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.
The recognition of microthrombi in the heart microcirculation has recently emerged from studies in COVID-19 decedents. The present study investigated the ultrastructure of coronary microthrombi in heart failure (HF) due to cardiomyopathies that are unrelated to COVID-19 infection. In addition, we have investigated the role of von Willebrand factor (VWF) and PECAM-1 in microthrombus formation. We used electron microscopy to investigate the occurrence of microthrombi in patients with HF due to dilated (DCM, n = 7), inflammatory (MYO, n = 6) and ischemic (ICM, n = 7) cardiomyopathy and 4 control patients. VWF and PECAM-1 was studied by quantitative immunohistochemistry and Western blot. In comparison to control, the number of microthrombi was increased 7-9 times in HF. This was associated with a 3.5-fold increase in the number of Weibel-Palade bodies (WPb) in DCM and MYO compared to control. A fivefold increase in WPb in ICM was significantly different from control, DCM and MYO. In Western blot, VWF was increased twofold in DCM and MYO, and more than threefold in ICM. The difference between ICM and DCM and MYO was statistically significant. These results were confirmed by quantitative immunohistochemistry. Compared to control, PECAM-1 was by approximatively threefold increased in all groups of patients. This is the first study to demonstrate the occurrence of microthrombi in the failing human heart. The occurrence of microthrombi is associated with increased expression of VWF and the number of WPb, being more pronounced in ICM. These changes are likely not compensated by increases in PECAM-1 expression.
Objectives . The transvascular closure of patent foramen ovale (PFO) with self-expanding devices carries the risk of left atrial thrombus formation related to material protruding into the left atrium. Thus, we developed a novel device with flat left atrial disc geometry. We evaluated feasibility, handling, and biocompatibility in a porcine animal model. Methods . Implantation of an Occlutech Figulla PFO device was performed in 10 mini pigs using fluoroscopy and intra-cardiac ultrasound after transseptal puncture of the interatrial septum. Angiographic follow-up was performed after six and twelve weeks. Results . Implantation was successful in 100%. There were no further implant related complications. One procedure related death occurred, as one animal died of ventricular tachycardia due to mispunture of the interatrial septum. Angiographic studies showed no residual shunt during follow-up. Histopathological evaluation could demonstrate partial neoendothelialization after 6 weeks with completion after 12 weeks. The devices were incorporated into connective tissue containing fibro muscular cells. An only mild inflammatory reaction was detected locally related to the polyester fibers. Conclusion . In terms of feasibility and handling, the new device does not seem to be inferior to other presently used implantation systems. Good biocompatibility was demonstrated with rapid and complete neoendothelialization.
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.
Microvascular perfusion, pivotal for adequate tissue oxygenation is potentially linked to outcome in critical care therapy. Mechanical ventilation (MV) and positive end-expiratory pressure (PEEP) as standard concepts of respiratory management are known to have deleterious effects on regional organ perfusion especially in the splanchnic area. As these effects have been attributed to different physiologic mechanisms, the purpose of this study was to investigate the effect of positive pressure ventilation on extra-abdominal tissue perfusion in non-surgical intensive care patients.Sublingual microcirculation was evaluated in 46 severely ill patients (group 1: n=26 requiring MV and PEEP; group 2: n=20 spontaneous breathing) admitted to the intensive care unit using sidestream darkfield intravitalmicroscopy. According to current guidelines, sublingual vessels were categorized by means of size and flow in semi-quantitative categories determining microvascular flow index (MFI). Total microvascular flow index (TMFI) was calculated for each patient as mean value of flow in all vessel categories.No significant difference was observed between both groups in microvascular flow index in each vessel category and in total microvascular flow index. Patients requiring mechanical ventilation presented with more comorbidities and higher acuity of illness scores resulting in a higher ICU mortality, which however was not accompanied by microcirculatory differences at the time of measurement.Mechanical ventilation and PEEP have no general deleterious effects on microvascular perfusion of the sublingual mucosa. However, further clinical studies are required to investigate potential effects of higher levels of ventilation pressure or PEEP on microvascular perfusion.
