Hemocompatibility Evaluation of a Novel Ambulatory Pulmonary Assist System Using a Lightweight Axial-Flow Pump.

The Pulmonary Assist System (PAS) is currently under development as a wearable respiratory assist system. In this study, the hemocompatibility of the PAS's axial-flow mechanical pump (AFP) was compared to other contemporary mechanical pumps in an acute ovine model. The PAS was attached to a normal sheep in a venovenous configuration using one of three pumps: 1) AFP, 2) ReliantHeart HeartAssist 5 (control), or 3) Abbott Pedimag (control) (n = 5 each). Each sheep was supported on the PAS for 12 hours with two L/minute of blood flow and four L/minute of sweep gas. Hemolysis, coagulation, inflammation, and platelet activation and loss were compared among the groups. In this study, the plasma-free hemoglobin (pfHb) was less than 10 mg/dl in all groups. The pfHb was significantly lower in the AFP group compared to other groups. There was no significant clot formation in the pumps and oxygenators in all groups. Furthermore, no significant differences in coagulation (oxygenator resistance, fibrinopeptide A), inflammation (white blood cell counts, IL-8), and platelet activation and loss (p-selectin, platelet counts) were observed among the groups (all, p > 0.05). This study demonstrates equivalent hemocompatibility of the PAS's AFP to other contemporary mechanical pumps with a reduced level of hemolysis on startup.

Midterm Outcomes After Aortic Valve Neocuspidization (Ozaki Procedure) in Adults.

BACKGROUND: Trileaflet aortic valve neocuspidization (AVN) using autologous pericardium (Ozaki procedure) is an emerging surgical treatment option for aortic valve diseases. Although excellent results have been reported from Japan, data pertaining to its use in the United States are sparse. METHODS: All adult patients who underwent AVN (AVN group) or surgical aortic valve replacement (SAVR) with a bioprosthetic valve (SAVR group) between 2015 and 2022 were identified. Propensity score matching was used to adjust the baseline characteristics between the 2 groups. RESULTS: A total of 101 patients underwent AVN, and 1816 patients underwent SAVR with a bioprosthetic valve. None in the AVN group required conversion to SAVR. Before matching, mean age in the AVN group was 68.5 ± 8.8 years, and 56 patients (55.4%) underwent concomitant procedures. Preoperatively, 3 (3%) had endocarditis. Bicuspid valve was observed in 38 (38.4%). None died at 30 days in the AVN group. The median follow-up duration was 3.2 years. After propensity score matching, the expected survival and freedom from at least moderate aortic regurgitation at 5 years was 91.7% ± 3.1% and 97.6% ± 1.7%, respectively. Propensity score matching yielded 77 patients in each group. The Kaplan-Meier curve demonstrated equivalent survival at 5 years between the 2 groups (P = .95). Additionally, freedom from at least moderate aortic regurgitation was comparable at 5 years (P = .23). CONCLUSIONS: AVN can be safely performed for a variety of aortic valve diseases, with or without concomitant operations. AVN demonstrated similar midterm outcomes compared with SAVR with a bioprosthetic valve in the United States adult population.

Infectious complications following contemporary left ventricular assist device implantation.

BACKGROUND: The aim of this study is to evaluate the source of infectious complications following contemporary left ventricular assist device (LVAD) implantation and to determine the impact of infections on patient outcomes. METHODS: All patients who underwent centrifugal LVAD implantation between 2014 and 2020 at a single center were retrospectively reviewed. Postimplant infections were categorized as VAD-specific, VAD-related, or non-VAD according to previously published definitions. Postoperative survival and freedom from readmission were assessed using Kaplan-Meier analysis. Univariable and multivariable analyses were performed to determine the risk factors for postoperative infectious complications. RESULTS: A total of 212 patients underwent centrifugal LVAD implantation (70 HeartMate 3, 142 HeartWare HVAD) during the study period. One hundred and two patients (48.1%) developed an infection, including 34 VAD-specific, 11 VAD-related, and 57 non-VAD. Staphylococcus species were the most common source of postoperative infection (n = 57, 33.7%). In multivariable analysis, diabetes significantly impacted overall postoperative infection rate. At 12 and 24 months, respectively, Kaplan-Meier survival was 81.1% and 61.6% in the infection group and 83.4% and 78.1% in the noninfection group (p = 0.006). Within the total cohort, 12- and 24-month freedom from infection were 46.2% and 31.9%, respectively. Patients with infectious complication had significantly lower rate of transplantation (16.4% vs. 43.6%; p < 0.001), increased overall mortality (46.3% vs. 17.3%, p < 0.001), and increased rates of noncardiac readmission (58.2% vs. 37.3%, p = 0.007). CONCLUSIONS: Infections are common following contemporary LVAD implantation and are most commonly non-VAD related. Patients with postoperative infectious complications have significantly reduced rates of transplantation, survival, and freedom from noncardiac readmission.

Pre-implant right ventricular free wall strain predicts post-LVAD right heart failure.

BACKGROUND: The aim of this study is to evaluate the predictive utility of preoperative right ventricular (RV) global longitudinal strain (GLS) and free wall strain (FWS) on outcomes following left ventricular assist devices (LVADs) implantation. METHODS: Preoperative transthoracic echocardiograms were retrospectively reviewed in adults undergoing continuous-flow LVAD implantation between 2004 and 2018 at a single center. Patients undergoing pump exchange were excluded. RV GLS and FWS were calculated using commercially available software with the apical four-chamber view. The primary outcome was RV failure as defined by the Interagency Registry for Mechanically Assisted Circulatory Support within 1-year post-LVAD insertion. RESULTS: A total of 333 patients underwent continuous-flow LVAD implantation during the study period and 137 had adequate preoperative studies for RV strain evaluation. RV FWS was found to be a significant predictor of postoperative RV failure in univariate analysis (odds ratio [OR] = 1.12, p = .03), and this finding persisted after risk adjustment in multivariable analysis (OR = 1.14, p = .04). Using the optimal cutoff value of -5.64%, the c-index of FWS in predicting RV failure was 0.65. RV GLS was not associated with post-LVAD RV failure (OR = 1.07, p = .29). PCWP was the only additional significant predictor of RV failure using multivariable analysis (OR = 0.90, p = .02). CONCLUSION: Pre-implant RV FWS is predictive of RV failure in the first postoperative year after LVAD implantation.

Neuroleptic Malignant Syndrome or Catatonia? A Case Report.

INTRODUCTION: A review of the literature has shown that there are many similarities in the presentation of neuroleptic malignant syndrome (NMS) and catatonia. Attempts to reconcile the differences have been made by suggesting that NMS and catatonia may represent different presentations of the same illness or that they lie within the same spectrum of a poorly understood clinical syndrome. The described case is of a patient who presented with NMS and catatonia which was difficult to diagnose, but which responded to treatment with intravenous diazepam. CASE PRESENTATION: The case concerns a 22-year-old male admitted for pulmonary hypertension to an intensive care unit (ICU). Three days following admission, he developed a high fever that did not respond to antibiotics. The patient then developed rigidity, nocturnal agitation, decreased responsiveness, and somnolence. Without the use of bromocriptine (Novartis, Basel, Switzerland) or dantrolene (Par Pharmaceuticals, Chestnut Ridge, USA) discontinuation of neuroleptics combined with intravenous diazepam (Pfizer, NY, USA) led to a very rapid response and marked improvement in the case. CONCLUSIONS: Early recognition and management of NMS and MC in a complex, gravely ill patient, may be accomplished in the ICU despite obfuscation of traditional signs and symptoms of the NMS and MC syndrome. Such interventions can have life-saving effects on patients in danger of fatal autonomic instability.

Outcomes of left ventricular assist device implantation in hypercoagulable patients.

BACKGROUND: The aim of this study was to evaluate outcomes of left ventricular assist devices (LVADs) in patients who tested positive for hypercoagulable hematologic disorders. METHODS: Adults undergoing continuous-flow LVAD implantation with preoperative hypercoagulability testing between 2004 and 2018 at a single center were reviewed. Hypercoagulability was defined as testing positive for antiphospholipid antibody, anticardiolipin antibody, lupus anticoagulant, protein C, protein S, factor V Leiden, and/or heparin-induced thrombocytopenia. The primary outcome was survival on the original LVAD. Secondary outcomes included rates of thromboembolic complications and readmission for intravenous heparin treatment. RESULTS: A total of 270 LVAD patients with pre-implant hypercoagulability testing were included, and 157 (58%) tested positive for a hypercoagulable disorder. Of those testing positive, 10 (6.4%) had a clinical pre-LVAD history of thromboembolic events. Survival was comparable between hypercoagulable and non-hypercoagulable patients (1 year: 73.3% vs 78.9%, P = .2195, 2-year: 60.7% vs 62.8%, P = .3627). Rates of pump thrombosis (14.0% vs 13.3%, P = .8618), hemolysis (4.5% vs 3.5%, P = .3536), stroke (18.5% vs 14.2%, P = .3483) and readmission for IV heparin therapy (87.3% (n = 137) vs 77.9% (n = 88), P = .7560) were similar. Outcomes were comparable in patients with positive hypercoagulable tests when stratified by pre-implant clinical history of hypercoagulability as well as stratified by recent preoperative exposure to heparin or warfarin. CONCLUSIONS: In this series, positive laboratory tests for hypercoagulability were common amongst patients undergoing LVAD implantation although few had positive clinical histories. Survival and freedom from thromboembolic complications were comparable to non-hypercoagulable patients. Hypercoagulability alone should therefore not serve as a contraindication to LVAD implantation.

A running suture line for aortic valve replacement does not increase the rate of postoperative complete heart block.

BACKGROUND: Surgical implantation of a prosthetic aortic valve is typically done with multiple interrupted sutures. We adapted a running suture line technique for prostheses implantation to decrease the rate of complete heart block necessitating permanent pacemaker. METHODS: 374 patients undergoing isolated aortic valve replacements were identified between 2015 and 2017. Patients with preoperative heart block, patients undergoing concomitant MAZE procedure and those undergoing multivalve procedures were excluded. Interrupted technique was performed with multiple non-pledgeted sutures. Running technique was performed with three 2-0 polypropylene sutures. Propensity-score matching (caliper distance = 0.10) was used to match based on patient age, gender, BMI, diabetes mellitus, renal failure, heart failure, arrythmias, use of anti-arrhythmics, and STS PROM. RESULTS: Propensity score matching yielded 103 pairs of running technique and interrupted technique patients for analysis. Within the propensity score-matched cohort, there were no differences in sustained complete heart block and need for pacemaker, 4 (3.8%) for running technique vs 3 (2.9%) for interrupted technique (p = 0.307). At 4 weeks, there was no difference in mean prosthetic aortic valve gradients calculated on transthoracic echocardiogram (6.39 ± 2.47 mmHg vs 6.46 ± 2.86, p = 0.850). There was no difference in paravalvular leak (0 (0%) vs 2 (1.9%), p = 0.070). CONCLUSIONS: Surgical implantation of a prosthetic aortic valve may be performed with a running suture technique without any significant increase in risk of heart block, need for permanent pacemaker or paravalvular leak. Long-term data will be critical to evaluate any development of paravalvular leaks in the future.

Distal Extent of Surgery for Acute Type A Aortic Dissection.

Acute type A aortic dissection (TAAD) is a complex disease associated with extremely high morbidity and mortality for which we advocate a coordinated, protocol-driven system of care delivery that begins at patient diagnosis and continues throughout and beyond aortic reconstruction. Essential components of TAAD repair include prompt restoration of true lumen blood flow with obliteration of the false lumen flow, resection of the primary tear sites, restoration of valvular competency, and elimination of any organ malperfusion. This article focuses specifically on extent of repair of the aortic arch and explains our protocols regarding cannulation location and technique, cerebral and distal organ protection strategy, management of the brachiocephalic vessels, and extent of distal aortic reconstruction. We describe an operative strategy for TAAD repair that includes (1) continuous neurocerebral monitoring in all cases, (2) uninterrupted antegrade and/or retrograde cerebral perfusion (depending upon extent of arch repair) during open arch reconstruction, (3) aortic arch replacement technique with or without brachiocephalic vessel replacement using a custom trifurcate graft, and (4) descending aortic stabilization with or without the use of an elephant or frozen elephant trunk (distal stent graft). Our protocol for extent of aortic arch and brachiocephalic reconstruction has been standardized and is predicated on distinct pathoanatomic findings and/or cerebral malperfusion that are outlined.

Clinical Outcomes and Modes of Death in Timothy Syndrome: A Multicenter International Study of a Rare Disorder.

OBJECTIVES: The objective of this study was to evaluate contemporary clinical outcomes and identify triggers for arrhythmias or sudden death in an international cohort of Timothy Syndrome (TS) patients including those with novel TS-associated CACNA1C mutations. BACKGROUND: TS is an extremely rare genetic disorder of the L-type cardiac channel Cav1.2 encoded by CACNA1C. The syndrome is characterized by multisystem abnormalities consisting of QT prolongation, congenital heart defects, syndactyly, facial dysmorphism, and neurological symptoms. METHODS: Patients diagnosed with TS between January 1, 1994, and April 1, 2016, from 12 international tertiary care pediatric centers were included in this retrospective study. Data were gathered via survey from the patients' electrophysiologists. RESULTS: Seventeen patients diagnosed with TS were identified. Length of follow-up was 4.9 years (range 3.0 to 19.0 years). Mean QTc was 640 ms (range 500 to 976 ms). All patients were treated with beta-blockers; 13 patients (76%) were also treated with an implantable defibrillator. Eleven patients experienced an episode of aborted cardiac arrest, 6 associated with general anesthesia and 2 with hypoglycemia. Four patients died suddenly due to ventricular fibrillation, 2 of whom had associated hypoglycemia. CONCLUSIONS: This study shows that mortality in TS patients is due to multifactorial mechanisms, which include ventricular arrhythmias, pulseless electrical activity, and hypoglycemia. A simple nomenclature for ongoing studies of TS and related syndromes is described. A worldwide prospective registry is needed for continued exploration of this syndrome.

Supraphysiologic control over HIV-1 replication mediated by CD8 T cells expressing a re-engineered CD4-based chimeric antigen receptor.

HIV is adept at avoiding naturally generated T cell responses; therefore, there is a need to develop HIV-specific T cells with greater potency for use in HIV cure strategies. Starting with a CD4-based chimeric antigen receptor (CAR) that was previously used without toxicity in clinical trials, we optimized the vector backbone, promoter, HIV targeting moiety, and transmembrane and signaling domains to determine which components augmented the ability of T cells to control HIV replication. This re-engineered CAR was at least 50-fold more potent in vitro at controlling HIV replication than the original CD4 CAR, or a TCR-based approach, and substantially better than broadly neutralizing antibody-based CARs. A humanized mouse model of HIV infection demonstrated that T cells expressing optimized CARs were superior at expanding in response to antigen, protecting CD4 T cells from infection, and reducing viral loads compared to T cells expressing the original, clinical trial CAR. Moreover, in a humanized mouse model of HIV treatment, CD4 CAR T cells containing the 4-1BB costimulatory domain controlled HIV spread after ART removal better than analogous CAR T cells containing the CD28 costimulatory domain. Together, these data indicate that potent HIV-specific T cells can be generated using improved CAR design and that CAR T cells could be important components of an HIV cure strategy.

Maternal mosaicism confounds the neonatal diagnosis of type 1 Timothy syndrome.

The presence of 2 distinct populations of somatic or germline cells within a single individual harboring different genotypes is termed mosaicism. Recent reports suggest that parental mosaicism is involved in the heritability of type 1 Timothy syndrome (TS1), an extremely rare and life-threatening multisystem disorder characterized by severe QT interval prolongation, syndactyly, and several other complications. Although full TS1 is caused by a single missense mutation in the CACNA1C-encoded cardiac calcium channel, mosaic TS1 parents can display isolated syndactyly without additional phenotypic manifestations. A newborn boy presented with syndactyly at birth. The presence of syndactyly in his mother led to a diagnosis of benign familial syndactyly. However, at 9 months of age, during his first syndactyly-corrective surgery, intraoperative electrocardiograms revealed extreme QT prolongation and 2:1 atrioventricular block. A comprehensive cardiac evaluation was performed, and both mother and child were tested genetically, confirming a clinical suspicion of TS1. Only the patient tested positive for the TS1 mutation; however, more extensive molecular testing revealed a limited presence of the mutation in maternally-derived DNA. This case illustrates the potential of parental mosaicism to confound the diagnosis of potentially life-threatening genetic diseases, such as TS1. Here, a mother with a partial TS1 phenotype and genetically confirmed mosaicism transmitted the TS1-causative mutation to her son, resulting in fully expressive TS1. Thus, a shared partial phenotype should not be dismissed as a benign or insignificant finding, but should be evaluated further to rule out the possibility of parental mosaicism concealing a potentially fatal heritable disease.