RESUMO
INTRODUCTION AND OBJECTIVES: Heart failure (HF) is a clinical syndrome associated with substantial morbidity, mortality, and healthcare costs. Dapagliflozin has proven efficacy in reducing the risk of death and hospitalization in HF patients, regardless of left ventricular ejection fraction (LVEF). This paper aimed to project the potential impact of dapagliflozin on healthcare costs related to HF subsequent hospitalizations (HFHs) in Portuguese hospitals. METHODS: The total number of HF-related hospitalizations (hHF), HFHs, and the average length of stay for patients with a primary diagnosis of HF from six Portuguese hospitals, between January 2019 and December 2021, were collected and aggregated by hospital classification. Costs associated with HFHs were calculated according to Portuguese legislation and considering conservative, average, and complex approaches. Cost-saving projections were based on extrapolations from hHF risk reductions reported in dapagliflozin clinical trials. RESULTS: Considering a 26% risk reduction in hHF reported on pooled-analysis of DAPA-HF and DELIVER as the expected reduction in HFHs, the use of dapagliflozin would be associated with cost savings ranging from EUR 1 612 851.54 up to EUR 6 587 360.09, when considering all hospitals and the different approaches, between 2019 and 2021. A similar projection is observed based on 24% RRR derived by weighting DAPA-HF and DELIVER sub-analyses and PORTHOS epidemiological data. CONCLUSIONS: In this projection, dapagliflozin use in all eligible hHF patients is associated with a significant reduction in direct costs. Our data support that, in addition to the improvements in HF-related outcomes, dapagliflozin may have a significant economic impact on healthcare costs in Portuguese hospitals.
RESUMO
Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in the MYPBC3 gene, which encodes the cardiac myosin-binding protein C (cMyBP-C). Most pathogenic variants in MYPBC3 are either nonsense mutations or result in frameshifts, suggesting that the primary disease mechanism involves reduced functional cMyBP-C protein levels within sarcomeres. However, a subset of MYPBC3 variants are missense mutations, and the molecular mechanisms underlying their pathogenicity remain elusive. Upon in vitro differentiation into cardiomyocytes, induced pluripotent stem cells (iPSCs) derived from HCM patients represent a valuable resource for disease modeling. In this study, we generated two iPSC lines from peripheral blood mononuclear cells (PBMCs) of a female with early onset and severe HCM linked to the MYBPC3: c.772G > A variant. Although this variant was initially classified as a missense mutation, recent studies indicate that it interferes with splicing and results in a frameshift. The generated iPSC lines exhibit a normal karyotype and display hallmark characteristics of pluripotency, including the ability to undergo trilineage differentiation. These novel iPSCs expand the existing repertoire of MYPBC3-mutated cell lines, broadening the spectrum of resources for exploring how diverse mutations induce HCM. They additionally offer a platform to study potential secondary genetic elements contributing to the pronounced disease severity observed in this individual.
Assuntos
Cardiomiopatia Hipertrófica , Proteínas de Transporte , Diferenciação Celular , Células-Tronco Pluripotentes Induzidas , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Cardiomiopatia Hipertrófica/genética , Cardiomiopatia Hipertrófica/etiologia , Feminino , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Diferenciação Celular/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Mutação de Sentido Incorreto/genética , Índice de Gravidade de Doença , Mutação/genética , Linhagem Celular , Mutação da Fase de Leitura/genética , Leucócitos Mononucleares/metabolismo , Células CultivadasRESUMO
OBJECTIVES: Activated clotting time (ACT) is commonly used to monitor anticoagulation during cardiac surgeries. Final ACT values may be essential to predict postoperative bleeding and transfusions, although ideal values remain unknown. Our aim was to evaluate the utility of ACT as a predictor of postoperative bleeding and transfusion use. METHODS: Retrospective study (722 patients) submitted to surgery between July 2018-October 2021. We compared patients with final ACT < basal ACT and final ACT ≥ basal ACT and final ACT < 140 s with ≥140 s. Continuous variables were analysed with the Wilcoxon rank-sum test; categorical variables using Chi-square or Fisher's exact test. A linear mixed regression model was used to analyse bleeding in patients with final ACT < 140 and ≥140. Independent variables were analysed with binary logistic regression models to investigate their association with bleeding and transfusion. RESULTS: Patients with final ACT ≥ 140 s presented higher postoperative bleeding than final ACT < 140 s at 12 h (P = 0.006) and 24 h (**P = 0.004). Cardiopulmonary bypass (CPB) time [odds ratio (OR) 1.009, 1.002-1.015, 95% confidence interval (CI)] and masculine sex (OR 2.842,1.721-4.821, 95% CI) were significant predictors of bleeding. Patients with final ACT ≥ 140 s had higher risk of UT (OR 1.81, 1.13-2.89, 95% CI; P = 0.0104), compared to final ACT < 140 s. CPB time (OR 1.019,1.012-1.026, 95% CI) and final ACT (OR 1.021,1.010-1.032, 95% CI) were significant predictors of transfusion. Female sex was a predictor of use of transfusion, with a probability for use of 27.23% (21.84-33.39%, 95% CI) in elective surgeries, and 60.38% (37.65-79.36%, 95% CI) in urgent surgeries, higher than in males. CONCLUSIONS: Final ACT has a good predictive value for the use of transfusion. Final ACT ≥ 140 s correlates with higher risk of transfusion and increased bleeding. The risk of bleeding and transfusion is higher with longer periods of CPB. Males have a higher risk of bleeding, but females have a higher risk of transfusion.
RESUMO
Familial hypertrophic cardiomyopathy (HCM) stands as a predominant heart condition, characterised by left ventricle hypertrophy in the absence of any associated loading conditions, with affected individuals having an increased risk of developing heart failure and sudden cardiac death (SCD). Two induced pluripotent stem cell (iPSC) lines were derived from peripheral blood mononuclear cells obtained from two unrelated individuals with previously reported nonsense mutations in the MYBPC3 gene. The first individual is a 48-year-old male (F26) with the MYBPC3 c.1731G > A HCM mutation, whereas the second individual is a 43-year-old female (F82) carrying the MYBPC3 c.2670G > A HCM mutation. The generated iPSCs exhibit appropriate expression of pluripotency markers, trilineage differentiation capacity and a normal karyotype. This resource contributes to gaining deeper insights into the pathophysiological mechanisms that underlie HCM.
Assuntos
Cardiomiopatia Hipertrófica Familiar , Células-Tronco Pluripotentes Induzidas , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Cardiomiopatia Hipertrófica Familiar/genética , Cardiomiopatia Hipertrófica Familiar/metabolismo , Códon sem Sentido , Células-Tronco Pluripotentes Induzidas/metabolismo , Leucócitos Mononucleares , Mutação , Proteínas do Citoesqueleto/genéticaRESUMO
Familial hypertrophic cardiomyopathy (HCM) is the most common inherited heart condition. HCM patients show left ventricle hypertrophy without any associated loading conditions, being at risk for heart failure and sudden cardiac death. Two induced pluripotent stem cell (iPSC) lines were generated from peripheral blood mononuclear cells obtained from two unrelated individuals, a 54-year-old male (F81) and a 44-year-old female (F93), both carrying the MYBPC3 c.1484G>A HCM mutation. iPSCs show expression of pluripotency markers, trilineage differentiation capacity and a normal karyotype. This resource enables further assessment of the pathophysiological development of HCM.
Assuntos
Cardiomiopatia Hipertrófica Familiar , Células-Tronco Pluripotentes Induzidas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cardiomiopatia Hipertrófica Familiar/genética , Cardiomiopatia Hipertrófica Familiar/metabolismo , Diferenciação Celular , Células-Tronco Pluripotentes Induzidas/metabolismo , Leucócitos Mononucleares/metabolismo , MutaçãoRESUMO
INTRODUCTION AND OBJECTIVES: Current epidemiological data on heart failure (HF) in Portugal derives from studies conducted two decades ago. The main aim of this study is to determine HF prevalence in the Portuguese population. Using current standards, this manuscript aims to describe the methodology and research protocol applied. METHODS: The Portuguese Heart Failure Prevalence Observational Study (PORTHOS) is a large, three-stage, population-based, nationwide, cross-sectional study. Community-dwelling citizens aged 50 years and older will be randomly selected via stratified multistage sampling. Eligible participants will be invited to attend a screening visit at a mobile clinic for HF symptom assessment, anthropomorphic assessment, N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing, one-lead electrocardiogram (ECG) and a sociodemographic and health-related quality of life questionnaire (EQ-5D). All subjects with NT-proBNP ≥125 pg/mL or with a prior history of HF will undergo a diagnostic confirmatory assessment at the mobile clinic composed of a 12-lead ECG, comprehensive echocardiography, HF questionnaire (KCCQ) and blood sampling. To validate the screening procedure, a control group will undergo the same diagnostic assessment. Echocardiography results will be centrally validated, and HF diagnosis will be established according to the European Society of Cardiology HF guidelines. A random subsample of patients with an equivocal HF with preserved ejection fraction diagnosis based on the application of the Heart Failure Association preserved ejection fraction diagnostic algorithm will be invited to undergo an exercise echocardiography. CONCLUSIONS: Through the application of current standards, appropriate methodologies, and a strong research protocol, the PORTHOS study will determine the prevalence of HF in mainland Portugal and enable a comprehensive characterization of HF patients, leading to a better understanding of their clinical profile and health-related quality of life.
Assuntos
Insuficiência Cardíaca , Qualidade de Vida , Humanos , Pessoa de Meia-Idade , Idoso , Estudos Transversais , Portugal/epidemiologia , Prevalência , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Volume Sistólico , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , BiomarcadoresRESUMO
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal condition that requires early diagnosis, management, and specific treatment. The availability of new disease-modifying therapies has made successful treatment a reality. Transthyretin amyloid cardiomyopathy can be either age-related (wild-type form) or caused by mutations in the TTR gene (genetic, hereditary forms). It is a systemic disease, and while the genetic forms may exhibit a variety of symptoms, a predominant cardiac phenotype is often present. This document aims to provide an overview of ATTR-CM amyloidosis focusing on cardiac involvement, which is the most critical factor for prognosis. It will discuss the available tools for early diagnosis and patient management, given that specific treatments are more effective in the early stages of the disease, and will highlight the importance of a multidisciplinary approach and of specialized amyloidosis centres. To accomplish these goals, the World Heart Federation assembled a panel of 18 expert clinicians specialized in TTR amyloidosis from 13 countries, along with a representative from the Amyloidosis Alliance, a patient advocacy group. This document is based on a review of published literature, expert opinions, registries data, patients' perspectives, treatment options, and ongoing developments, as well as the progress made possible via the existence of centres of excellence. From the patients' perspective, increasing disease awareness is crucial to achieving an early and accurate diagnosis. Patients also seek to receive care at specialized amyloidosis centres and be fully informed about their treatment and prognosis.
Assuntos
Neuropatias Amiloides Familiares , Cardiomiopatias , Humanos , Consenso , Pré-Albumina/genética , Neuropatias Amiloides Familiares/complicações , Neuropatias Amiloides Familiares/diagnóstico , Neuropatias Amiloides Familiares/terapia , Cardiomiopatias/diagnóstico , Cardiomiopatias/terapia , Cardiomiopatias/genéticaRESUMO
Importance: Left ventricular (LV) hypertrophy contributes to the onset and progression of heart failure (HF), particularly for patients with pre-HF (stage B) for whom no treatment has yet proven effective to prevent transition to overt HF (stage C). The ß3-adrenergic receptors (ß3ARs) may represent a new target, as their activation attenuates LV remodeling. Objective: To determine whether activation of ß3ARs by repurposing a ß3AR agonist, mirabegron, is safe and effective in preventing progression of LV hypertrophy and diastolic dysfunction among patients with pre- or mild HF. Design, Setting, and Participants: The Beta3-LVH prospective, triple-blind, placebo-controlled phase 2b randomized clinical trial enrolled patients between September 12, 2016, and February 26, 2021, with a follow-up of 12 months. The trial was conducted at 10 academic hospitals in 8 countries across Europe (Germany, Poland, France, Belgium, Italy, Portugal, Greece, and the UK). Patients aged 18 years or older with or without HF symptoms (maximum New York Heart Association class II) were screened for the presence of LV hypertrophy (increased LV mass index [LVMI] of ≥95 g/m2 for women or ≥115 g/m2 for men) or maximum wall thickness of 13 mm or greater using echocardiography. Data analysis was performed in August 2022. Intervention: Participants were randomly assigned (1:1) to mirabegron (50 mg/d) or placebo, stratified by the presence of atrial fibrillation and/or type 2 diabetes, for 12 months. Main Outcomes and Measures: The primary end points were LVMI determined using cardiac magnetic resonance imaging and LV diastolic function (early diastolic tissue Doppler velocity [E/e'] ratio assessed using Doppler echocardiography) at 12 months. Patients with at least 1 valid measurement of either primary end point were included in the primary analysis. Safety was assessed for all patients who received at least 1 dose of study medication. Results: Of the 380 patients screened, 296 were enrolled in the trial. There were 147 patients randomized to mirabegron (116 men [79%]; mean [SD] age, 64.0 [10.2] years) and 149 to placebo (112 men [75%]; mean [SD] age, 62.2 [10.9] years). All patients were included in the primary intention-to-treat analysis. At 12 months, the baseline and covariate-adjusted differences between groups included a 1.3-g/m2 increase in LVMI (95% CI, -0.15 to 2.74; P = .08) and a -0.15 decrease in E/e' (95% CI, -0.69 to 0.4; P = .60). A total of 213 adverse events (AEs) occurred in 82 mirabegron-treated patients (including 31 serious AEs in 19 patients) and 215 AEs occurred in 88 placebo-treated patients (including 30 serious AEs in 22 patients). No deaths occurred during the trial. Conclusions: In this study, mirabegron therapy had a neutral effect on LV mass or diastolic function over 12 months among patients who had structural heart disease with no or mild HF symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT02599480.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Adrenérgicos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hipertrofia Ventricular Esquerda , Estudos Prospectivos , IdosoRESUMO
AIMS: Multiple prediction score models have been validated to predict major adverse events in patients with heart failure. However, these scores do not include variables related to the type of follow-up. This study aimed to evaluate the impact of a protocol-based follow-up programme of patients with heart failure regarding scores accuracy for predicting hospitalizations and mortality occurring during the first year after hospital discharge. METHODS AND RESULTS: Data from two heart failure populations were collected: one composed of patients included in a protocol-based follow-up programme after an index hospitalization for acute heart failure and a second one-the control group-composed of patients not included in a multidisciplinary HF management programme after discharge. For each patient, the risk of hospitalization and/or mortality within a period of 12 months after discharge was calculated using four different scores: BCN Bio-HF Calculator, COACH Risk Engine, MAGGIC Risk Calculator, and Seattle Heart Failure Model. The accuracy of each score was established using the area under the receiver operating characteristic curve (AUC), calibration graphs, and discordance calculation. AUC comparison was established by the DeLong method. The protocol-based follow-up programme group included 56 patients, and the control group, 106 patients, with no significant differences between groups (median age: 67 years vs. 68.4 years; male sex: 58% vs. 55%; median ejection fraction: 28.2% vs. 30.5%; functional class II: 60.7% vs. 56.2%, I: 30.4% vs. 31.9%; P = not significant). Hospitalization and mortality rates were significantly lower in the protocol-based follow-up programme group (21.4% vs. 54.7%; P < 0.001 and 5.4% vs. 17.9%; P < 0.001, respectively). When applied to the control group, COACH Risk Engine and BCN Bio-HF Calculator had, respectively, good (AUC: 0.835) and reasonable (AUC: 0.712) accuracy to predict hospitalization. There was a significant reduction of COACH Risk Engine accuracy (AUC: 0.572; P = 0.011) and a non-significant accuracy reduction of BCN Bio-HF Calculator (AUC: 0.536; P = 0.1) when applied to the protocol-based follow-up programme group. All scores showed good accuracy to predict 1 year mortality (AUC: 0.863, 0.87, 0.818, and 0.82, respectively) when applied to the control group. However, when applied to the protocol-based follow-up programme group, a significant predictive accuracy reduction of COACH Risk Engine, BCN Bio-HF Calculator, and MAGGIC Risk Calculator (AUC: 0.366, 0.642, and 0.277, P < 0.001, 0.002, and <0.001, respectively) was observed. Seattle Heart Failure Model had non-significant reduction in its acuity (AUC: 0.597; P = 0.24). CONCLUSIONS: The accuracy of the aforementioned scores to predict major events in patients with heart failure is significantly reduced when they are applied to patients included in a multidisciplinary heart failure management programme.
Assuntos
Insuficiência Cardíaca , Alta do Paciente , Humanos , Masculino , Idoso , Seguimentos , Medição de Risco/métodos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , HospitalizaçãoRESUMO
INTRODUCTION AND OBJECTIVES: Heart failure (HF) has significant morbidity and mortality, and its prevalence will continue to increase in the future. This unfavorable evolution requires reflection as well as recommendations and decisions based on expert critical and strategic appraisal. METHODS: In the Acceleration on Heart Failure Empowerment and Awareness - the Portuguese Challenge (ATHENA-PT) study, a range of strategic factors that represent the strengths, weaknesses, threats, and opportunities (SWOT) of HF in Portugal were established. These factors were assessed quantitatively by experts, to create a final SWOT matrix for the management and prevention of HF in Portugal and to outline recommendations. RESULTS: For HF management, the panel emphasized the following strategic recommendations: (i) reimbursement of natriuretic peptides testing in primary healthcare; (ii) reimbursement of Doppler assessment in echocardiographic studies and promotion of detailed information in reports; (iii) intervention to improve the prognosis of patients with HF with preserved ejection fraction; (iv) ensuring effective healthcare transition between hospital and ambulatory units, using checklists/protocols; and (v) reinforcement and commitment to the training of primary health physicians and to the cardiac rehabilitation of patients. For the prevention of HF, the following recommendations/proposals were proposed: (i) campaigns to raise awareness of cardiovascular disease risk factors; (ii) promotion of physical exercise and healthy eating; and (iii) avoidance of therapeutic inertia in the management of risk factors. CONCLUSIONS: The acknowledgment of various strategic factors and their prioritization by experts made it possible to create and reinforce a range of new strategic recommendations for the management and prevention of HF.
Assuntos
Reabilitação Cardíaca , Insuficiência Cardíaca , Transição para Assistência do Adulto , Humanos , Portugal/epidemiologia , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/tratamento farmacológico , Prognóstico , Volume SistólicoRESUMO
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive and fatal condition that requires early diagnosis, management, and specific treatment. The availability of new disease-modifying therapies has made successful treatment a reality. Transthyretin amyloid cardiomyopathy can be either age-related (wild-type form) or caused by mutations in the TTR gene (genetic, hereditary forms). It is a systemic disease, and while the genetic forms may exhibit a variety of symptoms, a predominant cardiac phenotype is often present. This document aims to provide an overview of ATTR-CM amyloidosis focusing on cardiac involvement, which is the most critical factor for prognosis. It will discuss the available tools for early diagnosis and patient management, given that specific treatments are more effective in the early stages of the disease, and will highlight the importance of a multidisciplinary approach and of specialized amyloidosis centres. To accomplish these goals, the World Heart Federation assembled a panel of 18 expert clinicians specialized in TTR amyloidosis from 13 countries, along with a representative from the Amyloidosis Alliance, a patient advocacy group. This document is based on a review of published literature, expert opinions, registries data, patients' perspectives, treatment options, and ongoing developments, as well as the progress made possible via the existence of centres of excellence. From the patients' perspective, increasing disease awareness is crucial to achieving an early and accurate diagnosis. Patients also seek to receive care at specialized amyloidosis centres and be fully informed about their treatment and prognosis.
Assuntos
Humanos , Pré-Albumina , Amiloide , Cardiomiopatias , ConsensoRESUMO
OBJECTIVES: Endometriosis is a benign, estrogen-dependent, chronic inflammatory disease and is the commonest cause of chronic pelvic pain in younger women. Cardiovascular disease is the main cause of death worldwide. Because the relationship between endometriosis and CV disease is not well established, we performed a systematic review of longitudinal studies that assessed the occurrence of cardiovascular events in women with endometriosis compared to those without endometriosis. STUDY DESIGN: Systematic review with meta-analysis of longitudinal cohort/nested case-control studies with endometriosis patients and controls. A search was conducted of the MEDLINE, CENTRAL, and Embase databases from inception to November 2022. Random-effects meta-analysis was performed to estimate pooled hazard ratios (HR) and 95 % confidence intervals (95%CI). MAIN OUTCOME MEASURE: Cardiovascular outcomes such as ischemic heart disease and cerebrovascular disease. RESULTS: Six cohort studies were included, with a total of 254,929 participants. Meta-analysis showed that endometriosis was associated with a significantly increased risk of ischemic heart disease (HR 1.50, 95%CI 1.37-1.65; I2 = 0 %) and cerebrovascular disease (HR 1.17, 95%CI 1.07-1.29; I2 = 0 %). The one study that examined the relationship between cardiovascular mortality and endometriosis found a decreased risk in women with endometriosis relative to women without endometriosis (HR 0.55 (95%CI 0.47-0.65)). CONCLUSIONS: Endometriosis is associated with a significantly increased risk of cardiovascular disease, namely ischemic heart disease and cerebrovascular disease. Further studies are required to determine if endometriosis and/or its treatments are risk factors (particularly for cardiovascular mortality), and whether preventive measures could reduce the burden of cardiovascular disease in women with endometriosis. Study protocol registered at PROSPERO: CRD42022298830.
Assuntos
Doenças Cardiovasculares , Transtornos Cerebrovasculares , Endometriose , Isquemia Miocárdica , Humanos , Feminino , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Endometriose/complicações , Isquemia Miocárdica/complicações , Estudos de CoortesRESUMO
BACKGROUND: data regarding the effectiveness and safety of sacubitril/valsartan in heart failure and reduced ejection fraction (HFrEF) patients with chronic kidney disease (CKD) are scarse. OBJECTIVE: to evaluate the effectiveness and safety of sacubitril/valsartan in HFrEF and CKD in a real-world population. METHODS: we included consecutive ambulatory HFrEF patients that initiated sacubitril/valsartan between February 2017 and October 2020, stratified by CKD (KDIGO stage 5 excluded). PRIMARY OUTCOMES: the incidence rate per 100 patient-years and the annualized length of stay (LOS) of acute decompensated HF hospitalizations (HFH). SECONDARY OUTCOMES: all-cause mortality, NYHA improvement, and titration of sacubitril/valsartan. RESULTS: We included 179 patients, 77 with CKD, those being older (72 ± 10 vs. 65 ± 12 years, p < 0.001), had higher NT-proBNP (4623 ± 5266 vs. 1901 ± 1835 pg/mL, p < 0.001), and high anaemia incidence (p < 0.001). After 19 ± 11 months, a significant reduction in HFH adjusted incidence rate (57.5% decrease in CKD vs. 74.6%, p = 0.261) was observed, with 5 days there was a reduction in annualized LOS in both groups (p = 0.319). NYHA improved similarly in both groups (p = 0.670). CKD patients presented non-significant higher all-cause mortality (HR = 2.405, 95%CI: [0.841; 6.879], p = 0.102). Both groups had similar sacubitril/valsartan maximum dose achievement and drug withdrawal. CONCLUSION: sacubitril/valsartan was effective on reducing HFH and LOS without affecting all-cause mortality in a CKD real-world population.
RESUMO
Cardiac surgery is frequently associated with significant postoperative bleeding. Platelet-dysfunction is the main cardiopulmonary bypass (CPB)-induced hemostatic defect. Not only the number of platelets decreases, but also the remaining are functionally impaired. Although lipid metabolism is crucial for platelet function, little is known regarding platelet metabolic changes associated with CPB-dysfunction. Our aim is to explore possible contribution of metabolic perturbations for platelet dysfunction after cardiac surgery. DESIGN: Prospective cohort study. SETTING: Tertiary academic cardiothoracic-surgery ICU. PATIENTS: Thirty-three patients submitted to elective surgical aortic valve replacement. INTERVENTIONS: Samples from patients were collected at three time points (preoperative, 6- and 24-hr postoperative). Untargeted metabolic analysis using high-performance liquid chromatography-tandem mass spectrometry was performed to compare patients with significant postoperative bleeding with patients without hemorrhage. Principal component analyses, Wilcoxon matched-pairs signed-rank tests, adjusted to FDR, and pairwise comparison were used to identify pathways of interest. Enrichment and pathway metabolomic complemented the analyses. MEASUREMENTS AND MAIN RESULTS: We identified a platelet-related signature based on an overrepresentation of changes in known fatty acid metabolism pathways involved in platelet function. We observed that arachidonic acid (AA) levels and other metabolites from the pathway were reduced at 6 and 24 hours, independently from antiagreggation therapy and platelet count. Concentrations of preoperative AA were inversely correlated with postoperative chest tube blood loss but were not correlated with platelet count in the preoperative, at 6 or at 24 hours. Patients with significant postoperative blood-loss had considerably lower values of AA and higher transfusion rates. Values of postoperative interleukin-6 were strongly correlated with AA variability. CONCLUSIONS AND RELEVANCE: Our observations suggest that an inflammatory-related perturbation of AA metabolism is a signature of cardiac surgery with CPB and that preoperative levels of AA may be more relevant than platelet count to anticipate and prevent postoperative blood loss in patients submitted to cardiac surgery with CPB.
RESUMO
INTRODUCTION AND OBJECTIVES: Chronic heart failure (CHF) is a growing public health concern and diagnosis can be challenging, particularly in primary care. This study aims to estimate the budgetary impact of introducing N-terminal pro-B-type natriuretic peptide (NT-proBNP) for CHF diagnosis in a primary care setting from the perspective of the Portuguese health system. METHODS: A budget impact analysis was conducted over one-year from the patients' first presentation. The standard of care (SoC) was compared to NT-proBNP at the point-of-care (PoC) or laboratory (Lab). A decision tree model was used to estimate the downstream costs associated with each of the three pathways. RESULTS: An estimated 81 012 patients were expected to present to primary care with new onset CHF symptoms. The use of NT-proBNP as a primary diagnostic tool is estimated to generate annualized savings of EUR 935 657 and EUR 2 982 443 in the Lab and PoC setting, respectively. Estimated cost savings were due to the need for fewer medical visits, hospitalizations and echocardiograms (ECHO). The Lab and PoC settings led to similar reductions in hospitalizations (14.4%) and ECHO (27%), but the reduction in medical visits was higher in the PoC setting (38% compared to 2.5%), resulting in higher savings compared to Lab. CONCLUSIONS: Using NT-proBNP for CHF diagnosis in primary care could result in considerable costs savings for the public health system in Portugal. This evidence might support health policy makers to reconsider the resource management and define a new strategy to mitigate the impact of CHF.
RESUMO
BACKGOUND: Atrial Fibrillation (AF) is the most prevalent cardiac arrhythmia among older patients, associated with thromboembolic events. Direct Oral Anticoagulants (DOAC) are the treatment of choice for most patients, but its use may have risks on standard dose. However, it is still unclear the effects related with the use of a lower dose off labelled DOAC. OBJECTIVES: We conducted a systematic review and meta-analysis to assess the effects of off-label underdose use of DOAC in patients with AF. METHODS: MEDLINE, Cochrane Central Register of Controlled Trials, PsycINFO databases and EMBASE were searched for observational longitudinal studies evaluating the outcomes on off label underdosed patients compared with standard dosed patients with AF. We performed a random-effects meta-analysis to estimate the pooled Hazard Ratios (HR) with 95%Cis. RESULTS: Eighteen cohort studies evaluating 237,533 patients with AF were included. Off-label underdose DOAC use is associated with higher risk of all-cause mortality [HR = 1.27 (95%CI 1.09-1.48)] and cardiovascular composite outcomes [HR = 1.32 (95%CI 1.08-1.62)], when compared with standard dose DOAC use. The effects in thromboembolic events [HR = 1.14 (95%CI 1.00-1.31)], major bleeding [HR = 1.02 (95%CI 0.91-1.15)], and composite of ischemic and bleeding events [HR = 1.22 (95%CI 0.79-1.88)] were not statistically significant. The certainty in the evidence was low or very low. CONCLUSIONS: Off label underdose DOAC use is associated with higher risk of all-cause mortality and cardiovascular composite outcomes, compared with standard dose.
Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Tromboembolia , Administração Oral , Anticoagulantes , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Hemorragia/induzido quimicamente , Humanos , Uso Off-Label , Acidente Vascular Cerebral/etiologia , Tromboembolia/induzido quimicamente , Tromboembolia/epidemiologia , Tromboembolia/prevenção & controleRESUMO
AIMS: The interaction between common cardiovascular risk factors (CVRF) and hypertrophic cardiomyopathy (HCM) is poorly studied. We sought to explore the relation between CVRF and the clinical characteristics of patients with HCM enrolled in the EURObservational Research Programme (EORP) Cardiomyopathy registry. METHODS AND RESULTS: 1739 patients with HCM were studied. The relation between hypertension (HT), diabetes (DM), body mass index (BMI), and clinical traits was analysed. Analyses were stratified according to the presence or absence of a pathogenic variant in a sarcomere gene. The prevalence of HT, DM, and obesity (Ob) was 37, 10, and 21%, respectively. HT, DM, and Ob were associated with older age (P<0.001), less family history of HCM (HT and DM P<0.001), higher New York Heart Association (NYHA) class (P<0.001), atrial fibrillation (HT and DM P<0.001; Ob p = 0.03) and LV (left ventricular) diastolic dysfunction (HT and Ob P<0.001; DM P = 0.003). Stroke was more frequent in HT (P<0.001) and mutation-positive patients with DM (P = 0.02). HT and Ob were associated with higher provocable LV outflow tract gradients (HT P<0.001, Ob P = 0.036). LV hypertrophy was more severe in Ob (P = 0.018). HT and Ob were independently associated with NYHA class (OR 1.419, P = 0.017 and OR 1.584, P = 0.004, respectively). Other associations, including a higher proportion of females in HT and of systolic dysfunction in HT and Ob, were observed only in mutation-positive patients. CONCLUSION: Common CVRF are associated with a more severe HCM phenotype, suggesting a proactive management of CVRF should be promoted. An interaction between genotype and CVRF was observed for some traits.