Congestive Heart Failure Group Research Articles

Role of ERK and NF-KB pathway in neurally mediated enhanced expression and traffcking of SGLT2 in congestive heart failure

Congestive heart failure (CHF) is characterized by the activation of neurohumoral systems concomitant with avid fluid retention. Recently we showed enhanced expression of sodium-glucose cotransporter 2 (SGLT2) in rats with CHF. However, the exact molecular mechanism linking enhanced sympathetic tone and enhanced expression and translocation of SGLT2 in CHF is not clear. The objective of this study was to investigate the role of enhanced sympathetic tone on the expression and traffcking of SGLT2 via activation of protein kinase A (PKA), extracellular signal-regulated kinases (ERK), and nuclear factor kappa B (NF-KB) in the renal cortex of CHF rats. Male Sprague Dawley rats were subjected to either the left coronary artery ligation for the CHF group or Sham surgery. Four weeks after surgery, expression of protein levels (PKA, ERK and NF-KB) were assessed by Western blotting, whereas the location of SGLT2 expression was determined by immunohistological and immunofluorescent staining in the cortical region of kidneys from Sham and CHF rats. Effect of exogenous norepinephrine (NE) (10μM for 24hrs) on expression and traffcking of SGLT2, phosphorylation of ERK and NF-KB in HK2 cells were examined in an in vitro model. Expression of SGLT2 was significantly enhanced in the renal cortex of rats with CHF versus Sham (0.83±0.06 vs. 0.58±0.02). Also, the translocation of SGLT2 was significantly enhanced towards the membrane in CHF rats (0.92±0.11 vs. 0.33±0.07). Phosphorylation of PKA (0.05±0.01 vs. 0.01±0.01), ERK (0.32±0.02 vs. 0.23±0.02) and NF-KB (0.71±0.14 vs. 0.08±0.06) were significantly enhanced in CHF compared to Sham. NE treatment significantly increased expression of SGLT2 (0.26±0.03 vs. 0.15±0.02), traffcking of SGLT2 (0.45 ± 0.09 vs. 0.15 ± 0.03) towards membrane, phosphorylation of ERK (0.38±0.05 vs. 0.14±0.02) and NF-KB (0.61±0.08 vs. 0.17±0.07) in HK2 cells. Thus, NE treatment enhanced the phosphorylation of ERK, NF-kB as well as traffcking of SGLT2. Immunohistological and immunofluorescent staining demonstrated increased expression of SGLT2 in the kidneys of rats with CHF. Similar results were observed in immunofluorescent staining of human kidney cells treated with NE. In conclusion, these findings indicate that NE activates ERK and NF-KB pathways which leads to enhanced traffcking and overexpression of SGLT2 in CHF. These results provide a molecular link between enhanced sympathetic tone, ERK and NF-KB pathway and the traffcking of SGLT2 to the luminal membrane of renal proximal tubular cells and consequent increase in sodium retention in rats with CHF. This study was funded by NIH R01-DK-129311. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Association of congestive heart failure (CHF) with incidence rates of enteric infections and gram-negative sepsis (GNS) in patients with hepato-pancreatico-biliary cancers (HPBCs).

567 Background: ChronicCHF leads to volume overload and can cause bowel wall edema. This may compromise local immune defense and promote increased translocation of gut bacteria into the blood.HPBCs can cause biliary tract obstruction which is also associated with bacteremia. Additionally, cancer treatments are associated with an increased risk of clostridium difficile infection (CDI), regardless of antibiotic exposure. While associations between cancer and increased infection rates are well-established, we questioned whether concomitant CHF increases this risk further in the HPBC population. We therefore investigated whether concomitant CHF and HPBC influenced CDI, other infectious gastroenteritis (IGE), GNS rates or all-cause-hospital mortality. Methods: A retrospective study was conducted by obtaining patients with HPBC through the application of specific ICD 10 codes from the National Inpatient Sample 2020, a large publicly available database of inpatient hospital stays incorporating data from hospitals across 48 U.S. states. Among this cohort, patients with chronic CHF were further identified by applying all CHF-specific ICD 10 codes. All patients with HPBC were divided into two groups, one with CHF (group A) and the other without CHF (group B). Outcomes were compared between the two groups using multivariate regression analysis (MVRA) adjusting for demographic factors, hospital-specific characteristics like location, bed size, etc., comorbidities including obesity, diabetes, hypertension, prior cardiovascular events, HIV, CKD, OSA, etc., prior coronary intervention/surgery as well as alcohol, smoking or substance use. Results: 211,790 patients were identified with HPBC. 40.55% were female. 18,955 patients (9.95%) were found to have chronic CHF. The incidence of GNS was higher in group A compared to group B in the MVRA (Adjusted (Ad) OR: 1.4, CI 1.07-1.95, p=0.015). However, there was no difference in the incidence rate of CDI between groups A and B (Ad OR: 1.0, CI 0.71-1.50, p=0.86). Similarly, the two groups had no difference in other IGE (Ad OR: 1.0, CI 0.71-1.37, p=0.96). All-cause hospital mortality was slightly higher in group A than group B but failed to reach statistical significance (Ad OR: 1.1, CI: 0.99-1.29, p=0.069). Conclusions: GNS was more common in patients with HPBC who also had comorbid chronic CHF. Future investigations may focus on the effect of increased GNS on outcomes beyond hospitalization, correlation between the severity of CHF and GNS as well as primary site of HPBC and infection risk. Based on this signal-finding analysis, it is postulated that early inter-disciplinary collaboration between oncology and cardio-oncology/cardiology may have special significance in the management of patients with chronic CHF and HPBCs, the latter of which already carries a dismal prognosis.

Neutrophil-to-lymphocyte ratio is increased in dogs with acute congestive heart failure secondary to myxomatous mitral valve disease compared to both dogs with heart murmurs and healthy controls.

To retrospectively evaluate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as a biomarker for severity and short-term outcomes of congestive heart failure (CHF) secondary to myxomatous mitral valve disease (MMVD) in dogs. 47 dogs with CHF secondary to MMVD, 47 dogs with presumptive preclinical MMVD, and 47 control dogs. Medical record data (signalment, physical examination findings, medical treatments instituted, American College of Veterinary Internal Medicine MMVD stage, length of hospitalization, outcome, and hospital re-presentation due to CHF) from March 2012 through March 2022 for each dog were collected. Statistical analyses were performed with Mann-Whitney, Spearman correlation, and Fisher exact tests. NLR (but not PLR) was significantly higher in dogs with CHF secondary to MMVD (6.41) compared to presumptive preclinical MMVD dogs (4.66; P < .001) and control dogs (3.95; P < .001). Dogs with higher NLR and PLR received significantly higher cumulative dosages of loop-diuretic therapy during hospitalization (ρ = 0.3, P = .04; and ρ = 0.4, P = .02, respectively). There was a positive association between NLR and duration of oxygen supplementation within the CHF group (ρ = 0.4; P = .01). The increased diuretic dose and time receiving oxygen supplementation may represent increased disease severity for which NLR (and to a lesser extent PLR) may serve as a readily available marker. The data presented provide information regarding some of the systemic inflammatory changes seen in CHF secondary to MMVD in dogs. Future research should include prospective, longitudinal studies to provide insight into the long-term prognostic value of NLR and PLR in dogs with CHF.

A simple approach to determine loss of physiological complexity in heart rate series

There are several ways to assess complexity, but no method has yet been developed for quantitatively calculating the ‘loss of fractal complexity’ under pathological or physiological states. In this paper, we aimed to quantitatively evaluate fractal complexity loss using a novel approach and new variables developed from Detrended Fluctuation Analysis (DFA) log-log graphics. Three study groups were established to evaluate the new approach: one for normal sinus rhythm (NSR), one for congestive heart failure (CHF), and white noise signal (WNS). ECG recordings of the NSR and CHF groups were obtained from PhysioNET Database and were used for analysis. For all groups Detrended Fluctuation Analysis scaling exponents (DFAα 1, DFAα 2) were determined. Scaling exponents were used to recreate the DFA log-log graph and lines. Then, the relative total logarithmic fluctuations for each sample were identified and new parameters were computed. To do this, we used a standard log-log plane to standardize the DFA log-log curves and calculated the differences between the standardized and expected areas. We quantified the total difference in standardized areas using parameters called dS1, dS2, and TdS. Our results showed that; compared to the NSR group, DFAα 1 was lower in both CHF and WNS groups. However, DFAα 2 was only reduced in the WNSgroup and not in the CHFgroup. Newly derived parameters: dS1, dS2, and TdS were significantly lowerin the NSR group compared to the CHF and WNS groups. The new parameters derived from the DFA log-log graphs are highly distinguishing for congestive heart failure and white noise signal. In addition, it may be concluded that a potential feature of our approach can be beneficial in classifying the severity of cardiac abnormalities.

Complexity analysis from EEG data in congestive heart failure: A study via approximate entropy.

Congestive heart failure (CHF) is a very complex clinical syndrome that may lead to ischemic cerebral hypoxia condition. The aim of the present study is to analyze the effects of CHF on brain activity through electroencephalographic (EEG) complexity measures, like approximate entropy (ApEn). Twenty patients with CHF and 18 healthy elderly people were recruited. ApEn values were evaluated in the total spectrum (0.2-47 Hz) and main EEG frequency bands: delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-11 Hz), alpha 2 (11-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-45 Hz) to identify differences between CHF group and control. Moreover, a correlation analysis was performed between ApEn parameters and clinical data (i.e., B-type natriuretic peptides (BNP), New York Heart Association (NYHA), and systolic blood pressure (SBP)) within the CHF group. Statistical topographic maps showed statistically significant differences between the two groups in the total spectrum and theta frequency band. Within the CHF group, significant negative correlations were found between total ApEn and BNP in O2 channel and between theta ApEn and NYHA scores in Fp1, Fp2, and Fz channels; instead, a significant positive correlation was found between theta ApEn and SBP in C3 channel and a nearly significant positive correlation was obtained between theta ApEn and SBP in F4 channel. EEG abnormalities in CHF are very similar to those observed in cognitive-impaired patients, suggesting analogies between the effects of neurodegeneration and brain chronic hypovolaemia due to heart disorder and underlying high brain sensitivity to CHF.

Catheter ablation improved ejection fraction in persistent AF patients: a DECAAF-II sub analysis.

The aim of our study was to assess differences in post-ablation atrial fibrillation (AF) recurrence and burden and to quantify the change in LVEF across different congestive heart failure (CHF) subcategories of the DECAAF-II population. Differences in the primary outcome of AF recurrence between CHF and non-CHF groups was calculated. The same analysis was performed for the three subgroups of CHF and the non-CHF group. Differences in AF burden after the 3-month blanking period between CHF and non-CHF groups was calculated. Improvement in LVEF was calculated and compared across the three CHF groups. Improvement was also calculated across different fibrosis stages. There was no significant differences in AF recurrence and AF burden after catheter ablation between CHF and non-CHF patients and between different CHF subcategories. Patients with heart failure with reduced ejection fraction (HFrEF) experienced the greatest improvement in EF following catheter ablation (CA, 16.66% ± 11.98, P < 0.001) compared to heart failure with moderately reduced LVEF, and heart failure with preserved EF (10.74% ± 8.34 and 2.00 ± 8.34 respectively, P-value < 0.001). Moreover, improvement in LVEF was independent of the four stages of atrial fibrosis (7.71 vs. 9.53 vs. 5.72 vs. 15.88, from Stage I to Stage IV respectively, P = 0.115). Atrial fibrillation burden and recurrence after CA is similar between non-CHF and CHF patients, independent of the type of CHF. Of all CHF groups, those with HFrEF had the largest improvement in LVEF after CA. Moreover, the improvement in ventricular function seems to be independent of atrial fibrosis in patients with persistent AF.

Entropy of frequency domain of heart rate variability

Introduction. The heart rate variability (HRV) is based on measuring (time) intervals between R-peaks (of RR-intervals) of an electrocardiogram (ECG) and plotting a rhythmogram on their basis with its subsequent analysis by various mathematical methods which are classified as Time-Domain (TD), Frequency-Domain (FD) and Nonlinear [1, 2]. There are a number of popular Nonlinear methods used in HRV analysis, such as entropy-based measures that mostly applied for TD. Spectral Entropy (SE) is using for Frequency-Domain: it is defined to be the Shannon entropy of the power spectral density (PSD) of the data. An important characteristic of Frequency-Domain studies is sympatho-vagal balance, which has been overlooked by entropy-based analysis. This is due to the fact that good entropy analysis restricted the number of existing HRV data, which is shrinking in FD and also in total spectrum parts. Aim of the research. The goal of this paper is to provide a reliable formula for calculating entropy accurately for Frequency-domain of standard 5-min. HRV records and to show the advantages of such approach for analyzing of sympatho-vagal balance for healthy subjects (NSR), Congestive Heart Failure (CHF) and Atrial Fibrillation (AF) patients. Materials and Methods. We used MIT-BIH long-term HRV records for Normal Sinus Rhythm (NSR), Congestive Heart Failure (CHF) and Atrial Fibrillation (AF). The generalized form of the Robust Entropy Estimator (EnRE) for Frequency-domain of standard 5-min. HRV records was proposed and the key EnRE futures was shown. The difference between means of the two independent selections (NSR and CHF, before and after AF) has been determined by a t-test for independent samples; discriminant analysis and statistical calculations have been done by using the statistical package IBM SPSS 27. The results of the study. We calculate entropy for all valuable for HRV spectral interval, namely 0–0.4 Hz and to compare with existing results for Spectral Entropy: qualitatively we receive the same distribution number as [14] and significant difference (p &lt; 0.001) between entropy averages for NSR and CHF or AF patients. We define low-frequencies (LF) power spectrum components in the range of 0.04–0.15 Hz and high-frequencies (HF) power spectrum components in the range of 0.15–0.4 Hz [1]. The sympatho-vagal balance is a simple ratio LF/HF [1]. Then, we define an entropy eLF of the LF power spectrum components, an entropy eHF of the HF power spectrum components and entropy based sympatho-vagal balance as a ratio eLF/eHF. The difference between NSR and CHF groups are significant in both cases LF/HF and eLF/eHF with p &lt; 0.001, but in case of eLF/eHF the results are quite better (t = -4.8, compared to LF/HF where t = -4.4). The discriminant analysis shows total classification accuracy for eLF/eHF in 79.3 % (χ2 = 19.4, p &lt; 0.001) and for LF/HF in 72.4 % (χ2 = 16.6, p &lt; 0.001). We applied entropy-based Frequencies-domain analyzing for AF patients and showed that ratio eLF/eHF is significantly higher during AF than before AF (p &lt; 0.001). This is opposite to ordinary LF/HF where difference is insignificant due to high variation of this ratio. Conclusion. Proposed in the article is generalized form for Robust Entropy Estimator EnRE for Frequencies-domain, which allows, for time series of a limited length (standard 5-min. records), to find entropy value of HRV power spectrum (total spectrum, low- and high- frequencies bands). Using the proposed EnRE for MIT-BIH database of HRV records, we show for standard 5 min. HRV records the usage of EnRE of HRV power spectrum and entropy-based sympatho-vagal balance of Normal Sinus Rhythm (NSR) and Congestive Heart Failure (CHF) cases. It is demonstrated, that, entropy-based Frequencies-domain analyzing is applicable for case of Atrial Fibrillation (AF) even during AF episodes. We showed the significant difference (p &lt; 0.001) before and during AF for entropy of total spectrum, as well as for sympatho-vagal balance in form of eLF/eHF.

Effect of congestive heart failure on safety and efficacy of left atrial appendage closure in patients with non-valvular atrial fibrillation

ABSTRACT Objectives To evaluate the influence of congestive heart failure (CHF) on safety and efficacy of left atrial appendage closure (LAAC) in non-valvular atrial fibrillation (NVAF) patients. Methods A total of 401 patients who consecutively underwent LAAC with Watchman and LAmbre devices were divided into CHF (85 cases) and non-CHF (316 cases) groups. Comparisons between groups were performed against data. Results No significant differences were found in implantation success and periprocedural complication rates between the two groups. During a mean 2.2 years of follow-up, the incidence rate of thromboembolism, major bleeding, device-related thrombus, and non-cardiovascular death was comparable. However, patients with CHF had significantly increased risk of all-cause death (P = 0.015), cardiovascular death (P = 0.014), and combined efficacy endpoints (P = 0.02). After performing propensity score matching, the risk of all-cause death (P = 0.01), cardiovascular death (P = 0.01), and combined efficacy endpoints (P = 0.006) was still higher. The logistic regression analyses identified CHF (OR: 3.642, 95% CI: 1.296–10.232, P = 0.014) as an independent predictor of cardiovascular death. Conclusions Implantation of atrial appendage occluder is effective and safe in NVAF patients with CHF. The increased risk of mortality and combined efficacy endpoints in patients with CHF versus non-CHF after LAAC may be associated with the high risk of CHF itself.

Canine urinary lactate and cortisol metabolites in hypercortisolism, nonadrenal disease, congestive heart failure, and health.

Spontaneous hypercortisolism (HC) is a common endocrine disease of senior dogs, often overlapping in selected clinical signs and hematologic and blood biochemical abnormalities with nonadrenal diseases (NADs). HC and NAD could differentially affect cortisol metabolism, which is a complex 10-enzymatic pathway process. HC might also affect blood and urine lactate levels through its effects on mitochondrial function. We aimed to differentiate between HC and NAD via a urinary cortisol metabolites and lactate panel. We prospectively recruited 7 healthy dogs and 18 dogs with HC, 15 with congestive heart failure (CHF), and 9 with NAD. We analyzed urine by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. We normalized urinary lactate and cortisol metabolites to urine creatinine concentration, and then compared groups using a linear-mixed model and principal component (PC) analysis. A machine-learning classification algorithm generated a decision tree (DT) model for predicting HC. The least-squares means of normalized urinary 6β-hydroxycortisol and PC1 of the HC and CHF groups were higher than those of the healthy and NAD groups (p = 0.05). Creatinine-normalized urinary 6β-hydroxycortisol had better sensitivity (Se, 0.78; 95% CI: 0.55-0.91), specificity (Sp, 0.89; 95% CI: 0.57-0.99), and a likelihood ratio (LR; 7), than the Se (0.72; 95% CI: 0.49-0.88), Sp (0.89; 95% CI: 0.57-0.99), and LR (6.5) of PC1 for distinguishing HC from NAD. Lactate and dihydrocortisone had the highest decreasing node-weighted impurity value and were considered the most important features in the DT model; dihydrocortisol had no role in determining whether a dog had HC.

MO763: Clinical Outcomes in Patients on Hemodialysis with Congestive Heart Failure

Abstract BACKGROUND AND AIMS Hemodialysis (HD) is a unique treatment modality that offers a life-sustaining treatment option for patients with end-stage kidney disease (ESKD). However, the mortality of HD patients is still unacceptably high compared with the general population. Cardiovascular diseases (CVDs) (including myocardial infarction, heart failure and stroke) are the leading causes of death in dialysis-dependent ESKD patients, accounting for ∼40% of the mortality. Congestive heart failure (CHF) is a final common clinical pathway for several diseases. HD patients are at 12–36× risk for the development of CHF. In the general population, CHF increases the risk of death. However, there is no well-designed relevant study in the Chinese HD population addressing the risks associated with CHF. The aim of this study was to explore the impact of CHF on the clinical outcomes in HD patients. METHOD The DOPPS is an international prospective cohort study of in-center adult HD patients. China joined DOPPS in 2011. DOPPS China randomly selected an average of 30 patients from 15 dialysis facilities in each city of Beijing, Shanghai and Guangzhou. There were 1427 patients who participated in China DOPPS5 (2012–2015). Of the 1427 patients, 16 patients were excluded from the present analysis as their CHF history information was missing. Demographic data, comorbidity, Lab data and death records were extracted. CHF was defined by the diagnosis records upon study inclusion. Continuous variables were represented as mean ± SD or median (25th, 75th) according to the results of the normality test. Categorical variables were expressed as numbers and percentages. We stratified data by CHF and non-CHF groups. Our primary outcome was associations between CHF and all-cause and cardiovascular (CV) mortality; secondary outcomes were all-cause and cause-specific hospitalization risk. Associations between CHF and outcomes were evaluated using Cox regression models. Cox regression models were with five incremental levels of covariate adjustment. Stepwise multivariate logistic regression was used to identify the related risk factors, and subgroup analyses were carried out. RESULTS Of 1411 patients without missing CHF history information, 24.1% (340) had a CHF diagnosis at enrollment. In this cohort, male patients accounted for 54.9% of the patients. The median age was 60.0 (inter-quartile range, IQR 49.0–71.0) years and the median dialysis vintage was 2.6 (IQR 0.9–5.4, Table 1) years. The median follow-up period was 1.9 (IQR 1.2–2.1) years. Altogether, 203 (14.4%) patients died, where 103 (7.3%) died from CV disease. The CV death constituted half of the patient’s mortality. The overall mortality rates were 21.8% versus 12.0% (P &amp;lt; 0.001) in patients with and without CHF during entire follow-up, respectively. CHF was associated for higher all-cause mortality [adjusted HR 1.72, 95% confidence interval (95% CI) 1.17–2.53; P = 0.006, Fig. 1], and the association with CV death was of similar magnitude (HR 1.60, 95% CI 0.91–2.81; P = 0.105). CHF patients had more episodes of hospitalization due to heart failure (HR 2.93, 95% CI 1. 49– 5.76; P &amp;lt;0.01). However, compared with patients without CHF, the all-cause hospitalization risk was not much higher in CHF patients (HR 1.09, 95% CI 0.90–1.33; P = 0.39). CONCLUSION In this prospective cohort study, the prevalence of CHF was identified to be around one quarter, and all-cause mortality in patients with combined CHF and HD was found to be higher. CHF was associated with an increased risk of all-cause mortality and a cause-specific hospitalization risk in HD patients. The associations were not affected by adjustment for several potential confounding factors. Thus, CHF is found to be an outcome predictor for HD patients, and measures should be adopted to improve care for these patients to improve their survival.

Similarity Changes Analysis for Heart Rate Fluctuation Regularity as a New Screening Method for Congestive Heart Failure.

Congestive heart failure (CHF) is a chronic cardiovascular condition associated with dysfunction of the autonomic nervous system (ANS). Heart rate variability (HRV) has been widely used to assess ANS. This paper proposes a new HRV analysis method, which uses information-based similarity (IBS) transformation and fuzzy approximate entropy (fApEn) algorithm to obtain the fApEn_IBS index, which is used to observe the complexity of autonomic fluctuations in CHF within 24 h. We used 98 ECG records (54 health records and 44 CHF records) from the PhysioNet database. The fApEn_IBS index was statistically significant between the control and CHF groups (p < 0.001). Compared with the classical indices low-to-high frequency power ratio (LF/HF) and IBS, the fApEn_IBS index further utilizes the changes in the rhythm of heart rate (HR) fluctuations between RR intervals to fully extract relevant information between adjacent time intervals and significantly improves the performance of CHF screening. The CHF classification accuracy of fApEn_IBS was 84.69%, higher than LF/HF (77.55%) and IBS (83.67%). Moreover, the combination of IBS, fApEn_IBS, and LF/HF reached the highest CHF screening accuracy (98.98%) with the random forest (RF) classifier, indicating that the IBS and LF/HF had good complementarity. Therefore, fApEn_IBS effusively reflects the complexity of autonomic nerves in CHF and is a valuable CHF assessment tool.

Atrial appendage closure in patients with heart failure and atrial fibrillation: industry-independent single-centre study.

AimsTo evaluate outcomes of percutaneous left atrial appendage closure (LAAC) in patients with congestive heart failure (CHF) and non‐valvular atrial fibrillation (AF) in a consecutive, industry‐independent registry associated with periprocedural success and complications during long‐term follow‐up.Methods and resultsFor this analysis, we included patients who underwent transcatheter LAAC from January 2014 to December 2019 at the University Heart Center in Lübeck, Germany, and compared patients with presence of CHF defined as patients with a reduced left ventricular ejection fraction (LVEF ≤ 40%), patients with a mid‐range LVEF (LVEF 41–49%), patients with diastolic dysfunction and preserved LVEF (LVEF ≥ 50%), and patients with right‐sided heart failure and impaired right ventricular function (tricuspid annular plane systolic excursion < 17) to patients undergoing LAAC with no CHF. Primary endpoints were defined as periprocedural complications, and complications during long‐term follow‐up presented as major adverse cardiac and cerebrovascular events (MACCE). A total of 300 consecutive patients underwent LAAC. Of these, 96 patients in the CHF group were compared with 204 patients in the non‐CHF group. Implantation success was lower in CHF group in comparison with non‐CHF group (99.5% vs. 96%, P = 0.038); otherwise, there were no differences in periprocedural complications between groups. Patients with CHF showed a significantly higher incidence of MACCE rate (31.9% vs. 15.1%, P = 0.002) and more deaths (24.2% vs. 7%, P ≤ 0.001) during long‐term follow‐up. In Cox multivariable regression analysis, CHF was an independent predictor of mortality after LAAC implantation at long‐term follow‐up (hazard ratio 3.23, 95% confidence intervals 1.52–6.86, P = 0.002).ConclusionsImplantation of LAAC devices in patients with non‐valvular AF and CHF is safe. The increased mortality in patients with CHF compared with patients without CHF during the long‐term follow‐up is mainly attributed to comorbidities associated with CHF.

Detection of Congestive Heart Failure and Myocardial Dysfunction in Cats With Cardiomyopathy by Using Two-Dimensional Speckle-Tracking Echocardiography.

Congestive heart failure (CHF) is a life-threatening condition in cats with cardiomyopathy. We hypothesized that myocardial dysfunction may induce progression to CHF pathophysiology in cats with cardiomyopathy. However, no previous studies have evaluated the involvement of myocardial dysfunction in cats with CHF. In this study, we aimed to evaluate the relationship between CHF and myocardial function assessed using two-dimensional speckle-tracking echocardiography (2D-STE). Sixteen client-owned healthy cats and 32 cats with cardiomyopathy were enrolled in this study. Cats were classified into three groups: healthy cats, cardiomyopathy without CHF (CM group), and cardiomyopathy with CHF (CHF group). Left ventricular (LV) longitudinal and circumferential strains (SL and SC, respectively), and right ventricular (RV) SL were measured using 2D-STE. Logistic regression analysis was performed to assess the relationship between CHF and echocardiographic variables, including 2D-STE. Results comparing the healthy cats and CM vs. CHF groups showed that increased left atrial to aortic diameter ratio and decreased LV apical SC were significantly associated with the existence of CHF (odds ratio [95% confidence interval]: 1.40 [1.16–1.78] and 1.59 [1.06–2.36], respectively). Results comparing the CM vs. CHF group showed that increased end-diastolic RV internal dimension and decreased RV SL were significantly associated with the existence of CHF (odds ratio: 1.07 [1.00–1.13] and 1.34 [1.07–1.68], respectively). Left atrial enlargement and depressed LV apical myocardial function may be useful tools for predicting the progression to CHF in cats. Furthermore, RV enlargement and dysfunction may lead to the onset of CHF in asymptomatic cats with cardiomyopathy.

High level of growth differentiation factor 15 and lower left ventricular ejection fraction as predictors of left atrial thrombosis in patients with nonvalvular atrial fibrillation

Abstract Background The presence of left atrial/left atrial appendage (LA/LAA) thrombus is used as a surrogate marker of potential stroke in patients (pts) with atrial fibrillation (AF). Purpose To assess the role of growth differentiation factor 15 (GDF-15) level, clinical and echocardiographic (EchoCG) data as predictors of LA/LAA thrombus in pts with nonvalvular AF. Methods Out of 158 pts with nonvalvular AF admitted to Cardiology Center for radiofrequency ablation or elective cardioversion in 2019–2020 2 groups were formed according to transesophageal EchoCG results: group 1 included pts without LA/LAA thrombus (n=102, mean age 59.5±6.0 years) and group 2 (n=42, mean age 60.9±8.8 years) – pts with LA/LAA thrombus. Arterial hypertension was found in 93 pts of group 1 (91%) and in 40 pts of group 2 (95%, p=0.42), coronary artery disease - in 53 pts (52%) and 29 pts (69%), respectively (p=0.06). Both groups did not differ in frequency and spectrum of oral anticoagulants administration. General clinical assessment, EchoCG, and laboratory tests were performed, including GDF-15 (pg/ml) levels using Human GDF-15/MIC-1 ELISA kit and NT-proBNP (pg/ml) in blood. Results Pts with LA/LAA thrombus more often had persistent AF, while paroxysmal AF was more common in pts without thrombus. There was a tendency to more significant congestive heart failure in group 2. Mean CHA2DS2-VASc score was higher in pts with LA/LAA thrombus, also there was a tendency to a larger proportion of pts with scores ≥3. According to EchoCG data, sizes and volumes of both atria, right ventricle, end-systolic volume, left ventricular (LV) size, pulmonary artery systolic pressure and LV mass index were higher in group 2; LV ejection fraction (LVEF) was normal in both groups, but it was significantly lower in pts with LA/LAA thrombus: 59.1±5.1 and 64.0±7.3, respectively (p&amp;lt;0.001). GDF-15 and NT-proBNP levels were significantly higher in group 2 compared to group 1: p=0.00025 and p=0.ehab724.048801 respectively. According to ROC analysis cut-off were set at level &amp;gt;935.0 pg/ml for GDF-15 (AUC=0.705, 95% CI 0.609–0.800, p&amp;lt;0.001) and &amp;gt;143 pg/ml for NT-proBNP (AUC=0.759, 95% CI 0.670–0.849, p&amp;lt;0.001). Multivariate logistic regression revealed the following variables as independent predictors of LAAT: GDF-15 &amp;gt;935.0 pg/ml (OR=4.132, 95% CI 1.305–13.084) and LVEF (OR=0.859, 95% CI 0.776–0.951). According to ROC analysis, the model had a good quality: AUC=0.776 (p&amp;lt;0.001), sensitivity was 78.3%., specificity - 78.3%. Conclusion High level of GDF-15 (&amp;gt;935.0 pg/ml) along with lower LVEF are independent predictors of LA/LAA thrombus in pts with nonvalvular AF. Funding Acknowledgement Type of funding sources: None.

Fluid resuscitation and outcomes in heart failure patients with severe sepsis or septic shock: A retrospective case-control study.

BackgroundThe use of ≥30 mL/Kg fluid bolus in congestive heart failure (CHF) patients presenting with severe sepsis or septic shock remained controversial due to the paucity of data.MethodsThe retrospective case-control study included 671 adult patients who presented to the emergency department of a tertiary care hospital from January 01, 2017 to December 31, 2019 with severe sepsis or septic shock. Patients were categorized into the CHF group and the non-CHF group. The primary outcome was to evaluate the compliance with ≥30 mL/Kg fluid bolus within 6 hours of presentation. The comparison of baseline characteristics and secondary outcomes were done between the groups who received ≥30 mL/Kg fluid bolus. For the subgroup analysis of the CHF group, it was divided based on if they received ≥30 mL/Kg fluid bolus or not, and comparison was done for baseline characteristics and secondary outcomes. Univariate and multivariable analyses were performed to explore the differences between the groups for in-hospital mortality and mechanical ventilation.ResultsThe use of ≥30 mL/Kg fluid bolus was low in both the CHF and non-CHF groups [39% vs. 66% (p<0.05)]. Mortality was higher in the CHF group [33% vs 18% (p<0.05)]. Multivariable analysis revealed that the use of ≥30 mL/Kg fluid bolus decreased the chances of mortality by 12% [OR 0.88, 95% CI 0.82–0.95 (p<0.05)]. The use of ≥30 mL/Kg fluid bolus did not increase the odds of mechanical ventilation [OR 0.99, 95% CI 0.93–1.05 (p = 0.78)]. In subgroup analysis, the use of ≥30 mL/Kg fluid bolus decreased the chances of mortality by 5% [OR 0.95, 95% CI 0.90–0.99, (p<0.05)] and did not increase the odds of mechanical ventilation. The presence of the low ejection fraction did not influence the chance of getting fluid bolus.ConclusionThe use of ≥30 mL/Kg fluid bolus seems to confer protection against in-hospital mortality and is not associated with increased chances of mechanical ventilation in heart failure patients presenting with severe sepsis or septic shock.

Presentation of SARS-CoV-2 (COVID-19 in patients with congestive heart failure. A Retrospective study

Background and Aims: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has infected 86,468,659 people around the globe until 6/1/2021, with 1,869,808 mortalities. It is estimated that people with congestiveheart failure (CHF) are in a high risk category for mortality. Furthermore, persons with obesity who become ill and require intensive care present challenges in patient management as it is more difficult to intubate these persond, and this is especially true in Saudi Arabia and the region of Hail, where morbid obesity is at 33.6% of the population. Our aim is to establish an epidimiological link for our population between diabetes, obesity and percentage of intubated patients as we measured mortalities and readmissions in 30 days. Methods: A retrospective cohort study of 751 patients admitted as positive COVID 19 patients, from April 1, 2020 to July 31, 2020, covering a period of 4 months. We then categorised the patient in cohorts accordind to the existence of CHF or not, and categorised them according to their BMI index. We then correlated using statistical tool analysis - SPSS statistics tool - intubation, mortality,readmitance in 30 days in thes groups of patients Results: Around 12% of our cases were CHF. 16% of these cases intubated, instead of 5% of non CHF cases. Mortalities were higher in the CHF group as percentage ( 72% to 7%), and readmissions. Significant correlation between BMI and days of ICU stay in the CHF group Conclusions: There is significantly elevated morbidity and mortality at obese CHF cases with COVID 19

Identification, localization and expression of NHE isoforms in the alveolar epithelial cells.

Na+/H+ exchangers (NHEs), encoded by Solute Carrier 9A (SLC9A) genes in human, are ubiquitous integral membrane ion transporters that mediate the electroneutral exchange of H+ with Na+ or K+. NHEs, found in the kidney and intestine, play a major role in the process of fluid reabsorption together via Na+,K+-ATPase pump and Na+ channels. Nevertheless, the expression pattern of NHE in the lung and its role in alveolar fluid homeostasis has not been addressed. Therefore, we aimed to examine the expression of NHE specific isoforms in alveolar epithelial cells (AECs), and assess their role in congestive heart failure (CHF). Three NHE isoforms were identified in AEC and A549 cell line, at the level of protein and mRNA; NHE1, NHE2 and mainly NHE8, the latter was shown to be localized in the apical membrane of AEC. Treating A549 cells with angiotensin (Ang) II for 3, 5 and 24 hours displayed a significant reduction in NHE8 protein abundance. Moreover, the abundance of NHE8 protein was downregulated in A549 cells that were treated overnight with Ang II. NHE8 abundance in whole lung lysate was increased in rats with 1-week CHF compared to sham operated rats. However, lower abundance of NHE8 was observed in 4-week CHF group. In conclusion, we herein show for the first time, the expression of a novel NHE isoform in AEC, namely NHE8. Notably, Ang II decreased NHE8 protein levels. Moreover, NHE8 was distinctly affected in CHF rats, probably depending on the severity of the heart failure.

Catheter ablation for atrial fibrillation in patients with congestive heart failure

BackgroundWe evaluated the 1-year success rate of maintaining sinus rhythm after catheter ablation (CA) for atrial fibrillation (AF) in patients with or without congestive heart failure (CHF). MethodsIn this single-centre retrospective matched-pair cohort study of 3,018 AF patients who underwent initial CA between January 2012 and June 2018, 227 pairs with (CHF group) or without CHF (control group) were matched using propensity scores. In the CHF group, 108 patients were assigned to the arrhythmia-induced cardiomyopathy (AIC) group whose left ventricular systolic dysfunction was explained only by lasting AF or atrial tachycardia; the remaining 119 had organic heart diseases (non-AIC group). We evaluated the 1-year AF-free survival and changes in clinical findings before and after CA. ResultsThe CHF and control groups showed similar AF-free survival; however, AIC patients had significantly better survival than non-AIC patients. AF recurrence was significantly related to CHF re-hospitalisation, which was significantly more frequent in the non-AIC group than in the AIC group. The clinical outcomes of left atrial dilation, brain natriuretic peptide level, and left ventricular ejection function improved significantly before and after CA in both groups. The degree of improvement was significantly better in the AIC group than in the non-AIC group. ConclusionsThe 1-year success rate was not significantly different between the CHF and control groups. The 1-year success rate in the AIC group was similar to that in the AIC-control group and was better than that in the non-AIC group. CHF clinical outcomes were improved significantly.

Fuzzy logic approach for heart rate variability

Intrioution. The heart rate variability (HRV) is based on measuring (time) intervals between R-peaks (of RR-intervals) of an electrocardiogram (ECG) and plotting a rhythmogram on their basis with its subsequent analysis by various mathematical methods that are classified as Time Domain (TD), Frequency Domain (FD) and Nonlinear (NM) [1, 2]. Diversity of methods and approaches to analysis of HRV is stemming from complexity and nonlinearity of the phenomenon itself, as well as from greater diversity of physiological reactions of an organism, both in normal and pathological states. Therefore, it appears relevant and important to incorporate currently existing HRV indicators and norms into a unified Fuzzy Logic (FL) methodology, which in turn will allow to integrally assess each metric and HRV results as a whole. Objective. We propose a Fuzzy Logic algorithm for incorporating into a single view of each metric, – Time Domain, Frequency Domain, Nonlinear Methods and HRV as a whole. Materials and methods. We define by FL the extent of belonging to normal state both for each distinct HRV metric – TD, FD and NM, and for a patient's HRV in general. Membership functions of any HRV index and defuzzification rules for FL scores was defined. In order to implement the proposed algorithm, specified parameters of mean values of HRV (М) indicators and their standard deviation (σ) have been found in scientific publications on HRV [1, 3, 7, 8, 9, 10]. We use for FL algorithm demonstration a long-term HRV records by Massachusetts Institute of Technology - Boston’s Beth Israel Hospital (MIT-BIH) from [11], a free-access, on-line archive of physiological signals for Normal Sinus Rhythm (NSR) RR Interval, Congestive Heart Failure (CHF) RR Interval and Atrial Fibrillation (AF) Databases [12]. Conclusion. In this article, we have presented a comprehensive view of HRV by Fuzzy Logic technology and thoroughly examined the peculiarities of its application and interpretation. Of all considered examples of FL analysis, the worst result is demonstrated by a patient from the AF group, while the best one belongs to a patient from the NSR group. Difference in FL Scores between these patients from NSR and CHF groups is almost 4 times, while between patients from NSR and АF groups it is almost 6 times. It appears especially important to implement such a design in portable medical devices for quick and easy interpretation of numerous parameters measured by them.

Time irreversibility and complexity of heart rate variability

Intrioution. The heart rate variability is based on measuring (time) intervals between R-peaks (of RR-intervals) of an electrocardiogram and plotting a rhythmogram on their basis with its subsequent analysis by various mathematical methods. Using nonlinear methods in HRV and ECG analysis has proven to be very advantageous. Time irreversibility is a fundamental parameter of a system, it defines justification and necessity of applying nonlinear methods for analysis of a system’s dynamics. Objective. We propose an algorithm for testing the probability of a time series' irreversibility, showing its effectiveness in the process of HRV analysis. In this article, complexity of HRV will be described by two parameters: entropy EnRE [18] and correlation dimension D2 [19]. Naturally, the chosen parameters EnRE and D2 in no way can be used for comprehensive description of complexity of HRV, but we will be able to tress the necessary sufficiency of such an approach. Materials and methods. We used long-term HRV records by Massachusetts Institute of Technology – Boston’s Beth Israel Hospital (MIT-BIH) from [15], a free-access, on-line archive of physiological signals for Normal Sinus Rhythm (NSR) RR Interval, Congestive Heart Failure (CHF) RR Interval and Atrial Fibrillation (AF) Databases [16]. In [17], we have developed a special modification to the classic Mann-Whitney (MW) U-test in order to use the test for comparison of Time Series with an equal number of elements N – Time Series MW M-test. Here the new statistical -test was proposed for finding the probability of time series' irreversibility. Conclusion. In this article, we propose a statistical -test for assessment of probability of irreversibility of time series. It has been shown that the new statistical -test accurately identifies times series reversibility and irreversibility in known cases of synthetic data. For long-term HRV records of MIT-BIH database for NSR, CHF and AF groups, we have compared values of z-score, which statistically defines the limit of irreversibility of time series, and values of HRV complexity indicators: entropy EnRE [18] and correlation dimension D2 [19]. We have noted the following: HRV is time irreversible nonlinear dynamic process, with the exception of AF episodes; nonlinear indicators of HRV complexity – entropy EnRE and correlation dimension D2 – have been analyzed, and there is a conclusive difference between NSR and analyzed pathological states; analyzed time series have been presented in D2-z-EnRE phase space, and their reliable separability has been shown. It can be stated that the analyzed D2-z-EnRE phase space is sufficient for research of nonlinear HRV events in this case.