Global longitudinal strain by speckle tracking for infarct size estimation.

AIMS: To assess the utility of speckle tracking global longitudinal systolic strain (GLS) compared with traditional echocardiographic indices including left ventricular ejection fraction (LVEF), wall motion score index (WMSI), and end-systolic volume index (ESVI), in estimating the infarct size (IS) following a ST-elevation myocardial infarction (STEMI). METHODS AND RESULTS: The study includes 227 patients with STEMI and day 1 and day 30 echocardiograms, and myocardial perfusion imaging (MPI) only at day 30 to assess IS. IS was modelled by linear regression with echocardiographic parameters using MPI as reference. Resulting echocardiographic IS estimates were compared by ratios of standard deviations of model residuals (RSD). To estimate the resultant day 30 IS 1 day after a STEMI, GLS was more precise than LVEF (RSD: 0.91, P = 0.014) and ESVI (RSD: 0.88, P = 0.002), and comparable with WMSI (RSD 0.99, P = 0.86). To estimate IS from a day 30 echocardiogram, GLS was comparable with LVEF (RSD: 0.98, P = 0.68) and ESVI (RSD: 1.04, P = 0.40), but WMSI was more precise (RSD: 0.89, P = 0.006). Multiple linear regression revealed that on day 1 after STEMI, GLS significantly complemented the standard parameters separately (P-values all models <0.001) or combined [multivariable model: GLS (P = 0.001), WMSI (P = 0.03), LVEF (P = 0.40)]. On day 30, GLS significantly complemented LVEF and ESVI, but when WMSI was in the model, GLS's association with IS was not significant. CONCLUSION: On day 1 after revascularization for STEMI, GLS contains additional information about final IS compared with standard echocardiographic systolic function indices. Studies are needed to clarify whether this has prognostic implications.

Suppression of circulating free fatty acids with acipimox in chronic heart failure patients changes whole body metabolism but does not affect cardiac function.

Circulating free fatty acids (FFAs) may worsen heart failure (HF) due to myocardial lipotoxicity and impaired energy generation. We studied cardiac and whole body effects of 28 days of suppression of circulating FFAs with acipimox in patients with chronic HF. In a randomized double-blind crossover design, 24 HF patients with ischemic heart disease [left ventricular ejection fraction: 26 ± 2%; New York Heart Association classes II (n = 13) and III (n = 5)] received 28 days of acipimox treatment (250 mg, 4 times/day) and placebo. Left ventricular ejection fraction, diastolic function, tissue-Doppler regional myocardial function, exercise capacity, noninvasive cardiac index, NH(2)-terminal pro-brain natriuretic peptide (NT-pro-BNP), and whole body metabolic parameters were measured. Eighteen patients were included for analysis. FFAs were reduced by 27% in the acipimox-treated group [acipimox vs. placebo (day 28-day 0): -0.10 ± 0.03 vs. +0.01 ± 0.03 mmol/l, P < 0.01]. Glucose and insulin levels did not change. Acipimox tended to increase glucose and decrease lipid utilization rates at the whole body level and significantly changed the effect of insulin on substrate utilization. The hyperinsulinemic euglycemic clamp M value did not differ. Global and regional myocardial function did not differ. Exercise capacity, cardiac index, systemic vascular resistance, and NT-pro-BNP were not affected by treatment. In conclusion, acipimox caused minor changes in whole body metabolism and decreased the FFA supply, but a long-term reduction in circulating FFAs with acipimox did not change systolic or diastolic cardiac function or exercise capacity in patients with HF.

Cardiovascular and metabolic effects of 48-h glucagon-like peptide-1 infusion in compensated chronic patients with heart failure.

The incretin hormone glucagon-like peptide-1 (GLP-1) and its analogs are currently emerging as antidiabetic medications. GLP-1 improves left ventricular ejection fraction (LVEF) in dogs with heart failure (HF) and in patients with acute myocardial infarction. We studied metabolic and cardiovascular effects of 48-h GLP-1 infusions in patients with congestive HF. In a randomized, double-blind crossover design, 20 patients without diabetes and with HF with ischemic heart disease, EF of 30 +/- 2%, New York Heart Association II and III (n = 14 and 6) received 48-h GLP-1 (0.7 pmol.kg(-1).min(-1)) and placebo infusion. At 0 and 48 h, LVEF, diastolic function, tissue Doppler regional myocardial function, exercise testing, noninvasive cardiac output, and brain natriuretic peptide (BNP) were measured. Blood pressure, heart rate, and metabolic parameters were recorded. Fifteen patients completed the protocol. GLP-1 increased insulin (90 +/- 17 pmol/l vs. 69 +/- 12 pmol/l; P = 0.025) and lowered glucose levels (5.2 +/- 0.1 mmol/l vs. 5.6 +/- 0.1 mmol/l; P < 0.01). Heart rate (67 +/- 2 beats/min vs. 65 +/- 2 beats/min; P = 0.016) and diastolic blood pressure (71 +/- 2 mmHg vs. 68 +/- 2 mmHg; P = 0.008) increased during GLP-1 treatment. Cardiac index (1.5 +/- 0.1 l.min(-1).m(-2) vs. 1.7 +/- 0.2 l.min(-1).m(-2); P = 0.54) and LVEF (30 +/- 2% vs. 30 +/- 2%; P = 0.93), tissue Doppler indexes, body weight, and BNP remained unchanged. Hypoglycemic events related to GLP-1 treatment were observed in eight patients. GLP-1 infusion increased circulating insulin levels and reduced plasma glucose concentration but had no major cardiovascular effects in patients without diabetes but with compensated HF. The impact of minor increases in heart rate and diastolic blood pressure during GLP-1 infusion requires further studies. Hypoglycemia was frequent and calls for caution in patients without diabetes but with HF.

Amino acid transamination is crucial for ischaemic cardioprotection in normal and preconditioned isolated rat hearts--focus on L-glutamate.

We have found that cardioprotection by l-glutamate mimics protection by classical ischaemic preconditioning (IPC). We investigated whether the effect of IPC involves amino acid transamination and whether IPC modulates myocardial glutamate metabolism. In a glucose-perfused, isolated rat heart model subjected to 40 min global no-flow ischaemia and 120 min reperfusion, the effects of IPC (2 cycles of 5 min ischaemia and 5 min reperfusion) and continuous glutamate (20 mm) administration during reperfusion on infarct size and haemodynamic recovery were studied. The effect of inhibiting amino acid transamination was evaluated by adding the amino acid transaminase inhibitor amino-oxyacetate (AOA; 0.025 mm) during reperfusion. Changes in coronary effluent, interstitial (microdialysis) and intracellular glutamate ([GLUT](i)) concentrations were measured. Ischaemic preconditioning and postischaemic glutamate administration reduced infarct size to the same extent (41 and 40%, respectively; P < 0.05 for both), without showing an additive effect. Amino-oxyacetate abolished infarct reduction by IPC and glutamate, and increased infarct size in both control and IPC hearts in a dose-dependent manner. Ischaemic preconditioning increased [GLUT](i) before ischaemia (P < 0.01) and decreased the release of glutamate during the first 10 min of reperfusion (P = 0.03). A twofold reduction in [GLUT](i) from the preischaemic state to 45 min of reperfusion (P = 0.0001) suggested increased postischaemic glutamate utilization in IPC hearts. While IPC and AOA changed haemodynamics in accordance with infarct size, glutamate decreased haemodynamic recovery despite reduced infarct size. In conclusion, ischaemic cardioprotection of the normal and IPC-protected heart depends on amino acid transamination and activity of the malate-aspartate shuttle during reperfusion. Underlying mechanisms of IPC include myocardial glutamate metabolism.

Lack of cardioprotection from subcutaneously and preischemic administered liraglutide in a closed chest porcine ischemia reperfusion model.

BACKGROUND: Glucagon-like peptide 1 (GLP1) analogues are promising new treatment options for patients with type 2 diabetes, but may have both potentially beneficial and harmful cardiovascular effects. This may also be the case for the analogues of GLP1 for clinical use. The present study examined the effect of treatment with liraglutide, a long-acting GLP1 analogue, on myocardial ischemia and reperfusion in a porcine model. METHODS: Danish Landrace Pigs (70-80 kg) were randomly assigned to liraglutide (10 mug/kg) or control treatment given daily for three days before ischemia-reperfusion. Ischemia was induced by balloon occlusion of the left anterior descending artery for 40 minutes followed by 2.5 hours of reperfusion. The primary outcome parameter was infarct size in relation to the ischemic region at risk. Secondary endpoints were the hemodynamic parameters mean pulmonary pressure, cardiac output, pulmonary capillary wedge pressure as measured by a Swan-Ganz catheter as well as arterial pressure and heart rate. RESULTS: The infarct size in relation to ischemic risk region in the control versus the liraglutide group did not differ significantly: 0.46 +/- 0.14 and 0.54 +/- 0.12) (mean and standard deviation (SD), p = 0.21). Heart rate was significantly higher in the liraglutide group during the experiment, while the other hemodynamic parameters did not differ significantly. CONCLUSION: Liraglutide has a neutral effect on myocardial infarct size in a porcine ischemia-reperfusion model.

ST changes before and during primary percutaneous coronary intervention predict final infarct size in patients with ST elevation myocardial infarction.

BACKGROUND: In patients with ST elevation myocardial infarction (STEMI), spontaneous ST resolution (spontSTR) is a marker of successful microvascular reperfusion. The significance of increase in ST elevation during reperfusion therapy (the ST peak phenomenon), however, is controversial. AIMS: The purpose of the study was to evaluate whether preprocedural and periprocedural ST changes predict final infarct size (IS) in STEMI patients treated with primary percutaneous coronary intervention (primary PCI). METHODS: Twelve-lead electrocardiograms (ECGs) were acquired in the prehospital phase and on admission in 200 STEMI patients transferred for primary PCI. Continuous ST monitoring was performed during and 90 minutes after primary PCI. The exact timing of interventional procedures and the resulting thrombolysis in myocardial infarction (TIMI) flow were registered. A 1-month single-photon emission computerized tomography was performed to evaluate IS. Patients were stratified into groups according to preprocedural and periprocedural ST changes as follows: patients with spontSTR before primary PCI and without (A) or with (B) ST peak during primary PCI and patients with persistent ST elevation before primary PCI and without (C) or with (D) ST peak during primary PCI. FINDINGS: Groups A (n = 45), B (n = 10), C (n = 109), and D (n = 36) differed with regard to IS (median, 2%, 3%, 13% vs 22% of the left ventricle; P < .0001). In multivariable analysis adjusting for baseline characteristics, preprocedural and periprocedural ECG findings and routine angiography findings, spontSTR was associated with smaller IS (B = -8.6%; P < .001), whereas the ST peak phenomenon was associated with larger IS (B = +5.0%; P = .006). There was no difference in TIMI flow grades in relation to coronary interventions among patients with and without ST peak during primary PCI. CONCLUSIONS: In STEMI patients, spontSTR before primary PCI and the ST peak phenomenon during primary PCI predict minor vs extensive IS independent of angiographic patency grades. Further studies are needed to clarify whether the ST peak phenomenon is "a marker of injury before reperfusion" or "a marker of reperfusion-induced injury."

Proteomic analysis identifies mitochondrial metabolic enzymes as major discriminators between different stages of the failing human myocardium.

OBJECTIVES: Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM). METHODS: We studied biopsies from 9 patients with stable chronic heart failure undergoing coronary artery bypass surgery (CABG) (EF 34% +/- 3%) and from 4 patients with ESFM undergoing heart transplantation (EF 17% +/- 5%). In CABG patients paired echocardiographic studies before and 6 months after revascularization classified dysfunctional myocardium as RDM or IRDM. Regions with preserved contractile function served as control. We used two-dimensional gel electrophoresis (2D-PAGE) and computerized image analysis to investigate myocardial protein expression. Proteins were identified by in-gel digestion and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Among 3 significantly altered protein spots in RDM we identified 2 up-regulated glycolytic enzymes. In IRDM 15 proteins were signficantly altered of which we identified 10, among these 6 were down-regulated mitochondrial enzymes. In ESFM 9 of 12 significantly altered protein spots were identified. Six were down-regulated mitochondrial enzymes. CONCLUSION: Myocardial metabolism may be involved in the progression of heart failure to irreversible dysfunction and end-stage heart failure.

Long-term outcome of primary angioplasty compared with fibrinolysis across age groups: a Danish Multicenter Randomized Study on Fibrinolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI-2) substudy.

BACKGROUND: Primary angioplasty in patients with acute ST-elevation myocardial infarction has been shown to be superior to fibrinolysis. Whether elderly patients have the same long-term benefit from angioplasty, compared with fibrinolysis, as younger patients is unknown. METHODS: The effect of angioplasty versus fibrinolysis was investigated in 1,572 patients from the DANAMI-2 study across age groups. End points were total mortality and a composite end point of death, reinfarction, or disabling stroke. Follow-up was 3 years. RESULTS: Increasing age was associated with mortality (adjusted hazard ratio [HR] 2.45 per 10 year increment, 95% confidence interval [CI] 1.78-3.37, P < .0001) and a higher composite event rate (adjusted HR 1.51, CI 1.26-1.82, P < .0001). The long-term superiority of angioplasty over fibrinolysis on the combined outcome was independent of age: patients aged <56 years (HR 0.73, CI 0.41-1.31); 56 to 65 years (HR 0.83, CI 0.52-1.33); 66 to 75 years (HR 0.71, CI 0.48-1.04); and >75 years (HR 0.83, CI 0.59-1.17) (P = .006 for overall treatment effect and P = .5 for interaction between age and treatment). There was no long-term effect of angioplasty versus fibrinolysis on mortality and no interaction with age (P = .5 and P for interaction = .6). CONCLUSIONS: The long-term effect of primary angioplasty compared with fibrinolysis in patients with ST-elevation myocardial infarction is not affected by age.

Routine thrombectomy in percutaneous coronary intervention for acute ST-segment-elevation myocardial infarction: a randomized, controlled trial.

BACKGROUND: Distal embolization during primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction may result in reduced myocardial perfusion, infarct extension, and impaired prognosis. METHODS AND RESULTS: In a prospective randomized trial, we studied the effect of routine thrombectomy in 215 patients with ST-segment-elevation myocardial infarction lasting <12 hours undergoing primary PCI. Patients were randomized to thrombectomy pretreatment or standard PCI. The primary end point was myocardial salvage measured by sestamibi SPECT, calculated as the difference between area at risk and final infarct size determined after 30 days (percent). Secondary end points included final infarct size, ST-segment resolution, and troponin T release. Baseline variables, including ST-segment elevation and area at risk, were similar. Salvage was not statistically different in the thrombectomy and control groups (median, 13% [interquartile range, 9% to 21%] and 18% [interquartile range, 7% to 25%]; P=0.12), but 24 patients in the thrombectomy group and 12 patients in the control group did not have an early SPECT scan, mainly because of poor general or cardiac condition (P=0.04). In the thrombectomy group, final infarct size was increased (median, 15%; [interquartile range, 4% to 25%] versus 8% [interquartile range, 2% to 18%]; P=0.004). CONCLUSIONS: Thrombectomy performed as routine therapy in primary PCI for ST-elevation myocardial infarction does not increase myocardial salvage. The study suggests a possible deleterious effect of thrombectomy, resulting in an increased final infarct size, and does not support the use of thrombectomy in unselected primary PCI patients.

Simple risk stratification at admission to identify patients with reduced mortality from primary angioplasty.

BACKGROUND: Randomized trials comparing fibrinolysis with primary angioplasty for acute ST-elevation myocardial infarction have demonstrated a beneficial effect of primary angioplasty on the combined end point of death, reinfarction, and disabling stroke but not on all-cause death. Identifying a patient group with reduced mortality from an invasive strategy would be important for early triage. The Thrombolysis in Myocardial Infarction (TIMI) risk score is a simple validated integer score that makes it possible to identify high-risk patients on admission to hospital. We hypothesized that a high-risk group might have a reduced mortality with an invasive strategy. METHODS AND RESULTS: We classified 1527 patients from the Danish Multicenter Randomized Study on Fibrinolytic Therapy Versus Acute Coronary Angioplasty in Acute Myocardial Infarction (DANAMI-2) trial with information for all variables necessary for calculating the TIMI risk score as low risk (TIMI risk score, 0 to 4) or high risk (TIMI risk score > or =5) and investigated the effect of primary angioplasty versus fibrinolysis on mortality and morbidity in the 2 groups. Follow-up was 3 years. We classified 1134 patients as low risk and 393 as high risk. There was a significant interaction between risk status and effect of primary angioplasty (P=0.008). In the low-risk group, there was no difference in mortality (primary angioplasty, 8.0%; fibrinolysis, 5.6%; P=0.11); in the high-risk group, there was a significant reduction in mortality with primary angioplasty (25.3% versus 36.2%; P=0.02). CONCLUSIONS: Risk stratification at admission based on the TIMI risk score identifies a group of high-risk patients who have a significantly reduced mortality with an invasive strategy of primary angioplasty.

Sestamibi single photon emission computed tomography immediately after primary percutaneous coronary intervention identifies patients at risk for large infarcts.

BACKGROUND: Primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction results in TIMI 3 flow in most patients. However, despite TIMI 3 flow, some patients do not achieve adequate tissue perfusion and have large infarctions. Techniques that, in the acute setting, could identify these patients at increased risk would potentially enable specific interventions to enhance perfusion. The object of the present study was to test whether corrected TIMI frame count (CTFC), myocardial blush grade (MBG), ST-segment resolution, and myocardial perfusion imaging (MPI) can identify those patients who, despite successful treatment with primary PCI for ST-elevation myocardial infarction, are at risk for large infarcts. METHODS: In 61 patients with TIMI 3 flow after primary PCI, CTFC, MBG, ST-segment resolution, and quantitative MPI by technetium Tc 99m sestamibi single photon emission computed tomography were estimated immediately after primary PCI. Infarct size was assessed by peak lactate dehydrogenase (LDH) and by MPI after 3 months. RESULTS: Infarct size by MPI was 12% (4, 23), and peak LDH was 1410 U/L (870, 2220); these measures correlated (rho = 0.80, P < .001). The acute perfusion defect predicted infarct size using either method (MPI rho = 0.88, P < .001; LDH rho = 0.77, P < .001); ST-segment residual correlated weakly to infarct size, whereas CTFC and MBG did not. In multivariate analysis, the acute perfusion defect was the only significant predictor of infarct size. CONCLUSION: Myocardial perfusion imaging performed immediately after successful PCI can identify patients at increased risk for large infarcts due to impaired tissue perfusion. Acute MPI might serve as a tool for early identification of patients, who, despite epicardial TIMI 3 flow, have inadequate tissue level perfusion.

Adaptation of nonrevascularized human hibernating and chronically stunned myocardium to long-term chronic myocardial ischemia.

It is unknown whether human chronically ischemic dysfunctional myocardium degenerates over time or adapts to chronic ischemia. We studied whether perfusion, metabolism, and contractile function and reserve can be preserved in nonrevascularized human chronically stunned and hibernating myocardium. We studied 16 event-free, medically treated patients with ejection fractions of 31 +/- 2% and chronically stunned or hibernating myocardium in 56 +/- 5% of the left ventricle on technetium-99m sestamibi single-photon emission computed tomography/fluorine-18 fluorodeoxyglucose (FDG) positron emission tomography. Patients underwent repeat single-photon emission computed tomography, positron emission tomography, and tissue Doppler echocardiography at rest and during stress at follow-up after 25 +/- 4 months, and we investigated whether measurements of myocardial viability remained stable over time. Patients were stable with respect to New York Heart Association class and global left ventricular function (30 +/- 2%, p = 0.81). Wall motion score was unaltered in hibernating myocardium and chronically stunned regions, and a contractile reserve by tissue Doppler stress echocardiography was preserved. Overall, 74% of hibernating myocardium and chronically stunned regions retained their initial perfusion/metabolism pattern at follow-up. In hibernating myocardium, initial and follow-up sestamibi uptakes (53 +/- 1% and 53 +/- 2%, p = 0.85) and FDG uptakes (76 +/- 1% and 74 +/- 1%, p = 0.21) did not differ. In chronically stunned regions, sestamibi uptake displayed a minor decrease at follow-up (70 +/- 1% vs 67 +/- 1%, p <0.01) and FDG uptake remained constant (68 +/- 2% and 67 +/- 1%, p = 0.21). In conclusion, myocardial perfusion, FDG uptake, and contractile function in nonrevascularized chronically stunned and hibernating myocardium adapt to chronic ischemia in patients who are free of events. In chronically stunned regions, adaptation may be less complete than in hibernating myocardium.

Acute haemodynamic effects of erythropoietin alone and in combination with dopamine in a porcine model.

BACKGROUND: Previous studies in rodents from different kinds of shock models and isolated vessel models indicate that erythropoietin (EPO) has haemodynamic effects through interaction with sympathetic stimuli. This has relevance to the recently described non-haematopoietic effects of EPO, e.g. tissue protective effects. Studies describing the acute effects on integrated physiological haemodynamic variables in larger animal models are scarce though. AIM: To examine the acute effects of EPO on standard physiological haemodynamic parameters as well as a possible synergistic effect of a sympathetic agonist (dopamine) and EPO on these parameters. RESULTS AND DESIGN: A porcine model was applied. Invasive haemodynamic variables were recorded at baseline, during 2 h after EPO injection and with addition of dopamine. Significant changes were only seen with addition of dopamine. Thus cardiac output increased only significantly in control group (21% versus 4%, P<0.05), and accordingly a decline in systemic vascular resistance was only seen in the control group (19% versus 5%, P< 0.05) with addition of dopamine. Pulmonary vascular resistance increased in EPO group (42% versus unchanged, P<0.05). There was a trend towards increase in left ventricular contractility as measured by slope of the pressure-volume relation (E(max)) in EPO group with addition of dopamine. CONCLUSION: Erythropoietin has small but significant haemodynamic effects on the response to a sympathetic agonist in the present minimal invasive porcine model.

Three-year outcome after coronary stenting versus bypass surgery for the treatment of multivessel disease.

BACKGROUND: The primary results of Arterial Revascularization Therapy Study reported a greater need for repeated revascularization after percutaneous coronary intervention with stenting (PCI). However, PCI was less expensive than coronary artery bypass grafting (CABG) and offered the same degree of protection against death, stroke, and myocardial infarction. METHODS AND RESULTS: Patients with multivessel disease (n=1205) were randomly assigned to either CABG or PCI and followed up for up to 3 years. Survival rates without stroke or myocardial infarction were similar in each group at 1 year and 3 years (90.5% versus 91.4% for PCI versus CABG at 1 year and 87.2% versus 88.4% for PCI versus CABG at 3 years). However, the respective repeat revascularization rates were 21.2% and 26.7% at 1 and 3 years in patients allocated to PCI, compared with 3.8% and 6.6% in patients allocated to CABG (P<0.0001). Diabetes (P<0.0009) and maximal pressure for stent deployment (P<0.002) are the strongest independent predictors of events at 3 years after PCI, whereas left anterior descending coronary artery grafting (P<0.006) is the best predictor of event-free survival at 3 years after CABG. The incremental cost of surgery compared with PCI for an event-free patient was 19 257 at 1 year but decreased to 10 492 at 3 years. It remained at 142 391 at 3 years when revascularization procedures were excluded in the efficacy end point, however. CONCLUSIONS: Three-year survival rates without stroke and myocardial infarction are identical in both groups, and the cost/benefit ratio of stenting is determined primarily by the increasing need for revascularization in the PCI group.

Danish multicenter randomized study on fibrinolytic therapy versus acute coronary angioplasty in acute myocardial infarction: rationale and design of the DANish trial in Acute Myocardial Infarction-2 (DANAMI-2).

BACKGROUND: Randomized trials have indicated that primary coronary angioplasty performed in patients admitted directly to highly-experienced angioplasty centers offers certain advantages over intravenous fibrinolytic therapy. However, the large majority of patients with acute myocardial infarction are submitted to hospitals without a catheterization laboratory. This means that additional transportation will be necessary for many patients if a strategy of acute coronary angioplasty is to be introduced as routine treatment. The delay of treatment caused by transportation might negate (part of) the benefits of primary angioplasty compared to fibrinolytic therapy given immediately at the local hospital. STUDY DESIGN: The DANish trial in Acute Myocardial Infarction-2 (DANAMI-2) is the first large-scale study to clarify, in a whole community, which of the 2 treatment strategies is best. A total of 1900 patients with ST-elevation myocardial infarction are to be randomized: 800 patients will be admitted to invasive hospitals and 1100 patients will be admitted to referral hospitals. Half of the 1100 patients admitted to referral hospitals will immediately be transferred to an invasive center to be treated with primary angioplasty. IMPLICATIONS: If acute transfer from a local hospital to an angioplasty center is the superior strategy, primary angioplasty should be offered to all patients as routine treatment on a community basis.

Effect of carvedilol on microcirculatory and glucose metabolic regulation in patients with congestive heart failure secondary to ischemic cardiomyopathy.

In a randomized (2:1), double-blinded design study, we studied 25 patients with congestive heart failure (66 +/- 9 years, ejection fraction 30 +/- 7%) before and after 23-week treatment with the beta blocker carvedilol 25 mg twice daily (n = 17) or placebo (n = 8) in addition to standard therapy. Using dynamic positron emission tomography, myocardial perfusion at rest and perfusion reserve after dipyridamole (0.56 mg/kg/min) were measured. Myocardial glucose uptake and plasma levels of catecholamines were also estimated. Carvedilol treatment reduced the rate-pressure product (8,781 +/- 2,672 vs 6,342 +/- 1,346, p <0.01) and improved ejection fraction (29 +/- 7% vs 37 +/- 11%, p <0.001), whereas no changes were observed in the control group. Perfusion at rest was unchanged in the placebo group (0.81 +/- 0.17 vs 0.86 +/- 0.23 ml/g/min, p = NS), whereas the carvedilol-treated group showed a significant reduction (0.88 +/- 0.26 vs 0.75 +/- 0.16 ml/g/min, p <0.05). Dipyridamole-induced hyperemia was significantly reduced after carvedilol treatment (1.51 +/- 0.45 vs 1.31 +/- 0.51 ml/g/min, p <0.001), whereas myocardial perfusion reserve was unaltered. Carvedilol did not alter myocardial glucose uptake (0.33 +/- 0.14 vs 0.32 +/- 0.12 micromol/g/min, p = NS) or the plasma catecholamines levels. We therefore conclude that in patients with congestive heart failure, carvedilol reduced resting and hyperemic perfusion. No effect on glucose uptake or catecholamine levels was observed. The reduced perfusion at rest must reflect reduced perfusion demand and thereby a higher threshold for myocardial ischemia and protection against myocardial damage or malignant arrhythmia. These effects may serve as a pathophysiologic explanation for the reduced mortality in patients with congestive heart failure who receive carvedilol.

Effect of oral nitroglycerin and cold stress on myocardial perfusion in areas subtended by stenosed and nonstenosed coronary arteries.

Physical obstruction and coronary vasoconstriction mediated by adrenergic stress are believed to be responsible for episodes of myocardial hypoperfusion and angina. Nitroglycerin relieves symptoms by reducing preload and dilating epicardial vessels. The net perfusion change and relation to stenosis severity of nitroglycerin and adrenergic stress have been debated. This study aimed to evaluate whether oral nitroglycerin and adrenergic stress alters perfusion in myocardial segments subtended by stenosed and nonstenosed coronary arteries. Myocardial perfusion was quantified (using N-13-ammonia positron emission tomography [PET]) at rest, after oral nitroglycerin 400 microg, and after cold stress in 25 patients with coronary artery disease (62 +/- 9 years, 21 men) and in 30 controls (34 +/- 9 years, 22 men). Myocardial perfusion was quantified in areas supplied by stenosed (>70%) and nonstenosed (<30%) coronary arteries. The cold pressor test did not significantly alter myocardial perfusion in any of the groups. However, when normalized for rate-pressure product, the response in stenosed areas showed a significantly more pronounced reduction compared with nonstenosed areas (0.78 +/- 0.18 vs 0.64 +/- 0.19 ml/g/min, p <0.005 and 0.86 +/- 0.19 vs 0.73 +/- 0.24 ml/g/min, p <0.05, p <0.05) for intergroup comparison. In both stenosed areas and nonstenosed areas nitroglycerin increased perfusion (0.51 +/- 0.14 vs 0.60 +/- 0.17 ml/g/min, p <0.05 and 0.56 +/- 0.14 vs 0.61 +/- 0.17 ml/g/min, p <0.05). Nitroglycerin did not alter myocardial perfusion in the control group. There was a negative correlation between the cold pressor test response and stenosis severity (r(2) = 0.17, p <0.046), whereas this was not the case for nitroglycerin. In patients with coronary artery disease, myocardial segments supplied by stenosed coronary arteries showed an altered perfusion response to adrenergic stress. Oral nitroglycerin increased myocardial perfusion irrespective of the presence of a stenosis.

Impact of daily life myocardial ischemia in patients with chronic reversible and irreversible myocardial dysfunction.

Repetitive myocardial ischemia during daily life has been suggested as the underlying mechanism of reversible myocardial dysfunction, which may progress into a hibernating state. Thirty-seven patients with ischemic cardiomyopathy (ejection fraction 35 +/- 7%) underwent positron emission tomography (N-13 ammonia and 18-F-fluoro-2-deoxy-glucose [FDG]) and exercise testing before coronary artery bypass grafting (CABG) and 48- hour ambulatory electrocardiographic monitoring to detect ischemia before CABG and 6 months postoperatively. Reversibility of regional myocardial dysfunction was detected by echocardiographic follow-up at 5 days, 2 months, and 6 months after the operation. Preoperatively, ischemic episodes during daily activities were more common (2 [25th to 75th percentiles 0 to 4] vs 0 episodes, p <0.01) and duration of ischemia longer (9 [25th to 75th percentiles 0 to 37] vs 0 [25th to 75th percentiles 0 to 1] minutes, p <0.02) in patients with reversible dysfunction (n = 15) than in patients with irreversible dysfunction (n = 22). The number of ischemic episodes per patient correlated with the numbers of reversibly dysfunctional segments (p = 0.003), viable segments as seen by positron emission tomography (p <0.05), and flow-metabolic mismatch segments (p <0.05). CABG eliminated ambulatory ischemic episodes in patients with reversible dysfunction (0 episodes, p <0.05 vs before CABG). Preoperatively, all patients with reversible dysfunction had a positive exercise test (14 of 15 patients), whereas daily life ischemia was present in 60% of patients. Reversibly dysfunctional segments in patients with ambulatory ischemia had faster recovery of function (15 of 28 patients vs 2 of 12 patients recovered at 5 days, p <0.05), higher FDG uptake (0.86 +/- 0.19% vs 0.71 +/- 0.24%, p <0.05) than in patients without ambulatory ischemia, whereas perfusion was similar (0.63 +/- 0.20 and 0.62 +/- 0.19 ml/g/min). Thus, exercise-induced myocardial ischemia is associated with reversibility of myocardial dysfunction, but not all patients with reversible ischemic cardiomyopathy have ischemic attacks during daily life.

Revascularization in multivessel disease: comparison between two-year outcomes of coronary bypass surgery and stenting.

OBJECTIVE: The recent appreciation that stenting has improved the short- and long-term outcomes of patients treated with coronary angioplasty has made it imperative to reconsider the comparison between surgery and percutaneous interventions in patients with multivessel disease. METHODS: One thousand two hundred five patients were randomly assigned to undergo bypass surgery or angioplasty with stent implantation when there was consensus between the cardiac surgeon and interventional cardiologist as to equivalent treatability. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at 1 year. Major adverse cardiac and cerebrovascular events at 2 years constituted a secondary end point. RESULTS: At 2 years, 89.6% of the surgical group and 89.2% of the stent group were free from death, stroke, and myocardial infarction (log-rank test P =.65). Among patients who survived without stroke or myocardial infarction, 19.7% in the stent group underwent a second revascularization, as compared with 4.8% in the surgical group (P <.001). At 2 years, 84.8% of the surgical group and 69.5% of the stent group were event-free survivors (log-rank test P <.001), and 87.2% in the surgical cohort and 79.6 % in the stent group were angina-free survivors (P =.001). In the diabetes subgroup, 82.3% of the surgical group and 56.3% of the stent group were free from any events after 2 years (log-rank test P <.001). CONCLUSION: The difference in outcome between surgery and stenting observed at 1 year in patients with multivessel disease remained essentially unchanged at 2 years. Stenting was associated with a greater need for repeat revascularization. In view of the relatively greater difference in outcome in patients with diabetes, surgery clearly seems to be the preferable form of treatment for these patients.

Regional myocardial perfusion during chronic biventricular pacing and after acute change of the pacing mode in patients with congestive heart failure and bundle branch block treated with an atrioventricular sequential biventricular pacemaker.

BACKGROUND: Biventricular (BiV) pacing has been found to improve systolic function and exercise tolerance in patients with severe congestive heart failure and bundle branch block. The mechanisms behind this beneficial effect is still not sufficiently clarified. AIM: To evaluate the regional myocardial perfusion (MP) during BiV pacing and after acute change of the pacing mode to conventional dual chamber (DDD) pacing, and single chamber atrial (AAI) pacing in patients with severe congestive heart failure and prolonged QRS width treated with chronic BiV pacing. METHODS AND RESULTS: Fourteen patients (age 63+/-7 years, 13 male) were evaluated 13+/-7 months after implantation of a triple-chamber biventricular pacemaker. MP was quantified with 13N-labeled ammonia positron emission tomography during BiV pacing, DDD pacing, and AAI pacing. MP was assessed in the anterior, lateral, inferior, and septal regions, and the global mean MP was calculated. Clinical assessment was performed before pacemaker implantation and after at least 3 months of BiV pacing including a 6-min walk test (WT), New York Heart Association (NYHA) class functional score and echocardiography. Global mean MP (BiV: 0.65+/-0.20 vs. DDD: 0.65+/-0.21 vs. AAI: 0.65+/-0.18 mlg(-1)min(-1)) and MP in each of the four regions did not differ between the three pacing modes. The patients improved clinically during BiV pacing; 6 min WT increased (338+/-59 vs. 415+/-73 m, P<0.001), NYHA class score improved (class I/II/III/IV: 0/0/11/3 vs. 1/9/2/0, P<0.001), and left ventricular ejection fraction increased (21+/-5 vs. 29+/-8%, P=0.004). CONCLUSION: No differences in regional MP are detectable after chronic BiV pacing when the pacing mode is changed acutely in patients with severe congestive heart failure and bundle branch block. This finding indicates, that the clinical improvement caused by BiV pacing is not associated with any increase in the MP and thereby oxygen demand.