Sobrevida de Pacientes Transplantados Cardíacos com Doença de Chagas Sob Diferentes Regimes de Imunossupressores Antiproliferativos / Survival of Heart Transplant Patients with Chagas' Disease Under Different Antiproliferative Immunosuppressive Regimens

Resumo Fundamento A Doença de Chagas (DC) é uma causa importante de transplante cardíaco (TC). O principal obstáculo é a reativação da DC (RDC), normalmente associada a altas doses de imunossupressores. Estudos anteriores sugeriram uma associação do micofenolato de mofetila com aumento na RDC. No entanto, preditores de mortalidade são desconhecidos. Objetivos Identificar os fatores de risco de mortalidade em pacientes com DC após o TC e o impacto do regime antiproliferativo sobre a sobrevida. Métodos Estudo retrospectivo com pacientes chagásicos submetidos ao TC entre janeiro de 2004 e setembro de 2020, em protocolo de imunossupressão que priorizava o uso de azatioprina e sua mudança para micofenolato de mofetila em caso de rejeição. Realizamos regressão univariada para identificar preditores de mortalidade e comparamos sobrevida, rejeição, e evidência RDC entre os pacientes que usavam azatioprina, micofenolato de mofetila, e aqueles que mudaram de azatioprina para micofenolato (grupo "Mudança") após a alta. Um valor de p<0,05 foi considerado estatisticamente significativo. Resultados Foram incluídos 85 pacientes, 54,1% homens, idade mediana 49 (39-57) anos, e 91,8% com prioridade na lista de espera. Dezenove (22,4%) usavam azatioprina, 37 (43,5%) micofenolato de mofetila, e 29 (34,1%) trocaram a terapia; a sobrevida não foi diferente entre os grupos, 2,9 (1,6-5,0) x 2,9 (1,8-4,8) x 4,2 (2,0-5,0) anos, respectivamente; p=0,4. Não houve diferença na taxa de rejeição (42%, 73% e 59% respectivamente; p=0,08) ou de RDC (T. cruzi positiva na biópsia endomiocárdica 5% x 11% x 7%; p=0,7; uso benzonidazol 58% x 65% x 69%; p=0,8; PCR positiva para T. cruzi 20% x 68% x 42% respectivamente; p=0,1). Conclusões Este estudo retrospectivo com pacientes com DC e TC não mostrou diferença na sobrevida entre os diferentes regimes antiproliferativos. O uso de micofenolato de mofetila não foi associado com taxas significativamente mais altas de RDC ou rejeição do enxerto nesta coorte. Novos ensaios randomizados são necessários para abordar essa questão.

Abstract Background Chagas' disease (CD) is an important cause of heart transplantation (HT). The main obstacle is Chagas' disease reactivation (CDR), usually associated to high doses of immunosuppressants. Previous studies have suggested an association of mycophenolate mofetil with increased CDR. However, mortality predictors are unknown. Objectives To identify mortality risk factors in heart transplant patients with CD and the impact of antiproliferative regimen on survival. Methods Retrospective study with CD patients who underwent HT between January 2004 and September 2020, under immunosuppression protocol that prioritized azathioprine and change to mycophenolate mofetil in case of rejection. We performed univariate regression to identify mortality predictors; and compared survival, rejection and evidence of CDR between who received azathioprine, mycophenolate mofetil and those who changed from azathioprine to mycophenolate mofetil after discharge ("Change" group). A p-value < 0.05 was considered statistically significant. Results Eighty-five patients were included, 54.1% men, median age 49 (39-57) years, and 91.8% were given priority in waiting list. Nineteen (22.4%) used azathioprine, 37 (43.5%) mycophenolate mofetil and 29 (34.1%) switched therapy; survival was not different between groups, 2.9 (1.6-5.0) x 2.9 (1.8-4.8) x 4.2 (2.0-5.0) years, respectively; p=0.4. There was no difference in rejection (42%, 73% and 59% respectively; p=0.08) or in CDR (T. cruzi positive by endomyocardial biopsy 5% x 11% x 7%; p=0.7; benznidazole use 58% x 65% x 69%; p=0.8; positive PCR for T. cruzi 20% x 68% x 42% respectively; p=0.1) rates. Conclusions This retrospective study did not show difference in survival in heart transplant patients with CD receiving different antiproliferative regimens. Mycophenolate mofetil was not associated with statistically higher rates of CDR or graft rejection in this cohort. New randomized clinical trials are necessary to address this issue.

Estratégias Percutâneas em Doenças Estruturais: Foco em Insuficiência Cardíaca Crônica / Percutaneous Strategies in Structural Heart Diseases: Focus on Chronic Heart Failure

Resumo As inovações em dispositivos ao longo das últimas décadas proporcionaram uma melhora no diagnóstico e tratamento de pacientes com insuficiência cardíaca. Essas novas ferramentas progressivamente adaptaram-se a estratégias minimamente invasivas e as opções percutâneas multiplicaram-se de forma rápida. No presente artigo revisamos as direções atuais e futuras dos dispositivos utilizados como opções adjuvantes para o diagnóstico e tratamento adjuvante na insuficiência cardíaca crônica, o seu desenvolvimento, mecanismos e estudos mais recentes

Abstract Innovations in devices during the last decade contributed to enhanced diagnosis and treatment of patients with cardiac insufficiency. These tools progressively adapted to minimally invasive strategies with rapid, widespread use. The present article focuses on actual and future directions of device-related diagnosis and treatment of chronic heart failure.

Value-based health care in heart failure: Quality of life and cost analysis

Abstract Objectives: To measure Quality of Life (QoL) and costs of Heart Failure (HF) outpatients in Brazil as an introduction to the Value-Based Health Care (VBHC) concept. Materials and methods: Cross-sectional study, patients with HF, with ejection fraction <50%, were recruited from three hospitals in Brazil. Two QoL (36-Item Short Form Survey [SF-36] and Minnesota Living with Heart Failure Questionnaire [MLHFQ]) and two anxiety/depression questionnaires were applied. SF-36 scores were stratified by domains. Treatment costs were calculated using the Time-Driven Activity-Based Costing (TDABC) method. Results were stratified by NYHA functional class and sex. Results: From October 2018 to January 2021, 198 patients were recruited, and the median MLHFQ (49.5 [IQR 21.0, 69.0]) and SF-36 scores demonstrated poor QoL, worse at higher NYHA classes. A third of patients had moderate/severe depression and anxiety symptoms, and women had higher anxiety scores. Mean costs of outpatient follow-up were US$ 215 ± 238 for NYHA I patients, US$ 296 ± 399 for NYHA II and US$ 667 ± 1012 for NYHA III/IV. Lab/exam costs represented 30% of the costs in NYHA I, and 74% in NYHA III/IV (US $ 63.26 vs. US$ 491.05). Conclusion: Patients with HF in Brazil have poor QoL and high treatment costs; both worsen as the NYHA classification increases. It seems that HF has a greater impact on the mental health of women. Costs increase mostly related to lab/exams. Accurate and crossed information about QoL and costs is essential to drive care and reimbursement strategies based on value.

Prevalence and Association Between Cognition, Anxiety, and Depression in Patients Hospitalized with Heart Failure

Abstract Background Cognitive impairment, anxiety, and depression are present in patients with heart failure (HF), but their mutual correlation in hospitalized patients is not well established. Objectives The aims of this study were to identify the presence of cognitive impairment and the most affected domain, to investigate possible associations of cognitive impairment with depression and/or anxiety, and to observe whether they correlated with occurrence of readmission within 30 days following hospital discharge. Methods This is a prospective observational study including patients with HF from a private hospital. Psychological distress and cognition were evaluated by the Hospital Anxiety and Depression Scale (HADS) and by the Mini Mental State Exam (MMSE), respectively. Clinical data were obtained from the medical record at the time of inclusion, and outpatient follow-up was performed 30 days after discharge via telephone calls. Results This study included 71 patients (83% men, 75 ± 11 years). Cognitive impairment was present in 53.5% of the patients, and recall memory was the most altered cognitive domain. The proportion of possible/probable anxiety and depression was 21.1% and 34.2% in patients with cognitive impairment, respectively. However, only depression demonstrated association with cognitive impairment (p = 0.018). Cognitive impairment, anxiety, and depression showed no relationship with the occurrence of readmission within 30 days. Conclusions Cognitive impairment and depressive symptoms are prevalent and associated, and recall memory was the most altered cognitive domain in patients hospitalized with HF. However, there was no relationship between these factors and readmission within 30 days.

Índice Hemodinâmico Agudo Prediz Mortalidade Intra-Hospitalar de Pacientes com Insuficiência Cardíaca Aguda Descompensada / Acute Hemodynamic Index Predicts In-Hospital Mortality in Acute Decompensated Heart Failure

Resumo Fundamento O exame físico permite a avaliação prognóstica de pacientes com insuficiência cardíaca (IC) descompensada, porém não é suficientemente confiável e depende da experiência clínica do profissional. Considerando as respostas hemodinâmicas a situações do tipo "luta ou fuga" tais como a admissão no serviço de emergência, foi proposto o índice hemodinâmico agudo (IHA), calculado a partir da frequência cardíaca e pressão de pulso. Objetivo avaliar a capacidade prognóstica intra-hospitalar do IHA na IC descompensada. Métodos estudo prospectivo, multicêntrico e observacional baseado no registro BREATHE, incluindo dados de hospitais públicos e privados no Brasil. Foram utilizadas análises ROC (Receiver Operating Characteristic), de estatística c e de regressão multivariada, assim como o critério de informação de Akaike, para testar a capacidade prognóstica do IHA. O valor-p < 0,05 foi considerado estatisticamente significativo. Resultados Foram analisados dados de 463 pacientes com IC com fração de ejeção reduzida a partir do registro BREATHE. A mortalidade intra-hospitalar foi de 9%. A mediana do IHA foi considerada o valor de corte (4 mmHg⋅bpm). Um baixo IHA (≤ 4 mmHg⋅bpm) foi encontrado em 80% dos pacientes falecidos. O risco de mortalidade intra-hospitalar em pacientes com baixo IHA foi 2,5 vezes maior que aquele para pacientes com IHA > 4 mmHg⋅bpm. O IHA foi capaz de predizer independentemente a mortalidade intra-hospitalar na IC aguda descompensada [sensibilidade: 0,786; especificidade: 0,429; AUC (área sob a curva): 0,607 (0,540-0,674), p = 0,010] mesmo depois dos ajustes para comorbidades e uso de medicamentos [razão de chances (RC): 0,061 (0,007-0,114), p = 0,025]. Conclusões O IHA é capaz de predizer independentemente a mortalidade intra-hospitalar na IC aguda descompensada. Esse índice simples e realizado à beira do leito pode se mostrar útil em serviços de emergência. (Arq Bras Cardiol. 2021; 116(1):77-86)

Abstract Background The physical examination enables prognostic evaluation of patients with decompensated heart failure (HF), but lacks reliability and relies on the professional's clinical experience. Considering hemodynamic responses to "fight or flight" situations, such as the moment of admission to the emergency room, we proposed the calculation of the acute hemodynamic index (AHI) from values of heart rate and pulse pressure. Objective To evaluate the in-hospital prognostic ability of AHI in decompensated HF. Methods A prospective, multicenter, registry-based observational study including data from the BREATHE registry, with information from public and private hospitals in Brazil. The prognostic ability of the AHI was tested by receiver-operating characteristic (ROC) analyses, C-statistics, Akaike's information criteria, and multivariate regression analyses. p-values < 0.05 were considered statistically significant. Results We analyzed data from 463 patients with heart failure with low ejection fraction. In-hospital mortality was 9%. The median AHI value was used as cut-off (4 mmHg⋅bpm). A low AHI (≤ 4 mmHg⋅bpm) was found in 80% of deceased patients. The risk of in-hospital mortality in patients with low AHI was 2.5 times that in patients with AHI > 4 mmHg⋅bpm. AHI independently predicted in-hospital mortality in acute decompensated HF (sensitivity: 0.786; specificity: 0.429; AUC: 0.607 [0.540-0.674]; p = 0.010) even after adjusting for comorbidities and medication use [OR: 0.061 (0.007-0.114); p = 0.025). Conclusions The AHI independently predicts in-hospital mortality in acute decompensated HF. This simple bed-side index could be useful in an emergency setting. (Arq Bras Cardiol. 2021; 116(1):77-86)

C-Reactive protein level and left ventricular mass are associated with acute cellular rejection after heart transplant

OBJECTIVES: Acute cellular rejection (ACR) remains a major complication of heart transplant (HT). The gold standard for its diagnosis is endomyocardial biopsy (EMB), whereas the role of non-invasive biomarkers for detecting ACR is unclear. This study aimed to identify non-invasive biomarkers for the diagnosis of ACR in patients undergoing HT and presenting with normal left ventricular function. METHODS: We evaluated patients who underwent HT at a single center between January 2010 and June 2019. Patients were enrolled after HT, and those with left ventricular (LV) systolic dysfunction before EMB were excluded. We included only the results of the first EMB performed at least 30 days after HT (median, 90 days). Troponin, B-type natriuretic peptide (BNP), and C-reactive protein (CRP) levels were measured and echocardiography was performed up to 7 days before EMB. ACR was defined as International Society for Heart and Lung Transplantation grade 2R or 3R on EMB. We performed logistic regression analysis to identify the non-invasive predictors of ACR (2R or 3R) and evaluated the accuracy of each using area under the receiver operator characteristic curve analysis. RESULTS: We analyzed 72 patients after HT (51.31±13.63 years; 25 [34.7%] women); of them, 9 (12.5%) developed ACR. Based on multivariate logistic regression analysis, we performed forward stepwise selection (entry criteria, p<0.05). The only independent predictors that remained in the model were CRP level and LV mass index. The optimal cut-off point for CRP level was ≥15.9 mg/L (odds ratio [OR], 11.7; p=0.007) and that for LV mass index was ≥111 g/m2 (OR, 13.6; p=0.003). The area under the receiver operating characteristic curve derived from this model was 0.87 (95% confidence interval [CI], 0.75-0.99), with sensitivity of 85.7% (95% CI, 42.1%-99.6%), specificity of 78.4% (95% CI, 64.7%-88.7%), positive predictive value of 35.3% (95% CI, 14.3%-61.7%), and negative predictive value of 97.6% (95% CI, 87.1%-99.9%). CONCLUSIONS: Among patients undergoing HT, CRP level and LV mass were directly associated with ACR, but troponin and BNP levels were not.

Implante Percutâneo Transeptal de Bioprótese em Disfunção de Prótese Valvar Cirúrgica Mitral - Experiência Multicêntrica Brasileira / Percutaneous Transseptal Bioprosthetic Implantation in Failed Prosthetic Surgical Mitral Valve - Brazilian Multicenter Experience

Resumo Fundamento A intervenção percutânea em pacientes com disfunção de prótese biológica mitral apresenta-se como uma alternativa ao tratamento cirúrgico convencional. Objetivo Relatar a primeira experiência brasileira de implante transcateter de bioprótese valve-in-valve mitral via transeptal (TMVIV-via transeptal). Métodos Foram incluídos pacientes portadores de disfunção de bioprótese cirúrgica submetidos ao TMVIV-transeptal em 12 hospitais brasileiros. Foram considerados estatisticamente significativos valores de p<0,05. Resultados Entre junho/2016 e fevereiro/2019, 17 pacientes foram submetidos ao TMVIV-via transeptal. A mediana de idade foi 77 anos (IIQ,70-82), a mediana do escore STS-PROM foi 8,7% (IIQ,7,2-17,8). Todos os pacientes tinham sintomas limitantes de insuficiência cardíaca (CF≥III), tendo 5 (29,4%) sido submetidos a mais de uma toracotomia prévia. Obteve-se sucesso do TMVIV-via transeptal em todos os pacientes. A avaliação ecocardiográfica demonstrou redução significativa do gradiente médio (pré-intervenção, 12±3,8 mmHg; pós-intervenção, 5,3±2,6 mmHg; p<0,001), assim como aumento da área valvar mitral (pré-intervenção, 1,06±0,59 cm2; pós-intervenção, 2,18±0,36 cm2; p<0,001) sustentados em 30 dias. Houve redução significativa e imediata da pressão sistólica de artéria pulmonar, com redução adicional em 30 dias (pré-intervenção, 68,9±16,4 mmHg; pós-intervenção, 57,7±16,5 mmHg; 30 dias, 50,9±18,7 mmHg; p<0,001). Durante o seguimento, com mediana de 162 dias (IIQ, 102-411), observou-se marcada melhora clínica (CF≤II) em 87,5%. Um paciente (5,9%) apresentou obstrução de via de saída de ventrículo esquerdo (VSVE), evoluindo para óbito logo após o procedimento, e outro morreu aos 161 dias de seguimento.Conclusão: A primeira experiência brasileira de TMVIV-transeptal demonstra a segurança e a efetividade dessa nova técnica. A obstrução da VSVE é uma complicação potencialmente fatal, reforçando a importância da seleção dos pacientes e do planejamento do procedimento. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)

Abstract Background Percutaneous intervention in patients with bioprosthetic mitral valve dysfunction is an alternative to conventional surgical treatment. Objectives To report the first Brazilian experience with transseptal transcatheter bioprosthetic mitral valve-in-valve implantation (transseptal-TMVIV). Methods Patients with surgical bioprosthetic dysfunction submitted to transseptal-TMVIV in 12 Brazilian hospitals were included. The significance level adopted was p<0.05. Results From June/2016 to February/2019, 17 patients underwent transseptal-TMVIV. Their median age was 77 years (IQR,70-82) and median Society of Thoracic Surgeons predicted risk of mortality (STS-PROM) score was 8.7% (IQR,7.2-17.8). All patients had limiting symptoms of heart failure (FC≥III) and 5 (29.4%) had undergone more than one previous thoracotomy. Transseptal-TMVIV was successful in all patients. Echocardiographic assessment showed a significant reduction in mean mitral valve gradient (pre-intervention, 12±3.8 mmHg; post-intervention, 5.3±2.6 mmHg; p<0.001), in addition to an increase in mitral valve area (pre-intervention, 1.06±0.59 cm2; post-intervention, 2.18±0.36 cm2; p<0.001) sustained for 30 days. There was a significant and immediate reduction in the pulmonary artery systolic pressure, with an additional reduction in 30 days (pre-intervention, 68.9±16.4 mmHg; post-intervention, 57.7±16.5 mmHg; 30 days, 50.9±18.7 mmHg; p<0.001). During follow-up (median, 162 days; IQR, 102-411), significant clinical improvement (FC≤II) was observed in 87.5% of the patients. One patient (5.9%) had left ventricular outflow tract (LVOT) obstruction and died right after the procedure, and another died at 161 days of follow-up. Conclusion The first Brazilian experience with transseptal-TMVIV shows the safety and effectivity of the new technique. The LVOT obstruction is a potentially fatal complication, reinforcing the importance of patients' selection and of procedural planning. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)