Effects of endogenous serum neuregulin-1β on morbidity and mortality in patients with heart failure and left ventricular systolic dysfunction

Abstract

Context: Improved left ventricular ejection fraction (LVEF) following administration of recombinant human Neuregulin-1β (NRG), epidermal growth factor (EGF) involved in cardiomyocyte repair/survival, has been observed in patients with systolic heart failure (HF).

Methods: Serum NRG was measured by ELISA in 248 patients with NYHA class I–IV HF.

Results: NRG exhibited a marginally significant effect on LVEF trajectory over 11?months (p?=?0.07). There is no apparent level of NRG that predicts improved survival.

Conclusions: There is a potential relationship between serum NRG and improved LVEF, indicating the need to investigate the utility of NRG in predicting HF outcomes, including LVEF maintenance.     

Effect of Acute Hyperglycemia on Left Ventricular Contractile Function in Diabetic Patients with and without Heart Failure: Two Randomized Cross-Over Studies

Background

It is unknown whether changes in circulating glucose levels due to short-term insulin discontinuation affect left ventricular contractile function in type 2 diabetic patients with (T2D-HF) and without (T2D-nonHF) heart failure.

Materials and Methods

In two randomized cross-over-designed trials, 18 insulin-treated type 2 diabetic patients with (Ejection Fraction (EF) 36±6%, n = 10) (trial 2) and without systolic heart failure (EF 60±3%, n = 8) (trial 1) were subjected to hyper- and normoglycemia for 9–12 hours on two different occasions. Advanced echocardiography, bicycle exercise tests and 6-minute hall walk distance were applied.

Results

Plasma glucose levels differed between study arms (6.5±0.8 mM vs 14.1±2.6 mM (T2D-HF), 5.8±0.4 mM vs 9.9±2.1 mM (T2D-nonHF), p<0.001). Hyperglycemia was associated with an increase in several parameters: maximal global systolic tissue velocity (Vmax) (p<0.001), maximal mitral annulus velocity (S''max) (p<0.001), strain rate (p = 0.02) and strain (p = 0.05). Indices of increased myocardial systolic contractile function were significant in both T2D-HF (Vmax: 14%, p = 0.02; S''max: 10%, p = 0.04), T2D-nonHF (Vmax: 12%, p<0.01; S''max: 9%, p<0.001) and in post exercise S''max (7%, p = 0.049) during hyperglycemia as opposed to normoglycemia. LVEF did not differ between normo- and hyperglycemia (p = 0.17), and neither did peak exercise capacity nor catecholamine levels. Type 2 diabetic heart failure patients'' 6-minute hall walk distance improved by 7% (p = 0.02) during hyperglycemia as compared with normoglycemia.

Conclusions

Short-term hyperglycemia by insulin discontinuation is associated with an increase in myocardial systolic contractile function in type 2 diabetic patients with and without heart failure and with a slightly prolonged walking distance in type 2 diabetic heart failure patients. (Clinicaltrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00653510","term_id":"NCT00653510"}}NCT00653510)     

Plasma levels of adrenomedullin and atrial natriuretic peptide in patients with congestive heart failure of various etiologies

OBJECTIVE: The aim of this study was to evaluate the plasma levels of the adrenomedullin (ADM) and atrial natriuretic peptide (ANP) in adult and pediatric patients with congestive heart failure (CHF) of various etiologies and to investigate their relations with haemodynamic variables e.g. echocardiographic left ventricular ejection fraction (LVEF) and fractional shortening (FS). SUBJECTS AND METHODS: The study was made in 38 adult and 21 pediatric patients with CHF of various etiologies and compared with 15 adult and 10 pediatric normal healthy controls. Patients with CHF were classified according to the New York Heart Association (NYHA) functional classification into grades II to IV in adult patients and into grade IV in all pediatric patients. ADM and ANP plasma levels were determined prior to the treatment with enzyme immunoassay. RESULTS: A statistically significant difference in the plasma levels of ADM and ANP were found between pediatrics and adult patients and corresponding healthy controls. Their levels were progressively increased with severity of NYHA class in adult patients. We found a significant positive correlation between plasma levels of each of ADM and ANP and pulse rate, systolic and diastolic blood pressure; and a significant negative correlation between their plasma levels and echocardiographic LVEF and FS. A significant positive correlation between plasma levels of ADM and ANP in both pediatrics and adult patients were also found. CONCLUSION: Plasma levels of ADM and ANP increased in adult and pediatric patients with CHF irrespective of the cause. They were positively correlated with each other and negatively correlated with LVEF and FS. These findings might have important clinical implications in that a noninvasive blood test may be used to identify high-risk subjects for HF for more invasive procedures.     

Clinical impact of atrial fibrillation in patients with pulmonary hypertension

Background

Pulmonary hypertension (PH) is associated with progressive impairment of right ventricular function, reduced exercise capacity and a poor prognosis. Little is known about the prevalence, clinical manifestation and impact of atrial fibrillation (AF) on cardiac function in PH.

Methods

In a four year single-centre retrospective analysis 225 patients with confirmed PH of various origins were enrolled to investigate the prevalence of AF, and to assess the clinical manifestation, 6-minute walk distance, NT-proBNP levels, echocardiographic parameters and hemodynamics obtained by right heart catheterization in PH with AF.

Results

AF was prevalent in 31.1%. In patients with PH and AF, parameters of clinical deterioration (NYHA/WHO functional class, 6-minute walk distance, NT-proBNP levels) and renal function were significantly compromised compared to patients with PH and sinus rhythm (SR). In the total PH cohort and in PH not related to left heart disease occurrence of AF was associated with an increase of right atrial pressure (RAP) and right atrial dilatation. While no direct association was found between pulmonary artery pressure (PAP) and AF in these patients, right ventricular function was reduced in AF, indicating more advanced disease. In PH due to left heart failure the prevalence of AF was particularly high (57.7% vs. 23.1% in other forms of PH). In this subgroup, left atrial dilatation, increase of pulmonary capillary wedge pressure, PAP and RAP were more pronounced in AF than in SR, suggesting that more marked backward failure led to AF in this setting.

Conclusion

PH is associated with increased prevalence of AF. Occurrence of AF in PH indicates clinical deterioration and more advanced disease.     

Comparison of Baseline versus Posttreatment Left Ventricular Ejection Fraction in Patients with Acute Decompensated Heart Failure for Predicting Cardiovascular Outcome: Implications from Single-Center Systolic Heart Failure Cohort

Aims

The prognostic values of left ventricular ejection fraction (LVEF) during heart failure (HF) with acute decompensation or after optimal treatment have not been extensively studied. We hypothesized that posttreatment LVEF has superior predictive value for long-term prognosis than LVEF at admission does.

Methods and Results

In Protocol 1, 428 acute decompensated HF (ADHF) patients with LVEF ≤35% in a tertiary medical center were enrolled and followed for a mean period of 34.7 ± 10.8 months. The primary and secondary end points were all-cause mortality and HF readmission, respectively. In total, 86 deaths and 240 HF readmissions were recorded. The predictive values of baseline LVEF at admission and LVEF 6 months posttreatment were analyzed and compared. The posttreatment LVEFs were predictive for future events (P = 0.01 for all-cause mortality, P < 0.001 for HF readmission), but the baseline LVEFs were not. In Protocol 2, the outcomes of patients with improved LVEF (change of LVEF: ≥+10%), unchanged LVEF (change of LVEF: –10% to +10%), and reduced LVEF (change of LVEF: ≤–10%) were analyzed and compared. Improved LVEF occurred in 171 patients and was associated with a superior long-term prognosis among all groups (P = 0.02 for all-cause mortality, P < 0.001 for HF readmission). In Protocol 3, independent predictors of improved LVEF were analyzed, and baseline LV end-diastolic dimension (LVEDD) was identified as a powerful predictor in ADHF patients (P < 0.001).

Conclusions

In patients with ADHF, posttreatment LVEF but not baseline LVEF had prognostic power. Improved LVEF was associated with superior long-term prognosis, and baseline LVEDD identified patients who were more likely to have improved LVEF. Therefore, baseline LVEF should not be considered a relevant prognosis factor in clinical practice for patients with ADHF.     

Decreased Variability of the 6-Minute Walk Test by Heart Rate Correction in Patients with Neuromuscular Disease

Objective

The 6-minute walk test is widely used to assess functional status in neurological disorders. However, the test is subject to great inter-test variability due to fluctuating motivation, fatigue and learning effects. We investigated whether inter-test variability of the 6MWT can be reduced by heart rate correction.

Methods

Sixteen patients with neuromuscular diseases, including Facioscapulohumeral muscular dystrophy, Limb-girdle muscular dystrophy, Charcot-Marie-Tooths, Dystrophia Myotonica and Congenital Myopathy and 12 healthy subjects were studied. Patients were excluded if they had cardiac arrhythmias, if they received drug treatment for hypertension or any other medical conditions that could interfere with the interpretation of the heart rate and walking capability. All completed three 6-minute walk tests on three different test-days. Heart rate was measured continuously.

Results

Successive standard 6-minute walk tests showed considerable learning effects between Tests 1 and 2 (4.9%; P = 0.026), and Tests 2 and 3 (4.5%; P = 0.020) in patients. The same was seen in controls between Tests 1 and 2 (8.1%; P = 0.039)). Heart rate correction abolished this learning effect.

Conclusion

A modified 6-minute walk test, by correcting walking distance with average heart rate during walking, decreases the variability among repeated 6-minute walk tests, and should be considered as an alternative outcome measure to the standard 6-minute walk test in future clinical follow-up and treatment trials.     

Right Ventricular Systolic Dysfunction Is Common in Hypertensive Heart Failure: A Prospective Study in Sub-Saharan Africa

IntroductionRight ventricular (RV) systolic dysfunction is now recognized widely as a strong and independent predictor of adverse outcomes in patients with heart failure (HF). Reduction of RV systolic function more closely predicts impaired exercise tolerance and poor survival than does left ventricular (LV) systolic function. In spite of this, there is a dearth of data on RV function in hypertensive HF which is the commonest form of HF in sub-Saharan Africa. We therefore conducted a prospective cohort study of hypertensive HF patients presenting to the University of Abuja Teaching Hospital, Abuja, Nigeria over an 8 year period.MethodsEach subject had transthoracic echocardiography performed on them according to the guidelines of American Society of Echocardiography. RV systolic function was defined as a tricuspid annular plane systolic excursion (TAPSE) <15mm using M-mode echocardiography.ResultsRV systolic dysfunction was identified in 272 (44.5%) of the 611 subjects that were studied. Subjects with TAPSE less than 15mm had worse prognosis compared to those with TAPSE ≥15mm.There was a significant correlation between TAPSE and other adverse prognostic markers including left and right atrial area, LV size, LV mass, LV ejection fraction, restrictive mitral inflow and RV systolic pressure (RVSP). However, LV ejection fraction and right atrial area were the only independent determinants of RV systolic dysfunction.ConclusionsHypertensive HF is a major cause of RV systolic dysfunction even in a population with a low prevalence of coronary artery disease, and RV systolic dysfunction is associated with poor prognosis in hypertensive HF. Detailed assessment of RV function should therefore be part of the echocardiography evaluation of patients with hypertensive HF.     

Parathyroid hormone response to vitamin D insufficiency in elderly males with chronic heart failure

Secondary hyperparathyroidism (SHPT) may contribute to the systemic illness that accompanies chronic heart failure (CHF). Healthy elderly with vitamin D deficiency who did not develop hyperparathyroidism (functional hypoparathyroidism, FHPT) had lower mortality than those who did. This study was designed to examine determinants of the PTH response in the vitamin D insufficient CHF patients. Sixty five vitamin D insufficient males with NYHA class II and III and 20 control subjects age >/=55 years were recruited. Echocardiography, physical performance, NT-pro-BNP, PTH, 25-hydroxyvitamin D (25(OH)D), adiponectin and bone activity surrogate markers (OPG, RANKL, OC, beta-CTx) were assessed. Increased NYHA class was associated with SHPT, while physical performance was inferior compared to FHPT. SHPT was associated with lower left ventricular ejection fraction (LVEF) and flow mediated dilatation, but with higher left heart dimensions, left ventricular mass index and right ventricular systolic pressure. CHF patients with SHPT had increased NT-pro-BNP, adiponectin and bone markers, but decreased 25(OH)D compared to those with FHPT. Independent determinants for SHPT in CHF patients with vitamin D insufficiency were LVEF, adiponectin and beta-CTx, irrespective of renal function and serum vitamin D levels. In conclusion, increased PTH levels, but not low vitamin D, demonstrated close relation to CHF severity.     

左旋卡尼汀联合环磷腺苷葡胺治疗慢性充血性心力衰竭

目的:探究左旋卡尼汀联合环磷腺苷葡胺治疗慢性充血性心力衰竭(chronic congestive heart failure,CHF)的临床疗效。方法:选取我院心内科CHF患者58例,随机分为对照组28例与实验组30例,其中对照组28例,予地高辛、氢氯噻嗪、环磷腺苷葡胺常规治疗;实验组30例,在常规治疗的基础上加用左旋卡尼汀治疗。观察两组患者治疗前后心功能分级(NYHA)、6 min步行距离、左心室射血分数(LVEF)及左心室舒张末容积(LVEDD)等。结果:与对照组比较,实验组患者治疗后心率和NYHA心功能分级明显改善,6 min步行实验明显提高,患者LVEDD、LVEF明显改善,差异具有统计学意义(P<0.05);两组患者接受相应治疗后均未出现任何不良反应(P>0.05)。结论:左旋卡尼汀联合环磷腺苷葡胺能够明显改善慢性充血性心力衰竭,对临床具有指导意义,值得临床推广。     

Right ventricular function in dilated cardiomyopathy and ischemic heart disease: assessment with non-invasive imaging

Background

Dilated cardiomyopathy and ischaemic heart disease can both lead to right ventricular (RV) dysfunction. Direct comparisons of the two entities regarding RV size and function using state-of-the-art imaging techniques have not yet been performed. We aimed to determine RV function and volume in dilated cardiomyopathy and ischaemic heart disease in relation to left ventricular (LV) systolic and diastolic function and systolic pulmonary artery pressure.

Methods and results

A well-characterised group (cardiac magnetic resonance imaging, echocardiography, coronary angiography and endomyocardial biopsy) of 46 patients with dilated cardiomyopathy was compared with LV ejection fraction (EF)-matched patients (n = 23) with ischaemic heart disease. Volumes and EF were determined with magnetic resonance imaging, diastolic LV function and pulmonary artery pressure with echocardiography.After multivariable linear regression, four factors independently influenced RVEF (R² = 0.51, p < 0.001): LVEF (r = 0.54, p < 0.001), ratio of peak early and peak atrial transmitral Doppler flow velocity as measure of LV filling pressure (r = − 0.52, p < 0.001) and tricuspid regurgitation flow velocity as measure of pulmonary artery pressure (r = − 0.38, p = 0.001). RVEF was significantly worse in patients with dilated cardiomyopathy compared with ischaemic heart disease: median 48 % (interquartile range (IQR) 37–55 %) versus 56 % (IQR 48–63 %), p < 0.05.

Conclusions

In patients with dilated cardiomyopathy and ischaemic heart disease, RV function is determined by LV systolic and diastolic function, the underlying cause of LV dysfunction, and pulmonary artery pressure. It was demonstrated that RV function is more impaired in dilated cardiomyopathy.     

Diagnostic utility of MR-proANP and NT-proBNP in elderly outpatients with a high risk of heart failure: the Copenhagen heart failure risk study

Abstract

Background: Amino-terminal-pro-B-type-natriuretic-peptide (NT-proBNP) is a diagnostic biomarker for heart failure (HF), but plasma concentrations are influenced by numerous factors. Mid-regional-pro-atrial-natriuretic-peptide (MR-proANP) have comparable diagnostic value in acute HF. However, data are lacking in the non-acute setting. This study sought to assess the diagnostic utility of MR-proANP in outpatients with a high risk of HF.

Methods: This prospective study included 399 outpatients. Inclusion criteria were: age?≥?60?years, ≥1 risk factor for HF (diabetes, chronic kidney disease, vascular disease, atrial fibrillation, hypertension), without known or suspected HF. Unrecognized HF was diagnosed based on clinical signs, patient-reported symptoms and echocardiography. Plasma concentrations of MR-proANP and NT-proBNP were analysed.

Results: In total, 65 patients were diagnosed with HF or asymptomatic left ventricular systolic dysfunction (N?=?12 LVEF?≤?40%, N?=?7 LVEF?>?40% to ≤50%, N?=?46 LVEF?>?50%). Both MR-proANP (odds-ratio: 1.77; 95% CI:1.16–2.72; p?=?0.009) and NT-proBNP (odds-ratio: 1.49; 95% CI:1.22–1.82; p?<?0.001) were associated with HF. Area under receiver-operator characteristics curve (AUC) for the diagnosis of HF or asymptomatic left ventricular systolic dysfunction was higher for MR-proANP (AUC?=?0.886; p?<?0.001) and NT-proBNP (AUC?=?0.910; p?<?0.001) compared to patient-reported symptoms of HF (AUC?=?0.830), but NT-proBNP added more diagnostic information compared to MR-proANP (p?=?0.022).

Conclusions: Both NT-proBNP and MR-proANP are useful biomarkers in the diagnosis of HF or asymptomatic left ventricular systolic dysfunction in a non-acute setting. However, NT-proBNP added more diagnostic information compared to MR-proANP.     

Differences in oxidative stress markers based on the aetiology of heart failure: Comparison of oxidative stress in patients with and without coronary artery disease

Abstract

Various oxidative stress markers have been measured to evaluate the status of heart failure (HF). However, the relationships between these markers and the aetiology of HF have not been fully investigated. This study compared 8-hydroxy-2′-deoxyguanosine (8-OHdG) and biopyrrins levels in patients with ischemic and non-ischemic HF. Study subjects were divided into a coronary artery disease (CAD) group (n=70), a non-CAD group (n=61) and a control group (n=33). In the CAD group, 8-OHdG and biopyrrins levels increased with the severity of the New York Heart Association (NYHA) functional class and log BNP levels correlated with 8-OHdG and biopyrrins levels. However, non-CAD patients with NYHA class III/IV had significantly lower 8-OHdG levels than CAD patients with NYHA class III/IV and the levels did not correlate with log BNP levels. In the CAD group, 8-OHdG levels reflected the severity of atherosclerosis. These results indicate that the properties of oxidative stress markers should be carefully taken into consideration for the assessment of HF status.     

Relationship between physiological tremor and cognitive function in physically active older women

[Purpose]This study aimed to compare the physiological tremor, grip strength, and cognitive function of sedentary and physically active older adults.[Methods]Twenty-four older adults aged ≥65 years participated in this study and were divided into the sedentary (76.5±4.4 years, n=12) and physically active (73.5±3.3 years, n=12) groups. Each group completed the Mini-Mental State Examination (MMSE) for cognitive function assessment. Physiological tremor was measured using an accelerometer for both hands at rest and the left/right hand with a 1,000 g dumbbell on the palm in neutral positions and the elbow flexed at 90°. Physical fitness was measured by grip strength and completion of the Short Physical Performance Battery (SPPB) and the 6-min walk test.[Results]The physically active group showed a significantly lower level of physiological tremor in both hands at rest and the left/right hand with a 1,000 g dumbbell on the palm (P<0.05) than that in the sedentary group. For cognitive function, the physically active group showed significantly higher scores than those in the sedentary group (P<0.001). No significant correlation was found between cognitive function and left/right grip strength (left: r = 0.117, P = 0.585; right: r = 0.230, P = 0.279), physiological tremor in both hands at rest (left: r = -0.524, P < 0.001; right: r = -0.508, P < 0.05), and the left/right hand with a 1,000 g dumbbell on the palm (left: r = -0.505, P < 0.05; right: r = -0.458, P < 0.05).[Conclusion]Physiological tremor of the hands has the potential to be a useful predictor of cognitive function in older adults.     

Association between Dietary Fiber Intake and Physical Performance in Older Adults: A Nationwide Study in Taiwan

Background

Physical performance is a major determinant of health in older adults, and is related to lifestyle factors. Dietary fiber has multiple health benefits. It remains unclear whether fiber intake is independently linked to superior physical performance. We aimed to assess the association between dietary fiber and physical performance in older adults.

Methods

This was a cross-sectional study conducted with community-dwelling adults aged 55 years and older (n=2680) from the ongoing Healthy Aging Longitudinal Study (HALST) in Taiwan 2008-2010. Daily dietary fiber intake was assessed using a validated food frequency questionnaire. Physical performance was determined objectively by measuring gait speed, 6-minute walk distance, timed “up and go” (TUG), summary performance score, hand grip strength.

Results

Adjusting for all potential confounders, participants with higher fiber intake had significantly faster gait speed, longer 6-minute walk distance, faster TUG, higher summary performance score, and higher hand grip strength (all P <.05). Comparing with the highest quartile of fiber intake, the lowest quartile of fiber intake was significantly associated with the lowest sex-specific quartile of gait speed (adjusted OR, 2.18 in men [95% CI, 1.33-3.55] and 3.65 in women [95% CI, 2.20-6.05]), 6-minute walk distance (OR, 2.40 in men [95% CI, 1.38-4.17] and 4.32 in women [95% CI, 2.37-7.89]), TUG (OR, 2.42 in men [95% CI, 1.43-4.12] and 3.27 in women [95% CI, 1.94-5.52]), summary performance score (OR, 2.12 in men [95% CI, 1.19-3.78] and 5.47 in women [95% CI, 3.20-9.35]), and hand grip strength (OR, 2.64 in men [95% CI, 1.61-4.32] and 4.43 in women [95% CI, 2.62-7.50]).

Conclusions

Dietary fiber intake was independently associated with better physical performance.     

老年心力衰竭患者营养不良的影响因素分析及早期肠内营养对营养不良患者心功能、营养状况和肠道黏膜屏障功能的影响

摘要 目的：探讨老年心力衰竭（HF）患者营养不良的影响因素及早期肠内营养对营养不良患者心功能、营养状况和肠道黏膜屏障功能的影响。方法：选取2021年2月~2022年4月期间在我院接受治疗的180例老年HF患者作为研究对象。入院后采用微型营养评价简表（MNA-SF）评估患者的营养状况。根据MNA-SF评分结果分为营养不良组（n=83）和营养正常组（n=97）。应用单因素及多因素Logistic回归分析老年HF患者营养不良的危险因素。对老年HF营养不良患者给予早期肠内营养干预,观察其治疗前、治疗一周后心功能、营养状况和肠道黏膜屏障功能的变化情况。结果：老年HF患者营养不良与性别、居住地、饮酒史、病因、职业类别、谷丙转氨酶、血肌酐、收缩压（SBP）、舒张压（DBP）无关（P>0.05）,而与年龄、医保类型、病程、婚姻状况、美国纽约心脏病学会（NYHA）分级、文化程度、C反应蛋白（CRP）、家庭人均月收入、B型脑钠肽（BNP）、吸烟史、左心室射血分数（LVEF）有关（P<0.05）。Logistic回归分析结果显示：病程偏长、CRP偏高、BNP偏高、NYHA分级为IV级、年龄偏大、吸烟史是老年HF患者发生营养不良的危险因素（P<0.05）。治疗1周后,营养不良组老年HF患者的LVEF升高,BNP下降（P<0.05）。治疗1周后,营养不良组老年HF患者的前白蛋白（PA）、转铁蛋白（TRF）升高（P<0.05）。治疗1周后,营养不良组老年HF患者的D-乳酸（D-Lac）、二胺氧化酶（DAO）、肠脂肪酸结合蛋白（IFABP）下降（P<0.05）。结论：老年HF患者营养不良受到病程、CRP、BNP、NYHA分级、年龄、吸烟史等多种因素的影响,针对老年HF患者营养不良给予早期肠内营养,有助于改善患者心功能、营养状况和肠道黏膜屏障功能。     

Calcium-regulating peptide hormones and blood electrolytic balance in chronic heart failure

Calcium-regulating system is important for the functional activity of myocardium. However, little is known about the role of this system in the pathogenesis of cardiovascular diseases. Blood samples from the patients with chronic heart failure (CHF) caused by ischaemic disease (coronary artery disease) (NYHA class I-IV) were used to analyze the levels of calcium, inorganic phosphate, sodium, potassium, parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP). The heart beat rate and arterial blood pressure were chosen as additional tests for the functional status of cardiovascular system. The alteration of electrolytes homeostasis was found dependent on the severity of the pathology being maximally expressed in the NYHA class IV patients. Similar tendency was demonstrated for circulating PTH and PTHrP with the highest blood concentrations observed in patients of the NYHA class III and IV. The extent of these changes was found more pronounced in the female patients. It is suggested that the calcium-regulating hormonal system is involved in the pathogenesis of the ischaemic heart disease; however the sharp increase of PTH and PTHrP at the severe stages of pathology may play a compensatory role in maintaining the heart function.     

Development of a Novel Heart Failure Risk Tool: The Barcelona Bio-Heart Failure Risk Calculator (BCN Bio-HF Calculator)

Background

A combination of clinical and routine laboratory data with biomarkers reflecting different pathophysiological pathways may help to refine risk stratification in heart failure (HF). A novel calculator (BCN Bio-HF calculator) incorporating N-terminal pro B-type natriuretic peptide (NT-proBNP, a marker of myocardial stretch), high-sensitivity cardiac troponin T (hs-cTnT, a marker of myocyte injury), and high-sensitivity soluble ST2 (ST2), (reflective of myocardial fibrosis and remodeling) was developed.

Methods

Model performance was evaluated using discrimination, calibration, and reclassification tools for 1-, 2-, and 3-year mortality. Ten-fold cross-validation with 1000 bootstrapping was used.

Results

The BCN Bio-HF calculator was derived from 864 consecutive outpatients (72% men) with mean age 68.2±12 years (73%/27% New York Heart Association (NYHA) class I-II/III-IV, LVEF 36%, ischemic etiology 52.2%) and followed for a median of 3.4 years (305 deaths). After an initial evaluation of 23 variables, eight independent models were developed. The variables included in these models were age, sex, NYHA functional class, left ventricular ejection fraction, serum sodium, estimated glomerular filtration rate, hemoglobin, loop diuretic dose, β-blocker, Angiotensin converting enzyme inhibitor/Angiotensin-2 receptor blocker and statin treatments, and hs-cTnT, ST2, and NT-proBNP levels. The calculator may run with the availability of none, one, two, or the three biomarkers. The calculated risk of death was significantly changed by additive biomarker data. The average C-statistic in cross-validation analysis was 0.79.

Conclusions

A new HF risk-calculator that incorporates available biomarkers reflecting different pathophysiological pathways better allowed individual prediction of death at 1, 2, and 3 years.     

The Use of Bayesian Latent Class Cluster Models to Classify Patterns of Cognitive Performance in Healthy Ageing

The main focus of this study is to illustrate the applicability of latent class analysis in the assessment of cognitive performance profiles during ageing. Principal component analysis (PCA) was used to detect main cognitive dimensions (based on the neurocognitive test variables) and Bayesian latent class analysis (LCA) models (without constraints) were used to explore patterns of cognitive performance among community-dwelling older individuals. Gender, age and number of school years were explored as variables. Three cognitive dimensions were identified: general cognition (MMSE), memory (MEM) and executive (EXEC) function. Based on these, three latent classes of cognitive performance profiles (LC1 to LC3) were identified among the older adults. These classes corresponded to stronger to weaker performance patterns (LC1>LC2>LC3) across all dimensions; each latent class denoted the same hierarchy in the proportion of males, age and number of school years. Bayesian LCA provided a powerful tool to explore cognitive typologies among healthy cognitive agers.     

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.     

Factors associated with the 6-minute walk distance in patients with systemic sclerosis

Background

There is an ongoing debate regarding the relevance of the 6-minute walking distance (6MWD) in systemic sclerosis (SSc) assessment, widely used as a usual test in these patients as well as an outcome measure in clinical trials. In this work, we aimed to assess the associations between the 6MWD and various disease parameters in patients with SSc.

Methods

Consecutive patients followed in our SSc National Reference Centre were included in this cross-sectional study if they fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria for SSc. Data were systematically collected during a comprehensive standardized evaluation that included a 6-minute walk test, clinical assessment, biological results, pulmonary function tests, transthoracic echocardiography, composite scores (European Scleroderma Study Group Activity Index, Medsger severity score, Health Assessment Questionnaire–Disability Index (HAQ-DI)) and treatments.Associations of the 6MWD with various disease parameters were assessed by linear regression in univariate and multivariate analyses.

Results

The study population comprised 298 patients (females 81%; mean age 58.2?±?13.3 years; limited cutaneous SSc 82%; interstitial lung disease (ILD) 42%; pulmonary arterial hypertension (PAH) 6%). The 6MWD was significantly and independently associated with gender, age, body mass index, baseline heart rate (HR), HR variation during the test, PAH, history of arterial thrombosis and C-reactive protein levels, as well as with the HAQ-DI score in a sensitivity analysis. Muscle involvement, joint involvement and ILD were not independently associated with the 6MWD.

Conclusions

During SSc, the 6MWD is independently associated with initial HR and HR variation; with PAH but not ILD, suggesting that pulmonary vasculopathy may have a greater impact than parenchymal involvement on functional limitation; and with global markers of disease activity and patient disability. These results give clinicians further insight into how to interpret the 6MWD in the context of SSc.