Chronic Heart Failure Subjects Research Articles

Comparable Ventilatory Inefficiency at Maximal and Submaximal Performance in COPD vs. CHF subjects: An Innovative Approach.

Currently, excess ventilation has been grounded under the relationship between minute-ventilation/carbon dioxide output ( V ˙ E - V ˙ CO 2 ). Alternatively, a new approach for ventilatory efficiency ( η E V ˙ ) has been published. Our main hypothesis is that comparatively low levels of η E V ˙ between chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are attainable for a similar level of maximum and submaximal aerobic performance, conversely to long-established methods ( V ˙ E - V ˙ CO 2 slope and intercept). Both groups performed lung function tests, echocardiography, and cardiopulmonary exercise testing. The significance level adopted in the statistical analysis was 5%. Thus, nineteen COPD and nineteen CHF-eligible subjects completed the study. With the aim of contrasting full values of V ˙ E - V ˙ CO 2 and η V ˙ E for the exercise period (100%), correlations were made with smaller fractions, such as 90% and 75% of the maximum values. The two groups attained matched characteristics for age (62±6 vs. 59±9 yrs, p>.05), sex (10/9 vs. 14/5, p>0.05), BMI (26±4 vs. 27±3 Kg m2, p>0.05), and peak V ˙ O 2 (72±19 vs. 74±20 %pred, p>0.05), respectively. The V ˙ E - V ˙ CO 2 slope and intercept were significantly different for COPD and CHF (27.2±1.4 vs. 33.1±5.7 and 5.3±1.9 vs. 1.7±3.6, p<0.05 for both), but η V ˙ E average values were similar between-groups (10.2±3.4 vs. 10.9±2.3%, p=0.462). The correlations between 100% of the exercise period with 90% and 75% of it were stronger for η V ˙ E (r>0.850 for both). The η V ˙ E is a valuable method for comparison between cardiopulmonary diseases, with so far distinct physiopathological mechanisms, including ventilatory constraints in COPD.

Fatty Acid Binding Proteins 3 and 4 Predict Both All-Cause and Cardiovascular Mortality in Subjects with Chronic Heart Failure and Type 2 Diabetes Mellitus

Subjects with type 2 diabetes mellitus (T2D) are at increased risk for heart failure (HF). The cardiac-specific (FABP3) and adipose-tissue-specific (FABP4) types of the fatty acid binding proteins have been associated with both all-cause and cardiovascular (CV) mortality. The aim of this study was to explore the prognosis value of FABP3 and FABP4 in ambulatory subjects with chronic HF (CHF), with and without T2D. A prospective study involving 240 ambulatory CHF subjects was performed. Patients were followed-up for a mean of 5.78 ± 3.30 years and cause of death (if any) was recorded. Primary endpoints were defined as all-cause and CV death, and a composite endpoint that included CV death or hospitalization for HF was included as a secondary endpoint. Baseline serum samples were obtained and the serum FABP3 and FABP4 concentrations were assessed by sandwich enzyme-linked immunosorbent assay. Survival analysis was performed with multivariable Cox regressions, using Fine and Gray competing risks models when needed, to explore the prognostic value of FABP3 and FABP4 concentrations, adjusting for potential confounders. Type 2 diabetes mellitus was highly prevalent, accounting for 47.5% for total subjects with CHF. Subjects with T2D showed higher mortality rates (T2D: 69.30%; non-T2D: 50.79%, p = 0.004) and higher serum FABP3 (1829.3 (1104.9-3440.5) pg/mL vs. 1396.05 (820.3-2362.16) pg/mL, p = 0.007) and FABP4 (45.5 (27.6-79.8) ng/mL vs. 34.1 (24.09-55.3) ng/mL, p = 0.006) concentrations compared with non-T2D CHF subjects. In the whole study cohort, FABP3 was independently associated with all-cause death, and both FABP3 and FABP4 concentrations were associated with CV mortality. The predictive values of these two molecules for all-cause (FABP3: HR 1.25, 95% CI 1.09-1.44; p = 0.002. FABP4: HR 2.21, 95% CI 1.12-4.36; p = 0.023) and CV mortality (FABP3: HR 1.28, 95% CI 1.09-1.50; p = 0.002. FABP4: HR 4.19, 95% CI 2.21-7.95; p < 0.001) were only statistically significant in the subgroup of subjects with T2D. Notably, FABP4 (HR 2.07, 95% CI 1.11-3.87; p = 0.022), but not FABP3, also predicted the occurrence of the composite endpoint (death or hospitalization for HF) only in subjects with T2D. All these associations were not found in CHF subjects without T2D. Our findings support the usefulness of serum FABP3 and FABP4 concentrations as independent predictors for the occurrence of all-cause and CV mortality in ambulatory subjects with CHF with T2D.

Differential Expression of microRNAs in Acute and Chronic Heart Failure.

MicroRNAs modify protein expression at the post-transcriptional level, and their circulating levels may help identify the underlying molecular pathways. The purpose of this study was to assess the differential expression of microRNAs related to myocardial cell energy substrate, autophagy, and ischaemia in chronic and acute heart failure (HF). In this case-control study, we studied 19 patients with acute HF (AHF) and 19 patients with chronic HF (CHF). Basic demographic and clinical characteristics were collected from the patients upon arrival, at 48 hours, and at 120 hours. Blood samples for microRNAs measurements (miR-22, -92a, and -499), B-type natriuretic peptide (BNP), C reactive protein, and high sensitivity cardiac troponin I, were collected at all study points. In this study, we included subjects with a left ventricular ejection fraction of <40%. At baseline, circulating miR-22 levels were 1.9-fold higher (p<0.001), miR-92a levels were 1.25-fold higher (p=0.003), and miR-499 were 5-times lower (p<0.001) in AHF compared to CHF. Interestingly, circulating miR-499 was found to be associated with BNP levels (r=0.47, p=0.01). At follow-up, there was a stepwise increase in the levels of all three examined microRNAs (miR-22, p=0.001, miR-92a, p=0.001, and miR-499, p<0.001) for AHF but not for CHF subjects. MicroRNAs -22, -92a, and -499 are differentially expressed in chronic and acute HF subjects. MicroRNA signatures are also differentially expressed up to the discharge of the patients. These findings may have important implications for diagnosis, progression, and treatment of patients with chronic and acute heart failure.

Phenylacetylglutamine as a risk factor and prognostic indicator of heart failure.

AimsTo explore the associations between serum phenylacetylglutamine (PAGln) and chronic heart failure (HF).Methods and resultsTotally 956 subjects were enrolled consecutively from the Department of Cardiovascular Medicine, Ruijin Hospital. Baseline data were obtained from all participants, and 471 stable chronic HF subjects were followed up. Serum PAGln was analysed by liquid chromatography–tandem mass spectrometry. The association between PAGln and basic renal indicators was assessed by simple correlation analysis. Logistic regression analysis was conducted to measure the association between PAGln and HF risk. Event‐free survival was determined by Kaplan–Meier curves, and differences in survival were assessed using log‐rank tests. Cox proportional hazards analysis was used to assess the prognostic value of PAGln in HF. Serum PAGln levels were increased in patients with chronic HF (3.322 ± 8.220 μM vs. 1.249 ± 1.168 μM, P < 0.001) and were associated with HF after full adjustment [odds ratio (OR), 1.507; 95% confidence interval (CI): 1.213–1.873; P < 0.001]. PAGln levels were correlated with the levels of basic renal indicators. High PAGln levels indicated a high risk of renal dysfunction in HF (OR: 1.853; 95% CI: 1.344–2.556; P < 0.001), and elevated PAGln levels were associated with a high risk of cardiovascular death in patients with chronic HF (HR: 2.049; 95% CI: 1.042–4.029; P = 0.038).ConclusionsElevated PAGln levels are an independent risk factor for HF and are associated with a higher risk of cardiovascular death. High PAGln levels could indicate renal dysfunction in HF patients. PAGln can be a valuable indicator of HF.

Association Between Upper Limb Strength Through 1-Repetition Maximum Test and V’O2peak in Heart Failure

ABSTRACT Purpose: This study aimed to evaluate whether there is a correlation between the maximum strength of upper limb when performing a multijoint exercise and peak oxygen uptake (V’O2peak) in Chronic Heart Failure (CHF) subjects. Method: This cross-sectional study involved CHF subjects with a left ventricular ejection fraction (LVEF) less than 50%, who underwent a cardiopulmonary exercise test (CPET) on a treadmill and 1-repetition maximum (1-RM) test for upper limb strength using a bench press exercise. Results: The sample consisted of 16 individuals aged 54 ± 12 years with a LVEF of 37 ± 7%. The V’O2peak was 14.98 ± 5.4 ml·min−1·kg−1 and mean maximum load in the 1-RM test was 38 ± 16 kg. There was strong correlation of V’O2peak with the load in the 1-RM test (r = 0.70; p = .037; r2 = 0.48). Conclusion: There is a strong correlation between the load in 1-RM test for upper limb with V’O2peak in CHF individuals. It is a safe, inexpensive and reproducible way to assess the muscle strength in this population.

Clinical effects of the enhanced external counterpulsation therapy in patients with ischemic chronic heart failure exacerbation COVID-19

Abstract Objectives The aim of the study was to assess the effects of the enhanced external counterpulsation (EECP) therapy as a rehabilitation method in patients with ischemic chronic heart failure (CHF) after COVID-19. Methods 54 (n=54) stable symptomatic CHF (NYHA, functional class I-II; 35%≤LVEF≤50%) subjects (44 male and 10 female; mean age 61±9,8) with prior anamnesis of CAD, at least one myocardial infarction got the exacerbation of CHF after COVID-19 episode. They were randomized in a 2:1 manner into either 35 1-hour 250–300 mm Hg sessions of EECP (n=36; 30 male, 6 female) or Sham-EECP (n=18; 14 male, 4 female). All subjects had been received optimal CHF and CAD drug therapy. At baseline, a month and half a year after EECP course every subject was examined with echocardiography and 6-minute walk test. Results All 36 active EECP treatment group subjects improved by at least 1 NYHA class, 66% of them had no heart failure symptoms post treatment (p&amp;lt;0.01). 84% of treatment group pts. had sustained NYHA class improvement at half a year follow-up (p&amp;lt;0.01), compared with baseline. There was significant difference between LVEF 44±6,5% at baseline vs post-EECP LVEF 50±4,6% (p&amp;lt;0.01) in active EECP treatment group subjects. At the same time there were no significant changes of NYHA class and LVEF in Sham-EECP subjects. No one subject dies after half a year of follow up. Conclusions Enhanced external counterpulsation (EECP) therapy sustainably improves NYHA functional class and LVEF in patients with ischemic CHF exacerbation after COVID-19. Funding Acknowledgement Type of funding sources: None.

A Machine Learning Approach to the Interpretation of Cardiopulmonary Exercise Tests: Development and Validation.

Objective At present, there is no consensus on the best strategy for interpreting the cardiopulmonary exercise test's (CPET) results. This study is aimed at assessing the potential of using computer-aided algorithms to evaluate CPET data for identifying chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD). Methods Data from 234 CPET files from the Pulmonary Institute, at Sheba Medical Center, and the Givat-Washington College, both in Israel, were selected for this study. The selected CPET files included patients with confirmed primary CHF (n = 73), COPD (n = 75), and healthy subjects (n = 86). Of the 234 CPETs, 150 (50 in each group) tests were used for the support vector machine (SVM) learning stage, and the remaining 84 tests were used for the model validation. The performance of the SVM interpretive module was assessed by comparing its interpretation output with the conventional clinical diagnosis using distribution analysis. Results The disease classification results show that the overall predictive power of the proposed interpretive model ranged from 96% to 100%, indicating very high predictive power. Furthermore, the sensitivity, specificity, and overall precision of the proposed interpretive module were 99%, 99%, and 99%, respectively. Conclusions The proposed new computer-aided CPET interpretive module was found to be highly sensitive and specific in classifying patients with CHF or COPD, or healthy. Comparable modules may well be applied to additional and larger populations (pathologies and exercise limitations), thereby making this tool powerful and clinically applicable.

Clinical significance of the long non-coding RNA NEAT1/miR-129-5p axis in the diagnosis and prognosis for patients with chronic heart failure.

Chronic heart failure (CHF) is the leading cause of death worldwide. The regulatory interactions of long non-coding RNA (lncRNAs) and microRNAs (miRs) have important roles in multiple diseases. However, the clinical significance of the nuclear-enriched abundant transcript 1 (NEAT1)/miR-129-5p axis in CHF has remained elusive. The present study explored whether the NEAT1/miR-129-5p axis may be a suitable diagnostic and prognostic marker for CHF. The expression of lncRNA NEAT1 and miR-129-5p in the serum of patients with CHF was analyzed by reverse transcription-quantitative PCR. Furthermore, inter-indicator correlations were assessed by Pearson correlation coefficient analysis. Receiver operating characteristic (ROC) curves were generated to evaluate the ability of NEAT1, miR-129-5p and brain natriuretic peptide (BNP) to identify patients with CHF. The prognostic value of the NEAT1/miR-129-5p axis was analyzed by drawing Kaplan-Meier survival curves and by Cox logistic regression analysis. Baseline data were not significantly different between CHF (n=70) and control subjects (n=62). The serum level of NEAT1 was increased and the expression level of miR-129-5p was decreased in patients with CHF (all P<0.001). The ROC curves suggested that serum NEAT1 and miR-129-5p were of diagnostic value in patients with CHF and the combined diagnostic accuracy of NEAT1, miR-129-5p and BNP was significantly improved. Kaplan-Meier and multivariate Cox regression analysis suggested that low NEAT1 and high miR-129-5p were able to predict overall survival of patients with CHF (all P<0.01). In conclusion, the present study indicated that patients with CHF had increased NEAT1 and decreased miR-129-5p expression. The deregulated NEAT1/miR-129-5p axis may provide novel non-invasive biomarkers for the diagnosis and prognosis of CHF.

Short-period temporal repolarization dispersion in subjects with atrial fibrillation and decompensated heart failure.

The association between chronic heart failure (CHF) and permanent atrial fibrillation is very frequent. The repolarization duration was already found predictive for atrial fibrillation. Aim of this study was to evaluate the influence of atrial fibrillation on short period repolarization variables in decompensated CHF patients. We used 5 min ECG recordings to assess the mean, standard deviation (SD), and normalized variance (NV) of the following variables: QT end (QTe), QT peak (QTp), and T peak to T end (Te) in 121 decompensated CHF, of whom 40 had permanent atrial fibrillation, too. We reported also the 30-day mortality. QTpSD (p<.01), TeSD (p<.01), QTpVN (p<.01), and TeVN (p<.01) were higher in the atrial fibrillation than among sinus rhythm CHF subjects. Multivariable logistic analysis selected only TeSD (odd ratio, o.r.: 1.32, 95% confidence interval, c.i.: 1.06-1.65, p: .015) associated with atrial fibrillation. A total of 27 patients died during the 30-days follow-up (overall mortality rate 22%), 7 (18%), and 20 (25%) respectively in the atrial fibrillation and sinus rhythm patients. Furthermore, the following variables were associated to the morality risk: NT-pro Brain Natriuretic Peptide (o.r.: 1.00, 95% c.i.: 1.00-1.00, p: .041), left ventricular end diastolic diameter (o.r.: 0.81, 95% c.i.: 0.67-0.96, p: .010), and Te mean (o.r.: 1.04, 95% c.i.: 1.02-1.09, p: .012). In decompensated CHF subjects, Te mean seems be associated to mortality and TeSD to the permanent atrial fibrillation. We could hypothesize that, during severe CHF, the multi-level ionic CHF channel derangement could be critical in influencing these non-invasive markers. (ClinicalTrials.gov number, NCT04127162).

Differential Role of Circulating microRNAs to Track Progression and Pre-Symptomatic Stage of Chronic Heart Failure: A Pilot Study.

(1)Background: Chronic heart failure (CHF) contributes to the overall burden of cardiovascular disease. Early identification of at-risk individuals may facilitate the targeting of precision therapies. Plasma microRNAs are promising circulating biomarkers for their implications with cardiac pathologies. In this pilot study, we investigate the possible exploitability of circulating micro-RNAs (miRNAs) to track chronic heart failure (CHF) occurrence, and progression from NYHA class I to IV. (2)Methods: We screened 367 microRNAs using TaqMan microRNA Arrays in plasma samples from healthy controls (HC) and CHF NYHA-class I-to-IV patients (5/group). Validation was performed by singleplex assays on 10 HC and 61 CHF subjects. Differences in the expression of validated microRNAs were evaluated through analysis of covariance (ANCOVA). Associations between N-terminal pro-BNP (NT-proBNP), left ventricular end-diastolic volume (LVEDV) or peak oxygen uptake (VO2 peak) and plasma microRNA were assessed by multivariable linear regression analysis. (3)Results: Twelve microRNAs showed higher expression in CHF patients vs. HC. Seven microRNAs were associated with NT-proBNP concentration; of these, miR-423-5p was also an independent predictor of LVEDV. Moreover, miR-499-5p was a predictor of the VO2 peak. Finally, a cluster of 5 miRNAs discriminated New York Heart Association (NYHA) class-I from HC subjects. (4)Conclusions: Our data suggest that circulating miRNAs have the potential to serve as pathophysiology-based markers of HF status and progression, and as indicators of pre-symptomatic individuals.

C3a, C4a, and C5a Complement Anaphylatoxins Are Paradoxically Decreased in Acute and Chronic Heart Failure

Background Inflammation is a prerequisite for healing after physical insult or microbial invasion. However, sustained and chronic inflammation often leads to deleterious effects. Especially in heart failure (HF), inflammation plays a causative role in adverse cardiac remodeling and functional decline. An important part of the innate immune system, the complement cascade is associated with the initiation and propagation of inflammation for the purpose of clearing bacterial pathogens. Specifically, the anaphylatoxins C3a, C4a, and C5a are integral in the complement cascade, initiating and amplifying inflammation that may exacerbate HF. Hypothesis In light of prior evidence linking innate immune system activation to inflammation and the aggravation of HF, we hypothesize that increased complement activation, evidenced by higher concentrations of circulating anaphylatoxins, are indicative of HF severity and track with traditional HF risk factors. Method Blood and clinical values were obtained from healthy (non-HF), acute HF, and chronic HF subjects. To compare anaphylatoxin levels, serum from non-HF and HF subjects were assayed for circulating C3a, C4a, and C5a concentrations by cytometric bead array, then compared to clinical parameters. C3, the major complement initiating factor for the anaphylatoxins, was measured in serum by ELISA assay. Additionally, data from RNAseq analysis on cardiac tissue isolates from non-HF and dilated cardiomyopathy (DCM) patients were compared for differential expression in 22 complement-related genes. Results Compared to non-HF, Serum C3a was found to be decreased by 24.3% in chronic HF and 20.5% among all HF cohorts (P Conclusions Although inflammation is increased in HF, C3, C3a, and C4a were found to be paradoxically decreased in HF cohorts, while C5a conversely increased in acute HF alone. The significant decreases in anaphylatoxins may be explained by the decreased C3 expression observed in HF subjects. While contrary to our hypothesis, our findings suggest differential complement dynamism, dependent on acute versus chronic HF status.

Circulating Osteocrin Levels Do Not Track with Myocardial Function in Chronic Systolic Heart Failure

Background Osteocrin was originally classified as a muscular and bone secretory protein with the ability to modulate bone growth through osteoblast activity, yet it shares a similar sequence to the family of natriuretic peptides (NPs). Despite their sequence homology, it is yet unknown whether osteocrin exhibits similar properties to NPs. However, recent work has shown that osteocrin can limit C-type NPs and more definitively, that a transgenic osteocrin mouse strain exhibited improved outcomes and alleviated echocardiographic parameters, after myocardial infarction (MI). Hypothesis With previous evidence showing improved prognosis and cardiac function in osteocrin-overexpressing mice post-MI, we hypothesize that circulating osteocrin levels in chronic heart failure patients could track with echocardiographic indices and other heart failure (HF) biomarkers of interest. Method Eighty-seven symptomatic chronic HF subjects with LVEF ≤35% underwent detailed echocardiographic evaluation and measurements of plasma NPs and osteocrin by ELISA assay, with long-term follow-up for all-cause mortality, transplantation, or mechanical circulatory support. Results In our study cohort (mean age 57 years, 72% male, 44% ischemic), median plasma osteocrin level was 198.3 (IQR 131.5, 386.3) ng/L. Plasma osteocrin levels did not track with demographics, comorbidities, medications, or laboratory values including ANP and BNP. Furthermore, osteocrin did not correlate to major echocardiographic indices (Table) or long-term adverse clinical outcomes. Conclusions Although osteocrin shows similarity to NPs and has been shown to exert cardioprotective effects in mice after cardiac insult, we did not observe any relationship between circulating osteocrin levels and clinical or echocardiographic parameters in chronic HFrEF patients.

The relation between cardiac 123I-mIBG scintigraphy and functional response 1 year after CRT implantation.

Aims Cardiac resynchronization therapy (CRT) is a disease-modifying therapy in patients with chronic heart failure (CHF). Current guidelines ascribe CRT eligibility on three parameters only: left ventricular ejection fraction (LVEF), QRS duration, and New York Heart Association (NYHA) functional class. However, one-third of CHF patients does not benefit from CRT. This study evaluated whether 123I-meta-iodobenzylguanidine (123I-mIBG) assessed cardiac sympathetic activity could optimize CRT patient selection.Methods and results A total of 78 stable CHF subjects (age 66.8 ± 9.6 years, 73% male, LVEF 25.2 ± 6.7%, QRS duration 153 ± 23 ms, NYHA 2.2 ± 0.7) referred for CRT implantation were enrolled. Subjects underwent 123I-mIBG scintigraphy prior to implantation. Early and late heart-to-mediastinum (H/M) ratio and 123I-mIBG washout were calculated. CRT response was defined as either an increase of LVEF to >35%, any improvement in LVEF of >10%, QRS shortening to <150 ms, or improvement in NYHA class of >1 class. In 33 patients LVEF increased to >35%, QRS decreased <150 ms in 36 patients, and NYHA class decreased in 33 patients. Late H/M ratio and hypertension were independent predictors of LVEF improvement to >35% (P = 0.0014 and P = 0.0149, respectively). In addition, early H/M ratio, LVEF, and absence of diabetes mellitus (DM) were independent predictors for LVEF improvement by >10%. No independent predictors were found for QRS shortening to <150 ms or improvement in NYHA class.Conclusion Early and late H/M ratio were independent predictors of CRT response when improvement of LVEF was used as measure of response. Therefore, cardiac 123I-mIBG scintigraphy may be used as a tool to optimize selection of subjects that might benefit from CRT.

The Health Diary Telemonitoring and Hospital-Based Home Care Improve Quality of Life Among Elderly Multimorbid COPD and Chronic Heart Failure Subjects.

BackgroundElderly, multimorbid patients with advanced chronic obstructive pulmonary disease (COPD) and/or chronic heart failure (CHF) exhibit poor health-related quality of life (HRQoL). Telemonitoring, based on digital pen technology, supported by hospital-based home care (HBHC) significantly reduces the number of hospitalizations. We hypothesized that the same intervention would prevent the deterioration of HRQoL that follows upon disease progression.MethodsElderly computer-illiterate subjects with ≥2 hospitalizations the previous year were included. HRQoL was assessed at inclusion (baseline) and at 1, 6 and 12 months employing EuroQol-5 Dimensions (EQ-5D) and RAND-36 for general HRQoL, and Minnesota Living with Heart Failure Questionnaire (MLHFQ) and St. Georges Respiratory Questionnaire (SGRQ) for disease-specific HRQoL. Healthcare contacts, hospitalizations, as-needed medications, prescription changes and healthcare costs were registered.ResultsNinety-four patients were enrolled of which 53 subjects completed the 12-month study period. Compared to baseline, most domains of RAND-36 were improved significantly at 1 time-point or more. Only among COPD subjects, the disease-specific HRQoL was worsened at the 12 month evaluation. Measures of healthcare dependency were associated with poor HRQoL.ConclusionThe Health Diary system and HBHC together improve general HRQoL, and measures of healthcare dependency are associated with HRQoL variables.

Elderly patients with COPD require more health care than elderly heart failure patients do in a hospital-based home care setting.

BackgroundElderly patients with advanced stages of COPD or chronic heart failure (CHF) often require hospitalization due to exacerbations. We hypothesized that telemonitoring supported by hospital-based home care (HBHC) would detect exacerbations early, thus, reducing the number of hospitalization. We also speculated that patients with advanced COPD or CHF would present differences regarding exacerbation frequency and the need of HBHC.MethodsThe Health Diary system, based on digital pen technology, was employed. Patients aged ≥65 years with ≥2 hospitalizations the previous year were included. Exacerbations were categorized and treated as either COPD or CHF exacerbation by an experienced physician. All HBHC contacts (home visits or telephone consultations) were registered.ResultsNinety-four patients with advanced diseases were enrolled (36 COPD and 58 CHF subjects) of which 53 subjects (19 COPD and 34 CHF subjects) completed the 1-year study period. Death was the major reason for not finalizing the study. Compared to the 1-year prior inclusion, the intervention significantly reduced hospitalization. Although COPD subjects were younger with less comorbidity, exacerbations and HBHC contacts were significantly greater in this group.ConclusionsCOPD subjects exhibit exacerbations more frequently, mainly due to disease characteristics, thus, demanding much more HBHC.

Skeletal Muscle Abnormalities and Iron Deficiency in Chronic Heart FailureAn Exercise 31P Magnetic Resonance Spectroscopy Study of Calf Muscle.

Heart failure (HF) is often associated with iron deficiency (ID). Skeletal muscle abnormalities are common in HF, but the potential role of ID in this phenomenon is unclear. In addition to hemopoiesis, iron is essential for muscle bioenergetics. We examined whether energetic abnormalities in skeletal muscle in HF are affected by ID and if they are responsive to intravenous iron. Forty-four chronic HF subjects and 25 similar healthy volunteers underwent 31P magnetic resonance spectroscopy of calf muscle at rest and during exercise (plantar flexions). Results were compared between HF subjects with or without ID. In 13 ID-HF subjects, examinations were repeated 1 month after intravenous ferric carboxymaltose administration (1000 mg). As compared with controls, HF subjects displayed lower resting high-energy phosphate content, lower exercise pH, and slower postexercise PCr recovery. Compared with non-ID HF, ID-HF subjects had lower muscle strength, larger PCr depletion, and more profound intracellular acidosis with exercise, consistent with an earlier metabolic shift to anaerobic glycolysis. The exercise-induced PCr drop strongly correlated with pH change in HF group ( r=-0.71, P<0.001) but not in controls ( r=0.13, P=0.61, interaction: P<0.0001). Short-term iron administration corrected the iron deficit but had no effect on muscle bioenergetics assessed 1 month later. HF patients display skeletal muscle myopathy that is more severe in those with iron deficiency. The presence of ID is associated with greater acidosis with exercise, which may explain early muscle fatigue. Further study is warranted to identify the strategy to restore iron content in skeletal muscle.

Rate-Response Programming Tailored to the Force-Frequency Relationship Improves Exercise Tolerance in Chronic Heart Failure

ObjectivesThis study sought to examine whether the heart rate (HR) at which the force-frequency relationship (FFR) slope peaks (critical HR) could be used to tailor HR response in chronic heart failure (CHF) patients with cardiac pacemakers and whether this favorably influences exercise capacity. BackgroundCHF secondary to left ventricular (LV) systolic dysfunction is characterized by blunting of the positive relationship between HR and LV contractility known as the FFR. MethodsThis observational study was carried out in patients with CHF and healthy subjects with pacemaker devices. The study assessed the 3 important features of the FFR (critical HR, peak contractility, and the FFR slope), and their reproducibility was measured noninvasively using echocardiography. The investigators then undertook a double-blind, randomized, controlled crossover study comparing the effects of tailored pacemaker rate-response programming on the basis of the FFR with conventional rate-response programming on exercise time and maximal oxygen consumption. ResultsThe study enrolled 90 patients with CHF into the observational cohort study: mean age, 73.6 ± 8.9 years; mean left ventricular ejection fraction (LVEF), 33.5 ± 10.9%. The study investigated 15 control subjects with normal LV function (LVEF, 55.6 ± 5.3%). The critical HR (103 ± 22 beats/min vs. 126 ± 15 beats/min; p = 0.0002), peak contractility (3.8 ± 3.7 SBP/LVESVI vs. 9.8 ± 4.1 SBP/LVESVI; p = 0.0001), and the slope of the FFR (p < 10−15) were lower in patients with CHF than in control subjects. A total of 52 patients, with a mean LVEF of 32 ± 11% on optimal therapy, took part in the crossover study. Rate-response settings limiting HR rise to below the critical HR led to greater exercise time (475 ± 189 s vs. 425 ± 196 s; p = 0.003) and higher peak oxygen consumption (17.3 ± 4.6 ml/kg/min vs. 16.6 ± 4.7 ml/kg/min; p = 0.01). ConclusionsA personalized approach to rate-response programming, determined using a reproducible noninvasive method for assessing the FFR, improves exercise time in patients with CHF and pacemaker devices. (Bowditch Revisited: Defining the Optimum Heart Rate Range in Chronic Heart Failure; NCT02563873)

The relationship between serum uric acid level and concentration of proangiogenic endothelial progenitor cells in chronic heart failure patients

Serum uric acid (SUA) is considered as a marker of nature progression of chronic heart failure (CHF) mediated cardiovascular remodeling. Progression of CHF associates with declining of circulating endothelial progenitor cells (EPCs) in the peripheral circulation. t he objective of this study: to establish predictive relationship between the content of uric acid in the blood and the level of circulating endothelial progenitor cells in patients with CHF of ischemic origin. Methods: The study population was structured retrospectively in 126 subjects (54 male), aged 48 to 62 years, with mild-to-severe ischemic CHFSUA level was measured by enzymatic methods, NT-pro-BNP level was examined by immunoelectrochemiluminesence method. EPCs were determined as CD 34 + cells by the flowcytometric technique using High-Definition Fluorescence Activated Cell Sorter methodology. All biomarkers were measured at baseline. The study was approved by an institutional review committee. Results: Concentrations of SUA were distributed by quartiles (Me; IQR): QI=201,1 (190,6; 223,3) umol/l; QII=275,3 (232,0; 311,0) umol/l; QIII=358,0 (320,0; 390,0) mmol/l; and QIV=449,0 (400,0; 496,0) umol/l. We found an independent impact of SUA on counts of CD14 + CD309 + EPCs (r=-0.388; P=0.001) and CD14 + CD309 + Tie2 + MPCs (r=-0.414; P=0.001), but on CD45 + CD34 + EPCs (r=-0.214; P=0.22) and CD45 - CD34 + MPCs (r=-0.16; P=0.16) did not. Cox proportional adjusted Odds Ratios analyses for CD14 + CD309 + and CD14 + CD309 + Tie2 + EPCs by SUA Quartiles (Q) has showed that high Q (Q3 and Q4) of SUA versus low Q (Q1 and Q2) associated with increased risk of depletion of both CD14 + CD309 + and CD14 + CD309 + Tie2 + EPCs. The ROC analysis showed that there was the cut-off point for the SUA level with the best prognostic potential on the risk of decreasing EPCs in both models equal 315,0 umol/l. Conclusion: Circulating level of proangiogenic EPCs phenotyped as CD14 + CD309 + and CD14 + CD309 + Tie2 + is declined progressively depended on quartiles of SUA level in CHF subjects.

Could peak oxygen uptake be estimated from proposed equations based on the six-minute walk test in chronic heart failure subjects?

ObjectivesTo evaluate the agreement between the measured peak oxygen uptake (VO2peak) and the VO2peak estimated by four prediction equations based on the six-minute walk test (6MWT) in chronic heart failure patients. MethodThirty-six chronic heart failure patients underwent cardiopulmonary exercise testing and the 6MWT to assess their VO2peak. Four previously published equations that include the variable six-minute walk distance were used to estimate the VO2peak: Cahalin, 1996a (1); Cahalin, 1996b (2); Ross, 2010 (3); and Adedoyin, 2010 (4). The agreement between the VO2peak in the cardiopulmonary exercise testing and the estimated values was assessed using the Bland–Altman method. A p-value of <0.05 was considered statistically significant. ResultsAll estimated VO2peak values presented moderate correlation (ranging from 0.55 to 0.70; p<0.001) with measured VO2peak values. Equations 2, 3, and 4 underestimated the VO2peak by 30%, 15.2%, and 51.2%, respectively, showing significant differences from the actual VO2peak measured in the cardiopulmonary exercise testing (p<0.0001 for all), and the limits of agreement were elevated. The VO2peak estimated by equation 1 was similar to that measured by the cardiopulmonary exercise testing, and despite the agreement, bias increased as VO2peak increased. ConclusionsOnly equation 1 showed estimated VO2peak similar to the measured VO2peak; however, a large limits of agreement range (∼3 METs) does not allow its use to estimate maximal VO2peak.

Limitations of skeletal muscle oxygen delivery and utilization during moderate-intensity exercise in moderately impaired patients with chronic heart failure.

The extent and speed of transient skeletal muscle deoxygenation during exercise onset in patients with chronic heart failure (CHF) are related to impairments of local O2 delivery and utilization. This study examined the physiological background of submaximal exercise performance in 19 moderately impaired patients with CHF (Weber class A, B, and C) compared with 19 matched healthy control (HC) subjects by measuring skeletal muscle oxygenation (SmO2) changes during cycling exercise. All subjects performed two subsequent moderate-intensity 6-min exercise tests (bouts 1 and 2) with measurements of pulmonary oxygen uptake kinetics and SmO2 using near-infrared spatially resolved spectroscopy at the vastus lateralis for determination of absolute oxygenation values, amplitudes, kinetics (mean response time for onset), and deoxygenation overshoot characteristics. In CHF, deoxygenation kinetics were slower compared with HC (21.3 ± 5.3 s vs. 16.7 ± 4.4 s, P < 0.05, respectively). After priming exercise (i.e., during bout 2), deoxygenation kinetics were accelerated in CHF to values no longer different from HC (16.9 ± 4.6 s vs. 15.4 ± 4.2 s, P = 0.35). However, priming did not speed deoxygenation kinetics in CHF subjects with a deoxygenation overshoot, whereas it did reduce the incidence of the overshoot in this specific group (P < 0.05). These results provide evidence for heterogeneity with respect to limitations of O2 delivery and utilization during moderate-intensity exercise in patients with CHF, with slowed deoxygenation kinetics indicating a predominant O2 utilization impairment and the presence of a deoxygenation overshoot, with a reduction after priming in a subgroup, indicating an initial O2 delivery to utilization mismatch.