Relationship of heart failure with occurrence and development of tumors / 肿瘤

Previous studies have shown that the patients with long-term cancer often have complications such as heart failure. However, the recent studies have shown a heightened risk of incident malignancy in the patients with preexisting heart failure as compared with the normal; there are significant differences even after excluding common pathogenic factors such as obesity. This phenomenon suggests that heart failure may be a carcinogenic condition. Some researchers believe that the systemic pathological processes, such as inflammation and oxidative stress, may promote both heart failure and cancer, leading to the occurrence of these two diseases intersecting. Another hypothesis is that the active neurohormonal system caused by heart failure can directly affect the occurrence, development and prognosis of tumors. When the heart failure occurs, the activities of sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS) in the neurohormone system are greatly enhanced. The activation of SNS and RAAS is closely related to the tumor proliferation and angiogenesis, which may be an important way for heart failure to cause tumors. This paradigm is supported by both experimental researches and clinical investigations. On the one hand, tumor growth and metastatic spreading increase following the activation of SNS or RAAS invivo. On the other hand, the results of clinical observation have shown that the use of neurohormonal inhibitors, especially RAAS blockers, is associated with more favorable cancer outcomes. Exploring the relationship between heart failure and tumorigenesis, and then elucidating the key regulatory mechanisms of heart failure acting on tumors is now becoming a hot topic worldwide. This may provide a new basis for the clinical treatments of both heart failure and tumors.

Clinical study of milrinone injectionon acute heart failure with poor effect of digitalis and diuretics / 中国生化药物杂志

Objective To discussion the clinical study of milrinone injectionon on acute heart failure with poor effect of digitalis and diuretics.Metheds 90 cases of acute heart failure with poor effect of digitalis and diuretics patients from September 2014 to May 2016 in our hospital were selected,according to the random number table method is divided into control group and study group,45 cases in each groups,the control group was treated with conventional heart failure intervention program,the study group given milrinone injectionon on the basis of control group,two groups were treated for seven days.Serum neurohormonal factors,inflammatory factors and blood pressure were measured before and after treatment,and the clinical efficacy and complications were compared between two groups.Results Compared with before treatment,serum NT-proBNP,NE and ET-1 levels were decreased in two groups,NO content increased,the levels of serum TNF-α,IL-6 and Hs-CRP were decreased,the levels of LVEF and CI were increased,the levels of LVEDD and CTR were decreased,the differences were statistically significant(P<0.05).Compared with the control group,the levels of serum NT-proBNP,NE and ET-1 in the study group were lower,NO were higher,the levels of TNF-α,IL-6 and Hs-CRP in serum were lower,LVEF and CI were higher,LVEDD and CTR were lower,the differences were statistically significant(P<0.05).The effective rate of the study group was 86.67％,which was significantly higher than that of the control group(66.67％,P<0.05).All the patients were followed up and no cases were reported.There was no significant difference in the incidence of adverse reactions between the two groups.Conclusion Milrinone injectionon has a significant effect on acute heart failure with poor effect of digitalis and diuretics,can significantly reduce the neurotrophic factor and inflammatory factors,improve heart function,promote prognosis.

Antagonistas neurohormonales en el tratamiento de la insuficiencia cardiaca crónica / Neurohormonal antagonists in the treatment of chronic heart failure

La insuficiencia cardíaca crónica se caracteriza por presentar una importante activación neurohormonal que consiste principalmente en un aumento de la activación simpática y del sistema renina-angiotensina-aldosterona. Esta activación en un principio compensatoria, con el tiempo lleva al empeoramiento de la función ventricular y los síntomas en la insuficiencia cardíaca. El tratamiento médico debe ir dirigido a bloquear dicha activación y con ello disminuir la progresión de la enfermedad. Las estatinas, IECAS, ARA II, antagonistas de la aldosterona y los beta bloqueadores constituyen, fármacos antagonistas neurohormonales. Todos ellos han demostrado disminuir la morbimortalidad de la enfermedad...

The chronic heart failure is determined by an important neurohormonal activation that consists in the increase of the sympathetic activation and the renin-angiotensin-aldosterone system. This activation is at the beginning compensatory, but then it leads to a bigger damage of the ventricular function and chronic insufficiency symptoms. The physician must avoid this activation and diminish the progression of the disease. Statins, ACE inhibitor (angiotensin-converting-enzyme inhibitor), angiotensin receptor blockers (ARBs), aldosterone antagonists and beta blockers are the antagonist neurohormonal drugs. All of them have proven to decrease the morbimortality of the disease...

El "Continuum" de la insuficiencia cardíaca / The "Continuum" of heart failure / O "Continuum" da insuficiência cardíaca

Los diferentes fenotipos de insuficiencia cardíaca no son sólo el resultado del interjuego neurohormonal, hemodinamia e inflamación; sino que la activación aguda o crónica de estos sistemas sobre sustratos ventriculares definidos (fallas puramente sistólicas o puramente diastólicas) determinan un tipo particular de presentación clínica y fisiopatológica. Además, factores externos modificables y no modificables podrían determinar un fenotipo en particular. Son circunstancias o eventualidades, las del medio ambiente, los procesos patológicos, la capacidad o discapacidad adaptativa, los procesos reactivos, la presencia de factores tóxicos, exacerbación no controlada de factores de riesgo entre otros. Cada tipo de insuficiencia cardíaca es el resultado de la suma de factores que van desde un genotipo a un fenotipo determinado, influenciado por aquellas nuevas circunstancias que podrían ir modulando este escenario. Los avances en conceptos fisiopatológicos tendrán sin duda, un gran impacto terapéutico.

The different phenotypes of heart failure are not only the result of the interplay neurohormonal, hemodynamics and inflammation, but chronic or acute activation of these systems on substrates ventricular defined (purely failures or purely systolic diastolic) determine a particular type of clinical and pathophysiological presentation. In addition, external factors modifiable and not modifiable could determine a particular phenotype. Circumstances or contingencies are those of the environment, pathological processes, adaptive ability or disability, reactive processes, the presence of toxic factors, risk factors uncontrolled exacerbation, among others. Each type of heart failure is the result of a combination of factors ranging from a certain genotype to phenotype, influenced by these new circumstances that may be modulating this scenario. Advances in physiopathology have no doubt, a great therapeutic impact.

Os diferentes fenótipos de insuficiência cardíaca não são apenas o resultado da interação neurohormonal, hemodinâmica e inflamação, mas a ativação crônica ou aguda destes sistemas em substratos definidos (falhas puramente diastólica ou puramente sistólica) causa um tipo particular de apresentação clínica e patológica. Além disso, fatores externos modificáveis e não modificáveis poderia determinar um fenótipo particular. Circunstâncias ou imprevistos são as do meio ambiente, processos patológicos, a capacidade de adaptação ou incapacidade, processos de reação, a presença de elementos tóxicos, exacerbação fatores de risco não controlados, entre outros. Cada tipo de insuficiência cardíaca é o resultado de uma combinação de fatores que variam a partir de um determinado genótipo para o fenótipo, influenciados por estas novas circunstâncias que podem estar modulando este cenário. Avanços nos conceitos fisiopatológicos, sem dúvida, têm um grande impacto terapêutico.

A dieta com baixo teor de sódio é de fato indicada para todos os pacientes com insuficiência cardíaca estável? / Is the low-sodium diet actually indicated for all patients with stable heart failure? / ¿La dieta con bajo nivel de sodio es de hecho una recomendación que sirve a todos los pacientes con insuficiencia cardíaca estable?

Fundamento: Embora uma dietahipossódica seja indicada para a insuficiência cardíaca IC, não há evidência de que esta restrição seja benéfica para todos os pacientes. Objetivo: Estudar prospectivamente os efeitos agudos de uma dieta hipossódica em pacientes (pcs) com insuficiência cardíaca (IC). Métodos: Cinqüenta pacientes ambulatoriais estáveis, com IC leve a moderada, que relataram consumir previamente 6,6 g sal/dia foram estudados. Na Fase 1, todos os pcs foram submetidos a uma dieta com 2 g de sal durante 7 dias, seguido por randomização em dois subgrupos (fase 2), para receber 6 g de sal/dia (subgrupo 1) ou 2 g de sal/dia, por 7 dias (subgrupo II). Resultados: Fase 1: a dieta com 2 g de sal/dia reduziu o índice de massa corporal (IMC), sódio plasmático e sódio urinário, consumo de proteína, ferro, zinco, selênio e vitamina B12; aumentou os níveis plasmáticos de norepinefrina, nitrato, aldosterona sérica, e melhorou a qualidade de vida. Fase 2: para pcs com IMC baixo, o uso de 6 g de sal/dia diminuiu de forma aguda os níveis de norepinefrina, albumina e colesterol no plasma. Nenhuma diferença foi encontrada em pcs com IMC mais alto. Conclusão: A dieta com 2g de sal /dia para pcs com IC aumentou a ativação neuro-hormonal associada à progressão da IC. O IMC pode influenciar a resposta da ativação neurohormonal em uma dieta hipossódica na IC. Futuros estudos para testar a restrição à ingestão de sal por períodos mais longos são recomendados.

Background: Although a low-sodium diet is indicated for heart failure HF, there is no evidence this dietary restriction is beneficial to all patients. Objective: To prospectively study the acute effectsof a low-sodium diet in patients (pts) with heart failure (HF). Methods: Fifty stable outpatients with mild to moderate HF who reported previously consuming 6.6 g table salt/day were studied. In Phase 1, all pts were submitted to a diet with 2 g of salt during 7 days, followed by randomization in 2 subgroups (Phase 2): one to receive 6 g of salt (subgroup 1) and the other, 2 g of salt/day for 7 days (subgroup II). Results: Phase 1: the diet with 2 g of salt reduced the BMI, plasma and urinary sodium, protein consumption, iron, zinc, selenium and vitamin B12; it increased plasma levels of norepinephrine, nitrate, serum aldosterone and improved quality of life. Phase 2: for pts with low BMI, the use of 6 g salt/day acutely decreased the levels of norepinephrine, albumin and cholesterol in plasma. No difference was observed in pts with higher BMI. Conclusion: The diet with 2 g salt/day for pts with HF increased the neurohormonal activation associated to HF progression. The BMI can influence the response to the neurohormonal activation in a low-sodium diet in pts with HF. Further studies to test salt restriction for longer periods are recommended.

Fundamento: Aunque se indica una dieta hiposódica para la IC, no hay evidencia de que esta restricción es beneficiosa para todos los pacientes. Objetivo: Estudiar prospectivamente los efectos agudos de una dieta hiposódica en pacientes (pcs) con insuficiencia cardíaca (IC). Métodos: Fueron estudiados cincuenta pacientes ambulatorios estables con IC leve a moderada, que relataron consumir previamente 6,6 g sal/día. En la fase I, todos los pcs fueron sometidos a una dieta con 2g de sal durante 7 días, seguido por aleatorización en dos subgrupos (fase 2), para recibir 6g de sal (subgrupo I) o 2g de sal/día por 7 días (subgrupo II). Resultados: Fase 1: la dieta con 2g de sal redujo el índice de masa corporal (IMC), sodio plasmático y sodio urinario, consumo de proteína, hierro, zinc, selenio y vitamina B12; aumentó los niveles plasmáticos de norepinefrina, nitrato, aldosterona sérica, y mejoró la calidad de vida. Fase 2: para pcs con IMC bajo, el uso de 6g de sal/día disminuyó de forma aguda los niveles de norepinefrina, albúmina y colesterol en el plasma. No se encontró ninguna diferencia en pcs con IMC más alto. Conclusión: La dieta con 2g de sal/día para pcs con IC aumentó la activación neurohormonal asociada a la progresión de la IC. El IMC puede tener influencia en la respuesta de la activación neurohormonal en una hiposódica en la IC. Se recomiendan futuros estudios para probar la restricción a la ingesta de sal por períodos más largos.

Adaptación morfológica del corazón a la hipertensión arterial esencial: fisiopatología e implicaciones terapéuticas / Morphologic adaptation of the heart to high blood pressure: pathophysiology and therapeutic implications

El diseño experimental de los estudios prospectivos sobre el tratamiento de la hipertensión arterial esencial, ha ignorado un aspecto fundamental de la fisiopatología del paciente hipertenso: Los pacientes hipertensos no son homogéneos, en lo que respecta a los mecanismos responsables del aumento de la presión arterial. La adptación cardiovascular a la hipertensión arterial es anatómica y funcionalmente heterogénea. Investigaciones clínicas recientes indican que, esta heterogeneidad, puede ser minimizada con el uso de la eco-cardiografía. El análisis de los perfiles hemodinámicos y neurohormonales de los pacientes hipertensos permite distinguir la presencia de denominadores comunes: La hipertrofia ventricular concéntrica y la hipertrofia ventricular excéntrica representan los extremos opuestos de adaptación del corazón a la hipertensión arterial. El primero se caracteriza por tener una forma geométrica elíptica, con un perfil hemodinámico de gasto cardíaco normal y resistencias vasculares periféricas elevadas. Los niveles plasmáticos de renina y de los péptidos natriuréticos están elevados.

The experimental design of clinical studies, on the pharmacological treatment of essencial hypertension, has ignored a fundamental issue: Hypertensive patiens are not a homogenous population. The adaptation of the cardiovascular system to hypertension is structurally and funtionally heterogeneous. Recent clinical investigations suggest that this heterogeneity can be minimized by echocardiography. Thus, when the hemodynamic and neurohormonal profiles of untreated hypertensive patients are considered, in the particular context of the cardiac morphologic adaptation to high blood pressure, distinct common denominator emerge. Concentric Hypertrophy is characterized by an elliptic left ventricle, normal stroke volume and high peripheral vascular resistance. Its predominant neurohormonal profile includes elevated plasma renin and natriuretic peptide levels. Conversely, most patients with eccentric hypertrophy have a spheric left ventricle, increased stroke volume and low peripheral vascular resistance. Its corresponding neurohormonal profile shows low serum renin and anhanced sympathetic nervous activity. The therapeutic response, to angiotensin II antagonists and to beta-adrenergic blockers, of these two geometric patterns is also different. Concentric hypertrophy is substantially reversed by angiotensin II blockers, where as, eccentric hypertrophy is refractory to both, angiotensin II blockerds and atenol. These facts raise a relevant question: Should ventricular geometry be considered when deciding which antihypertensive drug is to be prescribed?.

Activación neurohormonal en la insuficiencia cardiaca congestiva crónica / Neurohormonal activation in chronic congestive heart failure

La insuficiencia cardiaca crónica es un síndrome clínico que aparece tardíamente en la evolución natural de distintas enfermedades cardiacas. Reconoce en la actualidad múltiples mecanismos patogénicos los cuales tienen importancia pronóstica e influyen en su manejo terapéutico. Entre estos mecanismos resaltan la activación de una serie de sistemas neurohormonales como: el sistema nervioso simpático y el sistema renina-angiotensina-aldosterona; estos participan en la perpetuación y progresión de la enfermedad, y ensombrecen la evolución clínica si no son modulados o inhibidos. Se exponen los efectos deletéreos de estos sistemas neurohumorales sobre la anatomía y función cardiovascular y el auténtico círculo vicioso que generan y conducen al fallo cardiaco irreversible y al incremento de la morbilidad y mortalidad, además de analizar los beneficios de fármacos que actúan sobre dichos sistemas.

Chronic heart failure is a clinical syndrome that appears lately in the natural evolution of different heart diseases. At present, multiple pathogenic mechanisms that have a prognostic importance and influence on their therapeutical management are recognized. The activation of a series of neurohormonal systems, such as the sympathetic nervous system and the renin-angiotensin-aldosterone system stand out among these mechanisms They participate in the perpetuation and progression of the disease and shadow the clinical evolution if they are not modulated or inhibited. The deleterious effects of these neurohormonal systems on the anatomy and cardiovascular function and the authentic vicious circle they generate are dealt with. They lead to an irreversible heart failure and to the increase of morbidity and mortality. The benefits of the drugs acting on these systems are also analyzed.