Benny Levenson

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.

Percutaneous coronary interventions (PCI)

3 Invasive PCI-bezogene Diagnostik . . . . . . . 516 3.1 Koronarangiographie . . . . . . . . . . . . . . . . . . 516 3.2 Intrakoronare diagnostische Katheterverfahren . 517 3.2.1 Intravaskulärer zweidimensionaler Ultraschall (IVUS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517 3.2.2 Intrakoronarer Doppler . . . . . . . . . . . . . . . . . 517 3.2.3 Intrakoronare Druckdrahtmessung . . . . . . . . . 517

Combined Assessment of Myocardial Perfusion and Late Gadolinium Enhancement in Patients After Percutaneous Coronary Intervention or Bypass Grafts : A Multicenter Study of an Integrated Cardiovascular Magnetic Resonance Protocol

OBJECTIVES We sought to assess the accuracy of an integrated cardiac magnetic resonance (CMR) protocol for the diagnosis of relevant coronary artery or bypass graft stenosis in patients with suspected coronary artery disease (CAD) or with previously performed percutaneous coronary intervention (PCI) or coronary bypass graft surgery (CABG). BACKGROUND CMR is suitable for diagnosing inducible myocardial ischemia in patients with suspected CAD and has been proven to be a helpful diagnostic tool for decision of further treatment. However, little is known about its diagnostic accuracy in patients with known CAD who previously were treated by PCI or CABG. METHODS A total of 477 patients with suspected CAD, 236 with previous PCI, and 110 after CABG referred for coronary X-ray angiography (CXA) underwent an integrated CMR examination before CXA. Myocardial ischemia was assessed using first-pass perfusion after vasodilator stress with adenosine (140 microg/kg/min for 3 min) using gadolinium-based contrast agents (0.1 mmol/kg). Late gadolinium enhancement (LGE) was assessed 10 min after a second contrast bolus. RESULTS CXA demonstrated a relevant coronary vessel stenosis (> or =70% luminal reduction) in 313 (38%) patients using quantitative coronary analysis. The combination of CMR perfusion and LGE assessment for detecting a relevant coronary stenosis in patients with suspected CAD yielded sensitivity and specificity of 0.94 and 0.87, in PCI patients 0.91 and 0.90, and in CABG patients 0.79 and 0.77, respectively. CONCLUSIONS A combined CMR protocol for the assessment of myocardial perfusion and LGE is feasible for the detection of relevant coronary vessel stenosis even in patients who previously were treated by PCI or CAG in a routine clinical setting. However, diagnostic accuracy is reduced in patients with CABG. This could be due to different flow and perfusion kinetic. Further studies are needed to optimize the clinical protocols especially in post-surgical patients.

Real life use of sirolimus-eluting coronary stents in Germany. Results from the prospective multi-centre German Cypher Registry.

„Drug-eluting“-Stents (DES) sind ein viel versprechender Ansatz zur Lösung der Rezidivstenoseproblematik bei der perkutanen transluminalen Koronarintervention (PCI). Die vorliegenden randomisierten Studien (RCT) schlossen jedoch nur Patienten mit relativ unproblematischen Läsionen ein. Wir untersuchten die Daten des deutschen Cypher-Register™-Registers, das parallel zur Zulassung des ersten DES, des Sirolimus beschichteten Cypher™-Koronarstents, im April 2002 begonnen wurde, bezüglich des Einsatzes dieses DES im klinischen Alltag. Von April 2002 bis März 2003 wurden 1638 Implantationen von Cypher™-Stents an 88 Kliniken in das deutsche Cypher™-Register eingeschlossen. Die mittlere Einschlussrate pro Zentrum und Monate war niedrig (< 3 Einschlüsse/ Monat und teilnehmender Klinik). Bei der Mehrzahl der Patienten lag eine stabile Angina pectoris (45,8%) vor. 6,4% der Patienten wurden jedoch wegen eines Nicht-ST-Hebungsinfarktes, 10,3% der Patienten wegen eines ST-Hebungsinfarktes und 1,7% der Patienten im kardiogenen Schock behandelt. Bei Patienten ohne einen ST-Hebungsinfarkt wurde eine de novo-Stenose in 68,4% der Fälle, eine Rezidivstenose in 4,1% und eine In-Stent Rezidivstenose in 25,5% der Fälle behandelt. Chronische Verschlüsse wurden bei 6,1% der Patienten behandelt. Eine Vor-Dilatation wurde bei 68,3% der Patienten durchgeführt und pro Patient wurden 1,05 ± 0,35 Cypher™-Stents mit einer medianen Länge von 18 mm (Quartile: 13–21 mm) implantiert. Zu einem PCI-assoziierten Todesfall kam es in 0,1% der Fälle und ein Q-Zacken-Myokardinfarkt entwickelte sich in 1,1% der Fälle. Eine erneute Notfall-PCI vor der Entlassung aus dem Krankenhaus erfolgte in 1,3% und eine notfallmäßige koronare Bypassoperation bei 0,1% der Fälle. Der Einsatz des Sirolimus beschichteten Cypher™-Stents im klinischen Alltag erwies sich während des Kliniksaufenthaltes als sicher bezüglich der akuten Komplikationen. In etwa der Hälfte der Fälle wurde der Sirolimus-Stent in der klinischen Routine bei Läsionen eingesetzt, die bislang nicht in randomisierten Studien untersucht wurden. Drugeluting stents (DES) are currently judged to be a “break-through” technology for the prevention of restenosis after percutaneous coronary interventions (PCI). However, experience is limited to randomised controlled clinical trials (RCT) in selected lesions and the currently available DES are more expensive compared to conventional “bare” stents. Therefore, actual clinical practice may be very different to RCT. We analysed the data of the German Cypher™ Registry, a nationwide registry which was initiated in parallel to the launch of the first DES, the Cypher™ sirolimus-eluting coronary stent, in April 2002. From April 2002 until March 2003, 1638 procedures at 88 hospitals were included in the German Cypher™ Registry . The mean inclusion rate per centre and month remained low (<3 procedures/month and participating hospital) during the whole inclusion period. Most patients presented with stable angina pectoris (45.8%); however, 6.4% of patients were treated for a non-ST elevation myocardial infarction, 10.3% of patients for ST elevation myocardial infarction and 1.7% in cardiogenic shock. In patients without ST elevation myocardial infarction, a de novo stenosis was treated in 68.4% of cases, a restenosis in 4.1%, and an in-stent restenosis in 25.5% of cases. Chronic total occlusions were treated in 6.1% of patients. Predilatation was performed in 68.3% of patients and 1.05 ± 0.35 Cypher™ stents were implanted per patient with a median (quartiles) stent length of 18 (13–21) mm. PCI-related death occurred in 0.1% of patients and a Q-wave myocardial infarction in 1.1%. Urgent re-PCI before hospital discharge was performed in 1.3% and urgent bypass surgery in 0.1% of cases. The use of the sirolimus-eluting coronary stents in this “real life” registry was found to be safe concerning acute complications. In about one half of the registry patients, the DES was implanted in lesions that were excluded from RCTs.

“Real life” use of sirolimus-eluting coronary stents in Germany

„Drug-eluting“-Stents (DES) sind ein viel versprechender Ansatz zur Lösung der Rezidivstenoseproblematik bei der perkutanen transluminalen Koronarintervention (PCI). Die vorliegenden randomisierten Studien (RCT) schlossen jedoch nur Patienten mit relativ unproblematischen Läsionen ein. Wir untersuchten die Daten des deutschen Cypher-Register™-Registers, das parallel zur Zulassung des ersten DES, des Sirolimus beschichteten Cypher™-Koronarstents, im April 2002 begonnen wurde, bezüglich des Einsatzes dieses DES im klinischen Alltag. Von April 2002 bis März 2003 wurden 1638 Implantationen von Cypher™-Stents an 88 Kliniken in das deutsche Cypher™-Register eingeschlossen. Die mittlere Einschlussrate pro Zentrum und Monate war niedrig (< 3 Einschlüsse/ Monat und teilnehmender Klinik). Bei der Mehrzahl der Patienten lag eine stabile Angina pectoris (45,8%) vor. 6,4% der Patienten wurden jedoch wegen eines Nicht-ST-Hebungsinfarktes, 10,3% der Patienten wegen eines ST-Hebungsinfarktes und 1,7% der Patienten im kardiogenen Schock behandelt. Bei Patienten ohne einen ST-Hebungsinfarkt wurde eine de novo-Stenose in 68,4% der Fälle, eine Rezidivstenose in 4,1% und eine In-Stent Rezidivstenose in 25,5% der Fälle behandelt. Chronische Verschlüsse wurden bei 6,1% der Patienten behandelt. Eine Vor-Dilatation wurde bei 68,3% der Patienten durchgeführt und pro Patient wurden 1,05 ± 0,35 Cypher™-Stents mit einer medianen Länge von 18 mm (Quartile: 13–21 mm) implantiert. Zu einem PCI-assoziierten Todesfall kam es in 0,1% der Fälle und ein Q-Zacken-Myokardinfarkt entwickelte sich in 1,1% der Fälle. Eine erneute Notfall-PCI vor der Entlassung aus dem Krankenhaus erfolgte in 1,3% und eine notfallmäßige koronare Bypassoperation bei 0,1% der Fälle. Der Einsatz des Sirolimus beschichteten Cypher™-Stents im klinischen Alltag erwies sich während des Kliniksaufenthaltes als sicher bezüglich der akuten Komplikationen. In etwa der Hälfte der Fälle wurde der Sirolimus-Stent in der klinischen Routine bei Läsionen eingesetzt, die bislang nicht in randomisierten Studien untersucht wurden. Drugeluting stents (DES) are currently judged to be a “break-through” technology for the prevention of restenosis after percutaneous coronary interventions (PCI). However, experience is limited to randomised controlled clinical trials (RCT) in selected lesions and the currently available DES are more expensive compared to conventional “bare” stents. Therefore, actual clinical practice may be very different to RCT. We analysed the data of the German Cypher™ Registry, a nationwide registry which was initiated in parallel to the launch of the first DES, the Cypher™ sirolimus-eluting coronary stent, in April 2002. From April 2002 until March 2003, 1638 procedures at 88 hospitals were included in the German Cypher™ Registry . The mean inclusion rate per centre and month remained low (<3 procedures/month and participating hospital) during the whole inclusion period. Most patients presented with stable angina pectoris (45.8%); however, 6.4% of patients were treated for a non-ST elevation myocardial infarction, 10.3% of patients for ST elevation myocardial infarction and 1.7% in cardiogenic shock. In patients without ST elevation myocardial infarction, a de novo stenosis was treated in 68.4% of cases, a restenosis in 4.1%, and an in-stent restenosis in 25.5% of cases. Chronic total occlusions were treated in 6.1% of patients. Predilatation was performed in 68.3% of patients and 1.05 ± 0.35 Cypher™ stents were implanted per patient with a median (quartiles) stent length of 18 (13–21) mm. PCI-related death occurred in 0.1% of patients and a Q-wave myocardial infarction in 1.1%. Urgent re-PCI before hospital discharge was performed in 1.3% and urgent bypass surgery in 0.1% of cases. The use of the sirolimus-eluting coronary stents in this “real life” registry was found to be safe concerning acute complications. In about one half of the registry patients, the DES was implanted in lesions that were excluded from RCTs.

The Sirolimus-eluting coronary stent in daily routine practice in Germany: trends in indications over the years. Results from the prospective multi-centre German Cypher Stent Registry.

BackgroundDrugeluting coronary stents (DES) are increasingly used during percutaneous coronary interventions (PCI). Due to limited budgets in Germany, no special reimbursement has been given for their use and therefore they were mainly used in selected patients.MethodsIn order to determine the change in indications in patients treated with a Sirolimus-eluting stent (SES) in daily clinical practice between 2002 and 2005, we analysed data from a prospective multi-centre DES registry, the German Cypher Stent Registry.ResultsFrom April 2002 until September 2005, 11 507 patients at 132 hospitals, who received at least one SES during their PCI, were included. Between 2002 and 2005, the median age of patients increased from 63 years to 66 years (p for trend <0.0001), whereas the prevalence of prior coronary bypass surgery (p<0.0001) and prior PCI (p<0.001) significantly decreased. Initial presentation of patients was stable over time, with a small increase of patients treated for non-ST elevation myocardial infarction (p=0.05). We found a significant increase in the treatment of complex stenoses (p<0.0001) as well as an increase in the proportion of chronic total occlusions (p<0.01). There was a steady increase in the proportion of patients treated for de novo lesions (p<0.0001), which was accompanied by a relative decrease in the proportion of patients treated for in-stent restenosis (p<0.0001). Concerning interventional characteristics a significant increase in the length of SES implanted per lesion, the numbers of SES implanted per lesion as well as an increase of the proportion of patients treated for more than one stenosis during one intervention could be observed (all p<0.0001). There was a significant decrease in the use of glycoprotein II b/IIIa antagonists during the PCI (2002: 26.5 to 14.2% in 2005, p<0.0001). MACE rates until hospital discharge did not change significantly over time.ConclusionsBetween 2002 and 2005 there were two trends in the use of SES: a) a significant increase in the use of SES for de novo lesions and b) a significant trend to use SES for longer lesions, smaller arteries, more complex lesions and more SES per lesion. In summary these findings indicate that still SES are mainly used in patients with lesions that are at high risk for restenosis.

Sirolimus-eluting stent treatment for unprotected versus protected left main coronary artery disease in widespread clinical routine: 6-month and 3-year clinical follow-up results from the prospective multicentre German Cypher Registry

Background: Percutaneous coronary intervention (PCI) of left main coronary artery (LMCA) disease in the bare stent era was limited by high restenosis rates which eventually resulted in sudden death in unprotected cases. Clinical and angiographic restenosis has been substantially reduced by drug-eluting stents, reviving therefore this indication for PCI despite the absence of direct comparative studies with coronary artery bypass graft surgery. Objective: To assess the acute, mid- and long-term outcomes of patients treated with sirolimus-eluting stents for unprotected LMCA stenoses and to compare them with those treated for protected LMCA disease in the same time period from the German Cypher Registry. Setting and patients: The German Cypher Registry included 6755 patients. Eighty-two patients treated for unprotected LMCA disease were compared with 118 patients treated for protected LMCA stenoses. All patients were treated by sirolimus-eluting stents. The primary end point was death, myocardial infarction (MI) and target vessel revascularisation at 6 months’ follow-up. Survival free of MI at the long term was considered as the safety end point. Results: One-third of the patients in both groups were treated for the distal left main bifurcation. Angiographic success was 98.5% for both groups. The cumulative combined incidence of all-cause death, non-fatal MI and target vessel revascularisation at 6 months was 14.1% in the unprotected LMCA group and 13.1% in the protected group (hazard ratio = 0.81 (95% CI 0.37 to 1.74), p = 0.8). At long-term, death/MI were reported among 20.2% (95% CI 13.5% to 29.6%) of the protected group versus 11.8% (95% CI 6.3% to 21.4%) of the unprotected group (p = 0.2). Conclusion: Sirolimus-eluting stent treatment of unprotected and protected LMCA stenoses is technically feasible in widespread routine clinical use. Acceptable long-term clinical results can be achieved, with no particular safety concerns about treatment of unprotected LMCA disease.

Implantation of sirolimus-eluting stents in saphenous vein grafts is associated with high clinical follow-up event rates compared with treatment of native vessels.

AimsThe clinical effectiveness of sirolimus-eluting stents (SES) for treatment of patients with saphenous vein graft disease is not well defined. This analysis sought to evaluate the clinical follow-up after treatment of stenotic saphenous vein grafts using SES in a large patient registry. Patients treated with SES for saphenous vein graft disease were compared with patients receiving SES in native vessel disease. MethodThis is a subanalysis from the prospective multicenter German Cypher Stent Registry. Only patients with completed 6 months clinical follow-up were included. The analysis comprises 344 patients with 353 lesions in saphenous vein grafts treated with 400 SES (Cypher, Cordis Inc., Cordis Corp., Warren, New Jersey, USA) and 6411 patients with 7607 native coronary artery lesions treated with 8725 SES. ResultsMean SES length per lesion was 22.6±11.7 mm and mean stent diameter 3.0±0.3 mm in saphenous vein graft lesions. Target vessel revascularization rate was 18.1% and major adverse cardiovascular events (MACE) rate was 23.8% at 6-month follow-up after SES implantation for saphenous vein graft lesions. Even after adjustment for different baseline characteristics, target vessel failure and MACE rate were significantly higher after SES implantation for saphenous vein graft lesions than for native coronary vessel stenosis [odds ratio: 2.10 (95% confidence interval: 1.40–3.13), P<0.001] and [odds ratio: 2.15 (95% confidence interval: 1.49–3.09), P<0.001], respectively. ConclusionTreatment of saphenous vein graft disease is associated with high target vessel revascularization and MACE rates also with the use of SES if applied to unselected patients. Target vessel revascularization and MACE rates remain significantly higher after SES for saphenous vein graft lesions than after SES in native vessel disease.

Prognostic value of the modified American College of Cardiology/American Heart Association lesion morphology classification for clinical outcome after sirolimus-eluting stent placement (results of the prospective multicenter German Cypher Registry)

The modified American College of Cardiology/American Heart Association (ACC/AHA) lesion morphology classification scheme has prognostic impact for early and late outcomes when bare-metal stents are used. Its value after drug-eluting stent placement is unknown. The predictive value of this lesion morphology classification system in patients treated using sirolimus-eluting stents included in the German Cypher Registry was prospectively examined. The study population included 6,755 patients treated for 7,960 lesions using sirolimus-eluting stents. Lesions were classified as type A, B1, B2, or C. Lesion type A or B1 was considered simple (35.1%), and type B2 or C, complex (64.9%). The combined end point of all deaths, myocardial infarction, or target vessel revascularization was seen in 2.6% versus 2.4% in the complex and simple groups, respectively (p = 0.62) at initial hospital discharge, with a trend for higher rates of myocardial infarction in the complex group. At the 6-month clinical follow-up and after adjusting for other independent factors, the composite of cumulative death, myocardial infarction, and target vessel revascularization was nonsignificantly different between groups (11.4% vs 11.2% in the complex and simple groups, respectively; odds ratio 1.08, 95% confidence interval 0.8 to 1.46). This was also true for target vessel revascularization alone (8.3% of the complex group, 9.0% of the simple group; odds ratio 0.87, 95% confidence interval 0.72 to 1.05). In conclusion, the modified ACC/AHA lesion morphology classification system has some value in determining early complications after sirolimus-eluting stent implantation. Clinical follow-up results at 6 months were generally favorable and cannot be adequately differentiated on the basis of this lesion morphology classification scheme.

Incidence and predictors of target vessel revascularization after sirolimus-eluting stent treatment for proximal left anterior descending artery stenoses among 2274 patients fromthe prospectivemulticenter German Cypher Stent Registry

BackgroundInvolvement of the proximal LAD is considered an indication for coronary artery bypass graft (CABG) surgery due to the high restenosis rates associated with this location after percutaneous coronary interventions (PCI). This seems to be different, however, when using sirolimus-eluting stents, a finding if proven to be true could have a major impact on clinical decision making regarding the optimal revascularization strategy for these patients.MethodsWe analyzed 2274 patients treated for proximal LAD stenoses using SES from the German Cypher Stent Registry. The incidence of TVR and other major clinical adverse events were determined and independent predictors of TVR were specified using a multiple logistic regression model.ResultsEvent-free survival was achieved in 89.5% of patients. TVR was performed in 179 patients (7.9%) and the combined incidence of all cause death, myocardial infarction and TVR was 10.5% (231 patients). Independent predictors of TVR were multivessel disease (OR 1.74, 95% CI 1.16–2.62, p = 0.008), stent diameter ≤ 2.75 mm (OR 1.61, 95% CI 1.10–2.40, p = 0.02) and the administration of GP IIb/ IIIa antagonists (OR 1.60, 95% CI 1.05–2.60, p = 0.03). TVR rate was as high as 11.2% for 2.5 mm SES and as low as 4.0% for 3.5 mm SES (p < 0.001 for trend test).ConclusionTVR among patients treated with SES for proximal LAD stenoses is low and is related in part to operator dependent factors. Treatment with SES should be considered as an effective treatment for these patients.