Virtual histology assessment of cardiac allograft vasculopathy following introduction of everolimus--results of a multicenter trial.

In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of cardiac allograft vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 ± 3.8% and 1.6 ± 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 ± 4.0 vs. 0.3 ± 3.1%; p = 0.02) and necrotic component (6.5 ± 8.5 vs. 1.1 ± 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx >5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.

WITHDRAWN: Quantitative Analysis of Dobutamine-Atropine Stress Echocardiography.

The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 169-177, . The duplicate article has therefore been withdrawn.

Effect of intravenous streptokinase on the relation between initial ST-predicted size and final QRS-estimated size of acute myocardial infarcts.

Thrombolytic therapy has been documented to reduce acute myocardial infarct size. The previously established relation between initial ST segment elevation and final electrocardiographic (ECG) myocardial infarct size in patients without coronary reperfusion might therefore be altered by thrombolytic therapy. The effect of intravenous streptokinase on this relation was therefore studied in 73 patients with initial acute myocardial infarction who had participated in the Second International Study of Infarct Survival (ISIS-2). Patients who received streptokinase were considered as one group and patients who did not receive streptokinase as a control group. Final myocardial infarct size, which was estimated from the QRS score, was predicted from the admission standard ECG by previously developed formulas based on ST segment elevation. In the 40 control patients there was no change from ST-predicted to final QRS-estimated infarct size (median 17.7% versus 18.3%; p = NS). In the 33 patients in the streptokinase group, there was a highly significant decrease from predicted to final myocardial infarct size (median 21.9% versus 16.2%; p less than 0.0002). This decrease was found for both anterior (median 23.7% versus 19.5%; p less than 0.03) and inferior (median 21.9% versus 12.0%; p = 0.001) infarct locations. Multiple regression analysis adjusting for differences in predicted infarct size confirmed the significance of streptokinase on the difference in infarct size (p = 0.006). Based on the variability of the percent change from predicted to final infarct size in the control group, a threshold decrease greater than or equal to 20% is required for identification of salvage.(ABSTRACT TRUNCATED AT 250 WORDS)

Predictors of coronary in-stent restenosis: importance of angiotensin-converting enzyme gene polymorphism and treatment with angiotensin-converting enzyme inhibitors.

OBJECTIVES: This study aimed to clarify the role of the angiotensin-converting enzyme (ACE) gene polymorphism in the development of in-stent restenosis. BACKGROUND: In-stent restenosis occurs after treatment of coronary artery stenosis in 12% to 32% of coronary interventions with stents. Experimental and clinical studies have suggested that the deletion/insertion (D/I) polymorphism of the ACE gene plays a role in this. METHODS: Quantitative coronary angiography before, immediately after and six months after stent implantation were compared in 369 patients, in whom D/I typing of the ACE gene was performed. RESULTS: At follow-up we found no differences between the three genotypes in minimal lumen diameter (homozygotes with two deletion alleles in the ACE gene [DD], 2.20 mm; heterozygotes with one deletion and one insertion allele in the ACE gene [DI], 2.19 mm; and homozygotes with two insertion alleles in the ACE gene [II], 2.25 mm). The corresponding diameter stenoses were: DD: 25%, DI: 27%, II: 27% (p = NS), and the frequency of restenosis (>50% diameter stenosis) was: DD: 15.7%, DI: 11.0% and II: 16.4% (p = NS). Logistic regression analysis identified diabetes (odds ratio [OR]: 3.0, 95% confidence interval [CI]: 1.0 to 8.7), lesion length (OR: 1.1, 95% CI: 1.01 to 1.30) and minimal lumen diameter immediately after the intervention (OR: 0.3, 95% CI: 0.14 to 0.85) as predictors of in-stent restenosis. In a post hoc analysis of patients treated versus those not treated with an ACE-inhibitor antagonist or an angiotensin receptor antagonist, we found an increased frequency of in-stent restenosis in the DD genotypes (40% vs. 12%, p = 0.006). CONCLUSIONS: The D/I polymorphism is not an independent predictor of coronary in-stent restenosis in general, but it may be of clinical importance in patients treated with ACE inhibitors or angiotensin receptor antagonists.

A comprehensive estimation of acute myocardial infarct size using enzymatic, electrocardiographic and mechanical methods.

This prospective study compares the estimated size of acute myocardial infarction (AMI) by cumulative serum creatine kinase isoenzyme MB (CK-MB), Selvester QRS score, and 2-dimensional (2-D) echocardiographic dyssynergy of the left ventricle in 63 consecutive patients with their first anterior (n = 31) or inferior AMI (n = 32). The correlations among these parameters were good for patients with anterior AMI (r = 0.74 to 0.78, standard error of the estimate = 29 to 33%) but only fair for those with inferior AMI (r = 0.35 to 0.47, standard error of the estimate = 38 to 73%). Based on previous autopsy studies, estimates of CK-MB and QRS score were then converted to percent of infarcted left ventricle. Linear regression analyses between mean percent AMI size by cumulative CK-MB plus QRS score vs the number of dyssynergic segments by 2-D echocardiography were used to develop a comprehensive formula for estimating AMI size by a combination of all 3 techniques. Thus, a formula is proposed that may optimally estimate AMI size derived from leakage of cytosolic enzymes, changes in the sequence of myocardial depolarization, and irregularities of left ventricular contraction.

Continuous monitoring of global left ventricular ejection fraction during percutaneous transluminal coronary angioplasty.

Continuous monitoring of left ventricular (LV) function during percutaneous transluminal coronary angioplasty (PTCA) was performed in 40 patients (53 +/- 2 years) with a miniature, nuclear detector system after labeling the patients' red blood cells with technetium-99m. Balloon dilation (113 seconds, range 60 to 240) induced on average a 0.12 ejection fraction (EF) unit (19%) decrease in the LVEF, which was explained by a 34% increase in end-systolic counts. Balloon dilation of the left anterior descending artery (n = 23) produced a decrease in the LVEF of 0.17 +/- 0.13 EF units compared with the decrease of 0.06 +/- 0.07 EF units in patients undergoing dilation of the left circumflex artery (n = 9) and 0.05 +/- 0.04 EF units in patients treated for a stenosis of the right coronary artery (n = 8), (p = 0.02). Balloon deflation was associated with an immediate return to pre-PTCA levels. In 10 patients with 2 identical balloon occlusions, the second occlusion led to a significantly less decrease in the LVEF (0.41 +/- 0.14 vs 0.44 +/- 0.15) and electrocardiographic ST-segment deviation (88 +/- 54 microV vs 65 +/- 42 microV) than the first. We conclude that PTCA is associated with an abrupt transient decrease in the LVEF. The effect of balloon occlusion of the left anterior descending artery is more pronounced than balloon occlusion of the left circumflex and the right coronary arteries. Neither single nor multiple balloon occlusions were associated with post-PTCA global LV dysfunction, whereas the lesser degree of LV dysfunction and electrocardiographic signs of myocardial ischemia during the second of 2 identical balloon occlusions suggests that preconditioning can be induced during PTCA.

Human bronchial artery blood flow after lung Tx with direct bronchial artery revascularization.

The inaccuracy of measuring human bronchial artery blood flow has previously been considerable. En bloc double-lung transplantation with bronchial artery revascularization (BAR) using a single conduit offers the unique opportunity of direct measurement of the total bronchial artery blood flow. In eight en bloc double-lung-transplanted patients with complete BAR, the basal blood flow was measured by using a 0.014-in. Doppler guide wire and arteriography. The average peak velocity in the conduit was 12-73 cm/s [+/-2.1 (SD) cm/s], and the conduit diameter was 1.7-3.1 mm [+/-0.10 (SD) mm], giving individual basal flow values between 19 and 67 ml/min [+/-5 (SD) ml/min], or 0.2-1.9% of estimated cardiac output. In three patients basal measurements were followed by injection of nitroglycerin and verapamil into the conduit. This increased the bronchial artery flow to 121-262% of basal values (31-89 ml/min). The measured values appear more physiologically plausible than previous bronchial artery blood flow measurements in humans.

Atrioventricular plane motion during dobutamine-atropine stress echocardiography: the biphasic response in healthy subjects revisited.

This study was undertaken to establish normal values for the systolic atrioventricular plane motion (AVPM) from base to apex during dobutamine-atropine stress echocardiography (DASE) and to compare them with those of patients with coronary artery disease. The AVPM was measured at baseline, low dose and peak dobutamine-atropine infusion in 20 patients referred for coronary angiography and in 20 control subjects. Atrioventricular plane motion was measured at the posterior, anterior, septal, and lateral positions of the mitral annulus in the apical 2- and 4-chamber views by an observer blinded to clinical and angiographic data. In healthy subjects undergoing DASE, AVPM initially increased but subsequently decreased to below baseline values at peak stress. Atrioventricular plane motion at any stage and the changes therein during DASE were within the normal reference interval in the majority of patients. In conclusion, AVPM decreased during DASE in healthy subjects and was not a sensitive marker of coronary artery disease.

Significance and management of early graft failure after coronary artery bypass grafting: feasibility and results of acute angiography and re-re-vascularization.

UNLABELLED: Perioperative ischaemia and infarction after CABG are associated with increased morbidity and mortality. OBJECTIVE: To study causes of perioperative ischaemia and infarction by acute re-angiography and to treat incomplete re-vascularization caused by graft failure or any other cause. METHODS: Between 1990 and 1995, 2003 patients underwent an isolated CABG operation. Myocardial ischaemia was suspected if one or more of the following criteria were present: New changes in the ST-segment in the ECG; a CKMB value greater than 80 U/L; new Q-waves in the ECG; recurrent episodes of, or sustained ventricular tachyarrhythmia; ventricular fibrillation; haemodynamic deterioration and left ventricular failure. Acute coronary angiography was performed in stable patients, while haemodynamically severely compromised patients were rushed to the operating room. RESULTS: A total of 71 (3.5%) patients of all CABGs with suspected graft failure were identified and included in the study. Patients were grouped according to whether they had an acute re-angiography (n = 59; group 1) or an immediate re-operation (n = 12; group 2) performed. In group 1, the acute re-angiography demonstrated graft failure/incomplete re-vascularization in 43 patients (73%). The angiographic findings were: Occluded vein graft(s) in 19 (32%); poor distal run-off to the grafted coronary artery in ten (17%); internal mammary artery stenosis in four (7%); internal mammary artery occlusion in three (5%); vein graft stenoses in three (5%); left mammary artery subclavian artery steal in two (3%); and the wrong coronary artery grafted in one (2%). Based on the angiography findings, 27 patients were re-operated and re-grafted. At the time of re-operation, 18 patients (67%) had evolving infarction documented by ECG or CKMB. Two patients (3%) experienced stroke in immediate relation to the re-angiography. The 30-day mortality was three (7%). In group 2, graft occlusions were found in 11 patients (92%). The 30-day mortality was six (50%). CONCLUSION: An acute re-angiography demonstrated graft failure or incomplete re-vascularization in the majority of patients with myocardial ischaemia early after CABG. Re-operation for re-re-vascularization was performed with low risk. Few patients with circulatory collapse could be saved by an immediate re-operation without preceding angiography.

The left ventricular end-systolic pressure and pressure-volume index. Comparison between invasive and auscultatory arm pressure measurements.

The slope of the left ventricular (LV) end-systolic pressure-volume relation (ESPVR) has been established as a valuable clinical method to assess LV contractile function independent of LV loading factors. The purpose of the present study was to evaluate whether the ESPVR could be reliably determined from auscultatory blood pressure (BP) measurements and from LV volume measurement by contrast ventriculography (CVG). Twenty-four patients with suspected or known ischemic heart disease were studied by cardiac catheterization with simultaneous, blinded, intravascular and auscultatory pressure measurements. LV volume was determined by CVG. The auscultatory mean arterial blood pressure (MAP) derived from: [formula: see text] was found to be a useful measure of the LV end-systolic pressure in this connection. The correlation between invasively measured LV end-systolic pressure (ESP) and MAP was highly significant (r = 0.82; SEE = 6.9 mmHg; p = 0.001). The correlation between invasively and semi-invasively measured ESPVR fell close to the line of identity (r = 0.99; SEE = 0.23 mmHg.mL-1; p < 0.001). The replacement of ESP by MAP induced only a minimal error in the assessment of the ESPVR. A complete noninvasive determination of the ESPVR and LV contractility therefore seems possible by using the MAP and by measuring the end-systolic volume by radionuclide ventriculography or by echocardiography.

[Exercise echocardiography. A new valuable method for demonstration or exclusion of myocardial ischemia]. / Arbejdsekkokardiografi. En ny voerdifuld metode til påvisning og udelukkelse af myokardieiskoemi.

The aim of our study was to assess the diagnostic value of exercise echocardiography compared with exercise ECG and coronary arteriography. Exercise echocardiography was performed in 60 consecutive patients referred for coronary arteriography because of suspected coronary artery disease. Echocardiography was carried out in combination with bicycle exercise ECG and was performed 1) at rest before exercise with the patient supine, 2) at peak exercise on the bicycle and 3) immediately after exercise in supine position. Conventional standard views were recorded by means of an image computer. For the regional wall motion analysis, images were displayed simultaneously from the rest, peak and post exercise situations in a quadscreen format. Ischemia was diagnosed when wall motion deteriorated from rest to peak or post exercise in at least one out of a total of 16 left ventricular segments. Analysis was made without knowledge of patient data or results of exercise ECG or coronary arteriography. No patient was excluded because of reduced echocardiographic image quality during exercise or other technical reason. Coronary arteriography was performed in all patients and used as reference. The sensitivity of exercise echocardiography was 91% and the specificity 100%. The predictive value of a positive test was 100% and the predictive value of a negative test 78%. For exercise ECG the corresponding values were 58%, 100%, 100% and 39% respectively. We conclude that exercise echocardiography seems to be useful for the diagnosis and exclusion of ischemic heart disease. This and other studies indicate that the method is more sensitive than exercise ECG.

[Sexual activity in ischemic heart disease. Risk and therapeutic possibilities]. / Seksuel aktivitet ved iskaemisk hjertesygdom. Risiko og behandlingsmuligheder.

A major concern of patients with ischaemic heart disease is whether sexual activity is safe. In addition, patients are often reluctant to discuss sexual problems, including erectile dysfunction. Fear of sexual failure or fear of an acute ischaemic cardiac event as a result of sexual activity may create anxiety and lead to avoidance of sexual activity, which can significantly affect quality of life. In patients with a recent acute myocardial infarction the participation in a cardiac rehabilitation program should be strongly encouraged. The results are an improvement in physical capacity and self confidence. The performance of an exercise test at the time of hospital discharge following acute myocardial infarction is mandatory, and can be used in both risk stratification and cardiac rehabilitation. Patients who can manage a work capacity of at least 100 Watt without evidence of myocardial ischaemia or arrhythmias may without concerns take part in an active sexual life. Comprehensive information and appropriate use of pharmacologic agents for erectile dysfunction can add significantly to quality of life.

[The effect of thrombolytic therapy on the outcome of early exercise test in patients with acute myocardial infarction]. / Effekt af trombolytisk behandling på udfaldet af tidlig arbejdstest hos patienter med akut myokardieinfarkt.

UNLABELLED: Exercise test variables, such as an impaired heart rate response, are known to be related to left ventricular function and patient prognosis following acute myocardial infarction. The present study was performed to compare exercise test variables in acute myocardial infarct patients following either intravenous thrombolysis or placebo. Symptom-limited bicycle ergometer tests, carried out one to two weeks from the infarction, were performed in 85 patients randomized to intravenous streptokinase (n = 41) or placebo (n = 44) given within 12 hours from onset of symptoms. Resting heart rate, systolic blood pressure and rate-pressure product were similar in the two groups. At maximum workload the streptokinase treated patients had a significantly higher median maximal heart rate than controls (136 vs. 126 min-1; p < 0.01) but only a trend towards higher systolic blood pressure was seen (175 vs. 163 mmHg; p = 0.09). Rate-pressure product at maximal exercise was 23.620 vs. 20.100 mmHg x min-1; p < 0.01). A significantly smaller number of patients in the streptokinase group had exercise capacity below 50 W (0% vs. 15.9%; p < 0.01). IN CONCLUSION: patients treated with intravenous streptokinase for acute myocardial infarction reach both higher heart rates and rate-pressure products at maximum workload than their controls thus indicating that the beneficial effects of thrombolysis after acute myocardial infarction are reflected in an improved heart rate response during exercise.

[Angiopeptin versus placebo for reductin of restenosis after PTCA treatment. A randomized, double-blind study]. / Angiopeptin versus placebo til reduktion af restenose efter PTCA-behandling. En randomiseret, dobbeltblind undersøgelse.

Angiopeptin, a somatostatin analogue, inhibits intimal hyperplasia after (percutaneous transluminal coronary angioplasty) (PTCA) in several animal models. This pilot study sought to determine the effect of subcutaneous infusion of angiopeptin on clinical events and restenosis in patients undergoing successful PTCA. One hundred and twelve patients were randomized to receive continuous subcutaneous angiopeptin (750 micrograms/day) or placebo infusion from the day before PTCA and for the following four days in a double-blind study. Eighty patients had a successful PTCA, and 75 of these patients with 94 lesions underwent angiography 6 +/- 2 months after PTCA. All 112 patients underwent clinical follow-up at 12 months. The 12-month event rate (death, myocardial infarction, coronary artery bypass grafting and re-PTCA) was reduced from 34% to 25% (p = 0.30) by angiopeptin by intention to treat analysis. Restenosis (> or = 50% diameter stenosis) was significantly reduced in lesions treated with angiopeptin (12% vs 40%; p = 0.003). Late lumen loss was also significantly reduced after angiopeptin treatment (0.12 +/- 0.46 mm vs 0.52 +/- 0.64 mm; p = 0.003). In conclusion, continuous subcutaneous angiopeptin infusion for five days tended to decrease clinical events and restenosis after PTCA.

[DANAMI. A Danish study of invasive versus conservative treatment of patients with post-infarction ischemia who had received thrombolytic therapy]. / DANAMI. En dansk undersøgelse af invasiv versus medicinsk behandling af trombolysebehandlede patienter med postinfarkt iskaemi.

INTRODUCTION: To compare an invasive strategy employing percutaneous transluminal coronary angioplasty (PTCA) or coronary artery by-pass grafting (CABG) with a medical strategy in patients who had received thrombolytic treatment for first acute myocardial infarction (AMI), and with signs of inducible ischaemia. METHODS: In a prospective study 1008 patients were randomized, 503 to invasive treatment, of whom 266 (52.9%) had PTCA, and 147 (29.2%) CABG, 505 to conservative treatment, of whom eight (1.6%) were revascularized within two months. RESULTS: After a median follow-up of 2.4 years the mortality in the invasive group was 3.6% vs. 4.4% (p = 0.45) in the conservative group, re-infarction incidence was 5.6% vs. 10.5% (p = 0.0038) and percentage of admissions with unstable angina was 17.9% vs. 29.5% (p < 0.00001). DISCUSSION: We conclude that post-infarct patients with inducible ischaemia should be referred to coronary angiography and revascularised accordingly.