慢性心衰患者血浆脑钠肽前体N端片段测定的价值

目的调查心功能Ⅰ～Ⅳ级心血管病患者血浆B型脑钠肽前体N端片段(NT-proBNP)水平,探讨心衰患者血浆NT-proBNP水平与心功能分级以及左室射血分数(LVEF)的关系。方法选择因慢性充血性左心衰(CHF)住院的38～80岁患者110例,对照组30例。心功能分级按照纽约心脏病协会(NYHA)对心衰患者进行分级。在RochElecsys2010全自动测定仪上使用电化学发光法测定血浆NT-proBNP浓度。结果CHF患者NT-proBNP中位数为272.15pg/ml,明显高于对照组(32.08pg/ml,P<0.01)。在CHF患者中,不同NY-HA分级的各组患者NT-proBNP水平均有显著的差异(P<0.01),随着心力衰竭严重程度的增加,NT-proB-NP水平不断升高。CHF患者NT-proBNP与LVEF值之间呈良好的负相关(r=-0.626,P<0.01);在对照组两者无相关性(P=0.647)。结论血浆NT-proBNP水平随心功能的下降而升高,临床上NT-proBNP的检测是判断心功能不全的一个非常敏感的指标。对诊断心衰有帮助,可能会成为临床应用的常规检测指标。     

糖化血红蛋白和N末端脑钠肽原与急性冠脉综合征心功能的相关性分析

目的：探讨糖化血红蛋白（HbA1c）和N末端脑钠肽原（NT-proBNP）与急性冠脉综合征（ACS）患者心功能的相关性。方法选取本院2009年1月60例ACS合并2型糖尿病（T2DM）患者，设定为T2DM组，并选取60例ACS患者，设定为ACS组，对其HbA1c、NT-proBNP含量检测，并分析其相关性。结果 ACS患者心功能与HbA1c、NT-proBNP存在明显正相关性， ACS患者HbA1c、NT-proBNP间存在正相关性。结论 HbA1c与NT-proBNP对ACS患者心功能受损情况具有促进效果，可当作ACS心功能受损检测指标应用。     

尿酸、NT-proBNP及hsCRP在慢性心力衰竭诊断中的临床价值

目的：探讨血尿酸、hsCRP及NT-proBNP在慢性心力衰竭（心衰）诊断方面的临床价值。方法选取41例慢性心衰患者及31例健康对照组,检测外周血尿酸、hsCRP及NT-proBNP的浓度,分析其与NYHA（纽约心脏病协会）心功能分级、LVEF（左室射血分数）及 LVEDD（左室舒张末期内径）的相关性。结果慢性心衰患者血尿酸、hsCRP 及 NT-proBNP 较对照组显著升高（ P ＜0.05）,不同心功能分级之间的血尿酸及NT-proBNP亦有统计学差异（P＜0.05）。尿酸及NT-proBNP与心功能分级及LVEDD呈正相关（r＝0.67,P＜0.05;r＝0.52,P＜0.05;r＝0.54,P＜0.05;r＝0.53,P＜0.05）,与LVEF呈负相关（r＝－0.61,P＜0.05;r＝－0.57,P＜0.05）。尿酸与NT-proBNP两者之间亦有一定的相关性（r＝0.46,P＜0.05）。结论慢性心衰患者血尿酸及NT-proBNP与疾病严重程度相关,是心功能评价的较好指标,而hsCRP在心衰诊断的临床价值不如尿酸及NT-proBNP。     

维持性血液透析对老年慢性肾衰竭合并心力衰竭患者心脏功能及血浆NT-proBNP的影响

目的 探讨维持性血液透析对老年慢性肾衰竭并心衰患者心脏功能及血浆NT-proBNP的影响.方法 选取收治的老年慢性肾衰患者68例,根据是否合并心衰将患者分为肾衰心衰组(n=38)和单纯肾衰组(n=30),选取同期体检健康人群30例作为对照组.2组肾衰患者均行维持性血液透析治疗3个月.比较3组治疗前血浆NT-proBNP和肾小球率过滤(eGFR)水平;比较2组肾衰患者治疗后NT-proBNP水平及肾衰心衰组治疗后左心室功能;并对NT-pro BNP水平与心功能分级及eGFR进行相关性分析.结果 与对照组比较,2组肾衰患者NT-proBNP明显升高,eGFR明显降低(P<0.05);随着心功能不全程度的加重,肾衰心衰组患者NT-proBNP逐渐升高,eGFR逐渐降低(P<0.05).治疗后,2组肾衰患者NT-proBNP水平均有所降低(P<0.05);肾衰心衰组患者LVEDd、LVEDs、IVST、LVMI均降低,LVEF和FS升高(P<0.05或<0.01).经Spearman相关性分析显示,NT-proBNP水平与心功能分级呈正相关(r=0.695,P<0.01),与LVEDd、LVEDs、IVST、LVMI呈正相关(r=0.325,r=0.214,r=0.289,r=0.326,P<0.05或<0.01),与LVEF呈负相关(r=-0.358,P<0.01),与eGFR呈负相关(r=-0.158,P<0.05).结论 慢性肾衰合并心衰患者NT-proBNP普遍升高,动态监测NT-proBNP可以密切观察容量负荷的变化,同时行规范的血液透析可降低NT-proBNP,延缓心衰进展.     

糖化血红蛋白和N末端脑钠肽原与急性冠脉综合征心功能的关系

目的 探讨糖化血红蛋白(HbA1c)和N-末端脑钠肽前体(NT-proBNP)的表达水平与急性冠脉综合征(ACS)患者心功能的关系.方法 检测ACS患者68例(A1组,38例,合并糖尿病;A2组,30例,无糖尿病)和健康体检者20名(B组)血清HbA1c和NT-proBNP水平.结果 A1组血清HbA1c水平明显高于A2组和B组[(9.47±1.62)％ vs.(5.86±0.31)％和(5.64±0.22)％](P＜0.01),但A2组和B组之间无统计学差异(P＞0.05).A1、A2组血清NT-proBNP均明显高于B组[(441.84±78.63) μg/ml、(217.31±34.52) μg/ml vs.(86.33±15.26) μg/ml] (P＜0.01),且A1组NT-proBNP高于A2组(P＜0.01).在ACS患者,血清HbA1c和NT-proBNP水平随着心功能病情加重而明显增加(P＜0.05或P＜0.01).ACS患者血清HbA1c和NT-proBNP水平呈显著正相关(r=0.524,P＜0.05).结论 ACS患者血清HbA1c和NT-proBNP水平明显升高;联合检测血清HbA1c和NT-proBNP可以用于ACS患者心功能的评估.     

N末端脑型钠尿肽定量监测与心力衰竭诊断的相关性研究

目的探讨血清N末端B型钠尿肽(NT-proBNP)浓度与心功能分级(NYHA)、左室射血分数(LVEF)等临床指标之间的关系,及其在心力衰竭诊断中的作用。方法选择心衰患者200例、非心衰患者25例,采用电化学发光法测定血清NT-proBNP浓度。超声心动图测定受试者LVEF。依据NYHA分级方法对心衰患者进行心功能分级,心衰诊断依据病史、症状、体征、客观检查等做出的综合判断为金标准。结果心衰组的NT-proBNP水平显著高于对照组;NYHA分级与NT-proBNP水平呈显著正相关(r=0.992 0),LVEF则与NT-proBNP水平呈负相关。结论NT-proBNP可以客观准确地评价心功能,可作为临床诊断心衰的实验室指标。     

2型糖尿病患者发生下肢动脉粥样硬化的影响因素

目的 探讨2型糖尿病(T2DM)患者糖化白蛋白(GA)、糖化血红蛋白(HbA1c)及GA/HbA1c水平与发生下肢动脉粥样硬化疾病(lower extremity atherosclerotic disease, LEAD)风险的关系。方法 选取2019年1月至2022年3月就诊的2型糖尿病患者566例,根据是否合并LEAD分为2型糖尿病组(T2DM组)288例,2型糖尿病合并LEAD组(T2DM+LEAD组)278例。比较2组生化指标、GA、HbA1c、GA/HbA1c比值水平,进一步分析T2DM合并LEAD危险因素。结果 GA与空腹血糖、餐后2 h血糖、HbA1c之间存在正相关(r=0.302、0.572、0.611,P=0.000)。Logistic回归分析发现高龄、有吸烟史、病程、总胆固醇、餐后2 h血糖、GA、GA/HbA1c比值是2型糖尿病LEAD的危险因素。结论 GA和GA/HbA1c比值是T2DM患者LEAD发生的危险因素。     

血清糖类抗原125对慢性心衰患者病情评估、疗效判定及预后预测价值的研究

目的探讨血清糖类抗原125（CA-125）对慢性心衰患者病情评估、疗效判定及预后预测的价值。方法连续选取慢性心衰患者120例（心衰组）,同时选取同期住院非心衰患者120例作为对照组,测定CA125、N端B型脑钠肽前体（NT-proBNP）水平及超声心动图指标,比较两组患者之间的差异;心衰组患者给予抗心衰治疗2周后复测CA125、NTproBNP水平,按照治疗效果分为显效组、有效组和无效组,分别比较治疗前后CA125水平的差异;心衰组按照CA125平均水平分为高水平组和低水平组,随访1年,比较两组患者再住院率和死亡率。结果心衰组CA125及NT-proBNP水平均明显高于对照组（P=0.000）,根据左室射血分数分组后,左心室射血保留心衰组（HFPEF组）和左心室射血分数下降心衰组（HFREF组）CA125及NT-proBNP水平均明显高于对照组（P值均为0.000）;心衰组按NYHA心功能分级,心功能越差CA125及NT-proBNP水平越高,差异有统计学意义（P〈0.05）;慢性心衰患者CA125水平与NT-proBNP水平呈正相关（r=0.72,P=0.006）,与LVEF呈负相关（r=-0.69,P=0.009）;心衰组抗心衰治疗2周,显效组和有效组治疗前后CA125及NTproBNP水平比较差异有统计学意义（P值均为0.000）,而无效组差异无统计学意义（P=0.104）;高CA125水平组1年再入院率、死亡率分别为34.04%和17.02%,明显高于低CA125水平组的14.50%和5.80%（P值为0.000和0.002）。结论 CA125水平不仅可以作为慢性充血性心力衰竭诊断的一项重要指标,还可以反映心衰程度及治疗效果,同时对预后判断具有参考价值。     

慢性心衰患者心脏超声诊断参数价值研究

目的探索飞利浦IE33超声心动图为慢性心衰患者提供心脏超声参数评价心脏功能的可靠性与全面性。方法采用前瞻性研究慢性心力衰竭患者100例,其中慢性心衰患者心功能包括1～4等级,同时给予患者抽血检查脑钠肽又称B型利钠肽（BNP）指标与超声检查,比较超声检查参数指标与BNP指标以及纽约心功能分级之间的关系。结果慢性心衰患者超声指数左室射血分数（LVEF）与血浆BNP水平呈负相关（r=-0.78）,P〈0.05,有统计学意义。说明LVEF与血浆BNP之间呈负相关趋势,另一方面心脏超声各种参数与心功能分级的Spearman相关及多元回归分析相关分析结果提示,LVEF和心功能分级呈负相关,r=-0.8,P〈0.01,有显著性统计学意义,其他超声参数均与心功能分级呈正相关,且均P〈0.05,有统计学意义。进行多元逐步回归分析以心脏超声参数为自变量,以心功能分级为因变量得到最优方程：心功能分级Y=5.21-2.08X（LVEF）。结论心脏超声提供参数能全面可靠的反映患者的心脏功能,具有很好的参考价值。值得在临床上推广。     

Apoptosis and Heart Failure

A large volume of experimental data supports the presence of apoptosis in failing hearts. Apoptosis in many types of cells results from exposure to cytotoxic cytokines or damaging agents. Cytotoxic cytokines such as tumor necrosis factor (TNF)-α; or Fas ligand (FasL) bind to their receptors to activate caspase-8, while damaging agents can cause mitochondrial release of cytochrome c, which can initiate activation of caspase-9. Caspase-8 or -9 can activate a cascade of caspases. The p53 protein is often required for damaging agent-induced apoptosis. An imbalance of proapoptotic factors versus prosurvival factors in the bcl-2 family precedes the activation of caspases. Given these typical changes of apoptosis found in many cell types, the apoptotic pathway in cardiomyocytes is somewhat unconventional since in vivo experimental data reveal that apoptosis does not appear to be controlled by TNF-α;, FasL, p53 or decrease of bcl-2. In vitro and in vivo studies suggest the importance of mitochondria and activation of caspases in cell death occurring in failing hearts. Oxidants, excessive nitric oxide, angiotensin II and catecholamines have been shown to trigger apoptotic death of cardiomyocytes. Eliminating these inducers reduces apoptosis and reverses the loss of contractile function in many cases, indicating the feasibility of the pharmacological application of antioxidants, nitric oxide synthetase inhibitors, ACE inhibitors, angiotensin II receptor antagonists and adrenergic receptor antagonists. Most inducers of apoptosis initiate a cascade of signaling events, including activation of the p38 mitogen-activated protein kinase. Small molecule inhibitors of p38 have been shown to be capable of preventing apoptosis and loss of contractile function associated with ischemia and reperfusion. Although further experimental work is needed, several studies have already indicated the beneficial effect of caspase inhibitors against cell loss and features of heart failure in vitro and in vivo. These studies indicate the importance of inhibiting apoptosis in therapeutic interventions against heart failure.     

Congestive Heart Failure

Left ventricular systolic dysfunction is associated with neurohormonal activation which contributes to progressive ventricular remodeling and worsening clinical heart failure. Renin-angiotensin-aldosterone and sympathetic nervous systems are activated, not only in patients with clinically overt heart failure, but also in patients with asymptomatic or minimally symptomatic left ventricular systolic dysfunction. Activation of the angiotensin and adrenergic systems produces deleterious effects on systemic and coronary hemodynamics, promotes myocyte hypertrophy and fibroblast growth, and myocyte necrosis and apoptosis. Thus, therapy of heart failure should consist of pharmacologic agents not only to relieve symptoms but also to prevent and attenuate ventricular remodeling and progressive heart failure, thereby improving prognosis. In patients who are symptomatic, ACE inhibitors along with digitalis and diuretics as initial therapy (triple therapy) have the greater potential to improve exercise tolerance and decrease the incidence of treatment failure compared with diuretics alone or a combination of diuretics and digitalis. Diuretics alone should not be considered for long-term therapy as plasma renin activity, angiotensin II, aldosterone, norepinephrine and vasopressin levels may increase. ACE inhibitors decrease mortality in patients with heart failure resulting from left ventricular systolic dysfunction. The results of presently available studies indicate that angiotensin II receptor blockers (ARBs) do not provide any advantage over ACE inhibitors regarding survival benefit but may be better tolerated. Long-term adrenergic inhibition with the use of ß-adrenoceptor antagonists added to ACE inhibitors is associated with attenuation of ventricular remodeling, improvement in ventricular function and clinical class and survival of patients with symptomatic systolic left ventricular failure. Thus, initial pharmacotherapy for systolic heart failure should consist of: (i) maximal tolerated dosages of ACE inhibitors; (ii) ARBs if ACE inhibitors are not tolerated because of intractable cough or angioedema; (iii) adequate dosages of hydralazine and isosorbide dinitrate if ACE inhibitors or ARBs are not tolerated; (iv) relatively low dosages of digoxin (serum concentrations of ≤ 1.0 ng/dl) if not contraindicated; and (v) diuretics to relieve congestive symptoms. Addition of spironolactone to ACE inhibitors can result in a significant reduction in the risk of sudden death in patients with symptomatic severe heart failure. Myocardial infarction resulting from ischemic heart disease is the most common cause of systolic left ventricular failure and the therapeutic modalities with potential to reduce the risks of myocardial infraction, such as risk factor modification, adequate control of diabetes and hypertension, antiplatelet agents and lipid-lowering agents, should also be included in the initial therapy.     

Chronic Heart Failure

Heart failure (HF) is a complex syndrome characterized by the inability of the heart to maintain a normal cardiac output without elevated intracardiac filling pressures, resulting in signs of pulmonary and peripheral edema and symptoms of dyspnea and fatigue. Central to the management of HF is a multifaceted pharmacological intervention to abate the harmful counter-regulatory effects of neurohormonal activation and avid salt and water retention. Whereas up to 40 years ago HF was managed with diuretics and leaf of digitalis, the cornerstones of therapy for HF patients with systolic dysfunction now include ACE inhibitors or angiotensin II type 1 receptor antagonists (angiotensin receptor blockers), β-adrenoceptor antagonists (β-blockers), and aldosterone antagonists, which have significantly improved survival. However, with the increasing number of beneficial therapies, there are challenges to implementing all of them. Specific cardiomyopathies also merit specific considerations with respect to treatment, and — unfortunately — there is no therapy for HF with preserved left ventricular ejection fraction that has been shown to improve survival. Although mortality has improved in HF, the biggest challenge to treatment lies in addressing the morbidity of this disease, which is now the most common reason for hospital admission in our aged population. As such, there are many therapies that may serve to improve the quality of life of HF patients. Future HF treatment regimens may include direct cellular therapy via hormone and cytokine signaling or cardiac regeneration through growth factors or cell therapy.     

慢性心衰的药物治疗

心衰内科治疗近10年有重大进展。轻中度心衰2级OPT治疗(Optimal Medical Therapy)应用ACE抑制剂与β受体阻滞剂可降低死亡率40％以上，如果再加CRT-D治疗可进一步降低死亡率超出60％。     

Device Therapy for Heart Failure

Surgical approaches to heart failure (HF) management have become a necessary strategy in response to a waiting list that is expanding in the face of a limited supply of organ donors. Multiple studies have supported the safety and efficacy of device-based therapy. Among the device-based therapy options, ventricular assist devices (VADs) represent an alternative to heart transplantation with the capability to function as short-term support, bridge-to-transplantation or recovery and as long-term support. VAD support may be considered in those with refractory cardiogenic shock or those with decompensated chronic HF that is unresponsive to maximized medical therapy. Composite scoring scales may be used to risk-stratify patients using clinical and laboratory values to allow more systematic patient selection. As the pursuit for a perfect device continues, so does the search for the best objective index to guide referral. Technologic advances will enhance device performance and extend VAD use into community practice. This discussion aims to highlight criteria for candidate selection and referral for VAD implantation.     

Immunosuppressive Therapy for Heart Failure

Therapy with β-adrenoceptor antagonists, ACE inhibitors and most recently, Spironolactone was established for reducing all-cause mortality in patients with congestive heart failure (CHF), improving patient clinical status and inhibiting the disease progression. Unfortunately, despite optimal therapy for CHF in some patients, the disease progresses and, as yet, no conclusive mechanism has been identified for deterioration of cardiac function in patients with heart failure. Defining the cause of CHF in patients with dilated cardiomyopathy may have prognostic and therapeutic implications. Clinical and experimental evidence suggests that long-term inflammation may play a key part in the development of heart failure in patients with cardiomyopathy due to ischemic heart disease and those with cardiomyopathy due to non-ischemic cases. Because chronic immune myocardial injury, found in patients with CHF is myocardial restricted, endomyocardial biopsy with immunohistological markers of immune-mediated injury may offer us new guidelines to patient selection for immunomodulatory therapies. Few randomized placebo controlled studies addressing the effectiveness of suppression and modulation of the immune system in patients with heart failure gave unequivocal results. Moreover, none of the abovementioned randomized studies has shown decreased mortality in the immunosuppressively treated patients compared with conventionally treated patients. In the US Myocarditis Treatment Trial, for example, mortality was 20% overall at 1 year and 56% at 4.3 years of follow-up. In addition, spontaneous improvement of left ventricular systolic function has been reported in 30–40% of conventionally treated patients with CHF due to dilated cardiomyopathy. Given the high proportion of patients who improve spontaneously, selection of patients for immunosuppressive therapy should be preceded by treating heart failure with the individualized conventional therapy (ACE inhibitors, β-adrenoceptor antagonists, Spironolactone) for at least 6 months. Final decision to use immunomodulatory therapies should be based on comprehensive clinical measures of disease progression.     

ACE Inhibitors in Heart Failure

ACE inhibitors have significantly decreased cardiovascular mortality, myocardial infarction (MI), and hospitalizations for heart failure (HF) in patients with asymptomatic or symptomatic left ventricular (LV) systolic dysfunction. Furthermore, the extended 12-year study of the SOLVD (Studies Of Left Ventricular Dysfunction) Prevention and Treatment trials (X-SOLVD) demonstrated a significant benefit with a reduction of cumulative all-cause death compared with placebo (50.9% vs 56.4%) [hazard ratio (HR) 0.86; 95% CI 0.79, 0.93; p < 0.001]. The survival benefits and significant reductions in cardiovascular morbidity related to treatment with ACE inhibitors are likely achieved by titrating the dose of ACE inhibitors to the target dose achieved in clinical trials. Although the ATLAS (Assessment of Treatment with Lisinopril And Survival) study, which randomly allocated HF patients to low- or high-dose lisinopril, showed no significant difference between groups for the primary outcome of all-cause mortality (HR 0.92; 95% CI 0.82, 1.03), the predetermined secondary combined outcome of all-cause mortality and HF hospitalization was reduced by 15% for the patients receiving high-dose lisinopril compared with low-dose (p < 0.001) with a 24% reduction in HF hospitalization (p = 0.002). Despite the use of ACE inhibitors, blockade of the renin angiotensin aldosterone system (RAAS) remains incomplete, with evidence of continued production of angiotensin II by non-ACE-dependent pathways. The safety and potential benefits of angiotensin receptor antagonists (angiotensin receptor blockers [ARBs]) in patients with impaired systolic function have been assessed in moderate to large clinical trials. In patients with impaired LV systolic function and HF, combination therapy with ARBs with recommended HF therapy including ACE inhibitors in patients who remain symptomatic may be considered for its morbidity benefit. Based on the CHARM (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity)-Added data, candesartan cilexetil in addition to standard HF therapy results in a further reduction of cardiovascular mortality. Close monitoring of renal function and serum potassium levels is needed in this setting. The VALIANT (VALsartan In Acute myocardial iNfarction Trial) results suggest that valsartan is as effective as captopril in patients following an acute MI with HF and/or LV systolic dysfunction and may be used as an alternative treatment in ACE inhibitor-intolerant patients. There was no survival benefit with valsartan-captopril combination compared with captopril alone in this trial. Despite these results, ACE inhibitors remain the first-choice therapeutic agent in post-MI patients, and ARBs can be used in patients with clear intolerance. Although the use of ACE inhibitors may be appealing in patients with HF and preserved LV systolic function, there is currently no evidence from large clinical trials to support this.     

小檗碱抗心力衰竭作用研究概况

小檗碱为异喹啉类生物碱，药理作用广泛，近年来药理学发现其具有治疗心力衰竭的作用。该文对小檗碱从心肌收缩力的正性肌力作用和负性肌力作用两方面在心力衰竭中的应用研究进行综述，并且提出了对小檗碱治疗舒张性心力衰竭的展望。