Effect of intraoperative haemoadsorption therapy on cardiac surgery for active infective endocarditis with confirmed Staphylococcus aureus bacteraemia.

OBJECTIVES: Sepsis caused by infective endocarditis (IE), due to Staphylococcus aureus, is associated with significant morbidity and mortality. Blood purification using haemoadsorption (HA) may attenuate the inflammatory response. We investigated the effect of intraoperative HA on postoperative outcomes in S. aureus IE. METHODS: Patients with confirmed S. aureus IE undergoing cardiac surgery were included in a dual-centre study between January 2015 and March 2022. Patients treated with intraoperative HA (HA group) were compared to patients not treated with HA (control group). The primary outcome was vasoactive-inotropic score within the first 72 h postoperatively and secondary outcomes were sepsis-related mortality (SEPSIS-3 definition) and overall mortality at 30 and 90 days. RESULTS: No differences in baseline characteristics were observed between groups (haemoadsorption group, n = 75, control group, n = 55). Significantly decreased vasoactive-inotropic score was observed in the haemoadsorption group at all time points [6 h: 6.0 (0-17) vs 17 (3-47), P = 0.0014; 12 h: 2 (0-8.3) vs 5.9 (0-37), P = 0.0138; 24 h: 0 (0-5) vs 4.9 (0-23), P = 0.0064; 48 h: 0 (0-2.1) vs 0.1 (0-13), P = 0.0192; 72 h: 0 (0) vs 0 (0-5), P = 0.0014]. Importantly, sepsis-related mortality (8.0% vs 22.8%, P = 0.02) and 30-day (17.3% vs 32.7%, P = 0.03) and 90-day overall mortality (21.3% vs 40%, P = 0.03) were also significantly lower with haemoadsorption. CONCLUSIONS: Intraoperative HA during cardiac surgery for S. aureus IE was associated with significantly lower postoperative vasopressor and inotropic requirements and resulted in lower sepsis-related and overall 30- and 90-day mortality. In this high-risk population, improved postoperative haemodynamic stabilization by intraoperative HA appears to improve survival and should be further tested in future randomized trials.

Four decades of experience of prosthetic valve endocarditis reflect a high variety of diverse pathogens.

Prosthetic valve endocarditis (PVE) remains a serious condition with a high mortality rate. Precise identification of the PVE-associated pathogen/s and their virulence is essential for successful therapy and patient survival. The commonly described PVE-associated pathogens are staphylococci, streptococci, and enterococci, with Staphylococcus aureus being the most frequently diagnosed species. Furthermore, multi-drug resistance pathogens are increasing in prevalence and continue to pose new challenges mandating a personalized approach. Blood cultures in combination with echocardiography are the most common methods to diagnose PVE, often being the only indication, it exists. In many cases, the diagnostic strategy recommended in the clinical guidelines does not identify the precise microbial agent, and frequently, false-negative blood cultures are reported. Despite the fact that blood culture findings are not always a good indicator of the actual PVE agent in the valve tissue, only a minority of re-operated prostheses are subjected to microbiological diagnostic evaluation. In this review, we focus on the diversity and the complete spectrum of PVE-associated bacterial, fungal, and viral pathogens in blood and prosthetic heart valve, their possible virulence potential, and their challenges in making a microbial diagnosis. We are curious to understand if the unacceptable high mortality of PVE is associated with the high number of negative microbial findings in connection with a possible PVE. Herein, we discuss the possibilities and limits of the diagnostic methods conventionally used and make recommendations for enhanced pathogen identification. We also show possible virulence factors of the most common PVE-associated pathogens and their clinical effects. Based on blood culture, molecular biological diagnostics, and specific valve examination, better derivations for the antibiotic therapy as well as possible preventive intervention can be established in the future.

Single-Centre Retrospective Evaluation of Intraoperative Hemoadsorption in Left-Sided Acute Infective Endocarditis.

BACKGROUND: Cardiac surgery in patients with infective endocarditis (IE) is still associated with high mortality and morbidity; an already present inflammation might further be aggravated due to a cardiopulmonary bypass-induced dysregulated immune response. Intraoperative hemoadsorption therapy may attenuate this septic response. Our objective was therefore to assess the efficacy of intraoperative hemoadsorption in active left-sided native- and prosthetic infective endocarditis. METHODS: Consecutive high-risk patients with active left-sided infective endocarditis were enrolled between January 2015 and April 2021. Patients with intraoperative hemoadsorption (Cytosorbents, Princeton, NJ, USA) were compared to patients without hemoadsorption (control). Endpoints were the incidence of postoperative sepsis, sepsis-associated death and in-hospital mortality. Predictors for sepsis-associated mortality and in-hospital mortality were analysed by multivariable logistic regression. RESULTS: A total of 202 patients were included, 135 with active left-sided native and 67 with prosthetic valve infective endocarditis. Ninety-nine patients received intraoperative hemoadsorption and 103 patients did not. Ninety-nine propensity-matched pairs were selected for final analyses. Postoperative sepsis and sepsis-related mortality was reduced in the hemoadsorption group (22.2% vs. 39.4%, p = 0.014 and 8.1% vs. 22.2%, p = 0.01, respectively). In-hospital mortality tended to be lower in the hemoadsorption group (14.1% vs. 26.3%, p = 0.052). Key predictors for sepsis-associated mortality and in-hospital mortality were preoperative inotropic support, lactate-levels 24 h after surgery, C-reactive protein levels on postoperative day 1, chest tube output, cumulative inotropes and white blood cell counts on postoperative day 2, and new onset of dialysis. Multivariate regression analysis revealed intraoperative hemoadsorption to be associated with lower sepsis-associated (OR 0.09, 95% CI 0.013-0.62, p = 0.014) as well as in-hospital mortality (OR 0.069, 95% CI 0.006-0.795, p = 0.032). CONCLUSIONS: Intraoperative hemoadsorption holds promise to reduce sepsis and sepsis-associated mortality after cardiac surgery for active left-sided native and prosthetic valve infective endocarditis.

Surgery for Aortic Prosthetic Valve Endocarditis in the Transcatheter Era.

Objectives: As surgical experience with infective endocarditis following transcatheter aortic valve replacement is scarce, this study compared the perioperative and short-term outcomes of patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement. Methods: Between January 2013 and December 2020, 468 consecutive patients were admitted to our center for surgery for IE. Among them, 98 were operated on for endocarditis following surgical aortic valve replacement and 22 for endocarditis following transcatheter aortic valve replacement. Results: The median EuroSCORE II (52.1 (40.6-62.0) v/s 45.4 (32.6-58.1), p = 0.207) and STS-PROM (1.8 (1.6-2.1) v/s 1.9 (1.4-2.2), p = 0.622) were comparable. Endocarditis following transcatheter aortic valve replacement accounted for 13.7% of the aortic prosthetic valve endocarditis between 2013 and 2015; this increased to 26.9% in the years 2019 and 2020.Concomitant procedures were performed in 35 patients (29.2%). The operative mortality was 26.5% in the endocarditis following surgical aortic valve replacement group and 9.1% in the endocarditis following transcatheter aortic valve replacement group (p = 0.098). Upon follow-up, survival at 6 months was found to be 98% in the group with endocarditis following surgical aortic valve replacement and 89% in the group with endocarditis following transcatheter aortic valve replacement (p = 0.081). Conclusions: Patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement present with comparable risk profiles and can be surgically treated with comparable results. Surgery as a curative option should not be rejected even in this intermediate-risk cohort.

Hybrid Surgery for Severe Mitral Valve Calcification: Limitations and Caveats for an Open Transcatheter Approach.

Background and Objectives: Mitral stenosis with extensive mitral annular calcification (MAC) remains surgically challenging in respect to clinical outcome. Prolonged surgery time with imminent ventricular rupture and systolic anterior motion can be considered as a complex of causal factors. The aim of our alternative hybrid approach was to reduce the risk of annual rupture and paravalvular leaks and to avoid obstruction of the outflow tract. A review of the current literature was also carried out. Materials and Methods: Six female patients (mean age 76 ± 9 years) with severe mitral valve stenosis and severely calcified annulus underwent an open implantation of an Edwards Sapien 3 prosthesis on cardiopulmonary bypass. Our hybrid approach involved resection of the anterior mitral leaflet, placement of anchor sutures and the deployment of a balloon expanded prosthesis under visual control. Concomitant procedures were carried out in three patients. Results: The mean duration of cross-clamping was 95 ± 31 min and cardiopulmonary bypass was 137 ± 60 min. The perioperative TEE showed in three patients an inconspicuous, heart valve-typical gradient on all implanted prostheses and a clinically irrelevant paravalvular leakage occurred in the anterior annulus. In the left ventricular outflow tract, mild to moderately elevated gradients were recorded. No adverse cerebrovascular events and pacemaker implantations were observed. All but one patient survived to discharge. Survival at one year was 83.3%. Conclusions: This "off label" implantation of the Edwards Sapien 3 prosthesis may be considered as a suitable bail-out approach for patients at high-risk for mitral valve surgery or deemed inoperable due to extensive MAC.

Tricuspid valve annuloplasty and mitral valve replacement are associated with bradyarrhythmia after mitral valve surgery.

INTRODUCTION: Mitral valve surgery has developed into a strong subspecialty of cardiac surgery with operative techniques and outcomes constantly improving. The development of bradyarrhythmias after mitral valve surgery is not completely understood. METHODS: We investigated a cohort of 797 patients requiring mitral valve surgery with and without concomitant procedures. Incidences and predictors of pacemaker requirement as well as survival were analyzed. RESULTS: In the complete follow-up period (median follow-up time: 6.09 years [95% confidence interval [CI]: 5.94-6.22 years, maximum 8.77 years) 80 patients (10% of the complete cohort) required pacemaker implantation for bradyarrhythmia. The cumulative rate of pacemaker implantation was 6.4% at 50 days (48 patients) with most (54.2%) requiring pacing for atrioventricular block. Mitral valve replacement (odds ratio [OR]: 1.905; 95% CI: 1.206-3.536; p = .041) and tricuspid ring annuloplasty (OR: 2.348; 95% CI: 1.165-4.730, p = .017) were identified as operative risk factors of pacemaker requirement after mitral valve surgery. Insulin-dependent diabetes mellitus was also identified as a predictor of pacemaker requirement (OR: 4.665; 95% CI: 1.975-11.02; p = .001). There was no difference in survival in the paced and unpaced groups. CONCLUSIONS: After mitral valve surgery, a relevant subgroup of patients requires pacemaker implantation-most for atrioventricular block. We identified mitral valve replacement and tricuspid ring annuloplasty as significant operative risk factors and insulin-dependent diabetes mellitus as a demographic risk factor. While anatomic relationships help explain the operative risk factors the role of diabetes mellitus is not completely understood.

Recent advances in patient selection and devices for transcatheter edge-to-edge mitral valve repair in heart failure.

Introduction: Secondary mitral regurgitation (MR) is a consequence of chronic heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) and left ventricular (LV) dilatation. Severe MR worsens prognosis and accelerates LV dilatation as well as decline in LV ejection fraction.Areas covered: In this review we summarize the available data of patients with chronic HF undergoing transcatheter edge-to-edge mitral valve repair (TMVR) with the MitraClip system for severe secondary MR, considering also results of recent MITRA-FR (Multicenter Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients With Severe Secondary Mitral Regurgitation) and COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trials. Furthermore, we discuss recent advances in devices for TMVR, focussing on the new MitraClip XTR as well as the Edwards PASCAL system.Expert opinion: Optimal patient selection for TMVR is still a matter of great debate due to contradictory results of MITRA-FR and COAPT. New edge-to-edge devices (MitraClip XTR and Edwards PASCAL) come with longer clip arms and the Edwards PASCAL system is the first device with the capability of independent grasping of anterior and posterior leaflet, providing interventionalists with more options to treat patients with secondary MR.

Bacterial infiltration in structural heart valve disease.

OBJECTIVES: The pathology of structural valvular heart disease (sVHD) ranges from basic diseases of rheumatologic origin to chronic degenerative remodeling processes after acute bacterial infections. Molecular genetic methods allow detection of the complete microbial spectrum in heart valve tissues independent of microbiological cultivation. In particular, whole-metagenome analysis is a sensitive and highly specific analytical method that allows a deeper insight into the pathogenicity of the diseases. In the present study we assessed the pathogen spectrum in heart valve tissue from 25 sVHD patients using molecular and microbiological methods. METHODS: Twenty-five sVHD patients were selected randomly from an observational cohort study (March 2016 to January 2017). The explanted native heart valves were examined using microbiological methods and immunohistological structural analysis. In addition, the bacterial metagenome of the heart valve tissue was determined using next-generation sequencing. RESULTS: The use of sonication as a pretreatment of valve tissue from 4 sVHD patients permitted successful detection of Clostridium difficile, Enterococcus faecalis, Staphylococcus saccharolyticus, and Staphylococcus haemolyticus using microbial cultivation. Histological staining revealed intramural localization. Metagenome analysis identified a higher rate of bacterial infiltration in 52% of cases. The pathogen spectrum included both gram-positive and gram-negative bacteria. CONCLUSIONS: Microbiological and molecular biological studies are necessary to detect the spectrum of bacteria in a calcified heart valve. Metagenome analysis is a valid method to gain new insight into the polymicrobial pathophysiology of sVHD. Our results suggest that an undetected proportion of sVHD might be triggered by chronic inflammation or influenced by secondary bacterial infiltration.

Whole blood platelet aggregation kinetics under cardiopulmonary bypass: A pilot study.

Assessing the platelets' functional status during surgery on cardiopulmonary bypass is challenging. This study used multiple electrode impedance aggregometry (Multiplate®) to create a timeline of platelet aggregation changes as induced by cardiopulmonary bypass in antiplatelet-naive patients undergoing elective surgery for mitral valve regurgitation. We performed six consecutive measurements (T1: pre-operatively, T2: after heparinization, T3: 3 min after establishment of cardiopulmonary bypass, T4: immediately after administration of cardioplegia, T5: 5 min after administration of cardioplegia, and T6: 45 min after administration of cardioplegia). Platelet aggregation was determined after stimulation with 3.2-µg/mL collagen, 6.4-µM adenosine diphosphate, and 32-µM thrombin receptor activating peptide. Five patients were included (age: 64 ± 10 years, one female). We observed a decrease in hematocrit levels by -17.1% ± 3.7% (T1 vs T6) with a drop after establishment of cardiopulmonary bypass (T2 vs T3) and slightly decreasing platelet counts by -6.2% ± 7.7% (T1 vs T6). Immediately after establishment of cardiopulmonary bypass (T2 vs T3), we observed reduced platelet aggregation responses for stimulation with adenosine diphosphate (-19.7% ± 12.8%) and thrombin receptor activating peptide (-19.3% ± 6.3%). Interestingly, we found augmented platelet aggregation for all stimuli 45 min after administration of cardioplegia (T5 vs T6) with the strongest increase for collagen (+83.4% ± 42.8%; adenosine diphosphate: +39.0% ± 37.2%; thrombin receptor activating peptide: +34.5% ± 18.5%). Thus, after an initial drop due to hemodilution upon establishment of cardiopulmonary bypass, platelet reactivity increased over time which was not outweighed by decreasing platelet counts due to mechanical platelet destruction and absorption. These findings have implications for rational transfusion, peri-operative antiplatelet therapy, and for the management of patients on other extracorporeal support, such as extracorporeal life support or extracorporeal membrane oxygenation.

Incidence and Surgical Outcomes of Patients With Native and Prosthetic Aortic Valve Endocarditis.

BACKGROUND: The aim of this study was to retrospectively evaluate the incidence and surgical outcomes of patients with native infective endocarditis (IE) and prosthetic aortic valve endocarditis (PVE) over the past decade at a single institution. METHODS: Between January 2005 and December 2015, 289 patients (mean age, 63.3 ± 14.2 years) suffering from native IE (n = 186) and PVE (n = 103) of the aortic valve underwent surgical procedures. Perioperative data were acquired retrospectively for statistical analysis. RESULTS: During the study period the mean incidence of endocarditis increased from 22.0 ± 4.2 (2005-2009) to 29.8 ± 10.1 (2010-2015) cases per year. In-hospital mortality was significantly increased in PVE (22.3%) versus IE (9.1%) patients (P < .001). In elective cases in-hospital mortality between the 2 groups was comparable (2.2% vs 4.6%; P = .288). Multivariate analysis identified urgent surgery (odds ratio [OR], 6.461; 95% CI, 1.941-21.509; P = .002), mitral regurgitation II (OR, 4.230; 95% CI, 1.249-14.331; P = .021), previous homograft operation (OR, 66.096; 95% CI, 2.369-1844.272; P = .0.14), and left ventricular ejection fraction < 40% (OR, 8.267; 95% CI, 1.931-35.388; P = .004) as independent risk factors for in-hospital mortality, whereas pathogen identification by preoperative blood cultures (OR, .228; 95% CI, 0.063-0.817; P = .023) was found to be independently protective. CONCLUSIONS: Surgery for native IE and PVE of the aortic valve may be performed with satisfactorily results at experienced cardiac surgical centers. In comparison PVE patients suffer from a more than twice as high in-hospital mortality, more postoperative complications, and inferior long-term survival. However preoperative identification of causative pathogens in IE and PVE allows for improved in-hospital survival.

Quantification of Multiple Bacteria in Calcified Structural Valvular Heart Disease.

Genome studies of heart valve tissue (HVT) in patients with structural valvular heart disease (sVHD) and acute infective endocarditis (aIE) showed polymicrobial infections. Subject of this study is the quantification of bacterial DNA in HVT of sVHD in comparison to aIE. It will be examined whether the bacterial DNA concentration can be used as surrogate marker to differentiate chronic and acute infections. DNA was isolated from HVT of 100 patients with sVHD and 23 microbiologically positively tested patients with aIE. Selected pathogens (Cutibacterium acnes, Enterococcus faecalis, Enterococcus faecium, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus agalactiae, Clostridium difficile, and Klebsiella pneumoniae) were quantified using TaqMan-qPCR. Polymicrobial infiltration of HVT was investigated by immunohistologic methods. Of 100 sVHD patients, 94 tested positive for bacteria by 16S-rDNA and 72 by TaqMan-qPCR. In 29% of the sVHD cohort and in 70% of the aIE cohort, a coinfection with more than 2 bacteria was observed as indication of a polymicrobial infection. The most common pathogens in the sVHD patients were C. acnes (59%; 5-4074 pg/mL), E. faecalis (16%, 174-2781 pg/mL), and S. aureus (15%, 8-105 pg/mL). The DNA concentration of E. faecalis (P = 0.0285) and S. aureus (P = 0.0149) is significantly lower in the sVHD cohort than in the aIE cohort. sVHD is associated with bacterial infection and infiltration of the HVT in a majority of cases. TaqMan-qPCR is a valid instrument for the specific detection of bacteria in HVT and allows discrimination between sVHD and aIE for E. faecalis and S. aureus.

Clinical impact of elevated tricuspid valve inflow gradients after transcatheter edge-to-edge tricuspid valve repair.

AIMS: The aim of this study was to compare the outcome of patients with a post-procedural tricuspid valve gradient (TVG) of >3 mmHg vs ≤3 mmHg after transcatheter edge-to-edge tricuspid valve repair (TTVR). METHODS AND RESULTS: Between March 2016 and October 2018 we treated 145 patients with severe tricuspid regurgitation (TR) with TTVR by placing 2.2±0.7 clips per patient. Device success (TR reduction ≥1° to at least moderate) was achieved in 125 patients (86.2%). TTVR resulted in an elevated TVG >3 mmHg in 25 (17.2%) patients. Device success (84% vs 86.7%, p=0.9), number of clips implanted (2.3±0.7 vs 2.2±0.7, p=0.33), clinical improvement including NYHA class (III/IV 24% vs 28%, p=0.92) and increase in six-minute walking test at one month (67 m [IQR 5-103 m] vs 56 m [IQR 8-97 m], p=0.93), mortality (HR 1.07, 95% CI: 0.43-2.65, plogrank=0.88) and the combined endpoint mortality and hospitalisation for heart failure at one year (HR 1.07, 95% CI: 0.46-2.48, plogrank=0.88) were similar between patients with a TVG >3 mmHg versus patients with a TVG ≤3 mmHg. CONCLUSIONS: A small cohort of patients demonstrated an elevated TVG higher than 3 mmHg at discharge. This elevation had no impact on clinical improvement, mortality or hospitalisation for heart failure.

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.

Root Replacement for Graft Infection Using an All-Biologic Xenopericardial Conduit.

BACKGROUND AND AIM OF THE STUDY: The management of graft infection following ascending aortic replacement (AAR) and/or aortic valve replacement (AVR) with destruction of the root remains a challenge. Besides technical issues, the choice of graft material is controversial. The study aim was to investigate the initial results of aortic root replacement (ARR) as redo-surgery for infection using the xenopericardial all-biologic conduit (BioIntegral) as an alternative to a homograft or prosthetic material. METHODS: Between February 2013 and January 2015, a total of 18 consecutive patients (16 males, two females; mean age 61 ± 14 years) were reoperated on for infection at a mean of 55 ± 61 months (range: 3 to 219 months) following previous AVR (n = 6), supracoronary aortic replacement (SAR, n = 2), AVR + SAR (n = 1), root replacement (n = 7), and root reconstruction (n = 2). Two patients (11%) had undergone more than one previous cardiac operation. Signs of infection were seen on computed tomography (CT) scanning in 17 patients (94%). Additional 18F-FDG PET-CT was performed in nine patients (50%). RESULTS: The cardiopulmonary bypass and crossclamp were 289 ± 77 min and 187 ± 59 min, respectively. Hypothermic circulatory arrest (HCA) + selective antegrade cerebral perfusion (SACP) was necessary in nine patients (50%) and concomitant procedures in 11 (61%). Postcardiotomy extracorporeal life support (ECLS) was necessary in five patients, and renal replacement therapy in eight. One patient died intraoperatively, and the overall 30-day mortality was 22% (n = 4) secondary to multi-organ failure. Risk factors for mortality were myocardial failure requiring ECLS (p = 0.02) and the need for root replacement following previous isolated AVR (p = 0.05). The mean follow up was 12 ± 5 months. Early graft reinfection occurred in one patient (6%), and another presented with pleural empyema without evidence of persisting conduit infection. Thus, freedom from graft reinfection was 94%. No case of structural valve deterioration was seen. CONCLUSIONS: Aortic root replacement using a xenopericardial conduit in patients with graft infection is technically feasible. Hemodynamics and surgical handling are comparable to that of homografts, but the off-the-shelf availability favors this approach. Mortality was substantial but comparable to that of other series and grafts, with low reinfection rates. Long-term outcome regarding the eradication of infection and durability of the graft remains to be demonstrated.

Coding and non-coding variants in the SHOX2 gene in patients with early-onset atrial fibrillation.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia with a strong genetic component. Molecular pathways involving the homeodomain transcription factor Shox2 control the development and function of the cardiac conduction system in mouse and zebrafish. Here we report the analysis of human SHOX2 as a potential susceptibility gene for early-onset AF. To identify causal variants and define the underlying mechanisms, results from 378 patients with early-onset AF before the age of 60 years were analyzed and compared to 1870 controls or reference datasets. We identified two missense mutations (p.G81E, p.H283Q), that were predicted as damaging. Transactivation studies using SHOX2 targets and phenotypic rescue experiments in zebrafish demonstrated that the p.H283Q mutation severely affects SHOX2 pacemaker function. We also demonstrate an association between a 3'UTR variant c.*28T>C of SHOX2 and AF (p = 0.00515). Patients carrying this variant present significantly longer PR intervals. Mechanistically, this variant creates a functional binding site for hsa-miR-92b-5p. Circulating hsa-miR-92b-5p plasma levels were significantly altered in AF patients carrying the 3'UTR variant (p = 0.0095). Finally, we demonstrate significantly reduced SHOX2 expression levels in right atrial appendages of AF patients compared to patients with sinus rhythm. Together, these results suggest a genetic contribution of SHOX2 in early-onset AF.

Long-term outcomes after resection of Stage IV cavoatrial tumour extension using deep hypothermic circulatory arrest.

OBJECTIVES: Renal neoplasms frequently expand into renal veins and inferior vena cava from the early stages of the disease. In this study, we set out to define the long-term outcomes of patients with Stage IV tumorous cavoatrial extension, undergoing radical nephrectomy with excision of cavoatrial extension in deep hypothermic circulatory arrest (DHCA). METHODS: Thirty-five patients with Stage IV cavoatrial extension of renal cell carcinoma underwent radical nephrectomy combined with en bloc excision of cavoatrial tumour-thrombus extension, performed in DHCA. The preoperative staging of the tumour and assessment of the intravascular position of the tumour were performed using standard imaging techniques, including computed tomography angiography, magnetic resonance imaging and echocardiography. Patient data were collected in the patient data bank and analysed retrospectively. RESULTS: In this study cohort, we demonstrate acceptable long-term results (the mean overall survival of 4.9 ± 1.0 years and the 5-year survival rate of 40%) and outline several clear predictors for postoperative long-term survival of the patients. Preoperative evidence of remote tumour metastases and tumourous lymph node involvement conversely predicts inferior postoperative survival. However, a high local postoperative tumour recurrence rate does not limit patient survival in this group. CONCLUSIONS: The data provide evidence for perioperative safety and acceptable long-term results of radical nephrectomy with excision of cavoatrial extension in DHCA in patients with Stage IV cavoatrial extension of renal neoplasm. Thus, this radical surgical procedure can provide effective long-term palliation in the absence of evident metastatic disease.

Immediate, Early and Late Failure after Transcatheter Aortic Valve Implantation: How to Deal with the Inoperable?

BACKGROUND: Currently, the use of transcatheter aortic valve implantation (TAVI) is constantly increasing, whilst cardiosurgical back-up varies substantially. Besides immediate conversion to surgical aortic valve replacement (SAVR) for periprocedural complications, SAVR for TAV failure may be necessary within the early or late post-implant course. The etiology, incidence, risk-stratification, management and outcome for both scenarios are largely unclear. The study aim was to provide details of the authors' experience of SAVR after the failure of TAVI at a single institution. METHODS: Nineteen patients (14 males, five females) underwent SAVR after TAVI at the authors' institution between June 2008 and December 2015. The patients' initial EuroSCORE II was 8.54 ± 9.81. In eight cases (42%; 50% transfemoral) an immediate conversion was necessary due to paravalvular leakage and insufficiency (n = 1), valve-malpositioning (n = 1), valve dislocation (n = 3), valve-trapping in mitral chordae (n = 1), and annular rupture (n = 2). The 50% transfemoral EuroSCORE II was 19.06 ± 8.61. In 11 patients transcatheter valve failure occurred at a mean of 18 ± 17 months after TAVI (two patients with structural valve failure and one with severe paravalvular leakage, seven with prosthetic valve endocarditis, and one patient with aortic aneurysm); the mean EuroSCORE II was 13.42 ± 13.06. RESULTS: For immediate conversion, the cardiopulmonary bypass (CPB) time and aortic cross-clamp time were 104 ± 40 min and 60 ± 16 min, respectively. Concomitant procedures were necessary in two patients, one patient required hypothermic circulatory arrest (HCA) and one died intraoperatively. For early and late failure, the CPB and cross-clamp times were 115 ± 32 min and 82 ± 20 min, respectively. HCA was necessary in one patient, and concomitant procedures in seven patients. The 30-day survival was 63% for immediate SAVR and 100% for early and late SAVR, even though one more patient died on postoperative day 31 after immediate SAVR. Besides, the longest follow up periods were 29 ± 15 months and 19 ± 14 months for immediate and early/late failure, respectively. In both groups, one patient died from cardiovascular-related causes, and one from non-valve-related causes. CONCLUSIONS: SAVR after previous TAVI will become increasingly relevant. Due to the increasing use of TAVI in medium- or lower-risk patients, adequate strategies must be established since, in comparison to multimorbid patients, not taking action in these patients is not an option. Due to potentially high-risk patients and unique technical implications, SAVR after TAVI differs from conventional (redo) AVR. Under optimal conditions, acceptable survival rates can be achieved, but effective interdisciplinary approaches are essential.

The relevance of 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in diagnosing prosthetic graft infections post cardiac and proximal thoracic aortic surgery.

OBJECTIVES: Diagnosis of prosthetic graft infection after cardiac and proximal aortic surgery is a challenge. Besides technical considerations, redo surgery is associated with substantial morbidity and mortality. Therefore, an accurate diagnosis is mandatory. We report on our experience with hybrid 18-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET)/computed tomography (CT) imaging, which is increasingly used to diagnose infections in the detection of graft infection after cardiac surgery. METHODS: Twenty-six patients who underwent (18)F-FDG PET/CT imaging after cardiac surgery between February 2010 and September 2014 for suspected graft infection were retrospectively analysed (81% male, age 54.3 ± 13.7 years). PET/CT imaging was performed 36.5 ± 70.5 (0.5-300) months after surgery. 2 patients (8%) had undergone aortic valve replacement (concomitant ascending and proximal arch replacement in 1), 1 (4%) aortic root reconstruction, 9 (35%) aortic root replacement (concomitant partial arch in 4, arch replacement and postoperative TEVAR in 1), 2 (8%) ascending aortic and partial arch replacement and 2 (8%) ascending aortic replacement along with frozen elephant trunk. In 10 (38%), more than one previous cardiac surgical procedure had been performed. Maximum standardized uptake values (SUVmax) were obtained for all patients. If the patients were reoperated on, the final diagnosis was derived from intraoperative findings and/or microbiological results. Otherwise, the longest clinical follow-up available served as a reference. RESULTS: Conventional CT was positive for infection in 13 cases (50%). In 22 (85%), PET was indicative of infection (SUVmax 10.5 ± 4.1). PET did not only confirm true-positive CT results in all but 1 case; in almost 30%, it provided substantial additional diagnostic information in comparison with CT alone. Receiver operating characteristic analysis identified an SUVmax of 7.25 to achieve maximum sensitivity (89%) and specificity (100%) in prediction of infection. Twelve patients (46%) required redo surgery for graft infection; in 1 additional patient (4%), sternal re-fixation was necessary. Furthermore, 2 patients had to be reoperated on for torn-out anastomosis and paraprosthetic perfusion (8%). CONCLUSIONS: PET provides functional data, confirms a CT diagnosis and may even increase diagnostic sensitivity in comparison with CT alone in selected cases. Specificity can be compromised by postoperative changes or chronic inflammatory reactions induced by the graft. CT and/or echocardiography should remain the first diagnostic step in case of a suspected infection because of their broad and fast availability. If confirmation is needed or diagnosis is not achievable using conventional methods, PET might be chosen as the next modality to gain additional information in experienced centres.

Immediate surgical coronary revascularisation in patients presenting with acute myocardial infarction.

BACKGROUND: The number of patients presenting with acute myocardial infarction (AMI) and being untreatable by interventional cardiologists increased during the last years. Previous experience in emergency coronary artery bypass grafting (CABG) in these patients spurred us towards a more liberal acceptance for surgery. Following a prospective protocol, patients were operated on and further analysed. METHODS: Within a two year interval, 127 patients (38 female, age 68±12 years, EuroScore (ES) II 6.7±7.2%) presenting with AMI (86 non-ST-elevated myocardial infarction (NSTEMI), 41 STEMI) were immediately accepted for emergency CABG and operated on within six hours after cardiac catheterisation (77% three-vessel-disease, 47% left main stem stenosis, 11% cardiogenic shock, 21% preoperative intraaortic balloon pump (IABP), left ventricular ejection fraction 48±15%). RESULTS: 30-day-mortality was 6% (8 patients, 2 NSTEMI (2%) 6 STEMI (15%), p=0.014). Complete revascularisation could be achieved in 80% of the patients using 2±1 grafts and 3±1 distal anastomoses. In total, 66% were supported by IABP, extracorporal life support (ECLS) systems were implanted in two patients. Logistic regression analysis revealed the ES II as an independent risk factor for mortality (p<0.001, HR 1.216, 95%-CI-Intervall 1.082-1.366). CONCLUSIONS: Quo ad vitam, results of emergency CABG for patients presenting with NSTEMI can be compared with those of elective revascularisation. Complete revascularisation obviously offers a clear benefit for the patients. Mortality in patients presenting with STEMI and cardiogenic shock is substantially high. For these patients, other concepts regarding timing of surgical revascularisation and bridging until surgery need to be taken into consideration.