Neurologic complications in patients receiving aortic versus subclavian versus femoral arterial cannulation for post-cardiotomy extracorporeal life support: results of the PELS observational multicenter study.

BACKGROUND: Cerebral perfusion may change depending on arterial cannulation site and may affect the incidence of neurologic adverse events in post-cardiotomy extracorporeal life support (ECLS). The current study compares patients' neurologic outcomes with three commonly used arterial cannulation strategies (aortic vs. subclavian/axillary vs. femoral artery) to evaluate if each ECLS configuration is associated with different rates of neurologic complications. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring post-cardiotomy ECLS between January 2000 and December 2020 present in the Post-Cardiotomy Extracorporeal Life Support (PELS) Study database. Patients with Aortic, Subclavian/Axillary and Femoral cannulation were compared on the incidence of a composite neurological end-point (ischemic stroke, cerebral hemorrhage, brain edema). Secondary outcomes were overall in-hospital mortality, neurologic complications as cause of in-hospital death, and post-operative minor neurologic complications (seizures). Association between cannulation and neurological outcomes were investigated through linear mixed-effects models. RESULTS: This study included 1897 patients comprising 26.5% Aortic (n = 503), 20.9% Subclavian/Axillary (n = 397) and 52.6% Femoral (n = 997) cannulations. The Subclavian/Axillary group featured a more frequent history of hypertension, smoking, diabetes, previous myocardial infarction, dialysis, peripheral artery disease and previous stroke. Neuro-monitoring was used infrequently in all groups. Major neurologic complications were more frequent in Subclavian/Axillary (Aortic: n = 79, 15.8%; Subclavian/Axillary: n = 78, 19.6%; Femoral: n = 118, 11.9%; p < 0.001) also after mixed-effects model adjustment (OR 1.53 [95% CI 1.02-2.31], p = 0.041). Seizures were more common in Subclavian/Axillary (n = 13, 3.4%) than Aortic (n = 9, 1.8%) and Femoral cannulation (n = 12, 1.3%, p = 0.036). In-hospital mortality was higher after Aortic cannulation (Aortic: n = 344, 68.4%, Subclavian/Axillary: n = 223, 56.2%, Femoral: n = 587, 58.9%, p < 0.001), as shown by Kaplan-Meier curves. Anyhow, neurologic cause of death (Aortic: n = 12, 3.9%, Subclavian/Axillary: n = 14, 6.6%, Femoral: n = 28, 5.0%, p = 0.433) was similar. CONCLUSIONS: In this analysis of the PELS Study, Subclavian/Axillary cannulation was associated with higher rates of major neurologic complications and seizures. In-hospital mortality was higher after Aortic cannulation, despite no significant differences in incidence of neurological cause of death in these patients. These results encourage vigilance for neurologic complications and neuromonitoring use in patients on ECLS, especially with Subclavian/Axillary cannulation.

Post-cardiotomy extracorporeal life support: A cohort of cannulation in the general ward.

OBJECTIVES: Post-cardiotomy extracorporeal life support (ECLS) cannulation might occur in a general post-operative ward due to emergent conditions. Its characteristics have been poorly reported and investigated This study investigates the characteristics and outcomes of adult patients receiving ECLS cannulation in a general post-operative cardiac ward. METHODS: The Post-cardiotomy Extracorporeal Life Support (PELS) is a retrospective (2000-2020), multicenter (34 centers), observational study including adult patients who required ECLS for post-cardiotomy shock. This PELS sub-analysis analyzed patients´ characteristics, in-hospital outcomes, and long-term survival in patients cannulated for veno-arterial ECLS in the general ward, and further compared in-hospital survivors and non-survivors. RESULTS: The PELS study included 2058 patients of whom 39 (1.9%) were cannulated in the general ward. Most patients underwent isolated coronary bypass grafting (CABG, n = 15, 38.5%) or isolated non-CABG operations (n = 20, 51.3%). The main indications to initiate ECLS included cardiac arrest (n = 17, 44.7%) and cardiogenic shock (n = 14, 35.9%). ECLS cannulation occurred after a median time of 4 (2-7) days post-operatively. Most patients' courses were complicated by acute kidney injury (n = 23, 59%), arrhythmias (n = 19, 48.7%), and postoperative bleeding (n = 20, 51.3%). In-hospital mortality was 84.6% (n = 33) with persistent heart failure (n = 11, 28.2%) as the most common cause of death. No peculiar differences were observed between in-hospital survivors and nonsurvivors. CONCLUSIONS: This study demonstrates that ECLS cannulation due to post-cardiotomy emergent adverse events in the general ward is rare, mainly occurring in preoperative low-risk patients and after a postoperative cardiac arrest. High complication rates and low in-hospital survival require further investigations to identify patients at risk for such a complication, optimize resources, enhance intervention, and improve outcomes.

Characteristics and Outcomes of Prolonged Venoarterial Extracorporeal Membrane Oxygenation After Cardiac Surgery: The Post-Cardiotomy Extracorporeal Life Support (PELS-1) Cohort Study.

OBJECTIVES: Most post-cardiotomy (PC) extracorporeal membrane oxygenation (ECMO) runs last less than 7 days. Studies on the outcomes of longer runs have provided conflicting results. This study investigates patient characteristics and short- and long-term outcomes in relation to PC ECMO duration, with a focus on prolonged (> 7 d) ECMO. DESIGN: Retrospective observational cohort study. SETTING: Thirty-four centers from 16 countries between January 2000 and December 2020. PATIENTS: Adults requiring post PC ECMO between 2000 and 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Characteristics, in-hospital, and post-discharge outcomes were compared among patients categorized by ECMO duration. Survivors and nonsurvivors were compared in the subgroup of patients with ECMO duration greater than 7 days. The primary outcome was in-hospital mortality. Two thousand twenty-one patients were included who required PC ECMO for 0-3 days (n = 649 [32.1%]), 4-7 days (n = 776 [38.3%]), 8-10 days (n = 263 [13.0%]), and greater than 10 days (n = 333 [16.5%]). There were no major differences in the investigated preoperative and procedural characteristics among ECMO duration groups. However, the longer ECMO duration category was associated with multiple complications including bleeding, acute kidney injury, arrhythmias, and sepsis. Hospital mortality followed a U-shape curve, with lowest mortality in patients with ECMO duration of 4-7 days (n = 394, 50.8%) and highest in patients with greater than 10 days ECMO support (n = 242, 72.7%). There was no significant difference in post-discharge survival between ECMO duration groups. In patients with ECMO duration greater than 7 days, age, comorbidities, valvular diseases, and complex procedures were associated with nonsurvival. CONCLUSIONS: Nearly 30% of PC ECMO patients were supported for greater than 7 days. In-hospital mortality increased after 7 days of support, especially in patients undergoing valvular and complex surgery, or who had complications, although the long-term post-discharge prognosis was comparable to PC ECMO patients with shorter support duration.

Features and outcomes of female and male patients requiring postcardiotomy extracorporeal life support.

OBJECTIVES: Although cardiogenic shock requiring extracorporeal life support after cardiac surgery is associated with high mortality, the impact of sex on outcomes of postcardiotomy extracorporeal life support remains unclear with conflicting results in the literature. We compare patient characteristics, in-hospital outcomes, and overall survival between females and males requiring postcardiotomy extracorporeal life support. METHODS: This retrospective, multicenter (34 centers), observational study included adults requiring postcardiotomy extracorporeal life support between 2000 and 2020. Preoperative, procedural, and extracorporeal life support characteristics, complications, and survival were compared between females and males. Association between sex and in-hospital survival was investigated through mixed Cox proportional hazard models. RESULTS: This analysis included 1823 patients (female: 40.8%; median age: 66.0 years [interquartile range, 56.2-73.0 years]). Females underwent more mitral valve surgery (females: 38.4%, males: 33.1%, P = .019) and tricuspid valve surgery (feamales: 18%, males: 12.4%, P < .001), whereas males underwent more coronary artery surgery (females: 45.9%, males: 52.4%, P = .007). Extracorporeal life support implantation was more common intraoperatively in feamales (females: 64.1%, females: 59.1%) and postoperatively in males (females: 35.9%, males: 40.9%, P = .036). Ventricular unloading (females: 25.1%, males: 36.2%, P < .001) and intra-aortic balloon pumps (females: 25.8%, males: 36.8%, P < .001) were most frequently used in males. Females had more postoperative right ventricular failure (females: 24.1%, males: 19.1%, P = .016) and limb ischemia (females: 12.3%, males: 8.8%, P = .23). In-hospital mortality was 64.9% in females and 61.9% in males (P = .199) with no differences in 5-year survival (females: 20%, 95% CI, 17-23; males: 24%, 95% CI, 21-28; P = .069). Crude hazard ratio for in-hospital mortality in females was 1.12 (95% CI, 0.99-1.27; P = .069) and did not change after adjustments. CONCLUSIONS: This study demonstrates that female and male patients requiring postcardiotomy extracorporeal life support have different preoperative and extracorporeal life support characteristics, as well as complications, without a statistical difference in in-hospital and 5-year survivals.

Long-term survival after surgical treatment for post-infarction mechanical complications: results from the Caution study.

BACKGROUND AND AIMS: Mechanical complications (MCs) are rare but potentially fatal sequelae of acute myocardial infarction (AMI). Surgery, though challenging, is considered the treatment of choice. The authors sought to study early and long-term results of patients undergoing surgical treatment for post-AMI MCs. METHODS: Patients undergone surgical treatment for post-infarction MCs between 2001 through 2019 in 27 centers worldwide were retrieved from the database of CAUTION study. In-hospital and long-term mortality were the primary outcomes. Cox proportional hazards regression models were used to determine independent factors associated with overall mortality. RESULTS: The study included 720 patients. The median age was 70.0 [62.0-77.0] years, with a male predominance (64.6%). The most common MC encountered was ventricular septal rupture (VSR) (59.4%). Cardiogenic shock was seen on presentation in 56.1% of patients. In-hospital mortality rate was 37.4%; in more than 50% of cases, the cause of death was low cardiac output syndrome (LCOS). Late mortality occurred in 133 patients, with a median follow-up of 4.4 [1.0-8.6] years. Overall survival at 1, 5 and 10 years was 54.0%, 48.1% and 41.0%, respectively. Older age (p < 0.001) and postoperative LCOS (p < 0.001) were independent predictors of overall mortality. For hospital survivors, 10-year survival was 65.7% and was significant higher for patients with VSR than those with papillary muscle rupture (long-rank P = 0.022). CONCLUSIONS: Contemporary data from a multicenter cohort study show that surgical treatment for post-AMI MCs continues to be associated with high in-hospital mortality rates. However, long-term survival in patients surviving the immediate postoperative period is encouraging.Trial registration number: NCT03848429.

Impact of COVID-19 on incidence and outcomes of post-infarction mechanical complications in Europe.

OBJECTIVES: Post-acute myocardial infarction mechanical complications (post-AMI MCs) represent rare but life-threatening conditions, including free-wall rupture, ventricular septal rupture and papillary muscle rupture. During the coronavirus disease-19 (COVID-19) pandemic, an overwhelming pressure on healthcare systems led to delayed and potentially suboptimal treatments for time-dependent conditions. As AMI-related hospitalizations decreased, limited information is available whether higher rates of post-AMI MCs and related deaths occurred in this setting. This study was aimed to assess how COVID-19 in Europe has impacted the incidence, treatment and outcome of MCs. METHODS: The CAUTION-COVID19 study is a multicentre retrospective study collecting 175 patients with post-AMI MCs in 18 centres from 6 European countries, aimed to compare the incidence of such events, related patients' characteristics, and outcomes, between the first year of pandemic and the 2 previous years. RESULTS: A non-significant increase in MCs was observed [odds ratio (OR) = 1.15, 95% confidence interval (CI) 0.85-1.57; P = 0.364], with stronger growth in ventricular septal rupture diagnoses (OR = 1.43, 95% CI 0.95-2.18; P = 0.090). No significant differences in treatment types and mortality were found between the 2 periods. In-hospital mortality was 50.9% and was higher for conservatively managed cases (90.9%) and lower for surgical patients (44.0%). Patients admitted during COVID-19 more frequently had late-presenting infarction (OR = 2.47, 95% CI 1.24-4.92; P = 0.010), more stable conditions (OR = 2.61, 95% CI 1.27-5.35; P = 0.009) and higher EuroSCORE II (OR = 1.04, 95% CI 1.01-1.06; P = 0.006). CONCLUSIONS: A non-significant increase in MCs incidence occurred during the first year of COVID-19, characterized by a significantly higher rate of late-presenting infarction, stable conditions and EuroSCORE-II if compared to pre-pandemic data, without affecting treatment and mortality.

The current clinical practice for management of post-infarction ventricular septal rupture: a European survey.

Aims: Many historical and recent reports showed that post-infarction ventricular septal rupture (VSR) represents a life-threatening condition and the strategy to optimally manage it remains undefined. Therefore, disparate treatment policies among different centres with variable results are often described. We analysed data from European centres to capture the current clinical practice in VSR management. Methods and results: Thirty-nine centres belonging to eight European countries participated in a survey, filling a digital form of 38 questions from April to October 2022, to collect information about all the aspects of VSR treatment. Most centres encounter 1-5 VSR cases/year. Surgery remains the treatment of choice over percutaneous closure (71.8% vs. 28.2%). A delayed repair represents the preferred approach (87.2%). Haemodynamic conditions influence the management in almost all centres, although some try to achieve patients stabilization and delayed surgery even in cardiogenic shock. Although 33.3% of centres do not perform coronarography in unstable patients, revascularization approaches are widely variable. Most centres adopt mechanical circulatory support (MCS), mostly extracorporeal membrane oxygenation, especially pre-operatively to stabilize patients and achieve delayed repair. Post-operatively, such MCS are more often adopted in patients with ventricular dysfunction. Conclusion: In real-life, delayed surgery, regardless of the haemodynamic conditions, is the preferred strategy for VSR management in Europe. Extracorporeal membrane oxygenation is becoming the most frequently adopted MCS as bridge-to-operation. This survey provides a useful background to develop dedicated, prospective studies to strengthen the current evidence on VSR treatment and to help improving its currently unsatisfactory outcomes.

On-Support and Postweaning Mortality in Postcardiotomy Extracorporeal Membrane Oxygenation.

BACKGROUND: Postcardiotomy venoarterial extracorporeal membrane oxygenation (VA ECMO) is characterized by discrepancies between weaning and survival-to-discharge rates. This study analyzes the differences between postcardiotomy VA ECMO patients who survived, died on ECMO, or died after ECMO weaning. Causes of death and variables associated with mortality at different time points are investigated. METHODS: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support Study (PELS) includes adults requiring postcardiotomy VA ECMO between 2000 and 2020. Variables associated with on-ECMO mortality and postweaning mortality were modeled using mixed Cox proportional hazards, including random effects for center and year. RESULTS: In 2058 patients (men, 59%; median age, 65 years; interquartile range [IQR], 55-72 years), weaning rate was 62.7%, and survival to discharge was 39.6%. Patients who died (n = 1244) included 754 on-ECMO deaths (36.6%; median support time, 79 hours; IQR, 24-192 hours), and 476 postweaning deaths (23.1%; median support time, 146 hours; IQR, 96-235.5 hours). Multiorgan (n = 431 of 1158 [37.2%]) and persistent heart failure (n = 423 of 1158 [36.5%]) were the main causes of death, followed by bleeding (n = 56 of 754 [7.4%]) for on-ECMO mortality and sepsis (n = 61 of 401 [15.4%]) for postweaning mortality. On-ECMO death was associated with emergency surgery, preoperative cardiac arrest, cardiogenic shock, right ventricular failure, cardiopulmonary bypass time, and ECMO implantation timing. Diabetes, postoperative bleeding, cardiac arrest, bowel ischemia, acute kidney injury, and septic shock were associated with postweaning mortality. CONCLUSIONS: A discrepancy exists between weaning and discharge rate in postcardiotomy ECMO. Deaths occurred during ECMO support in 36.6% of patients, mostly associated with unstable preoperative hemodynamics. Another 23.1% of patients died after weaning in association with severe complications. This underscores the importance of postweaning care for postcardiotomy VA ECMO patients.

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.

The importance of timing in postcardiotomy venoarterial extracorporeal membrane oxygenation: A descriptive multicenter observational study.

OBJECTIVES: Postcardiotomy extracorporeal membrane oxygenation (ECMO) can be initiated intraoperatively or postoperatively based on indications, settings, patient profile, and conditions. The topic of implantation timing only recently gained attention from the clinical community. We compare patient characteristics as well as in-hospital and long-term survival between intraoperative and postoperative ECMO. METHODS: The retrospective, multicenter, observational Postcardiotomy Extracorporeal Life Support (PELS-1) study includes adults who required ECMO due to postcardiotomy shock between 2000 and 2020. We compared patients who received ECMO in the operating theater (intraoperative) with those in the intensive care unit (postoperative) on in-hospital and postdischarge outcomes. RESULTS: We studied 2003 patients (women: 41.1%; median age: 65 years; interquartile range [IQR], 55.0-72.0). Intraoperative ECMO patients (n = 1287) compared with postoperative ECMO patients (n = 716) had worse preoperative risk profiles. Cardiogenic shock (45.3%), right ventricular failure (15.9%), and cardiac arrest (14.3%) were the main indications for postoperative ECMO initiation, with cannulation occurring after (median) 1 day (IQR, 1-3 days). Compared with intraoperative application, patients who received postoperative ECMO showed more complications, cardiac reoperations (intraoperative: 19.7%; postoperative: 24.8%, P = .011), percutaneous coronary interventions (intraoperative: 1.8%; postoperative: 3.6%, P = .026), and had greater in-hospital mortality (intraoperative: 57.5%; postoperative: 64.5%, P = .002). Among hospital survivors, ECMO duration was shorter after intraoperative ECMO (median, 104; IQR, 67.8-164.2 hours) compared with postoperative ECMO (median, 139.7; IQR, 95.8-192 hours, P < .001), whereas postdischarge long-term survival was similar between the 2 groups (P = .86). CONCLUSIONS: Intraoperative and postoperative ECMO implantations are associated with different patient characteristics and outcomes, with greater complications and in-hospital mortality after postoperative ECMO. Strategies to identify the optimal location and timing of postcardiotomy ECMO in relation to specific patient characteristics are warranted to optimize in-hospital outcomes.

The Relation Between Obesity and Mortality in Postcardiotomy Venoarterial Membrane Oxygenation.

BACKGROUND: Obesity is an important health problem in cardiac surgery and among patients requiring postcardiotomy venoarterial extracorporeal membrane oxygenation (V-A ECMO). Still, whether these patients are at risk for unfavorable outcomes after postcardiotomy V-A ECMO remains unclear. The current study evaluated the association between body mass index (BMI) and in-hospital outcomes in this setting. METHODS: The Post-cardiotomy Extracorporeal Life Support (PELS-1) study is an international, multicenter study. Patients requiring postcardiotomy V-A ECMO in 36 centers from 16 countries between 2000 and 2020 were included. Patients were divided in 6 BMI categories (underweight, normal weight, overweight, class I, class II, and class III obesity) according to international recommendations. Primary outcome was in-hospital mortality, and secondary outcomes included major adverse events. Mixed logistic regression models were applied to evaluate associations between BMI and mortality. RESULTS: The study cohort included 2046 patients (median age, 65 years; 838 women [41.0%]). In-hospital mortality was 60.3%, without statistically significant differences among BMI classes for in-hospital mortality (P = .225) or major adverse events (P = .126). The crude association between BMI and in-hospital mortality was not statistically significant after adjustment for comorbidities and intraoperative variables (class I: odds ratio [OR], 1.21; 95% CI, 0.88-1.65; class II: OR, 1.45; 95% CI, 0.86-2.45; class III: OR, 1.43; 95% CI, 0.62-3.33), which was confirmed in multiple sensitivity analyses. CONCLUSIONS: BMI is not associated to in-hospital outcomes after adjustment for confounders in patients undergoing postcardiotomy V-A ECMO. Therefore, BMI itself should not be incorporated in the risk stratification for postcardiotomy V-A ECMO.

Extracorporeal life support in mitral papillary muscle rupture: Outcome of multicenter study.

BACKGROUND: Post-acute myocardial infarction papillary muscle rupture (post-AMI PMR) may present variable clinical scenarios and degree of emergency due to result of cardiogenic shock. Veno-arterial extracorporeal life support (V-A ECLS) has been proposed to improve extremely poor pre- or postoperative conditions. Information in this respect is scarce. METHODS: From the CAUTION (meChanical complicAtion of acUte myocardial infarcTion: an InternatiOnal multiceNter cohort study) database (16 different Centers, data from 2001 to 2018), we extracted adult patients who were surgically treated for post-AMI PMR and underwent pre- or/and postoperative V-A ECLS support. The end-points of this study were in-hospital survival and ECLS complications. RESULTS: From a total of 214 post-AMI PMR patients submitted to surgery, V-A ECLS was instituted in 23 (11%) patients. The median age was 61.7 years (range 46-81 years). Preoperatively, ECLS was commenced in 10 patients (43.5%), whereas intra/postoperative in the remaining 13. The most common V-A ECLS indication was post-cardiotomy shock, followed by preoperative cardiogenic shock and cardiac arrest. The median duration of V-A ECLS was 4 days. V-A ECLS complications occurred in more than half of the patients. Overall, in-hospital mortality was 39.2% (9/23), compared to 22% (42/219) for the non-ECLS group. CONCLUSIONS: In post-AMI PMR patients, V-A ECLS was used in almost 10% of the patients either to promote bridge to surgery or as postoperative support. Further investigations are required to better evaluate a potential for increased use and its effects of V-A ECLS in such a context based on the still high perioperative mortality.

Low-Density Lipoprotein Receptor-Related Protein 8 at the Crossroad between Cancer and Neurodegeneration.

The low-density-lipoprotein receptors represent a family of pleiotropic cell surface receptors involved in lipid homeostasis, cell migration, proliferation and differentiation. The family shares common structural features but also has significant differences mainly due to tissue-specific interactors and to peculiar proteolytic processing. Among the receptors in the family, recent studies place low-density lipoprotein receptor-related protein 8 (LRP8) at the center of both neurodegenerative and cancer-related pathways. From one side, its overexpression has been highlighted in many types of cancer including breast, gastric, prostate, lung and melanoma; from the other side, LRP8 has a potential role in neurodegeneration as apolipoprotein E (ApoE) and reelin receptor, which are, respectively, the major risk factor for developing Alzheimer's disease (AD) and the main driver of neuronal migration, and as a γ-secretase substrate, the main enzyme responsible for amyloid formation in AD. The present review analyzes the contributions of LDL receptors, specifically of LRP8, in both cancer and neurodegeneration, pointing out that depending on various interactions and peculiar processing, the receptor can contribute to both proliferative and neurodegenerative processes.

[ANMCO Position paper: Care pathway for advanced heart failure patients candidate for heart transplantation/ventricular assist device]. / Position paper ANMCO: Percorso assistenziale del paziente con insufficienza cardiaca avanzata candidabile a trapianto/assistenza ventricolare meccanica.

Heart failure is a complex clinical syndrome with a severe prognosis, despite therapeutic progress. The management of the advanced stages of the syndrome is particularly complex in patients who are referred to palliative care as well as in those who are candidates for cardiac replacement therapy. For the latter group, a prompt recognition of the transition to the advanced stage as well as an early referral to the centers for cardiac replacement therapy are essential elements to ensure that patients follow the most appropriate diagnostic-therapeutic pathway. The aim of this document is to focus on the main diagnostic and therapeutic aspects related to the advanced stages of heart failure and, in particular, on the management of patients who are candidates for cardiac replacement therapy.

Cutaneous Ulcer Caused by Apixaban Treatment Is Resolved after Replacement with Dabigatran.

Nowadays, novel oral anticoagulants (NOACs) have shown improved safety profile and efficacy compared to vitamin K antagonists in the prevention of thromboembolic events occurring during different pathological conditions. However, there are concerns and safety issues, mostly related to adverse events following interactions with other drugs, in real-world practice. We report the case of an 83-year-old woman who developed a non-bleeding leg ulcer not caused by trauma or other evident pathological conditions after 10 days of treatment with apixaban 5 mg/q.d. She was switched from apixaban to dabigatran and the leg ulcer rapidly improved and completely cicatrized in 40 days. The resolution of the ulcer and the toleration of dabigatran therapy suggest an apixaban-specific reaction; however, the pathological mechanism of ulcer onset is currently unclear. Careful evaluation of hospital databases of Molise region (Southern Italy) hospitals identified two similar cases between 2019 and 2021. These cases underline the necessity of careful post-marketing surveillance, considering the rapidly increasing number of patients treated with NOACs and patient's risk factors such as old age, high polypharmacy rate, co-morbidities, and peculiar genetic background related to NOACs pharmacokinetic features.

Long-term effects of primary graft dysfunction after heart transplantation.

BACKGROUND: We studied the incidence of primary graft dysfunction (PGD), its impact on in-hospital and follow-up outcomes and searched for independent risk factors. METHODS: During an 18-year period, 508 individuals underwent heart transplantation at our institution. Patients were diagnosed with none, mild, moderate or severe PGD according to ISHLT criteria. RESULTS: Thirty-eight patients (7.5%) met the ISHLT criteria for mild PGD, 92 (18.1%) for moderate PGD and 23 (4.5%) for severe PGD. Patients were classified into none/mild PGD (77.4%) and moderate/severe PGD (22.6%) groups. In-hospital mortality was 12.4% (7.8% for none/mild PGD and 28.7% for moderate/severe PGD; p < .001). Survival at 1, 5, and 15 years was 85.5 ± 1.9% versus 67.2 ± 4.5%, 80 ± 2.2% versus 63.5 ± 4.7%, and 60.4 ± 3.6% versus 45.9 ± 8.4%, respectively (p < .001). Excluding the events occurring during the first month of follow-up, survival was comparable between the two groups (93.1 ± 1.4% vs. 94.7 ± 2.6 at 1 year and 65.6 ± 3.8% vs. 70.4 ± 10.4% at 15 years, respectively; p = .88). Upon multivariate logistic regression analysis preoperative mechanical circulatory support (odds ratio [OR] = 5.86) and preoperative intra-aortic balloon pump (IABP) (OR = 9.58) were independently associated with moderate/severe PGD. CONCLUSIONS: Our results confirm that PGD is associated with poor in-hospital outcome. The poor outcome does not extend beyond the first month of follow-up, with comparable survival between patients with none/mild PGD and moderate/severe PGD in the short and long-term. Mechanical circulatory support and preoperative IABP were found to be independent risk factors for moderate/severe PGD.

Organ Care System Heart™ in donors requiring high-risk excision of suspected neoplastic lesions.

Although Heart Transplant is still the gold standard treatment for end-stage heart failure patients, the limitation of this procedure is the discrepancy between the amount of waiting list patients and donors. Organ Care Systems, preventing the detrimental effects of cold ischemia, potentially increase donor pool. Herein we report three cases where high-risk excisions were required to clarify the nature of suspected lesions in donors. We decided to retrieve the organs and to place them in the devices before performing the excision. Our experience confirm the possibility to utilise this device as a time buffer in these peculiar scenarios.

Surgical treatment for post-infarction papillary muscle rupture: a multicentre study.

OBJECTIVES: Papillary muscle rupture (PMR) is a rare but potentially fatal complication of acute myocardial infarction. The aim of this study was to analyse the patient characteristics and early outcomes of the surgical management of post-infarction PMR from an international multicentre registry. METHODS: Patients underwent surgery for post-infarction PMR between 2001 through 2019 were retrieved from database of the CAUTION study. The primary end point was in-hospital mortality. RESULTS: A total of 214 patients were included with a mean age of 66.9 (standard deviation: 10.5) years. The posteromedial papillary muscle was the most frequent rupture location (71.9%); the rupture was complete in 67.3% of patients. Mitral valve replacement was performed in 82.7% of cases. One hundred twenty-two patients (57%) had concomitant coronary artery bypass grafting. In-hospital mortality was 24.8%. Temporal trends revealed no apparent improvement in in-hospital mortality during the study period. Multivariable analysis showed that preoperative chronic kidney disfunction [odds ratio (OR): 2.62, 95% confidence interval (CI): 1.07-6.45, P = 0.036], cardiac arrest (OR: 3.99, 95% CI: 1.02-15.61, P = 0.046) and cardiopulmonary bypass duration (OR: 1.01, 95% CI: 1.00-1.02, P = 0.04) were independently associated with an increased risk of in-hospital death, whereas concomitant coronary artery bypass grafting was identified as an independent predictor of early survival (OR: 0.38, 95% CI: 0.16-0.92, P = 0.031). CONCLUSIONS: Surgical treatment for post-infarction PMR carries a high in-hospital mortality rate, which did not improve during the study period. Because concomitant coronary artery bypass grafting confers a survival benefit, this additional procedure should be performed, whenever possible, in an attempt to improve the outcome. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT03848429.

Clinical and Hemodynamic Outcomes of Rapid-Deployment Aortic Bioprostheses.

Aim of this retrospective, multicenter study was to evaluate early and mid-term clinical and hemodynamic results of patients who underwent surgical aortic valve replacement (SAVR) with Intuity rapid-deployment bioprostheses (RDB) (Edwards Lifesciences, Irvine, CA). We analyzed data from the Italian Registry of Intuity Valve (INTU-ITA registry) that is a national, real-world and independent from the industry registry. Preoperative variables were defined according to EuroSCORE and postoperative outcomes according to Valve Academic Research Consortium (VARC). Survival distribution was evaluated using the Kaplan-Meier approach. A Cox-Proportional Hazard Model was employed to assess the effect of the covariates on patients' survival. The registry included 1687 patients from 23 centers (June 2012-September 2019). Aortic cross clamp time for isolated SAVR was 55 minutes (IQR: 45-70 minute). Postoperative pace-maker rate was 6.3%. At discharge transaortic peak and mean gradients were: 18 mm Hg (IQR: 14-23 mm Hg) and 10 mmHg (IQR: 8-13 mm Hg), respectively. Indexed effective orifice area was 1.10 cm2/m2 (IQR: 0.91-1.31 cm2/m2) and the incidence of severe patient-prosthesis mismatch was 0.6%. Hemodynamic data for all valve sizes remained stable during follow-up. Thirty-day overall mortality was 1.8% (30 patients), and at follow-up it was 5.3% (89 patients). Kaplan-Meier overall survival was 95.5% (94.3-96.7%); 90.7% (88.3-93.1%); 86.4% (82.6-90.4%) at 1, 3, and 5 years, respectively. Serum creatinine (HR: 1.36; 95%CI: 1.04-1.81; p = 0.0397) and cross-clamp time (HR: 1.01; 95%CI: 1.002-1.017; p = 0.0077) were identified as independent predictors of mortality. According to our data from the INTU-ITA registry, SAVR with RDB provides good early clinical and hemodynamic results that are confirmed at follow-up.