慢性心力衰竭伴铁缺乏患者静脉补充铁剂有效性和安全性的meta分析

目的 用meta分析的方法评价慢性心力衰竭伴铁缺乏患者静脉补充铁剂的有效性和安全性。方法 收集国内外关于慢性心力衰竭伴铁缺乏患者静脉补充铁剂的随机对照临床试验（RCT）,按照纳入与排除标准筛选文献,评价文献质量并提取有效数据,对其有效性和安全性进行meta分析。结果 共纳入相关英文研究5篇,其方法学质量较高,2篇文献的质量等级为A级,余为B级。Meta分析结果显示:①有效性:静脉注射铁剂能够改善患者血清铁蛋白［SMD=2.15,95%CI(0.84,3.45),P<0.01］、TSAT［MD=7.97,95%CI(5.71,10.23),P<0.01］、NYHA［MD=-0.56,95%CI(-0.97,-0.15),P<0.01］,减少因心力衰竭住院的人数［OR=0.27,95%CI(0.15,0.47),P<0.01］,但不能降低全因病死率［OR=0.83,95%CI(0.43,1.60),P>0.05］;②安全性:静脉注射铁剂未增加胃肠道不良反应［OR=1.11,95%CI(0.36,3.47),P>0.05］和总不良反应［OR=0.81,95%CI(0.26,2.46),P>0.05］。结论 静脉补充铁剂能够改善慢性心力衰竭伴铁缺乏患者的心衰症状,并具有良好的安全性,但不能改善临床预后。     

Increased iron absorption in patients with chronic heart failure and iron deficiency

BackgroundIron deficiency (ID) is common in patients with chronic heart failure (CHF), but the underlying causes are not fully understood. We investigated whether ID is associated with decreased iron absorption in patients with CHF.Methods and ResultsWe performed an oral iron-absorption test in 30 patients and 12 controls. The patients had CHF with reduced (n = 15) or preserved (n = 15) ejection fraction and ID, defined as s-ferritin < 100 µg/L, or s-ferritin 100–299 µg/L and transferrin saturation < 20%. The controls had no HF or ID and were of similar age and gender. Blood samples were taken before and 2 hours after ingestion of 100 mg ferroglycin sulphate. The primary endpoint was the delta plasma iron at 2 hours. The delta plasma iron was higher in the group with HF than in the control group (median increase 83.8 [61.5;128.5] µg/dL in HF vs 47.5 [30.7;61.5] µg/dL in controls, P = 0.001), indicating increased iron absorption. There was no significant difference between the groups with preserved or reduced ejection fraction (P = 0.46).ConclusionWe found increased iron absorption in patients with CHF and ID compared to controls without ID and HF, indicating that reduced iron absorption is not a primary cause of the high prevalence of ID in patients with CHF.Clinical Trial RegistrationEudraCT 2017-000158-21     

Effect of intravenous iron replacement on recurrent heart failure hospitalizations and cardiovascular mortality in patients with heart failure and iron deficiency: A Bayesian meta-analysis

Aims

Iron deficiency is common in patients with heart failure (HF) and reduced ejection fraction (HFrEF) and is associated with a poor prognosis. Whether intravenous iron replacement improves recurrent HF hospitalizations and cardiovascular mortality of these patients is uncertain although several trials were conducted. Moreover, none of the trials were powered to assess the effect of intravenous iron in clinically important subgroups. Therefore, we conducted a Bayesian analysis to derive precise estimates of the effect of intravenous iron replacement on recurrent HF hospitalizations and cardiovascular mortality in iron-deficient HFrEF patients using consistent subgroup definitions across trials.

Methods and results

Individual participant data were used from the FAIR-HF (n = 459), CONFIRM-HF (n = 304) and AFFIRM-AHF (n = 1108) trials. These data were re-analysed following as closely as possible the approach taken in the analyses of IRONMAN (n = 1137), for which study level data were used. Definitions of outcomes and subgroups from the FAIR-HF, CONFIRM-HF and AFFIRM-AHF were matched with those used in IRONMAN. The primary endpoint was recurrent HF hospitalizations and cardiovascular mortality. The analysis of recurrent events was based on rate ratios (RR) derived from the Lin-Wei-Yang-Ying model, and the data were pooled using Bayesian random-effects meta-analysis. Compared with placebo, intravenous iron significantly reduced the rates of recurrent HF hospitalizations and cardiovascular mortality (RR 0.73, 95% credible interval [CI] 0.48–0.99; between-trial heterogeneity tau = 0.16). The pooled treatment effects did not provide evidence for any differential effects for subgroups based on sex (ratio of rate ratios [RRR] 1.49 [95% CI 0.95–2.37], age <69.4 vs. ≥69.4 years) (RRR 0.68 [0.40–1.15]), ischaemic versus non-ischaemic aetiology of HF (RRR 0.73 [0.42–1.33]), transferrin saturation <20% vs. ≥20% (RRR 0.75 [0.40–1.34]), estimated glomerular filtration rate ≤60 versus >60 ml/min/1.73 m² (RRR 0.97 [0.56–1.68]), haemoglobin <11.8 versus ≥11.8 (RRR 0.95 [0.53–1.60]), ferritin <35 versus ≥35 μg/L (RRR 1.26 [0.72–2.48]) and New York Heart Association class II versus III/IV (RRR 0.91 [0.54–1.56]).

Conclusions

Treatment of iron-deficient HFrEF patients with intravenous iron – namely with ferric carboxymaltose or ferric derisomaltose – results in significant reduction in recurrent HF hospitalizations and cardiovascular mortality. Results were nominally consistent across the subgroups studied, but for several of these subgroups uncertainty remains present.     

Intravenous iron in patients with heart failure and iron deficiency: an updated meta-analysis

Aims

For patients with heart failure (HF) and iron deficiency (ID), randomized trials suggest that intravenous (IV) iron reduces hospitalizations for heart failure (HHF), but uncertainty exists about the effects in subgroups and the impact on mortality. We conducted a meta-analysis of randomized trials investigating the effect of IV iron on clinical outcomes in patients with HF.

Methods and results

We identified randomized trials published between 1 January 2000 and 5 November 2022 investigating the effect of IV iron versus standard care/placebo in patients with HF and ID in any clinical setting, regardless of HF phenotype. Trials of oral iron or not in English were not included. The main outcomes of interest were a composite of HHF and cardiovascular death (CVD), on HHF alone and on cardiovascular and all-cause mortality. Ten trials were identified with 3373 participants, of whom 1759 were assigned to IV iron. IV iron reduced the composite of recurrent HHF and CVD (rate ratio 0.75, 95% confidence interval [CI] 0.61–0.93; p < 0.01) and first HHF or CVD (odds ratio [OR] 0.72, 95% CI 0.53–0.99; p = 0.04). Effects on cardiovascular (OR 0.86, 95% CI 0.70–1.05; p = 0.14) and all-cause mortality (OR 0.93, 95% CI 0.78–1.12; p = 0.47) were inconclusive. Results were similar in analyses confined to the first year of follow-up, which was less disrupted by the COVID-19 pandemic. Subgroup analyses found little evidence of heterogeneity for the effect on the primary endpoint, although patients with transferrin saturation <20% (OR 0.67, 95% CI 0.49–0.92) may have benefited more than those with values ≥20% (OR 0.99, 95% CI 0.74–1.30) (heterogeneity p = 0.07).

Conclusion

In patients with HF and ID, this meta-analysis suggests that IV iron reduces the risk of HHF but whether this is associated with a reduction in cardiovascular or all-cause mortality remains inconclusive.     

Iron therapy for the treatment of iron deficiency in chronic heart failure: intravenous or oral?

This article considers the use and modality of iron therapy to treat iron deficiency in patients with heart failure, an aspect of care which has received relatively little attention compared with the wider topic of anaemia management. Iron deficiency affects up to 50% of heart failure patients, and is associated with poor quality of life, impaired exercise tolerance, and mortality independent of haematopoietic effects in this patient population. The European Society of Cardiology Guidelines for heart failure 2012 recommend a diagnostic work‐up for iron deficiency in patients with suspected heart failure. Iron absorption from oral iron preparations is generally poor, with slow and often inefficient iron repletion; moreover, up to 60% of patients experience gastrointestinal side effects. These problems may be exacerbated in heart failure due to decreased gastrointestinal absorption and poor compliance due to pill burden. Evidence for clinical benefits using oral iron is lacking. I.v. iron sucrose has consistently been shown to improve exercise capacity, cardiac function, symptom severity, and quality of life. Similar findings were observed recently for i.v. ferric carboxymaltose in patients with systolic heart failure and impaired LVEF in the double‐blind, placebo‐controlled FAIR‐HF and CONFIRM‐HF trials. I.v. iron therapy may be better tolerated than oral iron, although confirmation in longer clinical trials is awaited. Routine diagnosis and management of iron deficiency in patients with symptomatic heart failure regardless of anaemia status is advisable, and, based on current evidence, prompt intervention using i.v. iron therapy should now be considered.     

铁缺乏对老年慢性心力衰竭患者左心结构的影响

目的探讨铁缺乏对老年慢性心力衰竭患者左心结构的影响。方法入选306例慢性心力衰竭患者,根据铁蛋白及转铁蛋白饱和度水平,将患者分为铁缺乏组201例和非缺铁组105例。检测患者铁代谢指标(血清铁、总铁结合力、铁蛋白、转铁蛋白),并计算转铁蛋白饱和度。通过超声心动图测量患者左心结构,探讨铁缺乏对左心结构的影响。结果 2组左心房内径、左心室舒张末期内径、左心室收缩末期内径、左心室舒张末期容积、左心室收缩末期容积、室间隔厚度、左心室后壁厚度、左心室质量及左心室质量指数比较,差异均有统计学意义(P0.05)。控制年龄、心率、血压、体质量指数、空腹血糖等影响因素,铁蛋白与左心房内径(r=-0.502,P=0.002)、室间隔厚度(r=-0.318,P=0.040)、左心室后壁厚度(r=-0.534,P=0.001)、左心室质量指数(r=-0.365,P=0.044)呈显著负相关,血清铁与左心房内经(r=-0.538,P=0.000)、左心室质量指数(r=-0.422,P=0.033)、左心室舒张末期容积(r=-0.336,P=0.042)、左心室收缩末期容积(r=-0.321,P=0.048)呈显著负相关。多元线性回归显示,左心室质量指数与铁代谢水平显著相关,纳入铁代谢指标构建的回归模型具有统计学意义(F=2699.382,P=0.000)。结论铁缺乏有促进慢性心力衰竭患者左心重构的不利作用。有必要对慢性心力衰竭患者进行铁缺乏情况的检测及早期治疗。     

Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure

BACKGROUND: Congestive heart failure (CHF) is characterized by enhanced immune activation, and immune-mediated mechanisms may play a pathogenic role in this disorder. Based on the immunomodulatory effects of intravenous immunoglobulin (IVIG), we hypothesized that IVIG could downregulate inflammatory responses in CHF patients and have potential beneficial effects on the left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Forty patients with chronic symptomatic CHF and LVEF of <40%, stratified according to cause (ie, ischemic and idiopathic dilated cardiomyopathy), were randomized in a double-blind fashion to receive therapy with IVIG or placebo for a total period of 26 weeks. Our main findings were that (1) IVIG, but not placebo, induced a marked rise in plasma levels of the anti-inflammatory mediators interleukin (IL)-10, IL-1 receptor antagonist, and soluble tumor necrosis factor receptors; (2) significantly correlated with these anti-inflammatory effects, IVIG, but not placebo, induced a significant increase in LVEF from 26+/-2% to 31+/-3% (P:<0.01), and this was found independent of the cause of heart failure; and (3) N-terminal pro-atrial natriuretic peptide decreased significantly after induction therapy and continued to decrease toward the end of study during IVIG therapy (P:<0.001) but remained unchanged during placebo. CONCLUSIONS: We demonstrated an IVIG-induced change in the balance between inflammatory and anti-inflammatory cytokines that favored an anti-inflammatory net effect in CHF. This effect was significantly correlated with an improvement in LVEF, suggesting a potential for immunomodulating therapy in addition to optimal conventional cardiovascular treatment regimens in CHF patients.     

铁缺乏在慢性心力衰竭中作用的研究进展

慢性心力衰竭(CHF)是各种心血管疾病发展的终末阶段,尽管近年来有关CHF的规范化治疗得到推广,但其患病率和死亡率依然居高不下,部分原因是心力衰竭常伴随多种并发症,其中之一就是贫血和(或)铁缺乏,那么明确机体铁代谢过程并适时进行干预,及时选择合理方案纠正铁缺乏有望成为CHF患者治疗的一个新的突破点。     

静脉应用胺碘酮治疗充血性心力衰竭并发的室性心动过速

目的　观察静脉注射胺碘酮治疗充血性心力衰竭并发的室性心动过速的有效性及安全性。方法　对 5 1例充血性心力衰竭并发持续性室性心动过速的患者首剂给予胺碘酮突击量 3～ 5mg/kg ,15min无效再重复突击量。维持量为 6 0 0mg胺碘酮稀释于 5 0 0ml生理盐水中静脉点滴 2 4h。结果　本组 0 5h内平均负荷量 (2 71 5± 82 8)mg ,第 1个 2 4h胺碘酮静脉用量平均 (916 5± 15 3 4)mg。总有效率 88 2 % ,不良反应发生率 15 9% ,无心功能恶化。结论　静脉注射胺碘酮治疗充血性心力衰竭并发的室性心动过速有效 ,也较安全     

Safety and efficacy of resistance training in patients with chronic heart failure: research-based evidence

Although a rich body of research exists regarding the safety and efficacy of resistance training, health care providers continue to caution patients with heart failure not to engage in this type of exercise. Research studies utilizing resistance training demonstrate improvements in muscular strength and endurance, New York Heart Association functional class, and quality of life. Despite the hemodynamic changes which occur during resistance exercise, no negative outcomes have been reported. The purpose of this paper is to review the most current research regarding the use of resistance training with heart failure patients to provide assistance to clinicians and enable them to provide education and appropriate recommendations to their patients.     

Hemodynamic comparison of intravenous amrinone and dobutamine in patients with chronic congestive heart failure

Amrinone, a new inotropic agent, has been shown to be beneficial in patients with congestive heart failure. However, its hemodynamic effects have not been compared with those of currently useful catecholamines. In this study, the effects of intravenously administered dobutamine and amrinone were compared in eight patients with severe chronic congestive heart failure. Dobutamine was infused until a maximal increase in cardiac index was reached or undesirable effects were produced. This dose was then continued for 8 hours. After a return of hemodynamic values to baseline level, amrinone was infused at a rate of 40 μg/kg per min for 1 hour and then 10 μg/kg per min for 24 hours. Both drugs significantly improved cardiac index while simultaneously decreasing systemic vascular resistance and right atrial and pulmonary wedge pressures (p <0.05). Initially no differences could be found between the drugs. However, with prolonged infusion amrinone produced a sustained improvement whereas dobutamine had a decreased effectiveness. Thus, amrinone is comparable in effect with the optimal dose of dobutamine and would appear to be an extremely promising drug in the acute treatment of severe congestive heart failure.     

Vitamin D deficiency and clinical outcome in patients with chronic heart failure: A review

Aim

The aim of this review was to summarize evidence on the role of Vitamin D deficiency in heart failure (HF), from pathophysiological mechanisms to clinical effects of Vitamin D supplementation.

Prevalence and spectrum of iron deficiency in heart failure patients in south Rajasthan

ObjectiveTo estimate the prevalence and pattern of iron deficiency (ID) in heart failure (HF) patients with or without anemia.MethodsThis is a single-center observational study, conducted at a tertiary care hospital of south Rajasthan. Patients admitted to hospital with clinical diagnosis of HF based on validated clinical criteria were included in the study. ID was diagnosed based on complete Iron profile, including serum iron, serum ferritin, total iron binding capacity, and transferrin saturation (TSAT). Anemia was defined as hemoglobin (Hb) <13 g/dl for males and <12 g/dl for females, based on World Health Organization definition. Absolute ID was taken as serum ferritin < 100 μg/L and functional ID was defined as normal serum ferritin (100–300 μg/L) with low TSAT (<20%).ResultsA total of 150 patients of HF (68% males and 32% females) were studied. Most of the patients were of high-functional NYHA class (mean NYHA 2.89 ± 0.95). ID was present in 76% patients with 48.7% patients having absolute and 27.3% patients having functional ID. Females were having significantly higher prevalence of ID than males (91.6% vs 68.6%; p = 0.002). Nearly one-fourth of the patients were having ID but without anemia, signifying importance of workup of ID other than Hb.ConclusionOur study highlights the yet underestimated and neglected burden of ID in HF patients in India. This study suggests further large-scale studies to better characterize this easily treatable condition and considering routine testing in future Indian guidelines.     

铁缺乏与慢性心力衰竭

慢性心力衰竭(chronic heart failure,CHF)是当今最重要的心血管疾病之一,严重影响患者的生活质量.铁缺乏(iron deficiency,ID)是CHF普遍存在的合并症,与其不良预后独立相关,应用铁剂治疗可能改善患者的生活质量和运动能力以及预防再住院,进而降低心衰死亡率.2016欧洲心脏病学会(E...