Use of the ADHERE Risk Model as a Predictor of Risk of in-Hospital Worsening Heart Failure in a Cohort. / Uso do Modelo de Risco ADHERE como Preditor de Piora Intra-Hospitalar de Insuficiência Cardíaca em uma Coorte.

BACKGROUND: Patients admitted with acute decompensated heart failure (HF) are subject to developing worsening episodes that require more complex interventions. The Acute Decompensated Heart Failure National Registry (ADHERE) risk model was developed in the United States to predict the risk of in-hospital worsening HF. OBJECTIVE: To use the ADHERE risk model in the assessment of risk of in-hospital worsening HF and to determine its sensitivity and specificity in hospitalized patients. METHODS: This cohort study was conducted at a Brazilian public university hospital, and data from 2013 to 2020 were retrospectively collected. P values < 0.05 were considered statistically significant. RESULTS: A total of 890 patients with a mean age of 74 ± 8 years were included. The model showed that, in the group of 490 patients at risk, 254 (51.8%) developed in-hospital worsening HF. In the group of 400 patients not at risk, only 109 (27.2%) experienced worsening HF. The results demonstrated a statistically significant curve (area under the curve = 0.665; standard error = 0.018; P < 0.01; confidence interval = 0.609 to 0.701), indicating good accuracy. The model had a sensitivity of 69.9% and a specificity of 55.2%, with a positive predictive value of 52% and a negative predictive value of 72.7%. CONCLUSIONS: In this cohort, we showed that the ADHERE risk model was able to discriminate patients who in fact developed worsening HF during the admission period, from those who did not.

FUNDAMENTO: Pacientes hospitalizados com insuficiência cardíaca (IC) aguda descompensada estão sujeitos a desenvolver episódios de piora que requerem intervenções mais complexas. O modelo de predição de risco "Acute Decompensated Heart Failure National Registry" (ADHERE) foi desenvolvido nos Estados Unidos para prever o risco de piora intra-hospitalar da IC. OBJETIVO: Utilizar o modelo de predição de risco ADHERE para avaliar o risco de piora intra-hospitalar da IC e determinar a sua sensibilidade e especificidade em pacientes hospitalizados. MÉTODOS: O presente estudo de coorte foi realizado em um hospital universitário público brasileiro e os dados de 2013 a 2020 foram coletados retrospectivamente. Foram considerados estatisticamente significativos valores de p < 0,05. RESULTADOS: Foram incluídos 890 pacientes com idade média de 74 ± 8 anos. O modelo mostrou que no grupo de 490 pacientes de risco, 254 (51,8%) desenvolveram piora intra-hospitalar da IC. No grupo de 400 pacientes sem risco, apenas 109 (27,2%) apresentaram piora da IC. Os resultados demonstraram uma curva estatisticamente significativa (área sob a curva = 0,665; erro padrão = 0,018; p < 0,01; intervalo de confiança = 0,609 a 0,701), indicando boa precisão. O modelo apresentou sensibilidade de 69,9% e especificidade de 55,2%, com valor preditivo positivo de 52% e valor preditivo negativo de 72,7%. CONCLUSÕES: Na presente coorte, demonstramos que o modelo de predição de risco ADHERE foi capaz de discriminar pacientes que, de fato, desenvolveram piora da IC durante o período de internação daqueles que não desenvolveram.

Functional training improves peak oxygen consumption and quality of life of individuals with heart failure: a randomized clinical trial.

BACKGROUND: Functional training may be an effective non-pharmacological therapy for heart failure (HF). This study aimed to compare the effects of functional training with strength training on peak VO2 and quality of life in individuals with HF. METHODS: A randomized, parallel-design and examiner-blinded controlled clinical trial with concealed allocation, intention-to-treat and per-protocol analyses. Twenty-seven participants with chronic HF were randomly allocated to functional or strength training group, to perform a 12-week physical training, three times per week, totalizing 36 sessions. Primary outcomes were the difference on peak VO2 and quality of life assessed by cardiopulmonary exercise testing and Minnesota Living with Heart Failure Questionnaire, respectively. Secondary outcomes included functionality assessed by the Duke Activity Status Index and gait speed test, peripheral and inspiratory muscular strength, assessed by hand grip and manovacuometry testing, respectively, endothelial function by brachial artery flow-mediated dilation, and lean body mass by arm muscle circumference. RESULTS: Participants were aged 60 ± 7 years, with left ventricular ejection fraction 29 ± 8.5%. The functional and strength training groups showed the following results, respectively: peak VO2 increased by 1.4 ± 3.2 (16.9 ± 2.9 to 18.6 ± 4.8 mL.kg-1.min-1; p time = 0.011) and 1.5 ± 2.5 mL.kg-1.min-1 (16.8 ± 4.0 to 18.6 ± 5.5 mL.kg-1.min-1; p time = 0.011), and quality of life score decreased by 14 ± 15 (25.8 ± 14.8 to 10.3 ± 7.8 points; p time = 0.001) and 12 ± 28 points (33.8 ± 23.8 to 19.0 ± 15.1 points; p time = 0.001), but no difference was observed between groups (peak VO2: p interaction = 0.921 and quality of life: p interaction = 0.921). The functional and strength training increased the activity status index by 6.5 ± 12 and 5.2 ± 13 points (p time = 0.001), respectively, and gait speed by 0.2 ± 0.3 m/s (p time = 0.002) in both groups. CONCLUSIONS: Functional and strength training are equally effective in improving peak VO2, quality of life, and functionality in individuals with HF. These findings suggest that functional training may be a promising and innovative exercise-based strategy to treat HF. TRIAL REGISTRATION: NCT03321682. Registered date: 26/10/2017.

Reply to the letter "Understanding lactate and its clearance during extracorporeal membrane oxygenation for supporting refractory cardiogenic shock patients".

This is a reply to the letter titled "Understanding lactate and its clearance during extracorporeal membrane oxygenation for supporting refractory cardiogenic shock patients" by Eva Rully Kurniawati et al. In response to the concerns raised about our paper published in BMC Cardiovascular Disorders, titled "Association between serum lactate levels and mortality in patients with cardiogenic shock receiving mechanical circulatory support: a multicenter retrospective cohort study," we have addressed the confounding bias on the population included and the use of VA-ECMO and Impella CP. Furthermore, we have provided new data on the correlation of oxygen supply and lactate levels at admission of cardiogenic shock.

Donor heart selection: Evidence-based guidelines for providers.

The proposed donor heart selection guidelines provide evidence-based and expert-consensus recommendations for the selection of donor hearts following brain death. These recommendations were compiled by an international panel of experts based on an extensive literature review.

Uso do Modelo de Risco ADHERE como Preditor de Piora Intra-Hospitalar de Insuficiência Cardíaca em uma Coorte / Use of the ADHERE Risk Model as a Predictor of Risk of in-Hospital Worsening Heart Failure in a Cohort

Resumo Fundamento Pacientes hospitalizados com insuficiência cardíaca (IC) aguda descompensada estão sujeitos a desenvolver episódios de piora que requerem intervenções mais complexas. O modelo de predição de risco "Acute Decompensated Heart Failure National Registry" (ADHERE) foi desenvolvido nos Estados Unidos para prever o risco de piora intra-hospitalar da IC. Objetivo Utilizar o modelo de predição de risco ADHERE para avaliar o risco de piora intra-hospitalar da IC e determinar a sua sensibilidade e especificidade em pacientes hospitalizados. Métodos O presente estudo de coorte foi realizado em um hospital universitário público brasileiro e os dados de 2013 a 2020 foram coletados retrospectivamente. Foram considerados estatisticamente significativos valores de p < 0,05. Resultados Foram incluídos 890 pacientes com idade média de 74 ± 8 anos. O modelo mostrou que no grupo de 490 pacientes de risco, 254 (51,8%) desenvolveram piora intra-hospitalar da IC. No grupo de 400 pacientes sem risco, apenas 109 (27,2%) apresentaram piora da IC. Os resultados demonstraram uma curva estatisticamente significativa (área sob a curva = 0,665; erro padrão = 0,018; p < 0,01; intervalo de confiança = 0,609 a 0,701), indicando boa precisão. O modelo apresentou sensibilidade de 69,9% e especificidade de 55,2%, com valor preditivo positivo de 52% e valor preditivo negativo de 72,7%. Conclusões Na presente coorte, demonstramos que o modelo de predição de risco ADHERE foi capaz de discriminar pacientes que, de fato, desenvolveram piora da IC durante o período de internação daqueles que não desenvolveram.

Abstract Background Patients admitted with acute decompensated heart failure (HF) are subject to developing worsening episodes that require more complex interventions. The Acute Decompensated Heart Failure National Registry (ADHERE) risk model was developed in the United States to predict the risk of in-hospital worsening HF. Objective To use the ADHERE risk model in the assessment of risk of in-hospital worsening HF and to determine its sensitivity and specificity in hospitalized patients. Methods This cohort study was conducted at a Brazilian public university hospital, and data from 2013 to 2020 were retrospectively collected. P values < 0.05 were considered statistically significant. Results A total of 890 patients with a mean age of 74 ± 8 years were included. The model showed that, in the group of 490 patients at risk, 254 (51.8%) developed in-hospital worsening HF. In the group of 400 patients not at risk, only 109 (27.2%) experienced worsening HF. The results demonstrated a statistically significant curve (area under the curve = 0.665; standard error = 0.018; P < 0.01; confidence interval = 0.609 to 0.701), indicating good accuracy. The model had a sensitivity of 69.9% and a specificity of 55.2%, with a positive predictive value of 52% and a negative predictive value of 72.7%. Conclusions In this cohort, we showed that the ADHERE risk model was able to discriminate patients who in fact developed worsening HF during the admission period, from those who did not.

Pancreatitis as a Potential Trigger for Severe Accelerated Cardiac Allograft Vasculopathy Early Post Heart Transplant: A Case Report.

BACKGROUND: We present a case of severe accelerated cardiac allograft vasculopathy (CAV), an infrequent finding usually related to dismal prognosis, in a heart recipient with recurrent episodes of acute pancreatitis. CASE DESCRIPTION: A 38-year-old male was transplanted owing to advanced heart failure related to nonischemic dilated cardiomyopathy. On the fifth day after transplantation, a nonbiliary acute ischemic pancreatitis occurred. Recurrent relapses ensued within the following year requiring hospital readmissions for both supportive and pain management. The patient developed graft dysfunction by the 18th month post-transplant with severe multivessel CAV. A trial of bortezomib and percutaneous coronary interventions with drug-eluting stents at coronary arteries were attempted but the patient died suddenly, before the scheduled staged percutaneous coronary intervention for the coronary total occlusion was performed. DISCUSSION: The causal mechanisms of aggressive accelerated CAV are unclear, but it is suggested that important inflammatory and/or humoral responses may play a pivotal role in this life-threatening disease pathogenesis. Increased levels of biomarkers have been linked to advanced CAV, as well as pancreatitis pathogenesis, related to cytokine activation with remarkable systemic inflammatory response. Some of those inflammatory mediators have been reported as central in both pancreatitis and CAV, more specifically interleukin-6. CONCLUSION: A pro-inflammatory state due to recurrent acute pancreatitis early after transplantation may have contributed to severely accelerated CAV development in the presented case. Comprehensive evaluation of risk factors may assist in close surveillance and targeted therapies in the management of this challenging post-heart transplant scenario.

Meta-Analysis of Physical Training on Natriuretic Peptides and Inflammation in Heart Failure.

Physical training has been reported to attenuate myocardial stress and inflammation in heart failure (HF). We aimed to assess the impact of physical training on B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide (NT-proBNP), as well as biomarkers of inflammation-C-reactive protein, tumor necrosis factor α (TNF-α), and interleukins (ILs). A systematic electronic literature search was conducted up to May 2021 in PubMed, Cochrane Library, CINAHL, Embase, and SPORTDiscus to identify randomized clinical trials reporting associations between any formal physical training intervention and biomarker levels in patients with HF. Random-effects meta-analyses was used to calculate pooled correlations between physical training and blood biomarkers. Biomarker outcomes were expressed as mean difference or ratio of means and 95% confidence interval between the intervention and control groups, according to the normality of the data. A total of 38 trials were included in the final meta-analysis (2,652 randomized patients). Physical training was associated with decreased B-type natriuretic peptide (p = 0.02), NT-proBNP (p <0.01), C-reactive protein (p <0.00001), TNF-α (p = 0.03), IL-6 (p = 0.04), and IL-1ß (p = 0.001). Aerobic continuous training was associated with a 35% reduction in NT-proBNP (p = 0.01); ≥150 min/week of exercise was associated with a greater reduction in TNF-α levels (p = 0.0004), and aerobic interval training was associated with lower IL-6 levels (p = 0.01). In conclusion, physical training in patients with HF is associated with beneficial effects on natriuretic peptides and biomarkers of inflammation because they were all reduced by the intervention.

Impact of COVID-19 Infection Among Heart Transplant Recipients: A Southern Brazilian Experience.

PURPOSE: The coronavirus-2019 (COVID-19) infection is associated with a high risk of complications and death among heart transplant recipients. However, most cohorts are from high-income countries, while data from Latin America are sparse. METHODS: This is a retrospective cohort of heart transplant recipients followed at a hospital in Rio Grande do Sul, Brazil, between March 1st 2020 and October 1st 2021. RESULTS: Of the 62 heart transplant recipients on follow-up, 21 (34%) were infected by COVID-19, 58 (36-63) years of age, 67% male, body mass index of 26 (23-29) kg/m2, 48% with hypertension, 43% with chronic kidney disease, 5% with diabetes, within 2 (1-4) years of post-transplant follow-up. At presentation, the main symptoms were fever (62%), myalgia (33%), cough (33%), headache (33%), and dyspnea (19%). Hospitalization was required for 13 (62%) patients, with a time from first symptoms to the admission of 5 (1-12) days. In 38%, supplementary oxygen was needed, 19% required intensive care, and 10% mechanical ventilation. Three (14%) were infected after at least a first dose of COVID-19 vaccine. The main complications were bacterial pneumonia (38%), renal replacement therapy (19%), sepsis (10%) and venous thromboembolism (10%). Immunosuppression therapy was modified in 48%, with a reduction in the majority (89%). Two (10%) patients died in the hospital due to refractory hypoxemia and multiple organ dysfunction. The incidence of COVID-19 among transplant patients was comparable to the general population in the State of Rio Grande do Sul with a peak in December 2020. CONCLUSION: Heart transplant recipients shown a high rate of COVID-19 infection in Southern Brazil, with typical symptom presentation in most cases. There was an elevated rate of hospitalization, supplementary oxygen support, and complications. In-hospital lethality among infected heart transplanted recipients was similar to previously reported data worldwide despite the high rates of infection in Latin America.

Cardiogenic shock treated with temporary mechanical circulatory support in Brazil: The effect of learning curve.

AIMS: Treatment with mechanical circulatory support (MCS) has been proposed to mitigate mortality in cardiogenic shock (CS). However, there is a lack of data on MCS programs implementation and the effect of the learning curve on its outcomes in limited resources countries such as Brazil. METHODS: Prospective cohort of patients with CS admitted in four tertiary-care centers treated with Impella CP or veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Clinical outcomes were peri-procedural complications, short-term mortality rate, and the centers' learning curve. The cohort was divided into two periods: from April 2017 to July 2018 (n = 24), and from August 2018 to December 2020 (n = 25). RESULTS: The study enrolled 49 patients [age 59 (43-63) years; 34 (70%) males]. The most common causes for CS were acute myocardial infarction in 22 (45%) and acute decompensation of chronic heart failure in 10 (20%). VA-ECMO was employed in 35 (71%) and Impella CP in 14 (29%) of patients. Overall complications occurred in 37 (76%) of patients, where major bleeding in 19 (38%) was the most common. The overall mortality rate was 61%, but it was lower in the second period (40%) in comparison to the first period (83%), p = 0.002. The learning curve analysis showed a decrease in the mortality rate after 40 consecutive cases. CONCLUSIONS: Implementation of a temporary MCS program for refractory CS in a limited resource country is feasible. The learning curve effect might have played a role on survival rate since high morbimortality has decreased within time reaching optimal results by the end of the study.

Challenges for expansion of thoracic transplant clinical pharmacy in a developing country: comparison with U.S. accredited centres and call for action.

WHAT IS KNOWN AND OBJECTIVE: Clinical pharmacists' involvement in the care of solid organ transplant recipients has been discussed worldwide given its potential to improve clinical outcomes. As thoracic transplant activity grows in Brazil, it is important to understand how pharmacists are inserted in transplant programmes nationwide. We conducted a survey to explore clinical pharmacy activities in thoracic transplant centres in Brazil and compared them with accredited programmes in the United States. METHODS: An electronic questionnaire was distributed to all 40 heart and lung transplant centres registered in the Brazilian Organ Transplantation Agency (ABTO) in May 2019. Survey findings were compared to previously published data from accredited U.S. centres. RESULTS AND DISCUSSION: From 22 centre respondents, ten (45.5%) declared not to have a pharmacist at any part of the transplantation process, which translated into 158 (37.6%) transplant recipients without any direct pharmaceutical care. In centres with pharmacists (n = 12), none had a full-time professional dedicated to their heart and/or lung programmes. When compared to U.S. centres, there was a significantly lower insertion of clinical pharmacist activities among Brazilian centres. WHAT IS NEW AND CONCLUSION: Our findings point to an unmet need related to clinical pharmacy activity within thoracic transplant programmes, especially in a developing country, and highlight a call for action in order to reach higher accredited regulatory standards regarding pharmacist-driven workforce in transplant care worldwide.

Limited Predictive Role of the Revised Cardiac Risk Index in Kidney Transplant: Single Center Evaluation and Comparison With International Literature.

Perioperative risk factors predicting major cardiovascular events (MACE) and the performance of the Revised Cardiac Risk Index (RCRI) in a retrospective cohort of 325 consecutive adult patients undergoing kidney transplant from deceased donor grafts were assessed. Primary outcome was a composite of MACE up to 30 days post-transplant. Incidence of MACE was 5.8% at 30 days. Overall proportion of patients with RCRI ≥ 4 was 5%, but was higher (28%) among those who developed MACE. Patients with RCRI ≥ 4 had lower survival free of MACE compared to those with RCRI < 4 (P <0.001); however, in multivariable analysis, RCRI was not a predictor of cardiovascular events. The RCRI demonstrated poor discrimination to predict MACE at 30 days [area under the curve 0.64 (95% CI 0.49-0.78)]. Revised Cardiac Risk Index was not associated with reduced MACE-free survival adjusted analysis and its predictive ability was poor.

Donor-recipient predicted heart mass ratio and right ventricular-pulmonary arterial coupling in heart transplant.

OBJECTIVES: Right ventricular-pulmonary arterial (RV-PA) coupling interactions are largely unexplored in heart transplant patients. The outcome of this study was RV-PA coupling at 7 and 30 days after heart transplant and its association with donor-recipient size matching. METHODS: Clinical, echocardiographic and haemodynamic data from a retrospective cohort of heart transplant recipients and respective donors were reviewed. Coupling between RV-PA was examined by assessing the RV fractional area change and pulmonary artery systolic pressure ratio. Donor-recipient size matching was assessed by the predicted heart mass (PHM) ratio, and groups with a PHM ratio <1 and ≥1 were compared. RESULTS: Forty-four heart transplant recipients were included in this study (50 years, 57% male sex). Postoperative RV-PA coupling improved from 7 to 30 days (RV fractional area change/pulmonary artery systolic pressure 0.9 ± 0.3 vs 1.2 ± 0.3; P < 0.001). A positive association was found between an adequate PHM ratio and improvement of RV fractional area change/pulmonary artery systolic pressure at 30 days, independent of graft ischaemic time and pre-existent pulmonary hypertension (B coefficient 0.54; 95% confidence interval 0.11-0.97; P = 0.016; adjusted R2 = 0.24). CONCLUSIONS: These findings highlight the role of PHM as a metric to help donor selection and suggest its impact in RV-PA coupling interactions post-heart transplant.

Exercise training modalities for heart transplant recipients: a systematic review and network meta-analysis protocol.

INTRODUCTION: Heart transplantation is the gold standard treatment for selected patients with end-stage heart failure. Although this procedure can improve quality and prolong life expectancy, several of these patients persist with decreased exercise tolerance. Evidence suggests that exercise training can bring multifactorial benefits to heart transplant (HTx) recipients. However, it is unclear that exercise modality should be preferred. Therefore, the aim of this systematic review and network meta-analysis is to compare the efficacy and safety of different training modalities in HTx recipients. METHODS AND ANALYSIS: We will perform a comprehensive literature search in PubMed/MEDLINE, Embase, The Cochrane Library, CINAHL, Scopus, SportDISCUS, Web of Science Core Collection and PEDro from inception until November 2020. Two registries (ClinicalTrials.gov and REBEC) will also be searched for potential results in unpublished studies. There will be no restriction on language, date of publication, publication status or sample size. We will include randomised controlled trials enrolling adult HTx recipients with the presence of at least one exercise training group, which might be compared with another training modality and/or a non-exercise control group for a minimum of 4 weeks of intervention. The primary outcomes will be peak oxygen consumption and occurrence of adverse events. As secondary outcomes, the interaction between pulmonary ventilation, pulmonary perfusion and cardiac output, oxygen uptake efficiency slope, heart rate response, oxygen pulse, peak blood pressure and peak subjective perception of effort. In addition, we will evaluate the 6 min walking distance, health-related quality of life, endothelial function, muscle strength, body fat percentage and lean mass. Risk of bias will be assessed using the Cochrane RoB V.2.0 tool, and we plan to use the Confidence in Network Meta-Analysis tool to assess confidence in the results. All materials (raw data, processed data, statistical code and outputs) will be shared in a public repository. ETHICS AND DISSEMINATION: Given the nature of this study, no ethical approval will be required. We believe that the findings of this study may show which is the most efficacious and safe physical training modality for HTx recipients. The completed systematic review and network meta-analysis will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42020191192.

Association between serum lactate levels and mortality in patients with cardiogenic shock receiving mechanical circulatory support: a multicenter retrospective cohort study.

BACKGROUND: To evaluate the prognostic value of peak serum lactate and lactate clearance at several time points in cardiogenic shock treated with temporary mechanical circulatory support (MCS) using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella CP®. METHODS: Serum lactate and clearance were measured before MCS and at 1 h, 6 h, 12 h, and 24 h post-MCS in 43 patients at four tertiary-care centers in Southern Brazil. Prognostic value was assessed by univariable and multivariable analysis and receiver operating characteristic (ROC) curves for 30-day mortality. RESULTS: VA-ECMO was the most common MCS modality (58%). Serum lactate levels at all time points and lactate clearance after 6 h were associated with mortality on unadjusted and adjusted analyses. Lactate levels were higher in non-survivors at 6 h, 12 h, and 24 h after MCS. Serum lactate > 1.55 mmol/L at 24 h was the best single prognostic marker of 30-day mortality [area under the ROC curve = 0.81 (0.67-0.94); positive predictive value = 86%). Failure to improve serum lactate after 24 h was associated with 100% mortality. CONCLUSIONS: Serum lactate was an important prognostic biomarker in cardiogenic shock treated with temporary MCS. Serum lactate and lactate clearance at 24 h were the strongest independent predictors of short-term survival.