Donor-derived cell-free DNA (dd-cfDNA) is a reliable, noninvasive marker for detecting allograft rejection after heart transplantation (HT). We evaluated whether dd-cfDNA levels differ in recipients of ABO-compatible, nonidentical (mismatched) grafts. We performed a retrospective single-center cohort study of 219 adult HT recipients transplanted between January 2019 and May 2023, each with at least one dd-cfDNA sample collected between November 2019 and April 2024. ABO mismatch was defined as a donor blood type A, B, or AB that was compatible with but nonidentical to the recipient's type; only ABO-compatible transplants were included. dd-cfDNA was measured using a commercially available assay (AlloSure, CareDx, Brisbane, CA), and a level ≥0.20% was defined as positive. A total of 1,783 dd-cfDNA tests were analyzed, with a 16.0% overall positivity rate. Positivity was 20.1% in the mismatched group and 15.5% in the matched group, with no statistically significant difference whether dd-cfDNA was treated as a binary (p = 0.95) or continuous (p = 0.26) variable. No statistically significant differences were observed between groups in gene expression profiling, donor-specific antibodies, rejection, or survival. In this adult cohort, ABO-compatible nonidentical HT was not associated with higher dd-cfDNA levels, although the small mismatched subgroup limits statistical power.

Extracorporeal membrane oxygenation (ECMO) is associated with a high risk of neurologic injury in pediatric patients, and early detection of injury is often challenging because the clinical examination is frequently limited by illness, medication, and developmental factors. Quantitative electroencephalography (qEEG), derived from standard continuous electroencephalography (cEEG), offers a bedside, continuous, and objective approach to neuromonitoring. We present a case series of two pediatric patients supported on ECMO who underwent cEEG monitoring within 6 hours of cannulation. Quantitative electroencephalography metrics, including global suppression percentage (SP) and total power (TP), were analyzed in relation to clinically significant neurologic events. In both cases, acute neurologic insults, including cardiac arrest, cerebral infarction, and intracranial hemorrhage, were associated with marked increases in global SP and concurrent decreases in TP. These findings highlight an inverse relationship between SP and TP across different mechanisms of brain injury and support further investigation of qEEG as a real-time physiologic marker of cortical suppression during acute neurologic deterioration.

Antithrombin (AT) depletion is common in critical illness, and during venovenous extracorporeal membrane oxygenation (VV ECMO), blood-surface interactions further amplify coagulation and inflammation cascades. The prognostic value of baseline AT activity complications at ECMO initiation remains unclear. We conducted a single-center retrospective cohort study of adults receiving VV ECMO (2013-2023) to investigate associations between baseline AT activity and bleeding and thrombosis risk. Clinical outcomes included computed tomography (CT)-confirmed ischemic, thrombotic, and bleeding complications and death during ECMO. Analyses included logistic regression, cause-specific Cox models, and unsupervised methods. Among 734 patients, 64% were AT-deficient (< 77%). Antithrombin activity inversely correlated with inflammatory markers. Ischemic complications were more frequent in AT-deficient patients (7.6% vs. 1.9%, p < 0.01), while thrombotic and bleeding rates were similar. Antithrombin activity predicted reduced odds of ischemic events (odds ratio [OR]: 0.97 per 1% increase, 95% confidence interval [CI]: 0.95, 0.98), with an optimal AT threshold of 49 for prediction of ischemic complications (area under the curve [AUC] = 0.74). Three subphenotypes were identified: a consumptive phenotype with markedly reduced AT activity, which carried the highest burden of ischemic complications and mortality. Baseline AT activity and inflammatory status may identify VV ECMO patients at increased risk of ischemia and death, particularly those with a consumptive profile.

Autologous pericardium is commonly used for pulmonary artery (PA) reconstruction in congenital heart surgery but is not always available. Synthetic materials lack growth potential and may cause calcification or infection. Tissue-engineered vascular grafts (TEVGs), created by in-body tissue architecture, may overcome these limitations. This study evaluated mid-term outcomes of PA reconstruction using TEVG patches. From July 2014 to December 2024, TEVG molds were implanted in 19 patients; seven underwent PA reconstruction using 15 patches. Diagnoses included pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (n = 4), coarctation with aortic stenosis (n = 1), double outlet right ventricle with coarctation (n = 1), and tetralogy of Fallot (n = 1). Median follow-up was 2.8 years (range, 1.0-7.9 years). No mortality or patch-related calcification, aneurysm, or infection occurred. Restenosis developed in three of 15 patches (20%), all in the central PA near the right ventricle-to-PA conduit anastomosis; two patients required balloon angioplasty, with no surgical reintervention. No restenosis occurred in peripheral patches. Freedom from reintervention was 85.7% at 1 year and 71.4% at 5 years. TEVG patches demonstrated acceptable durability, particularly for peripheral PA augmentation, and may represent a reliable alternative to autologous pericardium.

Prolonged normothermic ex situ heart perfusion (NEHP) could expand the donor pool by decoupling procurement, transport, and implantation, but clinically used systems rarely exceed 4-6 hours. We evaluated pragmatic protein replacement strategies enabling 48-hour NEHP in adult porcine hearts without biologic cross-circulation. Thirteen juvenile pigs (50.6 ± 5.0 kg) underwent Langendorff NEHP and were randomly assigned to 65 kDa serum fractionate (SF65; n = 5), continuous infusion of serum fractionated to <65 kDa with hemofiltration; 120 kDa serum fractionate (SF120; n = 3), consisting of serum fractionated to <120 kDa with hemofiltration; or plasma exchange (PE, n = 5), consisting of unfractionated plasma with concomitant plasma filtration and intermittent hemofiltration. Hearts were perfused for 48 hours with intermittent working-mode assessments under predefined failure criteria. All hearts completed 48 hours without failure. PE demonstrated the lowest coronary resistance at 37-48 hours (0.13 ± 0.05 vs. 0.30 ± 0.13 SF65, 0.69 ± 0.31 SF120 mm Hg/ml/min); SF120 exhibited markedly higher aortic regurgitation (38.1% ± 27.7% vs. 5.7% ± 4.9% SF65, 5.0% ± 6.7% PE); SF65 showed the greatest edema (interventricular septal wall diameter [IVSd] increase 102% ± 23% vs. 37% ± 17% SF120, 33% ± 19% PE); and echocardiographic indices and composite histologic injury scores were similar among groups. Reproducible 48-hour NEHP of adult porcine hearts is feasible using clinically accessible protein replacement strategies. PE approximates the benefits of fractionated serum regimens while avoiding large-protein accumulation and represents a practical path toward translational long-duration heart perfusion.

The renin-angiotensin-aldosterone system (RAAS) is essential to cardiovascular homeostasis, particularly in heart failure (HF) and cardiogenic shock states. Relative angiotensin II depletion is a potential mechanism for postoperative hypotension and may be potentiated by pre-existing HF. The availability of exogenous AT2 allows for tailored vasoplegia management in a state of RAAS dysregulation. This prospective, single-institution pilot study aimed to characterize the expected reduction in angiotensin II (AT2) and angiotensin I (AT1) levels following cardiopulmonary bypass (CPB) in patients with and without chronic systolic HF, with enrollment of 10 patients in each arm. Preoperative AT2 and AT1 levels were significantly higher in patients with HF and remained so following cardiac surgery. A lower postoperative AT2 correlated with lower mean arterial pressure and a trend toward higher pressor requirements in HF patients only. No association was seen in HF or non-HF patients between CPB time and the change in AT1, AT2, or their ratio. Taken together, this pilot study suggests a role for characterizing RAAS function in patients with HF undergoing cardiac surgery for prediction and treatment of postcardiotomy vasoplegia.

The Impella microaxial flow pump is increasingly used in cardiogenic shock and high-risk coronary interventions. Hemolysis is a frequent complication, but established markers lack bedside availability. We report the first case of Impella obstruction by a chorda tendinea, causing massive hemolysis detected through severe methemoglobinemia. A 60-year-old male with non-ST-elevation myocardial infarction and cardiogenic shock underwent protected percutaneous coronary intervention with Impella CP SmartAssist support. After 42 hours, motor current increased abruptly while purge flow remained unchanged. Despite correct positioning and optimized volume status, hemoglobin fell from 9.2 to 4.6 g/dl within 14 hours, methemoglobin peaked at 10.2%, and anuric kidney injury developed. Device explantation revealed a native filamentous structure incorporated in the impeller, morphologically consistent with a chorda tendinea. Hemolysis resolved promptly post-explantation. The patient recovered and was discharged home after three months. Mobile cardiac structures can cause impeller obstruction leading to severe hemolysis. Methemoglobinemia-measured on routine blood gas analysis-may serve as an early indicator of evolving hemolysis during mechanical circulatory support and warrants prospective validation. Increased motor current with unchanged purge flow may differentiate intraluminal obstruction from thrombosis and guide targeted intervention.

Biventricular assist device (BiVAD) use has decreased in the pediatric population, partly driven by concerns that survival may be inferior compared with that achieved with isolated left ventricular assist devices (LVAD). We aimed to address whether the timing of right ventricular assist device (RVAD) impacts these outcomes. A retrospective analysis of prospectively collected data of patients who underwent BiVAD implantation between April 2018 and December 2022 and were enrolled in the Advanced Cardiac Therapies Improving Outcomes Network Registry was performed. Baseline clinical and demographic characteristics were compared between the primary (RVAD implanted at the same surgery as LVAD) and delayed (RVAD implanted within 60 days of LVAD) RVAD cohorts, and survival analysis was performed. There were 223 included patients, with 186 (83.4%) having a primary RVAD. Median age at implant was 5.48 years (interquartile range: 1.10, 12.52), 45.7% were female, and 23.3% had congenital heart disease. Primary RVAD patients were more likely to be on dialysis at the time of implantation (p = 0.028) and to have previous sternotomies (p = 0.004). Primary RVAD patients had better 1 year survival (p = 0.023). This suggests that mortality is impacted by RVAD timing in patients requiring BiVAD support. There should be a low threshold for implanting an RVAD during the same surgery as the LVAD in patients displaying signs of right heart failure.

Veno-arterial extracorporeal membrane oxygenation (ECMO) is used to support patients with high-risk pulmonary embolism (HR-PE) with cardiogenic shock, but data on mid- and long-term outcomes after reperfusion remain limited. We retrospectively compared outcomes after ECMO with embolectomy, ECMO with thrombolysis, or ECMO alone in patients with HR-PE supported at a tertiary-care hospital (2016-2024). Extracorporeal membrane oxygenation was used in 72 patients with HR-PE; 22 received ECMO with embolectomy, 28 received ECMO with thrombolysis, and 22 received ECMO alone. The median duration of ECMO support was 5 days (interquartile range: 4-6 days). In-hospital complications and support time did not differ significantly between groups. Weaning from ECMO was achieved significantly more often with embolectomy (n = 22, 100%) than with thrombolysis (n = 17, 60.7%) or ECMO alone (n = 8, 36.4%) (p < 0.01). Survival to hospital discharge was highest after ECMO with embolectomy (n = 18, 81.8%), as compared with ECMO with thrombolysis (n = 16, 57.1%) or ECMO alone (n = 4, 18.1%) (p < 0.01). One and 3 year survival was 81.8% and 72.7% after ECMO with embolectomy, 55.7% and 46.4% after ECMO with thrombolysis, and 18.2% and 18.2% after ECMO alone (p < 0.001). Extracorporeal membrane oxygenation with early percutaneous or surgical embolectomy may provide a survival benefit over ECMO alone in patients with HR-PE. Further prospective studies are warranted.

C-reactive protein (CRP) is an inflammatory biomarker with prognostic value in heart failure, but its role in HeartMate 3 (HM3) left ventricular assist device recipients is unclear. We retrospectively analyzed 188 adult HM3 recipients (2016-2025), stratified by preoperative CRP into low-CRP (≤10 mg/L, n = 65) and high-CRP (>10 mg/L, n = 123) groups. High-CRP patients presented with a sicker phenotype, with higher INTERMACS profile 1/preoperative extracorporeal membrane oxygenation (ECMO) support (50% vs. 3%) and greater renal, hepatic, hematologic, and nutritional derangement. In-hospital and 30 day mortality were higher with high CRP (23% vs. 5%, p = 0.001; 19% vs 3%, p = 0.003); overall mortality did not differ (47% vs. 40%, p = 0.360). In a parsimonious multivariable model adjusted for age, preoperative CRP (odds ratio [OR], 1.05 per 10 mg/L, p = 0.006) and albumin (OR, 0.32 per g/dl, p = 0.003) independently predicted in-hospital mortality; a seven-variable model was unstable due to INTERMACS-ECMO collinearity. C-reactive protein discriminated in-hospital mortality (area under the curve [AUC] = 0.77); a 10 mg/L threshold was sensitive (90%) but not specific (40%). High CRP was also associated with a 4.5-fold increase in tracheostomy (36% vs. 8%, p < 0.001) and prolonged ventilation. Preoperative CRP, interpreted with albumin, is a practical risk signal identifying a high-risk inflammatory-nutritional phenotype with greater perioperative morbidity in HM3 recipients.

Superior vena cava (SVC) syndrome is a clinical condition caused by an obstruction of blood flow through the SVC, which may complicate veno-venous extracorporeal membrane oxygenation (V-V ECMO). We report a case occurring early after initiation of femoro-femoral V-V ECMO in a 69 year old patient with severe acute respiratory distress syndrome (ARDS). Clinical presentation included facial and upper body edema, markedly elevated central venous pressure, and high-pressure alarms on all infusion pumps. Computed tomography demonstrated retrograde flow from a reinfusion cannula positioned in the right atrium toward the SVC, causing functional obstruction of venous return without anatomical stenosis. Cannula repositioning led to rapid resolution of symptoms and hemodynamic improvement. This case highlights key technical considerations in femoro-femoral V-V ECMO: reinfusion cannula tip position must avoid directed flow toward the SVC, particularly when distal segments are non-radiopaque; cannula length and diameter significantly influence reinfusion pressure; and indirect signs such as elevated central venous pressure and infusion pump alarms may facilitate early diagnosis. Optimization of cannula selection and positioning is essential to prevent this rare but severe complication.

Extracorporeal carbon dioxide removal (ECCO2R) has emerged as a promising therapeutic avenue to address the challenges of CO2 accumulation during chronic obstructive pulmonary disease (COPD) exacerbations. Current COPD exacerbation interventions rely on invasive mechanical ventilation to support respiration, which can rapidly induce diaphragmatic atrophy and frequently leaves patients indefinitely reliant on a ventilator. Extracorporeal carbon dioxide removal could be a suitable modality to stabilize these critically ill patients; however, current implementations rely on either purely bicarbonate dialysis, which does not address acidemia, or a gas exchanger, which necessitates high blood flow rates. Herein, we describe a custom hybrid system for combined bicarbonate and gaseous CO2 elimination, achieving 123 ± 4 ml/min CO2 removal with direct pH adjustment at blood flow rates of 250 ml/min. This is achieved through the combination of 101 ± 2 ml/min bicarbonate removal from a dialysis methodology and 21 ± 2 ml/min CO2 removal across a novel, custom-built gas exchange device. Hence, this system is for COPD patients with hypercapnic respiratory failure across the dynamic respiratory demands of an exacerbation event. This amalgamation not only amplifies CO2 removal rates but also enables a less invasive therapeutic approach.