Derivation and Validation of Thresholds Using Synthetic Data Methods for Single-Test Screening of Emergency Department Patients with Possible Acute Myocardial Infarction Using a Point-of-Care Troponin Assay.

BACKGROUND: Single-sample (screening) rule-out of acute myocardial infarction (AMI) with troponin requires derivation of a single-test screening threshold. In data sets with small event numbers, the lowest one or two concentrations of myocardial infarction (MI) patients dictate the threshold. This is not optimal. We aimed to demonstrate a process incorporating both real and synthetic data for deriving such thresholds using a novel pre-production high-precision point-of-care assay. METHODS: cTnI concentrations were measured from thawed plasma using the Troponin I Next (TnI-Nx) assay (i-STAT; Abbott) in adults on arrival to the emergency department with symptoms suggestive of AMI. The primary outcome was an AMI or cardiac death within 30 days. We used internal-external validation with synthetic data production based on clinical and demographic data, plus the measured TnI-Nx concentration, to derive and validate decision thresholds for TnI-Nx. The target low-risk threshold was a sensitivity of 99% and a high-risk threshold specificity of >95%. RESULTS: In total, 1356 patients were included, of whom 191 (14.1%) had the primary outcome. A total of 500 synthetic data sets were constructed. The mean low-risk threshold was determined to be 5 ng/L. This categorized 38% (95% CI, 6%-68%) to low-risk with a sensitivity of 99.0% (95% CI, 98.6%-99.5%) and a negative predictive value of 99.4% (95% CI, 97.6%-99.8%). A similarly derived high-risk threshold of 25 ng/L had a specificity of 95.0% (95% CI, 94.8%-95.1%) and a positive predictive value of 74.8% (95% CI, 71.5%-78.0%). CONCLUSIONS: With the TnI-Nx assay, we successfully demonstrated an approach using synthetic data generation to derive low-risk thresholds for safe and effective screening.

Type of Stressor and Medium-Term Outcomes After Takotsubo Syndrome: What Becomes of the Broken Hearted? (ANZACS-QI 59).

BACKGROUND: Takotsubo syndrome (TS) is often triggered by an acute physical or emotional stressor. We hypothesised that medium-term prognosis may be better for TS patients with an associated emotional stressor than for those with an acute physical illness. METHODS: We identified consecutive TS patients presenting in New Zealand (2006-2018). The clinical presentation and outcomes of TS patients according to types of stressor (physical, emotional or no stressor) were assessed. Post-discharge survival after TS was compared with age- and gender-matched patients after myocardial infarction (MI) and people in the community without known cardiovascular disease (CVD). RESULTS: Of 632 TS patients (95.9% women, mean age 65.0±11.1 years), 27.4% had an associated acute physical stressor, 46.4% an emotional stressor and 26.2% no evident stressor. In-hospital mortality was similar for each group (1.7%, 1.2%, 0.3% respectively, p=0.29). In a median 4.4 years post-discharge there were 54 deaths (53 non-cardiac). Compared with patients without known CVD, TS patients with physical stress and those with MI were less likely to survive (HR 4.46, 95%CI 3.10-6.42; HR 4.23, 95%CI 3.81-4.70 respectively) but survival for TS patients associated with emotional stress or no stressor was similar (HR 1.11, 95%CI 0.66-1.85; HR 1.08, 95%CI 0.54-2.18, respectively). Recurrence was similar among the three groups (p=0.14). CONCLUSION: Takotsubo syndrome associated with physical stressor has a post-discharge mortality risk as high as after MI. In contrast, prognosis for TS triggered by an emotional stressor is excellent, and similar to that of those without known CVD.

A comparison of the clinical features and outcomes of Takotsubo syndrome across five metropolitan hospitals in New Zealand.

AIM: Takotsubo syndrome (TS) mimics acute coronary syndrome but has a distinct pathophysiology. This study aimed to compare and contrast the clinical presentation, management and outcomes of patients with TS in five large New Zealand hospitals. METHODS: We identified 632 consecutive patients presenting to the five major tertiary hospitals in New Zealand (Middlemore Hospital, Auckland City Hospital, North Shore Hospital, Christchurch Hospital and Dunedin Hospital) between January 2006 and June 2018 and obtained clinical, laboratory, electrocardiography, echocardiography, coronary angiography and long-term follow-up data. RESULTS: Six hundred and thirty-two consecutive patients with TS (606 women, mean age 65.0+11.1 years) were included. An associated stressor was identified in two-thirds of patients, and emotional triggers were more frequent than physical triggers (62.9% and 37.1%, respectively). Overall, 12.7% of patient had depression and 11.7% anxiety but this was more common in patients from Christchurch Hospital (20.4% and 23.4%, respectively). The in-hospital mortality among the five hospitals ranges between 0 to 2.0%. The mean follow-up was 4.9+3.4 years (median 4.4 years). Fifty-four people died post-discharge, all but one from a non-cardiac cause. Forty patients had recurrent TS. Mortality post-discharge (p=0.63) and TS recurrence (p=0.38) did not differ significantly among the five hospitals. CONCLUSION: In this large New Zealand TS cohort, the clinical characteristics and presentation were similar among the five hospitals. A subset of patients had a complicated in-hospital course, but late deaths were almost all from non-cardiac causes and recurrence was infrequent. Mortality post-discharge and recurrence was similar between the hospitals.

Early kinetic profiles of troponin I and T measured by high-sensitivity assays in patients with myocardial infarction.

The early concentration kinetic profiles of cardiac troponin in patients with non-ST-elevated myocardial infarction (NSTEMI) measured by high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays have not been described. In intermediate-to-high-risk of NSTEMI patients we measured serial cTn concentrations on ED arrival, at 1, 2, 3, 6-12, 24 and 48-hours with hs-cTnI and hs-cTnT assays. Log-normal curves were fitted to concentrations from time from symptom onset, and the time to rule-out decision thresholds estimated (hs-cTnI: 2 ng/L and 5 ng/L; hs-cTnT: 5 ng/L). Among 164 patients there were 58 NSTEMI. The hs-cTnI to hs-cTnT ratio increased linearly over the first 6-12 h following symptom onset. The estimated times from symptom onset to the 2 ng/L and 5 ng/L thresholds for hs-cTnI were 1.8 (0.1-3.1) and 1.9 (1.1-3.5) hours, and to the 5 ng/L threshold for hs-cTnT 1.9 (1.1-3.8) hours. The estimated time to exceed 5 ng/L was ≥3 hours in 32.6% (95%CI: 20.0% to 48.1%) cases for hs-cTnI and 33.3% (19.6% to 50.0%) for hs-cTnT. cTnI concentrations increased at a much more rapid rate than cTnT concentrations in patients with NSTEMI. Concentrations of a high proportion of patients took longer than 3 hours from symptom onset to exceed the 5 ng/L rule-out decision threshold.

Repetitive stimulation of premotor cortex affects primary motor cortex excitability and movement preparation.

BACKGROUND: Repetitive transcranial magnetic stimulation can be used to explore functional connectivity between cortical areas. OBJECTIVE: To determine the effects of two theta burst stimulation (TBS) patterns (intermittent, iTBS; and continuous, cTBS) of left dorsal premotor cortex (PMd). METHODS: Left PMd was identified in 11 participants using functional magnetic resonance imaging (fMRI), during performance of complex sequential finger movements. Each participant received iTBS, cTBS, or sham TBS of left PMd in three separate sessions within a randomized, single-blind design. The speed and accuracy of simple and complex sequential reaction time (RT) task performance was measured before and after TBS. The excitability of primary motor cortex (M1) bilaterally, and interhemispheric facilitation from left PMd to right M1, were also measured before and after TBS. RESULTS: iTBS sped up the preparation of complex sequences performed with the right hand, with no detectable changes in M1 excitability. RT performance was maintained after cTBS, in the presence of increased left M1 excitability and suppressed right M1 excitability. CONCLUSIONS: Facilitatory and inhibitory TBS protocols applied to left PMd differentially alter corticomotor excitability and behavior, which suggests that these protocols affect different neuronal populations.