Soluble Suppression of Tumorigenicity 2 (sST2) in Patients with Predominantly Decompensated Right Heart Failure-A Prospective Observational Study.

Right heart failure is a major challenge in clinical practice. Soluble Suppression of Tumorigenicity-2 (sST2), a member of the interleukin-1-receptor family, may have clinical prognostic value. The aim of this study was to analyze whether sST2 correlates with signs of acute right heart decompensation. This prospective single-center study included 50 patients admitted for clinical signs of predominant right heart decompensation. Signs of reduced blood supply to other organs (e.g., renal function parameter, troponin T, NT-proBNP), diuretics, and signs of venous congestion (inferior vena cava (IVC) diameter) with fluid retention (weight gain, peripheral edema) resulting from reduced RV function were analyzed. The degree of peripheral edema was defined as none, mild (5-6 mm depressible, regression in 15-60 s) or severe (>7 mm depressible, regression in 2-3 min). sST2 levels were measured at the day of hospitalization. A total of 78.7% showed severe peripheral edema. The median concentration of sST2 was 35.2 ng/mL (25.-75. percentiles 17.2-46.7). sST2 is correlated with the peripheral edema degree (rSpearman = 0.427, p = 0.004) and the diameter of IVC (r = 0.786, p = 0.036), while NT-proBNP (r = 0.114, p = 0.456), troponin T (r = 0.123, p = 0.430), creatinine-based eGFR (r = -0.207, p = 0.195), or cystatin C-based eGFR (r = -0.032, p = 0.839) did not. sST2, but no other established marker, is correlated with peripheral and central fluid status in patients with decompensated right heart failure.

Which Factors Influence the Immensely Fluctuating CRT Implantation Rates in Europe? A Mixed Methods Approach Using Qualitative Content Analysis Based on Expert Interviews.

(1) Background: Cardiac resynchronisation therapy (CRT) is nowadays an indispensable treatment option for heart failure. Although the indication is subject to clear cross-national guidelines by the European Society of Cardiology (ESC), there is immense variation in the number of implantations per 100,000 inhabitants in Europe, especially in German-speaking countries (Germany, Austria and Switzerland). The aim of the present study was to identify possible factors for these differences using a qualitative research approach. (2) Methods: Semi-standardized interviews were conducted with 11 experts in the field of CRT therapy (3 experts from Germany, 4 from Austria and 4 from Switzerland) using a pre-prepared interview template and analysed according to Mayring's qualitative content analysis. (3) Results: The main factors identified were the costs of purchasing the devices and the financing systems of the respective healthcare systems, although cost pressure still seems to play a subordinate role in the German-speaking countries. Moreover, "lack of implementation of ESC guidelines", "insufficient training" and "lack of medical infrastructure" could be excluded as potential reasons. (4) Conclusions: Economic factors, but not a lack of adherence to ESC guidelines, seem to have a major influence on the fluctuating implantation figures in German-speaking countries, according to the unanimous assessment of renowned experts.

Impact of socioeconomic aspects on cardiac implantable electronic device treatment and application of the EHRA guidelines : A European comparison.

BACKGROUND: Cardiac implantable electronic devices (CIED) have become an indispensable part in everyday clinical practice in cardiology. The indications for CIED implantation are based on the guidelines of the European Heart Rhythm Association (EHRA). Nevertheless, numbers of CIED implantations in Europe are subject to considerable differences. We hypothesized that reimbursements linked to the respective health systems may influence implantation behavior. METHODS: Based on the EHRA White Book 2017, CIED implantation data as well as socioeconomic key figures were collected, in particular gross domestic product (GDP) and share of gross domestic product spent on healthcare. Implantation numbers for pacemakers, implantable cardioverter defibrillators and cardiac resynchronization treatment as well as all in total were assessed, compared with the health care expenditures and visualized using heat maps. RESULTS: Total implantation numbers per 100,000 inhabitants varied from 196.53 (Germany) to 2.81 (Kosovo). Higher implantation numbers correlated moderately with a higher GDP (r = 0.456, p 0.002) and higher health expenditure (r = 0.586, p < 0.001). The annual financial resources per inhabitant were also subject to fluctuations ranging from 9476 $ (Switzerland) to 140 $ (Ukraine); however, there were countries with high financial means, such as Switzerland or Scandinavian countries, which showed significantly lower implantation rates. CONCLUSION: There were considerable differences in CIED implantations in Europe. These seem to be explained in part by socioeconomic disparities within Europe. Also, a potential influence by the respective remuneration system is likely.

Endothelialization and Inflammatory Reactions After Intracardiac Device Implantation.

BACKGROUND: Due to the advances in catheter-based interventional techniques, a wide range of heart diseases can now be treated with a purely interventional approach. Little is yet known regarding biological effects at the intracardiac implantation site or the effects on endothelialization and vascular inflammation in an in vivo environment. Detailed knowledge of ongoing vascular response, the process of endothelialization, and possible systemic inflammatory reactions after implantation is crucial for the clinical routine, since implants usually remain in the body for a lifetime. METHODS: For this narrative review, we conducted an extensive profound PubMed analysis of the current literature on the endothelialization processes of intracardially implanted devices, such as persistent foramen ovale (PFO) occluders, atrial septal defect (ASD) occluders, left atrial appendage (LAA) occluders, transcatheter aortic valve implantations (TAVIs), and leadless pacemakers. Additionally, the known biological activities of common metallic and synthetic components of intracardiac devices in an "in vivo" setting have been evaluated. RESULTS: Nitinol, an alloy of nickel and titanium, is by far the most commonly used material found in intracardiac devices. Although allergies to both components are known, implantation can be performed safely in the vast majority of patients. Depending on the device used, endothelialization can be expected within a time frame of 3-6 months. For those patients with a known allergy, gold coating may be considered as a viable alternative. CONCLUSION: Based on our analysis, we conclude that the vast majority of devices are made of a material that is both safe to implant and nontoxic in long-term treatment according to the current knowledge. The literature on the respective duration of endothelialization of individual devices however is highly divergent.

Progression of Chronic Kidney Disease and All-Cause Mortality in Patients with Tricuspid Regurgitation.

Aim: The impact of chronic kidney disease (CKD) on patient-related outcomes in patients with tricuspid regurgitation (TR) is well known. However, the impact of the progression of CKD in patients with TR and potentially modifiable risk factors of progressing CKD is unknown. Methods: 444 consecutive adult patients with TR and CKD stage 1−4 admitted in an inpatient setting between January 2010 and December 2017 were included. During a median follow-up of two years, eGFR and survival status were collected. Independent risk factors for CKD progression and all-cause mortality were determined. Patient survival statuses were grouped according to different combinations of the presence or absence of CKD progression and the TR grade. Results: Progression of CKD (OR 2.38 (95% confidence interval 1.30−4.35), p = 0.005), the grade of TR (OR 2.38 (1.41−4.00), p = 0.001) and mitral regurgitation (OR 1.72 (1.20−2.46), p = 0.003) were independent risk factors for all-cause mortality. Haemoglobin at admission (OR 0.80 (0.65−0.99), p = 0.043) and the presence of type 2 diabetes (OR 1.67 (1.02−2.73), p = 0.042) were independent risk factors for CKD progression. The combination of the status of CKD progression and the TR grade showed a stepwise pattern for all-cause mortality (p < 0.001). Patients with CKD progression and TR grade 1 had comparable all-cause mortality with patients without CKD progression but with TR grade 2 or 3. Even in patients with TR grade 1, the risk for all-cause mortality doubled if CKD progression occurred (OR 2.49 (95% CI 1.38−4.47), p = 0.002). Conclusion: CKD progression appears to be a risk factor for all-cause mortality in patients with TR. Anaemia and diabetes are potential modifiers of CKD progression.

Incidence and risk factors for acute kidney injury in patients with cardiac implantable electronic devices undergoing transvenous lead removal.

BACKGROUND: This study aimed to investigate the incidence and potentially modifiable risk factors of acute kidney injury (AKI) in patients with cardiac implantable electronic devices (CIED) admitted for removal of infected and non-infected transvenous leads. MATERIALS AND METHODS: In this observational cohort study, data from 147 consecutive patients with CIED undergoing transvenous lead removal were analyzed. Study endpoint was AKI according to the KDIGO criteria. Multivariable logistic regression analysis was performed to identify independent risk factors for AKI. RESULTS: Lead removal was performed due to systemic infection (50.3%), isolated pocket infection (34.0%), pocket or lead perforation without infection (13.6%), and endocarditis (2.0%). Out of 147 patients, 34 (23.1%) developed AKI (82.4% stage 1, 8.8% stage 2, and 8.8% stage 3). There was no difference regarding incidence of AKI when separated by infectious vs. non-infectious lead status (25.5 vs. 25.0%) p = 0.605. Defibrillator lead type (HR 24.55, CI 2.41 - 249.97, p = 0.007), necessity to perform laser-assisted lead removal (HR 5.41, CI 1.12 - 26.13, p = 0.035), and time from initial implantation to lead removal (HR 1.01, CI 1.00 - 1.02, p = 0.013) were independent risk factors for AKI. Also, AKI was associated with in-hospital mortality (HR 8.44, CI 2.08 - 34.33, p = 0.003). CONCLUSION: Almost a quarter of patients undergoing transvenous lead removal developed AKI. Independent modifiable risk factors for AKI were identified. The role of procedure-related risk factors for AKI, such as lead type and use of laser, needs further evaluation in these patients.

Interventional Treatment of Access Site Complications During Transfemoral TAVI: A Single Center Experience.

Introduction: Transcatheter aortic valve implantation (TAVI) has rapidly developed over the last decade and is nowadays the treatment of choice in the elderly patients irrespective of surgical risk. The outcome of these patients is mainly determined not only by the interventional procedure itself, but also by its complications. Material and Methods: We analyzed the outcome and procedural events of transfemoral TAVI procedures performed per year at our institution. The mean age of these patients is 79.2 years and 49% are female. All the patients underwent duplex ultrasonography of the iliac arteries and inguinal vessels before the procedure and CT of the aorta and iliac arteries. Results: Transfemoral access route is associated with a number of challenges and complications, especially in the patients suffering from peripheral artery disease (PAD). The rate of vascular complications at our center was 2.76% (19/689). Typical vascular complications (VC) include bleeding and pseudoaneurysms at the puncture site, acute or subacute occlusion of the access vessel, and dissection or perforation of the iliac vessels. In addition, there is the need for primary PTA of the access pathway in the presence of additional PAD of the common femoral artery (CFA) and iliac vessels. Balloon angioplasty, implantation of covered and uncovered stents, lithoplasty, and ultrasound-guided thrombin injection are available to treat the described issues. Conclusion: Interventional therapy of access vessels can preoperatively enable the transfemoral approach and successfully treat post-operative VC in most of the cases. Training the heart team to address these issues is a key focus, and an interventional vascular specialist should be part of this team.

Is It Legitimate for Society to Intervene in the Way Citizens Live Their Lives When the Cost of Health Care Has to Be Borne by the General Public?-General Considerations and Special Implications During the Covid-19 Pandemic.

Over the last few decades, the perception of disease has changed significantly. In the concept of the sick person's role it should be the aim of every person to keep health at a good level for as long as possible. Several examples can be found where, however, a disease can be caused or worsened by a person. Examples include unhealthy diet, alcohol consumption leading to atherosclerosis and diabetes, or smoking, leading to lung cancer and COPD. There are also other appropriate examples where there is a potential for conflict between the autonomy of the individual and health. Improving public health should be the main objective of any health system. However, the more the impact is on personal freedom (and there is no extraneous danger), the more an attempt should be made to achieve this through the motivation of each individual to support the desire for a healthy lifestyle, rather than through legal prohibitions or penalties. The situation is even more complex in the case of the Covid-19 pandemic. In this context too, personal freedom is restricted in many areas and some people feel, for example, that compulsory masks or the prohibition of large crowds are serious encroachment on their autonomy. However, even in this case, the risk of possible external threats from the spread of the virus outweighs the right to personal choice and freedom. To sum up, it is necessary to balance the two principles - autonomy and interference in them in the interests of public health.

The Value of Fetuin-A as a Predictor to Identify Takotsubo Patients at Risk of Cardiovascular Events.

INTRODUCTION: Takotsubo cardiomyopathy (TTC) remains a life-threatening disease with the risk of decompensated heart failure and arrhythmias. Valid markers for the prediction of outcome are unavailable. The novel biomarkers fetuin-A, matrix metalloproteinases-2 (MMP-2), myeloperoxidase (MPO), Syndecan-1 and CD40-L show promising results for risk stratification of cardiovascular patients. Nevertheless, clinical implementation has not been investigated in TTC patients. METHODS: To investigate this issue, we evaluated clinical complications in 51 patients hospitalized for TTC and measured the serum levels of fetuin-A, MPO, MMP-2, Syndecan-1 and CD40-L within 24 h after admission. RESULTS: Serum levels of Fetuin-A correlated inversely with the risk of cardiac decompensation and all cause complications within the acute phase of TTC. Fetuin-A levels over 190.1 µg/mL (AUC: 0.738, sensitivity 87.5%, specificity: 52.6%) indicate an acute phase of TTC without cardiac decompensation. Despite lower fetuin-A levels in patients with all cause complications, the combined endpoint remained slightly unmet (p = 0.058, AUC: 0.655). Patients with fetuin-A levels over 213.3 µg/mL are at risk of experiencing hemodynamic relevant rhythm disorders (AUC: 0.794; sensitivity: 75.0%, specificity: 79.1%). Other biomarkers failed to reveal a prognostic impact. Pro-BNP and hs troponin levels at admission did not predict adverse cardiac events. CONCLUSION: Fetuin-A is a promising marker in our study and could be of benefit for the prediction of short-term adverse cardiac events in TTC patients. Therefore, fetuin-A might be of value to evaluate an individual's risk for complications within the acute phase of TTC and to individually choose the time of intensive care and hospitalization.

Direct Flow Medical vs. Edwards Sapien 3 Prosthesis: A Propensity Matched Comparison on Intermediate Safety and Mortality.

Aims: To compare intermediate performance and mortality rates in patients, who underwent transcatheter aortic valve implantation (TAVI) with two different types of prostheses: Edwards Sapien 3 (ES3) and Direct Flow Medical (DFM). Methods and Results: 42 consecutive patients implanted with a DFM prosthesis for severe aortic stenosis were matched 1:1 with an equal number of patients, who received an ES3 during the same period. Primary endpoint was mortality. MACE, as a composite of all-cause death, stroke, and re-do-procedure (valve-in-valve), was defined as secondary endpoint. Moreover, we compared NYHA class, NT-proBNP-levels and the extent of restenosis. Patients were followed for 2 years. DFM patients showed echocardiographic elevated mean pressure gradients compared to ES3 patients before discharge (11.2 mmHg ± 5.3 vs. 3.5 mmHg ± 2.7; p < 0.001) and upon 6-months follow-up (20.3 mmHg ± 8.8 vs. 12.3 mmHg ± 4.4; p < 0.001). ES3 candidates showed superior NYHA class at follow-up (p = 0.001). Kaplan-Meier analysis revealed significantly worse survival in patients receiving a DFM prosthesis compared to ES3 (Breslow p = 0.020). MACE occurred more often in DFM patients compared to ES3 (Breslow p = 0.006). Conclusions: Patients receiving DFM valve prostheses showed worse survival and higher rates in MACE compared to ES3. Prosthesis performance regarding mean pressure gradients and patients' NYHA class also favored ES3.

Natural course of tricuspid regurgitation and prognostic implications.

OBJECTIVE: Functional tricuspid regurgitation (TR) is a frequent finding in echocardiography. Literature suggests significant TR is associated with poor prognosis. Still, data remain limited. This study aimed to evaluate long-term prognostic implications in patients with TR. METHODS: In this observational cohort study, data from 1650 consecutive patients were analysed. Primary endpoint was all-cause mortality. Mean follow-up time was 1090 days. TR grades at baseline and follow-up were compared. Survival analyses were performed to identify prognostic factors. RESULTS: At baseline, 14.1% patients showed no, 63.8% mild, 17.4% moderate and 4.7% severe TR. 359 patients (21.8%) died within the study period. TR at baseline was associated with excess mortality. Moderate and severe TR were of prognostic implication in all subgroups irrespective of systolic pulmonary artery pressure (sPAP) (

Right Ventricular Longitudinal Strain Predicts Survival in Patients With Functional Tricuspid Regurgitation.

BACKGROUND: Functional tricuspid regurgitation (TR) is a frequent finding in echocardiography. Despite general consent that right ventricular (RV) dysfunction impacts outcome of patients with TR, it is still unknown which echocardiographic parameters most accurately reflect prognosis. In this study we aimed to evaluate the prevalence of RV dysfunction and its prognostic value in patients with TR. METHODS: Data from 1089 consecutive patients were analysed. Tricuspid annular plane systolic excursion (TAPSE), fractional area change, and right ventricular free wall longitudinal strain (RV strain) were used to define RV dysfunction. Patients were followed for 2-year all-cause mortality. For prediction of survival, reclassification and C statistics of RV functional parameters using TR grade as reference model were performed. RESULTS: Among the patients studied, 13.9% showed no TR, 61.2% had mild TR, 19.6% had moderate TR, and 5.3% had severe TR. The TR grade was associated with increased mortality (log rank, P < 0.001). Impaired RV strain and TAPSE were independent predictors for mortality (RV: hazard ratio [HR], 1.130; 95% confidence interval [CI], 1.099-1.160; P < 0.001; TAPSE: HR, 1.131; 95% CI, 1.085-1.175; P < 0.001). Both RV strain and TAPSE improved the reference model for survival prediction (RV: integrated discrimination improvement [IDI], 0.184; 95% CI, 0.146-0.221; P < 0.001; TAPSE: IDI, 0.057; 95% CI, 0.037-0.077; P < 0.001). CONCLUSIONS: Echocardiographic evaluation of RV function appears to useful for patients with TR. Assessment of RV strain provides additional value for prediction of 2-year mortality.

How low is "low-flow" in aortic stenosis? A retrospective analysis of patients with true low-flow/low-gradient aortic stenosis undergoing TAVI.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a valuable treatment option for patients with reduced left ventricular ejection fraction (LVEF) and low-flow/low-gradient (LF/LG) aortic stenosis (AS). According to current literature, the presence of severe AS is unlikely in case of severely reduced LVEF and mean pressure gradient (meanPG) below 30 mmHg. However, a considerable number of patients presenting with typical clinical symptoms of severe AS, show gradients below 30 mmHg. We hypothesized, that these patients undergoing TAVI do have a measurable clinical benefit and an improved LVEF. METHODS: In this single center retrospective cohort study, data from 1199 patients undergoing TAVI between 2013 and 2017 was analyzed. A 6-month follow-up was performed to assess changes in NT-proBNP, NYHA-class, and LVEF. RESULTS: Thirty patients presented with LVEF<35%, an aortic valve area (AVA<1 cm2), and a meanPG below 30 mmHg. Mean logistic EuroSCORE II was 24.05±10.9. Most patients (56%) showed improved NYHA-class upon follow-up. NT-proBNP-levels decreased from 3.901 pg/mL IQR 10.880 to 1.491 pg/mL IQR 2.245 (P<0.001). LVEF increased from 30% IQR 6.25 to 40% IQR 15 (P<0.001). CONCLUSIONS: Based on our findings TAVI represents a valuable treatment option even in patients with LF/LG AS and PGmean below 30mmHg.

Emerging trends in cardiovascular research: HFpEF in the spotlight. A bibliometric analysis of the years 2009-2016.

INTRODUCTION: Up to 50% of patients suffering from acute decompensated heart failure show normal or slightly reduced left ventricular ejection fraction (LVEF). This syndrome, which is known as heart failure with preserved ejection fraction (HFpEF) is associated with increasing age. Epidemiological studies could portrait an increasing importance and an even emerging prevalence in the past decades. Still, there is currently no evidenced based medical treatment option available. Our aims were to identify upcoming trends and emerging concepts and to point out important centers in the global research of HFpEF. EVIDENCE ACQUISITION: We performed a bibliometric study on current science in the field of HFpEF to identify study characteristics, impact factors and the countries of origin of basic and clinical studies that were published within the years 2009 to 2016. We further prepared density equalizing maps for visualization of the obtained data. EVIDENCE SYNTHESIS: A total of 5413 studies was screened, of which 794 were found eligible. The scientific output in clinical studies rose from 25 in 2009 to 165 in 2016. Most of the publications had a clinical topic, followed by studies on new imaging techniques. Basic research trials were by far beyond. The USA, Japan and Germany were identified as the most important national contributors to global scientific output. CONCLUSIONS: This first bibliometric study in the field of HFpEF shows a substantial increase of research within the last decade, mainly in the USA, Japan, and continental Europe. As an ongoing therapeutic trend in this field, we identified RAAS-blockade and 5-phosphodiesterase-inhibition.

Economic assessment of traditional surgical valve replacement versus use of transfemoral intervention in degenerative aortic stenosis.

INTRODUCTION: The aim of this study was to provide an economic assessment of interventional vs. surgical aortic valve replacement in the context of cost-effectiveness. Aortic stenosis represents the most common form of degenerative valvular heart diseases. As life expectancy increases, an even emerging prevalence is expected. Over decades, surgical replacement was considered as the method of choice. Up to one third of the patients were not eligible for surgery, as their estimated peri-operative risk was too high. In the early 2000s a catheter-based technique has been developed, being an alternative treatment option for patients, considered to be inoperable. EVIDENCE ACQUISITION: A systematic analysis of current literature was performed from September 2018 to December 2018. All suitable data in the field was obtained from Pubmed and Google/Google scholar. The search terms "TAVI AND costs," "TAVR and costs" and "aortic valve replacement AND costs" was entered in the search field, showing an overall amount of 317 publications. In a next step all obtained publications were screened by expert hand selection. EVIDENCE SYNTHESIS: Recently the Food and Drug Association (FDA) approved transcatheter aortic valve replacement (TAVR) in the low-risk setting. Nevertheless, concerns on the higher price remain. We performed an analysis of current literature on aortic stenosis and economic aspects. Out of 322 screened publications, 7 studies were found eligible by expert hand selection. Based on the predefined payment readiness of the analyzed healthcare system, TAVR appeared to have a slightly better cost effectiveness. Initial results within the early era seemed to be inconsistent. Recent publications showed, TAVR might be of more cost effectiveness when using the newest generation devices and a profound clinical experience is guaranteed. CONCLUSIONS: We assume, that TAVR will not only be the method of choice for the treatment of aortic stenosis in many patients. As the valves are getting cheaper, TAVR might even be superior to conventional heart surgery from an economic point of view.

Visualisation of the tricuspid valve using a new 3D echocardiographic scoring system.

With rising focus on interventional treatment of the tricuspid valve (TV), the need for good echocardiographic imaging increases. Aim of this study was to develop a scoring system describing how accurate three dimensional (3D) echocardiographic imaging of TV and its anatomical structures is. METHODS AND RESULTS: In this retrospective exploratory cohort study, we analysed data from consecutive patients undergoing transoesophageal echocardiography (TOE) and transthoracic echocardiography (TTE). 3D sequences were stored using eight different views. In each view, scoring focused on visualisation of five (in TOE 6) anatomical structures with a maximum of three points per structure for excellent imaging quality. We compared the scores of patients with and without relevant tricuspid regurgitation (TR) (cut-off effective regurgitant orifice 0.4 cm² measured in two-dimensional (2D) TTE using velocity time integral and proximal isovolumetric velocity area). 108 consecutive patients were examined, 40.7% presented with relevant TR. With the exception of coaptation, a higher score was achieved for all structures in TOE than in TTE. TV ring (TVR) was easiest to visualise with TOE in four-chamber view (4 CV) (2.42±0.67 points) presenting the highest score independent of anatomical structure and view. Posterior leaflet had best imaging scores in TOE in 4 CV (2.0±0.86) compared with TTE in 4 CV (1.64±0.80), p=0.001. Patients with relevant TR had significantly better 3D imaging scores in 4 CV compared with patients without relevant TR (TTE p<0.013, TOE p<0.002). CONCLUSION: 4 CV delivers the most detailed information in TTE, whereas multiple views deliver good scores in TOE. As TVR is easiest to visualise, most of the patients would be suitable for a ring-based echocardiography-guided intervention. The score enables a standardised comparison of image quality.

Potential mechanisms of endothelialisation in individuals implanted with a leadless pacemaker systems: An experimental in vitro study.

BACKGROUND: Leadless pacemaker technology is a promising upcoming field in clinical rhythmology. Today, the most commonly used system in the clinical setting is the Micra™ leadless pacemaker system (Medtronic). In autopsies of patients who witnessed non-pacemaker associated death, unexpected ingrowth/encapsulation within the wall of the right ventricle was reported. The occurrence of a complete encapsulation was not expected and the process of endothelialisation remains unclear. We hypothesized, that a local inflammatory response might be the cause of these findings. The aim of our experimental in-vitro study was to investigate the effect of the Micra™ system and its single components on inflammatory processes. METHODS: For this purpose, whole Micra™ pacemakers were incubated in heparin plasma from 25 healthy volunteers for 48 h at 37 °C. Furthermore, 1 g gold, steel, titanium, tungsten and nitinol wires were incubated in heparin plasma for 48 h at 37 °C as well (n = 10). To detect eventual inflammatory processes, interleukin- (IL) 1ß, IL-6, and tumor necrosis factor alpha (TNF-α), the chemokine IL-8 were measured using enzyme-linked immunosorbent assay (ELISA). Additionally, the level of transforming growth factor beta 1 (TGF-ß1) and vascular endothelial growth factor (VEGF) were analysed. RESULTS: ELISA analyses showed that the whole Micra system leads to a significant increase in the inflammatory cytokine IL-6 which correlates with the data gained by the incubation of whole blood with the different wires. In particular, 0.5 g of tungsten showed a significant rise of IL-6 which could also be found for IL-1ß and IL-8. CONCLUSIONS: The in vitro study of the Micra system showed that the material composition led to an onset of inflammatory processes in whole blood. Consequently, one may speculate that the composition of Micra pacemaker may have a local inflammatory, though subclinical, effects in patients implanted with a Micra™ pacemakers.

Disease-specific characteristics of vascular cell adhesion molecule-1 levels in patients with peripheral artery disease.

Peripheral arterial disease (PAD) is one of the most common manifestations of systemic atherosclerosis. The prevalence of unrecognized PAD is high, leading to a lack of opportunity to detect subjects at a high risk for cardiovascular events. Inflammatory processes play an important role in the disease initiation as well as in the disease progression. Vascular cell adhesion molecule 1 (VCAM-1), a biomarker of endothelial dysfunction, appears to be an important mediator in inflammatory processes. Therefore, we hypothesized that in patients with PAD, circulating VCAM-1 might be elevated due to its function in mediating adhesion of immune cells to the vascular endothelium in the process of endothelial dysfunction and inflammation, and, therefore, applicable as a diagnostic biomarker. A total of 126 non-consecutive patients were enrolled in this study, of whom 51 patients had typical clinical manifestations of PAD and as controls 75 patients with no history of PAD or cardiovascular disease. All serum samples were obtained either during hospitalization or during out-patient visits and analyzed for VCAM-1 by the ELISA. Compared with controls, median levels of VCAM-1 were significantly elevated in patients suffering from PAD (953 vs. 1352 pg/ml; p < 0.001). Furthermore, VCAM-1 appeared to be highly discriminative for the detection of PAD (AUC = 0.76; CI 0.67-0.83). We could not observe dynamics related to increasing disease stages according to Rutherford classes in patients with apparent PAD. VCAM-1 was shown to be a potential discriminator and biomarker for the severity of systemic atherosclerosis. In a logistic regression analysis, VCAM-1 was robustly associated with the diagnosis of PAD, even after correction for clinically relevant cofounders (namely age, arterial hypertension, diabetes and LDL levels). Thusly, VCAM-1 might serve as a biomarker for PAD screening and detection.

Visualization and appearance of artifacts of leadless pacemaker systems in cardiac MRI : An experimental ex vivo study.

BACKGROUND: Leadless pacemaker systems are an important upcoming device in clinical rhythmology. Currently two different products are available with the Micra system (Medtronic) being the most used in the clinical setting to date. The possibility to perform magnetic resonance imaging (MRI) is an important feature of modern pacemaker devices. Even though the Micra system is suitable for MRI, little is yet known about its impact on artifacts within the images. OBJECTIVE: The aim of our ex vivo study was to perform cardiac MRI to quantify the artifacts and to evaluate if artifacts limit or inhibit the assessment of the surrounding myocardium. METHODS: After ex vivo implantation of the leadless pacemaker (LP) in a porcine model, hearts were filled with saline solution and fixed on wooden sticks on a plastic container. The model was examined at 1.5 T and at 3 T using conventional sequences and T2 mapping sequences. In addition, conventional X­rays and computed tomography (CT) scans were performed. RESULTS: Correct implantation of the LP could be performed in all hearts. In almost all MRI sequences the right ventricle and the septal region surrounding the (LP) were altered by an artifact and therefore would sustain limited assessment; however, the rest of the myocardium remained free of artifacts and evaluable for common radiologic diagnoses. A characteristic shamrock-shaped artifact was generated which appeared to be even more intense in magnitude and brightness when using 3 T compared to 1.5 T. CONCLUSION: The use of the Micra system in cardiac MRI appeared to be feasible. In our opinion, it will still be possible to make important clinical cardiac MRI diagnoses (the detection of major ischemic areas or inflammatory processes) in patients using the Micra system. We suggest the use of 1.5 T as the preferred method in clinical practice.