Matthias Leschke

Paclitaxel-Coated Balloon Catheter Versus Paclitaxel-Coated Stent for the Treatment of Coronary In-Stent Restenosis

Background— Treatment of in-stent restenosis with paclitaxel-coated balloon catheter as compared with plain balloon angioplasty has shown surprisingly low late lumen loss at 6 months and fewer major adverse cardiac events up to 2 years. We compared the efficacy and safety of a paclitaxel-coated balloon with a paclitaxel-eluting stent as the current standard of care. Methods and Results— One hundred thirty-one patients with coronary in-stent restenosis were randomly assigned to treatment by a paclitaxel-coated balloon (3 &mgr;g/mm2) or a paclitaxel-eluting stent. The main inclusion criteria encompassed diameter stenosis of ≥70% and ≤22 mm in length, with a vessel diameter of 2.5 to 3.5 mm. The primary end point was angiographic in-segment late lumen loss. Quantitative coronary angiography revealed no differences in baseline parameters. At 6 months follow-up, in-segment late lumen loss was 0.38±0.61 mm in the drug-eluting stent group versus 0.17±0.42 mm (P=0.03) in the drug-coated balloon group, resulting in a binary restenosis rate of 12 of 59 (20%) versus 4 of 57 (7%; P=0.06). At 12 months, the rate of major adverse cardiac events were 22% and 9%, respectively (P=0.08). This difference was primarily due to the need for target lesion revascularization in 4 patients (6%) in the coated-balloon group, compared with 10 patients (15%) in the stent group (P=0.15). Conclusions— Treatment of coronary in-stent restenosis with the paclitaxel-coated balloon was at least as efficacious and as well tolerated as the paclitaxel-eluting stent. For the treatment of in-stent restenosis, inhibition of re-restenosis does not require a second stent implantation.

SeQuent Please World Wide Registry : Clinical Results of SeQuent Please Paclitaxel-Coated Balloon Angioplasty in a Large-Scale, Prospective Registry Study

OBJECTIVES This study sought to assess the safety and efficacy of paclitaxel-coated balloon (PCB) angioplasty in an international, multicenter, prospective, large-scale registry study. BACKGROUND In small randomized trials, PCB angioplasty was superior to uncoated balloon angioplasty for treatment of bare-metal stent (BMS) and drug-eluting stent (DES) restenosis. METHODS Patients treated with SeQuent Please PCBs were included. The primary outcome measure was the clinically driven target lesion revascularization (TLR) rate at 9 months. RESULTS At 75 centers, 2,095 patients with 2,234 lesions were included. The TLR rate was 5.2% after 9.4 months. Definite vessel thrombosis occurred in 0.1%. PCB angioplasty was performed in 1,523 patients (72.7%) with DES or BMS restenosis and 572 patients (27.3%) with de novo lesions. The TLR rate was significantly lower in patients with PCB angioplasty for BMS restenosis compared with DES restenosis (3.8% vs. 9.6%, p < 0.001). The TLR rate did not differ for PCB angioplasty of paclitaxel-eluting stent and non-paclitaxel-eluting sten restenosis (8.3% vs. 10.8%, p = 0.46). In de novo lesions (small vessels), the TLR rate was low and did not differ between PCB angioplasty with and without additional BMS implantation (p = 0.31). CONCLUSIONS PCB angioplasty in an all-comers, prospective, multicenter registry was safe and confirmed in a large population the low TLR rates seen in randomized clinical trials. PCB angioplasty was more effective in BMS restenosis compared with DES restenosis, with no difference regarding the type of DES.

Restenosis after elective coronary balloon angioplasty in patients with end stage renal disease: a case-control study using quantitative coronary angiography

Objective To assess the rate of angiographic restenosis in patients with end stage renal disease after elective coronary angioplasty. Design A retrospective case-control study of 20 patients with end stage renal disease and 20 sex and age matched controls without renal disease, who had undergone primarily successful coronary angioplasty. Control coronary angiography was performed regardless of worsening or renewed incidence of anginal symptoms. Main outcome measures Group comparison of coronary morphology, as evaluated by quantitative coronary angiography, and of cardiovascular risk factors. Results The rate of angiographic restenosis was 60% in patients with renal disease and 35% in controls. In patients with end stage renal disease the following differences (mean (SD) were found versus controls: raised plasma fibrinogen (483 (101)v 326 (62) mg/dl, p < 0.001); raised plasma triglyceride (269 (163) v 207 (176) mg/dl, p < 0.01); smaller diameter of the coronary reference segment (2.59 (0.87) v 2.90 (0.55) mm, p < 0.10); smaller minimum luminal diameter of the dilated stenosis (0.77 (0.46)v 0.97 (0.27) mm, p < 0.05). Discriminant analysis showed that minimum luminal diameter before angioplasty (r = −0.79) and fibrinogen (r = +0.34) had the highest statistical association with restenosis. Conclusions The high rate of angiographic restenosis in patients with end stage renal disease seems to be related to the size of the vessel dilated and to an increased prothrombotic risk, as indicated by higher fibrinogen concentrations.

Refractory angina pectoris in end-stage coronary artery disease: Evolving therapeutic concepts ☆ ☆☆ ★

Refractory angina pectoris in coronary artery disease is defined as the persistence of severe anginal symptoms despite maximal conventional antianginal combination therapy. Further, the option to use an invasive revascularization procedure such as percutaneous coronary balloon angioplasty or aortocoronary bypass grafting must be excluded on the basis of a recent coronary angiogram. This coronary syndrome, which represents end-stage coronary artery disease, is characterized by severe coronary insufficiency but only moderately impaired left ventricular function. Almost all patients demonstrated severe coronary triple-vessel disease with diffuse coronary atherosclerosis, had had one or more myocardial infarctions, and had undergone aortocoronary bypass grafting (70% of cases). We present three new approaches with antiischemic properties: long-term intermittent urokinase therapy, transcutaneous and spinal cord electrical nerve stimulation, and transmyocardial laser revascularization.

Long-term intermittent urokinase therapy in patients with end-stage coronary artery disease and refractory angina pectoris: A randomized dose-response trial

OBJECTIVES This dose-response study was designed to test two low dose regimens of urokinase administered over a prolonged time period in patients with chronic refractory angina pectoris with respect to effects on clinical symptoms and objective variables of myocardial ischemia. BACKGROUND Patients with severe and chronic refractory angina pectoris in end-stage coronary artery disease represent an increasing clinical problem. Favorable therapeutic effects on myocardial ischemia have been reported for long-term application of low dose urokinase. METHODS Ninety-eight patients with chronic refractory and end-stage coronary artery disease were randomly assigned to two treatment groups: group A (49 patients) received 50,000 IU and group B (49 patients) 500,000 IU of urokinase as an intravenous bolus infection three times a week over a period of 12 weeks. Variables evaluated were number of weekly anginal events, data from ergometric exercise testing with simultaneous electrocardiographic registration, semiquantitative evaluation of Tc-99m 2-methoxy isobutyl isonitrile (MIBI) scans and rheologic variables. RESULTS After 12 weeks of treatment, anginal symptoms (events/week) were reduced significantly in group B by 70% compared with 24% in group A (p < 0.001). Fibrinogen decreased by 3% in group A and by 33% in group B (p < 0.001). Plasma viscosity and red blood cell aggregation were reduced by 6.4% (p < 0.001) and 19.9% (p < 0.001), respectively, in group B. Objective variables of myocardial ischemia were improved significantly in group B only. No cumulation of coronary ischemic events was observed in group B. CONCLUSIONS Long-term intermittent urokinase therapy in an applied dose of 3 X 500,000 IU/week represents an effective anti-ischemic and antianginal approach for patients with refractory angina pectoris and end-stage coronary artery disease. Apart from rheologic improvement, antithrombotic properties and plaque regression are likely anti-ischemic mechanisms.

Ranolazine in the treatment of atrial fibrillation: Results of the dose-ranging RAFFAELLO (Ranolazine in Atrial Fibrillation Following An ELectricaL CardiOversion) study

BACKGROUND Currently available antiarrhythmic agents for the treatment of atrial fibrillation (AF) have important limitations, leaving an unmet need for safe and effective therapy. Ranolazine is an approved antianginal agent with a favorable safety profile and electrophysiologic properties suggesting a potential role in the treatment of AF. OBJECTIVE The purpose of this study was to assess the safety and efficacy of ranolazine in the prevention of AF recurrence after successful electrical cardioversion and to ascertain the most appropriate dose of this agent. METHODS This prospective, multicenter, randomized, double-blind, placebo-control parallel group phase II dose-ranging trial randomized patients with persistent AF (7 days to 6 months) 2 hours after successful electrical cardioversion to placebo, or ranolazine 375 mg, 500 mg, or 750 mg bid. Patients were monitored daily by transtelephonic ECG. The primary end-point was the time to first AF recurrence. RESULTS Of 241 patients randomized, 238 took at least 1 drug dose. Ranolazine proved to be safe and tolerable. No dose of the drug significantly prolonged time to AF recurrence. AF recurred in 56.4%, 56.9%, 41.7%, and 39.7% of patients in the placebo, ranolazine 375 mg, ranolazine 500 mg, and ranolazine 750 mg groups, respectively. The reduction in overall AF recurrence in the combined 500-mg and 750-mg groups was of borderline significance compared to the placebo group (P = .053) and significant compared to 375-mg group (P = .035). CONCLUSION No dose of ranolazine significantly prolonged time to AF recurrence. However, the 500-mg and 750 mg-groups combined reduced AF recurrences, suggesting a possible role for this agent in the treatment of AF.

Treatment of small coronary arteries with a paclitaxel-coated balloon catheter in the PEPCAD I study: are lesions clinically stable from 12 to 36 months?

AIMS The one-year outcome of lesions in small coronary arteries by using a paclitaxel-iopromide-coated (3 µg/mm²) balloon catheter (DCB) has yielded good six-month angiographic and one-year clinical data. We now report the three-year clinical follow-up. METHODS AND RESULTS One hundred and twenty patients with >70% stenoses <22 mm in length in small coronary vessels (vessel diameter: 2.25-2.8 mm) were treated with the DCB. The primary endpoint was angiographic in-segment late lumen loss. The secondary endpoints encompassed all other angiographic and clinical data up to three years post intervention. In total 82/120 (68.3%) patients with a vessel diameter of 2.35±0.19 mm were treated with the DCB only, and 32/120 (26.7%) patients required additional bare metal stent (BMS) deployment. Both the 12- and 36-month major adverse cardiac event rates were 5/82 (6.1%) for DCB only and 12/32 (37.5%) for DCB+BMS, primarily due to the need for target lesion revascularisation in 4/82 (4.9%) patients and 9/32 (28.1%) (p<0.001) patients, respectively. Total MACE rate after 36 months was 18/120 (15%; intention-to-treat). CONCLUSIONS Treatment of small vessel coronary artery disease with a paclitaxel-iopromide-coated balloon exhibited good six-month angiographic and one-year clinical data that persisted during the three-year follow-up period. Randomised trials will clarify its role as an alternative to drug-eluting stents in the treatment of small vessel coronary artery disease. (ClinicalTrials.gov Identifier: NCT00404144).

Repetitive Hemodilution in Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension: Effects on Pulmonary Hemodynamics, Gas Exchange, and Exercise Capacity

Background: In cor pulmonale associated with severe chronic obstructive pulmonary disease (COPD), disturbances of pulmonary microcirculation may contribute significantly to hypoxemia, pulmonary hypertension, and exercise intolerance. Objective: It was tested whether reduction of blood viscosity induced by repetitive hemodilution might improve pulmonary hemodynamics and oxygen uptake. Methods: Seven patients with stable COPD (forced expiratory volume in 1 s 33 ± 3 % of predicted, means ± SE) and pulmonary hypertension were phlebotomized 5–6 times over a period of 3 months with substitution of 6% hydroxyethyl starch (molecular weight 40,000). This resulted in a stepwise reduction of the hematocrit from 53.3 ± 2.6 to 45.8 ± 3.1% and a reduction of whole blood viscosity from 9.8 ± 0.6 to 8.8 ± 0.7 mPa × s at a shear rate of 2.0 s–1. Before and after the treatment period, patients underwent cardiopulmonary exercise testing and right heart catheterization. Results: Mean pulmonary artery pressure (PAm) decreased from 30 ± 3 to 22 ± 2 mm Hg and arterial oxygen partial pressure (PaO2) increased from 63.2 ± 2.2 to 71.8 ± 3.7 mm Hg at rest. During peak exercise, PAm decreased from 59 ± 7 to 53 ± 7 mm Hg and PaO2 increased from 54.0 ± 5.7 to 63.2 ± 2.4 mm Hg after hemodilution. Peak oxygen consumption rose from 573 ± 84 to 750 ± 59 ml × min–1, corresponding to an increase in cardiac index from 4.25 ± 0.5 to 5.88 ± 0.76 liters × min–1 × m–2. Pulmonary vascular resistance fell from 345 ± 53 to 194 ± 32 dyn × s × cm–5. The patients’ peak exercise capacity increased from 9.2 ± 2.0 before to 13.5 ± 3.2 kJ at the end of the study (p < 0.05 for all differences, paired t test). Conclusion: The findings suggest that a prolonged improvement of pulmonary microcirculation by reducing blood viscosity may improve pulmonary gas exchange, central hemodynamics, and exercise tolerance in patients with severe COPD and pulmonary hypertension.

Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis: the three-year results of the PEPCAD II ISR study.

AIMS Treatment of bare metal in-stent restenosis with the paclitaxel-coated balloon catheter based on the PACCOCATH® technology has yielded superior six-month angiographic and one-year clinical results compared to a paclitaxel-eluting stent. The three-year clinical follow-up is presented. METHODS AND RESULTS One hundred and thirty-one patients with coronary bare metal in-stent restenosis (>70%, length: <22 mm, vessel diameter: 2.5-3.5 mm) were randomly treated with the paclitaxel-coated balloon (DCB) (3 µg/mm²) or a paclitaxel-eluting stent (DES). Clinical follow-up information was requested from the patients and from their physicians. Quantitative angiographic and demographic baseline data were statistically not different between the groups. Per intention-to-treat analysis at 12 months, the lesion-related rates of major adverse cardiac events were 7.6% and 16.9% (p=0.11) while at 36 months the respective numbers were 9.1% and 18.5% (p=0.14). These differences were primarily due to reduced target lesion revascularisation (TLR) in DCB 4/66 (6.2%) compared to DES patients 10/65 (15.4%) (p=0.10). From 12 to 36 months, 1/65 (1.5%) DCB patients experienced a myocardial infarction while neither TLR nor death occurred in any study patient in either group during that period. CONCLUSIONS The six-month superiority of the paclitaxel-coated balloon compared to the paclitaxel-eluting stent in the treatment of bare metal coronary in-stent restenosis persisted throughout the three-year clinical follow-up period indicating stability of the lesions treated. (ClinicalTrials.gov Identifier: NCT00393315).

Incidence and therapy of peripheral arterial vascular complications after heart catheter examinations

Wir analysierten die Inzidenz und Therapie aller in unserer Klinik aufgetretenen signifikanten lokalen Gefäßkomplikationen an der Punktionsstelle nach invasiver diagnostischer und interventioneller Herzkatheterisierung. Während eines 7jährigen Untersuchungszeitraums wurden 27387 Herzkatheteruntersuchungen durchgeführt, es handelte sich um 19581 diagnostische und 7806 interventionelle Herzkatheter. Insgesamt traten bei 114 der insgesamt 27387 Herzkatheterisierungen (0,42%) signifikante periphere lokale Gefäßkomplikationen auf. In 36 Fällen (0,13%) handelte es sich um arterielle Verschlüsse am Ort der Punktion, bei 34 Patienten (0,12%) um bedeutsame Hämatome an der Punktionsstelle (OP oder Bluttransfusion erforderlich), bei 32 Patienten (0,12%) um persistierende Pseudoaneurysmen, bei 9 Patienten (0,03%) um eine AV-Fistel und bei 3 Patienten (0,01%) um andere schwerwiegende Komplikationen. Lokale Gefäßkomplikationen waren deutlich häufiger bei Frauen als bei Männern nachweisbar, außerdem war nach interventioneller Kathetertherapie unter Verwendung großlumiger Schleusen mit der Notwendigkeit einer effektiven Heparintherapie die Häufigkeit von Komplikationen deutlich gegenüber rein diagnostischen Untersuchungen erhöht. Bei vorbestehender arterieller Verschlußkrankheit war die Häufigkeit eines lokalen Gefäßverschlusses erhöht. Eine operative Revision der Gefäßkomplikation war bei 62 Patienten (54%) notwendig, 34 Patienten (30%) wurden konservativ behandelt. Bei 18 Patienten (17%) konnte durch Kathetertechniken (PTA, lokale Lyse, Stent-Implantation) ein Gefäßverschluß eröffnet werden. Insgesamt ist die Inzidenz einer signifikanten lokalen Gefäßkomplikation nach Herzkatheteruntersuchung selten. Zukünftig werden diese vaskulären Komplikationen zunehmend auch durch konservative Maßnahmen (z.B. lolake Kompressionsbehndlung bei Pseudoaneurysmen) oder Kathetertechniken (vor allem zur Rekanalisation von arteriellen Verschlüssen) behandelt werden können. We analyzed the incidence and management of major vascular complications at the arterial puncture site following diagnostic or interventional cardiac catheterization. 27387 cardiac catheterization procedures were performed for diagnostic (n = 19581) or interventional (n = 7806) purposed at our institution during a 7-year study period. A total number of 114 major vascular complications (0.42%) were identified. In 36 (0.13%) patients an arterial occlusion at the puncture site was detected, 34 patients (0.12%) had severe hematoma (blood transfusion or surgical repair necessary), 32 patients (0.12%) developed false aneurysms, 9 patients (0.03%( with av-fistulas and 3 patients (0.01%) had other complications. The following factors were predictive for a significant increase in the incidence of major vascular complications: Female gender, interventional catheterization using larger introducer sheaths and necessitating effective perioperative doses of heparine, and peripheral vascular disease. Operative repair was necessary in 62 patients (54%), 34 patients (30%) were treated conservatively. In 18 patients (17%) acute vascular occlusion could be managed by percutaneous transluminal balloon dilatation and intravascular thrombolysis of the obstructionn, in 3 patients additional stent-implantation was necessary in the presence of a large occlusive dissection. Overall the rate of clinically significant major vascular complications is low. In the future a greater number of vascular complications at the entry site for cardiac catheterization will be treated with nonoperative methods (e.g. manual compression of pseudoaneurysms or catheter-based techniques for recanalization of acutely occluded vessels).