Organ donation after extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest in a metropolitan cardiac arrest centre in Milan, Italy.

INTRODUCTION: Extracorporeal cardiopulmonary resuscitation (ECPR) may improve survival in refractory out-of-hospital cardiac arrest (OHCA) but also expand the donor pool as these patients often become eligible for organ donation. Our aim is to describe the impact of organ donation in OHCA patients treated with ECPR in a high-volume cardiac arrest centre. METHODS: Rate of organ donation (primary outcome), organs harvested, a composite of patient survival with favourable neurological outcome or donation of ≥1 solid organ (ECPR benefit), and the potential total number of individuals benefiting from ECPR (survivors with favourable neurological outcome and potential recipients of one solid organ) were analysed among all-rhythms refractory OHCA patients treated with ECPR between January 2013-November 2022 at San Raffaele Hospital in Milan, Italy. RESULTS: Among 307 adults with refractory OHCA treated with ECPR (95% witnessed, 66% shockable, low-flow 70 [IQR 58-81] minutes), 256 (83%) died during hospital stay, 33% from brain death. Donation of at least one solid organ occurred in 58 (19%) patients, 53 (17%) after determination of brain death and 5 (1.6%) after determination of circulatory death, contributing a total of 167 solid organs (3.0 [IQR 2.5-4.0] organs/donor). Overall, 196 individuals (29 survivors with favourable neurological outcome and 167 potential recipients of 1 solid organ) possibly benefited from ECPR. ECPR benefit composite outcome was achieved in 87 (28%) patients. Solid organ donation decreased from 19% to 16% in patients with low-flow <60 min and to 11% with low-flow <60 min and initial shockable rhythm. CONCLUSIONS: When ECPR fails in patients with refractory OHCA, organ donation after brain or circulatory death can help a significant number of patients awaiting transplantation, enhancing the overall benefit of ECPR. ECPR selection criteria may affect the number of potential organ donors.

Temporary mechanical circulatory support with Impella in cardiac surgery: A systematic review.

INTRODUCTION: Perioperative cardiogenic shock (CS) in cardiac surgery is still burdened by a high mortality risk. The introduction of Impella pumps in the therapeutic armory of temporary mechanical circulatory support (tMCS) has potential implications to improve the management of complex cases, although it has never been systematically addressed. We performed a systematic review of the reported use of tMCS with Impella in cardiac surgery. METHODS: We searched PubMed for all original studies on the Impella use in adult patients in cardiac surgery. RESULTS: Nineteen studies (out of 151 identified by search string) were included. All studies were observational and all but one (95%) were retrospective. Seven studies focused on the implantation of Impella in the pre-operative setting (coronary or valvular surgery), either as a prophylactic device in high-risk cases (3 studies) or in patients with CS as stabilization tool prior to cardiac surgery procedure (4 studies). Three studies reported the use of Impella as periprocedural support for percutaneous valvular procedure, three as bridge to heart replacement, and six for postcardiotomy CS. Impella support had a low complication rate and was successful in supporting hemodynamics pre-, intra- and postoperatively. Most consistently reported data were left-ventricular ejection fraction at implant, short-term survival and weaning rate. CONCLUSIONS: tMCS with Impella in cardiac surgery patients is feasible and successful. It can be applied in selected cardiac surgery patients and presents advantages over other types of support. Systematic prospective studies are needed to standardize indications for implant and management of surgical issues, and to identify which patients may benefit.

Extracorporeal cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: 10-year experience in a metropolitan cardiac arrest centre in Milan, Italy.

Introduction: Growing evidence supports extracorporeal cardiopulmonary resuscitation (ECPR) for refractory out-of-hospital cardiac arrest (OHCA) patients, especially in experienced centres. We present characteristics, treatments, and outcomes of patients treated with ECPR in a high-volume cardiac arrest centre in the metropolitan area of Milan, Italy and determine prognostic factors. Methods: Refractory OHCA patients treated with ECPR between 2013 and 2022 at IRCCS San Raffaele Scientific Institute in Milan had survival and neurological outcome assessed at hospital discharge. Results: Out of 307 consecutive OHCA patients treated with ECPR (95% witnessed, 66% shockable, low-flow 70 [IQR 58-81] minutes), 17% survived and 9.4% had favourable neurological outcome. Survival and favourable neurological outcome increased to 51% (OR = 8.7; 95% CI, 4.3-18) and 28% (OR = 6.3; 95% CI, 2.8-14) when initial rhythm was shockable and low-flow (time between CPR initiation and ROSC or ECMO flow) ≤60 minutes and decreased to 9.5% and 6.3% when low-flow exceeded 60 minutes (72% of patients). At multivariable analysis, shockable rhythm (aOR for survival = 2.39; 95% CI, 1.04-5.48), shorter low-flow (aOR = 0.95; 95% CI, 0.94-0.97), intermittent ROSC (aOR = 2.5; 95% CI, 1.2-5.6), and signs of life (aOR = 3.7; 95% CI, 1.5-8.7) were associated with better outcomes. Survival reached 10% after treating 104 patients (p for trend <0.001). Conclusions: Patients with initial shockable rhythm, intermittent ROSC, signs of life, and low-flow ≤60 minutes had higher success of ECPR for refractory OHCA. Favourable outcomes were possible beyond 60 minutes of low-flow, especially with concomitant favourable prognostic factors. Outcomes improved as the case-volume increased, supporting treatment in high-volume cardiac arrest centres.

Can Lung Ultrasound Be the Ideal Monitoring Tool to Predict the Clinical Outcome of Mechanically Ventilated COVID-19 Patients? An Observational Study.

BACKGROUND: During the COVID-19 pandemic, lung ultrasound (LUS) has been widely used since it can be performed at the patient's bedside, does not produce ionizing radiation, and is sufficiently accurate. The LUS score allows for quantifying lung involvement; however, its clinical prognostic role is still controversial. METHODS: A retrospective observational study on 103 COVID-19 patients with respiratory failure that were assessed with an LUS score at intensive care unit (ICU) admission and discharge in a tertiary university COVID-19 referral center. RESULTS: The deceased patients had a higher LUS score at admission than the survivors (25.7 vs. 23.5; p-value = 0.02; cut-off value of 25; Odds Ratio (OR) 1.1; Interquartile Range (IQR) 1.0-1.2). The predictive regression model shows that the value of LUSt0 (OR 1.1; IQR 1.0-1.3), age (OR 1.1; IQR 1.0-1.2), sex (OR 0.7; IQR 0.2-3.6), and days in spontaneous breathing (OR 0.2; IQR 0.1-0.5) predict the risk of death for COVID-19 patients (Area under the Curve (AUC) 0.92). Furthermore, the surviving patients showed a significantly lower difference between LUS scores at admission and discharge (mean difference of 1.75, p-value = 0.03). CONCLUSION: Upon entry into the ICU, the LUS score may play a prognostic role in COVID-19 patients with ARDS. Furthermore, employing the LUS score as a monitoring tool allows for evaluating the patients with a higher probability of survival.

Phlegmasia cerulea dolens superimposed on disseminated intravascular coagulation in COVID-19.

COVID-19 infection has several cardiovascular implications, and coagulopathy is a common abnormality in these patients, often coupled with elevated plasma fibrinogen and D-dimer levels, contributing to adverse outcomes. Phlegmasia cerulea dolens (PCD) is a rare manifestation of deep vein thrombosis. It is life-threatening and can rapidly lead to venous gangrene of the extremity. Only a few cases of COVID-19 associated with PCD are reported in the literature, despite thromboembolism being the common paradigm between the two diseases. We present the case of a 64-year-old adult with acute severe COVID-19 pneumonia who developed PCD despite constantly elevated activated partial thromboplastin time and international normalized ratio.

Vaginal delivery in a patient with severe aortic stenosis under epidural analgesia, a case report.

BACKGROUND: A history of previous cardiac disease increases the maternal mortality risk by as much as 100%. There is no consensus on the absolute contraindications to vaginal delivery in valvular heart disease, but central regional anesthesia is traditionally considered contraindicated in patients with severe aortic stenosis. CASE PRESENTATION: A 29-year-old primigravid woman with severe aortic stenosis was admitted to the obstetrics department for programmed labor induction. With epidural anesthesia and mini-invasive hemodynamic monitoring labor and operative vaginal delivery were well tolerated, and hemodynamic stability was always maintained. CONCLUSIONS: Epidural analgesia and oxytocin induction are possible for the labor management of parturients with severe aortic stenosis given that continuous non-invasive followed by invasive hemodynamic monitoring can be provided and given the absence of any obstetric or cardiologic contraindications and the strong will of the patient.

Assessment of Pleural Effusion and Small Pleural Drain Insertion by Resident Doctors in an Intensive Care Unit: An Observational Study.

Small-bore pleural drainage device insertion has become a first-line therapy for the treatment of pleural effusions (PLEFF) in the intensive care unit; however, no data are available regarding the performance of resident doctors in the execution of this procedure. Our aim was to assess the prevalence of complications related to ultrasound-guided percutaneous small-bore pleural drain insertion by resident doctors. In this single-center observational study, the primary outcome was the occurrence of complications. Secondary outcomes studied were as follows: estimation of PLEFF size by ultrasound and postprocedure changes in PaO2/FiO2 ratio. In all, 87 pleural drains were inserted in 88 attempts. Of these, 16 were positioned by the senior intensivist following a failed attempt by the resident, giving a total of 71 successful placements performed by residents. In 13 cases (14.8%), difficulties were encountered in advancing the catheter over the guidewire. In 16 cases (18.4%), the drain was positioned by a senior intensivist after a failed attempt by a resident. In 8 cases (9.2%), the final chest X-ray revealed a kink in the catheter. A pneumothorax was identified in 21.8% of cases with a mean size (±SD) of just 10 mm (±6; maximum size: 20 mm). The mean size of PLEFF was 57.4 mm (±19.9), corresponding to 1148 mL (±430) according to Balik's formula. Ultrasound-guided placement of a small-bore pleural drain by resident doctors is a safe procedure, although it is associated with a rather high incidence of irrelevant pneumothoraces.

Chronic treatment with the mitochondrial peptide humanin prevents age-related myocardial fibrosis in mice.

Cardiac fibrosis is a biological process that increases with age and contributes to myocardial dysfunction. Humanin (HN) is an endogenous mitochondria-derived peptide that has cytoprotective effects and reduces oxidative stress. The present study aimed to test the hypothesis that chronic supplementation of exogenous HN in middle-aged mice could prevent and reverse cardiac fibrosis and apoptosis in the aging heart. Female C57BL/6N mice at 18 mo of age received 14-mo intraperitoneal injections of vehicle (old group; n = 6) or HN analog (HNG; 4 mg/kg 2 times/wk, old + HNG group, n = 8) and were euthanized at 32 mo of age. C57BL/6N female mice (young group, n = 5) at 5 mo of age were used as young controls. HNG treatment significantly increased the ratio of cardiomyocytes to fibroblasts in aging hearts, as shown by the percentage of each cell type in randomly chosen fields after immunofluorescence staining. Furthermore, the increased collagen deposition in aged hearts was significantly reduced after HNG treatment, as indicated by picrosirius red staining. HNG treatment also reduced in aging mice cardiac fibroblast proliferation (5'-bromo-2-deoxyuridine staining) and attenuated transforming growth factor-ß1, fibroblast growth factor-2, and matrix metalloproteinase-2 expression (immunohistochemistry or real-time PCR). Myocardial apoptosis was inhibited in HNG-treated aged mice (TUNEL staining). To decipher the pathway involved in the attenuation of the myocardial fibrosis by HNG, Western blot analysis was done and showed that HNG upregulated the Akt/glycogen synthase kinase -3ß pathway in aged mice. Exogenous HNG treatment attenuated myocardial fibrosis and apoptosis in aged mice. The results of the present study suggest a role for the mitochondria-derived peptide HN in the cardioprotection associated with aging. NEW & NOTEWORTHY Cardiac fibrosis is a biological process that increases with age and contributes to myocardial dysfunction. Humanin is an endogenous mitochondria-derived peptide that has cytoprotective effects and reduces oxidative stress. Here, we demonstrate, for the first time, that exogenous humanin treatment attenuated myocardial fibrosis and apoptosis in aging mice. We also detected upregulated Akt/glycogen synthase kinase-3ß pathway in humanin analog-treated mice, which might be the mechanism involved in the cardioprotective effect of humanin analog in aging mice.

Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction.

BACKGROUND: MOTS-c is one of the newly identified mitochondrial-derived peptides which play a role in regulating metabolic homeostasis. The current study aimed to investigate whether circulating MOTS-c levels are also associated with endothelial dysfunction(ED) in patients without significant structural coronary lesions. METHODS: Forty patients undergoing coronary angiography and endothelial function testing for clinical indications of recurrent angina with no structural coronary lesions were included in the study. They were divided into two groups based on coronary blood flow response to intracoronary acetylcholine (ACh) as normal endothelial function (≥ 50% increase from baseline) or ED, (n=20 each). Aortic plasma samples were collected at the time of catheterization for analysis of circulating MOTS-c levels by ELISA. The effect of MOTS-c on vascular reactivity was assessed in organ chambers using aortic rings collected from rats and renal artery stenosis (RAS) mice. RESULTS: Baseline characteristics were similar between the two groups. MOTS-c plasma levels were lower in patients with ED compared with patients with normal endothelial function (p=0.007). Furthermore, plasma MOTS-c levels were positively correlated with microvascular (p=0.01) and epicardial (p=0.02) coronary endothelial function. Although MOTS-c did not have direct vasoactive effects, pretreating aortic rings from rats or RAS mice with MOTS-c (2µg/ml) improved vessel responsiveness to ACh compared with vessels without MOTS-c treatment. CONCLUSION: Lower circulating endogenous MOTS-c levels in human subjects are associated with impaired coronary endothelial function. In rodents, MOTS-c improves endothelial function in vitro. Thus, MOTS-c represents a novel potential therapeutic target in patients with ED.