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Background: Current guidelines on oral anticoagulation (OAC) in adults with congenital heart disease (ACHD) and atrial arrhythmias (AA) consist of heterogeneous and divergent recommendations with limited level of evidence, possibly leading to diverse OAC management and different outcomes. Therefore, we aimed to evaluate real-world implementation and outcome of three guidelines on OAC management in ACHD patients with AA. Methods: The ESC GUCH 2010, PACES/HRS 2014 and ESC atrial fibrillation (AF) 2016 guidelines were assessed for implementation. ACHD patients with recurrent or sustained non-valvular AA from 5 tertiary centers were identified using a national ACHD registry. After two years of prospective follow-up, thromboembolism, major bleeding and death were assessed. Results: In total, 225 adults (mean age 54 ± 15 years, 55% male) with various defects (simple 43%; moderate 37%; complex 20%) and AA were included. Following the most strict indication (OAC is recommended in all three guidelines), one should treat a mere 37% of ACHD patients with AA, whereas following the least strict indication (OAC is recommended in any one of the three guidelines), one should treat 98% of patients. The various guidelines were implemented in 54–80% of patients. From all recommendations, Fontan circulation, CHA2DS2-VASc ≥ 1 and AF were independently associated with OAC prescription. Superiority of any guideline in identifying outcome (n = 15) could not be demonstrated. Conclusions: The implementation of current guidelines on OAC management in ACHD patients with AA is low, probably due to substantial heterogeneity among guidelines. OAC prescription in daily practice was most consistent in patients with AF and CHA2DS2-VASc ≥ 1 or Fontan circulation.

Daily generation of novel platelets may compromise aspirin's platelet inhibitory action, especially near the end of the regular 24-h dosing interval. A contributor to this attenuation could be the endogenous circadian rhythm. The primary objective of this study was to assess platelet activity 12 and 24 h after different times of aspirin intake (c.q. 8.00 AM and 8.00 PM). A randomized open-label crossover study was conducted, comprising outpatients with stable cardiovascular disease taking aspirin once daily. We measured platelet aggregation with the platelet function analyzer (PFA)-200(®) and light transmission aggregometry (LTA). The attenuation of aspirin's inhibitory action was most apparent in the 8.00 AM regimen. The platelet function analyzer-closure time was 78 s faster at 24 h than at 12 h after intake in the 8.00 AM regimen (IQR: 166.8-301 vs. 132.8-301; p = 0.006) and 0 s faster at 24 h than at 12 h after intake in the 8.00 PM regimen (IQR: 198.8-837.0 vs. 169.8-301; p = 0.653). The adenosine diphosphate 1.0 µmol/L maximum amplitude was 5.40% higher at 24 h than at 12 h after intake in the 8.00 AM regimen (95% confidence interval (CI): -0.03--10.8; p = 0.040) and was 0.75% higher 24 h than at 12 h after intake in the 8.00 PM regimen (95% CI: -4.83-3.33; p = 0.705). The platelet inhibitory effect of aspirin decreases after 24 h, particularly after intake in the morning. These results suggest that patients might benefit from evening intake or twice daily intake regimens.

Contrast enhancement by microbubble infusion has proven its applicability in the field of diagnostic ultrasound. Recent studies also indicate a therapeutic effect of the combined use of ultrasound and microbubbles. Results from animal studies demonstrate that diagnostic ultrasound in combination with intravenous microbubbles can dissolve thrombi. So far, this effect has never been tested in patients with an acute ST-elevation myocardial infarction (STEMI). We recently launched a pilot study in acute STEMI patients to assess safety, feasibility and efficacy of the treatment in this patient group with transthoracic three-dimensional diagnostic ultrasound and intravenous microbubbles immediately after prehospital thrombolysis, but prior to primary percutaneous coronary intervention.

Contains fulltext : 81178.pdf (Publisher’s version ) (Closed access) BACKGROUND: In smokers treated with fibrinolysis for ST-elevation myocardial infarction (STEMI) a paradoxical beneficial short-term outcome has been reported. This was attributed to favorable clinical and angiographic baseline variables and a better response to fibrinolysis. During follow-up infarct artery reocclusion is an important prognosticator. We studied the effects of smoking on reocclusion and long-term cardiac outcome after successful fibrinolysis. METHODS: In the Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis trials (APRICOT-1 and -2) 499 STEMI patients with an open infarct artery

Background Whether late coronary patency after myocardial infarction has prognostic impact independent of left ventricular function remains a matter of debate. Reocclusion rates in the first year after fibrinolysis vary between 20% and 30%. Of all reocclusions, about 30% present as clinical reinfarction, associated with a 2-fold–increased risk of mortality. The clinical impact of reocclusion that presents without reinfarction has not been studied; but an association has been demonstrated with impaired contractile recovery of left ventricular function, the strongest prognosticator of long-term outcome. We therefore studied the impact of 3-month coronary patency after successful fibrinolysis on 10-year cardiac survival. Methods In the APRICOT-1 trial, 248 ST-elevation myocardial infarction patients with an open infarct artery 24 hours after fibrinolysis had 3-month repeated angiography. Ten-year clinical follow-up was complete in 99.6%. Results The reocclusion rate was 29% (71/248). Of these reocclusions, 24% presented as clinical reinfarction (17/71). Cardiac survival at 10 years was 73% in patients with a reoccluded infarct artery and 88% in patients with sustained patency (P Conclusions Sustained infarct artery patency in the first 3 months after successful fibrinolysis is a strong predictor of 10-year cardiac survival, independent of left ventricular function. Notably, this also holds true when reocclusion occurs without signs of clinical reinfarction or recurrent ischemia. Therefore, future preventive strategies should also focus on “clinically silent” reocclusions. Additional studies on better antithrombotic regimens and the combination with a routine invasive strategy early after successful fibrinolysis are warranted.

Background — Despite the use of aspirin, reocclusion of the infarct-related artery occurs in ≈30% of patients within the first year after successful fibrinolysis, with impaired clinical outcome. This study sought to assess the impact of a prolonged anticoagulation regimen as adjunctive to aspirin in the prevention of reocclusion and recurrent ischemic events after fibrinolysis for ST-elevation myocardial infarction. Methods and Results — At coronary angiography P P P P =NS). Conclusions — As adjunctive to aspirin, a 3-month-regimen of moderate-intensity coumarin, including heparinization until the target INR is reached, markedly reduces reocclusion and recurrent events after successful fibrinolysis. This conceptual study provides a mechanistic rationale to further investigate the role of prolonged anticoagulation after fibrinolytic therapy.

Background Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia. In non-high risk patients, with proven viability in the infarct-area, the VIAMI trial showed benefit of early in-hospital stenting of the infarct-related coronary artery for the composite of death, myocardial infarction (MI), or unstable angina (UA) at 1year follow-up. In this study we evaluated the long-term outcome (median 8years) of patients included in the VIAMI-trial. Methods After being stable during the first 48h of their acute MI, we randomly assigned 216 patients with viability to an invasive (PCI) or a conservative (ischemia-guided) strategy. The primary outcome was the composite endpoint of death from any cause, recurrent myocardial infarction, or unstable angina. The secondary outcome of this study was the need for (repeat) revascularization. Results The combined endpoint of death, recurrent MI and UA was 20.8% in the invasive group and 32.7% in the conservative group (hazard ratio 0.59; 95% CI 0.36–0.99, p=0.049). No differences were seen in death (8.5% vs. 8.2%, p=0.80) or MI (7.5% vs. 10.9%, p=0.48). Only UA showed a significant difference (4.7% vs. 13.6%, p=0.002). Repeated revascularization was performed in 22.6% of the invasive group and 41.8% of the conservative group (hazard ratio 0.43; 95% CI 0.29–0.74, p Conclusion In patients with acute MI (treated with thrombolysis or without reperfusion therapy) and proven viability in the infarct-area, we demonstrated a long-term benefit of early in-hospital stenting of the infarct-related coronary artery.

OBJECTIVES We sought to study the effect of early infusion of abciximab on coronary patency before primary angioplasty in patients with acute myocardial infarction. BACKGROUND Glycoprotein IIb/IIIa antagonists have proved to be effective in reducing ischemic events associated with coronary angioplasty. The present study explores whether abciximab alone, without administration of thrombolytic therapy, may induce reperfusion in patients with acute myocardial infarction. METHODS In the Glycoprotein Receptor Antagonist Patency Evaluation pilot study 60 patients with less than 6 h signs and symptoms of acute myocardial infarction eligible for primary angioplasty received in the emergency room a bolus of abciximab 250 μg/kg followed by a 12-h infusion of 10 μg/min. All patients were also treated with an oral dose of 160 mg aspirin and 5,000 IU of heparin intravenously. As soon as possible a diagnostic angiography was performed to evaluate the patency of the infarct-related artery. RESULTS The median time between onset of symptoms and the administration of the abciximab bolus was 150 min (range 45 to 345), and the median time between abciximab bolus and first contrast injection in the infarct-related artery was 45 min (range 10 to 150). In 24 patients (40%, 95% confidence interval 28% to 52%) Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 was observed at a median time of 45 min (range 10 to 150) after abciximab bolus; TIMI flow grade 3 was observed in 11 patients (18%, 95% confidence interval 9% to 28%). There was no difference in percentage of TIMI flow grade 2 or 3 between patients who received abciximab within 2.5 h after onset of symptoms or thereafter. CONCLUSIONS Abciximab therapy given in the emergency room in patients awaiting primary angioplasty is associated with full reperfusion (TIMI flow grade 3) in about 20% and with TIMI flow grade 2 or 3 in about 40% of the patients at a median time of 45 min. These figures are higher than those in primary angioplasty trials without such pretreatment. Randomized controlled trials of very early infusion of abciximab, either prehospital or in-hospital, in patients eligible for angioplasty are warranted.

Background Viability seems to be important in preventing ventricular remodeling after acute myocardial infarction (AMI). We investigated the influence of viability, as demonstrated with low-dose dobutamine echocardiography, and the role of early revascularization on the process of left ventricular (LV) remodeling after AMI. Methods We retrospectively investigated 224 patients who were initially included in the viability-guided angioplasty after acute myocardial infarction-trial (VIAMI-trial). Patients in the VIAMI-trial did not undergo a primary or rescue percutaneous coronary intervention and were stable in the early in-hospital phase. Patients underwent viability testing within 72 hours after AMI. Patients with viability were randomized to an invasive strategy or an ischemia-guided strategy. Follow-up echocardiography was performed at a mean of 205 days. In this echocardiographic substudy, patients were divided into three new groups: group 1, viable and revascularized before follow-up echocardiogram; group 2, viable, but medically treated; and group 3, non-viable patients. Results Group 1 showed preservation of LV volume indices. The ejection fraction (EF) increased significantly from 54.0% to 57.5% (P = 0.047). Group 2 showed a significant increase in LV volume indices with no improvement in EF (53.3% versus 53.0%, P = 0.86). Group 3 showed a significant increase in LV volume indices, with a decrease in EF from 53.5% to 49.1% (P = 0.043). Multivariate logistic regression analysis indicated the number of viable segments and revascularization during follow-up as independent predictors for EF improvement, especially in patients with lower EF at baseline. Conclusion Viability early after AMI is associated with improvement in LV function after revascularization. When viable myocardium is not revascularized, the LV tends to remodel with increased LV volumes, without improvement of EF. Absence of viability results in ventricular dilatation and deterioration of EF, irrespective of revascularization status. Trial registration NCT00149591 (assigned: 6 September 2005). Electronic supplementary material The online version of this article (doi:10.1186/1745-6215-15-329) contains supplementary material, which is available to authorized users.

Background: HMG-coA-reductase-inhibitors (statins) have been proven to reduce atherosclerosis progression as observed by carotid intima-media thickness in patients with known coronary heart disease, independent of lipid lowering. Cardiovascular complications are common in patients after successful coarctation repair. The effect of statins on cardiovascular risk in adults after successful coarctation repair has not yet been established.Methods: We designed a multicentre, prospective, randomised, open label trial to evaluate the effect of the HMGcoA-reductase-inhibitor (Atorvastatin) on atherosclerotic progression in adult post-coarctectomy patients. The primary endpoint in this study is the carotid intima-media thickness as measured by Bmode ultrasonography of the carotid arteries.Conclusion: This large prospective, randomised, open label trial will establish the effect of HMG-coA-reductase inhibitors (Atorvastatin) on cardiovascular risk in adult patients after successful coarctation repair. (C) 2011 Elsevier Inc. All rights reserved.

In non-high risk patients treated without primary PCI for acute myocardial infarction (AMI), the updated American Heart Association/American College of Cardiology guidelines recommend a selective pharmacoinvasive strategy (IIb, level C). Early risk assessment is essential to select patients with an increased risk for ischemic events or cardiac death. A potential prognostic value has been ascribed to viability in the infarct region. Viability-testing with Low Dose Dobutamine echocardiography (LDDE) can safely be performed in the early phase after AMI. Since the prognostic value of viability after acute myocardial infarction remains unclear and is still debated, we performed a meta-analysis of post-infarction studies to elucidate the importance and prognostic value of viability early after AMI. The literature was scanned by formal searches of electronic databases from 1966 to June 2010. We used the following selection criteria for inclusion in this meta-analysis: a) viability testing with LDDE within 14 days after Acute Myocardial Infarction (AMI), b) preserved left ventricular function (ejection fraction(EF) ≥40% or wall motion score index (WMSI) ≤1.9), c) prognosis scored by clinical endpoints (death, AMI or unstable angina (UA)). Eight observational studies were included in the meta-analysis (2301 patients). Results: The presence of viability was strongly associated with an increase in ischemic cardiac events [OR 5.0 (1.53 - 16.36), p=0.008]. No predictive value was found for mortality [OR 0.91 (0.38 - 2.18), p=0.84]. In conclusion, patients with preserved left ventricular function and proven viability early after AMI are at risk for ischemic cardiac events, without any difference in mortality (Metaanalysis, acute myocardial infarction, viability, echocardiography).

In animal studies, transthoracic ultrasound and microbubbles have shown to dissolve thrombi in ST elevation myocardial infarction (STEMI). To examine this effect in patients, we have initiated the Sonolysis trial. In this pilot study of 10 patients with a first acute STEMI, we investigated the safety and feasibility of this trial. After pretreatment in the ambulance, five patients were randomized to receive microbubbles with three-dimensional (3-D) guided high mechanical index impulses (1.18) for 15 min, whereas the control group received placebo without ultrasound. Subsequently, primary percutaneous coronary intervention (PPCI) was performed, if indicated. All patients successfully underwent study treatment and PPCI. No significant difference between treatment and control group in safety (minor adverse events 2/5 vs. 2/5, p = NS) and outcome (TIMI III flow 3/5 vs. 1/5 respectively, p = 0.23) was recorded. These results demonstrate that the study protocol is feasible in the acute cardiac care setting and safe during treatment and follow-up.

Contains fulltext : 81815.pdf (Publisher’s version ) (Closed access) BACKGROUND: Long-term addition of antithrombotics (clopidogrel, anticoagulants) to aspirin has improved outcome after acute coronary syndromes. Data on the impact after fibrinolysis are scarce. In Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis-2 (APRICOT-2), adjunctive moderate-intensity coumarin (median international normalized ratio 2.6) conferred a marked reduction in 3-month reocclusion and ischemic events. Given the association between reocclusion and long-term outcome, we performed long-term clinical follow-up. METHODS: Patients with thrombolysis in myocardial infarction (TIMI) 3 flow

Background Although percutaneous coronary intervention (PCI) is becoming the standard therapy in ST-segment elevation myocardial infarction (STEMI), to date most patients, even in developed countries, are reperfused with intravenous thrombolysis or do not receive a reperfusion therapy at all. In the post-lysis period these patients are at high risk for recurrent ischemic events. Early identification of these patients is mandatory as this subgroup could possibly benefit from an angioplasty of the infarct-related artery. Since viability seems to be related to ischemic adverse events, we initiated a clinical trial to investigate the benefits of PCI with stenting of the infarct-related artery in patients with viability detected early after acute myocardial infarction. Methods The VIAMI-study is designed as a prospective, multicenter, randomized, controlled clinical trial. Patients who are hospitalized with an acute myocardial infarction and who did not have primary or rescue PCI, undergo viability testing by low-dose dobutamine echocardiography (LDDE) within 3 days of admission. Consequently, patients with demonstrated viability are randomized to an invasive or conservative strategy. In the invasive strategy patients undergo coronary angiography with the intention to perform PCI with stenting of the infarct-related coronary artery and concomitant use of abciximab. In the conservative group an ischemia-guided approach is adopted (standard optimal care). The primary end point is the composite of death from any cause, reinfarction and unstable angina during a follow-up period of three years. Conclusion The primary objective of the VIAMI-trial is to demonstrate that angioplasty of the infarct-related coronary artery with stenting and concomitant use of abciximab results in a clinically important risk reduction of future cardiac events in patients with viability in the infarct-area, detected early after myocardial infarction.

Contains fulltext : 58311.pdf (Publisher’s version ) (Closed access) BACKGROUND: After successful thrombolysis, a high-grade stenosis at 24-hour angiography is strongly predictive of reocclusion and is often believed to result in high reinfarction rates. However, routine angioplasty did not reduce death or reinfarction in past trials. Systematic angiographic follow-up shows that reocclusion often occurs without clinical reinfarction. This study investigates whether the increased risk for reocclusion associated with a high-grade lesion translates into impaired clinical outcome. METHODS: In the ischemia-guided Antithrombotics in the Prevention of Reocclusion in COronary Thrombolysis (APRICOT-1) trial, 240 patients with ST-elevation MI who had an open infarct artery 24 hours after thrombolysis had 3-month repeat angiography to assess reocclusion, with clinical follow-up at 3 months and 3 years. RESULTS: On the basis of the optimal discriminative stenosis severity, the reocclusion rate was 40% (47/118) in patients with a high-grade residual stenosis and 16% (20/122) in patients with a low-medium-grade lesion (risk ratio [RR], 2.43; 95% CI, 1.54-3.84; P

Background Successful thrombolysis can prevent left ventricular dilatation after acute myocardial infarction. However, in almost 30% of patients, reocclusion occurs. The aim of this study was to assess the long-term implications of reocclusion on left ventricular size and function. Methods and Results Fifty-six patients were studied with two-dimensional echocardiography at baseline (2±1.6 days) and 5.0±1.4 years after first anterior myocardial infarction. All patients (a subset of those enrolled in the APRICOT trial) had a patent infarct-related artery when studied P =.008) and end-systolic volume index (ESVI; P =.039). Furthermore, patients without reocclusion demonstrated improvement in wall motion score index (WMSI; P =.0001) and ejection fraction (EF; P =.016), whereas patients with reocclusion did not. After 5 years, patients with reocclusion had significantly larger volume indexes (EDVI, 99±41 versus 76±22 mL/m 2 , P =.007; ESVI, 59±40 versus 39±20 mL/m 2 , P =.017) and more compromised left ventricular function (WMSI, 1.63±0.33 versus 1.39±0.32, P =.013; EF, 45±13% versus 51±11%, P =.077) than patients without reocclusion. Multivariate analysis identified baseline WMSI and reocclusion as significant independent predictors of left ventricular dilatation. Conclusions Reocclusion of the infarct-related artery within 3 months of successful thrombolysis is associated with left ventricular dilatation and is detrimental to functional recovery of left ventricular function 5 years after first anterior myocardial infarction.

Objectives.This study sought to assess the long-term clinical consequences of reocclusion after coronary thrombolysis.Background.After acute myocardial infarction successfully treated with thrombolysis, reocclusion occurs in ∼ 30% of patients and leads to poorer in-hospital outcome. However, the long-term effects of reocclusion are unknown.Methods.Three hundred patients with no history of coronary surgery and with a patent infarct-related artery at coronary angiography within 48 h after thrombolysis were enrolled in the Antithrombotics in the Prevention of Reocclusion in Coronary Thrombolysis (APRICOT) trial. At a mean (±SD) of 77 ± 23 days after thrombolysis, 248 patients (87%) underwent follow-up angiography. Reocclusion was observed in 71 (29%) of 248 patients. To compare outcome between 71 patients with and 177 without reocclusion an analysis of event-free survival, defined as a clinical course without death, reinfarction and revascularization, was performed.Results.Over a 3-year follow-up period, event-free survival was significantly better in patients without reocclusion: At 1 year it was 63% for patients with and 83% for those without reocclusion (p < 0.001). In the first year, two or more cardiac-related events occurred in 24% of patients with and 6% of those without reocclusion (p < 0.001). Patients with reocclusion had a markedly higher reinfarction and revascularization rate. At 1 year the reinfarction rate was 23% for patients with and 5% for those without reocclusion (p < 0.001).Conclusions.This analysis shows the adverse influence of reocclusion on long-term clinical outcome in relation to reinfarction and need for revascularization. To further optimize prognosis after thrombolysis, prevention of reocclusion should become a main priority. Future research should focus on the criteria and timing of elective revascularization procedures in the prevention of coronary reocclusion.

Objectives. In the APRICOT study (Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis), we sought to determine whether angiographic characteristics of the culprit lesion could predict reocclusion after successful thrombolysis and to analyze the influence of three antithrombotic treatment regimens.Background. After successful thrombolysis, reocclusion is a major problem. Prediction of reocclusion by angiographic data and choice of antithrombotic treatment would be important for clinical management.Methods. After thrombolysis, patients were treated with intravenous heparin until initial angiography was performed within 48 h. Patients with a patent infarct-related artery were eligible. Three hundred patients were randomly selected for treatment with coumadin, aspirin (300 mg once daily) or placebo. Patency on a second angiographic study after 3 months was the primary end point of the study.Results. Reocclusion rate was 25% with aspirin, 30% with coumadin and 32% with placebo (p = NS). Lesions with >90% stenosis reoccluded more frequently (42%) than did those with 90% to be an independent predictor of reocclusion (odds ratio 2.31, 95% confidence interval 1.28 to 4.18, p = 0.006).Conclusions. Angiographic features of the culprit lesion after successful coronary thrombolysis significantly predict the risk of reocclusion: high grade (>90%) stenoses reoccluded more frequently. Aspirin was effective only in complex and less severe lesions (

Objectives. We sought to determine the effect of high dose intravenous bolus heparin on early coronary patency before primary angioplasty.Background. Early coronary angiography after thrombolysis for acute myocardial infarction has shown better patency when intravenous heparin is used as an adjunct. The present study explores whether heparin alone can induce reperfusion.Methods. In the Heparin in Early Patency (HEAP) pilot study, 108 patients with signs and symptoms of acute myocardial infarction 2 h (p = 0.02). No significant bleeding was seen. Two patients (2%) died in the hospital. The patency results obtained in patients treated with the high dose bolus heparin were compared with those in 108 patients from a large primary angioplasty database, who were treated with standard therapy, including aspirin but not intravenous heparin, and were matched for clinical and angiographic characteristics with the HEAP pilot study patients. They showed an 18% patency rate (p < 0.001) of the IRA (TIMI flow grade 3 in 9%, TIMI flow grade 2 in 9%) before primary angioplasty.Conclusions. Early therapy with high dose heparin is associated with full coronary reperfusion in a considerable number of patients with acute myocardial infarction, especially in those treated early (