactivations. The appropriate CCL-A rate was 97% (550 of 565 CCL-As), of which 4.9% (n = 27) were false-positive. The inappropriate CCL-A rate was 2.7% (15 of 565 CCL-As) and the inappropriate CCL nonactivation rate was 3.6% (19 of 523 CCL nonactivations). Reasons for appropriate CCL nonactivation (n = 504) included nondiagnostic ST-segment elevation (n = 128, 25%), bundle branch block (n = 132, 26%), repolarization abnormality (n = 61, 12%), artefact (n = 72, 14%), no ischemic symptoms (n = 32, 6.3%), severe comorbidities (n = 26, 5.2%), transient ST-segment elevation (n = 20, 4.0%), and others. CONCLUSIONS: PH-ECG interpretation utilizing UGA with interventional cardiologist consultation accurately identified STEMI with low rates of inappropriate and false-positive CCL-As, whereas using UGA alone would have almost doubled CCL-As. The benefits of cardiologist consultation were identifying "masquerading" STEMI and avoiding unnecessary CCL-As.

Impact of Ticagrelor Versus Clopidogrel on Coronary Microvascular Function After Non-ST-Segment-Elevation Acute Coronary Syndrome.

BACKGROUND: Coronary microvascular dysfunction after acute coronary syndrome is an important predictor of long-term prognosis. Data is lacking on the effects of oral P2Y12-inhibitors on coronary microvascular function in non-ST-segment-elevation acute coronary syndrome. The aim of this study was to compare the acute effects of ticagrelor versus clopidogrel pretreatment on coronary microvascular function in non-ST-segment-elevation acute coronary syndrome patients. METHODS: Hospitalized non-ST-segment-elevation acute coronary syndrome patients were randomized (1:1) to ticagrelor or clopidogrel. The index of microcirculatory resistance, coronary flow reserve, and resistive reserve ratio were obtained using an intracoronary pressure-temperature sensor-tipped wire. RESULTS: In total, 128 patients were randomized between March 2018 and July 2020. Mean age 59.2±11.8 years, 84% were male, mean Global Registry of Acute Coronary Events score was 93.7±24.5. Intracoronary physiological measurements were obtained in 118 patients (60 ticagrelor, 58 clopidogrel). In the infarct-related artery, the ticagrelor group had lower baseline index of microcirculatory resistance (22.0 [13.0-34.9] versus 27.7 [19.3-29.8]; P=0.02) and higher baseline resistive reserve ratio (3.0 [2.3-4.4] versus 2.4 [1.7-3.4]; P=0.01) compared with the clopidogrel group. A total of 88 patients underwent percutaneous coronary intervention (PCI; 45 ticagrelor, 43 clopidogrel). The ticagrelor group had lower post-PCI index of microcirculatory resistance (22.0 [15.0-29.0] versus 27.0 [18.5-47.5]; P=0.02) and higher post-PCI resistive reserve ratio (3.0 [1.8-3.8] versus 1.8 [1.5-3.4]; P=0.006) compared with the clopidogrel group. The coronary flow reserve was not significantly different between the 2 groups at baseline or post-PCI. No between-group differences were seen in any of the indices in the non-infarct-related artery. CONCLUSIONS: In non-ST-segment-elevation acute coronary syndrome patients, ticagrelor significantly improved coronary microvascular function before and after PCI compared with clopidogrel. REGISTRATION: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12618001610224.

Cost effectiveness of a 1-hour high-sensitivity troponin-T protocol: An analysis of the RAPID-TnT trial.

BACKGROUND: To understand the economic impact of an accelerated 0/1-hour high-sensitivity troponin-T (hs-cTnT) protocol. OBJECTIVE: To conduct a patient-level economic analysis of the RAPID-TnT randomised trial in patients presenting with suspected acute coronary syndrome (ACS). METHODS: An economic evaluation was conducted with 3265 patients randomised to either the 0/1-hour hs-cTnT protocol (n = 1634) or the conventional 0/3-hour standard-of-care protocol (n = 1631) with costs reported in Australian dollars. The primary clinical outcome was all-cause mortality or new/recurrent myocardial infarction. RESULTS: Over 12-months, mean per patient costs were numerically higher in the 0/1-hour arm compared to the conventional 0/3-hour arm (by $472.49/patient, 95% confidence interval [95 %CI]: $-1,380.15 to $2,325.13, P = 0.617) with no statistically significant difference in primary outcome (0/1-hour: 62/1634 [3.8%], 0/3-hour: 82/1631 [5.0%], HR: 1.32 [95 %CI: 0.95-1.83], P = 0.100). The mean emergency department (ED) length of stay (LOS) was significantly lower in the 0/1-hour arm (by 0.62 h/patient, 95 %CI: 0.85 to 0.39, P < 0.001), but the subsequent 12-month unplanned inpatient costs was numerically higher (by $891.22/patient, 95 %CI: $-96.07 to 1,878.50, P = 0.077). Restricting the analysis to patients with hs-cTnT concentrations ≤ 29 ng/L, mean per patient cost remained numerically higher in the 0/1-hour arm (by $152.44/patient, 95 %CI:$-1,793.11 to $2,097.99, P = 0.988), whilst the reduction in ED LOS was more pronounced (by 0.70 h/patient, 95 %CI: 0.45-0.95, P < 0.001). CONCLUSIONS: There were no differences in resource utilization between the 0/1-hour hs-cTnT protocol versus the conventional 0/3-hour protocol for the assessment of suspected ACS, despite improved initial ED efficiency. Further refinements in strategies to improve clinical outcomes and subsequent management efficiency are needed.

Implementation of more sensitive cardiac troponin T assay in a state-wide health service.

AIMS: Explore the impact of deploying high-sensitivity (hs) cardiac troponin T (cTnT) assay across a state-wide health service. METHODS AND RESULTS: Presentations to emergency departments of six tertiary hospitals between January 2008 and August 2019 were included; standard cTnT assay was superseded by hs-cTnT in June 2011 without changing the reference range (≥30 ng/L reported as elevated), despite cTnT level of 30 ng/L being equivalent to ∼44 ng/L with hs-cTnT. Clinical outcomes were captured using state-wide linked health records. Interrupted time series analyses were used adjusted for seasonality and multiple co-morbidities using propensity score matching allowing for correlation within hospitals. In total, 614,847 presentations had ≥1 troponin measurement. Clinical ordering of troponin decreased throughout the study with no increase in elevated measurements amongst those tested with hs-cTnT. Small but statistically significant changes in index myocardial infarction (MI) diagnosis (-0.36%/year, 95%CI [confidence interval]:-0.48, -0.24,p < 0.001) and invasive coronary angiography (0.12%/year,95%CI:0, 0.24,p = 0.02) were seen, with no impact on death/MI at 30 days or 3-year survival in episodes of care (EOCs) with elevated cTnT after hs-cTnT implementation. Length of stay (LOS) was shorter among those with an elevated hs-cTnT (-4.44 h/year, 95%CI:-5.27, -3.60, p < 0.001). Non-elevated cTnT EOCs demonstrated shorter total LOS and improved 3-year survival (adjusted hazard ratio:0.90, 95%CI:0.83, 0.97,p = 0.008) although death/MI at 30 days was unchanged using hs-cTnT. CONCLUSION: Widespread implementation of hs-cTnT without altering clinical thresholds reported to clinicians provided significantly shorter LOS without a clinically significant impact on clinical outcomes. A safer cohort with non-elevated cTnT was identified by hs-cTnT compared to the standard cTnT assay.

Right ventricular myocardial infarction: pathophysiology, clinical implications and management.

Right ventricular myocardial infarction (RVMI) and right ventricular (RV) failure are complications from an acute occlusion of a dominant right coronary artery (RCA) or left anterior descending (LAD) artery. Although some patients have good long-term RV recovery, RVMI is associated with high rates of in-hospital morbidity and mortality driven by hemodynamic compromise, cardiogenic shock, and electrical complications. As such, it is important to identify specific clinical signs and symptoms, initiate resuscitation and commence reperfusion therapy with fibrinolytic therapy or percutaneous coronary intervention. This review will discuss RVMI pathophysiology, describe the current diagnostic measures, highlight current therapies, and explore future management options.

Reperfusion After Fibrinolytic Therapy (RAFT): An open-label, multi-centre, randomised controlled trial of bivalirudin versus heparin in rescue percutaneous coronary intervention.

BACKGROUND: The safety and efficacy profile of bivalirudin has not been examined in a randomised controlled trial of patients undergoing rescue PCI. OBJECTIVES: We conducted an open-label, multi-centre, randomised controlled trial to compare bivalirudin with heparin ± glycoprotein IIb/IIIa inhibitors (GPIs) in patients undergoing rescue PCI. METHODS: Between 2010-2015, we randomly assigned 83 patients undergoing rescue PCI to bivalirudin (n = 42) or heparin ± GPIs (n = 41). The primary safety endpoint was any ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) bleeding at 90 days. The primary efficacy endpoint was infarct size measured by peak troponin levels as a multiple of the local upper reference limit (Tn/URL). Secondary endpoints included periprocedural change in haemoglobin adjusted for red cells transfused, TIMI (Thrombolysis in Myocardial Infarction) bleeding, ST-segment recovery and infarct size determined by the Selvester QRS score. RESULTS: The trial was terminated due to slow recruitment and futility after an interim analysis of 83 patients. The primary safety endpoint occurred in 6 (14%) patients in the bivalirudin group (4.8% GPIs) and 3 (7.3%) in the heparin ± GPIs group (54% GPIs) (risk ratio, 1.95, 95% confidence interval [CI], 0.52-7.3, P = 0.48). Infarct size was similar between the two groups (mean Tn/URL, 730 [±675] for bivalirudin, versus 984 [±1585] for heparin ± GPIs, difference, 254, 95% CI, -283-794, P = 0.86). There was a smaller decrease in the periprocedural haemoglobin level with bivalirudin than heparin ± GPIs (-7.5% [±15] versus -14% [±17], difference, -6.5%, 95% CI, -0.83-14, P = 0.0067). The rate of complete (≥70%) ST-segment recovery post-PCI was higher in patients randomised to heparin ± GPIs compared with bivalirudin. CONCLUSIONS: Whether bivalirudin compared with heparin ± GPI reduces bleeding in rescue PCI could not be determined. Slow recruitment and futility in the context of lower-than-expected bleeding event rates led to the termination of this trial (ANZCTR.org.au, ACTRN12610000152022).

Classification performance of clinical risk scoring in suspected acute coronary syndrome beyond a rule-out troponin profile.

AIMS: High-sensitivity cardiac troponin strategies can provide risk stratification in patients with suspected acute coronary syndrome (ACS) in the emergency department (ED). This study evaluated whether clinical risk scoring improves the classification performance of a rule-out profile in suspected ACS. METHODS AND RESULTS: Patients presenting to ED with suspected ACS as part of the RAPID-TnT trial randomized to the intervention arm were included. Results ≥5 ng/L were available for all participants in this analysis. We evaluated the Thrombolysis In Myocardial Infarction (TIMI) risk score, History ECG Age Risk factors Troponin (HEART) score, and Emergency Department Assessment of Chest pain Score (EDACS) in addition to a rule-out profile based on the 0/1-h high-sensitivity cardiac troponin T protocol (<5 ng/L or ≤12 ng/L and a change of <3 ng/L at 1-h) using test performance parameters focusing on low-risk groups to identify the primary endpoint (TIMI ≤ 1, HEART ≤ 3, EDACS < 16). Primary endpoint was a composite of type 1/2 myocardial infarction (MI) at index presentation and all-cause mortality or type 1/2 MI at 30 days. A total of 3378 participants were enrolled between August 2015 and April 2019 of which 108 were ineligible/withdrew consent (intervention arm: n = 1638). Sensitivity, specificity, negative predictive value (NPV), and area under the curve (AUC) of the rule-out profile was 94.4%, 76.8%, 99.6%, and 0.86, respectively with 72.9% identified as 'low-risk'. Adding the clinical risk scores did not improve the sensitivity, NPV, or AUC with significantly lower specificity and 'low-risk' classified participants. CONCLUSIONS: Addition of clinical risk scores to rule-out profile did not demonstrate improved classification performance for identifying the composite of type 1/2 MI at index presentation and all-cause mortality or type 1/2 MI at 30 days. CLINICAL TRIALS REGISTRATION: URL: https://www.anzctr.org.au. Reg. No. ACTRN12615001379505.

Late Outcomes of the RAPID-TnT Randomized Controlled Trial: 0/1-Hour High-Sensitivity Troponin T Protocol in Suspected ACS.

BACKGROUND: High-sensitivity troponin assays are increasingly being adopted to expedite evaluation of patients with suspected acute coronary syndromes. Few direct comparisons have examined whether the enhanced performance of these assays at low concentrations leads to changes in care that improves longer-term outcomes. This study evaluated late outcomes of participants managed under an unmasked 0/1-hour high-sensitivity cardiac troponin T (hs-cTnT) protocol compared with a 0/3-hour masked hs-cTnT protocol. METHODS: We conducted a multicenter prospective patient-level randomized comparison of care informed by unmasked 0/1-hour hs-cTnT protocol (reported to <5 ng/L) versus standard practice masked hs-cTnT testing (reported to ≤29 ng/L) assessed at 0/3 hours and followed participants for 12 months. Participants included were those presenting to metropolitan emergency departments with suspected acute coronary syndromes, without ECG evidence of coronary ischemia. The primary end point was time to all-cause death or myocardial infarction using Cox proportional hazards models adjusted for clustering within hospitals. RESULTS: Between August 2015 and April 2019, we randomized 3378 participants, of whom 108 withdrew, resulting in 12-month follow-up for 3270 participants (masked: 1632; unmasked: 1638). Among these, 2993 (91.5%) had an initial troponin concentration of ≤29 ng/L. Deployment of the 0/1-hour hs-cTnT protocol was associated with reductions in functional testing. Over 12-month follow-up, there was no difference in invasive coronary angiography (0/1-hour unmasked: 232/1638 [14.2%]; 0/3-hour masked: 202/1632 [12.4%]; P=0.13), although an increase was seen among patients with hs-cTnT levels within the masked range (0/1-hour unmasked arm: 168/1507 [11.2%]; 0/3-hour masked arm: 124/1486 [8.3%]; P=0.010). By 12 months, all-cause death and myocardial infarction did not differ between study arms overall (0/1-hour: 82/1638 [5.0%] versus 0/3-hour: 62/1632 [3.8%]; hazard ratio, 1.32 [95% CI, 0.95-1.83]; P=0.10). Among participants with initial troponin T concentrations ≤29 ng/L, unmasked hs-cTnT reporting was associated with an increase in death or myocardial infarction (0/1-hour: 55/1507 [3.7%] versus 0/3-hour: 34/1486 [2.3%]; hazard ratio, 1.60 [95% CI, 1.05-2.46]; P=0.030). CONCLUSIONS: Unmasked hs-cTnT reporting deployed within a 0/1-hour protocol did not reduce ischemic events over 12-month follow-up. Changes in practice associated with the implementation of this protocol may be associated with an increase in death and myocardial infarction among those with newly identified troponin elevations. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12615001379505.

Prognostic Implications of High-Sensitivity Troponin T Levels Among Patients Attending Emergency Departments and Evaluated for an Acute Coronary Syndrome.

BACKGROUND: With increasing age, patients with suspected acute coronary syndromes (ACS) and elevated high-sensitivity troponin T (HsTnT) levels, type-1 myocardial infarction (MI) is diagnosed less often, though associations among these factors, gender, and prognosis is unclear. METHODS: Patients presenting to the emergency department (ED) with potential ACS who underwent HsTnT testing were prospectively identified and followed. Diagnoses were adjudicated according to the Fourth Universal Definition of MI as follows: type-1 MI, type-2 MI, acute myocardial injury, chronic myocardial injury, and other diagnoses. Age in years was categorized: younger (<65); elderly (65-79), and very elderly (≥80). RESULTS: Among 2738 patients with HsTnT measurements, 1611 were suitable for adjudication (42% ages 65 years and younger). Type-2 MI and chronic myocardial injury diagnoses were more common in those ages 65 years and older, whereas younger patients had more type-1 MI diagnoses. Late mortality rates at median 41 months (interquartile range [IQR] 10-57) were 44% (223 out of 506) in those ages 80 years and older, 22% (92 out of 423) in patients 65-79 years, and 7% (46 out of 682) in those 65 years and younger, irrespective of adjudicated diagnoses, log rank P ≤ .001. On multivariable analyses, the adjusted mortality hazard ratios for increasing HsTnT levels irrespective of diagnoses were attenuated in those age 80 years and older compared to younger patients. CONCLUSIONS: Patients ages 65 years and older constituted ~60% of ED attendances of patients with suspected ACS, and more had type 2 MI and chronic myocardial injury diagnoses compared to younger patients. The relative mortality impact of HsTnT levels was lower among elderly patients irrespective of adjudicated diagnoses.

Troponin elevation pattern and subsequent cardiac and non-cardiac outcomes: Implementing the Fourth Universal Definition of Myocardial Infarction and high-sensitivity troponin at a population level.

BACKGROUND: The Fourth Universal Definition of Myocardial Infarction (MI) differentiates MI from myocardial injury. We characterised the temporal course of cardiac and non-cardiac outcomes associated with MI, acute and chronic myocardial injury. METHODS: We included all patients presenting to public emergency departments in South Australia between June 2011-Sept 2019. Episodes of care (EOCs) were classified into 5 groups based on high-sensitivity troponin-T (hs-cTnT) and diagnostic codes: 1) Acute MI [rise/fall in hs-cTnT and primary diagnosis of acute coronary syndrome], 2) Acute myocardial injury with coronary artery disease (CAD) [rise/fall in hs-cTnT and diagnosis of CAD], 3) Acute myocardial injury without CAD [rise/fall in hs-cTnT without diagnosis of CAD], 4) Chronic myocardial injury [elevated hs-cTnT without rise/fall], and 5) No myocardial injury. Multivariable flexible parametric models were used to characterize the temporal hazard of death, MI, heart failure (HF), and ventricular arrhythmia. RESULTS: 372,310 EOCs (218,878 individuals) were included: acute MI (19,052 [5.12%]), acute myocardial injury with CAD (6,928 [1.86%]), acute myocardial injury without CAD (32,231 [8.66%]), chronic myocardial injury (55,056 [14.79%]), and no myocardial injury (259,043 [69.58%]). We observed an early hazard of MI and HF after acute MI and acute myocardial injury with CAD. In contrast, subsequent MI risk was lower and more constant in patients with acute injury without CAD or chronic injury. All patterns of myocardial injury were associated with significantly higher risk of all-cause mortality and ventricular arrhythmia. CONCLUSIONS: Different patterns of myocardial injury were associated with divergent profiles of subsequent cardiac and non-cardiac risk. The therapeutic approach and modifiability of such excess risks require further research.