The omics perspective on heart failure research / 药学学报

Heart failure is the end stage of many cardiovascular diseases. It seriously affects the safety and quality of life of nearly 40 million people worldwide. At present, the clinical and pathophysiological characteristics of some types of heart failure are unknown, and there is no effective diagnosis and treatment. In recent years, genomics, transcriptomics, epigenomics, proteomics, metabolomics and other omics technologies have been widely used in disease research, providing new opportunities for the prevention, diagnosis and treatment of diseases. These strategies have also brought hope for the reduction in heart failure mortality. Based on the current status of clinical treatment of heart failure, this article reviews the roles and potential applications of these various omics technologies and their opportunities in the study of the pathogenesis of heart failure, clinical diagnosis and treatment, and related drug pharmacodynamics and mechanism of action.

Effect of metoprolol in emergency treatment of chronic congestive heart failure / 中国基层医药

Objective To investigate the efficacy of metoprolol in the emergency treatment of chronic congestive heart failure.Methods From January 2016 to September 2018,300 cases of chronic congestive heart failure with acute attack in Zhoushan Hospital were selected.According to random number table method ,the patients were divided into two groups,with 150 cases in each group.The control group was given conventional heart failure treatment ,the observation group received conventional heart failure therapy combined with metoprolol.The clinical efficacy,heart color ultrasound indicator ,6 minutes walking distance ,NT－proBNP level,life quality score and adverse reactions were compared between the two groups.Results (1) The total effective rate of the observation group was 96.00%(141／150),which was higher than 87.33%(131／150) of the control group ( χ2 ＝7.375,P＜0.05).( 2) After treatment,the LVEDD[(58.12 ±3.89)mm],LVESD[(44.39 ±6.17) mm],NT－proBNP[(378.32 ±27.82)ng／mL] in the observation group were lower than those in the control group (t＝10.646,9.966,9.283,all P＜0.05),the LVEF [(49.36 ±6.25)%],SV[(76.29 ±6.24)mL] in the observation group were higher than those in the control group (t＝9.092,8.739,all P＜0.05).The 6－minute walking distance [(452.37 ±61.75) m] of the observation group was longer than that of the control group (t＝7.717,P＜0.05).The quality of life scores in the emotional field [(6.47 ± 1.29)points],physical field[(10.46 ±1.65)points],other fields[(10.51 ±1.32)points] and comprehensive score [(27.44 ±4.26) points] of the observation group were lower than those of the control group ( t＝9.030,9.024, 9.299,9.114,all P＜0.05).(3) During the treatment,no obvious adverse reactions occurred in the two groups. Conclusion In the emergency treatment of patients with chronic congestive heart failure,the application of conventional anti－heart failure treatment regimen metoprolol can effectively improve the patients＇heart function,and is conductive to improving their clinical efficacy and quality of life,with fewer adverse drug reactions and good safety.

Effect of metoprolol in emergency treatment of chronic congestive heart failure / 中国基层医药

Objective@#To investigate the efficacy of metoprolol in the emergency treatment of chronic congestive heart failure.@*Methods@#From January 2016 to September 2018, 300 cases of chronic congestive heart failure with acute attack in Zhoushan Hospital were selected.According to random number table method, the patients were divided into two groups, with 150 cases in each group.The control group was given conventional heart failure treatment, the observation group received conventional heart failure therapy combined with metoprolol.The clinical efficacy, heart color ultrasound indicator, 6 minutes walking distance, NT-proBNP level, life quality score and adverse reactions were compared between the two groups.@*Results@#(1)The total effective rate of the observation group was 96.00%(141/150), which was higher than 87.33%(131/150) of the control group (χ2=7.375, P<0.05). (2) After treatment, the LVEDD[(58.12±3.89)mm], LVESD[(44.39±6.17)mm], NT-proBNP[(378.32±27.82)ng/mL] in the observation group were lower than those in the control group (t=10.646, 9.966, 9.283, all P<0.05), the LVEF[(49.36±6.25)%], SV[(76.29±6.24)mL] in the observation group were higher than those in the control group(t=9.092, 8.739, all P<0.05). The 6-minute walking distance[(452.37±61.75)m] of the observation group was longer than that of the control group(t=7.717, P<0.05). The quality of life scores in the emotional field[(6.47±1.29)points], physical field[(10.46±1.65)points], other fields[(10.51±1.32)points]and comprehensive score[(27.44±4.26)points] of the observation group were lower than those of the control group(t=9.030, 9.024, 9.299, 9.114, all P<0.05). (3)During the treatment, no obvious adverse reactions occurred in the two groups.@*Conclusion@#In the emergency treatment of patients with chronic congestive heart failure, the application of conventional anti-heart failure treatment regimen metoprolol can effectively improve the patients' heart function, and is conductive to improving their clinical efficacy and quality of life, with fewer adverse drug reactions and good safety.

Rational use of mechanical circulatory support as a bridge to pediatric and congenital heart transplantation

Abstract Introduction: Donor shortage and organ allocation is the main problem in pediatric heart transplant. Mechanical circulatory support is known to increase waiting list survival, but it is not routinely used in pediatric programs in Latin America. Methods: All patients listed for heart transplant and supported by a mechanical circulatory support between January 2012 and March 2016 were included in this retrospective single-center study. The endpoints were mechanical circulatory support time, complications, heart transplant survival and discharge from the hospital. Results: Twenty-nine patients from our waiting list were assessed. Twelve (45%) patients were initially supported by extracorporeal membrane oxygenation (ECMO) and a centrifugal pump was implanted in 17 (55%) patients. Five patients initially supported by ECMO were bridged to another device. One was bridged to a centrifugal pump and four were bridged to Berlin Heart Excor®. Among the 29 supported patients, 18 (62%) managed to have a heart transplant. Thirty-day survival period after heart transplant was 56% (10 patients). Median support duration was 12 days (interquartile range [IQR] 4 - 26 days) per run and the waiting time for heart transplant was 9.5 days (IQR 2.5-25 days). Acute kidney injury was identified as a mortality predictor (OR=22.6 [CI=1.04-494.6]; P=0.04). Conclusion: Mechanical circulatory support was able to bridge most INTERMACS 1 and 2 pediatric patients to transplant with an acceptable complication rate. Acute renal failure increased mortality after mechanical circulatory support in our experience.

Analysis Treatment Guideline versus Clinical Practice Protocol in Patients Hospitalized due to Heart Failure / Análise de Diretriz de Tratamento versus Protocolo Assistencial em Pacientes Internados por Insuficiência Cardíaca

Background: Despite the availability of guidelines for treatment of heart failure (HF), only a few studies have assessed how hospitals adhere to the recommended therapies. Objectives: Compare the rates of adherence to the prescription of angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers (ACEI/ARB) at hospital discharge, which is considered a quality indicator by the Joint Commission International, and to the prescription of beta-blockers at hospital discharge, which is recommended by national and international guidelines, in a hospital with a case management program to supervise the implementation of a clinical practice protocol (HCP) and another hospital that follows treatment guidelines (HCG). Methods: Prospective observational study that evaluated patients consecutively admitted to both hospitals due to decompensated HF between August 1st, 2006, and December 31st, 2008. We used as comparing parameters the prescription rates of beta-blockers and ACEI/ARB at hospital discharge and in-hospital mortality. Results: We analyzed 1,052 patients (30% female, mean age 70.6 ± 14.1 years), 381 (36%) of whom were seen at HCG and 781 (64%) at HCP. The prescription rates of beta-blockers at discharge at HCG and HCP were both 69% (p = 0.458), whereas those of ACEI/ARB were 83% and 86%, respectively (p = 0.162). In-hospital mortality rates were 16.5% at HCP and 27.8% at HCG (p < 0.001). Conclusion: There was no difference in prescription rates of beta-blocker and ACEI/ARB at hospital discharge between the institutions, but HCP had lower in-hospital mortality. This difference in mortality may be attributed to different clinical characteristics of the patients in both hospitals.

Fundamento: Apesar da disponibilidade de diretrizes de tratamento para insuficiência cardíaca (IC), há poucos estudos avaliando a adesão dos hospitais ao tratamento preconizado. Objetivos: Comparar as taxas de adesão à prescrição de inibidor da enzima conversora da angiotensina ou antagonista do receptor de angiotensina II (IECA/BRA) na alta hospitalar, considerada indicadora de qualidade pela Joint Commission International, e à prescrição de betabloqueador na alta hospitalar, preconizada por diretrizes nacionais e internacionais, em um hospital que utiliza gerenciamento de casos para supervisionar a implementação de um protocolo assistencial (HPA) e outro que utiliza diretrizes de tratamento (HDT). Métodos: Estudo observacional prospectivo que avaliou pacientes consecutivamente admitidos em ambos os hospitais por IC descompensada entre 1º de agosto de 2006 a 31 de dezembro de 2008. Os parâmetros comparados entre os hospitais foram as taxas de prescrição de betabloqueador e IECA/BRA na alta hospitalar e a mortalidade intra-hospitalar. Resultados: Analisamos 1.052 pacientes (30% do sexo feminino, média de idade 70,6 ± 14,1 anos) dos quais 381 (36%) eram do HDT e 781 (64%) do HPA. No HDT e no HPA, as taxas de prescrição de betabloqueador na alta foram ambas de 69% (p = 0,458), e de prescrição de IECA/BRA foi de 83% e 86%, respectivamente (p = 0,162). A mortalidade intra-hospitalar foi de 16,5% no HPA e de 27,8% no HDT (p < 0,001). Conclusão: Não houve diferença entre as instituições em relação à prescrição de betabloqueador e IECA/BRA na alta hospitalar, mas a mortalidade intra-hospitalar foi menor no HPA. Esta diferença na mortalidade pode ser atribuída às características clínicas distintas dos pacientes em ambos os hospitais.

Effects of right ventricular septal pacing modes on acute cardiac function and ventricular synchronization in dogs with heart failure / 中国医师杂志

Objective To evaluate effects of right ventricular septal pacing modes on treatment of heart failure.Methods Twelve dogs with heart failure were performed in every dog at random,and the pacing modes employed in the test included right atrium-right ventricular apex (RVA),right atrium-right ventricular septal(RVS),and right atrium-biventricular (Bi-V) ; The pacing frequency was 180 times per minute.The results were measured before pacing and after 15 minutes when the pacing became stable in Color Doppler echocardiography,including left ventricular end-diastolic diameter (LVEDd),left ventricular ejection fraction (LVEF),interventricular mechanical delay (IVMD),interventricular septum and left ventricular posterior wall motion delay (SPWMD),and left ventricular 12-segment peak time standard deviation (Ts-SD).Results Right ventricular septal pacing mode:(1)Compared with parameter before pacing and RVA pacing,LVEDd,IVMD,SPWMD,and Ts-SD decreased and LVEF increased,and the difference was significant(P ＜0.05).(2)Compared with Bi-V pacing,LVEDd,IVMD,and SPWMDandTs-SD increased and LVEF decreased,and the difference was significant (P ＜ 0.05).Conclusions Right ventricular septal pacing could improve ventricular synchrony and cardiac function partly,and the effect was better than right ventricular apical pacing but less than biventricular pacing,also could not be a alternative models of cardiac resynchronization therapy for heart failure.

Study on the effects of different pacing modes of cardiac resynchronization therapy on dogs with heart failure / 中国医师杂志

Objective To evaluate advantages and disadvantages of different pacing modes of cardiac resynchronization therapy (CRT).Methods Twelve dogs with heart failure were performed in every dog at random,and the pacing modes employed in the test included right atrium-different sites of ventricle,and ventricular sites included right ventricular bifocal (RV-Bi),biventricular (Bi-V),left ventricular (LV).The pacing frequency was 180 times per minute,and the results were measured before pacing and after 15 minutes when the pacing became stable in Color Doppler echocardiography,including left ventricular enddiastolic diameter (LVEDd),left ventricular ejection fraction (LVEF),interventricular mechanical delay (IVMD),interventricular septum and left ventricular posterior wall motion delay (SPWMD),left ventricular 12-segment peak time standard deviation (Ts-SD).Results (1)Compared with before pacing,at the RV-Bi,Bi-V,and LV pacing modes,LVEDd,IVMD,SPWMD,and Ts-SD decreased,LVEF increased,the difference was statistically significant [(42.42 ± 3.94) mm vs (34.00 ± 4.07) mm,(34.17 ± 3.95)mm,(33.75 ±4.18)mm; (28.08 ±4.01)mm vs (13.00 ±3.64) mm,(11.95 ±2.54)mm,(12.08 ±3.51) mm; (75.00 ± 10.22)mm vs (51.75 ±9.84) mm,(20.66 ±7.41) mm,(20.75 ±7.56) mm; (25.08±4.16)mm vs (14.91 ± 3.31)mm,(7.50 ±4.24) mm,(7.41 ±3.39)mm;(32.91 ±4.46)mm vs (41.50 ±4.16)mm,(42.00 ±4.63) mm,(42.41 ±4.99)mm,P ＜0.05].(2)Compared with RV-Bi pacing mode,at the Bi-V,LV pacing modes,SPWMD and Ts-SD decreased,the difference was statistically significant(P ＜ 0.05); there was no significant difference among LVEDd,IVMD,and LVEF (P ＞0.05).(3)There was no significant difference in LVEDd,IVMD,SPWMD,Ts-SD and LVEF between LV and Bi-V pacing (P ＞ 0.05).Conclusions The hemodynamic effects of RV-Bi and LV pacing modes were similar to that of Bi-V pacing,and they can be used as CRT biventricular pacing alternative modes; however,the mechanisms of improving ventricular synchronization are not identical in above pacing modes.

Papel da medicina nuclear na terapia de ressincronização cardíaca: [revisão] / Role of nuclear medicine in the cardiac resinchronization therapy: [review]

A terapia de ressincronização cardíaca (TRC) surgiu como a mais promissora abordagem no tratamento da dissincronia cardíaca, em pacientes com insuficiência cardíaca refratária ao tratamento medicamentoso. Embora seus resultados clínicos e funcionais sejam de fato promissores, as análises das respostas individuais revelam que uma significativa parcela dos pacientes não responde ao tratamento. Nesta revisão, foi discutido o papel da medicina nuclear e imagem molecular na seleção de candidatos à TRC, por meio do estudo da dissincronia cardíaca, avaliação de viabilidade, perfusão e fluxo sanguíneo miocárdicos e atividade simpática cardíaca. O potencial uso dessa técnica, no aprimoramento da compreensão dos efeitos deletérios da dissincronia, sobre a função cardíaca e na avaliação e monitorização de resposta à TRC, foram também abordados. Outros alvos moleculares que caracterizam metabolismo glicolítico e de ácido graxo, apoptose, atividade da enzima conversora da angiotensina e angiogênese, que podem seravaliados e medidos por essa técnica, foram descritos.

Cardiac resynchronization therapy (CRT) emerged as one of the most promising approaches in the treatment of cardiac dyssynchrony in heart failure patients’ refractory to medical treatment. However, despite very promising clinical and functional results, individual response analyses show that a significant number of patients do not respond to treatment. The role of nuclear medicine and molecular imaging in the selection of CRT candidates by the assessment of cardiac dyssynchrony, myocardial viability, myocardial perfusion and blood flow and sympathetic cardiac activity has been discussed in this review. The potential utilization of this tool to improve the comprehension of detrimental effects of dyssynchrony on cardiac function and the evaluation and monitoring of the response to CRT were also considered. Other molecular targets that characterize glucose and fatty acid metabolism, apoptosis, angiotensin converting enzyme activity and angiogenesis that can be evaluated with this technique were described.

Efeito do carvedilol a curto prazo na atividade simpática cardíaca pela cintilografia com 123I-MIBG / Effects of short-term carvedilol on the cardiac sympathetic activity assessed by 123I-MIBG scintigraphy

FUNDAMENTO: Alterações autonômicas na insuficiência cardíaca estão associadas a um aumento da morbimortalidade. Vários métodos não invasivos têm sido empregados para avaliar a função simpática, incluindo a imagem cardíaca com 123I-MIBG. OBJETIVO: Avaliar a atividade simpática cardíaca, por meio da cintilografia com 123I-MIBG, antes e após três meses de terapia com carvedilol em pacientes com insuficiência cardíaca com fração de ejeção do VE <45 por cento (FEVE). MÉTODOS: Foram recrutados para o estudo 16 pacientes, com idade média de 56,3 ± 12,6 anos (11 do sexo masculino), fração de ejeção média de 28 por cento ± 8 por cento e sem uso prévio de betabloqueadores. Realizaram-se imagens da inervação cardíaca com 123I-MIBG, determinando os níveis séricos de catecolaminas (epinefrina, dopamina e norepinefrina), e empreendeu-se a ventriculografia radionuclídica antes e após o uso de carvedilol por três meses. RESULTADOS: Houve melhora da classe funcional dos pacientes: antes do tratamento, metade se encontrava em CF II (50 por cento) e metade em CF III. Após 3 meses, 7 pacientes encontravam-se em CF I (43,8 por cento) e 9 em CF II (56,2 por cento), (p = 0,0001). A FEVE média avaliada pela ventriculografia radionuclídica aumentou de 29 por cento para 33 por cento (p = 0,017). Não houve variação significativa da atividade adrenérgica cardíaca avaliada pelo 123I-MIBG (imagem precoce, tardia e taxa de washout). Não foi observada variação significativa nas dosagens das catecolaminas. CONCLUSÃO: O tratamento em curto prazo com carvedilol promoveu a melhora clínica e da FEVE. Entretanto, não foi associado à melhora da atividade adrenérgica cardíaca pela cintilografia com 123I-MIBG, bem como da dosagem das catecolaminas circulantes.

BACKGROUND: Autonomic alterations in heart failure are associated with an increase in morbimortality. Several noninvasive methods have been employed to evaluate the sympathetic function, including the Meta-Iodobenzylguanidine (123I-MIBG) scintigraphy imaging of the heart. OBJECTIVE: to evaluate the cardiac sympathetic activity through 123I-MIBG scintigraphy, before and after three months of carvedilol therapy in patients with heart failure and left ventricular ejection fraction (LVEF) < 45 percent. PATIENTS AND METHODS: Sixteen patients, aged 56.3 ± 12.6 years (11 males), with a mean LVEF of 28 percent ± 8 percent and no previous use of beta-blockers were recruited for the study. Images of the heart innervation were acquired with 123I-MIBG, and the serum levels of catecholamines (epinephrine, dopamine and norepinephrine) were measured; the radioisotope ventriculography (RIV) was performed before and after a three-month therapy with carvedilol. RESULTS: Patients' functional class showed improvement: before the treatment, 50 percent of the patients were FC II and 50 percent were FC III. After 3 months, 7 patients were FC I (43.8 percent) and 9 were FC II (56.2 percent), (p = 0.0001). The mean LVEF assessed by RIV increased from 29 percent to 33 percent (p = 0.017). There was no significant variation in cardiac adrenergic activity assessed by 123I-MIBG (early and late resting images and washout rate). No significant variation was observed regarding the measurement of catecholamines. CONCLUSION: The short-term treatment with carvedilol promoted the clinical and LVEF improvement. However, this was not associated to an improvement in the cardiac adrenergic activity, assessed by 123I-MIBG scintigraphy, as well as the measurement of circulating catecholamines.

Uso de levosimendana em diversos quadros de insuficiência cardíaca aguda: [revisão] / Levosimendan use in several scenarios of acute heart failure: [review]

Nos países em que é comercializada, a administração precoce de levosimendana deve ser considerada em pacientes que permanecem sintomáticos e com dispnéia em repouso apesar da terapia inicial, principalmente aqueles com história de insuficiência cardíaca crônica ou em tratamento prolongado com betabloqueadores. Pacientes hipotensos ou com isquemia ativa não são os melhores candidatos para receber infusão de levosimendana e precisam, primeiro, ter esses problemas tratados.

In countries where it is available, early levosimendan infusion can be considered for patients who remain symptomatic with dyspnea at rest despite initial therapy, particularly those with a history of chronic heart failure or chronically treated with beta-blockers. Hypotensive patients or patients with active ischemia are not the best candidates for levosimendan administration and should have these problems addressed first.