Acute normovolemic hemodilution in cardiac surgery: Rationale and design of a multicenter randomized trial.

BACKGROUND: Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain. METHODS: This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 mL as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions. RESULTS: The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications. CONCLUSION: The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB. STUDY REGISTRATION: This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

A Randomized Trial of Intravenous Amino Acids for Kidney Protection.

BACKGROUND: Acute kidney injury (AKI) is a serious and common complication of cardiac surgery, for which reduced kidney perfusion is a key contributing factor. Intravenous amino acids increase kidney perfusion and recruit renal functional reserve. However, the efficacy of amino acids in reducing the occurrence of AKI after cardiac surgery is uncertain. METHODS: In a multinational, double-blind trial, we randomly assigned adult patients who were scheduled to undergo cardiac surgery with cardiopulmonary bypass to receive an intravenous infusion of either a balanced mixture of amino acids, at a dose of 2 g per kilogram of ideal body weight per day, or placebo (Ringer's solution) for up to 3 days. The primary outcome was the occurrence of AKI, defined according to the Kidney Disease: Improving Global Outcomes creatinine criteria. Secondary outcomes included the severity of AKI, the use and duration of kidney-replacement therapy, and all-cause 30-day mortality. RESULTS: We recruited 3511 patients at 22 centers in three countries and assigned 1759 patients to the amino acid group and 1752 to the placebo group. AKI occurred in 474 patients (26.9%) in the amino acid group and in 555 (31.7%) in the placebo group (relative risk, 0.85; 95% confidence interval [CI], 0.77 to 0.94; P = 0.002). Stage 3 AKI occurred in 29 patients (1.6%) and 52 patients (3.0%), respectively (relative risk, 0.56; 95% CI, 0.35 to 0.87). Kidney-replacement therapy was used in 24 patients (1.4%) in the amino acid group and in 33 patients (1.9%) in the placebo group. There were no substantial differences between the two groups in other secondary outcomes or in adverse events. CONCLUSIONS: Among adult patients undergoing cardiac surgery, infusion of amino acids reduced the occurrence of AKI. (Funded by the Italian Ministry of Health; PROTECTION ClinicalTrials.gov number, NCT03709264.).

Stroke outcomes following durable left ventricular assist device implant in patients bridged with micro-axial flow pump: Insights from a large registry.

BACKGROUND: Stroke after durable left ventricular assist device (d-LVAD) implantation portends high mortality. The incidence of ischemic and hemorrhagic stroke and the impact on stroke outcomes of temporary mechanical circulatory support (tMCS) management among patients requiring bridge to d-LVAD with micro-axial flow-pump (mAFP, Abiomed) is unsettled. METHODS: Consecutive patients, who underwent d-LVAD implantation after being bridged with mAFP at 19 institutions, were retrospectively included. The incidence of early ischemic and hemorrhagic stroke after d-LVAD implantation (<60 days) and association of pre-d-LVAD characteristics and peri-procedural management with a specific focus on tMCS strategies were studied. RESULTS: Among 341 patients, who underwent d-LVAD implantation after mAFP implantation (male gender 83.6%, age 58 [48-65] years, mAFP 5.0/5.5 72.4%), the early ischemic stroke incidence was 10.8% and early hemorrhagic stroke 2.9%. The tMCS characteristics (type of mAFP device and access, support duration, upgrade from intra-aortic balloon pump, ECMELLA, ECMELLA at d-LVAD implantation, hemolysis, and bleeding) were not associated with ischemic stroke after d-LVAD implant. Conversely, the device model (mAFP 2.5/CP vs. mAFP 5.0/5.5: HR 5.6, 95%CI 1.4-22.7, p = 0.015), hemolysis on mAFP support (HR 10.5, 95% CI 1.3-85.3, p = 0.028) and ECMELLA at d-LVAD implantation (HR 5.0, 95% CI 1.4-18.7, p = 0.016) were associated with increased risk of hemorrhagic stroke after d-LVAD implantation. Both early ischemic (HR 2.7, 95% CI 1.9-4.5, p < 0.001) and hemorrhagic (HR 3.43, 95% CI 1.49-7.88, p = 0.004) stroke were associated with increased 1-year mortality. CONCLUSIONS: Among patients undergoing d-LVAD implantation following mAFP support, tMCS characteristics do not impact ischemic stroke occurrence, while several factors are associated with hemorrhagic stroke suggesting a proactive treatment target to reduce this complication.

Pulmonary artery elastance as a predictor of hospital mortality in heart failure cardiogenic shock.

AIMS: The initial bundle of cares strongly affects haemodynamics and outcomes in acute decompensated heart failure cardiogenic shock (ADHF-CS). We sought to characterize whether 24 h haemodynamic profiling provides superior prognostic information as compared with admission assessment and which haemodynamic parameters best predict in-hospital death. METHODS AND RESULTS: All patients with ADHF-CS and with available admission and 24 h invasive haemodynamic assessment from two academic institutions were considered for this study. The primary endpoint was in-hospital death. Regression analyses were run to identify relevant predictors of study outcome. We included 127 ADHF-CS patients [65 (inter-quartile range 52-72) years, 25.2% female]. Overall, in-hospital mortality occurred in 26.8%. Non-survivors were older, with greater CS severity. Among admission variables, age [odds ratio (OR) = 1.06; 95% confidence interval (CI): 1.02-1.11; Padj = 0.005] and CPIRAP (OR = 0.62 for 0.1 increment; 95% CI: 0.39-0.95; Padj = 0.034) were found significantly associated with in-hospital death. Among 24 h haemodynamic univariate predictors of in-hospital death, pulmonary elastance (PaE) was the strongest (area under the curve of 0.77; 95% CI: 0.68-0.86). PaE (OR = 5.98; 95% CI: 2.29-17.48; Padj < 0.001), pulmonary artery pulsatility index (PAPi, OR = 0.77; 95% CI: 0.62-0.92; Padj = 0.013) and age (OR = 1.06; 95% CI: 1.02-1.11; Padj = 0.010) were independently associated with in-hospital death. Best cut-off for PaE was 0.85 mmHg/mL and for PAPi was 2.95; cohort phenotyping based on these PaE and PAPi thresholds further increased in-hospital death risk stratification; patients with 24 h high PaE and low PAPi exhibited the highest in-hospital mortality (56.2%). CONCLUSIONS: Pulmonary artery elastance has been found to be the most powerful 24 h haemodynamic predictor of in-hospital death in patients with ADHF-CS. Age, 24 h PaE, and PAPi are independently associated with hospital mortality. PaE captures right ventriclar (RV) afterload mismatch and PAPi provides a metric of RV adaptation, thus their combination generates four distinct haemodynamic phenotypes, enhancing in-hospital death risk stratification.

A rare case report of an acquired aortopulmonary artery fistula after Bentall procedure: multimodality imaging approach may be the key?

Background: The acquired communication between the aorta and the pulmonary artery is a rare and potentially life-threatening condition. Its diagnosis is challenging and may require a multimodality imaging approach. Case summary: A 67-year-old Caucasian man, admitted for acute respiratory failure unresponsive to medical therapy and non-invasive ventilation, was diagnosed with an aortopulmonary fistula (APF) complicating a pseudoaneurysm of the aortic root. This condition developed after Bentall cardiac surgery, which entailed the use of a straight Dacron aortic graft coupled with a mechanical prosthesis. A multimodal imaging approach, combining echocardiography and computed tomography angiography, was diagnostic and supported the development of a surgical treatment strategy. The patient underwent successful surgical closure of the APF and correction of the aortic pseudoaneurysm. Discussion: Aortopulmonary fistula can result in rapid clinical deterioration if left untreated. The combination of echocardiography and computed tomography angiography techniques allowed for the diagnosis and surgical correction of the APF.

The intelligent Impella: Future perspectives of artificial intelligence in the setting of Impella support.

AIMS: Artificial intelligence (AI) has emerged as a potential useful tool to support clinical treatment of heart failure, including the setting of mechanical circulatory support (MCS). Modern Impella pumps are equipped with advanced technology (SmartAssist), enabling real-time acquisition and display of data related to both pump performance and the patient's haemodynamic status. These data emerge as an 'ideal' source for data-driven AI applications to predict the clinical course of an ongoing therapeutic protocol. Yet, no evidence of effective application of AI tools in the setting of Impella support is available. On this background, we aimed at identifying possible future applications of AI-based tools in the setting of temporary MCS with an Impella device. METHODS: We explored the state of research and development at the intersection of AI and Impella support and derived future potential applications of AI in routine Impella clinical management. RESULTS: We identified different areas where the future implementation of AI tools may contribute to addressing important clinical challenges in the setting of Impella support, including (i) early identification of the best suited pathway of care according to patients' conditions at presentation and intention to treat, (ii) prediction of therapy outcomes according to different possible therapeutic actions, (iii) optimization of device implantation procedures and evaluation of proper pump position over the whole course of support and (iv) prevention and/or rationale management of haemocompatibility-related adverse events. For each of those areas, we discuss the potential advantages, challenges and implications of harnessing AI-driven insights in the setting of MCS with an Impella device. CONCLUSIONS: Temporary MCS with an Impella device has great potential to benefit from the integration of AI-based tools. Such tools may indeed translate into groundbreaking innovation supporting clinical decision-making and therapy regulation, in particular in complex scenarios such as the multidevice MCS strategy.

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.

Low Versus High Blood Pressure Targets in Critically Ill and Surgical Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Hypotension is associated with adverse outcomes in critically ill and perioperative patients. However, these assumptions are supported by observational studies. This meta-analysis of randomized controlled trials aims to compare the impact of lower versus higher blood pressure targets on mortality. DATA SOURCES: We searched PubMed, Cochrane, and Scholar from inception to February 10, 2024. STUDY SELECTION: Randomized trials comparing lower versus higher blood pressure targets in the management of critically ill and perioperative settings. DATA EXTRACTION: The primary outcome was all-cause mortality at the longest follow-up available. This review was registered in the Prospective International Register of Systematic Reviews, CRD42023452928. DATA SYNTHESIS: Of 2940 studies identified by the search string, 28 (12 in critically ill and 16 in perioperative settings) were included totaling 15,672 patients. Patients in the low blood pressure target group had lower mortality (23 studies included: 1019/7679 [13.3%] vs. 1103/7649 [14.4%]; relative risk 0.93; 95% CI, 0.87-0.99; p = 0.03; I2 = 0%). This corresponded to a 97.4% probability of any increase in mortality with a Bayesian approach. These findings were mainly driven by studies performed in the ICU setting and with treatment lasting more than 24 hours; however, the magnitude and direction of the results were similar in the majority of sensitivity analyses including the analysis restricted to low risk of bias studies. We also observed a lower rate of atrial fibrillation and fewer patients requiring transfusion in low-pressure target groups. No differences were found in the other secondary outcomes. CONCLUSIONS: Based on pooled randomized trial evidence, a lower compared with a higher blood pressure target results in a reduction of mortality, atrial fibrillation, and transfusion requirements. Lower blood pressure targets may be beneficial but there is ongoing uncertainty. However, the present meta-analysis does not confirm previous findings and recommendations. These results might inform future guidelines and promote the study of the concept of protective hemodynamics.

Impella as Bridge to Durable Left Ventricular Assist Device in Acute Myocardial Infarction Cardiogenic Shock Patients.

Implantation of durable left ventricular assist device (LVAD) in cardiogenic shock (CS) patients after acute myocardial infarction (AMI) poses specific challenges (small left ventricular size, acute infarct area, need for antithrombotic therapy, status Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 1 with impaired organ function and derangements in coagulation and inflammatory parameters) which may affect outcomes. We reviewed data of all AMI-CS patients who were implanted LVAD after Impella support at a referral center with the aim to analyze feasibility, timing, and outcomes of durable LVAD implantation after tMCS with Impella due to AMI-CS. Twenty-one patients were treated between 2013 and 2023: all were in Society for Cardiovascular Angiography & Interventions (SCAI) class D-E and INTERMACS 1-2 at presentation, median LV ejection fraction (EF) and LV end-diastolic diameter (EDD) were 15 (10-20)% and 57 (54-60) mm, respectively. Eleven patients (52%) were supported with Impella CP, seven with Impella 5.0 (33%), and three (14%) with Impella 2.5. Axillary cannulation was performed in nine patients (43%). Five patients (24%) had concomitant venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. Median duration of Impella support was 12 (8-14) days. Overall, the use of Impella was characterized by low rate of complications and allowed successful bridge to durable LVAD in all patients, with 100% 30 day survival rate.

Long-term quality of life, psychological distress, and caregiver burden in octogenarians with LVAD: A single-centre experience.

With the general population aging, both life expectancy and the number of left ventricular assist device (LVAD) implantations in elderly patients are growing. Nevertheless, their perceived long-term quality of life, including psychological aspects, coupled with the respective caregiver's burden, remain under-reported. In light of the rising number of octogenarians with LVAD who necessitate broader healthcare provider involvement, we assessed the long-term quality of life, as defined by both the 36-item short-form health (SF-36) survey and the EuroQol 5 dimensions, 5-level questionnaire (EQ-5D-5L)-including the visual analog scale-in octogenarian LVAD patients who had received treatment at our institution. Additionally, we evaluated the psychological health of octogenarian LVAD patients using the psychological general well-being index (PGWBI), alongside their caregivers' well-being through the 22-item version of the Zarit Burden Interview (ZBI). Of 12 octogenarian LVAD patients, 5 were alive and willing to answer questionnaires. Mean age at implant was 74 ± 2 years. Median follow-up was 2464 (IQR = 2375-2745) days. Although variable, the degree of health and psychological well-being perceived by octogenarian patients with LVAD was "good." Interestingly, the burden of assistance reported by caregivers, though relevant, was greatly varied, suggesting the need to better define and address psychological long-term aspects related to LVAD implantation for both patients and caregivers with a broad-spectrum approach.

Cat Scratch Endocarditis.

We reported a case of blood culture-negative infective endocarditis on a native valve, where the clinical presentation was exclusively related to extensive cerebral ischemia secondary to multiple systemic septic cardioembolic events. The cause was ascribed to subacute Bartonella henselae infection, presumably transmitted by cat scratch, documented by positive serologic findings.

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.

Monitoring MCS patients on the intensive care unit: integrating haemodynamic assessment, laboratory data, and imaging techniques for timely detection of deterioration and recovery.

Monitoring of the patient supported with a temporary mechanical circulatory support (tMCS) is crucial in achieving the best possible outcome. Monitoring is a continuous and labour-intensive process, as cardiogenic shock (CS) patients can rapidly deteriorate and may require new interventions within a short time period. Echocardiography and invasive haemodynamic monitoring form the cornerstone of successful tMCS support. During monitoring, it is particularly important to ensure that adequate end-organ perfusion is achieved and maintained. Here, we provide a comprehensive overview of best practices for monitoring the CS patient supported by a micro-axial flow pump, veno-arterial extracorporeal membrane oxygenation, and both devices simultaneously (ECMELLA approach). It is a complex process that encompasses device control, haemodynamic control and stabilization, monitoring of interventions, and assessment of end-organ function. The combined, continuous, and preferably protocol-based approach of echocardiography, evaluation of biomarkers, end-organ assessment, and haemodynamic parameters is crucial in assessing this critically ill CS patient population.

Extracorporeal Membrane Oxygenation Without Invasive Ventilation for Respiratory Failure in Adults: A Systematic Review.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is an advanced treatment for acute severe respiratory failure. Patients on ECMO are frequently maintained sedated and immobilized until weaning from ECMO, first, and then from mechanical ventilation. Avoidance of sedation and invasive ventilation during ECMO may have potential advantages. We performed a systematic literature review to assess efficacy and safety of awake ECMO without invasive ventilation in patients with respiratory failure. DATA SOURCES: PubMed, Web of Science, and Scopus were searched for studies reporting outcome of awake ECMO for adult patients with respiratory failure. STUDY SELECTION: We included all studies reporting outcome of awake ECMO in patients with respiratory failure. Studies on ECMO for cardiovascular failure, cardiac arrest, or perioperative support and studies on pediatric patients were excluded. Two investigators independently screened and selected studies for inclusion. DATA EXTRACTION: Two investigators abstracted data on study characteristics, rate of awake ECMO failure, and mortality. Primary outcome was rate of awake ECMO failure (need for intubation). Pooled estimates with corresponding 95% CIs were calculated. Subgroup analyses by setting were performed. DATA SYNTHESIS: A total of 57 studies (28 case reports) included data from 467 awake ECMO patients. The subgroup of patients with acute respiratory distress syndrome showed a pooled estimate for awake ECMO failure of 39.3% (95% CI, 24.0-54.7%), while in patients bridged to lung transplantation, pooled estimate was 23.4% (95% CI, 13.3-33.5%). Longest follow-up mortality was 121 of 439 (pooled estimate, 28%; 95% CI, 22.3-33.6%). Mortality in patients who failed awake ECMO strategy was 43 of 74 (pooled estimate, 57.2%; 95% CI, 40.2-74.3%). Two cases of cannula self-removal were reported. CONCLUSIONS: Awake ECMO is feasible in selected patients, although the effect on outcome remains to be demonstrated. Mortality is almost 60% in patients who failed awake ECMO strategy.

Left ventricular assist devices promote changes in the expression levels of platelet microRNAs.

Introduction: MicroRNAs (miRs) emerged as promising diagnostic and therapeutic biomarkers in cardiovascular diseases. The potential clinical utility of platelet miRs in the setting of left ventricular assist device (LVAD) support is unexplored. Methods: We prospectively measured the expression levels of 12 platelet miRs involved in platelet activation, coagulation, and cardiovascular diseases in LVAD patients by quantitative real-time polymerase chain reaction. Data were longitudinally measured before LVAD implant and after 1, 6, and 12 months of LVAD support, and compared with those measured in healthy volunteers (controls). In silico analysis was also performed to identify pathways targeted by differentially expressed miRs. Results: Data from 15 consecutive patients and 5 controls were analyzed. Pre-implant expression levels of platelet miR-126, miR-374b, miR-223, and miR-320a were significantly different in patients vs. controls. The expression levels of platelet miR-25, miR-144, miR-320, and miR-451a changed significantly over the course of LVAD support; in silico analysis revealed that these miRs are implicated in both cardiac- and coagulation-associated pathways. Furthermore, the patients who suffered from bleeding (n = 5, 33%) had significantly higher pre-implant expression levels of platelet miR-151a and miR-454 with respect to the patients who did not. The same miRs were also differentially expressed in bleeders following LVAD implantation early before the clinical manifestation of the events. Discussion: This study provides a proof-of-concept evidence of significant modulation of platelet miRs expression driven by LVADs. The possible existence of a platelet miRs signature predictive of the development of bleeding events warrants further validation studies.

Longitudinal analysis of pump parameters over long-term support with the HeartMate 3 left ventricular assist device.

AIMS: Recurrence of heart failure emerged as the main cause of long-term mortality in patients implanted with the HeartMate 3 (HM3) left ventricular assist device (LVAD). We aimed at deriving a possible mechanistic rationale of clinical outcomes and analyzed longitudinal changes in pump parameters over prolonged HM3 support to investigate long-term effects of pump settings on left ventricular mechanics. METHODS: Data on pump parameters (i.e. pump speed, estimated flow, and pulsatility index) were prospectively recorded in consecutive HM3 patients following postoperative rehabilitation (baseline) and then at 6, 12, 24, 36, 48, and 60 months of support. RESULTS: Data of 43 consecutive patients were analyzed. Pump parameters were set according to regular patients' follow-up, including clinical and echocardiographic assessment. We recorded a significant progressive increase in pump speed over the course of support: from 5200 (5050-5300) rpm at baseline to 5400 (5300-5600) rpm at 60 months of support ( P  = 0.0007). Consistently with the increase in pump speed, a significant increase in pump flow ( P  = 0.007) and a decrease in pulsatility index ( P  = 0.005) were also recorded. CONCLUSION: Our results reveal unique features of the HM3 on left ventricular activity. The need for progressive increase in pump support suggests indeed a lack of recovery and worsening of left ventricular function, which emerge as a possible mechanistic rationale of heart failure related mortality in HM3 patients. New algorithms to optimize pump settings should be envisioned to further improve LVAD-LV interaction and, ultimately, clinical outcomes in the HM3 population. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT03255928. CLINICALTRIALSGOV IDENTIFIER: NCT03255928.

Coronary angiography findings in resuscitated and refractory out-of-hospital cardiac arrest: A systematic review and meta-analysis.

INTRODUCTION: Coronary angiography (CAG) frequently reveals coronary artery disease (CAD) after out-of-hospital cardiac arrest (OHCA), but its use is not standardized and often reported in different subpopulations. This systematic review and meta-analysis accurately describes angiographic features in resuscitated and refractory OHCA. METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched up to October 31, 2022. Studies reporting coronary angiography findings after OHCA were considered eligible. The primary outcome was location and rate of coronary lesions. Coronary angiography findings with 95% confidence intervals were pooled with a meta-analysis of proportion. RESULTS: 128 studies (62,845 patients) were included. CAG, performed in 69% (63-75%) of patients, found a significant CAD in 75% (70-79%), a culprit lesion in 63% (59-66%), and a multivessel disease in 46% (41-51%). Compared to patients with return of spontaneous circulation, refractory OHCA was associated with more severe CAD due to a higher rate of left main involvement (17% [12-24%] vs 5.7% [3.1-10%]; p = 0.002) and acute occlusion of left anterior descending artery (27% [17-39%] vs 15% [13-18%]; p = 0.02). Nonshockable patients without ST-elevation were those receiving CAG less frequently, despite significant disease in 54% (31-76%). Left anterior descending artery was the most frequently involved (34% [30-39%]). CONCLUSIONS: Patients with OHCA have a high prevalence of significant CAD caused by acute and treatable coronary lesions. Refractory OHCA was associated with more severe coronary lesions. CAD was also present in patients with nonshockable rhythm and without ST elevation. However, heterogeneity of studies and selection of patients undergoing CAG limit the certainty of findings.