Morbidity and Mortality of Heterotopic Partial Heart Transplantation in Rodent Models.

Unrepairable congenital heart valve disease is an unsolved problem in pediatric cardiac surgery because there are no growing heart valve implants. Partial heart transplantation is a new type of transplant that aims to solve this problem. In order to study the unique transplant biology of partial heart transplantation, animal models are necessary. This study aimed to assess the morbidity and mortality of heterotopic partial heart transplantation in rodent models. This study assessed two models. The first model involved transplanting heart valves from donor animals into the abdominal aortic position in the recipient animals. The second model involved transplanting heart valve leaflets into the renal subcapsular position of the recipient animals. A total of 33 animals underwent heterotopic partial heart transplantation in the abdominal aortic position. The results of this model found a 60.61% (n = 20/33) intraoperative mortality rate and a 39.39% (n = 13/33) perioperative mortality rate. Intraoperative mortality was due to vascular complications from the procedure, and perioperative mortality was due to graft thrombosis. A total of 33 animals underwent heterotopic partial heart transplantation in the renal subcapsular position. The results of this model found a 3.03% (n = 1/33) intraoperative mortality rate, and the remaining 96.97% survived (n = 32/33). We conclude that the renal subcapsular model has a lower mortality rate and is technically more accessible than the abdominal aortic model. While the heterotopic transplantation of valves into the abdominal aortic position had significant morbidity and mortality in the rodent model, the renal subcapsular model provided evidence for successful heterotopic transplantation.

Characterization of Green Fluorescent Protein in Heart Valves of a Transgenic Swine Model for Partial Heart Transplant Research.

A transgenic strain of pigs was created to express green fluorescent protein (GFP) ubiquitously using a pCAGG promoter. Here, we characterize GFP expression in the semilunar valves and great arteries of GFP-transgenic (GFP-Tg) pigs. Immunofluorescence was performed to visualize and quantify GFP expression and colocalization with nuclear staining. GFP expression was confirmed in both the semilunar valves and great arteries of GFP-Tg pigs compared to wild-type tissues (aorta, p = 0.0002; pulmonary artery, p = 0.0005; aortic valve; and pulmonic valve, p < 0.0001). The quantification of GFP expression in cardiac tissue allows this strain of GFP-Tg pigs to be used for future research in partial heart transplantation.

Cannabidiol Reduces Nicotine Withdrawal Severity and State Anxiety During an Acute E-cigarette Abstinence Period: A Novel, Open-Label Study.

Introduction: Despite efforts to curb nicotine use, 8.1 million adults in the United States use e-cigarettes. Notably, the majority of nicotine-containing e-cigarette users report wanting to quit in the near future, yet there is a dearth of research surrounding intervention efforts. Cannabidiol (CBD) has potential to facilitate e-cigarette quit attempts by decreasing withdrawal symptom intensity and anxiety during nicotine e-cigarette abstinence. Methods: This study employed an open-label, crossover design (n=20) to test the hypothesis that among daily nicotine-containing e-cigarette users, oral administration of 320 mg CBD would reduce self-reported nicotine withdrawal severity and state anxiety following a 4-h e-cigarette abstinence period compared to withdrawal and anxiety reported after abstinence in the absence of CBD. Results: After controlling for participants' positive CBD expectancies, results were consistent with hypotheses, suggesting CBD reduced both nicotine withdrawal symptom severity and state anxiety during e-cigarette abstinence. Conclusion: These preliminary findings suggest testing the impact of CBD on e-cigarette cessation attempts is warranted.

Outcomes of Over 1000 Heart Transplants Using Hepatitis C-Positive Donors in the Modern Era.

BACKGROUND: Advances in hepatitis C virus (HCV) treatment and the ongoing opioid epidemic have made HCV-positive donors increasingly available for heart transplantation (HT). This analysis reports outcomes of over 1000 HCV-positive HTs in the United States in the modern era. METHODS: The United Network of Organ Sharing registry was used to identify HTs between 2015 and 2021. Recipients were grouped by donor HCV status and by nucleic acid amplification test (NAT) positivity. The primary outcome was 1-year mortality, and secondary outcomes included 3-year mortality. A subanalysis compared HCV-positive HT outcomes between NAT-positive and NAT-negative donors. Risk adjustment was performed using Cox regression. Kaplan-Meier analysis was used to estimate survival. RESULTS: The frequency of HCV-positive HT increased from 0.12% of HTs in 2015 to 12.9% in 2021 (P < .001). Of 16,648 HTs, 1170 (7.0%) used an organ from an HCV-positive donor. Recipients of HCV-positive organs were more likely to be HCV seropositive, older, and White. Unadjusted 1- and 3-year survival rates were not significantly different between recipients of HCV-negative and HCV-positive organs. After risk adjustment HCV-positive donor status was not associated with an elevated risk for 1-year (hazard ratio, 0.92; 95% CI, 0.71-1.19; P = .518) or 3-year mortality. Among HCV-positive HTs 772 (61.7%) were NAT positive. After risk adjustment NAT positivity did not impact 1-year mortality. CONCLUSIONS: The proportion of HCV-positive HTs has increased over 100-fold in recent years. This analysis of the US experience demonstrates that recipients of HCV-positive hearts, including those that are NAT positive, have acceptable outcomes with similar early to midterm survival as recipients of HCV-negative organs.

Waitlist and transplant outcomes for patients bridged to heart transplantation with Impella 5.0 and 5.5 devices.

BACKGROUND: Impella devices are increasingly utilized as a bridge to heart transplantation (BTT) and are now prioritized as Status 2 under the current heart allocation policy. This study evaluated waitlist and post-transplant outcomes of patients supported with Impella 5.0/5.5 devices. METHODS: The United Network of Organ Sharing registry was used to identify adults waitlisted or transplanted with Impella 5.0 or 5.5 devices from 2010 to 2021. Separate analyses were performed for waitlist and transplantation outcomes for patients supported by Impella 5.0/5.5 devices. Competing outcomes for the waitlist analysis included rates of transplantation, recovery, and death or clinical deterioration. Among patients undergoing transplantation, the primary outcome was 1-year survival. Secondary outcomes included rates of rejection, new postoperative dialysis, stroke, and pacemaker implantation after transplantation. RESULTS: There were 344 patients waitlisted and 394 patients transplanted with an Impella 5.0 (n = 212 and 251) or 5.5 (n = 132 and 143) device. Competing risk regression demonstrated similar likelihood of transplant (subhazard ratio [SHR], 1.33 (0.98-1.81, p = 0.067)) and similar likelihood of death or clinical deterioration (SHR, 0.67 [0.27-1.69, p = 0.400]) for Impella 5.5 patients. In the transplanted cohort, unadjusted 1-year post-transplant survival was comparable at 91.3% versus 94.6% (log-rank p = 0.661) for patients supported by Impella 5.0 or 5.5 device, respectively, a finding that persisted after risk-adjustment (HR 1.22, p = 0.699). Post-transplant complication rates were also comparable between 5.0 and 5.5 patients. CONCLUSIONS: Impella devices can be used as a BTT with excellent survival and minimal post-transplant morbidity. Outcomes were comparable for Impella 5.0 and 5.5 devices.

A review of animal models for post-operative pericardial adhesions.

Post-operative pericardial adhesions remain a serious complication after cardiac surgery that can lead to increased morbidity and mortality. Fibrous adhesions can destroy tissue planes leading to injury of surrounding vasculature, lengthening of operation time, and increased healthcare costs. While animal models are necessary for studying the formation and prevention of post-operative pericardial adhesions, a standardized animal model for inducing post-operative pericardial adhesions has not yet been established. In order to address this barrier to progress, an analysis of the literature on animal models for post-operative pericardial adhesions was performed. The animal model, method used to induce adhesions, and the time to allow development of adhesions were analyzed. Our analysis found that introduction of autologous blood into the pericardial cavity in addition to physical abrasion of the epicardium caused more severe adhesion formation in comparison to abrasion alone or abrasion with desiccation (vs. abrasion alone p = 0.0002; vs. abrasion and desiccation p = 0.0184). The most common time frame allowed for adhesion formation was 2 weeks, with the shortest time being 10 days and the longest being 12 months. Finally, we found that the difference in adhesion severity in all animal species was similar, suggesting the major determinants for the choice of model are animal size, animal cost, and the availability of research tools in the particular model. This survey of the literature provides a rational guide for researchers to select the appropriate adhesion induction modality, animal model, and time allowed for the development of adhesions.

Palliative Repair of a Mycotic Aortic Arch Pseudoaneurysm With a Physician-Modified Endograft and In-Situ Laser Fenestration.

PURPOSE: Open aortic arch repair is the gold standard in the treatment of diseases involving the ascending aorta and aortic arch. However, due to the invasive nature of open repair, high-risk patients with multiple comorbidities are often not suitable candidates for open surgical repair. While endovascular aortic repair is far less invasive, endovascular arch repair remains a difficult challenge due to the aortic arch diameter and angulation, origin of the supra-aortic arteries, and the lack of commercially available thoracic branched devices in the United States. CASE REPORT: Here we describe palliation of a mycotic aortic arch pseudoaneurysm with a physician-modified endograft and in situ laser fenestration. Our technique allowed for rapid repair of the pseudoaneurysm with minimal physiologic disturbances and no perioperative complications in a high-risk surgical patient. CONCLUSION: Physician-modified endografts are feasible and may be an effective treatment option for palliation of acute aortic arch lesions in high-risk surgical patients.

Adhesion barriers in cardiac surgery: A systematic review of efficacy.

BACKGROUND: Postoperative pericardial adhesions have been associated with increased morbidity, mortality, and surgical difficulty. Barriers exist to limit adhesion formation, yet little is known about their use in cardiac surgery. The study presented here provides the first major systematic review of adhesion barriers in cardiac surgery. METHODS: Scopus and PubMed were assessed on November 20, 2020. Inclusion criteria were clinical studies on human subjects, and exclusion criteria were studies not published in English and case reports. Risk of bias was evaluated with the Cochrane Risk of Bias Tool. Barrier efficacy data was assessed with Excel and GraphPad Prism 5. RESULTS: Twenty-five studies were identified with a total of 13 barriers and 2928 patients. Polytetrafluoroethylene (PTFE) was the most frequently evaluated barrier (13 studies, 67% of patients) with adhesion formation rate of 37.31% and standardized tenacity score of 26.50. Several barriers had improved efficacy. In particular, Cova CARD had a standardized tenacity score of 15.00. CONCLUSIONS: Overall, the data varied considerably in terms of study design and reporting bias. The amount of data was also limited for the non-PTFE studies. PTFE has historically been effective in preventing adhesions. More recent barriers may be superior, yet the current data is nonconfirmatory. No ideal adhesion barrier currently exists, and future barriers must focus on the requirements unique to operating in and around the heart.

A Simplified Model for Heterotopic Heart Valve Transplantation in Rodents.

There is an urgent clinical need for heart valve replacements that can grow in children. Heart valve transplantation is proposed as a new type of transplant with the potential to deliver durable heart valves capable of somatic growth with no requirement for anticoagulation. However, the immunobiology of heart valve transplants remains unexplored, highlighting the need for animal models to study this new type of transplant. Previous rat models for heterotopic aortic valve transplantation into the abdominal aorta have been described, though they are technically challenging and costly. For addressing this challenge, a renal subcapsular transplant model was developed in rodents as a practical and more straightforward method for studying heart valve transplant immunobiology. In this model, a single aortic valve leaflet is harvested and inserted into the renal subcapsular space. The kidney is easily accessible, and the transplanted tissue is securely contained in a subcapsular space that is well vascularized and can accommodate a variety of tissue sizes. Furthermore, because a single rat can provide three donor aortic leaflets and a single kidney can provide multiple sites for transplanted tissue, fewer rats are required for a given study. Here, the transplantation technique is described, providing a significant step forward in studying the transplant immunology of heart valve transplantation.

Behavioral Assessment of the Negative Emotion Aspect of Distress Tolerance: Tolerance to Emotional Images.

The current behavioral tasks assessing distress tolerance measure tolerance to frustration and tolerance to physical discomfort, but do not explicitly assess tolerance to negative emotion. We closely evaluated the conceptual distinctions between current behavioral tasks and self-report tasks assessing distress tolerance, and then developed a new behavioral distress tolerance task called the Emotional Image Tolerance (EIT) task. The EIT task retains elements of existing behavioral tasks (e.g., indices of persistence) while augmenting the reliability and content sufficiency of existing measures by including multiple trials, including a variety of negative affect stimuli, and separating overall task persistence from task persistence after onset of distress. In a series of three studies, we found that the EIT correlated with extant behavioral measures of distress tolerance, the computerized mirror-tracing task and a physical cold pressor task. Across all of the studies, we also evaluated whether the EIT correlated with self-report measures of distress tolerance and measures of psychopathology (e.g., depression, anxiety, and binge eating). Implications for the refinement of the distress tolerance construct are discussed.

The dynamics of persisting through distress: Development of a Momentary Distress Intolerance Scale using ecological momentary assessment.

Distress tolerance, or the ability to withstand uncomfortable states, is thought to be a transdiagnostic risk factor for psychopathology. Distress tolerance is typically measured using self-report questionnaires or behavioral tasks, both of which construe distress tolerance as a trait and downplay the potential variability in distress tolerance across time and situation. The aim of the current study was to provide a method for assessing momentary distress tolerance using ecological momentary assessment to capture both within- and between-individual information. Participants (n = 86) responded to random prompts on their cell phones seven times per day for one week, which included 10 momentary distress tolerance items as well as momentary emotion. After examining item distributions and interclass correlations, we conducted a multilevel exploratory factor analysis using both within-individual and between-individual data to arrive at a brief, 3-item measure we call the Momentary Distress Intolerance Scale. Model fit and reliability indices were good for both within- and between-individual approaches. We found that distress tolerance varied significantly over time, and that average momentary distress intolerance and instability in momentary distress intolerance were associated with trait distress tolerance, emotion dysregulation and tendencies to use experiential avoidance. Neither average momentary distress intolerance nor instability in momentary distress intolerance correlated with behavioral distress tolerance tasks. We discuss the importance of construing distress tolerance from a dynamic perspective and provide recommendations toward future research. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Is the first cut really the deepest? Frequency and recency of nonsuicidal self-injury in relation to psychopathology and dysregulation.

Research on nonsuicidal self-injury (NSSI) has moved beyond examination of factors that associate with the mere presence or absence of the behavior, and into more nuanced examination of which discrete features of NSSI behavior relate to pathology. This study examined two features of NSSI, frequency of occurrence and recency, as cross-sectional predictors of psychopathology in a large community sample of adults with a history of NSSI (N = 315). Results of 2 × 2 factorial ANOVAs testing the interactive effects of NSSI frequency (clinical, subclinical) and recency (current, past) revealed that current NSSI was consistently associated with poorer emotional and behavioral health (e.g., greater symptoms of depression, panic, and anxiety, worse emotion regulation, greater alcohol misuse). Results for NSSI frequency were more variable, though preliminary evidence suggested significant interactions of current NSSI and clinical frequency on emotion dysregulation, general anxiety, and panic. Possible clinical and empirical implications of the NSSI disorder frequency criteria proposed in DSM-5 are discussed.