Harald Rittger

A randomized, multicenter, single-blinded trial comparing paclitaxel-coated balloon angioplasty with plain balloon angioplasty in drug-eluting stent restenosis: the PEPCAD-DES study.

OBJECTIVES This study sought to define the impact of paclitaxel-coated balloon angioplasty for treatment of drug-eluting stent restenosis compared with uncoated balloon angioplasty alone. BACKGROUND Drug-coated balloon angioplasty is associated with favorable results for treatment of bare-metal stent restenosis. METHODS In this prospective, single-blind, multicenter, randomized trial, the authors randomly assigned 110 patients with drug-eluting stent restenoses located in a native coronary artery to paclitaxel-coated balloon angioplasty or uncoated balloon angioplasty. Dual antiplatelet therapy was prescribed for 6 months. Angiographic follow-up was scheduled at 6 months. The primary endpoint was late lumen loss. The secondary clinical endpoint was a composite of cardiac death, myocardial infarction attributed to the target vessel, or target lesion revascularization. RESULTS There was no difference in patient baseline characteristics or procedural results. Angiographic follow-up rate was 91%. Treatment with paclitaxel-coated balloon was superior to balloon angioplasty alone with a late loss of 0.43 ± 0.61 mm versus 1.03 ± 0.77 mm (p < 0.001), respectively. Restenosis rate was significantly reduced from 58.1% to 17.2% (p < 0.001), and the composite clinical endpoint was significantly reduced from 50.0% to 16.7% (p < 0.001), respectively. CONCLUSIONS Paclitaxel-coated balloon angioplasty is superior to balloon angioplasty alone for treatment of drug-eluting stent restenosis. (PEPCAD DES-Treatment of DES-In-Stent Restenosis With SeQuent® Please Paclitaxel Eluting PTCA Catheter [PEPCAD-DES]; NCT00998439).

Intracoronary versus intravenous bolus abciximab during primary percutaneous coronary intervention in patients with acute ST-elevation myocardial infarction: a randomised trial.

BACKGROUND Intracoronary administration of an abciximab bolus during a primary percutaneous coronary intervention results in a high local drug concentration, improved perfusion, and reduction of infarct size compared with intravenous bolus application. However, the safety and efficacy of intracoronary versus standard intravenous bolus application in patients with ST-elevation myocardial infarction (STEMI) undergoing this intervention has not been tested in a large-scale clinical trial. METHODS The AIDA STEMI trial was a randomised, open-label, multicentre trial. Patients presenting with STEMI in the previous 12 h with no contraindications for abciximab were randomly assigned in a 1:1 ratio by a central web-based randomisation system to intracoronary versus intravenous abciximab bolus (0·25 mg/kg bodyweight) during percutaneous coronary intervention with a subsequent 12 h intravenous infusion 0·125 μg/kg per min (maximum 10 μg/min). The primary endpoint was a composite of all-cause mortality, recurrent infarction, or new congestive heart failure within 90 days of randomisation. Secondary endpoints were the time to occurrence of the primary endpoint, each individual component of that endpoint, early ST-segment resolution, thrombolysis in myocardial infarction (TIMI) flow grade, and enzymatic infarct size. A masked central committee adjudicated the primary outcome and its components. Treatment allocation was not concealed from patients and investigators. This trial is registered with ClinicalTrials.gov, NCT00712101. FINDINGS Between July, 2008, and April, 2011, 2065 patients were randomly assigned intracoronary abciximab (n=1032) or intravenous abciximab (n=1033). Intracoronary, as compared with intravenous abciximab, resulted in a similar rate of the primary composite clinical endpoint at 90 days in 1876 analysable patients (7·0%vs 7·6%; odds ratio [OR] 0·91; 95% CI 0·64-1·28; p=0·58). The incidence of death (4·5%vs 3·6%; 1·24; 0·78-1·97; p=0·36) and reinfarction (1·8%vs 1·8%; 1·0; 0·51-1·96; p=0·99) did not differ between the treatment groups, whereas less patients in the intracoronary group had new congestive heart failure (2·4%vs 4·1%; 0·57; 0·33-0·97; p=0·04). None of the secondary endpoints or safety measures differed significantly between groups. INTERPRETATION In patients with STEMI undergoing primary percutaneous coronary intervention, intracoronary as compared to intravenous abciximab did not result in a difference in the combined endpoint of death, reinfarction, or congestive heart failure. Since intracoronary abciximab bolus administration is safe and might be related to reduced rates of congestive heart failure the intracoronary route might be preferred if abciximab is indicated. FUNDING Lilly, Germany. University of Leipzig-Heart Centre. University of Leipzig, Clinical Trial Centre Leipzig, supported by the Federal Ministry of Education and Research (BMBF).

Incidence of oesophageal wall injury post-pulmonary vein antrum isolation for treatment of patients with atrial fibrillation

AIMS Oesophageal injury has been reported with delivery of radio-frequency lesions at the left atrium posterior wall in catheter ablation procedures for atrial fibrillation (AF). In this observational study we prospectively assessed endoscopical oesophageal wall changes after pulmonary vein antrum isolation (PVAI) in patients presenting for treatment of AF. METHODS AND RESULTS Twenty eight patients (18 men; mean age 55 +/- 11 years) were ablated using either a cooled-tip or an 8 mm tip ablation catheter. Endoscopy of the oesophagus was performed 24 h after PVAI. If oesophageal wall changes were detected post ablation, a proton-pump inhibitor (PPI) was started and repeat endoscopy was considered. Within 24 h post ablation oesophageal wall changes were confirmed in 47% of our study patients. Erythema was identified in 29% and necrotic or ulcer-like changes in 18% of patients. None of study patients experienced left atrial-oesophageal fistula. A significant correlation between Reflux-like symptoms and oesophageal wall changes was demonstrated. Complete recovery of oesophageal lesions was shown in all study patients 2-4 weeks post ablation. CONCLUSION A significant number of patients experienced oesophageal wall injury post PVAI. Initiating PPIs in this group of patients might facilitate recovery of oesophageal wall injuries caused by radio-frequency energy delivery.

Prospective randomised trial evaluating a paclitaxel-coated balloon in patients treated with endothelial progenitor cell capturing stents for de novo coronary artery disease

Background Percutaneous coronary intervention with stent implantation is limited by the occurrence of re-stenosis and the risk of stent thromboses. Objective To define the impact of paclitaxel-coated balloon angioplasty plus endothelial progenitor cell capturing (EPC) stent implantation in de novo coronary artery disease. This combination may reduce neointimal proliferation within the EPC stent and address the risk of stent thrombosis by facilitating rapid endothelialisation. Methods In this prospective single-blind multicentre randomised trial, 120 patients with a de novo lesion in a native coronary artery were randomly assigned to undergo treatment with paclitaxel-coated balloon plus EPC stent or EPC stent alone. Dual antiplatelet therapy was prescribed for 3 months. Angiographic follow-up was scheduled at 6 months. The primary endpoint was in-stent late lumen loss. The secondary clinical endpoint was a composite of death from a cardiac cause, myocardial infarction attributed to the target vessel or target lesion revascularisation. Results There was no difference in patient baseline characteristics or procedural results. The angiographic follow-up rate was 96%. Treatment with paclitaxel-coated balloon plus EPC stent was superior to EPC stent alone, with an in-stent late loss of 0.34±0.45 mm versus 0.88±0.48 mm (p<0.001). The re-stenosis rate was reduced from 23.2% to 5.1% (p=0.006) and the clinical endpoint was reduced from 17.2% to 4.8% (p=0.039). There was no definite or probable stent thrombosis. Conclusions Paclitaxel-coated balloon plus EPC stent implantation is superior to EPC stent implantation alone for treatment of de novo coronary artery disease. Trial registration NCT00732953.

Drug-coated balloons for treatment of coronary artery disease: updated recommendations from a consensus group

AbstractAims Drug-coated balloon catheters (DCB) are a new clinical treatment modality for coronary and peripheral artery disease. The goal of the consensus group is to develop recommendations for the clinical use of DCB based on randomized clinical trials and the best available clinical evidence. The present paper gives an update on the recommendations against the background of a variety of new data published since the first paper was presented.Methods and results The general concept of our recommendations for the coronary use of DCB includes the preparation of the lesion to facilitate drug delivery and to estimate the need for stent implantation, especially after relevant dissections. Lesion preparation includes conventional angioplasty. In more complex lesions, additional treatments and imaging or functional measurements are helpful. In case of no flow-limiting dissection and an acceptable but not stent-like primary result, DCB use without additional stent implantation may be considered. The proposed advantages of the DCB only concept over a direct stent approach include reduced restenosis rates in indications where DES show limited efficacy, the reduction of DAPT especially in patients with contraindications for prolonged DAPT, and the option of leaving no foreign object behind resulting in vascular restoration with potentially plaque regression instead of neo-atherosclerosis.ConclusionsDCB allow for local drug delivery in endovascular therapy leaving no permanent implant behind.

Intracoronary compared with intravenous bolus abciximab application during primary percutaneous coronary intervention: Design and rationale of the Abciximab Intracoronary versus intravenously Drug Application in ST-Elevation Myocardial Infarction (AIDA STEMI) trial

BACKGROUND Intravenous abciximab reduces major adverse cardiac events in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Intracoronary abciximab bolus application during PCI results in high local drug concentration, improved perfusion, reduction of infarct size, and less microvascular obstruction. The hypothesis of this trial is that abciximab bolus intracoronary in comparison to standard intravenous application will improve the outcome of patients undergoing primary PCI in STEMI. STUDY DESIGN The Abciximab Intracoronary versus intravenously Drug Application in STEMI (AIDA STEMI) study is a 1,912-patient, prospective, multicenter, randomized, open-label, controlled trial. The study is designed to compare the efficacy and safety of intracoronary versus intravenous bolus abciximab administration during primary PCI with subsequent intravenous infusion for 12 hours. Patients will be randomized in a 1:1 fashion to 1 of the 2 treatments. The primary efficacy end point of AIDA STEMI is the composite of all-cause mortality, recurrent MI, or new congestive heart failure within 90 days of randomization. The primary safety outcome assessment will be major bleeding. CONCLUSIONS The AIDA STEMI study addresses important questions regarding the efficacy and safety of intracoronary abciximab bolus administration during primary PCI in patients with STEMI, potentially optimizing the route of administration of glycoprotein IIb/IIIa inhibitors in the catheterization laboratory.

Comparison of Intracoronary Versus Intravenous Administration of Adenosine for Measurement of Coronary Fractional Flow Reserve

Background—Measurement of fractional flow reserve (FFR) constitutes the current gold standard to evaluate the hemodynamic significance of coronary stenoses. Limited data validate the intracoronary application of adenosine against standard intravenous infusion. We systematically compared FFR measurements during intracoronary and intravenous application of adenosine about agreement and reproducibility. Methods and Results—We included 114 patients with an intermediate degree of stenosis in coronary angiography. Two FFR measurements were performed during intracoronary bolus injection (40 &mgr;g for the right and 80 &mgr;g for the left coronary artery, FFRic), and 2 FFR measurements during continuous intravenous infusion of adenosine (140 &mgr;g/kg per minute, FFRiv). FFR value, the time to reach FFR and patient discomfort (on a subjective scale from 0 for no symptoms to 5 for maximal discomfort) were recorded for each measurement. Mean time to FFR was 100±27 s for continuous intravenous infusion versus 23±14 s for intracoronary bolus administration of adenosine (P<0.001). Reported discomfort after intracoronary application was significantly lower compared with intravenous adenosine (subjective scale >0 in 35.1% versus 87.7% of the patients; P<0.001). Correlation between FFRiv and FFRic was extremely close (r=0.99; P<0.001) with no systematic bias in Bland–Altman analysis (bias 0.002 [confidence interval, −0.001 to 0.005]) and low intermethod variability (1.56%). Intramethod variability was not different between intravenous and intracoronary administration (1.47% versus 1.33%; P=0.5). Conclusions—Intracoronary bolus injection of adenosine (40 &mgr;g for the right and 80 &mgr;g for the left coronary artery) yields identical FFR results compared with intravenous infusion (140 &mgr;g/kg per minute), while requiring less time and offering superior patient comfort.

Three-dimensional reconstruction allows accurate quantification and length measurements of coronary artery stenoses

AIMS The aim of this prospective study was to evaluate the feasibility and accuracy of a recently developed 3D system (CardiOp-B; Paieon Medical Ltd., Israel) as compared to a validated quantitative coronary angiography (QCA) system (Siemens Quantcor, Siemens Medical Solutions). METHODS AND RESULTS In patients scheduled for heart catheterisation, minimal lumen diameter (MLD) and diameter-derived percent stenosis (DPS) were obtained for CAS (>50%) using both QCA and the 3D-system. To estimate stenosis length, a non-inflated balloon was inserted into the stenosis and the distance between balloon markers was measured using both methods and then compared to the known distance between the markers. In 61 patients 79 lesions were analysed. MLD measurements showed a good agreement between QCA and 3D with a mean difference of 0.08+/-0.035 mm. Reference diameter was 2.61+/-0.67 for 3D and 2.42+/-0.61 mm for QCA and 54.79+/-9.20% vs. 58.75+/-8.15% for the %-stenosis range, respectively. The mean true balloon length was 12.8 mm+/-3.8 mm. Lengths determined by the 3D system were 13.0+/-4.0 mm and 11.3+/-3.8 mm by QCA, respectively. CONCLUSIONS Evaluation of CAS using the novel 3D system was feasible and showed equivalent results to validated QCA measurements. Length measurements seemed to be more accurate by the 3D system as compared to QCA. Therefore, this 3D-system can be used to guide decisions in interventional cardiology.

Intracoronary versus intravenous abciximab bolus in patients with ST-segment elevation myocardial infarction: 1-year results of the randomized AIDA STEMI trial.

To the Editor: In patients with ST-segment elevation myocardial infarction (STEMI), direct intracoronary as compared with standard intravenous bolus administration of the glycoprotein IIb/IIIa receptor antagonist abciximab acutely causes higher local drug concentrations, greater glycoprotein IIb/

Relation of recurrence of atrial fibrillation after successful cardioversion to renal function.

Angiotensin II exerts proinflammatory effects leading to atrial fibrosis that is associated with persistence of atrial fibrillation (AF). Renal function plays a major role in activation of the renin-angiotensin-aldosterone system. We examined whether the level of impaired renal function, defined by glomerular filtration rate (GFR), would influence the maintenance of sinus rhythm after successful external electric cardioversion (ECV). One hundred two consecutive patients with persistent AF underwent successful ECV. Patients were prospectively followed for recurrence of AF by telephone interviews, Holter electrocardiograms, and electrocardiograms sent by primary care providers. Repeated GFR assays were performed before and 1 month after ECV. Patients were divided into 4 groups according to baseline GFR (I >90 ml/min, II 60 to 90 ml/min, III 30 to 59 ml/min, IV <30 ml/min). AF recurrence rate was significantly higher in patients with moderately or severely decreased renal function (GFR <60 ml/min, p = 0.003). Patients with moderately (GFR 30 to 59 ml/min, p = 0.02) or only mildly (GFR 60 to 90 ml/min, p = 0.01) decreased renal function showed an increase in GFR if sinus rhythm was maintained at 1 month follow-up. In conclusion, impaired renal function was associated with an increased risk of AF recurrence after successful ECV.