A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23-4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 (p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1, identifier 20210641.

Difference between SARS-CoV-2, seasonal coronavirus, influenza, and respiratory syncytial virus infection in solid organ transplant recipients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been raging since the end of 2019 and has shown worse outcomes in solid organ transplant (SOT) recipients. The clinical differences as well as outcomes between respiratory viruses have not been well defined in this population. METHODS: This is a retrospective cohort study of adult SOT recipients with nasopharyngeal swab or bronchoalveolar lavage PCR positive for either SARS-CoV-2, seasonal coronavirus, respiratory syncytial virus (RSV) or influenza virus from January 2017 to October 2020. The follow up period was 3 months. Clinical characteristics and outcomes were evaluated. RESULTS: A total of 377 recipients including 157 SARS-CoV-2, 70 seasonal coronavirus, 50 RSV and 100 influenza infections were identified. The most common transplanted organ was kidney 224/377 (59.4%). Lower respiratory tract infection (LRTI) was found in 210/377 (55.7%) and the risk factors identified with multivariable analysis were SARS-CoV-2 infection, steroid use, and older age. Co- and secondary infections were seen in 77/377 (20.4%) recipients with bacterial pathogens as dominant. Hospital admission was seen in 266/377 (67.7%) recipients without significant statistical difference among viruses, however, ICU admission, mechanical ventilation and mortality were higher with SARS-CoV-2 infection. In the multivariable model, the risk factors for mortality were SARS-CoV-2 infection and older age. CONCLUSIONS: We found higher incidence of ICU admission, mechanical ventilation, and mortality among SARS-CoV-2 infected recipients. Older age was found to be the risk factor for lower respiratory tract infection and mortality for SARS-CoV-2, coronaviruses, RSV and influenza virus groups.

How Would We Treat Our Own Heart Transplantation Surgery: A Perioperative Look.

Heart failure is a disease affecting 6.2 million adults in the United States, resulting in morbidity and mortality in the short and long terms. Although options such as mechanical circulatory support and transplantation are considered a solution when medical management is insufficient, heart transplantation (HTX) is regarded as the better option, with a lower incidence of multiorgan failure. A limiting step for HTX is the inadequate donor pool, so options like donation after circulatory death and xenotransplantation have emerged as alternatives. The cardiac anesthesiologist plays a pivotal role in the perioperative management of donors and recipients. A full understanding of the nature of the disease, pathophysiology, and perioperative management is paramount to the success of an HTX program. The authors include an index case to illustrate the multidisciplinary approach to the disease and the implications of managing these complex patients presenting to the operating room.

Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure: The ARIES-HM3 Randomized Clinical Trial.

IMPORTANCE: Left ventricular assist devices (LVADs) enhance quality and duration of life in advanced heart failure. The burden of nonsurgical bleeding events is a leading morbidity. Aspirin as an antiplatelet agent is mandated along with vitamin K antagonists (VKAs) with continuous-flow LVADs without conclusive evidence of efficacy and safety. OBJECTIVE: To determine whether excluding aspirin as part of the antithrombotic regimen with a fully magnetically levitated LVAD is safe and decreases bleeding. DESIGN, SETTING, and PARTICIPANTS: This international, randomized, double-blind, placebo-controlled study of aspirin (100 mg/d) vs placebo with VKA therapy in patients with advanced heart failure with an LVAD was conducted across 51 centers with expertise in treating patients with advanced heart failure across 9 countries. The randomized population included 628 patients with advanced heart failure implanted with a fully magnetically levitated LVAD (314 in the placebo group and 314 in the aspirin group), of whom 296 patients in the placebo group and 293 in the aspirin group were in the primary analysis population, which informed the primary end point analysis. The study enrolled patients from July 2020 to September 2022; median follow-up was 14 months. Intervention: Patients were randomized in a 1:1 ratio to receive aspirin (100 mg/d) or placebo in addition to an antithrombotic regimen. MAIN OUTCOMES AND MEASURES: The composite primary end point, assessed for noninferiority (-10% margin) of placebo, was survival free of a major nonsurgical (>14 days after implant) hemocompatibility-related adverse events (including stroke, pump thrombosis, major bleeding, or arterial peripheral thromboembolism) at 12 months. The principal secondary end point was nonsurgical bleeding events. RESULTS: Of the 589 analyzed patients, 77% were men; one-third were Black and 61% were White. More patients were alive and free of hemocompatibility events at 12 months in the placebo group (74%) vs those taking aspirin (68%). Noninferiority of placebo was demonstrated (absolute between-group difference, 6.0% improvement in event-free survival with placebo [lower 1-sided 97.5% CI, -1.6%]; P < .001). Aspirin avoidance was associated with reduced nonsurgical bleeding events (relative risk, 0.66 [95% confidence limit, 0.51-0.85]; P = .002) with no increase in stroke or other thromboembolic events, a finding consistent among diverse subgroups of patient characteristics. CONCLUSIONS AND RELEVANCE: In patients with advanced heart failure treated with a fully magnetically levitated LVAD, avoidance of aspirin as part of an antithrombotic regimen, which includes VKA, is not inferior to a regimen containing aspirin, does not increase thromboembolism risk, and is associated with a reduction in bleeding events. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04069156.

Is the Omicron variant truly less virulent in solid organ transplant recipients?

Solid organ transplant (SOT) recipients are at high risk for severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Emerging variants of concern have disproportionately affected this population. Data on severity and outcomes with the Omicron variant in SOT recipients are limited. Thus we conducted this single-center, retrospective cohort study of SOT recipients diagnosed with SARS-CoV-2 infection from December 18, 2021 to January 18, 2022, when prevalence of the Omicron variant was more than 80%-95% in the community. Univariate and multivariate logistic regression analysis was performed to identify risk factors for hospital admission. We identified 166 SOT patients: 112 (67.5%) kidney, 22 (13.3%) liver, 10 (6.0%) lung, seven (4.2%) heart, and 15 (9.0%) combined transplants. SARS-CoV-2 vaccine series was completed in 59 (35.5%) recipients. Ninety-nine (59.6%) and 13 (7.8%) recipients received casirivimab/imdevimab and sotrovimab, respectively. Fifty-three (32%) recipients required hospital admission, of which 19 (35.8%) required intensive care unit level of care. Median follow-up was 50 (interquartile range, 25-59) days, with mortality reported in six (3.6%) patients. Risk factors identified for hospital admission were African American race (p < .001, odds ratio [OR] 4.00, 95% confidence interval [CI] 1.84-8.70), history of coronary artery disease (p = .031, OR 3.50, 95% CI 1.12-10.87), and maintenance immunosuppression with corticosteroids (p = .048, OR 2.00, 95% CI 1.01-4.00). In conclusion, contrary to that in the general population, we found a higher hospital admission rate in SOT recipients with omicron variant infection. Further studies to investigate the efficacy of newer treatments are necessary, even as outcomes continue to improve.

Malignancy: An Adverse Effect of Immunosuppression.

Benefits of solid organ transplantation in end stage organ diseases are indisputable. Malignancy is a feared complication of solid organ transplantation and is a leading cause of mortality in patients with organ transplantation. Iatrogenic immunosuppression to prevent graft rejection plays a crucial role in the cancer development in solid organ transplant recipients. Chronic exposure to immunosuppression increases the malignancy burden through deregulation of host immune defense mechanisms and unchecked proliferation of oncogenic viruses and malignancies associated with these viruses. Vigorous screening of candidates undergoing transplant evaluation for malignancies, careful assessment of donors, and vigilant monitoring of transplant recipients are necessary to prevent, detect, and manage this life-threatening complication.

Cefazolin plus ertapenem and heart transplantation as salvage therapy for refractory LVAD infection due to methicillin-susceptible Staphylococcus aureus: A case series.

The use of left ventricular assist devices (LVADs) is increasingly more common as the availability of donor organs in relation to failing hearts is outstandingly limited. Infections are the most common complications in LVAD recipients, particularly those caused by Staphylococcus spp. Refractory LVAD-related infections are not uncommon as achieving adequate source control is often not feasible before heart transplantation. Evidence suggest that cefazolin plus ertapenem is effective in refractory methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, but this approach has not been described in LVAD recipients. In this article, we report two cases of refractory MSSA bacteremia in LVAD recipients that were successfully treated with salvage therapy with cefazolin plus ertapenem and subsequent heart transplantation. This treatment strategy should be considered in patients with refractory LVAD-associated infection due to MSSA that are not responding to standard treatment.

Successful venoplasty of superior vena cava stenosis in a patient with a total artificial heart after orthotopic heart transplantation due to primary graft failure.

BACKGROUND: With the limited number of available suitable donor hearts resulting in plateaued numbers of heart transplantations, short- and long-term mechanical circulatory support devices, including the implantation of total artificial hearts (TAHs) are modalities that are increasingly being used as treatment options for patients with end-stage heart failure. The superior vena cava syndrome has been described in this context in various disease processes. We report successful venoplasty for superior vena cava syndrome in a patient with a TAH. CASE PRESENTATION: A 65-year-old man with a history of nonischemic cardiomyopathy had received a left ventricular assist device, and then 2 years later, underwent orthotopic heart transplantation using the bicaval anastomosis technique. The postprocedural course was complicated by primary graft failure, resulting in the need for implantation of a TAH. About 5 months after TAH implantation, he started to develop complications such as volume retention, swelling of the upper extremities, and was diagnosed to have a superior vena cava syndrome. The patient underwent a successful venoplasty of his superior vena cava by interventional radiology with resolution of upper body edema, normalization of renal, and liver function. CONCLUSION: Potential fatal complications caused by catheter or wire entrapment in the right-sided mechanical valve of a TAH have been reported. We describe a safe method for the treatment of superior vena cava syndrome in patients with TAH.

Clinical Utility of Imaging Left Ventricular Assist Devices with 320 Row Multidetector Computed Tomography.

Evaluation of left ventricular devices is becoming increasingly important as the implantation of these devices increases. Cardiac computed tomography angiography (CCTA) has many potential advantages compared with plain radiographs and echocardiography to troubleshoot these devices and potentially help guide therapy. Heart failure (HF) remains a deadly, progressive disease with substantive and increasing morbidity, mortality, cost, and prevalence. Use of left ventricular assist devices (LVAD) as treatment for refractory HF has been steadily rising during the last decade. Seventy-four LVAD recipients who met an indication for CCTA were referred for scanning at our center for a total of 94 studies. All recipients had received a Heart Mate II (Thoratec, Pleasanton, CA) LVAD at a previous time. All patients underwent gated CCTA on a 320 row multidetector scanner (Aquilion ONE, Toshiba Medical Systems, Irvine, California, USA). Images were then reconstructed and analysis was performed using multiple oblique views. All 94 studies had technically good images. In survival analysis, 43 of the 74 LVAD patients had normal CCTA findings while 31 had abnormal CCTA results. The 6, 12, and 18 months survival was 93%, 79%, and 77% in those with normal results and 71%, 61%, and 61%, respectively, in the abnormal CCTA findings. Overall survival was statistically significant in when comparing the two groups (p = 0.003). Cardiac computed tomography angiography may be used as an aid for risk stratification and a potential indicator of short- and long-term prognosis in LVAD patients.

Managing Cardiovascular Risk in the Post Solid Organ Transplant Recipient.

Solid organ transplantation is an effective treatment for patients with end-stage organ disease. The prevalence of cardiovascular diseases (CVD) has increased in recipients. CVD remains a leading cause of mortality among recipients with functioning grafts. The pathophysiology of CVD recipients is a complex interplay between preexisting risk factors, metabolic sequelae of immunosuppressive agents, infection, and rejection. Risk modification must be weighed against the risk of mortality owing to rejection or infection. Aggressive risk stratification and modification before and after transplantation and tailoring immunosuppressive regimens are essential to prevent complications and improve short-term and long-term mortality and graft survival.

A Randomized, Controlled Pilot Study of the Effects of Acupuncture on Circulating Endothelial Progenitor Cells in Coronary Heart Disease.

CONTEXT: Coronary heart disease (CHD) remains the number one killer of men and women in the United States, and despite traditional secondary prevention, individuals with the disease remain at risk. Endothelial progenitor cells (EPCs) may have beneficial effects on atherosclerosis, angiogenesis, and vascular repair and may contribute systemically to ongoing endogenous repair processes. Traditional acupuncture (TA), a modality used in the practice of Chinese medicine, appears to have beneficial effects in many areas associated with CHD. OBJECTIVE: The study examined the effects of TA on circulating EPCs in individuals with CHD. DESIGN: The research team performed a randomized, controlled pilot study. SETTING: All interventions were performed at the Cedars-Sinai Medical Center in Los Angeles, CA. PARTICIPANTS: The study included 13 participants in 3 groups: (1) TA (n = 5), (2) sham acupuncture (SA, n = 5), or (3) waiting control (WC, n = 3). INTERVENTION: The TA group received acupuncture treatments for 12 wk at CHD-specific sites, while the SA group received no-needle pressure at nonacupuncture sites for the same period, and the WC group received no intervention. OUTCOME MEASURES: The study measured the number of EPCs circulating in peripheral blood to determine cell surface markers for expressions of cluster of differentiation 34, 133 (CD34+/CD133+) and vascular endothelial growth factor receptor 2 (VEGF-R2+). RESULTS: Eight men and 5 women with a mean age of 59 ± 10.9 y were included. Compared with their measurements at baseline, members of the TA group had a significantly greater change in the level of EPCs expressing CD34+/VEGF-R2+ compared with the SA group (P = .04). No group differences were evident in immature EPCs expressing CD34+/CD133+. CONCLUSION: The study's results suggest that TA can alter the number of EPCs circulating in peripheral blood by increasing the mobilization of the VEGF-R2+ EPC subpopulations. Further studies are warranted to evaluate whether TA can beneficially affect CHD via augmentation of EPC regenerative pathways.