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1.
Crit Care ; 28(1): 105, 2024 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566212

RESUMO

BACKGROUND: Observational data suggest that the subset of patients with heart failure related CS (HF-CS) now predominate critical care admissions for CS. There are no dedicated HF-CS randomised control trials completed to date which reliably inform clinical practice or clinical guidelines. We sought to identify aspects of HF-CS care where both consensus and uncertainty may exist to guide clinical practice and future clinical trial design, with a specific focus on HF-CS due to acute decompensated chronic HF. METHODS: A 16-person multi-disciplinary panel comprising of international experts was assembled. A modified RAND/University of California, Los Angeles, appropriateness methodology was used. A survey comprising of 34 statements was completed. Participants anonymously rated the appropriateness of each statement on a scale of 1 to 9 (1-3 as inappropriate, 4-6 as uncertain and as 7-9 appropriate). RESULTS: Of the 34 statements, 20 were rated as appropriate and 14 were rated as inappropriate. Uncertainty existed across all three domains: the initial assessment and management of HF-CS; escalation to temporary Mechanical Circulatory Support (tMCS); and weaning from tMCS in HF-CS. Significant disagreement between experts (deemed present when the disagreement index exceeded 1) was only identified when deliberating the utility of thoracic ultrasound in the immediate management of HF-CS. CONCLUSION: This study has highlighted several areas of practice where large-scale prospective registries and clinical trials in the HF-CS population are urgently needed to reliably inform clinical practice and the synthesis of future societal HF-CS guidelines.


Assuntos
Insuficiência Cardíaca , Choque Cardiogênico , Humanos , Consenso , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Hospitalização , Estudos Prospectivos , Choque Cardiogênico/tratamento farmacológico
2.
Clin Transplant ; 36(7): e14733, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35652422

RESUMO

BACKGROUND: A growing proportion of transplant donors and recipients have a history of COVID-19 infection. This study sought to characterize clinical practice after recipient or donor COVID-19 infection. METHODS: An online survey was distributed to heart transplant clinicians through a professional society message board and social media. Responses were collected between September 29 and November 5, 2021. RESULTS: There were 222 health care professionals (68% transplant cardiologists, 22% transplant surgeons, 10% other) across diverse geographic regions who completed the survey. While there was significant variation in donor acceptance, as it relates to past and current COVID-19 infection, the respondents were fairly cautious: 28% would not typically accept a donor with a history of COVID-19 regardless of the infection course and > 80% would not accept donors who had evidence of myocardial dysfunction during past COVID-19 infection, or who died of COVID-19 or its complications. The timing of candidate reactivation on the waiting list after COVID-19 infection also varied and often diverged from scenarios addressed by social guidelines. Eighty-one percent of the respondents felt COVID-19 vaccine should be mandatory before transplant, but this rate varied by geographic region. CONCLUSION: Our results reflect evolving experience of the heart transplant field at a time of lack of high-quality evidence. In the absence of longer-term outcome data for donors and transplant candidates with history of COVID-19 infection, clinicians remain cautious; however, this approach will likely need to be refined as an increasing proportion of the population will continue to be infected with COVID-19.


Assuntos
COVID-19 , Transplante de Coração , COVID-19/epidemiologia , Vacinas contra COVID-19 , Humanos , Inquéritos e Questionários , Doadores de Tecidos , Transplantados
3.
Curr Opin Organ Transplant ; 27(1): 29-35, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34939962

RESUMO

PURPOSE OF REVIEW: Cardiovascular disease is one of the leading causes of death in solid organ transplant (SOT) recipients. Early identification of cardiovascular risk factors and their adequate management in this population is key for prevention and improved outcomes. RECENT FINDINGS: Approximately 80% of SOT present one or more cardiovascular risk factors, with increasing prevalence with time posttransplantation. They are due to the interplay of pretransplant conditions and metabolic consequences of immunosuppressive agents, mainly corticosteroids and calcineurin inhibitors. Among the pharmacological management strategies, statins have shown an important protective effect in SOT. SUMMARY: Strict surveillance of cardiovascular risk factors is recommended in SOT due to their high prevalence and prognostic implications. Further studies on the best managements strategies in this population are needed.


Assuntos
Doenças Cardiovasculares , Transplante de Órgãos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Fatores de Risco de Doenças Cardíacas , Humanos , Transplante de Órgãos/efeitos adversos , Fatores de Risco , Transplantados
4.
Am J Transplant ; 21(12): 3971-3979, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34291552

RESUMO

Recently published studies have found an impaired immune response after SARS-CoV-2 vaccination in solid organ recipients. However, most of these studies have not assessed immune cellular responses in liver and heart transplant recipients. We prospectively studied heart and liver transplant recipients eligible for SARS-CoV-2 vaccination. Patients with past history of SARS-CoV-2 infection or SARS-CoV-2 detectable antibodies (IgM or IgG) were excluded. We assessed IgM/IgG antibodies and ELISpot against the S protein 4 weeks after receiving the second dose of the mRNA-1273 (Moderna) vaccine. Side effects, troponin I, liver tests and anti-HLA donor-specific antibodies (DSA) were also assessed. A total of 58 liver and 46 heart recipients received two doses of mRNA-1273 vaccine. Median time from transplantation to vaccination was 5.4 years (IQR 0.3-27). Sixty-four percent of the patients developed SARS-CoV-2 IgM/IgG antibodies and 79% S-ELISpot positivity. Ninety percent of recipients developed either humoral or cellular response (87% in heart recipients and 93% in liver recipients). Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation. Local and systemic side effects were mild or moderate, and none presented DSA or graft dysfunction after vaccination. Ninety percent of our patients did develop humoral or cellular responses to mRNA-1273 vaccine. Factors associated with vaccine unresponsiveness were hypogammaglobulinemia and vaccination during the first year after transplantation, highlighting the need to further protect these patients.


Assuntos
COVID-19 , Transplante de Coração , Anticorpos Antivirais , Vacinas contra COVID-19 , Humanos , Imunidade Humoral , Fígado , SARS-CoV-2 , Transplantados
5.
Catheter Cardiovasc Interv ; 97(3): 376-383, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-32096926

RESUMO

BACKGROUND: Chronic total occlusion (CTO) is common in patients with diabetes mellitus. Data on the long-term outcomes after treatment of CTOs in this high-risk population are scarce. AIM: To compare the long-term clinical outcomes of CTO revascularization either by coronary artery bypass graft (CABG) or successful percutaneous coronary intervention (PCI) versus optimal medical treatment (MT) alone in patients with diabetes. METHODS AND RESULTS: A total of 538 consecutive patients with diabetes and at least one CTO were identified from 2010 to 2014 in our center. In the present analysis, patients were stratified according to the CTO treatment strategy that was selected. MT was selected in 61% of patients whereas revascularization in the remaining 39%. Patients undergoing revascularization were younger, had higher left ventricular ejection fraction (LVEF), lower ACEF score, and more positive myocardial ischemia detection results compared to the MT group (p < .001).Patients referred for CABG had higher rates of left main disease compared to the PCI and MT groups (32% vs. 3% and 11%, respectively; p < .001). Complete revascularization was more often achieved in the CABG group, compared to the PCI group (62% vs. 32% p < .001). Multivariable analysis showed that revascularization with CABG was associated with lower rates of all-cause and cardiac mortality rates compared to MT, [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.25-0.70, p < .001 and HR 0.40, 95% CI 0.20-81, p = .011, respectively]. Successful CTO-PCI showed a trend towards benefit in all-cause mortality (HR 0.58, 95% CI 0.33-1.04, p = .06). CONCLUSION: In our registry, CTO revascularization in diabetic patients, especially with CABG, was associated with lower long-term mortality rates as compared to MT alone.


Assuntos
Oclusão Coronária , Diabetes Mellitus , Intervenção Coronária Percutânea , Doença Crônica , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Diabetes Mellitus/diagnóstico , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Fatores de Risco , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
6.
Clin Transplant ; 34(8): e13994, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32463124

RESUMO

Vasoplegic syndrome (VS) is associated with poor outcomes after heart transplantation (HT). Our aim was to determine whether SAC/VALS is associated with VS after HT. We retrospectively analyzed all consecutive HT performed in three centers between January 2017 and August 2018. VS was defined as vasopressor need (norepinephrine or epinephrine >.5 mcg/kg/min or vasopressin) for more than 24 hours to maintain a mean arterial pressure >70 mm Hg. Ninety-six recipients underwent HT in the study period: 60 elective HT with no LVAD, 5 elective HT on long term LVAD, and 31 emergent HT: 3 on long-term LVAD and 28 on temporary mechanical circulatory support. Fourteen patients were on SAC/VALS treatment at the time of transplant, and 82 were not. The global incidence of VS was 15.6%, with no significant differences between the groups (7.14% in with SAC/VALS vs 17.07% in no-SAC/VALS). In conclusion, in our small cohort SAC/VALS was not associated with VS development.


Assuntos
Transplante de Coração , Coração Auxiliar , Vasoplegia , Aminobutiratos , Compostos de Bifenilo , Combinação de Medicamentos , Transplante de Coração/efeitos adversos , Humanos , Incidência , Estudos Retrospectivos , Valsartana , Vasoplegia/tratamento farmacológico , Vasoplegia/epidemiologia , Vasoplegia/etiologia
7.
Clin Transplant ; 33(7): e13596, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31102488

RESUMO

BACKGROUND AND AIMS: Heart transplantation (HT) is the treatment of choice for selected cases of advanced heart failure. There is an increasing rate of emergency HT in our country. The aim of this study was to determine the cost of HT in our hospital according to emergent vs. elective transplantation status. METHODS: The costs of all consecutive HTs performed in our center between January 2010 and May 2015 were analyzed. The cost of elective and emergent HT was compared. RESULTS: HT mean cost at our institution was €62 203 ± 47 976. Elective HT mean cost was €47 540 ± 25 140, whereas emergent HT cost was €102 733 ± 68 050 (emergency status 1, as regional priority, was €66 077 ± 28 067 and emergency status 0, as the highest national priority, was €136 056 ± 77 080; P < 0.001). Increased emergent HT cost was mainly related to a longer admission (32 ± 24 days vs. 69 ± 53 days; P = 0.006; accounting for a cost of €14 517 ± 12 475 vs. €37 846 ± 31 702; P < 0.001) and increased drug-related expenses (€6622 ± 7465 vs. €15,171 ± 15,758; P < 0.02). Elective HT survival rate was 96%, compared to 68% for emergent HT; P = 0.002. CONCLUSIONS: Elective HT showed a high survival rate with a relatively low and less variable cost, leading to a favorable economic balance in today's public health reimbursement system. In contrast, emergent HT showed a higher cost and a lower survival rate. New treatment strategies should be identified for heart failure patients at risk of requiring emergency HT.


Assuntos
Custos e Análise de Custo/métodos , Procedimentos Cirúrgicos Eletivos/economia , Emergências/economia , Transplante de Coração/economia , Hospitalização/economia , Adulto , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Seguimentos , Transplante de Coração/mortalidade , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida
8.
Clin Transplant ; 32(9): e13364, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30058129

RESUMO

BACKGROUND: Pulmonary hypertension (PH) after heart transplantation (HT) is associated to right ventricular (RV) dysfunction and increased morbidity and mortality. We present our experience with bosentan for the treatment of PH after HT. METHODS: A retrospective evaluation of patients with PH receiving bosentan post-transplant was performed. Pulmonary hemodynamics before and after bosentan (BG) and clinical outcomes were assessed and compared to a historical control group (CG) not receiving bosentan. RESULTS: Between 2013 and 2016, 21 patients were treated post-transplant with bosentan. Twenty-four hours after bosentan initiation, there were significant decreases in systolic (42.5 ± 8 to 38.1 ± 8 mm Hg, P = 0.015), diastolic (21.4 ± 4 to 17.8 ± 6 mm Hg, P = 0.008) and mean (29.6 ± 5 to 25 ± 6 mm Hg, P = 0.001) pulmonary artery pressures (PAP), transpulmonary gradient (13.1 ± 3 to 9.7 ± 4 mm Hg, P < 0.001), diastolic gradient (5.2 ± 4 to 2.3 ± 3 mm Hg, P = 0.001) and pulmonary vascular resistance (PVR) (2.2 ± 1 to 1.6 ± 1WU, P = 0.015). This effect was maintained at day 3. Compared with CG, BG showed significantly more decrease in PVR (0.7 ± 0.9 vs 0.3 ± 1.7WU, P = 0.025) and mean PAP (4.6 ± 5.2 vs 1.5 ± 4.4 mm Hg, P = 0.040). RV function 7 days post-transplant was significantly better in BG compared to CG, P = 0.004. There were not clinically significant interactions between bosentan and immunosuppressive treatment. CONCLUSIONS: Bosentan, initiated early post-transplant, was associated with a significant decrease in PVR. Bosentan was well tolerated and did not interact with immunosuppressive treatment.


Assuntos
Anti-Hipertensivos/uso terapêutico , Bosentana/uso terapêutico , Transplante de Coração/efeitos adversos , Hipertensão Pulmonar/tratamento farmacológico , Disfunção Ventricular Direita/prevenção & controle , Gerenciamento Clínico , Feminino , Seguimentos , Hemodinâmica , Humanos , Hipertensão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
11.
J Heart Lung Transplant ; 43(6): 1010-1020, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38360159

RESUMO

Heart transplantation remains the gold standard treatment for end-stage heart failure patients without contraindications. However, limited donor availability and long wait times have created a need for left ventricular assist devices (LVAD) to be used as a bridge to transplantation in appropriately selected patients. Improvements in LVAD technology have resulted in improved short- and long-term outcomes, further supporting the use of these devices for a bridge-to-transplant (BTT) indication. LVAD utilization as BTT exhibits notable disparities worldwide, mainly due to variations in organ availability, allocation policies, and financial constraints. Although Europe has experienced a consistent increase in the use of LVAD for this purpose, the United Network for Organ Sharing 2018 policy amendment resulted in a significant reduction in the number of LVADs used for BTT in the US. To overcome this issue, modifications in the US allocation policy to consider factors such as days on device support, age, and type of complications may be necessary to potentially increase implantation rates.The authors provide an overview comparing the current state of heart transplantation in the US and Europe, with a particular focus on how distinct allocation policies and organ availability impact medical practices. Additionally, the review will examine critical aspects ranging from patient selection and pre-implantation optimization to post-transplant outcomes.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Listas de Espera , Humanos , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/terapia , Europa (Continente) , Obtenção de Tecidos e Órgãos , Estados Unidos , Seleção de Pacientes
12.
Rev Esp Cardiol (Engl Ed) ; 77(4): 304-313, 2024 Apr.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37984703

RESUMO

INTRODUCTION AND OBJECTIVES: Posttransplant outcomes among recipients with a diagnosis of hypertrophic cardiomyopathy (HCM) or restrictive cardiomyopathy (RCM) remain controversial. METHODS: Retrospective analysis of a nationwide registry of first-time recipients undergoing isolated heart transplant between 1984 and 2021. One-year and 5-year mortality in recipients with HCM and RCM were compared with those with dilated cardiomyopathy (DCM). RESULTS: We included 3703 patients (3112 DCM; 331 HCM; 260 RCM) with a median follow-up of 5.0 [3.1-5.0] years. Compared with DCM, the adjusted 1-year mortality risk was: HCM: HR, 1.38; 95%CI, 1.07-1.78; P=.01, RCM: HR, 1.48; 95%CI, 1.14-1.93; P=.003. The adjusted 5-year mortality risk was: HCM: HR, 1.17; 95%CI, 0.93-1.47; P=.18; RCM: HR, 1.52; 95%CI, 1.22-1.89; P<.001. Over the last 20 years, the RCM group showed significant improvement in 1-year survival (adjusted R2=0.95) and 5-year survival (R2=0.88); the HCM group showed enhanced the 5-year survival (R2=0.59), but the 1-year survival remained stable (R2=0.16). CONCLUSIONS: Both RCM and HCM were linked to a less favorable early posttransplant prognosis compared with DCM. However, at the 5-year mark, this unfavorable difference was evident only for RCM. Notably, a substantial temporal enhancement in both early and late mortality was observed for RCM, while for HCM, this improvement was mainly evident in late mortality.


Assuntos
Cardiomiopatia Dilatada , Cardiomiopatia Hipertrófica , Cardiomiopatia Restritiva , Transplante de Coração , Humanos , Cardiomiopatia Restritiva/cirurgia , Estudos Retrospectivos , Prognóstico , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/cirurgia , Cardiomiopatia Dilatada/cirurgia , Sistema de Registros
13.
Rev Esp Cardiol (Engl Ed) ; 77(1): 69-78, 2024 Jan.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-37926340

RESUMO

Heart transplant (HT) remains the best therapeutic option for patients with advanced heart failure (HF). The allocation criteria aim to guarantee equitable access to HT and prioritize patients with a worse clinical status. To review the HT allocation criteria, the Heart Failure Association of the Spanish Society of Cardiology (HFA-SEC), the Spanish Society of Cardiovascular and Endovascular Surgery (SECCE) and the National Transplant Organization (ONT), organized a consensus conference involving adult and pediatric cardiologists, adult and pediatric cardiac surgeons, transplant coordinators from all over Spain, and physicians and nurses from the ONT. The aims of the consensus conference were as follows: a) to analyze the organization and management of patients with advanced HF and cardiogenic shock in Spain; b) to critically review heart allocation and priority criteria in other transplant organizations; c) to analyze the outcomes of patients listed and transplanted before and after the modification of the heart allocation criteria in 2017; and d) to propose new heart allocation criteria in Spain after an analysis of the available evidence and multidisciplinary discussion. In this article, by the HFA-SEC, SECCE and the ONT we present the results of the analysis performed in the consensus conference and the rationale for the new heart allocation criteria in Spain.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Adulto , Humanos , Criança , Espanha/epidemiologia , Insuficiência Cardíaca/cirurgia , Consenso , Choque Cardiogênico
14.
Clin Transplant ; 27(1): 25-31, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22861120

RESUMO

BACKGROUND: Increased pulmonary vascular resistance (PVR) is associated with increased right ventricular failure and mortality after heart transplantation. METHODS: In this prospective study, 22 patients considered high-risk candidates for heart transplantation because of severe pulmonary hypertension (PVR = 6 ± 2 Wood units; transpulmonary gradient 22 ± 7 mmHg), received bosentan 125 mg bid. Right heart catheterization was repeated after four months (n = 22) and 12 months (n = 9). Eleven patients who declined participation in the study were considered as control group. RESULTS: After four months, PVR decreased by 38% in patients receiving bosentan (n = 22), while it increased by 25% in the control group (p = 0.001). Those patients who received bosentan for 12 months (n = 9), experienced a 60% reduction in PVR compared to baseline (p = 0.003). Only three patients (14%) had no hemodynamic improvement with bosentan. After bosentan therapy, 14 patients (64%) underwent heart transplantation. Patients with high PVR who received bosentan showed a trend toward better one-yr survival after transplantation than patients with PVR ≤ 2.5 Wood units transplanted in the same period of time (93% vs. 83%). CONCLUSIONS: In patients considered high-risk candidates for heart transplantation because of high PVR, therapy with bosentan is associated with a significant reduction in PVR and a good outcome after transplantation.


Assuntos
Anti-Hipertensivos/uso terapêutico , Insuficiência Cardíaca/complicações , Transplante de Coração/mortalidade , Hipertensão Pulmonar/tratamento farmacológico , Sulfonamidas/uso terapêutico , Bosentana , Feminino , Seguimentos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Segurança
15.
Clin Transplant ; 27(6): E649-58, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24025040

RESUMO

We sought to determine the incidence, risk factors, and consequences of acute rejection (AR) after conversion from a calcineurin inhibitor (CNI) to a proliferation signal inhibitor (PSI) in maintenance heart transplantation. Relevant clinical data were retrospectively obtained for 284 long-term heart transplant recipients from nine centers in whom CNIs were replaced with a PSI (sirolimus or everolimus) between October 2001 and March 2009. The rejection rate at one yr was 8.3%, stabilizing to 2% per year thereafter. The incidence rate after conversion (4.9 per 100 patient-years) was significantly higher than that observed on CNI therapy in the pre-conversion period (2.2 per 100 patient-years). By multivariate analysis, rejection risk was associated with a history of late AR prior to PSI conversion, early conversion (<5 yr) after transplantation and age <50 yr at the time of conversion. Use of mycophenolate mofetil was a protective factor. Post-conversion rejection did not significantly influence the evolution of left ventricular ejection fraction, renal function, or mortality during further follow-up. Conversion to a CNI-free immunosuppression based on a PSI results in an increased risk of AR. Awareness of the clinical determinants of post-conversion rejection could help to refine the current PSI conversion strategies.


Assuntos
Inibidores de Calcineurina , Rejeição de Enxerto/etiologia , Transplante de Coração , Imunossupressores/uso terapêutico , Idoso , Proliferação de Células/efeitos dos fármacos , Everolimo , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Espanha/epidemiologia , Taxa de Sobrevida
16.
Front Cardiovasc Med ; 10: 1255503, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37859684

RESUMO

There is a growing interest in the evaluation of tricuspid regurgitation due to its increasing prevalence and detrimental impact on clinical outcomes. Historically, it has been coined the "forgotten" defect in the field of valvular heart disease due to the lack of effective treatments to improve prognosis. However, the development of percutaneous treatment techniques has led to a new era in its management, with promising results and diminished complication risk. In spite of these advances, a comprehensive exploration of the pathophysiological mechanisms is essential to establish clear indications and optimal timing for medical and percutaneous intervention. This review will address the most important aspects related to the diagnosis, pathophysiology and treatment of tricuspid regurgitation from a cardiorenal perspective, with a special emphasis on the interaction between right ventricular dysfunction and the development of hepatorenal congestion.

17.
J Pers Med ; 13(3)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36983628

RESUMO

Heart failure (HF) is classified according to the degree of reduction in left ventricular ejection fraction (EF) in HF with reduced, mildly reduced, and preserved EF. Biomarkers could behave differently depending on EF type. Here, we analyze the soluble form of the AXL receptor tyrosine kinase (sAXL) in HF patients with reduced and preserved EF. Two groups of HF patients with reduced (HFrEF; n = 134) and preserved ejection fraction (HFpEF; n = 134) were included in this prospective observational study, with measurements of candidate biomarkers and functional, clinical, and echocardiographic variables. A Cox regression model was used to determine predictors for clinical events: cardiovascular mortality and all-cause mortality. sAXL circulating values predicted outcome in HF: for a 1.0 ng/mL increase in serum sAXL, the mortality hazard ratio (HR) was 1.019 for HFrEF (95% CI 1.000 to 1.038) and 1.032 for HFpEF (95% CI 1.013 to 1.052). In a multivariable Cox regression analysis, sAXL and NT-proBNP were independent markers for all-cause and cardiovascular mortality in HFpEF. In contrast, only NT-proBNP remained significant in the HFrEF group. When analyzing the event-free survival at a mean follow-up of 3.6 years, HFrEF and HFpEF patients in the higher quartile of sAXL had a reduced survival time. Interestingly, sAXL is a reliable predictor for all-cause and cardiovascular mortality only in the HFpEF cohort. The results suggest an important role for AXL in HFpEF, supporting sAXL evaluation in larger clinical studies and pointing to AXL as a potential target for HF therapy.

18.
Vaccines (Basel) ; 11(12)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38140248

RESUMO

The aim of the present study was to determine humoral and T-cell responses after four doses of mRNA-1273 vaccine in solid organ transplant (SOT) recipients, and to study predictors of immunogenicity, including the role of previous SARS-CoV-2 infection in immunity. Secondarily, safety was also assessed. Liver, heart, and kidney transplant recipients eligible for SARS-CoV-2 vaccination from three different institutions in Barcelona, Spain were included. IgM/IgG antibodies and T cell ELISpot against the S protein four weeks after receiving four consecutive booster doses of the vaccine were analyzed. One hundred and forty-three SOT recipients were included (41% liver, 38% heart, and 21% kidney). The median time from transplantation to vaccination was 6.6 years (SD 7.4). In total, 93% of the patients developed SARS-CoV-2 IgM/IgG antibodies and 94% S-ELISpot positivity. In total, 97% of recipients developed either humoral or cellular response (100% of liver recipients, 95% of heart recipients, and 88% of kidney recipients). Hypogammaglobulinemia was associated with the absence of SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity after vaccination, whereas past symptomatic SARS-CoV-2 infection was associated with SARS-CoV-2 IgG/IgM antibodies and S-ELISpot reactivity. Local and systemic side effects were generally mild or moderate, and no recipients experienced the development of de novo DSA or graft dysfunction following vaccination.

19.
Clin Microbiol Infect ; 29(5): 655.e1-655.e4, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36641051

RESUMO

OBJECTIVES: To review the drug-drug interactions between tacrolimus and lopinavir/ritonavir in 23 patients who received solid organ transplant during the first wave of COVID-19 and to determine the efficacy as well as safety of prednisone monotherapy. METHODS: Observational study performed between March and June 2020 in solid organ transplant recipients admitted with an established diagnosis of SARS-CoV-2 infection who received lopinavir/ritonavir (≥2 doses). Once lopinavir/ritonavir therapy was initiated, calcineurin inhibitor treatment was temporarily switched to prednisone monotherapy (15-20 mg/d) to avoid drug-drug interactions and toxicity. After lopinavir/ritonavir treatment completion, immunosuppressive treatment was restarted with reduced doses of prednisone-tacrolimus (target minimum blood concentration -C0- approximately 5 ng/mL). Patients were observed for 3 months to confirm the absence of rejection. RESULTS: The median time from discontinuation of tacrolimus to initiation of lopinavir/ritonavir was 14 hours (interquartile range [IQR], 12-15) and from discontinuation of lopinavir/ritonavir to resumption of tacrolimus 58 hours (IQR, 47-81). The duration of lopinavir/ritonavir treatment was 7 days (IQR, 5-7). Nine of the 21 (42.8%) patients on tacrolimus treatment had C0 above the cutoff point after lopinavir/ritonavir initiation, despite having been substituted with prednisone before lopinavir/ritonavir initiation. Three patients had very high concentrations (>40 ng/mL) and developed toxicity. No episodes of acute rejection were diagnosed. DISCUSSION: We did not observe toxicity in patients for whom tacrolimus was discontinued 24 hours before starting lopinavir/ritonavir and reintroduced at half dose 48 to 72 hours after lopinavir/ritonavir discontinuation. Prednisone monotherapy during lopinavir/ritonavir therapy was safe with no episodes of acute rejection. Experience with lopinavir/ritonavir may be applicable to the use of nirmatrelvir/ritonavir, but larger multicentre studies are needed to confirm these findings.


Assuntos
COVID-19 , Transplante de Órgãos , Humanos , Ritonavir/efeitos adversos , Lopinavir/efeitos adversos , SARS-CoV-2 , Inibidores de Proteases , Tacrolimo/efeitos adversos , Prednisona/efeitos adversos , Tratamento Farmacológico da COVID-19 , Interações Medicamentosas , Transplantados
20.
J Clin Med ; 12(11)2023 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-37297919

RESUMO

(1) Background and aim: This study aimed to investigate the impact of prehabilitation on the postoperative outcomes of heart transplantation and its cost-effectiveness. (2) Methods: This single-center, ambispective cohort study included forty-six candidates for elective heart transplantation from 2017 to 2021 attending a multimodal prehabilitation program consisting of supervised exercise training, physical activity promotion, nutritional optimization, and psychological support. The postoperative course was compared to a control cohort consisting of patients transplanted from 2014 to 2017 and those contemporaneously not involved in prehabilitation. (3) Results: A significant improvement was observed in preoperative functional capacity (endurance time 281 vs. 728 s, p < 0.001) and quality-of-life (Minnesota score 58 vs. 47, p = 0.046) after the program. No exercise-related events were registered. The prehabilitation cohort showed a lower rate and severity of postoperative complications (comprehensive complication index 37 vs. 31, p = 0.033), lower mechanical ventilation time (37 vs. 20 h, p = 0.032), ICU stay (7 vs. 5 days, p = 0.01), total hospitalization stay (23 vs. 18 days, p = 0.008) and less need for transfer to nursing/rehabilitation facilities after hospital discharge (31% vs. 3%, p = 0.009). A cost-consequence analysis showed that prehabilitation did not increase the total surgical process costs. (4) Conclusions: Multimodal prehabilitation before heart transplantation has benefits on short-term postoperative outcomes potentially attributable to enhancement of physical status, without cost-increasing.

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