[Role of imaging in cardiac resynchronization therapy]. / Rolle der Bildgebung bei der kardialen Resynchronisationstherapie.

Several multicenter randomized clinical trials have established cardiac resynchronization as a safe and effective way to treat heart failure patients. This is reflected in the Focus Update of the European guidelines that describes a class IA indication in patients with NYHA class II-IV heart failure with LVEF≤35% and QRS≥120 ms (NYHA III/IV) or ≥150 ms (NYHA II). If applied in clinical practice, this patient selection results in ineffective treatment in about one third of patients implanted. Since the pathophysiological basis of the disease, a disorganized electromechanical function in patients with left bundle branch block (LBBB), is amenable to analysis with imaging methods, imaging has always played an important role in patient selection. None of the parameters used proved to be reliable for the prediction of cardiac resynchronization therapy success in the multicenter PROSPECT trial. Following the publication of PROSPECT in 2008, several new studies using echocardiography and cardiac magnetic resonance imaging were published. New publications are evaluated and analyzed in the context of earlier ones.

[Role of right heart failure in cardiac resynchronization]. / Rolle der Rechtsherzinsuffizienz im Rahmen der kardialen Resynchronisationstherapie.

During recent years cardiac resynchronization has become an important tool in the treatment of patients with signs and symptoms of heart failure and desynchronized contraction of the left ventricle. Among patients with heart failure, right ventricular involvement can occur because the underlying disease affects both ventricles or because the reduction of left ventricular function impairs the right ventricular function by altered coupling and increased right ventricular afterload. Irrespective of the underlying cause the reduction of right ventricular function confers an adverse prognosis that is further aggravated by the presence of pulmonary hypertension. The present article describes the relevance of reduced right ventricular function for the clinical syndrome of heart failure, the role of right ventricular resynchronization in patients with predominant right heart failure and the possible effects of left ventricular resynchronization on a preexisting impairment of right ventricular function.

[Is standard-echocardiography sufficient for identification of responders?]. / Reicht die Standard-Echokardiographie zur Identifizierung von Respondern aus?

During recent years cardiac re-synchronization has become an important tool in the treatment of patients with signs and symptoms of heart failure and de-synchronized contraction of the heart. This article describes the pathophysiological basis of de-synchronized contraction due to left bundle branch block and the use of conventional echocardiography to unmask whether the electrical abnormality is accompanied by an asynchronous contraction in the individual patient. The altered contraction in the de-synchronized heart is analysed on different levels: atrioventricular dyssynchrony describes the disturbed mechanical coupling of the ventricles and atria, interventricular dyssynchrony describes the disturbed mechanical coupling of the left and right ventricle, and intraventricular dyssynchrony describes the uncoordinated contraction of the left ventricle. Since tissue Doppler imaging is implemented only in the top level echo machines of the respective manufacturers, this article uses parameters derived from standard echo techniques to analyse the different aspects of dyssynchrony.

Primary fibrosarcoma of the liver infiltrating the right atrium of the heart.

A rare case of a primary fibrosarcoma of the liver infiltrating the right heart is described in a 72-year-old woman. The patient presented with a history of progressive dyspnea and ascites and her general condition was poor. Preoperative cardiac magnetic resonance (CMR) imaging revealed a large mass, which originated from the liver and had infiltrated the right atrium via the inferior vena cava. The patient underwent tumor resection yet died shortly afterwards. Histologically the mass was classified as a fibrosarcoma with positive immunostaining for vimentin. We report the CMR imaging characteristics in this uncommon case. Preoperative CMR proved to be useful for clinical decision making and the planning of surgery.

Determinants of myocardial response in CMR perfusion imaging using Gd-BOPTA (Multihance).

PURPOSE: Different centers and vendors use different sequences and contrast agent application schemes for MR myocardial perfusion imaging. The purpose of this study was to evaluate the role of different sequences, dosages, and injection speeds of contrast media for semiquantitative MR-perfusion assessment. METHODS: In a pilot study with 58 consecutive patients three of the most commonly used sequences for MR myocardial perfusion imaging (T1-GrE, GrE-EPI or SSFP) were compared to each other in terms of peak myocardial enhancement and image quality. For the main part of the study dynamic first pass MR perfusion imaging (Philips Intera CV, Best, Tthe Netherlands) was performed in 24 patients using the most favorable sequence from the pilot study (SSFP) after peripheral i.v. administration of Gd-BOPTA during adenosine stress. Two doses (0.05 mmol/kg bw and 0.025 mmol/kg bw) and four different injection speeds (8, 4, 3, 2 ml/s) were used. Signal intensity time curves were determined in the LV and myocardial segments supplied by normal coronary arteries and correlation between LV and myocardial upslope as well as peak enhancement were noted. RESULTS: The SSFP-sequence showed a higher peak enhancement when using 0.05 mmol/kg bw of Gd-BOPTA and a superior image quality for both dosage regimen compared with the other sequences and was consequently applied for the main study. A significant correlation was found between the upslopes in the LV and the myocardium (r square = 0.85, p < 0.001). However, LV and myocardial upslopes were largely independent of the dosage. Myocardial upslope was significantly slower at an injection rate of 2 ml/s compared to 3 and 4 ml/s. Higher Gd-doses led to significantly higher enhancement (p < 0.001). CONCLUSION: In healthy myocardial segments, the myocardial upslope is mainly determined from the LV upslope. Both myocardial enhancement and upslope are largely independent from the injection rate of a contrast agent bolus as long as the injection speed is not below 3 ml/s. Myocardial enhancement, however, is dose dependent. Thus, a simple correction for LV upslope allows to normalize a wide variety of input parameters. Differences of myocardial upslope or peak signal intensity after correction should be mainly dependent on blood flow.

[Is the implantation of titanium stems in hip prostheses really obsolete?]. / Ist die Implantation von Titan-Schäften in der Hüftendoprothetik wirklich obsolet?

AIM: Due to several bad results of studies, titanium is no longer used as an implant material in cemented total hip arthroplasty. This study attempts figure out by means of a meta-analysis if the material titanium itself was responsible for the bad results of some studies or if specific implant characteristics contributed to implant failure, independent of titanium. METHOD: Studies between 1960 and July 2002 were analysed concerning failure rates of cemented titanium total hip arthroplasties regarding their specific implant characteristics. RESULTS: Specific implant characteristics such as roughness of the surface and geometrical features led to significantly different failure rates. Stems of titanium with a dull surface and a wide proximal geometry could achieve such good results as those of the cobalt-chromium stems published in the study results of Malchau. CONCLUSION: Titanium is justified as a cementable material in total hip arthroplasty. By respecting specific implant characteristics, very good failure rates can be achieved. The high failure rates, published in several studies, are based upon implant characteristics which are not suitable for cementing techniques and not upon the implant material titanium itself.

Comparison of dobutamine stress magnetic resonance, adenosine stress magnetic resonance, and adenosine stress magnetic resonance perfusion.

BACKGROUND: Dobutamine stress MR (DSMR) is highly accurate for the detection of inducible wall motion abnormalities (IWMAs). Adenosine has a more favorable safety profile and is well established for the assessment of myocardial perfusion. We evaluated the diagnostic value of IWMAs during dobutamine and adenosine stress MR and adenosine MR perfusion compared with invasive coronary angiography. METHODS AND RESULTS: Seventy-nine consecutive patients (suspected or known coronary disease, no history of prior myocardial infarction) scheduled for cardiac catheterization underwent cardiac MR (1.5 T). After 4 minutes of adenosine infusion (140 microg x kg(-1) x min(-1) for 6 minutes), wall motion was assessed (steady-state free precession), and subsequently perfusion scans (3-slice turbo field echo-echo planar imaging; 0.05 mmol/kg Gd-BOPTA) were performed. After a 15-minute break, rest perfusion was imaged, followed by standard DSMR/atropine stress MR. Wall motion was classified as pathological if > or =1 segment showed IWMAs. The transmural extent of inducible perfusion deficits (<25%, 25% to 50%, 51% to 75%, and >75%) was used to grade segmental perfusion. Quantitative coronary angiography was performed with significant stenosis defined as >50% diameter stenosis. Fifty-three patients (67%) had coronary artery stenoses >50%; sensitivity and specificity for detection by dobutamine and adenosine stress and adenosine perfusion were 89% and 80%, 40% and 96%, and 91% and 62%, respectively. Adenosine IWMAs were seen only in segments with >75% transmural perfusion deficit. CONCLUSIONS: DSMR is superior to adenosine stress for the induction of IWMAs in patients with significant coronary artery disease. Visual assessment of adenosine stress perfusion is sensitive with a low specificity, whereas adenosine stress MR wall motion is highly specific because it identifies only patients with high-grade perfusion deficits. Thus, DSMR is the method of choice for current state-of-the-art treatment regimens to detect ischemia in patients with suspected or known coronary artery disease but no history of prior myocardial infarction.

[The cement-free modular revision prosthesis MRP-hip revision stem prosthesis in clinical follow-up]. / Die zementfreie modulare MRP-Hüftrevisionsschaftendoprothese im "klinischen Follow-up"

INTRODUCTION: We present prospective medium-term results of the modular revision prostheses "MRP-TITANIUM". MATERIAL AND METHODS: 45 patients (n = 48 prostheses) were evaluated. The mean follow-up was 4.7 years (min.-max.: 1.0-9.0 years). Pre- and postoperatively the Harris hip score (differentiated to Paprosky I-III) was examined. 66.67 % of the cases had extensive bony defects (> or = Paprosky II b). By means of X-ray examinations, the stability of the prostheses, periprosthetic bone remodelling, the presence of radiolucent lines as well as bone defect regeneration were assessed postoperatively. RESULTS: The mean Harris hip score improved from 25.6 preoperative to 71.4 postoperative (p < or = 0.05). In 44 cases the X-ray showed stable fixation without secondary migration. In one case the stem (stand time 2.36 years) was revised due to secondary migration (> or = 5 mm). The survival rate (Kaplan-Meier) was 97 %. Bone transplantation with consecutive defect regeneration was (n = 30) complete in all cases. In six cases (12.5 %) a postoperative dislocation occurred with subsequent successful closed reposition four times (8.3 %). In two cases (4.2 %) an open reposition was done with correction of the antetorsion angle of the prostheses. CONCLUSION: The "MRP-TITANIUM modular revision prostheses" has proved to be reliable in cases of revision surgery with extensive bony defects. The failure rate was 2.1 % for 48 prospectively examined prostheses.

Calculation of individual cardiovascular risk in a primary prevention setting shows a high number of patients with a high risk score.

On occasion of the annual convention of the European Society of Cardiology, general awareness was used to stage an event to inform the public about cardiovascular risk and cardiovascular disease. After the measurement of blood pressure, HDL and total cholesterol and after answering questions on smoking and medication visitors received a printout showing their individual calculated cardiovascular event rate over the next ten years. For the calculation of the expected event rate, the algorithm of the Adult Treatment Panel III was used. Of the 43,500 visitors 1513 were screened, 651 male, 862 female. Of those screened in this primary prevention setting 143 male (22.07%) and 9 female (1.02%) had an expected cardiovascular event rate of 20% or more over the next ten years requiring immediate action according to the current guidelines. The calculated risk scores are considerably lower than would be expected in a representative sample from the population. This indicates that patients with a high cardiovascular risk possibly do not take part in unstructured primary screening events.

[[F-18]-fluorodeoxyglucose (FDG) positron emission tomography (PET) as a diagnostic for hip endoprosthesis loosening]. / Die [F-18]-Fluorodeoxyglucose (FDG) Positronenemissionstomographie (PET) als Differenzialdiagnostikum der Hüftendoprothesenlockerung.

AIM: The purpose of this study was to examine the FDG-PET in respect of its diagnostic valency with regard to septic/aseptic loosening of lower limb prostheses. METHOD: 28 patients with 41 lower limb prostheses were examined by means of FDG-PET to evaluate septic/aseptic loosening of their hip prostheses. Therefore, a differentiated FDG-PET result interpretation subdivided into five categories was developed. The final diagnosis was based on operative findings with following culture and histological outcome. RESULTS: The worked-out categories showed a high agreement to the intraoperative macroscopic and histological results (n = 23 correctly positive, n = 1 false positive, n = 1 correctly negative and n = 3 false negative). CONCLUSION: With a subtly differentiated interpretation (categories I - V) of the qualitative glucose metabolism safe statements can be made regarding septic/aseptic endoprostheses loosening. This was impressively confirmed by the agreement of the FDG results with the histological results.

[A new coating method for cemented femur shaft implants--biocompatibility, stability during sterlization and adhesive strength]. / Eine neue Beschichtungsmethode für zementierte Femurschaftimplantate--Biokompatibilität, Sterilisierbarkeit und Verbundfestigkeit.

The main cause of aseptic loosening of cemented stems in total hip arthroplasty is the hydrolytic degradation of the metal-cement interface. In order to prevent this debonding a new multilayer method of coating the implant surface involving the use of a silica-/silane technique to create a durable adhesive bond between metal stem and bone cement has been developed. The biocompatibility of all the elements of the multilayer system was confirmed using a human osteoblast cell culture test. For sterilization purposes, gamma irradiation with a 25 kGy effective dose proved to be the method of choice. The proven biocompatibility and successful sterilization of the coated implants are the main prerequisites for in-vivo usage. On the technical side, the bonding effectiveness of the multilayer coating system was demonstrated by the tensile test, which revealed a significant improvement in the adhesive strength of the cement-metal bond under prolonged moist conditions similar to those met with in the human body.

[FDG PET as an early nuclear medical diagnostic tool for aseptic wear-induced loosening of hip joint endoprostheses--a report of two cases]. / Die FDG-PET als frühes nuklearmedizinisches Diagnostikum einer aseptischen durch Abrieb induzierten Hüftendoprothesenlockerung--Zwei Fallberichte.

To date, 2-[F-18]fluoro-2-deoxy-D-glucose PET (FDG PET) is used as a tool in oncology as well as myocardiological and cerebral functional diagnostics in the clinical routine. False positive results of tumor search imply new possibilities for use in diagnostics of inflammation. The two case reports presented here on aseptic loosening of endoprostheses caused by the rub of polyethylene with histological and immunohistological refurbishing call attention to the possible diagnostic valency of FDG PET as an early warning system regarding aseptic artificial limb loosening induced by the rub of polyethylene. By quantification of glucose metabolism with the "standard uptake value" (SUV) as well as specific storage samples from around the artificial limb, it is the aim of our study group in further examinations to develop an algorithm which permits to distinguish between septic and aseptic loosening.

[Technical principles for removal of femoral bone cements in hip prosthesis implant revision]. / Technische Prinzipien zur Entfernung femoralen Knochenzements in der Revisionshüftendoprothetik.

As the removal of femoral bone cement is one of the most challenging tasks in cemented total Hip Revision, a lot of different technical devices have been developed to aid the surgeon. All of their pros and cons are partly consequences of the specific system-design but mainly arise from the basic physical principles used. The known methods and devices as well as their data-handling have therefore been analysed, reduced to their principles according to the criteria of systematic engineering design and systematized in order to provide a better comparability and starting point for the development of new devices.

[Recurrent pigmented villonodular synovitis (PVNS)]. / Rezidiv einer pigmentierten villo-nodulären Synovialitis (PVNS).

AIM: The pigmented vilionodular synovitis (PVNS) is a tumour like disease of unknown origin that often shows recurrence. The pathogenesis is still unknown and therefore the question of the right therapy is not resolved. MATERIAL: With a case report of a patient with recurrence after two arthroscopic synovectomies, PVNS is discussed against the background of the clinical, histological, and radiological features. RESULTS: We performed an open synovectomy and cystic lesions in both condyles of the femur and proximal tibia were filled with homologous and autologous cancellous bone. Three months later the patient had no pain and the bone density in the former cystic lesions was appropriate. DISCUSSION: The pathogenesis is still unknown. Diagnosis often is obtained much too late due to missing specific symptoms. PVNS occurs in local forms as well as in a diffuse growth pattern. Recurrence rates of up to 78% are very high. Besides arthroscopic and open synovectomy, the treatment with radiosynoviorthesis must be considered. Depending on the growth pattern, the tumour masses, and the affected joint, the therapy has to be chosen very carefully and sometimes different forms have to be combined if a recurrence--free result is to be achieved.

Improvement of the long-term adhesive strength between metal stem and polymethylmethacrylate bone cement by a silica/silane interlayer system.

A loss of adhesive strength between metal stem and bone cement is clinically found to be a serious problem in total hip arthroplasty and causes many operative revisions. The objective of this study was to improve the long-term adhesive strength at this interface. A new silica/silane interlayer coating system is introduced. The layers are designed to bond the metal stem surface to the polymethylmethacrylate bone cement marginally leakage free. In vitro tensile tests were performed on specimens of TiAl6V4 and CoCrMo that were cemented by pairs with different bone cements with and without the new coating system. The specimens were stored in isotonic saline solution up to 150 days. The adhesive strength decreased about 75% within 30 days of storage on specimens of both metal alloys that were conventionally cemented without the new interlayer system. With the new coating, the high initial adhesive strength (40-50 MPa) could be stabilized for TiAl6V4 over 150 days. For the same 150-day storage period, the adhesive strength of the coated CoCrMo alloy still decreased but the decrease was only half that experienced by the uncoated CoCrMo. The loss of adhesive strength on CoCrMo specimens could be reduced if the metal surface was activated by a plasma treatment. The new coating interface system could help to considerably reduce revision operations caused by debonding effects at the interface metal/polymethylmethacrylate bone cement.

The apoptotic regulatory protein ARC (apoptosis repressor with caspase recruitment domain) prevents oxidant stress-mediated cell death by preserving mitochondrial function.

ARC is an apoptotic regulatory protein expressed almost exclusively in myogenic cells. It contains a caspase recruitment domain (CARD) through which it has been shown to block the activation of some initiator caspases. Because ARC also blocks caspase-independent events associated with apoptosis, such as hypoxia-induced cytochrome c release, we examined its role in cell death triggered by exposure to hydrogen peroxide (H(2)O(2)) in the myogenic cell line, H9c2. Cell death in this model was caspase-independent and characterized by dose-dependent reduction in ARC expression accompanied by disruption of the mitochondrial membrane potential (Delta psi(m)) and loss of plasma membrane integrity, typical of necrotic cell death. Ectopic expression of ARC prevented both H(2)O(2)-induced mitochondrial dysfunction and cell death without affecting the stress kinase response, suggesting that ARCs protective effects were downstream of early signaling events and not due to quenching of H(2)O(2). ARC was also effective in blocking H(2)O(2)-induced loss of membrane integrity and/or disruption of Delta psi(m) in two human cell lines in which it is not normally expressed. These results demonstrate that, in addition to its ability to block caspase-dependent and -independent events in apoptosis, ARC also prevents necrosis-like cell death via the preservation of mitochondrial function.

Progressive outer retinal necrosis syndrome in a lymphoma patient with good visual outcome.

PURPOSE: To report an HIV-negative lymphoma patient who developed progressive outer retinal necrosis syndrome and who had a good visual outcome after treatment with two-drug antiviral therapy and intravenous immunoglobulin. METHODS: Case report. RESULTS: A 43-year-old man with small lymphocytic lymphoma was diagnosed with progressive outer retinal necrosis in his left eye. Treatment was initiated with intravenous foscarnet and ganciclovir as well as intravenous gammaglobulin at a dose of 0.5 gm/kg per day for 5 days. On the second hospital day he was started on decadron 4 mg orally four times daily. No further posterior retinitis progression was observed despite severe immunosuppression. Visual acuity remained stable at 20/30 with 10 months' follow-up. CONCLUSIONS: The benefit of using gammaglobulin in progressive outer retinal necrosis is unknown. Given the rapid improvement seen in this patient's retinitis, it may be reasonable to consider the use of gammaglobulin in other cases of infectious retinitis in immunocompromised patients.

Apoptosis in cardiac disease--what is it--how does it occur.

This review will present a summary of a description of apoptotic pathways in the heart, followed by ways to measure it and the experimental and clinical evidence for the role of apoptosis in cardiac disease. An evaluation of the effectiveness of pharmacological and other therapeutic interventions in the prevention of apoptosis in the context of cardiac disease will also be presented.

Angiotensin II directly increases transforming growth factor beta1 and osteopontin and indirectly affects collagen mRNA expression in the human heart.

OBJECTIVES: Angiotensin II (Ang II) induces fibroblast proliferation and collagen synthesis in the myocardium, but its precise mechanisms of action in human hearts are still unknown. Therefore, we investigated whether Ang II directly affects the collagen mRNA content in the human myocardium and in isolated human cardiac fibroblasts or whether the growth factors TGFbeta-1 and osteopontin are involved in this process. METHODS AND RESULTS I: In a first set of experiments, the direct effect of Ang II on collagen I, TGFbeta-1 and osteopontin mRNA content in fresh samples of human atrial myocardium was determined by the use of a short stimulation period. After 4 h, Ang II-stimulated atrial samples gave a significantly higher expression of both TGFbeta-1 (183+/-21% of control, p<0.05) and osteopontin mRNA (275+/-58%, p<0.02) than the controls. In contrast, the expression of collagen I mRNA was unchanged (95+/-8%). Stimulation with TGFbeta-1 led to an increase in collagen I and III mRNA (127+/-10%, p<0.05; 140+/-15%, p<0.02). METHODS AND RESULTS II: In a second protocol, to assess the effects of longer stimulation periods, we determined the effects of Ang II and its potential mediator TGFbeta-1 on collagen I, III and fibronectin mRNA expression and on proliferation of cultured human cardiac fibroblasts. Ang II caused a dose-dependent stimulation of proliferation but did not affect collagen I, II or fibronectin mRNA content after 24 h. In contrast, TGFbeta-1 stimulation significantly increased collagen I and III mRNA expression (124+/-5% and 128+/-5%, p<0.002). CONCLUSIONS: In the human heart, Ang II does not directly increase collagen or fibronectin mRNA, but it does increase TGFbeta-1 and osteopontin mRNA expression. Since TGFbeta-1 induces collagen I and III mRNA in atrial samples and in isolated cardiac fibroblasts, it may represent a necessary mediator of the Ang II effects in the human heart.