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.

Comparison of Late Cardiac Death and Myocardial Infarction Rates in Women Vs Men With ST-Elevation Myocardial Infarction.

Women and patients with incomplete revascularization (IR) have a worse prognosis after ST elevation myocardial infarction (STEMI). However, the extent to which IR affects outcomes for women with STEMI compared with men is not well characterized. Thus, we examined late outcomes of 589 consecutive STEMI patients who received percutaneous coronary intervention and assessed SYNTAX scores (SS), both at baseline and after all procedures (residual SS). A residual SS >8 defined IR. The primary end point was cardiac death or myocardial infarction (MI), with median follow-up of 3.6 years [interquartile range [IQR] 2.6 to 4.7]. Women (n = 123) had lower baseline SSs 15.0 [IQR 9 to 20], than men (n = 466), 16.0 [IQR 9 to 20; p = 0.02. After all planned procedures, the residual SS was 5.0 [IQR 0 to 9] in women and 5.0 (IQR 1 to 11] in men, p = 0.37. Cardiac death or MI occurred in (97/589) patients (16%), 24% (30/123) in women and 14% (67/466) in men (hazard ratio [HR] 1.75; 95% confidence intervals [CI] 1.14 to 2.69; p = 0.01). In patients with residual SYNTAX score (rSS) >8 cardiac death or MI occurred in 43% (15/35) of women and 23% 36/158 men (HR 2.14; 95% CI 1.17 to 3.91; p = 0.01). In patients with rSS = 0 to 8 cardiac death or MI occurred in 17% (15/88) of women and 10% of men (31/308) (HR 1.68; 95% CI 0.91 to 3.12; p = 0.10; interaction p value 0.58). Multivariate analysis found women were 1.77 times more likely than men to experience cardiac death or MI (95% CI 1.13 to 2.77; p = 0.01). In conclusion, we found despite a lower burden of disease at presentation and no difference in rates of IR between men and women, outcome differences were substantial. Women with rSS >8 were twice as likely as men with the same rSS to experience cardiac death or MI post-STEMI. Differences remained significant postrisk adjustment.

Mortality at 5 Years Among Very Elderly Patients Undergoing High Sensitivity Troponin T Testing for Suspected Acute Coronary Syndromes.

BACKGROUND: Patients aged ≥80 years old often present to Emergency Departments (ED) with symptoms potentially due to an acute coronary syndrome (ACS). This study aimed to evaluate associations between baseline level(s) of high sensitivity troponin T (HsTnT), adjudicated diagnoses and outcomes. METHODS: Consecutive patients aged ≥80 years were studied, who presented to the ED at Liverpool Hospital, NSW, Australia during the 4 months period March to June 2014 (inclusive) with symptoms suggestive of an ACS, and who had at least one HsTnT assay performed. Diagnoses were based on the fourth universal definition of MI (myocardial infarction) including type-1 MI, type-2 MI, acute myocardial injury, chronic myocardial injury; the rest were termed "other diagnoses". Patients were categorised by baseline HsTnT levels 1) ≤14 ng/L, 2) 15-29 ng/L, 3) 30-49 ng/L and 4) ≥50 ng/L. RESULTS: Of 2,773 patients screened, 545 were aged ≥80 years (median age 85 [IQR 82-88]); median follow-up was 32 months (IQR 5-56). The respective rates of adjudicated diagnoses were type-I MI 3.1%, type-2 MI 13%, acute myocardial injury 9.5%, chronic myocardial injury 56% and 18.6% had other diagnoses. Mortality rates increased, irrespective of adjudicated diagnoses with increasing HsTnT levels (ng/L): 17% (16/96) for ≤14; 35% (67/194) for 15-29; 51% (65/127) for 30-49; and 64% (82/128) for ≥50 ng/L; log rank p≤0.001. On multi-variable analyses, after adjusting for potential confounding factors including age, hypertension, chronic kidney disease (CKD) and chronic obstructive pulmonary disease (COPD), MI type was not associated with late mortality. CONCLUSIONS: Among patients aged ≥80 years higher HsTnT levels, irrespective of adjudicated diagnoses, were associated with increased mortality. Most very elderly patients presenting with symptoms suggestive of an ACS undergoing HsTnT testing in EDs had elevated levels most commonly due to chronic myocardial injury. Whether any interventions can modify outcomes require prospective evaluation.

Type-II myocardial infarction and chronic myocardial injury rates, invasive management, and 4-year mortality among consecutive patients undergoing high-sensitivity troponin T testing in the emergency department.

AIMS: As assessment of patients with suspected acute coronary syndromes (ACS) in emergency departments (EDs) represents a major workload because high-sensitivity troponin (HsTn) T and I levels are frequently measured, and a minority of patients have final diagnosis of myocardial infarction (MI). We determined the relative frequencies of three patients groups: Type-I MI, Type-II MI (including acute myocardial injury). METHODS AND RESULTS: Among 2738 consecutive patients with suspected ACS presenting to ED at Liverpool Hospital, Australia, between March and June 2014. We studied the use of invasive and pharmacological therapies, and 4-year outcomes. Adjudication of MI was according to the 4th universal definition as follows: (i) Type-I MI; (ii) Type-II MI (including acute myocardial injury), and (iii) chronic myocardial injury. Of 995 patients (36%) [median age 76 years (interquartile range 65-83)] with ≥2 HsTnT measurements and one >14 ng/L, 727 (73%) had chronic myocardial injury, 171 (17%) had Type-II MI, and 97 (9.7%) had Type-I MI; respective late mortality rates to 48 months were 33%, 43%, and 14% (P < 0.001). In-hospital angiography rates were 95% for patients with Type-I MI, [62% had percutaneous coronary intervention (PCI)] 24% (7% PCI) for those with Type-II MI, and 3.4% for chronic myocardial injury. On Cox modelling for mortality relative to Type 1 MI, adjusted hazard ratios were 1.94 [95% confidence intervals (CIs) 1.06-3.57]; P = 0.032 for Type 2 MI, and for chronic myocardial injury 1.14 (95% CIs 0.64-2.02); P = 0.66. CONCLUSION: Among unselected patients undergoing HsTnT testing in EDs, Type-II MI including acute myocardial injury was more common than Type-I MI. Chronic myocardial injury, which occurred in three of four patients. Whereas patients with Type-II MI had higher late mortality than those with Type-I MI, after multivariable analyses mortality rates were marginally different.

The impact of incomplete revascularization on early and late outcomes in ST-elevation myocardial infarction.

BACKGROUND: In ST-elevation myocardial infarction (STEMI) in patients with multivessel disease, there is a lack of consensus regarding the importance of complete revascularization and the timing of treatment of nonculprit stenoses. Our objective was to investigate the impact of incomplete revascularization in STEMI patients using the residual Synergy Between PCI with TAXUS and Cardiac Surgery score (rSS) to define completeness of revascularization. METHODS: This study examined associations between incomplete revascularization, determined by the rSS, and the combined outcome of cardiac death and myocardial infarction (MI). Patients were divided into groups: rSS = 0 (complete revascularization), rSS = 1-8 (incomplete revascularization with a low burden of residual disease), or rSS >8 (incomplete revascularization with a high burden of residual disease). RESULTS: The rSS score was calculated in 589 consecutive patients; 25% had an rSS of 0, 42% rSS 1-8, and 33% rSS >8. At median follow-up of 3.5 years, cardiac death and MI occurred in 5% of rSS = 0 patients, 15% rSS = 1-8, and 26% with rSS >8 (P < .001). The rSS was powerful independent predictor of cardiac death and MI (hazard ratio 5.05, CI 2.89-12.00, rSS >8 vs rSS 0, P < .001 and hazard ratio 2.96, CI 1.31-6.69, rSS = 1-8 vs rSS = 0, P = .009), respectively, and an independent predictor of mortality, MI, unplanned revascularization, and major adverse cardiovascular events. CONCLUSIONS: In patients with STEMI, the rSS independently predicts cardiac death and MI. Patients with an rSS >8 had substantially higher rates of cardiac death or MI. The rSS can be used to define incomplete revascularization in STEMI and predict adverse outcomes.

Synthesis of aromatic and indole alpha-glucosinolates.

Aromatic and indole glucosinolates are important members of the glucosinolate family of compounds du to their potential medicinal properties. They are known to exert antioxidant and anti-carcinogenic activity either by the natural products themselves, or their metabolic products including indole-3-carbinol and isothiocyanates. Natural glucosinolates are all ß-glucosinolates; however, α-glucosinolates are also promising compounds for medicinal applications and hence have to be produced synthetically for any bio-activity studies. Here we report on the successful synthesis of a series of α-glucosinolates: α-neoglucobrassicin, α-4-methoxyglucobrassicin, 2,3-dichlorophenyl-α-glucosinolate for the first time. Testing for anti-inflammatory properties of these synthetic GLs, however, did not yield the expected activity.

Adverse diastolic remodeling after reperfused ST-elevation myocardial infarction: An important prognostic indicator.

OBJECTIVES: We sought to determine the relationship of adverse diastolic remodeling (ie, worsening diastolic or persistent restrictive filling) with infarct scar characteristics, and to evaluate its prognostic value after ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Severe diastolic dysfunction (restrictive filling) has known prognostic value post STEMI. However, ongoing left ventricular (LV) remodeling post STEMI may alter diastolic function even if less severe. METHODS AND RESULTS: There were 218 prospectively recruited STEMI patients with serial echocardiograms (transthoracic echocardiography) and cardiac magnetic resonance imaging (CMR) performed, at a median of 4 days (early) and 55 days (follow-up). LV ejection fraction and infarct characteristics were assessed by CMR, and comprehensive diastolic function assessment including a diastolic grade was evaluated on transthoracic echocardiography. 'Adverse diastolic remodeling' occurred if diastolic function grade either worsened (≥1 grade) between early and follow-up imaging, or remained as persistent restrictive filling at follow-up. Follow-up infarct scar size (IS) predicted adverse diastolic remodeling (area under the curve 0.86) and persistent restrictive filling (area under the curve 0.89). The primary endpoint of major adverse cardiovascular events (MACE) occurred in 48 patients during follow-up (mean, 710±79 days). Kaplan-Meier analysis showed that adverse diastolic remodeling (n=50) and persistent restrictive filling alone (n=33) were significant predictors of MACE (both P<.001). Multivariate Cox analysis, when adjusted for TIMI risk score and CMR IS, microvascular obstruction, and LV ejection fraction, showed adverse diastolic remodeling (HR 3.79, P<.001) was an independent predictor of MACE, as was persistent restrictive filling alone (HR 2.61, P=.019). CONCLUSIONS: Larger IS is associated with adverse diastolic remodeling. Following STEMI, adverse diastolic remodeling is a powerful prognostic marker, and identifies a larger group of 'at-risk' patients, than does persistent restrictive filling alone.

Electrocardiographic measurement of infarct size compared to cardiac MRI in reperfused first time ST-segment elevation myocardial infarction.

BACKGROUND: Myocardial infarct size (IS) following ST-segment elevation myocardial infarction (STEMI) is an important prognostic factor. We assessed the Selvester 32-point QRS score from the 12-lead ECG for measurement of IS in STEMI patients receiving reperfusion therapy compared to cardiac magnetic resonance imaging (CMRI). Furthermore we sought to explore the impact of microvascular obstruction (MVO) on the scoring system, and determine factors contributing to discrepancies between CMRI IS and Selvester score. METHODS: We examined 70 patients (55 men, 15 women), mean age 57±10years with a first time STEMI (46 anterior, 24 non-anterior). QRS scores were calculated early and at follow-up (mean 2±1 and 59±14days post-STEMI). Myocardial core scar size (5SD) was measured at 5.3±3.3 and 57.8±13.5days post-infarction by CMRI. MVO was determined on initial MRI. Logistic regression analysis was performed to determine factors contributing to discordant scores, defined as a difference between CMRI and Selvester IS of >6% myocardium. RESULTS: QRS scoring of anterior infarcts correlated with CMRI IS both early (r=0.734, p<0.0001) and at follow-up (r=0.716, p<0.0001); however no correlation was seen among non-anterior infarcts. QRS scoring overestimated IS at all time points. There was better agreement between ECG and CMRI measured IS in patients without MVO at both time points. Anterior infarction was inversely predictive of discordant IS estimation acutely, and larger Selvester scores were predictive of inaccurate scoring at both time periods. CONCLUSIONS: Selvester QRS score correlates well with CMRI IS for anterior infarcts. MVO did not independently affect the score.

Prognostic value of high sensitivity troponin T after ST-segment elevation myocardial infarction in the era of cardiac magnetic resonance imaging.

AIMS: To determine if high sensitivity troponin T (hs-TnT) measurements performed during the 'plateau phase' of troponin release (≥48 h) following ST-segment elevation myocardial infarction (STEMI) can predict major adverse cardiovascular endpoints (MACE), and to evaluate its prognostic value compared with cardiac magnetic resonance imaging (CMRI) parameters. METHODS AND RESULTS: We prospectively recruited 201 first presentation STEMI patients. Serial hs-TnT levels were measured at admission, peak (highest), 24, 48 and 72 h. CMRI and transthoracic echocardiography were performed (4 days median) post-STEMI, evaluating infarct scar characteristics and left ventricular ejection fraction (LVEF). Associations were determined between hs-TnT levels and CMRI parameters early after STEMI with MACE (comprising mortality, re-infarction, new or worsening of heart failure, cerebrovascular accident, and sustained ventricular arrhythmias) at medium-term follow-up. After 602 days (median), 33 (17%) patients had MACE. Upper tertile hs-TnT levels at 48 and 72 h were associated with MACE (Kaplan-Meier P = 0.002 and P = 0.012, respectively). Multivariate Cox analyses, incorporating diabetes, CMRI scar size, LVEF and hs-TnT levels (applied at a single hs-TnT time point) showed that 48 and 72 h hs-TnT levels were independent predictors for MACE (HR = 1.20, P = 0.002, and HR = 1.21, P = 0.035 respectively). CONCLUSION: Measurement of hs-TnT in the plateau phase after STEMI is an inexpensive method of prognostic risk assessment.

High-sensitivity troponin T predicts infarct scar characteristics and adverse left ventricular function by cardiac magnetic resonance imaging early after reperfused acute myocardial infarction.

BACKGROUND: Late gadolinium enhancement cardiac magnetic resonance imaging (CMRI) is the current standard for evaluation of myocardial infarct scar size and characteristics. Because post-ST-segment elevation myocardial infarction (STEMI) troponin levels correlate with clinical outcomes, we sought to determine the sampling period for high-sensitivity troponin T (hs-TnT) that would best predict CMRI-measured infarct scar characteristics and left ventricular (LV) function. METHODS AND RESULTS: Among 201 patients with first presentation with STEMI who were prospectively recruited, we measured serial hs-TnT levels at admission, peak, 24 hours, 48 hours, and 72 hours after STEMI. Indexed LV volumes, LV ejection fraction (LVEF) and infarct scar characteristics (scar size, scar heterogeneity, myocardial salvage index, and microvascular obstruction) were evaluated by CMRI at a median of 4 days post-STEMI. Peak and serial hs-TnT levels correlated positively with early indexed LV volumes and infarct scar characteristics, and negatively correlated with myocardial salvage index and LVEF. Both 48- and 72-hour hs-TnT levels similarly predicted "large" total infarct scar size (odds ratios [ORs] 3.08 and 3.53, both P < .001), myocardial salvage index (ORs 1.68 and 2.30, both P < .001), and LVEF <40% (ORs 2.16 and 2.17, both P < .001) on univariate analyses. On multivariate analyses, 48- and 72-hour hs-TnT levels independently predicted large infarct scar size (ORs 2.05 and 2.31, both P < .001), reduced myocardial salvage index (OR 1.39 [P = .031] and OR 1.55 [P = .009]), and LVEF <40% (OR 1.47 [P = .018] and OR 1.43 [P = .026]). All measured hs-TnT levels had a modest association and similar capacity to predict microvascular obstruction. CONCLUSIONS: Levels of hs-TnT at 48 and 72 hours, measured during the "plateau phase" post-STEMI, predicted infarct scar size, poor myocardial salvage, and LVEF. These levels also correlated with scar heterogeneity and microvascular obstruction post-STEMI. Since ascertaining peak levels after STEMI is challenging in routine practice, based on the biphasic kinetics of hs-TnT, a measurement at 48 to 72 hours (during the plateau phase) provides a useful and simple method for early evaluation of LV function and infarct scar characteristics.