Distal Reoperations after Repair of Acute Type A Aortic Dissection—Incidence, Causes and Outcomes

Background and Aim of the Study: In patients with acute type A aortic dissection (A-AAD) whether initial repair should include also aortic arch replacement is still debated. We aimed to assess if extensive aortic repair prevents from reoperations patients with A-AAD. Methods: Outcomes after distal reoperation following repair of A-AAD (n = 285; 1977 to 2018) were analysed in 22 of 226 who underwent ascending aorta/hemiarch replacement (Group 1R) and 7 of 59 who had ascending aorta/arch replacement (Group 2R). Results: Distal reoperation was more common in Group 1R (n = 22) than in Group 2R (n = 0) (p < 0.001) while thoracic endovascular stenting was more frequent in Group 2R (7 vs 3, p < 0.001). Indications for reoperation were pseudoaneurysm at distal anastomosis (n = 4, 18%) and progression of aortic dissection (n = 18, 82%) in Group 1R. Indication for thoracic endovascular stenting was progressive aortic dissection in 3 patients of Group 1R and in 6 of Group 2R. Second reoperation was required in 2 patients from Group 1R (2%) during a mean follow-up of 5 years. Median follow-up was 4 years in Group 1R and 7 years in Group 2R (p = 0.36). Hospital mortality was 14% in Group 1R and 0% in Group 2R (p = 0.3). Actuarial survival is 68 ± 10%, and 62 ± 11% for Group 1R and 100% for Group 2R at 5 and 10 years (p = 0.076). Conclusions: Distal reoperations after A-AAD repair have an acceptable mortality. An extensive initial repair has lower rate of reoperation and better mid-term survival and should be indicated especially for young patients in experienced centers

Heart Transplantation in High-Risk Recipients Employing Donor Marginal Grafts Preserved With Ex-Vivo Perfusion

Extending selection criteria to face donor organ shortage in heart transplantation (HTx) may increase the risk of mortality. Ex-vivo normothermic perfusion (EVP) limits ischemic time allowing assessment of graft function. We investigated the outcome of HTx in 80 high-risk recipients transplanted with marginal donor and EVP-preserved grafts, from 2016 to 2021. The recipients median age was 57 years (range, 13–75), with chronic renal failure in 61%, impaired liver function in 11% and previous cardiac surgery in 90%; 80% were mechanically supported. Median RADIAL score was 3. Mean graft ischemic time was 118 ± 25 min, “out-of-body” time 420 ± 66 min and median cardiopulmonary bypass (CPB) time 228 min (126–416). In-hospital mortality was 11% and ≥moderate primary graft dysfunction 16%. At univariable analysis, CPB time and high central venous pressure were risk factors for mortality. Actuarial survival at 1 and 3 years was 83% ± 4%, and 72% ± 7%, with a median follow-up of 16 months (range 2–43). Recipient and donor ages, pre-HTx extracorporeal life support and intra-aortic balloon pump were risk factors for late mortality. In conclusion, the use of EVP allows extension of the graft pool by recruitment of marginal donors to successfully perform HTx even in high-risk recipients

The longevity-associated BPIFB4 gene supports cardiac function and vascularization in ageing cardiomyopathy

Aims The ageing heart naturally incurs a progressive decline in function and perfusion that available treatments cannot halt. However, some exceptional individuals maintain good health until the very late stage of their life due to favourable gene-environment interaction. We have previously shown that carriers of a longevity-associated variant (LAV) of the BPIFB4 gene enjoy prolonged health spans and lesser cardiovascular complications. Moreover, supplementation of LAV-BPIFB4 via an adeno-associated viral vector improves cardiovascular performance in limb ischaemia, atherosclerosis, and diabetes models. Here, we asked whether the LAV-BPIFB4 gene could address the unmet therapeutic need to delay the heart's spontaneous ageing. Methods and results Immunohistological studies showed a remarkable reduction in vessel coverage by pericytes in failing hearts explanted from elderly patients. This defect was attenuated in patients carrying the homozygous LAV-BPIFB4 genotype. Moreover, pericytes isolated from older hearts showed low levels of BPIFB4, depressed pro-angiogenic activity, and loss of ribosome biogenesis. LAV-BPIFB4 supplementation restored pericyte function and pericyte-endothelial cell interactions through a mechanism involving the nucleolar protein nucleolin. Conversely, BPIFB4 silencing in normal pericytes mimed the heart failure pericytes. Finally, gene therapy with LAV-BPIFB4 prevented cardiac deterioration in middle-aged mice and rescued cardiac function and myocardial perfusion in older mice by improving microvasculature density and pericyte coverage. Conclusions We report the success of the LAV-BPIFB4 gene/protein in improving homeostatic processes in the heart's ageing. These findings open to using LAV-BPIFB4 to reverse the decline of heart performance in older people

Induction of leaf senescence in Arabidopsis thaliana by long days through a light-dosage effect

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74662/1/j.1399-3054.1996.tb00463.x.pd

Survival and Recurrence of Endocarditis following Mechanical vs. Biological Aortic Valve Replacement for Endocarditis in Patients Aged 40 to 65 Years: Data from the INFECT-Registry

Background: Infective endocarditis (IE) is a serious disease, and in many cases, surgery is necessary. Whether the type of prosthesis implanted for aortic valve replacement (AVR) for IE impacts patient survival is a matter of debate. The aim of the present study is to quantify differences in long-term survival and recurrence of endocarditis AVR for IE according to prosthesis type among patients aged 40 to 65 years. Methods: This was an analysis of the INFECT-REGISTRY. Trends in proportion to the use of mechanical prostheses versus biological ones over time were tested by applying the sieve bootstrapped t-test. Confounders were adjusted using the optimal full-matching propensity score. The difference in overall survival was compared using the Cox model, whereas the differences in recurrence of endocarditis were evaluated using the Gray test. Results: Overall, 4365 patients were diagnosed and operated on for IE from 2000 to 2021. Of these, 549, aged between 40 and 65 years, underwent AVR. A total of 268 (48.8%) received mechanical prostheses, and 281 (51.2%) received biological ones. A significant trend in the reduction of implantation of mechanical vs. biological prostheses was observed during the study period (p < 0.0001). Long-term survival was significantly higher among patients receiving a mechanical prosthesis than those receiving a biological prosthesis (hazard ratio [HR] 0.546, 95% CI: 0.322–0.926, p = 0.025). Mechanical prostheses were associated with significantly less recurrent endocarditis after AVR than biological prostheses (HR 0.268, 95%CI: 0.077–0.933, p = 0.039). Conclusions: The present analysis of the INFECT-REGISTRY shows increased survival and reduced recurrence of endocarditis after a mechanical aortic valve prosthesis implant for IE in middle-aged patients

Extracorporeal Membrane Oxygenation for Graft Dysfunction Early After Heart Transplantation: A Systematic Review and Meta-analysis

Introduction: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO. Methods and Results: We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%–39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%–57%). Recipient age (odds ratio 1.02, 95% CI 1.01–1.04) and prior sternotomy (OR 1.57, 95% CI 0.99–2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death. Conclusions: One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT

Phylogenetic Identification of Fungi Isolated from the Marine Sponge Tethya aurantium and Identification of Their Secondary Metabolites

Fungi associated with the marine sponge Tethya aurantium were isolated and identified by morphological criteria and phylogenetic analyses based on internal transcribed spacer (ITS) regions. They were evaluated with regard to their secondary metabolite profiles. Among the 81 isolates which were characterized, members of 21 genera were identified. Some genera like Acremonium, Aspergillus, Fusarium, Penicillium, Phoma, and Trichoderma are quite common, but we also isolated strains belonging to genera like Botryosphaeria, Epicoccum, Parasphaeosphaeria, and Tritirachium which have rarely been reported from sponges. Members affiliated to the genera Bartalinia and Volutella as well as to a presumably new Phoma species were first isolated from a sponge in this study. On the basis of their classification, strains were selected for analysis of their ability to produce natural products. In addition to a number of known compounds, several new natural products were identified. The scopularides and sorbifuranones have been described elsewhere. We have isolated four additional substances which have not been described so far. The new metabolite cillifuranone (1) was isolated from Penicillium chrysogenum strain LF066. The structure of cillifuranone (1) was elucidated based on 1D and 2D NMR analysis and turned out to be a previously postulated intermediate in sorbifuranone biosynthesis. Only minor antibiotic bioactivities of this compound were found so far

Patient and Management Variables Associated With Survival After Postcardiotomy Extracorporeal Membrane Oxygenation in Adults: The PELS-1 Multicenter Cohort Study

Background Extracorporeal membrane oxygenation (ECMO) has been increasingly used for postcardiotomy cardiogenic shock, but without a concomitant reduction in observed in-hospital mortality. Long-term outcomes are unknown. This study describes patients' characteristics, in-hospital outcome, and 10-year survival after postcardiotomy ECMO. Variables associated with in-hospital and postdischarge mortality are investigated and reported. Methods and Results The retrospective international multicenter observational PELS-1 (Postcardiotomy Extracorporeal Life Support) study includes data on adults requiring ECMO for postcardiotomy cardiogenic shock between 2000 and 2020 from 34 centers. Variables associated with mortality were estimated preoperatively, intraoperatively, during ECMO, and after the occurrence of any complications, and then analyzed at different time points during a patient's clinical course, through mixed Cox proportional hazards models containing fixed and random effects. Follow-up was established by institutional chart review or contacting patients. This analysis included 2058 patients (59% were men; median [interquartile range] age, 65.0 [55.0-72.0] years). In-hospital mortality was 60.5%. Independent variables associated with in-hospital mortality were age (hazard ratio [HR], 1.02 [95% CI, 1.01-1.02]) and preoperative cardiac arrest (HR, 1.41 [95% CI, 1.15-1.73]). In the subgroup of hospital survivors, the overall 1-, 2-, 5-, and 10-year survival rates were 89.5% (95% CI, 87.0%-92.0%), 85.4% (95% CI, 82.5%-88.3%), 76.4% (95% CI, 72.5%-80.5%), and 65.9% (95% CI, 60.3%-72.0%), respectively. Variables associated with postdischarge mortality included older age, atrial fibrillation, emergency surgery, type of surgery, postoperative acute kidney injury, and postoperative septic shock. Conclusions In adults, in-hospital mortality after postcardiotomy ECMO remains high; however, two-thirds of those who are discharged from hospital survive up to 10 years. Patient selection, intraoperative decisions, and ECMO management remain key variables associated with survival in this cohort. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03857217

Therapeutic decision-making for patients with fluctuating mitral regurgitation

Mitral regurgitation (MR) is a common, progressive, and difficult-to-manage disease. MR is dynamic in nature, with physiological fluctuations occurring in response to various stimuli such as exercise and ischaemia, which can precipitate the development of symptoms and subsequent cardiac events. In both chronic primary and secondary MR, the dynamic behaviour of MR can be reliably examined during stress echocardiography. Dynamic fluctuation of MR can also have prognostic value; patients with a marked increase in regurgitant volume or who exhibit increased systolic pulmonary artery pressure during exercise have lower symptom-free survival than those who do not experience significant changes in MR and systolic pulmonary artery pressure during exercise. Identifying patients who have dynamic MR, and understanding the mechanisms underlying the condition, can potentially influence revascularization strategies (such as the surgical restoration of coronary blood flow) and interventional treatment (including cardiac resynchronization therapy and new approaches targeted to the mitral valve)

Heterogeneity in clinical practices for post-cardiotomy extracorporeal life support: A pilot survey from the PELS-1 multicenter study

Background: High-quality evidence for post-cardiotomy extracorporeal life support (PC-ECLS) management is lacking. This study investigated real-world PC-ECLS clinical practices. Methods: This cross-sectional, multi-institutional, international pilot survey explored center organization, anticoagulation management, left ventricular unloading, distal limb perfusion, PC-ECLS monitoring, and transfusion practices. Twenty-nine questions were distributed among 34 hospitals participating in the Post-cardiotomy Extra-Corporeal Life Support Study. Results: Of the 32 centers [16 low-volume (50%); 16 high-volume (50%)] that responded, 16 (50%) had dedicated ECLS specialists. Twenty-six centers (81.3%) reported using additional mechanical circulatory supports. Anticoagulation practices were highly heterogeneous: 24 hospitals (75%) reported using patients bleeding status as a guide, without a specific threshold in 54.2% of cases. Transfusion targets ranged from 7 to 10 g/dL. Most centers used cardiac venting on a case-by-case basis (78.1%) and regular distal limb perfusion (84.4%). Nineteen (54.9%) centers reported dedicated monitoring protocols, including daily echocardiography (87.5%), Swan-Ganz catheterization (40.6%), cerebral near-infrared spectroscopy (53.1%), and multimodal assessment of limb ischemia. Inspection of the circuit (71.9%), oxygenator pressure drop (68.8%), plasma free hemoglobin (75%), d-dimer (59.4%), lactate dehydrogenase (56.3%), and fibrinogen (46.9%) are used to diagnose hemolysis and thrombosis. Conclusions: This study shows remarkable heterogeneity in clinical practices for PC-ECLS management. More standardized protocols and better implementation of the available evidence are recommended