New insights into valve-related intramural and intracellular bacterial diversity in infective endocarditis.

AIMS: In infective endocarditis (IE), a severe inflammatory disease of the endocardium with an unchanged incidence and mortality rate over the past decades, only 1% of the cases have been described as polymicrobial infections based on microbiological approaches. The aim of this study was to identify potential biodiversity of bacterial species from infected native and prosthetic valves. Furthermore, we compared the ultrastructural micro-environments to detect the localization and distribution patterns of pathogens in IE. MATERIAL AND METHODS: Using next-generation sequencing (NGS) of 16S rDNA, which allows analysis of the entire bacterial community within a single sample, we investigated the biodiversity of infectious bacterial species from resected native and prosthetic valves in a clinical cohort of 8 IE patients. Furthermore, we investigated the ultrastructural infected valve micro-environment by focused ion beam scanning electron microscopy (FIB-SEM). RESULTS: Biodiversity was detected in 7 of 8 resected heart valves. This comprised 13 bacterial genera and 16 species. In addition to 11 pathogens already described as being IE related, 5 bacterial species were identified as having a novel association. In contrast, valve and blood culture-based diagnosis revealed only 4 species from 3 bacterial genera and did not show any relevant antibiotic resistance. The antibiotics chosen on this basis for treatment, however, did not cover the bacterial spectra identified by our amplicon sequencing analysis in 4 of 8 cases. In addition to intramural distribution patterns of infective bacteria, intracellular localization with evidence of bacterial immune escape mechanisms was identified. CONCLUSION: The high frequency of polymicrobial infections, pathogen diversity, and intracellular persistence of common IE-causing bacteria may provide clues to help explain the persistent and devastating mortality rate observed for IE. Improved bacterial diagnosis by 16S rDNA NGS that increases the ability to tailor antibiotic therapy may result in improved outcomes.

Proteome profiles of HDL particles of patients with chronic heart failure are associated with immune response and also include bacteria proteins.

Besides modulation of reverse cholesterol transport, high density lipoprotein (HDL) is able to modulate vascular function by stimulating endothelial nitric oxide synthase. Recently, it could be documented that this function of HDL was significantly impaired in patients with chronic heart failure (CHF). We investigated alterations in the HDL proteome in CHF patients. Therefore, HDL was isolated from 5 controls (HDLhealthy) and 5 CHF patients of NYHA-class IIIb (HDLCHF). Proteome analysis of HDL particles was performed by two-dimensional liquid chromatography-mass spectrometry (SCX/RP LC-MS/MS). In total, we identified 494 distinct proteins, of which 107 proteins were commonly found in both groups (HDLCHF and HDLhealthy) indicating a high inter-subject variability across HDL particles. Several important proteins (e.g. ITGA2, APBA1 or A2M) varied in level. Functional analysis revealed regulated pathways. A minor proportion of bacteria-derived proteins were also identified in the HDL-particles. The extension of the list of HDL-associated proteins allows besides their mere description new insights into alterations in HDL function in diseases. In addition, the detection of bacterial proteins bound to HDL will broaden our view of HDL not only as a cholesterol carrier but also as a carrier of proteins.

A minimally invasive off-pump implantation technique for continuous-flow left ventricular assist devices: early experience.

BACKGROUND: The HeartWare (HeartWare International, Inc. Framingham, MA) ventricular assist device (HVAD) is approved for implantation through a sternotomy with cardiopulmonary bypass. We report on our initial experience with this device implanted off-pump via thoracotomy. METHODS: A total of 26 patients were included in this review. All patients were Interagency Registry for Mechanically Assisted Circulatory Support categories 2 or 3 and underwent implantation of an HVAD as an elective procedure via thoracotomy and mini sternotomy approach. Three-dimensional echocardiography was used to assess the ventricle and was also used to facilitate proper pump positioning. Patients were managed during follow-up using anti-coagulants at a target international normalized ratio 2.0 to 2.5 as well as anti-platelet agents. RESULTS: Implantation was performed without the use of cardiopulmonary bypass, but 1 patient did require conversion to on-pump surgery. There were no perioperative deaths or right heart failure events. The mean intensive care unit stay was 1.5 days. Transfusions of 1 to 3 units of packed red blood cells were required in 16 patients, whereas 10 patients maintained a stable perioperative hematocrit of at least 30% and did not require transfusion. Survival through 90 days was 100%, and survival through 180 days was 87%. CONCLUSIONS: Our experience was favorable in respect to outcome, safety, and use of blood products. Our technique can be used as an alternative approach for left ventricular assist device implantation using the HVAD.