Should VV ECMO be considered as treatment option in COVID-19 infection after kidney transplant? A word of caution.

Several reports have shown that hospitalized kidney transplant recipients (KTR) had high mortality rates when infected with COVID-19. Extracorporeal Membrane Oxygenation (ECMO) has been shown to be an option for refractory respiratory failure in COVID-19 patients with variable rates of recovery. The outcome of ECMO in respiratory failure is highly related to cohort investigated and patient selection. Over a 10-month period in the height of COVID-19 pandemic 5 KTR patients were placed on ECMO with none of the patients surviving to discharge. All patients experienced multisystem organ failure (MSOF) and hematologic pathology while on ECMO. We concluded that COVID-19 in KTR patients presents with a refractory MSOF that is not well supported with ECMO in a traditional approach. Future work is needed to determine how to best support refractory respiratory failure in KTR patients with COVID-19.

Delayed mortality among solid organ transplant recipients hospitalized for COVID-19.

INTRODUCTION: Most studies of solid organ transplant (SOT) recipients with COVID-19 focus on outcomes within one month of illness onset. Delayed mortality in SOT recipients hospitalized for COVID-19 has not been fully examined. METHODS: We used data from a multicenter registry to calculate mortality by 90 days following initial SARS-CoV-2 detection in SOT recipients hospitalized for COVID-19 and developed multivariable Cox proportional-hazards models to compare risk factors for death by days 28 and 90. RESULTS: Vital status at day 90 was available for 936 of 1117 (84%) SOT recipients hospitalized for COVID-19: 190 of 936 (20%) died by 28 days and an additional 56 of 246 deaths (23%) occurred between days 29 and 90. Factors associated with mortality by day 90 included: age > 65 years [aHR 1.8 (1.3-2.4), p =<0.001], lung transplant (vs. non-lung transplant) [aHR 1.5 (1.0-2.3), p=0.05], heart failure [aHR 1.9 (1.2-2.9), p=0.006], chronic lung disease [aHR 2.3 (1.5-3.6), p<0.001] and body mass index ≥ 30 kg/m 2 [aHR 1.5 (1.1-2.0), p=0.02]. These associations were similar for mortality by day 28. Compared to diagnosis during early 2020 (March 1-June 19, 2020), diagnosis during late 2020 (June 20-December 31, 2020) was associated with lower mortality by day 28 [aHR 0.7 (0.5-1.0, p=0.04] but not by day 90 [aHR 0.9 (0.7-1.3), p=0.61]. CONCLUSIONS: In SOT recipients hospitalized for COVID-19, >20% of deaths occurred between 28 and 90 days following SARS-CoV-2 diagnosis. Future investigations should consider extending follow-up duration to 90 days for more complete mortality assessment.

Changing trends in mortality among solid organ transplant recipients hospitalized for COVID-19 during the course of the pandemic.

Mortality among patients hospitalized for COVID-19 has declined over the course of the pandemic. Mortality trends specifically in solid organ transplant recipients (SOTR) are unknown. Using data from a multicenter registry of SOTR hospitalized for COVID-19, we compared 28-day mortality between early 2020 (March 1, 2020-June 19, 2020) and late 2020 (June 20, 2020-December 31, 2020). Multivariable logistic regression was used to assess comorbidity-adjusted mortality. Time period of diagnosis was available for 1435/1616 (88.8%) SOTR and 971/1435 (67.7%) were hospitalized: 571/753 (75.8%) in early 2020 and 402/682 (58.9%) in late 2020 (p < .001). Crude 28-day mortality decreased between the early and late periods (112/571 [19.6%] vs. 55/402 [13.7%]) and remained lower in the late period even after adjusting for baseline comorbidities (aOR 0.67, 95% CI 0.46-0.98, p = .016). Between the early and late periods, the use of corticosteroids (≥6 mg dexamethasone/day) and remdesivir increased (62/571 [10.9%] vs. 243/402 [61.5%], p < .001 and 50/571 [8.8%] vs. 213/402 [52.2%], p < .001, respectively), and the use of hydroxychloroquine and IL-6/IL-6 receptor inhibitor decreased (329/571 [60.0%] vs. 4/492 [1.0%], p < .001 and 73/571 [12.8%] vs. 5/402 [1.2%], p < .001, respectively). Mortality among SOTR hospitalized for COVID-19 declined between early and late 2020, consistent with trends reported in the general population. The mechanism(s) underlying improved survival require further study.

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.

Long-term survival: Achilles heel of lung transplantation.

Long-term survival after lung transplantation has dramatically increased over recent years. But it still falls short of providing a solid extended life expectancy of more than 10 to 15 years. Patients and their families have to informed about this observation so that they can make informed descisions.

Should there be an age limit for advanced therapies?

Combined heart lung transplant has become a rare procedure. However, there is a significant number of patients potentially benefitting from replacement of both heart and lungs. This represents a quite diverse patient population. Decisions in patient selection have to be adjusted to individual needs and distinct constellation of the patient. Age may be a risk factor, but should be carefully integrated into the evaluation of perioperative and long term risks.

Infections in LVAD patients.

Infections in left ventricular assist device (LVAD) patients remain common. Differentiating into device related and non-device related infection is crucial. The incidence of non-device related infections seems to be more determined by the overall condition of the LVAD recipient. Device related infections can be treated by innovative surgical approaches or by transplant. Infection increases the risk of mortaility while on LVAD.

Adding complexity to complexity: The role of concomitant cardiac surgery in lung transplantation.

Outcomes of lung transplantation have greatly improved over recent years. While patients with concomitant cardiac pathology used to be excluded from lung transplant, today, most of these cardiac conditions can be addressed safely and effectively. Interventional techniques should be preferred. Lung transplant performed by cardiac surgeons allows for concomitant interventions.

Risk factors of bronchial dehiscence after primary lung transplantation.

Complications of the bronchial anastomosis in lung transplantation, once the Achilles heel of the procedure, have become quite rare. The surgical technique is well established and safe. Risks contributing to anastomotic complications are primarily related to patients pre-existing conditions. The key factor is good blood flow to the bronchial stump. Postoperative infection can also contribute to the breakdown of the anastomosis. This may be the reason why different immunosuppressive regimes lead to differences in the incidence of bronchial dehiscence.

Left ventricular assist device placement in the setting of congenital VSD.

We describe the management of a 59-year-old female with an unrepaired congenital ventricular septal defect (VSD) and end stage nonischemic cardiomyopathy necessitating placement of a left ventricular assist device (LVAD) as a destination treatment. Simultaneous repair of the VSD was performed during the LVAD implantation under a beating heart. The patient remained hemodynamically stable throughout her postoperative course, without signs of hypoxia or cyanosis. Following discharge, outpatient surveillance echocardiogram demonstrated successful VSD closure and no residual shunt.

COVID-19 in hospitalized lung and non-lung solid organ transplant recipients: A comparative analysis from a multicenter study.

Lung transplant recipients (LTR) with coronavirus disease 2019 (COVID-19) may have higher mortality than non-lung solid organ transplant recipients (SOTR), but direct comparisons are limited. Risk factors for mortality specifically in LTR have not been explored. We performed a multicenter cohort study of adult SOTR with COVID-19 to compare mortality by 28 days between hospitalized LTR and non-lung SOTR. Multivariable logistic regression models were used to assess comorbidity-adjusted mortality among LTR vs. non-lung SOTR and to determine risk factors for death in LTR. Of 1,616 SOTR with COVID-19, 1,081 (66%) were hospitalized including 120/159 (75%) LTR and 961/1457 (66%) non-lung SOTR (p = .02). Mortality was higher among LTR compared to non-lung SOTR (24% vs. 16%, respectively, p = .032), and lung transplant was independently associated with death after adjusting for age and comorbidities (aOR 1.7, 95% CI 1.0-2.6, p = .04). Among LTR, chronic lung allograft dysfunction (aOR 3.3, 95% CI 1.0-11.3, p = .05) was the only independent risk factor for mortality and age >65 years, heart failure and obesity were not independently associated with death. Among SOTR hospitalized for COVID-19, LTR had higher mortality than non-lung SOTR. In LTR, chronic allograft dysfunction was independently associated with mortality.

En-Bloc Simultaneous Heart-Liver Transplantation in Adult Patients.

INTRODUCTION: Complexity of combined heart-liver transplantation has resulted in low adoption rates. We report a case series of adult patients receiving en-bloc heart-liver transplantation (HLTx), describe technical aspects, and discuss benefits of the technique. METHODS: Retrospective review of patients receiving en-bloc HLTx over 18 months, with clinical follow up to 1 year. Primary outcomes included postoperative mortality and major complications. Secondary outcomes included 1-year survival, cardiac or hepatic allograft rejection, and infection. RESULTS: Five patients received en-bloc HLTx. Mean recipient age was 43 years (26-63), and 3 patients were male. Total operative time was 430 minutes (393-480), cold and warm ischemic times of 85 (32-136) and 37.5 (31-47) minutes. Hospital survival was 80%. One patient died on postoperative day 55 due to fungal sepsis. Major postoperative complications included prolonged mechanical ventilation in 2 of 5 patients (40%), and renal insufficiency requiring hemodialysis in 2 of 5 patients (40%). Among patients discharged from hospital 1-year survival was 100%, with no evidence of rejection or infectious complications. CONCLUSION: En-bloc HLTx technique is a safe and effective strategy, decreasing operative times, and allograft ischemic times, whereas offering protection of implanted allografts during early stages of reperfusion while patient is hemodynamically supported on cardiopulmonary bypass.

Parallel veno-venous and veno-arterial extracorporeal membrane circuits for coexisting refractory hypoxemia and cardiovascular failure: a case report.

BACKGROUND: The complexity of extracorporeal membrane oxygenation (ECMO) techniques continues to evolve. Different cannulation methods and configurations have been proposed as a response to a challenging cardiovascular and pulmonary physiology of the patients. The use of parallel ECMO circuits represents a unique and novel approach for patients with refractory respiratory failure and cardiovascular collapse with very large body surface areas. CASE PRESENTATION: We present the case of a 25-year-old morbidly obese male patient admitted for severe acute respiratory distress syndrome (ARDS) and refractory hypoxemia, requiring institution of double cannulation for veno-venous ECMO. Since his hypoxemia persisted, likely due to insufficient flows given his large body surface area, an additional drainage venous cannula was implemented to provide higher flows, temporarily addressing his oxygenation status. Unfortunately, the patient developed concomitant cardiogenic shock refractory to inotropic support and extracorporeal fluid removal, further worsening his oxygenation status, thus the decision was to institute four-cannulation/parallel-circuits veno-venous and veno-arterial ECMO, successfully controlling both refractory hypoxemia and cardiogenic shock. CONCLUSIONS: Our case illustrates a novel and complex approach for combined severe ARDS and cardiovascular collapse through the use of parallel veno-venous and veno-arterial ECMO circuits, and exemplifies the expansion of ECMO techniques and its life-saving capabilities when conservative approaches are futile.

A principal components analysis of factors associated with successful implementation of an LVAD decision support tool.

BACKGROUND: A central goal among researchers and policy makers seeking to implement clinical interventions is to identify key facilitators and barriers that contribute to implementation success. Despite calls from a number of scholars, empirical insights into the complex structural and cultural predictors of why decision aids (DAs) become routinely embedded in health care settings remains limited and highly variable across implementation contexts. METHODS: We examined associations between "reach", a widely used indicator (from the RE-AIM model) of implementation success, and multi-level site characteristics of nine LVAD clinics engaged over 18 months in implementation and dissemination of a decision aid for left ventricular assist device (LVAD) treatment. Based on data collected from nurse coordinators, we explored factors at the level of the organization (e.g. patient volume), patient population (e.g. health literacy; average sickness level), clinician characteristics (e.g. attitudes towards decision aid; readiness for change) and process (how the aid was administered). We generated descriptive statistics for each site and calculated zero-order correlations (Pearson's r) between all multi-level site variables including cumulative reach at 12 months and 18 months for all sites. We used principal components analysis (PCA) to examine any latent factors governing relationships between and among all site characteristics, including reach. RESULTS: We observed strongest inclines in reach of our decision aid across the first year, with uptake fluctuating over the second year. Average reach across sites was 63% (s.d. = 19.56) at 12 months and 66% (s.d. = 19.39) at 18 months. Our PCA revealed that site characteristics positively associated with reach on two distinct dimensions, including a first dimension reflecting greater organizational infrastructure and standardization (characteristic of larger, more established clinics) and a second dimension reflecting positive attitudinal orientations, specifically, openness and capacity to give and receive decision support among coordinators and patients. CONCLUSIONS: Successful implementation plans should incorporate specific efforts to promote supportive and mutually informative interactions between clinical staff members and to institute systematic and standardized protocols to enhance the availability, convenience and salience of intervention tool in routine practice. Further research is needed to understand whether "core predictors" of success vary across different intervention types.

Don't pig(!) the wrong heart!

Cardiac xenotransplantation is believed to have approached clinical application. However, this approach to advanced heart failure is burdened with a multitude of ethical issues. These issues need to be addressed openly and be broadly discussed in public. Only through an honest and transparent approach, it will be possible to engage the lay audience in the evaluation of pig to human transplant.

Cesarean section in patient with metastatic Ewing sarcoma requiring VA-ECMO support.

A 26-year-old pregnant woman, with multiple metastatic Ewing sarcoma, presented with a sternal mass that began enlarging during pregnancy. Due to high-risk pregnancy, the patient was discussed in a multidisciplinary meeting and intubation was considered too risky without cardiopulmonary support. Computed tomography showed extrinsic tumor compression of the right ventricle outflow tract. Veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) was initiated before general anesthesia, followed by Cesarean section (C-section). VA ECMO was initiated with the patient in the awake position, ECMO support was discontinued when the patient had stable ventilation and hemodynamics. This case represents a unique indication of VA ECMO, during C-section, with maternal and fetal survival.

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.

Aorto-pulmonary bypass shunt for intraoperative right ventricular support during LVAD implantation.

We describe a simple modification of the cardiopulmonary bypass (CPB) circuit that allows selective intraoperative circulatory support of the right ventricle during left ventricular assist device (LVAD) implantation. The addition of a side branch to the arterial line and an intermediate line connector allows selective venting and perfusion through a cannula inserted in the main pulmonary artery. This modification of the CPB circuit allows for selective evaluation of right ventricular function, titration of inotropic support, and early identification of patients that require right ventricular assist device (RVAD) support.

"Heart and kidney transplant from donor with recent veno-arterial extracorporeal cardiopulmonary resuscitation".

OBJETIVES: ECMO is progressively being adopted as a last resort to stabilize patients receiving cardiopulmonary resuscitation (ECMO CPR). A significant number of these patients will present recovery of end-organ function, but evolve with brain death, accounting for only 30% of patients discharged from the hospital alive. Harvesting organs from donors on VA ECMO has recently been proposed as a strategy to expand the pool of available organs for transplantation. METHODS: We present a case of combined heart and kidney transplantation from a brain death donor with recent out of hospital cardiac arrest rescued with eCPR. RESULTS: A 31 year old male patient was admitted to local hospital with diagnosis of drowning after seizure episode. Patient received two rounds of CPR for 8 and 30 minutes respectively, and required emergency insertion of VA ECMO. Patient developed compartment syndrome of right lower extremity (RLE) with CPK = 30,720, prompting discontinuation of ECMO support within 48 hours as cardiac function had recovered, reflected on echocardiographic and enzymatic parameters. Patient was declared brain death and became organ donor. Multiple organ procurement was performed. Combined heart and right kidney transplant was then performed on a 61-year-old male with uneventful course, and with normal function of all implanted allografts at 3 months follow up. CONCLUSION: Our experience supports the concept that VA ECMO is not a contraindication for solid organ donation. Individual evaluation of organ function can lead to successful transplantation of multiple organs from donors with recent history of VA ECMO support.

Advanced heart failure therapies in patients with stable HIV infection.

BACKGROUND: Human immunodeficiency virus (HIV) infection affects nearly 38 million people worldwide. Patients living with HIV (PLHIV) on modern highly active antiretroviral therapy face significant morbidity and mortality related to the progression of chronic diseases, which lead to an increase in the burden of end-stage organ disease and organ failure. PLHIV present a two fold increased risk of heart failure as compared with the general population, with a prevalence of clinical heart failure of 6.5 %. Orthotopic heart transplantation (OHT) is rarely performed in HIV-positive patients despite the fact that HIV-associated cardiomyopathy is a major long-term complication of HIV infection. MATERIAL AND METHODS: We present a case of PLHIV presenting with decompensated heart failure, requiring initial therapy with left ventricular assist device, followed by heart transplantation, accompanied by an update on current concepts, and experience in the field. DISCUSSION AND CONCLUSION: HIV-associated cardiomyopathy is a major long-term complication of HIV infection. LVAD support or OHT should also be encouraged among HIV-positive patients as current data indicates that AHFT is safe in carefully selected HIV-positive patients and outcomes are similar to those of HIV-negative patients.