Replacement of the massive amino acid losses induced by hemodialysis: A new treatment option proposal for a largely underestimated issue.

BACKGROUND: A series of interesting literature reports acknowledges the notable loss of essential and non-essential amino acids (EAAs and NEAAs) during hemodialysis sessions. These losses may exceed 800 g/year, thus contributing towards accelerating the onset of malnutrition in hemodialysis patients (HD). OBJECTIVE: A novel tailored amino acid formula for oral administration was developed to replace total amounts of each individual amino acid lost during dialysis diffusive/convective HD strategies, monitoring the effects produced on nutritional and hematological status. METHODS: A three-month randomized double-blind study was conducted on 30 subjects over the age of 70 years extrapolated from a total population of 86 hemodialysis patients. The 30 patients were randomly assigned to two groups: a treatment group of 15 HD patients (TG) to whom a novel mixture containing 5.4 g of AAs was administered solely on interdialytic days, and a control group of 15 HD patients (CG) who received no amino acid supplementation. The AAs mixture was administered post-dialysis at an extended interval from the end of solute and compartmental rebound to replace AA losses and optimize their role in protein anabolism. RESULTS: The results obtained highlighted a significant improvement in protein intake g/kg/day (Protein Catabolic Rate, p = 0.014), and increased IgG (p = 0.008) and C3 serum levels (p = 0.003) in the TG group alone. Fat mass losses were initially confirmed by means of bioelectrical impedance analysis (BIA) (p = 0.011) and plicometry (p < 0.001) in the CG group alone, although the main objective was to preserve nutritional status and, particularly, muscle mass. The study was extended to investigate the effects produced on anemia, yielding evidence of continued positive effects three months after the end of the study in the TG group alone based on an increase in Hb levels from 11.2 ± 0.6 to 12.1 ± 0.6 (p = 0.004) associated with a reduced demand for erythropoietin i.v. from 12928 ± 9033 to 9286 ± 5398 U.I/week (p = 0.012) and iron i.v. from 75.9 ± 55 to 71.4 ± 33.4 mg/week (p = 0.045). CONCLUSIONS: The results obtained following oral administration of this novel tailored AA replacement mixture aimed at reinstating the high AA losses produced during hemodialysis suggest the mixture should be prescribed as a standard procedure to all HD patients.

Effects of a Novel Amino Acid Formula on Nutritional and Metabolic Status, Anemia and Myocardial Function in Thrice-Weekly Hemodialysis Patients: Results of a Six-Month Randomized Double-Blind Placebo-Controlled Pilot Study.

(1) Background: Chronic Kidney Disease (CKD) induces metabolic derangement of amino acid (AA) kinetics, eliciting severe damage to the protein anabolism. This damage is further intensified by a significant loss of AAs through hemodialysis (HD), affecting all tissues with a high metabolic turnover, such as the myocardium and body muscle mass. (2) Aim: to illustrate the effects of a novel AA mixture in boosting mitochondrial energy production. (3) Methods: A strict selection of 164 dialysis patients was carried out, allowing us to finally identify 22 compliant patients who had not used any form of supplements over the previous year. The study design envisaged a 6-month randomized, double-blind trial for the comparison of two groups of hemodialysis patients: eleven patients (67.2 ± 9.5 years) received the novel AA mix (TRG), whilst the other eleven (68.2 ± 10.5 years) were given a placebo mix that was indistinguishable from the treatment mix (PLG). (4) Results: Despite the 6-month observation period, the following were observed: maintenance of target hemoglobin values with a reduced need for erythropoiesis-stimulating agents in TRG > 36% compared to PLG (p < 0.02), improved phase angle (PhA) accompanied by an increase in muscle mass solely in the TRG group (p < 0.05), improved Left Ventricular Ejection Fraction (LVEF > 67%) in the TRG versus PLG group (p < 0.05) with early but marked signs of improved diastolic function. Increased sensitivity to insulin with greater control of glycemic levels in TRG versus PLG (p = 0.016). (5) Conclusions: the new AA mix seemed to be effective, showing a positive result on nutritional metabolism and cardiac performance, stable hemoglobin levels with the need for lower doses of erythropoietin (EPO), insulin increased cell sensitivity, better muscle metabolism with less loss of mass.

Prognostic significance of ultrasound-assessed jugular vein distensibility in heart failure.

AIMS: Jugular venous distension is a classical sign of heart failure (HF) but it can be difficult to assess clinically. METHODS AND RESULTS: Outpatients with HF and control subjects were assessed. Internal jugular vein diameter (JVD) was measured using a linear high-frequency ultrasound probe (10 MHz) at rest, after a Valsalva manoeuvre and during deep inspiration. JVD ratio was calculated as the maximum diameter during Valsalva to that measured at rest. 311 patients (mean age 71 years, mean left ventricular EF 42%, median (IQR) amino-terminal pro-brain natriuretic peptide 979 (441-2007) ng/L) and 66 controls were included. JVD (median and IQR range) at rest was smaller in controls (0.16 (0.14-0.20) cm) than in patients with HF (0.23 (0.17-0.33) cm; p<0.001) but similar during Valsalva (1.03 (0.90-1.16) cm vs 1.08 (0.90-1.25) cm; p=0.28). Consequently, JVD ratio was greater in controls (6.3 (4.9-7.6)) than in patients (4.5 (2.9-6.1); p<0.001). During a median follow-up of 516 (IQR 335-622) days, 48 patients (15%) with HF died or were hospitalised for HF. In multivariable models, among clinical, echocardiographic or biochemical variables, only increasing NT-proBNP and ultrasound assessment of internal jugular vein were independently associated with prognosis. Comparing top and bottom tertiles of JVD ratio (2.3 (IQR 1.7-2.9) versus 6.8 (6.1-7.7)), the tertile with lower values had a 10-fold greater risk of an adverse event (HR 10.05, 95% CI 3.07 to 32.93). CONCLUSIONS: Ultrasound assessment of the internal jugular vein identifies outpatients with HF who have a higher risk of an adverse outcome. CLINICAL TRIAL REGISTRATION: NCT01872299.

If home telemonitoring reduces mortality in heart failure, is this just due to better guideline-based treatment?

UNLABELLED: To investigate, in a 'real-world' setting, the impact of home telemonitoring (HTM) compared to usual care on achieved dose of guideline-recommended medication, hospitalisation rate and mortality in patients with heart failure (HF). METHODS: We retrospectively analyzed data on 333 patients with HF referred to a HTM service supported by a nurse-specialist (mean age 71±12 years, mean left ventricular ejection fraction (LVEF) 36 ± 11% and median N-Terminal pro B-type Natriuretic Peptide (NT-proBNP) 2,972 ng/L (interquartile range (IQR): 1,447-7,801 ng/L)). Most patients (n = 278) accepted HTM (HTM-group) but 55 refused and received usual care (UC-group). In the HTM-group, weight, heart rate, blood pressure and symptom severity were measured daily. RESULTS: At referral, respectively 90%, 90%, 67% and 94% of patients with LVEF ≤40% (n = 229) were treated with ß-blockers (BB), angiotensin converting enzyme-inhibitors (ACE-I) or angiotensin receptor blockers (ARB), mineralocorticoid receptor antagonists (MRA) and diuretics, with rates similar between groups. After 6 months, prescription of BB (92% vs 83%), ACE-I/ARB (92% vs 90%) and MRA (68% vs 67%) did not differ significantly between groups. The proportions of patients who achieved ≥50% and ≥100% of target doses of BB, ACE-I/ARB and MRA were also similar in each group. However, during a median follow-up of 1094 days (IQR 767-1419) fewer patients who chose HTM died (33% vs 49%; P = 0.002). CONCLUSION: Patients who choose HTM have a better prognosis than those who do not but this does not appear to be mediated through greater prescription of key HF medications.

Prescribing patterns to optimize heart rate: analysis of 1,000 consecutive outpatient appointments to a single heart failure clinic over a 6-month period.

OBJECTIVES: This study sought to characterize patients attending a community heart failure (HF) clinic and identified those who were eligible for optimization of beta-blockers (BB) or ivabradine. BACKGROUND: Among patients with HF due to left ventricular systolic dysfunction in sinus rhythm, those with higher resting heart rate have a worse prognosis. Reducing sinus rate to 50 to 60 beats/min might improve outcomes. METHODS: A total of 1,000 consecutively scheduled HF clinic follow-up appointments over a 6-month period were reviewed. Demographic, clinical, and echocardiographic data were collected for patients who attended (824 unique patients; 555 men). Mean age was 74 ± 11 years, median N-terminal pro-B-type natriuretic peptide levels were 1,002 ng/l (interquartile range: 367 to 2,151 ng/l), and the mean left ventricular ejection fraction (LVEF) was 44 ± 11%. A total of 202 (25%), 252 (31%), and 370 (45%) patients had LVEFs of ≤35%, 36% to 49%, and ≥50%, respectively. Of patients with LVEF ≤35%, 142 (70%) were in sinus rhythm. RESULTS: At 70 clinic visits, 58 patients with LVEFs of ≤35% were in sinus rhythm and had heart rates ≥70 beats/min. Of these, 13 patients had their BB dose increased, 20 were potentially eligible for, but did not have, BB uptitration, 15 were already taking target doses of BBs, and 10 patients were reported to be intolerant of higher doses. Thus, 25 patients were potentially eligible for ivabradine according to European Society of Cardiology guidelines; this number dropped to 14 when the United Kingdom National Institute for Health and Care Excellence guidelines were applied. CONCLUSIONS: Among patients with LVEFs of ≤35%, most are treated with BBs and have a heart rate at rest of <70 beats/min; 12% of these patients might be eligible for ivabradine.