A prospective cohort study to assess the relevance of vedolizumab drug level monitoring in IBD patients.

BACKGROUND: Vedolizumab (VDZ) drug monitoring strategies in inflammatory bowel disease (IBD) patients have not been systematically investigated so far. We evaluated the correlation between VDZ trough levels (VTL) and the treatment response in IBD. METHODS: Fifty-one patients with active IBD on or starting a therapy with VDZ were enrolled in this prospective and observational single centre study. Disease activity indices, blood tests, and anthropometric parameters were assessed over a time period of 6 months. One hundred and fifty-five VDZ serum trough levels were measured directly before the next scheduled application using liquid chromatography mass spectrometry (LC-MS/MS). RESULTS: VDZ treatment was found to be clinically effective (Harvey Bradshaw Index (HBI) dropping from 10 to 5.5 points (p < .0005) in Crohn's disease (CD) patients; partial Mayo score (pMS) from 4.4 to 2.1 points (p < .0005) in ulcerative colitis patients (UC). CRP levels tended to decrease and haemoglobin levels to increase under VDZ therapy. CD patients with a serum CRP level lower than 5 mg/l exhibited significantly higher VTL than those with elevated CRP levels (34.9 versus 21.7 µg/ml, p = .00153). UC patients with haemoglobin levels higher 12 g/dl at the time of VTL measurement had significantly higher VTL compared to patients with lower haemoglobin levels (35.4 versus 15.6 µg/ml, p < .0005). CONCLUSIONS: Our data suggest a significant correlation between VTL and response to therapy in IBD patients (higher VTL associated with better response).

White-Light or Narrow-Band Imaging Colonoscopy in Surveillance of Ulcerative Colitis: A Prospective Multicenter Study.

BACKGROUND & AIMS: Early detection of neoplastic lesions is essential in patients with long-standing ulcerative colitis but the best technique of colonoscopy still is controversial. METHODS: We performed a prospective multicenter study in patients with long-standing ulcerative colitis. Two colonoscopies were performed in each patient within 3 weeks to 3 months. In white-light (WL) colonoscopy, stepwise random biopsy specimens (4 biopsy specimens every 10 cm), segmental random biopsies (2 biopsy specimens in 5 segments), and targeted biopsy specimens were taken. In NBI colonoscopy, segmental and targeted biopsy specimens were taken. The sequence of WL and NBI colonoscopy was randomized. RESULTS: In 36 of 159 patients enrolled (22.6%), 54 lesions with intraepithelial neoplasia (IN) were found (51 low-grade, 3 high-grade). In WL colonoscopy we found 11 IN in stepwise biopsy specimens, 4 in segmental biopsy specimens, and 15 in targeted biopsy specimens. In NBI colonoscopy 7 IN were detected in segmental biopsy specimens and 24 IN were detected in targeted biopsy specimens. Almost all IN were found with one technique alone (κ value of WL vs NBI, -0.86; P < .001). Statistically equivalent numbers of IN were found in NBI colonoscopy with targeted and segmental biopsy specimens as in WL colonoscopy with targeted and stepwise biopsy specimens, but with fewer biopsy specimens (11.9 vs 38.6 biopsy specimens, respectively; P < .001), and less withdrawal time was necessary (23 vs 13 min, respectively; P < .001). CONCLUSIONS: Stepwise biopsy specimens are indispensable in WL colonoscopy. The combination of targeted and segmental biopsy specimens in the NBI technique is as sensitive as targeted together with stepwise biopsy specimens in WL colonoscopy, but requires fewer biopsy specimens and less time. The highest sensitivity should be reached by combining the WL and NBI techniques by switching between the modes.

Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction (HORIZONS-AMI): final 3-year results from a multicentre, randomised controlled trial.

BACKGROUND: Primary results of the HORIZONS-AMI trial have been previously reported. In this final report, we aimed to assess 3-year outcomes. METHODS: HORIZONS-AMI was a prospective, open-label, randomised trial undertaken at 123 institutions in 11 countries. Patients aged 18 years or older were eligible for enrolment if they had ST-segment elevation myocardial infarction (STEMI), presented within 12 h after onset of symptoms, and were undergoing primary percutaneous coronary intervention. By use of a computerised interactive voice response system, we randomly allocated patients 1:1 to receive bivalirudin or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI; pharmacological randomisation; stratified by previous and expected drug use and study site) and, if eligible, randomly allocated 3:1 to receive a paclitaxel-eluting stent or a bare metal stent (stent randomisation; stratified by pharmacological group assignment, diabetes mellitus status, lesion length, and study site). We produced Kaplan-Meier estimates of major adverse cardiovascular events at 3 years by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00433966. FINDINGS: Compared with 1802 patients allocated to receive heparin plus a GPI, 1800 patients allocated to bivalirudin monotherapy had lower rates of all-cause mortality (5·9%vs 7·7%, difference -1·9% [-3·5 to -0·2], HR 0·75 [0·58-0·97]; p=0·03), cardiac mortality (2·9%vs 5·1%, -2·2% [-3·5 to -0·9], 0·56 [0·40-0·80]; p=0·001), reinfarction (6·2%vs 8·2%, -1·9% [-3·7 to -0·2], 0·76 [0·59-0·99]; p=0·04), and major bleeding not related to bypass graft surgery (6·9%vs 10·5%, -3·6% [-5·5 to -1·7], 0·64 [0·51-0·80]; p=0·0001) at 3 years, with no significant differences in ischaemia-driven target vessel revascularisation, stent thrombosis, or composite adverse events. Compared with 749 patients who received a bare-metal stent, 2257 patients who received a paclitaxel-eluting stent had lower rates of ischaemia-driven target lesion revascularisation (9·4%vs 15·1%, -5·7% [-8·6 to -2·7], 0·60 [0·48-0·76]; p<0·0001) after 3 years, with no significant differences in the rates of death, reinfarction, stroke or stent thrombosis. Stent thrombosis was high (≥4·5%) in both groups. INTERPRETATION: The effectiveness and safety of bivalirudin monotherapy and paclitaxel-eluting stenting are sustained at 3 years for patients with STEMI undergoing primary percutaneous coronary intervention. FUNDING: Boston Scientific and The Medicines Company.

Five-year results of the Multicenter Randomized Controlled Open-Label Study of the CYPHER Sirolimus-Eluting Stent in the Treatment of Diabetic Patients with De Novo Native Coronary Artery Lesions (SCORPIUS) study: a German multicenter investigation on the effectiveness of sirolimus-eluting stents in diabetic patients.

BACKGROUND: Because a delayed arterial healing response after drug-eluting stent implantation has raised concerns about safety in diabetic patients, long-term effects of treatment with sirolimus-eluting stent (SES), as compared with bare-metal stent (BMS), have to be established. The aim of the 5-year follow-up of the randomized, controlled, open-label multicenter SCORPIUS study was to assess long-term safety and efficacy of the CYPHER (Cordis, Johnson & Johnson, Bridgewater, NJ) SES in percutaneous coronary intervention of diabetic patients. METHODS: A total of 190 patients with type 2 diabetes mellitus were randomized to receive either a SES (n = 95) or a BMS (n = 95). Dual-antiplatelet therapy (aspirin plus clopidogrel) was prescribed for at least 6 months. Clinical follow-up data were scheduled at 1, 8, and 12 months and 5 years. RESULTS: Treatment with SES resulted in a 16% decrease in the rate of major adverse cardiac events (36% vs 52%; hazard ratio 0.6, 95% CI 0.4-0.9; P = .02). This reduction in major adverse cardiac events with SES at 5 years was mostly attributable to a lower number of repeat target lesion revascularization (13% vs 29%; hazard ratio 0.4, 95% CI 0.2-0.7; P = .003). No differences between groups were observed for safety end points (all-cause mortality 21% vs 21%, cardiac death 15% vs 13%, repeat myocardial infarction 8% vs 9%, and stent thrombosis 5% vs 6%) at 5 years. CONCLUSIONS: The 5-year follow-up of the SCORPIUS trial demonstrates the long-term antirestenotic efficacy of SES in diabetic patients with significantly reduced target lesion revascularization and comparable rates of mortality, myocardial infarction, and stent thrombosis compared with BMS.

Bivalirudin during primary PCI in acute myocardial infarction.

BACKGROUND: Treatment with the direct thrombin inhibitor bivalirudin, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in similar suppression of ischemia while reducing hemorrhagic complications in patients with stable angina and non-ST-segment elevation acute coronary syndromes who are undergoing percutaneous coronary intervention (PCI). The safety and efficacy of bivalirudin in high-risk patients are unknown. METHODS: We randomly assigned 3602 patients with ST-segment elevation myocardial infarction who presented within 12 hours after the onset of symptoms and who were undergoing primary PCI to treatment with heparin plus a glycoprotein IIb/IIIa inhibitor or to treatment with bivalirudin alone. The two primary end points of the study were major bleeding and combined adverse clinical events, defined as the combination of major bleeding or major adverse cardiovascular events, including death, reinfarction, target-vessel revascularization for ischemia, and stroke (hereinafter referred to as net adverse clinical events) within 30 days. RESULTS: Anticoagulation with bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, resulted in a reduced 30-day rate of net adverse clinical events (9.2% vs. 12.1%; relative risk, 0.76; 95% confidence interval [CI] 0.63 to 0.92; P=0.005), owing to a lower rate of major bleeding (4.9% vs. 8.3%; relative risk, 0.60; 95% CI, 0.46 to 0.77; P<0.001). There was an increased risk of acute stent thrombosis within 24 hours in the bivalirudin group, but no significant increase was present by 30 days. Treatment with bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, resulted in significantly lower 30-day rates of death from cardiac causes (1.8% vs. 2.9%; relative risk, 0.62; 95% CI, 0.40 to 0.95; P=0.03) and death from all causes (2.1% vs. 3.1%; relative risk, 0.66; 95% CI, 0.44 to 1.00; P=0.047). CONCLUSIONS: In patients with ST-segment elevation myocardial infarction who are undergoing primary PCI, anticoagulation with bivalirudin alone, as compared with heparin plus glycoprotein IIb/IIIa inhibitors, results in significantly reduced 30-day rates of major bleeding and net adverse clinical events. (ClinicalTrials.gov number, NCT00433966 [ClinicalTrials.gov].).

Successful interdisciplinary treatment of a rare cause of acute myocardial ischaemia from intermittent tumour-associated obstruction of the left main coronary artery: a case report.

BACKGROUND: A papillary fibroelastoma of the aortic valve has been reported as a rare cause of myocardial ischaemia. An advanced combined interventional and surgical approach leading to sufficient therapy for the patient is presented in this case report. CASE SUMMARY: A 56-year-old female patient presented in an emergency room of a hospital with an acute coronary syndrome. Over 1.5 years, recurrent stable angina had been known in the patient and significant coronary artery disease has already been ruled out in a previous coronary angiogram. The patient was immediately transferred to the catheter laboratory due to cardiogenic shock where a drug-eluting stent was implanted to, firstly, recanalize the left main coronary artery (LMCA) and, secondly, to protect the left main ostium from obstruction by an echocardiographic-proven mass. During subsequent deterioration of haemodynamics caused by decreasing left ventricular function and acute severe mitral insufficiency, firstly an intra-aortic balloon pump and secondly a veno-arterial extracorporeal membrane oxygenation was established through the femoral vessels. The patient was transferred to our cardiac surgery unit and was successfully operated utilizing a valve-sparing technique by extracting the tumour mass from the left coronary cusp and extracting the stent carefully from the LMCA. Histology revealed a papillary fibroelastoma. CONCLUSION: A papillary fibroelastoma of the aortic valve with intermittent obstruction of the coronary arteries requires surgical therapy. Interventional recanalization and extracorporeal support might be useful strategies to ensure the patient's safety as a bridge to surgery.

Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial.

BACKGROUND: In the HORIZONS-AMI trial, patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) who were treated with the thrombin inhibitor bivalirudin had substantially lower 30-day rates of major haemorrhagic complications and net adverse clinical events than did patients assigned to heparin plus a glycoprotein IIb/IIIa inhibitor (GPI). Here, we assess whether these initial benefits were maintained at 1 year of follow-up. METHODS: Patients aged 18 years or older were eligible for enrolment in this multicentre, open-label, randomised controlled trial if they had STEMI, presented within 12 h after the onset of symptoms, and were undergoing primary PCI. 3602 eligible patients were randomly assigned by interactive voice response system in a 1:1 ratio to receive bivalirudin (0.75 mg/kg intravenous bolus followed by 1.75 mg/kg per h infusion; n=1800) or heparin plus a GPI (control; 60 IU/kg intravenous bolus followed by boluses with target activated clotting time 200-250 s; n=1802). The two primary trial endpoints were major bleeding and net adverse clinical events (NACE; consisting of major bleeding or composite major adverse cardiovascular events [MACE; death, reinfarction, target vessel revascularisation for ischaemia, or stroke]). This prespecified analysis reports data for the 1-year follow-up. Analysis was by intention to treat. Patients with missing data were censored at the time of withdrawal from the study or at last follow-up. This trial is registered with ClinicalTrials.gov, number NCT00433966. FINDINGS: 1-year data were available for 1696 patients in the bivalirudin group and 1702 patients in the control group. Reasons for participant dropout were loss to follow-up and withdrawal of consent. The rate of NACE was lower in the bivalirudin group than in the control group (15.6%vs 18.3%, hazard ratio [HR] 0.83, 95% CI 0.71-0.97, p=0.022), as a result of a lower rate of major bleeding in the bivalirudin group (5.8%vs 9.2%, HR 0.61, 0.48-0.78, p<0.0001). The rate of MACE was similar between groups (11.9%vs 11.9%, HR 1.00, 0.82-1.21, p=0.98). The 1-year rates of cardiac mortality (2.1%vs 3.8%, HR 0.57, 0.38-0.84, p=0.005) and all-cause mortality (3.5%vs 4.8%, HR 0.71, 0.51-0.98, p=0.037) were lower in the bivalirudin group than in the control group. INTERPRETATION: In patients with STEMI undergoing primary PCI, anticoagulation with bivalirudin reduced the rates of net adverse clinical events and major bleeding at 1 year compared with treatment with heparin plus a GPI. This finding has important clinical implications for the selection of optimum treatment strategies for patients with STEMI. FUNDING: Cardiovascular Research Foundation, with unrestricted grant support from Boston Scientific Corporation and The Medicines Company.

Management of inflammatory bowel diseases during pregnancy.

Inflammatory bowel diseases (IBD) have a high prevalence in younger patients with child-bearing potential. Usually, pregnancies in women with IBD will develop normally, if the patient is in remission or has minor disease activity at the time of conception. In contrast, the frequency of normal pregnancies is significantly reduced and the frequency of adverse outcomes like preterm birth or miscarriage is increased, when conception occurs in phases with active IBD. Therefore, it is generally recommended to women with IBD to conceive at a time with minor disease activity or in remission. IBD patients who plan to become pregnant or are pregnant should be treated adequately. Currently, it is widely accepted that the treatment of IBD with corticosteroids and 5-ASA derivatives does not increase the risk of malformations or adverse outcomes in pregnant IBD patients. However, a slight increase in the number of pre-term deliveries or reduced birth weight is observed. More recently, it has also been appreciated that azathioprine and 6-MP and presumably also infliximab and other TNF-alpha blockers can be safely used during pregnancy in IBD, as no significant increase of malformations, miscarriages or adverse pregnancy outcomes is observed. Information on cyclosporine and tacrolimus during pregnancy is scarcer, but it may be continued or started in some situations if clinically needed. Methotrexate is contraindicated, as this drug is known to significantly increase the risk of malformations and spontaneous abortion. Patients, who wish to nurse their babies, may be treated with steroids and 5-ASA derivatives without a significantly increased risk for the newborn.

Apical and midventricular transient left ventricular dysfunction syndrome (tako-tsubo cardiomyopathy): frequency, mechanisms, and prognosis.

BACKGROUND: The frequency and potential differences between patients with apical ("typical") and midventricular ("atypical") ballooning have not been described. METHODS: Consecutive patients with the diagnosis of a troponin-positive acute coronary syndrome (ACS) were prospectively included into a registry (n = 3,265). Of those, 2,944 patients underwent left-heart catheterization and form the study population. Demographic, clinical, and angiographic data including assessment of microvascular dysfunction (Thrombolysis in Myocardial Infarction [TIMI] blush grade, corrected TIMI frame count), as well as clinical outcome were assessed in all patients. RESULTS: In patients with troponin-positive ACS, the frequency of transient cardiomyopathy was 1.2% (35 of 2,944 patients). Typical apical wall motion abnormality was observed in 21 of 35 patients (60%), as compared to an atypical (midventricular) pattern in 14 of 35 patients (40%). Both groups did not differ regarding demographic, clinical, laboratory, or angiographic parameters. Scintigraphy and PET studies were performed in 17 of 35 patients (49%) with transient cardiomyopathy, and showed a strong correlation between location of wall motion abnormality and myocardial metabolism defects, with a significantly higher apical decrease in glucose uptake in patients with a typical pattern. CONCLUSIONS: Transient cardiomyopathy affects approximately 1% of patients with a troponin-positive ACS. A typical apical wall motion abnormality is seen in only 60% of patients. Transient cardiomyopathy, also termed Tako-Tsubo cardiomyopathy, therefore should no longer be regarded as an exclusively apical ballooning syndrome, but rather a transient left ventricular dysfunction syndrome with an apical or midventricular pattern of wall motion abnormality.

Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: the ACUITY Timing trial.

CONTEXT: In patients with moderate- and high-risk acute coronary syndromes (ACS) who undergo an early, invasive treatment strategy, current guidelines recommend administration of platelet glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibitors, either upstream to all patients prior to angiography or deferred for selective use in the catheterization laboratory just prior to angioplasty. The preferred approach is undetermined. OBJECTIVE: To determine the optimal strategy for the use of Gp IIb/IIIa inhibitors in patients with moderate- and high-risk ACS undergoing an early, invasive treatment strategy. DESIGN: Prospective, randomized, open-label trial with 30-day clinical follow-up. SETTING: Four hundred fifty academic and community-based institutions in 17 countries. PATIENTS: A total of 9207 patients with moderate- and high-risk ACS undergoing an invasive treatment strategy. INTERVENTIONS: Patients were randomly assigned to receive either routine upstream (n=4605) or deferred selective (n=4602) Gp IIb/IIIa inhibitor administration, respectively. MAIN OUTCOME MEASURES: The primary outcome was assessment of noninferiority of deferred Gp IIb/IIIa inhibitor use compared with upstream administration for the prevention of composite ischemic events (death, myocardial infarction, or unplanned revascularization for ischemia) at 30 days, using a 1-sided alpha level of .025. Major secondary end points included noninferiority or superiority of major bleeding and net clinical outcomes (composite ischemia or major bleeding). RESULTS: Glycoprotein IIb/IIIa inhibitors were used more frequently (98.3% vs 55.7%, respectively) and for a significantly longer duration (median, 18.3 vs 13.1 hours; P<.001) in patients in the upstream group compared with the deferred group. Composite ischemia at 30 days occurred in 7.9% of patients assigned to deferred use compared with 7.1% of patients assigned to upstream administration (relative risk, 1.12; 95% confidence interval, 0.97-1.29; P = .044 for noninferiority; P = .13 for superiority); as such, the criterion for noninferiority was not met. Deferred use compared with upstream use resulted in reduced 30-day rates of major bleeding (4.9% vs 6.1%, respectively; P<.001 for noninferiority; P = .009 for superiority) and similar rates of net clinical outcomes (11.7% vs 11.7%; P<.001 for noninferiority; P = .93 for superiority). CONCLUSIONS: Among patients with moderate- and high-risk ACS undergoing an invasive treatment strategy, deferring the routine upstream use of Gp IIb/IIIa inhibitors for selective administration in the cardiac catheterization laboratory only to patients undergoing percutaneous coronary intervention resulted in a numerical increase in composite ischemia that, while not statistically significant, did not meet the criterion for noninferiority. This finding was offset by a significant reduction in major bleeding. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00093158.

Impact of infarct-related artery flow on QT dynamicity in patients undergoing direct percutaneous coronary intervention for acute myocardial infarction.

BACKGROUND: Complete coronary artery reperfusion in acute myocardial infarction (AMI) has been shown to significantly improve survival. Electrical stability may be the decisive mechanism for this beneficial effect. Because electrical stability is largely dependent on ventricular repolarization, we sought to determine the impact of a modern reperfusion strategy (ie, direct percutaneous coronary intervention [PCI]) on QT dynamicity in AMI and examined its association with infarct-related artery flow. METHODS AND RESULTS: We prospectively investigated QT dynamicity in 128 patients undergoing direct PCI for a first AMI. Slopes and correlation coefficients of the linear QT/RR regression were determined in the time interval before reperfusion, within the initial hour after reperfusion, and within the remaining recording period from Holter ECG recordings, which were initiated on admission. Subgroup analysis based on TIMI 3 (n=100) and TIMI 2 (n=28) flow after PCI revealed no significant differences in QT/RR slope before PCI (0.145+/-0.12 versus 0.160+/-0.19,P=NS). After PCI, QT/RR slopes increased only in the TIMI 2 subgroup (P<0.05). In TIMI 2 patients, QT/RR slopes were significantly steeper in the hour after PCI and in the remaining recording period, respectively (0.155+/-0.12 versus 0.192+/-0.15,P<0.05, and 0.159+/-0.10 versus 0.210+/-0.17,P<0.01). CONCLUSIONS: Alterations of QT dynamicity in patients with incomplete reperfusion may suggest an altered electrical restitution, potentially providing a substrate for serious ventricular arrhythmias. Thus, our findings offer new insights into mechanisms by which complete reperfusion may affect electrical stability.

Reflex cardiac activity in ischemia and reperfusion: heart rate turbulence in patients undergoing direct percutaneous coronary intervention for acute myocardial infarction.

BACKGROUND: Abnormal heart rate turbulence (HRT) is associated with an increased risk of mortality in the chronic phase of myocardial infarction (MI) in the prethrombolytic and thrombolytic eras. However, the impact of direct percutaneous coronary intervention (PCI) on HRT in the acute phase of MI and its association to the epicardial infarct-related arterial flow has not been examined. METHODS AND RESULTS: We investigated HRT in 126 patients undergoing direct PCI for a first MI. Turbulence onset and turbulence slope were determined before reperfusion, during the initial 2 hours after reperfusion, and during hours 6 to 24 after reperfusion. HRT significantly improved after PCI. There were no significant differences in baseline clinical characteristics between Thrombolysis in Myocardial Infarction Trial classification (TIMI) 2 (n=28) and TIMI 3 (n=98) flow. After PCI, turbulence slope increased (13.2+/-11 to 18.1+/-12 ms/beat, P<0.001) and turbulence onset decreased (-0.008+/-0.04% to -0.023+/-0.04%, P<0.01) in patients with TIMI 3 flow after PCI, whereas there were no significant alterations of turbulence slope (12.2+/-10 to 12.8+/-6.5 ms/beat) and turbulence onset (-0.009+/-0.05% to -0.003+/-0.03%) in patients with TIMI 2 flow. CONCLUSIONS: The improvement of HRT after successful reperfusion is a previously unreported effect of direct PCI for acute MI, reflecting rapid restoration of baroreceptor response. The persistent impairment of HRT after PCI in patients with TIMI 2 flow indicates a sustained blunted baroreflex response and may reflect a more severe microvascular dysfunction.

Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

BACKGROUND: The utility of N-terminal proBNP (NT-proBNP) to predict the occurrence of death and hospitalization was prospectively evaluated in the COPERNICUS study, which enrolled patients with an ejection fraction <25% and symptoms of chronic congestive heart failure at rest or on minimal exertion. METHODS AND RESULTS: Baseline plasma concentrations of NT-proBNP were measured in a subgroup of 814 men and 197 women with symptoms at rest or on minimal exertion who were enrolled in the COPERNICUS study and were randomized to placebo (n=506) or carvedilol (n=505). Values of NT-proBNP were markedly increased despite the requirement that patients be euvolemic before the start of treatment (mean+/-SD, 3235+/-4392 pg/mL; median, 1767 pg/mL). By univariate Cox regression analysis, NT-proBNP was found to be a powerful predictor of subsequent all-cause mortality (relative risk [RR], 2.7; 95% CI, 1.7 to 4.3; P=0.0001 for above versus below median) and all-cause mortality or hospitalization for heart failure (RR, 2.4; 95% CI, 1.8 to 3.4; P=0.0001 for above versus below median). The predictive value of NT-proBNP was similar when both placebo and carvedilol patients were analyzed separately. No significant interaction was found between NT-proBNP and treatment group (P=0.93 for above- versus below-median NT-proBNP). CONCLUSIONS: NT-proBNP was consistently associated with increased risk for all-cause mortality and for all-cause mortality or hospitalization for heart failure in patients with severe congestive heart failure, even in those who were clinically euvolemic. This marker therefore may be a useful tool in risk stratification of patients with severe congestive heart failure.

Differential outcome after intracoronary radiation therapy is related to a simple classification based on lesion length and reference diameter.

OBJECTIVE: We sought to develop a prognostic lesion classification based on simple angiographic parameters, lesion length and reference diameter that predicts differential outcome in patients undergoing intracoronary radiation. METHODS AND RESULTS: Three types of lesions were identified: Type A characterized by lesion length less than or equal to 30 mm, reference diameter > 2.5 mm to less than or equal to 4.0 mm (short lesion: normal diameter), Type B by lesion length less than or equal to 30 mm, reference diameter less than or equal to 2.5 mm or > 4 mm (short lesion: extreme diameter), and Type C by lesion length > 30 mm (long lesion). A total of 1,151 lesions (77.7% in-stent restenosis) in 1,098 consecutive patients undergoing brachytherapy were classified into these 3 lesion types. Overall, 79.9%, 10.3% and 9.8% patients met the criteria for Type A, B and C lesions. While the in-hospital major adverse cardiac event (MACE) rate was 1.4%, 3.6% and 3.8% (p = 0.026), the 6-month MACE rate was 16.1%, 22.5% and 32.1% (p < 0.001), the angiographic restenosis rate was 21.3%, 32.4% and 42.4% (p < 0.001), and the late thrombosis rate was 4.1%, 9.0% and 11.3%, (p < 0.001) in Type A, B and C lesions, respectively. Consequently, with increasing lesion severity, 3 risk groups with low, medium and high risk were defined. Multivariate analysis showed that Type B and C lesions were independent predictors of 6-month MACE (OR, 1.5 and 1.9, respectively). CONCLUSION: The proposed novel and easily applicable lesion classification effectively predicts early and medium term outcome, and may be used for appropriate therapeutic decision making in patients undergoing brachytherapy.

Temporal repolarization inhomogeneity and reperfusion arrhythmias in patients undergoing successful primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction: impact of admission troponin T.

BACKGROUND: The presence of admission cardiac troponin-T (cTnT) is a means of identifying a high-risk subgroup in patients with acute ST-segment elevation myocardial infarction (AMI). Because a substantial number of these patients has malignant ventricular arrhythmias, we hypothesized that there is a relation between cTnT status on admission and inhomogeneity of ventricular repolarization, and we tested this assumption in the setting of primary percutaneous coronary intervention (PCI). METHODS: Temporal fluctuations of ventricular repolarization were studied during and after primary PCI (Thrombolysis In Myocardial Infarction [TIMI] 2 and 3) in 94 consecutive patients with a first AMI by continuous beat-to-beat QT-interval measurement, performed with Holter monitoring initiated on admission. Troponin-T levels on admission were >0.1 ng/mL in 53 patients (cTnT+) and <0.1 ng/mL in 41 patients (cTnT-). There were no significant differences in baseline clinical characteristics between the groups. RESULTS: The incidence of severe reperfusion arrhythmias (RAs) was significantly higher in patients in the cTnT+ group within the first 2 hours after recanalization. The course of the QT interval revealed a significant decline (P <.001) after recanalization of the infarcted vessel within 10 hours in both groups; however, hourly values were significantly lower and normalization of the QT parameters was more rapid in patients in the cTnT- group than patients in the cTnT+ in this period (QTc, 438.5 +/- 28.3 ms vs 449.3 +/- 35.3 ms [hour 1, P <.01]; 413.6 +/- 35.8 ms vs 420.1 +/- 39.2 ms [hour 10, P <.05]). QT-interval variability also significantly declined within 4 hours after PCI (P <.001), and likewise, patients in the cTnT- group exhibited lower values in this period (QTSD, 29.7 +/- 6.8 ms vs 33.5 +/- 10.5 ms [hour 1, P <.01]; 23.0 +/- 6.1 ms vs 25.9 +/- 7.5 ms [hour 4, P <.01]). CONCLUSIONS: Positivity of cTnT on admission is associated with a significantly higher temporal inhomogeneity of ventricular repolarization and a higher incidence of malignant RAs, which suggests more advanced microvascular injury. Early successful primary PCI ultimately results in a significant recovery of parameters of QT interval and mean RR interval in all patients, although it was significantly delayed in patients in the cTnT+ group.

NT-proBNP in severe chronic heart failure: rationale, design and preliminary results of the COPERNICUS NT-proBNP substudy.

BACKGROUND: Neither profiles nor prognostic value of cardiac N-terminal proBNP (NT-proBNP) have been prospectively evaluated in a sufficient number of patients with severe chronic heart failure (CHF) treated with carvedilol or placebo. METHODS: Baseline and follow-up plasma concentrations of NT-proBNP were measured in the European part of the COPERNICUS Trial. This study enrolled patients with an ejection fraction <25% and symptoms of CHF at rest or on minimal exertion, equally randomized to placebo or carvedilol. RESULTS: NT-proBNP concentrations were increased at baseline (mean+/-S.D.=579+/-822 pmol/l, median=322.5 pmol/l) with a marked decrease during follow-up in the carvedilol, but not in the placebo group. One-year mortality rates were 3.9, 12 and 27.9% in the lower, middle and upper tertiles of NT-proBNP, respectively. When mortality was calculated separately in the placebo and carvedilol group, rates were 0.8, 6.3 and 19.1% in the carvedilol treated but 6.7, 17.9 and 36.9% in the placebo treated patients. CONCLUSIONS: NT-proBNP was a powerful predictor of subsequent all-cause mortality in patients with severe CHF. This marker should therefore be further evaluated for risk stratification and monitoring of therapy in CHF.

Results of intracoronary beta-brachytherapy administered by 60 mm transfer device/radiation source train: a subgroup analysis from the RENO registry.

UNLABELLED: To investigate the safety and efficacy of a 60 mm transfer device, delivering 60 mm radiation source train, in the treatment of coronary lesions by b-brachytherapy employing the BetaCath system (Novoste, Norcross, Georgia). METHODS AND RESULTS: As part of the REgistry NOvoste (RENO), the first large-scale registry of intracoronary beta-radiation applied in routine clinical practice, 46 centers registered 1,098 consecutive patients undergoing brachytherapy with the BetaCath system. Of these, 49 patients with 56 lesions were treated with a 60 mm transfer device/radiation source train (TD/RST) in at least 1 vessel, constituting the study population. With 75.4% in-stent restenosis (ISR), 3.6% graft lesions, long lesions (30.9 +/- 14.7 mm) and 19% diabetes, the cohort had a high-risk for recurrence. The in-hospital major adverse cardiac event (MACE) rate was 4.1%. The 6-month follow-up revealed 2.0% death, 4.1% myocardial infarction, 8.2% target vessel revascularization, 12.2% MACE, 82.6% improved angina, 16.7% binary restenosis and 4.1% late thrombosis. The results were comparable to all other patients in the registry treated with standard source lengths of 30 mm and 40 mm, although much longer lesions were treated by the 60 mm device (18.4 +/- 11.3 mm versus 30.9 +/- 14.7 mm; p < 0.0001). In the ISR subgroup (mean lesion length, 32.03 +/- 14.99 mm), the 6-month MACE rate was 12.8%, while the angiographic restenosis rate was 16.0% and the late thrombosis rate was 2.6%. CONCLUSION: Beta-brachytherapy with 60 mm TD/RST was safe, feasible and effective in this broad population of high-risk patients presenting in day-to-day practice. Its efficacy in long-segment ISR, where conventional interventional strategies have poor outcome rates, is particularly noteworthy.

An unusual complication in ulcerative colitis during treatment with azathioprine and infliximab: Isospora belli as 'Casus belli'.

The treatment of ulcerative colitis is based on systemic corticosteroids, immunomodulators such as cyclosporine and azathioprine and TNF-α antagonists. Patients undergoing such immunosuppressive treatment are more susceptible for infectious pathogens. Here, we report the case of a patient with a 13-year history of ulcerative colitis, treated initially with systemic corticosteroids in combination with immunomodulators, and subsequently with infliximab. The patient presented with severe watery diarrhoea, abdominal cramps, weight loss and low-grade fever. Stool examinations for cytomegalovirus, bacteria and parasites were negative. Following detection of numerous oocytes of Isospora belli (IB) in direct smear preparations of the diarrhoeic stool samples, the patient was successfully treated with trimethoprim-sulfamethoxazole (co-trimoxazole).

Impact of infarct-related artery patency before primary PCI on outcome in patients with ST-segment elevation myocardial infarction: the HORIZONS-AMI trial.

AIMS: We assessed the impact of early infarct-related artery (IRA) recanalisation on the outcomes of patients in the recently conducted, large-scale, multicentre HORIZONS-AMI trial. METHODS AND RESULTS: Of the 3,602 patients enrolled in the HORIZONS-AMI trial, 3,093 patients (85.9%) were treated with percutaneous coronary intervention (PCI) to a single artery. We analysed one-year outcomes in these patients according to the presence or absence of early IRA patency, defined as Thrombolysis in Myocardial Infarction (TIMI) 2 or 3 flow in the IRA. Baseline coronary angiography showed early IRA patency in 1,121 patients (36.2%), while 1,972 patients (63.8%) had TIMI 0 or 1 flow. The presence compared with the absence of early IRA patency was associated with better angiographic results after primary PCI with more TIMI 3 flow after PCI (93.2% vs. 82.9%, p<0.0001) and myocardial blush grade 2 or 3 (84.4% vs. 71.1%, p<0.0001). Early IRA patency was associated with lower rates of one-year mortality (2.5% vs. 3.9%, p=0.04) and definite or probable stent thrombosis (2.0% vs. 4.0%, p=0.002). In multivariable analysis, early IRA patency at baseline angiography was an independent predictor of reduced mortality at one year (HR 0.58, 95% CI: 0.36-0.98, p=0.02). CONCLUSIONS: Early IRA patency in patients with STEMI undergoing primary PCI is associated with better TIMI flow and myocardial blush post PCI and is an independent predictor of lower one-year mortality. ClinicalTrials.gov identifier NCT00433966.