Complement activation products in acute heart failure: Potential role in pathophysiology, responses to treatment and impacts on long-term survival.

BACKGROUND: Previous studies have indicated a correlation between heart failure, inflammation and poorer outcome. However, the pathogenesis and role of inflammation in acute heart failure (AHF) is incompletely studied and understood. The aim of our study was to explore the potential role of innate immunity - quantified by complement activation products (CAPs) - in pathophysiology, responses to treatment and impacts on long-term survival in AHF. METHODS: In a prospective study enrolling 179 unselected patients with AHF, plasma concentrations of C4d, C3a and sC5b-9 were measured in a blinded fashion on the first day of hospitalisation and prior to discharge. The final diagnosis, including the AHF phenotype, was adjudicated by two independent cardiologists. Long-term follow-up was obtained. Findings in AHF were compared to that obtained in 75 healthy blood donors (control group). RESULTS: Overall, concentrations of all three CAPs were significantly higher in patients with AHF than in healthy controls (all p < 0.001). In an age-adjusted subgroup analysis, significant differences could be confirmed for concentrations of C4d and sC5b-9, and these parameters further increased after 6 days of in-hospital treatment ( p < 0.001). In contrast, C3a levels in AHF patients did not differ from those of the control group in the age-adjusted subgroup analysis and remained constant during hospitalisation. Concentrations of C4d, C3a and sC5b-9 were significantly higher when AHF was triggered by an infection as compared to other triggers ( p < 0.001). In addition, CAP levels significantly correlated with each other ( r = 0.64-0.76), but did not predict death within 2 years. CONCLUSIONS: Activation of complement with increased plasma levels of C4d and sC5b-9 at admission and increasing levels during AHF treatment seems to be associated with AHF, particularly when AHF was triggered by an infection. However, CAPs do not have a prognostic value in AHF.

Gender-specific uncertainties in the diagnosis of acute coronary syndrome.

BACKGROUND: It is unknown whether higher rates of delayed diagnosis and misdiagnosis of acute coronary syndrome (ACS) in women might have contributed to the poorer outcome of women. METHODS: In a prospective diagnostic multicenter study, we recruited patients presenting to the emergency department (ED) with any kind of chest discomfort/chest pain with onset or peak within the last 12 h. We quantified early diagnostic uncertainty for the presence of ACS among treating physicians at the ED after 90 min, possibly responsible for delayed diagnosis, using a visual analogue scale. Late diagnostic uncertainty, possibly responsible for misdiagnosis, was defined as disagreement among two independent cardiologists' adjudication of the final diagnosis after complete work-up. RESULTS: Among 2795 patients (897 women and 1898 men), ACS was the adjudicated final diagnosis in 24 % of women and 35 % of men. Early diagnostic accuracy of clinical judgment of the ED physician for ACS as quantified by the area under the receiver-operating characteristics curve was 0.89 (95 % CI 0.87-0.92) in women and 0.86 (95 % CI 0.85-0.88) in men (p = 0.046). Late diagnostic uncertainty regarding the diagnosis of ACS was 5 % in women and 7 % in men (p = 0.069). CONCLUSION: Diagnostic uncertainty for the presence of ACS in women is not more common as compared to men and does, therefore, not explain the poorer outcome observed in women with ACS. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00470587.

Impact of haemoconcentration during acute heart failure therapy on mortality and its relationship with worsening renal function.

AIMS: Treatment goals in acute heart failure (AHF) are poorly defined. We aimed to characterize further the impact of in-hospital haemoconcentration and worsening renal function (WRF) on short- and long-term mortality. METHODS AND RESULTS: Haematocrit, haemoglobin, total protein, serum creatinine, and albumin levels were measured serially in 1019 prospectively enrolled AHF patients. Haemoconcentration was defined as an increase in at least three of four of the haemoconcentration-defining parameters above admission values at any time during the hospitalization. Patients were divided into early (Day 1-4) and late haemoconcentration (>Day 4). Ninety-day mortality was the primary endpoint. Haemoconcentration occurred in 392 (38.5%) patients, with a similar incidence of the early (44.6%) and late (55.4%) phenotype. Signs of decongestion (reduction in BNP blood concentrations, P = 0.003; weight loss, P = 0.002) were significantly more pronounced in haemoconcentration patients. WRF was more common in haemoconcentration patients (P = 0.04). After adjustment for established risk factors for AHF mortality, including WRF and HF therapy at discharge, haemoconcentration was significantly associated with a reduction in 90-day mortality [hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.37-0.95, P = 0.01]. The beneficial effect of haemoconcentration seemed to be exclusive for late haemoconcentration (late vs. early: adjusted HR 0.41, 95% CI 0.19-0.90, P = 0.03) and persisted in patients with or without WRF. CONCLUSIONS: Haemoconcentration represents an inexpensive and easily assessable pathophysiological signal of adequate decongestion in AHF and is associated with lower mortality. WRF in the setting of haemoconcentration does not appear to offset the benefits of haemoconcentration.

Safety and efficacy of the 0 h/3 h protocol for rapid rule out of myocardial infarction.

BACKGROUND: The early and accurate diagnosis of acute myocardial infarction (AMI) is an important medical and economic challenge. We aimed to prospectively evaluate the performance of the new European Society of Cardiology rapid 0-hour/3-hour (0 h/3 h) rule out protocol for AMI. METHODS: We enrolled 2,727 consecutive patients presenting with suspected AMI without persistent ST-segment elevation to the emergency department in a prospective international multicenter study. The final diagnosis was adjudicated by 2 independent cardiologists. The performance of the 0 h/3 h rule out protocol was evaluated using 4 high-sensitivity (primary analysis) and 3 sensitive cardiac troponin (cTn) assays. RESULTS: Acute myocardial infarction was the final diagnosis in 473 patients (17.3%). Using the 4 high-sensitivity cTn assays, the 0-hour rule out protocol correctly ruled out 99.8% (95% [confidence interval] CI, 98.7%-100%), 99.6% (95% CI, 98.5%-99.9%), 100% (95% CI, 97.9%-100%), and 100% (95% CI, 98.0%-100%) of late presenters (>6 h from chest pain onset). The 3-hour rule out protocol correctly ruled out 99.9% (95% CI, 99.1%-100%), 99.5% (95% CI, 98.3%-99.9%), 100% (95% CI, 98.1%-100%), and 100% (95% CI, 98.2%-100%) of early presenters (<6 h from chest pain onset). Using the 3 sensitive cTn assays, the 0-hour rule out protocol correctly ruled out 99.6% (95% CI, 98.6%-99.9%), 99.0% (95% CI, 96.9%-99.7%), and 99.1% (95% CI, 97.2%-99.8%) of late presenters; and the 3-hour rule out protocol correctly ruled out 99.4% (95% CI, 98.3%-99.8%), 99.2% (95% CI, 97.3%-99.8%), and 99.0% (95% CI, 97.2%-99.7%) of early presenters. Overall, the 0 h/3 h rule out protocol assigned 40% to 60% of patients to rule out. None of the patients assigned rule out died during 3-months follow-up. CONCLUSIONS: The 0 h/3 h rule out protocol seems to allow the accurate rule out of AMI using both high-sensitivity and sensitive cTn measurements in conjunction with clinical assessment. Additional studies are warranted for external validation.

Incremental value of copeptin in suspected acute myocardial infarction very early after symptom onset.

BACKGROUND: Patients presenting very early after chest pain onset may provide a diagnostic challenge even when using a high-sensitivity cardiac troponin (hs-cTnT). We hypothesized that in these patients the incremental value of copeptin in the early diagnosis of acute myocardial infarction (AMI) may be substantial. METHODS: We aimed to investigate the incremental value of copeptin in a pre-specified subgroup analysis of patients presenting with suspected AMI to the emergency department within 2 hours of symptom onset in a multicenter study. Copeptin was measured in a blinded fashion. Two independent cardiologists adjudicated the final diagnosis using all available clinical informations, including high-sensitivity cardiac troponin T (hs-cTnT). RESULTS: Overall, 2000 patients were enrolled, of whom 519 (26%) arrived within 2 hours of symptom onset. Of these, 102 patients (20%) had an AMI. The additional use of copeptin did not increase diagnostic accuracy as quantified by the area under the receiver-operating characteristic curve (AUC) of hs-cTnT (0.87 (95% confidence interval (CI): 0.83-0.90) for hs-cTnT alone to 0.86 (95% CI: 0.82-0.90) for the combination; p = NS). Copeptin (using 9 pmol/L as a cut-off) increased the negative predictive value (NPV) of hs-cTnT (using 14 ng/L as a cut-off) alone from 93% (95% CI: 90-95%) to 96% (95% CI: 93-98%). The NPV for the combination of hs-cTnT and copeptin was lower in patients arriving in the first 2 hours than in those arriving after 2 hours: 96% (95% CI: 93-98%) versus 99% (95% CI: 99-100%), respectively. CONCLUSIONS: The additional use of copeptin on top of hs-cTnT seems to lead to a small increase in NPV, but no increase in AUC. Routine use of copeptin in early presenters does not seem warranted.

Clinical benefit of high-sensitivity cardiac troponin I in the detection of exercise-induced myocardial ischemia.

BACKGROUND: A pilot study using a novel high-sensitivity cardiac troponin I (hs-cTnI) assay suggested that cTnI might be released into blood during exercise-induced myocardial ischemia. We investigated the potential clinical value of this signal. METHODS: We included 819 patients with suspected exercise-induced myocardial ischemia referred for rest/bicycle myocardial perfusion single-photon emission computed tomography. The treating cardiologist used all available clinical information to quantify clinical judgment regarding the presence of myocardial ischemia using a visual analog scale twice: prior and after stress testing. High-sensitivity cTnI measurements were obtained before, immediately after peak stress, and 2 hours after stress testing in a blinded manner. Myocardial ischemia was adjudicated using perfusion single-photon emission computed tomography and coronary angiography findings. RESULTS: Exercise-induced myocardial ischemia was detected in 278 (34%) patients. High-sensitivity cTnI levels were significantly higher at all time points in patients with myocardial ischemia as compared with those without (P < .001 for all). Combining clinical judgment prior exercise testing with baseline hs-cTnI levels increased diagnostic accuracy as quantified by the area under the receiver operating characteristics curve (AUC) from 0.672 to 0.757 (P < .001). Combining clinical judgment after exercise testing (AUC 0.704) with baseline or poststress hs-cTnI levels also increased the diagnostic accuracy (AUC 0.761-0.771, P < .001 for all). In contrast, exercise-induced changes in hs-cTnI during exercise did not seem useful, as they were small and similar in patients with or without myocardial ischemia. CONCLUSIONS: High-sensitivity cTnI concentrations at rest and after exercise, but not its exercise-induced changes, provide substantial incremental value to clinical judgment including exercise electrocardiography regarding the presence of myocardial ischemia.

Incidence and Predictors of Cardiomyocyte Injury in Elective Coronary Angiography.

OBJECTIVE: Coronary angiography is considered to be a safe tool for the evaluation of coronary artery disease and performed in approximately 12 million patients each year worldwide. The aim of our study was to investigate the frequency and predictors of cardiomyocyte injury in patients undergoing elective coronary angiography. METHODS: A total of 749 consecutive patients who were scheduled to undergo elective coronary angiography were prospectively analyzed. High-sensitivity cardiac troponin T concentrations were measured both before and after elective coronary angiography (without intervention). Acute cardiomyocyte injury was predefined as an absolute increase in high-sensitivity cardiac troponin T of at least 7 ng/L (if also fulfilling a relative change of >20%). RESULTS: Acute cardiomyocyte injury was observed in 101 patients (13.5%, 95% confidence interval [CI], 11.1-16.2). It was independently associated with aortic valve stenosis (odds ratio [OR], 5.4; 95% CI, 3.0-9.8; P <.001), age (OR, 1.05; 95% CI, 1.02-1.08; P <.001), female sex (OR, 3.5; 95% CI, 1.8-6.8; P <.001), contrast volume (OR, 1.006; 95% CI, 1.001-1.012; P = .019 per 10 mL of contrast volume), documented cardiomyopathy (OR, 2.5; 95% CI, 1.0-6.0; P = .045), and mitral regurgitation (OR, 2.3; CI, 1.0-4.9; P = .033). In contrast, operator experience and extent of coronary artery disease were not found to be associated with acute cardiomyocyte injury. CONCLUSIONS: Cardiomyocyte injury accompanies elective coronary angiography in 1 of 8 patients. Sex, age, contrast agent volume, and ventricular disease, rather than the extent of coronary artery disease, independently predict cardiomyocyte injury. Further research aiming to reduce the incidence of cardiomyocyte injury seems warranted.

Incremental value of heart-type fatty acid-binding protein in suspected acute myocardial infarction early after symptom onset.

BACKGROUND: The early diagnosis of acute myocardial infarction (AMI) very soon after symptom onset remains a major clinical challenge, even when using high-sensitivity cardiac troponin (hs-cTnT). METHODS AND RESULTS: We investigated the incremental value of heart-type fatty acid-binding protein (hFABP) in a pre-specified subgroup analysis of patients presenting with suspected AMI within 1 h of symptom onset to the emergency department (ED) in a multicentre study. HFABP was measured in a blinded fashion. Two independent cardiologists using all available clinical information, including hs-cTnT, adjudicated the final diagnosis. Overall, 1411 patients were enrolled, of whom 105 patients presented within 1 h of symptom onset. Of these, 34 patients (32.4%) had AMI. The diagnostic accuracy as quantified by the area under the receiver-operating characteristics curve (AUC) of hFABP was high (0.84 (95% CI 0.74-0.94)). However, the additional use of hFABP only marginally increased the diagnostic accuracy of hs-cTnT (AUC 0.88 (95% CI 0.81-0.94) for hs-cTnT alone to 0.90 (95% CI 0.83-0.98) for the combination; p=ns). After the exclusion of 18 AMI patients with ST-segment elevation, similar results were obtained. Among the 16 AMI patients without ST-segment elevation, six had normal hs-cTnT at presentation. Of these, hFABP was elevated in two (33.3%) patients. CONCLUSIONS: hFABP does not seem to significantly improve the early diagnostic accuracy of hs-cTnT in the important subgroup of patients with suspected AMI presenting to the ED very early after symptom onset.

Delayed release of brain natriuretic peptide to identify myocardial ischaemia.

BACKGROUND: A recent pilot study suggested that exercise-induced myocardial ischaemia may lead to a delayed release of cardiac biomarkers, so that later sampling, for example, at 4 h after exercise could be used for diagnostic purpose. MATERIALS AND METHODS: In an observational study, we enrolled 129 consecutive patients referred for evaluation of a suspected coronary artery disease by rest/stress myocardial perfusion single-photon emission computed tomography. The treating cardiologist used all available clinical information to quantify clinical judgment regarding the presence of myocardial ischaemia using a visual analogue scale twice: prior and after stress testing. BNP levels were determined in a blinded fashion at rest, at peak stress and 4 h after peak stress. The presence of myocardial ischaemia was adjudicated based on perfusion single-photon emission computed tomography and coronary angiography findings by an independent cardiologist. RESULTS: Myocardial ischaemia was detected in 58 patients (45%). Patients with myocardial ischaemia had significantly higher BNP levels at all times, compared to patients without ischaemia: BNP rest (99 vs. 61 pg/mL P = 0·007), BNP stress (125 vs. 77 pg/mL P = 0·02) and BNP 4 h (114 vs. 71 pg/mL P = 0·018). Diagnostic accuracy as quantified by the area under the receiver operating characteristics curve (AUC) was moderate for all time points (AUC 0·64-0·66). The change in BNP between rest and 4 h did not provide added value, neither to the baseline BNP level nor to clinical judgment. CONCLUSION: In contrast to our hypothesis, myocardial ischaemia did not lead to a differential delayed release of BNP. Late sampling did not seem clinically useful.

Prediction of mortality using quantification of renal function in acute heart failure.

BACKGROUND: Renal function, as quantified by the estimated glomerular filtration rate (eGFR), is a predictor of death in acute heart failure (AHF). It is unknown whether one of the clinically-available serum creatinine-based formulas to calculate eGFR is superior to the others for predicting mortality. METHODS AND RESULTS: We quantified renal function using five different formulas (Cockroft-Gault, MDRD-4, MDRD-6, CKD-EPI in patients<70 years, and BIS-1 in patients≥70 years) in 1104 unselected AHF patients presenting to the emergency department and enrolled in a multicenter study. Two independent cardiologists adjudicated the diagnosis of AHF. The primary endpoint was the accuracy of the five eGFR equations to predict death as quantified by the time-dependent area under the receiver-operating characteristics curve (AUC). The secondary endpoint was the accuracy to predict all-cause readmissions and readmissions due to AHF. In a median follow-up of 374 days (IQR: 221 to 687 days), 445 patients (40.3%) died. eGFR as calculated by all equations was an independent predictor of mortality. The Cockcroft-Gault formula showed the highest prognostic accuracy (AUC 0.70 versus 0.65 for MDRD-4, 0.55 for MDRD-6, and 0.67 for the combined formula CKD-EPI/BIS-1, p<0.05). These findings were confirmed in patients with varying degrees of renal function and in three vulnerable subgroups: women, patients with severe left ventricular dysfunction, and the elderly. The prognostic accuracy for readmission was poor for all equations, with an AUC around 0.5. CONCLUSIONS: Calculating eGFR using the Cockcroft-Gault formula assesses the risk of mortality in patients with AHF more accurately than other commonly used formulas.

Incremental value of a single high-sensitivity cardiac troponin I measurement to rule out myocardial ischemia.

BACKGROUND: The aim of this study was to investigate the value of a novel high-sensitivity cardiac troponin I measurement to rule out exercise-induced myocardial ischemia in patients without known coronary artery disease. METHODS: We included 714 patients without previously known coronary artery disease who were referred for rest/stress myocardial perfusion single photon emission tomography. All clinical information available to the treating cardiologist was used to quantify the clinical judgment regarding the presence of exercise-induced myocardial ischemia using a visual analogue scale twice: once before and once after bicycle exercise stress testing. High-sensitivity cardiac troponin I measurements were obtained before stress testing in a blinded manner. The presence of exercise-induced myocardial ischemia was adjudicated on the basis of myocardial perfusion single photon emission tomography combined with coronary angiography findings. RESULTS: Exercise-induced myocardial ischemia was detected in 167 participants (23.4%). High-sensitivity cardiac troponin I levels were significantly higher in patients with exercise-induced myocardial ischemia (4.0 ng/L [95% confidence interval, 2.8-8.6] vs 2.6 ng/L [95% confidence interval, 1.8-4.1], P < .001) and remained an independent predictor of ischemia in multivariable analysis (P < .001). Combining clinical judgment before exercise testing with high-sensitivity cardiac troponin I levels increased diagnostic accuracy as quantified by the area under the receiver operating curve from 0.64 to 0.73 (P < .001), which also tended to be superior to clinical judgment after exercise testing (0.69, P = .056). A single resting high-sensitivity cardiac troponin I measurement provided similar diagnostic accuracy as integrated clinical judgment after exercise testing including work load, as well as symptoms and electrocardiogram changes (0.70 vs 0.69, P = not significant). CONCLUSIONS: High-sensitivity cardiac troponin I measurements seem to complement noninvasive clinical assessment in patients with suspected coronary artery disease.

Accelerated diagnostic protocol using high-sensitivity cardiac troponin T in acute chest pain patients.

BACKGROUND: We aimed to evaluate the efficacy and safety of using high-sensitivity cardiac troponin T (hs-cTnT) within an accelerated diagnostic protocol (ADP) in patients presenting with symptoms suggestive of acute myocardial infarction (AMI) for rapid rule-out of AMI. METHODS: In two independent large multicenter studies, levels of hs-cTnT at presentation and at 2 h were combined with the Thrombolysis In Myocardial Infarction (TIMI) risk score and ECG findings. The ADP defined patients with normal levels of hs-cTnT at presentation and 2 h, a TIMI score ≤1, and normal ECG findings as candidates for rapid rule-out of AMI and rapid discharge. Major adverse cardiac events (MACEs) occurring within 30-days were centrally adjudicated by two independent cardiologists. RESULTS: In the derivation cohort, among 1085 consecutive patients 198 patients (18.2%) had a MACE. The ADP classified 374 patients (34.5%) as low-risk. None of these patients had a MACE at 30 days, resulting in a negative predictive value (NPV) of 100% (95% CI, 99.0-100%) and a sensitivity of 100% (95% CI, 98.2%-100%). In the validation cohort, among 1590 consecutive patients 231 patients (14.5%) had a MACE. The ADP classified 641 patients (40.3%) as low-risk. 6 of these patients had a MACE at 30 days, resulting in a NPV of 99.1% (95% CI, 98.0-99.6%) and a sensitivity of 97.4% (95% CI, 94.5-98.8%). CONCLUSIONS: The ADP including hs-cTnT allows early identification 35 to 40% of patients to be at extremely low risk of MACE and therefore ideal candidates for outpatient management.

Prevalence, characteristics and outcome of non-cardiac chest pain and elevated copeptin levels.

OBJECTIVE: Copeptin, a quantitative marker of endogenous stress, seems to provide incremental value in addition to cardiac troponin in the early rule-out of acute myocardial infarction (AMI). Prevalence, characteristics and outcome of acute chest pain patients with causes other than AMI and elevated copeptin are poorly understood. METHODS: A total of 984 consecutive patients with non-cardiac chest pain were selected from a prospective multicentre study of acute chest pain patients presenting to the emergency department. Levels of copeptin were determined in a blinded fashion and considered elevated if above 13 pmol/L (the 97,5th centile of healthy individuals). The final diagnosis was adjudicated by two independent cardiologists. Median duration of follow-up was 756 days. RESULTS: Elevated copeptin levels were seen in 215 patients (22%). In comparison to patients with normal copeptin levels, patients with elevated levels were older, had more pre-existing cardiac and non-cardiac disorders, more silent cardiomyocyte injury and increased haemodynamic stress as quantified by levels of high-sensitivity cardiac troponin T (9.6 ng/L (3.6-18.3) vs 5.8 ng/L (2.9-9.4)) and B-type natriuretic peptide (75 ng/L (37-187) vs 35 ng/L (15-77)) (both p<0.001), more electrocardiographic abnormalities, more often an adjudicated diagnosis of gastroesophageal reflux or bronchitis/pneumonia and higher 2- year mortality (HR 2.9, 95% CI 1.5  to 5.7). The increased mortality rate seemed to be largely explained by age and comorbidities. CONCLUSIONS: Elevated levels of copeptin are present in about one in five patients with non-cardiac chest pain and are associated with aging, cardiac and non-cardiac comorbidities as well as mortality.

Direct comparison of high-sensitivity-cardiac troponin I vs. T for the early diagnosis of acute myocardial infarction.

AIM: It is unknown whether cardiac troponin (cTn) I or cTnT is the preferred biomarker in the early diagnosis of acute myocardial infarction without ST segment elevation (NSTEMI). METHODS AND RESULTS: In a prospective multicentre study, we measured cTnI and cTnT using clinically available high-sensitivity assays (hs-cTnI Abbott and hs-cTnT Roche) and compared their diagnostic and prognostic accuracies in consecutive patients presenting to the emergency department with acute chest pain. The final diagnosis was adjudicated by two independent cardiologists using all information pertaining to the individual patient. The mean follow-up was 24 months. Among 2226 consecutive patients, 18% had an adjudicated final diagnosis of NSTEMI. Diagnostic accuracy at presentation as quantified by the area under the receiver-operating-characteristics curve (AUC) for NSTEMI was very high and similar for hs-cTnI [AUC: 0.93, 95% confidence interval (CI) 0.92-0.94] and hs-cTnT (0.94, 95% CI: 0.92-0.94) P = 0.62. In early presenters (<3 h since chest pain onset) hs-cTnI showed a higher diagnostic accuracy (AUC: 0.92, 95% CI: 0.89-0.94) when compared with hs-cTnT AUC (0.89, 95% CI: 0.86-0.91) (P = 0.019), while hs-cTnT was superior in late presenters [AUC hs-cTnT 0.96 (95% CI: 0.94-0.96)  vs. hs-cTnI 0.94 (95% CI: 0.93-0.95); P = 0.007]. The prognostic accuracy for all-cause mortality, quantified by AUC, was significantly higher for hs-cTnT (AUC: 0.80; 95% CI: 0.78-0.82) when compared with hs-cTnI (AUC: 0.75; 95% CI: 0.73-0.77; P < 0.001). CONCLUSION: Both hs-cTnI and hs-cTnT provided high diagnostic and prognostic accuracy. The direct comparison revealed small but potentially important differences that might help to further improve the clinical use of hs-cTn.

Sex-specific chest pain characteristics in the early diagnosis of acute myocardial infarction.

IMPORTANCE: Whether sex-specific chest pain characteristics (CPCs) would allow physicians in the emergency department to differentiate women with acute myocardial infarction (AMI) from women with other causes of acute chest pain more accurately remains unknown. OBJECTIVE To improve the management of suspected AMI in women by exploring sex-specific CPCs. DESIGN, SETTING, AND PARTICIPANTS: From April 21, 2006, through August 12, 2012, we enrolled 2475 consecutive patients (796 women and 1679 men) presenting with acute chest pain to 9 emergency departments in a prospective multicenter study. The final diagnosis of AMI was adjudicated by 2 independent cardiologists. INTERVENTIONS: Treatment of AMI in the emergency department. MAIN OUTCOMES AND MEASURES: Sex-specific diagnostic performance of 34 predefined and uniformly recorded CPCs in the early diagnosis of AMI. RESULTS: Acute myocardial infarction was the adjudicated final diagnosis in 143 women (18.0%) and 369 men (22.0%). Although most CPCs were reported with similar frequency in women and men, several CPCs were reported more frequently in women (P < .05). The accuracy of most CPCs in the diagnosis of AMI was low in women and men, with likelihood ratios close to 1. Thirty-one of 34 CPCs (91.2%) showed similar likelihood ratios for the diagnosis of AMI in women and men, and only 3 CPCs (8.8%) seemed to have a sex-specific diagnostic performance with P < .05 for interaction. These CPCs were related to pain duration (2-30 and >30 minutes) and dynamics (decreasing pain intensity). However, because their likelihood ratios were close to 1, the 3 CPCs did not seem clinically helpful. Similar results were obtained when examining combinations of CPCs (all interactions, P ≥ .05). CONCLUSIONS AND RELEVANCE: Differences in the sex-specific diagnostic performance of CPCs are small and do not seem to support the use of women-specific CPCs in the early diagnosis of AMI. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00470587.

Serial changes in high-sensitivity cardiac troponin I in the early diagnosis of acute myocardial infarction.

BACKGROUND: Current guidelines require a change (rise and/or fall) in levels of cardiac troponin (cTn) for the diagnosis of acute myocardial infarction (AMI). It is unknown whether absolute or relative changes provide higher accuracy when using high-sensitivity cTnI assays. METHODS: In a prospective international multicentre study, we assessed the diagnostic accuracy of early absolute and relative changes in cTnI measured with two novel pre-commercial high-sensitivity assays (Siemens and Beckman Coulter) in 943 unselected patients presenting to the ED with suspected AMI. The final diagnosis of AMI was adjudicated using all available data including serial hs-cTnT levels by two independent cardiologists. RESULTS: The diagnostic accuracy of absolute changes in the diagnosis of AMI as quantified by the area under the receiver operating characteristics curve (AUC) was very high (e.g. at 2 h, Siemens high-sensitivity cTnI AUC 0.93, 95%Cl 0.90-0.96; Beckman Coulter high-sensitivity cTnI AUC 0.93, 95%Cl 0.90-0.96) and superior to relative changes at all time points (p < 0.001). The results were consistent in clinically important subgroups. Direct comparison of the absolute changes in the two high-sensitivity cTnI assays showed similar accuracy. When combined with the baseline cTnI levels, the difference between absolute and relative changes became much smaller and remained statistically significant only for the Siemens assay. CONCLUSIONS: As single variables early absolute changes in high-sensitivity cTnI levels have significantly higher diagnostic accuracy than relative changes. When combined with the baseline cTn level, reflecting clinical practice, both absolute and relative changes provided very high accuracy with much smaller differences between both approaches.