Pig-to-human heart xenotransplantation in two recently deceased human recipients.

Genetically modified xenografts are one of the most promising solutions to the discrepancy between the numbers of available human organs for transplantation and potential recipients. To date, a porcine heart has been implanted into only one human recipient. Here, using 10-gene-edited pigs, we transplanted porcine hearts into two brain-dead human recipients and monitored xenograft function, hemodynamics and systemic responses over the course of 66 hours. Although both xenografts demonstrated excellent cardiac function immediately after transplantation and continued to function for the duration of the study, cardiac function declined postoperatively in one case, attributed to a size mismatch between the donor pig and the recipient. For both hearts, we confirmed transgene expression and found no evidence of cellular or antibody-mediated rejection, as assessed using histology, flow cytometry and a cytotoxic crossmatch assay. Moreover, we found no evidence of zoonotic transmission from the donor pigs to the human recipients. While substantial additional work will be needed to advance this technology to human trials, these results indicate that pig-to-human heart xenotransplantation can be performed successfully without hyperacute rejection or zoonosis.

Thoracoabdominal normothermic regional perfusion in donation after circulatory death does not restore brain blood flow.

Use of thoracoabdominal normothermic regional perfusion (TA-NRP) during donation after circulatory death (DCD) is an important advance in organ donation. Prior to establishing TA-NRP, the brachiocephalic, left carotid, and left subclavian arteries are ligated, thereby eliminating anterograde brain blood flow via the carotid and vertebral arteries. While theoretical concerns have been voiced that TA-NRP after DCD may restore brain blood flow via collaterals, there have been no studies to confirm or refute this possibility. We evaluated brain blood flow using intraoperative transcranial Doppler (TCD) in two DCD TA-NRP cases. Pre-extubation, anterior and posterior circulation brain blood flow waveforms were present in both cases, similar to the waveforms detected in a control patient on mechanical circulatory support undergoing cardiothoracic surgery. Following declaration of death and initiation of TA-NRP, no brain blood flow was detected in either case. Additionally, there was absence of brainstem reflexes, no response to noxious stimuli and no respiratory effort. These TCD results demonstrate that DCD with TA-NRP did not restore brain blood flow.

Donation after circulatory death heart transplantation using normothermic regional perfusion:The NYU Protocol.

Objective: This study aimed to evaluate the impact of cardiopulmonary bypass for thoraco-abdominal normothermic regional perfusion on the metabolic milieu of donation after cardiac death organ donors before transplantation. Methods: Local donation after cardiac death donor offers are assessed for suitability and willingness to participate. Withdrawal of life-sustaining therapy is performed in the operating room. After declaration of circulatory death and a 5-minute observation period, the cardiac team performs a median sternotomy, ligation of the aortic arch vessels, and initiation of thoraco-abdominal normothermic regional perfusion via central cardiopulmonary bypass at 37 °C. Three sodium chloride zero balance ultrafiltration bags containing 50 mEq sodium bicarbonate and 0.5 g calcium carbonate are infused. Arterial blood gas measurements are obtained every 15 minutes after every zero balance ultrafiltration bag is infused, and blood is transfused as needed to maintain hemoglobin greater than 8 mg/dL. Cardiopulmonary bypass is weaned with concurrent hemodynamic and transesophageal echocardiogram evaluation of the donor heart. The remainder of the procurement, including the abdominal organs, proceeds in a similar controlled fashion as is performed for a standard donation after brain death donor. Results: Between January 2020 and May 2022, 18 donation after cardiac death transplants using the thoraco-abdominal normothermic regional perfusion protocol were performed at our institution. The median donor age was 42.5 years (range, 20-51 years), and 88.9% (16/18) were male. The mean total donor cardiopulmonary bypass time was 88.8 ± 51.8 minutes. At the beginning of cardiopulmonary bypass, the average donor lactate was 9.4 ± 1.5 mmol/L compared with an average final lactate of 5.3 ± 2.7 mmol/L (P<.0001). The average beginning potassium was 6.5 ± 1.8 mmol/L compared with an average end potassium of 4.2 ± 0.4 mmol/L (P<.0001) . The average beginning hemoglobin was 6.8 ± 0.7 g/dL, and the average end hemoglobin was 8.2 ± 1.3 g/dL (P<.001) . On average, donation after cardiac death donors received transfusions of 2.3 ± 1.5 units of packed red blood cells. Of the 18 donors who underwent normothermic regional perfusion, all hearts were deemed suitable for recovery and successfully transplanted, a yield of 100%. Other organs successfully recovered and transplanted include kidneys (80.6% yield), livers (66.7% yield), and bilateral lungs (27.8% yield). Conclusions: The use of cardiopulmonary bypass for thoraco-abdominal normothermic regional perfusion is a burgeoning option for improving the quality of organs from donation after cardiac death donors. Meticulous intraoperative management of donation after cardiac death donors with a specific focus on improving their metabolic milieu may lead to improved graft function in transplant recipients.

Right heart thrombus in transit: Raising bar in the management of cardiac arrest.

Right heart thrombus represents medical emergency as it is associated with acute pulmonary embolism. Right heart thrombus can manifest acutely in a dramatic fashion as cardiac arrest. Bedside echocardiography is a key to rapid diagnosis and allow early intervention. We report a case of elderly female who was admitted to our hospital after a mechanical fall and found to have hip fracture. Despite an initial uncomplicated course, she experienced cardiopulmonary arrest with right heart clot in transit identified on transesophageal echocardiography (TEE). We highlight the utility of point-of-care ultrasound as well as use of TEE to establish cause of cardiopulmonary arrest.

Endobronchial mucormycosis: A rare clinical entity diagnosed by endobronchial cryobiopsy.

Mucormycosis is a rare fungal infection caused by fungi of the order Mucorales. The rhino-cerebral form of mucormycosis is most commonly seen in patients with diabetes mellitus, whereas pulmonary mucormycosis is a rare manifestation in patients with hematological malignancy and transplant recipients. We report a case of a 40-year-old male, with history of poorly controlled diabetes, who presented to the emergency room with a one-week history of hemoptysis. Computed Tomography (CT) of the chest was concerning for a lung mass or abscess. Flexible bronchoscopy revealed an endobronchial lesion that was biopsied with a cryoprobe. Histopathologic examination showed non-septate right-angle branching hyphae, typical of mucormycosis. He underwent surgical resection of the right middle and lower lobes and treatment with antimycotic agents with a complete recovery. This case highlights the importance of early histopathological diagnosis of pulmonary mucormycosis in preventing a fatal outcome.

Minimally Invasive Off-Pump Technique for Temporary Left Ventricular Support.

Use of short-term mechanical circulatory support (MCS) for cardiogenic shock has rapidly increased. Most common initial MCS strategies entail institution of peripheral extracorporeal membrane oxygenation (ECMO) or temporary ventricular assist devices. For patients with anatomically small peripheral arteries or insufficient circulatory support, sternotomy and central cannulation techniques may be necessary. These invasive approaches are associated with increased risk of bleeding and other significant complications. We describe a minimally invasive, off-pump technique to provide adequate hemodynamic support and left ventricular unloading, allowing early postoperative ambulation, and ability to easily provide additional right ventricular/ECMO support if needed.

Invasive Aortic Valve Endocarditis: Clinical and Tissue Findings From a Prospective Investigation.

BACKGROUND: Advanced aortic valve infective endocarditis (IE) with progression and destruction beyond the valve cusps-invasive IE-is incompletely characterized. This study aimed to characterize further the invasive disease extent, location, and stage and correlate macroscopic operative findings with microscopic disease patterns and progression. METHODS: A total of 43 patients with invasive aortic valve IE were prospectively enrolled from August 2017 to July 2018. Of these patients, 23 (53%) had prosthetic valve IE, 2 (5%) had allograft IE, and 18 (42%) had native aortic valve IE. Surgical findings and intraoperative photography were analyzed for invasion location, extent, and stage. Surgical samples were formalin fixed and analyzed histologically. The time course of disease and management were evaluated. RESULTS: Pathogens included Staphylococcus aureus in 17 patients (40%). Invasion predominantly affected the non-left coronary commissure (76%) and was circumferential in 15 patients (35%) (14 had prosthetic valves). Extraaortic cellulitis was present in 29 patients (67%), abscess in 13 (30%), abscess cavity in 29 (67%), and pseudoaneurysm in 8 (19%); 7 (16%) had fistulas. Histopathologic examination revealed acute inflammation, abscess formation, and lysis of connective tissue but not of myocardium or elastic tissue. Median time from onset of symptoms to antibiotics was 5 days, invasion confirmation 15 days, and surgery 37 days. Patients with S aureus had a 21-day shorter time course than patients non-S aureus. New or worsening heart block developed in 8 patients. CONCLUSIONS: Advanced invasive aortic valve IE demonstrates consistent gross patterns and stages correlating with histopathologic findings. Invasion results from a confluence of factors, including pathogen, time, and host immune response, and primarily affects the fibrous skeleton of the heart and expands to low-pressure regions.

Patterns of Hepatocellular Carcinoma After Direct Antiviral Agents and Pegylated-Interferon Therapy.

INTRODUCTION:  The impact of direct-acting antiviral agents (DAAs) on the development of hepatocellular carcinoma (HCC) is controversial and a part of the scientific community believes it as a biased interpretation of data. Many studies have reported an aggressive pattern of HCC after DAA use. In this study, we attempted to assess the changes in the pattern of HCC after treatment with DAAs or PI (PEG, pegylated-interferon). METHODS:  A total of 37 HCC patients after DAA treatment and 21 HCC patients after PI treatment were included. The diagnosis of HCC was made and information about demographics, HCC infiltrative pattern, portal vein thrombosis (PVT), time at initial presentation, Child-Turcotte-Pugh (CTP) score, and Barcelona Clinic Liver Cancer (BCLC) stage were compared in the two groups. RESULTS:  The total number of male patients in the DAA group was 62% while either gender was almost equal in PI. The age group of 40-60 was more prevalent in the DAA group while the PI group comprised more patients who were above 60 years. Patients in the DAA group presented after 3.35 years on average while patients in the PI group presented after about seven years. Most of the patients presented with the CTP stage of A. That is true for both groups. For BCLC staging, most of the patients had stage C, which means multiple lesions. At the initial presentation, most of the patients presented with multifocal lesions. CONCLUSION:  Our study found no significant difference in the initial presentation between both groups. However, HCC patients with prior DAA therapy presented early than those with PI therapy.

COVID-19 in recent heart transplant recipients: Clinicopathologic features and early outcomes.

BACKGROUND: The impact of COVID-19 on heart transplant (HTx) recipients remains unclear, particularly in the early post-transplant period. METHODS: We share novel insights from our experience in five HTx patients with COVID-19 (three within 2 months post-transplant) from our institution at the epicenter of the pandemic. RESULTS: All five exhibited moderate (requiring hospitalization, n = 3) or severe (requiring ICU and/or mechanical ventilation, n = 2) illness. Both cases with severe illness were transplanted approximately 6 weeks before presentation and acquired COVID-19 through community spread. All five patients were on immunosuppressive therapy with mycophenolate mofetil (MMF) and tacrolimus, and three that were transplanted within the prior 2 months were additionally on prednisone. The two cases with severe illness had profound lymphopenia with markedly elevated C-reactive protein, procalcitonin, and ferritin. All had bilateral ground-glass opacities on chest imaging. MMF was discontinued in all five, and both severe cases received convalescent plasma. All three recent transplants underwent routine endomyocardial biopsies, revealing mild (n = 1) or no acute cellular rejection (n = 2), and no visible viral particles on electron microscopy. Within 30 days of admission, the two cases with severe illness remain hospitalized but have clinically improved, while the other three have been discharged. CONCLUSIONS: COVID-19 appears to negatively impact outcomes early after heart transplantation.

Analgesic Use in Patients With Advanced Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Pain is common in patients with chronic kidney disease (CKD). Analgesics may be appropriate for some CKD patients. OBJECTIVES: To determine the prevalence of overall analgesic use and the use of different types of analgesics including acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), adjuvants, and opioids in patients with CKD. DESIGN: Systematic review and meta-analysis. SETTING: Interventional and observational studies presenting data from 2000 or later. Exclusion criteria included acute kidney injury or studies that limited the study population to a specific cause, symptom, and/or comorbidity. PATIENTS: Adults with stage 3-5 CKD including dialysis patients and those managed conservatively without dialysis. MEASUREMENTS: Data extracted included title, first author, design, country, year of data collection, publication year, mean age, stage of CKD, prevalence of analgesic use, and the types of analgesics prescribed. METHODS: Databases searched included MEDLINE, CINAHL, EMBASE, and Cochrane Library. Two reviewers independently screened all titles and abstracts, assessed potentially relevant articles, and extracted data. We estimated pooled prevalence of analgesic use and the I 2 statistic was computed to measure heterogeneity. Random-effects models were used to account for variations in study design and sample populations, and a double arcsine transformation of the prevalence variables was used to accommodate potential overweighting of studies with very large or very small prevalence measurements. Sensitivity analyses were performed to determine the magnitude of publication bias and assess possible sources of heterogeneity. RESULTS: Forty studies were included in the analysis. The prevalence of overall analgesic use in the random-effects model was 50.8%. The prevalence of acetaminophen, NSAIDs, and adjuvant use was 27.5%, 17.2%, and 23.4%, respectively, while the prevalence of opioid use was 23.8%. Due to the possibility of publication bias, the actual prevalence of acetaminophen use in patients with advanced CKD may be substantially lower than this meta-analysis indicates. A trim-and-fill analysis decreased the pooled prevalence estimate of acetaminophen use to 5.4%. The prevalence rate for opioid use was highly influenced by 2 large US studies. When these were removed, the estimated prevalence decreased to 17.3%. LIMITATIONS: There was a lack of detailed information regarding the analgesic regimen (such as specific analgesics used within each class and inconsistent accounting for patients on multiple drugs and the use of over-the-counter analgesics such as acetaminophen and NSAIDs), patient characteristics, type of pain being treated, and the outcomes of treatment. Data on adjuvant use were very limited. These results, therefore, must be interpreted with caution. CONCLUSIONS: There was tremendous variability in the prescribing patterns of both nonopioid and opioid analgesics within and between countries suggesting widespread uncertainty about the optimal pharmacological approach to treating pain. Further research that incorporates robust reporting of analgesic regimens and links prescribing patterns to clinical outcomes is needed to guide optimal clinical practice.

CONTEXTE: La douleur est fréquente chez les patients atteints d'insuffisance rénale chronique (IRC). La prise d'analgésiques peut être nécessaire chez certains patients atteints d'IRC. OBJECTIFS: Établir la prévalence globale de la prise d'analgésiques chez les patients atteints d'IRC puis de la consommation des différents types d'analgésiques (acétaminophène, anti-inflammatoires non stéroïdiens [AINS], adjuvants, opioïdes). TYPE D'ÉTUDE: Revue systématique et méta-analyse. CADRE: Les études observationnelles et interventionnelles présentant des données depuis l'an 2000. Ont été exclus les cas d'insuffisance rénale aigüe et les études portant sur une population, une cause, un symptôme ou une comorbidité en particulier. SUJETS: Des adultes atteints d'IRC de stade 3 à 5, incluant des patients dialysés et des patients non dialysés pris en charge de façon conservatrice. MESURES: Le titre de l'article, le nom de l'auteur principal, le type d'étude, le pays où s'est tenue l'étude, l'année de collection des données, l'année de publication, l'âge médian des sujets, le stade de l'IRC, la prévalence de la prise d'analgésiques et les types d'analgésiques prescrits. MÉTHODOLOGIE: Les données ont été colligées dans MEDLINE, CINAHL, EMBASE et la bibliothèque Cochrane. Deux examinateurs ont trié les titres et les abrégés, évalué les articles potentiellement pertinents et extrait les données de façon indépendante. La prévalence combinée de la prise d'analgésiques a été évaluée et la statistique I 2 a été calculée pour mesurer l'hétérogénéité. Des modèles à effets aléatoires ont été employés pour tenir compte des variations entre les différents types d'études et de populations échantillonnées. Les variables de prévalence ont subi une double transformation arc-sinus pour tenir compte d'une potentielle surpondération des études comportant des mesures de prévalence très importantes ou très faibles. Des analyses de sensibilité ont été effectuées pour mesurer l'ampleur des biais de publication et évaluer de possibles sources d'hétérogénéité. RÉSULTATS: L'analyse porte sur un total de 40 études. Dans les modèles à effets aléatoires, la prévalence globale de prise d'analgésiques était de 50,8 %. Quant à la prévalence selon le type d'analgésique elle s'établissait à 27,5 % pour l'acétaminophène, à 17,2 % pour les AINS, à 23,4 % pour les adjuvants et à 23,8 % pour les opioïdes. Chez les patients atteints d'IRC de stade avancé, de possibles de biais de publication font en sorte que la prévalence réelle de l'acétaminophène pourrait s'avérer nettement inférieure à ce qu'indique cette méta-analyse. Une analyse par la méthode « trim and fill ¼ a réduit à 5,4 % la prévalence groupée estimée pour la prise d'acétaminophène. Le taux de prévalence pour la prise d'opioïdes était fortement influencé par deux vastes études américaines; en les retirant de l'analyse, la prévalence estimée passait à 17,3 %. LIMITES: Ces résultats doivent être interprétés avec prudence puisque des informations détaillées manquaient sur le schéma posologique (analgésiques particuliers utilisés dans chaque classe, comptabilisation incohérente pour les patients prenant plusieurs médicaments, prise d'analgésiques en vente libre tels que l'acétaminophène et les AINS), les caractéristiques des patients, les types de douleurs traitées et les résultats des traitements. De plus, les données sur la prise d'adjuvants étaient très limitées. CONCLUSION: Une très grande variabilité a été observée dans les profils de prescription tant pour les analgésiques opioïdes que pour les non-opioïdes. Une variabilité qui s'observe aussi tant dans un même pays qu'entre les différents pays, ce qui suggère une incertitude généralisée quant à la meilleure approche pharmacologique dans le traitement de la douleur. D'autres recherches intégrant une description rigoureuse du schéma posologique et reliant les profils de prescription aux résultats cliniques sont nécessaires pour guider l'optimisation des pratiques cliniques.

Association of Surgical Treatment With Survival in Patients With Prosthetic Valve Endocarditis.

BACKGROUND: Prosthetic valve endocarditis (PVE) is a serious condition with high morbidity and mortality. This study investigated the association of surgical treatment with survival among patients with PVE. METHODS: A retrospective cohort study was done of patients with PVE hospitalized over 8 years in a large referral center. Association of surgery with survival was evaluated with multivariable Cox proportional hazards regression, adjusting for propensity to be accepted for surgery, and analyzing surgery as a time-dependent covariate. Survival was also compared separately in a 1:1 propensity score-matched cohort of patients accepted for surgery and control patients consigned to nonsurgical treatment. RESULTS: Of 523 patients (mean [SD] age, 61 [14] years; 370 [71%] men; 393 [75%] initially accepted for surgery), 404 ultimately underwent surgery and 119 received nonsurgical treatment alone. Surgical treatment was associated with significantly lower hazard of death in the entire cohort (hazard ratio [HR] = 0.32; 95% confidence interval [CI]: 0.22-0.48; P < .001) and in the 1:1 matched cohort (HR = 0.33; 95% CI: 0.19-0.57; P < .001). Initial acceptance for surgery was associated with significantly lower odds of in-hospital death (odds ratio [OR] = 0.26; 95% CI: 0.11-0.59; P < .001), death or readmission within 90 days (OR = 0.17; 95% CI: 0.07-0.43; P < .001), and death within 1 year (OR = 0.16; 95% CI: 0.08-0.34; P < .001). CONCLUSIONS: Surgical treatment is associated with a large survival benefit in PVE. A decision to pursue nonsurgical treatment in PVE should entail close follow-up for any development of an indication for surgery.

Current AATS guidelines on surgical treatment of infective endocarditis.

The 2016 American Association for Thoracic Surgery (AATS) guidelines for surgical treatment of infective endocarditis (IE) are question based and address questions of specific relevance to cardiac surgeons. Clinical scenarios in IE are often complex, requiring prompt diagnosis, early institution of antibiotics, and decision-making related to complications, including risk of embolism and timing of surgery when indicated. The importance of an early, multispecialty team approach to patients with IE is emphasized. Management issues are divided into groups of questions related to indications for and timing of surgery, pre-surgical work-up, preoperative antibiotic treatment, surgical risk assessment, intraoperative management, surgical management, surveillance, and follow up. Standard indications for surgery are severe heart failure, severe valve dysfunction, prosthetic valve infection, invasion beyond the valve leaflets, recurrent systemic embolization, large mobile vegetations, or persistent sepsis despite adequate antibiotic therapy for more than 5-7 days. The guidelines emphasize that once an indication for surgery is established, the operation should be performed as soon as possible. Timing of surgery in patients with strokes and neurologic deficits require close collaboration with neurological services. In surgery infected and necrotic tissue and foreign material is radically debrided and removed. Valve repair is performed whenever possible, particularly for the mitral and tricuspid valves. When simple valve replacement is required, choice of valve-mechanical or tissue prosthesis-should be based on normal criteria for valve replacement. For patients with invasive disease and destruction, reconstruction should depend on the involved valve, severity of destruction, and available options for cardiac reconstruction. For the aortic valve, use of allograft is still favored.

Surgical treatment of right-sided infective endocarditis.

OBJECTIVE: Right-sided infective endocarditis is increasing because of increasing prevalence of predisposing conditions, and the role and outcomes of surgery are unclear. We therefore investigated the surgical outcomes for right-sided infective endocarditis. METHODS: From January 2002 to January 2015, 134 adults underwent surgery for right-sided infective endocarditis. Patients were grouped according to predisposing condition. Hospital outcomes, time-related death, and reoperation for infective endocarditis were analyzed. RESULTS: A total of 127 patients (95%) had tricuspid valve and 7 patients (5%) pulmonary valve infective endocarditis; 66 patients (49%) had isolated right-sided infective endocarditis, and 68 patients (51%) had right- and left-sided infective endocarditis. Predisposing conditions included injection drug use (30%), cardiac implantable devices (26%), chronic vascular access (19%), and other/none (25%). One native tricuspid valve was excised, 76% were repaired or reconstructed, and 23% were replaced. Intensive care unit and postoperative hospital stays were similar among groups. Injection drug users had the best early survival (no hospital mortality), and patients with chronic vascular access had the worst late survival (18% at 5 years). Survival was worst for concomitant mitral valve versus isolated right-sided infective endocarditis or concomitant aortic valve infective endocarditis. Survival after tricuspid valve replacement was worse than after repair/reconstruction. Estimated glomerular filtration rate was the strongest risk factor for death, not predisposing condition. Eleven patients underwent 12 reoperations for infective endocarditis; more reoperations occurred in injection drug users (P = .03). CONCLUSIONS: Overall outcomes after surgery are variable and affected by patient condition, not predisposing condition. Injection drug use carries a higher risk of reoperation for infective endocarditis. Earlier surgery may permit more valve repairs and improve outcomes. Whenever possible, tricuspid valve replacement should be avoided.

Early and mid-term results of autograft rescue by Ross reversal: A one-valve disease need not become a two-valve disease.

OBJECTIVES: Risk of reoperation and loss of a second native valve are major drawbacks of the Ross operation. Rather than discarding the failed autograft, it can be placed back into the native pulmonary position by "Ross reversal." We review our early and mid-term results with this operation. METHODS: From 2006 to 2017, 39 patients underwent reoperation for autograft dysfunction. The autograft was successfully rescued in 35 patients: by Ross reversal in 30, David procedure in 4, and autograft repair in 1. Medical records were reviewed for patient characteristics (mean age was 46 ± 13 years, range 18-67 years, and 23 were male), previous operations, indications for reoperation, hospital outcomes, and echocardiographic findings for the 30 patients undergoing successful Ross reversal. Follow-up was 4.1 ± 3.5 years (range 7 months-11 years). RESULTS: Median interval between the original Ross procedure and Ross reversal was 12 years (range 5-19 years). Eight patients also had absolute indications for replacement of the pulmonary allograft. There was no operative mortality. One patient required reoperation for bleeding. Another had an abdominal aorta injury from use of an endoballoon clamp. There was no other major postoperative morbidity, and median postoperative hospital stay was 7.2 days (range 4-41 days). No patient required reoperation during follow-up. Twenty-four patients had acceptable pulmonary valve function, and 6 had clinically well-tolerated moderate or severe pulmonary regurgitation. CONCLUSIONS: Ross reversal can be performed with low morbidity and acceptable pulmonary valve function, reducing patient risk of losing 2 native valves when the autograft fails in the aortic position.