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BACKGROUND: The relationship between age of a heart transplant (HT) program and outcomes has not been explored. METHODS: We performed a retrospective cohort analysis of the United Network for Organ Sharing database of all adult HTs between 2009 and 2019. For each patient, we created a variable that corresponded to program age: new (<5), developing (≥5 but <10) and established (≥10) years. RESULTS: Of 20 997 HTs, 822 were at new, 908 at developing, and 19 267 at established programs. Patients at new programs were significantly more likely to have history of cigarette smoking, ischemic cardiomyopathy, and prior sternotomy. These programs were less likely to accept organs from older donors and those with a history of hypertension or cigarette use. As compared to patients at new programs, transplant patients at established programs had less frequent rates of treated rejection during the index hospitalization (HR 0.43 [95% CI, 0.36-0.53] p < 0.001) and at 1 year (HR 0.58 [95% CI, 0.49-0.70], p < 0.001), less frequently required pacemaker implantations (HR 0.50 [95% CI, 0.36-0.69], p < 0.001), and less frequently required dialysis (HR 0.66 [95% CI, 0.53-0.82], p < 0.001). However, there were no significant differences in short- or long-term survival between the groups (log-rank p = 0.24). CONCLUSION: Patient and donor selection differed between new, developing, and established HT programs but had equivalent survival. New programs had increased likelihood of treated rejection, pacemaker implantation, and need for dialysis. Standardized post-transplant practices may help to minimize this variation and ensure optimal outcomes for all patients.
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Transplante de Coração , Humanos , Transplante de Coração/mortalidade , Feminino , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Seguimentos , Taxa de Sobrevida , Adulto , Prognóstico , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Sobrevivência de Enxerto , Fatores de Risco , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/etiologia , Complicações Pós-Operatórias/mortalidade , Doadores de Tecidos/provisão & distribuição , Fatores Etários , IdosoRESUMO
BACKGROUND: Among heart transplant (HT) recipients who develop advanced graft dysfunction, cardiac re-transplantation may be considered. A smaller subset of patients will experience failure of their second allograft and undergo repeat re-transplantation. Outcomes among these individuals are not well-described. METHODS: Adult and pediatric patients in the United Network for Organ Sharing (UNOS) registry who received HT between January 1, 1990 and December 31, 2020 were included. RESULTS: Between 1990 and 2020, 90 individuals received a third HT and three underwent a fourth HT. Recipients were younger than those undergoing primary HT (mean age 32 years). Third HT was associated with significantly higher unadjusted rates of 1-year mortality (18% for third HT vs. 13% for second HT vs. 9% for primary HT, p < .001) and 10-year mortality (59% for third HT vs. 42% for second HT vs. 37% for primary HT, p < .001). Mortality was highest amongst recipients aged >60 years and those re-transplanted for acute graft failure. Long-term rates of CAV, rejection, chronic dialysis, and hospitalization for infection were also higher. CONCLUSIONS: Third HT is associated with higher morbidity and mortality than primary HT. Further consensus is needed regarding appropriate organ stewardship for this unique subgroup.
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Transplante de Coração , Adulto , Humanos , Criança , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Rejeição de Enxerto/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Since the 2018 allocation system change in heart transplantation (HT), ischemic times have increased, which may be associated with peri-operative and post-operative complications. This study aimed to compare ischemia reperfusion injury (IRI) in hearts preserved using ice-cold storage (ICS) and the Paragonix SherpaPak TM Cardiac Transport System (CTS). METHODS: From January 2021 to June 2022, consecutive endomyocardial biopsies from 90 HT recipients were analyzed by a cardiac pathologist in a single-blinded manner: 33 ICS and 57 CTS. Endomyocardial biopsies were performed at three-time intervals post-HT, and the severity of IRI manifesting histologically as coagulative myocyte necrosis (CMN) was evaluated, along with graft rejection and graft function. RESULTS: The incidence of IRI at weeks 1, 4, and 8 post-HT were similar between the ICS and CTS groups. There was a 59.3% statistically significant reduction in CMN from week 1 to 4 with CTS, but not with ICS. By week 8, there were significant reductions in CMN in both groups. Only 1 out of 33 (3%) patients in the ICS group had an ischemic time >240 mins, compared to 10 out of 52 (19%) patients in the CTS group. During the follow-up period of 8 weeks to 12 months, there were no significant differences in rejection rates, formation of de novo donor-specific antibodies and overall survival between the groups. CONCLUSION: The CTS preservation system had similar rates of IRI and clinical outcomes compared to ICS despite longer overall ischemic times. There is significantly more recovery of IRI in the early post operative period with CTS. This study supports CTS as a viable option for preservation from remote locations, expanding the donor pool.
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Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Coração , Preservação de Órgãos , Humanos , Transplante de Coração/efeitos adversos , Masculino , Feminino , Preservação de Órgãos/métodos , Pessoa de Meia-Idade , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Prognóstico , Adulto , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Criopreservação/métodos , Doadores de Tecidos/provisão & distribuição , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
BACKGROUND: Belatacept (BTC), a fusion protein, selectively inhibits T-cell co-stimulation by binding to the CD80 and CD86 receptors on antigen-presenting cells (APCs) and has been used as immunosuppression in adult renal transplant recipients. However, data regarding its use in heart transplant (HT) recipients are limited. This retrospective cohort study aimed to delineate BTC's application in HT, focusing on efficacy, safety, and associated complications at a high-volume HT center. METHODS: A retrospective cohort study was conducted of patients who underwent HT between January 2017 and December 2021 and subsequently received BTC as part of their immunosuppressive regimen. Twenty-one HT recipients were identified. Baseline characteristics, history of rejection, and indication for BTC use were collected. Outcomes included renal function, graft function, allograft rejection and mortality. Follow-up data were collected through December 2023. RESULTS: Among 776 patients monitored from January 2017 to December 2021 21 (2.7%) received BTC treatment. Average age at transplantation was 53 years (± 12 years), and 38% were women. BTC administration began, on average, 689 [483, 1830] days post-HT. The primary indications for BTC were elevated pre-formed donor-specific antibodies in highly sensitized patients (66.6%) and renal sparing (23.8%), in conjunction with reduced calcineurin inhibitor dosage. Only one (4.8%) patient encountered rejection within a year of starting BTC. Graft function by echocardiography remained stable at 6 and 12 months posttreatment. An improvement was observed in serum creatinine levels (76.2% of patients), decreasing from a median of 1.58 to 1.45 (IQR [1.0-2.1] to [1.1-1.9]) over 12 months (p = .054). eGFR improved at 3 and 6 months compared with 3 months pre- BTC levels; however, this was not statistically significant (p = .24). Treatment discontinuation occurred in seven patients (33.3%) of whom four (19%) were switched back to full dose CNI. Infections occurred in 11 patients (52.4%), leading to BTC discontinuation in 4 patients (19%). CONCLUSION: In this cohort, BTC therapy was used as alternative immunosuppression for management of highly sensitized patients or for renal sparing. BTC therapy when combined with CNI dose reduction resulted in stabilization in renal function as measured through renal surrogate markers, which did not, however, reach statistical significance. Patients on BTC maintained a low rejection rate and preserved graft function. Infections were common during BTC therapy and were associated with medication pause/discontinuation in 19% of patients. Further randomized studies are needed to assess the efficacy and safety of BTC in HT recipients.
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Transplante de Coração , Transplante de Rim , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Abatacepte , Estudos Retrospectivos , Transplante de Rim/efeitos adversos , Imunossupressores , Inibidores de Calcineurina/uso terapêutico , Linfócitos T , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/etiologia , Transplantados , Sobrevivência de EnxertoRESUMO
Letermovir is a novel agent for the prevention of cytomegalovirus (CMV) infection and disease that, unlike traditional CMV DNA polymerase inhibitors, does not carry the risk of myelosuppression. The purpose of this study was to evaluate the safety, efficacy, and clinical application of letermovir for CMV prophylaxis in heart transplant (HT) recipients. Between November 1, 2019, and October 1, 2021, at a single, tertiary care hospital, 17 HT recipients were initiated on letermovir due to leukopenia while on valganciclovir. Fifteen (88%) had high-risk mismatch (CMV D+/R-). Median time on letermovir was 5 months (interquartile range, 2-8 months.) At the end of the study period, nine of 17 patients (52.9%) were still on letermovir and four of the 17 (23.5%) had successfully completed the prophylaxis window on letermovir and been switched to the pre-emptive strategy. One patient developed clinically significant CMV viremia in the setting of being unable to obtain medication due to insurance barriers but was later successfully restarted on letermovir. One patient was unable to tolerate letermovir due to symptoms of headache and myalgias. Two patients developed low-level non-clinically significant CMV viremia and were switched back to valacyclovir. All patients had tacrolimus dosages reduced at time of letermovir initiation to minimize the risk of supratherapeutic tacrolimus concentration. One patient required hospitalization due to symptomatic tacrolimus toxicity. For HT recipients who cannot tolerate valganciclovir, letermovir presents an alternative for CMV prophylaxis. Close monitoring for breakthrough CMV and calcineurin inhibitor levels is necessary. Larger studies are required to further delineate its use and help provide further evidence of its safety and efficacy.
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Infecções por Citomegalovirus , Transplante de Coração , Humanos , Citomegalovirus/genética , Valganciclovir/uso terapêutico , Antivirais/uso terapêutico , Tacrolimo/uso terapêutico , Viremia , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/prevenção & controle , TransplantadosRESUMO
We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p = .027).
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COVID-19 , Transplante de Órgãos , Adulto , Humanos , Terapia de Imunossupressão , SARS-CoV-2 , TransplantadosRESUMO
BACKGROUND: Interventricular interaction, which refers to the impact of left ventricular (LV) function on right ventricular (RV) function and vice versa, has been implicated in the pathogenesis of RV failure in LV assist device (LVAD) recipients. We sought to understand more about interventricular interaction by quantifying changes in the RV systolic and diastolic function with varying LVAD speeds. METHODS AND RESULTS: Four patients (ages 22-69 years, 75% male, and 25% with ischemic cardiomyopathy) underwent a protocolized hemodynamic ramp test within 12 months of LVAD implantation where RV pressure-volume loops were recorded with a conductance catheter. The end-systolic PV relationship and end-diastolic PV relationship were compared using the V20 and V10 indices (volumes at which end-systolic PV relationship and end-diastolic PV relationship reach a pressure of 20 and 10 mm Hg, respectively). The ∆V20 and ∆V10 refer to the change in V20 and V10 from the minimum to maximum LVAD speeds. RV PV loops demonstrated variable changes in systolic and diastolic function with increasing LVAD speed. The end-systolic PV relationship changed in 1 patient (patient 2, ∆V20â¯=â¯23.5 mL), reflecting a decrease in systolic function with increased speed, and was unchanged in 3 patients (average ∆V20â¯=â¯7.4 mL). The end-diastolic PV relationship changed with increasing speed in 3 of 4 patients (average ∆V10â¯=â¯12.5 mL), indicating an increase in ventricular compliance, and remained unchanged in one participant (patient 1; ∆V10â¯=â¯4.0 mL). CONCLUSIONS: Interventricular interaction can improve RV compliance and impair systolic function, but the overall effect on RV performance in this pilot investigation is heterogeneous. Further research is required to understand which patient characteristics and hemodynamic parameters influence the net impact of interventricular interaction.
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Insuficiência Cardíaca , Coração Auxiliar , Disfunção Ventricular Direita , Adulto , Idoso , Feminino , Insuficiência Cardíaca/terapia , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Função Ventricular Direita , Pressão Ventricular , Adulto JovemRESUMO
Eosinophilic myocarditis, a rare and under-recognized disease process, occurs due to cytotoxic inflammation of the endomyocardium that over time may lead to a restrictive cardiomyopathy. We report clinical, multimodality imaging, and pathologic findings in a 45-year-old woman over a 17-month period as she progressed from suspected acute eosinophilic myocarditis to phenotypic endomyocardial fibrosis resulting in recurrent ascites. Interval echocardiograms demonstrate definitive pathologic structural changes that reflect the hemodynamic consequences of the underlying cardiomyopathy. Despite a negative myocardial biopsy, characteristic findings on cardiovascular magnetic resonance imaging clarified the diagnosis which led to successful treatment with endomyocardial resection and valve replacements.
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Cardiomiopatia Restritiva , Fibrose Endomiocárdica , Miocardite , Biópsia , Progressão da Doença , Fibrose Endomiocárdica/complicações , Feminino , Coração , Humanos , Pessoa de Meia-Idade , MiocárdioRESUMO
BACKGROUND: Women differ from men in their left ventricular (LV) structure, function and remodeling with age and diseases. The LV assist device (LVAD) unloads the LV and reversely remodels the heart. We sought to define the effects of sex on longitudinal reverse remodeling after LVAD implantation. METHODS AND RESULTS: Cardiac structure and function were assessed by serial echocardiograms. Mixed effect regression models were constructed to assess the independent contribution of sex to longitudinal changes in cardiac structure and function. A total of 355 consecutive patients with advanced heart failure received continuous flow LVADs between 2006 and 2016. The average age was 56 ± 13 years, 73% were men, and 67% were black. Early (within 3 months) after LVAD implantation, women had a greater reduction in LV dimensions and a greater increase in LV ejection fraction compared with men. These differences were independent of age, body surface area, device type, or ischemic etiology of heart failure. At long-term follow-up, LV dimensions increased slightly over time in women compared with men, but overall, earlier changes were maintained. CONCLUSION: Women had significantly more favorable longitudinal changes in cardiac structure and function in response to LV unloading compared with men. Understanding the cause of sex difference in reverse remodeling after LVAD may help to devise novel therapeutic strategies for women with advanced heart failure.
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Insuficiência Cardíaca , Coração Auxiliar , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Caracteres Sexuais , Função Ventricular Esquerda , Remodelação VentricularRESUMO
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.
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Aloenxertos/patologia , COVID-19/imunologia , Endocárdio/patologia , Rejeição de Enxerto/patologia , Transplante de Coração/efeitos adversos , Miocárdio/patologia , Idoso , Aloenxertos/imunologia , Aloenxertos/ultraestrutura , Biópsia , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/patologia , Teste de Ácido Nucleico para COVID-19 , Endocárdio/imunologia , Endocárdio/ultraestrutura , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Miocárdio/imunologia , Miocárdio/ultraestrutura , Cidade de Nova Iorque/epidemiologia , Pandemias , Estudos Retrospectivos , SARS-CoV-2/imunologia , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença , Fatores de TempoRESUMO
BACKGROUND: Although much attention has been paid to admission and transfer patterns for cardiogenic shock, contemporary data are lacking on decompensated heart failure (HF) admissions and transfers and the impact of advanced therapy centers (ATCs) on outcomes. METHODS: HF hospitalizations were obtained from the Nationwide Readmissions Database 2016 to 2019. Centers performing at least 1 heart transplant or left ventricular assist device were classified as ATCs. Patient characteristics, outcomes, and procedural volume were compared among 3 cohorts: admissions to non-ATCs, admissions to ATCs, and transfers to ATCs. A secondary analysis evaluated outcomes for severe HF hospitalizations (cardiogenic shock, cardiac arrest, and mechanical ventilation). Multivariable logistic regression was performed to adjust for the presence of HF decompensations and significant clinical variables during univariate analysis. RESULTS: A total of 2â 331â 690 hospitalizations (81.2%) were admissions to non-ATCs (94.5% of centers), 525â 037 (18.3%) were admissions to ATCs (5.5% of centers), and 15â 541 (0.5%) were transferred to ATCs. Patients treated at ATCs (especially those transferred) had higher rates of HF decompensations, procedural frequency, lengths of stay, and costs. Unadjusted mortality was 2.6% at non-ATCs and was higher at ATCs, both for directly admitted (2.9%, P<0.001) and transferred (11.2%, P<0.001) patients. However, multivariable-adjusted mortality was significantly lower at ATCs, both for directly admitted (odds ratio, 0.82 [95% CI, 0.78-0.87]; P<0.001) and transferred (odds ratio, 0.66 [95% CI, 0.57-0.78]; P<0.001) patients. For severe HF admissions, unadjusted mortality was 37.2% at non-ATCs and was lower at ATCs, both for directly admitted (25.3%, P<0.001) and transferred (25.2%, P<0.001) patients, with similarly lower multivariable-adjusted mortality. CONCLUSIONS: Patients with HF treated at ATCs were sicker but associated with higher procedural volume and lower adjusted mortality.
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Parada Cardíaca , Insuficiência Cardíaca , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/complicações , Choque Cardiogênico/complicações , Hospitalização , Mortalidade HospitalarRESUMO
In patients supported by the HeartMate 3 left ventricular assist device (HM3 LVAD), pump speed adjustments may improve hemodynamics. We investigated the hemodynamic implications of speed adjustments in HM3 recipients undergoing hemodynamic ramp tests. Clinically stable HM3 recipients who underwent routine invasive hemodynamic ramp tests between 2015 and 2022 at our center were included. Filling pressure optimization, defined as central venous pressure (CVP) <12 mm Hg and pulmonary capillary wedge pressure (PCWP) <18 mm Hg, was assessed at baseline and final pump speeds. Patients with optimized pressures were compared to nonoptimized patients. Overall 60 HM3 recipients with a median age of 62 years (56, 71) and time from LVAD implantation of 187 days (124, 476) were included. Optimized filling pressures were found in 35 patients (58%) at baseline speed. Speed was adjusted in 84% of the nonoptimized patients. Consequently, 39 patients (65%) had optimized pressures at final speed. There were no significant differences in hemodynamic findings between baseline and final speeds ( p > 0.05 for all). Six and 12 month readmission-free rates were higher in optimized compared with nonoptimized patients ( p = 0.03 for both), predominantly due to lower cardiac readmission-free rates ( p = 0.052). In stable outpatients supported with HM3 who underwent routine ramp tests, optimized hemodynamics were achieved in only 2 of 3 of the patients. Patients with optimized pressures had lower all-cause readmission rates, primarily driven by fewer cardiac-related hospitalizations.
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Coração Auxiliar , Hemodinâmica , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Hemodinâmica/fisiologia , Idoso , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/cirurgia , Estudos Retrospectivos , Pressão Propulsora Pulmonar/fisiologiaRESUMO
Background: Previous studies have shown that women have worse outcomes for cardiogenic shock (CS) than men. Patients who receive care in CS "hubs" have also been shown to have improved outcomes when compared to those treated at "spokes." This study aimed to examine the presence of sex disparities in the outcomes of CS in relation to hospital type. Methods: Hospitalizations of adults with a diagnosis of CS were identified using data from the 2016-2019 Nationwide Readmissions Database. CS "hubs" were defined as any centers receiving at least 1 interhospital transfer with CS, while those without such transfers were classified as "spokes." Data were combined across years and multivariable logistic regression modeling was used to evaluate the association of sex with in-hospital mortality, invasive procedures, and transfer to hubs. Results: There were a total of 618,411 CS hospitalizations (62.2% men) with CS related to acute myocardial infarction comprising 15.3 to 17.3% of women hospitalizations and 17.8 to 20.3% of men hospitalizations. In-hospital mortality was lower at hubs (34.5% for direct admissions, 31.6% for transfers) than at spokes (40.3%, all P < .01). Women underwent fewer invasive procedures (right heart catheterization, percutaneous coronary intervention, mechanical circulatory support) and had higher mortality than men. Female sex was independently associated with decreased transfers to hubs (odds ratio, 0.93; 95% CI, 0.89-0.96) and increased mortality (odds ratio, 1.09; 95% CI, 1.05-1.12). Conclusions: Women with CS were less likely to be treated at a hub or transferred to a hub, had higher in-hospital mortality, and had a lower likelihood of receiving CS-related procedures than men. Further research is needed to understand sex-specific gaps in CS outcomes.
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Objectives: To evaluate the clinical implications of adjunctive molecular gene expression analysis (MMDx ) of biopsy specimens in heart transplant (HT ) recipients with suspected rejection. Introduction: Histopathological evaluation remains the standard method for rejection diagnosis in HT. However, the wide interobserver variability combined with a relatively common incidence of "biopsy-negative" rejection has raised concerns about the likelihood of false-negative results. MMDx, which uses gene expression to detect early signs of rejection, is a promising test to further refine the assessment of HT rejection. Methods: Single-center prospective study of 418 consecutive for-cause endomyocardial biopsies performed between November 2022 and May 2024. Each biopsy was graded based on histology and assessed for rejection patterns using MMDx. MMDx results were deemed positive if borderline or definitive rejection was present. The impact of MMDx results on clinical management was evaluated. Primary outcomes were 1-year survival and graft dysfunction following MMDx-guided clinical management. Secondary outcomes included changes in donor-specific antibodies, MMDx gene transcripts, and donor-derived cell-free DNA (dd-cfDNA) levels. Results: We analyzed 418 molecular samples from 237 unique patients. Histology identified rejection in 32 cases (7.7%), while MMDx identified rejection in 95 cases (22.7%). Notably, in 79 of the 95 cases where MMDx identified rejection, histology results were negative, with the majority of these cases being antibody-mediated rejection (62.1%). Samples with rejection on MMDx were more likely to show a combined elevation of dd-cfDNA and peripheral blood gene expression profiling than those with borderline or negative MMDx results (36.7% vs 28.0% vs 10.3%; p<0.001). MMDx results led to the implementation of specific antirejection protocols or changes in immunosuppression in 20.4% of cases, and in 73.4% of cases where histology was negative and MMDx showed rejection. 1-year survival was better in the positive MMDx group where clinical management was guided by MMDx results (87.0% vs 78.6%; log rank p=0.0017). Conclusions: In our cohort, MMDx results more frequently indicated rejection than histology, often leading to the initiation of antirejection treatment. Intervention guided by positive MMDx results was associated with improved outcomes.
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OBJECTIVE: The long-term use of milrinone is associated with increased mortality in chronic heart failure. A recent meta-analysis suggested that it might increase mortality in patients undergoing cardiac surgery. The authors conducted an updated meta-analysis of randomized trials in patients undergoing cardiac surgery to determine if milrinone impacted survival. DESIGN: A meta-analysis. SETTING: Hospitals. PARTICIPANTS: One thousand thirty-seven patients from 20 randomized trials. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Biomed, Central, PubMed, EMBASE, the Cochrane central register of clinical trials, and conference proceedings were searched for randomized trials that compared milrinone versus placebo or any other control in adult and pediatric patients undergoing cardiac surgery. Authors of trials that did not include mortality data were contacted. Only trials for which mortality data were available were included. Overall analysis showed no difference in mortality between patients receiving milrinone versus control (12/554 [2.2%] in the milrinone group v 10/483 [2.1%] in the control arm; relative risk [RR] = 1.15; 95% confidence interval [CI], 0.55-2.43; p = 0.7) or in analysis restricted to adults (11/364 [3%] in the milrinone group v 9/371 [2.4%] in the control arm; RR = 1.17; 95% CI, 0.54-2.53; p = 0.7). Sensitivity analyses in trials with a low risk of bias showed a trend toward an increase in mortality with milrinone (8/153 [5.2%] in the milrinone arm v 2/152 [1.3%] in the control arm; RR = 2.71; 95% CI, 0.82-9; p for effect = 0.10). CONCLUSIONS: Despite theoretic concerns for increased mortality with intravenous milrinone in patients undergoing cardiac surgery, the authors were unable to confirm an adverse effect on survival. However, sensitivity analysis of high-quality trials showed a trend toward increased mortality with milrinone.
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Procedimentos Cirúrgicos Cardíacos/mortalidade , Cardiotônicos/uso terapêutico , Milrinona/uso terapêutico , Adulto , Cardiotônicos/administração & dosagem , Criança , Pré-Escolar , Interpretação Estatística de Dados , Humanos , Milrinona/administração & dosagem , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background: Cardiovascular events have been reported to occur in one in five patients receiving chimeric antigen receptor T-cell (CAR-T) therapy. Commonly reported effects including cardiomyopathy, heart failure, myocardial infarction (MI), and arrhythmia. Here, we present a novel case of a patient who developed acute ST segment elevations during CAR-T cell infusion. Case summary: A 76-year-old man with diffuse large B cell lymphoma was admitted for an investigational CD-19 directed, autologous CAR-T cell therapy. Less than 5â min into the CAR-T cell infusion, he developed severe chest pain, dyspnea, flushing, hypotension, and tachycardia. Electrocardiogram (EKG) showed inferior ST elevations and reciprocal lateral ST depressions. Emergent coronary angiography revealed mild non-obstructive coronary disease. ST segment changes and patient symptoms resolved after catheterization. Discussion: Given the complete resolution of symptoms and EKG abnormalities in the context of non-obstructive coronary artery disease, this clinical presentation was thought to be most consistent with ST elevation MI due to coronary vasospasm. The mechanism of this vasospasm is as yet not understood and may be related to an anaphylactic reaction or a cardiotoxicity related to the cell therapy agent. As the use of CAR-T therapy continues to expand, there is a need to further characterize the full spectrum of its cardiotoxic effects.
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BACKGROUND: Hemodynamic-guided management with a pulmonary artery pressure sensor (CardioMEMS) is effective in reducing heart failure hospitalization in patients with chronic heart failure. This study aims to determine the feasibility and clinical utility of the CardioMEMS heart failure system to manage patients supported with left ventricular assist devices (LVADs). METHODS: In this multicenter prospective study, we followed patients with HeartMate II (n=52) or HeartMate 3 (n=49) LVADs and with CardioMEMS PA Sensors and measured pulmonary artery pressure, 6-minute walk distance, quality of life (EQ-5D-5 L scores), and heart failure hospitalization rates through 6 months. Patients were stratified as responders (R) and nonresponders to reductions in pulmonary artery diastolic pressure (PAD). RESULTS: There were significant reductions in PAD from baseline to 6 months in R (21.5-16.5 mm Hg; P<0.001), compared with an increase in NR (18.0-20.3; P=0.002), and there was a significant increase in 6-minute walk distance among R (266 versus 322 meters; P=0.025) compared with no change in nonresponder. Patients who maintained PAD <20 compared with PAD ≥20 mm Hg for more than half the time throughout the study (averaging 15.6 versus 23.3 mm Hg) had a statistically significant lower rate of heart failure hospitalization (12.0% versus 38.9%; P=0.005). CONCLUSIONS: Patients with LVAD managed with CardioMEMS with a significant reduction in PAD at 6 months showed improvements in 6-minute walk distance. Maintaining PAD <20 mm Hg was associated with fewer heart failure hospitalizations. Hemodynamic-guided management of patients with LVAD with CardioMEMS is feasible and may result in functional and clinical benefits. Prospective evaluation of ambulatory hemodynamic management in patients with LVAD is warranted. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03247829.
Assuntos
Insuficiência Cardíaca , Coração Auxiliar , Humanos , Artéria Pulmonar , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Qualidade de Vida , Estudos ProspectivosRESUMO
AIMS: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly being used to support patients in cardiogenic shock (CS). Early determination of disposition is paramount, as longer durations of support have been associated with worse outcomes. We describe a stepwise, bedside weaning protocol to assess cardiopulmonary recovery during VA-ECMO. METHODS AND RESULTS: Over 1 year, we considered all patients on VA-ECMO for CS for the Weaning Protocol (WP) at our centre. During the WP, patients had invasive haemodynamic monitoring, echocardiography, and blood gas analysis while flow was reduced in 1 LPM decrements. Ultimately, the circuit was clamped for 30 min, and final measures were taken. Patients were described as having durable recovery (DR) if they were free of pharmacological and mechanical support at 30 days post-decannulation. Over 12 months, 34 patients had VA-ECMO for CS. Fourteen patients were eligible for the WP at 4-12 days. Ten patients tolerated full flow reduction and were successfully decannulated. Twenty-four per cent of the entire cohort demonstrated DR with no adverse events during the WP. Patients with DR had significantly higher ejection fraction, cardiac index, and smaller left ventricular size at lowest flow during the WP. CONCLUSIONS: We describe a safe, stepwise, bedside weaning protocol to assess cardiac recovery during VA-ECMO. Early identification of patients more likely to recover may improve outcomes during ECMO support.
Assuntos
Oxigenação por Membrana Extracorpórea , Oxigenação por Membrana Extracorpórea/métodos , Coração , Humanos , Choque Cardiogênico/etiologia , Volume Sistólico , Função Ventricular EsquerdaRESUMO
Elevations in troponin levels have been shown to predict mortality in patients with coronavirus disease 2019 (COVID-19). The role of inflammation in myocardial injury remains unclear. We sought to determine the association of elevated troponin with mortality in a large, ethnically diverse population of patients hospitalized with COVID-19, and to determine the association of elevated inflammatory markers with increased troponin levels. We reviewed all patients admitted at our health system with COVID-19 from March 1 to April 27, 2020, who had a troponin assessment within 48 hours of admission. We used logistic regression to calculate odds ratios (ORs) for mortality during hospitalization, controlling for demographics, co-morbidities, and markers of inflammation. Of 11,159 patients hospitalized with COVID-19, 6,247 had a troponin assessment within 48 hours. Of these, 4,426 (71%) patients had normal, 919 (15%) had mildly elevated, and 902 (14%) had severely elevated troponin. Acute phase and inflammatory markers were significantly elevated in patients with mildly and severely elevated troponin compared with normal troponin. Patients with elevated troponin had significantly increased odds of death for mildly elevated compared with normal troponin (adjusted OR, 2.06; 95% confidence interval, 1.68 to 2.53; p < 0.001) and for severely elevated compared with normal troponin (OR, 4.51; 95% confidence interval, 3.66 to 5.54; p < 0.001) independently of elevation in inflammatory markers. In conclusion, patients hospitalized with COVID-19 and elevated troponin had markedly increased mortality compared with patients with normal troponin levels. This risk was independent of cardiovascular co-morbidities and elevated markers of inflammation.
Assuntos
COVID-19/sangue , COVID-19/mortalidade , SARS-CoV-2 , Troponina/sangue , Idoso , Biomarcadores/sangue , COVID-19/diagnóstico , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
Although statin therapy is a primary treatment to prevent cardiac allograft vasculopathy (CAV), its use may be delayed due to pharmacologic interactions in the early post-transplant period among heart transplant (HT) recipients with hepatitis C virus positive (HCV+) donors. Further examination of the possible benefits of early, nonstatin lipid-lowering therapies (LLT), such as PCSK9 inhibitors (PCSK9i), among this specific subset of transplant recipients is therefore becoming increasingly important. We report a 60-year-old man who received a HT from a HCV+ donor for end-stage ischemic cardiomyopathy. In the early post-transplant period, there was concern for drug-drug interactions between statin, immunosuppressant, and direct acting antiviral (DAA) therapy. In addition, prior to transplant, he reported statin-associated muscle symptoms in response to multiple statins, which persisted despite attempts to re-challenge and use an every-other-day dosing strategy. Therefore, the patient was started on PCSK9i therapy after transplantation and while receiving curative DAA therapy for HCV. As the number of HT recipients of HCV+ donors continue to rise, investigation into the safety and benefits of early use of PCSK9i for the reduction of CAV and improved cardiovascular and mortality outcomes should be pursued.