Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity: The CECCY Trial.

BACKGROUND: Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with ß-blockers remains controversial. OBJECTIVES: This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity. METHODS: The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction. RESULTS: Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057). CONCLUSIONS: In this largest clinical trial of ß-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450).

High-Intensity Interval Training in Heart Transplant Recipients: A Systematic Review with Meta-Analysis.

Heart transplantation (HTx) is considered an efficient and gold-standard procedure for patients with end-stage heart failure. After surgery, patients have lower aerobic power (VO2max) and compensatory hemodynamic responses. The aim of the present study was to assess through a systematic review with meta-analysis whether high-intensity interval training (HIIT) can provide benefits for those parameters. This is a systematic review with meta-analysis, which searched the databases and data portals PubMed, Web of Science, Scopus, Science Direct and Wiley until December 2016 (pairs). The following terms and descriptors were used: "heart recipient" OR "heart transplant recipient" OR "heart transplant" OR "cardiac transplant" OR "heart graft". Descriptors via DeCS and Mesh were: "heart transplantation'' OR "cardiac transplantation". The words used in combination (AND) were: "exercise training" OR "interval training" OR "high intensity interval training" OR "high intensity training" OR "anaerobic training" OR "intermittent training" OR "sprint training". The initial search identified 1064 studies. Then, only those studies assessing the influence of HIIT on the post-HTx period were added, resulting in three studies analyzed. The significance level adopted was 0.05. Heart transplant recipients showed significant improvement in VO2peak, heart rate and peak blood pressure in 8 to 12 weeks of intervention.

High-Intensity Interval Training in Heart Transplant Recipients: A Systematic Review with Meta-Analysis / Treinamento Intervalado de Alta Intensidade em Transplantados de Coração: Uma Revisão Sistemática com Meta-Análise

Abstract Heart transplantation (HTx) is considered an efficient and gold-standard procedure for patients with end-stage heart failure. After surgery, patients have lower aerobic power (VO2max) and compensatory hemodynamic responses. The aim of the present study was to assess through a systematic review with meta-analysis whether high-intensity interval training (HIIT) can provide benefits for those parameters. This is a systematic review with meta-analysis, which searched the databases and data portals PubMed, Web of Science, Scopus, Science Direct and Wiley until December 2016 (pairs). The following terms and descriptors were used: "heart recipient" OR "heart transplant recipient" OR "heart transplant" OR "cardiac transplant" OR "heart graft". Descriptors via DeCS and Mesh were: "heart transplantation'' OR "cardiac transplantation". The words used in combination (AND) were: "exercise training" OR "interval training" OR "high intensity interval training" OR "high intensity training" OR "anaerobic training" OR "intermittent training" OR "sprint training". The initial search identified 1064 studies. Then, only those studies assessing the influence of HIIT on the post-HTx period were added, resulting in three studies analyzed. The significance level adopted was 0.05. Heart transplant recipients showed significant improvement in VO2peak, heart rate and peak blood pressure in 8 to 12 weeks of intervention.

Resumo O transplante de coração é considerado procedimento eficiente e padrão ouro para pacientes com quadro de insuficiência cardíaca terminal. Verifica-se que após o procedimento cirúrgico os pacientes apresentam menor valor de potência aeróbia (VO2máx) e respostas hemodinâmicas descompensadas. O objetivo do presente estudo foi de verificar por meio de uma revisão sistemática com meta-análise se o treinamento intervalado de alta intensidade é capaz de proporcionar benefícios a tais capacidades. Trata-se de uma revisão sistemática com meta-análise, que realizou buscas em pares nas bases e portais de dados PubMed, Web of Science, Scopus, Science Direct e Wiley até dezembro de 2016. Para busca dos artigos utilizaram-se os termos e descritores: "heart recipient" OR "heart transplant recipient" OR "heart transplant" OR "cardiac transplant" OR "heart graft". Os descritores pelo DeCS e Mesh foram: "heart transplantation'' OR "cardiac transplantation". As palavras utilizadas em combinação (AND) foram "exercise training" OR "interval training" OR "high intensity interval training" OR "high intensity training" OR "anaerobic training" OR "intermittent training" OR "sprint training". A busca inicial identificou 1064 estudos. Em seguida, apenas os estudos que analisaram a influência do treinamento intervalado de alta intensidade no período pós transplante foram adicionados, sendo, assim, três estudos analisados. O nível adotado nas análises estatísticas para determinar significância foi de 0,05. Verificou-se que, entre 8 e 12 semanas de intervenção, os pacientes transplantados de coração apresentaram melhoras significativas em VO2pico, frequência cardíaca e pressão arterial pico.

Functional Class in Children with Idiopathic Dilated Cardiomyopathy. A pilot Study / Classe Funcional em Crianças Portadoras de Miocardiopatia Dilatada Idiopática. Estudo Piloto

Abstract Background: Idiopathic dilated cardiomyopathy (IDCM), most common cardiac cause of pediatric deaths, mortality descriptor: a low left ventricular ejection fraction (LVEF) and low functional capacity (FC). FC is never self reported by children. Objective: The aims of this study were (i) To evaluate whether functional classifications according to the children, parents and medical staff were associated. (iv) To evaluate whether there was correlation between VO2 max and Weber's classification. Method: Prepubertal children with IDCM and HF (by previous IDCM and preserved LVEF) were selected, evaluated and compared. All children were assessed by testing, CPET and functional class classification. Results: Chi-square test showed association between a CFm and CFp (1, n = 31) = 20.6; p = 0.002. There was no significant association between CFp and CFc (1, n = 31) = 6.7; p = 0.4. CFm and CFc were not associated as well (1, n = 31) = 1.7; p = 0.8. Weber's classification was associated to CFm (1, n = 19) = 11.8; p = 0.003, to CFp (1, n = 19) = 20.4; p = 0.0001and CFc (1, n = 19) = 6.4; p = 0.04). Conclusion: Drawing were helpful for children's self NYHA classification, which were associated to Weber's stratification.

Resumo Fundamento: A cardiomiopatia dilatada idiopática (CMDid) possui poucos preditores de mortalidade descritos: a baixa fração de ejeção de ventrículo esquerdo (FEVE) e a baixa capacidade funcional, sendo esta subjetiva. Objetivo: Os objetivos desse estudo foram (i) Avaliar se as classes funcionais propostas pela NYHA, modificada para crianças, estiveram associadas entre a percepção médica (CFm), dos pais ou representantes (CFp) e das próprias crianças avaliadas (CFc). (ii) Avaliar se houve correlação entre VO2 max e a classificação proposta por Weber. Método: Crianças com CMDid e com IC por CMDid prévia com FEVE preservada, na fase pré-puberdade foram selecionadas submetidas a avaliações de ergoespirometria e classificação da classe funcional. As crianças utilizaram uma representação gráfica para se intitular quanto à classe funcional. Resultado: O teste Chi-quadrado mostrou que houve associação ente a CFm e CFp (1, n = 31) = 20,6; p = 0,002. Não houve associação significativa entre CFp e CFc (1, n = 31) = 6,7; p = 0,4. As CF segundo médico e CFc não foram, tampouco, associadas (1, n = 31) = 1,7; p = 0,8. A classificação de Weber foi significativamente associada às três classes funcionais (classificação de Weber e CFm (1, n = 19) = 11,8; p = 0,003; classificação de Weber e CFp (1, n = 19) = 20,4; p = 0,0001; classificação de Weber e CFc (1, n = 19) = 6.4; p = 0.04.). Conclusão: A representação gráfica serviu para que as crianças pudessem se classificar segundo a NYHA, que se demonstrou associada com a estratificação de Weber.

A meta-analysis of cardiopulmonary exercise testing in pre-pubertal healthy children produces new information / Metanálise de testes de exercícios cardiopulmonares em crianças pré-púberes saudáveis

The objective of the paper was to analyze cardiopulmonary data and functional capacity in healthy children who have undergone ergospirometry. A systematic meta-analysis review of ergospirometry in children was performed based on reports indexed in PubMed, Bireme, and Embase. End points were age, sex, body mass index, maturation evaluation, the type of ergometer used for ergospirometry, and cardiopulmonary related values (peak heart rate and peak oxygen consumption [VO2]). Twenty articles were selected, which included 3,808 children, averaging 9.1years of age. A treadmill was used in 55% of the trials, and a cycle ergometer in the other 45% studies included in this analysis. The following statistically significant results were found: on subgroup analysis, peak VO2 values in boys on the treadmill was 20% higher than peak VO2 values in girls on the cycle ergometer; peak VO2 values in boys on the treadmill were 18% greater than that for girls on the same ergometer. BMI was inversely correlated with peak VO2 in the total analysis, and in female subjects on cycle ergometers. Peak heart rate during the ergospirometrical test was 5.6 BPM higher than the estimated 95% maximum heart rate. Most of the ergospirometrical parameters had not been reported in the original trials analyzed here. We conclude that peak VO2 value for pre-pubertal children are circa 18% higher in boys vs. girls and overall higher in treadmill vs. cycle ergometers.

O objetivo do trabalho foi analisar dados relativos à função cardiopulmonar e capacidade funcional em crianças saudáveis submetidas a ergoespirometria. Uma revisão meta-analítica sistemática de ergoespirometria em crianças foi realizada com base na literatura indexada no PubMed, Bireme, e Embase. Os parâmetros pesquisados foram: idade, sexo, índice de massa corporal, avaliação da maturação, tipo de ergômetro utilizado para ergoespirometria, e os valores cardiopulmonares relacionados (frequência cardíaca máxima e consumo máximo de oxigênio [VO2]). Vinte artigos foram selecionados, que incluíram 3808 crianças, com uma média de 9,1 anos de idade. Esteiras erogmétricas foram utilizadas em 55% dos ensaios, e bicicletas erogmétricas em outros 45% incluídos nesta análise. Os seguintes resultados estatisticamente significantes foram encontradas: em análise de subgrupo, valores de VO2 de pico em meninos, obtidos na esteira foram 20% maiores do que os respectivos valores em meninas na bicicleta ergométrica valores de VO2 pico em meninos na esteira foram 18% maiores do que para meninas no mesmo ergômetro. O Índice de massa corpórea correlacionou-se inversamente com VO2 de pico na análise total e em meninas testadas em ciclo-ergômetro. A frequência cardíaca máxima durante o teste ergo-espirométrico foi 5,6 BPM superior aos 95% da freqüência cardíaca máxima prevista. A maior parte dos parâmetros ergo-espirométricos não havia sido relatada nos estudos originais por nós analisados. A conclusão desta metanálise é que o valor de VO2 de pico para crianças pré-púberes é cerca de 18% maior nos meninos versus meninas e em esteira vs. ciclo-ergômetro.

Postexercise Hypotension after Heart Transplant: Water- versus Land-Based Exercise.

PURPOSE: Heart transplant recipients (HTx) have a high prevalence of hypertension. Although exercise training promotes blood pressure (BP) reduction in HTx, the effects of a single exercise bout are unknown. Thus, we analyzed the acute effects of heated water-based exercise (HEx) versus land-based exercise (LEx) on ambulatory BP (ABP) in HTx. METHODS: Eighteen (six females) clinically stable HTx (time since surgery = 5.0 ± 0.7 yr) age 45.7 ± 2.7 yr underwent 30 min of HEx (walking inside the pool), LEx (walking on a treadmill), and nonexercise control (CON) intervention in random order (2-5 d between interventions). HEx and LEx intensity was set at 11-13 in the 6-20 RPE scale. Twenty-four-hour (24-h) ABP monitoring was performed after each intervention. RESULTS: No significant differences between interventions were found in 24-h and nighttime BP. However, daytime diastolic BP was significantly lower after HEx than CON (-4 ± 1.6 mm Hg, P = 0.03), and daytime diastolic BP tended to be lower after LEx than CON (-2.3 ± 1.1 mm Hg, P = 0.052). Hourly analysis showed that systolic and diastolic BP values were lower after HEx (average reductions of 6.6 to 12.3 mm Hg, P < 0.01) and LEx (average reductions of 5 to 8.3 mm Hg, P < 0.05) than after CON in several hours. No significant differences between HEx and LEx were found in any ABP data. CONCLUSION: HEx and LEx promoted similar reductions in ABP of heart transplant recipients, which suggests that they may be a tool to counteract hypertension in this high-risk population.

Reverse Auction: A Potential Strategy for Reduction of Pharmacological Therapy Cost / Pregão: Estratégia para Redução do Custo da Terapia Farmacológica em Insuficiência Cardíaca e Transplante Cardíaco

Background:Polypharmacy is a significant economic burden.Objective:We tested whether using reverse auction (RA) as compared with commercial pharmacy (CP) to purchase medicine results in lower pharmaceutical costs for heart failure (HF) and heart transplantation (HT) outpatients.Methods:We compared the costs via RA versus CP in 808 HF and 147 HT patients followed from 2009 through 2011, and evaluated the influence of clinical and demographic variables on cost.Results:The monthly cost per patient for HF drugs acquired via RA was $10.15 (IQ 3.51-40.22) versus $161.76 (IQ 86.05‑340.15) via CP; for HT, those costs were $393.08 (IQ 124.74-774.76) and $1,207.70 (IQ 604.48-2,499.97), respectively.Conclusion:RA may reduce the cost of prescription drugs for HF and HT, potentially making HF treatment more accessible. Clinical characteristics can influence the cost and benefits of RA. RA may be a new health policy strategy to reduce costs of prescribed medications for HF and HT patients, reducing the economic burden of treatment.

Fundamento:A polifarmácia tem um significativo peso econômico.Objetivo:Testar se o uso de pregão em comparação ao de farmácias comerciais (FC) para a compra de medicamentos reduz o custo do tratamento de pacientes ambulatoriais de insuficiência cardíaca (IC) e transplante cardíaco (TC).Métodos:Comparação dos custos do tratamento através de pregão versus FC em pacientes de IC (808) e TC (147) acompanhados de 2009 a 2011, avaliando-se a influência de variáveis clínicas e demográficas no custo.Resultados:Os custos mensais por paciente para medicamentos de IC adquiridos através de pregão e através de FC foram $10,15 (IQ 3,51-40,22) e $161,76 (IQ 86,05-340,15), respectivamente. Para TC, aqueles custos foram $393,08 (IQ 124,74-774,76) e $1.207,70 (IQ 604,48-2.499,97), respectivamente.Conclusão:O pregão pode reduzir o custo dos medicamentos prescritos para IC e TC, podendo tornar o tratamento de IC mais acessível. As características clínicas podem influenciar o custo e os benefícios do pregão, que pode ser uma nova estratégia de política de saúde para baixar os custos dos medicamentos prescritos para IC e TC, diminuindo o peso econômico do tratamento. (Arq Bras Cardiol. 2015; [online].ahead print, PP.0-0).

Reverse auction: a potential strategy for reduction of pharmacological therapy cost.

BACKGROUND: Polypharmacy is a significant economic burden. OBJECTIVE: We tested whether using reverse auction (RA) as compared with commercial pharmacy (CP) to purchase medicine results in lower pharmaceutical costs for heart failure (HF) and heart transplantation (HT) outpatients. METHODS: We compared the costs via RA versus CP in 808 HF and 147 HT patients followed from 2009 through 2011, and evaluated the influence of clinical and demographic variables on cost. RESULTS: The monthly cost per patient for HF drugs acquired via RA was $10.15 (IQ 3.51-40.22) versus $161.76 (IQ 86.05­340.15) via CP; for HT, those costs were $393.08 (IQ 124.74-774.76) and $1,207.70 (IQ 604.48-2,499.97), respectively. CONCLUSION: RA may reduce the cost of prescription drugs for HF and HT, potentially making HF treatment more accessible. Clinical characteristics can influence the cost and benefits of RA. RA may be a new health policy strategy to reduce costs of prescribed medications for HF and HT patients, reducing the economic burden of treatment.

Determinants of peak VO2 in heart transplant recipients.

OBJECTIVE: To establish the determinants of the peak VO2 in heart transplant recipients. METHODS: Patient's assessment was performed in two consecutive days. In the first day, patients performed the heart rate variability assessment followed by a cardiopulmonary exercise test. In the second day, patients performed a resting echocardiography. Heart transplant recipients were eligible if they were in a stable condition and without any evidence of tissue rejection diagnosed by endomyocardial biopsy. Patients with pacemaker, noncardiovascular functional limitations such as osteoarthritis and chronic obstructive pulmonary disease were excluded from this study. RESULTS: Sixty patients (68% male, 48 years and 64 months following heart transplantation) were assessed. Multivariate analysis selected the following variables: receptor's gender (P=0.001), receptor age (P=0.049), receptor Body Mass Index (P=0.005), heart rate reserve (P <0.0001), left atrium diameter (P=0.016). Multivariate analysis showed r=0.77 and r2=0.6 with P <0.001. Equation: peakVO2=32.851 - 3.708 (receptor gender) - 0.067 (receptor age) - 0.318 (receptor BMI) + 0.145 (heart rate reserve) - 0.111 (left atrium diameter). CONCLUSION: The determinants of the peak VO2 in heart transplant recipients were: receptor sex, age, Body Mass Index, heart rate reserve and left atrium diameter. Heart rate reserve was the unique variable positively associated with peak VO2. This data suggest the importance of the sympathetic reinnervation in peak VO2 in heart transplant recipients.

Determinants of peak VO2 in heart transplant recipients / Determinantes do pico de VO2 em transplantados cardíacos

Objective: To establish the determinants of the peak VO2 in heart transplant recipients. Methods: Patient's assessment was performed in two consecutive days. In the first day, patients performed the heart rate variability assessment followed by a cardiopulmonary exercise test. In the second day, patients performed a resting echocardiography. Heart transplant recipients were eligible if they were in a stable condition and without any evidence of tissue rejection diagnosed by endomyocardial biopsy. Patients with pacemaker, noncardiovascular functional limitations such as osteoarthritis and chronic obstructive pulmonary disease were excluded from this study. Results: Sixty patients (68% male, 48 years and 64 months following heart transplantation) were assessed. Multivariate analysis selected the following variables: receptor's gender (P=0.001), receptor age (P=0.049), receptor Body Mass Index (P=0.005), heart rate reserve (P <0.0001), left atrium diameter (P=0.016). Multivariate analysis showed r=0.77 and r2=0.6 with P <0.001. Equation: peakVO2=32.851 - 3.708 (receptor gender) - 0.067 (receptor age) - 0.318 (receptor BMI) + 0.145 (heart rate reserve) - 0.111 (left atrium diameter). Conclusion: The determinants of the peak VO2 in heart transplant recipients were: receptor sex, age, Body Mass Index, heart rate reserve and left atrium diameter. Heart rate reserve was the unique variable positively associated with peak VO2. This data suggest the importance of the sympathetic reinnervation in peak VO2 in heart transplant recipients. .

Objetivo: Estabelecer os determinantes do VO2 pico em transplantados de coração. Métodos: Avaliação do paciente foi realizada em dois dias consecutivos. No primeiro dia, os pacientes realizaram a avaliação da variabilidade da frequência cardíaca seguida de um teste de esforço cardiopulmonar. No segundo dia, os pacientes realizaram ecocardiografia de repouso. Os transplantados foram elegíveis se estivessem em uma condição estável e sem qualquer evidência de rejeição diagnosticada por biópsia endomiocárdica. Pacientes com marca-passo, limitações funcionais não cardiovasculares, tais como osteoartrite e doença pulmonar obstrutiva crônica foram excluídos deste estudo. Resultados: Sessenta pacientes (68% do sexo masculino, 48 anos e 64 meses após o transplante cardíaco) foram avaliados. A análise multivariada selecionou as seguintes variáveis: sexo (P=0,001), idade (P=0,049), Índice de Massa Corporal (P=0,005), frequência cardíaca de reserva (P <0,0001), diâmetro do átrio esquerdo (P=0,016), variáveis do receptor. A análise multivariada mostrou r=0,77 e r2=0,6, com P <0,001. Equação: VO2=32,851 - 3,708 (sexo receptor) - 0,067 (idade receptor) - 0,318 (IMC receptor) + 0,145 (frequência cardíaca de reserva) - 0,111 (diâmetro de átrio esquerdo). Conclusão: Os determinantes do pico de VO2 em transplantados de coração foram: sexo receptor, idade, Índice de Massa Corporal, frequência cardíaca de reserva e diâmetro do átrio esquerdo. A frequência cardíaca de reserva foi a única variável positivamente associada com o pico de VO2. Estes dados sugerem a importância da reinervação simpática no pico de VO2 em transplantados de coração. .

Prescribing and Regulating Exercise with RPE after Heart Transplant: A Pilot Study.

PURPOSE: The objective of this study is to analyze the use of the 6-20 RPE scale for prescribing and self-regulating heated water-based exercise (HEx) and land-based exercise (LEx) in heart transplant recipients. METHODS: Fifteen (five females) clinically stable heart transplant recipients (time since surgery = 4.0 ± 2.5 yr) age 46.7 ± 11.8 yr underwent a symptom-limited maximal graded exercise test on a treadmill to determine their HR at anaerobic threshold (HRAT), respiratory compensation point (HRRCP), and maximal effort (HRmax). After a week, patients were randomized to perform 30 min of both HEx (walking inside the pool) and LEx (treadmill walking) sessions at a pace between 11 and 13 on the 6-20 RPE scale and had their HR measured every 4 min. The interval between sessions was 48-72 h. RESULTS: No significant differences between sessions were found in the average HR during HEx and LEx. Patients showed a delay in HR increase during both interventions, with the stabilization beginning after 8 min of exercise. Exercise HR was maintained between the HRAT and HRRCP (in the aerobic exercise training zone) for the most part of both HEx (72% of HR measurements) and LEx (66% of HR measurements). Only a few HR measurements stayed below HRAT (HEx = 9%, LEx = 13%) or above HRRCP (HEx = 19%, LEx = 21%) during both exercise sessions. CONCLUSION: Exercise HR was maintained in the aerobic exercise training zone (between HRAT and HRRCP) for the most part of both sessions, suggesting that the 6-20 RPE scale may be an efficient tool for prescribing and self-regulating HEx and LEx in heart transplant recipients.

Left cardiac sympathetic denervation for treatment of symptomatic systolic heart failure patients: a pilot study.

AIMS: To evaluate the feasibility, safety, and potential beneficial effects of left cardiac sympathetic denervation (LCSD) in systolic heart failure (HF) patients. METHODS AND RESULTS: In this prospective, randomized pilot study, inclusion criteria were New York Heart Association (NYHA) functional class II or III, left ventricular ejection fraction (LVEF) ≤40%, sinus rhythm, and resting heart rate >65 b.p.m., despite optimal medical therapy (MT). Fifteen patients were randomly assigned either to MT alone or MT plus LCSD. The primary endpoint was safety, measured by mortality in the first month of follow-up and morbidity according to pre-specified criteria. Secondary endpoints were exercise capacity, quality of life, LVEF, muscle sympathetic nerve activity (MSNA), brain natriuretic peptide (BNP) levels and 24 h Holter mean heart rate before and after 6 months. We studied clinical effects in long-term follow-up. Ten patients underwent LCSD. There were no adverse events attributable to surgery. In the LCSD group, LVEF improved from 25 ± 6.6 to 33 ± 5.2 (P = 0.03); 6 min walking distance improved from 167 ± 35 to 198 ± 47 m (P = 0.02). Minnesota Living with Heart Failure Questionnaire (MLWHFQ) score physical dimension changed from 21 ± 5 to 15 ± 7 (P = 0.06). The remaining analysed variables were unchanged. During 848 ± 549 days of follow-up, in the MT group, three patients either died or underwent cardiac transplantation (CT), while in the LCSD group six were alive without CT. CONCLUSIONS: LCSD was feasible and seemed to be safe in systolic HF patients. Its beneficial effects warrant the development of a larger randomized trial. Trail registration: NCT01224899.

Exercício físico e microRNAs: novas fronteiras na insuficiência cardíaca / Physical exercise and microRNAs: new frontiers in heart failure

Embora recentemente tenha sido questionado o impacto do exercício na sobrevida de pacientes com insuficiência cardíaca, o treinamento físico melhora a qualidade de vida, a capacidade funcional, a inflamação, a função autonômica e a função endotelial. Nos últimos anos, vem crescendo o interesse em um grupo de pequenos RNAs não codificadores de proteína chamados microRNAs. Estudos têm demonstrado que a expressão dessas moléculas se modifica em diversas condições patológicas, como a hipertrofia miocárdica, a isquemia miocárdica e a insuficiência cardíaca, e, quando ocorre melhora clínica, elas parecem se normalizar. Com o potencial de aplicabilidade prática, já foram identificados marcadores que poderão ser úteis na avaliação diagnóstica e prognóstica da insuficiência cardíaca, como o miR-423-5p. Além disso, resultados de estudos experimentais indicam haver possíveis efeitos terapêuticos dos microRNAs. Implicados na regulação da expressão genética durante o desenvolvimento fetal e no indivíduo adulto, os microRNAs aumentam ou diminuem no coração em resposta a estresse fisiológico, injúria ou sobrecarga hemodinâmica. Assim, o estudo do comportamento dessas moléculas no exercício físico vem trazendo informações importantes quanto aos efeitos dessa modalidade terapêutica e representa uma nova era no entendimento da insuficiência cardíaca. Esta revisão tem por objetivo integrar as evidências sobre microRNAs na insuficiência cardíaca com maior relevância no estudo do exercício físico.

Although the impact of exercise on survival of patients with heart failure has been recently questioned, exercise training improves quality of life, functional capacity, inflammation, endothelial and autonomic function. In recent years, interest has increased regarding a group of small non-protein coding RNAs called microRNAs. Studies have shown that the expression of these molecules changes in several pathological conditions, such as myocardial infarction, myocardial ischemia and heart failure, and when clinical improvement occurs, they seem to normalize. With the potential for practical applicability, markers that may be useful in diagnostic and prognostic assessment of heart failure have been identified, such as miR-423-5p. In addition, results of experimental studies have indicated that there are potential therapeutic effects of microRNAs. MicroRNAs are involved in the regulation of gene expression during fetal development and in adult individuals, increasing or decreasing in the heart in response to physiological stress, injury or hemodynamic overload. Thus, the study of the behavior of these molecules in physical exercise has brought important information about the effects of this therapeutic modality and represents a new era in the understanding of heart failure. This review aims to integrate the evidence on microRNAs in heart failure with greater relevance in the study of physical exercise.

MicroRNAs: um novo paradigma no tratamento e diagnóstico da insuficiência cardíaca? / MicroRNAs: a new paradigm in the treatment and diagnosis of Heart failure? / MicroRNAs: ¿un nuevo paradigma en el tratamiento y diagnóstico de la insuficiencia cardíaca?

MicroRNAs (miRNAs) são um grupo recém-descoberto de pequenos RNAs, não codificantes, que representam uma das áreas mais estimulantes da ciência médica moderna por modularem uma enorme e complexa rede regulatória da expressão dos genes.Recentemente, linhas de evidências sugerem que os miRNAs desempenham um papel crucial na patogênese da insuficiência cardíaca. Alguns miRNAs altamente expressos no coração como o miR-1, miR-133 e miR-208 estão fortemente associados ao desenvolvimento da hipertrofia cardíaca, enquanto o exato papel de miR-21 no sistema cardiovascular permanece controverso. Os níveis séricos de miRNAs circulantes como o miR-423-5p estão sendo avaliados como potenciais biomarcadores no diagnóstico e prognóstico da insuficiência cardíaca.Por outro lado, a manipulação dos níveis de miRNAs usando técnicas como os mimetizadores de miRNAs (miRmimics) e miRNAs antagônicos(antagomiRs) está tornando cada vez mais evidente o enorme potencial dos miRNAs como promissoras estratégias terapêutica sna insuficiência cardíaca.

MicroRNAs (miRNAs) are a group of newly discovered small RNAs, non-coding, which represent one of the most exciting areas of modern medical science as they modulate a huge and complex regulatory network of gene expression. Lines of evidence have recently suggested that miRNAs play a key role in the pathogenesis of heart failure. Some miRNAs highly expressed in the heart, such as miR-1, miR-133 and miR-208, are strongly associated with the development of cardiac hypertrophy, while the exact role of miR-21 in the cardiovascular system remains controversial. Serum levels of circulating miRNAs such as miR-423-5p are being evaluated as potential biomarkers in the diagnosis and prognosis of heart failure. On the other hand, the manipulation of levels of miRNAs using techniques such as mimicking the miRNAs (miRmimics) and antagonistic miRNAs (antagomiRs) is making increasingly evident the enormous potential of miRNAs as promising therapeutic strategies in heart failure.

MicroRNAs(miRNAs) son un grupo recién descubierto de pequeños RNAs, no codificantes, que representan una de las áreas más estimulantes de la ciencia médica moderna por modular en una enorme y compleja red regulatoria de la expresión de los genes. Recientemente, líneas de evidencias sugieren que los miRNAs desempeñan un papel crucial en la patogénesis de la insuficiencia cardíaca. Algunos miRNAs altamente expresados en el corazón como el miR-1, miR-133 y miR-208 están fuertemente asociados al desarrollo de la hipertrofia cardíaca, mientras que el exacto papel de miR-21 en el sistema cardiovascular permanece controvertido. Los niveles séricos de miRNAs circulantes como el miR-423-5p están siendo evaluados como potenciales biomarcadores en el diagnóstico y pronóstico de la insuficiencia cardíaca. Por otro lado, la manipulación de los niveles de miRNAs usando técnicas como los mimetizadores de miRNAs (miRmimics) y miRNAs antagónicos (antagomiRs) está volviendo cada vez más evidente el enorme potencial de los miRNAs como promisorias estrategias terapéuticas en la insuficiencia cardíaca.

Endothelial function in pre-pubertal children at risk of developing cardiomyopathy: a new frontier

Although it is known that obesity, diabetes, and Kawasaki's disease play important roles in systemic inflammation and in the development of both endothelial dysfunction and cardiomyopathy, there is a lack of data regarding the endothelial function of pre-pubertal children suffering from cardiomyopathy. In this study, we performed a systematic review of the literature on pre-pubertal children at risk of developing cardiomyopathy to assess the endothelial function of pre-pubertal children at risk of developing cardiomyopathy. We searched the published literature indexed in PubMed, Bireme and SciELO using the keywords 'endothelial', 'children', 'pediatric' and 'infant' and then compiled a systematic review. The end points were age, the pubertal stage, sex differences, the method used for the endothelial evaluation and the endothelial values themselves. No studies on children with cardiomyopathy were found. Only 11 papers were selected for our complete analysis, where these included reports on the flow-mediated percentage dilatation, the values of which were 9.80±1.80, 5.90±1.29, 4.50±0.70, and 7.10±1.27 for healthy, obese, diabetic and pre-pubertal children with Kawasaki's disease, respectively. There was no significant difference in the dilatation, independent of the endothelium, either among the groups or between the genders for both of the measurements in children; similar results have been found in adolescents and adults. The endothelial function in cardiomyopathic children remains unclear because of the lack of data; nevertheless, the known dysfunctions in children with obesity, type 1 diabetes and Kawasaki's disease may influence the severity of the cardiovascular symptoms, the prognosis, and the mortality rate. The results of this study encourage future research into the consequences of endothelial dysfunction in pre-pubertal children.

Treinamento físico na distrofia muscular de becker associada à insuficiência cardíaca / Physical training in becker muscular dystrophy associated with heart failure / Entrenamiento físico en la distrofia muscular de becker asociada a la insuficiencia cardíaca

A distrofia muscular de Becker (DMB) integra as distrofinopatias que ocorrem devido a mutações genéticas que expressam a proteína distrofina no cromossomo X. O início dos sintomas neuromusculares normalmente precede o comprometimento da função cardíaca, podendo acontecer inversamente pela insuficiência cardíaca (IC). O treinamento físico é bem estabelecido na IC, porém, quando associada à DMB, é controverso e sem fundamento científico. Apresentamos o caso de um paciente com DMB associada à IC em fila de transplante cardíaco submetido a um programa de treinamento físico.

Becker muscular dystrophy (BMD) integrates dystrophy occurring due to genetic mutations that express the dystrophin protein in chromosome X. The onset of neuromuscular symptoms usually precedes the impairment of cardiac function, and may conversely happen by heart failure (HF). Physical training is well established in HF, however, when combined with BMD, it is controversial and without any scientific basis. This study presents the case of a patient with BMD associated with HF in cardiac transplant waiting list undergoing a physical training program.

La distrofia muscular de Becker (DMB) integra las distrofinopatías que ocurren debido a mutaciones genéticas que expresan la proteína distrofina en el cromosoma X. El inicio de los síntomas neuromusculares normalmente precede el compromiso de la función cardíaca, pudiendo acontecer inversamente por la insuficiencia cardíaca (IC). El entrenamiento físico es bien establecido en la IC, sin embargo, cuando está asociada a la DMB, es controvertido y sin fundamento científico. Presentamos el caso de un paciente con DMB asociada a la IC en fila de transplante cardíaco sometido a un programa de entrenamiento físico.