Metabolomic insights in advanced cardiomyopathy of chronic chagasic and idiopathic patients that underwent heart transplant.

Heart failure (HF) studies typically focus on ischemic and idiopathic heart diseases. Chronic chagasic cardiomyopathy (CCC) is a progressive degenerative inflammatory condition highly prevalent in Latin America that leads to a disturbance of cardiac conduction system. Despite its clinical and epidemiological importance, CCC molecular pathogenesis is poorly understood. Here we characterize and discriminate the plasma metabolomic profile of 15 patients with advanced HF referred for heart transplantation - 8 patients with CCC and 7 with idiopathic dilated cardiomyopathy (IDC) - using gas chromatography/quadrupole time-of-flight mass spectrometry. Compared to the 12 heart donor individuals, also included to represent the control (CTRL) scenario, patients with advanced HF exhibited a metabolic imbalance with 21 discriminating metabolites, mostly indicative of accumulation of fatty acids, amino acids and important components of the tricarboxylic acid (TCA) cycle. CCC vs. IDC analyses revealed a metabolic disparity between conditions, with 12 CCC distinctive metabolites vs. 11 IDC representative metabolites. Disturbances were mainly related to amino acid metabolism profile. Although mitochondrial dysfunction and loss of metabolic flexibility may be a central mechanistic event in advanced HF, metabolic imbalance differs between CCC and IDC populations, possibly explaining the dissimilar clinical course of Chagas' patients.

Extracorporeal Membrane Oxygenation for Graft Dysfunction Early After Heart Transplantation: A Systematic Review and Meta-analysis.

INTRODUCTION: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO. METHODS AND RESULTS: We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%-39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%-57%). Recipient age (odds ratio 1.02, 95% CI 1.01-1.04) and prior sternotomy (OR 1.57, 95% CI 0.99-2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death. CONCLUSIONS: One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT.

Valor prognóstico do escore SYNTAX residual nos desfechos clínicos intra- hospitalares e de acompanhamento em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST submetidos à estratégia farmacoinvasiva / Prognostic value of residual SYNTAX score on in-hospital and follow-up clinical outcomes in patients with ST-segment elevation myocardial infarction undergoing pharmacoinvasive strategy

Introdução: A doença arterial coronariana multiarterial é um desafio na prática clínica. Uma abordagem individualizada deve considerar não apenas as características do paciente, mas também um enfoque multidisciplinar, com o Heart Team. Diversos escores angiográficos foram propostos com o objetivo de quantificar o risco associado à doença arterial coronariana multiarterial. O escore SYNTAX residual foi proposto como um método para caracterizar e quantificar a doença coronariana residual, de forma sistemática, após intervenção coronária percutânea. Existem poucos dados na literatura que correlacionam o escore SYNTAX residual em pacientes com infarto do miocárdio com supradesnivelamento do segmento ST submetidos a uma estratégia farmacoinvasiva. O objetivo deste estudo foi avaliar o escore SYNTAX e o escore SYNTAX residual como preditores de desfechos intra-hospitalares e de médio prazo (180 a 380 dias), em pacientes com doença coronária multiarterial no contexto de infarto do miocárdio com supradesnivelamento do segmento ST, após terapia fibrinolítica bem-sucedida. Métodos: Em um estudo transversal, analítico e prospectivo, avaliamos o escore SYNTAX residual como preditor de desfechos intra-hospitalares e de médio prazo (6 meses a 1 ano), em pacientes com doença arterial coronariana multiarterial, no contexto de infarto do miocárdio com supradesnivelamento do segmento ST após estratégia farmacoinvasiva. Resultados: Entre agosto de 2019 e dezembro de 2020, foram analisados 108 pacientes com infarto do miocárdio com supradesnivelamento do segmento ST após fibrinólise, com critérios de reperfusão. O escore SYNTAX médio foi 13,98 (±4,87) e o escore SYNTAX residual médio foi 7,56 (±4,47). O escore SYNTAX residual elevado foi associado à nefropatia induzida por contraste e evento cardíaco adverso maior. Também foi um preditor independente de evento cardíaco adverso maior, com risco aumentado 9,69 vezes (p=0,0274). Conclusão: O escore SYNTAX residual elevado confere pior prognóstico em pacientes com infarto do miocárdio com elevação do segmento ST após estratégia farmacoinvasiva.

Background: Multivessel coronary artery disease is a challenge in clinical practice. An individualized approach should consider not only the patient characteristics, but also a multidisciplinary approach, together with the Heart Team. Multiple angiographic scores have been proposed with the aim of quantifying the risk associated with multivessel coronary artery disease. Residual SYNTAX score has been proposed as a method to systematically characterize and quantify residual coronary disease after percutaneous coronary intervention. There are few data in the literature correlating the residual SYNTAX score in patients with ST-segment elevation myocardial infarction undergoing pharmacoinvasive strategy. The objective of this study was to evaluate the SYNTAX score and residual SYNTAX score as predictors of in-hospital and medium-term outcomes (180 to 380 days) in patients with multivessel coronary artery disease in the setting of ST-segment elevation myocardial infarction, after successful fibrinolytic therapy. Methods: In a cross-sectional, analytical, and prospective study, we evaluated residual SYNTAX score as predictor of in-hospital and medium-term outcomes (6 months to 1 year), in patients with multivessel coronary artery disease, in the setting of ST-segment elevation myocardial infarction after pharmacoinvasive strategy. Results: Between August 2019 and December 2020, 108 patients with ST-segment elevation myocardial infarction after fibrinolysis, with reperfusion criteria, were analyzed. The mean SYNTAX score was 13.98 (±4.87) and the mean residual SYNTAX score was 7.56 (±4.47). High residual SYNTAX score was associated with contrast-induced nephropathy and major adverse cardiac event. It was also an independent predictor of major adverse cardiac event with a 9.69-fold increased risk (p=0.0274). Conclusion: High residual SYNTAX score confers worse prognosis in patients with ST-segment elevation myocardial infarction after pharmacoinvasive strategy.

Acute Cellular Rejection in Heart Transplant Patients: Insights of Global Longitudinal Strain, Myocardial Work, and an Exclusive Group of Chagas Disease.

Background: Echocardiographic markers associated with asymptomatic acute cellular rejection (ACR) in patients with orthotopic heart transplant (HT) are still under investigation. The aim of our study was to determine clinical and myocardial strain imaging (MSI) variables evaluated by echocardiography associated with ACR in the first year of HT. A separate analysis was performed to compare variables during the first 6 months of HT, when ACR has a prevalence in 60% of patients. Another analysis evaluated an exclusive population with Chagas disease as the cause of HT. Methods: We prospectively studied 67 patients with less than 1 year of HT, 36 patients without ACR (41% men, age 49 ± 12 years, 52% Chagas disease as the cause of heart failure), and 31 patients with ACR (59% men, age 55 ± 8 years, 74% Chagas disease as the cause of heart failure). Conventional echocardiographic measurements and MSI by global longitudinal strain (GLS) from the left ventricle (LV) and right ventricle free wall (RV-FWLS) and myocardial work (MW) from the left ventricle were obtained by experienced echocardiologists. Clinical variables, such as the presence of diabetes, hypertension, and immunosuppressant drugs, were compared between groups. Results: HT patients with ACR were older and used more cyclosporine for immunosuppression. The positive ACR group had an increased relative wall thickness and LV mass index and similar LVGLS and RV-FWLS compared to the negative ACR group. Nevertheless, MW analysis observed increased global work efficiency (GWE) in positive ACR. Multivariate analysis identified older age, cyclosporine use, LV mass index, and GWE as independent predictors for detecting rejection. A separate analysis was performed for patients with less than 6 months of HT. Similar MSI was observed in both groups, with a trend for increased GWE in patients with ACR and significantly increased LV mass index in the ACR group. An exclusive group of Chagas patients as the primary cause of HT was analyzed, and similar MSI results for LVGLS, RV-FWLS, and MW were observed for both ACR and the no rejection groups. Additionally, the survival rates at 2 years were similar between the Chagas disease groups. Conclusion: LVGLS and RV-FWLS were similar between patients with or without ACR in the first year after HT. Conversely, GWE, a derivative of LVGLS, and LV mass index were increased in positive ACR and could be markers for rejection. Increased LV mass index was also found in a subgroup analysis of patients less than 6 months after HT; however, MSI was similar regardless of ACR. For chagasic patients, rejection in the first year did not increase mortality at the 2-year follow-up, and MSI parameters were similar between patients with or without ACR. In a multivariate analysis to predict ACR, the independent parameters in this study were older age, cyclosporine use, LV mass index, and GWE.

Combined Heart and Kidney Transplantation: Initial Clinical Experience.

INTRODUCTION: Combined solid organ transplantation is infrequently performed in Brazil. The objective of this article is to present our initial experience with combined heart and kidney transplantation. METHODS: From January 2007 to December 2019, four patients were submitted to combined heart and kidney transplantation. Their mean age was 55.7±4.4 years, and three (75%) patients were males. All patients had Chagas cardiomyopathy, two were hospitalized and inotrope dependent, and all patients were on preoperative dialysis (median of 12 months prior to transplant). RESULTS: All patients survived and were in New York Heart Association functional class I at the latest follow-up (mean 34.7±17.5 months). Mean retarded kidney graft function was 22.9±9.7 days. One patient lost the kidney graft two years after the transplant due to Polyomavirus infection. CONCLUSION: Our initial experience of combined heart and kidney transplantation was favorable in selected patients with advanced heart failure and end-stage kidney disease. It requires involvement of a dedicated multispecialty team throughout all the diagnostics and treatment steps.

Combined Heart and Kidney Transplantation: Initial Clinical Experience

ABSTRACT Introduction: Combined solid organ transplantation is infrequently performed in Brazil. The objective of this article is to present our initial experience with combined heart and kidney transplantation. Methods: From January 2007 to December 2019, four patients were submitted to combined heart and kidney transplantation. Their mean age was 55.7±4.4 years, and three (75%) patients were males. All patients had Chagas cardiomyopathy, two were hospitalized and inotrope dependent, and all patients were on preoperative dialysis (median of 12 months prior to transplant). Results: All patients survived and were in New York Heart Association functional class I at the latest follow-up (mean 34.7±17.5 months). Mean retarded kidney graft function was 22.9±9.7 days. One patient lost the kidney graft two years after the transplant due to Polyomavirus infection. Conclusion: Our initial experience of combined heart and kidney transplantation was favorable in selected patients with advanced heart failure and end-stage kidney disease. It requires involvement of a dedicated multispecialty team throughout all the diagnostics and treatment steps.

Outcomes of Orthotopic Heart Transplantation in the Setting of Acute Kidney Injury and Renal Replacement Therapy.

OBJECTIVE: Heart transplantation in the setting of renal insufficiency is controversial. The objective of this study was to perform a descriptive analysis of patients who underwent orthotopic heart transplantation and renal replacement therapy (RRT) due to acute kidney injury (AKI). DESIGN: An observational cohort study with retrospective data collection. SETTING: A tertiary care hospital. PARTICIPANTS: Fifty-one patients underwent orthotopic heart transplantation with cardiogenic shock under inotrope dependence, with nine patients having preoperative RRT and 42 patients not having preoperative RRT. INTERVENTIONS: There were no interventions. MEASUREMENTS AND MAIN RESULTS: Hospital mortality occurred in eight (15.6%) patients. Although there were no significant differences between the study groups (preoperative RRT 33.3% v controls 11.9%, p = 0.1), this study was underpowered to detect differences in mortality. Dialysis also was required in 52.4% of patients who were not on preoperative RRT. All survivors had full recovery of kidney function with similar timing after transplant (18.5 days v 15 days, p = 0.75). Actuarial survival was 82.4%, 76.5%, and 66.5% at six months, one year, and five years, respectively. A cold ischemic time greater than 180 minutes (hazard ratio [HR] 4.37 95% confidence interval [CI] 1.51-12.6; p = 0.006) and pretransplant RRT (HR = 7.19 95% CI 1.13-45.7; p = 0.04) were independent predictors of long-term mortality. CONCLUSIONS: In a health system with limited funding and availability of mechanical circulatory support, heart transplantation in the setting of AKI, RRT, and low Interagency Registry for Mechanically Assisted Circulatory Support profile was associated with important hospital mortality. Among hospital survivors, however, all patients had full renal recovery and by 25 months there was no difference in mortality between those who required preoperative RRT and those who did not.

Recurrent Cardiac Sarcoma Resection With Modified Partial Autotransplantation.

Primary cardiac sarcomas are very aggressive, being a challenge to cardio-oncology specialty. Surgical planning and innovative techniques have enhanced the possibility of resection. We have described a case of recurrent primary left atrium angiosarcoma, successfully resected with a modified partial autotransplantation technique, planned using a 3-dimensional model created from computed tomography. (Level of Difficulty: Intermediate.).

Left Ventricular Remodeling Shortly after Open Mitral Valve Replacement for Rheumatic Mitral Stenosis.

INTRODUCTION: Left ventricular dysfunction after surgical treatment of mitral stenosis is uncommon. We intend to determine the pattern of left ventricular remodeling, shortly after open mitral valve replacement for rheumatic mitral stenosis, with in-hospital postoperative outcomes and the determinants of postoperative worsening of left ventricular ejection fraction. METHODS: From January 2008 to January 2015, 107 adult patients with rheumatic mitral stenosis were submitted to open mitral valve replacement. Their mean age was 45±11 years and 93 (86.9%) were women. Left ventricular morphology and function were studied longitudinally with echocardiography. The end point was postoperative worsening of left ventricular ejection fraction, defined by a decrease of 10% compared to preoperative basal assessment. Determinants of worsening left ventricular ejection fraction were determined by multivariable logistic regression analysis. RESULTS: The end point occurred in 18 patients (16.8%). We tested clinical and echocardiographic parameters to verify independent variables related to the decrease in postoperative ejection fraction. Lower body weight (P=0.005; odds ratio [OR]=0.89) and smaller preoperative mitral valve area (P=0.02; OR=0.02) were independent predictors of left ventricular dysfunction. These patients presented higher mortality and morbidity rates. CONCLUSION: Left ventricular remodeling patterns differed among patients with predominant rheumatic mitral stenosis undergoing open mitral valve replacement. Lower preoperative body weight and mitral valve area were independent determinants of deteriorating ejection fraction with increased end-systolic volumes, indicating that this specific problem may occur in anthropometric smaller patients with more extensive rheumatic disease.

Correction: Mortality risk prediction in high-risk patients undergoing coronary artery bypass grafting: Are traditional risk scores accurate?

[This corrects the article DOI: 10.1371/journal.pone.0255662.].

Mortality risk prediction in high-risk patients undergoing coronary artery bypass grafting: Are traditional risk scores accurate?

BACKGROUND: The performance of traditional scores is significantly limited to predict mortality in high-risk cardiac surgery. The aim of this study was to compare the performance of STS, ESII and HiriSCORE models in predicting mortality in high-risk patients undergoing CABG. METHODS: Cross-sectional analysis in the international prospective database of high-risk patients: HiriSCORE project. We evaluated 248 patients with STS or ESII (5-10%) undergoing CABG in 8 hospitals in Brazil and China. The main outcome was mortality, defined as all deaths occurred during the hospitalization in which the operation was performed, even after 30 days. Five variables were selected as predictors of mortality in this cohort of patients. The model's performance was evaluated through the calibration-in-the-large and the receiver operating curve (ROC) tests. RESULTS: The mean age was 69.90±9.45, with 52.02% being female, 25% of the patients were on New York Heart Association (NYHA) class IV and 49.6% had Canadian Cardiovascular Society (CCS) class 4 angina, and 85.5% had urgency or emergency status. The mortality observed in the sample was 13.31%. The HiriSCORE model showed better calibration (15.0%) compared to ESII (6.6%) and the STS model (2.0%). In the ROC curve, the HiriSCORE model showed better accuracy (ROC = 0.74) than the traditional models STS (ROC = 0.67) and ESII (ROC = 0.50). CONCLUSION: Traditional models were inadequate to predict mortality of high-risk patients undergoing CABG. However, the HiriSCORE model was simple and accurate to predict mortality in high-risk patients.

Left Ventricular Remodeling Shortly after Open Mitral Valve Replacement for Rheumatic Mitral Stenosis

Abstract Introduction: Left ventricular dysfunction after surgical treatment of mitral stenosis is uncommon. We intend to determine the pattern of left ventricular remodeling, shortly after open mitral valve replacement for rheumatic mitral stenosis, with in-hospital postoperative outcomes and the determinants of postoperative worsening of left ventricular ejection fraction. Methods: From January 2008 to January 2015, 107 adult patients with rheumatic mitral stenosis were submitted to open mitral valve replacement. Their mean age was 45±11 years and 93 (86.9%) were women. Left ventricular morphology and function were studied longitudinally with echocardiography. The end point was postoperative worsening of left ventricular ejection fraction, defined by a decrease of 10% compared to preoperative basal assessment. Determinants of worsening left ventricular ejection fraction were determined by multivariable logistic regression analysis. Results: The end point occurred in 18 patients (16.8%). We tested clinical and echocardiographic parameters to verify independent variables related to the decrease in postoperative ejection fraction. Lower body weight (P=0.005; odds ratio [OR]=0.89) and smaller preoperative mitral valve area (P=0.02; OR=0.02) were independent predictors of left ventricular dysfunction. These patients presented higher mortality and morbidity rates. Conclusion: Left ventricular remodeling patterns differed among patients with predominant rheumatic mitral stenosis undergoing open mitral valve replacement. Lower preoperative body weight and mitral valve area were independent determinants of deteriorating ejection fraction with increased end-systolic volumes, indicating that this specific problem may occur in anthropometric smaller patients with more extensive rheumatic disease.

Does the anthropometric profile influence infection morbidity after coronary artery bypass grafting?

BACKGROUND: Infection after cardiovascular surgery is multifactorial. We sought to determine whether the anthropometric profile influences the occurrence of infection after isolated coronary artery bypass grafting (CABG). METHODS: Between January 2011 and June 2016, 1777 consecutive adult patients were submitted to isolated coronary artery bypass grafting. Mean age was 61.7 ± 9.8 years and 1193 (67.1%) were males. Patients were divided into four groups according to the body mass index (BMI) classification: underweight (BMI < 18.5 kg/m2 ; N = 17, 0.9%), normal range (BMI: 18.5-24.99 kg/m2 ; N = 522, 29.4%), overweight (BMI: 25-29.99 kg/m2 ; N = 796, 44.8%), and obese (BMI > 30 kg/m2 ; N = 430, 24.2%). In-hospital outcomes were compared and independent predictors of infection were obtained through multiple Poisson regression with a robust variation. RESULTS: Independent predictors of any infection morbidity were female sex (relative ratio [RR], 1.47; p = .002), age > 60 years (RR, 1.85; p < .0001), cardiopulmonary bypass > 120 min (RR, 1.89; p = .0007), preoperative myocardial infarction < 30 days (RR, 1.37; p = .01), diabetes mellitus (RR, 1.59; p = .0003), ejection fraction < 48% (RR, 2.12; p < .0001), and blood transfusion (RR, 1.55; p = .0008). Among other variables, obesity, as well as diabetes mellitus, were independent predictors of superficial and deep sternal wound infection. CONCLUSIONS: Other factors rather than the anthropometric profile are more important in determining the occurrence of any infection after CABG. However, surgical site infection has occurred more frequently in obese patients. Appropriate patient selection, control of modifiable factors, and application of surgical bundles would minimize this important complication.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: rationale and design of the RIVER trial

Background The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. Design RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. Summary RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Innovative Approaches to Assess Intermediate Cardiovascular Risk Subjects: A Review From Clinical to Metabolomics Strategies.

Current risk stratification strategies for coronary artery disease (CAD) have low predictive value in asymptomatic subjects classified as intermediate cardiovascular risk. This is relevant because not all coronary events occur in individuals with traditional multiple risk factors. Most importantly, the first manifestation of the disease may be either sudden cardiac death or acute coronary syndrome, after rupture and thrombosis of an unstable non-obstructive atherosclerotic plaque, which was previously silent. The inaccurate stratification using the current models may ultimately subject the individual to excessive or insufficient preventive therapies. A breakthrough in the comprehension of the molecular mechanisms governing the atherosclerosis pathology has driven many researches toward the necessity for a better risk stratification. In this Review, we discuss how metabolomics screening integrated with traditional risk assessments becomes a powerful approach to improve non-invasive CAD subclinical diagnostics. In addition, this Review highlights the findings of metabolomics studies performed by two relevant analytical platforms in current use-mass spectrometry (MS) hyphenated to separation techniques and nuclear magnetic resonance spectroscopy (NMR) -and evaluates critically the challenges for further clinical implementation of metabolomics data. We also discuss the modern understanding of the pathophysiology of atherosclerosis and the limitations of traditional analytical methods. Our aim is to show how discriminant metabolites originated from metabolomics approaches may become promising candidate molecules to aid intermediate risk patient stratification for cardiovascular events and how these tools could successfully meet the demands to translate cardiovascular metabolic biomarkers into clinical settings.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.