Creation of Knock-In Alleles of Insulin Receptor Tagged by Fluorescent Proteins mCherry or EYFP in Fruit Fly Drosophila melanogaster.

The insulin/insulin-like growth factor-like signaling (IIS) pathway is highly conserved across metazoans and regulates numerous physiological functions, including development, metabolism, fecundity, and lifespan. The insulin receptor (InR), a crucial membrane receptor in the IIS pathway, is known to be ubiquitously expressed in various tissues, albeit at generally low levels, and its subcellular localization remains incompletely characterized. In this study, we employed CRISPR-mediated mutagenesis in the fruit fly Drosophila to create knock-in alleles of InR tagged with fluorescent proteins (InR::mCherry or InR::EYFP). By inserting the coding sequence of the fluorescent proteins mCherry or EYFP near the end of the coding sequence of the endogenous InR gene, we could trace the natural InR protein through their fluorescence. As an example, we investigated epithelial cells of the male accessory gland (AG), an internal reproductive organ, and identified two distinct patterns of InR::mCherry localization. In young AG, InR::mCherry accumulated on the basal plasma membrane between cells, whereas in mature AG, it exhibited intracellular localization as multiple puncta, indicating endocytic recycling of InR during cell growth. In the AG senescence accelerated by the mutation of Diuretic hormone 31 (Dh31), the presence of InR::mCherry puncta was more pronounced compared to the wild type. These findings raise expectations for the utility of the newly created InR::mCherry/EYFP alleles for studying the precise expression levels and subcellular localization of InR. Furthermore, this fluorescently tagged allele approach can be extended to investigate other membrane receptors with low abundance, facilitating the direct examination of their true expression and localization.

The Association Between Preoperative Pectoralis Muscle Quantity and Outcomes After Cardiac Transplantation.

BACKGROUND: Sarcopenia is underappreciated in advanced heart failure and is not routinely assessed. In patients receiving a left ventricular assist device, preoperative sarcopenia, defined by using computed-tomography (CT)-derived pectoralis muscle-area index (muscle area indexed to body-surface area), is an independent predictor of postoperative mortality. The association between preoperative sarcopenia and outcomes after heart transplant (HT) is unknown. OBJECTIVES: The primary aim of this study was to determine whether preoperative sarcopenia, diagnosed using the pectoralis muscle-area index, is an independent predictor of days alive and out of the hospital (DAOHs) post-transplant. METHODS: Patients who underwent HT between January, 2018, and June, 2022, with available preoperative chest CT scans were included. Sarcopenia was diagnosed as pectoralis muscle-area index in the lowest sex-specific tertile. The primary endpoint was DAOHs at 1 year post-transplant. RESULTS: The study included 169 patients. Patients with sarcopenia (n = 55) had fewer DAOHs compared to those without sarcopenia, with a median difference of 17 days (320 vs 337 days; P = 0.004). Patients with sarcopenia had longer index hospitalizations and were also more likely to be discharged to a facility other than home. In a Poisson regression model, sarcopenia was a significant univariable and the strongest multivariable predictor of DAOHs at 1 year (parameter estimate = -0.17, 95% CI -0.19 to -14; P = < 0.0001). CONCLUSIONS: Preoperative sarcopenia, diagnosed using the pectoralis muscle-area index, is an independent predictor of poor outcomes after HT. This parameter is easily measurable from commonly obtained preoperative CT scans and may be considered in transplant evaluations.

Transitional dynamics in oncology clinical trials: evaluating the impact of Clinical Trials Act on cooperative groups.

OBJECTIVE: large-scale multicentre clinical trials conducted by cooperative groups have generated a lot of evidence to establish better standard treatments. The Clinical Trials Act was enforced on 1 April 2018, in Japan, and it has remarkably increased the operational burden on investigators, but its long-term impact on cancer cooperative groups is unknown. METHODS: a survey was conducted across the nine major cooperative groups that constitute the Japan Cancer Trials Network to assess the impact of Clinical Trials Act on the number of newly initiated trials from fiscal year (from 1 April to 31 March) 2017 to 2022 and that of ongoing trials on 1 April in each year from 2018 to 2023. RESULTS: the number of newly initiated trials dropped from 38 trials in fiscal year 2017 to 26 trials in fiscal year 2018, surged to 50 trials in fiscal year 2019, but then gradually decreased to 25 trials by fiscal year 2022. Specified clinical trials decreased from 32 trials in fiscal year 2019 to 12 trials in fiscal year 2022. The number of ongoing trials was 220 trials in 2018, peaked at 245 trials in 2020, but then gradually decreased to 219 trials by 2023. The number of specified clinical trials has been in consistent decline. By April 2023, of the 20 ongoing non-specified clinical trials, nine adhered to Clinical Trials Act and 11 followed the Ethical Guidelines for Medical and Health Research Involving Human Subjects. CONCLUSION: the number of multicentre clinical trials in oncology gradually decreased after the Clinical Trials Act's enforcement, which underscores the need for comprehensive amendment of the Clinical Trials Act to streamline the operational process.

Impact of controlled hypothermic preservation on outcomes following heart transplantation.

BACKGROUND: Severe primary graft dysfunction (PGD) is a major cause of early mortality after heart transplant, but the impact of donor organ preservation conditions on severity of PGD and survival has not been well characterized. METHODS: Data from US adult heart-transplant recipients in the Global Utilization and Registry Database for Improved Heart Preservation-Heart Registry (NCT04141605) were analyzed to quantify PGD severity, mortality, and associated risk factors. The independent contributions of organ preservation method (traditional ice storage vs controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression. RESULTS: Among 1,061 US adult heart transplants performed between October 2015 and December 2022, controlled hypothermic preservation was associated with a significant reduction in the incidence of severe PGD compared to ice (6.6% [37/559] vs 10.4% [47/452], p = 0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% [17/281] vs 12.1% [34/281], respectively; p = 0.018). The Kaplan-Meier terminal probability of 1-year mortality was 4.2% for recipients without PGD, 7.2% for mild or moderate PGD, and 32.1%, for severe PGD (p < 0.001). The probability of severe PGD increased for both cohorts with longer ischemic time, but donor hearts stored on ice were more likely to develop severe PGD at all ischemic times compared to controlled hypothermic preservation. CONCLUSIONS: Severe PGD is the deadliest complication of heart transplantation and is associated with a 7.8-fold increase in probability of 1-year mortality. Controlled hypothermic preservation significantly attenuates the risk of severe PGD and is a simple yet highly effective tool for mitigating post-transplant morbidity.

Utility of a fusion protein T-cell co-stimulation blocker Belatacept in heart transplant recipients: Real world experience from a high volume center.

BACKGROUND: Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. METHODS: A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023. RESULTS: Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (± 12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p = .054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p = .24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%). CONCLUSION: In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.

Case report of pregnancy complicated by severe pulmonary hypertension from mitral stenosis and placenta accreta spectrum disorder: management of two life-threatening conditions.

Background: Antenatal cardiovascular disease is a major cause of maternal morbidity and mortality. Severe rheumatic mitral stenosis is especially poorly tolerated during pregnancy. Case Summary: We present a young woman with severe pulmonary hypertension secondary to rheumatic mitral stenosis. She presented at 25 weeks 4 days gestation for evaluation of a pregnancy complicated by placenta accreta spectrum disorder. Invasive hemodynamic testing was carried out to delineate her hemodynamics, and a multidisciplinary cardio-obstetrics team collaborated closely with the patient and her partner to create a management plan. Ultimately, the patient was initiated on veno-arterial extracorporeal membrane oxygenation and underwent caesarean section delivery followed by hysterectomy and subsequent valve replacement surgery. Discussion: This case describes the treatment options considered to balance the risk of decompensation in the setting of severe pulmonary hypertension with hemorrhage associated with placenta accreta spectrum disorder. It highlights the importance of a multidisciplinary, team-based approach to the management of high-risk cardiac conditions throughout pregnancy.

Mechanical Circulatory Support During Surgical Revascularization for Ischemic Cardiomyopathy.

BACKGROUND: This study aimed to describe the use of perioperative mechanical circulatory support (MCS) and its impact on outcomes in patients with ischemic cardiomyopathy who were undergoing surgical revascularization. METHODS: Patients with an ejection fraction <35% who underwent isolated coronary artery bypass grafting (CABG) from 2015 to 2021 were identified (N = 378). Patients were divided into no MCS, preoperative MCS, and postoperative MCS groups on the basis of timing of MCS initiation, which included intraaortic balloon pump, extracorporeal membrane oxygenation, or Impella device (Abiomed) use. The primary outcome of interest was operative mortality. RESULTS: The median Society of Thoracic Surgeons Predicted Risk of Mortality was 2.4%. Sixty-six percent (n = 246) of patients had a previous myocardial infarction, and 61.8% of these patients were within 21 days of CABG. Twenty-one patients (5.6%) presented in cardiogenic shock. The preoperative MCS cohort consisted of 31 patients (8.2%) who underwent CABG a median of 2 days after MCS initiation. Thirty (7.9%) patients required postoperative MCS. Independent risk factors for requiring postoperative MCS included the preoperative ejection fraction (odds ratio, 0.93; P = .01 and the presence of preoperative MCS (odds ratio, 3.06; P = .02). Overall, operative mortality was 3.4%, and 3-year survival was 87.0%. Operative mortality in patients who did and did not receive preoperative MCS was 7.7% and 2.9% (P = .12) with no difference in long-term survival (P = .80), whereas patients requiring postoperative MCS had significantly increased operative (16.7%) and late mortality (63%; P <.01). CONCLUSIONS: CABG can be performed safely in patients with ischemic cardiomyopathy with selective use of perioperative MCS. Despite advanced disease severity, patients requiring preoperative MCS demonstrate acceptable short- and long-term survival. Patients requiring postoperative MCS have increased postoperative morbidity and mortality.

Ventricular assist device using a thoracotomy-based implant technique: Multi-Center Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy (HM3 SWIFT).

OBJECTIVES: The HeartMate 3 (Abbott) left ventricular assist device provides substantial improvement in long-term morbidity and mortality in patients with advanced heart failure. The Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study compares thoracotomy-based implantation clinical outcomes with standard median sternotomy. METHODS: We conducted a prospective, multicenter, single-arm study in patients eligible for HeartMate 3 implantation with thoracotomy-based surgical technique (bilateral thoracotomy or partial upper sternotomy with left thoracotomy). The composite primary end point was survival free of disabling stroke (modified Rankin score >3), or reoperation to remove or replace a malfunctioning device, or conversion to median sternotomy at 6-months postimplant (elective transplants were treated as a success). The primary end point (noninferiority, -15% margin) was assessed with >90% power compared with a propensity score-matched cohort (ratio 1:2) derived from the Multi-Center Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 continued access protocol. RESULTS: The study enrolled 102 patients between December 2020 and July 2022 in the thoracotomy-based arm at 23 North American centers. Follow-up concluded in December 2022. In the Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study group, noninferiority criteria was met (absolute between-group difference, -1.2%; Farrington Manning lower 1-sided 95% CI, -9.3%; P < .0025) and event-free survival was not different (85.0% vs 86.2%; hazard ratio, 1.01; 95% CI, 0.58-2.10). Length of stay with thoracotomy-based implant was longer (median, 20 vs 17 days; P = .03). No differences were observed for blood product utilization, adverse events (including right heart failure), functional status, and quality of life between cohorts. CONCLUSIONS: Thoracotomy-based implantation of the HeartMate 3 left ventricular assist device is noninferior to implantation via standard full sternotomy. This study supports thoracotomy-based implantation as an additional standard for surgical implantation of the HeartMate 3 left ventricular assist device.

Data resource profile of an online database system for forensic mental health services.

This paper introduces a forensic psychiatry database established in Japan and discusses its significance and future issues. The purpose of this Database, created under the Medical Treatment and Supervision Act (MTSA) Database Project, is to improve the quality of forensic psychiatry treatment. It can collect monthly data on "basic information," "Orders and hospitalizations under the MTSA," "Treatment process," "Criminal and medical treatment history," and "problematic behavior in the unit." The online system has accumulated data on more than 8,000 items in 24 broad categories. Medical data are exported from the medical care assisting system of 32 designated inpatient facilities in XML format and then saved on USB memory sticks. The files are imported into the Database system client, which sends the data to the Database server via a virtual private network. This system minimizes errors and efficiently imports patient data. However, there is a limitation that it is difficult to set items that need to be analyzed to solve everyday clinical problems into the database system because they tend to change over time. By evaluating the effectiveness of the Database, and collecting appropriate data, it is expected to disseminate a wide range of knowledge that will contribute to the future development of mental health and welfare care.

Hemodynamic Optimization by Invasive Ramp Test in Patients Supported With HeartMate 3 Left Ventricular Assist Device.

In patients supported by the HeartMate 3 left ventricular assist device (HM3 LVAD), pump speed adjustments may improve hemodynamics. We investigated the hemodynamic implications of speed adjustments in HM3 recipients undergoing hemodynamic ramp tests. Clinically stable HM3 recipients who underwent routine invasive hemodynamic ramp tests between 2015 and 2022 at our center were included. Filling pressure optimization, defined as central venous pressure (CVP) <12 mm Hg and pulmonary capillary wedge pressure (PCWP) <18 mm Hg, was assessed at baseline and final pump speeds. Patients with optimized pressures were compared to nonoptimized patients. Overall 60 HM3 recipients with a median age of 62 years (56, 71) and time from LVAD implantation of 187 days (124, 476) were included. Optimized filling pressures were found in 35 patients (58%) at baseline speed. Speed was adjusted in 84% of the nonoptimized patients. Consequently, 39 patients (65%) had optimized pressures at final speed. There were no significant differences in hemodynamic findings between baseline and final speeds (p > 0.05 for all). Six and 12 month readmission-free rates were higher in optimized compared with nonoptimized patients (p = 0.03 for both), predominantly due to lower cardiac readmission-free rates (p = 0.052). In stable outpatients supported with HM3 who underwent routine ramp tests, optimized hemodynamics were achieved in only 2 of 3 of the patients. Patients with optimized pressures had lower all-cause readmission rates, primarily driven by fewer cardiac-related hospitalizations.

Left-Ventricular Unloading With Impella During Refractory Cardiac Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation: A Systematic Review and Meta-Analysis.

OBJECTIVES: Extracorporeal cardiopulmonary resuscitation (ECPR) is the implementation of venoarterial extracorporeal membrane oxygenation (VA-ECMO) during refractory cardiac arrest. The role of left-ventricular (LV) unloading with Impella in addition to VA-ECMO ("ECMELLA") remains unclear during ECPR. This is the first systematic review and meta-analysis to characterize patients with ECPR receiving LV unloading and to compare in-hospital mortality between ECMELLA and VA-ECMO during ECPR. DATA SOURCES: Medline, Cochrane Central Register of Controlled Trials, Embase, and abstract websites of the three largest cardiology societies (American Heart Association, American College of Cardiology, and European Society of Cardiology). STUDY SELECTION: Observational studies with adult patients with refractory cardiac arrest receiving ECPR with ECMELLA or VA-ECMO until July 2023 according to the Preferred Reported Items for Systematic Reviews and Meta-Analysis checklist. DATA EXTRACTION: Patient and treatment characteristics and in-hospital mortality from 13 study records at 32 hospitals with a total of 1014 ECPR patients. Odds ratios (ORs) and 95% CI were computed with the Mantel-Haenszel test using a random-effects model. DATA SYNTHESIS: Seven hundred sixty-two patients (75.1%) received VA-ECMO and 252 (24.9%) ECMELLA. Compared with VA-ECMO, the ECMELLA group was comprised of more patients with initial shockable electrocardiogram rhythms (58.6% vs. 49.3%), acute myocardial infarctions (79.7% vs. 51.5%), and percutaneous coronary interventions (79.0% vs. 47.5%). VA-ECMO alone was more frequently used in pulmonary embolism (9.5% vs. 0.7%). Age, rate of out-of-hospital cardiac arrest, and low-flow times were similar between both groups. ECMELLA support was associated with reduced odds of mortality (OR, 0.53 [95% CI, 0.30-0.91]) and higher odds of good neurologic outcome (OR, 2.22 [95% CI, 1.17-4.22]) compared with VA-ECMO support alone. ECMELLA therapy was associated with numerically increased but not significantly higher complication rates. Primary results remained robust in multiple sensitivity analyses. CONCLUSIONS: ECMELLA support was predominantly used in patients with acute myocardial infarction and VA-ECMO for pulmonary embolism. ECMELLA support during ECPR might be associated with improved survival and neurologic outcome despite higher complication rates. However, indications and frequency of ECMELLA support varied strongly between institutions. Further scientific evidence is urgently required to elaborate standardized guidelines for the use of LV unloading during ECPR.

Liberal use of veno-arterial extracorporeal membrane oxygenation in combined sequential heart-liver transplantation.

Combined heart-liver transplantation (CHLT) is a rarely though increasingly performed procedure with evolving indications. Despite CHLT being performed at only a handful of centers, the use of intraoperative mechanical circulatory support to optimize hemodynamics and facilitate dual-organ transplantation varies widely. At our center, we liberally utilize veno-arterial extracorporeal membrane oxygenation (V-A ECMO) when a veno-venous shunt is anticipated to be insufficient in mitigating the hemodynamic perturbations associated with liver reperfusion. In this series, we describe our experience with V-A ECMO in sequential (heart-first) CHLT and demonstrate highly favorable outcomes with this strategy.

Acute right ventricular geometric change predicts outcomes in HeartMate 3 patients.

BACKGROUND: The physiological response of the right ventricle (RV) following left ventricular assist device (LVAD) implantation is difficult to predict. We aimed to investigate RV geometric and functional changes after LVAD insertion and their effects on clinical outcomes. METHODS: We retrospectively reviewed 188 patients who underwent HeartMate 3 implantation at our center between November 2014 and September 2021. The RV end-diastolic diameter (RVEDD) and RV end-diastolic area (RVEDA) were measured on preoperative and predischarge transthoracic echocardiography. The nonadapted group included patients with increased RVEDD and RVEDA at discharge. The composite outcome was defined as death or readmission due to worsening right heart failure. RESULTS: There were 82 patients (44%) who had a nonadapted and 106 patients (56%) who had an adapted RV. Preoperatively, the nonadapted group had smaller RVEDD (46 vs 49 mm, p < 0.001) and RVEDA (27 vs 31 cm2, p < 0.001). At discharge, the nonadapted group had larger RVEDD (51 vs 43 mm, p < 0.001) and RVEDA (33 vs 27 cm2, p < 0.001). Kaplan-Meier analysis demonstrated worse 3-year survival (77% vs 91%, p = 0.006) and freedom from composite outcome (58% vs 85%, p < 0.001) in the nonadapted group. A multivariable Cox proportional hazards model showed that nonadaption (hazard ratio [HR] 3.09, 95% confidence interval [CI] 1.29-7.40, p = 0.01) and age (HR 3.73, 95% CI 1.42-9.77, p = 0.007) were independent predictors of composite outcome. CONCLUSIONS: Acute RV dimensional changes after LVAD insertion may represent intrinsic RV function and may be a useful prognostic marker.

Myocardial Recovery With HeartMate 3 Left Ventricular Assist Device: An Attainable Goal That Needs Better Precision.

Despite advances in our understanding of myocardial recovery among left ventricular assist device (LVAD) patients, with 10-30% of patients achieving substantial myocardial improvement, the rates of LVAD support cessation remain extremely low (1-2%). These numbers are in stark contrast to clinical trial data where successful LVAD cessation is reported in up to 47% of patients. The majority of LVAD programs lack structured recovery programs and targeted protocols, likely underscoring the heterogeneity that exists among LVAD patients with myocardial recovery. This perspective summarizes the current medical and surgical challenges with respect to 1) identifying the appropriate candidates for LVAD cessation; 2) methods to wean LVAD support; 3) reviewing surgical techniques for cessation of current generation HeartMate 3 LVAD; and 4) approaching shared decision making for LVAD cessation between patients and providers given the uncertainties that remain in the field.

Increasing waiting times for status 2 patients in new United Network for Organ Sharing allocation system: Impact on waitlist and posttransplant outcomes.

OBJECTIVE: Since the heart transplant allocation policy change in 2018, there has been an increase in temporary mechanical circulatory support for Status 2 patients. We sought to examine the temporal pattern of waitlist and posttransplant outcomes for Status 2 patients. METHODS: Adult patients in the United Network for Organ Sharing registry who were listed as Status 2 from January 2019 to June 2022 were included. Temporal trends in waitlist time, waitlist events, and posttransplant outcomes were assessed. Probability of transplant or death after being listed was compared over time. Multivariable regression was performed to identify risk factors for mortality after transplant. RESULTS: A total of 6310 patients were included. From 2019 to 2022, the number of Status 2 patients listed increased from 4.2 to 5.9 per day. Microaxial ventricular assist devices at Status 2 listing increased over time (P < .001). During the study period, median waitlist time (18 days vs 23 days, P < .001) as well as Status 2 days (8 days vs 12 days, P < .001) increased. Waitlist mortality remained stable (5.5%); however, probability of transplant within 90 days of Status 2 listing progressively declined (P < .001). Finally, longer waitlist duration was independently associated with 30-day posttransplant mortality (odds ratio, 1.01; 95% confidence interval, 1.00-1.01, P = .02). CONCLUSIONS: Since the allocation policy change there has been a steady rise in the number of patients listed for Status 2. This has led to increasing waitlist times and lower probability of transplantation for Status 2 patients, which may have negative consequences for posttransplant outcomes.

The Hemodynamic Effects of Aortic Regurgitation in Patients Supported by a HeartMate 3 Left Ventricular Assist Device.

BACKGROUND: Aortic regurgitation (AR) is a common complication following left ventricular assist device (LVAD) implantation. We evaluated the hemodynamic implications of AR in patients with HeartMate 3 (HM3) LVAD at baseline and in response to speed changes. METHODS AND RESULTS: Clinically stable outpatients supported by HM3 who underwent a routine hemodynamic ramp test were retrospectively enrolled in this analysis. Patients were stratified based on the presence of at least mild AR at baseline speed. Hemodynamic and echocardiographic parameters were compared between the AR and non-AR groups. Sixty-two patients were identified. At the baseline LVAD speed, 29 patients (47%) had AR, while 33 patients (53%) did not. Patients with AR were older and supported on HM3 for a longer duration. At baseline speed, all hemodynamic parameters were similar between the groups including central venous pressure, pulmonary capillary wedge pressure, pulmonary arterial pressures, cardiac output and index, and pulmonary artery pulsatility index (p > 0.05 for all). During the subacute assessment, AR worsened in some, but not all, patients, with increases in LVAD speed. There were no significant differences in 1-year mortality or hospitalization rates between the groups, however, at 1-year, ≥ moderate AR and right ventricular failure (RVF) were detected in higher rates among the AR group compared to the non-AR group (45% vs. 0%; p < 0.01, and 75% vs. 36.8%; p = 0.02, respectively). CONCLUSIONS: In a cohort of stable outpatients supported with HM3 who underwent a routine hemodynamic ramp test, the presence of mild or greater AR did not impact the ability of HM3 LVADs to effectively unload the left ventricle during early subacute assessment. Although the presence of AR did not affect mortality and hospitalization rates, it resulted in higher rates of late hemodynamic-related events in the form of progressive AR and RVF.

Acute kidney injury during extracorporeal life support in cardiogenic shock: Does flow matter?

BACKGROUND: This study examines the role of extracorporeal life support flow in the development of acute kidney injury in cardiogenic shock. METHODS: We performed a retrospective analysis of 465 patients placed on extracorporeal life support at our institution between January 2015 and December 2020 for cardiogenic shock. Flow index was calculated by dividing mean flow by body surface. Stages of acute kidney injury were determined according to Kidney Disease: Improving Global Outcomes (KDIGO) organization guidelines. RESULTS: There were 179 (38.5%) patients who developed acute kidney injury, 63.1% of which were classified as Stage 3--the only subgroup associated with 1-year mortality (hazard ratio = 2.03, p < .001). Risk of kidney injury increased up to a flow index of 1.6 L/min/m2, and kidney injury was more common among patients with flow index greater than 1.6 L/min/m2 (p = .034). Those with kidney injury had higher baseline lactate levels (4.4 vs 3.1, p = .04), and Stage 3 was associated wit higher baseline creatinine (p < .001). CONCLUSIONS: In our cohort, kidney injury was common and Stage 3 kidney injury was associated with worse outcomes compared to other stages. Low flow was not associated with increased risk of kidney injury. Elevated baseline lactate and creatinine among patients with acute kidney injury suggest underlying illness severity, rather than flow, may influence kidney injury risk.