A porcine large animal model of radiofrequency ablation-induced left bundle branch block.

Background: Electrocardiographic (ECG) features of left bundle branch (LBB) block (LBBB) can be observed in up to 20%-30% of patients suffering from heart failure with reduced ejection fraction. However, predicting which LBBB patients will benefit from cardiac resynchronization therapy (CRT) or conduction system pacing remains challenging. This study aimed to establish a translational model of LBBB to enhance our understanding of its pathophysiology and improve therapeutic approaches. Methods: Fourteen male pigs underwent radiofrequency catheter ablation of the proximal LBB under fluoroscopy and ECG guidance. Comprehensive clinical assessments (12-lead ECG, bloodsampling, echocardiography, electroanatomical mapping) were conducted before LBBB induction, after 7, and 21 days. Three pigs received CRT pacemakers 7 days after LBB ablation to assess resynchronization feasibility. Results: Following proximal LBB ablation, ECGs displayed characteristic LBBB features, including QRS widening, slurring in left lateral leads, and QRS axis changes. QRS duration increased from 64.2 ± 4.2 ms to 86.6 ± 12.1 ms, and R wave peak time in V6 extended from 21.3 ± 3.6 ms to 45.7 ± 12.6 ms. Echocardiography confirmed cardiac electromechanical dyssynchrony, with septal flash appearance, prolonged septal-to-posterior-wall motion delay, and extended ventricular electromechanical delays. Electroanatomical mapping revealed a left ventricular breakthrough site shift and significantly prolonged left ventricular activation times. RF-induced LBBB persisted for 3 weeks. CRT reduced QRS duration to 75.9 ± 8.6 ms, demonstrating successful resynchronization. Conclusion: This porcine model accurately replicates the electrical and electromechanical characteristics of LBBB observed in patients. It provides a practical, cost-effective, and reproducible platform to investigate molecular and translational aspects of cardiac electromechanical dyssynchrony in a controlled and clinically relevant setting.

Analysing and improving preoperative medication management in cardiac surgery.

AIMS: The objective of this study was to analyse the preoperative medication management within the cardiac surgery patient population and measure the effectiveness of an interprofessional intervention in routine care. METHODS: A jointly developed preoperative medication management was implemented in routine care on multiple levels (inclusion in admission letter to primary care, hotline for inquiries, pocket cards for physicians and correspondence with referring centres). The effectiveness was evaluated by analysing preoperative management before and after implementation. The primary endpoint was the number of drugs managed correctly according to the guidelines after implementation. Secondary endpoints consisted amongst others of bleeding on the intensive care unit, re-thoracotomy, postoperative infarction and cerebrovascular complications. Additionally, possible associations between the correct management and different variables were investigated by multivariate analysis. RESULTS: After the implementation, the number of drugs managed correctly according to guidelines increased from 54.0 to 73.5% (P < .001). The effect was more prominent for direct oral anticoagulants and prophylactic aspirin where the guideline adherence increased from 29.2 to 74.5% and from 78.6 to 95.1%, respectively. No difference was seen for sodium-glucose transporter-2 inhibitors, metformin, vitamin-K antagonists and dual-antiplatelet therapy. Secondary endpoints showed no safety signals with regard to bleeding or thrombotic events. In multivariate analysis, the intervention was effective (odds ratio 2.17, 95% confidence interval [1.32-3.62]) after adjusting for possible confounders. CONCLUSION: An interprofessional programme was effective to improve preoperative medication management in cardiac surgery patients. Sodium-glucose transporter-2 inhibitors, metformin and direct oral anticoagulants appear to be especially at risk for incorrect management before cardiac surgery with possible adverse events.

New Wound Management of Driveline Infections with Cold Atmospheric Plasma.

The use of ventricular assist devices as a bridge to transplant or as destination therapy has increased. Wound complications increase morbidity in this cohort. Cold atmospheric plasma is a source of reactive oxygen and nitrogen species and can reduce the microbial load in skin wounds without negative effects on the surrounding tissue. We evaluated our cold atmospheric plasma treatment for LVAD driveline infections in a retrospective single-center study for peri- and postintervention outcome analysis. Between April 2019 and September 2019, 15 male patients were included (5 HVAD, 10 HeartMate III). The wounds were treated for a mean of 368.5 s with a reduction of bacterial load in treated wounds in 60% of patients, regardless of the pathogen. The most common pathogen was staphylococcus aureus (n = 8 patients). There was a significant reduction of the wound scale (scale 2.80 vs. 1.18; p < 0.001) plus a significant reduction in size (16.08 vs. 1.90 cm3; p = 0.047). Seven patients (46.6%) were free from any signs of local or systemic infection during 1-year follow-up. Five patients (33%) received a heart transplantation. Cold atmospheric plasma treatment is a potent, safe, and painless adjuvant technique for treating driveline infection without the need for repeating surgical interventions.

Graft Preservation Solution DuraGraft® Alleviates Vascular Dysfunction Following In Vitro Ischemia/Reperfusion Injury in Rats.

Vascular ischemia/reperfusion injury (IRI) in patients undergoing coronary artery bypass grafting can result in graft failure and the need for repeat revascularization procedures. DuraGraft® has been shown to protect structure and function in saphenous vein grafts against IRI. We compared the effect of DuraGraft® to saline solution on arterial grafts submitted to IRI. Rat thoracic aortic rings were harvested and immediately mounted in organ bath chambers (control, n = 7 rats) or underwent cold ischemic preservation either in saline (IR, n = 9 rats) or DuraGraft® (IR+Dura, n = 9 rats). Vascular function was measured ex vivo and immunohistochemistry was performed. Impaired maximum vasorelaxation (Rmax) to ACh in the IR-group compared to controls was ameliorated by DuraGraft®, indicating an improvement in endothelial function (Rmax to ACh (%): IR + Dura 73 ± 2 vs. IR 48 ± 3, p < 0.05). Additionally, decreased aortic ring sensitivity to ACh (pD2-value: -log 50% maximum response) seen after IR in the saline group was increased by DuraGraft® (pD2 to ACh: IR+Dura 7.1 ± 0.1 vs. IR 6.3 ± 0.2, p < 0.05). Impaired maximum contractile response to phenylephrine and high potassium chloride concentrations in the IR group compared to controls was significantly improved by DuraGraft®. DuraGraft® alleviates vascular dysfunction following IRI by reducing nitro-oxidative stress and the expression of ICAM-1, without leukocytes engagement.

Renal Safety of Hydroxyethyl starch 130/0.42 After Cardiac Surgery: A Retrospective Cohort Analysis.

INTRODUCTION: The risk for renal complications from hydroxyethyl starch 130/0.42 (HES) impacts treatment decisions in patients after cardiac surgery. OBJECTIVE: The objective of this study was to determine the impact of postoperatively administered HES on renal function and 90-day mortality compared to sole crystalloid administration in patients after elective cardiac surgery. METHODS: Using electronic health records from a university hospital, confounding-adjusted models analyzed the associations between postoperative HES administration and the occurrence of postoperative acute kidney injury. In addition, 90-day mortality was evaluated. The impact of HES dosage and timing on renal function on trajectories of estimated glomerular filtration rates over the postoperative period was investigated using linear mixed-effects models. RESULTS: Overall 1009 patients (45.0%) experienced acute kidney injury. Less acute kidney injury occurred in patients receiving HES compared with patients receiving only crystalloids for fluid resuscitation (43.7% vs 51.2%, p = 0.008). In multivariate acute kidney injury models, HES had a protective association (odds ratio: 0.89; 95% confidence interval 0.82-0.96). Crystalloids were not as protective as HES (odds ratio: 0.98; 95% confidence interval 0.95-1.00). There was no association between HES and 90-day mortality (odds ratio: 1.05; 95% confidence interval 0.88-1.25). Renal function trajectories were dose dependent and biphasic, HES appeared to slow down the late postoperative decline. CONCLUSIONS: This study showed no association between HES and the postoperative occurrence of acute kidney injury and thus further closes the evidence gap on HES safety in cardiac surgery patients. Although this was a retrospective cohort study, the results indicated that HES might be safely administered to cardiac surgery patients with regard to renal outcomes, especially if it was administered early and dosed appropriately.

Impact of skeletonized harvesting of the internal thoracic artery on intrasternal microcirculation considering preparation quality.

OBJECTIVES: Previous studies have demonstrated the impact of internal thoracic artery (ITA) harvesting on microcirculation in parasternal tissues. However, the impact of skeletonized ITA harvesting on intrasternal microcirculation is unknown. Intraskeletal tissue perfusion has been proven to be crucial for deep wound healing. Furthermore, the impact of different levels of surgical preparation quality on intrasternal microcirculation has not been investigated yet. METHODS: Sternal microcirculation (sLDP) was monitored with a novel Laser Doppler Perfusion needle probe, while the ITA was skeletonized in a pig model. To mimic different levels of preparation quality, satellite veins were either coagulated or not during preparation. To show the effect of ideally avoiding any surgical manipulation on sLDP, the ITA was clipped in a third sham-harvested group. RESULTS: sLDP was reduced highly significant to 71 [standard deviation (SD): 9]% (P < 0.001) after skeletonized harvesting of the ITA. Coagulation of the satellite veins as a detrimental surgical factor resulted in a significantly stronger reduction of sLDP to 56 (SD: 11)% (P < 0.05) compared to sLDP with non-coagulated satellite veins. ITA clipping reduced sLDP highly significant to 71 (SD: 8)% (P < 0.001) in the sham-operated group. CONCLUSIONS: ITA harvesting markedly impairs microcirculation of the sternum but remains unavoidable when coronary artery bypass grafting should be performed. Nevertheless, excessive surgical damage and coagulation of satellite veins is avoidable and should be reduced to a minimum to minimize the risk of deep sternal wound healing complications.

Alginate hydrogel polymers enable efficient delivery of a vascular-targeted AAV vector into aortic tissue.

Gene therapeutic approaches to aortic diseases require efficient vectors and delivery systems for transduction of endothelial cells (ECs) and smooth muscle cells (SMCs). Here, we developed a novel strategy to efficiently deliver a previously described vascular-specific adeno-associated viral (AAV) vector to the abdominal aorta by application of alginate hydrogels. To efficiently transduce ECs and SMCs, we used AAV9 vectors with a modified capsid (AAV9SLR) encoding enhanced green fluorescent protein (EGFP), as wild-type AAV vectors do not transduce ECs and SMCs well. AAV9SLR vectors were embedded into a solution containing sodium alginate and polymerized into hydrogels. Gels were surgically implanted around the adventitia of the infrarenal abdominal aorta of adult mice. Three weeks after surgery, an almost complete transduction of both the endothelium and tunica media adjacent to the gel was demonstrated in tissue sections. Hydrogel-mediated delivery resulted in induction of neutralizing antibodies but did not cause inflammatory responses in serum or the aortic wall. To further determine the translational potential, aortic tissue from patients was embedded ex vivo into AAV9SLR-containing hydrogel, and efficient transduction could be confirmed. These findings demonstrate that alginate hydrogel harboring a vascular-targeting AAV9SLR vector allows efficient local transduction of the aortic wall.

The diagnostic benefit of 16S rDNA PCR examination of infective endocarditis heart valves: a cohort study of 146 surgical cases confirmed by histopathology.

AIMS: Upon suspicion of infective endocarditis, the causative microorganism must be identified to optimize treatment. Blood cultures and culturing of removed valves are the mainstay of this diagnosis and should be complemented by growth-independent methods. We assessed the diagnostic benefit of examining removed endocarditis valves by broad-range bacterial PCR to detect causative bacteria in cases where culturing was not available, negative, or inconclusive because a skin commensal was detected, in patients from our clinical routine practice. METHODS AND RESULTS: Patients from Heidelberg University Hospital with suspicion of endocarditis, followed by valve replacement and analysis by 16S rDNA PCR, between 2015 and 2018, were evaluated. 146 patients with definite infective endocarditis, confirmed by the valve macroscopics and/or histology, were included. Valve PCRs were compared to corresponding blood and valve culture results. Overall, valve PCR yielded an additional diagnostic benefit in 34 of 146 cases (23%) and was found to be more sensitive than valve culture. In 19 of 38 patients with both negative blood and valve cultures, valve PCR was the only method rendering a pathogen. In 23 patients with positive blood cultures detecting skin commensals, 4 patients showed discordant valve PCR results, detecting a more plausible pathogen, and in 11 of 23 cases, valve PCR confirmed commensals in blood culture as true pathogens. Only the remaining 8 patients had negative valve PCRs. CONCLUSION: Valve PCR was found to be a valuable diagnostic tool in surgical endocarditis cases with negative blood cultures or positive blood cultures of unknown significance. TRIAL REGISTRATION: S-440/2017 on 28.08.2017 retrospectively registered. Subdividing of all infective endocarditis patients in this study, showing that valve PCR yields valuable information for patients with skin commensals in blood cultures, which were either confirmed by the same detection in valve PCR or refuted by the detection of a different and typical pathogen in valve PCR. Additionally, benefit was determined in patients with negative or not available blood cultures and only positive detection in valve PCR. +: Positive; -: negative; n/a: not available results.