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Long-term Clinical and Echocardiographic Follow-up After Surgical Correction of Hypertrophic Obstructive Cardiomyopathy With Extended Myectomy and Reconstruction of the Subvalvular Mitral Apparatus

BACKGROUND The standard surgical approach to hypertrophic obstructive cardiomyopathy (HOCM) was modified in the present series with a combination of extended myectomy with partial excision and mobilization of the papillary muscles. METHODS AND RESULTS Between 1979 and 1992, 58 patients (38 men and 20 women; mean age, 49 +/- 24 years) with HOCM were operated on with the use of this different technique. Their intraventricular gradients were 79 +/- 33 (+/- SD) mm Hg at rest and increased to 147 +/- 48 mm Hg with provocative maneuvers. Mild-to-moderate mitral regurgitation was present in 60% of the patients, and severe regurgitation was present in 5%. Ten patients required additional aortocoronary bypass graft surgery. Follow-up (mean, 84 months) was complete (100%). Hemodynamic improvement was documented by a significant (P < .01) decrease in left ventricular end-diastolic pressure from 19 +/- 9 to 14 +/- 6 mm Hg and reduction of basal outflow tract gradients to 5 +/- 7 mm Hg at rest and 16 +/- 24 mm Hg after provocation. Late mortality was 1.4% per patient-year, and no sudden cardiac deaths occurred during follow-up. Functional status was excellent for 84% of the patients; 8 patients were in New York Heart Association functional class III, and none were in class IV. Echocardiography revealed no outflow tract obstruction. CONCLUSIONS Extended myectomy and reconstruction of the subvalvular mitral apparatus in HOCM result in excellent functional improvement with relief of outflow tract obstruction. The technique can be performed safely despite its more aggressive surgical nature and allows an individualized strategy depending on the patients extent and distribution of left ventricular hypertrophy.

Long term angiographic and clinical follow up in patients with stent implantation for symptomatic myocardial bridging

OBJECTIVE To assess long term results of coronary stent implantation in patients with symptomatic myocardial bridging. METHODS Intracoronary stent implantation was performed within the intramural course of the left anterior descending coronary artery in 11 patients with objective signs of myocardial ischaemia and absence of other cardiac disorders. All had myocardial bridging of the central portion of the left anterior descending coronary artery. Quantitative coronary angiography was performed before and after stent deployment, and again at seven weeks and six months. Clinical evaluation was done at two years. RESULTS After stent deployment, quantitative coronary angiography showed absence of systolic compression along the left anterior descending coronary artery; the minimum luminal diameter (mean (SD)) increased from 0.6 (0.3) mm before stent implantation to 1.9 (0.3) mm after implantation (p < 0.05). Intravascular ultrasound showed an increase in cross sectional area from 3.3 (1.3) mm2 at baseline to 6.8 (0.9) mm2 (p < 0.005) after stent deployment. Coronary flow reserve was normalised from 2.6 (0.5) at baseline to 4.0 (0.5) (p < 0.005) after stent implantation. At seven weeks, quantitative coronary angiography showed mild to moderate or severe in-stent stenosis in five of the 11 patients; four of these underwent repeat target vessel revascularisation (percutaneous transluminal coronary angioplasty in two; coronary artery bypass grafting in two). At six months, all patients (n = 9) showed good angiographic results, including those who had target vessel revascularisation. On clinical evaluation at two years, all patients (including those with target vessel revascularisation) remained free of angina and cardiac events. CONCLUSIONS Intracoronary stent implantation prevents external compression of bridged coronary artery segments, with increase in luminal diameter and alleviation of symptoms. The incidence of in-stent stenosis requiring target vessel revascularisation (36%) is comparable with that of lesions of 25 mm length in coronary artery disease. The symptom free and event free two year follow up data suggest that stent implantation is a useful way of treating symptomatic patients with myocardial bridges.

Effects of gold coating of coronary stents on neointimal proliferation following stent implantation

Experimental studies suggest a reduced neointimal tissue proliferation in vascular stainless steel stents coated with gold. This prospective multicenter trial evaluated the impact of gold coating on neointimal tissue proliferation in patients undergoing elective stent implantation. The primary end point was the in-stent tissue proliferation measured by intravascular ultrasound at 6 months comparing stents of identical design with or without gold coating (Inflow). Two hundred four patients were randomized to receive uncoated (group A, n = 101) or coated (group B, n = 103) stents. Baseline parameters did not differ between the groups. Stent length and balloon size were comparable, whereas inflation pressure was slightly higher in group A (14 +/- 3 vs 13 +/- 3 atm, p = 0.013). Procedural success was similar (A, 97%; B, 96%). The acute angiographic result was better for group B (remaining stenosis 4 +/- 12% vs 10 +/- 11%, p = 0.002). Six-month examinations revealed more neointimal proliferation in group B. By ultrasound, the neointimal volume within the stent was 47 +/- 25 versus 41 +/- 23 mm(3) (p = 0.04), with a ratio of neointimal volume-to-stent volume of 0.45 +/- 0.12 versus 0.40 +/- 0.12 (p = 0.003). The angiographic minimal luminal diameter was smaller in group B (1.47 +/- 0.57 vs 1.69 +/- 0.70 mm, p = 0.04), with a higher late luminal loss of 1.17 +/- 0.51 versus 0.82 +/- 0.56 mm (p = 0.001). Thus, gold coating of the tested stent type resulted in more neointimal tissue proliferation.

Myocardial Bridging in Absence of Coronary Artery Disease: Proposal of a New Classification Based on Clinical-Angiographic Data and Long-Term Follow-Up

Background: There is no widely accepted classification to guide therapy in patients with symptomatic myocardial bridging (MB). Methods: A retrospective analysis of 157 patients with chest pain, angiographic MB of the left anterior descending artery without obstructive coronary artery disease (CAD) was performed. Patients were evaluated for clinical symptoms, objective signs of ischemia by stress test, intracoronary Doppler flow measurement and coronary flow reserve. 100 patients without CAD or MB served as controls. Results: There was no difference in clinical symptoms and objective signs of ischemia between controls and patients with MB. The length of MB was 22.6 ± 7.8 mm, maximal systolic luminal diameter reduction 71 ± 16%, and maximal mid-diastolic luminal reduction 34.7 ± 13% as demonstrated by quantitative coronary angiography (QCA). Intracoronary Doppler showed significantly increased average peak flow velocity (APV), average systolic peak velocity (ASPV), average diastolic peak flow velocity (ADPV), and maximal peak velocity (MPV) in MB versus proximal and distal segments at rest and after maximal vasodilatation (p < 0.001 for all parameters). Coronary flow reserve was significantly higher proximally (2.9 ± 0.9) compared with segments distal to the MB (2.0 ± 0.6, p < 0.01). We propose a new MB classification for symptomatic patients with MB:Type A:incidental finding on angiography, no objective signs of ischemia; Type B: objective signs of ischemia, and Type C: with or without objective signs of ischemia and altered intracoronary hemodynamics (by QCA/CFR/intracoronary Doppler). 5-Year follow-up data based on this classification showed that types B and C responded well to β-blockers or calcium channel antagonists. Patients with type C refractory to medical therapy were treated with stenting of the MB. Conclusion: Patients with MB without CAD did not have a higher prevalence of chest pain or abnormal non-invasive stress tests compared to patients without CAD or MB. Intracoronary hemodynamic measurement is a novel approach that may be valuable in defining the functional significance of MB. We propose a classification of symptomatic patients with MB without CAD using non-invasive and invasive parameters to guide therapeutic choices.

Post-stenotic coronary blood flow at rest is not altered by therapeutic doses of the oral antidiabetic drug glibenclamide in patients with coronary artery disease

Objective: To investigate whether blood flow in normal and post-stenotic coronary arteries is altered by therapeutic doses of the sulfonylurea agent glibenclamide. Patients: 12 patients with a high grade stenosis of the left anterior descending coronary artery (n = 10) or left circumflex coronary artery (n = 2), and an angiographically normal corresponding left circumflex artery or left anterior descending artery, respectively. Design: Two Doppler ultrasound wires were positioned in the “normal” and post-stenotic artery for simultaneous measurements of coronary blood flow velocity under baseline conditions and after intravenous glibenclamide, 0.05 mg/kg body weight. Local coronary blood flow was calculated from the average peak velocity and the cross sectional area derived from quantitative coronary angiographic analysis. Coronary flow reserve was determined after intracoronary injection of 30 μg adenosine and 12 mg papaverine. Results: One hour after glibenclamide, serum insulin increased from (mean (SD)) 7.4 (2.0) to 44.8 (25.5) mU/l (p < 0.005), and C peptide from 1.4 (0.4) to 3.4 (1.2) ng/l (p = 0.005). In normal coronary arteries coronary flow reserve was 2.6 (0.4) after adenosine and 3.0 (0.4) after papaverine, while in post-stenotic arterial segments it was 1.2 (0.3) after adenosine (p = 0.005) and 1.3 (0.3) after papaverine (p = 0.005). There was no significant difference after glibenclamide. In non-stenotic arteries, average peak velocity (18.8 (5.2) cm/s) and calculated coronary blood flow (23.8 (10.7) ml/min) were not altered by glibenclamide (18.3 (5.2) cm/s and 22.8 (10.4) ml/min, respectively). In post-stenotic arteries, baseline average peak velocity was 13.3 (4.9) ml/min and coronary blood flow was 9.1 (3.0) ml/min, without significant change after glibenclamide (13.3 (5.2) cm/s, 9.0 (3.2) ml/min). Conclusions: Glibenclamide, 0.05 mg/kg intravenously, is effective in increasing serum insulin, suggesting a KATP channel blocking effect in pancreatic β cells. It does not compromise coronary blood flow and vasodilatation in response to adenosine and papaverine in post-stenotic and angiographically normal coronary arteries at rest.

Mechanismen und Therapiekonzepte der Stentrestenose

ZusammenfassungDie Stentrestenose hat sich in den letzten Jahren zu einem relevanten Problem der interventioneilen Kardiologie entwickelt, vor allem infolge der zunehmenden Implantations-frequenz sowie der Ausweitung der Implantationsindikationen. Die Restenoserate wird aufgrund dieser Umstände deutlich über den zuvor kalkulierten Ergebnissen der Benestent- und STRESS-Studie erwartet. Morphologisch ist die Stentrestenose charakterisiert durch eine frühe Aktivierung glatter Muskelzellen, die nach einigen Wochen großteilig durch extrazelluläre Matrix ersetzt wird.Klinische, angiographische und intravaskuläre Ultraschalluntersuchungen haben eine Vielzahl von Prädiktoren der Stentrestenose identifiziert: Diabetes mellitus, Therapie von Restenosen, Implantation multipler Stents, kleine, kalzifizierte Gefäße, venöse Bypass-Gefäße, Ostium- und Y-Stenosen und komplexe Stenosemorphologie.Standardtherapie der Stentrestenose ist derzeit die Ballondilatation. Bei kurzen, fokalen Stenosen (<10 mm) sind die Ergebnisse der einfachen PTCA befriedigend mit Restenoseraten zwischen 15 und 35%. Die Intervention ist in der Regel sicher mit nur geringen Begleitkomplikationen. Bei langstreckigen, diffusen Stentrestenosen (≥10 mm) führt die PTCA zu einer hohen Re-Restenoserate von bis zu>80%. Guer werden Vorteile von sogenannten „Debulking-Techniken” erwartet: direktionelle Koronaratherektomie (DCA), Excimer-Laserangioplastie (ELCA) oder Rotablation. Alle Debulking-Techniken gehen mit einer deutlichen Reduktion der Neointima innerhaib des Stents einher und erzielen in Kombination mit Ballondilatation größere postinterventionelle Lumendurchmesser. Ergebnisse über die Re-Restenoserate nach Anwendung dieser Techniken liegen nur sehrbegrenzt vor. Randomisiert kontrollierte Untersuchungen zum Vergleich mit Ballondilatation gibt es bisher nicht. Drei randomisierte multizentrische Studien laufen (LARS, ARTIST und TWISTER). um den Effekt von ELCA und Rotablation versus PTCA bei diffusen Stentrestenosen zu überprüfen.Die medikamentöse Begleittherapie nach Behandlung von Stentrestenosen ist im wesentlichen auf die Gabe von ASS beschränkt, eine klare Indikation für Ticlopidin besteht derzeit nicht, positive Einflüsse werden langfristig von einer lokalen Bestrahlungstherapie (emittierende Stents oder Afterloading) erwartet.Mit weiter steigenden Stentimplantationsraten und Implantationsindikationen wird bei einer niedrig kalkulierten Restenoserate von 20% für 1997 mit bis zu 80 000 Stentrestenosen gerechnet. Endgültige Empfehlungen für eine optimale Therapie dieser Patienten liegen bislang nicht vor.SummaryDemonstration of a reduced restenosis rate after stent implantation (Benestent, STRESS) has initiated rapid increase in stent implantation rates with widening indications. At present, the majority of stents are implanted in “none-Benestent/STRESS-lesions” with the consequence of a higher restenosis rate as previously expected. Stent restenosis has therefore become a relevant problem in interventional cardiology. In contrast to balloon angioplasty, where acute and subacute recoil represents the major mechanism of restenosis, stent restenosis is exclusively attributed to neointima proliferation. Morphological studies have demonstrated that neointima is caused by early smooth muscle cell ingrowth with a maximum after 7 days which is then gradually replaced by extracellular matrix. Systematic clinical, angiographic and intravascular ultrasound studies have identified several risk factors for increased stent restenosis such as: diabetes mellitus, treatment of restenosis, serial stent implantation, small and calcified vessels, ostial lesions, venous bypass grafts and complex stenosis morphology. In addition, there is increasing evidence that aggressive implantation techniques with high pressures and oversized balloons may also induce higher restenosis rates.Optimal treatment of instent restenosis has not been determined so far. Balloon angioplasty is at present considered the therapeutic option of choice. Several small studies have shown, that in short, discrete lesions (<10 mm) results of simple PTCA are acceptable with re-restenosis rates between 15 and 35%. The intervention is considered safe with low complication rates. In 10 to 15% additional stent implantation is necessary, usually due to dissections proximal or distal to the treated stent. In long, diffuse stent restenosis (≧10 mm), however, PTCA results in high re-restenosis rates up to >80%. This is most likely due to insufficient early balloon angioplasty results with minimal luminal diameters (MLD) significantly below the previous stent diameter. Therefore, debulking techniques have been used to reduce neointima burden within the stent. At present 3 techniques are available: directional coronary atherectomy (DCA), Excimerlaser angioplasty (ELCA) or high frequency rotablation. All of these techniques achieve a significant reduction in plaque volume within the stent and in combination with balloon angioplasty allow larger MLDs than PTCA alone. Limited experiences with ELCA and rotablation have shown that the techniques are safe without major periinterventional complications. DCA, however, has been accompanied with stent destruction and therefore should be considered with large care, especially in stents with coil design. At present, no randomized controlled trials for the comparison of debulking techniques with or without balloon angioplasty versus balloon angioplasty alone are available. Three multicenter trials have been initiated (LARS, ARTIST and TWISTER) to compare debulking techniques versus balloon angioplasty in diffuse stent restenosis.Adjunct medical treatment after interventions for stent restenosis is usually limited to ASS alone, indications for additional application of Ticlopidine have not been verified so far. Positive results are expected for the use of local radiation therapy either by radioactive stent implantation or afterloading techniques.With increasing stent implantation rates and indications, about 400 000 stents will be implanted in 1997 worldwide. Considering a low restenosis rate of 20%, 80 000 stent restenosis will occur within one year. Final recommendations for optimal treatment of these patients are not yet available.

Effect of nitroglycerin and nicorandil on regional poststenotic quantitative coronary blood flow in coronary artery disease : A combined digital quantitative angiographic and intracoronary Doppler study

Little information is available concerning the effects of nitrates and potassium channel openers on local poststenotic blood flow in coronary artery disease (CAD). Combined quantitative digital angiography (QCA) and intracoronary Doppler (IVADO) velocity measurements were used to determine changes in absolute poststenotic blood flow after intracoronary injection of 0.2 mg nitroglycerin and 0.5 mg nicorandil. Quantitative blood flow (QBF) was calculated from average peak-flow velocity (APV) and angiographic cross-sectional area (CSA): QBF (ml/min) = CSA x APV x 0.5. In group I (n = 9), 0.5 mg nicorandil i.c. was identified as optimal to achieve maximal vasodilatation. In patients with CAD (group II, n = 12), i.c. injection of 0.5 mg nicorandil induced a significant increase in poststenotic CSA (+38%) and QBF (+50%). In contrast, 0.2 mg nitroglycerin (group III, n = 12) increases poststenotic CSA (+38%) without a significant change in QBF (+23%). Additional application of nicorandil in these patients induced further significant increases in CSA (+55%) and QBF (+48%) compared with baseline. There were no significant changes in stenosis area. Poststenotic blood flow can be increased by nicorandil after application of nitroglycerin. This effect is most likely mediated by the potassium channel-opening effect of nicorandil. Combined use of QCA and IVADO is a unique approach to measure local poststenotic QBF in patients with CAD.

Lebensbedrohliche Akut-Komplikationen der Dobutamin-Atropin-Streßechokardiographie – ein kasuistischer Beitrag

Über zwei seltene Komplikationen der Dobutamin-Atropin Streßechokardiographie wird berichtet. Bei einem 66jährigen Patienten entwickelten sich klinische, elektro- und echokardiographische Zeichen eines akuten Vorderwandinfarktes nach der zweiten Atropin-Bolusgabe unter maximaler Dobutamin-Stimulation mit 40 μg/kg/min. Die akut durchgeführte Koronarangiographie zeigte einen proximalen Verschluß des Ramus interventricularis anterior, welcher primär erfolgreich rekanalisiert werden konnte. Ein zweiter Patient wurde nach Stimulation mit 40 μg/kg/min Dopamin und zusätzlicher Gabe von 0,5 mg Atropin reanimations- und intubationspflichtig im Rahmen einer akuten Hinterwandischämie mit Kammerflimmern. Die möglichen Ursachen und Inzidenzen solcher lebensbedrohlicher Komplikationen werden diskutiert und der konventionellen Fahrradergometrie gegenübergestellt. Die beschriebenen lebensbedrohlichen Komplikationen weisen auf die Bedeutung entsprechender notfallmedizinischer Einrichtungen als Voraussetzung zur Durchführung einer medikamentösen Streßechokardiographie hin. The presented case report describes lifethreatening complications of pharmacological stress echocardiography with dobutamine. A 66-year old male suffered an acute anterior wall myocardial infarction during dobutamine-atropine stress echocardiography. Symptoms and signs of myocardial infarction developed after maximal dobutamine-dose (40 μg/kg/min) and the additional application of atropine. Emergency coronary angiography revealed extensive coronary artery disease with proximal occlusion of the left anterior descending artery which was successfully recanalized. In a second patient ventricular fibrillation echocardiography and electrocardiographic signs of acute myocardial ischemia developed after high-dose dobutamine stress and required prolonged resuscitation. The possible mechanisms, incidence and risk of acute myocardial ischemia during dobutamine-atropine stress are discussed and compared to bicycle ergometry. The presented lifethreatening complications of dobutamine-atropine stress echocardiography emphasize the importance of available and adequate emergency facilities.

STENT-RESTENOSE: THERAPIEKONZEPTE UND MOGLICHKEITEN DER PRAVENTION

Zusammenfassung□ HintergrundDie Stent-Restenose hat sich zu einem relevanten Problem in der interventionellen Kardiologie entwickelt. Aufgrund pathogenetischer Unterschiede ist unklar, ob ein einheitliches Schema zur Therapie dieser Erkrankung sinnvoll erscheint.□ TherapieIn den meisten Fällen wird die Stent-Restenose mit einer erneuten Ballondilatation therapiert, doch weist diese Methode äußerst ungünstige Langzeitergebnisse bei diffusen und langstreckigen Läsionen auf. Daher erscheinen gewebeabladierende Verfahren bei komplexen Stent-Restenosen vorteilhaft. Der Stellenwert der intrakoronaren Strahlentherapie sowie der lokalen Medikamentenapplikation oder des lokalen Gentransfers ist trotz des großen Potentials derzeit unklar.□ PräventionDer Prävention der „iatrogenen” Erkrankung Stent-Restenose durch eine sorgfältige Indikationsstellung und Therapieplanung kommt somit besondere Bedeutung zu.Abstract□ BackgroundIn-stent restenosis has become a significant problem for interventional cardiologists. Due to different pathogenic causes it remains unclear whether a uniform therapeutic regimen is appropriate.□ TreatmentRedilatation has predominantly been used for the treatment of instent restenosis, however, in long and diffuse restenotic stents, long-term results are reported to be poor. Therefore, tissue-debulking techniques may have beneficial effects in complex cases of in-stent restenosis. The therapeutic benefit of intracoronary radiation, local drug delivery or gene transfer has not been evaluated so far.□ PreventionTherefore, prevention of the iatrogenic entity in-stent restenosis has become more important.BACKGROUND In-stent restenosis has become a significant problem for interventional cardiologists. Due to different pathogenic causes it remains unclear whether a uniform therapeutic regimen is appropriate. TREATMENT Redilatation has predominantly been used for the treatment of instent restenosis, however, in long and diffuse restenotic stents, long-term results are reported to be poor. Therefore, tissue-debulking techniques may have beneficial effects in complex cases of in-stent restenosis. The therapeutic benefit of intracoronary radiation, local drug delivery or gene transfer has not been evaluated so far. PREVENTION Therefore, prevention of the iatrogenic entity in-stent restenosis has become more important.

Therapie und Risikostratifizierung der Hypertrophen Kardiomyopathie

Hypertrophic cardiomyopathy (HCM) is a relatively common disease of the cardiac sarcomere with broad heterogeneity in terms of the disease-causing gene mutation, phenotypic expression, therapy and prognosis.    Besides the standard drug treatment, there are several therapeutic options available for severe refractory symptomatic HCM with obstruction. Dual-chamber pacing and transcoronary ablation of septal hypertrophy (TASH) have recently emerged as alternatives to myectomy. However, myectomy remains the current gold standard of therapy for HCM until the promising initial follow-up data for TASH can be transferred into a long-term follow-up period, or prospective randomized comparative trials between these therapies are available. However, even now, TASH represents an important therapeutic alternative in patients with relevant co-morbidities and a high operative risk.    Despite significant gradient reduction and amelioration of clinical symptoms, none of these treatment strategies has a proven influence on the natural history of HCM. Hence, regarding the long-term prognosis of the disease, risk stratification of sudden cardiac death using non-invasive risk assessment has become of paramount importance, while genotyping might become the determinant and stratifying marker in the near future.    At present, according to secondary prevention, treatment with an implanted cardioverter-defibrillator ± amiodarone therapy is mandatory, while according to primary prevention treatment should particularly depend on the individual risk profile. Die hypertrophe Kardiomyopathie (HCM) ist eine relativ häufige genetisch bedingte Erkrankung des kardialen Sarkomers mit einer ausgeprägten Heterogenität in Bezug auf die ursächliche Genmutation, die phänotypische Expression, die Therapie und die Prognose.    Neben der medikamentösen Basistherapie stehen vor allem für die obstruktive Variante der HCM mehrere Therapieoptionen zur Verfügung. Die Zweikammerschrittmachertherapie mit einem DDD-System und die transkoronare Ablation der Septumhypertrophie (TASH) haben sich zuletzt zu therapeutischen Alternativen entwickelt. Dennoch muss die operative Myektomie derzeit weiterhin als der therapeutische Goldstandard angesehen werden, zumindest solange bis die erfolgversprechenden initialen Follow-up-Daten der TASH-Behandlung in Langzeitnachuntersuchungen bestätigt werden können, oder randomisierte prospektive Vergleichsstudien zu den Therapien vorliegen. Bei Patienten mit relevanten Ko-Morbiditäten und einem dementsprechend hohen operativen Risiko stellt TASH aber bereits jetzt die bevorzugte therapeutische Alternative dar.    Obwohl alle hier beschriebenen Therapiestrategien die Obstruktion reduzieren und die Symptomatik lindern, teilweise sogar eine komplette Beschwerdefreiheit erzielen, hat keine dieser Behandlungsformen einen bislang nachgewiesenen Effekt auf den natürlichen Verlauf der HCM. Daher hat die Risikostratifizierung des plötzlichen Herztodes, vor allem in Bezug auf die Langzeitprognose der Erkrankung, eine wesentliche Bedeutung erlangt. Neben den nicht-invasiven Verfahren werden in Zukunft vor allem die Möglichkeiten der Genotypisierung bei der Entscheidungsfindung einer prophylaktischen Therapie zunehmend an Bedeutung gewinnen. Zum jetzigen Zeitpunkt muss die Therapie mit einem implantierten Cardioverter-Defibrillator ± Amiodaron im Rahmen der Sekundärprävention als verpflichtend und im Rahmen der Primärprävention in Abhängigkeit vom Risikoprofil beurteilt werden.