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1.
N Engl J Med ; 388(23): 2121-2131, 2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-37285526

RESUMEN

BACKGROUND: Data showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited. METHODS: We conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation. RESULTS: A total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, -3 percentage points; 90% CI, -10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation. CONCLUSIONS: In this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.).


Asunto(s)
Muerte Encefálica , Trasplante de Corazón , Obtención de Tejidos y Órganos , Adulto , Humanos , Supervivencia de Injerto , Preservación de Órganos , Donantes de Tejidos , Muerte , Seguridad del Paciente
2.
Circulation ; 148(17): 1316-1329, 2023 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-37401479

RESUMEN

BACKGROUND: Right ventricular failure (RVF) is a leading driver of morbidity and death after major cardiac surgery for advanced heart failure, including orthotopic heart transplantation and left ventricular assist device implantation. Inhaled pulmonary-selective vasodilators, such as inhaled epoprostenol (iEPO) and nitric oxide (iNO), are essential therapeutics for the prevention and medical management of postoperative RVF. However, there is limited evidence from clinical trials to guide agent selection despite the significant cost considerations of iNO therapy. METHODS: In this double-blind trial, participants were stratified by assigned surgery and key preoperative prognostic features, then randomized to continuously receive either iEPO or iNO beginning at the time of separation from cardiopulmonary bypass with the continuation of treatment into the intensive care unit stay. The primary outcome was the composite RVF rate after both operations, defined after transplantation by the initiation of mechanical circulatory support for isolated RVF, and defined after left ventricular assist device implantation by moderate or severe right heart failure according to criteria from the Interagency Registry for Mechanically Assisted Circulatory Support. An equivalence margin of 15 percentage points was prespecified for between-group RVF risk difference. Secondary postoperative outcomes were assessed for treatment differences and included: mechanical ventilation duration; hospital and intensive care unit length of stay during the index hospitalization; acute kidney injury development including renal replacement therapy initiation; and death at 30 days, 90 days, and 1 year after surgery. RESULTS: Of 231 randomized participants who met eligibility at the time of surgery, 120 received iEPO, and 111 received iNO. Primary outcome occurred in 30 participants (25.0%) in the iEPO group and 25 participants (22.5%) in the iNO group, for a risk difference of 2.5 percentage points (two one-sided test 90% CI, -6.6% to 11.6%) in support of equivalence. There were no significant between-group differences for any of the measured postoperative secondary outcomes. CONCLUSIONS: Among patients undergoing major cardiac surgery for advanced heart failure, inhaled pulmonary-selective vasodilator treatment using iEPO was associated with similar risks for RVF development and development of other postoperative secondary outcomes compared with treatment using iNO. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03081052.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Insuficiencia Cardíaca , Humanos , Administración por Inhalación , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Epoprostenol/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/cirugía , Óxido Nítrico , Vasodilatadores
3.
Am Heart J ; 274: 130-133, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38866442

RESUMEN

BACKGROUND: Patients with obesity and advanced heart failure requiring left ventricular assist device (LVAD) support are more likely to experience LVAD complications and may be disproportionately Black and/or female when compared to patients without obesity. Among these patients, obesity may represent a barrier to transplant eligibility and a marker of inequity in heart transplantation and health outcomes in advanced heart failure. METHODS: To better understand this issue at our institution, we examined our active LVAD cohort and found that almost one-third of all patients had severe obesity with BMI ≥ 35 kg/m2. RESULTS: Patients with LVADs and severe obesity were significantly younger and more likely to self-identify as Black, and numerically more likely to be female. CONCLUSION: Weight management in this group represents a vital area for improved equity in health outcomes and barriers to heart transplantation. TRIAL REGISTRATION: NA.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Obesidad Mórbida , Humanos , Femenino , Masculino , Insuficiencia Cardíaca/terapia , Persona de Mediana Edad , Obesidad Mórbida/complicaciones , Índice de Masa Corporal , Adulto , Anciano , Estudios Retrospectivos
4.
Pediatr Transplant ; 28(3): e14708, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38553812

RESUMEN

BACKGROUND: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. METHODS: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance. RESULTS: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. CONCLUSION: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.


Asunto(s)
Ácidos Nucleicos Libres de Células , Trasplante de Corazón , Adulto , Humanos , Niño , Estudios Prospectivos , Biomarcadores , Rechazo de Injerto , Donantes de Tejidos
5.
Artif Organs ; 48(2): 157-165, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37814840

RESUMEN

BACKGROUND: As heart transplant guidelines evolve, the clinical indication for 73% of durable left ventricular assist device (LVAD) implants is now destination therapy. Although completely magnetically levitated LVAD devices have demonstrated improved durability relative to previous models, LVAD replacement procedures are still required for a variety of indications. Thus, the population of patients with a replaced LVAD is growing. There is a paucity of data regarding the outcomes and risk factors for those patients receiving first-time LVAD replacements. METHODS: The study cohort consisted of all consecutive patients between 2006 and 2020 that received a first-time LVAD replacement at a single institution. Preoperative clinical and laboratory variables were collected retrospectively. The primary endpoint was death or need for an additional LVAD replacement. Data were subjected to Kaplan-Meier, univariate, and multivariate Cox hazard ratio analyses. RESULTS: In total, 152 patients were included in the study, of which 101 experienced the primary endpoint. On multivariate analysis, patients receiving HeartMate 3 (HM3) LVADs as the replacement device showed superior outcomes (HR 0.15, 95% CI 0.065-0.35, p < 0.0001). Independent risk factors for death or need for additional replacement included preoperative extracorporeal membrane oxygenation (ECMO) (HR 4.44, 95% CI 1.87-14.45, and p = 0.00042), increased number of sternotomies (HR 5.20, 95% CI 1.87-14.45, and p = 0.0016), and preoperative mechanical ventilation (HR 1.98, 95% CI 1.01-3.86, and p = 0.045). CONCLUSIONS: Replacement with HM3 showed superior outcomes compared to all other pump types when controlling for both initial pump type and other independent predictors of death or LVAD replacement. Preoperative ECMO, mechanical ventilation, and multiple sternotomies also increased the odds for death or the need for subsequent replacement.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Auxiliar , Humanos , Corazón Auxiliar/efectos adversos , Estudios Retrospectivos , Insuficiencia Cardíaca/terapia , Trasplante de Corazón/efectos adversos , Morbilidad , Resultado del Tratamiento
6.
Am J Transplant ; 23(7): 1048-1057, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37059177

RESUMEN

Nontuberculous mycobacteria are emerging pathogens, yet data on the epidemiology and management of extrapulmonary nontuberculous mycobacteria infections in orthotopic heart transplantation (OHT) and ventricular assist device (VAD) recipients are scarce. We retrospectively reviewed records of OHT and VAD recipients who underwent cardiac surgery at our hospital and developed Mycobacterium abscessus complex (MABC) infection from 2013 to 2016 during a hospital outbreak of MABC linked to heater-cooler units. We analyzed patient characteristics, medical and surgical management, and long-term outcomes. Ten OHT patients and 7 patients with VAD developed extrapulmonary M. abscessus subspecies abscessus infection. The median time from presumed inoculation during cardiac surgery to the first positive culture was 106 days in OHT and 29 days in VAD recipients. The most common sites of positive cultures were blood (n = 12), sternum/mediastinum (n = 8), and the VAD driveline exit site (n = 7). The 14 patients diagnosed when alive received combination antimicrobial therapy for a median of 21 weeks, developed 28 antibiotic-related adverse events, and underwent 27 surgeries. Only 8 (47%) patients survived longer than 12 weeks after diagnosis, including 2 patients with VAD who experienced long-term survival after an explantation of infected VADs and OHT. Despite aggressive medical and surgical management, OHT and VAD patients with MABC infection experienced substantial morbidity and mortality.


Asunto(s)
Trasplante de Corazón , Corazón Auxiliar , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Humanos , Corazón Auxiliar/efectos adversos , Estudios Retrospectivos , Trasplante de Corazón/efectos adversos , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/epidemiología
7.
J Card Fail ; 29(1): 67-75, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36351494

RESUMEN

BACKGROUND: Primary graft dysfunction (PGD), the leading cause of early mortality after heart transplantation, is more common following donation after circulatory death (DCD) than donation after brain death (DBD). We conducted a single-center, retrospective cohort study to compare the incidence, severity and outcomes of patients experiencing PGD after DCD compared to DBD heart transplantation. METHODS AND RESULTS: Medical records were reviewed for all adult heart transplant recipients at our institution between March 2016 and December 2021. PGD was diagnosed within 24 hours after transplant according to modified International Society for Heart and Lung Transplant criteria. A total of 459 patients underwent isolated heart transplantation during the study period, 65 (14%) following DCD and 394 (86%) following DBD. The incidence of moderate or severe PGD in DCD and DBD recipients was 34% and 23%, respectively (P = 0.070). DCD recipients were more likely to experience severe biventricular PGD than DBD recipients (19% vs 7.4%; P = 0.004). Among patients with severe PGD, DCD recipients experienced shorter median (Q1, Q3) duration of post-transplant mechanical circulatory support (6 [4, 7] vs 9 [5, 14] days; P = 0.039), shorter median post-transplant hospital length of stay (17 [15, 29] vs 52 [26, 83] days; P = 0.004), and similar 60-day survival rates (100% [95% CI: 76.8%-100%] vs 80.0% [63.1%-91.6%]; P = 0.17) and overall survival (log-rank; P = 0.078) compared with DBD recipients. CONCLUSIONS: DCD heart transplant recipients were more likely to experience severe, biventricular PGD than DBD recipients. Despite this, DCD recipients with severe PGD spent fewer days on mechanical circulatory support and in the hospital than similar DBD patients. These findings suggest that patterns of graft dysfunction and recovery may differ between donor types, and they support the expansion of the heart-donor pool with DCD.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Disfunción Primaria del Injerto , Obtención de Tejidos y Órganos , Adulto , Humanos , Muerte Encefálica , Estudios Retrospectivos , Disfunción Primaria del Injerto/diagnóstico , Disfunción Primaria del Injerto/epidemiología , Disfunción Primaria del Injerto/etiología , Donantes de Tejidos , Trasplante de Corazón/efectos adversos , Supervivencia de Injerto
8.
Clin Transplant ; 37(5): e14959, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36965001

RESUMEN

BACKGROUND: Heart transplantation (HT) has historically been limited by organ availability. Use of donation after circulatory death (DCD) donors addresses this limitation by utilizing previously unused hearts through use of the Organ Care System (OCS). OBJECTIVES: This study aimed to determine the impact of procurement and transportation method on allograft structure and function using early post-transplant cardiac magnetic resonance imaging (MRI). METHODS: Patients who underwent HT at our institution from February 1, 2020, through April 30, 2021 who underwent cardiac MRI imaging <60 days from transplant were included. Recipient and donor characteristics, clinical outcomes, and MRI findings were compared between those who underwent DCD transplantation using the OCS device (DCD-OCS), brain dead donation (DBD) using the OCS device (DBD-OCS), and DBD transported via cold storage (DBD-cold storage) using one-way analysis of variance. RESULTS: A total of 85 patients underwent HT with a cardiac MRI during the study period. Thirty-one (36%) patients received a DCD organ, 16 (19%) received a DBD-OCS organ and 38 (45%) received a DBD-cold storage organ. Rates of primary graft dysfunction (PGD) were significantly higher in DCD transplants (19.5% DCD vs. .0% DBD-OCS and 5.3% DBD-cold storage; p < .050 across three groups), but with no differences in mortality or rejection. There were no differences in cardiac MRI findings between the three transplant types, including presence of gadolinium hyperenhancement after transplant (all p > .050). CONCLUSIONS: We observed no differences in early cardiac MRI findings between patients that received DCD and DBD-OCS heart transplants compared with those receiving DBD-cold storage transplants.


Asunto(s)
Trasplante de Corazón , Obtención de Tejidos y Órganos , Humanos , Donantes de Tejidos , Muerte Encefálica , Imagen por Resonancia Magnética , Supervivencia de Injerto , Estudios Retrospectivos , Muerte
9.
Clin Transplant ; 37(10): e15048, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37363857

RESUMEN

INTRODUCTION: The advent of new technologies to reduce primary graft dysfunction (PGD) and improve outcomes after heart transplantation are costly. Adoption of these technologies requires a better understanding of health care utilization, specifically the costs related to PGD. METHODS: Records were examined from all adult patients who underwent orthotopic heart transplantation (OHT) between July 1, 2013 and July 30, 2019 at a single institution. Total costs were categorized into variable, fixed, direct, and indirect costs. Patient costs from time of transplantation to hospital discharge were transformed with the z-score transformation and modeled in a linear regression model, adjusted for potential confounders and in-hospital mortality. The quintile of patient costs was modeled using a proportional odds model, adjusted for confounders and in-hospital mortality. RESULTS: 359 patients were analyzed, including 142 with PGD and 217 without PGD. PGD was associated with a .42 increase in z-score of total patient costs (95% CI: .22-.62; p < .0001). Additionally, any grade of PGD was associated with a 2.95 increase in odds for a higher cost of transplant (95% CI: 1.94-4.46, p < .0001). These differences were substantially greater when PGD was categorized as severe. Similar results were obtained for fixed, variable, direct, and indirect costs. CONCLUSIONS: PGD after OHT impacts morbidity, mortality, and health care utilization. We found that PGD after OHT results in a significant increase in total patient costs. This increase was substantially higher if the PGD was severe. SUMMARY: Primary graft dysfunction after heart transplantation impacts morbidity, mortality, and health care utilization. PGD after OHT is costly and investments should be made to reduce the burden of PGD after OHT to improve patient outcomes.

10.
J Cardiothorac Vasc Anesth ; 37(11): 2236-2243, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37586950

RESUMEN

OBJECTIVES: To investigate whether recipient administration of thyroid hormone (liothyronine [T3]) is associated with reduced rates of primary graft dysfunction (PGD) after orthotopic heart transplantation. DESIGN: Retrospective cohort study. SETTING: Single-center, university hospital. PARTICIPANTS: Adult patients undergoing orthotopic heart transplantation. INTERVENTIONS: A total of 609 adult heart transplant recipients were divided into 2 cohorts: patients who did not receive T3 (no T3 group, from 2009 to 2014), and patients who received T3 (T3 group, from 2015 to 2019). Propensity-adjusted logistic regression was performed to assess the association between T3 supplementation and PGD. MEASUREMENTS AND MAIN RESULTS: After applying exclusion criteria and propensity-score analysis, the final cohort included 461 patients. The incidence of PGD was not significantly different between the groups (33.9% no T3 group v 40.8% T3 group; p = 0.32). Mortality at 30 days (3% no T3 group v 2% T3 group; p = 0.53) and 1 year (10% no T3 group v 12% T3 group; p = 0.26) were also not significantly different. When assessing the severity of PGD, there were no differences in the groups' rates of moderate PGD (not requiring mechanical circulatory support other than an intra-aortic balloon pump) or severe PGD (requiring mechanical circulatory support other than an intra-aortic balloon pump). However, segmented time regression analysis revealed that patients in the T3 group were less likely to develop severe PGD. CONCLUSIONS: These findings indicated that recipient single-dose thyroid hormone administration may not protect against the development of PGD, but may attenuate the severity of PGD.


Asunto(s)
Trasplante de Corazón , Disfunción Primaria del Injerto , Adulto , Humanos , Estudios Retrospectivos , Disfunción Primaria del Injerto/diagnóstico , Disfunción Primaria del Injerto/epidemiología , Disfunción Primaria del Injerto/etiología , Trasplante de Corazón/efectos adversos , Hormonas Tiroideas , Suplementos Dietéticos
11.
Am J Transplant ; 22(12): 3021-3030, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36056456

RESUMEN

Surgical site infections (SSI) are severe complications of solid organ transplant (SOT). This retrospective study assessed the epidemiology of and outcomes associated with invasive primary SSI (IP-SSI) occurring within 3 months of transplantation in adult SOT recipients at Duke University over a 5-year period (2015-2019). Among 2073 consecutive SOT recipients, 198 IP-SSI were identified. The IP-SSI rate declined over the period (14.4% in 2015 vs. 8.3% in 2019) and was higher among multi-organ compared with single-organ transplants (33.9% vs. 8.1%, p < .01). SOT recipients with IP-SSI had longer hospital stays than patients without SSI (30.0 vs. 17.0 days, p < .01). Transplant hospitalization (9.6% vs. 2.2%, p < .01), 6-month (11.6% vs. 3.3%, p < .01), and 1-year mortality (15.7% vs. 5.8%, p < .01) were higher in SOT recipients with IP-SSI than in those without. While Gram-positive bacteria were the most common pathogens, urogenital Mollicute and atypical Mycobacteria were identified as an unexpected cause of IP-SSI, particularly among lung transplant recipients. The median time to IP-SSI was 24.0 (IQR 13.8-48.3) days, although the time to IP-SSI varied based on organ transplanted and the causative pathogen. IP-SSI is an important and potentially modifiable complication of SOT, associated with prolonged hospitalizations and reduced survival, particularly in the lung transplant population.


Asunto(s)
Trasplante de Órganos , Infección de la Herida Quirúrgica , Adulto , Humanos , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/etiología , Trasplante de Órganos/efectos adversos , Receptores de Trasplantes , Tiempo de Internación
12.
J Card Fail ; 28(3): 467-476, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34752907

RESUMEN

Advanced heart failure affects tens of thousands of people in the United States alone with high morbidity and mortality. Cardiac transplantation offers the best treatment strategy, but has been limited historically by donor availability. Recently, there have been significant advances in organ allocation, donor-recipient matching, organ preservation, and expansion of the donor pool. The current heart allocation system prioritizes the sickest patients to minimize waitlist mortality. Advances in donor organ selection, including predicted heart mass calculations and more sophisticated antibody detection methods for allosensitized patients, offer more effective matching of donors and recipients. Innovations in organ preservation such as with organ preservation systems have widened the donor pool geographically. The use of donors with hepatitis C is possible with the advent of effective direct-acting antiviral agents to cure donor-transmitted hepatitis C. Finally, further expansion of the donor pool is occurring with the use of higher risk donors with advanced age, medical comorbidities, and left ventricular dysfunction and advances in donation after circulatory death. This review provides an update on the new technologies and transplantation strategies that serve to widen the donor pool and more effectively match donors and recipients so that heart transplant candidates may derive the best outcomes from heart transplantation.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Hepatitis C Crónica , Hepatitis C , Obtención de Tejidos y Órganos , Antivirales , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/métodos , Humanos , Donantes de Tejidos , Estados Unidos
13.
J Card Fail ; 28(9): 1456-1463, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35447338

RESUMEN

Heart transplantation remains the gold-standard therapy for end-stage heart failure; the expected median survival range is 12-13 years. More than 30,000 heart transplants have been performed globally in the past decade alone. With advances in medical and surgical therapies for heart failure, including durable left ventricular assist devices, an increasing number of patients are living with end-stage disease. Last year alone, more than 2500 patients were added to the heart-transplant waitlist in the United States. Despite recent efforts to expand the donor pool, including an increase in transplantation of hepatitis C-positive and extended-criteria donors, supply continues to fall short of demand. Donation after circulatory death (DCD), defined by irreversible cardiopulmonary arrest rather than donor brain death, is widely used in other solid-organ transplants, including kidney and liver, but has not been widely adopted in heart transplantation. However, resurging interest in DCD donation and the introduction of ex vivo perfusion technology has catalyzed recent clinical trials and the development of DCD heart-transplantation programs. Herein, we review the history of DCD heart transplantation, describe the currently used procurement protocols for it and examine clinical challenges and outcomes of such a procedure.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Obtención de Tejidos y Órganos , Supervivencia de Injerto , Insuficiencia Cardíaca/cirugía , Humanos , Donantes de Tejidos
14.
Clin Transplant ; 36(1): e14509, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34649304

RESUMEN

BACKGROUND: Cell-free DNA is an emerging biomarker. While donor fraction may detect graft events in heart transplant recipients, the prognostic value of total nuclear cell-free DNA (ncfDNA) itself is largely unexplored. OBJECTIVE: Explore the relationship between ncfDNA and clinical events in heart transplant recipients. METHODS: We conducted a multi-center prospective study to investigate the value of cell-free DNA in non-invasive monitoring following heart transplantation. Over 4000 blood samples were collected from 388 heart transplant patients. Total ncfDNA and donor fraction were quantified. Generalized linear models with maximum likelihood estimation for repeated measures with subjects as clusters were used to explore the relationship of ncfDNA and major adverse events. Receiver operating characteristic curves were used to help choose cutpoints. RESULTS: A ncfDNA threshold (50 ng/ml) was identified that was associated with increased risk of major adverse events. NcfDNA was elevated in patients who suffered cardiac arrest, required mechanical circulatory support or died post heart transplantation as well as in patients undergoing treatment for infection. CONCLUSIONS: Elevated ncfDNA correlates with risk for major adverse events in adult and pediatric heart transplant recipients and may indicate a need for enhanced surveillance after transplant.


Asunto(s)
Ácidos Nucleicos Libres de Células , Trasplante de Corazón , Adulto , Niño , Rechazo de Injerto/diagnóstico , Rechazo de Injerto/etiología , Trasplante de Corazón/efectos adversos , Humanos , Estudios Prospectivos , Donantes de Tejidos , Receptores de Trasplantes
15.
Pediatr Transplant ; 26(4): e14264, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35258162

RESUMEN

BACKGROUND: Clinical rejection (CR) defined as decision to treat clinically suspected rejection with change in immunotherapy based on clinical presentation with or without diagnostic biopsy findings is an important part of care in heart transplantation. We sought to assess the utility of donor fraction cell-free DNA (DF cfDNA) in CR and the utility of serial DF cfDNA in CR patients in predicting outcomes of clinical interest. METHODS: Patients with heart transplantation were enrolled in two sequential, multi-center, prospective observational studies. Blood samples were collected for surveillance or clinical events. Clinicians were blinded to the results of DF cfDNA. RESULTS: A total of 835 samples from 269 subjects (57% pediatric) were included for this analysis, including 28 samples associated with CR were analyzed. Median DF cfDNA was 0.43 (IQR 0.15, 1.36)% for CR and 0.10 (IQR 0.07, 0.16)% for healthy controls (p < .0001). At cutoff value of 0.13%, the area under curve (AUC) was 0.82, sensitivity of 0.86, specificity of 0.67, and negative predictive value of 0.99. There was serial decline in DF cfDNA post-therapy, however, those with cardiovascular events (cardiac arrest, need for mechanical support or death) showed significantly higher levels of DF cfDNA on Day 0 (2.11 vs 0.31%) and Day 14 (0.51 vs 0.22%) compared to those who did not have such an event (p < .0001). CONCLUSION: DF cfDNA has excellent agreement with clinical rejection and, importantly, serial measurement of DF cfDNA predict clinically significant outcomes post treatment for rejection in these patients.


Asunto(s)
Ácidos Nucleicos Libres de Células , Trasplante de Corazón , Biomarcadores , Niño , Rechazo de Injerto , Humanos , Donantes de Tejidos
16.
J Cardiothorac Vasc Anesth ; 36(10): 3740-3746, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35871044

RESUMEN

OBJECTIVES: The prediction of right heart failure (RHF) after left ventricular assist device (LVAD) implantation remains a challenge. Recently, risk scores were derived from analysis of the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) data, the EUROMACS-RHF, and the modified postoperative EUROMACS-RHF. The authors assessed the performance characteristics of these 2 risk score formulations in a continuous-flow LVAD cohort at their institution. DESIGN: A retrospective, observational study. SETTING: At a tertiary-care academic medical center. PARTICIPANTS: Adult patients who underwent durable LVAD implantation between 2015 and 2018. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Early post-LVAD RHF was defined as follows: (1) need for right ventricular assist device, or (2) inotropic or inhaled pulmonary vasodilator support for ≥14 postoperative days. The authors used logistic regression and examined receiver operating characteristic (ROC) curves to evaluate the ability of the 2 risk scores to distinguish between outcome groups. A total of 207 patients met the inclusion criteria. Of the patients, 16% developed RHF (33/207). The EUROMACS-RHF score was not predictive of RHF in the authors' cohort (odds ratio [OR] 1.25; 95% CI [0.99-1.60]; p = 0.06), but the postoperative EUROMACS-RHF CPB score was significantly associated (OR 1.38; 95% CI [1.03-1.89]; p = 0.03). The scores had similar ROC curves, with weak discriminatory performance: 0.601 (95% CI [0.509-0.692]) and 0.599 (95% CI [0.505-0.693]) for EUROMACS-RHF and postoperative EUROMACS-RHF, respectively. CONCLUSIONS: In the authors' single-center retrospective analysis, the EUROMACS-RHF risk score did not predict early RHF. An optimized risk score for the prediction of RHF after LVAD implantation remains an urgent unmet need.


Asunto(s)
Insuficiencia Cardíaca , Corazón Auxiliar , Disfunción Ventricular Derecha , Adulto , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/cirugía , Corazón Auxiliar/efectos adversos , Humanos , Sistema de Registros , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
17.
J Card Surg ; 37(12): 4621-4627, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36378929

RESUMEN

BACKGROUND: Heart donation after donor brain death from cardiac arrest despite successful resuscitation may be associated with worse recipient outcomes due to potential graft ischemia or underlying rhythmic/structural defects. However, selected grafts from such donors often have normal cardiac function and anatomy. We investigated whether a cardiovascular mechanism of donor brain death (CV-DBD) was associated with worse recipient outcomes. METHODS: We queried the United Network for Organ Sharing (UNOS) database for first-time, single-organ, adult (age 18+) heart transplant recipients and their associated donors between January 2005 and March 2021. Recipients were stratified by donor status (CV-DBD vs. non-CV-DBD). We performed multivariable Cox proportional hazards modeling to ascertain whether receiving a CV-DBD graft was independently associated with mortality. RESULTS: Of 35,833 included recipients, 2,702 (7.5%) received CV-DBD grafts. The associated donors were significantly more likely to be female, older, and have a history of diabetes, hypertension, and substance use (all p < .001). On unadjusted Kaplan-Meier analysis, CV-DBD recipients had a significantly reduced median survival than non-CV-DBD recipients (12.0 vs. 13.1 years, log-rank p = .04). However, after adjusting for donor/recipient age, recipient comorbidities, annualized center volume, and transplantation era, CV-DBD organ status was not associated with recipient mortality (hazard ratio: 1.05, 95% confidence interval: 0.96-1.13, p = .28). CONCLUSION: In this analysis of over 35,000 heart transplants, CV-DBD status was not associated with adjusted recipient survival. Donor brain death due to cardiac arrest should not be an absolute contraindication to heart donation, although graft function should be carefully assessed before transplantation.


Asunto(s)
Paro Cardíaco , Trasplante de Riñón , Obtención de Tejidos y Órganos , Adulto , Humanos , Femenino , Adolescente , Masculino , Muerte Encefálica , Supervivencia de Injerto , Donantes de Tejidos , Estudios Retrospectivos , Muerte
18.
Clin Infect Dis ; 72(7): 1232-1240, 2021 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-32133489

RESUMEN

BACKGROUND: We recently mitigated a clonal outbreak of hospital-acquired Mycobacterium abscessus complex (MABC), which included a large cluster of adult patients who developed invasive infection after exposure to heater-cooler units during cardiac surgery. Recent studies have detailed Mycobacterium chimaera infections acquired during cardiac surgery; however, little is known about the epidemiology and clinical courses of cardiac surgery patients with invasive MABC infection. METHODS: We retrospectively collected clinical data on all patients who underwent cardiac surgery at our hospital and subsequently had positive cultures for MABC from 2013 through 2016. Patients with ventricular assist devices or heart transplants were excluded. We analyzed patient characteristics, antimicrobial therapy, surgical interventions, and clinical outcomes. RESULTS: Ten cardiac surgery patients developed invasive, extrapulmonary infection from M. abscessus subspecies abscessus in an outbreak setting. Median time from presumed inoculation in the operating room to first positive culture was 53 days (interquartile range [IQR], 38-139 days). Disseminated infection was common, and the most frequent culture-positive sites were mediastinum (n = 7) and blood (n = 7). Patients received a median of 24 weeks (IQR, 5-33 weeks) of combination antimicrobial therapy that included multiple intravenous agents. Six patients required antibiotic changes due to adverse events attributed to amikacin, linezolid, or tigecycline. Eight patients underwent surgical management, and 6 patients required multiple sternal debridements. Eight patients died within 2 years of diagnosis, including 4 deaths directly attributable to MABC infection. CONCLUSIONS: Despite aggressive medical and surgical management, invasive MABC infection after cardiac surgery caused substantial morbidity and mortality. New treatment strategies are needed, and compliance with infection prevention guidelines remains critical.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Mycobacterium , Adulto , Antibacterianos/uso terapéutico , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Humanos , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/etiología , Estudios Retrospectivos
19.
J Card Fail ; 27(12): 1462-1465, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34407451

RESUMEN

The recently concluded prospective Portable Organ Care System (OCS) Heart trial to Evaluate the Safety and Effectiveness of The Portable Organ Care System Heart for Preserving and Assessing Expanded Criteria Donor Hearts for Transplantation (EXPAND) demonstrated that the use of ex vivo perfusion for expanded-criteria hearts may be a viable method for increasing the use of donor hearts. We sought to estimate the potential impact of ex vivo expanded-criteria heart perfusion on the donor pool in the United States by using a large national transplant registry. After applying the inclusion criteria of EXPAND, 8637 potentially eligible donors were identified in the U.S. between January 1, 2015, and June 30, 2019, representing a substantial potential increase in the donor pool.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Humanos , Perfusión , Estudios Prospectivos , Donantes de Tejidos , Estados Unidos
20.
J Cardiothorac Vasc Anesth ; 35(12): 3735-3742, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33388220

RESUMEN

Temporary left ventricular support aims to decompress the left ventricle and provide adequate forward flow into the arterial circulation. This can be accomplished with endovascular devices such as the Impella with an internal motor, or with the implementation of cannulae to drain the left ventricle or left atrium and then return to the arterial circulation using an external pump. In this report, the authors describe the transesophageal echocardiography-guided placement of a single-cannula system with the Protek Duo RD (TandemLife, LivaNova) via a left ventricular apical approach to provide minimally invasive left ventricular support in a high-risk Jehovah's Witness patient.


Asunto(s)
Corazón Auxiliar , Testigos de Jehová , Cánula , Ecocardiografía Transesofágica , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/cirugía , Humanos
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