Myocardial perfusion scintigraphy in Germany in 2009: utilization and state of the practice.

PURPOSE: Since 2006, the working group Cardiovascular Nuclear Medicine of the German Society of Nuclear Medicine, in cooperation with the working group Nuclear Cardiology of the German Cardiac Society, has been surveying the utilization and technical realization of myocardial perfusion scintigraphy (MPS) in Germany. This paper presents the results of the reporting year 2009. METHODS: A total of 291 centres participated in the inquiry, including 179 private practices (PP), 86 hospitals (HO) and 26 university hospitals (UH). RESULTS: MPS of 98,103 patients were reported. The MPS numbers per million population (pmp) were estimated at 2,360; 76% of the MPS were performed in PP, 17% in HO and 7% in UH. The ratio of MPS to coronary angiography to revascularization was 0.5 to 2.3 to 1. Data from 134 centres which participated in the surveys from 2005 to 2009 showed a decrease in MPS utilization of 2.2%. Nearly half of the MPS were requested by ambulatory care cardiologists. Of all MPS studies, 89% were conducted with (99m)Tc perfusion tracers. Ergometry was the preferred stress test (69%). Adenosine was used in 16%, adenosine + exercise in 7%, dipyridamole in 3%, dipyridamole + exercise in 5% and dobutamine in <1%. Gated single proton emission computed tomography (SPECT) acquisition was performed in 56% of all rest MPS and in 56% of all stress MPS. Both rest and stress MPS were ECG gated in 41%. Only 33% of the centres always performed a quantification of the perfusion studies, whereas 51% did not apply any quantification; 4% of the MPS studies were corrected for attenuation, and 17 centres used transmission sources of 12 CT-based systems. CONCLUSION: A scan activity of 2,380 MPS pmp is in the upper third of the European range. The ratios to coronary angiography and to revascularization suggest that angiography dominates diagnosis and management of coronary artery disease (CAD). The clinical and technical realizations reveal that the predominant goals of further trainings to optimize MPS are in the field of gated SPECT and quantitative perfusion SPECT.

Intracoronary compared with intravenous bolus abciximab application during primary percutaneous coronary intervention: design and rationale of the Abciximab Intracoronary versus intravenously Drug Application in ST-Elevation Myocardial Infarction (AIDA STEMI) trial.

BACKGROUND: Intravenous abciximab reduces major adverse cardiac events in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Intracoronary abciximab bolus application during PCI results in high local drug concentration, improved perfusion, reduction of infarct size, and less microvascular obstruction. The hypothesis of this trial is that abciximab bolus intracoronary in comparison to standard intravenous application will improve the outcome of patients undergoing primary PCI in STEMI. STUDY DESIGN: The Abciximab Intracoronary versus intravenously Drug Application in STEMI (AIDA STEMI) study is a 1,912-patient, prospective, multicenter, randomized, open-label, controlled trial. The study is designed to compare the efficacy and safety of intracoronary versus intravenous bolus abciximab administration during primary PCI with subsequent intravenous infusion for 12 hours. Patients will be randomized in a 1:1 fashion to 1 of the 2 treatments. The primary efficacy end point of AIDA STEMI is the composite of all-cause mortality, recurrent MI, or new congestive heart failure within 90 days of randomization. The primary safety outcome assessment will be major bleeding. CONCLUSIONS: The AIDA STEMI study addresses important questions regarding the efficacy and safety of intracoronary abciximab bolus administration during primary PCI in patients with STEMI, potentially optimizing the route of administration of glycoprotein IIb/IIIa inhibitors in the catheterization laboratory.

Positioning a Novel Transcutaneous Bone Conduction Hearing Implant: a Systematic Anatomical and Radiological Study to Standardize the Retrosigmoid Approach, Correlating Navigation-guided, and Landmark-based Surgery.

HYPOTHESIS: Anatomical and radiological evaluation improves safety and accuracy of the retrosigmoid approach for positioning a transcutaneous bone conduction implant and provides anatomical reference data for standardized, landmark-based implantation at this alternative site. BACKGROUND: The primary implantation site for the floating mass transducer of a novel bone conduction hearing implant is the mastoid. However, anatomical limitations or previous mastoid surgery may prevent mastoid implantation. Therefore, the retrosigmoid approach has been introduced as an alternative. METHODS: Mastoid and retrosigmoid implantation sites were radiologically identified and evaluated in preoperative computed tomography scans of anatomical head specimens. Navigation-guided implantation was then performed in the retrosigmoid site (n = 20). The optimal retrosigmoid position was determined in relation to both the asterion and the mastoid notch as surgical landmarks in an anatomical coordinate system. RESULTS: Preoperative radiological analysis revealed spatial limitations in the mastoid in 45% of the specimens. Navigation-guided retrosigmoid implantation was possible without affecting the sigmoid sinus in all the specimens. The optimal implantation site was located 1.9 ±â€Š0.1 cm posterior/1.7 ±â€Š0.1 cm inferior to the asterion and 3.3 ±â€Š0.2 cm posterior/2.1 ±â€Š0.1 cm superior to the mastoid notch.Retrosigmoid skull thickness was 6.6 ±â€Š0.4 mm, measured anatomically, 7.0 ±â€Š0.4 mm, measured radiologically and 6.7 ±â€Š0.5 mm, measured with the navigation software. CONCLUSION: The navigation-guided retrosigmoid approach seemed to be a reliable procedure in all the specimens. Measurements of bone thickness revealed the need for spacers in 95% of the specimens. Reference coordinates of the optimal implantation site are provided and can confirm image-guided surgery or facilitate orientation if a navigation system is not available.

[Policy paper nuclear cardiology - update 2018 - Current status of clinical practice]. / Positionspapier Nuklearkardiologie ­ Update 2018.

The joint position paper of the working community "Cardiovascular Nuclear Medicine" of the German Society of Nuclear Medicine (DGN) and the working group "Nuclear Cardiology Diagnostics" of the German Cardiac Society (DKG) updates the former 2009 paper. It is the purpose of this paper to provide an overview about the application fields, the state-of-the-art and the current value of nuclear cardiology imaging. The topics covered are chronic coronary artery disease, including viability imaging, furthermore cardiomyopathies, infective endocarditis, cardiac sarcoidosis and amyloidosis.

Short communication: decreasing soluble CD30 and increasing IFN-gamma plasma levels are indicators of effective highly active antiretroviral therapy.

It was previously reported that without highly active antiretroviral therapy (HAART), secretion of Th1 cytokines and antiviral IFN-gamma in HIV-infected patients is decreased, whereas the production of Th2 cytokines, proinflammatory cytokines, and TNF-alpha is increased. We studied the effect of HAART on Th1-, Th2-, and monocyte-derived cytokines, and on the Th2-type immune response marker soluble (s)CD30 in HIV-1-infected hemophilia patients. Viral Load (VL), CD4+ lymphocyte counts, and plasma levels of sIL-1RA, IL-2, sIL-2R, IL-3, IL-4, IL-6, sIL-6R, IL-7, IL-10, TNF-alpha, TGF-beta2, IFN-gamma, and sCD30 were measured in 18 patients who received HAART. Nine patients were initially treatment-naive and were monitored after the initiation of HAART. sCD30 median levels were significantly higher in treatment-naive patients than in patients who were on HAART (77 vs. 30 U/ml, p = 0.005). A strong association was observed between sCD30 and VL (r = 0.85, p = 0.004). After the initiation of HAART, sCD30 levels decreased and remained low (at 1 year, 38; at 2 years, 41 U/ml; p = 0.012 and p = 0.021, respectively, as compared to baseline level) and this was accompanied by a decrease in VL and monocyte-derived IL-6 and an increase in CD4+ lymphocyte counts and Th1-derived IFN-gamma. One year after the initiation of HAART a strong inverse correlation was observed between IFN-gamma and VL (r = -0.83, p = 0.006). In contrast to sCD30 and IFN-gamma, CD4 counts and plasma IL-6 did not correlate with VL at any time. Our data suggest that decreasing sCD30 and increasing IFN-gamma plasma levels are indicators of effective HAART treatment and CD4 Th1 cell recovery in HIV-infected patients.

[Myokard-Perfusions-SPECT. Myocardial perfusion SPECT - Update S1 guideline]. / Myokard-Perfusions-SPECT. Update S1-Leitlinie1.

The S1 guideline for myocardial perfusion SPECT has been published by the Association of the Scientific Medical Societies in Germany (AWMF) and is valid until 2/2022. This paper is a short summary with comments on all chapters and subchapters wich were modified and amended.

Technical note on microcatheter implantation for local inner ear drug delivery: surgical technique and safety aspects.

HYPOTHESIS: Despite its invasiveness, the temporary implantation of a microcatheter into the middle ear cavity is an appropriately safe method for providing continuous drug delivery to the inner ear. BACKGROUND: For the application of drugs to the inner ear, different delivery strategies are available ranging from intratympanic injections to temporarily implanted microcatheters. It has recently been demonstrated that the choice of the drug delivery system influences the pharmacokinetics in the inner ear. If a continuous drug application over several weeks is required, a secure placement of the delivery device (i.e., the microcatheter) is necessary to guarantee efficient drug delivery and to avoid unwanted side effects. STUDY DESIGN: Retrospective chart review. MATERIALS AND METHODS: During 2000 to 2005, 25 patients with acute unilateral severe-to-profound hearing loss or anacusis and failure of systemic high-dose glucocorticoid and rheological therapy were offered an intratympanic delivery of glucocorticoids via a temporarily implanted catheter and an external pump for up to 4 weeks as a salvage treatment option. The standardized surgical implantation and fixation technique developed for the microcatheter were characterized by six elements: 1) a medial and a lateral tunnel connected by a groove in the posterior wall of the bony ear canal, 2) stabilization of the catheter with bone wax and soft tissue plugs in the tunnels, 3) an ear canal packing, 4) a series of fixating sutures along the catheter, 5) an adhesive dressing, and 6) additional tapes at the connecting line between pump and catheter. At the end of the implantation period, the catheter was removed by a second surgical procedure allowing for evaluation of the catheter position and the condition of the middle ear space. RESULTS: Adverse events included catheter dislocation, catheter obstruction, formation of mild granulation tissue in the middle ear cavity, tympanic membrane defects, and ear canal skin defects. With introduction of an improved implantation and fixation technique, the number of catheter dislocations could be significantly reduced. No complications were observed on long-term follow-up. CONCLUSION: If the pharmacokinetics or pharmacodynamics of a specific local inner ear therapy approach requires a continuous intratympanic drug application (e.g., to restore hearing in patients with severe or profound hearing loss), the temporary implantation of a microcatheter by a standardized surgical technique is a feasible and appropriately safe method for providing continuous drug delivery to the inner ear.

Inhaled nitric oxide therapy in adults: European expert recommendations.

BACKGROUND: Inhaled nitric oxide (iNO) has been used for treatment of acute respiratory failure and pulmonary hypertension since 1991 in adult patients in the perioperative setting and in critical care. METHODS: This contribution assesses evidence for the use of iNO in this population as presented to a expert group jointly organised by the European Society of Intensive Care Medicine and the European Association of Cardiothoracic Anaesthesiologists. CONCLUSIONS: Expert recommendations on the use of iNO in adults were agreed on following presentation of the evidence at the expert meeting held in June 2004.

Outcomes research analysis of continuous intratympanic glucocorticoid delivery in patients with acute severe to profound hearing loss: basis for planning randomized controlled trials.

CONCLUSIONS: The data presented herein form the basis for conducting randomized placebo-controlled clinical trials evaluating the safety and efficacy of salvage treatment in patients with idiopathic sudden severe sensorineural hearing loss (but not anacusis) refractory to initial systemic therapy. Comparison of different application protocols and drug delivery systems will allow assessment of the value of continuous versus intermittent intratympanic glucocorticoid drug delivery. OBJECTIVES: To describe and critically evaluate the results of continuous intratympanic glucocorticoid delivery in patients with acute unilateral severe and profound sensorineural hearing loss refractory to initial systemic therapy and to compare the outcome with a historical control group. MATERIAL AND METHODS: In a retrospective chart review, treatment results were analyzed in 23 patients with acute severe and profound hearing loss and failure of systemic standard therapy who received a continuous intratympanic delivery of glucocorticoids as a salvage treatment. Audiological results were compared within the local therapy group and with the results of an historical control group who did not receive salvage treatment. The study and control groups were matched with respect to hearing loss after initial systemic treatment failure. RESULTS: The average pure-tone threshold after intratympanic salvage treatment showed a statistically significant improvement of 15 dB (95% CI 7-24 dB; p<0.001). After exclusion of patients with complete anacusis, i.e. a non-measurable hearing threshold, the local therapy group showed a significantly better improvement (mean 19 dB; 95% CI 6-32 dB) than the historical control group (mean 5 dB; 95% CI -2-11 dB; p<0.05).

Surgical-handling properties of the titanium prosthesis in ossiculoplasty.

Despite the wide variety of ossiculoplasty techniques that are available, success rates are limited. Current use indicates that surgeons prefer ceramic, autograft bone, and plastic pore prostheses. During the past decade, titanium prostheses have been used with great promise. Although their use is not widespread, satisfaction rates are high. An earlier study of ossiculoplasty showed that titanium prostheses were effective in reducing conductive hearing loss. To date, the surgical-handling attributes of titanium middle ear prostheses have not been assessed. We report the results of our survey of 32 otologic surgeons who used the open Tübingen titanium prosthesis for primary and revision ossiculoplasty during tympanoplasty in 400 patients at 12 academic and nonacademic otolaryngology clinics, most of them in Germany. Because the audiometric efficacy of titanium prostheses has been previously reported, our primary outcomes measures included ease of use with respect to the amount of time required to prepare the implants for placement and the surgeons' overall impression of the intraoperative handling characteristics of the implants, taking into consideration factors such as positioning, length adjustment, visibility, and the stability of the coupling. Surgeons also compared the properties of the titanium implant with those of gold, ceramic, and autograft implants that they had used in the past. Based on the results of 383 of the 400 ossiculoplasties, our survey revealed that the titanium implant was significantly superior to the others in all measured respects.

Reduced hemoglobin after heart transplantation is no independent risk factor for survival but is associated closely with impaired renal function.

BACKGROUND: Reduced hemoglobin (Hb) levels after heart transplantation (HTX) are common; however, there are only limited data on the association of posttransplant anemia with survival. METHODS: In the present study, the effect of Hb levels determined 7 to 12 months after HTX on survival was investigated in 156 heart transplant recipients (129 men and 27 women; age at transplantation, 51.3+/-10.45 years; follow-up, 6.77+/-3.6 years) by univariate and multivariate analyses including a broad range of clinical and demographic patient characteristics. RESULTS: Anemia by standard definition was found in 141 of 156 (91.6%) patients. According to Hb levels above or below the gender-specific median (men, 12.07 g/dL; women, 11.69 g/dL), patients were separated into a high- or low-Hb group, respectively. Kaplan-Meier analysis demonstrated significantly worse survival in the low-Hb group (P =0.033). Those patients showed significantly lower body weight, higher serum creatinine levels, and lower calculated creatinine clearance; the association of creatinine clearance and Hb levels was highly significant (P <0.0001). No differences were demonstrated between groups for age, preoperative cardiac diagnosis, diabetes, azathioprine, steroid or angiotensin-converting enzyme inhibitor medication, leukocyte and thrombocyte levels, rejection index, or cytomegalovirus (CMV) infection or serostatus. Multivariate Cox stepwise regression analysis demonstrated that CMV infection, diabetes, and female donor gender were significant risk factors for post-HTX survival. An Hb level below the median was, however, completely lost as a risk factor (P =0.44); instead, a strong trend for reduced creatinine clearance could be demonstrated (P =0.09). Subsequently, a significant association was demonstrated between low calculated creatinine clearance and impaired survival by separate Kaplan-Meier analysis (P =0.02). CONCLUSIONS: Low Hb levels after HTX do not represent an independent risk factor for reduced survival, but the demonstrated correlation appears to be primarily caused by concomitant functional renal impairment. Further studies will be required to investigate the role of post-HTX anemia as a sensitive indicator of functional renal impairment and the effects of anemia treatment on long-term survival.

Dissociation of CD4(+) cell counts from viral load and association with immune complexes in HIV(+) hemophilia patients.

OBJECTIVE: We have postulated that the host autoimmune response regulates and mediates CD4 depletion during HIV infection by opsonization of circulating CD4(+) lymphocytes carrying autoreactive immune complexes (IC) consisting of complement-fixing IgM and IgG, and during advanced stages of HIV disease of IgM/ IgG/gp120 complexes. In this retrospective study, we investigated whether HIV causes CD4 depletion by direct cytotoxicity or indirectly by induction of a host autoimmune response. PATIENTS AND METHODS: In 1996, 12 HIV(+) hemophilia patients were converted to highly active antiretroviral therapy (HAART), while 10 other patients were maintained on conventional antiretroviral treatment and another 11 patients refused to be treated with antiretroviral drugs. The host immune response of these 33 HIV(+) patients was studied during the periods of minimum viral replication (Interval 1), subsequent rise in viral replication with strong replication dynamic (Interval 2), and maximum viral replication (Interval 3). The patients were categorized into three groups according to viral load (VL). Group A: patients with low level VL (n=10) showed a modest increase from <80 to <4 log 10 HIV-1 RNA copies per milliliter plasma during the observation period; Group B: patients with medium level VL (n=12) showed a stronger increase from <80 to >4 log 10 copies per milliliter plasma; and Group C: patients with high level VL (n=11) consistently had a median of >4 log 10 copies per milliliter plasma, during Intervals 1-3, with the exception of one patient who during Interval 2 had 4800 copies per milliliter. Blood lymphocyte subpopulations, proportions of CD4(+) blood lymphocytes coated with IgM, IgG, C3d and/or gp120, in vitro responses to mitogens and pooled allogeneic stimulator cells, as well as numbers of HIV-1 RNA copies per milliliter plasma were measured. RESULTS: Sequential analysis of VL, IC load on CD4(+) blood lymphocytes and CD4 counts showed that an increasing VL was not associated with CD4 depletion, when the proportion of IC-coated circulating CD4(+) blood lymphocytes remained stable. When, CD4 counts and IC load were analyzed during corresponding intervals of retroviral replication in the three patient groups, a higher VL was associated with lower CD4 counts only when the IC load (IgG or gp120/IgG) on CD4(+) lymphocytes was higher as well. CONCLUSION: These data suggest that HIV regulates and mediates CD4 depletion in part by the induction of autoreactive ICs against CD4(+) lymphocytes, especially complement-fixing autoreactive IgG and gp120/IgG complexes.

Allograft rejection of ISHLT grade >/=3A occurring late after heart transplantation--a distinct entity?

BACKGROUND: The significance of International Society of Heart and Lung Transplantation (ISHLT) grade >/=3A rejection detected by routine endomyocardial biopsies beyond 2 years post-transplant remains uncertain. METHODS: We performed a retrospective analysis of our single-institution database consisting of 4,041 biopsies (188 patients) from 1986 to 2001. Incidence, clinical correlates and outcome of ISHLT grade >/=3A rejection beyond 2 years post-transplant were analyzed. RESULTS: A total of 307 ISHLT grade >/=3A rejection episodes was diagnosed up to 10 years after transplantation, 69 of which occurred later than 2 years post-transplant in 33 of 139 patients ("late rejection") at therapeutic levels of immunosuppression. Late rejection was only marginally correlated with the incidence of moderate rejection within the first 2 post-transplant years (p = 0.09). The incidence of moderate rejection per patient-year decreased from 1.05 in Year 1 over 0.11 in Year 5 to 0.04 in Year 10. The technical failure rate of biopsies remained low throughout the post-transplant period (range 0.7% to 2.4%). Spontaneous resolution of ISHLT grade >/=3A rejection beyond 2 years post-transplant occurred in all 17 patients in whom specific anti-rejection therapy had been electively withheld. Mortality beyond 2 years post-transplant was lower (p = 0.033) in the "late rejecting" group (n = 33) than in the control group (n = 106). CONCLUSIONS: Endomyocardial biopsy continues to detect episodes of moderate rejection even very late after heart transplantation, without a close correlation with the rejection frequency in the early post-transplant period. Even without specific treatment, late rejection carries a benign clinical prognosis and may represent a separate biologic entity. Potential long-term effects-for instance, on the pathogenesis of transplant vasculopathy-need further elucidation.

Safe and reliable sound threshold measures with direct vibration of the ossicular chain.

OBJECTIVES: The aim of the study was to evaluate the safety and feasibility of piezoelectric malleus vibration audiometer (MVA), which presents micromechanical vibrations to the umbo membranae tympani. STUDY DESIGN: Phase I study performed in a tertiary referral center (University Hospital). METHODS: The coupling rod of the MVA was moved slowly through the outer ear canal toward the eardrum with a micromanipulator. Coupling was completed when the rod tip touched the umbo membranae tympani. Basic audiologic measures of sound threshold obtained with direct stimulation of the malleus are presented. We used MANOVA (multivariate repeated measures ANOVA) to investigate the repeatability of MVA thresholds from one day to the other and when decoupling and retracting the coupling rod 2 mm off the umbo. We also selected the MANOVA to test for unwanted bone-conduction threshold shifts after MVA application. We assessed normality of the data by quantile-quantile plots of the residuals. RESULTS: Twenty-eight male and 10 female subjects with normal hearing, 22.2 to 34.6 years old (median age, 27.2 yr) underwent an examination. Thirty-six subjects underwent MVA, because 2 of the 38 subjects who volunteered for the study have not undergone the procedure due to the external auditory canal anatomy preventing application of the MVA. The results show that it is possible to safely and reliably measure thresholds of direct vibration of the ossicular chain. Using pure tone audiograms, no pure tone bone- and/or air-conduction threshold shifts occurred after the procedure. None of the subjects reported any other ear-related symptoms such as vertigo, tinnitus, or dizziness. Geometric mean vibratory displacements at threshold ranged from 0.55 nm at 250 Hz to 0.03 nm at 6 kHz. MANOVA demonstrated a repeatability of MVA thresholds. CONCLUSION: Malleus vibration audiometry will not allow exact linkage of actual implantable hearing aid. But the present study demonstrates that MVA can provide an audiometric tool for assessing ossicular function and integrity prior to implantation of an electronic hearing amplifier.

Patient selection for incus body coupling of a totally implantable middle ear implant.

OBJECTIVE: To evaluate audiologic selection criteria for incus body coupling (IBC) of a totally implantable middle ear implant (TI-MEI) for the treatment of sensorineural hearing loss (SNHL). MATERIAL AND METHODS: The protocol is specified in the Investigational Device Exemption of a Food and Drug Administration-approved multicenter clinical trial. The prospective study compared pre- and postoperative hearing levels using each patient as their own control. In addition, an implant on/off comparison was made. All patients had a follow-up interval of at least 6 months. Audiologic assessment tests included speech discrimination in quiet as the primary efficacy variable and pure-tone audiometry (aided thresholds), gain, speech recognition in noise and subject satisfaction using standardized questionnaires and visual analog scales (VASs) as secondary efficacy variables. The study group of patients (n = 13) was divided into 3 subgroups based on their pure-tone and speech discrimination scores: Group A consisted of 6 patients, Group B 9 patients and Group C of all 13 patients. All patients suffered from long-standing bilateral moderate to severe SNHL. Five patients were dissatisfied hearing aid (HA) users and eight subjects could not wear HAs. All patients were implanted with a TI-MEI which was coupled to the incus body. The amplification level of the device was set postoperatively using inductive digital fitting based on "most comfortable loudness" specifications. RESULTS: The implant produced median improvements from 30% (optimally fit bilateral HAs; n = 5) and 50% (HA non-users; n = 8) to 70% word recognition at 60 dB SPL. Average word recognition scores at 60, 80 and 90 dB SPL in Groups A and B showed increases from 42% (interquartile range +27%, -12%) to 93.5% (+3%, -5%) and 92.5% (+3%, -7%), respectively. In the presence of background noise, the sentence recognition threshold ranged from -2 to 1 dB signal-to-noise ratio. Maximum amplification was 50 dB at 3 kHz and 55 dB at 4 kHz. In Groups A and B, VASs revealed improvements in both natural sound impression and clarity from 62-70% of a natural sound impression to maximum scores of 100%. Using the standardized Gothenburg profile, subjective evaluations of hearing, orientation, social behavior and self-confidence reached 96-98%, 92-96% and 84-92% of the maximum score for Groups A-C, respectively. CONCLUSIONS: In selected cases, IBC of the TI-MEI investigated herein may be indicated for the treatment of SNHL, provided the following four conditions are met. First, the patient does not derive sufficient benefit from conventional HAs. Second, the specific indication for IBC is restricted to situations that do not allow the coupling of the MEI to the long incus process (e.g. due to an anatomical variation of facial nerve location). Third, IBC is restricted to patients with a steeply sloped moderate to severe high frequency SNHL, amounting to 90 dB HL from 3 to 8 kHz. Patients with low frequency SNHL should not be operated on with the IBC technique, as maximum low frequency hearing loss at 0.5 kHz must not exceed 30 dB. Fourth, Schueller's X-ray should reveal normal mastoid pneumatization. Being restricted to a 6-month follow-up period, this paper provides early clinical results and no clinical evidence of long-term efficiency of the implant.

Phase III results with a totally implantable piezoelectric middle ear implant: speech audiometry, spatial hearing and psychosocial adjustment.

OBJECTIVE: To evaluate the treatment efficacy of an electromechanical middle ear amplifier implant (AI) in patients with chronic moderate-to-severe sensorineural hearing loss (SNHL). The AI is a piezoelectric system with a sound processor and a rechargeable battery within a hermetically sealed titanium canister. Its titanium-sealed microphone is placed in the bony region of the ear canal. The incus-coupled transducer (actuator), which is also inside a titanium casing, is fastened to the adjacent bone. MATERIAL AND METHODS: This was a phase III study comprising 20 intention-to-treat patients. Telemetrical adjustments followed electromechanical amplifier implantations. We used a word recognition test as our primary efficacy measure (Freiburg Speech Recognition Test: DIN 45621). Secondary efficacy measures were the sentence comprehension test (Goettinger Satztest, 1996) for auditory orientation within noisy and quiet environments and a psychosocial adjustment test (Gothenburg Profile Test, 1998). The 6-month follow-up comprised a complete medical examination. Nineteen patients completed the study (per-protocol patients; 100% reference). RESULTS: Seventeen patients (89%) demonstrated improved binaural recognition of phonetically balanced monosyllables. Fourteen postoperative patients (74%) attained a perfect score (100%) on this test, compared to only 3 preoperative patients (16%). Thirteen patients (68%) reached the sentence recognition threshold at a 2:1 dB signal-to-noise ratio during noisy trials. Correct identification of the noise source direction in the horizontal plane occurred in 89% of the trials. The Gothenburg Profile Test scores showed that the subjective evaluation of hearing, orientation, social behavior and self-confidence increased from 48% to 88%. Three patients did not benefit from the implant. CONCLUSION: Treatment of SNHL with a totally implantable hearing system can be an efficient method for those patients unable to wear hearing aids. However, in order to avoid implantation in non-responders, there is a need for more specific audiological indication criteria.

Challenges in treating elderly patients with haemophilia: a focus on cardiology.

Seventy years ago, the average life expectancy for patients with severe haemophilia A was less than 17 years. Today, due to the availability of safe and effective clotting factor concentrates, life expectancy is nearly normal, at least in patients without viral infections. More individuals are living into their 70s and 80s, acquiring a range of diseases that are common in elderly persons. One of the most important challenges includes the treatment of comorbidities, especially cardiovascular diseases. Although most evidence suggests that haemophilia, at least the severe manifestation, partially protects against myocardial infarction, stroke and venous thromboembolism, typical cardiovascular risk factors can still be present despite the clotting defect. Patients with haemophilia are equally or even more prone to obesity, hypertension, diabetes, and dyslipidaemia, and this is especially true for HIV-infected individuals using highly active antiretroviral therapy. The management of elderly haemophilia patients with cardiovascular comorbidities is hampered by a lack of evidence-based guidelines. Nevertheless, experience in treating cardiovascular disease is growing amongst the haemophilia community, and several authors have published their own recommendations for managing a variety of commonly encountered cardiovascular scenarios in haemophilia patients. Basic recommendations exist for risk-factor management, the adaptation of factor replacement therapy in the at-risk elderly, management of coronary revascularization, the management of acute coronary syndrome and atrial fibrillation. This review outlines our current knowledge about cardiovascular risk in elderly haemophilia patients, recommendations for clinical decision making, and our own experiences of managing individuals with coronary heart disease and atrial fibrillation.

Beriate® P in the treatment of patients with haemophilia A: results of a long-term pharmacovigilance study.

BACKGROUND: The German Beriate(®) P pharmacovigilance study started in 2003 and is planned to run until December 2013. MATERIALS AND METHODS: This analysis included data from 84 haemophilia A patients treated with the high-purity, plasma-derived coagulation factor VIII concentrate Beriate(®) P. Prior to study start, 69 of the 80 patients for whom data were available had received previous treatment with Beriate(®) P (mean treatment period 7.1 ± 5.4 years). The mean study duration from the start of pharmacovigilance was 43.3 ± 30.3 months (median 43.5 months; range 0-101.9months). The most common treatment at the last visit was prophylaxis (65.7% of patients), which was most commonly administered at a frequency of three infusions/week in 47.3% of patients. RESULTS: Most patients experienced up to six minor bleeds/year. For 1,311 bleeding episodes, a median of one infusion/bleed was administered (mean 2.8 ± 4.7; range 0-83). The clinical response to Beriate(®) P was rated "excellent"/"good" in 94% of 32 visits of patients with major bleeding. The clinical response for patients with minor bleeding was rated "excellent"/"good" in 98.5% of 377 visits. One clinically relevant inhibitor in a previously untreated patient was documented during the study course. There were no reports of virus transmissions suspected to be caused by Beriate(®) P prior to the study start or during the study. CONCLUSIONS: These findings confirm the excellent efficacy, safety, and tolerability of Beriate(®) P in the treatment of a wide spectrum of previously untreated patients up to adult patients with haemophilia A.

Intracoronary compared with intravenous bolus abciximab application during primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: cardiac magnetic resonance substudy of the AIDA STEMI trial.

OBJECTIVES: The aim of the AIDA STEMI (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction) cardiac magnetic resonance (CMR) substudy was to investigate potential benefits of intracoronary versus intravenous abciximab bolus administration on infarct size and reperfusion injury in ST-segment elevation myocardial infarction. BACKGROUND: The AIDA STEMI trial randomized 2,065 patients to intracoronary or intravenous abciximab and found similar rates of major adverse cardiac events at 90 days with significantly less congestive heart failure in the intracoronary abciximab group. CMR can directly visualize myocardial damage and reperfusion injury, thereby providing mechanistic and pathophysiological insights. METHODS: We enrolled 795 patients in the AIDA STEMI CMR substudy. CMR was completed within 1 week after ST-segment elevation myocardial infarction. Central core laboratory-masked analyses for quantified ventricular function, volumes, infarct size, microvascular obstruction, hemorrhage, and myocardial salvage were performed. RESULTS: The area at risk (p = 0.97) and final infarct size (16% [interquartile range: 9% to 25%] versus 17% [interquartile range: 8% to 25%], p = 0.52) did not differ significantly between the intracoronary and the intravenous abciximab groups. Consequently, the myocardial salvage index was similar (52 [interquartile range: 35 to 69] versus 50 [interquartile range: 29 to 69], p = 0.25). There were also no differences in microvascular obstruction (p = 0.19), intramyocardial hemorrhage (p = 0.19), or ejection fraction (p = 0.95) between both treatment groups. Patients in whom major adverse cardiac events occurred had significantly larger infarcts, less myocardial salvage, and more pronounced ventricular dysfunction. CONCLUSIONS: This largest multicenter CMR study in ST-segment elevation myocardial infarction patients to date demonstrates no benefit of intracoronary versus intravenous abciximab administration on myocardial damage and/or reperfusion injury. Infarct size determined by CMR was significantly associated with major adverse cardiac events.

Prognostic relevance of papillary muscle infarction in reperfused infarction as visualized by cardiovascular magnetic resonance.

BACKGROUND: The prognostic significance of papillary muscle infarction (PapMI) on hard clinical outcomes has not been investigated in patients with reperfused ST-segment-elevation myocardial infarction. Noninvasive investigation by gadolinium-enhanced cardiac MRI enables the detection of PapMI with high spatial resolution. The aim of our study was (1) to assess the incidence, determinants, and clinical characteristics of PapMI in a large multicenter cohort of patients with ST-segment-elevation myocardial infarction and (2) to assess the prognostic significance of PapMI at 1-year follow-up. METHODS AND RESULTS: We enrolled 738 patients with ST-segment-elevation myocardial infarction reperfused by primary angioplasty (<12 hours after symptom onset) in this cardiac MRI study at 8 centers. Cardiac MRI was completed within 1 week after infarction using a standardized protocol. Central core laboratory-masked analyses for the presence of PapMI were performed. The primary clinical end point of the study was the occurrence of major adverse cardiac events. PapMIs were detected in 104 patients (14%). The presence of PapMI was associated with larger infarcts (P<0.001), less myocardial salvage (P<0.001), impaired left ventricular function (P<0.001), and more pronounced reperfusion injury (P=0.02). Patients with PapMI had a significantly higher mortality (8 [7.7%] versus 12 [1.9%]) and major adverse cardiac events (21 [20.2%] versus 31 [4.9%]) rate at 12-month follow-up (P<0.001, respectively). PapMI was identified as a significant independent predictor of major adverse cardiac events (hazard ratio, 4.41 [confidence interval, 2.54-7.68]; P<0.001). CONCLUSIONS: The presence of PapMI is associated with decreased myocardial salvage, larger infarcts, and more pronounced reperfusion injury with subsequent significantly increased major adverse cardiac event rates. Consequently, our data underscore the importance of PapMI as a marker of poor outcome in patients with ST-segment-elevation myocardial infarction.