Beata Morawiec

Direct Comparison of 4 Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I

Background: Four strategies for very early rule-out of acute myocardial infarction using high-sensitivity cardiac troponin I (hs-cTnI) have been identified. It remains unclear which strategy is most attractive for clinical application. Methods: We prospectively enrolled unselected patients presenting to the emergency department with symptoms suggestive of acute myocardial infarction. The final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnI levels were measured at presentation and after 1 hour in a blinded fashion. We directly compared all 4 hs-cTnI–based rule-out strategies: limit of detection (LOD, hs-cTnI<2 ng/L), single cutoff (hs-cTnI<5 ng/L), 1-hour algorithm (hs-cTnI<5 ng/L and 1-hour change<2 ng/L), and the 0/1-hour algorithm recommended in the European Society of Cardiology guideline combining LOD and 1-hour algorithm. Results: Among 2828 enrolled patients, acute myocardial infarction was the final diagnosis in 451 (16%) patients. The LOD approach ruled out 453 patients (16%) with a sensitivity of 100% (95% confidence interval [CI], 99.2%–100%), the single cutoff 1516 patients (54%) with a sensitivity of 97.1% (95% CI, 95.1%–98.3%), the 1-hour algorithm 1459 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%–99.2%), and the 0/1-hour algorithm 1463 patients (52%) with a sensitivity of 98.4% (95% CI, 96.8%–99.2%). Predefined subgroup analysis in early presenters (⩽2 hours) revealed significantly lower sensitivity (94.2%, interaction P=0.03) of the single cutoff, but not the other strategies. Two-year survival was 100% with LOD and 98.1% with the other strategies (P<0.01 for LOD versus each of the other strategies). Conclusions: All 4 rule-out strategies balance effectiveness and safety equally well. The single cutoff should not be applied in early presenters, whereas the 3 other strategies seem to perform well in this challenging subgroup. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Myocardial infarct size and mortality depend on the time of day-a large multicenter study.

Background Different studies have shown circadian variation of ischemic burden among patients with ST-Elevation Myocardial Infarction (STEMI), but with controversial results. The aim of this study was to analyze circadian variation of myocardial infarction size and in-hospital mortality in a large multicenter registry. Methods This retrospective, registry-based study was based on data from AMIS Plus, a large multicenter Swiss registry of patients who suffered myocardial infarction between 1999 and 2013. Peak creatine kinase (CK) was used as a proxy measure for myocardial infarction size. Associations between peak CK, in-hospital mortality, and the time of day at symptom onset were modelled using polynomial-harmonic regression methods. Results 6,223 STEMI patients were admitted to 82 acute-care hospitals in Switzerland and treated with primary angioplasty within six hours of symptom onset. Only the 24-hour harmonic was significantly associated with peak CK (p = 0.0001). The maximum average peak CK value (2,315 U/L) was for patients with symptom onset at 23:00, whereas the minimum average (2,017 U/L) was for onset at 11:00. The amplitude of variation was 298 U/L. In addition, no correlation was observed between ischemic time and circadian peak CK variation. Of the 6,223 patients, 223 (3.58%) died during index hospitalization. Remarkably, only the 24-hour harmonic was significantly associated with in-hospital mortality. The risk of death from STEMI was highest for patients with symptom onset at 00:00 and lowest for those with onset at 12:00. Discussion As a part of this first large study of STEMI patients treated with primary angioplasty in Swiss hospitals, investigations confirmed a circadian pattern to both peak CK and in-hospital mortality which were independent of total ischemic time. Accordingly, this study proposes that symptom onset time be incorporated as a prognosis factor in patients with myocardial infarction.

Copeptin: a new marker in cardiology.

Copeptin, the C-terminal part of the prohormone of vasopressin (AVP), is released together with AVP in stoichiometric concentrations reflecting an individuals stress level. Copeptin has come to be regarded as an important marker for identifying high-risk patients and predicting outcomes in a variety of diseases. It improves the clinical value of commonly used biomarkers and the tools of risk stratification. Elevated AVP activation and higher copeptin concentrations have been previously described in acute systemic disorders. However, the field that could benefit the most from the introduction of copeptin measurements into practice is that of cardiovascular disease. Determination of copeptin level emerges as a fast and reliable method for differential diagnosis, especially in acute coronary syndromes. A particular role in the diagnosis of acute myocardial infarction (AMI) is attributed to the combination of copeptin and troponin. According to available sources, such a combination allows AMI to be ruled out with very high sensitivity and negative predictive value. Moreover, elevated copeptin levels correlate with a worse prognosis and a higher risk of adverse events after AMI, especially in patients who develop heart failure. Some authors suggest that copeptin might be valuable in defining the moment of the introduction of treatment and its monitoring in high-risk patients. The introduction of copeptin into clinical practice might also provide a benefit on a larger scale by suggesting changes in the allocation of financial resources within the health system. Although very promising, further larger trials are required in order to assess the clinical benefits of copeptin in everyday practice and patient care.

0/1-Hour Triage Algorithm for Myocardial Infarction in Patients With Renal Dysfunction

Background: The European Society of Cardiology recommends a 0/1-hour algorithm for rapid rule-out and rule-in of non–ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin (hs-cTn) concentrations irrespective of renal function. Because patients with renal dysfunction (RD) frequently present with increased hs-cTn concentrations even in the absence of non–ST-segment elevation myocardial infarction, concern has been raised regarding the performance of the 0/1-hour algorithm in RD. Methods: In a prospective multicenter diagnostic study enrolling unselected patients presenting with suspected non–ST-segment elevation myocardial infarction to the emergency department, we assessed the diagnostic performance of the European Society of Cardiology 0/1-hour algorithm using hs-cTnT and hs-cTnI in patients with RD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2, and compared it to patients with normal renal function. The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including cardiac imaging. Safety was quantified as sensitivity in the rule-out zone, accuracy as the specificity in the rule-in zone, and efficacy as the proportion of the overall cohort assigned to either rule-out or rule-in based on the 0- and 1-hour sample. Results: Among 3254 patients, RD was present in 487 patients (15%). The prevalence of non–ST-segment elevation myocardial infarction was substantially higher in patients with RD compared with patients with normal renal function (31% versus 13%, P<0.001). Using hs-cTnT, patients with RD had comparable sensitivity of rule-out (100.0% [95% confidence interval {CI}, 97.6–100.0] versus 99.2% [95% CI, 97.6–99.8]; P=0.559), lower specificity of rule-in (88.7% [95% CI, 84.8–91.9] versus 96.5% [95% CI, 95.7–97.2]; P<0.001), and lower overall efficacy (51% versus 81%, P<0.001), mainly driven by a much lower percentage of patients eligible for rule-out (18% versus 68%, P<0.001) compared with patients with normal renal function. Using hs-cTnI, patients with RD had comparable sensitivity of rule-out (98.6% [95% CI, 95.0–99.8] versus 98.5% [95% CI, 96.5–99.5]; P=1.0), lower specificity of rule-in (84.4% [95% CI, 79.9–88.3] versus 91.7% [95% CI, 90.5–92.9]; P<0.001), and lower overall efficacy (54% versus 76%, P<0.001; proportion ruled out, 18% versus 58%, P<0.001) compared with patients with normal renal function. Conclusions: In patients with RD, the safety of the European Society of Cardiology 0/1-hour algorithm is high, but specificity of rule-in and overall efficacy are decreased. Modifications of the rule-in and rule-out thresholds did not improve the safety or overall efficacy of the 0/1-hour algorithm. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Direct Comparison of Cardiac Myosin-Binding Protein C with Cardiac Troponins for the Early Diagnosis of Acute Myocardial Infarction

Background: Cardiac myosin-binding protein C (cMyC) is a cardiac-restricted protein that is more abundant than cardiac troponins (cTn) and is released more rapidly after acute myocardial infarction (AMI). We evaluated cMyC as an adjunct or alternative to cTn in the early diagnosis of AMI. Methods: Unselected patients (N=1954) presenting to the emergency department with symptoms suggestive of AMI, concentrations of cMyC, and high-sensitivity (hs) and standard-sensitivity cTn were measured at presentation. The final diagnosis of AMI was independently adjudicated using all available clinical and biochemical information without knowledge of cMyC. The prognostic end point was long-term mortality. Results: Final diagnosis was AMI in 340 patients (17%). Concentrations of cMyC at presentation were significantly higher in those with versus without AMI (median, 237 ng/L versus 13 ng/L, P<0.001). Discriminatory power for AMI, as quantified by the area under the receiver-operating characteristic curve (AUC), was comparable for cMyC (AUC, 0.924), hs-cTnT (AUC, 0.927), and hs-cTnI (AUC, 0.922) and superior to cTnI measured by a contemporary sensitivity assay (AUC, 0.909). The combination of cMyC with hs-cTnT or standard-sensitivity cTnI (but not hs-cTnI) led to an increase in AUC to 0.931 (P<0.0001) and 0.926 (P=0.003), respectively. Use of cMyC more accurately classified patients with a single blood test into rule-out or rule-in categories: Net Reclassification Improvement +0.149 versus hs-cTnT, +0.235 versus hs-cTnI (P<0.001). In early presenters (chest pain <3 h), the improvement in rule-in/rule-out classification with cMyC was larger compared with hs-cTnT (Net Reclassification Improvement +0.256) and hs-cTnI (Net Reclassification Improvement +0.308; both P<0.001). Comparing the C statistics, cMyC was superior to hs-cTnI and standard sensitivity cTnI (P<0.05 for both) and similar to hs-cTnT at predicting death at 3 years. Conclusions: cMyC at presentation provides discriminatory power comparable to hs-cTnT and hs-cTnI in the diagnosis of AMI and may perform favorably in patients presenting early after symptom onset. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Comparison of First- and Second-Generation Drug-Eluting Stents in an All-Comer Population of Patients with Diabetes Mellitus (from Katowice-Zabrze Registry)

Background This study compared safety and efficacy of first- and second-generation DES in an unrestricted, real-life population of diabetic patients undergoing PCI. Material/Methods The study was a subanalysis of diabetic patients from the all-comer Katowice-Zabrze Registry of patients undergoing PCI with the implantation of either first- (Paclitaxel-, Sirolimus-eluting stents) or second-generation DES (Zotarolimus-, Everolimus-, Biolimus-eluting stents). Efficacy defined as major adverse cardiac and cerebrovascular events (MACCE: death, myocardial infarction, target vessel revascularization, stroke) and safety defined as stent thrombosis (ST) were evaluated at 1 year. Results From the total of 1916 patients, 717 were diabetics. Among them, 257 (36%) were treated with first-generation DES (230 [89%] Paclitaxel-eluting stents, 27 [11%] Sirolimus-eluting stents), 460 with second-generation DES (171 [37%] Zotarolimus-eluting stents, 243 [53%] Everolimus-eluting stents, 46 [10%] Biolimus-eluting stents). Rate of MACCE was equal in both groups (p=0.54). Second-generation DES had a better safety profile than first-generation DES (log-rank for cumulative ST at 1 year p<0.001). First-generation DES was a risk factor for ST (HR 5.75 [1.16–28.47], p=0.03) but not for MACCE (HR 0.89 [0.6–1.32], p=0.57). Conclusions In a real-life setting of diabetic patients undergoing PCI, second-generation DES had lower risk of ST and similar MACCE rate compared to first-generation DES.

Prohormones in the Early Diagnosis of Cardiac Syncope

Background The early detection of cardiac syncope is challenging. We aimed to evaluate the diagnostic value of 4 novel prohormones, quantifying different neurohumoral pathways, possibly involved in the pathophysiological features of cardiac syncope: midregional–pro‐A‐type natriuretic peptide (MRproANP), C‐terminal proendothelin 1, copeptin, and midregional‐proadrenomedullin. Methods and Results We prospectively enrolled unselected patients presenting with syncope to the emergency department (ED) in a diagnostic multicenter study. ED probability of cardiac syncope was quantified by the treating ED physician using a visual analogue scale. Prohormones were measured in a blinded manner. Two independent cardiologists adjudicated the final diagnosis on the basis of all clinical information, including 1‐year follow‐up. Among 689 patients, cardiac syncope was the adjudicated final diagnosis in 125 (18%). Plasma concentrations of MRproANP, C‐terminal proendothelin 1, copeptin, and midregional‐proadrenomedullin were all significantly higher in patients with cardiac syncope compared with patients with other causes (P<0.001). The diagnostic accuracies for cardiac syncope, as quantified by the area under the curve, were 0.80 (95% confidence interval [CI], 0.76–0.84), 0.69 (95% CI, 0.64–0.74), 0.58 (95% CI, 0.52–0.63), and 0.68 (95% CI, 0.63–0.73), respectively. In conjunction with the ED probability (0.86; 95% CI, 0.82–0.90), MRproANP, but not the other prohormone, improved the area under the curve to 0.90 (95% CI, 0.87–0.93), which was significantly higher than for the ED probability alone (P=0.003). An algorithm to rule out cardiac syncope combining an MRproANP level of <77 pmol/L and an ED probability of <20% had a sensitivity and a negative predictive value of 99%. Conclusions The use of MRproANP significantly improves the early detection of cardiac syncope among unselected patients presenting to the ED with syncope. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01548352.

Long-Term Percutaneous Coronary Intervention Outcomes of Patients with Chronic Kidney Disease in the Era of Second-Generation Drug-Eluting Stents

Background: The following registry (Katowice-Zabrze retrospective registry) aimed to assess the influence of a chronic kidney disease (CKD) on long-term clinical outcomes in patients undergoing percutaneous coronary intervention (PCI) using either first-generation (DES-I) or second-generation (DES-II) drug-eluting stents. Methods: The study group consisted of 1,908 consecutive patients, of whom 331 (17.3%) had CKD. CKD was defined as an estimated glomerular filtration rate of <60 mL/min/m2. We evaluated the major adverse cardiac and cerebral events (MACCE), i.e., the composite of death, myocardial infarction (MI), stroke, and target vessel revascularization at the 12-month follow-up. Results: CKD patients had a lower left ventricular ejection fraction and more often a history of MI and PCI. Coronary angiography revealed that multivessel coronary artery disease, intracoronary thrombus, and extensive calcifications were more frequent in patients with CKD. However, the SYNTAX score did not vary between patients with or without CKD. There was a higher rate of in-hospital bleedings requiring blood transfusion in patients with CKD. At the 1-year follow-up, MACCE (17.8 vs. 12.6%, HR = 1.46 [95% CI 1.05-2.03], p = 0.009) and death (8.4 vs. 2.3%, HR = 3.9 [95% CI 2.0-7.5], p < 0.001) were more often observed in CKD patients. Multivariable Cox analysis revealed that CKD was an independent risk predictor of death after PCI at the 1-year follow-up (HR = 2.1 [95% CI 1.2-3.6], p = 0.004). In comparison to DES-I, the use of DES-II did not decrease the adverse effect of CKD on MACCE. Conclusion: CKD patients had an increased risk of in-hospital bleeding requiring blood transfusion and a higher risk of MACCE and death at the 12-month follow-up. The use of second-generation DES did not improve clinical outcomes in patients with CKD at the 12-month follow-up.

First- Versus Second-Generation Drug-Eluting Stents in Acute Coronary Syndromes (Katowice-Zabrze Registry)

Background There are sparse data on the performance of different types of drug-eluting stents (DES) in acute and real-life setting. Objective The aim of the study was to compare the safety and efficacy of first- versus second-generation DES in patients with acute coronary syndromes (ACS). Methods This all-comer registry enrolled consecutive patients diagnosed with ACS and treated with percutaneous coronary intervention with the implantation of first- or second-generation DES in one-year follow-up. The primary efficacy endpoint was defined as major adverse cardiac and cerebrovascular event (MACCE), a composite of all-cause death, nonfatal myocardial infarction, target-vessel revascularization and stroke. The primary safety outcome was definite stent thrombosis (ST) at one year. Results From the total of 1916 patients enrolled into the registry, 1328 patients were diagnosed with ACS. Of them, 426 were treated with first- and 902 with second-generation DES. There was no significant difference in the incidence of MACCE between two types of DES at one year. The rate of acute and subacute ST was higher in first- vs. second-generation DES (1.6% vs. 0.1%, p < 0.001, and 1.2% vs. 0.2%, p = 0.025, respectively), but there was no difference regarding late ST (0.7% vs. 0.2%, respectively, p = 0.18) and gastrointestinal bleeding (2.1% vs. 1.1%, p = 0.21). In Cox regression, first-generation DES was an independent predictor for cumulative ST (HR 3.29 [1.30-8.31], p = 0.01). Conclusions In an all-comer registry of ACS, the one-year rate of MACCE was comparable in groups treated with first- and second-generation DES. The use of first-generation DES was associated with higher rates of acute and subacute ST and was an independent predictor of cumulative ST.

Diagnostic Contribution of Cardiac Magnetic Resonance in Patients with Acute Coronary Syndrome and Culprit-Free Angiograms

Background In spite of robust knowledge about underlying ischemic myocardial damage, acute coronary syndromes (ACS) with culprit-free angiograms raise diagnostic concerns. The present study aimed to evaluate the additional value of cardiac magnetic resonance (CMR) over commonly available non-CMR standard tests, for the differentiation of myocardial injury in patients with ACS and non-obstructed coronary arteries. Material/Methods Patients with ACS, elevated hs-TnT, and a culprit-free angiogram were prospectively enrolled into the study between January 2009 and July 2013. After initial evaluation with standard tests (ECG, echocardiography, hs-TnT) and provisional exclusion of acute myocardial infarction (AMI) in coronary angiogram, patients were referred for CMR with the suspicion of myocarditis or Takotsubo cardiomyopathy (TTC). According to the result of CMR, patients were reclassified as having myocarditis, AMI, TTC, or non-injured myocardium as assessed by late gadolinium enhancement. Results Out of 5110 patients admitted with ACS, 75 had normal coronary angiograms and entered the study; 69 of them (92%) were suspected for myocarditis and 6 (8%) for TTC. After CMR, 49 patients were finally diagnosed with myocarditis (65%), 3 with TTC (4%), 7 with AMI (9%), and 16 (21%) with non-injured myocardium. The provisional diagnosis was changed or excluded in 23 patients (31%), with a 9% rate of unrecognized AMI. Conclusions The study results suggest that the evaluation of patients with ACS and culprit-free angiogram should be complemented by a CMR examination, if available, because the initial work-up with non-CMR tests leads to a significant proportion of misdiagnosed AMI.