Comparison of Acute Versus Subacute Coronary Angiography in Patients With NON-ST-Elevation Myocardial Infarction (from the NONSTEMI Trial).

The optimal timing of coronary angiography (CAG) in high-risk patients with acute coronary syndrome without persisting ST-segment elevation (NST-ACS) remains undetermined. The NON-ST-Elevation Myocardial Infarction trial aimed to compare outcomes in NSTE-ACS patients randomized to acute CAG (STEMI-like approach) with patients randomized to medical therapy and subacute CAG. We randomized 496 patients with suspected NST-ACS based on symptoms and significant regional ST depressions and/or elevated point-of-care troponin T (POC-cTnT) (≥50 ng/l) to either acute CAG (<2 hours, n = 245) or subacute CAG (<72 hours, n = 251). The primary end point was a composite of all-cause death, reinfarction, and readmission with congestive heart failure within 1 year from randomization. A final acute coronary syndrome (ACS) diagnosis was assigned to 429 (86.5%) patients. The median time from randomization to revascularization was 1.3 hours in the acute CAG group versus 51.1 hours in the subacute CAG group (p <0.001). The composite end point occurred in 25 patients (10.2%) in the acute CAG group and 29 (11.6%) in the subacute CAG group, p = 0.62. The acute CAG group had a 1-year all-cause mortality of 5.7% compared with 5.6% in the subacute CAG group, p = 0.96. In conclusion, neither the composite end point of all-cause death, reinfarction, and readmission with congestive heart failure nor mortality differed between an acute and subacute CAG approach in NSTE-ACS patients. However, identification of NSTE-ACS patients in the prehospital phase and direct triage to an invasive center is feasible, safe and may facilitate early diagnosis and revascularization.

Editor's Choice-Acute versus subacute angiography in patients with non-ST-elevation myocardial infarction - the NONSTEMI trial phase I.

BACKGROUND: The 2015 European Society of Cardiology non-ST-elevation myocardial infarction (NSTEMI) guidelines recommend angiography within 24 h in high-risk patients with NSTEMI. An organized STEMI-like approach with pre-hospital or immediate in-hospital triage for acute coronary angiography (CAG) may be of therapeutic benefit but it remains unknown whether the patients can be properly diagnosed in the pre-hospital setting. We aim to evaluate whether it is feasible to diagnose patients with NSTEMI in the pre-hospital phase or immediately upon admission. METHODS AND RESULTS: We randomized 250 patients to either acute or subacute CAG (i.e. <72 h of admission). Pre-hospital electrocardiogram acquisition and point-of-care troponin-T measurement ensured that 148 (59%) patients were identified already in the ambulance, whereas the remaining 102 (41%) patients were identified immediately after hospital admission. An acute coronary syndrome was verified in 215 (86%) and NSTEMI in 159 (64%) patients. The CAG rate was significantly higher in the acute CAG group (98% vs. 87%, p<0.001). A culprit lesion was identified in 74% and 64% of the patients underwent coronary revascularization: acute CAG group: 53% percutaneous coronary intervention, 5% hybrid, 7% coronary artery bypass grafting; conventional treatment: 48% percutaneous coronary intervention, 2% hybrid, 14% coronary artery bypass grafting, p=0.32. In patients randomized to acute CAG, time from randomization to CAG was 1.1 h; in patients randomized to subacute CAG it was two days. Time from randomization to initial revascularization was 1.3 h versus 2.4 days, and the median hospital stay was 4.0 days versus 4.5 days. Among patients randomized to subacute CAG, 17% crossed over to acute CAG and 5% developed STEMI before catheterization. CONCLUSION: Diagnosing NSTEMI patients in the pre-hospital phase or immediately upon hospital admission is feasible. Acute CAG may impact the mode of revascularization and is associated with earlier revascularization and shorter hospital stay. The clinical benefit of acute CAG in NSTEMI patients remains to be clarified.

Impact of type 2 diabetes on nitric oxide and adrenergic modulation of myocardial perfusion.

Type 2 diabetic patients are characterized by a reduced adenosine-induced hyperemic myocardial perfusion, which may contribute to their increased cardiovascular morbidity. We hypothesized that the reduced hyperemia can be explained by functional changes in endothelial or autonomic nervous regulation. In 12 type 2 diabetic patients without signs of ischemic heart disease and 14 age-matched control subjects, myocardial perfusion was measured at rest, during adenosine, and during adenosine and alpha-receptor blockade (phentolamine) using positron emission tomography on two separate days: 1) with, and 2) without nitric oxide (NO) inhibition with N(G)-nitro-L-arginine methyl ester. Myocardial perfusion during adenosine was lower in type 2 diabetic patients compared with control subjects (P = 0.05). No significant effect of NO inhibition on myocardial perfusion during adenosine was found in any of the groups. In control subjects, alpha-receptor blockade increased hyperemic myocardial vascular resistance during NO inhibition, whereas no effect was observed in type 2 diabetic patients. At rest, a significant correlation was observed between rate-pressure product and myocardial perfusion in control subjects. NO inhibition and type 2 diabetes abolished this correlation. Endothelial and cardiac autonomic nerve function seems to play only a minimal role in the reduced hyperemic myocardial perfusion in type 2 diabetic patients. However, the linear correlation between resting perfusion and cardiac work appears to be abolished in type 2 diabetes and during NO synthase inhibition.

Evaluation of iterative reconstruction (OSEM) versus filtered back-projection for the assessment of myocardial glucose uptake and myocardial perfusion using dynamic PET.

PURPOSE: Iterative reconstruction methods based on ordered-subset expectation maximisation (OSEM) has replaced filtered backprojection (FBP) in many clinical settings owing to the superior image quality. Whether OSEM is as accurate as FBP in quantitative positron emission tomography (PET) is uncertain. We compared the accuracy of OSEM and FBP for regional myocardial (18)F-FDG uptake and (13)NH(3) perfusion measurements in cardiac PET. METHODS: Ten healthy volunteers were studied. Five underwent dynamic (18)F-FDG PET during hyperinsulinaemic-euglycaemic clamp, and five underwent (13)NH(3) perfusion measurement during rest and adenosine-induced hyperaemia. Images were reconstructed using FBP and OSEM +/- an 8-mm Gaussian post-reconstruction filter. RESULTS: Filtered and unfiltered images showed agreement between the reconstruction methods within +/-2SD in Bland-Altman plots of K (i) values. The use of a Gaussian filter resulted in a systematic underestimation of K (i) in the filtered images of 11%. The mean deviation between the reconstruction methods for both unfiltered and filtered images was 1.3%. Agreement within +/-2SD between the methods was demonstrated for perfusion rate constants up to 2.5 min(-1), corresponding to a perfusion of 3.4 ml g(-1) min(-1). The mean deviation between the two methods for unfiltered data was 2.7%, and for filtered data, 5.3%. CONCLUSION: The (18)F-FDG uptake rate constants showed excellent agreement between the two reconstruction methods. In the perfusion range up to 3.4 ml g(-1) min(-1), agreement between (13)NH(3) perfusion obtained with OSEM and FBP was acceptable. The use of OSEM for measurement of perfusion values higher than 3.4 ml g(-1) min(-1) requires further evaluation.

Impact of type 2 diabetes on myocardial insulin sensitivity to glucose uptake and perfusion in patients with coronary artery disease.

BACKGROUND AND HYPOTHESIS: Myocardial insulin resistance (IR) is a feature of coronary artery disease (CAD) with reduced left ventricular ejection fraction (LVEF). Whether type 2 diabetes mellitus (T2DM) with CAD and preserved LVEF induces myocardial IR and whether insulin in these patients acts as a myocardial vasodilator is debated. METHODS: We studied 27 CAD patients (LVEF > 50%): 12 with T2DM (CAD+DM), 15 without T2DM (CAD-NoDM). Regional myocardial and skeletal glucose uptake, myocardial and skeletal muscle perfusion were measured with positron emission tomography. Myocardial muscle perfusion was measured at rest and during hyperemia in nonstenotic and stenotic regions with and without acute hyperinsulinemia. RESULTS: Myocardial glucose uptake was similar in CAD+DM and CAD-NoDM in both nonstenotic and stenotic regions [0.38 +/- 0.08 and 0.36 +/- 0.11 micromol/g.min; P value nonsignificant (NS)] and (0.35 +/- 0.09 and 0.37 +/- 0.13 micromol/g.min; P = NS). Skeletal glucose uptake was reduced in CAD+DM (0.05 +/- 0.04 vs. 0.10 +/- 0.05 micromol/g.min; P = 0.02), and likewise, whole-body glucose uptake was reduced in CAD+DM (4.0 +/- 2.8 vs. 7.0 +/- 2.4 mg/kg.min; P = 0.01). Insulin did not alter myocardial muscle perfusion at rest or during hyperemia. Insulin increased skeletal muscle perfusion in CAD-NoDM (0.11 +/- 0.03 vs. 0.06 +/- 0.03 ml/g.min; P = 0.02), but not in CAD+DM (0.08 +/- 0.04 and 0.09 +/- 0.05 ml/g.min; P = NS). CONCLUSION: Myocardial IR to glucose uptake is not an inherent feature in T2DM patients with preserved LVEF. Acute physiological insulin exposure exerts no coronary vasodilation in CAD patients irrespective of T2DM.

Does diabetes mellitus abolish the beneficial effect of primary coronary angioplasty on long-term risk of reinfarction after acute ST-segment elevation myocardial infarction compared with fibrinolysis? (A DANAMI-2 substudy).

Little is known about the effect of diabetes mellitus on long-term clinical outcome after primary percutaneous coronary intervention (pPCI) compared with fibrinolysis in patients who have acute ST-elevation myocardial infarction. We analyzed 3-year clinical outcome in diabetic patients and nondiabetic patients who had been randomized to fibrinolysis or pPCI in the DANAMI-2 trial to compare long-term clinical outcome. The primary end point was a composite of death, clinical reinfarction, or disabling stroke. Median follow-up was 3.8 years. Among 1,572 consecutive patients who had ST-elevation myocardial infarction and were randomized to pPCI or fibrinolysis, 173 (11.0%) had diabetes mellitus; 60 of these patients received metformin treatment and were excluded. After 3 years no difference was found between diabetic patients who underwent pPCI versus fibrinolysis (combined event p=0.37, reinfarction p=0.06 in favor of fibrinolysis), whereas pPCI was superior to fibrinolysis in nondiabetic patients (combined event p=0.002, clinical reinfarction p<0.001). Three-year incidence of clinical reinfarction analyzed with Cox's regression showed that pPCI compared with fibrinolysis increased the relative risk of clinical reinfarction in diabetic patients (relative risk 2.57, 95% confidence interval 1.48 to 4.46, p <0.001) but decreased the risk in nondiabetic patients (relative risk 0.52, 95% confidence interval 0.36 to 0.74, p<0.001). In conclusion, from the DANAMI-2 trial we hypothesize that diabetes may abolish the beneficial effect of pPCI on long-term risk of clinical reinfarction.

Insulin-stimulated myocardial glucose uptake and the relation to perfusion and the nitric oxide system.

In skeletal muscle, insulin increases glucose uptake through endothelium-derived nitric oxide (EDNO)-dependent vasodilation. Insulin also enhances myocardial glucose uptake, but it is unknown whether vasodilation participates in the underlying mechanism. We studied whether insulin-stimulated myocardial glucose uptake (MGU) is associated with perfusion changes and whether MGU is EDNO dependent. Myocardial perfusion (MBF) and MGU were measured three times with positron emission tomography in 8 healthy volunteers (56 +/- 6 years): (1). During a hyperinsulinemic euglycemic clamp (clamp), (2). during clamp and blockage of the nitric oxide synthesis by L-NMMA and (3). during clamp and nitric oxide stimulation with nitroglycerin. We measured MBF at rest before and during clamp utilizing (13)N-ammonia and (18)F-fluoro-deoxy-glucose as perfusion and glucose tracers, respectively. Hemodynamics were affected neither by insulin nor by L-NMMA. Nitroglycerin reduced rate-pressure product. Insulin did not affect MBF. L-NMMA reduced MBF (0.60 +/- 0.15 vs. 0.66 +/- 0.14 ml/g/min; p < 0.05), while MGU was unchanged. Nitroglycerin did not alter MBF, while MGU was reduced (0.44 +/- 0.11 vs. 0.52 +/- 0.13 micromol/g/min; p = 0.05). Insulin-stimulated MGU does not rely on a simultaneous increment of MBF. Myocardial glucose uptake can be stimulated even when MBF decreases, suggesting that autoregulation of MGU is preserved despite uncoupling of vascular autoregulation.