Return to work after percutaneous coronary intervention: the predictive value of self-reported health compared to clinical measures.

AIMS: Coronary heart disease is prevalent in the working-age population. Traditional outcome measures like mortality and readmission are of importance to evaluate the prognosis but are hardly sufficient. Ability to work is an additional outcome of clinical and societal significance. We describe trends and predictors of Return To Work (RTW) after PCI and describe a possible benefit using patient-reported measures in risk stratification of RTW. METHODS: A total of 1585 patients aged less than 67 years treated with PCI in 2006-2008 at the Aarhus University Hospital were enrolled. Clinical information was provided through the West Denmark Heart Registry, and 4 weeks after PCI we mailed a questionnaire regarding self-rated health (response rate 83.5%). RTW was defined at weekly basis using extensive register data on transfer payments. Predictors of RTW were analysed as time to event. ROC curves constructed by logistic regression of predicting variables were evaluated by the c-statistic. RESULTS: Four weeks before PCI 50% of the patients were working; the corresponding figures were 25% after 4 weeks, 36% after 12 weeks, and 43% after one year. The patients' self-rated health one month after the procedure was a significant better predictor of RTW compared to other variables including LVEF, both at short (12 weeks) and long (one year) term. CONCLUSIONS: The patient's self-rated health four weeks after the procedure was a stronger predictor than left ventricular ejection fraction (LVEF), and consequently useful when patients seek medical advice with respect to RWT.

Prehospital troponin T testing in the diagnosis and triage of patients with suspected acute myocardial infarction.

Prehospital electrocardiographic (ECG) diagnosis has improved triage and outcome in patients with acute ST-elevation myocardial infarction. However, many patients with acute myocardial infarction (AMI) present with equivocal ECG patterns making prehospital ECG diagnosis difficult. We aimed to investigate the feasibility and ability of prehospital troponin T (TnT) testing to improve diagnosis in patients with chest pain transported by ambulance. From June 2008 through September 2009, patients from the central Denmark region with suspected AMI and transported by ambulance were eligible for prehospital TnT testing with a qualitative point-of-care test (cutpoint 0.10 ng/ml). Quantitative TnT was measured at hospital arrival and after 8 and 24 hours (cutpoint 0.03 ng/ml). A prehospital electrocardiogram was recorded in all patients. Prehospital TnT testing was attempted in 958 patients with a 97% success rate. In 258 patients, in-hospital TnT values were increased (≥0.03 ng/ml) during admission. The prehospital test identified 26% and the first in-hospital test detected 81% of patients with increased TnT measurements during admission. A diagnosis of AMI was established in 208 of 258 patients with increased TnT. The prehospital test identified 30% of these patients, whereas the first in-hospital test detected 79%. Median times from symptom onset to blood sampling were 83 minutes (46 to 167) for the prehospital sample and 165 minutes (110 to 276) for the admission sample. In conclusion, prehospital TnT testing is feasible with a high success rate. This study indicates that prehospital implementation of quantitative tests, with lower detection limits, could identify most patients with AMI irrespective of ECG changes.

Metabolic fingerprint of ischaemic cardioprotection: importance of the malate-aspartate shuttle.

The convergence of cardioprotective intracellular signalling pathways to modulate mitochondrial function as an end-target of cytoprotective stimuli is well described. However, our understanding of whether the complementary changes in mitochondrial energy metabolism are secondary responses or inherent mechanisms of ischaemic cardioprotection remains incomplete. In the heart, the malate-aspartate shuttle (MAS) constitutes the primary metabolic pathway for transfer of reducing equivalents from the cytosol into the mitochondria for oxidation. The flux of MAS is tightly linked to the flux of the tricarboxylic acid cycle and the electron transport chain, partly by the amino acid l-glutamate. In addition, emerging evidence suggests the MAS is an important regulator of cytosolic and mitochondrial calcium homeostasis. In the isolated rat heart, inhibition of MAS during ischaemia and early reperfusion by the aminotransferase inhibitor aminooxyacetate induces infarct limitation, improves haemodynamic responses, and modulates glucose metabolism, analogous to effects observed in classical ischaemic preconditioning. On the basis of these findings, the mechanisms through which MAS preserves mitochondrial function and cell survival are reviewed. We conclude that the available evidence is supportive of a down-regulation of mitochondrial respiration during lethal ischaemia with a gradual 'wake-up' during reperfusion as a pivotal feature of ischaemic cardioprotection. Finally, comments on modulating myocardial energy metabolism by the cardioprotective amino acids glutamate and glutamine are given.

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.

Remote Ischemic Conditioning in Patients With Myocardial Infarction Treated With Primary Angioplasty: Impact on Left Ventricular Function Assessed by Comprehensive Echocardiography and Gated Single-Photon Emission CT.

BACKGROUND: we have found that remote ischemic conditioning (rIC), adjunctive to primary angioplasty, increases myocardial salvage in patients with ST-segment elevation myocardial infarction (STEMI) and extensive myocardial area at risk (AAR). The present substudy aimed to evaluate the short-term effects of rIC on left ventricular (LV) function. METHODS AND RESULTS: patients with a first STEMI were randomized to rIC (4 cycles of 5 minutes upper-limb ischemia) during transfer to primary percutaneous coronary intervention (pPCI) (n=123) versus pPCI alone (n=119). Ejection fraction (EF), LV volumes, (2D and 3D echocardiography and myocardial perfusion imaging), and speckle-tracking global longitudinal strain were compared between treatment groups. There was no significant difference in LV function at day 1 (EF-2D, 0.51±0.10 versus 0.49±0.10; P=0.22) and after 30 days (EF-2D, 0.54±0.08 versus 0.53±0.10) between the rIC and the pPCI-alone groups. In patients with extensive AAR ≥35% of LV (n=53), EF after 30 days was higher after rIC than after pPCI alone (EF-2D, 0.51±0.07 versus 0.46±0.09; P=0.05). In patients with anterior infarction (n=97), rIC preserved LV function on day 1 (EF-2D, 0.51±0.11 versus 0.46±0.11; P=0.03) and persistently after 30 days (EF-2D, 0.55±0.08 versus 0.50±0.11; P=0.04; EF-myocardial perfusion imaging, 0.55±0.10 versus 0.49±0.12; P=0.02). These patients had similar AAR, whereas rIC reduced infarct size from 16% to 7% of LV (P=0.01). CONCLUSIONS: although no significant overall effect was observed, rIC seemed to result in modest improvement in LV function in high-risk patients prone to develop large myocardial infarcts. These results need to be confirmed in larger trials.

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.

A UPLC-MS/MS application for profiling of intermediary energy metabolites in microdialysis samples--a method for high-throughput.

Research within the field of metabolite profiling has already illuminated our understanding of a variety of physiological and pathological processes. Microdialysis has added further refinement to previous models and has allowed the testing of new hypotheses. In the present study, a new ultra-performance liquid chromatography/electrospray-tandem mass spectrometry (UPLC-ESI-MS/MS) method for the simultaneous detection and quantification of intermediary energy metabolites in microdialysates was developed. The targeted metabolites were mainly from the citric acid cycle in combination with pyruvic acid, lactic acid, and the ATP (adenosine triphosphate) hydrolysis product adenosine along with metabolites of adenosine. This method was successfully applied to analyze the microdialysates obtained from an experimental animal study giving insight into the hitherto unknown concentration of many interstitial energy metabolites, such as succinic acid and malic acid. With a total cycle time of 3 min, injection to injection, this method permits analysis of a much larger number of samples in comparison with conventional high performance liquid chromatography/tandem mass spectrometry HPLC-MS/MS strategies. With this novel combination where microdialysis and high sensitivity UPLC-MS/MS technique is combined within cardiologic research, new insights into the intermediary energy metabolism during ischemia-reperfusion is now feasible.

Inhibition of the malate-aspartate shuttle by pre-ischaemic aminooxyacetate loading of the heart induces cardioprotection.

AIMS: Preserved mitochondrial function is essential for protection against ischaemia-reperfusion (IR) injury. The malate-aspartate (MA) shuttle constitutes the principal pathway for transport of reducing cytosolic equivalents for mitochondrial oxidation. We hypothesized that a transient shut-down of the MA-shuttle by aminooxyacetate (AOA) during ischaemia and early reperfusion modulates IR injury by mechanisms comparable to ischaemic preconditioning (IPC). METHODS AND RESULTS: Isolated perfused rat hearts exposed to 40 min global no-flow ischaemia were studied in: (i) control, (ii) pre-ischaemic AOA (0.1 mM), (iii) IPC, and (iv) AOA+IPC hearts. IR injury was evaluated by infarct size and haemodynamic recovery. Tracer-estimated glucose oxidation and metabolic changes in glycogen, lactate, pyruvate, tricarboxylic acid (TCA) cycle intermediates, and ATP degradation products were measured. The effects of AOA on complex I respiration and reactive oxygen species (ROS) production were examined in isolated rabbit mitochondria. Treatment with AOA, IPC, or AOA+IPC induced significant infarct reduction; 28 ± 6, 30 ± 3, and 18 ± 1%, respectively, vs. 52 ± 5% of left ventricular (LV) mass for control (P < 0.01 for all). LV-developed pressure improved to 60 ± 3, 63 ± 5 and 53 ± 4 vs. 31 ± 5 mmHg (P < 0.01 for all) after 2 h reperfusion. Pre-ischaemic AOA administration inhibited glycolysis and increased glucose oxidation during post-ischaemic reperfusion similar to IPC, and suppressed complex I respiration and ROS production in the non-ischaemic heart. Changes in lactate, pyruvate, TCA intermediates, and ATP end products suggested an AOA inhibition of the MA-shuttle during late ischaemia and early reperfusion. CONCLUSION: Inhibition of the MA-shuttle during ischaemia and early reperfusion is proposed as a mechanism to reduce IR injury.

Time to treatment and three-year mortality after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction-a DANish Trial in Acute Myocardial Infarction-2 (DANAMI-2) substudy.

In patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention (pPCI), early reperfusion is believed to improve left ventricular systolic function and reduce mortality; however, long-term (>1 year) data are sparse. In the DANish Trial in Acute Myocardial Infarction-2 (DANAMI-2) study, 686 patients with ST-segment elevation myocardial infarction were treated with pPCI. Long-term mortality was obtained during 3 years of follow-up. We classified the patients according to the symptom-to-balloon time (<3, 3 to 5, and > or =5 hours). The groups were compared using a Cox proportional hazards regression model adjusted for confounding factors. The left ventricular systolic ejection fraction was estimated by echocardiography before discharge. Coronary flow was evaluated using the Thrombolysis In Myocardial Infarction score. Mortality did not differ between the 2 earliest symptom-to-balloon groups, and they were therefore combined into 1 group in the analysis of survival. Mortality was significantly increased for patients with a symptom-to-balloon time > or =5 hours (hazard ratio 2.36, 95% confidence interval 1.51 to 3.67, p <0.001), a difference that remained significant after controlling for confounding factors (adjusted hazard ratio 2.44, 95% confidence interval 1.31 to 4.54, p = 0.007). The symptom-to-balloon time was inversely associated with a left ventricular systolic ejection fraction of < or =40% (19.7% vs 22.8% vs 33.1%, p = 0.036), with the latter a major predictor of 3-year mortality in this cohort (hazard ratio 6.02, 95% confidence interval 3.68 to 9.85, p <0.001). A shorter symptom-to-balloon time was associated with greater rates of Thrombolysis In Myocardial Infarction 3 flow after pPCI (86.5% vs 80.9% vs 75.7%, p = 0.002). In conclusion, a shorter symptom-to-balloon time was associated with improved coronary flow, an increased likelihood of subsequent left ventricular systolic ejection fraction >40%, and greater 3-year survival in patients with ST-segment elevation myocardial infarction treated with pPCI.

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.

Long-term prognostic value of ST-segment resolution in patients treated with fibrinolysis or primary percutaneous coronary intervention results from the DANAMI-2 (DANish trial in acute myocardial infarction-2).

OBJECTIVES: The purpose of this study was to determine the prognostic value of ST-segment resolution after primary percutaneous coronary intervention (pPCI) versus fibrinolysis. BACKGROUND: Resolution of the ST-segment has been used as a surrogate end point in trials evaluating reperfusion in acute myocardial infarction; however, its prognostic significance may be limited to patients treated with fibrinolysis. METHODS: In the DANAMI-2 (DANish trial in Acute Myocardial Infarction-2) substudy, including 1,421 patients, the ST-segment elevation at baseline, pre-intervention, 90 min, and 4 h was assessed. The ST-segment resolution was grouped as follows: 1) complete > or =70%; 2) partial 30% to <70%; and 3) no resolution <30%. End points were 30-day and long-term mortality and reinfarction. RESULTS: The ST-segment resolution at 90 min was more pronounced after pPCI (median 60% vs. 45%, p < 0.0001), and a catch-up phenomenon was observed at 4 h. In the fibrinolysis group, 30-day and long-term mortality rates were significantly higher among patients without ST-segment resolution, whereas reinfarction rates were higher with complete ST-segment resolution. The ST-segment resolution was not associated with the 2 end points in the pPCI group. By multivariate analysis, ST-segment resolution at 4 h was an independent predictor of lower mortality, but higher reinfarction rates among patients receiving fibrinolytic therapy. CONCLUSIONS: The ST-segment resolution at 90 min was more complete after pPCI, suggesting better epicardial and microvascular reperfusion, whereas no difference between treatment strategies was seen at 4 h. The ST-segment resolution at 4 h correlated with decreased mortality, but increased reinfarction rates among patients receiving fibrinolytic therapy, whereas no association was seen for patients receiving pPCI. Consequently, 4-h ST-segment resolution remains an important prognosticator after fibrinolysis, but may be overemphasized as a surrogate end point after pPCI.

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.

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."

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.

Does postsystolic motion or shortening predict recovery of myocardial function after primary percutanous coronary intervention?

OBJECTIVE: The purpose of the study was to evaluate whether presence of postsystolic motion or shortening defined by Doppler tissue imaging may predict recovery of regional myocardial function in patients with ST-elevation myocardial infarction. METHODS: Echocardiography was performed a few hours after primary percutanous coronary intervention and at a 3-month follow-up visit in 83 patients with ST-elevation myocardial infarction. Based on visual assessment of wall thickening in a 16-segment model, segments were classified into those with: dyskinesia/akinesia (type A, n = 63) or hypokinesia (type B, n = 141) in the acute phase and no recovery of function at follow-up; dyskinesia/akinesia in the acute phase and partial recovery of function at follow-up (type C, n = 86); dyskinesia/akinesia/hypokinesia in the acute phase and complete recovery of function at follow-up (type D, n = 243); and normal myocardial function in the acute phase (type E, n = 759). RESULTS: There were no differences among type A, B, C, and D segments with regard to the proportion presenting postsystolic tissue velocity equal to or greater than 1.0 cm/s (0.52, 0.54, 0.60, and 0.47, respectively, P = .20) or with respect to postsystolic negative increase in strain (median -2.9, -1.9, -1.8, and -1.5%, respectively, P = .13) in the acute phase. However, type E segments less often presented postsystolic tissue velocity greater than 1.0 cm/s and presented lower postsystolic increase in strain (0.39 and -1.0%, respectively, P < .001 as compared with type A-D segments). In initially dysfunctional segments, presence of postsystolic contraction was not associated with improvement in strain or wall-motion score at follow-up. CONCLUSION: In patients with ST-elevation myocardial infarction postsystolic motion or shortening appears more frequently in the acute phase in myocardial segments with impaired systolic function compared with normally functioning segments. However, presence of postsystolic contraction is not associated with improvement in strain or wall-motion score at follow-up, and does not seem to be a marker of viability.

Left ventricular volume measurement in mice by conductance catheter: evaluation and optimization of calibration.

The conductance catheter (CC) allows thorough evaluation of cardiac function because it simultaneously provides measurements of pressure and volume. Calibration of the volume signal remains challenging. With different calibration techniques, in vivo left ventricular volumes (V(CC)) were measured in mice (n = 52) with a Millar CC (SPR-839) and compared with MRI-derived volumes (V(MRI)). Significant correlations between V(CC) and V(MRI) [end-diastolic volume (EDV): R(2) = 0.85, P < 0.01; end-systolic volume (ESV): R(2) = 0.88, P < 0.01] were found when injection of hypertonic saline in the pulmonary artery was used to calibrate for parallel conductance and volume conversion was done by individual cylinder calibration. However, a significant underestimation was observed [EDV = -17.3 microl (-22.7 to -11.9 microl); ESV = -8.8 microl (-12.5 to -5.1 microl)]. Intravenous injection of the hypertonic saline bolus was inferior to injection into the pulmonary artery as a calibration method. Calibration with an independent measurement of stroke volume decreased the agreement with V(MRI). Correction for an increase in blood conductivity during the in vivo experiments improved estimation of EDV. The dual-frequency method for estimation of parallel conductance failed to produce V(CC) that correlated with V(MRI). We conclude that selection of the calibration procedure for the CC has significant implications for the accuracy and precision of volume estimation and pressure-volume loop-derived variables like myocardial contractility. Although V(CC) may be underestimated compared with MRI, optimized calibration techniques enable reliable volume estimation with the CC in mice.