Prediction of all-cause mortality with hypoalbuminemia in patients with heart failure: a meta-analysis

Abstract

Objective: The prognostic utility of serum albumin level for mortality in heart failure patients has received considerable attention. This meta-analysis sought to examine the prognostic significance of hypoalbuminemia for prediction of all-cause mortality in patients with heart failure.

Materials and methods: Pubmed and Embase databases were systematically searched up to 10 March 2019 to identify eligible studies. Epidemiological studies reporting a multivariable-adjusted risk estimate of all-cause mortality associated with hypoalbuminemia in acute or chronic heart failure patients were included.

Results: Nine studies from 10 articles involving 16,763 heart failure patients were included in the final analysis. Hypoalbuminemia was associated with an increased in-hospital mortality (risk ratio [RR] 4.90; 95% confidence interval [CI] 2.96–8.10) and long-term all-cause mortality (RR 1.75; 95% CI 1.35–2.27) in acute heart failure patients. Chronic heart failure patients with hypoalbuminemia exhibited a 3.5-fold (95% CI 1.29–9.73) higher risk for long-term all-cause mortality.

Conclusions: Hypoalbuminemia is possibly an independent predictor of all-cause mortality in patients with acute or chronic heart failure. However, the current findings should be further confirmed in future prospective studies. Moreover, future well-designed randomized controlled trials would be required to investigate whether correcting hypoalbuminemia in heart failure patients has potential to improve survival outcome.     

Plasma levels and diagnostic value of catestatin in patients with heart failure

Catestatin (CST) is an endogenous neuropeptide with multiple cardiovascular activities. The study is to investigate circulating CST levels in heart failure (HF) patients and to evaluate the role of CST as a biomarker for HF. Plasma CST concentrations were measured by enzyme-linked immunosorbent assay in 228 HF patients and 172 controls. Plasma CST gradually increased in patients from NYHA class I to class IV. No significant differences in CST were found among NYHA I, NYHA II patients and controls. Plasma CST in NYHA III and IV patients was higher compared to other groups. Plasma CST levels in HF patients after treatment were similar to admission, but still higher than controls. In a subgroup analysis among the patients with NYHA class III or IV, patients with ischemic etiology had significantly higher CST. Plasma CST levels were similar between patients with preserved and reduced ejection fraction. Multivariable analysis showed that NYHA classes, the etiology of HF (ischemic or not) and estimated glomerular filtration rate independently predicted plasma LogCST levels (P < 0.05). The area under ROC for CST and BNP in moderate to severe HF diagnosis was 0.626 and 0.831, respectively, combining CST and BNP did not improve the accuracy.     

Uncovering heart failure with preserved ejection fraction in patients with type 2 diabetes in primary care: time for a change

Undetected heart failure appears to be an important health problem in patients with type 2 diabetes and aged ≥ 60 years. The prevalence of previously unknown heart failure in these patients is high, steeply rises with age, and is overall higher in women than in men. The majority of the patients with newly detected heart failure have a preserved ejection fraction. A diagnostic algorithm to detect or exclude heart failure in these patients with variables from the medical files combined with items from history taking and physical examination provides a good to excellent accuracy. Annual screening appears to be cost-effective. Both unrecognised heart failure with reduced and with preserved ejection fraction were associated with a clinically relevant lower health status in patients with type 2 diabetes. Also the prognosis of these patients was worse than of those without heart failure. Existing disease-management programs for type 2 diabetes pay insufficient attention to early detection of cardiovascular diseases, including heart failure. We conclude that more attention is needed for detection of heart failure in older patients with type 2 diabetes.     

Intracellular magnesium in elderly patients with heart failure: Effects of diabetes and renal dysfunction

Hypomagnesemia is frequent in diabetes mellitus (DM), while renal dysfunction (RD) may be associated with hypermagnesemia. Severe cardiac arrhythmias and other adverse clinical manifestations are frequent in heart failure (HF), in DM and in RD. Depletion of intracellular magnesium (icMg), which may coexist with normal serum Mg, might contribute to these deleterious effects. However, icMg content in normomagnesemic HF patients with RD or DM has not been studied. We assessed total icMg in peripheral blood mononuclear cells (PBMC) from 80 normomagnesemic furosemide-treated HF patients who were divided as follows: subgroups A (DM), B (RD), C (DM and RD), and D (free of DM or RD). PBMC from 18 healthy volunteers served as controls. IcMg content (μg/mg cell protein) in HF was lower compared to controls (1.68±0.2 vs. 2.4±0.39, p<0.001). In the entire HF group, a significant inverse correlation was evident between icMg and serum creatinine (r=−0.37) and daily furosemide dosages (r=−0.121). IcMg in the HF subgroups A, B, C, and D was 1.79±0.23, 1.57±0.23, 1.61±0.25, and 1.79±0.39, respectively (p=0.04 between A and B, p=0.08 between B and D, and non-significant in the remaining comparisons). Serum Mg, potassium, calcium, furosemide dosages and left ventricular ejection fraction were comparable in all subgroups. In conclusion, icMg depletion was demonstrable in PBMC, which may be responsible for some of the adverse clinical manifestations in HF patients. In particular, icMg depletion in RD might contribute to cardiac arrhythmias in this patient group. Mg supplementation to normomagnesemic HF patients might therefore prove beneficial.     

Intracellular calcium and the relationship to contractility in an avian model of heart failure

Global contractile heart failure was induced in turkey poults by furazolidone feeding (700 ppm). Abnormal calcium regulation appears to be a key factor in the pathophysiology of heart failure, but the cellular mechanisms contributing to changes in calcium fluxes have not been clearly defined. Isolated ventricular myocytes from non-failing and failing hearts were therefore used to determine whether the whole heart and ventricular muscle contractile dysfunctions were realized at the single cell level. Whole cell current- and voltage-clamp techniques were used to evaluate action potential configurations and L-type calcium currents, respectively. Intracellular calcium transients were evaluated in isolated myocytes with fura-2 and in isolated left ventricular muscles using aequorin. Action potential durations were prolonged in failing myocytes, which correspond to slowed cytosolic calcium clearing. Calcium current-voltage relationships were normal in failing myocytes; preliminary evidence suggests that depressed transient outward potassium currents contribute to prolonged action potential durations. The number of calcium channels (as measured by radioligand binding) were also similar in non-failing and failing hearts. Isolated ventricular muscles from failing hearts had enhanced inotropic responses, in a dose-dependent fashion, to a calcium channel agonist (Bay K 8644). These data suggest that changes in intracellular calcium mobilization kinetics and longer calcium-myofilament interaction may be able to compensate for contractile failure. We conclude that the relationship between calcium current density and sarcoplasmic reticulum calcium release is a dynamic process that may be altered in the setting of heart failure at higher contraction rates. Accepted: 1 March 2000     

Listing criteria for heart transplantation in the Netherlands

The updated listing criteria for heart transplantation are presented on behalf of the three heart transplant centres in the Netherlands. Given the shortage of donor hearts, selection of those patients who may expect to have the greatest benefit from a scarce societal resource in terms of life expectancy and quality of life is inevitable. The indication for heart transplantation includes end-stage heart disease not remediable by more conservative measures, accompanied by severe physical limitation while on optimal medical therapy, including ICD/CRT‑D. Assessment of this condition requires cardiopulmonary stress testing, prognostic stratification and invasive haemodynamic measurements. Timely referral to a tertiary centre is essential for an optimal outcome. Chronic mechanical circulatory support is being used more and more as an alternative to heart transplantation and to bridge the progressively longer waiting time for heart transplantation and, thus, has become an important treatment option for patients with advanced heart failure.Supplementary InformationThe online version of this article (10.1007/s12471-021-01627-x) contains supplementary material, which is available to authorized users.     

Preexisting heart failure is an underestimated risk factor in cardiac surgery

Background

Heart failure is characterised as a strong risk factor for systemic failure after cardiac surgery. However, the impact has never been substantiated.

Methods

Patients with heart failure (n = 48) - scheduled for elective ventricular reconstruction or external constraint device-were compared with a one-to-one matched control group of patients without heart failure undergoing cardiac surgery between 2006 and 2009.

Results

As expected, patients with heart failure more frequently experienced complications definitely related to pump failure (p = 0.01). However, complications not related to their pump failure were also more often observed, such as prolonged mechanical ventilation, sepsis and vasoplegia (p = 0.01). Overall, organ dysfunction-circulatory, renal, and pulmonary failure-was often observed in heart failure patients, contributing to a prolonged stay in the intensive care unit (p < 0.001) as well as in hospital (p = 0.01).

Conclusion

The adverse postoperative course in patients with heart failure is not only directly related to circulatory failure, but merely reflects a systemic dysregulation. Our findings suggest that heart failure impacts outcome and should therefore be included in prevailing risk classification systems. Offensive perioperative treatment strategies, focused on the main complications in patients with heart failure, will lead to improved results after cardiac surgery.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-012-0257-y) contains supplementary material, which is available to authorized users.     

卡维地洛加安体舒通治疗慢性充血性心力衰竭疗效观察

目的:观察卡维地洛加安体舒通治疗慢性充血性心力衰竭(CHF)的疗效。方法:将CHF患者63例随机分成观察组与对照组,在常规强心、利尿基础上,观察组加卡维地洛、安体舒通治疗。对照组加依那普利治疗。时间为三个月。结果:两组对CHF患者心功能均明显改善,总有效率观察组为80％,对照组为67％。观察组优于对照组,P<0.05。观察组不良反应轻,对照组有3例患者分别出现咳嗽、皮疹。结论:卡维地洛加安体舒通治疗CHF优于依那普利,且无明显不良反应。     

Real-world heart failure management in 10,910 patients with chronic heart failure in the Netherlands

Aims

Data from patient registries give insight into the management of patients with heart failure (HF), but actual data from unselected real-world HF patients are scarce. Therefore, we performed a cross sectional study of current HF care in the period 2013–2016 among more than 10,000 unselected HF patients at HF outpatient clinics in the Netherlands.

Methods

In 34 participating centres, all 10,910 patients with chronic HF treated at cardiology centres were included in the CHECK-HF registry. Of these, most (96%) were managed at a specific HF outpatient clinic. Heart failure was typically diagnosed according to the ESC guidelines 2012, based on signs, symptoms and structural and/or functional cardiac abnormalities. Information on diagnostics, treatment and co-morbidities were recorded, with specific focus on drug therapy and devices. In our cohort, the mean age was 73 years (SD 12) and 60% were male. Frequent co-morbidities reported in the patient records were diabetes mellitus 30%, hypertension 43%, COPD 19%, and renal insufficiency 58%. In 47% of the patients, ischaemia was the origin of HF. In our registry, the prevalence of HF with preserved ejection fraction was 21%.

Conclusion

The CHECK-HF registry will provide insight into the current, real world management of patient with chronic HF, including HF with reduced ejection fraction, preserved ejection fraction and mid-range ejection fraction, that will help define ways to improve quality of care. Drug and device therapy and guideline adherence as well as interactions with age, gender and co-morbidities will receive specific attention.

     

Potential of resveratrol in the treatment of heart failure

The concept of food has expanded beyond its traditional role of survival and hunger satisfaction, to include a role in the prevention and treatment of disease. Polyphenols are classes of compounds that are synthesized by plants to serve a wide variety of functions including growth pollination and defense. These compounds have recently received increased attention in medical research. In this group, one of the most studied has been resveratrol (3,5,4,-trihydroxystilbene), a polyphenol, which is found predominantly in grapes and berries. Over the past two decades, researchers have studied the ability of resveratrol to prevent or reverse the development of abnormalities in heart structure and function in animal models of heart disease and heart failure. The results from animal studies have been promising, and very recently, this knowledge has been translated into examining the efficacy of resveratrol in humans with heart disease/failure. In this review we will discuss the current status of resveratrol research on cardioprotection.     

伊伐布雷定治疗高龄老年射血分数中间值心衰患者的疗效观察

目的 评价伊伐布雷定治疗高龄老年射血分数中间值心衰(HFmrEF)患者的临床疗效.方法 选择我院治疗的120例高龄老年HFmrEF患者,按随机数字表法分为观察组和对照组各60例,对照组给予规范化抗心衰治疗,观察组在此基础上加用伊伐布雷定治疗.随访6个月后,比较两组治疗前后静息心率(RHR)、氨基末端脑钠肽前体(NT-p...     

Low YKL-40 in chronic heart failure may predict beneficial effects of statins: analysis from the controlled rosuvastatin multinational trial in heart failure (CORONA)

Context and objective: To evaluate if YKL-40 can provide prognostic information in patients with ischemic heart failure (HF) and identify patients who may benefit from statin therapy.

Materials and methods: The association between serum YKL-40 and predefined outcome was evaluated in 1344 HF patients assigned to rosuvastatin or placebo.

Results: YKL-40 was not associated with outcome in adjusted analysis. In YKL-40 tertile 1, an effect on the primary outcome (HR 0.50, p?=?0.006) and CV death (HR 0.54, p?=?0.040) was seen by rosuvastatin in adjusted analysis.

Conclusions: A beneficial modification of outcome was observed with statin therapy in patients with low YKL-40 levels.     

Heart failure with preserved ejection fraction in women: the Dutch Queen of Hearts program

Heart failure (HF) poses a heavy burden on patients, their families and society. The syndrome of HF comes in two types: with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The latter is on the increase and predominantly present in women, especially the older ones. There is an urgent need for mortality-reducing drugs in HFpEF, a disease affecting around 5 % of those aged 65 years and over. HFpEF develops in patients with risk factors and comorbidities such as obesity, hypertension, diabetes, COPD, but also preeclampsia. These conditions are likely to drive microvascular disease with involvement of the coronary microvasculature, which may eventually evolve into HFpEF. Currently, the diagnosis of HFPEF relies mainly on echocardiography. There are no biomarkers that can help diagnose female microvascular disease or facilitate the diagnosis of (early stages of) HFpEF. Recently a Dutch consortium was initiated, Queen of Hearts, with support from the Netherlands Heart Foundation, with the aim to discover and validate biomarkers for diastolic dysfunction and HFpEF in women. These biomarkers come from innovative blood-derived sources such as extracellular vesicles and circulating cells. Within the Queen of Hearts consortium, we will pursue female biomarkers that have the potential for further evolution in assays with point of care capabilities. As a spin-off, the consortium will gain knowledge on gender-specific pathology of HFpEF, possibly opening up novel treatment options.     

Plasma levels of alpha-1-antichymotrypsin are elevated in patients with chronic heart failure,but are of limited prognostic value

Background

There is increasing interest in utilising novel markers of cardiovascular disease risk in patients with chronic heart failure (HF). Recently, it was shown that alpha-1-antichymotrypsin (ACT), an acute-phase protein and major inhibitor of cathpesin G, plays a role in the pathophysiology of HF and may serve as a marker for myocardial distress.

Objective

To assess whether ACT is independently associated with long-term mortality in chronic HF patients.

Methods

ACT plasma levels were categorised into quartiles. Survival times were analysed using Kaplan-Meier curves and Cox proportional hazards regression, without and with correction for clinically relevant risk factors, including sex, age, duration of HF, kidney function (MDRD), ischaemic HF aetiology and NT-proBNP.

Results

Twenty healthy individuals and 224 patients (mean age 71 years, 72 % male, median HF duration 1.6 years) with chronic HF were included. In total, 159 (71 %) patients died. The median survival time was 5.3 (95 % CI 4.5–6.1) years. ACT was significantly elevated in patients (median 433 μg/ml, IQR 279–680) in comparison with controls (median 214 μg/ml, IQR 166–271; p < 0.001). Cox regression analysis demonstrated that ACT was not independently related to long-term mortality in chronic HF patients (crude HR = 1.03, 95 % CI 0.75–1.41, p = 0.871; adjusted HR = 1.12, 95 % CI 0.78–1.60, p = 0.552), which was confirmed by Kaplan-Meier curves.

Conclusion

ACT levels are elevated in chronic HF patients, but no independent association with long-term mortality can be established.     

Left ventricular assist device for end-stage heart failure: results of the first LVAD destination program in the Netherlands

PurposeMechanical circulatory support with a continuous-flow left ventricular assist device (LVAD) may be a valuable treatment in end-stage heart failure patients for an extended period of time. The purpose of this study was to evaluate the safety and efficacy of implantation of a continuous-flow LVAD in end-stage heart failure patients within the first destination program in the Netherlands.MethodsA third-generation LVAD was implanted in 16 heart failure patients (age 61 ± 8; 81 % male; left ventricular ejection fraction 20 ± 6 %) as destination therapy. All patients were ineligible for heart transplant. At baseline, 3 and 6 months, New York Heart Association (NYHA) functional class, quality-of-life and exercise capacity were assessed. Clinical adverse events were registered.ResultsSurvival at 30 days and 6 months was 88 and 75 %, respectively. In the postoperative phase, 6 (38 %) patients required continuous veno-venous haemofiltration for renal failure and 2 (13 %) patients required extracorporeal membrane oxygenation because of severe right ventricular failure. During follow-up, NYHA functional class and quality-of-life improved from 3.7 ± 0.1 to 2.3 ± 0.1 and 57 ± 5 to 23 ± 3 at 6 months (P < 0.001), respectively. The 6 min walking distance improved from 168 ± 42 m to 291 ± 29 m at 6 months (P = 0.001).ConclusionContinuous-flow LVAD therapy is a promising treatment for patients with end-stage heart failure ineligible for heart transplant.     

Circulating and cardiac levels of apelin,the novel ligand of the orphan receptor APJ,in patients with heart failure

The orphan receptor APJ and its recently identified endogenous ligand, apelin, are expressed in the heart. However, their importance in the human cardiovascular system is not known. This study shows that apelin-like immunoreactivity is abundantly present in healthy human heart and plasma. Gel filtration HPLC analysis revealed that atrial and plasma levels of high molecular weight apelin, possibly proapelin, were markedly higher than those of mature apelin-36 itself. As assessed by quantitative RT-PCR analysis, left ventricular apelin mRNA levels were increased 4.7-fold in chronic heart failure (CHF) due to coronary heart disease (p<0.01) and 3.3-fold due to idiopathic dilated cardiomyopathy (p<0.05), whereas atrial apelin mRNA levels were unchanged. Atrial and plasma apelin-like immunoreactivity as well as atrial and ventricular APJ receptor mRNA levels were significantly decreased in CHF. Our results suggest that a new cardiac regulatory peptide, apelin, and APJ receptor may contribute to the pathophysiology of human CHF.     

慢性充血性心力衰竭血浆血管活性水平及临床意义

目的：探讨慢性心力衰竭患者血浆B型利钠肽（BNP）、心钠素（ANF）、胱抑素C（CysC）的水平及临床意义。方法：选择70例CHF患者,按NYHA分级;20例健康者作为对照。采用放射免疫法检查BNP和ANF水平;采用免疫比浊法检查CysC。比较不同心衰等级以及不同BNP水平的上述指标的变化。结果：CHF患者血浆BNP、ANF、CysC水平与对照比较显著升高（P〈0．05）,并随NYHA等级增高而升高（P〈0．05）。与BNP〈400pg／ml组比较,400pg／ml≤BNP〈800pg／ml组和BNP≥800pg／ml组心力衰竭患者Cr、BUN水平显著增高（P〈0．05）;相反地,HDL水平显著降低。结论：血浆B型利钠肽（BNP）、心钠素（ANF）及胱抑素c参与．了CHF的发生发展过程．联合测定箕合号的变化．对CHF患者的诊断、评估及詹．险分层具有一定的临床意义．     

A pilot study on the effect of advance care planning implementation on healthcare utilisation and satisfaction in patients with advanced heart failure

BackgroundPatients with advanced heart failure may benefit from palliative care, including advance care planning (ACP). ACP, which can include referral back to the general practitioner (GP), may prevent unbeneficial hospital admissions and interventional/surgical procedures that are not in accordance with the patient’s personal goals of care.AimTo implement ACP in patients with advanced heart failure and explore the effect of ACP on healthcare utilisation as well as the satisfaction of patients and cardiologists.MethodsIn this pilot study, we enrolled 30 patients with New York Heart Association class III/IV heart failure who had had at least one unplanned hospital admission in the previous year because of heart failure. A structured ACP conversation was held and documented by the treating physician. Primary outcome was the number of visits to the emergency department and/or admissions within 3 months after the ACP conversation. Secondary endpoints were the satisfaction of patients and cardiologists as established by using a five-point Likert scale.ResultsMedian age of the patients was 81 years (range 33–94). Twenty-seven ACP documents could be analysed (90%). Twenty-one patients (78%) did not want to be readmitted to the hospital and subsequently none of them were readmitted during follow-up. Twenty-two patients (81%) discontinued all hospital care. All patients who died during follow-up (n = 12, 40%) died at home. Most patients and cardiologists indicated that they would recommend the intervention to others (80% and 92% respectively).ConclusionACP, and subsequent out-of-hospital care by the GP, was shown to be applicable in the present study of patients with advanced heart failure and evident palliative care needs. Patients and cardiologists were satisfied with this intervention.     

Symptoms associated with an abnormal echocardiogram in elderly primary care hypertension patients

Background

The prevalence and diagnostic value of heart failure symptoms in elderly primary care patients with hypertension is unknown.

Aim

To assess the prevalence, sensitivity, specificity, positive and negative predictive value of symptoms in association with an abnormal echocardiogram.

Design and setting

Cross-sectional screening study in five general practices in the south-east of the Netherlands.

Method

Between June 2010 and January 2013, 591 primary care hypertension patients aged between 60 and 85 years were included, without known heart failure and not treated by a cardiologist. All patients underwent an echocardiogram and a structured interview including assessment of heart failure symptoms: shortness of breath, fatigue, oedema, cold extremities, and restless sleep.

Results and conclusion

Restless sleep was reported by 25 %, cold extremities by 23 %, fatigue by 19 %, shortness of breath by 17 %, and oedema by 13 %. Oedema was the only symptom significantly associated with an abnormal echocardiogram (positive predictive value was 45 %, sensitivity 20 %, and specificity 90 %, OR 2.12; 95 % CI = 1.23–3.64), apart from higher age (OR 1.06; 95 % CI = 1.03–1.09), previous myocardial infarction (OR 3.00; 95 % CI = 1.28–7.03), and a systolic blood pressure of >160 mmHg (OR 1.62; 95 % CI = 1.08–2.41). Screening with echocardiography might be considered in patients with oedema.     

慢性充血性心力衰竭血浆血管活性水平及临床意义

目的:探讨慢性心力衰竭患者血浆B型利钠肽(BNP)、心钠素(ANF)、胱抑素C(CysC)的水平及临床意义。方法:选择70例CHF患者,按NA分级;20例健康者作为对照。采用放射免疫法检查BNP和ANF水平;采用免疫比浊法检查Cys C。比较不同心衰等级以及不同BNP水平的上述指标的变化。结果:CHF患者血浆BNP、ANF、CysC水平与对照比较显著升高(P<0.05),并随NYHA等级增高而升高(P<0.05)。与BNP<400pg/ml组比较,400pg/ml≤BNP<800pg/ml组和BNP≥800pg/ml组心力衰竭患者Cr、BUN水平显著增高(P<0.05);相反地,HDL水平显著降低。结论:血浆B型利钠肽(BNP)、心钠素(ANF)及胱抑素C参与了CHF的发生发展过程,联合测定其含量的变化,对CHF患者的诊断、评估及危险分层具有一定的临床意义。