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ObjectivesRevascularization in patients with severely reduced left ventricular function and coronary artery disease (CAD) is associated with a high perioperative risk. In this setting, implantation of a durable left ventricular assist device (LVAD) might be an alternative.MethodsWe retrospectively compared the outcomes of adult patients with CAD and a left ventricular ejection fraction (LVEF) ≤ 25% who underwent coronary artery bypass grafting (CABG) vs. LVAD implantation. Propensity score (PS) matching was performed for statistical analysis, resulting in 168 pairs.ResultsIn the PS-matched cohorts, the mean age was 62 years; one third had a history of myocardial infarction, 11% were resuscitated, half of the patients were on inotropic support, and 20% received preoperative mechanical circulatory support. LVAD patients required significantly longer ventilation (58 h [21, 256] vs. 16 h [9, 73], p

Background: Delirium is a frequent and serious complication of cardiac procedures that can lead to serious long-term health restrictions. As primary prevention is more effective in reducing rate of delirium than the therapy itself, this study aimed to investigate the effect of a multidisciplinary delirium prevention bundle on the postoperative delirium rate in patients undergoing cardiac procedures. Methods: In this system-based quality improvement study, a four-component delirium prevention bundle was implemented in patients undergoing cardiac procedures at a single high-volume center. The program included preoperative delirium risk stratification, multidisciplinary education of consensus guidelines, written memory aids, and post-anesthetic visits with delirium screening until postoperative day three. Results: Overall, 234 patients were included and analyzed during the 6-month study period. The overall delirium incidence rate was 12.4%. After the first 3-month baseline implementation period, the delirium rate was 17.2%, compared with 7.6% (p = 0.026) after implementation of the delirium prevention bundle. Multivariate analysis revealed independent risk factors such as age [adjusted odds ratio (OR): 1.046; 95% confidence interval (CI): 1.002–1.092; p = 0.042], double valve surgery [adjusted OR: 13.1; 95% CI: 3.240–52.974; p < 0.0001], and peripheral artery disease [adjusted OR: 8.131; 95% CI: 2.336–28.306; p < 0.001]. Hospital stay was significantly longer in patients with delirium [median 13 (12–19.5) versus 12 (11–14) days, p = 0.009]. Conclusions: This multidisciplinary system-based quality improvement study demonstrated a beneficial effect on the delirium rate after the implementation of a four-component delirium prevention bundle in patients undergoing cardiac surgery or intervention. Furthermore, multivariate analysis revealed important independent risk factors for delirium development. This might improve early risk stratification and strategies for this high-risk patient collective.

TMEM43 (LUMA) is a ubiquitously expressed protein with unknown function. The protein is phylogenetically highly conserved and also found in Drosophila melanogaster (Klinke et al., 2022). TMEM43-p.S358L is a rare, fully penetrant mutation that leads to arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5). To understand the function of the ARVC5-associated mutation it is first important to understand the function of the TMEM43 protein. Therefore, a TMEM43 knockout induced pluripotent stem cell (iPSC) line was generated using the CRISPR/Cas9 genome editing system.The resulting cell line had a deficiency of TMEM43 and showed normal morphology and a stable karyotype. The colonies were positive for pluripotency markers and could be differentiated into the three germ layers.

Heart surgery patients are at high risk for psychological trauma and comorbid psychological disorders. Depression, anxiety, and post-traumatic stress disorders in this patient group are predictors of outcomes after cardiac surgery. Medical hypnosis is effective for non-pharmacologic prevention and treatment of psychological disorders and has been associated with improved health-related quality of life and better cardiovascular outcomes. This contribution makes note of evidence of the effectiveness of medical hypnosis in a discussion of the clinical experience with specific hypnotherapeutic tools and interventions from the perspective of the mental health team in one large cardiac center in Germany. Based on our experience, we encourage heart centers to educate their heart surgery care teams about the core concepts of medical hypnosis and to make hypnotherapeutic techniques available as an adjunctive therapy.

Abstract Aims Implantation of left ventricular‐assist devices (LVAD) to treat end‐stage heart failure is of increasing relevance due to donor shortage. Infections of the driveline are common adverse events. LVAD infections can lead to high urgency listings for transplantation. However, transplantation in patients with infection leads to worse post‐transplantation outcomes. This study aims to evaluate specific risk factors for driveline infections at the time of implantation. Methods and results Four hundred forty‐one patients receiving either Heartmate II or Heartware system from August 2009 to October 2013 were assessed. An expert committee sorted patients into four different groups concerning the likeliness of infection. Twenty‐eight (6%) of discussed infection cases were judged as secured, 33 (7%) as likely, 18 (4%) as possible, and 20 (4%) as unlikely. The remaining 342 (78%) subjects showed either no signs of infection at all times (329 [75%]) or developed signs of infection in a second observation period within 1 year after ending of the first observation period (13 [3%]). For a better discriminatory power, cases of secured and likely infections were tested against the group with no infection at all times in a Cox proportional hazard model. Among all variables tested by univariate analysis (significance level P

Transcatheter edge-to-edge repair (TEER) is the most widely used approach for tricuspid regurgitation in patients with prohibitive surgical risk. However, TEER might not be feasible in advanced tricuspid regurgitation. In such cases, a stepwise approach with initial annuloplasty and subsequent TEER can be a worthwhile alternative, which is reported in this series. (Level of Difficulty: Intermediate.)

Abstract Aim Due to improved therapy in childhood, many patients with congenital heart disease reach adulthood and are termed adults with congenital heart disease (ACHD). ACHD often develop heart failure (HF) as a consequence of initial palliative surgery or complex anatomy and subsequently require advanced HF therapy. ACHD are usually excluded from trials evaluating heart failure therapies, and in this context, more data about heart failure trajectories in ACHD are needed to guide the management of ACHD suffering from HF. Methods and results The pAtients pResenTing with cOngenital heaRt dIseAse Register (ARTORIA‐R) will collect data from ACHD evaluated or listed for heart or heart‐combined organ transplantation from 16 countries in Europe and the Asia/Pacific region. We plan retrospective collection of data from 1989–2020 and will include patients prospectively. Additional organizations and hospitals in charge of transplantation of ACHD will be asked in the future to contribute data to the register. The primary outcome is the combined endpoint of delisting due to clinical worsening or death on the waiting list. The secondary outcome is delisting due to clinical improvement while on the waiting list. All‐cause mortality following transplantation will also be assessed. The data will be entered into an electronic database with access to the investigators participating in the register. All variables of the register reflect key components important for listing of the patients or assessing current HF treatment. Conclusion The ARTORIA‐R will provide robust information on current management and outcomes of adults with congenital heart disease suffering from advanced heart failure.

In heart failure, increased CaMKII activity is decisively involved in arrhythmia formation. Here, the authors introduce the neuronal sodium channel NaV1.8 as a CaMKII downstream target as its specific knock-out reduces arrhythmias and improves survival in a CaMKII-overexpressing mouse model.

BackgroundDue to its close anatomical proximity to the annular plane of the tricuspid valve (TV), the right coronary artery (RCA) is at risk of injury and distortion during surgical and interventional repair. Recently, reversible, non-flow limiting, purse-string like deformations of the RCA following percutaneous TV annuloplasty have been described. In contrast, there are only anecdotal reports on RCA deformation following conventional TV surgery.Materials and methodsA retrospective analysis of all patients undergoing TV surgery in our hospital between 2009 and 2019 was performed including all patients who received a post-operative coronary angiography (POCA). Angiographic footage was reviewed for RCA affections.ResultsA total of 1,383 patients underwent TV surgery (replacement and repair) for tricuspid regurgitation in our center. TV repair was performed in 1,248 (90.2%) patients and 135 (9.8%) patients underwent isolated TV surgery. Sixty-five patients (4.7%) underwent POCA within 48 h after surgery due to suspected myocardial ischemia, representing the final study population. Mean age was 70.3 ± 11.3 years, 56.3% were female. Mean EuroSCORE II was 9.8 ± 11.6%. Patients with the need for POCA due to suspected myocardial injury suffered from a higher mortality compared to event-free patients over the long-term follow up period (median 2.9 years) regardless of the observed coronary status. RCA affections were observed in 24 (36.9%) patients. A new RCA deformation without flow-impairment or vascular damage was found in 16 (24.6%) of the cases and was managed conservatively. There was no significantly worse outcome observed as compared to patients without RCA affections. Six (9.2%) patients showed an RCA deformation accompanied by subtotal occlusion. A complete RCA-occlusion was observed in 2 (3.1%) patients. Revascularization by percutaneous coronary intervention could be successfully performed in these patients. RCA deformation occurred exclusively after TV repair while no cases were observed after TV replacement.ConclusionRight coronary artery deformation without flow-limitation following surgical TV repair is a specific/typical phenomenon which might not impair patients’ outcome and could be managed conservatively in most of the cases. RCA injury indicating further interventional therapy is a rare complication of TV surgery. However, the need for immediate POCA in general appears to be associated with a worsened intermediate-term outcome.

Abstract Aims Heart transplantation (HTx) represents optimal care for advanced heart failure. Left ventricular assist devices (LVADs) are often needed as a bridge‐to‐transplant (BTT) therapy to support patients during the wait for a donor organ. Prolonged support increases the risk for LVAD complications that may affect the outcome after HTx. Methods and results A total of 342 patients undergoing HTx after LVAD as BTT in a 10‐year period in two German high‐volume HTx centres were retrospectively analysed. While 73 patients were transplanted without LVAD complications and with regular waiting list status (T, n = 73), the remaining 269 patients were transplanted with high urgency status (HU) and further divided with regard to the observed leading LVAD complications (infection: HU1, n = 91; thrombosis: HU2, n = 32; stroke: HU3, n = 38; right heart failure: HU4, n = 41; arrhythmia: HU5, n = 23; bleeding: HU6, n = 18; device malfunction: HU7, n = 26). Postoperative hospitalization was prolonged in patients with LVAD complications. Analyses of perioperative morbidity revealed no differences regarding primary graft dysfunction, renal failure, and neurological events except postoperative infections. Short‐term survival, as well as Kaplan–Meier survival analysis, indicated comparable results between the different study groups without disadvantages for patients with LVAD complications. Conclusions Left ventricular assist device therapy can impair the outcome after HTx. However, the occurrence of LVAD complications may not impact on outcome after HTx. Thus, we cannot support the prioritization or discrimination of HTx candidates according to distinct mechanical circulatory support‐associated complications. Future allocation strategies have to respect that device‐related complications may define urgency but do not impact on the outcome after HTx.

Abstract Aims Timely referrals for transplantation and left ventricular assist device (LVAD) play a key role in favourable outcomes in patients with advanced heart failure (HF). The purpose of the Catheter Ablation for atrial fibrillation in patientS with end‐sTage heart faiLure and Eligibility for Heart Transplantation (CASTLE‐HTx) trial is to test the hypothesis that atrial fibrillation (AF) ablation has beneficial effects on mortality and morbidity during ‘waiting time’ for heart transplantation (HTx) or to prolong the time span until LVAD implantation. Methods and Results CASTLE‐HTx is a randomized evaluation of ablative treatment of AF in patients with severe left ventricular dysfunction who are candidates and eligible for HTx. The primary endpoint is the composite of all‐cause mortality, worsening of HF requiring a high urgent transplantation, or LVAD implantation. The secondary study endpoints are all‐cause mortality, cardiovascular mortality, cerebrovascular accidents, worsening of HF requiring unplanned hospitalization, AF burden reduction, unplanned hospitalization due to cardiovascular reason, all‐cause hospitalization, quality of life, number of delivered implantable cardioverter defibrillator therapies, time to first implantable cardioverter defibrillator therapy, number of device‐detected ventricular tachycardia/ventricular fibrillation episodes, left ventricular function, exercise tolerance, and percentage of right ventricular pacing. Ventricular myocardial tissue will be obtained from patients who will undergo LVAD implantation or HTx to assess the effect of catheter ablation on human HF myocardium. CASTLE‐HTx will randomize 194 patients over a minimum time period of 2 years. Conclusions CASTLE‐HTx will determine if AF ablation has beneficial effects on mortality in patients with end‐stage HF who are eligible for HTx.

Summary: Recombinant SaCas9 is useful for a broad range of applications in the context of genome editing, especially when the specific protospacer adjacent motifs of other Cas9 derivatives are missing. Here, we describe a detailed protocol for the expression and purification of recombinant SaCas9. We detail the main steps for immobilized metal affinity chromatography and size exclusion chromatography. In addition, we present an assay for activity determination of SaCas9. Active SaCas9 can be purified in a week by using this protocol.

Abstract Aims Sufficient myocardial recovery with the subsequent explantation of a left ventricular assist device (LVAD) occurs in approximately 1–2% of the cases. However, follow‐up data about this condition are scarcely available in the literature. This study aimed to report the long‐term outcomes and clinical management following LVAD explantation. Methods and results An analysis of the European Registry for Patients with Mechanical Circulatory Support was performed to identify all adult patients with myocardial recovery and successful explantation. Pre‐implant characteristics were retrieved and compared with the non‐recovery patients. The follow‐up data after explantation were collected via a questionnaire. A Kaplan–Meier analysis for freedom of the composite endpoint of death, heart transplantation, LVAD reimplantion, or heart failure (HF) relapse was conducted. A total of 45 (1.4%) cases with myocardial recovery resulting in successful LVAD explantation were identified. Compared with those who did not experience myocardial recovery, the explanted patients were younger (44 vs. 56 years, P < 0.001), had a shorter duration of cardiac disease (P < 0.001), and were less likely to have ischaemic cardiomyopathy (9% vs. 41.8%, P < 0.001). Follow‐up after explantation could be acquired in 28 (62%) cases. The median age at LVAD implantation was 43 years (inter‐quartile range: 29–52), and 23 (82%) were male. Baseline left ventricular ejection fraction was 18% (inter‐quartile range: 10–20%), and 60.7% of the patients had Interagency Registry for Mechanically Assisted Circulatory Support Profile 1 or 2. Aetiologies of HF were dilated cardiomyopathy in 36%, myocarditis in 32%, and ischaemic in 14% of the patients, and 18% had miscellaneous aetiologies. The devices implanted were HeartMate II in 14 (50%), HVAD in 11 (39%), HeartMate 3 in 2 (7%), and 1 unknown with a median duration of support of 410 days (range: 59–1286). The median follow‐up after explantation was 26 months (range 0.3–73 months), and 82% of the patients were in New York Heart Association Class I or II. Beta‐blockers were prescribed to 85%, angiotensin‐converting enzyme inhibitors to 71%, and loop diuretics to 50% of the patients, respectively. Freedom from the composite endpoint was 100% after 30 days and 88% after 2 years. Conclusions The survival after LVAD explantation is excellent without the need for heart transplantation or LVAD reimplantation. Only a minority of the patients suffer from a relapse of significant HF.

The aim of the current paper is to summarize the results of the International CytoSorb Registry. Data were collected on patients of the intensive care unit. The primary endpoint was actual in-hospital mortality compared to the mortality predicted by APACHE II score. The main secondary endpoints were SOFA scores, inflammatory biomarkers and overall evaluation of the general condition. 1434 patients were enrolled. Indications for hemoadsorption were sepsis/septic shock (N = 936); cardiac surgery perioperatively (N = 172); cardiac surgery postoperatively (N = 67) and "other" reasons (N = 259). APACHE-II-predicted mortality was 62.0±24.8%, whereas observed hospital mortality was 50.1%. Overall SOFA scores did not change but cardiovascular and pulmonary SOFA scores decreased by 0.4 [-0.5;-0.3] and -0.2 [-0.3;-0.2] points, respectively. Serum procalcitonin and C-reactive protein levels showed significant reduction: -15.4 [-19.6;-11.17] ng/mL; -17,52 [-70;44] mg/L, respectively. In the septic cohort PCT and IL-6 also showed significant reduction: -18.2 [-23.6;-12.8] ng/mL; -2.6 [-3.0;-2.2] pg/mL, respectively. Evaluation of the overall effect: minimal improvement (22%), much improvement (22%) and very much improvement (10%), no change observed (30%) and deterioration (4%). There was no significant difference in the primary outcome of mortality, but there were improvements in cardiovascular and pulmonary SOFA scores and a reduction in PCT, CRP and IL-6 levels. Trial registration: ClinicalTrials.gov Identifier: NCT02312024 (retrospectively registered).

Background: The benefit of prophylactic left ventricular (LV) unloading during venoarterial extracorporeal membrane oxygenation (VA-ECMO) in selected patients at risk of developing LV distension remains unclear. Methods: We enrolled 136 patients treated with Impella pump decompression during VA-ECMO therapy for refractory cardiogenic shock. Patients were stratified by specific indication for LV unloading in the prophylactic vs. bail-out group. The bail-out unloading strategy was utilized to treat LV distension in VA-ECMO afterload-associated complications. The primary endpoint was all-cause 30-day mortality after VA-ECMO implantation. The secondary endpoint was successful myocardial recovery, transition to durable mechanical circulatory support (MCS), or heart transplantation. Results: After propensity score matching, prophylactic unloading was associated with a significantly lower 30-day mortality risk (risk ratio 0.38, 95% confidence interval 0.23–0.62, and p < 0.001) and a higher probability of myocardial recovery (risk ratio 2.9, 95% confidence interval 1.48–4.54, and p = 0.001) compared with the bail-out strategy. Heart transplantation or durable MCS did not differ significantly between groups. Conclusions: Prophylactic unloading compared with the bail-out strategy may improve clinical outcomes in selected patients on VA-ECMO. Nevertheless, randomized trials are needed to validate these results.

The telemonitoring of heart failure (HF) patients is becoming increasingly important. This study aimed to evaluate the benefit of telemonitoring in end-stage HF patients with a ventricular-assistance device (VAD). A total of 26 HF-patients (66 ± 11 years, 88% male) on VAD therapy with an implantable cardioverter-defibrillator (ICD) or a cardiac resynchronization defibrillator (CRT-D) including telemonitoring function were enrolled. The long-term follow-up data (4.10 ± 2.58 years) were assessed. All the patients (n = 26, 100%) received daily ICD/CRT-D telemonitoring. In most of the patients (73%, n = 19), the telemedical center had to take action for a mean of three times. An acute alert due to sustained ventricular arrhythmias (VAs) occurred in 12 patients (63%) with 50% of them (n = 6) requiring ICD shock delivery. Eight patients (67%) were hospitalized due to symptomatic VAs. In 11 patients (92%), immediate medication adjustments were recommended. Relevant lead issues were revealed in thirteen patients (50%), with six patients (46%) undergoing consecutive lead revisions. Most of the events (83%) were detected within 24 h. Daily telemonitoring significantly reduced the number of in-hospital device controls by 44% (p < 0.01). The telemonitoring ensured that cardiac arrhythmias and device/lead problems were identified early, allowing pre-emptive and prompt interventions. In addition, the telemonitoring significantly reduced the number of in-hospital device controls in this cohort of HF patients.

Desmin is the major intermediate filament protein of all three muscle cell types, and connects different cell organelles and multi-protein complexes such as the cardiac desmosomes. Several pathogenic mutations in the DES gene cause different skeletal and cardiac myopathies. However, the significance of the majority of DES missense variants is currently unknown, since functional data are lacking. To determine whether desmin missense mutations within the highly conserved 1A coil domain cause a filament assembly defect, we generated a set of variants with unknown significance and systematically analyzed the filament assembly using confocal microscopy in transfected SW-13, H9c2 cells and cardiomyocytes derived from induced pluripotent stem cells. We found that mutations in the N-terminal part of the 1A coil domain affect filament assembly, leading to cytoplasmic desmin aggregation. In contrast, mutant desmin in the C-terminal part of the 1A coil domain forms filamentous structures comparable to wild-type desmin. Our findings suggest that the N-terminal part of the 1A coil domain is a hot spot for pathogenic desmin mutations, which affect desmin filament assembly. This study may have relevance for the genetic counselling of patients carrying variants in the 1A coil domain of the DES gene.

Desmocollin‐2 (DSC2) is a desmosomal protein of the cadherin family. Desmosomes are multiprotein complexes, which are involved in cell adhesion of cardiomyocytes and of keratinocytes. The molecular structure of the complete extracellular domain (ECD) of DSC2 was recently described, revealing three disulfide bridges, four N‐glycosylation sites, and four O‐mannosylation sites. However, the functional relevance of these post‐translational modifications for the protein trafficking of DSC2 to the plasma membrane is still unknown. Here, we generated a set of DSC2 mutants, in which we systematically exchanged all N‐glycosylation sites, O‐mannosylation sites, and disulfide bridges within the ECD and investigated the resulting subcellular localization by confocal laser scanning microscopy. Of note, all single and double N‐glycosylation‐ deficient mutants were efficiently incorporated into the plasma membrane, indicating that the absence of these glycosylation sites has a minor effect on the protein trafficking of DSC2. However, the exchange of multiple N‐glycosylation sites resulted in intracellular accumulation. Colocalization analysis using cell compartment trackers revealed that N‐glycosylation‐ deficient DSC2 mutants were retained within the Golgi apparatus. In contrast, elimination of the four O‐mannosylation sites or the disulfide bridges in the ECD has no obvious effect on the intracellular protein processing of DSC2. These experiments underscore the importance of N‐glycosylation at multiple sites of DSC2 for efficient intracellular transport to the plasma membrane.

Arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC-5) is a dominantly inherited cardiomyopathy caused by the mutation TMEM43-p.S358L. An induced pluripotent stem cell (iPSC) line (HDZi001-A) from an adult male mutation carrier was generated, using the CytoTune Sendai Kit. The resulting iPSCs carried the mutation TMEM43-p.S358L, had a normal morphology, a stable karyotype and were positive for the expression of pluripotency markers. This iPSC line can be differentiated into the three germ layers and might be a useful model for the characterization of ARVC-5 associated pathomechanism.

Background: Bone marrow stem cell clonal dysfunction by somatic mutation is suspected to affect post-infarction myocardial regeneration after coronary bypass surgery (CABG). Methods: Transcriptome and variant expression analysis was studied in the phase 3 PERFECT trial post myocardial infarction CABG and CD133+ bone marrow derived hematopoetic stem cells showing difference in left ventricular ejection fraction (∆LVEF) myocardial regeneration Responders (n=14; ∆LVEF +16% day 180/0) and Non-responders (n=9; ∆LVEF -1.1% day 180/0). Subsequently, the findings have been validated in an independent patient cohort (n=14) as well as in two preclinical mouse models investigating SH2B3/LNK antisense or knockout deficient conditions. Findings: 1. Clinical: R differed from NR in a total of 161 genes in differential expression (n=23, q

Bacterial infections of vascular grafts represent a major burden in cardiovascular medicine, which is related to an increase in morbidity and mortality. Different factors that are associated with this medical field such as patient frailty, biofilm formation, or immunosuppression negatively influence antibiotic treatment, inhibiting therapy success. Thus, further treatment strategies are required. Bacteriophage antibacterial properties were discovered 100 years ago, but the focus on antibiotics in Western medicine since the mid-20th century slowed the further development of bacteriophage therapy. Therefore, the experience and knowledge gained until then in bacteriophage mechanisms of action, handling, clinical uses, and limitations were largely lost. However, the parallel emergence of antimicrobial resistance and individualized medicine has provoked a radical reassessment of this approach and cardiovascular surgery is one area in which phages may play an important role to cope with this new scenario. In this context, bacteriophages might be applicable for both prophylactic and therapeutic use, serving as a stand-alone therapy or in combination with antibiotics. From another perspective, standardization of phage application is also required. The ideal surgical bacteriophage application method should be less invasive, enabling highly localized concentrations, and limiting bacteriophage distribution to the infection site during a prolonged time lapse. This review describes the latest reports of phage therapy in cardiovascular surgery and discusses options for their use in implant and vascular graft infections.

Currently, little is known about the genetic background of restrictive cardiomyopathy (RCM). Herein, we screened an index patient with RCM in combination with atrial fibrillation using a next generation sequencing (NGS) approach and identified the heterozygous mutation DES-c.735G>C. As DES-c.735G>C affects the last base pair of exon-3, it is unknown whether putative missense or splice site mutations are caused. Therefore, we applied nanopore amplicon sequencing revealing the expression of a transcript without exon-3 in the explanted myocardial tissue of the index patient. Western blot analysis verified this finding at the protein level. In addition, we performed cell culture experiments revealing an abnormal cytoplasmic aggregation of the truncated desmin form (p.D214-E245del) but not of the missense variant (p.E245D). In conclusion, we show that DES-c.735G>C causes a splicing defect leading to exon-3 skipping of the DES gene. DES-c.735G>C can be classified as a pathogenic mutation associated with RCM and atrial fibrillation. In the future, this finding might have relevance for the genetic understanding of similar cases.

The present article is the first official report of ESPAMACS (Spanish Registry for Mechanical Circulatory Support) and summarises the registry activity from when it began operating in October 2014–May 2016. During this period, 369 mechanical circulatory support devices, implanted in 18 different centres of our country have been registered, 319 for short-term support (86.4%), and 50 for long-term support (13.6%). An analysis is presented of the profile of the assisted patients (demographic data, comorbidities, underlying disease, grade of heart failure), type of implanted devices, indications, surgical data and outcomes (post-operative outcome, duration of support, level of achieving objectives, adverse events, survival, and causes of death).

During aging, senescent cells accumulate in various tissues accompanied by decreased regenerative capacities of quiescent stem cells, resulting in deteriorated organ function and overall degeneration. In this regard, the adult human heart with a generally low regenerative potential is of extreme interest as a target for rejuvenating strategies with blood borne factors that might be able to activate endogenous stem cell populations. Here, we investigated for the first time the effects of human blood plasma and serum on adult human cardiac stem cells (hCSCs) and showed significantly increased proliferation capacities and metabolism accompanied by a significant decrease of senescent cells, demonstrating a beneficial serum-mediated effect that seemed to be independent of age and sex. However, RNA-seq analysis of serum-treated hCSCs revealed profound effects on gene expression depending on the age and sex of the plasma donor. We further successfully identified key pathways that are affected by serum treatment with p38-MAPK playing a regulatory role in protection from senescence and in the promotion of proliferation in a serum-dependent manner. Inhibition of p38-MAPK resulted in a decline of these serum-mediated beneficial effects on hCSCs in terms of decreased proliferation and accelerated senescence. In summary, we provide new insights in the regulatory networks behind serum-mediated protective effects on adult human cardiac stem cells.