Stage Heart Failure Research Articles

Evaluation of the relationship between end-tidal carbon dioxide level and heart failure classification.

Heart failure is a disease with cardiac dysfunction, and its morbidity and mortality are associated with the degree of dysfunction. The New York Heart Association classifies the heart failure stages based on the severity of symptoms and physical activity. End-tidal carbon dioxide refers to the level of carbon dioxide that a person exhales with each breath. End-tidal carbon dioxide levels can be used in many clinical conditions such as heart failure, asthma, and chronic obstructive pulmonary disease. The aim of the study was to reveal the relationship between end-tidal carbon dioxide levels and the New York Heart Association classification of heart failure stages. This study was conducted at Kahramanmaraş Sütçü İmam University Faculty of Medicine Adult Emergency Department between 01/03/2019 and 01/09/2019. A total of 80 patients who presented to the emergency department with a history of heart failure or were diagnosed with heart failure during admission were grouped according to the New York Heart Association classification of heart failure stages. The laboratory parameters, ejection fraction values, and end-tidal carbon dioxide levels of the patients were measured and recorded in the study forms. End-tidal carbon dioxide levels and ejection fraction values were found to be significantly lower in the stage 4 group compared to the other groups. Furthermore, pro-B-type natriuretic peptide (BNP) values were found to be significantly higher in stage 4 group compared to the other groups. It was concluded that end-tidal carbon dioxide levels could be used together with pro-BNP and ejection fraction values in determining the severity of heart failure.

A diagnostic prediction model for the early detection of heart failure following primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction.

In this study, we aimed to construct a robust diagnostic model that can predict the early onset of heart failure in patients with ST-elevation myocardial infarction (STEMI) following a primary percutaneous coronary intervention (PCI). This diagnostic model can facilitate the early stratification of high-risk patients, thereby optimizing therapeutic management. We performed a retrospective analysis of 664 patients with STEMI who underwent their inaugural PCI. We performed logistic regression along with optimal subset regression and identified important risk factors associated with the early onset of heart failure during the time of admission. Based on these determinants, we constructed a predictive model and confirmed its diagnostic precision using a receiver operating characteristic (ROC) curve. The logistic and optimal subset regression analyses revealed the following three salient risk factors crucial for the early onset of heart failure: the Killip classification, the presence of renal insufficiency, and increased troponin T levels. The constructed prognostic model exhibited excellent discriminative ability, which was indicated by an area under the curve value of 0.847. The model's 95% confidence interval following 200 Bootstrap iterations was found to be between 0.767 and 0.925. The Hosmer-Lemeshow test revealed a chi-square value of 3.553 and a p-value of 0.938. Notably, the calibration of the model remained stable even after 500 Bootstrap evaluations. Furthermore, decision curve analysis revealed a substantial net benefit of the model. We have successfully constructed a diagnostic prediction model to predict the incipient stages of heart failure in patients with STEMI following primary PCI. This diagnostic model can revolutionize patient care, allowing clinicians to quickly identify and create individualized interventions for patients at a higher risk.

Body composition and functional activity in men with heart failure

Aim. To assess the body composition and functional activity (FA) parameters in men with heart failure (HF) of various nature depending on the stage, class and echocardiographic characteristics of the disease.Material and methods. The study included 100 men aged 23-70 years. The main group consisted of 60 men with HF, the control group — 40 men without HF. Quantitative body composition assessment (fat, lean and bone body mass) was carried out using dual-energy X-ray absorptiometry (DXA). Physical activity was assessed using handgrip test, short physical performance battery (SPPB) test, 6-minute walk test (6MWT), and Timed Up and Go (TUG) test.Results. In the HF group, there were a significant decrease in total bone mass, trunk and limb bone mass, total muscle mass, trunk and limbs’ muscle mass, appendicular skeletal muscle index (ASMI), and FA as HF class increased. Fat mass did not differ in individuals with different HF class and stage. HF class was an independent factor in the reduction of total bone mass (b=-301,9, p=0,015), total muscle mass (b=-1903, p=0,03), limb bone mass (b=-147,6, p=0,013) and appendicular muscle mass (AMM) (b=-1903, p=0,001). Total bone mass (b=-2,637, p=0,02) and AMM (b=-3,512, p=0,01) were independently associated with the Vasilenko-Strazhesko HF stage. AMM also had an independent association with left ventricular ejection fraction (LVEF) (b=0,274, p=0,03). The average body composition scores did not differ between the study and control groups, while the scores of handgrip test, 6MWT, SPPB and TUG test were significantly worse in the HF group. NYHA HF class, stage of HF, LVEF, left ventricular end-diastolic volume (LVEDV) and pulmonary artery systolic pressure (PASP) made an independent contribution to FA decrease in men with HF.Conclusion. In patients with HF, there was deterioration in musculoskeletal parameters depending on HF class, stage and LVEF, without significant differences compared to the control group. There was no association of fat mass with the disease, clinical and echocardiographic characteristics. The average parameters of muscle strength and tests of FA were reduced in men with HF compared with the control group and depended on the NYHA class and stage of HF, LVEF, LVEDV, and PASP.

Chymase-independent vascular Ang-(1–12)/Ang II pathway and TXA2 generation are involved in endothelial dysfunction in the murine model of heart failure

The angiotensin (Ang)-(1–12)/Ang II pathway contributes to cardiac pathology. However, its involvement in the development of peripheral endothelial dysfunction associated with heart failure (HF) remains unknown. Therefore, this study aimed to characterise the effect of exogenous Ang-(1–12) and its conversion to Ang II on endothelial function using the murine model of HF (Tgαq*44 mice), focusing on the role of chymase and vascular-derived thromboxane A2 (TXA2).Ex vivo myographic assessments of isolated aorta showed impaired endothelium-dependent vasodilation in late-stage HF in 12-month-old Tgαq*44 mice. However, endothelium-dependent vasodilation was fully preserved in the early stage of HF in 4-month-old Tgαq*44 mice and 4- and 12-month-old FVB control mice. Ang-(1–12) impaired endothelium-dependent vasodilation in 4- and 12-month-old Tgαq*44 mice, that was associated with increased Ang II production. The chymase inhibitor chymostatin did not inhibit this response. Interestingly, TXA2 production reflected by TXB2 measurement was upregulated in response to Ang-(1–12) and Ang II in aortic rings isolated from 12-month-old Tgαq*44 mice but not from 4-month-old Tgαq*44 mice or age-matched FVB mice. Furthermore, in vivo magnetic resonance imaging showed that Ang-(1–12) impaired endothelium-dependent vasodilation in the aorta of Tgαq*44 mice and FVB mice. However, this response was inhibited by angiotensin I converting enzyme (ACE) inhibitor; perindopril, angiotensin II receptor type 1 (AT1) antagonist; losartan and TXA2 receptor (TP) antagonist-picotamide in 12-month-old-Tgαq*44 mice only.In conclusion, the chymase-independent vascular Ang-(1–12)/Ang II pathway and subsequent TXA2 overactivity contribute to systemic endothelial dysfunction in the late stage of HF in Tgαq*44 mice. Therefore, the vascular TXA2 receptor represents a pharmacotherapeutic target to improve peripheral endothelial dysfunction in chronic HF.

Heart rate variability, interoceptive accuracy and functional connectivity in middle-aged and older patients with depression

Background and objectiveMajor depressive disorder (MDD) is associated with increased cardiac morbidity. Reduced heart rate variability (HRV) as well as lower interoceptive accuracy (IAc) have been observed in MDD as possible sympathomimetic mechanisms related to insula activity. The salience network (SN) anchored by the insula has been posited as a crucial functional network for cardiac sensations and the default mode network (DMN) for MDD. This study aimed to investigate the relation between insula-centered and depression-related brain networks, IAc and HRV in patients with depression as a possible mechanism by which MDD increases cardiac morbidity. Methods30 depressed inpatients and 30 healthy subjects (derived from the population-based “Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression” cohort study, STAAB) all over 50 years were examined. HRV and IAc were assessed via electrocardiogram and a heartbeat perception task prior to a 3 T resting-state functional magnetic resonance imaging. Seed-to-voxel resting-state functional connectivity (FC) analysis was conducted with six seeds in the insula and two seeds in the DMN. ResultsDepressed patients on the one hand showed decreased FC between insula cortex and frontal as well occipital cortical brain regions compared to controls. Depressed patients on the other hand exhibited higher FC between the medial prefrontal cortex and the insula cortex compared to controls. However, depressed patients did not differ in HRV nor in IAc compared to controls. ConclusionThus, differences in insula-related brain networks in depression in our study were not mirrored by differences in HRV and IAc. Future research is needed to define the mechanism by which depression increases cardiac morbidity.

Myocardial Angiotensin-Converting Enzyme 2 Protein Expression in Ischemic Heart Failure.

The angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis plays a significant role in regulating myocardial remodeling and the development of heart failure (HF), with ACE2 being the primary focus. However, contemporary understanding of the membrane-bound form of the human ACE2 protein remains insufficient. The purpose of this study was to determine the expression of ACE2 protein in different cells of the left ventricular myocardium in non-diseased hearts and at various stages of ischemic HF. A total of 103 myocardial tissue samples from the left ventricle underwent quantitative and semi-quantitative immunohistochemical analysis. Upon assessing ACE2 immunostaining in all myocardial cells through unselective digital image analysis, there was no change in the stage A HF group. Nevertheless, the expression of ACE2 membrane protein in cardiomyocytes showed a tendency to increase, while non-cardiomyocyte ACE2 expression decreased significantly (p < 0.001). In the stage B HF group, the intensity of ACE2 immunostaining continued to increase with rising cardiomyocyte ACE2 expression (p < 0.001). Non-cardiomyocyte expression, in contrast, remained similar to that observed in the stage A HF group. In the stages C/D HF group, ACE2 expression reached its highest level in cardiomyocytes (p < 0.001), while ACE2 expression in non-cardiomyocytes was the lowest (p < 0.001). These changes in ACE2 protein levels are associated with left ventricular remodeling in ischemic HF.

Proposed New Cutoff Value for Troponin in the Diagnosis of Acute Myocardial Infarction (AMI) in Patients with Congestive Heart Failure (CHF) and/or End Stage Renal Disease (ESRD)

Abstract Introduction/Objective In a recent publication, we assessed the efficacy of two serum biomarkers for AMI, cardiac Troponin I (cTnI) and creatine kinase-MB (CK-MB), for patients presenting to our emergency department (ED) with acute chest pain. We found that two conditions, CHF and ESRD in 85 patients, caused a significant number of false positive results that resulted in lowering the specificity and positive predictive value of both tests, which were already reduced by the low prevalence of AMI in our patient population. Removal of these patients resulted in significant increases in the two latter parameters. In this study, we focus on cTnI to determine if changing the cutoff value can increase the sensitivity and specificity of diagnosing acute MI in patients with CHF and ESRD. Methods/Case Report A cohort of 380 patients who presented with acute chest pain in the ED and worked up for acute MI were included, 85 of whom had CHF and/or ESRD. A total of 47 patients (15.4% prevalence) were definitively diagnosed with AMI. An initial serum cTnI sample was collected for each patient. Specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) were then compared using the routine cutoff cTnI value (0.05 ng/mL) and the higher cutoff of 0.2 ng/mL. Results (if a Case Study enter NA) Using the original cutoff of 0.05 ng/mL for cTnI in the patients with CHF or ESRD, the sensitivity and NPV were both 100%, while the specificity and PPV were low at 40.3% and 23%, respectively. Interestingly, when the cutoff was raised from 0.05 to 0.2 ng/mL, the sensitivity decreased by about 8% to 92.3 (12 out of 13 patients with AMI), and the specificity increased almost two-fold to 76.4%. The PPV increased to 40.4% and NPV was 98.2%. These values are comparable with the sensitivity, specificity, PPV and NPV of the total population at 85.3%, 82.4%, 38.7% and 97.7%, respectively. Conclusion The original cutoff value for cTnI in patients with ESRD and CHF produces a very low specificity and PPV. The results of this study suggest that an acceptable cutoff for cTnI to rule-out AMI patients who have CHF and or ESRD is 0.2 ng/mL which is four times higher than the original, but has comparable specificity, sensitivity, PPV and PPV to the total patient population. We note that this study must be regarded as a pilot study since the numbers of patients are small. We recommend a larger study to determine the validity of these conclusions.

Knowing the Patient: Understanding Readmission Reasons in Complex Heart Failure.

Heart failure (HF) is a complex problem characterized by frequent hospitalizations and high 30-day readmission rates. Researchers studying HF readmission report that patients and clinicians have different perspectives on readmission and preventability when unadjusted for disease severity. The aim of this study was to gather patient, caregiver, nurse, and physician subjective reason(s) for 30-day HF readmission and perceptions of preventability with contextual factors to evaluate differences. A convergent, parallel, mixed-methods design was used with interviews and chart reviews to evaluate contextual factors from the current and index hospital stay. Adults readmitted within 30 days of a previous inpatient stay with a coded HF diagnosis were enrolled and interviewed, followed by interviews with associated caregivers, attending physicians, and assigned nurses. Interviews were conducted with patients (n = 44), caregivers (n = 6), physicians (n = 24), and nurses (n = 44). Readmissions were emergent/urgent (95%) and occurred within 14.9 days (SD, 8.1; 2-28 days) on average after discharge. Index stay coding revealed that most patients (73%) had a high severity of illness (73%) and risk of mortality (68%). Heart failure stage was inconsistently documented. Patients reported acute symptomatic reasons, with only 32% describing readmission as preventable. Physicians reported diagnostic reasons, 38% of which were preventable. Nurses reported behavioral reasons, with 59% being preventable. Patient/clinician agreement on readmission reason was low (30%). Patient/clinician perspectives on readmission varied among the patients with complex HF. Care planning based on HF stage and other contextual factors is needed to ensure a shared understanding of disease severity and a tailored symptom management approach to prevent readmission.

Systemic mapping of organ plasma extravasation at multiple stages of chronic heart failure.

Introduction: Chronic Heart failure (CHF) is a highly prevalent disease that leads to significant morbidity and mortality. Diffuse vasculopathy is a commonmorbidity associated with CHF. Increased vascular permeability leading to plasma extravasation (PEx) occurs in surrounding tissues following endothelial dysfunction. Such micro- and macrovascular complications develop over time and lead to edema, inflammation, and multi-organ dysfunction in CHF. However, a systemic examination of PEx in vital organs among different time windows of CHF has never been performed. In the present study, we investigated time-dependent PEx in several major visceral organs including heart, lung, liver, spleen, kidney, duodenum, ileum, cecum, and pancreas between sham-operated and CHF rats induced by myocardial infarction (MI). Methods: Plasma extravasation was determined by colorimetric evaluation of Evans Blue (EB) concentrations at 3days, ∼10weeks and 4months following MI. Results: Data show that cardiac PEx was initially high at day 3 post MI and then gradually decreased but remained at a moderately high level at ∼10weeks and 4months post MI. Lung PEx began at day 3 and remained significantly elevated at both ∼10weeks and 4months post MI. Spleen PExwas significantly increased at ∼10weeks and 4months but not on day 3 post MI. Liver PEx occurred early at day 3 and remain significantly increased at ∼10weeks and 4months post MI. For the gastrointestinal (GI) organs including duodenum, ileum and cecum, there was a general trend that PEx level gradually increased following MI and reached statistical significance at either 10weeks or 4months post MI. Similar to GI PEx, renal PEx was significantly elevated at 4months post MI. Discussion: In summary, we found that MI generally incites a timedependent PEx of multiple visceral organs. However, the PEx time window for individual organs in response to the MI challenge was different, suggesting that different mechanisms are involved in the pathogenesis of PEx in these vital organs during the development of CHF.

Population data-based federated machine learning improves automated echocardiographic quantification of cardiac structure and function: the Automatisierte Vermessung der Echokardiographie project.

Machine-learning (ML)-based automated measurement of echocardiography images emerges as an option to reduce observer variability. The objective of the study is to improve the accuracy of a pre-existing automated reading tool ('original detector') by federated ML-based re-training. Automatisierte Vermessung der Echokardiographie was based on the echocardiography images of n = 4965 participants of the population-based Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression Cohort Study. We implemented federated ML: echocardiography images were read by the Academic Core Lab Ultrasound-based Cardiovascular Imaging at the University Hospital Würzburg (UKW). A random algorithm selected 3226 participants for re-training of the original detector. According to data protection rules, the generation of ground truth and ML training cycles took place within the UKW network. Only non-personal training weights were exchanged with the external cooperation partner for the refinement of ML algorithms. Both the original detectors as the re-trained detector were then applied to the echocardiograms of n = 563 participants not used for training. With regard to the human referent, the re-trained detector revealed (i) superior accuracy when contrasted with the original detector's performance as it arrived at significantly smaller mean differences in all but one parameter, and a (ii) smaller absolute difference between measurements when compared with a group of different human observers. Population data-based ML in a federated ML set-up was feasible. The re-trained detector exhibited a much lower measurement variability than human readers. This gain in accuracy and precision strengthens the confidence in automated echocardiographic readings, which carries large potential for applications in various settings.

DEL-1 deficiency aggravates pressure overload-induced heart failure by promoting neutrophil infiltration and neutrophil extracellular traps formation

Recent studies have shown that neutrophils play an important role in the development and progression of heart failure. Developmental endothelial locus-1 (DEL-1) is an anti-inflammatory glycoprotein that has been found to have protective effects in various cardiovascular diseases. However, the role of DEL-1 in chronic heart failure is not well understood. In a mouse model of pressure overload-induced non-ischemic cardiac failure, we found that neutrophil infiltration in the heart increased and DEL-1 levels decreased in the early stages of heart failure. DEL-1 deficiency worsened pressure overload-induced cardiac dysfunction and remodeling in mice. Mechanistically, DEL-1 deficiency promotes neutrophil infiltration and the formation of neutrophil extracellular traps (NETs) through the regulation of P38 signaling. In vitro experiments showed that DEL-1 can inhibit P38 signaling and NETs formation in mouse neutrophils in a MAC-1-dependent manner. Depleting neutrophils, inhibiting NETs formation, and inhibiting P38 signaling all reduced the exacerbation of heart failure caused by DEL-1 deletion. Overall, our findings suggest that DEL-1 deficiency worsens pressure overload-induced heart failure by promoting neutrophil infiltration and NETs formation.

Abnormal workload-indexed blood pressure response to exercise in patients at risk of or with overt heart failure

Abstract Background Conflicting evidence exists regarding the functional and prognostic significance of hypertensive response to exercise (HRE), commonly defined as peak systolic blood pressure (SBP) &amp;gt;210 mmHg in males and &amp;gt;190 mmHg in females. No study yet has explored the impact of sex-specific, workload-indexed HRE in patients at different stages of the heart failure (HF) spectrum, as defined by the American College of Cardiology/American Heart Association HF staging system. Purpose We evaluated the SBP/Workload slope during exercise across the HF spectrum and investigated the hemodynamic, functional and prognostic correlates of HRE. Methods Fifty-eight healthy controls, 201 subjects at risk of developing HF (HF Stages A-B), and 369 patients with a definite diagnosis of HF (Stage C) were enrolled; among the latter, 143 had preserved (HFpEF) and 226 reduced (HFrEF) left ventricular ejection fraction. All patients underwent a combined cardiopulmonary-exercise stress echocardiography test. For each patient, we recorded at least two BP measurements during exercise: the first within the first minute of exercise and the last at peak effort. The SBP/Workload slope was calculated as the difference in SBP over the corresponding increment in watts (W): (SBPpeak – SBPfirst)/(Wpeak – Wfirst). In each ACC/AHA HF Stage, we divided patients according to SBP/Workload slope tertiles; HRE was defined as the highest sex-specific SBP/Workload slope tertile. A composite of all-cause mortality and hospitalization for cardiovascular reasons was chosen as the primary outcome. Results The median SBP/Workload slope was 0.53 (interquartile range 0.36-0.72) mmHg/W and was steeper in women than in men in all subgroups (p&amp;lt;0.0001). After adjusting for age and sex, SBP/Workload slope was significantly higher in Stages A-B (0.61, 0.47-0.75 mmHg/W) and HFpEF (0.63, 0.42-0.86 mmHg/W) compared to controls (0.43, 0.35-0.57 mmHg/W) and HFrEF (0.47, 0.30-0.63 mmHg/W, Figure 1). In all subgroups, patients with HRE showed significantly lower peak oxygen consumption and peripheral oxygen extraction (Table). After a median follow-up of 16 months, HRE was an independent predictor of adverse outcomes (Hazard Ratio 2.05, 95% confidence interval 1.81-5.18), while rest and peak absolute SBP values did not. Kaplan-Meier analysis confirmed a worse survival probability for patients with HRE in Stages A-B and HFpEF but not in HFrEF. After adjusting for confounding factors, the patients with the highest SBP/Workload slope had a 47% higher risk of the primary outcome than subjects in the lowest tertile (Figure 2). Conclusions Across the HF spectrum, patients with HRE, as evaluated by the SBP/Workload slope, present with peculiar pathophysiological features and impaired functional capacity. This is especially true for those in Stages A-B and patients with HFpEF. In these subgroups, HRE may portend an increased risk of adverse cardiovascular outcomes.SBP/workload slopesKaplan-Meier curves and Hazard Ratios

Hand-held echocardiography-based heart failure screening in hypertensive or diabetic patients in community: a pilot study

Abstract Background There is lack of solid data on screening methods for preclinical heart failure (HF) in primary care settings. Standard echocardiography is not regarded as a routine test due to high cost and need of operation by specialists. Hand-held echocardiography (HHE) has been used in various clinical settings with easier access and lower price but has never been integrated into HF screening programme. Purpose This study aimed to explore the feasibility and cost-effectiveness of hand HHE-based HF screening strategies in patients with risk factors in community. Methods The registered patients with hypertension or diabetes at two Chinese community health service centres (CHSCs) who had not been diagnosed previously as HF were recruited. Every patient received symptom assessment (dyspnea and/or lower limb edema), blood test for N-terminal-probrain natriuretic peptide (NT-proBNP ≥ 125 pg/ml regarded as positive), and HHE for any indexed abnormality in the dedicated protocol with focused and semiquantitative scanning [i.e. left ventricular (LV) dilation, left atrial (LA) dilation, interventricular septum (IVS) thickening, LV systolic dysfunction by calipers, as well as region wall motion abnormality, valvular stenosis, ≥moderate valvular regurgitation, significant pericardial effusion by eyeballing). By using the results of all the three modalities for screening compared to the concurrent guidelines, the patients were categorized into HF stages A, B, or C as the "gold standard". Three screening strategies were proposed (Figure 1), of which Strategy I was designed as a single test, Strategy II as a combined test, and Strategy III as a stratified stepwise test. Diagnostic accuracy and cost-effectiveness of each strategy was calculated in comparison with the "gold standard". Results A total of 423 patients (70 ± 9 years; 46.6% males) were enrolled. There were 166 (39.2%) symptomatic patients, while 106 (25.1%) patients had elevated NT-proBNP. HHE abnormalities were found in 286 (67.0%) patients, of which IVS thickening was the most common finding (47.0%), followed by LA enlargement (30.0%). LV systolic dysfunction was identified in 18 (4.3%) patients. 232 (54.8%) and 59 (13.9%) patients were reclassified as HF stage B and C, respectively. As shown in Figure 2, the stepwise Strategy III of using symptoms for the first stratification, followed by choosing HHE or NT-proBNP test led to a 100% accuracy and a 35.6% reduction in cost. Conclusions HHE-based focused screening detects HF earlier in high-risk populations. The screening strategy combined with symptoms, NT-proBNP, and HHE is feasible for identifying underdiagnosed HF stage B or C that may be considered in primary care.Scheme of HF stage screening strategiesHF Screening and cost-effectiveness

Longitudinal association of subclinical cardiac function with cognitive function

Abstract Background Cognitive impairment and heart disease frequently co-exist due to shared disease processes and pathological mechanisms. The presence of one may lead to and/or worsen the other. This bidirectional relationship between cognitive impairment and heart disease acts as a vicious cycle that increases the burden of both diseases. Our previous findings have demonstrated that cognitive impairment is a strong predictor of post-discharge readmission or death in heart failure, second only to heart failure severity. However, whether heart failure and cognitive impairment has a causal relationship remains unknown. This study sought to determine the relationship between subclinical cardiac function and cognitive function. Methods This study included 1977 consecutive patients (62% men, aged 73±13 years) with heart failure ranging from stage A to C. These patients were followed up for 36 months. At both baseline and follow-up, subclinical cardiac function was measured by echocardiography, and cognitive function was measured using Montreal Cognitive Assessment (MOCA). Other measurements included blood biochemistry, comorbidities, physical measurements and questionnaires. Results Cognitive function was strongly associated with both readmission and death in patients with heart failure, particularly among those with stage C. Among patients with heart failure stage A or B, left atrial volume index (LAVI) and E/e’ were associated with a reduction of MOCA score and higher risks of newly developed cognitive impairment at 36-month follow-up (OR = 1.04 [95% CI:1.02-1.07] per 1ml/m2 LAVI, and OR = 1.07 [95% CI:1.01-1.15] per 1 unit E/e’). Patients with cognitive impairment have significantly enlarged left atrium, compared with those with normal cognition (p&amp;lt;0.001). While almost all (93%) of patients with consistent cognitive impairment from baseline to follow-up had an enlarged left atrium, 71% of those who became cognitively impaired at follow-up had an enlarged left atrium. Conclusions The longitudinal relationship between diastolic cardiac function and cognitive function suggests a causal pathway between these two. Assessment of cognitive function is recommended in patients with impaired cardiac function.

Prevalence and implications of heart failure stages A-D in patients with chronic kidney disease

Abstract Background Heart failure (HF) is a frequent comorbidity among patients with chronic kidney disease (CKD). Echocardiography allows for simple, non-invasive evaluation of structural and functional heart disease that could potentially classify patients at high risk of HF. Purpose This study aimed to assess the prevalence of HF stages A-D defined by the AHA/ACC/HFSA in CKD patients, and to report the incidence rates of renal outcomes and mortality of these stages. Methods This is a prospective cohort study. Patients aged 30 to 75 years with estimated glomerular filtration rate (eGFR) stages G1 to G5 pre-dialysis were included. All participants were examined using a pre-defined echocardiographic protocol. HF stages B and C/D were defined based on ejection fraction, global longitudinal strain, TAPSE, left ventricular mass, left ventricular diameter, left atrial volume index, and valvular heart disease in accordance with the AHA/ACC/HFSA guidelines. The outcomes examined were (1) a composite of kidney transplantation and dialysis and (2) all-cause mortality. Results A total of 825 patients with CKD were included. Mean age was 58±13 years and 37% were female. The participants were categorized as follows: Stage A HF: 352 (42.7%); stage B HF: 295 (35.8%); and stage C/D HF: 122 (14.8%). In total, 56 participants did not fulfil the criteria of HF stage A, B, C, or D and were classified as HF stage 0. Figure 1 displays the prevalence of HF stages across CKD stages. Poorer eGFR (P for trend 0.001) and urine albumin/creatine ratio (P for trend 0.005) were both significantly associated with increasing HF stages in linear regression models (including age, sex, and systolic blood pressure). During a median follow-up of 4 years, 115 patients (13.9%) developed the composite renal outcome and 74 patients (9.0%) died. Incidence rate per 100 patient-years for the composite renal outcome according to HF-stages was 2.3 (95%CI: [0.95;5.5]) for stage 0, 3.3 (95%CI: [2.5;4.5]) for stage A, 3.8 (95%CI: [2.8;5.1]) for stage B, and 6.3 (95%CI: [4.3;9.3]) for stage C/D. The incidence rate did only significantly differ between stage C/D and stage 0 (p = 0.026), and HF stage C/D was the only stage associated with the composite renal outcome in univariable Cox regression (HR = 2.80 (95%CI: [1.07;7.31], p = 0.036)). Incidence rate of death (per 100 patient-years) by 0, A, B, and C/D HF-stages were 1.3 (95%CI: [0.43;4.2]), 1.0 (95%CI: [0.63;1.7]), 2.5 (95%CI: [1.7.;3.6]), and 7.3 (95%CI: [5.1;10]), respectively. Incidence of death was only significantly higher in stage C/D compared with stage 0 (p&amp;lt;0.001). Also, stage C/D was the only stage that was significantly associated with all-cause mortality in univariable Cox regression (HR = 5.47 (95%CI: [1.67;17.9], p = 0.005)). Conclusion Among patients with CKD, worse HF stages became more prevalent with worsening kidney function, and both incidence rates of the composite renal outcome and of death were higher in HF stage C/D.HF stages distributed on CKD stages

Abstract 16481: Comparative Measures of Physical Performance in Healthy Subjects and Patients With Subclinical Heart Failure or Coronary Artery Calcium in the Project Baseline Health Study

Introduction: While exercise stress test is the traditional method for assessing cardiorespiratory fitness, 6-minute walk test (6MWT) and 10-meter walk test (10MWT) can be inexpensive alternatives for physical activity and fitness evaluation. We aim to identify conditions where 6MWT and 10MWT show comparable diagnostic yield to metabolic equivalents of task (MET). Methods: All participants in the Project Baseline Health Study (PBHS) with no missing data were included. Participants were assigned a heart failure (HF) stage according to the 2022 AHA/ACC HF guidelines. Mean and standard deviation (SD) were described for each measurement by HF stages: 0 (healthy), A (presence of risk factors (RF)), and B (presence of RF and LVEF&lt;50%, diastolic dysfunction or LVH); and by coronary artery calcium (CAC) score subgroups: 0, 1-99, ≥100 Agatson units (AU). Multinomial regression was applied to estimate the association of each measurement with HF stage and CAC subgroups adjusted for relevant covariates. Results: 2,181 (87%) of 2,502 PBHS participants had complete data on METs, 6MWT, and 10MWT. The mean (SD) age was 50.1 (17.1) years, with 1224 (56.1%) females. The cohort consisted of participants with Stage 0, A, B (n=711, 742, 372) and CAC = 0, 1-99, ≥ 100 (n=1275, 471, 348). The overall mean (SD) for 6MWT, 10MWT, and METs were 479.8 (79.1) m, 2.0 (0.5) m/s, and 11.6 (4.3), respectively. Each SD decrease of METs was significantly associated with increased odds for more advanced HF stages and CAC subgroups ( Figure A1-B2 ). The 10MWT and 6MWT were also able to differentiate significantly between subclinical stages of HF and compare CAC subgroups 1-99 and ≥100 to CAC=0, although with smaller odds ratios (Figure A1, A2, B1). Conclusions: METs, as measured in a graded exercise test, demonstrated the strongest association with HF stage or CAC subgroup. Based on our findings, there is potential for utilizing the simpler assessments of 10MWT and 6MWT to differentiate between subclinical HF stages.

Abstract 12736: Prevalence, Characteristics, and Outcomes of Infective Endocarditis in Patients With Liver Disease in the United States

Introduction: Infective endocarditis (IE) is common in patients with liver disease. Data regarding IE in liver disease are limited. Hypothesis: We analyzed IE admissions to determine inpatient outcomes among patients with liver disease in the United States. Methods: We used the 2017 National Readmission Database to identify index admission of adults with IE, based on the International Classification of Disease, 10th revision codes. The primary outcome was 30-day readmission. Secondary outcomes were mortality and predictors of hospitalization readmission. Results: We identified 40,413 IE admissions. Figure 1 presents prevalence of variables associated with liver disease in this cohort. Patients who were readmitted were more likely to have a history of hepatitis C virus (19.4% vs 12.3%, p &lt; 0.001), hyponatremia (25% vs 21%, p &lt; 0.001), and thrombocytopenia (20.3% vs 16.3%, p &lt;0.001). After adjusting for age, hypertension, heart failure, diabetes mellitus, and end stage renal disease, hyponatremia (odds ratio (OR): 1.25; 95% confidence intervals [CI]: 1.17 to 1.35; p &lt; 0.001) and thrombocytopenia (OR: 1.16; 95% CI: 1.08 to 1.24; p &lt; 0.001) correlated with higher odds of 30-day readmission. Mortality was higher among patients with hyponatremia (29% vs 22%, p &lt; 0.001), thrombocytopenia (29% vs 17%, p &lt; 0.001), coagulopathy (12% vs 5%, p &lt; 0.001), cirrhosis (6% vs 4%, p &lt; 0.001), ascites (7% vs 3%, p &lt;0.001), liver failure (18% vs 3%, p &lt; 0.001), and portal hypertension (3% vs 1.5%, p &lt; 0.001) (Figure 2). Conclusions: Important liver disease related variables correlate with higher risks of hospital readmission and mortality in patients with IE. Targeting such variables may improve outcomes in this patient population.

Abstract 12486: Predictive Value of Chronotropic Incompetence for Clinical Outcomes in Heart Failure: Findings From the MyoVasc Study

Introduction: Chronotropic incompetence (CI), an important aspect of exercise intolerance, is related to adverse clinical outcomes in heart failure (HF). However, the lack of standardized evaluation of CI results in inconsistent evidence. Aim: To evaluate CI with regard to clinical and medical determinants and relationship to clinical outcomes in HF. Methods: Data from the MyoVasc study (NCT04064450), a prospective cohort on HF, were analyzed. Subjects underwent deep clinical phenotyping, including cardiopulmonary exercise testing on a cycle ergometer. Measures of CI were evaluated, with continuous predicted heart rate reserve (pHRR) emerging as the most clinically relevant definition for operationalizing CI. Clinical and medical determinants of CI were assessed in multivariable linear regression models and outcomes in Cox regression models. Results: The analysis sample included 886 subjects (median age 63 years [interquartile range (IQR) 55; 72]; 29.9% women) who achieved maximal exertion (respiratory exchange ratio&gt;1.0). Symptomatic HF stage C/D was present in 42.8% (379) of the subjects. Sixteen drug groups were identified as CI modulators including β-blockers (β-estimate per SD -0.83 [95% confidence interval -0.95;-0.70], p&lt;0.0001) and antiarrhythmics (β SD -0.93 [-1.30;-0.56], p&lt;0.0001). New York Heart Association functional class, smoking, fatty liver index (FLI), and diabetes mellitus (DM) were the strongest determinants of CI in all subjects independently of sex, age, and previously identified medication. Determinants differed according to left ventricular ejection fraction [LVEF] (≥50 vs &lt;50%), being strongly associated with markers of HF (NT-proBNP) and lung function (FEV1) in HF with reduced EF and more linked to DM or the FLI in HF with preserved EF. In Cox regression analysis adjusted for clinical profile, pHRR independently predicted all-cause death (HR SD 1.86 [1.41;2.45], p&lt;0.0001) and worsening of HF (HR SD 1.37 [1.04;1.81], p=0.025). Conclusions: CI strongly predicted clinical outcomes and revealed relevant differences between HF with preserved and reduced EF. This highlights the relevance of impaired response to exercise in the clinical course of HF with implication for risk stratification and intervention.

Abstract 12961: Heart Failure Redesign Across a Newly Integrated Health System

Introduction: Heart Failure (HF) challenges are magnified when healthcare mergers and expansions occur requiring significant integration of operational and clinical effort. With enterprise support, we brought HF teams together from a newly merged system to 'redesign' HF care aiming to provide high level, consistent, evidence-based, patient-centered care in a novel, adaptive model where such roadmaps do not exist. Hypothesis: Integrated care across a large network can be patient centered, of high value, with a proper framework. Methods: Representatives from 3 distinct, newly aligned regions of Intermountain Health completed a care redesign program aimed to integrate HF services. Current processes, tools, education were evaluated then mapped to identify barriers and most impactful areas to guide redesign. Results: Over 6 months, 45 multidisciplinary HF specialists met weekly. Current state was mapped for 9 markets across 3 regions reaching &gt;38,089 patients. Baseline data revealed areas for improvement: readmissions, mortality, advanced care planning, transitions in care. 141 barriers were identified, 39 of high impact, 15 are the primary focus; includes increasing access to stage-based care, implementing a guideline-directed referral pathway and providing market-specific resources. 4 teams built an operating system to support a new HF standard (image). Elements culminated in a consistent care path across the HF Stages for the newly formed enterprise. Implementation is underway; outcomes will be forthcoming. Conclusion: Building HF care across a large healthcare organization takes both clinical and operational leadership through shared learning. With a vision and framework this redesigned system aims to increase ease and access while providing high quality, patient-centered, consistent care regardless of location. Attention to high areas of opportunity requires operational prioritization, subject matter expertise, and resource support.

Abstract 14527: AI-ECG is a Cost-Effective Early Screening Tool for Heart Failure With Reduced Ejection Fraction

Background: Early diagnosis of heart failure with reduced ejection fraction (HFrEF) can lead to reduced healthcare costs and improved outcomes. In this study, we evaluated the economic effectiveness of an AI algorithm for detecting low ejection fraction using 12-lead ECG data. Aims: The primary aim was to estimate the health economic impact of the AI-ECG algorithm intervention to detect low ejection fraction. Methods: The study population consisted of 113,719 individuals without a prior history of HFrEF who visited a multistate health system between 2010-2018 with 12-lead ECG data and an echocardiogram within 1 year. The AI-ECG algorithm was run retrospectively, and projected costs were estimated assuming each patient incurred the average cost based on their age group and AI-detected heart failure stage. Hospitalization costs were estimated using Medicare reimbursement rates, and economic benefits from increased survival were estimated using a willingness to pay of $50,000 per quality-adjusted life year (QALY) gained. Results: At the optimal model threshold, the total cost savings per patient (including benefits from QALYs gained) for the AI-ECG algorithm vs. standard-of-care on the overall study population were projected to be $79.11 (95% CI: [$53.77, $104.44]) and $124.93 (95% CI: [$83.99, $165.88]) for the 2 and 4 year periods, respectively. For patients over 50 years old, the projected total cost savings were $85.56 (95% CI: [$56.35, $114.78]) and $135.28 (95% CI: [$88.18, $182.38]) per patient for the 2 and 4 year periods, respectively. See Figure. Conclusions: The AI-ECG algorithm to detect low ejection fraction is a cost-effective early screening tool for HFrEF.