Innere Medizin Research Articles

Electrophysiological remodeling in tachycardia-induced cardiomyopathy

Abstract Background Tachycardia-induced cardiomyopathy (TCM) is a reversible and likely underrecognized form of heart failure. Thus, a better understanding of the TCM-pathophysiology is warranted as the underlying early mechanisms that mediate the progression of TCM remain unclear. Purpose This study aimed to identify the cellular mechanisms of TCM. Methods and results Human induced pluripotent stem cell cardiomyocytes (iPSC-CM) were utilized as a translational human-based model. We performed chronic tachycardic (120 bpm) or normofrequent (control, 60bpm) cell culture pacing to study cellular changes during TCM progression. Already after 24h of tachycardic stimulation of iPSC-CM, we detected a decrease in Ca transient amplitude compared to control (Fura-2, n=49/44 cells/9 differentiations). Diastolic Ca levels and cytosolic Ca elimination were not affected after 24h of tachycardia (n=49/44/9). We detected no difference in sarcoplasmic reticulum (SR) Ca load (assessed via caffeine application) or SERCA activity (Ksys-Kcaff) after 24h of tachycardia (n=13/15/5). However, demonstrating the progress of TCM, 7d of tachycardia resulted in progressive decline of Ca transient amplitude together with an impaired Ca elimination, while diastolic Ca concentration was unchanged (n=73/66/8). These changes may underlie the reduced systolic force and impaired relaxation in TCM. We could explain these results by a significantly reduced SR Ca load and a diminished SERCA activity after 7d tachycardia (n=13/7 vs. 13/4). Using confocal microscopy (Fluo-4) we detected no difference in SR Ca spark frequency after 24h of tachycardia (n=82/66/8), while 7d of tachycardia caused an increase of Ca spark frequency (n=76/79/7), which is a typical hallmark of maladaptive remodeling in HF and likely underlie the reduced SR Ca load. Voltage clamp data of late Na current (INaL) showed no difference in INaL after 24h of stimulation (n=17/6 vs. 19/7), whereas INaL was increased after 7d of tachycardia (n=26/7 vs. 19/6). Accordingly, whole-cell current clamp experiments revealed a prolongation of the action potential after 7d of tachycardia compared to control (n=21/6 vs. 19/5), while no difference of action potential duration could be detected after 24h (n=37/31/8). Resting membrane potential and action potential amplitude were not changed. Finally, we investigated tachycardia-mediated effects on explanted human failing hearts. 8h of tachycardic stimulation (120 bpm) of human failing ventricular trabeculae already compromised systolic force, and diastolic tension and relaxation time were markedly increased compared to control (60bpm, n=8/6 trabeculae /7/6 human hearts). Conclusion This study demonstrates that persistent tachycardia adversely alters cardiomyocyte excitation-contraction coupling via electrophysiological cellular remodeling. Our translational investigation in human myocardium may help to understand the pathophysiology of an underrated but prevalent disease. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Else Kröner-Fresenius-Stiftung (EKFS)Deutsche Gesellschaft für Innere Medizin

Therapy of Type 2 Diabetes

The Clinical Practice Guidelines of the German Diabetes Society/Deutsche Diabetes Gesellschaft (DDG) together with the German Society for Internal Medicine/Deutschen Gesellschaft für Innere Medizin (DGIM) are based on the contents of the National Treatment Guideline (Nationale Versorgungsleitlinie (NVL)) “Type 2 Diabetes” [1]. The modifications in therapy and their justifications made in the present Clinical Practice Guidelines were updated on the basis of new randomized controlled trials (RCTs) and meta-analyses.

100-OR: Association of Recent Myocardial Infarction with Insulin Resistance and Fatty Liver Disease in Type 2 Diabetes

Insulin resistance and nonalcoholic fatty liver disease (NAFLD) frequently associate with type 2 diabetes (T2D) and cardiovascular disease and worsen their prognosis. We hypothesized that people with recent myocardial infarction (MI) have lower left ventricular ejection fraction (EF) and higher degree of insulin resistance (IR) , hepatocellular lipid content (HCL) and risk of hepatic fibrosis than matched people without MI. Thus, participants of the “DIabetes and ST-Elevation MI (DISTEMI) Study” were examined 6-12 weeks after MI (MI+; n=53, 28% T2D) and compared to age-, sex-, BMI-matched people without MI (MI-; n=48, 31% T2D) . Insulin sensitivity was assessed during fasting (Homeostasis Model Assessment (HOMA) 2-IR) and hyperinsulinemic-euglycemic clamps (M-value) . EF, HCL and liver stiffness, associated with fibrosis stages, were quantified by 1H-magnetic resonance imaging, spectroscopy and elastography, respectively. MI+ had a lower EF (47±2 vs. 58±1 %, p<0.0001) and M-value (7.3±0.4 vs. 8.2±0.4 mg*kg-1*min-1, p<0.05) compared to MI-, which was mainly due to a difference between the T2D groups (EF: 39±6 vs. 52±2 %, p<0.001; M-value: 4.2±0.5 vs. 6.1±0.6 mg*kg-1*min-1, p<0.05) . HCL (3.4±0.8 vs. 5.8±0.9 %) and liver stiffness (2.2±0.1 vs. 2.3±0.1 kPa) were comparable between MI+ and MI-. HCL correlated negatively with M-value (r=-0.95, p<0.05) and positively with systolic blood pressure (r=0.91, p<0.05) in MI+ with T2D. In MI+ without T2D, HCL correlated positively with HOMA2-IR (r=0.58, p<0.01) and BMI (r=0.53, p<0.01) . In conclusion, recent myocardial infarction in people with type 2 diabetes associates with decreased ejection fraction and increased insulin resistance. The correlation between insulin resistance and liver fat content suggests that HCL can serve as a non-invasive cardiovascular marker and may identify persons with a worse outcome after myocardial infarction. Disclosure C.Möser: None. M.Roden: Advisory Panel; Eli Lilly and Company, Research Support; Boehringer Ingelheim International GmbH, Nutricia, Speaker's Bureau; Novo Nordisk. O.P.Zaharia: n/a. F.C.Michlotti: None. Y.Kupriyanova: None. V.Schrauwen-hinderling: None. P.Bobrov: None. V.Burkart: None. M.Kelm: Board Member; DGIM-Deutsche Geselleschaft für Innere Medizin, DGK-Deutsche Gesellschaft für Kardiologie, DSHF-Deutsche Stiftung für Herzforschung, ESC- European Society of Cardiology, Other Relationship; Abiomed , Bayer AG, diaplan, Kel Con GmbH, Research Support; Abiomed Europe GmbH, B.Braun, Edwards Lifesciences Corporation, European Union, IPP Med GmbH - Institut für Pharmakologie u. präventive Medizin GmbH, Mars Scientific Advisory Council (MSAC) , Medicure Inc., Microvision Medical. J.M.Szendroedi: Consultant; Boehringer Ingelheim International GmbH. Funding Research Network SFB 1116 of the German Research Foundation

Effects of atrial fibrillation on ventricular remodeling in the human heart

Abstract Atrial fibrillation (AF) is often found in patients with heart failure (HF). Clinical data indicated that the arrhythmic component of AF alone could contribute to left-ventricular (LV) dysfunction. However, the effects of non-tachycardic AF with arrhythmic excitation of the human LV, are unknown. We investigated human LV myocardium from patients with sinus rhythm (SR) or normofrequent AF (mean EF>50%, matched clinical data, derived from septal resections during AVR). In histological analysis we detected no difference between SR (n=17 patients) and AF patients (n=18) regarding the amount and distribution of fibrosis. We isolated human LV cardiomyocytes (CM) and studied cellular Ca-handling (Fura-2). Systolic Ca-transient amplitude of LV CM was reduced in patients suffering from AF (n=8 AF patients vs. 11 SR), while diastolic Ca-levels and Ca-transient kinetics were not significantly changed. These results were confirmed in LV CM from non-failing donors (NF) with AF (n=4 AF patients vs. 8 SR). For the standardized investigation of a normofrequent arrhythmia, we simulated AF in vitro by using arrhythmic (60 bpm, 40% beat-to-beat variability) or rhythmic (60 bpm) field stimulation. Human LV CM from NF SR patients (n=8) showed an impaired Ca-transient amplitude after 24h arrhythmic culture pacing without changes in diastolic Ca and Ca-transient kinetics. For studying a model suitable for more standardized chronic pacing, we utilized human iPSC cardiomyocytes (iPSC-CM) from healthy donors (n=6). After 7 days, arrhythmically paced iPSC-CM exhibited a reduced systolic Ca-transient amplitude, a trend towards a prolonged Ca-elimination time and a reduced sarcoplasmic reticulum Ca-load. Confocal line-scans of arrhythmically paced cells (Fluo-4 AM) showed an increased diastolic Ca-leak from the sarcoplasmic reticulum, possibly underlying the reduced Ca-load. Coupled with the Ca changes, cytosolic Na was elevated after arrhythmia. We found an increased late INa, which could explain the detrimentally altered Ca/Na-interplay. Accordingly, Patch-clamp experiments revealed a prolonged action potential duration after arrhythmia. We further elucidated the underlying mechanisms of this electrophysiological remodeling by showing that oxidative stress (H2O2, LPO) is increased in the LV of patients suffering from AF (n=6 AF patients vs. 6 SR), which was associated with an enhanced NOX2/-4 activity. Consecutively, Ca2+/calmodulin-dependent protein kinase IIδ (CaMKII) was found to be more oxidized (CaMKII-Met281/282) in the LV of AF patients (n=7 AF patients vs. 7 SR) leading to an increased CaMKII activity, which adversely regulated EC-coupling protein phosphorylation including RyR2 hyperphosphorylation. Normofrequent arrhythmia/AF impairs human ventricular EC-coupling via increased oxidative stress and enhanced CaMKII. Thus, this translational study provides the first mechanistic characterization and the potential negative impact of isolated AF on the human LV. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Else Kröner-Fresenius-Stiftung (EKFS) and Deutsche Gesellschaft für Innere Medizin

62nd ASH Annual Meeting and Exposition.

Andreas Hochhaus (Klinik für Innere Medizin II, Jena, Germany) presented results from the phase 3 ASCEMBL randomised trial of asciminib versus bosutinib in patients with previously treated chronic myeloid leukaemia (CML) in the chronic phase. Asciminib is a first-in-class STAMP inhibitor, with a different mechanism of action to other approved tyrosine-kinase inhibitors. 233 adult patients with heavily pretreated CML were enrolled and randomly assigned (2:1) to asciminib 40 mg twice daily (n=157) or bosutinib 500 mg once daily (n=76).

Beta-Carotene concentration in blood serum of cows from herds with impaired fertility

Beta-Carotene concentration in blood serum of cows from herds with impaired fertility

403. Prognostic Factors in 260 Adults With Invasive Scedosporiosis From Literature and FungiScope™

BackgroundInvasive scedosporiosis (iS) and lomentosporiosis (iL) are an increasing concern due to intrinsic resistance of such pathogens to antifungal therapy. Guidelines recommend voriconazole, amphotericin B and surgery to treat scedosporiosis, irrespective of the causative species. Scedosporium spp. are often resistant to amphotericin B but susceptible to posaconazole and voriconazole, whereas Lomentospora prolificans (LoPro) is usually pan-resistant. Mortality rates rise to 90%, despite comprehensive treatment. Here, we describe the epidemiology of iS/L.MethodsA retrospective analysis of patients with iS/iL was conducted to evaluate clinical characteristics and outcomes. Cases diagnosed from January 2000 until August 2017 were selected from the literature and the FungiScope™ registry. In vitro susceptibility to approved and new antifungals was determined according to EUCAST and CLSI methods.ResultsWe identified 208 cases with infection caused by Scedosporium spp. and 56 by LoPro. iS was most frequently reported in patients after solid organ transplantation (27.9%), iL in patients with underlying malignancy (51.9%). Skin, lung, CNS, and eye were most frequently involved in iS cases, whereas involvement of lung, eye, and blood stream infection were most common in iL cases. Posaconazole and voriconazole showed good in vitro activity against most Scedosporium spp. isolates, but not LoPro. The new antifungal drug Olorofim was highly active against all isolates tested in vitro, also LoPro. All-cause mortality in Scedosporium spp. cases ranged from 12.5% in trauma patients to 55.2% in patients with malignancy, in the LoPro group from 28.6% in surgical patients to 85.2% in patients with malignancy. In iS cases worse outcome was associated with disseminated disease and CNS involvement in transplant recipients, and lung involvement in patients with malignancy. In iL cases, malignancy and fungemia were associated with worse outcome.ConclusionClinical presentation and outcome vary between iS and iL cases. Blood stream infection and CNS involvement are associated with worse outcome. Activity of Olorofim against Scedosporium spp. and LoPro will be evaluated in an upcoming phase III trial.Disclosures J. Vehreschild, Merck / MSD: Consultant, Research Contractor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. Gilead: Consultant, Research Contractor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. Pfizer: Research Contractor and Speaker’s Bureau, Research grant and Speaker honorarium. Astellas Pharma: Consultant, Research Contractor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. Basilea: Consultant, Research Contractor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. Deutsches Zentrum für Infektionsforschung: Member, Research Contractor and Speaker’s Bureau, Research grant and Speaker honorarium Uniklinik Freiburg / Kongress und Kommunikation: Speaker’s Bureau, Speaker honorarium. Akademie für Infektionsmedizin: Speaker’s Bureau, Speaker honorarium. Universität Manchester: Speaker’s Bureau, Speaker honorarium, Deutsche Gesellschaft für Infektiologie: Member and Speaker’s Bureau, Speaker honorarium. Ärztekammer Nordrhein: Speaker’s Bureau, Speaker honorarium. Uniklinik Aachen: Speaker’s Bureau, Speaker honorarium. Back Bay Strategies: Speaker’s Bureau, Speaker honorarium. Deutsche Gesellschaft für Innere Medizin: Member and Speaker’s Bureau, Speaker honorarium. M. J. G. T. Vehreschild, Pfizer: Speaker’s Bureau, Speaker honorarium. MSD/Merck: Consultant and Speaker’s Bureau, Consulting fee and Speaker honorarium. Gilead Sciences: Research Contractor and Speaker’s Bureau, Research grant and Speaker honorarium. Organobalance: Speaker’s Bureau, Speaker honorarium Astellas Pharma: Consultant, Research Contractor and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium. 3M: Research Contractor, Research grant. DaVolterra: Research Contractor, Research grant. Berlin Chemie: Consultant, Consulting fee O. A. Cornely, Amplyx Pharmaceuticals, Basilea Pharmaceutica, F2G, Gilead Sciences, MSD Sharp and Dohme, Scynexis Inc.: Consultant, Consulting feeAmplyx Pharmaceuticals, Basilea Pharmaceutica, F2G, Gilead Sciences, MSD Sharp and Dohme, Scynexis Inc.: Grant Investigator, Research grantBasilea Pharmaceutica, Gilead Sciences, MSD Sharp and Dohme, Pfizer: Speaker’s Bureau, Speaker honorarium

Choosing wisely recommendations in nephrology

The German Society of Internal Medicine ("Deutsche Gesellschaft für Innere Medizin", DGIM) founded the Choosing wisely initiative in order to address diagnostic and therapeutic procedures that are frequently inappropriately applied, whether this be in terms of over-, under-, or misuse of health services. The German Society of Nephrology ("Deutsche Gesellschaft für Nephrologie," DGfN) strongly supports the initiative and has contributed five positive and five negative recommendations. These ten recommendations are discussed in the current publication. The positive recommendations reflect the importance of early recognition of renal disease via simple blood and urine tests, the use of radiocontrast media in cases of impaired renal function, as well as the problems associated with low vaccination rates. Three of the negative recommendations are focused on hydration and diuretics. The remaining two negative recommendations concern angioplasty in cases of renal artery stenosis and the unconsidered use of nonsteroidal anti-inflammatory drugs.

Late‐breaking abstracts

Late‐breaking abstracts

FOXO3A elicits vascular smooth muscle cell apoptosis through release of MMP-13 and subsequent degradation of the extracellular matrix

FOXO3A elicits vascular smooth muscle cell apoptosis through release of MMP-13 and subsequent degradation of the extracellular matrix

Coexistence of primary myelofibrosis and chronic lymphocytic leukemia

Coexistence of primary myelofibrosis and chronic lymphocytic leukemia Sonja Burgstaller, Josef Thaler Klinikum Wels-Grieskirchen, Abteilung für Innere Medizin IV, Wels, AustriaAbstract: Coexistence of two hematologic malignancies in one patient is generally a rare phenomenon. The topic of this article is the coincidence of primary myelofibrosis and chronic lymphocytic leukemia, which has been reported up to now in only 16 patients. In summary, simultaneous detection of both diseases was notable in half of the patients at presentation. In the case of a subsequent diagnosis of both disorders, primary myelofibrosis preceded the lymphoproliferative disease in the majority of patients. The clinical course seems to be more benign than for each disorder itself. A substantial proportion of patients did not require any treatment at all. Knowledge about the pathogenetic mechanisms, treatment approaches, and prognosis of these patients is limited.Keywords: primary myelofibrosis, chronic lymphocytic leukemia, coexistent

Blood Pressure Control and Predictors of Uncontrolled Hypertension

Background: Improving blood pressure control requires the identification of covariates associated with uncontrolled hypertension. Objective: To evaluate blood pressure control and predictors for uncontrolled hypertension. Design: A Cross-Sectional Study. Setting: Cardiology Out-patient Department, Salmaniya Medical Complex. Method: We documented personal factors, comorbidities, blood pressure measurements and the use of anti-hypertensive medications in 371 hypertensive patients from 1 January 2012 to 30 April 2012. Ordinal logistic regression was used to identify factors associated with poor blood pressure control. Result: The mean age of the patients was 54.6 ± 11.8 years. Two hundred forty-six (66.3%) patients had a mean blood pressure of 140/90. Age group 45-65 years, multidrug regimen, and poorly controlled diabetes were independent predictors of poor blood pressure control. Three hundred thirty-eight (91.1%) patients were on polytherapy receiving an average of three medications. The poorest blood pressure control was among diabetics, 207 (55.8%) and renal impairment patients 67 (18.1%). Conclusion: The rate of BP control could be improved in the Cardiology Secondary Care Ambulatory Department. Most of the patients were on triple combination therapy. Diabetes and renal impairment are the main risk factors for poor blood pressure control. ______________________________________________________________________________ * Consultant Adult Cardiologist Assistant Professor Department of Internal Medicine, Cardiology Unit Arabian Gulf University Salmaniya Medical Complex Kingdom of Bahrain ** Cardiology fellow Heart Center King Faisal Hospital and Research center Riyadh, Kingdom of Saudi Arabia ***Klinik fur Innere Medizin III Universitatsklinikum des Saarlandes Homburg, Germany Email: abdullarashed@yahoo.com

Underdetection of ventricular tachycardia by an implantable cardioverter–defibrillator due to a locally prolonged arrhythmia cycle length

We report the case of a 69-year-old man with idiopathic dilated cardiomyopathy, biventricular implanted cardioverter–defibrillator (ICD) and a spontaneous ventricular tachycardia during device follow-up that was not automatically treated by the ICD. Four years before a dilated left ventricle (end-diastolic diameter, 92 mm) with a severely reduced ejection fraction (EF 20 %), congestive heart failure (NYHA class III), left bundle branch block (QRS duration 200 ms) and syncope during sustained ventricular tachycardia (VT) were noted. Subsequently, a biventricular ICD (Sorin Ovatio CRT-D, leads: RA: Medtronic 4076; RV: Guidant 0185; LV: Medtronic 4194) had been implanted for secondary prevention of sudden cardiac death (SCD) and for cardiac resynchronization. On the day after implantation an electrical storm had occurred and six effective shocks had been delivered. Amiodarone therapy was initiated and no further sustained ventricular arrhythmias occurred. However, due to skeletal muscle myopotential oversensing ventricular episodes were inadequately diagnosed by the ICD. Therefore, two further defibrillation testings were performed to ensure proper sensing of VF after stepwise increasing of the sensing threshold. The last test was performed with a sensing of 2.2 mV, and permanent ICD sensitivity was set to 1.6 mV. Sensing (RA: 4 mV; RV: 15 mV) and pacing thresholds (RA: 0.75 mV/0.35 ms; RV: 0.75 mV/0.35 ms; LV: 0.75 mV/0.35 ms) remained stable during the following years and no further noise signals were detected. At device follow-up 4 years after implantation, a sustained polymorphic VT (*200 bpm) occurred spontaneously (Fig. 1) during determination of ventricular sensing. The tachycardia was hemodynamically relevant with fainting of the patient, but ICD therapy was not delivered. The ICD even performed ventricular backup-pacing during the VT. ICD detection settings were: slow VT—120/bpm, 12 cycles; VT—150/bpm, 12 cycles; FVT—200/bpm, 10 cycles; VF—240/bpm. Intracardiac electrogram (IEGM) showed undersensing of the ventricular tachycardia due to the previously programmed low sensitivity. An internal manual shock was delivered that terminated the VT. Revision of the ICD was performed on the next day. Assuming that the combination of an integrated bipolar lead with the sensing algorithm and/or signal processing of the ICD manufacturer was responsible for the previous oversensing of myopotentials, only generator exchange (Boston Scientific Cognis 100-D CRT-D) was targeted at first. For intraoperative testing, ventricular sensing was set to 1.2 mV and a polymorphic fast VT was induced by T-wave shock. Now, there was no undersensing but underdetection of the induced arrhythmia, i.e. the local V–V interval detected by the ICD was clearly longer than the apparent cycle length in the ECG resulting in failure to diagnose VT (see Fig. 2). A manually applied ICD shock with 41 J terminated the arrhythmia. Programmed ventricular stimulation using the implanted RV electrode (apical position) revealed a locally long effective refractory period (ERP) of 400 ms (basic cycle length 500 ms, 3 times threshold). A new pace-sense electrode (Medtronic 5076) was placed in septal position and an ERP of 300 ms could be measured there. During ICD testing, the induced ventricular arrhythmia was appropriately detected using a I.-O. Lee (&) C. Ukena M. Bohm A. Buob H.-R. Neuberger Klinik fur Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitatsklinikum des Saarlandes, 66421 Homburg/Saar, Germany e-mail: illkyu@hotmail.com

P367 Compliance to the scheduled treatment with infliximab. Experience in a tertiary care hospital

Background: Scheduled infliximab infusions are effective inducing and maintaining remission in IBD. Compliance with the schedule is important to avoid infusional reactions and loss of response. The aim of this report is to assess the compliance to this treatment in our Unit. Methods: All infliximab infusions received in the IBD Day Care Centre of our hospital since its opening in March 2007 were recorded. Treatment schedule consists in an induction phase 0, 2, 6 weeks and maintenance every 8 weeks. Treatment intensification was prescribed following medical criteria. Infusion delay was defined when the interval between two maintenance doses exceeded 63 days (9 weeks) or when infusion was delayed more than 5 days from calculated date in the induction phase. Intervals when treatment was stopped due to pregnancy, “drug holidays” by medical criteria, etc were excluded. We define “non-adherent patient” when at least three doses and 25% of the total are delayed. Results: 128 patients received 1508 infliximab infusions in our hospital from March 2007 to October 2011. Mean number of infusions was 11.78 (SD 8.9). 60 patients (46.9%) were male and 68 (53.1%) female. The indication was Crohn’s disease in 98 patients (76.5%) and ulcerative colitis in 30 (23.4%). Age at start of the therapy was 39 years (SD 14.6 range 15 77). 74 patients (57.81%) had some dose delayed, being 1.73 the mean number of infusion delayed (SD 2.4). Mean delay was 11.97 days (SD 16.4 median 7 days). Only 19 (14.84%) patients had at least one interval between doses greater than 12 weeks. 13 patients were defined as non-adherent (10,15%) 8 male (53.3%) and 5 female. The type of disease was Crohn in 9 cases (69.2%) and ulcerative colitis in 4 (30.8%). Differences between adherent (AP) and non-adherent patients (NAP) were analyzed: there is no difference in gender or type of disease. Statistically significant differences were found in mean age at start of the therapy (39.44 SD 14.6 AP vs 25.67 SD 5.6 NAP, p < 0.001), number of doses received 11.78 SD 8.9 AP vs 19.15 SD 7.9, NAP p < 0.001), and time on therapy (202.25 SD 9.6 AP vs 99.3 SD 94.9 NAP, p < 0.001). There is no difference in treatment intensification need between both groups; 24 of 115 patients (20.8%) in adherent vs 3 of 13 (23%) in non-adherent (p =NS). Conclusions: Our patients have a good scheduled doses compliance on infliximab therapy in our Unit, even after years of treatment. Risk factors for poor compliance are young patients and need of prolonged therapy. P368 Routine practice of iron infusion therapy in IBD T. Iqbal1 *, G. Rogler2, C. Hoffman3, J. Stein4. 1University Hospital Birmingham, Gastroenterology, Birmingham, United Kingdom, 2University Hospital Zurich, Klinik fur Gastroenterologie und Hepatologie Department fur Innere Medizin, Zurich, Switzerland, 3Vifor Pharma Ltd., Glattbrugg, Switzerland, 4Interdisciplinary Crohn Colitis Centre Rhein Main, Frankfurt, Germany

Diabetes prevalence and metabolic risk profile in an unselected population visiting pharmacies in Switzerland

BackgroundDiabetes represents one of the major health challenges in Switzerland, and early diagnosis and treatment is mandatory to prevent or delay diabetes-related morbidity and mortality. For the purpose of identifying affected individuals, early screening in pharmacies is a valuable option. In this survey, we aimed to determine blood glucose and metabolic control in an unselected population of individuals visiting Swiss pharmacies.MethodsThe subjects responded to a short questionnaire and underwent a single capillary blood glucose test for screening purposes. They were classified as normal, indeterminate, impaired fasting glucose, and diabetes according to predefined blood glucose levels.ResultsA total of 3135 individuals (mean age 56 years) in 18 cantons were screened in November 2010; of these, 4.2% (95% confidence interval [CI] 3.5–4.9) had previously been diagnosed with diabetes. Diabetes was newly diagnosed in 1.9% (95% CI 1.5–2.4), and 11.5% (95% CI 10.4–12.6) had impaired fasting glucose. Subjects with impaired glucose control had an increased body mass index, a frequent family history of diabetes, hypertension, hypercholesterolemia, smoking, and a low level of physical activity. Prevalence of impaired glucose control was different between the French/Italian-speaking part of Switzerland (new diabetes 4.9%; impaired fasting glucose 12.7%) and the German-speaking part (new diabetes 1.9%; impaired fasting glucose 10.3%).ConclusionOur study shows a 6.1% prevalence of diabetes, of which about a third (1.9%) was previously undiagnosed, and 11.5% had impaired fasting glucose. Therefore, screening initiatives in pharmacies may be suitable for detecting people with undiagnosed diabetes.

Severe dyspnoea during late pregnancy in a woman with history of asthma

Sirs: Dyspnoea is a common complaint of about 75% of healthy women during late pregnancy [1] which in many cases is not clinically relevant. However, asthma is the most common medical condition to complicate pregnancy, with episodes of severe exacerbation reported in about 10% of the women with history of asthma [2]. Moreover, 0.5–2% of all pregnancies in Western countries are also complicated by cardiovascular disease and clinical differentiation might be challenging. Cardiomyopathies are rare diseases but are thought to be the main cardiac cause for maternal mortality during pregnancy [3]. A 31-year-old woman who was regularly attending our pneumology outpatient clinic for asthma underwent routine cardiac evaluation in summer 2010 with normal findings on echocardiography examination and a NT-pro-BNP concentration of 76 pg/ml. In February 2011, the now pregnant woman (34th week of pregnancy) was introduced for pneumological consultancy with suspected exacerbation of the known asthma. The asthma was well controlled during the pregnancy so far with rare application of the quickrelief inhaler. For the preceding 10 days the patient reported progressive dyspnoea and coughing during day and night times corresponding to NYHA functional class III–IV with severe trouble sleeping and no effect of the short-acting beta agonist inhaler. Additional application of a steroid inhaler for 3 days did not improve symptoms substantially. On physical examination there was no evidence of wheezing, but bilaterally decreased breathing sound throughout basilar lung fields consistent with high diaphragm due to advanced pregnancy. Spirometry showed reduced vital capacity (2.1 l, 54% of predicted) and normal FEV1/VC ratio of 80%. Laboratory tests showed a minor proteinuria (0.8 g/24 h), normal liver enzymes and platelet count, no signs of haemolysis, Troponin T \ 0.1 lg/l and a NT-pro-BNP concentration of 1,519 pg/ml. An exacerbation of a hypereosinophilic syndrome by pregnancy was unlikely given a peripheral-blood eosinophilia rate of 0.2%. On echocardiography, the left ventricle was dilated (end-diastolic diameter 61 mm) and left-ventricular systolic function was reduced (ejection fraction 40%) with a moderate mitral-valve regurgitation, increased systolic pulmonary-arterial pressure (55–60 mmHg) and large bilateral pleural effusion (Fig. 1). The pleural effusion was drained subsequently and heart failure treatment was started with furosemide (2 9 40 mg/ day) and metoprolol (1 9 23.75 mg/day). Due to refractory heart failure symptoms and increasing evidence of placenta insufficiency after 3 days of heart failure treatment, a Caesarean section was decided which was well tolerated by the patient and the baby. Six days post section echocardiography showed further decrease of the leftventricular function (EF 25%). Relapsing pleural effusion was drained again and heart failure medication was carefully up-titrated to bisoprolol (1 9 5 mg/day), ramipril (1 9 5 mg/day), torasemide (1 9 20 mg/day) which was paralleled by symptomatic improvement (NYHA II-III). In addition, bromocriptine (2 9 2.5 mg/day) was given to stop lactation. An echocardiography examination 2 months after delivery showed an improvement of left-ventricular function (EF 39%) with only mild mitral-valve regurgitation and no evidence for pulmonary hypertension. Peripartum cardiomyopathy is an idiopathic form of dilated cardiomyopathy characterized by depressed R. Pfister (&) K. F. Frank S. Rosenkranz G. Michels Medizinische Klinik III fur Innere Medizin, Herzzentrum der Universitat zu Koln, Kerpener Str. 62, 50924 Cologne, Germany e-mail: roman.pfister@uk-koeln.de

Editorial on the manuscript entitled “Impact of Troponin I-Autoantibodies in Chronic Dilated and Ischemic Cardiomyopathy” by Andreas O. Doesch and co-workers

Despite advances in medical treatment, the prognosis of heart failure due to left ventricular systolic dysfunction is poor. In many cases in which disease progression cannot be inhibited by pharmacotherapy, heart transplantation remains the only therapeutic option. The most common causes of heart failure due to myocardial diseases are coronary heart disease, valve diseases, and cardiomyopathies [4]. Dilated cardiomyopathy (DCM) is the third most common cause of heart failure and the most frequent reason for heart transplantation [18]. This myocardial disease is characterized by ventricular chamber enlargement and progressive systolic dysfunction. In approximately 20–35% of DCM cases, a genetic background has been reported [18]. In addition, both experimental and clinical data indicate that viral infection and inflammatory processes may be involved in the pathogenesis of DCM [3, 6, 11, 27]. Abnormalities of the cellular immune system are a common feature of myocarditis and DCM. For patients with DCM, immunohistological methods have been introduced for diagnosis of myocardial inflammation. The term ‘‘inflammatory cardiomyopathy’’ has therefore been coined to describe the etiology of acquired cardiomyopathy [18]. Infiltrations with lymphocytes and mononuclear cells, as well as increased expression of cell adhesion molecules, are frequent phenomena in DCM [14, 21, 26]. These findings support the hypothesis that the immune process is still active. Patients with myocarditis and DCM demonstrate abnormalities of the humoral immune system as well. Furthermore, various autoantibodies have been detected in DCM patients: these include antibodies against mitochondrial proteins [23], cardiac myosin [2], cardiac b1-adrenergic receptors [25], muscarinergic receptors [8], and the sarcolemmal Na-K-ATPase [1]. The functional role of cardiac autoantibodies in DCM is under debate. Antibodies may reflect an inflammatory response to myocyte necrosis, thereby representing an epiphenomenon or, alternatively, may play an active role in the disease process. In patients with chronic myocarditis and cardiomyopathy, the prevalence of antibodies against cardiac myosin is associated with the deterioration of cardiac function [15]. Experimental data indicate that certain cardiac autoantibodies may play a functional role in DCM: antibodies against the ADP/ATP carrier interact with the calcium channel and possess cardiotoxic properties [23]. In the plasma of patients with DCM, negative inotropic antibodies are detectable that decrease the calcium transients of isolated cardiomyocytes [7]. A recent study by Li et al. [17] demonstrated that anti-cardiac myosin antibodies induced by immunization of rats with cardiac myosin target the b-adrenergic receptor on the heart cell surface. Passive transfer of purified antibodies from cardiac myosinimmunized rats results in IgG deposition and apoptosis in the heart, leading to a cardiomyopathic heart disease phenotype in recipients. Immunization of rodents against peptides derived from cardiovascular G-protein receptors induces morphological changes of myocardial tissue resembling DCM [9, 19]. A recent study by Jahns et al. [12] investigated the pathogenic significance of autoantibodies that target cardiac b1-adrenoceptors in DCM: rats immunized against the second extracellular loop of cardiac b1-receptors developed progressive left-ventricular dilatation and dysfunction. Sera transferred from these immunized animals to unsensitized S. B. Felix (&) Klinik fur Innere Medizin B, Ernst-Moritz-Arndt-Universitat Greifswald, Friedrich-Loeffler Str. 23a, 17475 Greifswald, Germany e-mail: felix@uni-greifswald.de

The year 2009 in Clinical Research in Cardiology

Clinical Research in Cardiology is going to enter its fourth year as the journal of the German Cardiac Society with a focus on scientific aspects of clinical research and clinical education in cardiology. It is a member of the Journals’ Club of the European National Societies, who reported their principles of publication in 2008 [1]. Compared to the year 2008 [2], the journal has further improved its visibility as shown by the latest data from the Institute for Scientific Information (ISI). As evidenced by the increased number of submitted manuscripts, there is evidence that there is an increased acceptance in the scientific community of clinical cardiology. From 1 December 2008 until 30 November 2009, 372 papers were submitted (including 39 resubmissions from 2008). The acceptance rate was 30.5% corresponding to 69.5% rejection rate. Time to first decision was 31.4 days. During the last year, 692 reviews were invited. Among those, 453 reviewers completed their reviews and 138 declined to review the manuscripts. 34 reviewers did not respond to the invitation. The majority of manuscripts were accepted or rejected after initial submission or after first revision. The details can be viewed in Table 1. Figure 1 shows the number of impact factor relevant articles from 2006 to 2009. These types of articles only include reviews and original papers but not clinical correspondence contributions, editorials and abstracts. There was a decline in the number of published reviews and original papers, whereas the number of clinical correspondence articles, editorials and abstracts remained similar (not shown). In parallel, citations steadily increased from 2006 to 2009 from 31 to 726 (the column in 2009 covered all articles which were published until 30 November 2009). These citations also include the impact factor relevant articles as well as clinical correspondence articles, which also contribute to the impact factor in a positive way when they are cited. The number of citations includes all citations of previously published articles in Clinical Research in Cardiology. For the impact factor 2009 (which will be published in 2010) only the citations to articles of the publication years 2007 and 2008 will be relevant. Figure 2 summarizes the impact factor of the ‘‘Zeitschrift fur Kardiologie’’ (left panel) and of Clinical Research in Cardiology (right panel). The impact factor in 2008 is already higher than those ever achieved by the ‘‘Zeitschrift fur Kardiologie’’. However, much to our satisfaction, the impact factor 2008, published in 2009 by the Institute for Scientific Information was 2.418 indicating that the development of the journal’s visibility reflected by citations of articles of the relevant years is improving. Again, there was a list of well-published articles. In Table 2, the ten best cited articles from the years 2007 and 2009 are listed. It can be seen that those articles published already in 2007 tended to have higher citation numbers. However, some articles are also well cited after the first years of publication [5, 9, 10]. Among the best publications, there were not only original articles [3, 6, 8, 9, 12] but also reviews [4, 5, 10, 11] and one article as a meeting update [7]. In particular, from those recently published M. Bohm (&) H. Katus Universitatsklinikum des Saarlandes, Klinik fur Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Kirrberger Str. 1, 66424 Homburg/Saar, Germany e-mail: boehm@uks.eu

Leukocytoclastic vasculitis and myocardial infarction as presenting manifestations of infective endocarditis: a case report

In April 2009, a 32-year-old female patient was referred to our hospital with acute chest pain. She was diabetic, nicotine dependent and had a family history of coronary heart disease. The electrocardiogram showed a previously documented complete left bundle branch block. Cardiac troponin T was elevated (1.18 ng/ml, CK and CK-MB normal, LDH 333 U/l), C-reactive protein serum concentration was 157 mg/l (normal \ 5), white blood count was normal. Coronary angiography showed a thrombotic occlusion of the mid-LAD as culprit lesion (Fig. 1a, left panel). Additionally, a smooth lesion in the small PDA of the right coronary artery could be detected (Fig. 1a, right panel). The patient’s past medical history was complex. Aortic valve replacement with a biological prosthesis had been performed in 2006 due to infective endocarditis. Interestingly, 6 months before the acute coronary syndrome, i.e. in November 2008, the patient had been admitted to an external department with diffuse, non-symmetric arthralgia and a recurrent purpuric rash over her distal lower extremities. Hemorrhagic leukocytoclastic vasculitis had been diagnosed by skin biopsy (Fig. 1b). Laboratory tests conducted at that time had revealed a profound reduction in renal clearance (creatinine 2.4 mg/dl, cystatin C 3.3 mg/l, GFR 16-20 ml/min). Urinanalysis had shown proteinuria (0.84 g/24 h) and glomerular hematuria with detection of acanthocytes. These findings suggest that renal impairment had been caused by a glomerulonephritis. Monotherapy with prednisolone had been performed followed by chemotherapy with cyclophosphamid due to recurrence of symptoms after dose reduction of prednisolone. At the current admission to our department with an acute coronary syndrome, revascularization was performed by direct implantation of a bare metal stent in the midLAD. Because of the small vessel diameter there was no indication for a PCI of the PDA. However, the unusual lesion pattern in two distinct coronary vessels in a young patient with no further evidence of coronary heart disease was highly suspicious for coronary embolism, particularly in the light of the patient’s history of valve replacement 2 years earlier. During admission, the patient was recurrently subfebrile (\38 C), serum concentration of C-reactive protein remained elevated. Transesophageal echocardiography was performed twice. No typical endocarditic vegetations could be detected. However, thickening of the cusps of the bioprosthesis only two years after implantation as well as a mild aortic regurgitation were noticed. Immunosuppressant therapy was stopped. Serial blood cultures drawn at consecutive days yielded Granulicatella adiacens which proved to be highly sensitive to penicillin (MIC 0.004 mg/l). In one additional sample a b-lactamase positive, penicillin-resistant Staphylococcus aureus was obtained which was tested to be sensitive to oxacillin (MIC 0.25 mg/l). These positive microbiological results and the assumed embolic coronary event made the diagnosis of prosthetic valve endocarditis very likely and J. Poss M. Bohm H. Kilter (&) Universitatsklinikum des Saarlandes, Klinik fur Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Kirrberger Strase, 66421 Homburg/Saar, Germany e-mail: heiko.kilter@uks.eu

Patients with insulin-dependent diabetes or coronary heart disease following rehabilitation express serum fractalkine levels similar to those in healthy control subjects

The chemokine and adhesion molecule fractalkine and its receptor CX(3)CR1 have emerged as interesting regulators in inflammation and related atherosclerosis. The pro-inflammatory status may be counteracted by appropriate treatment, such as in rehabilitation. We compared serum fractalkine concentrations of 46 patients with coronary heart disease (CHD) and 47 insulin-dependent diabetic patients (IDDM) following rehabilitation with those of 50 control subjects. Following rehabilitation serum fractalkine levels (477 + or - 225 pg/mL) in CHD patients were similar to those in control subjects (572 + or - 205 pg/mL; P = 0.303), whereas fractalkine levels were lower in IDDM patients (430 + or - 256 pg/mL; P = 0.042). No significant difference between CHD and IDDM patients was present (P = 0.319). Postprandial hyperlipemia may influence inflammation; thus, we investigated fractalkine levels four and eight hours after inducing postprandial hyperlipemia. However, we did not find any significant alterations in CHD and diabetic patients, whereas the fractalkine levels in controls were reduced. In vitro, lipofundin used as a hyperlipemic stimulus was added to vessel wall cells and reduced fractalkine levels. Low fractalkine levels in patients attending rehabilitation indicate a beneficial effect of the rehabilitation procedure on innate inflammatory pathways, such as the chemokine and adhesion molecule fractalkine.