Markers to define ischemia: Are they ready for prime time use in patients with acute coronary syndromes?

Optimal treatment of patients who present with chest pain is predicated on accurate identification of those patients with a cardiac etiology of their discomfort. Serial troponins and electrocardiograms are very sensitive for the detection of myocardial infarction but they are insensitive for the detection of ischemia. There are many analytes that are being actively evaluated for routine use to facilitate the identification of patients with myocardial ischemia. At present, only one assay is US Food and Drug Administration-approved for the exclusion of ischemia; many other analytes are under clinical evaluation and are briefly reviewed. At present, none of these analytes are yet appropriate for routine clinical use.     

Does on‐ versus off‐hours presentation impact in‐hospital outcomes of ST‐segment elevation myocardial infarction patients transferred to a tertiary care center?

Objectives : To determine whether in‐hospital outcome differs for transferred patients with ST‐segment elevation myocardial infarction (STEMI) presenting during business (ON) hours vs. after (OFF) hours. Background : Door‐to‐device (DTD) time is a prognostic factor in patients with STEMI and is longer during OFF hours. However, the in‐hospital mortality is controversial. Methods : This registry study included 786 consecutive patients with STEMI referred for primary percutaneous coronary intervention to a tertiary care center with an on‐site cardiac catheterization team 24 hrs a day/7 days (24/7) a week. ON hours were defined as weekdays 8 a.m. to 5 p.m., while OFF hours were defined as all other times, including holidays. The primary outcomes were in‐hospital death, reinfarction, and length of stay (LOS). Results : ON hours (29.5%, n = 232) and OFF hours (70.5%, n = 554) groups had similar demographic and baseline characteristics. A significantly higher proportion of patients presenting ON hours had a DTD time ≤120 min compared to OFF hours patients (32.6% vs. 22.1%, P = 0.007). The rates of in‐hospital death (8.2% vs. 6%), reinfarction (0% vs. 1.1%), and mean LOS (5.7 ± 6 vs. 5.7 ± 5) were not significantly different in the ON vs. OFF hours groups, all P = nonsignificant. Conclusion : In a tertiary care center with an on‐site cardiac catheterization team 24/7, there are no differences in in‐hospital outcomes of transferred patients with STEMI during ON vs. OFF hours. © 2010 Wiley‐Liss, Inc.     

Plasma amino‐terminal pro‐brain natriuretic peptide levels in subjects presenting to the Emergency Department with suspected acute coronary syndrome: possible role in selecting patients for follow up?

Background: Plasma amino‐terminal pro‐brain natriuretic peptide (NT‐proBNP) level is a sensitive and specific indicator of cardiac dysfunction. Aim: To determine whether plasma NT‐proBNP level is elevated at the time of presentation with acute coronary syndrome (ACS) and whether it may assist in the diagnosis of heart failure and myocardial ischaemia in the Emergency Department. Methods: Plasma NT‐proBNP levels were measured prospectively in 201 unselected presentations to the Emergency Department with suspected ACS where cardiac injury markers were requested by clinicians as part of routine assessment. NT‐proBNP levels were correlated with clinical, electrocardiogram (ECG), biochemical and radiological findings. Results: Elevated NT‐proBNP level detected heart failure with high sensitivity (95–96%). Among patients without heart failure, NT‐proBNP levels were increased more frequently in patients with previously diagnosed ischaemic heart disease. Elevated NT‐proBNP level predicted cardiomegaly and a cardiac cause of presentation. However, the NT‐proBNP level was not associated with ECG or biochemical markers of myocardial ischaemia, and only one‐third of patients with ACS showed an increase of 40% or more in NT‐proBNP level at repeat measurement of cardiac injury markers 5 h after presentation. Conclusions: Although elevated NT‐proBNP level detected heart failure with high sensitivity, NT‐proBNP level did not assist in the diagnosis of acute myocardial ischaemia. These findings indicate that the major determinant of elevated NT‐proBNP level on presentation with suspected ACS was underlying cardiac dysfunction rather than acute myocardial ischaemia. This suggests that NT‐proBNP measurement in patients with a suspected cardiac reason for presentation to the Emergency Department may identify a previously unrecognized group of patients without acute ischaemia who may nevertheless benefit from further investigation of cardiac function. (Intern Med J 2001; 31: 211–219)     

Characteristics and outcome of patients with dual hepatitis B and C‐associated hepatocellular carcinoma: are they different from patients with single virus infection?

Background: Patients with hepatocellular carcinoma (HCC) caused by dual hepatitis B and C virus (HBV, HCV) infection may constitute a distinct disease group that is different from patients with single virus infection. This study compared the clinical characteristics and outcomes of patients with HBV, HCV and dual virus infection. Methods: A prospective database of 1215 HCC patients with chronic hepatitis B, C or dual virus infection was investigated. Results: Patients with HCV infection (n=388) were significantly older (mean age, 69 years) than patients with dual virus (n=75, 65 years) and HBV (n=752; 60 years) infection (P<0.0001). The male‐to‐female ratios for the HBV, dual virus and HCV groups were 5.2, 3.4 and 1.3 respectively (P<0.0001). Patients in the HBV group more often had higher total tumour volume (mean, 409 cm³) than those in the dual virus group (244 cm³) and HCV (168 cm³) group (P<0.0001). No significant differences of the severity of liver cirrhosis, performance status, cancer staging and tumour cell differentiation were noted among the three groups. Patients in the HCV group had a significantly poor survival in comparison with the HBV group only in the subset of patients with small tumour volume (<50 cm³) in the Cox proportional hazards model (relative risk, 1.44; P=0.041). Conclusions: Dual HBV and HCV virus infection does not accelerate the speed of HCC formation in patients with chronic hepatitis B, and appears to have a modified course of carcinogenesis pathway that is diverted away from the biological behaviour of HBV and HCV infection.     

Dobutamine stress cardiac magnetic resonance versus echocardiography for the assessment of outcome in patients with suspected or known coronary artery disease. Are the two imaging modalities comparable?

Purpose

To compare the value of Dobutamine stress echocardiography (DSE) with that provided by Dobutamine Cardiac Magnetic Resonance (DCMR) for the non-invasive risk stratification of patients with suspected or known coronary artery disease (CAD).

Methods

Patients with suspected or known CAD underwent either DSE or DCMR using the same standardized protocol. Patient matching was then performed retrospectively for age, gender and risk factors. Outcome data including cardiac death and non-fatal myocardial infarction (defined as hard cardiac events) and ‘late’ revascularization performed > 90 days after the diagnostic procedures were collected during at least 6 months.

Results

Follow-up data were available in 1852 patients who completed either DSE (n = 884) or DCMR (n = 884) during a mean follow-up duration of 4.1 ± 2.4 and 3.9 ± 1.9 years, respectively (p = NS). Matched patients exhibited an overall high risk profile (69 ± 9 years; 69% male, 70% history of CAD and 26% diabetes mellitus in both groups). Using multivariable analysis, both modalities successfully identified patients with inducible ischemia at higher risk for subsequent hard cardiac events, surpassing the value of conventional risk factors like age, male gender and diabetes (HR = 9.2; 95%CI = 5.6–14.9 for DCMR versus 2.5; 95%CI = 1.7–3.7 for DSE). By testing for interaction the predictive capacity of DCMR was higher than that provided by DSE (p = 0.02). Patients with negative DCMR exhibited lower event rates compared to those with negative DSE (annual hard cardiac event rate of 0.8% versus 3.2%, p = 0.002).

Conclusions

DSE & DCMR aid the risk stratification of CAD patients. However, inducible WMA during DCMR are associated with a higher risk for subsequent cardiac events. Patients with negative DCMR on the other hand, exhibited a lower event rate compared to those with negative DSE.     

Searching for the right outcome? A systematic review and meta‐analysis of controlled trials using carotid intima‐media thickness or pulse wave velocity to infer antiatherogenic properties of thiazolidinediones

Introduction: Recent meta‐analyses cast doubt over purported beneficial effects of Peroxisome Proliferator Activated Receptor‐Gamma (PPAR‐γ) receptor agonists. Thiazolidinedione (TZD) trials using surrogate outcomes to postulate an antiatherogenic paradigm have been criticised as misinformative. We conducted an independent systematic review and meta‐analysis of controlled TZD studies incorporating carotid intima‐media thickness (CIMT) or pulse wave velocity (PWV) as primary outcome measures. The aim was to provide an evidence‐based overview of TZD intervention studies using markers prospectively linked to vascular outcome in type 2 diabetes. Methods: Systematic search of known databases for TZD intervention trials using mean thickness CIMT(n = 9) and ankle‐brachial PWV(n = 6) as primary outcome measures was performed. CIMT and PWV pooled weighted mean difference was calculated using a random effects model accounting for heterogeneity and publication bias. An indirect meta‐analysis provided a comparison of rosiglitazone and pioglitazone effects. Results: A composite of combined placebo and comparator controlled trials demonstrated a significant weighted mean difference of–0.06 mm for CIMT (95% CI–0.09 to–0.02, p = 0.001) and–0.72 ms^?1 for PWV (95% CI–1.28 to–0.16, p = 0.011) in favour of thiazolidiendione treatment. No TZD intraclass variation in CIMT (p = 0.96) or PWV (p = 0.33) change was observed. Conclusion: TZDs exhibit significant beneficial effects on aorto‐carotid atherosclerosis when assessed using prospectively validated non‐invasive techniques. Inferring clinical benefit in the absence of confirmatory outcome trials is questionable and caution should be exercised when interpreting intervention data with surrogate endpoints. TZD‐induced congestive cardiac failure or other unknown PPAR‐γ adverse effects are plausible explanations for the conflicting results of intervention trials using markers of atherosclerosis and clinical event outcomes.     

Bivalirudin is superior to heparins alone with bailout GP Ⅱb / Ⅲa inhibitors in patients with ST-segment elevation myocardial infarction transported emergently for primary percutaneous coronary intervention: a pre-specified analysis from the EUROMAX tria

Aims In the HORIZONS trial, in-hospital treatment with bivalirudin reduced bleeding and mortality in primary percutaneous coronary intervention(PCI) compared with heparin and routine glycoprotein Ⅱb / Ⅲa inhibitors(GPI). It is unknown whether this advantage of bivalirudin is observed in comparison with heparins only with GPI used as bailout. Methods and results In the EUROMAX study, 2198 patients with ST-segment elevation myocardial infarction(STEMI) were randomized during transport for primary PCI to bivalirudin or to heparins with optional GPI. Primary and principal outcome was the composites of death or nonCABG-related major bleeding at 30 days. This pre-specified analysis compared patients receiving bivalirudin(n = 1089) with those receiving heparins with routine upstream GPI(n = 649) and those receiving heparins only with GPI use restricted to bailout(n = 460). The primary outcome death and major bleeding occurred in5.1% with bivalirudin, 7.6% with heparin plus routine GPI(HR 0.67 and 95% CI 0.46-0.97, P = 0.034),and 9.8% with heparins plus bailout GPI(HR 0.52 and 95% CI 0.35-0.75, P = 0.006). Following adjustment by logistic regression, bivalirudin was still associated with significantly lower rates of the primary outcome(odds ratio 0.53, 95% CI 0.33-0.87) and major bleeding(odds ratio 0.44, 95% CI 0.24 – 0.82) compared with heparins alone with bailout GPI. Rates of stent thrombosis were higher with bivalirudin(1.6 vs. 0.6 vs.0.4%, P = 0.09 and 0.09). Conclusion Bivalirudin, started during transport for primary PCI, reduces major bleeding compared with both patients treated with heparin only plus bailout GPI and patients treated with heparin and routine GPI, but increased stent thrombosis.