Índice de masa corporal y eficacia y seguridad del ticagrelor frente al prasugrel en pacientes con síndrome coronario agudo / Body mass index and efficacy and safety of ticagrelor versus prasugrel in patients with acute coronary syndromes

Introducción y objetivos Siguen sin estudio la eficacia y la seguridad del ticagrelor frente al prasugrel en pacientes con síndrome coronario agudo (SCA) según el índice de masa corporal (IMC). Se evaluaron la eficacia y la seguridad del ticagrelor frente a prasugrel en pacientes con SCA según el IMC. Métodos Se agrupó a los pacientes (n=3.987) en 3 categorías: con peso normal (IMC <25; n=1.084), sobrepeso (IMC ≥ 25 <30; n=1.890) y obesidad (IMC ≥ 30; n=1.013). El objetivo primario de eficacia fue la incidencia de muerte por cualquier causa, infarto de miocardio o accidente cerebrovascular a 1 año. El objetivo secundario de seguridad fue la incidencia de hemorragias de tipo 3-5 de la Bleeding Academic Research Consortium a 1 año. Resultados El objetivo primario se produjo en 63 pacientes asignados a ticagrelor y 39 asignados a prasugrel en el grupo de peso normal (el 11,7 frente al 7,5%; HR=1,62; IC95%, 1,09-2,42; p=0,018), 78 pacientes asignados a ticagrelor y 58 asignados a prasugrel en el grupo de sobrepeso (el 8,3 frente al 6,2%; HR=1,36; IC95%, 0,97-1,91; p=0,076) y 43 pacientes asignados a ticagrelor y 37 asignados a prasugrel en el grupo de obesidad (el 8,6 frente al 7,3%; HR=1,18; IC95%, 0,76-1,84; p=0,451). La incidencia de eventos hemorrágicos a 1 año en los pacientes con peso normal (el 6,5 frente al 6,6%; p=0,990), sobrepeso (el 5,6 frente al 5,0%; p=0,566) u obesidad (el 4,4 frente al 2,8%; p=0,219) no difirió entre el ticagrelor y el prasugrel. No hubo una interacción significativa entre el brazo de tratamiento y el IMC en relación con el objetivo primario (pinteracción=0,578) o el secundario (pinteracción=0,596). Conclusiones En pacientes con SCA, el IMC no influyó significativamente en el efecto del tratamiento con ticagrelor en términos de eficacia o seguridad frente al prasugrel (AU)

Introduction and objectives The efficacy and safety of ticagrelor vs prasugrel in patients with acute coronary syndromes (ACS) according to body mass index (BMI) remain unstudied. We assessed the efficacy and safety of ticagrelor vs prasugrel in patients with ACS according to BMI. Methods Patients (n=3987) were grouped into 3 categories: normal weight (BMI <25kg/m2; n=1084), overweight (BMI ≥ 25 to <30kg/m2; n=1890), and obesity (BMI ≥ 30kg/m2; n=1013). The primary efficacy endpoint was the 1 year incidence of all-cause death, myocardial infarction, or stroke. The secondary safety endpoint was the 1 year incidence of Bleeding Academic Research Consortium type 3 to 5 bleeding. Results The primary endpoint occurred in 63 patients assigned to ticagrelor and 39 patients assigned to prasugrel in the normal weight group (11.7% vs 7.5%; HR, 1.62; 95%CI, 1.09-2.42; P=.018), 78 patients assigned to ticagrelor and 58 patients assigned to prasugrel in the overweight group (8.3% vs 6.2%; HR, 1.36; 95%CI, 0.97-1.91; P=.076), and 43 patients assigned to ticagrelor and 37 patients assigned to prasugrel in the obesity group (8.6% vs 7.3%; HR, 1.18; 95%CI, 0.76-1.84; P=.451). The 1-year incidence of bleeding events did not differ between ticagrelor and prasugrel in patients with normal weight (6.5% vs 6.6%; P=.990), overweight (5.6% vs 5.0%; P=.566) or obesity (4.4% vs 2.8%; P=.219). There was no significant treatment arm-by-BMI interaction regarding the primary endpoint (Pint=.578) or secondary endpoint (Pint=.596). Conclusions In patients with ACS, BMI did not significantly impact the treatment effect of ticagrelor vs prasugrel in terms of efficacy or safety (AU)

[ESC/EACTS guidelines on myocardial revascularization 2018 : The most important innovations]. / ESC/EACTS-Leitlinien zur Myokardrevaskularisation 2018 : Die wichtigsten Neuerungen.

The guidelines on myocardial revascularization published in 2018 are a joint initiative of the European Society of Cardiology and the European Association for Cardio-Thoracic Surgery. To establish indications for myocardial revascularization by percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), evidence of the functional relevance of coronary artery stenoses is needed either by non-invasive imaging function tests or intravascular hemodynamic measurements. The prognostic and symptomatic benefits of myocardial revascularization depend on whether complete revascularization can be achieved. This needs to be considered when choosing the most appropriate revascularization strategy. In addition, the individual operative risk, the technical feasibility, the presence of diabetes mellitus and the anatomical complexity of coronary artery disease, as assessed by the SYNTAX score, are key criteria when choosing the optimal method of revascularization. For PCI radial artery access and the general use of drug-eluting stents are recommended. For CABG multiple arterial grafts should be strived for including the radial artery for treatment of high-grade coronary stenosis.

High on-treatment platelet reactivity and P2Y12 antagonists in clinical trials.

Dual antiplatelet therapy with aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) and in patients with acute coronary syndromes (ACS) has substantially decreased the rate of cardiovascular events. Within the past decade, the variability in pharmacodynamic response as well as the moderate antiplatelet efficacy of clopidogrel has raised major concerns, since high on-clopidogrel platelet reactivity has consistently been associated with increased risk for ischaemic events in PCI patients. The variability in response could be linked to genetic polymorphisms impacting on activity of cytochrome P450 enzymes as well as clinical and demographic variables, but, taken together, factors identified so far can explain only up to approximately 12% of this variability in adenosine diphosphate-induced platelet aggregation on clopidogrel. Regulatory agencies as well as major cardiac societies suggest the use of other anti-platelet medications or alternative dosing strategies for clopidogrel in patients with reduced effectiveness of clopidogrel. This review will focus on the current status of alternate strategies for more sufficient suppression of high platelet reactivity.

Personalizing antiplatelet therapy with clopidogrel.

Dual antiplatelet therapy with aspirin and clopidogrel is the accepted standard for prevention of ischemic complications after percutaneous coronary intervention and has been shown to reduce cardiovascular events in patients with acute coronary syndromes (ACSs). There is substantial interindividual variability in antiplatelet response to clopidogrel. Various clinical studies have demonstrated that patients with high on-clopidogrel platelet reactivity incur an increased risk for ischemic events. In recent years, several clinical and demographic variables as well as multiple genetic factors contributing to the variability in antiplatelet response to clopidogrel have been identified. We discuss strategies based on platelet function testing or genotyping for improvement of antiplatelet effects of clopidogrel and thereby clinical outcome.

Micro-array profiling exhibits remarkable intra-individual stability of human platelet micro-RNA.

Platelets play an important role in haemostasis and thrombus formation. Latest research identified platelets harbouring so called microRNAs (miRNA). MiRNAs are short single-stranded RNAs modulating gene expression by targeting mRNAs. Limited data exist on inter-individual variability of platelet miRNA profile while no data are available on intra-individual variability. We assessed platelet miRNA profile in five volunteers at five time points over a time course of 10 days; 24 hours prior to the last blood sampling, subjects took 500 mg acetylsalicylic acid (ASA). Platelet miRNA was isolated from leucocyte-depleted platelet-rich plasma, and miRNA array-analysis was performed. Temporal patterns and ASA effect were explored by a linear mixed effects model for each miRNA. For the 20 most abundantly expressed platelet miRNAs, target gene search was performed and an annotation network was created. MiRNA expression profiling of 1,281 human miRNAs revealed relevant expression of 221 miRNAs consistently expressed in all samples at all time points. Correlation of platelet miRNA ranks was highly significant to other studies. Global distribution of miRNA expression was relatively similar in all subjects. No miRNA exhibited a significant effect of time at level 0.05. After 24 hours, no significant effect of ASA was found. Concerning functional implications of the 20 most abundantly expressed miRNAs, we found six functional themes. In conclusion, platelet miRNA profile is remarkably stable over the time period studied. Single-point analysis of platelet miRNA profile is reasonable when inter-individual differences are studied. The functional annotation network points toward extra-platelet effects of platelet miRNAs.

Acute and long-term outcome of Silverhawk assisted atherectomy for femoro-popliteal lesions according the TASC II classification: a single-center experience.

BACKGROUND: Directional atherectomy (DA) has become popular in some centers to remove atherosclerotic plaques in femoro-popliteal lesions. Although immediate and also short - term outcome data are promising, solid long-term data are warranted to justify the widespread use in daily practice. PATIENTS AND METHODS: In this prospective study de novo and restenotic lesions of the femoro-popliteal segments were treated with the Silverhawk device. 161 consecutive patients (164 lesions) with peripheral artery disease (PAD) Rutherford classes 2 to 5 were included from June 2002 to October 2004 and October 2006 to June 2007 (59 % male, mean age 67 +/- 11 years, range 40 to 88) and the outcome analyzed according to the TASC II classification. RESULTS: DA alone was performed successfully in 28 % (n = 46), adjunctive balloon angioplasty in 65 % (n = 107) and stenting in 7 % (n = 11). The overall technical success rate was 76 % (124 / 164) and the procedural success rate 95 % (154 / 164). At 12 months primary patency rate was 61 % (85 / 140) and the secondary patency rate was 75 % (105 / 140) in the entire cohort, being less favourable in TASC D compared to TASC A to C lesions (p = 0.034 and p < 0.001, respectively). Furthermore the restenosis rate differed trendwise (p = 0.06) between de novo and restenotic lesions. Changes in the ABI and the Rutherford classes were significantly in favour of TASC A to C lesions compared to TASC D after 12 months (p = 0.004). The event free survival (MI, TIA, or restenosis) was 48 % at 12 months and 38.5 % at 24 months. Predictor for restenosis in the multivariable analysis was only male gender (p=0.04). CONCLUSIONS: The results in TASC D lesions are inferior to those in the lesser stages. DA of femoro-popliteal arteries leads shows a trend to better long-term technical and clinical outcome in de novo lesions compared to restenotic lesions.

Mechanical compression versus haemostatic wound dressing after femoral artery sheath removal: a prospective, randomized study.

BACKGROUND: Bleeding complications in the groin are one of the major disadvantages of femoral catheter procedures. The immobilisation of the patient and the compression bandages can jeopardize the patients' comfort. Aim of the study was a randomized comparison of safety and patient comfort of mechanical pressure followed by pressure bandage overnight using two different haemostatic pads after femoral artery sheath removal. PATIENTS AND METHODS: Nine hundred and eight consecutive patients undergoing diagnostic or therapeutic procedures via a 5 or 6 F femoral sheath were randomly selected either for mechanical compression therapy followed by a compression bandage (302 patients, group 1), or manual compression with application of a calcium ion releasing device (compression bandage only after application of > 5000 IU of heparin; 303 patients; group 2), or manual compression with a thrombin covered PAD without compression bandage (303 patients, group 3). RESULTS: No major hemorrhage or death occurred. A false aneurysm was found in 10 (3.3%), 13 (4.3%), and 10 patients (3.3%) of group 1, 2, and 3, respectively (p = 0.38). Three patients (0.3%) needed surgical treatment. 69 (22.7%) patients in thrombin covered PAD-group required a compression bandage overnight due to seeping hemorrhage after 15 minutes. In the calcium ion releasing PAD-group 124 (40.9%) patients had continued bandaging, 46 (15.2%) due to seeping hemorrhage after 15 min, and 78 (25.7%) due to application of heparin > 5000 IU. CONCLUSIONS: The use of mechanical compression combined with a pressure bandage, and the use of haemostatic wound dressing assisted sheath removal technique offer a comparable level of safety. Patient comfort is improved with the usage of PAD devices, however the technical failure rate of the PAD should be taken into account.

Lumbar artery aneurysm.

The purpose of this report is to present a rare case of lumbar artery aneurysm. We report the case of a 54-years-old male patient who was misdiagnosed over years having a chronic infrarenal aortic aneurysm. A 64-slice CT at our institution revealed a large lumbar artery aneurysm. The conclusion of this case report is that a lumbar or accessory renal artery aneurysm has to be taken into consideration if there is a localized enlargement of the lower abdominal aorta and a high resolution CT-scan is strongly recommended to make the exact diagnosis.

Incidence of venous thrombosis following peripheral arterial interventions. A prospective study.

BACKGROUND: The objective of the study was to investigate the incidence of deep vein thrombosis (DVT) at the puncture site following peripheral interventions and to assess if there is a difference between using a vascular closure by means of vascular closure systems or compression bandages. PATIENTS AND METHODS: We prospectively included 474 consecutive patients after peripheral arterial interventions. The day after peripheral arterial intervention we performed venous compression ultrasound to exclude DVT in the area of the groin. We recorded management of arterial closure and subsequent antithrombotic treatment of the patient. Four weeks after intervention follow-up was performed by phone to exclude clinical DVT, pulmonary embolism (PE), and death. RESULTS: We included 474 consecutive patients (mean age 69 y; 298 male / 176 female). All patients were under oral antiplatelet therapy. Vascular closure was achieved in 296 patients (62.44%) by Femostoptrade mark followed by compression bandage and in 178 (37.56 %) by using a vascular closure device alone. Sonography revealed no DVT the day after intervention, no clinical PE occurred. Four weeks follow-up showed no DVT, but there was one patient in the compression bandage group who had PE without proven deep vein thrombosis. Two patients died from other reasons than PE. CONCLUSIONS: The immediate and mid-term risk of DVT after peripheral arterial interventions is extremely low and is not increased if compression bandages are used for vascular closure.

Long term outcome after balloon angioplasty and stenting of subclavian artery obstruction: a single centre experience.

INTRODUCTION: Percutaneous transluminal angioplasty is an accepted and successful treatment strategy in obstructive disease of the subclavian artery. The purpose of this study was to evaluate the technical and clinical long-term outcome following endovascular therapy. PATIENTS AND METHODS: We retrospectively analyzed 99 patients (mean age of 65 +/- 10 years) with 100 interventions of the subclavian arteries and the brachiocephalic trunk with different aetiologies [atherosclerosis (90%); Takayasu's arteritis (5%); thromboembolism (2%); external compression (1%); iatrogenic dissection (1%) and occlusion after graft implantation in type B dissection (1%)]. RESULTS: Primary success rate was 97% (100% for stenoses and 90% for total occlusions). Treatment modalities included balloon angioplasty (PTA) alone (16%), stent implantation (78%), rotational thrombectomy (2%) and atherectomy (1%). The primary 1-year patency rate of the whole study cohort was 87% being not significantly lower after PTA (75%) compared to stent assisted angioplasty (89%). After thrombectomy and atherectomy no relevant restenosis were found. Multivariable analysis of 1-year restenosis-free survival revealed younger age (p = 0.03) and stenting (p = 0.04) as independent predictor. The blood pressure difference between both limbs at baseline was 42 +/- 24 mmHg and dropped to 10 +/- 14 mmHg after the intervention and 15 +/- 20 mmHg after 12 months, respectively (p = 0.01). CONCLUSIONS: Endovascular therapy of subclavian artery obstructions of various aetiologies offers good acute success rates even in total occlusions. Long-term patency rate is in favour of stent placement.

Histological verification of non-specific aorta-arteritis (Takayasu's arteritis) using percutaneous transluminal atherectomy.

Diagnosis of non-specific aorto-arteritis (NSAA, Takaysu's arteritis) is typically based on clinical and investigational parameters. We report here about two patients with clinically suspected diagnosis of a Takayasu's arteritis already under anti-inflammatory therapy in whom percutaneous transluminal atherectomy of subclavian and axillary artery stenoses was performed to relief the patients from symptoms--intermittent dyspraxia of the arms--and to verify the clinical diagnosis by histology. In the first case aorto-arteritis could be histologically confirmed through the analysis of plaque material including media structures excised from the subclavian and axillary arteries using a new device for atherectomy. The biopsy showed diffuse inflammation and granulomatous lesions with giant cells typically for Takayasu's disease. In the second patient, biopsy showed no acute or chronic inflammatory signs but only atherosclerotic lesions. Percutaneous transluminal atherectomy is therefore not only an interventional but also a diagnostic tool and should be used in every case of interventional therapy of suspected aorto-arteritis to make the clinical diagnosis and as a major consequence the initiation of an aggressive anti-inflammatory medical therapy more reliable.

Impact of diabetes mellitus on long-term outcome after unstable angina and non-ST-segment elevation myocardial infarction treated with a very early invasive strategy.

AIMS/HYPOTHESIS: We sought to evaluate the impact of diabetes mellitus on long-term outcome in patients with unstable angina and non-ST-segment elevation myocardial infarction treated with a very early invasive strategy. METHODS: We carried out a prospective cohort study in 270 diabetic and 1163 non-diabetic patients with unstable angina and non-ST-segment elevation myocardial infarction. All patients underwent coronary angiography and, if appropriate, subsequent revascularisation within 24 hours of admission. The primary endpoint was all-cause mortality during follow-up for up to 60 months. RESULTS: Diabetic patients had less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infarction. Percutaneous coronary intervention was performed in 53% of diabetic patients and 56% of non-diabetic patients. Coronary artery bypass grafting was done in 21% of diabetic patients and 12% of non-diabetic patients. In-hospital mortality (4.1% vs 1.3%; hazard ratio 3.47; 95% CI: 1.57 to 7.64; p=0.002) and long-term mortality (9.7% vs 4.9%; hazard ratio 2.11; 95% CI: 1.33 to 3.36; p=0.002) were significantly higher in diabetic patients. After adjustment for differences in baseline characteristics, diabetes mellitus was no longer an independent predictor of long-term mortality (hazard ratio 1.43; 95% CI: 0.74 to 2.78; p=0.292). CONCLUSIONS/INTERPRETATION: Diabetic patients treated with a very early invasive strategy for unstable angina and non-ST-segment elevation myocardial infarction have a higher in-hospital and long-term mortality that is largely explained by their less favourable baseline characteristics including more advanced coronary artery disease and more severe unstable angina and non-ST-segment elevation myocardial infarction.

Renal function and long term mortality after unstable angina/non-ST segment elevation myocardial infarction treated very early and predominantly with percutaneous coronary intervention.

OBJECTIVES: To quantify the impact of baseline renal function on in-hospital and long term mortality in patients with unstable angina/non-ST elevation acute myocardial infarction (UA/NSTEMI) treated with a very early invasive strategy. DESIGN: Prospective cohort study of 1400 consecutive patients with UA/NSTEMI undergoing coronary angiography and subsequent coronary stenting of the culprit lesion as the primary revascularisation strategy within 24 hours of admission. Patients were stratified according to calculated glomerular filtration rate (GFR) on admission. RESULTS: In-hospital mortality was 0% among patients with a GFR > or = 130 ml/min/1.73 m2, 0.4% with a GFR of 90-129 ml/min/1.73 m2, 2.6% with a GFR of 60-89 ml/min/1.73m2, and 5.1% with a GFR of < 60 ml/min/1.73 m2. Cumulative three year survival rates were 92.6%, 95.5%, 91.9%, and 76.8%, respectively. Patients with a GFR of < 60 ml/min/1.73 m2 were four times more likely to die in hospital (hazard ratio (HR) 4.0, 95% confidence interval (CI) 1.8 to 9.1; p = 0.001) and four times more likely to die during long term follow up (HR 4.0, 95% CI 2.5 to 6.4; p < 0.001). After adjusting for potential confounders, a GFR of < 60 ml/min/1.73 m2 remained a strong independent predictor of long term mortality (HR 2.6, 95% CI 1.5 to 4.5; p = 0.001). CONCLUSIONS: Baseline renal function is a strong independent predictor of in-hospital and long term mortality after UA/NSTEMI treated with very early revascularisation.

Recommendations on percutaneous coronary intervention for the reperfusion of acute ST elevation myocardial infarction.

Little information is currently available from the various societies of cardiology on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Since primary PCI is the main method of reperfusion in AMI in many centres, and since of all cardiac emergencies AMI represents the most urgent situation for PCI, recommendations based on scientific evidence and expert experience would be useful for centres practising primary PCI, or those looking to establish a primary PCI programme. To this aim, a task force for primary PCI in AMI was formed to develop a set of recommendations to complement and assist clinical judgment. This paper represents the product of their recommendations.

[Initial clinical experience with a new percutaneous peripheral atherectomy device for the treatment of femoro-popliteal stenoses]. / Erste klinische Erfahrungen mit einem neuen Atherektomiekatheter zur Behandlung femoro-poplitealer Stenosen.

BACKGROUND: Evaluation of the efficacy and safety of a new 7F-atherectomy device (30-day endpoint) for the treatment of short and mid-length arterial lesions with a reference diameter of 2.5-7 mm. MATERIAL AND METHODS: Fifty-eight femoto-popliteal stenoses in 46 patients (67% male, mean age 66 +/- 9 years) with chronic peripheral occlusive disease of the lower limbs [Rutherford stage 2: n = 13 (28%); stage 3: n = 29 (63%), stage 4: 2 (4%), stage 5: n = 2 (4%)], were treated with directional atherectomy. Target lesion characteristics: Common femoral artery: n = 1 (2%), superficial femoral artery: n = 47 (81%); popliteal artery, n = 10 (17%); in stent n = 3 (5 %). Thirty (65 %) of the interventions were performed using an antegrade approach, 16 (35%) interventions in cross-over technique. Mean degree of stenosis was 83 +/- 11 mm, mean length of lesion was 37 +/- 37 mm. RESULTS: 6.5 +/- 2 (4-10) passes of the lesion were performed with the catheter. Three lesions were treated after predilatation, 55 (95%) interventions as primary atherectomy. In 31/58 lesions (53%) additional balloon angioplasty was performed, in 1 lesion (2%) additional stent placement was needed. The mean degree of stenosis after atherectomy was reduced to 29 +/- 20% (0-60%) after additional balloon angioplasty, it was 11 +/- 10% (0-30 %). A residual stenosis of < 50% after plain atherectomy was achieved in 55 (95%) lesions, of < 30% in 49 (84%). COMPLICATIONS: 3 (6.5%) cases of embolism of debris were detected and treated successfully by aspiration. The mean ankle-brachial index increased from 0.62 +/- 0.12 to 0.92 +/- 0.36 before discharge, and to 0.86 +/- 0.17 after 30 days. Rutherford stage after 30 days: stage 0: n = 038 (83%); Stage 1: n = 4 (8%); Stage 2: n = 3 (6%); Stage 5: n = 1 (2%). CONCLUSION: Lesions up to 8 cm in length of the femoropopliteal arteries can be treated successfully in most cases with the new atherectomy catheter. Embolism, the only complication that occurred, can be avoided by cleaning the nose cone after at least 4 passes of the lesion.

Treatment of acute embolic occlusions of the subclavian and axillary arteries using a rotational thrombectomy device.

Acute embolic or local thrombotic ischaemia of the upper limbs can be treated by embolectomy or by endovascular techniques. We report here on the endovascular thrombectomy of acute embolic occlusions of subclavian and axillary arteries in two patients using a rotational thrombectomy device and give an overview about the actual literature. Two female patients, each with a history of multivessel coronary disease and intermittent atrial fibrillation, complained of sudden onset of pain at rest and paleness of the left and right arm, respectively. Duplex ultrasound showed a localized embolic occlusion of the left subclavian artery and the bifurcation of the brachial artery in the first patient and a localized embolic occlusion of the distal right subclavian and axillary artery in the second patient. In the first patient, the left subclavian artery was reopened using a 8F-Rotarex device via the femoral access, while the bifurcation of the brachial artery was reopened by local thrombolysis using 25 mg rt-PA because of the insufficient length of the thrombectomy device of 80 cm. In the second patient, the right subclavian and axillary arteries were reopened using a 6F-Rotarex device. Follow-up examinations before discharge and after 6 months showed normalized perfusion of the arms of both patients.

Specific stimulation of peripheral blood mononuclear cells from patients with acute myocarditis by peptide-bound flavin adenine dinucleotide (FAD), a naturally occurring autologous hapten.

The tryptic FAD-peptide carrying the flavin in 8alpha-(N3)histidyl linkage as natural hapten was isolated by HPLC from the bacterial enzyme 6-hydroxy-d-nicotine oxidase. The same flavin protein linkage is found in the mitochondrial succinate dehydrogenase flavoprotein subunit, the predominant flavoprotein with covalently bound FAD in mitochondria of cardiomyocytes. Peripheral blood mononuclear cells (PBMC) were isolated from four patients with acute myocarditis, seven patients with dilated cardiomyopathy (DCM) and from four healthy control individuals. The response of PBMC to the FAD-peptide was evaluated by measuring proliferation ([3H]-dThd incorporation) and cytokine secretion [interferon (IFN)-gamma]. PBMC from all patients with acute myocarditis showed positive responses to the FAD-peptide, in contrast to PBMC from patients with DCM or control individuals. Following the recovery of the patients from the acute inflammation of the heart, PBMC no longer exhibited a proliferation response to the FAD-peptide. A chemically synthesized FAD-free peptide with identical amino acid sequence induced no response of PBMC. The results are consistent with a recall response by activated T cells, specific for the normally cryptic mitochondrial flavin-hapten, which may be liberated following cardiomyocyte destruction during the inflammation of the heart.

White blood cell count and long term mortality after non-ST elevation acute coronary syndrome treated with very early revascularisation.

OBJECTIVE: To evaluate the predictive value of white blood cell count (WBC) for short and long term mortality in patients with non-ST elevation acute coronary syndromes (NSTACS) treated with a very early invasive strategy. DESIGN: Prospective cohort study in 1391 consecutive patients with NSTACS undergoing very early revascularisation. Patients were stratified according to quartiles of WBC determined on admission. RESULTS: Kaplan-Meier survival analysis showed a cumulative three year survival of 93.8% in the first quartile of WBC (< 6800/mm(3)), 94.4% in the second quartile (6800-8000/mm(3)), 95.1% in the third quartile (8000-10000/mm(3)), and 82.4% in the fourth quartile (> 10000/mm(3)) at 36 months (p < 0.001 by log rank). Relative to patients in the three lower WBC quartiles, patients in the highest quartile were three times more likely to die during the hospitalisation (hazard ratio 3.2, 95% confidence interval (CI) 1.5 to 7.1; p = 0.003) and during long term follow up (hazard ratio 3.4, 95% CI 2.2 to 5.3; p < 0.001). By multivariate Cox regression analysis including baseline demographic, clinical, and angiographic covariables, WBC in the highest quartile remained a strong independent predictor of mortality (hazard ratio 3.3, 95% CI 1.9 to 5.6; p < 0.001). CONCLUSIONS: WBC is a strong independent predictor of short and long term mortality after NSTACS treated with very early revascularisation.