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BACKGROUND: Dual antiplatelet therapy (DAPT) prevents thrombotic events after coronary stent implantation but may induce bleedings, specifically in elderly patients. However, a competitive risk analysis is lacking. OBJECTIVES: To assess the determinants of major bleeding and the balance between the competing risks of major bleeding and thrombotic events during prasugrel-based DAPT after stent implantation. METHODS: Overall, 2,291 patients randomized to drug-eluting or bare metal stents and treated with prasugrel 10mg/day for 1 year were followed over 2 years for major bleeding (BARC 3/5) and thrombotic events (cardiac death, myocardial infarction, definitive/probable stent thrombosis). Prasugrel dose was reduced to 5mg in patients >75 years and/or <60kg. Predictors of major bleeding and competing risks of major bleeding and thrombotic events were assessed. RESULTS: Two-year rates of major bleeding and thrombotic events were 2.9% and 9.0%, respectively. The only independent predictor of major bleeding was age (hazard ratio per year increase 1.05 [1.02,1.07], p<0.001). The relationship between major bleeding and age was non-linear, with lowest hazard ratios at 57 years and an exponential increase only above 65 years. In contrast, the relationship between thrombotic events and age was linear and continuously increasing with older age. While the competing risk of thrombotic events was higher than that of major bleeding in younger patients, the two risks were similar in older patients. After discontinuation of prasugrel, bleeding events leveled off in all patients, while thrombotic events continued to increase. CONCLUSIONS: In prasugrel-based DAPT, age is the strongest risk factor for major bleeding, increasing exponentially >65 years. In younger patients, thrombotic events represent a higher risk than bleeding, while thrombotic and bleeding risks were similar in older patients. Important clinical implications relate to prasugrel dose in the elderly, duration of DAPT and

We aimed at assessing stent geometry and in-stent contrast attenuation with 64-slice CT in patients with various coronary stents. Twenty-nine patients (mean age 60 ± 11years; 24 men) with 50 stents underwent CT within 2weeks after stent placement. Mean in-stent luminal diameter and reference vessel diameter proximal and distal to the stent were assessed with CT, and compared to quantitative coronary angiography (QCA). Stent length was also compared to the manufacturer's values. Images were reconstructed using a medium-smooth (B30f) and sharp (B46f) kernel. All 50 stents could be visualized with CT. Mean in-stent luminal diameter was systematically underestimated with CT compared to QCA (1.60 ± 0.39mm versus 2.49 ± 0.45mm; P < 0.0001), resulting in a modest correlation of QCA versus CT (r = 0.49; P < 0.0001). Stent length as given by the manufacturer was 18.2 ± 6.2mm, correlating well with CT (18.5 ± 5.7mm; r = 0.95; P < 0.0001) and QCA (17.4 ± 5.6mm; r = 0.87; P < 0.0001). Proximal and distal reference vessel diameters were similar with CT and QCA (P = 0.06 and P = 0.03). B46f kernel images showed higher image noise (P < 0.05) and lower in-stent CT attenuation values (P < 0.001) than images reconstructed with the B30f kernel. 64-slice CT allows measurement of coronary artery in-stent density, and significantly underestimates the true in-stent diameter compared to QCA

Aims To investigate the efficacy and outcome of emergency percutaneous coronary interventions (PCI) in patients with stent thrombosis. Methods and results Between 1995 and 2003, 6058 patients underwent bare-metal stent implantation, of which 95 (1.6%) patients suffered from stent thrombosis. The timing of stent thrombosis was acute in 10 (11%), subacute in 61 (64%), and late in 24 (25%) patients. Procedural and clinical outcomes of emergency PCI for treatment of stent thrombosis were investigated. Emergency PCI was successful in 86 (91%), complicated by death in 2 (2%), and coronary artery bypass grafting in 2 (2%) patients. Myocardial infarction occurred in 77 (81%) patients with a peak creatine kinase level of 1466±1570 U/L. Left ventricular ejection fraction declined from 0.54±0.19 prior to 0.48±0.16 (P<0.05) at the time of stent thrombosis after emergency PCI. A 6 month major adverse clinical events comprised death (11%), reinfarction (16%), and recurrent stent thrombosis (12%) after emergency PCI. Multivariable logistic regression analysis identified the achievement of TIMI 3 flow (OR=0.1, CI 95% 0.01-0.54, P<0.001) and diameter stenosis <50% (OR=0.06, CI 95% 0.01-0.32, P<0.001) during emergency PCI to be independently associated with a reduced risk of cardiac death. Recurrent stent thrombosis was independently predicted by the omission of abciximab (OR=4.3, CI 95% 1.1-17.5). Conclusion Emergency PCI for treatment of stent thrombosis effectively restores vessel patency and flow. Patients presenting with stent thrombosis are at risk for recurrent myocardial infarction and recurrent stent thrombosis

Objective: Female gender is associated with reduced tolerance against acute ischemic events and a higher degree of left ventricular hypertrophy under chronic pressure overload. We tested whether female and male rats with left ventricular hypertrophy present the same susceptibility to demand ischemia. Methods: Hearts from hypertrophied female and male salt-resistant and salt-sensitive Dahl rats (n=8 per group) underwent 30min of demand ischemia induced by rapid pacing (7Hz) and an 85% reduction of basal coronary blood flow, followed by 30min of reperfusion on an isovolumic red cell perfused Langendorff model. Results: In female hearts, high-salt diet induced a pronounced hypertrophy of the septum (2.38±0.09 vs 2.17±0.08mm; p≪0.01), whereas male hearts showed the greatest increase in the anterior/posterior wall of the left ventricle (LV) (3.19±0.22 vs 2.01±0.16mm; p≪0.05) compared with salt-resistant controls. At baseline, LV-developed pressure/g LV was significantly higher in female than male hearts (200±13 and 196±14 vs 161±10 and 152±15mmHgg−1; p≪0.01), independent of hypertrophy, indicating greater contractility in females. During ischemia, LV-developed pressure decreased in all groups; at the end of reperfusion, hypertrophied female and male hearts showed higher developed pressures independent of gender (148±3 and 130±8 vs 100±7 and 85±6mmHg; p≪0.01). In contrast, diastolic pressure was more pronounced in female than in male hypertrophied hearts during ischemia and reperfusion (24±3 vs 12±2mmHg; p≪0.01). Conlusions: In the pressure overload model of the Dahl salt-sensitive rat, female gender is associated with a more pronounced concentric hypertrophy, whereas male hearts develop a more eccentric type of remodeling. Although present at baseline, after ischemia/reperfusion systolic function is gender-independent but more determined by hypertrophy. In contrast, diastolic function is gender-dependent and aggravated by hypertrophy, leading to pronounced diastolic dysf

Primary diastolic failure is typically seen in patients with hypertensive or valvular heart disease as well as in hypertrophic or restrictive cardiomyopathy but can also occur in a variety of clinical disorders, especially tachycardia and ischemia. Diastolic dysfunction has a particularly high prevalence in elderly patients and is generally associated, with low mortality but high morbidity. The pathophysiology of diastolic dysfunction includes delayed relaxation, impaired LV filling and/or increased stiffness. These conditions result typically in an upward displacement of the diastolic pressure-volume relationship with increased end-diastolic, left atrial and pulmo-capillary wedge pressure leading to symptoms of pulmonary congestion. Diagnosis of diastolic heart failure requires three conditions: (1) presence of signs or symptoms of heart failure; (2) presence of normal or slightly reduced LV ejection fraction (EF>50%) and (3) presence of increased diastolic filling pressure. Assessment of diastolic function can be performed with several non-invasive (2D- and Doppler-echocardiography, color Doppler M-mode, Doppler tissue imaging, MR-myocardial tagging, radionuclide ventriculography) and invasive techniques (micromanometry, angiography, conductance method). Doppler-echocardiography is the most useful tool to routinely measure diastolic function. Different techniques can be used alone or in combination to assess LV diastolic function, but most of them are dependent on heart rate, pre- and afterload. The transmitral flow pattern remains the starting point, since it is easy to acquire and rapidly categorizes patients into normal (E>A), delayed relaxation (E

Objectives: The goal of this clinical study was to assess the influence of hyperemic ipsilateral, collateral and contralateral vascular resistance changes on the coronary flow velocity reserve (CFVR) of the collateral-receiving (i.e. ipsilateral) artery, and to test the validity of a model describing the development of collateral steal. Methods: In 20 patients with one- to two-vessel coronary artery disease (CAD) undergoing angioplasty of one stenotic lesion, adenosine induced intracoronary (i.c.) CFVR during vessel patency was measured using a Doppler guidewire. During stenosis occlusion, simultaneous i.c. distal ipsilateral flow velocity and pressure (Poccl, using a pressure guidewire) as well as contralateral flow velocity measurements via a third i.c. wire were performed before and during intravenous adenosine. From those measurements and simultaneous mean aortic pressure (Pao), a collateral flow index (CFI), and the ipsilateral, collateral, and contralateral vascular resistance index (Ripsi, Rcoll, Rcontra) were calculated. The study population was subdivided into groups with CFI<0.15 and with CFI≥0.15. Results: The percentage-diameter coronary artery stenosis (%-S) to be dilated was similar in the two groups: 78±10% versus 82±12% (NS). CFVR was not associated with %-S. In the group with CFI≥0.15 but not with CFI<0.15, CFVR was directly and inversely associated with Rcoll and Rcontra, respectively. Conclusions: A hemodynamic interaction between adjacent vascular territories can be documented in patients with CAD and well developed collaterals among those regions. The CFVR of a collateralized region may, thus, be more dependent on hyperemic vascular resistance changes of the collateral and collateral-supplying area than on the ipsilateral stenosis severity, and may even fall below 1

Objective: Clopidogrel has become the standard of care to prevent thrombotic complications following cardiological interventions, in particular intracoronary stenting. In addition, patients with aspirin intolerance and those with carotid and peripheral vascular disease are also increasingly treated with clopidogrel. Platelet inhibition may become a concern for hemostasis in patients treated with clopidogrel who need emergency and undelayed surgery. Methods: We prospectively analyzed the intra- and postoperative outcome of 505 consecutive patients who underwent isolated CABG and compared two groups: those with clopidogrel exposure until 72 h prior to surgery (n=136) with those without exposition to clopidogrel (n=369). Patients undergoing emergency surgery because of failed PTCA and cardiogenic shock, associated valvular surgery, redo-CABG, and those with additional platelet IIb/IIIa receptor inhibitor exposure were excluded. Patients who received aspirin and/or heparin treatment prior to surgery were not excluded. Results: Patients who received clopidogrel had a higher prevalence of angina class III or IV (67 vs 39%, P<0.01), received more often revascularization within 48 h (41 vs 14%, P=0.02), and had received more frequently stenting (57 vs 13%). Chest tube drainage was significantly increased during the first 24 h following CABG in the group of patients who had clopidogrel treatment (1485 vs 780 ml, P=0.003) These patients also required more transfusion of platelets and fresh frozen plasma. Overall re-exploration rate because of bleeding was significantly higher in the clopidogrel group (5.9 vs 1.2%, P<0.01). Platelets transfused before chest closure had a beneficial effect on preservation of the hemostasis. Conclusions: Clopidogrel exposure 3 days or less prior to CABG surgery significantly increases the risk of postoperative bleeding, the need for perioperative transfusion and the incidence of re-exploration. Surgery should be performed using standard heparini

Objectives: The effects of exercise training on LV remodelling following large anterior myocardial infarction (MI) remains controversial. Blockade of the renin-angiotensin system has been shown to prevent ventricular dilation and deleterious remodeling. We therefore tested, in a rat model of chronic MI, whether any potentially deleterious effects of exercise on post-MI remodelling could be ameliorated by angiotensin II receptor blockade. Methods: Male Wistar rats underwent coronary ligation or sham operation. Treatment with losartan (10 mg/kg/day) began 1 week post-MI and moderate treadmill exercise (25 m/min, 60 min/day, 5 days/week) was initiated 2 weeks post-MI. Systolic and diastolic pressure-volume relationships were measured in isolated, red-cell perfused, isovolumically beating hearts 8 weeks post-MI. Morphometric measurements were performed in trichrome stained cross sections of the heart. Five groups of animals were compared: sham (n=13), control MI (MI; n=11), MI plus losartan (MI-Los; n=13), MI plus exercise (MI-Ex; n=10) and MI plus exercise and losartan (MI-Ex-Los; n=12). Results: Infarct size (% of left ventricle, LV) was similar among the infarcted groups [MI=43±4%, MI-Los=49±2%, MI-Ex=45±1%, MI-Ex-Los=48±2% (NS)]. Exercise, losartan and exercise+losartan treatments all attenuated LV dilation post-MI to a similar degree. Exercise training increased LV developed pressure in both untreated and losartan treated hearts (P<0.05 vs. other MI groups). In addition, exercise resulted in additional scar thinning in untreated hearts, while no additional scar thinning was seen in post-infarct hearts receiving both losartan and exercise. Conclusions: Following large anterior MI, losartan attenuated LV dilation and scar thinning. In untreated animals, exercise decreased dilation, but also contributed to scar thinning. Therefore, exercise concurrent with blockade of the renin-angiotensin system may provide optimal therapeutic benefit following large anterior MI

Aims Percutaneous coronary intervention (PCI) in diabetic patients is associated with an increased risk of restenosis and major adverse cardiac events (MACE). We assessed the impact of diabetes on long-term outcome after PCI with sirolimus-eluting (SES) and paclitaxel-eluting (PES) stents. Methods and results In the SIRTAX trial, 1012 patients were randomized to treatment with SES (n = 503) or PES (n = 509). A stratified analysis of outcomes was performed according to the presence or absence of diabetes. Baseline characteristics were well balanced between SES and PES in patients with (N = 201) and without diabetes (N = 811). Clinical outcome was worse in diabetic compared with non-diabetic patients regarding death (9.0% vs. 4.1%, P = 0.004) and MACE (defined as cardiac death, myocardial infarction, or TLR; 19.9% vs. 12.7%, P = 0.007) at 2 years. Among diabetic patients, SES reduced MACE by 47% (14.8% vs. 25.8%, HR = 0.52, P = 0.05) and TLR by 61% (7.4% vs. 17.2%, HR = 0.39, P = 0.03) compared with PES at 2 years. Conclusion Diabetic patients have worse prognosis than non-diabetic patients undergoing PCI with DES. Among the diabetic patient population of this trial, SES reduce repeat revascularization procedures and MACE more effectively than PES and to a similar degree as in non-diabetic patients

Aims Late acquired incomplete stent apposition (ISA) is more common after drug-eluting stent (DES) than bare metal stent (BMS) implantation and has been associated with vascular hypersensitivity and stent thrombosis (ST). We investigated the impact of incidentally discovered ISA as assessed by intravascular ultrasound (IVUS) 8 months after DES implantation on the long-term clinical outcome. Methods and results A total of 194 patients with 221 lesions were prospectively followed through 5 years. At 8 months, IVUS showed evidence of ISA among 37 patients with 39 lesions (18%) (mean ISAmax 4.7 ± 5.0 mm2), whereas no ISA was observed among 157 patients with 182 lesions. Incomplete stent apposition was more prevalent among segments treated with sirolimus-eluting (n = 103) than paclitaxel-eluting stents (n = 118) (27 vs. 9%, P = 0.001). Between IVUS investigation at the 8-month and 5-year follow-up, major adverse cardiac events occurred more frequently in patients with (18.9%, n = 7) than without ISA (7.0%, n = 11) (HR = 2.71, 95% CI: 1.05-6.96, P = 0.031). While there were no differences with respect to death, the rate of myocardial infarction was higher among patients with (13.5%, n = 5) than without ISA (1.9%, n = 3) (HR = 7.53, 95% CI: 1.79-31.6, P = 0.001). Very late ST was more common among patients with than without ISA [Academic Research Consortium-definite ST:13.5% (n = 5) vs. 0.6% (n = 1) HR = 23.2, 95% CI: 2.65-203, P < 0.001]. Conclusion In the present study, the presence of ISA as assessed by IVUS 8 months after DES implantation was associated with a higher rate of myocardial infarction and very late stent thrombosis during long-term follow-up. The prognostic impact of ISA on long-term clinical outcomes requires further investigation

BACKGROUND: In most patients with secundum atrial septal defects (ASD), transcatheter closure is the preferred treatment strategy, but whether device size affects clinical outcomes is unknown. We sought to study the efficacy and safety of large closure devices compared to the use of smaller devices. METHODS: Using a single-center, prospective registry of adult patients undergoing transcatheter ASD closure, patients receiving a large closure device (waist diameter ≥25 mm, n = 41) were compared to patients receiving smaller devices (waist diameter ≤24 mm, n = 66). We analyzed pre-interventional clinical, hemodynamic and echocardiographic data, interventional success and complication rates, and 6-month clinical and echocardiographic outcomes. The primary efficacy outcome was successful ASD closure achieved by a single procedure and confirmed by lack of a significant residual shunt at 6 months. The primary safety outcome was a composite of device embolization, major bleeding, and new-onset atrial arrhythmia occurring within 6 months. RESULTS: Transcatheter ASD closure using large devices was successful in 90 % compared to 97 % of patients receiving smaller devices as defined by the primary efficacy outcome (p = 0.20). The primary safety outcome occurred in 4 patients of the large and 6 patients of the small device group, resulting in an event-free rate of 90 and 91 %, respectively (p = 0.89). Similar significant symptomatic improvement was observed in both treatment groups after 6 months, indicated by a 50 % increase in the fraction of patients in NYHA class I (p < 0.0001 vs. baseline). CONCLUSIONS: Transcatheter closure in this cohort of patients with large or small ASD was effective with similar complication rates during short-term follow-up irrespective of the size of the implanted device.