Damian Kawecki

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.

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.

Clinical Significance of Viral Genome Persistence in the Myocardium of Patients with Dilated Cardiomyopathy

Background: The impact of myocardial viral persistence on the clinical outcome of patients with dilated cardiomyopathy (DCM) is still open to question. Methods: Fifty-two patients with DCM were enrolled and followed for a median of 3.8 years with respect to death or heart transplantation. Studied patients were clinically stable for at least 6 months before hospitalization. They underwent coronary angiography and endomyocardial biopsy. Specimens were examined by histo- and immunohistochemistry, and the viral genomes of parvovirus B19, cytomegalovirus (CMV), Coxsackie B virus (CVB), and hepatitis B and C viruses were studied by real-time polymerase chain reaction. Results: Forty-two out of 52 patients were available for clinical follow-up. The viral genome was detected in the myocardium of 32 out of 42 patients. Among the viruses studied, CMV and CVB were the most frequently found. Nine out of 42 patients achieved the predefined study end point. No statistically significant correlation was found between the presence of a persistent viral genome and study end point. No statistically significant relationship between viral genomes studied and immunohistology results was detected. Conclusions: High prevalence of a viral genome in the myocardium of patients with DCM did not have an influence on their long-term clinical outcome.

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.

Response to Inhaled Nitric Oxide, But neither Sodium Nitroprusside nor Sildenafil, Predicts Survival in Patients with Dilated Cardiomyopathy Complicated with Pulmonary Hypertension

Introduction: Pulmonary hypertension in patients with dilated cardiomyopathy is associated with higher mortality. Objectives: The aim of the study was to assess the predictive value of the vasodilator response to three different drugs, sodium nitroprusside, inhaled nitric oxide, and oral sildenafil, in patients with dilated cardiomyopathy complicated with pulmonary hypertension. Patients and methods: Twenty-nine patients with dilated cardiomyopathy complicated with postcapillary pulmonary hypertension (left ventricle ejection fraction (LVEF) 20.6 ± 8.2%, mean pulmonary artery pressure (mPAP) 42.49 ± 7.27 mmHg, transpulmonary gradient (TPG)>12 mmHg or pulmonary vascular resistance index (PVRI)>5 WU/m2) underwent single-session vaso reactivity testing with sodium nitroprusside, inhaled nitric oxide (120 ppm), oral sildenafil (50 mg), and a combination of sildenafil and inhaled nitric oxide. The vasodilator responders were defined as those participants who achieved a reduction of PVRI<5 WU/m2 and TPG<12 mmHg. The primary study endpoint was death in the 30-month-long follow-up. Kaplan-Meier analysis and Cox proportional hazard modelling were used to identify the predictors of survival. Results: In the follow-up, eight patients died (six patients with irreversible pulmonary hypertension). Six patients underwent successful heart transplantation. Multivariate Cox proportional hazard analysis disclosed a response to nitric oxide as the only predictor of longer survival (HR=11.77, 95% CI=1.12-123.9 at P=0.04). Conclusions: Vasodilator response to inhaled nitric oxide predicts longer survival in patients with dilated cardiomyopathy complicated with pulmonary hypertension.

Role of copeptin in dual–cardiac marker strategy for patients with chest pain presented to ED

OBJECTIVE The objective of the study is to evaluate the role of copeptin in the diagnosis of acute coronary syndrome (ACS) and its role in dual-cardiac marker diagnostic strategy with troponin. DESIGN A prospective cohort study was carried out from May 2012 to October 2012. SETTING The study was conducted at the emergency department (ED) of a public hospital in a cluster of Hong Kong. METHODS Patients aged at least 18 years presented with chest pain to ED who have intermediate or high likelihood of ACS were included. All patients had blood taken in the ED for copeptin and troponin I. The adjudicated diagnoses of ACS were made by 2 independent physicians based on the universal definition. Diagnostic characteristics were calculated. Receiver operating characteristic curves were created. Areas under the curves were compared for copeptin, troponin I, and dual-marker strategy with copeptin and troponin I. RESULTS A total of 637 patients were recruited. Seventy-eight had been diagnosed to be ACS. The negative predictive value of copeptin for ACS was 0.881 (0.849-0.907) compared with troponin I, 0.937 (0.913-0.956). The areas under the receiver operating characteristic curves of copeptin, troponin I, and dual-marker strategy were 0.68, 0.859, and 0.880, respectively. CONCLUSIONS Addition of copeptin to troponin does not have significant improvement of the diagnostic accuracy of ACS in patients presented with chest pain.