Background: ERAS (Enhanced Recovery After Surgery) is a multidisciplinary and integrative approach with the goal of optimizing the postoperative recovery. We aimed to analyze the economic impact of a newly established ERAS protocol in minimally invasive heart valve surgery at our institution. Methods: ERAS protocol was implemented in 61 consecutive patients who were referred for elective minimally-invasive aortic or mitral valve surgery, between February 1, 2018 and March 31, 2019 (ERAS-group). Another 69 patients who underwent elective minimally-invasive heart valve surgery during the same time period were managed according to the hospital standards (Control-group). A detailed cost comparison analysis was carried out from a hospital perspective using a micro-costing approach. Results: The total in-hospital stay was significantly shorter in the ERAS-group compared to the Control-group (6.1 ± 2.6 vs 7.7 ± 3.8 days; p = 0.008) resulting in significant cost savings of €1087.2 per patient (p = 0.003). Due to the intensified physiotherapy in the ERAS protocol, the costs for physiotherapy were €94.3 higher compared to the Control-group (p < 0.001). The total costs in the ERAS cohort were €11,200.0 ± 3029.6/patient compared to € 13,109.8 ± 4527.5/patient in the Control-Group resulting in cost savings of €1909.8 patient due to the implementation of the ERAS protocol (p = 0.006). Conclusion: Implementation of an ERAS-protocol in minimally-invasive cardiac surgery can be carried out safely with a fast postoperative recovery of the patient. ERAS results in a financial benefit of up to €1909 per patient and therefore will play a key role in modern cardiac surgery in the near future.

Rationale: 3′,5′-cAMP is a ubiquitous second messenger which, upon β-AR (β-adrenergic receptor) stimulation, acts in microdomains to regulate cardiac excitation-contraction coupling by activating phosphorylation of calcium handling proteins. One crucial microdomain is in vicinity of the cardiac RyR2 (ryanodine receptor type 2) which is associated with arrhythmogenic diastolic calcium leak from the sarcoplasmic reticulum often occurring in heart failure. Objective: We sought to establish a real-time live-cell imaging approach capable of directly visualizing cAMP in the vicinity of mouse and human RyR2 and to analyze its pathological changes in failing cardiomyocytes under β-AR stimulation. Methods and Results: We generated a novel targeted fluorescent biosensor Epac1 (exchange protein directly activated by cAMP 1)-JNC (junctin) for RyR2-associated cAMP and expressed it in transgenic mouse hearts as well in human ventricular myocytes using adenoviral gene transfer. In healthy cardiomyocytes, β ₁ -AR but not β ₂ -AR stimulation strongly increased local RyR2-associated cAMP levels. However, already in cardiac hypertrophy induced by aortic banding, there was a marked subcellular redistribution of PDEs (phosphodiesterases) 2, 3, and 4, which included a dramatic loss of the local pool of PDE4. This was also accompanied by measurable β ₂ -AR/AMP signals in the vicinity of RyR2 in failing mouse and human myocytes, increased β ₂ -AR–dependent RyR2 phosphorylation, sarcoplasmic reticulum calcium leak, and arrhythmia susceptibility. Conclusions: Our new imaging approach could visualize cAMP levels in the direct vicinity of cardiac RyR2. Unexpectedly, in mouse and human failing myocytes, it could uncover functionally relevant local arrhythmogenic β ₂ -AR/cAMP signals which might be an interesting antiarrhythmic target for heart failure.

Children with congenital heart defects (CHDs) are at high risk for myocardial failure after operative procedures with cardiopulmonary bypass (CPB). Recent studies suggest that microRNAs (miRNA) are involved in the development of CHDs and myocardial failure. Therefore, the aim of this study was to determine alterations in the miRNA profile in heart tissue after cardiac surgery using CPB. In total, 14 tissue samples from right atrium were collected from patients before and after connection of the CPB. SurePrint™ 8 × 60K Human v21 miRNA array and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were employed to determine the miRNA expression profile from three patients before and after connection of the CPB. Enrichment analyses of altered miRNA expression were predicted using bioinformatic tools. According to miRNA array, a total of 90 miRNAs were significantly altered including 29 miRNAs with increased and 61 miRNAs with decreased expression after de-connection of CPB (n = 3) compared to before CPB (n = 3). Seven miRNAs had been validated using RT-qPCR in an independent cohort of 11 patients. Enrichment analyses applying the KEGG database displayed the highest correlation for signaling pathways, cellular community, cardiovascular disease and circulatory system. Our result identified the overall changes of the miRNome in right atrium tissue of patients with CHDs after CPB. The differentially altered miRNAs lay a good foundation for further understanding of the molecular function of changed miRNAs in regulating CHDs and after CPB in particular.

Background: Valvular heart diseases are frequent and increasing in prevalence. Minimally invasive heart valve surgery embedded in an interdisciplinary enhanced recovery after surgery (ERAS) program may have potential benefits with regard to reduced length of stay and improved patient reported outcomes. However, no prospective randomized data exist regarding the superiority of ERAS program for the patients’ outcome. Methods: We aim to randomize (1:1) a total of 186 eligible patients with minimally invasive heart valve surgery to an ERAS program vs. standard treatment at two centers including the University Medical Center Hamburg-Eppendorf, Germany, and the University Hospital Augsburg, Germany. The intervention is composed out of pre-, peri-, and postoperative components. The preoperative protocol aims at better preparation for the operation with regard to physical activity, nutrition, and psychological preparedness. Intraoperative anesthesiologic and surgical management are trimmed to enable an early extubation. Patients will be transferred to a specialized postoperative anesthesia care unit, where first mobilization occurs 3 h after surgery. Transfer to low care ward will be at the next day and discharge at the fifth day. Participants in the control group will receive treatment as usual. Primary endpoints include functional discharge at discharge and duration of in-hospital care during the first 12 months after index surgery. Secondary outcomes include health-related quality of life, health literacy, and level of physical activity. Discussion: This is the first randomized controlled trial evaluating the effectiveness of an ERAS process after minimally invasive heart valve surgery. Interprofessional approach is the key factor of the ERAS process and includes in particular surgical, anesthesiological, physiotherapeutic, advanced nursing, and psychosocial components. A clinical implication guideline will be developed facilitating the adoption of ERAS model in other heart teams. Trial registration: The study has been registered in ClinicalTrials.gov (NCT04977362 assigned July 27, 2021).

Bicuspid aortic valve (BAV) disease is the most common congenital malformation of the human heart with a prevalence of 1–2% in the general population. More than half of patients with a BAV present with a dilated proximal aorta (so-called bicuspid aortopathy) which is associated with an enhanced risk of life-threatening aortic complications. Up to now, the pathogenesis of bicuspid aortopathy as well as the risk stratification of aortic complications has not yet been sufficiently clarified. Recent findings have shown that bicuspid aortopathy features phenotypic heterogeneity. Two distinct valvulo-aortic phenotypes, the so-called root phenotype, as well as a dilation of the tubular ascending aorta, coincide with a significantly different risk for aortal complications. However, the phenotype-based classification that is only based on these two clinical forms is not sufficient to estimate the risk of aortal complications in a prognostically relevant way. Therefore, there is growing clinical interest to assess novel approaches in BAV research and to introduce circulating biomarkers as an elegant diagnostic tool to improve risk stratification in BAV aortopathy. A large scale epidemiological cohort study, ranking from apparently healthy individuals to disease patients, and comprehensive biobanks provide the opportunity to study BAV disease and its complications and to identify novel biomarkers for BAV aortopathy surveillance and prognosis. Firstly, the data indicate that several protein-based biomarkers and non-coding RNA molecules, in particular circulating microRNAs, can serve as relevant molecular biomarkers to predict the course of BAV-associated aortopathy. Here, we review the current literature and knowledge about BAV from a clinical point of view, and report about novel approaches in BAV biomarker research.

Background: Minimally-invasive (MIS) mitral valve (MV) surgery has become standard therapy in many cardiac surgery centers. While femoral arterial perfusion is the preferred cannulation strategy in MIS mitral valve surgery, retrograde arterial perfusion is known to be associated with an increased risk for cerebral atheroembolism, particularly in atherosclerosis patients. Therefore, antegrade perfusion may be beneficial in such cases. This analysis aimed to compare outcomes of antegrade axillary vs. retrograde femoral perfusion in the MIS mitral valve surgery.Methods: This analysis includes 50 consecutive patients who underwent MIS between 2016 and 2020 using arterial cannulation of right axillary artery (Group A) due to severe aortic arteriosclerosis. Perioperative outcomes of the study group were compared with a historical control group of retrograde femoral perfusion (Group F) which was adjusted for age and gender (n = 50). Primary endpoint of the study was in-hospital mortality and perioperative cerebrovascular events.Results: Patients in group A had a significantly higher perioperative risk as compared to Group F (EuroSCORE II: 3.9 ± 2.5 vs. 1.6 ± 1.5; p = 0.001; STS-Score: 2.1 ± 1.4 vs. 1.3 ± 0.6; p = 0.023). Cardiopulmonary bypass time (group A: 172 ± 46; group F: 178 ± 51 min; p = 0.627) and duration of surgery (group A: 260 ± 65; group F: 257 ± 69 min; p = 0.870) were similar. However, aortic cross clamp time was significantly shorter in group A as compared to group F (86 ± 20 vs. 111 ± 29 min, p < 0.001). There was no perioperative stroke in either groups. In-hospital mortality was similar in both groups (group A: 1 patient; group F: 0 patients; p = 0.289). In group A, one patient required central aortic repair due to intraoperative aortic dissection. No further cardiovascular events occurred in Group A patients.Conclusion: Selective use of antegrade axillary artery perfusion in patients with systemic atherosclerosis shows similar in-hospital outcomes as compared to lower risk patients undergoing retrograde femoral perfusion. Patients with higher perioperative risk and severe atherosclerosis can be safely treated via the minimally invasive approach with antegrade axillary perfusion.