A. Athanasiadis

Insertion/Deletion Polymorphism of the Angiotensin I-Converting Enzyme Gene Is Associated With Coronary Artery Plaque Calcification As Assessed by Intravascular Ultrasound

OBJECTIVES We evaluated the influence of the insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene on coronary plaque morphology and calcification in patients with angiographically documented coronary artery disease (CAD). BACKGROUND The ACE I/D polymorphism has been associated with an increased risk of myocardial infarction in patients with the DD genotype but not with the presence of native CAD. METHODS We studied 146 patients undergoing percutaneous transluminal coronary angioplasty for stable angina pectoris by means of preinterventional intravascular ultrasound (IVUS). Qualitative and quantitative criteria were used to classify the target lesions as poorly or highly echoreflective or as calcified. Genomic deoxyribonucleic acid was analyzed by polymerase chain reaction (PCR) to identify the I/D polymorphism, with a second insertion-specific PCR in DD genotypes to prevent mistyping. RESULTS The ACE genotype groups (DD 46, ID 68, II 32) were well matched for the basic characteristics. Patients with the DD genotype had significantly more calcified lesions (DD 80%, ID 57%, II 66%; unadjusted odds ratio [OR] 2.88, 95% confidence interval [CI] 1.30 to 6.92, p = 0.008) and more calcifications >180 degrees of the vessel circumference (DD 22%, ID 10%, II 6%; OR 2.80, 95% CI 1.05 to 7.63, p = 0.03). The prevalence of myocardial infarction was not significantly associated with coronary calcification (OR 1.44, 95% CI 0.72 to 2.88, p = 0.31). CONCLUSIONS Patients with CAD and the ACE DD genotype have a significantly higher incidence and greater extent of coronary lesion calcification, as determined by IVUS. This finding indicates that the ACE I/D gene polymorphism is related to the development or progression of atherosclerotic plaque calcification.

Local and systemic delivery of low molecular weight heparin following PTCA: Acute results and 6‐month follow‐up of the initial clinical experience with the porous balloon (PILOT‐study)

The purpose of this study was to assess safety and feasibility of intracoronary delivery of reviparin using a porous balloon following percutaneous transluminal coronary angioplasty. The 2.7 mm porous balloon used in this study had 35 holes arranged in a spiral pattern. Eighteen patients (male n = 10, female n = 8, age 63 ± 9 years) undergoing successful PTCA in coronary arteries with a vessel diameter of 2.5 to 3.0 mm determined by online QCA (LAD = 11, RCX = 3, RCA = 4) were included. They received a bolus of 7,000 anti-Xa-IU reviparin followed by local delivery of 1,500 anti-Xa-IU in 4 ml with an injection pressure of 2 atm. The patients received additionally 10500 anti-Xa-units intravenously during the following 24 hours and a daily dose of 7000 anti-Xa-units reviparin subcutaneously for the following 28 days. Angiograms were obtained before and after PTCA, directly after local delivery, at 24 hours postintervention and after 6 months. The primary success rate was 100%. Quantitative coronary angiography showed a minimum luminal diameter of 0.42 ± 0.14 mm before PTCA, 1.87 ± 0.45 after PTCA, 1.67 ± 0.43 after LDD, 1.63 ± 0.46 after 24 hours, and 1.06 ± 0.6 after 6 months. Angiographic follow-up was obtained in all patients. No major complications occurred during the 6-month follow-up period. The angiographic restenosis rate was 28% (5/18) at follow-up. This study demonstrates safety and feasibility of local intracoronary delivery of reviparin with a porous balloon following PTCA even in smaller diameter coronary arteries. Cathet. Cardiovasc. Diagn. 44:267–274, 1998.

Reliability of quantitative coronary angiography of the target lesion immediately and 1 day after coronary balloon and excimer laser angioplasty

OBJECTIVES This prospective trial was performed to evaluate the impact of the morphologic complications of angioplasty on the reliability and results of quantitative angiographic assessment of the residual stenosis. BACKGROUND Postintervention quantitative coronary analysis is limited by a variety of such complications. METHODS In 199 patients undergoing an early control angiographic study within 24 h after coronary balloon or excimer laser angioplasty (24-h study), detailed quantitative angiographic measurements were performed on the target lesion immediately after intervention and at the 24-h study. Reproducibility of quantitative arteriography was determined by repeat measurements on the same angiogram. RESULTS Intraobserver/interobserver variability was significantly higher (p < 0.0001/p < 0.03) for the postintervention angiogram than for the 24-h angiogram. Patients were classified into three subgroups with respect to the occurrence of angiographic complications or chest pain after intervention. In patients with angiographic complications after balloon angioplasty alone/stand-alone laser angioplasty/laser angioplasty with adjunctive balloon dilation, a significant difference in mean minimal lumen diameter (p = 0.0001/p = 0.03/p = 0.035) was observed between the immediate postintervention and 24-h angiogram. In patients without angiographic complications or patients with recurrent chest pain undergoing balloon angioplasty, stand-alone or adjunctive laser angioplasty, mean minimal lumen diameter remained nearly unchanged (p = NS). CONCLUSIONS Angiographic measurements of the target lesion immediately after angioplasty were significantly less reliable than measurements obtained at 24 h after angioplasty in patients with angiographic complications. The occurrence of postintervention vascular complications was associated with significant early lesion changes between the immediate postangioplasty and the 24-h angiogram.

Einfluß der Schwere der Gefäßdissektion auf das Langzeitergebnis nach transluminaler perkutaner koronarer Angioplastie

Der Einfluß der Gefäßdissektionen auf das Langzeitergebnis nach PTCA ist in den vergangenen Jahren kontrovers diskutiert worden. Während zahlreiche tierexperimentelle Untersuchungen einen Einfluß des Dissektionsausmaßes auf die Inzidenz einer Rezidivstenose zeigten, war der Einfluß von Dissektionen in klinischen Langzeitstudien nur gering. Dabei wurde meist keine Differenzierung der morphologisch unterschiedlichen Schweregrade der Gefäßdissektionen vorgenommen. Im Rahmen der vorliegenden Untersuchung sollte daher der Einfluß einer Dissektion sowie deren Schweregrad und Konfiguration auf die Restenosierung nach PTCA untersucht werden. Dabei sollte die prognostische Bedeutung der Dissektionsklassifikation nach den National-Heart-Lung-and-Blood-Institute-Kriterien und nach einer weiteren Einteilung angiographischer Komplikationen überprüft werden, um so Aufschlußüber mögliche Pathomechanismen als Ursache der Restenosierung zu erhalten. Die Studie erfolgte bei 141 Patienten mit 143 stabilen Dissektionen nach PTCA. Eine Nachuntersuchung wurde im Mittel 13 Monate nach erfolgter PTCA durchgeführt. Im Rahmen dieser Untersuchung wurden klinische, symptomatische und funktionelle Aspekte der Patienten erhoben. In diesem Patientenkollektiv zeigten Typ-C-Dissektionen nach der Klassifikation nach Dorros et al. ein erheblich erhöhtes Risiko für ein klinisches Ereignis (41,0%) innerhalb der ersten 7 bis 25 Monate nach PTCA. Typ A erwies ein nur geringes Risiko (10,0%), bei Typ B stellte sich ein mäßiggradiges Risiko (18,0%) für ein nachteiliges Langzeitergebnis heraus. Typ-D-Dissektionen zeigten im Vergleich zu Typ-C-Dissektionen eine geringere klinische Ereignisrate von 33,3%. Die Einteilung der postinterventionellen Gefäßmorphologie nach der AC-Klassifikation (61) konnte in der vorliegenden Studie ein ungünstiges Langzeitergebnis nach PTCA besser voraussagen (p = 0,0003) als die übliche Klassifikation nach Dorros et al. (p = 0,0056). Schlußfolgerung: Der Grad der Dissektion zeigte sowohl bei der Einteilung nach der Dorros-Klassifikation als auch bei der AC-Klassifikation eine signifikante Korrelation zu einem späten ischämischen Ereignis nach PTCA (p = 0,0056/p = 0,0003). Aus der speziellen Anlehnung der AC-Klassifikation an das angiographisch bestimmte Ausmaß der Gefäßverletzung ergibt sich die Schlußfolgerung, daß Ausprägung und Tiefe der Dissektion mit dem Langzeitergebnis nach Koronarangioplastie korrelieren. The influence of a coronary dissection on long-term outcome after PTCA has been controversely discussed in the past. Whereas diverse experimental studies have shown a positive relation between dissection and the incidence of restenosis, clinical trials could not document an influence of dissection on long-term outcome. However, most of the trials did not distinguish between the different morphologic configuration of the vascular dissection. Thus, the aim of the present study was to determine the influence of dissections on restenosis in regard to their amount and morphologic configuration. The prognostic importance of the National Heart, Lung, and Blood Institute classification on dissection as well as the importance of an additional classification of angiographic complications after PTCA were investigated to determine possible pathophysiologic mechanisms of the restenosis process. The study included 141 consecutive patients with 143 stable dissections after PTCA. A follow-up study was performed 13 months in mean after successful PTCA, which included clinical, symptomatic, and functional aspects of patients. In this patient population, type C dissections (Dorros et al.) showed a relevantly increased risk of a clinical adverse event (41.0%), whereas patients with a type A dissection had only a small risk of an adverse event (10.0%) over the investigation period. Type B dissections revealed an intermediate risk (18.0%), and type D dissections showed a risk of 33.3% of an adverse event, which was lower than that observed for type C dissections. The AC-classification of the postinterventional coronary morphology was a stronger predicter of an adverse outcome after PTCA (p = 0.0003) than was the Dorros-classification (p = 0.0056). Conclusions: The grade of a coronary dissection was highly, positively related to an ischemic event after PTCA using both the Dorros and the AC-classification (p = 0.0056/p = 0.0003). In regard to the special association of the AC-class with the amount of vascular injury, we conclude that the amount and configuration of coronary dissection correlates with the long-term outcome after PTCA.

Einsatz von Abciximab bei drohendem Gefäßverschluss nach PTCA

The administration of GP IIb/IIIa antagonists has been shown to be effective in reducing myocardial infarction and cardial death when given before PTCA. This prospective study was performed to determine the efficacy of abciximab in a bail-out situation to manage threatened or acute vessel closure.¶   Methods: Acute or threatened vessel closure was observed in 104 (5.5%) out of 1903 consecutive patients treated with PTCA in our institution. Of the 104 patients 46 (44%) were treated for unstable angina (CCS IV). Abciximab was administered in bail-out situations in a dosage of 0.25mg/kg given as a bolus, which was followed by an intravenous infusion of 10μg/min over 12 hours. Repeat PTCA was performed shortly after the administration of the abciximab bolus. After the procedure, the sheathe was left in place and control angiography was carried out 24 h later.¶   Results: In 100 of the 104 patients TIMI flow III could be restored by abciximab therapy and RePTCA. In 4 patients an additional stent implantation was necessary due to persistent flow limitation. One day post PTCA, early follow-up angiography demonstrated patency of all vessels except two. In-hospital events occurred in 4 patients. Three of these patients underwent emergency CABG due to subacute vessel closure a few hours after PTCA and died during or directly after surgery. Follow-up after one year included clinical status and control angiography of the target vessel. During long-term follow-up, MACE occured in 15 patients (2 MI, 8 CABG and 5 RePTCA).¶   Conclusion: The results of this prospective trial demonstrate the efficacy of abciximab therapy in bail-out situations occurring during or early after PTCA. The use of abciximab in bail-out situations appears clinically beneficial. Further studies have to compare the efficacy of this approach with prophylactic abciximab treatment. Die klinische Wirksamkeit von GP IIb/IIIa Antagonisten wurde bei präinterventioneller prophylaktischer Applikation in großen klinischen Studien nachgewiesen. Ziel dieser prospektiven Studie war es, die Wirksamkeit von Abciximab bei der Anwendung in „bail-out” Situationen zu untersuchen.¶   Methoden: Insgesamt wurden bei 104 (5,5%) der 1903 Patienten, welche im Beobachtungszeitraum in unserem Zentrum dilatiert wurden, akute oder drohende Gefäßverschlüsse beobachtet. In dieser Situation wurde Abciximab in einer Dosierung von 0,25mg/kg als Bolus, gefolgt von einer Infusion von 10μg/min über 12 Stunden appliziert. Kurz nach der Gabe des Bolus wurde eine erneute PTCA durchgeführt. Am Ende der Intervention wurde die Schleuse belassen und nach 24 Std. eine Kontrollangiographie durchgeführt.¶   Ergebnisse: Bei 100 der 104 Patienten konnte ein ausreichender (TIMI III) Fluss wiederhergestellt werden. Bei 4 Patienten war die zusätzliche Implantation eines Stents notwendig. Eine Kontrollangiographie am Folgetag zeigte in allen bis auf 2 Fälle offene Gefäße mit gutem antegraden Fluss (TIMI III). Bei 4 Patienten trat nach der Intervention ein subakuter Gefäßverschluss auf. Drei von ihnen verstarben trotz einer sofort durchgeführten Notfall-ACVB OP. Das 12 Monats Follow-up beinhaltet den klinischen Status sowie eine Kontrollangiographie des Zielgefäßes. Während des Nachbeobachtungszeitraums kam es bei 15 Patienten zu einem klinischen Ereignis (2 MI, 8 ACVB, 5 Re-PTCA).¶   Schlussfolgerung: Die Ergebnisse dieser prospektiven Studie zeigen die hohe Wirksamkeit von Abciximab in „bail-out” Situationen während oder direkt nach der PTCA. Weitere Studien sollten dieses Konzept mit dem der prophylaktischen Behandlung vergleichen.

Ultrasound guidance: technique and results of aggressive ultrasound-guided PTCA. The UPSIZE Pilot Trial.

Stenting results in a larger lumen than conventional balloon angioplasty. This is the major determinant of a good acute and long-term result. In this non-randomised, single centre trial, intravascular ultrasound was used preinterventionally to guide the choice of the balloon size. The aim was to achieve a maximum lumen area with balloon angioplasty only. We included 346 patients with 360 lesions. The diameter of the external elastic lamina by intravascular ultrasound was 4.67 mm. A mean balloon size of 4.0 mm was chosen. The initial luminal gain was 1.82 mm, the lumen area post intervention was 6.6 mm 2 . Dissections occurred frequently but the incidence of major adverse events was not increased. At one year follow-up, the overall event free survival was 81%. Target lesion revascularisation was performed in 34 patients (10%). An angiographic follow-up was available for 261 patients (76%). Restenosis (> 50% diameter Stenosis) was found in 21%. The results show, that ultrasound guidance of balloon angioplasty provides a means to achieve a large initial luminal gain without the routine use of stents. The acute and long-term results suggest that the approach is safe and efficient. The data compare favorably with similar studies using advanced intravascular diagnostic tools to guide the angioplasty procedure.

Vorteile des Einsatzes des intravasalen Ultraschalls bei der perkutanen transluminalen Koronarangiographie

Neuere klinische Studien zeigen, daß durch die intrakoronare Implantation eines Stents die Restenoserate gesenkt werden kann. Dieser Effekt wird als das Ergebnis eines höheren Lumengewinns durch die Stentimplantation im Vergleich zur perkutanen transluminalen koronaren Angioplastie (PTCA) verstanden. Unsere Studie basiert auf der Annahme, daß eine durch intravasalen Ultraschall (IVUS) gesteuerte und an den äußeren Gefäßdurchmessder angepaßte PTCA zu ähnlich guten Langzeitergebnissen führen kann wie die Implantation eines Stents. Ziel der vorliegenden Untersuchung war es zu prüfen, ob 1. eine IVUS-gesteuerte PTCA mit einem vertretbaren Risiko durchführbar ist und 2. die Rate der klinischen Ereignisse und der angiographischen Restenoserate reduziert werden kann. Von April ’95 bis März ’96 wurde bei 107 Patienten mit 108 nativen koronaren Läsionen eine präinterventionelle intravaskuläre Ultraschalluntersuchung zur Bestimmung der Gefäßdiameter durchgeführt. Aufgrund der On-line-Registrierung des äußeren Gefäßdiameters (maximale Distanz Adventitia/Adventitia) erfolgte die Wahl der Ballondilatationskatheter, deren mittlerer Ballondiameter bei 4,1±0,5 mm lag. Der Erfolg der Intervention wurde angiographisch und mittels intravaskulärem Ultraschall überprüft. Als erfolgreich wurde eine Intervention dann bewertet, wenn angiographisch eine Restenose von <30% vorlag und im intravaskulären Ultraschall eine Lumenerweiterung >30% ohne Reduktion des antegraden Flusses erreicht wurde. Im Rahmen der Intervention verstarb ein Patient nach dem erfolglosen Versuch einer operativen Revaskularisation, ein weiterer wurde erfolgreich operiert. Im Langzeitverlauf (12±5 Mon.) erlitten 11 Patienten ein kardiales Ereignis im Zielgefäß. Ein Kontrollangiogramm wurde bei 83 Patienten durchgeführt und zeigte eine Rezidivstenose (NHLBI Krit. 5 >50%) in 17 Zielgefäßen (21%). Die ultraschallgesteuerte Ballonangioplastie von Koronarstenosen ist sicher und effektiv: Eine Restenoserate von 21% ist gering. Eine randomisierte Studie zur Bestätigung dieser Ergebnisse ist erforderlicb. Recent randomized clinical trials reported a reduction of restenosis using intracoronary stents and suggested that this restenosis reduction is a result of the higher immediate luminal gain in comparison to conventional percutaneous transluminal coronary angioplasty (PTCA). The hypothesis of this sutdy is based on the assumption that IVUS guided PTCA leads to equivalent long term PTCA results as compared to PTCA and the additional placement of a stent. Thus, the purpose of this non-randomized single center study was to evaluate (1) the safety and efficacy and (2) the long term outcome of vessel size adapted PTCA in patients with native coronary lesions. From April 1995 to March 1996 the morphological dimensions of the target lesions were determined in 107 patients with 108 lesions by intravascular ultrasound prior to conventional balloon angioplasty. Quantitative parameters of the vascular dimensions were assessed on-line and the diameter of the balloon catheter was adapted to the external elastic membrane (EEM) at the lesion site minus 10%. Using this strategy, mean balloon diameter was 4.1±0.5 mm. Acute and one year clinical follow-up results were obtained in all 107 patients. Angiographic success was defined as a final percent diameter stenosis of <30%. The following criteria determined by postinterventional IVUS were also used to define a successful PTCA: luminal CSA gain of >30% with an angiographically patent flow (TIMI 3). Acute events occurred in two patients (one death and one successful acute surgical revascularisation). During one year follow-up, 11 patients had a clinical event including death, Q-wave MI, surgical revascularization, and repeat PTCA. In 83 patients (78%), control angiography was performed and revealed an angiographic restenosis rate of 21% using the NHLBI criterion of a diameter stenosis >50%. Conclusion: The use of balloon diameters following these measurements is safe in the acute setting with a low number of in hospital events and effective in reducing clinical events as well as angiographic restenosis rates during one year follow-up. These promising results warrant vertification in larger scale randomized trials.

Acute vessel closure following excimer laser coronary angioplasty: can we predict it?

SummaryOf 124 consecutive patients undergoing elective excimer laser coronary angioplasty, 33 (26%) had periprocedural occlusion following excimer laser irradiation. Successful management (reopened vessel, no death, no myocardial infarction, no emergency bypass surgery) including repeat lasing, subsequent percutaneous transluminal coronary angioplasty, use of intracoronary nitroglycerin or streptokinase was achieved in 32 of the patients with acute occlusion following excimer laser coronary angioplasty. In one patient a nonfatal anterior myocardial infarction occurred. A late event occurred in two patients despite patency at the control angiography 24 h later. Multiple logistic regression modeling was used to examine the relationship between various characteristics and the risk of acute vessel closure. The preprocedural and procedural variables analyzed included progressive spasm prior to occlusion and lesion morphology after intervention (angiography complications after percutaneous transluminal coronary angioplasty were prospectively divided into class 0, no complication, and classes 1–3, according to purely descriptive morphological characteristics). These showed a multivariate correlation with acute occlusion during excimer laser coronary angioplasty. These results suggest that acute vessel closure during stand-alone excimer laser coronary angioplasty is a benign but unpredictable event.