HFrEF Patients Research Articles

Clinical characteristics and outcomes of patients admitted with acute heart failure: insights from a single-center heart failure registry in South India

BackgroundThe epidemiology of HF in India is largely unexplored. Current resources are based on a few hospital-based and a community-based registry from North India. Thus, we present the data from a single hospital-based registry in South India. Patients admitted with acute heart failure over a period of 1 year were enrolled in the registry and were characterized based on their ejection fraction (EF) measured by echocardiogram. The clinical profile of the patients was assessed, including their in-hospital outcomes. One-way ANOVA and univariate analysis were performed for comparison between three EF-based groups and for the assessment of in-hospital outcomes.ResultsA total of 449 patients were enrolled in the registry, of which 296, 90, and 63 patients were categorized as, HFrEF, HFmrEF, and HFpEF, respectively. The prevalence of HFrEF was higher (65.99%). The mean age (SD) of the study cohort was 59.9±13.3. The majority of the patients presented with acute denovo HF (67%) and were more likely to be males (65.9%). The majority of patients presented with warm and wet clinical phenotype (86.4%). In hospital mortality was higher in HFmrEF (3.3%).ConclusionPatients with HFrEF had high adherence to guideline-directed medical therapy (GDMT). HFrEF patients were also likely to have longer hospital stay along with a worsening of renal function. The in-hospital mortality was comparable between the EF-based groups. Additionally, the association of clinical phenotypes with outcome highlighted that patients in warm and wet phenotype had a longer length of hospital stay, whereas the mortality and worsening renal function rates were found to be significantly higher in the cold and wet group.

Clinical characteristics of heart failure with recovered ejection fraction

Objective: To summarize the clinical characteristics of heart failure patients with recovered ejection fraction (HFrecEF) and identify variables capable of predicting left ventricular ejection fraction (LVEF) recovery. Methods: This case control study included patients with heart failure, who admitted to Department of Cardiology of Beijing Hospital from January 1, 2009 to December 31, 2017. The patients were divided into 3 groups based on the baseline LVEF and changes of LVEF: heart failure with reduced ejection fraction (HFrEF, baseline LVEF≤40%, follow-up LVEF≤40% or follow-up LVEF>40% but LVEF increase<10% from baseline), HFrecEF(baseline LVEF≤40%, follow-up LVEF>40% and increase≥10% from baseline), and heart failure with preserved ejection fraction (HFpEF, baseline LVEF>40%). Clinical data were collected and endpoint events (all-cause death, cardiovascular death and sudden death) were recorded. The Log-rank test was used to evaluate the differences of terminal events in different groups, and Kaplan-Meier survival analysis was performed. Logistic regression equation was used to identify prognostic factors of HFrecEF. Results: A total of 310 patients with heart failure were included. There were 91(29.4%) HFrEF patients, 38(12.3%) HFrecEF patients and 181(58.4%) HFpEF patients. Compared with HFrEF patients and HFpEF patients, HFrecEF patients were featured by younger age, more likely to be female, higher systolic blood pressure, diastolic blood pressure and resting heart rate (all P<0.05). Dilated cardiomyopathies were more common, while old myocardial infarctions were less common in HFrecEF (both P<0.05). During a median follow-up of 36.7(18.0, 63.9) months, Kaplan-Meier survival analysis found that HFrecEF patients had the lowest all-cause mortality (Log-rank P=0.047, HFrecEF vs. HFpEF P=0.017, HFrecEF vs. HFrEF P=0.016, and HFpEF vs. HFrEF P=0.782).The cardiovascular mortality ranged from low to high was in HFrecEF patients, HFpEF patients, and HFrEF patients (Log-rank P<0.001, HFrecEF vs. HFpEF P=0.029, HFrecEF vs. HFrEF P<0.001, HFrEF vs. HFpEF P=0.005). Sudden death rate was similar among the three groups (Log-rank P=0.520). Logistic regression analysis showed that left ventricular end-diastolic diameter (LVEDD)≤55 mm (OR=5.922, 95%CI 1.685-20.812, P=0.006), higher diastolic blood pressure (OR=1.058, 95%CI 1.017-1.100, P=0.005), faster resting heart rate (OR=1.042, 95%CI 1.006-1.080, P=0.024), absence of old myocardial infarction (OR=5.343, 95%CI 1.731-16.488, P=0.004) were independent prognostic factors of LVEF recovery after clinical treatment. Conclusions: Patients with HFrecEF are associated with a better prognosis as compared to patients with HFrEF and HFpEF. LVEDD≤55 mm, higher diastolic blood pressure, faster heart rate,and absence of old myocardial infarction are independent prognostic factors of LVEF recovery after clinical treatment.

Serum uric acid and outcomes in patients with chronic heart failure through the whole spectrum of ejection fraction phenotypes: Analysis of the ESC-EORP Heart Failure Long-Term (HF LT) Registry

BackgroundRetrospective analyses of clinical trials indicate that elevated serum uric acid (sUA) predicts poor outcome in heart failure (HF). Uric acid can contribute to inflammation and microvascular dysfunction, which may differently affect different left ventricular ejection fraction (LVEF) phenotypes. However, role of sUA across LVEF phenotypes is unknown. ObjectivesWe investigated sUA association with outcome in a prospective cohort of HF patients stratified according to LVEF. MethodsThrough the Heart Failure Long-Term Registry of the European Society of Cardiology (ESC-EORP-HF-LT), 4,438 outpatients were identified and classified into: reduced (<40% HFrEF), mid-range (40–49% HFmrEF), and preserved (≥50% HFpEF) LVEF. Endpoints were the composite of cardiovascular death/HF hospitalization, and individual components. ResultsMedian sUA was 6.72 (IQ:5.48-8.20) mg/dl in HFrEF, 6.41 (5.02-7.77) in HFmrEF, and 6.30 (5.20-7.70) in HFpEF. At a median 372-day follow-up, the composite endpoint occurred in 648 (13.1%) patients, with 176 (3.6%) deaths and 538 (10.9%) HF hospitalizations. Compared with lowest sUA quartile (Q), Q-III and Q-IV were significantly associated with the composite endpoint (adjusted HR 1.68: 95% CI 1.11–2.54; 2.46: 95% CI 1.66–3.64, respectively). By univariable analyses, HFrEF and HFmrEF patients in Q-III and Q-IV, and HFpEF patients in Q-IV, showed increased risk for the composite endpoint (P<0.05 for all); after model-adjustment, significant association of sUA with outcome persisted among HFrEF in Q-IV, and HFpEF in Q-III-IV. ConclusionsIn a large, contemporary-treated cohort of HF outpatients, sUA is an independent prognosticator of adverse outcome, which can be appreciated in HErEF and HFpEF patients.

Hematocrit-Related Alterations of Circulating microRNA-21 Levels in Heart Failure Patients with Reduced Ejection Fraction: A Preliminary Study.

Aim: Circulating microRNA-21 (miR-21) has been utilized as a diagnostic tool in the assessment of heart failure (HF). Blood constitution may be altered when HF occurs and miR-21 may affect hematopoiesis. Sample hemolysis may influence the determination of circulating miRNAs, challenging the diagnostic use of miRNAs. Methods: We examined the relationship between blood measurements and miR-21 levels in ambulant chronic HF patients with reduced ejection fraction (HFrEF; n = 19). Healthy volunteers (n = 11) served as controls. Serum miR-21 levels were measured through quantitative reverse transcription polymerase chain reaction (RT-qPCR) and we calculated the hemolysis score (H-score). Study was approved by an Institutional Review Board (EK FaF UK 02/2018). Results: MiR-21 serum levels were reduced in HFrEF patients compared with the controls (p < 0.05), without relationship to New York Heart Association class, left ventricular ejection fraction or N-terminal prohormone of brain natriuretic peptide levels. MiR-21 levels decreased markedly in anemic patients, compared with those with normal hematocrits (p < 0.05). We found a significant relationship between miR-21 to hematocrit (p < 0.05) and hemoglobin concentration (p < 0.05). Importantly, we found a correlation between hematocrit and sample H-score (p < 0.05) in the cohort of HFrEF patients; however, there was no correlation between hemolysis and miR-21. Conclusion: Circulating miR-21 levels were decreased in HFrEF patients and hematocrit was identified as a factor associated with this abnormality. This suggests that miR-21 mirrors other characteristics of HFrEF patients rather than the standard identifiers of HF severity and progression.

The effect of physician prescribing patterns based on ESC guidelines on morbidity improvement among heart failure patients

Data from Basic Health Research shows the prevalence of heart failure in Indonesia is between 0.1% to 0.3% of the entire Indonesian population. This number is predicted to increase from year to year. Heart failure is a complex syndrome that can cause abnormalities in the structure and function of the heart. Based on the ejection fraction values, there are three types of heart failure, namely HFrEF (EF: &lt; 40%), HFmrEF (EF: 40-49%), and HFpEF (EF: ≥ 50%). Considering that the type of heart failure requiring treatment according to ESC guidelines is only HFrEF, however, this study would also evaluate the effect of physician prescribing patterns on the morbidity of HFmrEF. The recommendations from ESC guidelines to the treatment of HFrEF that can reduce morbidity and mortality are three medication combinations, namely ACE inhibitors/angiotensin receptor blockers, beta-blockers, and aldosterone antagonists. Therefore, this study aims to determine the effect of the suitability of physician prescribing patterns according to ESC guidelines on improving the morbidity of heart failure patients in HFrEF and HFmrEF type. Improvements in morbidity can be seen from the quality of life score and frequency of hospitalization by using questionnaires. The study was conducted in the cardiology outpatient clinic of Dr. Saiful Anwar General Hospital and Islamic Hospital of Aisyiyah in April-May 2019. Subjects who participated in the study were 57 patients. The One-way ANOVA test results showed no significant difference between physician prescribing patterns of quality of life scores on HFrEF (p = 0.944) while the Kruskal Wallis test for the same parameters on HFmrEF also showed insignificant results (p = 0.210). The Kruskal Wallis test results showed no significant difference between the patterns of physician prescribing to the frequency of hospitalization in both HFrEF and HFmrEF (p = 0.260; p = 0.428). The results showed that physician prescribing patterns in accordance with ESC guidelines resulted in the best quality of life scores on HFrEF. The lowest frequency of hospitalization was also shown in HFrEF patients who received treatment according to ESC guidelines.

Will a Rising SGLT2 Inhibitor Tide Lift All GDMT Boats

<h3>Purpose</h3> The addition of SGLT2 inhibitors (SGLT2i) to goal directed medical therapy (GDMT) in HFrEF patients has been shown to reduce morbidity and mortality, and there are potential but unstudied benefits in LVAD patients. A provider education program and SGLT2i initiation protocol sought to optimize SGLT2i use in an outpatient LVAD clinic. The purpose of this evaluation was to determine the impact of this initiative on the prescribing of other GDMT. <h3>Methods</h3> This was a retrospective, cross-sectional cohort study in a single outpatient LVAD clinic. The primary outcome was the difference in utilization of GDMT prior to (May/June 2019) and after (May/June 2020) protocol development and provider education on initiation of SGLT2i. The protocol and educational initiative placed no systematic emphasis on improving prescribing of HF or antidiabetic agents aside from SGLT2i. Chi-square and t-tests were used to compare categorical and continuous variables, respectively. <h3>Results</h3> A total of 272 patient encounters were assessed. Between the two cohorts, there were no differences in patient demographics, LVAD support characteristics, clinical status, or provider type (Table 1). The rate of SGLT2i utilization increased significantly as a result of the education and protocol (22% vs 0%, p<0.0001). Additionally, the utilization of ACEi/ARB/ARNIs (56% vs 20%, p<0.0001), beta blockers (51% vs 24%, p<0.0001), and GLP-1 receptor agonists (12% vs 2%, p=0.049) increased significantly, while sulfonylurea usage declined (1% vs 15%, p=0.003) (Figure 1). <h3>Conclusion</h3> In addition to the anticipated increase in SGLT2i prescribing, there were significant improvements in adherence to GDMT in an outpatient LVAD population following a focused SGLT2i education effort and initiation protocol. There were no differences in patient or clinical characteristics which would contribute to the improvement in therapy optimization. An enhanced focus on the role of a single therapeutic class can result in an improvement in prescribing patterns for all GDMT in LVAD patients.

Unsupervised cluster analysis of patients with recovered left ventricular ejection fraction identifies unique clinical phenotypes.

BackgroundPatients with heart failure (HF) with recovered ejection fraction (HFrecEF) are a recently identified cohort that are phenotypically and biologically different from HFrEF and HFpEF patients. Whether there are unique phenotypes among HFrecEF patients is not known.MethodsWe studied all patients at a large medical center, who had an improvement in LVEF from ≤ 35% to ≥ 50% (LVrecEF) between January 1, 2005 and December 31, 2013. We identified a set of 11 clinical variables and then performed unsupervised clustering analyses to identify unique clinical phenotypes among patients with LVrecEF, followed by a Kaplan-Meier analysis to identify differences in survival and the proportion of LVrecEF patients who maintained an LVEF ≥ 50% during the study period.ResultsWe identified 889 patients with LVrecEF who clustered into 7 unique phenotypes ranging in size from 37 to 420 patients. Kaplan-Meier analysis demonstrated significant differences in mortality across clusters (logrank p<0.0001), with survival ranging from 14% to 87% at 1000 days, as well as significant differences in the proportion of LVrecEF patients who maintained an LVEF ≥ 50%.ConclusionThere is significant clinical heterogeneity among patients with LVrecEF. Clinical outcomes are distinct across phenotype clusters as defined by clinical cardiac characteristics and co-morbidities. Clustering algorithms may identify patients who are at high risk for recurrent HF, and thus be useful for guiding treatment strategies for patients with LVrecEF.

Global longitudinal strain in heart failure with reduced ejection fraction: Prognostic relevance across disease severity as assessed by automated cluster analysis

BackgroundEjection fraction (EF) is still widely used to categorize heart failure (HF) patients but has limitations. Global longitudinal strain (GLS) has emerged as a new prognosticator in HF, independent of EF. AimWe investigated the incremental predictive benefit of GLS over different risk profiles as identified by automated cluster analysis of simple echocardiographic parameters. Methods and resultsIn 797 HFrEF patients (age 66 ± 12y; mean EF 30 ± 7%), unsupervised cluster analysis of 10 routine echocardiographic variables (without GLS) was performed. Median follow-up was 37 months. End-point was all-cause mortality. Association between risk profiles, GLS, and mortality was assessed by Cox proportional-hazard modeling with interaction term.Cluster analysis allocated patients to 3 different risk phenogroups (PG): PG-1 (mild diastolic dysfunction [DD], moderate systolic dysfunction, no pulmonary hypertension, normal right ventricular [RV] function); PG-2 (moderate DD, mild pulmonary hypertension, normal RV function); PG-3 (severe DD, advanced systolic dysfunction, pulmonary hypertension, RV dysfunction). Compared to PG-1, PG-2 and PG-3 showed increased adjusted-hazard ratio (1.71; 95% CI:1.05–2.77, P = 0.30; and 2.58; 95% CI:1.50–4.44, P < 0.001, respectively). GLS was independently associated with outcome in the whole population (adjusted-HR: 1.11; 95% CI: 1.05–1.17, P = 0.001); however, profile membership modified the relationship between GLS and outcome which was no longer significant in PG-3 (P for interaction = 0.003). ConclusionsWithin HFrEF populations, clustering of routine echocardiography parameters can automatically identify patients with different risk profiles; further assessment by GLS may be useful for patients with not advanced disease.

Evaluation of the prescribing practice of guideline-directed medical therapy among ambulatory chronic heart failure patients

BackgroundStudies have demonstrated that heart failure (HF) patients who receive direct pharmacist input as part of multidisciplinary care have better clinical outcomes. This study evaluated/compared the difference in prescribing practices of guideline-directed medical therapy (GDMT) for chronic HF patients between two multidisciplinary clinics—with and without the direct involvement of a pharmacist.MethodsA retrospective audit of chronic HF patients, presenting to two multidisciplinary outpatient clinics between March 2005 and January 2017, was performed; a Multidisciplinary Ambulatory Consulting Service (MACS) with an integrated pharmacist model of care and a General Cardiology Heart Failure Service (GCHFS) clinic, without the active involvement of a pharmacist.ResultsMACS clinic patients were significantly older (80 vs. 73 years, p < .001), more likely to be female (p < .001), and had significantly higher systolic (123 vs. 112 mmHg, p < .001) and diastolic (67 vs. 60 mmHg, p < .05) blood pressures compared to the GCHF clinic patients. Moreover, the MACS clinic patients showed more polypharmacy and higher prevalence of multiple comorbidities. Both clinics had similar prescribing rates of GDMT and achieved maximal tolerated doses of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in HFrEF. However, HFpEF patients in the MACS clinic were significantly more likely to be prescribed ACEIs/ARBs (70.5% vs. 56.2%, p = 0.0314) than the GCHFS patients. Patients with both HFrEF and HFpEF (MACS clinic) were significantly less likely to be prescribed β-blockers and mineralocorticoid receptor antagonists. Use of digoxin in chronic atrial fibrillation (AF) in MACS clinic was significantly higher in HFrEF patients (82.5% vs. 58.5%, p = 0.004), but the number of people anticoagulated in presence of AF (27.1% vs. 48.0%, p = 0.002) and prescribed diuretics (84.0% vs. 94.5%, p = 0.022) were significantly lower in HFpEF patients attending the MACS clinic. Age, heart rate, systolic blood pressure (SBP), anemia, chronic renal failure, and other comorbidities were the main significant predictors of utilization of GDMT in a multivariate binary logistic regression.ConclusionsLower prescription rates of some medications in the pharmacist-involved multidisciplinary team were found. Careful consideration of demographic and clinical characteristics, contraindications for use of medications, polypharmacy, and underlying comorbidities is necessary to achieve best practice.

Clinical, Echocardiographic, and Therapeutic Characteristics of Heart Failure in Patients with Preserved, Mid-Range, and Reduced Ejection Fraction: Future Directions.

BackgroundHeart failure (HF) is recognized as a worldwide epidemic. Definitions and risk stratification are usually based upon measurements of left ventricular ejection fraction (LVEF) but such classifications reflect an underlying spectrum of different pathologic, phenotypic, and therapeutic patterns.MethodsThis was a retrospective cohort study of HF patients in Saudi Arabia. Patients were divided into three categories based on LVEF: those with preserved ejection fraction (EF) (EF≥50%, HFpEF); those with mid-range EF (EF 40–49%, HFmrEF); and those with reduced EF (EF <40%, HFrEF). Their demographics, co-morbid conditions, echocardiographic findings, pharmacological treatments and all-cause mortality (ACS) after a follow-up period of 24 months were compared.ResultsA total of 293 HF patients were identified (mean age: 63 years). In total, 65% were males, 79% were Saudi nationals, and 70% had type 2 diabetes mellitus (DM). Classification based on EF was established in 288 patients: HFpEF (105 patients, 36.5%), HFmrEF (49, 17.0%), and HFrEF (134, 46.5%). The 3 groups differed in sex distribution: 51% females in the HFpEF group and 78% males in the HFrEF group (P<0.001). Body mass index (BMI) was highest in the HFpEF group and lowest in the HFrEF group (31.5 vs 26.6; P<0.001). Although systolic blood pressure (SBP in mmHg) was highest in patients with HFpEF, left ventricular mass index (LVMI in g/cm2) was highest in patients with HFrEF 121.00 (94.50, 151.50), and eccentric hypertrophy was the dominant LV geometrical characteristic (54.6%). HFrEF patients had the highest use of ACE inhibitors (60.5%), loop diuretics (79.9%), and aldosterone receptor antagonists (56.7%) (P values; 0.009, 0.007, and <0.001, respectively). A total of 42 deaths occurred during follow-up: HFpEF (17 events), HFmrEF (3 events) and HFrEF (22 events) (Logrank test P=0.189).ConclusionThis Saudi HF population shows similarities to other populations: EF category distribution, sex distribution, therapeutic trends, and survival outcomes. However, findings related to the underlying risk factors, namely type 2 DM and obesity, have identified HFpEF as an emerging threat in this (relatively) young population.

Comorbidities and survival after acute decompensated heart failure hospitalisation

Heart failure (HF) presents a poor prognosis and is frequently associated with comorbidities. Less is known on interplays between comorbidities and HF type on survival. To precise the relationship between comorbidities, HF type and two-years survival after acute HF (AHF) episode. A local PMSI register was retrospectively screened to include all discharged patients in two cardiology centers, in 2013. Fifteen comorbidities were collected and tertilized, depending on the number and nature of comorbidities (C): cardiovascular (CVC) and non-cardiovascular (NCVC). The three HF type were defined according to left ventricular ejection fraction (LVEF) and ESC 2016 guidelines: reduced (HF-rEF), mid-range (HF-mrEF) and preserved EF (HF-pEF). All-cause mortality two years after discharge was the main end-point. Among 577 patients recruited, mean age was 78 years (55% male) and 37% had rEF, 21% mrEF and 42% pEF. Two-years overall mortality was 42% and did not differ in the three HF population. Mean number of all comorbidities (AC) was 4.4, CVC 1.9 and NCVC 2.5, similar in the three HF populations ( Table 1 ). HF-rEF patients were younger male with coronary artery disease. HF-pEF had higher proportions of women, atrial fibrillation and hypertension. The HF-mrEF group presented intermediate profile. High number of comorbidities were associated with impaired survival ( Fig. 1 ). After stratification on LVEF, mortality in HF-rEF population significantly increased with the augmentation of AC, CVC and NCVC. HF-mrEF population tended to look like HF-rEF one, showing a significant increasing mortality with the augmentation of AC and NCVC, but not in CVC. There was no association between mortality and co-morbidities in HF-pEF population. Comorbidities are associated with increased 2-year mortality after AHF episode. After stratification, mortality increases with comorbidities in HF-rEF and HF-mrEF, but not in HF-pEF population.

Study of patients with iron deficiency and HF in Ireland: prevalence and treatment budget impact.

This study aims to present the screening, prevalence and treatment of heart failure (HF) patients with iron deficiency in an Irish hospital and use an economic model to estimate the budget impact of treating eligible patients with intravenous ferric carboxymaltose (IV FCM). Retrospective data were collected on 151 HF patients over a one-year period from all newly referred HF patients to a secondary care hospital. This included 36 patients with preserved ejection fraction (HFpEF) and 115 with reduced ejection fraction (HPrEF). An existing budget impact model was adapted to incorporate Irish unit cost and resource use data to estimate the annual budget impact of treating patients with IV FCM. The total number of HFrEF patients who met criteria for iron replacement was 44 (38% of total HFrEF patients); of this, only nine (20%) were treated. The budget impact model estimates that treating all eligible patients with IV FCM in this single centre would save 40 bed-days and over €7,600/year. To improve the quality of life and reduce hospitalisation, further identification and treatment of iron deficient patients should be implemented. Expanding the use of IV iron nationally would be cost and bed saving.

The Monocyte To High-Density Lipoprotein Cholesterol Ratio Predicts The Mortality in Patients With Reduced Ejection Fraction Heart Failure

Objective: We purposed to evaluate the association between Monocyte To High-Density Lipoprotein Cholesterol Ratio (MHR) and mortality during a year follow-up in patients with reduced efection fraction heart failure (HFrEF).&#x0D; Method: We included total of 552 patients with HFrEF into the study. The main outcome was mortality at 1-year follow-up. Sociodemographic characteristics, hemogram and biochemical parameters, ejection fractions of patients were recorded. MHR was was computed by splitting monocyte into high-density lipoprotein cholesterol (HDL-C).&#x0D; Results: The HFrEF population were seperated into different groups as non-survivors (n=45) and survivors (n=507). When the groups are compared the non-survivors group was older (p=0.04) and chronic renal failure incidence was higher in non-survivors (p=0.001). The MHR was notably higher in the non-survivors group (p=0.000). We have shown that MHR had a positive correlation with mortality (r=0.146 p=0.001). Also higher MHR was found as a strong paramer to predict of mortality (Odds ratio: 2.471, 95% confidence interval: 1.729–4.092, P=0.005). The cut-off values of 6,39 might be applied for predicting the mortality with 88% sensitivity and 97% specificity [Area under curve:0.831 (95% Confidence Interval: 0.799-0.869) p=0.001].&#x0D; Conclusion: MHR can be used as an easy and usefull tool to predict mortality in HFrEF patients.

Abstract 16900: Exertional Hemodynamics Among Patients With HFrEF Based on Resting HF Profile

Introduction: HFrEF can be classified by profiles A, B, C or L based on resting pulmonary capillary wedge pressure (PCWP) and cardiac output (Qc). We characterized exertional hemodynamics by HF profile. Methods: HFrEF patients (N=34) completed invasive exercise testing with Swan-Ganz and radial arterial catheterization on upright bicycle. Oxygen uptake was monitored by indirect calorimetry. Data were recorded at supine and upright rest, two exercise stages below ventilatory threshold (steady states 1 and 2), and peak exercise. Participants were stratified into HF profiles based on supine resting hemodynamics including PCWP and cardiac index (CI): Profile A (warm-dry) PCWP≤16mmHg, CI≥2.5L/min/m 2 ; Profile B (warm-wet) PCWP&gt;16mmHg; CI≥2.5L/min/m 2 ; Profile C (cold-wet) PCWP&gt;16mmHg; CI&lt;2.5L/min/m 2 ; Profile L (cold-dry) PCWP≤16mmHg, CI&lt;2.5L/min/m 2 . Results: Demographics are displayed in the table . Peak oxygen uptake (VO 2 ) was severely reduced in all participants ( figure 1 ). Throughout exercise, profile C and L patients had lower stroke volume and Qc, but higher (A-V)O2 difference than profiles A and B ( figure 2 ). Profile B and C patients had higher resting and exertional pulmonary arterial and PCWP filling pressures compared to profiles A and L. Conclusion: Exercise performance among HFrEF patients is not uniform. Exertional hemodynamics vary substantially based on HF profile.

Abstract 17275: The SGLT2 Inhibitor Empagliflozin Ameliorates Left Atrial Dilatation in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction: A Secondary Analysis of the EMPATROPISM Trial

Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on left atrial (LA) dilatation has not yet been studied Hypothesis:: Empagliflozin ameliorates left atrial dilatation in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). LA Volumes were quantified by CMR using the Simpson method (the number of slices in the usual short axis SSFP cine sequence was increased to cover both LV and the whole of LA. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in maximal and minimal LA volumes (ΔMax LA Vol and ΔMin LA Vol) at the end of 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either maximal or minimal LA volume (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p&lt;0.001; and ΔLVEF 6±4 vs 0±4%, p&lt;0.001 for EMPA vs placebo). EMPA-treated patients exhibited a reduction of both maximal LA volume (ΔMax LA Vol -16.2±17.8 vs 11.4±25.9mL for EMPA vs placebo, p&lt;0.001) and minimal LA volume (ΔMin LA Vol -11.3±13.3 vs 6.4±19.3mL for EMPA vs control, p&lt;0.001) Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates left atrial dilatation. As LA volume is a surrogate for chronic filling pressures, this reduced LA volume suggest improved diastolic function with EMPA

Abstract 17157: The SGLT2 Inhibitor Empagliflozin Ameliorates Interstitial Myocardial Fibrosis and Aortic Stiffness in Non-Diabetic Patients With Heart Failure With Reduced Ejection Fraction: A Secondary Analysis of the EMPATROPISM Trial

Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on interstitial myocardial fibrosis (IMF) and aortic stiffness has not yet been studied Hypothesis: Empagliflozin ameliorates IMF and aortic stiffness in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial (NCT 03485222) investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). IMF was assessed by CMR using extracellular volume (ECV) by T1 mapping. Aortic stiffness was quantified by pulse wave velocity (PWV) by CMR. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in ECV (ΔECV) and PWV (ΔPWV) at 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either ECV or PWV (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p&lt;0.001; and ΔLVEF 6±4 vs 0±4%, p&lt;0.001 for EMPA vs placebo). EMPA-treated patients exhibited a reduction in ECV (ΔECV -1.25±1.5 vs 0.3±1.4% for EMPA vs placebo, p&lt;0.001), which demonstrates IMF regression with SGLT2i. EMPA-treated patients exhibited a reduction in PWV (ΔECV -0.6±1 vs 0.6±1.4 m/s for EMPA vs control, p&lt;0.001), which indicates amelioration of aortic stiffness with SGLT2i Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates IMF and aortic stiffness. This may explain the benefits of SGLT2i in HFrEF even in the absence of diabetes

Abstract 16412: The Predictors of Hemodynamic Response to Phosphodiesterase-5a Inhibition in Advanced HFrEF

Introduction: In advanced HFpEF, acute phosphodiesterase 5 (PDE5) inhibition leads to favorable change in pulmonary vascular resistance (PVR) and to an increased cardiac output (CO) of variable degree. The determinants of the response are poorely understood. Methods: 47 HFrEF patients (85% males, 57±11 years, NYHA 2.9±0.5, 55% non-ischemic, PAmean 42±8 mmHg, 43% RV dysfunction) underwent clinical exam, echocardiography, biochemical tests and right heart catheterization (RHC) before and after I.V. administration of sildenafil (20 mg). Baseline predictors of absolute and relative (%diff) change of PVR and CO were studied. Results: PDE5i led to highly significant (p&lt;0.001) reduction of pulmonary artery (PA) mean pressure (-11±9 mmHg), PVR (-2.2±1.6 WU;-42±24%), PA wedge pressure (-5.2±7.3 mmHg), CVP (-3.2±2.3 mmHg) and to increase in cardiac output (+0.6±0.7 l/min; +18±23%). PVR decreased more than systemic resistance (PVR/SVR -27±30%diff). Predictors of high CO response (COdiff%) were: low BMI, no diabetes, low baseline CO and severity of mitral or tricuspid regurgitation (r=0.53 or =0.43, both p&lt;0.003). The strongest predictor of high PVR%diff was plasma potassium level. HF etiology, renal function, gender, RAAS inhibitor dose, renin or aldosterone levels were unelated to pulmonary vasoreactivity. Patients who dropped PVR&lt;3 WU after PDE5i had higher plasma K+ (4.1±0.5 vs 4.5±0.3 mmol/L, p=0.01) than those who did not, similar relation was found for K+ and PDE5i-induced change of transpulmonary gradient. Conclusions: The largest increase in CO after PDE5i is observed in HFrEF patients with severe mitral (or tricuspid) regurgitation, probably due to chamber unloading and reduction of regurgitant SV. Pulmonary vasodilator response to PDE5i may be influenced by plasma potassium level. High-normal plasma potassium levels may preserve normal pulmonary vasoreactivity in HFrEF, perhaps by influencing K-channels in pulmonary vascular smooth muscle cells.

Abstract 17469: Comparing the Effect of CRT Implantation on Quality of Life in Older Patients Compared With Younger Patients: Systematic Review and Meta-Analysis

Background: CRT had been accepted as standard of care for patients with HFrEF who qualify for the therapy. The pivotal CRT trials enrolled patients significantly younger than the typical HFrEF patients seen in the community. Benefits of CRT in older HFrEF patients is largely unknown. We sought to evaluate the change in quality of life in older patients undergoing CRT in comparison to younger patients. Hypothesis: CRT implantation is associated with comparable improvements in quality of life in younger patients (age &lt;70) and older patients (age 70 and above). Methods: PubMed, The Cochrane Library, Scopus, and Web of Science were queried for comparative effectiveness studies of CRT in older HFrEF patients. We gathered data for Quality of life measurements including improvement in NYHA class, MLHFQ, Six minute walk test. MLHFQ, Six minute walk test data was analyzed qualitatively as data was insufficient to impute Standard deviation for mean change. Changes in NYHA class was analyzed quantitatively. Random effects meta-analysis of improvement in NYHA class and relative risk (RR) is reported along with estimates of heterogeneity Results: Seven studies [n=2494 for younger group and n=1035 for older group] were included in changes in NYHA class meta-analysis. Older age group patients had similar improvement in NYHA class compared to younger age group patients. Relative risk 0.99 with 95%CI 0.93-1.06 (figure). Five studies reported Baseline and follow up MLHFQ scores for both the groups. All the five studies reported improvements in MLHFQ in both the groups. Three studies reported change in six minute walk test in meters before and after CRT implantation. All the studies reported improvement in six minute walk test both in younger and older group. Conclusions: People older than 70 years of age with heart failure with reduced ejection fraction who qualify for CRT derive similar benefits with improvement in quality of life compared to patients aged less than 70 years of age.

Abstract 14608: Prognostic Value of Diuretic Resistance in Patients Admitted for Acute Decompensated Heart Failure With Reduced, Mid-range, or Preserved Left Ventricular Ejection Fraction

Background: Diuretic resistance is associated with poor clinical outcome in patients with acute decompensated heart failure (ADHF). However, little information is available on the prognostic significance of diuretic resistance in ADHF patients, relating to reduced, mid-range, or preserved left ventricular ejection fraction (LVEF). Methods: We studied 400 consecutive patients who were admitted for ADHF and survived to discharge. Diuretic resistance (DR) was defined by furosemide dose per body weight (BW) at discharge. Patients were classified by DR, and high dose group (higher DR) was defined by furosemide dose of &gt; median value of DR (0.580). The endpoint was a composite of all-cause mortality and unplanned hospitalization for worsening heart failure. Results: There were 139 patients with heart failure with reduced LVEF (HFrEF, LVEF&lt;40%), 86 with mid-range LVEF (HFmrEF, 40%≤LVEF&lt;50%) and 175 with preserved LVEF (HFpEF, LVEF≥50%). There was no significant difference in DR among the three groups (HFrEF; median 0.541 [IQR 0.360-0.786] mg/kg vs HFmrEF; 0.606 [0.398-0.820] mg/kg vs HFpEF; 0.624 [0.380-0.935] mg/kg, p=NS). During follow-up of 2.4±1.6 years, 195 patients reached the endpoint (HFrEF, n=67, HFmrEF, n=44, and HFpEF, n=84). In multivariate Cox analysis, DR was significantly associated with the endpoint independently of age, estimated glomerular filtration rate, plasma brain natriuretic peptide level and LVEF only in HFpEF patients (p&lt;0.0001). Kaplan-Meier analysis showed that the risk of the endpoint was significantly higher in the patients with higher DR in HFpEF patients, but not in HFrEF or HFmrEF patients (Figure). Conclusions: In this study, higher DR was shown to be associated with poor clinical outcome in HFpEF patients admitted with ADHF.

Abstract 16271: Resolution of Left Bundle Branch Block With Sacubitril/Valsartan in Patients With Heart Failure With Reduced Ejection Fraction

Introduction: Sacubitril/valsartan is associated with structural and functional reverse remodeling. It is uncertain if a subset of patients with HFrEF and LBBB treated with sacubitril/valsartan have resolution of LBBB. We aim to assess the effect of sacubitril/valsartan on QRS duration and LVEF in patients with HFrEF and LBBB. Methods: We performed a retrospective study of HFrEF patients treated with Sacubitril/Valsartan from January 2014 to June 2019. Minimum duration of treatment and follow-up was 3 months. Electrocardiographic and echocardiographic parameters were reviewed at four time points. Patients with baseline LBBB were identified. Patients with CRT ≧3 months after sacubitril/valsartan initiation were included and censored following CRT implantation. Results: Among 368 patients that met study criteria, 56 (15%) had baseline LBBB. Mean age was 64 (± 13.5), 53.6% were male and 78.6% had nonischemic cardiomyopathy. During median (IQR) follow-up of 9.1 months (5-18 mo), five (9%) had resolution of LBBB to normal conduction and two (4%) had improvement to non-specific IVCD. Examples of ECGs illustrating LBBB resolution are shown in Figure 1. Time to resolution of LBBB ranged from 1.2-5.7 months. Long term follow-up was only available in one patient with resolution of LBBB lasting at least 25.6 months after initiation of Entresto. The majority (n=4/5, 80%) had nonischemic cardiomyopathy. There was a trend towards greater improvement in LVEF in those with LBBB resolution vs. persistence (23 ± 6% vs. 9 ± 15%, p=0.11) as well as a trend towards greater reduction in LVIDd (-1.2 ± 0.8 cm vs. -0.5 ±0.7 cm, p=0.08). Conclusion: A small subset of patients with LBBB and HFrEF have resolution of LBBB with Sacubitril/Valsartan therapy. This may have important ramifications for timing of CRT implantation and highlights the potential importance of assessing the underlying rhythm in patients that receive a CRT device.