Stage Heart Failure Research Articles

S-12-5: IMPAIRMENT OF RENAL BLOOD FLOW AUTOREGULATION AND PRESSURE-NATRIURESIS: ROLE IN THE DEVELOPMENT OF HEART FAILURE IN REN-2 TRANSGENIC HYPERTENSIVE RATS

Objective: The prognosis of patients with heart failure (HF), particularly those who were hypertensive before the onset of HF, remains poor and new therapeutic strategies are needed, based on understanding the pathophysiology of the progression of HF. We hypothesized that the kidney is here not simply a victim but also a culprit of the progression. Specifically, we hypothesized that the impairment of renal blood flow (RBF) autoregulation and pressure-natriuresis relationship is present in the very early HF phase, and precedes HF decompensation. Design and method: In Ren-2 transgenic rats (TGR), a model of hypertension with increased endogenous activity of the renin-angiotensin system (RAS), HF was induced by volume overload achieved by creation of the aorto-caval fistula (ACF). One week after ACF creation or sham-operation animals were prepared for studies evaluating in vivo RBF autoregulatory capacity and pressure-natriuresis relationship after stepwise changes in renal arterial pressure (RAP) that were induced by aortic clamps. Sham-operated TGR were evaluated at physiological level of RAP, then at RAP reduced to 125, 100, 90 and 80 mmHg. In ACF TGR RAP was reduced to 100, 90 and 80 mmHg, followed by period of RAP increased to 125 mmHg. Results: In sham-operated TGR as compared with ACF TGR the basal mean arterial pressure (156 ± 3 vs. 98 ± 3 mmHg), RBF (11.45 ± 0.6 vs. 8.13 ± 0.3 ml.min-1.g-1), urine flow (UF) (38.3 ± 3.1 vs. 8.7 ± 1.0 μl.min-1.g-1) and absolute sodium excretion (UNaV) (4.77 ± 0.54 vs. 0.46 ± 0.11 μmol.min-1.g-1) were all significantly lower. In sham-operated TGR reductions in RAP resulted in significant decreases in RBF whereas in ACF TGR it did not change in response to RAP alterations. Stepwise reductions in RAP resulted in marked decreases in UF and UNaV in sham-operated as well as in ACF TGR, however, these decreases were significantly greater in the former. Conclusions: Our data show that at the physiological RAP level ACF TGR displayed marked reduction in RBF, UF and UNaV as compared with sham-operated TGR. However, in contrast to sham-operated TGR, ACF TGR displayed well-maintained RBF autoregulatory capacity and better slope of pressure-natriuresis relationship. Thus, even in the very early HF stage the renal dysfunction is demonstrable but such dysfunction and the subsequent onset of HF decompensation cannot be simply ascribed to impaired RBF autoregulation and pressure-natriuresis relationship, at least not in the high-output HF model of originally RAS-dependent hypertensive rat.

Clinical, laboratory changes and fibroblast growth factor in patients with myocarditis

Annotation. The relevance of the problem of diagnosis and treatment of myocarditis in the world and in Ukraine is growing. The prevalence of myocarditis is up to 20% of all non-coronary heart lesions. According to the results of the study of the sudden death causes in young people, the detection of inflammatory lesions of the myocardium varies in the range of 2-42%. The article analyzes the course of acute myocarditis of unknown etiology in 48 adult patients (31 patients with a moderate-severe course and 17 patients with a severe course), establishes clinical features of the course of the disease and laboratory markers associated with the severity of the course of the disease and myocardial fibrosis. The severity of the course of the disease was determined based on the volume of myocardial damage, the stage and functional class (FC) of heart failure, the presence of systolic heart dysfunction and life-threatening rhythm and conduction disorders. Statistical processing of the research results was carried out using the created database of examined patients in the StatSoft Statistica v 10.0 program, with a known number of observations (n). The Mann-Whitney test was used to determine differences between quantitative traits. Spearman's rank correlation coefficient was calculated to determine the degree of statistical dependence between indicators. It was established that myocarditis mostly had a course of moderate severity (64,6 %) with the presence of heart failure of II A stage in 54,8 % of inspected patients, and was accompanied by combined complex rhythm and conduction disorders in 38,7 % of patients. A reliable correlation was established between the increase in markers of inflammation (CRP, fibrinogen), cardiomyocyte lysis (CFC-MV) and fibroblast growth factor 23 (FGF-23), which indicates an increase in profibrotic processes as a result of myocardium inflammatory damage. It is important to carry out a detailed study of the clinical features of myocarditis with the further perspective of developing diagnostic methods for timely etiopathogenetic treatment and forecasting the adverse course of the disease.

CARDIAC CACHEXIA AND CLINICAL OUTCOME OF CHRONIC HEART FAILURE DUE TO RHEUMATIC HEART DISEASE

Background: Rheumatic Heart Disease (RHD) is still a significant cause of cardiovascular morbidity and death in developing countries like Indonesia. However, despite being one of the most preventable chronic diseases, RHD still receives less attention, especially in Southeast Asia. PJR that is not treated immediately can develop into chronic heart failure. When heart failure has entered the stage of congestive heart failure, there is activation of a complex network of metabolic, immune, and characteristic neurohormonal factors that can result in cachexia. Cachexia can be an indicator of decreased survival in patients with chronic heart failure due to RHD. Objective: To determine the relationship between cachexia and clinical outcomes of chronic heart failure due to RHD at RSUD Dr. Soetomo. Methods: This study was an analytic observational study using a retrospective cohort design. Data were collected by taking secondary data in the form of patient medical records. There were 106 patients who were taken by non-probability sampling technique. Correlation was determined using Mann-Whitney test and Chi-square test. Result: A total of 106 patients consisted of 53 people with cachexia and 53 people without cachexia, represented both groups dominated by female (57.6%), with largest age range was late adulthood (36-45 years) in both groups (32.1%). Education level data mostly came from secondary schools with a total of 71 people (66.9%) in both groups. The most common type of valve lesion in both groups was mitral stenosis (53.7%). The frequency of hospitalization in patients with cachexia was more frequent with an average of 1.25 times compared to patients without cachexia with an average of 1.02 times. Mortality was higher in patients with cachexia as many as 7 per 53 people (0.13%) compared to patients without cachexia as many as 3 per 53 people (0.06%). With Mann-Whitney and chi-square tests, it was found that cachexia had no effect on the hospitalization frequency (p=0.453) and mortality (p=0.319). Conclusion: Clinical outcomes in chronic heart failure patients due to RHD with cachexia are found to be higher in hospitalization frequency and mortality compared to patients with no cachexia.

373 ADONHERS (AGED DONOR HEART RESCUE BY STRESS ECHO) PROTOCOL FOR HEART DONATION FROM MARGINAL DONOR HEARTS: MONOCENTRIC RETROSPECTIVE STUDY ON RECIPIENT'S SURVIVAL AFTER 10-YEAR FOLLOW-UP

Abstract Backgorund Amelioration of therapies and increased survival in heart failure (HF) is leading to a growing number of patients affected by advanced HF, with an overall 1-year prognosis ranging from 25 to 75%. The gold standard treatment for end stage HF is heart transplantation (Htx), but lack of organs donors remains an important limitation. Marginal hearts can potentially improve and be utilized after a re-evaluation by “aggressive” assessment of donor left ventricular function. Purpose In our study we analysed if recipients of marginal donor hearts, selected by dipyridamole stress echocardiography, had different outcome compared to recipients with acceptable donor hearts. Methods Data collected from 2006 and 2014 of patients who received orthotopic Htx from marginal heart donors (group 1) and were retrospectively analysed and compared with recipients of acceptable heart donors (group 2). Bedside standard echocardiography and dipyridamole stress echo was performed for the selection of marginal hearts > 55 years old or < 55 with comorbidities/mildly dysfunctional left ventricle. Clinical, laboratory and instrumental features of the two groups of recipients were evaluated and patients with homogenous baseline characteristics were selected to reduce biases among the two groups. Follow-up through routine heart transplant surveillance included visit, echocardiography, blood tests, serial endomyocardial biopsies and coronary angiography. Results Twenty-two recipients were included in the study. Mean donors age was 41 ± 23, 45 ± 29 years for group 1 vs 36 ± 12 for group 2. The average follow-up was 113 months. Age, cardiovascular risk and morpho-functional characteristics of the left ventricle were comparable between the two population (P> 0.05). Left atrial size was significantly higher in marginal hearts (Optimal: p=0.007; Marginal: p=0.003). Acceptable recipients showed a higher impact of CAV (p= 0.019) together with more elevated values of cholesterol and triglycerides (p = 0.048 and p = 0.012 respectively). No differences concerning cellular or humoral rejection were found between the two groups. Four patients deceased, 3 had received a standard donor heart and 1 was from the marginal donor group, with and overall median time to death of 124 months. Conclusions Our small pilot study shows how the evaluation of marginal donor hearts with echo stress result to no affect recipients survival compared with controls of acceptable hearts. A well-controlled selection of marginal hearts could therefore improve the shortage of organs, reducing the long line of patients waiting for a heart.

177 TRANSCATHETER EDGE-TO-EDGE REPAIR OF SEVERE FUNCTIONAL MITRAL REGURGITATION TO OVERCOME ACUTE DECOMPENSATION IN A YOUNG MAN CANDIDATE TO HEART TRANSPLANTATION.

Abstract Background Chronic severe functional mitral regurgitation (FMR) is common in patients with HF as it reflects left ventricle dysfunction and portends poor prognosis. Case report A 42 years old man with cardiovascular risk factors (former smoker, obesity) but without previous cardiological history presented anterior ST-elevation myocardial infarction (STEMI) treated with primary PCI of the anterior descending artery. He developed severe ventricular dysfunction leading to congestive heart failure (HF) requiring early re-hospitalization for pulmonary edema. Despite optimal medical therapy patient remained symptomatic (NYHA class III, INTERMACS 6) with persistence of left ventricle ejection fraction (LVEF) depression, therefore he received an implantable cardiac defibrillator for primary prevention and was referred to our institution for further evaluation. Trans-esophageal echocardiography showed severe left ventricle dilatation and disfunction (EDD 6.9 cm, iEDV 113 ml/m2, LVEF 24%) and presence of severe FMR with EROA 37 mm2 and RV 44 ml. Right heart catheterization (RHC) revealed combined pulmonary hypertension (mean PA pressure 43 mmHg, PCWP 32 mmHg, PVR 4.6 WU) with severely reduced cardiac index obtained (CO 3.4 l/min, CI 1.9 l/min/m2). After infusion of inodilator (enoximone) a decrease of PA pressure and PVR was reported, concluding for reversible pulmonary hypertension. After screening for non-cardiac contraindications, the patient was listed for heart transplantation. Chances to get a donation with a short waiting list time were low because of patient's high BMI and blood group B. Therefore, after Heart Team evaluation, transcatheter edge-to-edge repair of the mitral valve (TEER) was performed as bridge to transplant. A single NTR clip was used, placed centrally between A2-P2 segments, reducing regurgitation from severe to mild. Patient was discharged on heart transplantation waiting list. At three months follow up he presented clinical improvement with reduction of NYHA class from III to II. RHC was repeated and showed normal filling pressures, reduction of pulmonary pressure (mPAP 20 mmHg) and increased cardiac output (CO 5.2 l/min, CI 2.5 l/min/m2). According to his preferences, the patient was suspended from the waiting list with indication to continue outpatient follow-up. At 1-year control he was stable in NYHA II class and the daily diuretic dose had been reduced, echocardiography showed severe LVEF depression (28%) with mild to moderate residual mitral regurgitation. Conclusions TEER recently emerged as an option for patients with FMR who are not suitable for surgery. Latest guidelines suggest its use in presence of specific criteria (LVEF 20-50%, ESD < 7 cm, sPAP <70 mmHg, hemodynamic stability, absence of right ventricle disfunction and severe TR) rarely fulfilled by patients with advanced HF requiring evaluation for transplant. On the other hand, access to surgical strategies for end stage HF is limited by scarce availability of donors and by temporary or definitive contraindications. Evidences are emerging that in this population TEER can improve hemodynamic profile and lead to reduction of pulmonary hypertension, providing temporary stability before definitive treatment or allowing candidacy. In this setting, TEER might be performed to reduce symptoms. Considering TEER as bridge strategy to transplant, candidacy or decision can expand the number of patients suitable for heart transplantation or delay urgency.

Current state of knowledge and information sharing among home healthcare professionals involved in heart failure management

BackgroundThe current state of knowledge related to disease management of heart failure (HF) and information coordination practices provided by non-physician healthcare professionals such as nurses and therapists working at home-visit nursing stations in Japan are not well known. MethodsA questionnaire survey of healthcare professionals working at home-visit nursing stations was conducted in Kochi Prefecture. Data collected from 151 nurses and therapists were analyzed. ResultsRegarding the basic characteristics of the respondents, the majority were in their 30s and 40s, and approximately 75 % were nurses. In terms of HF knowledge, 53.7 % of respondents said that they “knew” about the New York Heart Association classification. A total of 40.0 % of respondents said that they were “aware of the existence of the HF handbook”, and only 29.3 % of respondents said that they “knew” the classification of HF stages. When they were asked about their level of satisfaction related to all medical information provided by the hospital and hospital wards, no one was “very satisfied”, and the most common response (66.2 %) was “not very satisfied”. In the essential medical information that respondents wanted to obtain from hospitals and hospitals wards for managing HF patients at home, “medication at discharge”, “current medical history”, “fluid intake and restrictions”, “symptoms, signs, and response to exacerbation”, and “ideal body weight” were the top five contents. ConclusionIn the cross-sectional study targeted healthcare professionals working at home-visit nursing stations in Kochi Prefecture, the current state of knowledge related to HF and information coordination practices among healthcare professionals were not fully satisfactory in HF management. It is necessary to increase educational opportunities regarding HF for them and further promote information sharing.

ACC/AHA/HFSA 2022 and ESC 2021 guidelines on heart failure comparison.

The 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America (ACC/AHA/HFSA) and the 2021 European Society of Cardiology (ESC) both provide evidence-based guides for the diagnosis and treatment of heart failure (HF). In this review, we aimed to compare recommendations suggested by these guidelines highlighting the differences and latest evidence mentioned in each of the guidelines. While the staging of HF depends on left ventricular ejection fraction, the Universal Definition of HF, suggested in 2021, is described in 2022 ACC/AHA/HFSA guidelines. Both guidelines recommend invasive and non-invasive tests to diagnose. Despite being identical in the backbone, some differences exist in medical therapy and devices, which can be partially attributed to the recent trials published that are presented in the American guidelines. The recommendation of implantable cardioverter defibrillator for prevention in HF with reduced ejection fraction (HFrEF) patients, made by ACC/AHA/HFSA guidelines, is among the bold differences. It seems that ACC/AHA/HFSA guidelines emphasize the quality of life, cost-effectiveness, and optimization of care given to patients. On the other hand, the ESC guidelines provide recommendations for certain comorbidities. This comparison can guide clinicians in choosing the proper approach for their own settings and the writing committees in addressing the differences in order to have better consistency in future guidelines.

Inflammation across universal definition of heart failure stages: the CASABLANCA study.

We sought to investigate the association of inflammatory biomarkers with incident heart failure (HF) events in patients at different stages of HF. Overall, 1231 study participants undergoing diagnostic coronary and/or peripheral angiography were categorized by Universal Definition of HF (UDHF) stage A (at risk), stage B (pre-HF), and stages C or D (HF, including end-stage). Twenty-four inflammatory biomarkers were collected prior to angiography and unsupervised machine learning categorized levels of inflammation into three groups (low, medium, and high). Cox proportional hazard regression was implemented to assess the associations of inflammation level with incident HF hospitalization in each UDHF stage. Using machine learning, study participants were grouped into low (n=443), medium (n=570) and high inflammation categories (n=230). Significantly higher concentrations of natriuretic peptide, troponin, and soluble ST2 were observed among those with high inflammation levels (p < 0.001). During 3.7 years of follow-up, 123 (15.1%) HF hospitalizations occurred in stage A/B and 180 (41.8%) HF hospitalizations occurred in stage C/D. In multivariable model considering low inflammation level as a reference, among patients with stage A/B, the hazard ratio (HR) (95% confidence interval [CI]) of incident HF was 2.31 (1.40-3.80) for moderate inflammation level, and 4.16 (2.35-7.37) for high inflammation level. Among patients with stage C/D, the corresponding HR (95% CI) of HF hospitalization was 1.98 (1.28-3.04) for moderate inflammation level, and 2.69 (1.69-4.28) for high inflammation level. Patterns of inflammation severity may have differing prognostic meaning across UDHF stages.

Early administration of ivabradine in patients admitted for acute decompensated heart failure.

Heart rate (HR) control is important in heart failure (HF) patients with reduced ejection fraction, and ivabradine is indicated for patients with chronic HF and sinus rhythm. However, ivabradine is limited in initiation of ivabradine at acute stage of HF. This multi-institutional retrospective study enrolled 30,639 patients who were admitted for HF from January 01, 2013 to December 31, 2018 at Chang Gung Memorial Hospitals. After applying selection criteria, the eligible patients were divided into ivabradine and non-ivabradine groups according to the initiation of ivabradine at the index hospitalization. HR, clinical outcomes including HF hospitalization, all-cause hospitalization, mortality, the composite of cardiovascular (CV) death or HF hospitalization and newly developed atrial fibrillation, and left ventricular ejection fraction (LVEF) and left atrium size were compared between the ivabradine and non-ivabradine groups after inverse probability of treatment weighting (IPTW) analysis after 12 months. The HR at admission in the ivabradine group (n = 433) was 99.04 ± 20.69/min, compared to 86.99 ± 20.34/min in the non-ivabradine group (n = 9,601). After IPTW, HR was lower in the ivabradine group than that in the non-ivabradine group after 12 months (74.14 ± 8.53 vs. 81.23 ± 16.79 bpm, p = 0.079). However, there were no significant differences in HF hospitalization (HR = 1.02; 95% CI, 0.38-2.79), all-cause hospitalization (HR = 0.95; 95% CI, 0.54-1.68), mortality (HR = 0.87; 95% CI, 0.69-1.08), the composite of CV death or HF hospitalization (HR = 0.87; 95% CI, 0.69-1.08) and newly developed AF between the two groups. In addition, LVEF increased with time in both groups, but there were no significant differences during the observation period. Ivabradine was beneficial in controlling HR when initiated in patients with acute stage of HF, but it did not seem to provide any benefits in reducing HF hospitalization, all-cause hospitalization, and mortality in 1 year after discharge.

Prevalence of Perceived Depressive Symptoms and Its Association With Stages of Heart Failure among Outpatients in a Public Hospital in Malaysia

Heart failure (HF) patients with depression usually have poor prognosis. This study aimed to determine the prevalence of perceived depressive symptoms among outpatients with HF and its association with the New York Heart Association (NYHA) class. This was a cross-sectional survey conducted at the Heart Failure Clinic in Hospital Pulau Pinang (HPP) over 3 months period starting January 2020 using a convenience sampling method. All patients were included except patients under 18 years old, pregnant patients, diagnosed with psychiatric or depressive disorders and HF inpatients. A validated English and Malay version of Patient-Health Questionnaire-9 (PHQ-9) was used for screening of depressive symptoms. High scorers (≥ 10) were regarded as depressive. Results were reported in percentage (%) or median ± interquartile range (IQR). Fisher’s exact test with a 95% confidence interval was used. A total of 177 patients were recruited. The prevalence of perceived depressive symptoms among HF outpatients in HPP was 14.1%. The NYHA class was significantly associated with depressive status (p = 0.003). Depressive symptoms were common among these outpatients diagnosed with HF. A higher NYHA class suggested a higher depressive symptoms score. Screening for perceived depression especially patients with higher NYHA class was recommended.

Predictors of sinus rhythm restoration in patients with long-term episodes of persistent atrial fibrillation

The aim – to compare clinical, laboratory and instrumental characteristics of patients with persistent atrial fibrillation (AF) and duration of AF episode ≥ 90 days, undergoing direct current (DC) cardioversion, in groups with or without further sinus rhythm (SR) restoration, for the purpose of determining the predictors of SR restoration.Materials and methods. The cohort single-center study analyzed clinical, laboratory and instrumental data from 115 persistent AF patients with duration of its episode ≥ 90 days, who underwent an elective direct current cardioversion. Patients were subdivided into the groups depending on SR restoration effectiveness: 59 (51.3 %) and 56 (48.7 %) patients with restored and non-restored SR, respectively.Results and discussion. The group of patients with non-effective DC cardioversion was characterized more severe heart failure (HF) and more frequent percutaneous coronary intervention (PCI) cases, as opposed to the group with restored SR. The studied groups differed significantly by the certain echo parameters, characterizing the structure and function of left heart chambers. The transthoracic echocardiography (TTE) revealed a higher left ventricular (LV) dilatation and more frequent pulmonary hypertension (PH) cases in non-restored SR group. According to transesophageal echocardiography (TEE) data, both groups demonstrated the deterioration of left atrial (LA) function, namely the decrease of LA appendage flow velocity ≤ 40 cm/s in more than 60 % of patients. Additionally, the LA spontaneous echo contrast (SEC) was visualized in vast majority of non-restored SR patients (94.6 %). At the same time, only 2 (3.6 %) patients with non-effective DC cardioversion were free from SEC, as compared to 44 (74.6 %) restored SR patients (р &lt; 0.001). The multivariable logistic regression analysis revealed SEC as an independent predictor of SR restoration.Conclusions. Persistent AF patients with duration of its episode ≤ 90 days and non-effective elective DC cardioversion demonstrated higher stage of HF, more frequent demand for PCI, the higher LV dilatation, and presence of PH (TTE) and LA SEC (TEE). Among other associated factors, the freedom from LA SEC appeared to be the only independent predictor of SR restoration in such patients.

Temporal lipid profiling in the progression from acute to chronic heart failure in mice and ischemic human hearts

Background and aimsMyocardial infarction (MI) is a leading cause of heart failure (HF). After MI, lipids undergo several phasic changes implicated in cardiac repair if inflammation resolves on time. However, if inflammation continues, that leads to end stage HF progression and development. Numerous studies have analyzed the traditional risk factors; however, temporal lipidomics data for human and animal models are limited. Thus, we aimed to obtain sequential lipid profiling from acute to chronic HF. MethodsHere, we report the comprehensive lipidome of the hearts from diseased and healthy subjects. To induce heart failure in mice, we used a non-reperfused model of coronary ligation, and MI was confirmed by echocardiography and histology, then temporal kinetics of lipids in different tissues (heart, spleen, kidney), and plasma was quantitated from heart failure mice and compared with naïve controls. For lipid analysis in mouse and human samples, untargeted liquid chromatography-linear trap quadrupole orbitrap mass spectrometry (LC-LTQ-Orbitrap MS) was performed. ResultsIn humans, multivariate analysis revealed distinct cardiac lipid profiles between healthy and ischemic subjects, with 16 lipid species significantly downregulated by 5-fold, mainly phosphatidylethanolamines (PE), in the ischemic heart. In contrast, PE levels were markedly increased in mouse tissues and plasma in chronic MI, indicating possible cardiac remodeling. Further, fold change analysis revealed site-specific lipid biomarkers for acute and chronic HF. A significant decrease in sulfatides (SHexCer (34:1; 2O)) and sphingomyelins (SM (d18:1/16:0)) was observed in mouse tissues and plasma in chronic HF. ConclusionsOverall, a significant decreased lipidome in human ischemic LV and differential lipid metabolites in the transition of acute to chronic HF with inter-organ communication could provide novel insights into targeting integrative pathways for the early diagnosis or development of novel therapeutics to delay/prevent HF.

Abstract 15703: Outcomes of Non-ST Segment Myocardial Infarction in Patients With Heart Failure and End Stage Renal Disease

Introduction: Non-ST Segment Myocardial Infarction (NSTEMI) occurs frequently in patients with pre-existing Heart Failure (HF) and End Stage Renal Disease (ESRD). However, outcomes with invasive approaches such as percutaneous coronary intervention (PCI) or medical management remain uncertain. Hypothesis: Given severe comorbidity burden, patients with HF and ESRD admitted for NSTEMI may experience higher in-hospital mortality with an invasive strategy of PCI. Methods: We utilized the National Inpatient Sample to capture hospitalizations in the United States from 2006-2014. Admissions for NSTEMI were identified by the International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) code 401.7x. The sample was further narrowed by coexisting diagnoses of HF (ICD-9-CM: 428.xx) and ESRD (ICD-9-CM 585.6). The cohort was divided into those that received PCI or medical management only. Multivariable logistic regression was used to compare the primary outcome of in-hospital mortality between invasive and medical management only groups. Results: During the study period, 14,333 hospitalizations were identified for NSTEMI in patients with coexisting HF and ESRD. Within this cohort, 3,549 (25%) underwent PCI (age: 66±11 years,42% female) and 10,784 (75%) were managed with medications (age: 69±12 years, 45% female) only. In-hospital mortality was 5% in the PCI group in comparison to 10% in those managed with medications only (p&lt;0.01). After adjustment for clinical covariates including age, sex and diabetes mellitus, PCI was associated with lower odds of death during hospitalization (aOR: 0.52, 95% CI: 0.44-0.61, p&lt;0.01). Conclusions: Patients with HF and ESRD admitted for NSTEMI do not incur greater in-hospital mortality with PCI, despite a high burden of comorbidities. Invasive percutaneous revascularization may be reasonable for appropriately selected patients with HF and ESRD.

Abstract 13132: Uncontrolled Diabetes is Associated With Adverse Cardiovascular Disease Outcomes in Those With Stage B Heart Failure

Background: Among persons with stage B heart failure (HF) (subclinical cardiac dysfunction), diabetes is associated with markedly increased risk of progression to clinical HF. Whether stage B HF indicates greater risk for other cardiovascular disease (CVD) outcomes in the presence of diabetes is unknown. Methods: We included ARIC Visit 5 (2011-13) participants without clinical HF who met criteria for stage A (HF risk factors) or stage B (subclinical cardiac dysfunction by echocardiogram or elevated cardiac biomarkers) HF. Across HF stages A and B, we calculated incidence rates and their differences and used Cox models to estimate hazard ratios for overall mortality, CVD mortality, coronary heart disease (CHD), and HF associated with controlled diabetes (HbA1c &lt;7%) and uncontrolled diabetes (HbA1c ≥ 7%), compared to no diabetes. Results: 4,774 participants (mean age 75.4, 58.3% women, 20.2% black) were followed for a median 7.3 years, with 867 deaths, 237 CVD deaths, 228 CHD events, and 470 HF events. There were significant additive interactions (increased absolute risk) associated with uncontrolled diabetes (vs. no diabetes) for total mortality, CVD death, CHD, and HF for stage B, but not stage A (Table). The incidence rate differences (per 1000 person-years) associated with uncontrolled diabetes (vs. no diabetes) were greater in stage B vs stage A for all outcomes (Table). In multivariable adjusted models, uncontrolled diabetes (vs. no diabetes) was associated with statistically significant hazard ratios (increased relative risk) for all CVD outcomes in stage B, but did not have significant associations with any CVD outcomes in stage A (Table). Conclusion: In stage B HF, diabetes is associated with global CVD risk. Intensive preventive efforts to avert various forms of CVD may be indicated for those with diabetes and subclinical cardiac dysfunction.

Abstract 9927: Insufficient Monitoring and Inaccurate Evaluation Characterize the Heart Failure Symptom Perception Process

Perceiving symptoms is needed before one can respond to symptoms, but little is known about the difficulties experienced by patients with heart failure (HF) as they engage in the complex processes of symptom monitoring, awareness, and evaluation. Aim: To explore difficulties in symptom perception and describe the characteristics of patients who consistently perceive HF symptoms. Methods: Using a convergent mixed methods design, we enrolled a purposeful sample of 40 adults with an unplanned hospitalization for HF symptom exacerbation. Quantitative data were obtained from the electronic health record and the Self-Care of Heart Failure Index (SCHFI v 7.2, scale scores 0-100, higher score = better self-care). Qualitative data from 1:1 semi-structured interviews exploring the symptom perception process were analyzed using directed content analysis. For data integration, individual difficulties in the SCHFI symptom perception processes of monitoring, awareness, and evaluation were anchored on the qualitative data. Two groups with different symptom perception consistency were identified from interviews. Group differences were examined using independent T, Mann-Whitney, Chi 2 , and Fisher’s Exact tests. Results: The sample was 50% male, 45% non-white, mean age 62 years, and 75% NYHA III-IV. Most (72.5%) demonstrated adequate symptom perception (SCHFI score ≥70). The consistent symptom perception group (n=27, 67.5%) had no difficulties in symptom monitoring, awareness, and evaluation while the inconsistent group reported insufficient symptom monitoring and/or inaccurate symptom evaluation. The consistent group was more experienced with HF and visited the emergency department more frequently in the past year. There were no group differences in age, gender, race, NYHA class, and HF stage (Table 1). Conclusion: Symptom perception interventions may be particularly useful early in the HF trajectory to enhance symptom monitoring and evaluation abilities.

Abstract 15694: Mitochondrial Dysfunction and Fatty Acid Metabolism Derangement in Pediatric Single Ventricle Congenital Heart Disease

Introduction: Cardiac dysfunction is a common complication in pediatric patients with single ventricle (SV) physiology. While many factors contribute to the development of SV heart failure (HF), metabolic switch from fatty acid utilization to carbohydrate metabolism has been shown to contribute to cardiac dysfunction in adult HF. Hypothesis: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from pediatric SV HF patients exhibit reduced fatty acid utilization and decreased contractility when compared with hiPSC-CMs from healthy control individuals. Methods: We differentiated iPSCs from pediatric patients with hypoplastic left heart syndrome (HLHS) who developed early onset HF and from healthy control individuals to generate hiPSC-CMs. We plated hiPSC-CMs on hydrogel micropattern for single-cell plating and measured their contractile phenotype using the Sony SI8000 cell motion imaging system. We used Seahorse XF assay to measure metabolism in hiPSC-CMs. Furthermore, we performed metabolomic profiling of day 20 and day 45 hiPSC-CMs. Results: HLHS hiPSC-CMs demonstrated metabolic derangement with significant reduction in ATP production (p &lt;0.001) and in basal and maximal respiration (p &lt;.001). We also found that HLHS hiPSC-CMs have impaired contractility when compared to WT hiPSC-CMs. Contraction force and acceleration were decreased on HLHS hiPSC-CMs compared to WT hiPSC-CMs (p&lt;0.01). Our metabolomic profiling identified a reduction of tricarboxylic acid (TCA) cycle metabolites such as succinyl carnitine (p = 0.002) and alpha-ketoglutarate (p = 0.056) in HLHS cells compared to healthy controls at day 20 and day 45 of differentiation. In addition, succinate, fumarate, malate, itaconate and citraconate/ glutaconate were also significantly reduced in day 20 media of HLHS hiPSC-CMs and trended lower in day 45 HLHS hiPSC-CMs. Conclusions: The disrupted fatty acid metabolism in hiPSC-CMs from patients with SV HF provides new insight into the pathogenesis of this disease and may help to develop novel metabolic biomarkers that may be useful for identifying pediatric patients at an earlier stage of SV HF.

Abstract 10206: Misleading Transvalvular Hemodynamics for Patients With Moderate Aortic Stenosis

Introduction: Aortic stenosis (AS) is a progressive disease that leads to cardiac remodeling. Appropriate management depends on accurate assessment of AS severity. Transvalvular gradients are central to echocardiographic assessment of AS though can be impacted by any conditions that decrease transvalvular flow. Hypothesis: 1) Decline in peak transvalvular gradient over time is associated with more significant cardiac remodeling and 2) Cardiac damage is associated with lower transvalvular flow and masks progression of AS. Methods: Retrospective single center study of patients with moderate AS (defined as peak gradient 25-40mmHg) from 2013-2020 with &gt; 1 transthoracic echocardiogram (TTE). Each TTE was classified into established stages of cardiac damage: no damage (Stage 0), left ventricular damage (Stage 1), left atrial or mitral valve damage (Stage 2), pulmonary vasculature or tricuspid valve damage (Stage 3), or right ventricular damage or subclinical heart failure (Stage 4). Results: Sixty patients with at least 1 follow-up TTE were included. The mean age was 73.5 +/- 11 years with 47% women (28/60) and median time of 381 days (IQR 12.7 months) between echocardiograms. On initial assessment, mean AVA and peak AV gradient were 1.2cm 2 +/- 0.33 and 37mmHg +/- 11.3 respectively. At follow-up, the mean AVA and peak AV gradient were 1.1cm 2 +/- 0.20 and 38mmHg +/- 12.6. Forty-three of 60 patients (72%) had evidence of cardiac damage on initial assessment compared to 55 of 60 patients (92%) on follow-up. Thirty-five (58%) patients displayed a decrease in peak AV gradient over time (average decrease -16% +/- 0.12). Twenty-one of the patients with declining peak gradients (60%) demonstrated progressive cardiac damage compared to 9 of 25 patients (36%) with increasing peak gradients (p= 0.06). Conclusions: Over half of patients with moderate AS demonstrated a decrease in peak AV gradient over time. Reliance on transvalvular gradients as a reflector of AS severity can be misleading as there was a trend toward more significant cardiac damage in this subset of patients. The presence of underlying cardiac damage can obscure traditional echocardiographic assessment and progression of AS and should be incorporated into assessments of disease severity and progression.

Machine Learning Models Predicting Cardiovascular and Renal Outcomes and Mortality in Patients with Hyperkalemia.

Hyperkalemia is associated with increased risks of mortality and adverse clinical outcomes. The treatment of hyperkalemia often leads to the discontinuation or restriction of beneficial but potassium-increasing therapy such as renin-angiotensin-aldosterone inhibitors (RAASi) and high-potassium diet including fruits and vegetables. To date, limited evidence is available for personalized risk evaluation in this heterogeneous and multifactorial pathophysiological condition. We developed risk prediction models using extreme gradient boosting (XGB), multiple logistic regression (LR), and deep neural network. Models were derived from a retrospective cohort of hyperkalemic patients with either heart failure or chronic kidney disease stage ≥3a from a Japanese nationwide database (1 April 2008-30 September 2018). Studied outcomes included all-cause death, renal replacement therapy introduction (RRT), hospitalization for heart failure (HHF), and cardiovascular events within three years after hyperkalemic episodes. The best performing model was further validated using an external cohort. A total of 24,949 adult hyperkalemic patients were selected for model derivation and internal validation. A total of 1452 deaths (16.6%), 887 RRT (10.1%), 1,345 HHF (15.4%), and 621 cardiovascular events (7.1%) were observed. XGB outperformed other models. The area under receiver operator characteristic curves (AUROCs) of XGB vs. LR (95% CIs) for death, RRT, HHF, and cardiovascular events were 0.823 (0.805-0.841) vs. 0.809 (0.791-0.828), 0.957 (0.947-0.967) vs. 0.947 (0.936-0.959), 0.863 (0.846-0.880) vs. 0.838 (0.820-0.856), and 0.809 (0.784-0.834) vs. 0.798 (0.772-0.823), respectively. In the external dataset including 86,279 patients, AUROCs (95% CIs) for XGB were: death, 0.747 (0.742-0.753); RRT, 0.888 (0.882-0.894); HHF, 0.673 (0.666-0.679); and cardiovascular events, 0.585 (0.578-0.591). Kaplan-Meier curves of the high-risk predicted group showed a statistically significant difference from that of the low-risk predicted groups for all outcomes (p &lt; 0.005; log-rank test). These findings suggest possible use of machine learning models for real-world risk assessment as a guide for observation and/or treatment decision making that may potentially lead to improved outcomes in hyperkalemic patients while retaining the benefit of life-saving therapies.

Metformin confers longitudinal cardiac protection by preserving mitochondrial homeostasis following myocardial ischemia/reperfusion injury.

Myocardial ischemia-reperfusion (I/R) injury is associated with systemic oxidative stress, cardiac mitochondrial homeostasis, and cardiomyocyte apoptosis. Metformin has been recognized to attenuate cardiomyocyte apoptosis. However, the longitudinal effects and pathomechanism of metformin on the regulation of myocardial mitohormesis following I/R treatment remain unclear. This study aimed to investigate the longitudinal effects and mechanism of metformin in regulating cardiac mitochondrial homeostasis by serial imaging with the 18-kDa translocator protein (TSPO)-targeted positron emission tomography (PET) tracer 18F-FDPA. Myocardial I/R injury was established in Sprague-Dawley rats, which were treated with or without metformin (150mg/kg per day). Serial gated 18F-FDG and 18F-FDPA PET imaging wereperformed at 1, 4, and 8weeks after surgery, followed by analysis of ventricular remodelling and cardiac mitochondrial homeostasis. The correlation between Hsp60 and 18F-FDPA uptake was analyzed. After PET imaging, the activity of antioxidant enzymes, immunostaining, and western blot analysis were performed to analyze the spatio-temporal effects and pathomechanism of metformin for cardiac protection after myocardial I/R injury. Oxidative stress and apoptosis increased 1week after myocardial I/R injury (before significant progression of ventricular remodelling). TSPO expression was correlated with Hsp60 expression and was co-localized with inflammatory CD68+ macrophages in the infarct area, and TSPO uptake was associated with an upregulation of AMPK-p/AMPK and a downregulation of Bcl-2/Bax. However, these effects were reversed with metformin treatment. Eight weeks after myocardial I/R injury (representing the advanced stage of heart failure), 18F-FDPA uptake in myocardial cells in the distal non-infarct area increased without CD68+ expression, whereas the activity decreased with metformin treatment. Taken together, these results show that a prolonged metformin treatment has pleiotropic protective effects against myocardial I/R injury associated with a regional and temporal dynamic balance between mitochondrial homeostasis and cardiac outcome, which were assessed by TSPO-targeted imaging during cardiac remodelling.

Association between adipokines and cardiac remodeling in obese patients in preclinical heart failure

Introduction. Association of left ventricular hypertrophy (LVH) in obesity and accompanying metabolic risks with adipokines levels at the different stage of heart failure (HF) is still debatable.The aim of study was to investigate the relationship of circulating adipokines levels with LVH in obese patients at preclinical stage of HF.Materials and methods. The study included 74 obese patients: 43% had no markers of LVH (stage A HF, group 1); 57% had LVH (stage B HF, group 2). Transthoracic echocardiography, laboratory assessment of N-terminal fragment of the brain natriuretic peptide, soluble suppression of tumorigenesis-2 (sST2), circulating leptin and adiponectin levels, homeostasis model assessment of insulin resistance (IR) (HOMA-IR) were done. Matched-pairs analysis was applied.Results. Negative correlations of LVH with leptin levels in group 1 (stage A HF) and with adiponectin levels in group 2 (stage B HF) were detected (all p &lt; 0.05). Positive correlations of the sST2 / adiponectin ratio and HOMA-IR with the parameters of LVH were detected in group 2 (all p &gt;&lt; 0.05). Conclusion. The direction of the associations between circulating adipokines and LVH varies with the preclinical stage of HF. The data obtained may reflect a relationship between heart remodeling in response to molecular mechanisms of inflammation and IR in obese patients at the certain stage of cardiovascular continuum. Keywords: leptin, adiponectin, insulin resistance, HOMA-IR, inflammation, sST2, left ventricular hypertrophy&gt;˂ 0.05). Positive correlations of the sST2 / adiponectin ratio and HOMA-IR with the parameters of LVH were detected in group 2 (all p ˂ 0.05).Conclusion. The direction of the associations between circulating adipokines and LVH varies with the preclinical stage of HF. The data obtained may reflect a relationship between heart remodeling in response to molecular mechanisms of inflammation and IR in obese patients at the certain stage of cardiovascular continuum.