Prognostic role of renal replacement therapy among hospitalized patients with heart failure in the Brazilian national public health system.

Introduction: Data on patients hospitalized with acute heart failure in Brazil scarce. Methods: We performed a cross-sectional, retrospective, records-based study using data retrieved from a large public database of heart failure admissions to any hospital from the Brazilian National Public Health System (SUS) (SUS Hospital Information System [SIHSUS] registry) to determine the in-hospital all-cause mortality rate, in-hospital renal replacement therapy rate and its association with outcome. Results: In total, 910,128 hospitalizations due to heart failure were identified in the SIHSUS registry between April 2017 and August 2021, of which 106,383 (11.7%) resulted in in-hospital death. Renal replacement therapy (required by 8,179 non-survivors [7.7%] and 11,496 survivors [1.4%, p < 0.001]) was associated with a 56% increase in the risk of death in the univariate regression model (HR 1.56, 95% CI 1.52 -1.59), a more than threefold increase of the duration of hospitalization, and a 45% or greater increase of cost per day. All forms of renal replacement therapy remained independently associated with in-hospital mortality in multivariable analysis (intermittent hemodialysis: HR 1.64, 95% CI 1.60 -1.69; continuous hemodialysis: HR 1.52, 95% CI 1.42 -1.63; peritoneal dialysis: HR 1.47, 95% CI 1.20 -1.88). Discussion: The in-hospital mortality rate of 11.7% observed among patients with acute heart failure admitted to Brazilian public hospitals was alarmingly high, exceeding that of patients admitted to North American and European institutions. This is the first report to quantify the rate of renal replacement therapy in patients hospitalized with acute heart failure in Brazil.

Cardiac magnetic resonance assessment of right ventricular remodeling after anthracycline therapy.

There are limited data on the effects of anthracyclines on right ventricular (RV) structure, function, and tissue characteristics. The goal of this study was to investigate the effects of anthracyclines on the RV using cardiac magnetic resonance (CMR). This was a post-hoc analysis of a prospective study of 27 breast cancer (BC) patients (51.8 ± 8.9 years) using CMR prior, and up to 3-times after anthracyclines (240 mg/m2) to measure RV volumes and mass, RV extracellular volume (ECV) and cardiomyocyte mass (CM). Before anthracyclines, LVEF (69.4 ± 3.6%) and RVEF (55.6 ± 9%) were normal. The median follow-up after anthracyclines was 399 days (IQR 310-517). The RVEF reached its nadir (46.3 ± 6.8%) after 9-months (P < 0.001). RV mass-index and RV CM decreased to 13 ± 2.8 g/m2 and 8.13 ± 2 g/m2, respectively, at 16-months after anthracyclines. The RV ECV expanded from 0.26 ± 0.07 by 0.14 (53%) to 0.40 ± 0.1 (P < 0.001). The RV ECV expansion correlated with a decrease in RV mass-index (r = -0.46; P < 0.001) and the increase in CK-MB. An RV ESV index at baseline above its median predicted an increased risk of LV dysfunction post-anthracyclines. In BC patients treated with anthracyclines, RV atrophy, systolic dysfunction, and a parallel increase of diffuse interstitial fibrosis indicate a cardiotoxic response on a similar scale as previously seen in the systemic left ventricle.

Change of BNP between admission and discharge after ST-elevation myocardial infarction (Killip I) improves risk prediction of heart failure, death, and recurrent myocardial infarction compared to single isolated measurement in addition to the GRACE score.

OBJECTIVE: In ST-elevation myocardial infarction, 7-15% of patients admitted as Killip I will develop symptomatic heart failure or decreased ejection fraction. However, available clinical scores do not predict the risk of severe outcomes well, such as heart failure, recurrent myocardial infarction, and sudden death in these Killip I individuals. Therefore, we evaluated whether one vs two measurements of BNP would improve prediction of adverse outcomes in addition to the GRACE score in ST-elevation myocardial infarction/Killip I individuals. METHODS: Consecutive patients with ST-elevation myocardial infarction/Killip I (n=167) were admitted and followed for 12 months. The GRACE score was calculated and plasma BNP levels were obtained in the first 12 h after symptom onset (D1) and at the fifth day (D5). RESULTS: Fifteen percent of patients admitted as Killip I developed symptomatic heart failure and/or decreased ejection fraction in 12 months. The risk of developing symptomatic heart failure or ejection fraction <40% at 30 days was increased by 8.7-fold (95% confidence interval: 1.10-662, p=0.046) per each 100 pg/dl increase in BNP-change. Both in unadjusted and adjusted Cox-regressions, BNP-change as a continuous variable was associated with incident sudden death/myocardial infarction at 30 days (odds ratio 1.032 per each increase of 10 pg/dl, 95% confidence interval: 1.013-1.052, p<0.001), but BNP-D1 was not. The GRACE score alone showed a moderate C-statistic=0.709 (p=0.029), but adding BNP-change improved risk discrimination (C-statistic=0.831, p=0.001). Net reclassification confirmed a significant improvement in individual risk prediction by 33.4% (95% confidence interval: 8-61%, p=0.034). However, GRACE +BNP-D1 did not improve risk reclassification at 30 days compared to GRACE (p=0.8). At 12 months, BNP-change was strongly associated with incident sudden death/myocardial infarction, but not BNP-D1. CONCLUSIONS: Only BNP-change following myocardial infarction was associated with poorer short- and long-term outcomes. BNP-change also improves risk reclassification in addition to the GRACE score.

Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical Manifestations of Heart Disease.

OBJECTIVES: The goal of this study was to demonstrate that cardiac magnetic resonance could reveal anthracycline-induced early tissue remodeling and its relation to cardiac dysfunction and left ventricular (LV) atrophy. BACKGROUND: Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy, lack specificity for the mechanism of myocardial tissue alterations. METHODS: A total of 27 women with breast cancer (mean age 51.8 ± 8.9 years, mean body mass index 26.9 ± 3.6 kg/m2), underwent cardiac magnetic resonance before and up to 3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV ejection fraction, normalized T2-weighted signal intensity for myocardial edema, extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime (τic; a marker of cardiomyocyte size), and late gadolinium enhancement. RESULTS: At baseline, patients had a relatively low (10-year) Framingham cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 ± 3.6%), and normal LV mass index (51.4 ± 8.0 g/m2), a mean ECV of 0.32 ± 0.038, mean τic of 169 ± 69 ms, and no late gadolinium enhancement. At 351 to 700 days after anthracycline therapy (240 mg/m2), mean LV ejection fraction had declined by 12% to 58 ± 6% (p < 0.001) and mean LV mass index by 19 g/m2 to 36 ± 6 g/m2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 ± 0.04 (p = 0.004), while mean τic had decreased by 62 ms to 119 ± 54 ms (p = 0.004). Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was associated with τic (ß = 4.1 ± 1.5 g/m2 per 100-ms increase in τic, p = 0.007) but not with ECV. Cardiac troponin T (mean 4.6 ± 1.4 pg/ml at baseline) increased significantly after anthracycline treatment (p < 0.001). Total LV cardiomyocyte mass, estimated as: (1 - ECV) × LV mass, declined more rapidly after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no evidence for any significant interaction between 10-year cardiovascular event risk and the effect of anthracycline therapy. CONCLUSIONS: A decrease in LV mass after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating that mechanisms other than interstitial fibrosis and edema can raise ECV. The loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury, assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin-Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients; NCT03000036).

P-wave duration is a predictor for long-term mortality in post-CABG patients.

Risk stratification in secondary prevention has emerged as an unmet clinical need in order to mitigate the Number-Needed-to-Treat and make expensive therapies both clinically relevant and cost-effective. P wave indices reflect atrial conduction, which is a sensitive marker for inflammatory, metabolic, and pressure overload myocardial cell remodeling; the three stimuli are traditional mechanisms for adverse clinical evolution. Accordingly, we sought to investigate the predictive role of P-wave indices to estimate residual risk in patients with chronic coronary artery disease (CAD). The cohort included 520 post-Coronary Artery Bypass Grafting patients with a median age of 60 years who were followed for a median period of 1025 days. The primary endpoint was long-term all-cause death. Cubic spline model demonstrated a linear association between P-wave duration and incidence rate of long-term all-cause death (p = 0.023). P-wave >110ms was a marker for an average of 425 days shorter survival as compared with P-wave under 80ms (Logrank p = 0.020). The Cox stepwise regression models retained P-wave duration as independent marker (HR:1.37; 95%CI:1.05-1.79,p = 0.023). In conclusion, the present study suggests that P-wave measurement may constitute a simple, inexpensive and accessible prognostic tool to be added in the bedside risk estimation in CAD patients.

Myocardial tissue remodeling after orthotopic heart transplantation: a pilot cardiac magnetic resonance study.

After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47 ± 7 years, 30 % female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5 ± 15 years; LVEF 63.5 ± 7 %). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3 ± 11 %) with higher LV mass relative to age-matched healthy volunteers (114 ± 27 vs. 85.8 ± 18 g; p < 0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39 ± 0.06 vs. 0.28 ± 0.03, p < 0.0001; τic: 0.12 ± 0.08 vs. 0.08 ± 0.03, p < 0.001). ECV was associated with LV mass (r = 0.74, p < 0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35 ± 0.02 for 0R vs. 0.45 ± 0, p < 0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.

Tratamento da sca no paciente diabético: o que mostram as evidências / Treatment of acs in the diabetic patient: what the evidence shows

O diabete mellitus (DM) é uma comorbidade muito frequente entre os pacientes com síndrome coronariana aguda (SCA), acometendo, aproximadamente, 20 a 37% desses. Além de ser um preditor de risco independente, também está relacionado a uma maior prevalência de quadros atípicos de SCA. Apesar disso, é importante ressaltar que no caso da SCA, a maioria dos pacientes com DM apresenta o mesmo quadro clínico que os pacientes sem a doença. Assim como para os pacientes não diabéticos, os scores de risco devem ser aplicados. Entretanto, essa comorbidade por si própria já prediz uma maior gravidade. Inclusive é mais aconselhável utilizar para esses pacientes uma estratégia invasiva precoce. Em relação ao tratamento medicamentoso da SCA, não há alterações significativas no tratamento dos pacientes com DM para os pacientes sem DM. Já no que diz respeito à terapia de reperfusão, muito se extrapola dos conhecimentos em angina estável, em que há uma superioridade do tratamento cirúrgico sobre o percutâneo para os pacientes com DM, ainda que haja falta de evidências no contexto agudo. Finalmente, o conjunto de evidências não é definitivo para indicar a melhor estratégia para o controle da hiperglicemia, entretanto, sabe-se que tanto a hiperglicemia quanto à hipoglicemia durante a internação está relacionada aos piores desfechos. Portanto, é importante evitar valores de glicemia superiores a 180 mg/dL e inferiores a 90 mg/dL, ficando a estratégia de controle rigoroso de glicemia com insulina intravenosa restrita aos pacientes selecionados.

Diabetes mellitus (DM) is a frequent comorbidity among patients with acute coronary syndrome (ACS), affecting about 20% to 37% of these patients. Besides being an independent risk predictor, it is also related to a higher prevalence of atypical presentations of ACS. Despite this, it is important to emphasize that in the case of ACS the majority of patients with DM have the same clinical presentation as patients without the disease. Just as for non-diabetic patients, risk scores should be applied. However, this comorbidity per se predicts a greater severity. Also, it is preferable to use an early invasive strategy for these patients. Regarding the medicinal treatment of ACS, there are no significant differences between the treatment of patients with DM and those without DM. In relation to reperfusion therapy, much of it is extrapolated from knowledge of stable angina, in which surgical treatment takes precedence over percutaneous treatment for patients with DM, despite the lack of evidence in the acute context. Finally, there is no definitive body of evidence to indicate the best strategy to control hyperglycemia, but it is known that both hyperglycemia and hypoglycemia during hospitalization are associated with worse outcomes. Thus, it is important to avoid glycemia values above 180 mg/dL and below 90 mg/dL, restricting the strategy of strict glycemic control with intravenous insulin to selected patients.

Terapia anticoagulante nas síndromes coronarianas agudas / Anticoagulant therapy in acute coronary syndromes

A necessidade de anticoagulação tem sido crescente em pacientes com síndromes coronarianas agudas, devido à fibrilação atrial com risco de tromboembolismo, presença de tromboembolismo venoso, doenças valvares ou próteses e à maior prevalência em idosos. Nesse cenário, a escolha da terapia antitrombótica mais adequada, notadamente para os pacientes que recebem tratamento percutâneo com inserção de stents, tem sido revista em diretrizes baseadas em estudos recentes, que incluíram novos anticoagulantes e antiplaquetários, em comparação com a estratégia padrão com anti-vitamina K e uso de terapia antiplaquetária dupla, com aspirina e tienopiridínico. Nesta revisão, incluímos estudos que fundamentam as estratégias atuais para o uso combinado de anticoagulantes orais e antiplaquetários em síndromes coronarianas agudas e as diferenças para o uso de anticoagulante em intervenções percutâneas eletivas

The need for anticoagulation is increasing in subjects with acute coronary syndromes, due to atrial fibrillation with risk of thromboembolism, the presence of venous thromboembolism, valve diseases or prostheses, and higher prevalence in the elderly. In this scenario, the choice of most appropriate antithrombotic therapy, particularly for patients who receive percutaneous treatment with the insertion of stents, has been reviewed in guidelines based on recent studies, which included new anticoagulants and antiplatelet agents in comparison with the standard strategy with anti-vitamin K and the use of dual antiplatelet therapy, with aspirin and thienopyridine. This review includes studies that form the basis of the current strategies for the combined use of oral anticoagulant and antiplatelets in acute coronary syndromes and the differences for the use of an anticoagulant in elective percutaneous interventions

Statin-associated muscle symptoms: position paper from the Luso-Latin American Consortium.

In the last two decades, statin therapy has proved to be the most potent isolated therapy for attenuation of cardiovascular risk. Its frequent use has been seen as one of the most important elements for the reduction of cardiovascular mortality in developed countries. However, the recurrent incidence of muscle symptoms in statin users raised the possibility of causal association, leading to a disease entity known as statin associated muscle symptoms (SAMS). Mechanistic studies and clinical trials, specifically designed for the study of SAMS have allowed a deeper understanding of the natural history and accurate incidence. This set of information becomes essential to avoid an unnecessary risk of severe forms of SAMS. At the same time, this concrete understanding of SAMS prevents overdiagnosis and an inadequate suspension of one of the most powerful prevention strategies of our times. In this context, the Luso-Latin American Consortium gathered all available information on the subject and presents them in detail in this document as the basis for the identification and management of SAMS.

Terapia antitrombótica na fase aguda das síndromes coronarianas aguda / Antithrombotic therapy in acute phase of acute coronary syndrome

A morbidade e a mortalidade nas síndromes coronarianas agudas – causadas principalmente pela instabilidade da placa aterosclerótica, levando à formação de trombos – foi bastante reduzida com o advento de antiplaquetários, antitrombóticos e revascularização precoce. Hoje, dispomos de quatro antitrombóticos para uso nestas condições: a heparina não fracionada, a de baixo peso molecular, o fondaparinux e a bivalirudina – sendo apenas as três primeiras disponíveis no Brasil. Como são agentes antiocoagulantes, o risco de sangramento não é desprezível e deve ser apropriadamente dosado com o fim de trazer o máximo benefício antitrombótico, sem grande risco hemorrágico. Nesta revisão sumarizamos o atual estado da arteno uso de antitrombóticos no Brasil...

Morbidity and mortality in the acute coronary syndromes – caused in the majorly by atherosclerotic plaque instability, with consequent thrombus formation – was drastically reduced by the advent of antiplatelet and antithrombotic agents, and by early revascularization. Nowadays, we have 4 antithrombotic agents: unfractionated heparin, low molecular weight heparin, fondaparinux and bivalirudin – with only the first 3 available in Brazil. As they comprise anticoagulant effects, the risk of bleedingis high and must be taken into account when prescribed, in order to bring the greater benefits without higher bleeding risk. In this review we summarized the current state of the art about the use of these agents in our country...