Peter Grewe

Acute and chronic tissue response to coronary stent implantation: pathologic findings in human specimen.

OBJECTIVES The aim of our study was to analyze the cellular components of neointimal tissue regeneration after coronary stenting. BACKGROUND High restenosis rates are a major limiting factor of coronary stenting. To reduce the occurrence of restenoses, more insights into the mechanisms leading to proliferation and expression of extracellular matrix are necessary. METHODS Twenty-one autopsy cases with coronary stents implanted 25 h to 340 days before death were studied. The stented vessel segments were analyzed postmortem by light microscopy and immunohistochemical staining. RESULTS In the initial phase stents are covered by a thin multilayered thrombus. Alpha-actin-positive smooth muscle cells (SMCs) are found as the main cellular component of the neointimal tissue. Later (>6 weeks) extracellular matrix increases and fewer SMCs can be found. In every phase the SMC layers are loosely infiltrated by inflammatory cells (T lymphocytes). In the early postinterventional phase all endothelial cells are destroyed. The borderline between the vessel lumen and the vascular wall is constituted by a thin, membranous thrombus. Six weeks after stenting, SMCs form the vessel surface. Complete reendothelialization is first found 12 weeks after stenting. CONCLUSIONS Stent integration is a multifactorally triggered process with proliferating SMCs generating regenerative tissue. In the early phase predominantly thrombotic material can be observed at the site of stenting, followed by the invasion of SMCs, T lymphocytes and macrophages. The incidence of delayed reendothelializations and the occurrence of deep dissections may be associated with excessive SMC hyperplasia.

Saline-irrigated, cooled-tip radiofrequency ablation is an effective technique to perform the maze procedure.

BACKGROUND We evaluated the effectiveness of the saline-irrigated-cooled-tip-radiofrequency ablation (SICTRA) to produce linear intraatrial lesions. METHODS Thirty patients with chronic atrial fibrillation and mitral valve disease were consecutively randomized to have mitral valve operation either with a Maze procedure (group A) or without (group B). Intraatrial linear lesions were made with an SICTRA catheter (20 to 32 W; 200 to 320 mL/h saline). An echocardiography and 24-hour electrocardiogram were obtained 12 months postoperatively. RESULTS The cumulative frequencies of sinus rhythm in group A and B were 0.80 and 0.27 (p < 0.01). Restored biatrial contraction was present in 66.7% (6 of 9) of the group A patients in sinus rhythm. One patient from each group received a permanent pacemaker because of bradycardia. A fatal renal bleeding and mediastinitis occurred in 2 group A patients, 6 weeks postoperatively. One group A patient had sudden cardiac death at home, 4 months after operation. One patient from each group had lethal respiratory failure, 7 and 10 months after operation. Survival after 12 months for group A and B was 73% and 93% (p = 0.131). CONCLUSIONS The SICTRA appeared to be an effective technique to perform the Maze procedure.

Left atrial versus bi-atrial maze operation using intraoperatively cooled-tip radiofrequency ablation in patients undergoing open-heart surgery: Safety and efficacy

OBJECTIVES We sought to determine whether limited left atrial Maze surgery encircling each of the pulmonary veins, using cooled-tip radiofrequency (RF) ablation, is as effective as the bi-atrial approach? BACKGROUND The original Cox/Maze operation effectively restores sinus rhythm (SR) in patients with atrial fibrillation (AF). Ablation procedures aimed at eliminating pulmonary vein foci have produced promising short-term success. METHODS This was a prospective analysis of patients with chronic AF undergoing open-heart surgery in addition to the Maze operation, using intraoperatively cooled-tip RF ablation either in the left atrium alone (group A) or in both atria (group B). RESULTS Patients in group A (n = 21) and group B (n = 49) did not differ in terms of their baseline characteristics. Concomitant open-heart surgical procedures included mitral valve replacement (3 vs. 25), mitral valve plasty (0 vs. 2), mitral and aortic valve replacement (1 vs. 1), aortic valve replacement (4 vs. 6) and coronary artery bypass grafting (13 vs. 15) in groups A and B, respectively. Follow-up ranged from 1 to 50 months. The overall cumulative rates of SR were 82% in group A and 75% in group B, without a statistically significant difference (p = 0.571). Bi-atrial contraction was revealed in 92.3% of patients in SR in group A and in 79.2% in group B. The cumulative survival rates were 90.5% in group A and 77.9% in group B (p = 0.880). CONCLUSIONS A left or bi-atrial Maze operation using intraoperatively cooled-tip RF ablation can safely be combined with open-heart surgery. A left atrial Maze procedure seems to be as effective as the bi-atrial procedure and restores SR in 82% of patients.

SEGMENTATION OF 3D INTRAVASCULAR ULTRASONIC IMAGES BASED ON A RANDOM FIELD MODEL

Segmentation of intravascular ultrasound images provides important information about the degree of vessel obstruction as well as about the shape and size of plaques. To address the problems of inter- and intra-observer variances associated with conventional manual tracing, a fully automated segmentation was developed. The algorithm is based on the optimisation of a maximum a posteriori estimator, implementing the Rayleigh distribution of speckle and a priori information about the contours. Within 3D image sets, additional information by the blood flow resulting in a decorrelation of the pixels within the luminal boundary is used to initialise the segmentation. To accelerate the estimation, dynamic programming was used. The segmentation algorithm was realised as a Windows 95 application on a Pentium II/233 MHz and delivered reliable and reproducible results independent of the catheter position and the total image brightness (except overflow). In contrast, contours drawn by two physicians for an evaluation of 29 clinical cases showed large intra- and inter-observer variances. In vivo images were acquired with a 20 MHz transducer array (EndoSonics InVision). Comparison with the contours drawn by the physicians and histology demonstrates the potential of the segmentation algorithm.

Catheter Ablation of Electrical Storm in a Collaborative Hospital Network

An electrical storm (ES) is defined as multiple ventricular arrhythmia episodes leading to implantable cardioverter defibrillator interventions. Although conventional rhythm stabilization might be of help acutely, ES involves high mortality and morbidity. We evaluated the effect of catheter ablation strategies in the setting of an interhospital collaborative network on the recurrence of ventricular arrhythmia episodes and mortality in patients with ES. Consecutive patients presenting for invasive treatment of ES from December 2007 to December 2009 were included. All patients underwent catheter ablation of ventricular arrhythmia. The strategies were adapted to the individual cardiac pathologic features. The follow-up examination constituted periodic implantable cardioverter defibrillator interrogation. A total of 32 patients were included. Of the 32 patients, 29 (91%) had monomorphic ventricular tachycardia and 3 ventricular fibrillation. The mean number of implantable cardioverter defibrillator-treated episodes within 7 days before ablation was 16 ± 11. Of the 32 patients, 27 underwent ablation within 24 hours after admission, and 5 underwent acute ablation within 8 hours. In 3 patients, epicardial ablation was performed. In all but 2 patients (6%), the clinical arrhythmia was successfully ablated. During a median follow-up of 15 months, 10 patients (31%) had recurrences of sustained ventricular arrhythmia, including 2 patients (6%) with recurrent ES. Three patients (9%) died during the follow-up period. In conclusion, catheter ablation effectively suppressed ventricular arrhythmia midterm recurrences in patients presenting with ES. Catheter ablation is complex in these severely sick patients. The recurrence rate of ventricular arrhythmia appears to be 31% and the mortality rate to be 9%. Collaborative hospital networks to increase the prompt availability of ES ablation might help to optimize the ES outcome.

Substrate-modification using electroanatomical mapping in sinus rhythm to treat ventricular tachycardia in patients with ischemic cardiomyopathy.

Ventrikuläre Tachykardien (VT) bei Patienten mit ischämischer Kardiomyopathie (KHK) sind mittels konventioneller Katheterablation häufig nur schwer behandelbar. Bei 25 konsekutiven Patienten mit häufigen symptomatischen medikamenten-refraktären VTs (rezidivierende Schockabgaben des ICD) auf dem Boden einer KHK (EF 37±12%) wurde ein linksventrikuläres (LV) elektroanatomisches Narbenmapping (Biosense Webster CARTO™) durchgeführt. Narbengewebe wurde als bipolare Voltage <0.5mV definiert. Vor Ablation wurde mittels Ventrikelstimulation die Anzahl der induzierbaren monomorphen VTs dokumentiert. Die grobe Lokalisation der Zielregion erfolgte mittels „pace-mapping“ und lineare Katheterablationen (8 mm Katheterspitze, 70 Watt, 70 °C) wurden basierend auf den zugrundeliegenden Narbenarealen in einer vermuteten Isthmus-Region durchgeführt. Der Follow-Up erfolgte klinisch sowie mittels ICD-Holter-Aufzeichnungen und EKG- und Langzeit-EKG-Untersuchungen. Im Mittel ließen sich pro Patient 2,4±0,8 unterschiedliche VT-Morphologien induzieren. Die klinische VT konnte in 23/25 (92%) durch lineare Ablation eliminiert werden. Bei 16/23 Patienten (70%) konnten durch Ablation (1,7(±1,0) Ablationslinien pro Patient) alle vorher auslösbaren VTs eliminiert werden (Kompletterfolg). Bei den restlichen 7 Patienten (30%) ließen sich nach erfolgreicher Ablation der klinischen VT weitere VTs auslösen, welche nicht abladiert werden konnten (Teilerfolg). Es traten keine Prozedur-bezogenen Komplikationen auf. Während des Follow-up (10±4 Monate; 3 bis 18) traten bei 4 Patienten (16%) (3 Patienten mit initialem Teilerfolg und 1 Patient mit komplettem Ablationserfolg) neue VTs auf (Zykluslänge kürzer als die klinisch, abladierte VT). Während es keinen Unterschied in Basis-Parametern der Patienten mit Kompletterfolg verglichen mit Patienten mit Teilerfolg gab zeigte sich ein statistisch signifikanter Unterschied bezogen auf die mittelfristige Ryhthmuserfolgsrate (93 vs. 48% Arrhythmiefreiheit, p=0.03). Ischämische VTs können sicher und mit einer Effektivität von über 90% basierend auf elektroanatomischem Narbenmapping während Sinusrhythmus linear abladiert werden. Bei 70% der Patienten können so durch lineare Ablation zwischen elektrisch stummen Hindernissen alle induzierbaren VTs mit hohem mittelfristigem Erfolg abladiert werden. Bei Patienten mit nur Teil-Ablationserfolg (nach Ablation weiterhin VTs auslösbar) traten in über 50% neue VTs während der mittelfristigen Nachsorge (2 bis 6 Monate) auf. The treatment especially of frequent ischemic VT remains a challenge for medical and catheter ablation procedures. We evaluated the efficacy of a substrate-based procedure to eliminate clinical VTs in this patient collective. In 25 consecutive patients (ejection fraction 37±12%) with frequent symptomatic medically refractory ischemic VT (with recurrent ICD-shocks), left ventricular anatomic scar mapping (Biosense Webster CARTO™) was performed in order to modify the underlying myocardial substrate. Scar tissue was identified as having bipolar voltages <0.5 mV. Prior to the procedure an electrophysiological study (EPS) to determine number and morphology of inducible VTs was performed. Linear ablation procedures (8 mm tip, 70 Watts, 70 °C) were based on the findings of scar areas and proximity to anatomic obstacles. Correct location of ablation was documented by similarity of the morphology during pace-mapping. Follow-up included clinical evaluation, ICD holter interrogation plus holter ECG recording. The clinical VT was eliminated by linear catheter ablation in 23/25 patients (92%) (failure due to unstable catheter position during transaortic approach in 1 and epicardial origin of VT in 1). In 16/23 patients (70%) complete success could be produced with no VT inducible after substrate modification (1.7±1.0 lines per patient). In 7 patients (30%) only partial success was documented with further VTs inducible after ablation. No procedure-related complications occurred. During follow- up (10±4 months) 4 patients (16%) had occurrences of new VTs documented on ICD holter (3 patients with initially partial success and 1 with initial complete success) differing in cycle length and morphology from the clinical VT. Comparing patients with complete to those with partial success, there was a statistically significant difference of 93 vs. 48% freedom of arrhythmia (p=0.03). No difference in regard to baseline characteristics existed in these two patient subgroups. Ablation of frequent VTs in patients with ischemic cardiomyopathy can be safely performed using electro-anatomic scar mapping with a high procedural success of 90%. Based on the morphological findings, linear ablation can suppress inducibility of all VTs in 70% of patients with high mid-term efficacy. In patients with only partial ablation success, non-clinical VTs often occur early during follow-up (50%).

Ossification in atherosclerotic carotid arteries.

Background. Heterotopic ossification as newly formed bone in extraosseous tissue is an uncommon finding in ahterosclerotic lesions. The exact mechanisms and development of bone formation in regard to late stage calcified atherosclerosis still remains under debate. Methods. We studied 400 autopsy carotid probes and 306 samples of atherosclerotic carotid endatherectomy. Radiographic analysis and classification of calcification was performed followed by light microscopy. In probes with detected ossifications further analysis using immunohistochemistry, scanning electron microscopy (SEM) and energy dispersive x-ray microanalysis (EDX) including calcium mapping was performed. Results. Ossification in ahterosclerotic carotid arteries was a finding in only a minority of samples (5%) and occurred at sites of large calcific deposits. Histomorphology of bone formation equaled skeletal bone showing osteoblastic cells, osteocytes included in osteoid matrix, bone marrow and osteolytic giant multinucleated cells. Closely related to newly formed bone zones of neovascularization were found. Development of ossification seemed to occur in five stages (lipidous plaque, fibrous cellular plaque, fibrous acellular plaque, calcified plaque and osteogenesis). The environment of sites of ossification was characterized by a varying texture of extracellular fibrous matrix, foam cells, smooth muscle cells, fibroblasts and calcified deposits. Conclusions. Heterotopic ossifications of atherosclerotic plaques seem to be a specific differentiation of fibrous plaques. Components of atherosclerotic lesions like vascular wall cells, neovessels and matrix structures seem to be involved in the process of transformation to mature bone tissue.

Catheter ablation of electrical storm.

Electrical storm (ES) is defined as the occurrence of ≥ three distinct episodes of ventricular arrhythmia (VA) in patients with implanted defibrillators within 24 h. Whereas conventional strategies for acute rhythm stabilization may be effective in some patients the occurrence of ES impairs survival and predicts recurrent VA. Catheter ablation in the setting of ES is complex and involves decisive strategies for individualized ablation approaches adapted to the patient’s cardiac abnormalities. Success rates have been documented to be between 79 and 94% in larger studies and effective ablation improves survival and freedom from any VA. Ablation should be considered early in the treatment plan and availability may be improved by interhospital collaboration with highly experienced VA intervention centers.

Usefulness of a limited linear ablation of post-myocardial infarction ventricular tachycardia using a standardized approach based on sinus rhythm mapping.

The ablation of ventricular tachycardia (VT) can be achieved using anatomically guided approaches using differentiated mapping and ablation techniques. The aim of this study was to evaluate the efficacy of limited linear ablation in the VT exit region identified during sinus rhythm mapping alone. One hundred fifteen consecutive patients presenting for ablation of post-myocardial infarction VT were included. After induction of the target VT during invasive electrophysiology, left ventricular substrate mapping during sinus rhythm to identify scar and border zone on the basis of endocardial bipolar voltage was performed. The exit site of the target VT was regionalized by a simplified vector pace mapping approach and targeted using limited linear ablation within the scar border zone. Seventy-seven percent of all inducible VT was successfully ablated. In 71 patients (62%), no sustained VT was inducible at the end of ablation procedure (complete success). During a median follow-up period of 16 + or - 10 months, 89 patients (77%) had no documented sustained ventricular arrhythmia. Seven patients (2%) had recurrences of the initially ablated VT, and 16 (14%) had new-onset VT. Patients with complete success had a significantly lower number of ventricular arrhythmia reoccurrences than patients with incomplete ablation success (11% vs 37%, p = 0.002). In conclusion, postinfarct VT was effectively ablated in 97% of patients without mapping during ongoing VT using a simplified regional linear ablation approach targeting the scar border zone. Freedom from any ventricular arrhythmia was achieved in 77% of patients during midterm follow-up.

Atherosclerotic carotid arteries--calcification and radio-morphological findings.

Objectives: Are there any predictable factors influencing the process of calcification in carotid arteries? Background: The carotid arteries and especially the carotid bifurcation are one of the predisposed regions of atherosclerotic disease. Whether topography of the carotid sinus, flow patterns or different patient characteristics (e.g., diabetes mellitus, age, sex) are a factor determining calcification of atherosclerotic lesion is still hardly understood. Methods: Morphological and morphometrical analysis including radiographic classification of different degrees of calcification on postmortal carotid arteries (90 men and 19 women) and 306 surgical samples after intramural desobliterations of carotid arteries 202 patients with diabetes, 104 patients without diabetes). Results. Most common localization of radiographically identified calcified deposits are the carotid bulb (76%) especially on the lateral wall opposite the flow divider and the internal carotid artery (55%) especially the proximal 1 cm section. No difference in degree of calcification was found when comparing patients with and without diabetes (intermediate calcification in 59% of patients with diabetes and 50% without diabetes). More female patients with diabetes show calcification when compared to the group of patients without diabetes. Females produce calcification in atherosclerotic carotid lesions at an older age compared to male patients. Conclusions: Calcification is a frequent finding in advanced atherosclerotic carotid lesions. There is no difference in regard to degree, pattern of calcification or age distribution when comparing patients with and without diabetes mellitus. Atherosclerotic lesions more frequently found in female patients with diabetes may be due to less vasoprotection by estrogenes.