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Background Although oral P2Y12 inhibitors are key in the management of patients with non-ST elevation acute coronary syndrome (NSTE-ACS), the optimal timing of their administration is not well defined. Objective to compare downstream and upstream oral P2Y12 inhibitors administration strategies in NSTE-ACS patients undergoing invasive management. Methods We performed a randomized, adaptive, open-label, multi-center, clinical trial. Patients were randomly assigned to receive pre-treatment with ticagrelor before angiography (upstream group) or no pre-treatment (downstream group). Patients in the downstream group undergoing percutaneous coronary intervention (PCI) were further randomized to receive ticagrelor or prasugrel. The primary hypothesis was superiority of the downstream over the upstream strategy on the combination of efficacy and safety events (net clinical benefit). Results We randomized 1449 patients to downstream or upstream oral P2Y12 inhibitor administration. A prespecified stopping rule for futility at interim analysis led the trial to be stopped. The rate of the primary endpoint, a composite of death due to vascular causes, non-fatal myocardial infarction or non-fatal stroke, and Bleeding Academic Research Consortium (BARC) type 3, 4 and 5 bleedings through day 30, did not differ significantly between the downstream and upstream groups (Absolute Risk Reduction (ARR%) -0.46 [-2.90; 1.90]).These results were confirmed among patients undergoing PCI (72% of population) and regardless of the timing of coronary angiography (within or after 24 hours from enrolment). Conclusions Downstream and upstream oral P2Y12 inhibitors administration strategies were associated with low incidence of ischemic and bleeding events and minimal numerical difference of event rates between treatment groups. These findings led to premature interruption of the trial and suggest the unlikelihood of enhanced efficacy of one strategy over the other. [Funded by the Italian Society of Interventional Cardiology (SICI-GISE)]

Reduction of kidney function and heart disease frequently coexisted in the seam patient. The relation between renal and heart function is quite complex and bring out some unresolved questions about diagnosis (mostly related to the biomarkers levels interpretation), pharmacological therapy (mostly related to drugs kinetics and efficacy), and non-pharmacological therapy. Patients with kidney dysfunction (KD) are frequently excluded and underrepresented in the large trials. It is well-known that coronary revascularization reduces mortality also in KD patients presenting with acute coronary syndrome. However, acute kidney injury (AKI), primarily related at contrast medium administration, is worse prognosis. For this reason, prevention, early diagnosis, and effective therapy of ACK are key elements in assistance of these patients. In this context, recently, some new biomarkers of renal function have been proposed. Frequently, patients with acute coronary syndromes and kidney disease are undertreated, worsening their prognosis. Undertreatment and comorbidities associated with renal dysfunction explain the higher mortality of these patients.

Poor exercise capacity, abnormal heart rate responses, and electrocardiographic abnormalities during treadmill exercise testing independently predict mortality. The combined relationship of these 3 variables to determine the incremental increase in mortality was compared in groups with and without known cardiovascular disease (CVD).Patients referred for treadmill exercise testing during 1986 to 1991 were included. Exercise capacity74% (of age- and gender-predicted value), heart rate reserve of68 beat/min, and horizontal or down-sloping ST depression ofor =1 mm were considered abnormal. Cox proportional hazards regression was used to determine all-cause mortality (average follow-up of 16 years) based on the number of exercise test abnormalities (0, 1, 2, or all 3).Among 10,897 patients, 20.9% (n = 2,277) had CVD. Poor exercise capacity and limited heart rate reserve were associated with increased risk of mortality (P.0001) in both groups; however, abnormal exercise electrocardiogram was associated with an increased risk of mortality in the no-CVD group only (P.0001). A graded increase in mortality was observed with increase in number of abnormal exercise test results in both groups. Patients without CVD having 2 or 3 abnormal exercise test results had a similar age-adjusted risk of long-term mortality as those with CVD but normal exercise test results, with a hazard ratio comparing these groups = 1.01 (95% CI 0.79-1.28).The combinatorial approach validates the prognostic significance of multiple exercise test variables. The presence ofor =2 exercise test abnormalities may constitute a "CVD risk equivalent" in patients without CVD.

It has been known for 50 years that transaminase activity increases in patients with acute myocardial infarction. With the development of creatine kinase (CK), biomarkers of cardiac injury began to take a major role in the diagnosis and management of patients with acute cardiovascular disease. In 2000 the European Society of Cardiology and the American College of Cardiology recognized the pivotal role of biomarkers and made elevations in their levels the “cornerstone” of diagnosis of acute myocardial infarction. At that time, they also acknowledged that cardiac troponin I and T had supplanted CK-MB as the analytes of choice for diagnosis. In this review, we discuss the science underlying the use of troponin biomarkers, how to interpret troponin values properly and how to apply these measurements to patients who present with possible cardiovascular disease. Troponin is the biomarker of choice for the detection of cardiac injury. To use it properly, one must understand how sensitive the specific assay being used is for detecting cardiac injury, the fact that elevated troponin levels are highly specific for cardiac injury and some critical issues related to the basic science of the protein and its measurement. In this article, we review the biology of troponin, characteristics of assays that measure serum troponin levels and how to apply these measurements to patients who present with possible cardiovascular disease. We also discuss other clinical situations in which troponin levels may be elevated.

To the Editor: Constrictive pericarditis (CP) often is a challenging diagnosis despite sophisticated modalities ([1–4][1]). If a simple test could alert physicians to the possibility of CP in patients with evidence of heart failure, it would be valuable. Recent data ([5][2]) suggest that brain

Refractory cardiogenic shock is characterized by severe hemodynamic instability with high mortality rate. In most critical patients extracorporeal membrane oxygenation (ECMO) is the only therapy available nowadays that gives a possibility to survive. It guarantees continuous organs perfusion with

Elevations in troponin level have prognostic importance in critically ill patients, including those with gastrointestinal (GI) bleeding. However, there are no data addressing the independent association of troponin levels and mortality, adjusted for the severity of the underlying disease, in patients with GI bleeding.This study was designed to determine whether troponin T elevations are independently associated with in-hospital, short-term (30 days), and long-term mortality in medical intensive care unit patients with GI bleeding after adjusting for the severity of disease measured by the Acute Physiology, Age, and Chronic Health Evaluation score prognostic system.Retrospective study.We examined the Acute Physiology, Age, and Chronic Health Evaluation III database and cardiac troponin T levels from patients consecutively admitted to the medical intensive care unit at Mayo Clinic, Rochester, MN, with acute GI bleeding.Between August 2000 and July 2005, 1076 patients with acute GI bleeding consecutively admitted to the medical intensive care units.In-hospital, short-term (30 days), and long-term all-cause mortality.During hospitalization, 8.0% of deaths occurred in patients with troponin T0.01% and 11.9% with troponin Tor = 0.01 (p = 0.083). At 30 days, mortality was 10.1% and 18.8% in patients without and with elevations of troponins, respectively (p0.001). The Kaplan-Meier expected probability of survival at 1-, 2-, and 3-yr follow-up was 54.2%, 40.8%, and 30.4% with troponin Tor = 0.01 microg/L and 78.3%, 69.3%, and 61.5% with troponin T0.01 microg/L (p0.001). After adjustment for severity of disease and baseline characteristics, cardiac troponin levels were associated only with long-term mortality (p0.001).This is a retrospective, single-center study which included only patients in whom troponin level was determined upon admission.In patients with GI bleeding severe enough to require admission to the medical intensive care unit, admission troponin T elevations are associated with long-term but not short-term mortality.

Background Cardiac troponins are the markers of choice for the diagnosis of acute myocardial infarction. The objective of this study was to compare the frequency of “aborted myocardial infarction” (no detectable myocardial injury) determined by measurement of troponin versus that determined by creatine kinase (CK) and creatine kinase–muscle brain (CK-MB) measurement criteria among patients with ST-elevation myocardial infarction (STEMI) who received reperfusion therapy. Methods Since 2004, the Mayo Clinic (Rochester, MN) has had a standard reperfusion protocol for the treatment of patients with STEMI. During the study period, 767 patients presented with new or presumed new ST elevation or left bundle block. Results The diagnosis of STEMI was confirmed in 765 (99.7%) patients. Using the 99th percentile cutoff value, troponin T elevations occurred in 765 (100%) of 765 patients when serial samples were available. Creatine kinase–MB levels of twice or more the upper limit of normal occurred in 681 (90.1%) of 749 patients with serial samples for CK-MB, and CK equal or greater than twice the gender-specific upper limits of normal occurred in 521 (78.8%) of 661 patients with serial samples for CK available. Conclusion The frequency of aborted myocardial infarction is 0% when using troponin at the 99th percentile cutoff as recommended by contemporary guidelines from the European Society of Cardiology (Nice, France) and American College of Cardiology (Washington, DC).

We recently cared for several patients with chest discomfort characteristic of coronary disease, electrocardiogram (ECG) changes, and increasing troponin concentrations. Coronary angiography revealed mild or no coronary artery disease (CAD), so we evaluated these patients with contrast-enhanced cardiac MRI. Our data suggest that these patients had myocardial infarction (MI). With Institutional Review Board permission, we reviewed our angiography database for patients with normal coronary arteries or mild coronary artery disease during the period from January 2005 to November 1, 2006, to augment those cases we found clinically. Inclusion criteria included presentation with acute coronary syndrome, increased serum troponin T concentration (>0.01 μg/L), or mild or absent CAD by angiography and a contrast-enhanced cardiac MRI (CE-CMR) considered diagnostic for infarction. Patients with prior infarction, known CAD, heart failure, pulmonary embolism, or suspected pericarditis/myocarditis were excluded. Eight patients met these criteria. All angiogram results were reviewed by one of the investigators (V.M.). CE-CMR studies performed on a GE Signa CVi system …

We evaluated relationships among two circulating molecular forms of brain natriuretic peptide (BNP32 and NT-proBNP), severity of hypertension (HTN), and cardiac hypertrophy in subjects with mild, moderate, and severe HTN. We prospectively studied 78 patients (43 males; mean age 51.4 ± 11 yr) with essential HTN and 28 age- and sex-matched controls. BNP32 and NT-proBNP were measured by radioimmunoassay. In grade 1 HTN, BNP32 was not elevated and NT-proBNP was reduced ( P = 0.030) compared with controls. However, log-transformed values of BNP32 and NT-proBNP were both increased with severity of HTN from grade 1 to 3 ( P

The diagnosis of acute myocardial infarction (AMI) as defined by the World Health Organization (WHO) was based for many years on the presence of two of three possible criteria: clinical symptoms compatible with AMI, typical electrocardiogram changes, and increases in markers of cardiac injury. However, because of the very good sensitivity and specificity of creatine kinase-MB (CK-MB), it eventually became rare to diagnose AMI in the absence of elevations of this biomarker. Thus, although never formally embraced by WHO, the clinical diagnosis of AMI became dependent on elevation of a biomarker of myocardial injury in the appropriate clinical setting. This approach evolved further with the development of cardiac troponin and its integration into the definition of MI by the European Society of Cardiology and the American College of Cardiology. The present diagnostic standard for MI is thus based on the following biomarker criteria: Maximal concentration of troponin T or I exceeding the decision limit (99th percentile of the values for a reference control group) manifesting a dynamic pattern on at least one occasion during the first 24 h after the index clinical event; if the value is between the 99th percentile and the 10% coefficient of variation level, caution is warranted because analytic false-positive results can occur. In the unusual situation in which troponin assays are not available, the value of CK-MB (preferably CK-MB mass) exceeding the 99th percentile of the value for a reference control group and manifesting a dynamic pattern can be used for diagnosis.

Aims The objectives of this study are to evaluate the prognostic role of pre-operative stratification in patients undergoing elective major vascular surgery, the timing of adverse outcomes, and the predictive role of troponin (cTn). Methods and results Consecutive vascular surgery candidates (n ¼ 391) were prospectively stratified and treated according to the ACC/AHA guidelines. The patients were categorized into three groups: (1) with coronary revascularization in the past 5 years, (2) with intermediate clinical risk predictors, and (3) with minor or no clinical risk predictors. cTnI was measured post-operatively. By 18 months, 18.7% of subjects had experienced death or acute myocardial infarction (MI) (by the ACC/ESC criteria). The hazard ratio (HR) was 5.21 (95% CI ¼ 2.60–10.43; P , 0.0001) in group 1 and 2.58 (95% CI ¼ 1.27–4.38; P ¼ 0.004) in group 2 when compared with group 3. Most events occurred within 30 days. Elevations of cTnI were associated with adverse outcomes even after multivariable adjustment at long-term (adjusted overall HR ¼ 4.73, 95% CI ¼ 2.92–7.65; P , 0.0001) and at 30 days (adjusted HR ¼ 5.52, 95%CI ¼ 3.23–9.42; P , 0.0001). Conclusion After pre-operative stratification, patients undergoing elective major vascular surgery remain at high risk of MI and death. Events occur mainly early after surgery. cTnI elevations are frequent and independently associated with increased risk. These findings suggest the need for a major re-evaluation of our approach to these patients.