[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.

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.

[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.

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.

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.

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.

Assessment of pulmonary endothelial function during invasive testing in children and adolescents with idiopathic pulmonary arterial hypertension.

OBJECTIVES: The purpose of our study was to assess pulmonary endothelial function by vasodilator response to acetylcholine (Ach) administered in segmental pulmonary arteries in children with idiopathic pulmonary arterial hypertension (IPAH). We hypothesized that there was a relationship among pulmonary endothelial response to Ach, severity of the disease, and clinical outcome. BACKGROUND: IPAH may be associated with pulmonary endothelial dysfunction; however, data regarding the impact of endothelial dysfunction on severity and prognosis of this disease are limited. METHODS: Forty-three children and adolescents (mean age: 10.4 ± 5.5 years) with IPAH were included in the study. Changes in pulmonary blood flow in response to Ach were determined using intravascular Doppler flow measurements. Pulmonary flow reserve (PFR) was calculated as the ratio of pulmonary blood flow velocity in response to Ach relative to baseline values. RESULTS: Mean PFR of all patients was 1.58 ± 0.67. Mean follow-up after catheterization was 55.7 ± 41.9 months. Freedom from serious cardiovascular events (lung transplantation or death) was 83% after 2 years, 76% after 3 years, and 57% after 5 years. PFR was related significantly to World Health Organization functional class. Receiver-operating characteristic curves revealed a PFR of 1.4 as the best cutoff value. Kaplan-Meier analysis demonstrated that a PFR of <1.4 was highly predictive for cardiovascular events (log-rank [Mantel Cox] chi-square: 12.49, p < 0.0001). CONCLUSIONS: Our study demonstrates a strong relationship between pulmonary endothelial response to Ach and prognosis of children with IPAH. As an adjunct to the usual testing protocol, this method provides additional information for therapeutic guidance.

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.

Increased peripheral blood leukocyte subsets with regulatory phenotype in clinically stable long-term HIV-infected hemophilia patients on HAART may be beneficial and contribute to a decrease in autoimmunity.

After initiation of highly-active antiretroviral therapy (HAART), long-term HIV-infected hemophilia patients have been shown to lose autoantibodies against CD4(+) peripheral blood leukocytes (PBL), suggesting that HAART induces autoimmunity-blocking mechanisms. We compared cytokine levels and subpopulations of lymphocytes and dendritic cells (DC) in the blood of 40 long-term HIV(+) patients with those of 13 long-term HIV(-) hemophilia patients; 23 HIV(+) patients had a detectable retroviral load. Cell subsets were determined using flow cytometry and cytokine levels were measured using ELISA. HIV(+) patients showed higher proportions of DC subpopulations with immunostimulatory phenotypes (p < 0.01), CD8(+) PBL (p < 0.001), and IL-2 (p < 0.001) and sIL-2R plasma levels (p = 0.002) than HIV(-) patients. They also exhibited increased proportions of T PBL with immunosuppressive phenotypes such as CD3(+)CD4(+)CD25(+)Foxp3(+) (p = 0.001), and CD3(+)CD8(+)CD28(-)Foxp3(+) PBL (p < 0.001), and a decreased IL-7R expression on CD3(+)CD8(+) PBL (p = 0.001) compared to HIV(-) patients. Frequencies of CD3(+)CD4(+)CD25(+) PBL producing IL-2, IL-4, IL-10, IL-12, and/or IFN-gamma, and of CD3(+)CD4(+)CD28(-) PBL secreting IL-2 and/or IL-4 were lower in HIV(+) than in HIV(-) patients (p

Randomized, double blind, placebo controlled trial on the safety and efficacy of continuous intratympanic dexamethasone delivered via a round window catheter for severe to profound sudden idiopathic sensorineural hearing loss after failure of systemic therapy.

OBJECTIVES: To study the safety and efficacy of continuous intratympanic dexamethasone-phosphate (Dex-P) for severe to profound sudden idiopathic sensorineural hearing (ISSHL) or sudden idiopathic anacusis after failure of systemic therapy. STUDY DESIGN: Randomized, double-blind, placebo controlled multicenter trial. METHODS: Patients with ISSHL and insufficient recovery (mean 4PTA = 97 dB HL) after systemic high dose glucocorticoid therapy received either Dex-P (4 mg/ml) or placebo (NaCl 0.9%) continuously applied for 14 days into the round window niche via a temporarily implanted catheter. For ethical reasons, intratympanic treatment was continued with Dex-P in all patients for another 14 days after the placebo-controlled study period. According to a two-step adaptive study design an interim analysis was performed after inclusion of 23 patients. RESULTS: Intention-to-treat analysis for the primary outcome criterion (4PTA: 0.5-3 kHz) during the placebo controlled study period (14 days) showed an average hearing improvement in the treatment group of 13.9 dB (SD: 21.3) and in the placebo group of 5.4 dB (SD: 10.4). This difference in hearing improvement between the two groups (mean: 8.4 dB, SD: 17.0, 95% CI: -7.1-24.1) was statistically not significant (p = .26). Of the secondary outcome parameters, the largest benefit of local salvage therapy was found for maximum speech discrimination with an improvement of 24.4% (SD: 32.0) in the treatment and 4.5% (SD: 7.6) in the placebo group (p = 0.07). After a 3 month follow-up period (i.e. after all patients received intratympanic Dex-P) hearing improvement in the two groups was very similar. No serious adverse events were observed. Sample size calculation after the interim analysis resulted in stopping of the trial. CONCLUSIONS: The tendency toward better hearing improvement in the treatment group, the rather conservative inclusion criteria, the limited placebo-controlled observation period and the absence of serious adverse events supports further investigation local inner ear drug delivery as a first or second line treatment option for ISSHL.

Normal or even increased dendritic cell and peripheral blood lymphocyte subsets with regulatory phenotype in clinically stable long-term HIV-infected patients with hemophilia on highly active antiretroviral therapy.

Defective regulatory components of the immune system seem to contribute to HIV disease progression. Highly active antiretroviral therapy (HAART) was reported to restore malfunctioning immunologic regulatory components. To corroborate this hypothesis, we studied different dendritic-cell (DC) and T-cell subsets with regulatory phenotype in 41 clinically stable patients with hemophilia more than 25 years after infection with HIV and 10 years after initiation of HAART. Compared with healthy controls, patients showed normal DC1 and DC2 levels, increased CD8 peripheral blood lymphocyte (PBL) counts and T helper (Th) 2 proportions, and decreased Th1, CD3CD4CD127, and CD3CD8CD127 PBL proportions. High viral load was associated with high DC1, whereas high CD8 PBL counts were associated with low DC2. CD3CD4CD25Foxp3 (regulatory T [Treg] cell) and CD3CD8CD28Foxp3 PBL counts (suppressor T [Ts] cell) exhibited normal levels in patients with undetectable retroviral load, were increased in parallel to retroviral load, and were associated with low CD8 T lymphocytes and low CD19 B lymphocytes. Normal or even increased levels of DCs and normal or even increased levels of PBL with a Treg or Ts phenotype that coincide with viral load increases and CD8 T- and CD19 B-lymphocyte decreases suggest a functioning immunoregulatory system that reacts to HIV replication. Increased CD8 PBL counts imply immunocompetence. Increased CD8 PBL counts and normal or even upregulated immunoregulatory cells might stabilize our long-term HIV-infected patients with hemophilia clinically.

Association of IL-12+ DC with High CD3+CD4-DR+ lymphocyte counts in long-term HIV-infected hemophilia patients with clinically stable disease.

We investigated dendritic cell (DC) subsets as well as cellular and humoral immune parameters in long-term HIV-infected hemophilia patients with clinically stable disease. DC subsets were determined by their function to produce either IL-10 or IL-12. CD11c(+)CD83(+)CD40(+)IL-10(+) and CD11c(+)CD83(+)CD40(+)IL-12(+) DC were studied in freshly obtained blood samples of 28 HIV(+) and 15 HIV(-) patients and 39 healthy controls using four-color flow cytometry, and were analyzed in relation to blood lymphocyte subpopulation counts, proportions of IgG-coated CD4(+) blood lymphocytes, neopterin, and HIV-1 viral load in the plasma, and in vitro responses of patient lymphocytes to mitogens. Proportions and ratios of IL-10(+) DC and IL-12(+) DC were similar in HIV(+) and HIV(-) patients and healthy controls. Whereas IL-12(+) DC in HIV(+) patients were associated with high CD3(+)CD4(-)DR(+) lymphocyte counts, IL-10(+) DC were associated with the proportion of IgG-coated CD4(+) blood lymphocytes. These data suggest that long-term HIV-infected hemophilia patients with clinically stable disease have normal levels of functional IL-10(+) DC and IL-12(+) DC that might be involved in halting the progression of disease.

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.

Impaired release of bioactive parathyroid hormone-related peptide in patients with pulmonary hypertension and endothelial dysfunction.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) is an endothelial-derived vasoactive peptide. This study investigated whether bioactive PTHrP is locally released in a pressure-dependent way. METHODS: A PTHrP antibody directed against the midregional part of PTHrP was used to analyze PTHrP in plasma samples. The biological activity of this PTHrP-like peptide was investigated in vitro. Plasma values were determined in samples from the left pulmonary artery and the arteria femoralis, taken under basal conditions and after the application of oxygen or iloprost to lower the pulmonary pressure. Twenty young patients (mean age 6.5 years), who were catheterized for an analysis of the reactivity of the pulmonary bed, were investigated. Endothelial function was investigated by acetylcholine responsiveness. RESULTS: The antibody recognized a 30-kDa protein with in vitro PTHrP-like activity. In 11 patients (responders) with intact endothelial function, the PTHrP values determined in the left pulmonary artery were higher than those in the arteria femoralis. The local increase in the PTHrP concentration was reduced when either oxygen or iloprost lowered the pressure. Nine patients with endothelial dysfunction did not show any concentration gradients at any time (nonresponders). CONCLUSIONS: The local concentration of bioactive PTHrP is increased in patients with pulmonary hypertension and normal endothelial function.

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.

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).