In-Hospital Management and Long-term Clinical Outcomes and Adherence in Patients With Acute Decompensated Heart Failure: Primary Results of the First Brazilian Registry of Heart Failure (BREATHE).

BACKGROUND: Heart failure (HF), a common cause of hospitalization, is associated with poor short-term clinical outcomes. Little is known about the long-term prognoses of patients with HF in Latin America. METHODS: BREATHE was the first nationwide prospective observational study in Brazil that included patients hospitalized due to acute heart failure (HF). Patients were included during 2 time periods: February 2011-December 2012 and June 2016-July 2018 SUGGESTION FOR REPHRASING: In-hospital management, 12-month clinical outcomes and adherence to evidence-based therapies were evaluated. RESULTS: A total of 3013 patients were enrolled at 71 centers in Brazil. At hospital admission, 83.8% had clear signs of pulmonary congestion. The main cause of decompensation was poor adherence to HF medications (27.8%). Among patients with reduced ejection fraction, concomitant use of beta-blockers, renin-angiotensin-aldosterone inhibitors and spironolactone decreased from 44.5% at hospital discharge to 35.2% at 3 months. The cumulative incidence of mortality at 12 months was 27.7%, with 24.3% readmission at 90 days and 44.4% at 12 months. CONCLUSIONS: In this large national prospective registry of patients hospitalized with acute HF, rates of mortality and readmission were higher than those reported globally. Poor adherence to evidence-based therapies was common at hospital discharge and at 12 months of follow-up.

Covid-19 Automated Diagnosis and Risk Assessment through Metabolomics and Machine Learning.

COVID-19 is still placing a heavy health and financial burden worldwide. Impairment in patient screening and risk management plays a fundamental role on how governments and authorities are directing resources, planning reopening, as well as sanitary countermeasures, especially in regions where poverty is a major component in the equation. An efficient diagnostic method must be highly accurate, while having a cost-effective profile. We combined a machine learning-based algorithm with mass spectrometry to create an expeditious platform that discriminate COVID-19 in plasma samples within minutes, while also providing tools for risk assessment, to assist healthcare professionals in patient management and decision-making. A cross-sectional study enrolled 815 patients (442 COVID-19, 350 controls and 23 COVID-19 suspicious) from three Brazilian epicenters from April to July 2020. We were able to elect and identify 19 molecules related to the disease's pathophysiology and several discriminating features to patient's health-related outcomes. The method applied for COVID-19 diagnosis showed specificity >96% and sensitivity >83%, and specificity >80% and sensitivity >85% during risk assessment, both from blinded data. Our method introduced a new approach for COVID-19 screening, providing the indirect detection of infection through metabolites and contextualizing the findings with the disease's pathophysiology. The pairwise analysis of biomarkers brought robustness to the model developed using machine learning algorithms, transforming this screening approach in a tool with great potential for real-world application.

Epipericardial fat necrosis as cause of chest pain in patient after heart transplantation.

Epipericardial fat necrosis is an uncommon clinical condition of unknown etiology. It typically presents as acute pleuritic chest pain and should be differentiated from acute pulmonary embolism and acute coronary syndrome. This condition is diagnosed by characteristic chest computed tomography findings of an ovoid mediastinal fatty lesion with intrinsic and surrounding soft-tissue stranding. Treatment of epipericardial fat necrosis includes the administration of anti-inflammatory agents, and symptoms usually resolve within a few days after treatment initiation. This disease entity has rarely been reported since it was first described in 1957. Most current knowledge of epipericardial fat necrosis is based on case reports that describe this condition in previously healthy individuals. We present the case of a 39-year-old woman with a history of heart transplant, who presented with chest pain secondary to epipericardial fat necrosis. Serial computed tomography revealed lesion resolution after appropriate treatment.

Predictors of one-year outcomes in chronic heart failure: the portrait of a middle income country.

BACKGROUND: Heart failure (HF) is a major public health problem with increasing prevalence worldwide. It is associated with high mortality and poor quality of life due to recurrent and costly hospital admissions. Several studies have been conducted to describe HF risk predictors in different races, countries and health systems. Nonetheless, understanding population-specific determinants of HF outcomes remains a great challenge. We aim to evaluate predictors of 1-year survival of individuals with systolic heart failure from the GENIUS-HF cohort. METHODS: We enrolled 700 consecutive patients with systolic heart failure from the SPA outpatient clinic of the Heart Institute, a tertiary health-center in Sao Paulo, Brazil. Inclusion criteria were age between 18 and 80 years old with heart failure diagnosis of different etiologies and left ventricular ejection fraction ≤50% in the previous 2 years of enrollment on the cohort. We recorded baseline demographic and clinical characteristics and followed-up patients at 6 months intervals by telephone interview. Study data were collected and data quality assurance by the Research Electronic Data Capture tools. Time to death was studied using Cox proportional hazards models adjusted for demographic, clinical and socioeconomic variables and medication use. RESULTS: We screened 2314 consecutive patients for eligibility and enrolled 700 participants. The overall mortality was 6.8% (47 patients); the composite outcome of death and hospitalization was 17.7% (123 patients) and 1% (7 patients) have been submitted to heart transplantation after one year of enrollment. After multivariate adjustment, baseline values of blood urea nitrogen (HR 1.017; CI 95% 1.008-1.027; p < 0.001), brain natriuretic peptide (HR 1.695; CI 95% 1.347-2.134; p < 0.001) and systolic blood pressure (HR 0.982;CI 95% 0.969-0.995; p = 0.008) were independently associated with death within 1 year. Kaplan Meier curves showed that ischemic patients have worse survival free of death and hospitalization compared to other etiologies. CONCLUSIONS: High levels of BUN and BNP and low systolic blood pressure were independent predictors of one-year overall mortality in our sample. TRIAL REGISTRATION: Current Controlled Trials NTC02043431, retrospectively registered at in January 23, 2014.

Implementation of Heart Transplantation Program to Advanced Heart Failure Patients in Brazil.

PURPOSE: Heart transplantation is the gold standard treatment for advanced heart failure. Left ventricular assist devices (LVADs), despite being a good option for these patients, are not quite available in developing countries. Time spent in heart transplant waiting list has increased lately even in regions where the number of transplants has also risen showing that a new strategy should be sought. RECENT FINDINGS: Transplant process organization combined with multidisciplinary work are linked to better outcomes while improvement in donor's care and in pre-transplant evaluation might be opportunities to change the long waiting list scenario. For the first time in Brazil, a survey with the most expressive heart transplant centers has been made, which allows an overview of treatment of advanced heart failure in a developing country. We also described a model of heart transplant team, which has proved to be a success when compared to the largest heart transplant centers in Latin America.

Exhaled Breath Analysis in Heart Failure.

Heart failure (HF) is a clinical condition that presents high morbidity and mortality and is one of the main reasons for hospital admissions all over the world. Although biochemical processes that occur in the body during heart failure are known, this syndrome is still associated to poor prognosis. Exhaled breath analysis has emerged as a promising noninvasive tool in different clinical conditions and, recently, it has been also tested in patients with HF. This review presents the main breath HF biomarkers, which reflect metabolic changes that occur in this complex syndrome. It also discusses the diagnostic and prognostic value of exhaled breath compounds for HF and makes a short description of the main technologies involved in this analysis. Some perspectives on the area are presented as well.

Genetic and ElectroNic medIcal records to predict oUtcomeS in Heart Failure patients (GENIUS-HF) - design and rationale.

BACKGROUND: Studies adopting electronic medical records and genomic information are becoming widespread. Through this new modality in research, it is possible to study how genetic variants influence susceptibility towards chronic conditions and can improve patient care.Our aim is to develop a biobank with 2,000 heart failure patients treated in a tertiary cardiology hospital containing electronic medical records data and biologic samples for performing genome-wide association studies for validation and development of medical decision routines aimed at helping the clinical management of patients. METHODS/DESIGN: Patients between 18 and 80 years old with heart failure diagnosis of different etiologies and left ventricular ejection fraction ≤ 50% in the past 2 years will be eligible for enrollment on the cohort. After consent, patients will be submitted to clinical baseline, echocardiography, cardiograph impedance and biochemical evaluation. Study data will be collected and managed using Research Electronic Data Capture tools. The follow up will take place every 6 months to assess cardiovascular outcomes (all-cause mortality, cardiovascular mortality, hospitalization for worsening heart failure and current medication use). Initial analytical strategy will focus on the establishment of the accuracy of electronic medical records extraction protocols for main predictor factors of morbidity and mortality in heart failure. DISCUSSION: Building a biobank with biologic samples and clinical data of 2,000 heart failure patients we will perform genome-wide association studies. By this way, we pretend to study how genetic variants influence susceptibility towards chronic conditions. Besides, it will be created a working group focused on the development and implementation of algorithms for validation and application of medical routines using the electronic medical records of the Heart Institute (InCor - HCFMUSP). TRIAL REGISTRATION: Current Controlled Trials NTC02043431.

Necropsy findings in heart transplant recipients with or without primary graft dysfunction.

BACKGROUND: Primary graft dysfunction (PGD) is the leading cause of death in the first year after heart transplant (HT), but pathophysiology and histology are not completely understood. This study describes and compares morphological findings of hearts of patients with and without PGD. METHODS: We included adult patients submitted to HT in a single center who died within the first 14 days after HT and were submitted to necropsy. Clinical and histological data were recorded retrospectively. All heart slides were reviewed by a blinded pathologist. We categorized patients in two groups (PGD and non-PGD) and compared findings between them. RESULTS: Among 322 HTs, 26 patients were included. Median age was 51.5 years, 57.7% were male, 46.1% had non-ischemic cardiomyopathy, 30.8% Chagas cardiomyopathy and 23% ischemic cardiomyopathy. Eleven patients presented PGD, while 15 patients did not. PGD was severe in 72.7% of cases and moderate in 27.3%. PGD group had longer ischemic time (p=0.08), higher incidence of mechanical circulatory support (p=0.004), lower post-transplant biventricular ejection fraction (p=0.005). However, necropsy findings were similar between groups. Necrosis was detected in 80.7% of all cases (p=0.907 comparing groups), taking ≥ 10% of myocardial area in 46.1% of them, and 4 types of necrosis were found either in patients with and without PGD. CONCLUSION: Cardiac pathological findings were similar in HT patients with or without PGD who died within 14 days after the transplant and necrosis was frequent in both groups, raising the hypothesis necrosis is not the cause of cardiac dysfunction in PGD.

Comparing plasma and skin imprint metabolic profiles in COVID-19 diagnosis and severity assessment.

As SARS-CoV-2 continues to produce new variants, the demand for diagnostics and a better understanding of COVID-19 remain key topics in healthcare. Skin manifestations have been widely reported in cases of COVID-19, but the mechanisms and markers of these symptoms are poorly described. In this cross-sectional study, 101 patients (64 COVID-19 positive patients and 37 controls) were enrolled between April and June 2020, during the first wave of COVID-19, in São Paulo, Brazil. Enrolled patients had skin imprints sampled non-invasively using silica plates; plasma samples were also collected. Samples were used for untargeted lipidomics/metabolomics through high-resolution mass spectrometry. We identified 558 molecular ions, with lipids comprising most of them. We found 245 plasma ions that were significant for COVID-19 diagnosis, compared to 61 from the skin imprints. Plasma samples outperformed skin imprints in distinguishing patients with COVID-19 from controls, with F1-scores of 91.9% and 84.3%, respectively. Skin imprints were excellent for assessing disease severity, exhibiting an F1-score of 93.5% when discriminating between patient hospitalization and home care statuses. Specifically, oleamide and linoleamide were the most discriminative biomarkers for identifying hospitalized patients through skin imprinting, and palmitic amides and N-acylethanolamine 18:0 were also identified as significant biomarkers. These observations underscore the importance of primary fatty acid amides and N-acylethanolamines in immunomodulatory processes and metabolic disorders. These findings confirm the potential utility of skin imprinting as a valuable non-invasive sampling method for COVID-19 screening; a method that may also be applied in the evaluation of other medical conditions. KEY MESSAGES: Skin imprints complement plasma in disease metabolomics. The annotated markers have a role in immunomodulation and metabolic diseases. Skin imprints outperformed plasma samples at assessing disease severity. Skin imprints have potential as non-invasive sampling strategy for COVID-19.

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

BACKGROUND: Central Illustration : Percutaneous Strategies in Structural Heart Diseases: Focus on Chronic Heart Failure Transcatheter devices for monitoring and treating advanced chronic heart failure patients. PA: pulmonary artery; LA: left atrium; AFR: atrial flow regulator; TASS: Transcatheter Atrial Shunt System; VNS: vagus nerve stimulation; BAT: baroreceptor activation therapy; RDN: renal sympathetic denervation; F: approval by the American regulatory agency (FDA); E: approval by the European regulatory agency (CE Mark). BACKGROUND: 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.

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

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. To identify mortality risk factors in heart transplant patients with CD and the impact of antiproliferative regimen on survival. 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. 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. 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.

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. Identificar os fatores de risco de mortalidade em pacientes com DC após o TC e o impacto do regime antiproliferativo sobre a sobrevida. 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. 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). 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.

Characteristics and Outcomes of Heart Transplant Recipients With Coronavirus-19 Disease in a High-volume Transplant Center.

BACKGROUND: Heart transplant (HT) recipients may be at higher risk of acquiring SARS-CoV-2 infection and developing critical illness. The aim of this study is to describe characteristics and outcomes of HT recipients infected by SARS-COV-2, from a high-volume transplant center. METHODS: We have described data of all adult HT recipients with confirmed coronavirus disease 2019 by RT-PCR in nasopharyngeal samples from April 5, 2020, to January 5, 2021. Outcomes and follow-up were recorded until February 5, 2021. RESULTS: Forty patients were included. Twenty-four patients (60%) were men; the median age was 53 (40-60) y old; median HT time was 34 mo; and median follow-up time 162 d. The majority needed hospitalization (83%). Immunosuppressive therapy was reduced/withdrawn in the majority of patients, except from steroids, which were maintained. Seventeen patients (42.5%) were classified as having severe disease according to the ordinal scale developed by the World Health Organization Committee. They tended to have lower absolute lymphocyte count (P < 0.001) during follow-up when compared with patients with mild disease. Thirty-day mortality was 12.5%. However, a longer follow-up revealed increased later mortality (27.5%), with median time to death around 35 d. Bacterial nosocomial infections were a leading cause of death. Cardiac allograft rejection (10%) and ventricular dysfunction (12.5%) were also not negligible. CONCLUSIONS: Major findings of this study corroborate other cohorts' results, but it also reports significant rate of later events, suggesting that a strict midterm surveillance is advisable to HT recipients with coronavirus disease 2019.

Coronavirus Disease 2019 and the Myocardium. / Doença de Coronavírus-19 e o Miocárdio.

Infection with the coronavirus known as COVID-19 has promoted growing interest on the part of cardiologists, emergency care specialists, intensive care specialists, and researchers, due to the study of myocardial involvement based on different clinical forms resulting from immunoinflammatory and neurohumoral demodulation.Myocardial involvement may be minimal and identifiable only by electrocardiographic changes, mainly increased cardiac troponins, or, on the other side of the spectrum, by forms of fulminant myocarditis and takotsubo syndrome.The description of probable acute myocarditis has been widely supported by the observation of increased troponin in association with dysfunction. Classical definition of myocarditis, supported by endomyocardial biopsy of inflammatory infiltrate, is rare; it has been observed in only one case report to date, and the virus has not been identified inside cardiomyocytes.Thus, the phenomenon that has been documented is acute myocardial injury, making it necessary to rule our obstructive coronary disease based on increased markers of myocardial necrosis, whether or not they are associated with ventricular dysfunction, likely associated with cytokine storms and other factors that may synergistically promote myocardial injury, such as sympathetic hyperactivation, hypoxemia, arterial hypotension, and microvascular thrombotic phenomena.Systemic inflammatory and myocardial phenomena following viral infection have been well documented, and they may progress to cardiac remodeling and myocardial dysfunction. Cardiac monitoring of these patients is, therefore, important in order to monitor the development of the phenotype of dilated myocardiopathy.This review presents the main etiological and physiopathological findings, a description of the taxonomy of these types of cardiac involvement, and their correlation with the main clinical forms of the myocardial component present in patients in the acute phase of COVID-19.

Bone Metabolism Impairment in Heart Transplant: Results From a Prospective Cohort Study.

BACKGROUND: Data on the prevention of fractures after heart transplant (HTx) are controversial in the literature. Understanding the effects of HTx on bone may guide appropriate treatments in this high-risk population. METHODS: Seventy adult HTx patients were followed for 12 months. Clinical and laboratory parameters, bone mineral density, microarchitecture, and vertebral fractures were assessed at baseline (after intensive care unit discharge) and at 6 and 12 months. Patients received recommendations regarding calcium intake and vitamin D supplementation after HTx. RESULTS: At baseline, 27% of patients had osteoporosis, associated with the length of hospitalization before HTx (P = 0.001). Bone mineral density decreased in the first 6 months, with partial recovery later. Bone microarchitecture deteriorated, mainly in the trabecular bone in the first 6 months and cortical bone in the subsequent 6 months. At baseline, 92.9% of patients had vitamin D levels <30 ng/mL and 20.0% <10 ng/mL. Patients also had calcium at the lower limit of normal, high alkaline phosphatase, and high bone resorption biomarker. These abnormalities were suggestive of impaired bone mineralization and normalized at 6 months with correction of vitamin D deficiency. The majority of vertebral fractures were identified at baseline (23% of patients). After multivariate analyses, only a lower fat mass persisted as a risk factor for vertebral fractures (odds ratio, 1.23; 95% confidence interval, 1.04-1.47; P = 0.012). CONCLUSIONS: High frequencies of densitometric osteoporosis, vitamin D deficiency, bone markers abnormalities, and vertebral fractures were observed shortly after HTx. Calcium and vitamin D supplementation should be the first step in correcting bone mineralization impairment before specific osteoporosis treatment.

A Comprehensive and Contemporary Review on Immunosuppression Therapy for Heart Transplantation.

Heart transplantation is the standard of therapy for patients with end-stage heart disease. Since the first human-to-human heart transplantation, performed in 1967, advances in organ donation, surgical techniques, organ preservation, perioperative care, immunologic risk assessment, immunosuppression agents, monitoring of graft function and surveillance of long-term complications have drastically increased recipient survival. However, there are yet many challenges in the modern era of heart transplantation in which immunosuppression may play a key role in further advances in the field. A fine-tuning of immune modulation to prevent graft rejection while avoiding side effects from over immunosuppression has been the vital goal of basic and clinical research. Individualization of drug choices and strategies, taking into account the recipient's clinical characteristics, underlying heart failure diagnosis, immunologic risk and comorbidities seem to be the ideal approaches to improve post-transplant morbidity and survival while preventing both rejection and complications of immunosuppression. The aim of the present review is to provide a practical, comprehensive overview of contemporary immunosuppression in heart transplantation. Clinical evidence for immunosuppressive drugs is reviewed and practical approaches are provided. Cardiac allograft rejection classification and up-to-date management are summarized. Expanding therapies, such as photophoresis, are outlined. Drug-to-drug interactions of immunosuppressive agents focused on cardiovascular medications are summarized. Special situations involving heart transplantation such as sarcoidosis, Chagas diseases and pediatric immunosuppression are also reviewed. The evolution of phamacogenomics to individualize immunosuppressive therapy is described. Finally, future perspectives in the field of immunosuppression in heart transplantation are highlighted.

Exhaled breath acetone for predicting cardiac and overall mortality in chronic heart failure patients.

AIMS: Exhaled breath acetone (EBA) has been described as a new biomarker of heart failure (HF) diagnosis. EBA concentration increases according to severity of HF and is associated with poor prognosis, especially in acute decompensated HF. However, there are no data on chronic HF patients. The aim is to evaluate the role of EBA for predicting cardiac and overall mortality in chronic HF patients. METHODS AND RESULTS: In GENIUS-HF cohort, chronic patients were enrolled between August 2012 and December 2014. All patients had left ventricular ejection fraction ≤ 50%, and the diagnosis was established according to Framingham criteria. After consent, patients were submitted to clinical evaluation and exhaled breath collection. EBA identification and quantitative determination were done by spectrophotometry. The clinical characteristics associated with acetone were identified. All participants were followed for 18 months to assess cardiac and overall mortality. Around 700 participants were enrolled in the current analysis. Patients were 55.4 ± 12.2 years old, 67.6% male patients, and 81% New York Heart Association I/II with left ventricular ejection fraction of 32 ± 8.6%. EBA median concentration was 0.6 (0.3-1.2) ug/L. Acetone levels increased with the number of symptoms of HF and were associated with right HF signs/symptoms and liver biochemical changes. EBA at highest quartile (EBA > 1.2ug/L) was associated with a significantly worse prognosis (log rank test, P < 0.001). Cox proportional multivariable regression model revealed that EBA > 1.20ug/L was an independent predictor of cardiac (P = 0.011) and overall (P = 0.010) mortality in our population. CONCLUSIONS: This study shows that EBA levels reflect clinical HF features, especially right HF signs/symptoms. EBA is an independent predictor of cardiac and overall mortality in chronic HF patients.

Biomarkers for prediction of mortality in left-sided infective endocarditis.

BACKGROUND: Evidence regarding biomarkers for risk prediction in patients with infective endocarditis (IE) is limited. We aimed to investigate the value of a panel of biomarkers for the prediction of in-hospital mortality in patients with IE. METHODS: Between 2016 and 2018, consecutive IE patients admitted to the emergency department were prospectively included. Blood concentrations of nine biomarkers were measured at admission (D0) and on the seventh day (D7) of antibiotic therapy: C-reactive protein (CRP), sensitive troponin I (s-cTnI), procalcitonin, B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL6), tumor necrosis factor α (TNF-α), proadrenomedullin, alpha-1-acid glycoprotein, and galectin 3. The primary endpoint was in-hospital mortality. RESULTS: Among 97 patients, 56% underwent cardiac surgery, and in-hospital mortality was 27%. At admission, six biomarkers were independent predictors of in-hospital mortality: s-cTnI (OR 3.4; 95%CI 1.8-6.4; P<0.001), BNP (OR 2.7; 95%CI 1.4-5.1; P=0.002), IL-6 (OR 2.06; 95%CI 1.3-3.7; P=0.019), procalcitonin (OR 1.9; 95%CI 1.1-3.2; P=0.018), TNF-α (OR 1.8; 95%CI 1.1-2.9; P=0.019), and CRP (OR 1.8; 95%CI 1.0-3.3; P=0.037). At admission, S-cTnI provided the highest accuracy for predicting mortality (area under the ROC curve: s-cTnI 0.812, BNP 0.727, IL-6 0.734, procalcitonin 0.684, TNF-α 0.675, CRP 0.670). After 7 days of antibiotic therapy, BNP and inflammatory biomarkers improved their performance (s-cTnI 0.814, BNP 0.823, IL-6 0.695, procalcitonin 0.802, TNF-α 0.554, CRP 0.759). CONCLUSION: S-cTnI concentration measured at admission had the highest accuracy for mortality prediction in patients with IE.

Heart Failure Management of Patients with Amyloid Cardiomyopathy

Abstract Cardiac amyloidosis (CA) can lead to progressive heart failure (HF) by depositing insoluble amyloid fibrils within the myocardial extracellular space, resulting in an infiltrative and restrictive cardiomyopathy. Although CA was previously perceived as rare and incurable, recent advances in diagnostics and emerging therapies have been changing this outlook. It is crucial to spread awareness about CA to facilitate earlier diagnosis and proper therapeutic interventions, enhancing patient prognosis and survival. Currently, there is an estimated delay of 2 years from symptom onset to diagnosis, typically involving consultation with an average of 5 different professionals. Advances in cardiovascular imaging have facilitated earlier and more accurate diagnosis, reducing the necessity for invasive procedures, such as endomyocardial biopsy. Presently, tafamidis is the only drug that has been shown to offer prognostic benefits in ATTR-CA. Tafamidis is a highly specific medication targeting the circulating TTR protein, stabilizing the TTR tetramer to prevent its dissociation into amyloidogenic monomers that deposit in the myocardium. Alongside specific amyloidosis therapy, supportive HF treatment may be required; however, managing CA with medications typically used for HF with reduced ejection fraction (HFrEF) can be challenging due to potential intolerance. The effectiveness of guideline-directed medical therapy (GDMT) remains undetermined and still requires evaluation through randomized controlled clinical trials (RCCTs). Thus, the treatment cornerstone remains the judicious use of loop diuretics and mineralocorticoid receptor antagonists to control volume overload. Due to the safety profile, not adversely affecting hemodynamics or renal function, sodium-glucose transport protein 2 (SGLT2) inhibitors may be an effective treatment for CA, but they also still require evaluation through RCCTs.