Predictors of sustained ventricular arrhythmia episodes in patients with primary ICD indication: male gender and AF in primary ICD prophylaxis.

AIMS: Implantable cardioverter-defibrillators (ICD) reduce mortality in patients with severely impaired left ventricular function. In randomized studies, female patients are underrepresented and data on ICD therapy is limited. Atrial fibrillation (AF) is a determinant of poor prognosis but has not been consistently evaluated. We evaluated the risk factors for the occurrence of ventricular arrhythmia episodes in patients with primary ICD prophylaxis. METHODS: Consecutive patients after ICD implantation for primary prophylaxis were followed. During follow-up, detected sustained episodes of ventricular arrhythmia were documented. Multivariate analysis controlled for propensity score was used to evaluate the correlation between gender, history of AF, and the occurrence of ventricular arrhythmia episodes. RESULTS: A total of 400 patients (19.8% female; n = 79) were included. During follow-up, 64 patients (16%) had appropriate ICD therapy episodes. Men (18%) had significantly more often episodes than women (8%; p = 0.025). Patients with a history of AF (102, 25.5%) had significantly more often episodes (30%) compared to patients without a history of AF (11%; p < 0.001). In a multivariate model, only gender (p = 0.02) and history of AF (p < 0.001) were significantly associated predictors of the occurrence of appropriate ICD therapies during follow-up. Based on the propensity score model, the adjusted hazard ratio for male gender was 2.7 (p = 0.02) and 2.6 (p = 0.0004) for history of AF. CONCLUSION: Male gender and history of AF are independent predictors for the occurrence of sustained ventricular arrhythmia in primary ICD prophylaxis. Further studies need to evaluate whether history of AF in female patients might be an indicator for higher risk of sudden cardiac arrhythmic death.

Gender differences in onset of symptoms in AV nodal re-entrant and accessory pathway-mediated re-entrant tachycardia.

PURPOSE: Is onset of symptoms in AV nodal re-entrant tachycardia (AVNRT) and accessory pathway-mediated re-entrant tachycardia (AVRT) patients gender-specific? METHODS: Intra- and inter-gender differences in onset of symptoms and mechanism of supraventricular tachycardia in adult patients undergoing catheter ablation for AVNRT or AVRT (N=230) were documented. RESULTS: Women with AVNRT were significantly younger at onset of symptoms compared to men (38+/-18, 51+/-18 years, p=0.01). Male AVNRT patients were significantly older at onset of symptoms compared to male AVRT patients (51+/-18, 25+/-11 years, p=0.04) but there was no difference in women. Symptoms beginning <30 years in men predicted AVRT in 73%, and beginning >or=30 years the predominant mechanism was AVNRT (85%). In women AVNRT was the most likely mechanism independent of symptom onset (>75%). CONCLUSIONS: Symptoms beginning in patients with AVNRT and AVRT prior to age 30 correlates with a 70% incidence of AVRT in men and a 80% incidence of AVNRT in women. Onset of palpitations >or= age 30 relates to AVNRT in 85% of patients.

[Optimized programming during cardiac resynchronization therapy]. / Optimierte Programmierung der atrio-ventrikulären und ventrikulo-ventrikulären Verzögerungszeiten bei Patienten unter biventrikulärer Stimulation - ein pragmatischer Ansatz.

Cardiac resynchronization (CRT) has evolved as a therapeutic add-on tool in patients with refractory heart failure. Additional pacing of the left ventricle leads to relevant clinical and hemodynamic improvement. Optimized programming of these pacing systems may modulate therapeutic efficacy. Optimal atrio-ventricular (AV) and ventriculo-ventricular (VV) delay programming is documented to increase invasively and non-invasively determined parameters of cardiac hemodynamics. In this manuscript different options for determining optimal AV and VV delay are discussed and a pragmatic approach to optimize CRT programming is detailed. VV delay needs to be optimized as a first step of programming. Different techniques may estimate the individual need for sequential ventricular pacing. Especially electrocardiographic criteria during right and left ventricular pacing may approximate the time-delay for pre-excitation. Delay between aortic and pulmonic valve ejection can be determined using Doppler echocardiography may identify patients who benefit from sequential pacing. Optimizing AV delay is a domain of Doppler echocardiography where using a simple formula the AV delay that produces the best diastolic resynchronization of left atrial contraction and left ventricular ejection can be calculated.Using the above mentioned techniques a pragmatic, easy and fast method for increasing CRT performance can be established. In cases of worsening heart failure or relevant changes of left ventricular dimensions adaptions (re-optimization) of VV and AV delay may be needed.

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

UNLABELLED: 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. METHODS: 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 degrees 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. RESULTS: 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. CONCLUSIONS: 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%).

Human coronary morphology after beta radiation brachytherapy of in-stent restenosis.

This case report discusses the human coronary morphological findings 18 hours after brachytherapy (beta radiation) of an in-stent restenosis. Brachytherapy produced aseptic inflammation of the periadventitial connective tissue integrating the vasa vasorum in the acute phase. The stent neointima eight months after stenting and acutely 18 hours after radiation consisted of the same cellular components as human stent neointima of specimen not additionally treated with radiation. No evidence of necrosis or excessive fibrotic alterations of the arterial vessel wall have been found.

[Intraoperative cooled-tip radiofrequency ablation in patients with atrial fibrillation undergoing open heart surgery]. / Sicherheit und Effektivität der intraoperativen gekühlten linearen Hochfrequenzstromablation bei Patienten mit Vorhofflimmern während eines kardiochirurgischen Eingriffs.

METHODS: A total of 113 patients with chronic permanent (104) or paroxysmal (9) atrial fibrillation underwent open heart surgery plus an additional antiarrhythmic procedure using saline-irrigated cooled-tip radiofrequency ablation (SICTRA) for biatrial or left atrial linear lesions. Ablation was performed with steps of short (5 seconds) ablation around the pulmonary vein ostia and interconnecting lines. Postoperative complications and conversions to sinus rhythm were followed up (mean follow-up duration 17+/-14 months). RESULTS: Of the 113 patients, 16 died during follow-up (day 3 up to 33 months) resulting in a cumulative survival of 79% (2 sudden cardiac deaths, 2 gastrointestinal bleedings, 1 renal bleeding, 2 mediastinitis, 1 endocarditis, 1 hemorrhagic insult, 2 respiratory insufficiencies and 2 unknown). Three patients died between day 3 and 6 (30-day mortality 3%) due to low cardiac output. Complications occurred in 19% of the patients including 4% bleeding, 1% pneumothorax, 3% sternal dehiscence, 3% reversible low cardiac output, 6% reversible respiratory insufficiency, 2% TIAs and 1% intra aortal balloon pump implantation. Conversion to sinus rhythm usually occurred spontaneously within 6 months resulting in a cumulative percentage of 80% in sinus rhythm. In these patients, 85% showed biatrial contraction. CONCLUSIONS: SICTRA to treat atrial fibrillation can safely and effectively be combined with different surgical procedures. Mortality and complication rates are comparable to cardiac surgery without antiarrhythmic procedures. No severe procedure-related complications were noted when a stepwise ablation approach during open heart surgery was used. Antiarrhythmic surgical procedures are highly effective in restoring sinus rhythm in patients with atrial fibrillation. Is a modified approach using intraoperatively cooled-tip radiofrequency ablation to induce linear lesions safe and effective in the treatment of atrial fibrillation in cardiosurgical patients?

Efficacy of an additional MAZE procedure using cooled-tip radiofrequency ablation in patients with chronic atrial fibrillation and mitral valve disease. A randomized, prospective trial.

AIMS: This study is the first prospective randomized trial evaluating the efficacy of an antiarrhythmic surgical procedure in patients with chronic atrial fibrillation undergoing mitral valve replacement. METHODS AND RESULTS: Thirty consecutive patients with chronic atrial fibrillation undergoing mitral valve replacement were randomized for an additional modified MAZE-operation using intra-operatively cooled-tip radiofrequency ablation (group A) or mitral valve replacement alone (group B). Biatrial contraction was studied and functional capacity was evaluated in spiro-ergometry 6 months after surgery. Thirty-day mortality was 0% in both groups. After 12 months, sinus rhythm was reinstituted significantly more often in patients of group A (cumulative rate of sinus rhythm 0.800) compared to patients in group B (0.267) (P<0.01). 66.7% of patients in sinus rhythm of group A had documented biatrial contraction. Electrocardioversion showed long-term success in only 17% of patients in group A and 0% in group B. Maximal aerobic uptake at the 6-month spiro-ergometry revealed no significant difference (9.3 vs 8.5 ml x min(-1) kg(-1), P=0.530). CONCLUSIONS: A modified MAZE operation using cooled-tip radiofrequency ablation can be safely combined with mitral valve surgery and is highly effective in restoring sinus rhythm. Biatrial contraction is found in 66.7% of patients with sinus rhythm undergoing mitral valve replacement plus the MAZE operation.

[Stent-induced changes of coronary morphology--pathologic-anatomic and experimental findings after balloon expansion]. / Stent bedingte Veränderungen der Koronarmorphologie--Pathologisch-anatomische und experimentelle Befunde nach Ballonexpansion.

BACKGROUND: Restenosis after coronary stenting still remains a major limitation of implanted endoluminal endoprostheses. To minimize-device related complications, a better understanding of the mechanisms leading to vessel wall alterations is needed. AIM: To study the morphological effects of coronary stenting in correlation to design changes of the endoprostheses after intraluminal dilation. METHODS: 1) Postmortem analysis of the changes in coronary artery morphology and venous bypass specimens of 35 stents inserted in 27 patients (24 hours up to 4 years after implantation). 2) Standardized postmortem stenting of 20 highly stenosed (> 90% in postmortem selective coronary angiography) and calcified coronary artery segments. Artifact-free microscopical analysis and measurements were performed on cross sections obtained by methylmethacrylate embedding and hard-cut grinding histological preparation. RESULTS: Light microscopy revealed inhomogeneous stent expansion in all artery cross sections resulting in twisted stent filaments. Calcified plaque areas were not deformed by the stent dilation. In eccentric stenoses only over-dilation of the fibrotic plaque segments led to enlargement of the vessel's cross section. Dissections were seen on the edges of atherosclerotic plaques reaching into the arterial medial lamina. Underlying vessel morphology and not implantation pressure determined stent symmetry. Ruptured stent filaments were a seldom but crucial complication of changes in stent design after balloon dilation. CONCLUSIONS: The expansion pattern of coronary stents is determined mostly by the underlying degree of atherosclerotic disease, which is the major factor influencing results of coronary stenting and leading to limiting thrombotic and myofibroblastic stent occlusions.

Ossification in atherosclerotic carotid arteries.

BACKGROUND: Heterotopic ossification as newly formed bone in extraosseous tissue is an uncommon finding in atherosclerotic 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 micro-analysis (EDX) including calcium mapping was performed. RESULTS: Ossification in atherosclerotic 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.

[Minimally invasive percutaneous contrast-ultrasound guided thrombin occlusion of iatrogenic pseudoaneurysm]. / Die perkutane Kontrast-ultraschallgesteuerte Thrombin-Injektion zur minimal-invasiven Therapie des iatrogen entstandenen Pseudoaneurysma.

BACKGROUND: Complicating femoral artery puncture aneurysms may occur resulting in the need for surgical or newer, non- or minimal-invasive therapy: A new minimal-invasive method is the percutaneous occlusion injecting bovine thrombin. The high thrombogenous potential of thrombin bears the risk of iatrogenic artery occlusion by artificial intravascular instillation. AIM: Is the contrast-ultrasound guided thrombin injection safe and effective in occluding femoral aneurysms? METHODS: During 1/99 to 12/00, 33 femoral artery aneurysms as a complication coronary catheterization were diagnosed. In 32 patients the aneurysm (mean dimensions 32 x 35 x 24 mm) was punctured during ultrasound guidance. By injecting ultrasound contrast medium, the flow pattern perfusing the aneurysm was documented. In the canula position where no contrast medium exited the aneurysm thrombin was injected. RESULTS: Complete occlusion of the aneurysm was achieved in 96.9% (31 out of 32) of the patients by contrast-ultrasound guided thrombin occlusion. Follow-up for up to 3 months after the procedure revealed complete occlusion and no clinical or sonographical complications. In one case, a large aneurysm (50 mm x 62 mm x 27 mm) had already led to skin alterations and was only partly occluded by thrombin injection. CONCLUSIONS: Contrast-ultrasound guided thrombin occlusion of femoral artery aneurysms is safe and highly effective.

Coronary morphologic findings after stent implantation.

Clinical studies demonstrated a reduction of acute complications by high-pressure stenting. This study was performed to correlate the histomorphologic changes of the vessel wall after coronary stenting with stent expansion pressure. We studied the effects of intravital and postmortem stenting on coronary morphology in human hearts. Artifact-free analysis and morphometry of the artery segments' cross section was performed after plastic resin embedding and cutting and grinding sectioning. By comparing intra- and postmortem findings we demonstrated that postmortem stent implantation can serve as an adequate model to study the mechanical effects of coronary stenting. A consistent histologic feature was eccentric stent expansion. Larger calcified areas of the vessel wall were not deformed by implanted stents. The highest degree of vessel injury and deformation was apparent in anatomically "nondiseased" or only slightly fibrotic parts of the arterial wall. Dissections were predominantly located directly adjacent to calcified plaques and appeared as "half-moon"-like tears reaching into the arterial media. A statistically significant stent lumen gain was found when the implantation pressure was increased up to 15 atm. Stent symmetry was not influenced by the applied implantation pressure but depended mostly on local coronary morphology. Thus, increasing implantation pressures during coronary stenting seemed to improve the stenting result up to 15 atm. When applying histomorphologic criteria, the higher pressures (>15 atm) did not cause further optimization of stent expansion. Morphometric analysis of stents implanted postmortemly and intravitally revealed comparable results. Postmortem stenting seems to be an appropriate model for studying stent expansion and stenting results in human coronary arteries.

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 lesions 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 estrogens.

[Scanning electron microscopic analysis of vessel wall reactions after coronary stenting]. / Rasterelektronenmikroskopische Analyse der reaktiven und reparativen Veränderungen humaner Koronararterien nach Stentimplantation.

High restenosis rates are still a major factor limiting the use of minimal invasive coronary stenting. Tissue reactions to the implanted alloplastic endoprostheses are still barely understood. 18 coronary artery segments 32 hours up to 340 days after stent implantation of 16 patients were post-mortem investigated. The pathomorphological findings of the vessel wall after stent insertion were studied by scanning electron microscopy (SEM). Stent integration can be divided with intraindividual differences in three phases: In the acute phase (<6 weeks) the border between vascular lumen and arterial wall is constituted by a thin, multi-layered thrombus. During the time course of integration, increasing amounts of Smooth Muscle Cells (SMC) and extracellular matrix can be detected. No endothelial cells can be found in the implantation zone. In the intermediate phase (6 weeks to 12 weeks) the neointima consists of extracellular matrix and increasing numbers of SMC. The borderline between lumen and neointima is generated by SMC and extracellular matrix. Increasing amounts of endothelial cells are found on the luminal surface of the stent neointima. Complete reendothelization is first noted in the chronic phase three months after stenting. Matrix structures are increasing whereas the amount of SMC decreases. In all phases of stent incorporation, the alloplastic stent material is covered by a thin (few nanometer) proteinaceous layer.

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.

[Structural analysis of 16 different coronary stent systems]. / Strukturanalyse von 16 verschiedenen Koronarstentsystemen.

Parallel with the increasing number of coronary stent implantation procedures, new or more elaborate coronary stents were introduced into clinical use almost every month in 1996. We have studied the architecture, surface-morphology, and shape-conversion of 16 different coronary stent systems. The objective of our study was to detect possible specific design and surface features which might influence the healing process in stent restenosis and stent thrombosis. Using electron microscopy we found ultrasmooth surfaces on 5 stents. All other coronary stents revealed individually varying and partly sharp-edged surface irregularities. Video-based morphometry showed covering between 8.3% and 26.4%. Stent shortening after in-vitro expansion ranged from 0% up to 10.5% of the initial stent length. In some stent systems balloon dilation lead to over-expansion of the stent margin. This over-expansion amounted up to 20% of the balloon diameter and the stents revealed a rather biconcave than homogeneous expansion pattern. This phenomenon was also found after postmortal stent implantation in 20 autopsied hearts.