Stable Chronic Heart Failure Patients Research Articles

Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: Rationale and design of the HF-REVERT trial.

Inhibition of microRNA (miR)-132 effectively prevents and reverses adverse cardiac remodelling, making it an attractive heart failure (HF) target. CDR132L, a synthetic antisense oligonucleotide selectively blocking pathologically elevated miR-132, demonstrated beneficial effects on left ventricular (LV) structure and function in relevant preclinical models, and was safe and well tolerated in a Phase 1b study in stable chronic HF patients. Patients with acute myocardial infarction (MI) and subsequent LV dysfunction and remodelling have limited therapeutic options, and may profit from early CDR132L treatment. The HF-REVERT (Phase 2, multicenter, randomized, parallel, 3-arm, placebo-controlled Study to Assess Efficacy and Safety of CDR132L in Patients with Reduced Left Ventricular Ejection Fraction after Myocardial Infarction) evaluates the efficacy and safety of CDR132L in HF patients post-acute MI (n = 280), comparing the effect of 5 and 10 mg/kg CDR132L, administered as three single intravenous doses 28 days apart, in addition to standard of care. Key inclusion criteria are the diagnosis of acute MI, the development of systolic dysfunction (LV ejection fraction ≤45%) and elevated N-terminal pro-B-type natriuretic peptide. The study consists of a 6-month double-blinded treatment period with the primary endpoint LV end-systolic volume index and relevant secondary endpoints, followed by a 6-month open-label observation period. The HF-REVERT trial may underpin the concept of miR-132 inhibition to prevent or reverse cardiac remodelling in post-MI HF. The results will inform the design of subsequent outcome trials to test CDR132L in HF.

Eligibility and prescribing rates of SGLT2 inhibitors for ambulatory patients with heart failure and reduced ejection fraction in a multidisciplinary heart failure management programme

Abstract Introduction Sodium-glucose cotransporter 2 (SGLT2) inhibitors dapagliflozin or empagliflozin are recommended, in addition to optimal medical therapy (OMT), for patients with heart failure with reduced ejection fraction (HFrEF) regardless of diabetes status.(1) Both have been licensed for use in the UK NHS by NICE,(2,3) but the proportion of 'real world' heart failure (HF) patients for whom these guidelines are applicable is unknown. For those eligible, multidisciplinary HF management programmes (HF-MPs), may enable more rapid translation of guidelines into practice.(1) Purpose We aimed to identify the patients eligible to start, and those prescribed, SGLT2 inhibitors amongst patients attending a HF-MP at a tertiary centre in the UK. We also assessed for variation by age and sex. Methods In this single-centre retrospective study we selected consecutive patients who attended a heart failure clinic appointment between 01 November 2020 - 01 March 2021. We extracted information pertaining to baseline demographics, investigations, and therapies relevant to eligibility for SGLT2 inhibitors, and prescription of SGLT2 inhibitors at baseline and 2-year follow-up. Differences in SGLT2 inhibitor prescription by age and sex were analysed using the χ2 test. All tests were two-sided, and statistical significance was considered as p value <0.05. Results Over this period, 296 stable chronic HF patients attended the centre. The majority of patients had HFrEF (53%),4 and there was a broad age distribution including the very elderly (28% > 80 years) (Table 1). Patients with HFrEF were well optimised [beta blocker (86%), angiotensin-converting enzyme/ angiotensin receptor blocker (61%), sacubitril- valsartan (23%), mineralocorticoid receptor antagonist (50%)] (Table 1). Of the whole cohort, 107 (36%) patients met eligibility for SGLT2 inhibitor prescription, with 24 (8%) already receiving a SGLT2 inhibitor at the point of guideline implementation, of whom 15 (5%) had diabetes mellitus (Figure 1). At 2-year follow-up 64 eligible individuals (22%) were prescribed a SGLT2 inhibitor, meaning that prescription amongst eligible individuals had increased from 22% to 60%, with greater improvement in younger individuals (Figure 1). Age-stratified analysis revealed that at least 30% of clinic attendees in each decile were eligible for SGLT2 inhibitors, and almost half of sexagenarian attendees (47%). Though there was not a disparity in prescription of SGLT2 inhibitors for women compared to men (51% vs 64% p=0.22), those aged ≥80 years less frequently received SGLT2 inhibitors compared with younger individuals (33% vs 69%, p<0.001). Conclusions Among stable HF patients in a ‘real world’ setting, a significant proportion are eligible for SGLT2 inhibitors. Patients attending a HF-MP have benefitted from early implementation of novel guidelines, though there are age-determined gaps in SGLT2 inhibitor prescription that represent an actionable target.Table 1Figure 1

ПОЛИМОРФИЗМ RS247616 ГЕНА CETP У ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ И ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА: ОСОБЕННОСТИ ЛИПИДНОГО ОБМЕНА И ЭФФЕКТИВНОСТИ ТЕРАПИИ СТАТИНАМИ

Abstract. Introduction. Dyslipidemia is a modifiable risk factor for cardiovascular complications in patients with chronic ischemia-induced heart failure. Being the best-known class of drugs, statins effectively reduce cardiovascular mortality in all age groups. Effectiveness of using lipid-lowering drugs is determined by some factors, including genetic ones. Polymorphism rs247616 of the CETP (cholesterol ester transfer protein) gene is associated with changing high-density lipoprotein levels in blood serum. Aim. To analyze the clinical parameters and effectiveness of lipid-lowering therapy in stable chronic ischemia-induced heart failure patients with the rs247616 polymorphism of the CETP gene. Materials and Methods. We examined 517 patients with chronic ischemia-induced heart failure, aged 66.4±10.4 years, of both sexes. A genetic control of 118 conditionally healthy individuals was included. We analyzed the allele frequency of the CETP rs247616 occurrences, clinical characteristics, statin administration frequency, dose range, and achieving the lipid metabolism goals, including in relation to the genotype. Results and Discussion. Statins were prescribed to 28.8% of patients with chronic heart failure, with 42.3% receiving the minimum dosage and 35.6% receiving the average therapeutic dosage. Frequency of TT-genotype and T allele of the CETP rs247616 was higher in patients with chronic heart failure compared with controls (13.2% and 10.2%, p=0.026, 35% and 26.7%, p=0.014). It was found that CC-genotype has a protective effect against the development of chronic heart failure (CC vs CT+TT, OR=0.57, 95%CI:0.38-0.86). In patients with CC-genotype chronic heart failure, a lower level of high-density lipoproteins was observed (1.12±0.37 and 1.25±0.37 mmol/l, p=0.012), as compared to the carriers of T allele (CT+TT). Percentage of individuals with total cholesterol levels below 4.5 mmol/l (33.3%, 29.7%, and 37.5%) and triglyceride levels < 1.7 mmol/l (36.5%, 25%, and 37.5%) did not differ between CC-, CT-, and TT-genotypes, respectively. There is a trend towards an increase in the proportion of the carriers of T allele and TT-genotype with low-density lipoprotein levels < 1.8 mmol/l (30.8%, 45.5%, and 50%) and non-high-density lipoproteins levels<2.6 mmol/l (29.4%, 31.2%, and 50%). Conclusions. Effectiveness of statin therapy is low: 38.1 % of patients had the total cholesterol levels < 4.5 mmol/l, 11% had low-density lipoprotein levels <1.8 mmol/l, 50.6% had triglyceride levels <1.7 mmol/l, and 12.2% of patients had non-high-density lipoprotein levels <2.6 mmol/l. Protective effect of CC-genotype was found regarding the genesis of chronic heart failure.

Resting pulmonary function and artery pressure and cardiopulmonary exercise testing in chronic heart failure patients in Taiwan − a prospective observational cross-sectional study comparing healthy subjects and interstitial lung disease patients

Background Restrictive ventilatory defects and elevated pulmonary artery pressure (PAP) are common in patients with chronic heart failure (CHF) and those with interstitial lung disease (ILD). However, as oxyhemoglobin desaturation seldom occurs in stable CHF patients at peak exercise, we hypothesized that the pathophysiology may be different between them. This study aimed to investigate: (1) PAP and lung function at rest, (2) pulmonary gas exchange (PGX) and breathing patterns at peak exercise, (3) mechanisms of dyspnea at peak exercise in patients with CHF compared to healthy subjects and ILD patients. Methods We consecutively enrolled 83 participants (27 with CHF, 23 with ILD, and 33 healthy controls). The CHF and ILD groups had similar functional status. Lung function and cardiopulmonary exercise tests with Borg Dyspnea Score were performed. PAP was estimated using echocardiography. Resting lung function, PAP and peak exercise data in the CHF group were compared to the healthy and ILD groups. Correlation analysis was performed to elucidate the mechanisms of dyspnea in the CHF and ILD groups. Results Compared to the healthy group, the CHF group had normal lung function, PAP at rest, and normal dyspnea score and PGX at peak exercise, whereas the ILD group had abnormal values compared to the CHF group. Dyspnea score was positively correlated with pressure gradient, lung expansion capabilities, and expiratory tidal flow in the CHF group (all p < 0.05), but inversely correlated with inspiratory time-related variables in the ILD group (all p < 0.05). Conclusion Normal lung function and PAP at rest, and dyspnea scores and PGX at peak exercise indicated that pulmonary hypertension and fibrosis were insignificant in the patients with CHF. The factors affecting dyspnea at peak exercise were different between the CHF and ILD groups. As the sample size in this study was small, large-scale studies are warranted to confirm our findings.

The acute effect of respiratory muscle training on microcirculation in patients with chronic heart failure

Background: Patients with chronic heart failure (CHF) present microcirculation alterations and vascular endothelial dysfunction. Exercise training programs have been shown to improve the functional status of these patients, however less is known yet about the acute systemic effect of exercise on peripheral muscle microcirculation. The aim of the present study was to investigate the acute effect of a respiratory muscle exercise bout on the microcirculation of non-exercising muscles (systemic effect). Materials and Methods: Thirty-four (30♂/4♀) stable CHF patients, with a mean age of61.4±9.2 years, ejection fraction (EF): 33.9±7.8%, maximal inspiratory pressure (MIP): 78.2±27.1 cmH2O, VO2max: 17.5±4.05 ml/kg/min, VE/VCO2 slope: 32.7±6.4 and a New York Heart Association classification (NYHA) ≥ ΙΙ participated in the study. Microcirculatory assessment was performed at rest and immediately after the respiratory exercise program (5 sets/10 repetitions, training load: 60% of MIP). Basal tissue oxygen saturation (StO2),oxygen consumption rate (OCR) and reperfusion rate (RR) were measured utilizing near-infrared spectroscopy(NIRS) at the thenar muscle along with the vascular occlusion test (VOT). Results: RR (%/min), following the release of vascular occlusion, as well as OCR (%/min) increased after the respiratory exercise program (from 3.4±1.6 to 3.9±1.7, p=0.007, and from 12.7±3.8 to 13.2±3.9, p=0.021 respectively), whereas the corresponding basal StO2values difference did not reach the level of statistical significance (from 85.5±6.4. to 84.7±6.2, p=0.065). Conclusions: In the present study, concerning patients with CHF, after an acute respiratory exercise bout, dynamic microcirculatory indices assessed by NIRS in peripheral, non-exercising muscles, were significantly altered.

Prognostic value of temporal patterns of global longitudinal strain in patients with chronic heart failure.

We investigated whether repeatedly measured global longitudinal strain (GLS) has incremental prognostic value over repeatedly measured left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP), and a single "baseline" GLS value, in chronic heart failure (HF) patients. In this prospective observational study, echocardiography was performed in 173 clinically stable chronic HF patients every six months during follow up. During a median follow-up of 2.7 years, a median of 3 (25th-75th percentile:2-4) echocardiograms were obtained per patient. The endpoint was a composite of HF hospitalization, left ventricular assist device, heart transplantation, cardiovascular death. We compared hazard ratios (HRs) for the endpoint from Cox models (used to analyze the first available GLS measurements) with HRs from joint models (which links repeated measurements to the time-to-event data). Mean age was 58 ± 11 years, 76% were men, 81% were in New York Heart Association functional class I/II, and all had LVEF < 50% (mean ± SD: 27 ± 9%). The endpoint was reached by 53 patients. GLS was persistently decreased over time in patients with the endpoint. However, temporal GLS trajectories did not further diverge in patients with versus without the endpoint and remained stable during follow-up. Both single measurements and temporal trajectories of GLS were significantly associated with the endpoint [HR per SD change (95%CI): 2.15(1.34-3.46), 3.54 (2.01-6.20)]. In a multivariable model, repeatedly measured GLS maintained its prognostic value while repeatedly measured LVEF did not [HR per SD change (95%CI): GLS:4.38 (1.49-14.70), LVEF:1.14 (0.41-3.23)]. The association disappeared when correcting for repeatedly measured NT-proBNP. Temporal evolution of GLS was associated with adverse events, independent of LVEF but not independent of NT-proBNP. Since GLS showed decreased but stable values in patients with adverse prognosis, single measurements of GLS provide sufficient information for determining prognosis in clinical practice compared to repeated measurements, and temporal GLS patterns do not add prognostic information to NT-proBNP.

Assessment of functional capacity of patients with chronic heart failure by the use of echocardiography right atrial volume index

Introduction: Heart failure (HF) is a chronic syndrome that influences survival &amp; quality of life. over the past 20 years, hospitalizations for heart failure have almost tripled, making heart failure the most common cause of hospitalization. Objective: evaluation of relationship between functional capacity by duke activity status index(DASI) in chronic heart failure patients and the right atrial volume index. Materials and methods: study was conducted on 40 patients who were admitted in the hospital with heart failure.All patients were subjected to detailed history, physical examination, electrocardiography, laboratory investigations, 2D echocardiography &amp; tissue Doppler imaging and assessment of functional capacity using DASI. Results: Out of 40 patients, 10 (25%) had DASI&lt;10 and 30 (75%) patients had DASI&gt;10, according to functional capacity between the two groups, group I Vo2 peak (ml/min) mean is 12.98±1.45 and DASI score ranged from (4.5-9.95) with a median 8.6, in group II Vo2 peak (ml/min) mean is 21.89±4 and DASI score ranged from (23.3- 36.7) with a median 28.7with p value &lt;0.001. RAVI had a significant correlation between the two groups with p-value &lt;0.001. Also, DASI have a strong correlation with RAVI (r=1.139 &amp; p=0.029). Conclusions: RAVI predicts functional capacity in chronic stable heart failure patients.

Temporal evolution of liver function parameters predicts clinical outcome in chronic heart failure patients (Bio-SHiFT Study)

Abstract Background Liver dysfunction contributes to worse clinical outcome in heart failure (HF) patients, and cholestatic enzymes are associated with mortality in the setting of chronic HF (CHF). However, the temporal evolutions of liver function parameters in stable CHF patients, and their associations with clinical outcome, have not yet been investigated. Purpose We aimed to investigate in detail the temporal patterns of alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGTP), total bilirubin (TBIL) and albumin (ALB), and their relation with clinical outcome, in patients with stable CHF with reduced ejection fraction (HFrEF). Methods During 2.2 (1.4–2.5) years of follow-up, we collected 1984 tri-monthly plasma samples in 263 patients. We selected 749 samples in the 250 HFrEF patients included in the study - all baseline samples, the last two samples before censoring in event-free patients, and the last two samples preceding the primary endpoint (PEP; composite of cardiac death, heart transplantation, LVAD implantation, and hospitalization for the management of acute or worsened HF). In these samples ALP, GGTP, and ALB were measured using colorimetric assays, TBIL using diazomethod, all by Roche/Hitachi Cobas c analyser. The relationship between repeatedly measured biomarker levels and the PEP was evaluated by joint models. Results Mean age was 68±18 years; 74% were men, 25% in NYHA class III or IV. 66 patients (26%) reached the PEP. Repeatedly measured levels of TBIL, ALP, GGTP and ALB were associated with the PEP in a model adjusted for NT-proBNP and hs-TnT (hazard ratio (HR) [95% confidence interval] per doubling of biomarker level: 1.98 [1.32; 2.95], p=0.002; 1.84 [1.09; 3.05], p=0.018, 1.33 [1.08; 1.63], p=0.006 and 1.14 [1.09; 1.20], p&amp;lt;0.001, respectively). Serially measured ALP and GGTP remained significantly associated with the PEP after adjustment for clinical covariates (HR [95% CI]: 1.13 [1.07; 1.19], p=0.018; 1.03 [1.01; 1.06], p=0.006, respectively). The levels of ALP and GGTP were higher in patients who experienced the PEP than in event-free patients long before the PEP occurred (&amp;gt;2 years), and as the PEP approached, levels diverged slightly between those with and without the PEP (Figure 1). Conversely, levels of ALB were higher in those with subsequent PEP, &amp;gt;2 years before the PEP, and subsequently fell; while TBIL levels rose less than 1 year before the PEP in those with subsequent PEP. The slopes of the temporal evolution of ALB and TBIL, adjusted for clinical variables, were also significantly associated with the PEP (HR [95% CI] per 20% decrease in the slope for albumin and increase in the slope of TBIL per year: 1.61 [1.43; 1.84], p&amp;lt;0.001 and 1.72 [1.28; 2.55], p&amp;lt;0.001, respectively). Conclusions Changes in serum levels of TBIL, ALP, GGTP and ALB precede adverse cardiovascular events in patients with CHF. These routine liver function parameters may provide additional prognostic information in HFrEF patients in clinical practice. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Jaap Schouten Foundation (Rotterdam, the Netherlands)Noordwest Academie (Alkmaar, the Netherlands)

Prognostic value of a disease-specific health-related quality score in acute heart failure

Abstract Background Despite the striking therapeutic progress made in the treatment of heart failure (HF), rehospitalization rate and mortality remain a major and often unpredictable problem. Previous studies have shown the prognostic value of Kansas City Cardiomyopathy Questionnaire (KCCQ), a score assessing disease-specific health-related quality of life in stable chronic HF patients. Recently, a large study including 4898 patients with acute HF (AHF) enrolled in China reported the incremental predictive ability of KCCQ for a composite outcome of death and rehospitalization. However, these findings were not yet confirmed. In order to address this unmet need, the aim of this study was to examine the prognostic value of KCCQ in another AHF cohort. Purpose To validate the prognostic value of the KCCQ in AHF. Methods Goal-directed AfterLoad Reduction in Acute Congestive Cardiac Decompensation Study (GALACTIC) was a prospective, multicenter (n=10), randomized, interventional controlled trial enrolling adult patients presenting with AHF. KCCQ was assessed shortly after admission. We focused on the prognostic value of the short version KCCQ-12, explored the association with the composite of all-cause mortality and AHF rehospitalization within 30- and 180-day follow-up and compared it to the original score. Patients were grouped into quartiles according their KCCQ: high-risk (0–&amp;lt;25), moderate- to high-risk (25–&amp;lt;50), low- to moderate-risk (50–&amp;lt;75) and low-risk group (75–100). Cumulative incidence of assessed endpoints was displayed in Kaplan-Meier curves. Covariate adjustments were made using Cox regression. Prognostic accuracy over N-terminal pro-B-type natriuretic peptide (NT-proBNP) was evaluated by time-dependent area under the curve. Results Among 781 patients, 419 (median age 78, 35% female, 32% new onset of HF) had a complete set of variables to calculate KCCQ. Follow-up was available in all patients up to 180 days. 29 (7%) and 122 (29%) patients died or were rehospitalized for AHF within 30- and 180-days, respectively. Median KCCQ-12 was 37.5 with 25% of patients attaining the high- and 8% the low-risk group. After adjustment, each 10-point decrease in the KCCQ was associated with a 10% increase in 180-day risk regardless of new onset or acute decompensated chronic HF, age, sex, comorbidities, systolic blood pressure, creatinine, NT-proBNP and sodium levels. The prognostic ability for a 30-day risk was not significant. Using the same adjustments, a 10-point decrease in the original KCCQ was significant for a 20% and a 11% increase in risk for the short- and long-term composite outcome. The prognostic accuracy of KCCQ was comparable to NT-proBNP. Conclusions Health status, measured by the KCCQ-12 among patients with AHF, is significantly associated with a long-term composite outcome of all-cause mortality and AHF rehospitalization. The original KCCQ overall score is an independent predictor for both, the 30- and 180-day composite outcome. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union, the Swiss National Science Foundation

Effects of High-Intensity Aerobic Interval Training on Cardiopulmonary Function in Patients With Chronic Heart Failure at The University Teaching Hospital, Lusaka, Zambia

Chronic heart failure patients present with a wide variety of symptoms such as, fatigue and dyspnea, which adversely affect their quality of life. Heart failure is a complex disease and a major cause of morbidity and mortality in developed and developing countries including Zambia. Through studies undertaken, high intensity aerobic interval training has been recommended in patients with chronic heart failure, to help improve symptoms and consequently the quality of life. Minimal research pertaining to effectiveness of aerobic exercise on various physiological parameters such as peripheral oxygen saturation, cardiopulmonary capacity and quality of life have been done in Africa and Zambia. Methods: This study evaluated the physiological effects of high intensity aerobic interval training on the cardiopulmonary function in New York Heart Association (NYHA) Class II and III chronic heart failure patients with a focus on peripheral oxygen delivery/saturation, cardiopulmonary capacity and the quality of life. This study utilised the Randomised Clinical Trial (RCT) study design and the study population was selected from the University Teaching Hospital-Heart clinic in Lusaka, Zambia. Results: A total number of 42 patients participated, and were randomly assigned to the two arms of the study. Twenty-one (21) were assigned to the interventional group (IG) and 21 to the control group (CG) respectively. The IG underwent a 12 week aerobic HIIT exercise-training program, while the CG was subjected to 30 minutes’ walk on a treadmill for the same period of 12 weeks. The expected primary outcomes were the baseline to endline differences in oxygen delivery/saturation readings, cardiopulmonary capacity test readings and the quality of life (measured using the Minnesota questionnaire) for both groups. The results obtained from the pulse oximeter readings, showed an increase in the oxygen saturation readings (97.90 to 98.62%), 6-minute walk distance readings (360.05 m to 429 m) and the questionnaire score totals of the different dimensions (physical, emotional/mental and socio-psychological factors) of the questionnaire (p-value ;0.0001) of the IG. The CG oxygen saturation readings (97.38 % to 97.90%) and 6-minute walk tests scores (359.14 to 370.9 m) showed minimal change. While, the questionnaire scores showed a statistical difference in the emotional/mental (p-value &lt; 0.0001), physical (p=0.005) and socio-psychological factors (p- value &lt; 0.0001). Conclusion: High intensity aerobic interval training has shown to improve the peripheral oxygen delivery, cardiopulmonary capacity and quality of life in chronic heart failure patients hence, must be considered as an adjunct therapy aside pharmacological management in stable chronic heart failure patients in Zambia.

Bending oxygen saturation index and risk of worsening heart failure events in chronic heart failure.

Bendopnea is a clinical symptom of advanced heart failure with uncertain prognostic value. We aimed to evaluate whether bendopnea and the change in oxygen saturation when bending forward (bending oxygen saturation index [BOSI]) are associated with adverse outcomes in ambulatory chronic heart failure (CHF) patients. We prospectively evaluated 440 subjects with symptomatic CHF. BOSI was defined as the difference between sitting and bending oxygen saturation (SpO2 ). The endpoint was the total number of worsening heart failure (WHF) events (heart failure hospitalization or urgent heart failure visit requiring parenteral diuretic therapy). The mean age was 74 ± 10 years, 257 (58.6%) were male, and 226 (51.4%) had a left ventricular ejection fraction <50%. Bendopnea was present in 94 (21.4%) patients, and 120 (27.3%) patients had a BOSI ≥-3%. The agreement between BOSI ≥-3% and bendopnea was moderate (Gwet's AC 0.482, p< 0.001). At a median (p25%-p75%) follow-up of 2.17 years (0.88-3.16), we registered 441 WHF events in 148 patients. After multivariable adjustment, BOSI was independently associated with the risk for total WHF episodes (overall, p< 0.001). Compared to improvement/no change in SpO2 when bending (BOSI 0%), those with BOSI ≥-3% showed an increased risk of WHF events (incidence rate ratio [IRR] 2.16, 95% confidence interval [CI] 1.67-2.79; p< 0.001). In contrast, bendopnea was not associated with the risk of total WHF episodes (IRR 1.04, 95% CI 0.83-1.31; p= 0.705). In ambulatory and stable CHF patients, BOSI ≥-3% and not bendopnea was independently associated with an increased risk of total (first and recurrent) WHF episodes. Awareness of SpO2 while assessing bendopnea may be a useful tool for predicting heart failure decompensations.

Related factors and changes of angiopoietin-like protein 2 with chronic heart failure patients participating in phase III cardiac rehabilitation

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): the research grant D2 from Kansai Medical University Objectives Angiopoietin-like protein 2 (ANGPTL2) is a protein, whose structure is similar to that of angiopoietin, but binds to a different receptor. Overexpression of ANGPTL2 promotes chronic inflammation and relates to the development of aging-related diseases. ANGPTL2 has been reported to be mainly secreted by adipose tissue. Although ANGPTL2 has been implicated in the pathogenesis of heart failure, there are no studies about serum ANGPTL2 levels in patients with heart failure participating in cardiac rehabilitation program. The aim of this study was to investigate the characteristics, related factors and changes of ANGPTL2 in patients with chronic heart failure during phase III of cardiac rehabilitation program. Methods The subjects included 57 patients (70.1 ± 10.2 years old; 46 men) with chronic heart failure whose serum ANGPTL2 levels were measured during the maintenance phase of cardiac rehabilitation program. Furthermore, we classified 25 patients (70.6 ± 7.5 years old; 23 men) from the 6-month course into a reduced group and an unchanged group to characterize change in ANGPTL2. We excluded patients who were admitted or discharged within 3 months of the evaluation of serum ANGPTL2. We evaluated exercise tolerance using the cardiopulmonary exercise test, grip strength, body composition using a body composition analyzer, blood examinations, and echocardiography. Serum ANGPTL2 was measured by solid-phase sandwich enzyme-linked immunosorbent assay (ELISA). Results The median value of ANGPTL2 was 4.05 ng/ml. ANGPTL2 was positively correlated with body weight, body mass index, body fat mass, body fat percentage, C-reactive protein (CRP) and total protein (TP) levels, and negatively correlated with skeletal muscle mass percentage and anaerobic threshold (AT). From the result of the logistic regression analysis, AT (OR=0.68, 95% CI:0.47-0.97and TP (OR=20.1, 95% CI:2.52-160.63) were extracted as independent factors related to the level of ANGPTL2. In addition, overall serum ANGPTL2 levels decreased significantly after 6 months. Changes in ANGPTL2 in the reduced group showed a positive correlation between baseline peak VO2, left ventricular ejection fraction and skeletal muscle rate, and a negative correlation with baseline ANGPTL2, CRP, body fat mass. In an unchanged group, HbA1c increased, but no significant change was observed in other factors. Conclusions Exercise tolerance in patients with chronic heart failure during maintenance phase might be related to the inflammation marker ANGPTL2. Serum ANGPTL2 levels with stable chronic heart failure patients decreased significantly 6 months after continued cardiac rehabilitation.

Acute on chronic heart failure-Which variations on B-type natriuretic peptide levels?

ObjectiveNatriuretic peptides are useful diagnostic and prognostic markers in patients presenting to the emergency department (ED) with acute shortness of breath. However, B‐type natriuretic peptide (BNP) level represents a single snapshot in time, while changes relative to a patient's baseline may be useful in risk stratification. We aimed to define the variation of BNP levels between chronic stable and acute decompensated heart failure (ADHF) that is associated with significant clinical outcomes.MethodsWe performed a retrospective cohort chart review study of chronic heart failure (HF) patients followed in an outpatient clinic from 2010 to 2013. Inclusion criteria were available hospital and clinic BNP levels and at least 1 year of follow‐up care. ADHF was defined as a hospital admission for acute HF. Dry BNP was defined as its concentration after >3 months of optimal treatment and no variations in New York Heart Association class. Dry BNP was compared to the BNP at a subsequent ED visit that was associated with hospitalization because of ADHF.ResultsOverall, 253 patients were included. Their median (interquartile range [IQR]) dry BNP was 191(83–450) pg/mL. There were 67 ADHF admissions, occurring 15 ± 15 months after patient's dry BNP was established. At subsequent ED admission, the median (IQR) BNP was 1505 (72–2620) pg/mL. Patients requiring inpatient admission had a BNP ∼250% higher than their stable BNP (404 vs 164 pg/mL, p < 0.001).ConclusionsIn this group of chronic stable HF patients, a doubling of BNP was observed in patients who required hospitalization for acute decompensated HF. BNP doubling may represent a useful parameter to reflect clinically relevant acute decompensated HF.

Use of loop diuretics in chronic heart failure: do we adhere to the Hippocratian principle 'do no harm'?

Use of loop diuretics in chronic heart failure: do we adhere to the Hippocratian principle 'do no harm'?

Exercise training early after acute ST-elevation myocardial infarction and its effect on ventricular remodeling

Abstract Funding Acknowledgements Type of funding sources: None. Background Deterioration of left ventricular function after acute myocardial infarction is common, particular in ST-elevation myocardial infarction (STEMI). This often leads to heart failure with reduced ejection fraction (HFrEF). Exercise training has shown to be beneficial in stable chronic heart failure patients. However, effects of exercise training have been rarely investigated during very early phases of STEMI. Purpose The Exercise in Acute Myocardial Infarction (Ex-AMI) pilot study wanted to investigate whether exercise training has beneficial effects on ventricular remodeling under the following conditions: a) started early after myocardial infarction b) exclusively after STEMI c) performed with higher intensity. The hypothesis of this study was that exercise training early after acute myocardial infarction performed for 24 weeks is superior to usual care, regarding the improvement of echocardiographic parameters. It was also assumed that higher-intensity interval training is more effective than moderate continuous training. Methods Therefore, we randomized 19 patients with STEMI (58.0 ± 7.1 years, 5% female) and left ventricular ejection fraction (LVEF) &amp;lt;55% to: 1. Moderate continuous training (MCT; 50-60% VO2peak; n = 6) 2. Higher intensity interval training (HIIT; MCT interspersed by intervals of 80-85% VO2peak; n = 6) 3. Usual care (UC; n = 7) Exercise groups (EG: MCT and HIIT) started seven days after STEMI (run-in period for two weeks, followed by a tailored supervised exercise program for 22 weeks). Three-dimensional echocardiography and cardiopulmonary exercise testing were performed at the beginning and at the end of the training period. Patients were also continuously monitored for adverse events. Results At baseline, LVEF (46.3 ± 6,5%) as well as exercise capacity (VO2peak: 17.8 ± 4.4·kg-1·min-1) were impaired. In both exercise groups (EG: MCT and HIIT) LVEF improved significantly more than in the control group (mean change +7.3 ± 3.5% in EG vs. 2.3 ± 2.3% in UC; p = 0.007). Furthermore HIIT was not superior to MCT (mean change 7.6 ± 3.6% in HIIT vs. 6.7 ± 4.1% in MCT; p = 0.78) in terms of LVEF. There were no training associated adverse events. Conclusion Exercise training early after acute STEMI seems to have anti-remodeling effects. There is a need for more randomized controlled trials to confirm these findings, in order to find the optimal timing and dose of exercise after STEMI. Abstract Figure. Changes in LVEF (in %) after 24 weeks

Bioimpedance vector analysis in stable chronic heart failure patients: Level of agreement between single and multiple frequency devices.

The accuracy of estimating body composition compartments is critical in the clinical setting. Currently, there are different bioelectrical impedance analysis (BIA) devices available for obtaining raw BIA parameters. The aim of this study was to determine the level of agreement between multiple frequency (MF)-BIA and single frequency (SF)-BIA devices in obtaining raw BIA measurements (resistance (R), reactance (Xc), and phase angle (PhA)), as well as the agreement on the classification of hydration status and body cell mass by the bioelectrical impedance vector analysis (BIVA) method. This cross-sectional study included 406 outpatients with stable chronic heart failure (HF). The raw BIA measurements at 50kHz obtained by tetrapolar MF-BIA (Bodystat QuadScan 4000) were compared with those obtained by tetrapolar SF-BIA (RJL Quantum X). In addition, the patients were classified by their hydration status and body cell mass according to the BIVA method. Strong and significant correlations were observed between the two methods in all raw BIA variables (r≥0.90). Lin's concordance correlation coefficient (CCC) values were almost perfect for R (CCC=0.99; 95% CI 0.997 to 0.998), moderate for Xc (CCC=0.93; 95% CI 0.92 to 0.94), and poor for PhA (CCC=0.88; 95% CI 0.85 to 0.90). The agreement obtained in the two classifications (quadrants and hydration status) was >0.81. MF-BIA and SF-BIA demonstrated good agreement for measurement of the R parameter; however, the Xc and PhA parameters must be used carefully due to the previously reported variability. Likewise, the agreement in all classifications by the BIVA method was almost perfect.

Prediction of serum NGAL levels using comorbidity AHEAD score and two-year prognosis in stable chronic heart failure patients (FAR NHL registry)

Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL) is marker of renal function and is strongly associated with presence of comorbidities. AHEAD comorbidity score is commonly used to predict survival in acute heart failure patients and could predict events even in chronic heart failure. Methods 547 stable patients with chronic heart failure patients with left ventricular ejection fraction &amp;lt;50% were included in FARmacology and NeuroHumoraL activation (FAR NHL) registry. Three cardiological centres from The Czech Republic with speciality in heart failure were participating. Results Median age was 66 years, 80.3% were men. The etiology of heart failure was in 54% ischemic heart disease, in 40% dilatated cardiomyopathy, in 0.5% hypertrophic cardiomyopathy. 60% of patients were in NYHA class II. In the first two years of follow-up, 74 events (13.5%) occurred, including all-cause death, left ventricle assist device implantation or orthotopic heart transplantation. The AHEAD comorbidity score (Atrial fibrillation, low Haemoglobin level &amp;lt;120 g/L in female or &amp;lt;130 g/L in male, Elderly &amp;gt;70 years; Abnormal renal parameters with creatinine &amp;gt;130 μmol/L, Diabetes mellitus; 1 point for each comorbidity present) was set in this registry. Patients with AHEAD 0–1 survived without event in 89.2%, AHEAD 2–3 in 82.4% and AHEAD 4–5 only in 63.5% (p&amp;lt;0.001; pairwise comparison 0.034, &amp;lt;0.001, 0.021). Also levels of NGAL are higher when comorbidities from AHEAD score are present: Atrial fibrillation (62 vs. 50 ng/mL; p&amp;lt;0.001), Haemoglobin level (Spearman's rank correlation coefficient −0.240; p&amp;lt;0.001), Eldery (Spearman's coefficient 0.425; p&amp;lt;0.001), Abnormal creatinine level (Spearman's coefficient 0.528; p&amp;lt;0.001), Diabetes mellitus (57 vs. 51 ng/mL; p=0.006). NGAL levels are singificantly higher in patients with higher AHEAD score. Mean level of NGAL in AHEAD 0–1 (N=320) is 51 ng/mL, in AHEAD 2–3 (N=190) is 78 ng/mL and in AHEAD 4–5 (N=37) is 142 ng/mL (Kruskal-Wallis test p&amp;lt;0.001, pairwise comparision all &amp;lt;0.001). Conclusion In stable chronic heart failure registry FAR NHL, comorbidity score AHEAD can predict events. Serum NGAL level is significantly higher when AHEAD score comorbidities are present: Atrial fibrillation, low Haemoglobin, Eldery, Abnormal renal function and Diabetes mellitus. Funding Acknowledgement Type of funding source: None

Prognostic value of health-related quality of life in patients with acute dyspnea

Abstract Background Previous studies have shown the prognostic value of health-related quality of life (HRQL) in stable and ambulatory chronic heart failure patients. However, it is unknown whether HRQL can predict all-cause mortality in patients presenting to the emergency department (ED) after acute onset of symptoms. In order to address this unmet need, the aim of this study was to assess the prognostic value of HRQL in patients with acute dyspnea caused by acute heart failure (AHF) and other dyspnea aetiologies for 360-day mortality. Purpose To assess prognostic value of HRQL using the generic EQ-5D and visual analogue scale (EQ VAS) in patients with acute dyspnea. Methods Basics in Acute Shortness of Breath EvaLuation (BASEL V) is a prospective, multicenter, diagnostic study enrolling adult patients presenting with acute dyspnea to the ED. For this analysis, only patients with a complete set of variables necessary for calculation of EQ-5D (range 0–10; with higher score indicating worse HRQL) and EQ VAS (range 0–100; with 100 being the best imaginable health state) at baseline were included. The endpoint was the prognostic value of EQ-5D and EQ VAS at 360 days of follow-up regarding all-cause death. Prognostic accuracy was calculated using c-statistics. In a cox regression analysis EQ-5D was treated as both, a continuous and categorical variable. Adjustments were made for clinically relevant covariates (age, sex, orthopnoea, edema, level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) at presentation, history of coronary artery disease and chronic obstructive pulmonary disease, diuretics, β-blockers and ACE-inhibitors at discharge). Results Among 2605 patients enrolled, 1141 (43,8%) had a complete set of variables allowing the calculation of EQ-5D and EQ VAS. Of these patients 594 (52.1%) had an adjudicated final diagnosis of AHF. 211 (18.5%) patients died within 360 days of follow-up. Median EQ-5D was 3 (interquartile range (IQR) 1.5–5) and median EQ VAS was 50 (IQR 40–70). The prognostic accuracy for 360-day mortality was 0.65 (95% confidence interval ((CI) 0.61–0.69) and 0.58 (95% CI 0.54–0.62) for EQ-5D and EQ VAS, respectively (p=0.002). After combining EQ-5D and EQ VAS in a logistic regression model c-statistics regarding all-cause mortality within 360 days did not improve. The prognostic accuracy of EQ-5D was comparable to that of NT-proBNP (c-statistics 0.69, p=0.385). In an adjusted cox regression analysis the hazard ratio for patients with EQ-5D &amp;gt;4 was 2.2 (95% CI 1.7–2.9; p&amp;lt;0.001). Conclusions In patients presenting with acute dyspnea HRQL is a strong prognostic instrument. Independently of the aetiology of the dyspnea the prognostic value of the generic EQ-5D for 360-day mortality is comparable to NT-proBNP. Patients with an EQ-5D &amp;gt;4 are at significantly higher risk for mortality within 360 days. Figure 1. Prognostic value of HRQL Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation, Swiss Heart Foundation

Compression therapy for leg oedema in patients with heart failure.

The presence of chronic heart failure (CHF) results in a significant risk of leg oedema. Medical compression (MC) treatment is one of the basic methods of leg oedema elimination in patients with chronic venous disease and lymphedema, but it is not routinely considered in subjects with CHF‐related swelling. In the study, an overview of the current knowledge related to the benefits and risk of using MC in the supportive treatment of leg oedema in CHF patients is presented. The available studies dedicated the comprehensive management of leg swelling using MC in CHF patients published in the English language literature till December 2019 were evaluated in term of the treatment efficacy and safety. In studies performed on CHF populations, manual lymphatic drainage, MC stocking, multilayer bandaged, as well as intermittent pneumatic compression or electric calf stimulations were used. The current evidence is based on non‐randomized studies, small study cohorts, as well as very heterogenous populations. The use of the intermittent pneumatic compression in CHF patients significantly increases the right auricular pressure and mean pulmonary artery pressures as well as decreases systemic vascular resistance in most patients without the clinical worsening. The transient and rapid increase in the human atrial natriuretic peptide, after an application of the MC stocking in New York Heart Association (NYHA) class II patients was observed without clinical exacerbation. An application of the multilayer bandages in NYHA classes III and IV patients lead a significant increase in the right arterial pressure and lead to transient deterioration of the right and the left ventricular functions. In the manual lymphatic drainage study, aside from expected leg circumference reduction, no clinical worsening was observed. In a pilot study performed in a small cohort of CHF patients, electrical calf stimulation use resulted in a reduction in the lean mass of the legs without cardiac function worsening. The use of local leg compression can be considered stable CHF patients without decompensated heart function for both CHF‐related oedema treatment and for treatment of the concomitant diseases leading to leg swelling occurrence. The use of MC in more severe classes of CHF (NYHA III and IV) should be the subject of future clinical studies to select the safest and most efficient compression method as well as to select the patients who benefit most from this kind of treatment.

Hypoalbuminemia as a marker of protein metabolism disarrangement in patients with stable chronic heart failure.

Despite therapeutic advances, chronic heart failure (CHF)-related mortality and hospitalization is still unacceptably high. Evidence shows that muscular wasting, sarcopenia, cachexia are independent predictors of mortality and morbidity in CHF and are signs of protein metabolism disarrangement (PMD), which involve all body proteins including circulating one. We postulate that circulating human serum albumin (HSA) could be a marker of PMD and catabolic low-grade inflammation (LGI) in CHF patients. One hundred sixty-six stable CHF patients (73% males), with optimized therapy referred to cardiac rehabilitation, were retrospectively divided into three groups based on their HSA concentration: ≥3.5 g/dL (normal value), 3.2-3.49 g/dL (low value); ≤3.19 g/dL (severe value). Hematochemical analyses (including circulating proteins and inflammatory markers) and body mass composition (by Bioelectrical Impedance Vector Analysis) were collected and compared. Correlations and multivariate regression were performed. Despite being overweight (BMI=27 kg/m2), 75% of patients had reduced HSA (<3.5 g/dL) with suspectable sarcopenia, and 35% of all patients had remarkably lower albumin concentrations (<3.19 g/dL). Hypoalbuminemic patients were disable, older, with reduced muscular proteins, bilirubin and hemoglobin, increased extracellular water and LGI (P<0.01). HSA correlated with all of these parameters (all: P<0.01). Age, LGI, BMI, free-fat Mass, and bilirubin were independent predictors of HSA concentration. All these findings were male-dependent. HSA could be considered a simple marker of PMD and LGI in CHF patients. Evaluation of PMD and gender differences should be considered in new CHF clinical trials.