Controlled Study of Central Hemodynamic Changes in Inspiratory Exercise with Different Loads in Heart Failure. / Estudo Controlado das Alterações Hemodinâmicas Centrais de uma Sessão de Exercício Inspiratório com Diferentes Cargas na Insuficiência Cardíaca.

Background Inspiratory muscle weakness contributes to exercise intolerance and decreased quality of life in patients with heart failure. Studies with inspiratory muscle training show improvement in inspiratory muscle strength, functional capacity and quality of life. However, little is known about the central hemodynamic response (CHR) during inspiratory exercise (IE). Objective To evaluate CHR in a single IE session with different loads (placebo, 30% and 60%) in heart failure. Methods Randomized placebo-controlled clinical trial in patients with heart failure with reduced ejection fraction, functional class II and III. Twenty patients aged 65 ± 11 years completed a single session of inspiratory exercise, in 3 cycles of 15 minutes, with a 1-hour washout, involving loads of 30% (C30), 60% (C60) and placebo, using a linear load resistor (PowerBreathe Light). The noninvasive hemodynamic study was performed by cardiothoracic bioimpedance (Niccomo™ CardioScreen®). Statistical analysis was performed with Student's t-test and Pearson's correlation, and P≤0.05 was considered significant. Results An increase in heart rate (HR) was observed with C30 (64 ± 15 vs 69 ± 15 bpm; p = 0.005) and C60 (67 ± 14 vs 73 ± 14 bpm, p = 0.002). A decrease was observed in systolic volume (SV) with C30 (73 ± 26 vs 64 ± 20 ml; p = 0.004). Cardiac output (CO), on its turn, increased only with C60 (4.6 ± 1.5 vs 5.3 ± 1.7 l/min; p = -0.001). Conclusion When using the 60% load, in a single IE session, changes in CHR were observed. HR and CD increased, as did the Borg scales and subjective sensation of dyspnea. The 30% load reduced the SV. (Arq Bras Cardiol. 2020; 114(4):656-663).

Estudo Controlado das Alterações Hemodinâmicas Centrais de uma Sessão de Exercício Inspiratório com Diferentes Cargas na Insuficiência Cardíaca / Controlled Study of Central Hemodynamic Changes in Inspiratory Exercise with Different Loads in Heart Failure

Resumo Fundamento A fraqueza muscular inspiratória contribui para a intolerância ao exercício e diminuição da qualidade de vida dos pacientes com insuficiência cardíaca. Estudos com treinamento da musculatura inspiratória demonstram melhora da força muscular inspiratória, da capacidade funcional e da qualidade de vida. Porém, pouco se sabe sobre a resposta hemodinâmica central (RHC) durante o exercício inspiratório (EI). Objetivo Avaliar a RHC em uma única sessão de EI com diferentes cargas (placebo, 30 e 60%) na insuficiência cardíaca. Métodos Ensaio clínico randomizado placebo-controlado, em pacientes com insuficiência cardíaca com fração de ejeção reduzida, classe funcional II e III. Vinte pacientes, com idade de 65±11 anos, completaram uma sessão única de exercício inspiratório, em 3 ciclos de 15 minutos, com washout de 1 hora, envolvendo cargas de 30% (C30), 60% (C60) e placebo, utilizando um resistor de carga linear ( PowerBreathe Light ). O estudo hemodinâmico não invasivo foi realizado por bioimpedância cardiotorácica ( Niccomo™CardioScreen® ). Análise estatística foi feita com o Teste t de Student e a correlação de Pearson, considerado significante p≤0,05. Resultados Foi observado aumento da frequência cardíaca (FC) com a C30 (64±15 vs 69±15 bpm; p=0,005) e C60 (67±14 vs 73±14 bpm, p=0,002). No volume sistólico (VS), observou-se diminuição com a C30 (73±26 vs 64±20 ml; p=0,004). O débito cardíaco (DC) apresentou aumento apenas com a C60 (4,6±1,5 vs 5,3±1,7 l/min; p=-0,001). Conclusão Quando utilizada a carga de 60%, em uma sessão única de EI, foram observadas alterações na RHC. A FC e o DC aumentaram, assim como as escalas de Borg e sensação subjetiva de dispneia. Já a carga de 30% promoveu diminuição do VS. (Arq Bras Cardiol. 2020; 114(4):656-663)

Abstract Background Inspiratory muscle weakness contributes to exercise intolerance and decreased quality of life in patients with heart failure. Studies with inspiratory muscle training show improvement in inspiratory muscle strength, functional capacity and quality of life. However, little is known about the central hemodynamic response (CHR) during inspiratory exercise (IE). Objective To evaluate CHR in a single IE session with different loads (placebo, 30% and 60%) in heart failure. Methods Randomized placebo-controlled clinical trial in patients with heart failure with reduced ejection fraction, functional class II and III. Twenty patients aged 65 ± 11 years completed a single session of inspiratory exercise, in 3 cycles of 15 minutes, with a 1-hour washout, involving loads of 30% (C30), 60% (C60) and placebo, using a linear load resistor (PowerBreathe Light). The noninvasive hemodynamic study was performed by cardiothoracic bioimpedance (Niccomo™ CardioScreen®). Statistical analysis was performed with Student's t-test and Pearson's correlation, and P≤0.05 was considered significant. Results An increase in heart rate (HR) was observed with C30 (64 ± 15 vs 69 ± 15 bpm; p = 0.005) and C60 (67 ± 14 vs 73 ± 14 bpm, p = 0.002). A decrease was observed in systolic volume (SV) with C30 (73 ± 26 vs 64 ± 20 ml; p = 0.004). Cardiac output (CO), on its turn, increased only with C60 (4.6 ± 1.5 vs 5.3 ± 1.7 l/min; p = -0.001). Conclusion When using the 60% load, in a single IE session, changes in CHR were observed. HR and CD increased, as did the Borg scales and subjective sensation of dyspnea. The 30% load reduced the SV. (Arq Bras Cardiol. 2020; 114(4):656-663)

Rationale and design of the Statins Evaluation in Coronary procedUres and REvascularization: The SECURE-PCI Trial.

BACKGROUND: Previous evidence suggests that acute treatment with statins reduce atherosclerotic complications, including periprocedural myocardial infarction, but currently, there are no large, adequately powered studies to define the effects of early, high-dose statins in patients with acute coronary syndrome (ACS) and planned invasive management. OBJECTIVES: The main goal of Statins Evaluation in Coronary procedUres and REvascularization (SECURE-PCI) Trial is to determine whether the early use of a loading dose of 80 mg of atorvastatin before an intended percutaneous coronary intervention followed by an additional dose of 80 mg 24 hours after the procedure will be able to reduce the rates of major cardiovascular events at 30 days in patients with an ACS. DESIGN: The SECURE-PCI study is a pragmatic, multicenter, double-blind, placebo-controlled randomized trial planned to enroll around 4,200 patients in 58 different sites in Brazil. The primary outcome is the rate of major cardiovascular events at 30 days defined as a composite of all-cause mortality, nonfatal acute myocardial infarction, nonfatal stroke, and coronary revascularization. SUMMARY: The SECURE PCI is a large randomized trial testing a strategy of early, high-dose statin in patients with ACS and will provide important information about the acute treatment of this patient population.

Effect of Loading Dose of Atorvastatin Prior to Planned Percutaneous Coronary Intervention on Major Adverse Cardiovascular Events in Acute Coronary Syndrome: The SECURE-PCI Randomized Clinical Trial.

Importance: The effects of loading doses of statins on clinical outcomes in patients with acute coronary syndrome (ACS) and planned invasive management remain uncertain. Objective: To determine if periprocedural loading doses of atorvastatin decrease 30-day major adverse cardiovascular events (MACE) in patients with ACS and planned invasive management. Design, Setting, and Participants: Multicenter, double-blind, placebo-controlled, randomized clinical trial conducted at 53 sites in Brazil among 4191 patients with ACS evaluated with coronary angiography to proceed with a percutaneous coronary intervention (PCI) if anatomically feasible. Enrollment occurred between April 18, 2012, and October 6, 2017. Final follow-up for 30-day outcomes was on November 6, 2017. Interventions: Patients were randomized to receive 2 loading doses of 80 mg of atorvastatin (n = 2087) or matching placebo (n = 2104) before and 24 hours after a planned PCI. All patients received 40 mg of atorvastatin for 30 days starting 24 hours after the second dose of study medication. Main Outcomes and Measures: The primary outcome was MACE, defined as a composite of all-cause mortality, myocardial infarction, stroke, and unplanned coronary revascularization through 30 days. Results: Among the 4191 patients (mean age, 61.8 [SD, 11.5] years; 1085 women [25.9%]) enrolled, 4163 (99.3%) completed 30-day follow-up. A total of 2710 (64.7%) underwent PCI, 333 (8%) underwent coronary artery bypass graft surgery, and 1144 (27.3%) had exclusively medical management. At 30 days, 130 patients in the atorvastatin group (6.2%) and 149 in the placebo group (7.1%) had a MACE (absolute difference, 0.85% [95% CI, -0.70% to 2.41%]; hazard ratio, 0.88; 95% CI, 0.69-1.11; P = .27). No cases of hepatic failure were reported; 3 cases of rhabdomyolysis were reported in the placebo group (0.1%) and 0 in the atorvastatin group. Conclusions and Relevance: Among patients with ACS and planned invasive management with PCI, periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days. These findings do not support the routine use of loading doses of atorvastatin among unselected patients with ACS and intended invasive management. Trial Registration: clinicaltrials.gov Identifier: NCT01448642.

Polimorfismo G894T da óxido nítrico-sintetase endotelial e o prognóstico na insuficiência cardíaca / Genetic polymorphism G894T and the prognosis of heart failure outpatients

FUNDAMENTO: Estudos prévios avaliaram o papel do polimorfismo genético da enzima óxido nítrico-sintetase endotelial sobre o prognóstico na insuficiência cardíaca. Entretanto, faltam estudos relacionando o G894T e a insuficiência cardíaca na população brasileira. OBJETIVO: Avaliar a associação do G894T com o prognóstico de amostra de pacientes brasileiros com insuficiência cardíaca. MÉTODOS: Coorte com 145 pacientes com insuficiência cardíaca sistólica, num segmento de 40 meses (média = 22 meses), em dois hospitais universitários do Estado do Rio de Janeiro. Foi avaliada a relação do G894T com os desfechos: remodelamento reverso; melhora da classe funcional (NYHA); taxas de mortalidade e hospitalização. Os diâmetros do átrio e ventrículo esquerdos e a fração de ejeção do ventrículo esquerdo foram medidos na admissão e após 6 meses, para avaliação do remodelamento reverso. A melhora na classe funcional foi avaliada após 6 meses e as taxas de mortalidade e de hospitalização durante todo o seguimento. A raça foi autodeclarada. O polimorfismo G894T foi analisado por reação em cadeia de polimerase e por análise do polimorfismo dos fragmentos de restrição. RESULTADOS: A frequência genotípica foi GG (40%), GT (48,3%) e TT (11,7%), e a frequência alélica foi guanina (64,1%) e tiamina (35,8%). Não houve diferença entre as frequências genotípica ou alélica conforme a raça autodeclarada, tampouco conforme as características basais. Não houve relação entre o genótipo ou a frequência alélica e os desfechos analisados. CONCLUSÃO: Não se observou associação do polimorfismo G894T (Glu298Asp) com o prognóstico de amostra de pacientes ambulatoriais brasileiros com insuficiência cardíaca sistólica.

BACKGROUND: Previous studies have analyzed the role of the genetic polymorphism of endothelial nitric oxide synthase on heart failure prognosis. However, there are no studies relating the G894T and heart failure in Brazil. OBJECTIVE: To evaluate the association between G894T GP and the prognosis of a sample of Brazilian outpatients with heart failure. METHODS: Cohort study included 145 patients with systolic heart failure, followed for up to 40 months (mean = 22), at two university hospitals, in the State of Rio de Janeiro. We evaluated the relationship between G894T and the following outcomes: reverse remodeling, improvement in functional class (NYHA), and mortality and hospitalization rates. The diameters of the left atrium and ventricle, as well as the ejection fraction of the left ventricle, were evaluated at baseline and at 6 months to assess reverse remodeling. The improvement in functional class was evaluated after 6 months, and mortality rate and hospitalization were evaluated during follow-up. Race was self-declared. G894T polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The genotypic frequencies were GG (40%), GT (48.3%) and TT (11.7%). The allele frequency was guanine (64.1%) and thiamine (35.8%). There were no differences between the genotype or allelic frequencies according to self-declared race, either as baseline characteristics. There was no relationship between genotype or allele frequency and the outcome measures. CONCLUSION: No association was observed between the G894T polymorphism (Glu298Asp) and prognosis in this sample of Brazilian outpatients with systolic heart failure.

Genetic polymorphism G894T and the prognosis of heart failure outpatients.

BACKGROUND: Previous studies have analyzed the role of the genetic polymorphism of endothelial nitric oxide synthase on heart failure prognosis. However, there are no studies relating the G894T and heart failure in Brazil. OBJECTIVE: To evaluate the association between G894T GP and the prognosis of a sample of Brazilian outpatients with heart failure. METHODS: Cohort study included 145 patients with systolic heart failure, followed for up to 40 months (mean = 22), at two university hospitals, in the State of Rio de Janeiro. We evaluated the relationship between G894T and the following outcomes: reverse remodeling, improvement in functional class (NYHA), and mortality and hospitalization rates. The diameters of the left atrium and ventricle, as well as the ejection fraction of the left ventricle, were evaluated at baseline and at 6 months to assess reverse remodeling. The improvement in functional class was evaluated after 6 months, and mortality rate and hospitalization were evaluated during follow-up. Race was self-declared. G894T polymorphism was analyzed by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The genotypic frequencies were GG (40%), GT (48.3%) and TT (11.7%). The allele frequency was guanine (64.1%) and thiamine (35.8%). There were no differences between the genotype or allelic frequencies according to self-declared race, either as baseline characteristics. There was no relationship between genotype or allele frequency and the outcome measures. CONCLUSION: No association was observed between the G894T polymorphism (Glu298Asp) and prognosis in this sample of Brazilian outpatients with systolic heart failure.

ß-adrenergic receptor polymorphisms in susceptibility, response to treatment and prognosis in heart failure: implication of ethnicity.

Common functional polymorphisms in ß-adrenergic receptor (ßAR) genes have been associated with heart failure (HF) phenotypes and pharmacogenetic interactions with ßAR blockers. This study evaluated the association between ßAR polymorphisms and carvedilol drug response and prognosis in patients with HF. In this prospective cohort controlled study, 326 volunteers were enrolled [146 HF patients (ejection fraction (EF)<50% by Simpson) and 180 healthy controls]. Drug response was evaluated by echocardiography and outcomes were mortality and hospitalization. DNA was extracted from peripheral blood leukocytes, fragments were amplified by the polymerase reaction and genotyped by restriction fragment length polymorphism (RFLP) for Ser49Gly and Arg389Gly ßAR-1 polymorphisms and Gln27Glu and Arg16Gly ßAR-2 polymorphisms. The study population was in Hardy­Weinberg equilibrium. The survival rate was adjusted using the Kaplan-Meier method. HF patients showed the following characteristics: EF 35±9%, 69.9% male, age 59±13 years, 50.7% self-identified as black, 46% had ischemic etiology. The mean follow-up of 23 months showed 18 mortalities and 46 hospitalizations. The genotypes Glu27Glu (24.7 vs. 6.1%, p=0.0004) and Arg16Arg (72.6 vs. 22.8, p<0.0001) of ßAR2 polymorphisms and Gly49Gly (33.6 vs. 4.3%, p<0.0001) of the ßAR1 polymorphism were higher in HF patients compared with controls. Patients with hospital admission showed a significantly higher Gly389 allelic frequency (54.9 vs. 42.1%, p=0.039), and the trend prevailed among patients who succumbed to the disease (61.1%, p=0.047). Black patients with the Ser49Ser genotype showed a reduced survival compared with the Gly49Gly or Ser49Gly genotypes (p=0.028). There was no association between improved LVEF >20% and ßAR polymorphisms. HF patients with ß-blocker therapy and the Gly389 allele have reduced event-free survival compared to those carrying the Arg389 allele. Additionally, systolic HF outpatients undergoing ß-blocker therapy, self­identified as black and homozygous for Ser49Ser may have reduced event-free survival, while Glu27Glu, Arg16Arg and Gly49Gly genotypes may be associated with risk for HF.

Summary of the II Brazilian Guideline update on Acute Heart Failure 2009/2011.

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

Sumário de atualização da II Diretriz Brasileira de Insuficiência Cardíaca Aguda 2009/2011 / Summary of the II Brazilian Guideline Update on Acute Heart Failure 2009/2011

Nos últimos dois anos, observamos diversas modificações na abordagem diagnóstica e terapêutica dos pacientes com Insuficiência Cardíaca aguda (IC aguda), o que nos motivou quanto à necessidade da realização de um sumário de atualização da II Diretriz Brasileira de Insuficiência Cardíaca Aguda de 2009. Na avaliação diagnóstica, o fluxograma diagnóstico foi simplificado e foi fortalecido o papel da avaliação clínica e ecocardiograma. Na avaliação clínico-hemodinâmica admissional, o ecocardiograma hemodinâmico ganhou destaque no auxilio da definição dessa condição no paciente com IC aguda na sala de emergência. Na avaliação prognóstica, os biomarcadores tiveram seu papel mais bem estabelecido, e a síndrome cardiorrenal teve seus critérios e valor prognóstico mais bem definidos. Os fluxogramas de abordagem terapêutica foram revistos, tornando-se mais simples e objetivos. Dentre os avanços na terapêutica medicamentosa destacam-se a segurança e a importância da manutenção ou introdução dos betabloqueadores na terapêutica admissional. A anticoagulação, de acordo com as novas evidências, ganha um espectro maior de indicações. O edema agudo de pulmão tem bem estabelecido os seus modelos hemodinâmicos de apresentação com suas distintas formas de abordagens terapêuticas, com novos níveis de indicação e evidência. No tratamento cirúrgico da IC aguda, a revascularização miocárdica, a abordagem das lesões mecânicas e o transplante cardíaco foram revistos e atualizados. Este sumário de atualização fortalece a II Diretriz Brasileira de Insuficiência Cardíaca Aguda por mantê-la atualizada e rejuvenescida. Todos os clínicos cardiologistas que lidam com pacientes com IC aguda encontrarão na diretriz e em seu sumário de atualização importantes instrumentos no auxílio da prática clínica para o melhor diagnóstico e tratamento de seus pacientes.

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

Polimorfismos beta1-adrenérgico associados com Fibrilação Atrial na Insuficiência Cardíaca Sistólica / Beta1-adrenergic receptor polymorphisms associated with atrial fibrillation in systolic heart failure

FUNDAMENTO: O sistema nervoso simpático apresenta grande importância na patogênese da fibrilação atrial na insuficiência cardíaca sistólica. A identificação de polimorfismos no gene ADBR1 do receptor beta1-adrenérgico representa um importante passo no conhecimento dessa patogênese. OBJETIVO: Este estudo analisou a associação entre os dois polimorfismos funcionais do gene ADBR1 do receptor beta1-adrenérgico, Ser49Gly e Arg389Gly, e a presença da fibrilação atrial em pacientes com insuficiência cardíaca sistólica. MÉTODOS: Estudo caso-controle com 144 pacientes portadores de insuficiência cardíaca sistólica, dos quais 24 com fibrilação atrial (casos) e 120 sem fibrilação atrial (controles). O DNA genômico foi extraído de leucócitos do sangue periférico e os genótipos dos polimorfismos Ser49Gly e Arg389Gly foram identificados em todos os indivíduos por PCR/RFLP (polymerase chain reaction / restriction fragment length polymorphism). RESULTADOS: A média etária foi 59 ± 13 anos, 70% dos pacientes eram do sexo masculino, 42% apresentavam causa isquêmica e 74% apresentavam hipertensão arterial sistêmica. Os genótipos Ser49Ser e Arg389Arg apresentaram associação significativa com fibrilação atrial (p = 0,005 e p = 0,01; respectivamente). Por meio de regressão logística, ambos ajustados para o tamanho do átrio esquerdo e idade, mantiveram associação significativa (Arg389Arg - odds ratios: 2,78; intervalo de confiança de 95% = 1,02 - 7,56 e Ser49Ser - odds ratios: 8,02; intervalo de confiança de 95% = 1,02 - 63,82). CONCLUSÃO: Ambos os genótipos associaram-se com fibrilação atrial nos pacientes estudados, porém apenas o polimorfismo Ser49Gly apresentava-se em equilíbrio de Hardy-Weinberg.

BACKGROUND: The sympathetic nervous system is of great importance in the pathogenesis of atrial fibrillation in systolic heart failure. The identification of polymorphisms in the beta1-adrenergic receptor gene (ADBR1) represents an important step in understanding this pathogenesis. OBJECTIVE: This study assessed the association between the two functional polymorphisms of the beta1-adrenergic receptor gene (ADBR1), Ser49Gly and Arg389Gly, and the presence of atrial fibrillation in patients with systolic heart failure. METHODS: Case-control study with 144 patients with systolic heart failure, including 24 with atrial fibrillation (cases) and 120 without atrial fibrillation (controls). Genomic DNA was extracted from peripheral blood leukocytes and the genotypes of Ser49Gly and Arg389Gly polymorphisms were identified in all individuals by PCR/RFLP (polymerase chain reaction / restriction fragment length polymorphism). RESULTS: Mean age was 59 ± 13 years, 70% of patients were males, 42% had ischemic causes and 74% had hypertension. Genotypes Ser49Ser and Arg389Arg were significantly associated with atrial fibrillation (p = 0.005 and p = 0.01, respectively). After logistic regression, both adjusted for left atrial size and age, the significant association persisted (Arg389Arg - odds ratios: 2.78, 95% confidence interval = 1.02 to 7.56 and Ser49Ser - odds ratios: 8.02, 95% confidence interval = 1.02 to 63.82). CONCLUSION: Both genotypes were associated with atrial fibrillation in patients; however, only Ser49Gly polymorphism was is in Hardy-Weinberg equilibrium.

Beta1-adrenergic receptor polymorphisms associated with atrial fibrillation in systolic heart failure.

BACKGROUND: The sympathetic nervous system is of great importance in the pathogenesis of atrial fibrillation in systolic heart failure. The identification of polymorphisms in the beta1-adrenergic receptor gene (ADBR1) represents an important step in understanding this pathogenesis. OBJECTIVE: This study assessed the association between the two functional polymorphisms of the beta1-adrenergic receptor gene (ADBR1), Ser49Gly and Arg389Gly, and the presence of atrial fibrillation in patients with systolic heart failure. METHODS: Case-control study with 144 patients with systolic heart failure, including 24 with atrial fibrillation (cases) and 120 without atrial fibrillation (controls). Genomic DNA was extracted from peripheral blood leukocytes and the genotypes of Ser49Gly and Arg389Gly polymorphisms were identified in all individuals by PCR/RFLP (polymerase chain reaction / restriction fragment length polymorphism). RESULTS: Mean age was 59 ± 13 years, 70% of patients were males, 42% had ischemic causes and 74% had hypertension. Genotypes Ser49Ser and Arg389Arg were significantly associated with atrial fibrillation (p = 0.005 and p = 0.01, respectively). After logistic regression, both adjusted for left atrial size and age, the significant association persisted (Arg389Arg - odds ratios: 2.78, 95% confidence interval = 1.02 to 7.56 and Ser49Ser - odds ratios: 8.02, 95% confidence interval = 1.02 to 63.82). CONCLUSION: Both genotypes were associated with atrial fibrillation in patients; however, only Ser49Gly polymorphism was is in Hardy-Weinberg equilibrium.

Sintomas depressivos e hospitalizações por insuficiência cardíaca: prevalência, preditores e mortalidade / Depressive symptoms and hospitalizations for heart failure: prevalence, predictors and mortality

Fundamentos. Estudos sobre sintomas depressivos (SD) têm sido feitos em pacientes hospitalizados por insuficiência cardíaca (IC) e tem sido ignorada a influência de várias características. Objetivos. Avaliar prevalência, preditores e correlação da gravidade dos SD e a mortalidade em hospitalizações por IC. Métodos. Estudo prospectivo que analisou hospitalizações consecutivas por IC. Foram analisados dados sociodemográficos, clínicos e o desfecho considerado foi óbito. Na análise dos SD foi utilizado o Inventário de Depressão de Beck. Foi feita análise comparativa entre grupos com e sem SD e submetidos a regressão logística as variáveis com p entre 0,05 e 0,1. Avaliou-se a relação entre a gravidade de SD e mortalidade. Foi utilizado teste qui-quadrado ou exato de Fisher para variáveis categóricas e t de student para contínuas. Foi considerado estatisticamente significante p<0,05. Resultados. Foram avaliados 103 pacientes, sendo 63,1% mulheres, 50,5% casados e alfabetizados 73,8%. O total de 75,2% estava em classe funcional II e III de New York Heart Association (NYHA). Hipertensão arterial sistêmica foi a comorbidade mais comum (92,2%). A presença de SD foi presente em 69 (67%) pacientes. Os preditores de SD foram: estado civil (p=0,03) e na regressão logística: sexo (p<0,0001), modo de vida (0,002) e etiologia da IC (p<0,0001). A mortalidade relacionou-se à SD em sintomas moderados (p=0,04) e graves (0,01). Conclusão. Os SD são comuns em hospitalizações por IC. A prevalência varia conforme características clínicas dos pacientes. Os preditores foram sexo, estado civil, modo de vida e etiologia da IC. A mortalidade relacionouse a SD moderados e graves.

Background. Studies of depressive symptoms (DS) has been made in patients hospitalized for heart failure (HF) and the influence of various characteristics has been ignored. Objectives. To assess prevalence, predictors and correlated to the severity of DS and mortality in HF hospitalizations. Methods. This prospective study examined consecutive hospitalizations for HF. We analyzed sociodemographic data and clinical outcome was death. In analysis of DS was used Beck Depression Inventory II. Comparative analysis were made between groups with and without DS and subjected to logistic regression variables with p between 0.05 and 0.1. We evaluated the relationship between the severity of SD and mortality. It was considered statistically significant p <0.05. Results: We evaluated 103 patients, 63.1% women, 50.5% were married and 73.8% literate. A total of 75.2% were in New York Heart Association (NYHA) functional class II and III. Hypertension was the most common comorbidity (92.2%). The DS was present in 69 (67%) patients. The predictors of DS were: marital status (p=0.03) and logistic regression: sex (p<0.0001), lifestyle (0.002) and etiology of HF (p<0.0001). Mortality was related to the DS in moderate symptoms (p=0.04) and severe (0.01). Conclusion. The DS are common in HF hospitalizations. The prevalence varies according to clinical characteristics of patients. The predictors were gender, marital status, lifestyle and etiology of HF. Mortality was related to moderate and severe DS.

[Adrenergic receptor polymorphisms in heart failure: what can genetics explain?].

Heart failure (HF) is a complex disease, which involves several physiopathological mechanisms and different genetic polymorphisms. The adrenergic system is directly related to this pathology, as it participates in cardiovascular autoregulation and has a crucial role in the deterioration of cardiac function. The beta-blockers appeared as a great advance in cardiology for the treatment of HF; however, the drug response varies according to each patient, as several factors are associated, such as the genetic one. This review aims at assessing the genetic involvement in the development of HF, the drug response and the prognosis.

Os polimorfismos dos receptores adrenérgicos na insuficiência cardíaca: o que a genética explica? / Adrenergic receptor polymorphisms in heart failure: what can genetics explain?

A insuficiência cardíaca (IC) é uma doença complexa, onde diversos mecanismos fisiopatológicos atuam e diferentes polimorfismos genéticos estão envolvidos. O sistema adrenérgico está diretamente relacionado a esta patologia participando da auto-regulação cardiovascular, tendo papel crucial na deteriorização da função cardíaca. Os beta-bloqueadores surgiram como um grande avanço da cardiologia no tratamento da IC, no entanto a resposta medicamentosa varia para cada paciente podendo estar relacionado a diversos fatores, entre eles o genético. A determinação pela genética do desenvolvimento da IC, da resposta medicamentosa e prognóstico são questões que serão abrangidas nesta revisão.

Heart failure (HF) is a complex disease, which involves several physiopathological mechanisms and different genetic polymorphisms. The adrenergic system is directly related to this pathology, as it participates in cardiovascular autoregulation and has a crucial role in the deterioration of cardiac function. The beta-blockers appeared as a great advance in cardiology for the treatment of HF; however, the drug response varies according to each patient, as several factors are associated, such as the genetic one. This review aims at assessing the genetic involvement in the development of HF, the drug response and the prognosis.

Temas de atualização e revisão em clínica médica: impedância cardiográfica: o avanço tecnológico na tomada de decições / Themes of updating and revision in medical clinic: impedance cardiography: technological advance in taking decisions

A impedância cardiográfica é uma tecnologia baseada nas leis de Ohm, que nos permite avaliar, de forma não invasiva e com alta acurácia (1), parâmetros hemodinâmicos, através das diferentes propriedades elétricas dos tecidos, como músculo, osso, gordura e sangue. Pode ser utilizada em nível hospitalar ou ambulatorial e aplicada em diversas doenças, principalmente na hipertensão arterial resistente e insuficiência cardíaca. É capaz de identificar a causa da dispneia na sala de emergência, predizer a descompensação por insuficiência cardíaca e titular doses do tratamento medicamentoso nesta síndrome. Mais recentemente, tem sido utilizada na otimização dos marcapassos cardíacos.

The impedance cardiography (ICG) isa technology based on Ohm's laws, whick allows to assess hemodynamic parameters, in a non-invasive and with high accuracy, through the different electrical properties of tissues such as muscle, bone, fat and blood. Can be used in hospital or outpatient and applied in various diseases, especially in resistant hypertension and heart failure. Is is able to identify the cause of dyspnea in the emergency room, to predict decompensated heart failure and titration of doses of the drug in this syndrome. More recently, it has been used in optimization of cardiac pacemakers.

Endothelial nitric oxide synthase Glu298Asp gene polymorphism in a multi-ethnical population with heart failure and controls.

Brazilian population has a multi-ethnical profile and the prevalence of endothelial nitric oxide synthase enzyme (eNOS) polymorphism in heart failure (HF) has not been previously studied. Therefore the present study assessed the association of eNOS Glu298Asp polymorphism in patients with HF and controls. In a crossover study, was analysed the distribution of the Glu298Asp in 100 outpatients with HF, and 103 healthy controls. Self-reported race were analyzed. Left atria and left ventricle diameters and ejection fraction were evaluated in patients group. Glu298Asp was analysed by polymerase chain reaction and restriction fragment length polymorphism. The patient's average age was 59 years, 66% males, 49% Afro-descendants. The allelic frequency in patient group was Glu298=72%/Asp298=28% and the genotype frequency (GF) was Glu298Glu:49%; Glu298Asp:47%; Asp298Asp:4%. In control group, 60% Glu298 and 40% Asp298; 35% Glu298Glu, 49.5% Glu298Asp and 15.5% Asp298Asp. The prevalence of allele Glu298 was significantly higher in patients (p=0.009) as genotype Glu298Glu (p=0.03). The Glu298 in Afro-Brazilians (79%) and white patients (67%) were similar, although there was significant difference (p=0.03) in GF Glu298Glu between Afro-Brazilians and whites. There was an increased prevalence of hypertension and increased atria in Glu298Glu patients comparing with combined genotype Glu298Asp and Asp298Asp. This study suggests a regional variation in the distribution of Glu298Asp. The comparison of this distribution in African-Brazilian suggests a synergistic effect of African-descendent, Glu298Glu genotype and HF. Also demonstrated an increased frequency of Glu298 and Glu298Glu, suggesting interaction of them with HF. In HF patients, the clinical, echocardiograph and genotype analysis suggests an association of Glu298 allele and hypertension.

Medicina individualizada aplicada à cardiologia / Personalized medicine applied to cardiology

Atualmente, a farmacogenômica está recebendo grande atenção da comunidade médica e do público em geral devido à promessa da medicina personalizada. Aincorporação dos conceitos da farmacogenética já estão fortemente presentes no dia a dia da oncologia e começam a ser aceitos na prática cardiológica. A base racional da farmacogenética envolve o desenvolvimento de medicamentos específicos para determindado grupo de pacientes, maximizando a resposta terapêutica e reduzindo efeitos adversos. Este artigo de atualização visa a reunir as principais informações da biologia molecular aplicadas à cardiologia.