Chronic Heart Failure Population Research Articles

Examining health-related quality of life in ambulatory adult patients with chronic heart failure: insights from Malaysia using EQ-5D-5L.

Health-related quality-of-life (HRQoL) data for the chronic heart failure (HF) population in Malaysia are lacking. Using EQ-5D-5L, this study intended to describe their HRQoL, identify predictors of worse HRQoL, and derive EQ-5D-5L index scores for use in economic evaluations. A cross-sectional survey was conducted between April and September 2023 to collect EQ-5D-5L, sociodemographic, and clinical data from outpatients with HF across seven public specialist hospitals in Malaysia. Multivariable logistic and linear regression models were used to identify independent predictors of reported problems in the EQ-5D-5L dimensions, and predictors of index scores and EQ-VAS, respectively. EQ-5D-5L data from 424 outpatients of multi-ethnic background (mean age: 57.1years, 23.8% female, mean left ventricular ejection fraction: 35.7%, 89.7% NYHA class I-II) were collected using either Malay, English, or Chinese, achieving a 99.8% completion rate. Nearly half of the respondents reported issues in the Mobility, Usual Activities, and Pain/Discomfort dimensions. Mean EQ-5D-5L index was 0.820, lower than the general population, and significantly lower with NYHA class III-IV (0.747) versus NYHA class I (0.846) and NYHA class II (0.805). Besides NYHA class, independent predictors of worse HRQoL included Indian ethnicity, living alone, lower education, unemployment due to ill-health, and proxy-reported HRQoL, largely aligning with existing literature. Community-dwelling Malaysians with HF reported poorer HRQoL compared to the general population. The observed disparities in HRQoL among HF patients may be linked to specific patient characteristics, suggesting potential areas for targeted interventions. HRQoL assessment using EQ-5D-5L proves feasible and should be considered for routine implementation in local clinics.

Cost Effectiveness of Dapagliflozin for Heart Failure Across the Spectrum of Ejection Fraction: An Economic Evaluation Based on Pooled, Individual Participant Data From the DELIVER and DAPA-HF Trials.

The sodium glucose cotransporter-2 inhibitors are guideline-recommended to treat heart failure across the spectrum of left ventricular ejection fraction; however, economic evaluations of adding sodium glucose cotransporter-2 inhibitors to standard of care in chronic heart failure across a broad left ventricular ejection fraction range are lacking. We conducted a US-based cost-effectiveness analysis of dapagliflozin added to standard of care in a chronic heart failure population using pooled, participant data from the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials. The 3-state Markov model used estimates of transitional probabilities, effectiveness of dapagliflozin, and utilities from the pooled trials. Costs estimates were obtained from published sources, including published rebates in dapagliflozin cost. Adding dapagliflozin to standard of care was estimated to produce an additional 0.53 quality-adjusted life years (QALYs) compared with standard of care alone. Incremental cost effectiveness ratios were $85 554/QALY when using the publicly reported full (undiscounted) Medicare cost ($515/month) and $40 081/QALY, at a published nearly 50% rebate ($263/month). The addition of dapagliflozin to standard of care would be of at least intermediate value (<$150 000/QALY) at a cost of <$872.58/month, of high value (<$50 000/QALY) at <$317.66/month, and cost saving at <$40.25/month. Dapagliflozin was of at least intermediate value in 92% of simulations when using the full (undiscounted) Medicare list cost in probabilistic sensitivity analyses. Cost effectiveness was most sensitive to the dapagliflozin cost and the effect on cardiovascular death. The addition of dapagliflozin to standard of care in patients with heart failure across the spectrum of ejection fraction was at least of intermediate value at the undiscounted Medicare cost and may be potentially of higher value on the basis of the level of discount, rebates, and price negotiations offered. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01035255 & NCT01920711.

Role of dietary sodium restriction in chronic heart failure: systematic review and meta-analysis

BackgroundDietary sodium restriction remains a guidelines-approved lifestyle recommendation for chronic heart failure (CHF) patients. However, its efficacy in clinical outcome improvement is dubious.ObjectiveThe study evaluated whether dietary sodium restriction in CHF reduces clinical events.MethodsWe performed a systematic review of the following databases: Academic Search Ultimate, ERIC, Health Source Nursing/Academic Edition, MEDLINE, Embase, Clinicaltrials.gov and Cochrane Library (trials) to find studies analysing the impact of sodium restriction in the adult CHF population. Both observational and interventional studies were included. Exclusion criteria included i.e.: sodium consumption assessment based only on natriuresis, in-hospital interventions or mixed interventions—e.g. sodium and fluid restriction in one arm only. The review was conducted following PRISMA guidelines. Meta-analysis was performed for the endpoints reported in at least 3 papers. Analyses were conducted in Review Manager (RevMan) Version 5.4.1.ResultsInitially, we screened 9175 articles. Backward snowballing revealed 1050 additional articles. Eventually, 9 papers were evaluated in the meta-analysis. All-cause mortality, HF-related hospitalizations and the composite of mortality and hospitalisation were reported in 8, 6 and 3 articles, respectively. Sodium restriction was associated with a higher risk of the composite endpoint (OR 4.12 [95% CI 1.23–13.82]) and did not significantly affect the all-cause mortality (OR 1.38 [95% CI 0.76–2.49]) or HF hospitalisation (OR 1.63 [95% CI 0.69–3.88]).ConclusionsIn a meta-analysis, sodium restriction in CHF patients worsened the prognosis in terms of a composite of mortality and hospitalizations and did not influence all-cause mortality and HF hospitalisation rate.Graphical abstract

Estimating cardiorespiratory fitness in heart failure patients with self-reported questionnaires

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiorespiratory fitness (CRF), assessed by peak oxygen uptake (VO2peak), is a powerful predictor of cardiovascular morbidity and mortality. However, performance of a cardiopulmonary exercise test (CPET) is often not feasible or desirable in (older) frail patients, because of physical limitations, transport difficulties, costs and the additional exposure to risks. Other CRF assessment tools, such as questionnaires, are potential alternatives, but have not been validated in frail elderly populations with chronic cardiovascular disease. Purpose The purpose of this study was to investigate the accuracy of two self-reported questionnaires, the FitMáx©-questionnaire and The Fitness Calculator, for assessment of CRF in chronic heart failure (CHF) patients. Methods CHF patients referred for CPET as part of a cardiac rehabilitation programme were eligible for the study. VO2peak was measured with a symptom limited maximal CPET. Participants completed two questionnaires to estimate VO2peak: the FitMáx-questionnaire and The Fitness Calculator. The FitMáx-questionnaire consists of three questions on walking, cycling and climbing stairs [1], and The Fitness Calculator is based on the HUNT3 study [2] and is currently advised by the American heart association as a non-exercise estimate for CRF [3]. Results 29 CHF patients (21 men, 64.2 years ± 12.0) were included with mean VO2peak of 15.7 ± 4.2 mL/kg/min at CPET. Correlation analysis indicated a moderate association between VO2peak assessed by the FitMáx-questionnaire and measured by CPET (r = 0.52) with a mean bias of 1.7 mL/kg/min (95% CI -6.0 – 9.4, p = 0.03). No association was found between VO2peak assessed by CPET and The Fitness Calculator (r = 0.24), mean bias 14.6 mL/kg/min (95% CI -0.5 – 29.7, p &amp;lt;.01). Conclusion The FitMáx©-questionnaire is a moderately accurate tool for estimating CRF in the CHF population. For use in individual patients, efforts should be made to improve the accuracy in this specific patient group. To establish its clinical utility, additional research is needed to evaluate its reproducibility and sensitivity to detect interventional changes in this population.

Phenotypic patient profiling for improved implementation of guideline-directed medical therapy: An exploratory analysis in a large real-world chronic heart failure cohort.

Aims: Implementation of guideline-recommended pharmacological treatment in heart failure (HF) patients remains challenging. In 2021, the European Heart Failure Association (HFA) published a consensus document in which patient profiles were created based on readily available patient characteristics and suggested that treatment adjusted to patient profile may result in better individualized treatment and improved guideline adherence. This study aimed to assess the distribution of these patient profiles and their treatment in a large real-world chronic HF cohort. Methods and results: The HFA combined categories of heart rate, blood pressure, presence of atrial fibrillation, chronic kidney disease, and hyperkalemia into eleven phenotypic patient profiles. A total of 4,455 patients with chronic HF and a left ventricular ejection fraction ≤40% with complete information on all characteristics were distributed over these profiles. In total, 1,640 patients (36.8%) could be classified into one of the HFA profiles. Three of these each comprised >5% of the population and consisted of patients with a heart rate >60 beats per minute with normal blood pressure (>90/60mmHg) and no hyperkalemia. Conclusion: Nearly forty percent of a real-world chronic HF population could be distributed over the eleven patient profiles as suggested by the HFA. Phenotype-specific treatment recommendations are clinically relevant and important to further improve guideline implementation.

Early repolarization pattern on ECG predicts worse outcomes in patients hospitalized due to chronic heart failure decompensation

BackgroundTo improve the outcomes of patients with chronic heart failure (CHF), it is important to identify reliable prognostic tools. Early repolarization pattern (ER) on 12‑lead electrocardiogram (ECG) is a predictor of worse outcomes, which has been widely researched in the general population but not in the CHF population. ObjectiveTo evaluate the incidence and prognostic value of ER and compare its prognostic significance with other non-invasive diagnostic methods for CHF outcomes and hospital readmissions. MethodsThe study included 301 patients (166 men and 135 women) hospitalized for CHF decompensation. CHF diagnosis was confirmed according to the current guidelines. The patients underwent standard tests and impedance cardiography (ICG) at enrollment and on the day of discharge. ResultsThirty-one confirmed ER cases (10.3%) were enrolled. During a median follow-up period of 18 months, 128 cardiac-related deaths were observed (42.5%), with 23 (74.2%) and 105 (38.9%) patients in the ER and non-ER groups, respectively (p < 0.001). The ER group had more readmissions than the non-ER group did at 6-months (2 [1, 2] vs. 1 [1, 2]; p=0.04) and 12-months (3 [2–4] vs. 2 [1–3]; p<0.001). ER on ECG (hazard ratio [HR] 2.59; 95% confidence interval [CI] 1.64–4.07; p<0.001), N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels ≥425.5 pmoL/L (HR 5.1; 95% CI 3.33–7.83; p < 0.001), thoracic fluid content (TFC) ≥36.9 1/kΩ (HR 4.6; 95% CI 2.7–7.85, p < 0.001), and left ventricular ejection fraction (LVEF) ≤40% (HR 4.94; 95% CI 2.83–8.65; p < 0.001) were independently and significantly associated with cardiac death. ConclusionsThe combination of ER, LVEF ≤40%, NT-proBNP, or TFC provides an incremental prognostic value for cardiac-related death in patients with CHF.

Data-driven, patient-specific simulations of long-term heart rate variability and cardiac alternans formation.

Individuals suffering from chronic heart failure (CHF) have a greater risk for death mediated by ventricular arrhythmias, which may be related to changes in heart rate. Heart rate constantly fluctuates from beat-to-beat on a timescale ranging from seconds to hours under physiological conditions, termed heart rate variability (HRV). Individuals with CHF have reduced HRV and faster heart rates, both of which influence the formation of pro-arrhythmic alternans, a beat-to-beat alternation in the action potential duration (APD) and intracellular calcium (Ca) levels. It is unclear how long-term changes in heart rate influence alternans and arrhythmia formation. We obtained sequences of RR intervals (time between successive R waves in an electrocardiogram) from individuals with normal sinus rhythm (NSR) and CHF from a Physionet database. These RR-sequences are used to define the pacing period for a discrete-time coupled map model of APD and intracellular Ca cycling for a single cardiac myocyte, modified to account for human heart rates and pathological Ca-remodeling in CHF. These modifications include fitting human ventricular myocyte APD restitution parameters, including a new term for Ca leak from the sarcoplasmic reticulum (SR), and scaling SR Ca-related parameters. Importantly, this minimal model enables simulation of long-term trends, on the order of 24 hours, in large populations. We find that the alternations in APD and Ca vary over time, such that there are periods with both small and large beat-to-beat differences in both populations. However, the CHF population tends to have a larger alternations magnitude, demonstrating that CHF-associated heart rates promotes more pro-arrhythmic phenomena. Future work will extend this methodology to determine what statistical properties govern the CHF RR-sequences, and further to test to what extent pro-arrhythmic alternans depends on CHF-related changes in heart rate or remodeling.

Using the 6-minute walking test to evaluate the effect of high-intensity interval training on the functional capacity in heart failure patients: a systematic review and meta-analysis

Abstract Background Determining the effect of training on exercise capacity in chronic heart failure (CHF) patients is mainly done by measuring peak oxygen uptake (VO2 peak) through cardiopulmonary exercise testing (CPET) [1,2]. However, CPET is not always available, especially in low-and middle-income countries. On the contrary, the 6-minute walk test (6MWT), a simpler and inexpensive alternative can be utilized, even in low resource settings [2,3]. Moderate continuous intensity training (MCIT) is commonly recommended in CHF patients [4], but growing evidence demonstrates the superior benefits of high-intensity interval training (HIIT) on the exercise capacity [5,6]. However, the benefits are predominantly measured with the CPET and expressed in VO2 peak [1,2]. Especially for low resource settings, there is a need for studies describing the effect of HIIT in CHF patients using the 6MWT as an outcome measure. To the best of our knowledge, there is no systematic review on the effect of HIIT in CHF patients, measured solely with the 6MWT. Purpose This study aims to synthesize the literature on the effect of HIIT on the exercise capacity using the 6MWT in CHF patients. Methods We systematically searched within the PubMed, EBSCOhost, Cochrane and PEDro electronic databases to identify randomized controlled trials published until August 2020 with no date of publication or language restrictions. We included studies that met the following criteria: 1) a randomized controlled trial; 2) performed in a CHF population; 3) the use of the 6MWT as an outcome measure with a pre-and post-exercise measurement of the distance; 4) HIIT without the combination of another type of exercise training. The funnel plot was used to estimate publication bias and the Tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEX) was used for quality assessment [7]. Results We found 169 studies, of which 164 were excluded for not meeting inclusion criteria, resulting in the inclusion of five studies (n=315, mean age = 61 years, 71.4% male). Three studies (n=163, mean age=58 years, 64.4% % male) used MCIT and two studies (n=152, mean age = 65 years, 78.5% male) usual care as the control group. The HIIT showed significant improvements on 6MWT distance (MD= 40.78 m; 95% CI 24.55–57.01; p value &amp;lt;0.00001; I2=56%) compared to control groups (Figure 1). The funnel plot (Figure 2) shows asymmetry upon visual examination and could indicate presence of publication bias. The quality assessment score was between 10–12 points with an overall median score of 11.2. Conclusions The distance on the 6MWT significantly improves with HIIT compared to sedentary controls and MCIT. However, our results are based on a small number of studies with heterogeneity across the control groups. Nevertheless, this study does provide information for physical therapist from low-resource settings about the expected effect on the 6MWT, when providing HIIT to CHF patients. Funding Acknowledgement Type of funding sources: None.

Oral iron supplementation in patients with heart failure: a systematic review and meta-analysis.

This review aimed to assess whether oral iron supplementation in a chronic heart failure (HF) population with iron deficiency (ID) or mild anaemia is safe and effective according to evidence-based medicine. We retrieved 1803 records from the PubMed, Embase, and the Cochrane Library databases from 1 January 1991 to 15 September 2021. The clinical outcome of oral iron supplementation for ID anaemia in patients with HF was the primary endpoint. The primary safety measures included adverse events and all-cause mortality, and efficacy measures included transferrin saturation (Tsat), ferritin levels, and the 6-min walk test (6MWT). The rate ratio (RR) was used to pool the efficacy measures. Five randomized controlled trials that compared oral iron treatment for patients with the placebo group and included a combined total of 590 participants were analysed. No significant difference was found in all-cause death between oral iron treatment and placebo groups (RR = 0.77; 95% confidence intervals (CI), 0.46-1.29, Z = 0.98; P = 0.33). However, adverse events were not significantly higher in the iron treatment group (RR = 0.83; 95% CI, 0.60-1.16, Z = 1.07; P = 0.28). In addition, ferritin levels and Tsat were slightly increased after iron complex administration in patients with HF but were not statistically significant (ferritin: mean difference [MD] = 2.70, 95% CI, -2.41 to 7.81, Z = 1.04; P = 0.30; Tsat: MD = 27.42, 95% CI, -4.93 to 59.78, Z = 1.66; P = 0.10). No significant difference was found in exercise capacity, as indicated by the 6MWT results (MD = 59.60, 95% CI, -17.89 to 137.08, Z = 1.51; P = 0.13). We also analysed two non-randomized controlled trials with follow-up results showing that oral iron supplementation increased serum iron levels (MD = 28.87, 95% CI, 1.62-56.12, Z = 2.08; P = 0.04). Based on the current findings, oral iron supplementation can increase serum iron levels in patients with HF and ID or mild anaemia but does not improve Tsat and 6MWT. In addition, oral iron supplementation is relatively safe.

Performance of a HeartLogicTM Based Care Path in the Management of a Real-World Chronic Heart Failure Population

AimEarly detection of impending fluid retention and timely adjustment of (medical) therapy can prevent heart failure related hospitalizations. The multisensory cardiac implantable electronic device (CIED) based algorithm HeartLogicTM aims to alert in case of impending fluid retention. The aim of the current analysis is to evaluate the performance of the HeartLogicTM guided heart failure care path in a real-world heart failure population and to investigate whether the height of the index and the duration of the alert state are indicative of the degree of fluid retention.MethodsConsecutive adult heart failure patients with a CIED and an activated HeartLogicTM algorithm were eligible for inclusion. Patients were followed up according to the hospital's heart failure care path. The device technician reviewed alerts for a technical CIED checkup. Afterwards, the heart failure nurse contacted the patient to identify impending fluid retention. An alert was either true positive or false positive. Without an alert a patient was true negative or false negative.ResultsAmong 107 patients, [82 male, 70 (IQR 60–77) years, left ventricular ejection fraction 37 ± 11%] 130 HeartLogicTM alerts were available for analysis. Median follow up was 14 months [IQR 8–23]. The sensitivity to detect impending fluid retention was 79%, the specificity 88%. The positive predictive was value 71% and the negative predictive value 91%. The unexplained alert rate was 0.23 alerts/patient year and the false negative rate 0.17 alerts/patient year. True positive alerts [42 days (IQR 28–63)] lasted longer than false positive alerts [28 days (IQR 21–44)], p = 0.02. The maximal HeartLogicTM index was higher in true positive alerts [26 (IQR 21–34)] compared to false positive alerts [19 (IQR 17–24)], p < 0.01. Patients with higher HeartLogicTM indexes required more intense treatment (index height in outpatient setting 25 [IQR 20–32], day clinic treatment 28 [IQR 24–36] and hospitalized patients 45 [IQR 35–58], respectively), p < 0.01.ConclusionThe CIED-based HeartLogicTM algorithm facilitates early detection of impending fluid retention and thereby enables clinical action to prevent this at early stage. The current analysis illustrates that higher and persistent alerts are indicative for true positive alerts and higher index values are indicative for more severe fluid retention.

LRP6 Polymorphisms Is Associated With Sudden Cardiac Death in Patients With Chronic Heart Failure in the Chinese Han Population.

Low-density lipoprotein receptor-related protein 6 (LRP6) plays a critical role in cardiovascular homeostasis. The deficiency of LRP6 is associated with a high risk of arrhythmias. However, the association between genetic variations of LRP6 and sudden cardiac death (SCD) remains unknown. This study aims to explore the association between common variants of LRP6 and the prognosis of chronic heart failure (CHF) patients. From July 2005 to December 2009, patients with CHF were enrolled from 10 hospitals in China. The single-nucleotide polymorphism (SNP) rs2302684 was selected for the evaluation of the effect of LRP6 polymorphisms on the survival in patients with CHF. A total of 1,437 patients with CHF were finally included for the analysis. During a median follow-up of 61 months (range 0.4–129 months), a total of 546 (38.0%) patients died, including 201 (36.8%) cases with SCD and 345 (63.2%) cases with non-SCD. Patients carrying A allele of rs2302684 had an increased risk of all-cause death (adjusted HR 1.452, 95% CI 1.189–1.706; P < 0.001) and SCD (adjusted HR 1.783, 95% CI 1.337–2.378; P < 0.001). Therefore, the SNP rs2302684 T>A in LRP6 indicated higher risks of all-cause death and SCD in patients with CHF. LRP6 could be added as a novel predictor of SCD and might be a potential therapeutic target in the prevention of SCD in the CHF population.

Left atrial strain predicts exercise capacity in heart failure independently of left ventricular ejection fraction.

AimsWe hypothesized that left atrial (LA) remodelling and function are associated with poor exercise capacity as prognostic marker in chronic heart failure (CHF) across a broad range of left ventricular ejection fraction (LVEF).Methods and resultsOne hundred seventy‐one patients with CHF were analysed [age 65 ± 11 years, 136 males (80%); 86 heart failure with reduced ejection fraction (HFrEF), 27 heart failure with mid‐range ejection fraction (HFmrEF), 58 heart failure with preserved ejection fraction (HFpEF)]. All patients underwent echocardiography and maximal cardiopulmonary exercise testing and were classified according to a prognostic cut‐off of peak VO2 (pVO2; 14 mL/kg/min). Seventy‐seven (45%) patients reached pVO2 < 14 and 94 (55%) pVO2 ≥ 14 mL/kg/min. Between the two groups, there was a considerable difference in both left atrial volume (LAVi, 53 ± 24 vs. 44 ± 18 mL/m2, P = 0.005) and function (LA reservoir strain 12 ± 5 vs. 20 ± 10%, P < 0.0001). Receiver‐operating characteristic curves identified LA reservoir strain (area under the curve: 0.73 [0.65–0.80], P < 0.0001) as strong predictor for impaired pVO2 among all echocardiographic variables; LA reservoir strain < 23% had 37% specificity but a very high sensitivity (96%) in identifying a severely reduced pVO2. In logistic regression analysis, LA reservoir strain < 23% was associated with a highly increased risk of pVO2 < 14 mL/kg/min (odds ratio 16.0 [4.7–54.6]; P < 0.0001). The multivariate analysis showed that a reduced LA reservoir strain was associated with pVO2 < 14 mL/kg/min after adjustment for age, body mass index (BMI), and clinical variables, that is, New York Heart Association class, atrial fibrillation, haemoglobin, and creatinine (b 0.22 [95% confidence interval, CI, 0.12–0.31]; P < 0.0001), and after adjustment for echocardiographic variables, that is, LVEF or left ventricular global longitudinal strain (LVGLS) and tricuspid annular plane systolic excursion (TAPSE) (b 0.16 [95% CI 0.08–0.24]; P < 0.0001). Patients with HFrEF, HFmrEF, and HFpEF were separately analysed. Among LA reservoir strain, LAVi, LVEF, LVGLS, and TAPSE, LA reservoir strain was the only one significantly associated with pVO2 in all subgroups (after adjustment for sex and BMI, P = 0.003, 0.04, and 0.01, respectively).ConclusionsIn patients with CHF, an impaired LA reservoir function is independently associated with a severely reduced pVO2. LA dysfunction represents a marker of poor prognosis across LVEF borders in the CHF population.

Properties of Two While-Alive Estimands for Recurrent Events and Their Potential Estimators

Chronic diseases are often characterized through the repeated occurrence of unfavorable events. In chronic heart failure (CHF), recurrent hospitalizations characterize disease burden but the risk of death is not negligible. This leads to two main challenges. First, the definition of a clinically interpretable treatment effect measure (estimand) needs careful attention. Second, finding suitable analysis methods (estimators) that target the estimand of interest is difficult. In this article,we study the two estimands using the while-alive strategy described by Schmidli et al. For realistic CHF populations based on joint frailty model assumptions, we calculate the estimand values analytically and discuss their clinical interpretability. We also show that quasi-Poisson regression leads to an asymptotically unbiased estimator for the two estimands using the while-alive strategy, and that Lin-Wei-Yang-Ying is asymptotically unbiased under constant event rate conditional on being alive, by both analytic derivation and numerical simulations. We also investigate these estimators, together with the method-of-moments-estimator, in two CHF clinical trials. The findings in this article support the claim that treatment effect measures can be defined based on recurrent event endpoints that are clinically interpretable and statistically estimable.

Clinical and prognostic significance of the inflammatory markers GlycA and GlycB in chronic heart failure of both ischemic and non-ischemic etiologies

Abstract Background N-acetylglucosamine/galactosamine (GlycA) and sialic acid (GlycB) constitute evolving nuclear magnetic resonance (NMR) biomarkers of systemic inflammation. They have been increasingly studied and associated with cardiovascular (CV) disease and incident heart failure (HF), but little is known about its value in chronic HF population. Purpose We aimed to examine the association on long-term CV outcomes of GlycA and GlycB in chronic HF relative to aetiology. Methods We prospectively included a cohort of 429 HF patients admitted to an ambulatory HF Unit. Plasma GlycA and GlycB concentrations were determined using NMR spectroscopy. The primary endpoint was a composite of CV death and readmission due to HF. Competing risk regression models were performed with non-CV death as the competing event. Because an interaction existed between GlycA and GlycB with ischemic etiology (p&amp;lt;0.01), we examined this further. Results The mean (SD) follow-up was 4.5±2.9 years. Median concentrations (IQR) for GlycA and GlycB were 5.4 (4.9–6.2) mmol/L and 1.9 (1.7–2.2) mmol/L, respectively. A total of 92 (41.1%) and 123 (60.0%) patients from non-ischemic and ischemic etiology, respectively, the clinical endpoint. In ischaemic HF patients (47.8%; n=205) both markers were not associated with the primary endpoint. Conversely, in non-ischemic HF patients (52.2%; n=224), GlycA and GlycB exhibited association with the primary endpoint in univariable and after multivariable adjustment (HR 1.14; 95% confidence interval [CI]: 1.02–1.28, p=0.018 and HR 1.91; 95% CI: 1.27–2.88, p=0.002; respectively. Figure 1 and 2). In this subgroup, a correlation analysis with well-known biomarkers (NT-proBNP, hs-TnT and ST2) only evidenced a positively and significantly correlation of GlycB with ST2 (r=0.26, p&amp;lt;0.001). No association was found with NYHA functional class. Conclusions GlycA and GlycB represent an evolving approach of inflammation status with prognostic value of long-term CV related events in non-ischemic HF patients. Funding Acknowledgement Type of funding sources: None. Figure 1. Probability of MACE by GlycA tertilesFigure 2. Probability of MACE by GlycB tertiles

Performance of the multisensory cardiac implantable electronic device algorithm HeartLogic in a real-world ambulant chronic heart failure population

Abstract Background Early detection of an upcoming episode of decompensated heart failure (HF) and timely adjustment of medical therapy may prevent a HF hospitalization. The novel multisensory cardiac implantable electronic device (CIED) based algorithm entitled HeartLogic™ (HL) aims to alert in case of upcoming fluid retention. This study investigates the performance of an HL alert in chronic HF patients in an ambulant HF care-path. Methods All chronic HF patients with a CIED and an activated HL algorithm implanted in our centre since 2018 were included. Patients were followed from 01–01–2018 until 01–02–2021 according to the HL-based care-path (Figure 1). The HL index was automatically generated from sensors assessing S3, S3/S1, thoracic impedance, respiratory- and night heartrate. Indexes were monitored continuously and an alert was issued when the pre-set threshold of 16 was surpassed. An alert was classified as true positive when the patient had at least two symptoms and/or signs of congestion during the alert episode. An alert was considered false positive when the patient had not more than one symptom or sign of congestion during the alert episode. If a patient had at least two symptoms and/or signs of congestion without an HL alert, the episode was classified as false negative. Results In total, 100 patients (median age 69 years [IQR 60–77], 78% male) were included. The etiology of HF was ischemic in 45% and 71% had a CRT-D device. Median follow-up was 13 months [IQR 6–23] and in total the follow-up comprised 126 patient-years. In 56 patients, there were 132 alerts, mean alert rate was 1.05 per patient-year. As it was unfeasible to strictly follow the specific HL care-path in 13 alert episodes, these alerts were excluded from further analyses. Based on the remaining 119 alert episodes, the positive predictive value for early detection of congestion was 77% and the negative predictive value was 97%. Sensitivity was 79% and specificity 97%. Conclusion In a real-world HF population, the HL algorithm can accurately predict an upcoming episode of decompensated heart failure. Funding Acknowledgement Type of funding sources: None. Overview of the HL based care-path

Inflammation-Related Biomarkers Are Associated with Heart Failure Severity and Poor Clinical Outcomes in Patients with Non-Ischemic Dilated Cardiomyopathy.

Inflammation-related biomarkers are associated with clinical outcomes in mixed-etiology chronic heart failure populations. Inflammation-related markers tend to be higher in ischemic than in non-ischemic dilated cardiomyopathy (NI-DCM) patients, which might impact their prognostic performance in NI-DCM patients. Therefore, we aimed to assess the association of inflammation-related biomarkers with heart failure severity parameters and adverse cardiac events in a pure NI-DCM patient cohort. Fifty-seven patients with NI-DCM underwent endomyocardial biopsy. Biopsies were evaluated by immunohistochemistry for CD3+, CD45ro+, CD68+, CD4+, CD54+, and HLA-DR+ cells. Blood samples were tested for high-sensitivity C-reactive protein (hs-CRP), interleukin-6, tumor necrosis factor-α (TNF-α), soluble urokinase-type plasminogen activator receptor and adiponectin. During a five-year follow-up, twenty-seven patients experienced at least one composite adverse cardiac event: left ventricle assist device implantation, heart transplantation or death. Interleukin-6, TNF-α and adiponectin correlated with heart failure severity parameters. Patients with higher levels of interleukin-6, TNF-α, adiponectin or hs-CRP, or a higher number of CD3+ or CD45ro+ cells, had lower survival rates. Interleukin-6, adiponectin, and CD45ro+ cells were independently associated with poor clinical outcomes. All patients who had interleukin-6, TNF-α and adiponectin concentrations above the threshold experienced an adverse cardiac event. Therefore, a combination of these cytokines can identify high-risk NI-DCM patients.

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'?

Development and evaluation of physiologically based pharmacokinetic drug-disease models for predicting captopril pharmacokinetics in chronic diseases

The advancement in the processing speeds of computing machines has facilitated the development of complex physiologically based pharmacokinetic (PBPK) models. These PBPK models can incorporate disease-specific data and could be used to predict pharmacokinetics (PK) of administered drugs in different chronic conditions. The present study aimed to develop and evaluate PBPK drug-disease models for captopril after incorporating relevant pathophysiological changes occurring in adult chronic kidney disease (CKD) and chronic heart failure (CHF) populations. The population-based PBPK simulator Simcyp was used as a modeling and simulation platform. The visual predictive checks and mean observed/predicted ratios (ratio(Obs/pred)) of the PK parameters were used for model evaluation. The developed disease models were successful in predicting captopril PK in all three stages of CKD (mild, moderate, and severe) and CHF, as the observed and predicted PK profiles and the ratio(obs/pred) for the PK parameters were in close agreement. The developed captopril PBPK models can assist in tailoring captopril dosages in patients with different disease severity (CKD and CHF).

Position of Patients with Mid-Range Ejection Fraction in the General Chronic Heart Failure Population

The European society of cardiology guideline for the diagnosis and treatment of acute and chronic heart failure (CHF) in 2016 identified a new group of patients with mid-range left ventricular ejection fraction (LVEF) with reference interval in the range of 40-49 %. This review highlights the issues of epidemiology and etiology of CHF, outlines the echocardiographic portrait, biomarker profile and patients` dynamic phenotypes, considers the guidelines of their managements and the prognosis of the disease determiner’s factors. Special attention is paid to the peculiarities of the formation of this heterogeneous cohort of patients and the feasibility of expanding the existing CHF classification by introducing two transitional phenotypes.

FACE: Phenotyping analysis of chronic heart failure (CHF) patients with sleep disordered breathing (SDB) indicated for adaptive servoventilation (ASV): 2-year follow-up results

FACE collected real life clinical data and long-term follow-up (FU) in a CHF population with SDB eligible for ASV. We previously identified 6 clinically meaningful clusters using Latent class analysis. We investigate herein whether these clusters may have different morbi-mortality outcomes. Reduced (HFrEF), middle range (HFmrEF) and preserved (HFpEF) CHF classes were included. Eligible SDB were central sleep apnea (CSA), coexistent obstructive central SA not controlled under CPAP and CPAP emergent CSA. ASV was offered to all. Controls were patients who refused ASV at inclusion. Morbi-mortality events were collected for 2 years. Primary endpoint in the time-to event analysis was the first event of death, unplanned hospitalization for worsening HF or cardiac transplant. 503 patients were included in the ITT analysis at 2-year FU. ASV was protective for primary outcome ( P = 0.01, Fig. 1 A). Cluster behavior regarding primary outcome was different, the worst prognosis was for HFrEF with CSA ( Fig. 1 B). ASV did not benefit in the HFrEF with CSA or OSA clusters ( Fig. 1 C) but was protective for 2 clusters: obese HFpEF with CSA and severe hypoxemic patients with OSA ( Fig. 1 D). These results align with recent studies that showed no impact on morbi-mortality of ASV in HFrEF but a protective effect in two HFpEF clusters.