HF Outcomes Research Articles

Proposing a typology to examine the health impact of Housing First: a systematic review and meta-analysis

This is an inclusive systematic review and meta-analysis to understand the health impact of Housing First. Sixty articles relating to HF programmes in America, Australia and Canada were included. Evidence was reviewed using a novel biopsychosocial typology. Collectively, findings suggest that Housing First could play a wider role in customer’s health by moving people toward restoring normality in their social roles and the development of positive subjective experiences. The proposed typology could serve as a theoretical framework to improve understanding of HF’s impact on health, and allow generalisation of HF outcomes in other countries, where HF’s principles are less revolutionary.

Assessment of frailty and related outcomes in older patients with heart failure: A cohort study

ObjectiveHeart failure (HF) is a common cause of morbidity and mortality in older patients. Frailty is prevalent and complicates the course of HF. We sought to investigate the impact of frailty on HF outcomes. MethodsPatients over 65 years old hospitalized with acute decompensated HF and mildly reduced or preserved EF, between September 2017 and September 2019 were enrolled in the study. Before hospital discharge at euvolemic state, patients underwent six-minute walk test (6MWT) and frailty assessment using FRIED and modified SOF scores. Predictors of death, readmissions, and increase in diuretic dose were analyzed by multivariable logistic regression models. ResultsWe enrolled 193 consecutive patients (mean age 78.6 ± 8.4 years, 29.5% males, 59.6% with HF and preserved EF). All patients had at least one comorbidity (40.9% coronary artery disease, 71% diabetes, and 86% hypertension). The mean 6MWT distance was 316.2 meters. According to FRIED score, 4.7% were normal and 17.6% were categorized as pre-frail and 77.7% as frail, while according to SOF index 9.8% were normal, 15% were categorized as pre-frail and 75.1% as frail. Frail patients according to both indices had a higher risk of 90-day readmissions, uptitration of diuretics within 90 days (p < 0.001 for both) and numerically but not significantly higher risk of death. Frailty status was independently associated with higher risk of 90-day readmissions, uptitration of diuretics, and higher BNP at 90 days. ConclusionsFrailty in older patients with HF is common and associated with worse prognosis. Pre-discharge frailty assessment may aid in identification of patients at high-risk for short-term complications.

Artificial Intelligence-Enabled Electrocardiogram Predicted Left Ventricle Diameter as an Independent Risk Factor of Long-Term Cardiovascular Outcome in Patients With Normal Ejection Fraction.

BackgroundHeart failure (HF) is a global disease with increasing prevalence in an aging society. However, the survival rate is poor despite the patient receiving standard treatment. Early identification of patients with a high risk of HF is important but challenging. Left ventricular end-diastolic diameter (LV-D) increase was an independent risk factor of HF and adverse cardiovascular (CV) outcomes. In this study, we aimed to develop an artificial intelligence (AI) enabled electrocardiogram (ECG) system to detect LV-D increase early.ObjectiveWe developed a deep learning model (DLM) to predict left ventricular end-diastolic and end-systolic diameter (LV-D and LV-S) with internal and external validations and investigated the relationship between ECG-LV-D and echocardiographic LV-D and explored the contributions of ECG-LV-D on future CV outcomes.MethodsElectrocardiograms and corresponding echocardiography data within 7 days were collected and paired for DLM training with 99,692 ECGs in the development set and 20,197 ECGs in the tuning set. The other 7,551 and 11,644 ECGs were collected from two different hospitals to validate the DLM performance in internal and external validation sets. We analyzed the association and prediction ability of ECG-LVD for CV outcomes, including left ventricular (LV) dysfunction, CV mortality, acute myocardial infarction (AMI), and coronary artery disease (CAD).ResultsThe mean absolute errors (MAE) of ECG-LV-D were 5.25/5.29, and the area under the receiver operating characteristic (ROC) curves (AUCs) were 0.8297/0.8072 and 0.9295/0.9148 for the detection of mild (56 ≦ LV-D < 65 mm) and severe (LV-D ≧ 65 mm) LV-D dilation in internal/external validation sets, respectively. Patients with normal ejection fraction (EF) who were identified as high ECHO-LV-D had the higher hazard ratios (HRs) of developing new onset LV dysfunction [HR: 2.34, 95% conference interval (CI): 1.78–3.08], CV mortality (HR 2.30, 95% CI 1.05–5.05), new-onset AMI (HR 2.12, 95% CI 1.36–3.29), and CAD (HR 1.59, 95% CI 1.26–2.00) in the internal validation set. In addition, the ECG-LV-D presents a 1.88-fold risk (95% CI 1.47–2.39) on new-onset LV dysfunction in the external validation set.ConclusionThe ECG-LV-D not only identifies high-risk patients with normal EF but also serves as an independent risk factor of long-term CV outcomes.

Aerobic exercise and telomere length in patients with systolic heart failure: protocol study for a randomized controlled trial

BackgroundHeart failure (HF) with reduced ejection fraction (HFrEF) is a syndrome that leads to fatigue and reduced functional capacity due to disease-related pathophysiological mechanisms. Aerobic exercise (AERO) plays a key role in improving HF outcomes, such as an increase in peak oxygen uptake (VO2peak). In addition, HF promotes cell senescence, which involves reducing telomere length. Several studies have shown that patients with a worse prognosis (i.e., reduced VO2 peak) also have shorter telomeres. However, the effects of AERO on telomere length in patients with HFrEF are still unknown. In an attempt to fill this gap, we designed a study to determine the effects of 16 weeks of aerobic training (32 sessions) on telomere length in HFrEF patients.MethodsIn this single-center randomized controlled trial, men and women between 50 and 80 years old will be allocated into two different groups: a moderate-intensity aerobic training and a control grouTelomere length, functional capacity, echocardiographic variables, endothelial function, and walking ability will be assessed before and after the 16-week intervention period.DiscussionUnderstanding the role of physical exercise in biological aging in HFrEF patients is relevant. Due to cell senescence, these individuals have shown a shorter telomere length. AERO can delay biological aging according to a balance in oxidative stress through antioxidant action. Positive telomere length results are expected for the aerobic training group.Trial registrationClinicalTrials.gov NCT03856736. Registered on February 27, 2019

Impact of Daily Bedside Echocardiographic Assessment on Readmissions in Acute Heart Failure: A Randomized Clinical Trial.

Acute heart failure (AHF) management is challenging, with high morbidity and readmission rates. There is little evidence of the benefit of HF monitoring during hospitalization. The aim of the study was to assess whether daily bedside echocardiographic monitoring (JetEcho) improved outcomes in AHF. In this prospective, open, two parallel-arm study (clinicaltrials.gov: NCT02892227), participants from two university hospitals were randomized to either standard of care (SC) or daily treatment adjustment including diuretics guided by JetEcho evaluating left ventricular filling pressure and volemia. The primary outcome was 30-day readmission rate. Key secondary outcomes were six-month cumulative incidence death, worsening HF during hospitalization and increasing of myocardial and renal biomarkers. From 250 included patients, 115 were finally analyzed in JetEcho group and 112 in SC group. Twenty-two (19%) patients were readmitted within 30 days in JetEcho group and 17 (15%) in SC group (relative risk [RR] 1.26; 95% confidence interval [CI], 0.70–2.24; p = 0.4). Worsening HF occurred in 17 (14%) patients in the JetEcho group and 24 (20%) in the SC group (RR 0.7; 95% [CI] 0.39 to 1.2; p = 0.2). No significant difference was found between the two groups concerning natriuretic peptides and renal function (p > 0.05 for all). The cumulative incidence rate of death from any cause at six months from discharge was 8.7% in the JetEcho group and 11.6% in the SC group (HR 0.63, 95% [CI] 0.3–1.4, p = 0.3). In AHF patients, a systematic daily bedside echocardiographic monitoring did not reduce 30-day readmission rate for HF and short-term clinical outcomes.

Association Of Kidney And Cardiovascular Outcomes: Insights From The Empagliflozin Cardiovascular Outcome Event Trial In Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) Trial

<h3>Introduction</h3> Cardiovascular and kidney disease are closely inter-related. In EMPA-REG OUTCOME, empagliflozin (10 or 25mg once daily) reduced the risk of hospitalization for heart failure (HHF) and kidney events in patients with type 2 diabetes and established cardiovascular (CV) disease. <h3>Hypothesis</h3> We evaluated whether kidney events increase risk for subsequent HF or CV outcomes and vice versa. <h3>Methods</h3> Bi-directional associations of kidney events and subsequent CV events were explored using Cox regression with time-varying covariates. <h3>Results</h3> Of 2,061 placebo patients, 18.8% experienced a kidney event (progression to macroalbuminuria with urine albumin-creatinine ratio [UACR] >300mg/g, doubling of serum creatinine with estimated glomerular filtration rate [eGFR] ≤45 ml/min/1.73 m², initiation of renal-replacement therapy or renal death). Factors significantly associated with risk of experiencing a kidney event included: low baseline eGFR, albuminuria ≥30mg/g, high uric acid and LDL-C, prior HF but no coronary artery disease. In placebo patients, occurrence of a non-fatal kidney event increased subsequent HHF risk (hazard ratio [95% CI]) (2.40 [1.42,4.05]) but not 3P-MACE (1.30 [0.89,1.91]) (panel A). Vice versa, HHF (2.03 [1.22,3.39]) but not myocardial infarction (MI)/stroke (0.94 [0.56,1.56]) increased subsequent kidney event risk in the placebo arm (panel B). For 3-P MACE following kidney event, risk was significantly increased in the empagliflozin and overall groups although to a lesser extent and not significant from placebo (panel A). <h3>Conclusions</h3> These findings demonstrate strong bi-directional inter-relationship between HHF and kidney events. Strategies to optimize the use of therapies such as empagliflozin, reducing both kidney and HF outcomes, are warranted, as their benefits may be compounded.

The Common Phenotype Of Polycythemia And Hypervolemia In Hospitalized Heart Failure Patients

<h3>Background</h3> : Heart failure patients have wide variations in intravascular volumes which form the basis for disease initiation and progression and contribute to confusion in treatment strategies. Blood volume analysis (BVA) is a bedside blood test that measures with 98% accuracy intravascular volumes of a HF patient, including plasma and red blood cell volume (RBCV). Extremes in excess of red blood cell volume (polycythemia (P)) in HF patients have been associated with poorer outcomes including mortality. A not uncommon BVA phenotype is that of secondary P, with or without hypervolemia(P/Hypervol). We sought to further clarify the clinical correlates and outcomes associated with this phenotype in a mixed LVEF cohort of hospitalized HF patients and whether this phenotype would be detectable utilizing pHct or Hgb measures. <h3>Methods/Results</h3> : In a cohort of 245 consecutively admitted HF patients (142 men/103 women) with mixed EFs who underwent BVA guided care, 25 patients (10.2%) had P/Hypervol and 3 patients (1.2%) had P with normal or low total blood volume. The presence of this phenotype was equal in patients with HFrEF and HFpEF (52%/48%). P/Hypervol was observed less frequently in patients over 75 (p=0.03), and among patients with BMI>35 (p=0.07). Despite P, the peripheral Hct (pHct) was either normal (57.1%), or >10% below normal (39.3%), indicating that in a majority of patients excess red cells were accompanied by an excess of plasma and that pHct would not indicate P. The BVA-provided RBCV showed that in 93% of patients with P that diuresis alone would not be able to achieve euvolemia without extreme hemoconcentration. Patients with P or P/Hypervol were treated with therapeutic phlebotomy or sent for hematology consults to achieve euvolemia. In terms of outcomes at 30 days post-discharge, 12% of the phenotype were readmitted, similar to those with other phenotypes; no deaths occurred in the P/Hypervol phenotype within 30 days or 365 days. 30-day readmissions did occur (56%) in the phenotype similar to other phenotypes (62.3%). <h3>Conclusions</h3> : The P/Hypervol phenotype is common and worrisome for several reasons. Neither the pHct, the BMI or age is sufficient to identify this phenotype. The plasma and red blood cell volume (RBCV) expansion may hasten disease progression accounting for underrepresentation of older patients in this cohort. Further, the discrepancy in the pHct might lead clinicians to suspect that the patient has a dilutionally low pHct, when, in fact, they have an increased RBCV and a diuretic strategy alone will only hemoconcentrate the patient, increasing viscosity and risk of thrombotic events while not achieving euvolemia. BVA-guided assessment demonstrated the specificity to identify this phenotype. and raise the value of therapeutic phlebotomy to optimize volume and RBCV; this cohort merits improved BVA-guided evaluation to better discern the impact of this phenotype on HF outcomes.

Abstract 9946: Dapagliflozin versus Empagliflozin for Improving Outcomes of Type 2 Diabetes Mellitus Patients with Heart Failure and Reduced Ejection Fraction

Introduction: The co-morbidity of chronic heart failure and Type 2 diabetes mellitus (DM) is associated with a very high risk for CVmortality and HF-related hospitalizations (HHF). The Sodium-Glucose Transport protein 2 inhibitors (SGLT2i) dapagliflozin and empagliflozin improve the outcomes of this patient population. We aimed to compare their value for money for this indication. Hypothesis: Empagliflozin and dapagliflozin have comparable value for money for improving the HF outcomes of patients with HFrEF and DM. Methods: SGLT2i data was extracted from published results of empagliflozin and dapagliflozin in the subgroups of patients with co-morbidity of DM. The clinical outcome measure was HHF or CV mortality events. The economic measure was the cost needed to treat (CNT) to prevent one event, calculated by multiplying the one-year number needed to treat (NNT) to prevent one event by the annual cost of each therapy. Drug costs were based on the 2021 US National Average Drug Acquisition Cost prices. Secondary outcomes were the CNT to prevent one event of HHF and CV mortality as separate clinical outcomes. Sensitivity analysis was performed to mitigate differences between the trial’s populations Results: Treatment with empagliflozin in EMPEROR-REDUCED has resulted in an NNT of 17 (95% CI: 12-36) compared to 24 (95% CI: 16-60) with dapagliflozin in DAPA-HF. Accordingly the cost needed to treat to prevent one event of CVM or HHF was $81,550 (95% CI: $57,565-$172,694) and $108,563 (95% CI: $72,376-$271,408), respectively. The sensitivity analysis confirmed the primary results. The CNT to prevent CV mortality events is significantly lower with dapagliflozin and prevent HHF significantly lower with empagliflozin (Fig. 1). Conclusions: Empagliflozin and dapagliflozin have comparable value for money for improving HF outcomes of patients with HFrEF, with an advantage for dapagliflozin in CV mortality and for empagliflozin in preventing HHF.

Abstract 10062: Administrative Data Algorithms Can Identify Patients with Advanced Heart Failure

Introduction: Advanced or “Stage D” heart failure (Adv HF) patients are at high risk of poor outcomes. However, recognition of Adv HF is limited as diagnostic criteria are complex. Administrative algorithms to identify Adv HF could enable better understanding of who has advanced HF and lead to enhanced therapeutics development, dissemination, and outcomes. Methods: In a population-based cohort of all Olmsted County, Minnesota residents with ≥1 HF billing code 2007-2017 (n=9881), we identified all patients with Adv HF (n=753) by applying the gold standard European Society of Cardiology Adv HF criteria via manual medical review by a HF cardiologist. The Adv HF index date was the date the patient first met all ESC criteria. We then developed candidate algorithms to identify Adv HF using only administrative data (billing codes and HF prescriptions or comorbidities known to affect HF outcomes), applied them to the entire HF cohort and assessed their ability to identify patients with Adv HF on or after their Adv HF index date. Results: A single hospitalization (Hsp) for HF or ventricular arrhythmias (VA, 2007-2017) identified all patients with Adv HF (sensitivity 100%), but the PPV was low (36.4%). Requiring more Hsp, other signs of Adv HF such as hyponatremia, acute kidney injury, hypotension or high-dose diuretic use decreased the sensitivity but improved specificity and PPV. As Adv HF was relatively uncommon, negative predictive values (NPV) were high regardless of algorithm characteristics. Conclusions: Algorithms using administrative data can identify patients with Adv HF with clinically useful accuracy.

Abstract 10191: Dapagliflozin versus Empagliflozin for Improving Outcomes of Non-Diabetic Patients with Heart Failure and Reduced Ejection Fraction

Introduction: Patients with HF and reduced ejection fraction (HFrEF) are at high risk for CV mortality and HF-related hospitalizations (HHF). The Sodium-Glucose Transport protein 2 inhibitors (SGLT2i) dapagliflozin and empagliflozin improve the outcomes of non-diabetic patients with HFrEF. We aimed to compare their value for money for this indication. Hypothesis: Empagliflozin and dapagliflozin have comparable value for money for improving the HF outcomes of non-diabetic patients with HFrEF. Methods: SGLT2i data was extracted from published results of empagliflozin and dapagliflozin in the subgroups of patients without diabetes. The primary clinical outcome measure was a composite of HHF or CV mortality events. The economic measure was the cost needed to treat (CNT) to prevent one event, calculated by multiplying the one-year number needed to treat (NNT) to prevent one event by the annual cost of each therapy. Drug costs were based on the 2021 US National Average Drug Acquisition Cost prices. Secondary outcomes were the CNT to prevent one event of HHF and CV mortality as separate clinical outcomes. Sensitivity analysis was performed to mitigate differences between the trial’s populations Results: Treatment with empagliflozin in EMPEROR-REDUCED has resulted in an NNT of 29 (95% CI: 18-212) compared to 32 (95% CI: 21-72) with dapagliflozin in DAPA-HF. Accordingly the CNT to prevent one event of CVM or HHF was $139,115 (95% CI: $86,347-$1,016,976) and $144,751 (95% CI: $94,993-$325,690), respectively. The sensitivity analysis confirmed the primary results, but the CNT to prevent CV mortality is significantly lower with dapagliflozin (Fig. 1) Conclusions: Empagliflozin and dapagliflozin have comparable value for money for improving HF outcomes of non-diabetic patients with HFrEF, with an advantage for dapagliflozin in CV mortality.

Abstract 11709: The Impact of Hypertension on Disease Expression in Hypertrophic Cardiomyopathy

Introduction: Pressure overload from hypertension (HTN) is an important cause of left ventricular hypertrophy (LVH) in the general population, however its impact on disease expression in hypertrophic cardiomyopathy (HCM), and differences based on the presence/absence of a sarcomeric gene variant are not well characterized. Hypothesis: HTN is associated with more prominent manifestations of HCM. Methods: Genotyped HCM patients in the Sarcomeric Human Cardiomyopathy Registry were designated SARC+ ((likely) pathogenic sarcomeric variant present) or SARC- and categorized as having HTN (≥140/90 mmHg) or normal blood pressure (nonHTN; &lt;140/90 mmHg). Heart failure (HF; LVEF&lt;35%, NYHA III-IV, transplant/LVAD), ventricular arrhythmias (VA; sudden death, resuscitated arrest, appropriate ICD discharge), atrial fibrillation (AF), and an overall composite (HF, VA, AF, death) were assessed by Kaplan-Meier analysis and logistic regression. Results: Of 1706 patients (62% male), 445 (26%) had HTN. Median follow up was 4.2 years. SARC+ nonHTN patients were youngest and SARC- HTN patients oldest (p&lt;0.001; Table). Obstructive physiology was most common in SARC- HTN. SARC+ nonHTN patients had the greatest wall thickness, although absolute differences were minimal (Table). HTN was associated with HF and the overall composite outcome, but not VA or AF (Figure). On multivariable analysis, HTN predicted the HF composite (OR 1.59 [95% CI 1.07-2.26], p=0.02), especially in SARC+ patients (OR 2.34 [95% 1.33-4.11], p=0.003). Conclusions: HTN is associated with worse HF outcomes in HCM, especially among SARC+ patients, but has minimal impact on the degree of cardiac remodeling.

One year outcomes of heart failure multispecialty multidisciplinary team virtual meetings

Abstract Heart Failure is frequently associated with several comorbidities such as ischaemic heard disease, diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease and frailty. This level of complexity is best dealt with by a multispecialty multidisciplinary team (MDT) model. This was a single centre observational study (January 2020-December 2020) that was undertaken in a British university hospital looking at effect of HF multispecialty virtual MDT meetings on HF outcomes. Patients acted as their own controls outcomes compared for equal period pre versus post MDT meeting. The multi-specialty meeting was conducted once monthly via video-conferencing. It consisted of heart failure cardiologists (from primary secondary and tertiary care), heart failure specialist nurses (hospital and community), nephrologist, endocrinologist, palliative care specialists, chest physician, pharmacist, pharmacologist and geriatrician. Recommendations were made as consensus from the multispecialty meeting. The main outcome measures were 1) number of hospitalisations and 2) outpatient clinic attendances 3) cost savings. A total of 189 patients were discussed from January-December 2020. This was uninterrupted during the COVID-19 pandemic. The mean age was 70.3±18.1 years and median follow-up 6 months (range 1–13 months). The mean Charlson Co-morbidity score was 5.3±1.2 and Rockwood Frailty Score was 4.9±1. The mean number of outpatient clinic attendances avoided was 1.7±0.4. This reduced inconvenience to patients, saved patients money (transport and parking costs) and led to carbon footprint reduction. The MDT meeting total costs were £15,400 and the 31 clinic appointments they generated cost an estimated £3720. However, the MDT meetings prevented 277 clinic appointments (cost saving £33,352). Finally, the mean number of hospitalisations pre-MDT was 0.7 Vs 0.2 post MDT (p&amp;lt;0.01) with a saving of around 730 bed days (estimated cost-saving £260,000). The HF multispecialty virtual MDT approach provides seamless integration of primary care community services with secondary and tertiary care. Consensus decision from MDT meetings provides holistic approach for HF patients with comorbidities and frailty, and reduces inconvenience to patients by preventing the need to attend multiple specialty clinics. This approach can also lead to significant cost-savings to the healthcare system. Funding Acknowledgement Type of funding sources: None.

ASSOCIATION OF KIDNEY AND CARDIOVASCULAR OUTCOMES IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: INSIGHTS FROM THE EMPA-REG OUTCOME TRIAL

BACKGROUND In the EMPA-REG OUTCOME trial, empagliflozin (10 or 25mg once daily) reduced the risk of hospitalization for heart failure (HHF) as well as kidney events in patients with type 2 diabetes (T2D) and established cardiovascular (CV) disease by 35-39%. We aimed to evaluate the yet ill-defined bi-directional relationship between kidney and CV outcomes in this population. METHODS AND RESULTS Of the 2,061 patients on placebo in our analysis, 388 (18.8%) experienced a kidney event (progression to macroalbuminuria with UACR >300mg/g, doubling of serum creatinine with eGFR ≤45 ml/min/1.73 m², initiation of renal-replacement therapy or renal death). Low baseline eGFR, albuminuria ≥30mg/g, high uric acid and LDL-C were among the factors significantly associated with the risk of experiencing a kidney event, also prior HF but no coronary artery disease. Associations of kidney events and subsequent CV events and vice versa were explored using Cox regression with time-varying covariates and adjustment for various baseline factors. In the placebo arm, the occurrence of a non-fatal kidney event (excluding renal death) increased the risk of subsequent HHF (HR 2.40, 95% CI 1.42, 4.05) but not 3P-MACE (HR 1.30, 95% CI 0.89, 1.91) (panel A). Also, seemingly vice versa, HHF (HR 2.03, 95% CI 1.22, 3.39) but not myocardial infarction (MI) or stroke (HR 0.94, 95% CI 0.56, 1.56) increased the risk of subsequent kidney event in the placebo arm (panel B). The associations for kidney event following MI/Stroke were consistent in the pooled empagliflozin arm and in the overall population (panel B). For 3-P MACE following kidney event, the risk was significantly increased in the empagliflozin and overall groups although to a lesser extent and not significant from placebo (panel A). CONCLUSION Our results demonstrate strong and bidirectional inter-relationship between HHF and kidney events. Strategies to optimize the use of therapies such as empagliflozin, reducing both kidney and HF outcomes, are warranted, as their benefits may be thereby compounded. In the EMPA-REG OUTCOME trial, empagliflozin (10 or 25mg once daily) reduced the risk of hospitalization for heart failure (HHF) as well as kidney events in patients with type 2 diabetes (T2D) and established cardiovascular (CV) disease by 35-39%. We aimed to evaluate the yet ill-defined bi-directional relationship between kidney and CV outcomes in this population. Of the 2,061 patients on placebo in our analysis, 388 (18.8%) experienced a kidney event (progression to macroalbuminuria with UACR >300mg/g, doubling of serum creatinine with eGFR ≤45 ml/min/1.73 m², initiation of renal-replacement therapy or renal death). Low baseline eGFR, albuminuria ≥30mg/g, high uric acid and LDL-C were among the factors significantly associated with the risk of experiencing a kidney event, also prior HF but no coronary artery disease. Associations of kidney events and subsequent CV events and vice versa were explored using Cox regression with time-varying covariates and adjustment for various baseline factors. In the placebo arm, the occurrence of a non-fatal kidney event (excluding renal death) increased the risk of subsequent HHF (HR 2.40, 95% CI 1.42, 4.05) but not 3P-MACE (HR 1.30, 95% CI 0.89, 1.91) (panel A). Also, seemingly vice versa, HHF (HR 2.03, 95% CI 1.22, 3.39) but not myocardial infarction (MI) or stroke (HR 0.94, 95% CI 0.56, 1.56) increased the risk of subsequent kidney event in the placebo arm (panel B). The associations for kidney event following MI/Stroke were consistent in the pooled empagliflozin arm and in the overall population (panel B). For 3-P MACE following kidney event, the risk was significantly increased in the empagliflozin and overall groups although to a lesser extent and not significant from placebo (panel A). Our results demonstrate strong and bidirectional inter-relationship between HHF and kidney events. Strategies to optimize the use of therapies such as empagliflozin, reducing both kidney and HF outcomes, are warranted, as their benefits may be thereby compounded.

Operationalization of heart failure patients engagement with mHealth

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The computing and communication features of mobile devices have been leveraged in mobile Health (mHealth) interventions to provide comprehensive and tailored support that may have positive outcomes in patients with heart failure (HF. However, the effects of the interventions have shown mixed evidence. Considering that patients’ engagement is a prerequisite for the effectiveness of the interventions, understanding how patients engage with the interventions, and the effects of patients’ engagement on HF outcomes may explain the mixed findings. Objective This study aimed to synthesize current evidence on measures of HF patients’ engagement with mHealth interventions, and the effects of the interventions on HF outcomes. Method In accordance with the Arksey and O’Malley framework for scoping review, a comprehensive search of the literature was conducted in 7 databases for relevant studies published in the English language from 2009 to Feb. 2021. The descriptive characteristics of the studies were reported. Thematic analysis was conducted to identify themes that described patients’ engagement in the qualitative studies included in the review. Results The review synthesized 29 studies that operationalized engagement with mHealth interventions in 3665 patients with HF, ranging from a sample of 7 to 1571, with a median of 80 patients. Patients’ engagement with mHealth interventions was measured quantitively based on system usage data (82.7%, 24/29), qualitatively by semi-structured interviews and focus groups (10.3%, 3/29), and by mixed methods or combination of qualitative and system usage data (17.2%, 5/29). System usage data were evaluated using 7 metrics: (1) number of physiological parameters measured (88.5%, 3/26); (2) duration of use or time spent (3.8%, 6/26); (3) features accessed/screen viewed (11.5%, 3/26); (4) number of HF educational videos viewed (7.7%, 2/26); (5) number of SMS response (3.8%, 1/26); (6) number of HF questionnaire completed (3.8%, 1/26; (7)numbers of logins (5%, 1/19). There is a lack of consistency in how system usage metrics were reported across the studies; 73.7 % of the studies reported only the descriptive statistics of the System usage data. Intervention usage was the most identified subtheme in the qualitative measure. The effect of patients’ engagement with mHealth interventions on HF-related outcomes was inconclusive. Conclusion The operational definitions of patients’ engagement with mHealth interventions are underreported and lack consistency. The application of inferential analytical methods to the engagement data is extremely limited, which indicates a gap in mHealth research in patients with HF. More research focusing on developing optimal and standardized measures of patients’ engagement that may be applied across different study designs is warranted

National Trends in the Burden of Atrial Fibrillation During Hospital Admissions for Heart Failure.

BackgroundHeart failure (HF) and atrial fibrillation (AF) frequently coexist and may be associated with worse HF outcomes, but there is limited contemporary evidence describing their combined prevalence. We examined current trends in AF among hospitalizations for HF with preserved (HFpEF) ejection fraction or HF with reduced ejection fraction (HFrEF) in the United States, including outcomes and costs.Methods and ResultsUsing the National Inpatient Sample, we identified 10 392 189 hospitalizations for HF between 2008 and 2017, including 4 250 698 with comorbid AF (40.9%). HF hospitalizations with AF involved patients who were older (average age, 76.9 versus 68.8 years) and more likely White individuals (77.8% versus 59.1%; P<0.001 for both). HF with preserved ejection fraction hospitalizations had more comorbid AF than HF with reduced ejection fraction (44.9% versus 40.8%). Over time, the proportion of comorbid AF increased from 35.4% in 2008 to 45.4% in 2017, and patients were younger, more commonly men, and Black or Hispanic individuals. Comorbid hypertension, diabetes mellitus, and vascular disease all increased over time. HF hospitalizations with AF had higher in‐hospital mortality than those without AF (3.6% versus 2.6%); mortality decreased over time for all HF (from 3.6% to 3.4%) but increased for HF with reduced ejection fraction (from 3.0% to 3.7%; P<0.001 for all). Median hospital charges were higher for HF admissions with AF and increased 40% over time (from $22 204 to $31 145; P<0.001).ConclusionsAF is increasingly common among hospitalizations for HF and is associated with higher costs and in‐hospital mortality. Over time, patients with HF and AF were younger, less likely to be White individuals, and had more comorbidities; in‐hospital mortality decreased. Future research will need to address unique aspects of changing patient demographics and rising costs.

Epicardial Adiposity in Relation to Metabolic Abnormality, Circulating Adipocyte FABP, and Preserved Ejection Fraction Heart Failure.

Epicardial adipose tissue (EAT) as a source of pro-inflammatory cytokines tightly linked to metabolic abnormalities. Data regarding the associations of EAT with adipocyte fatty acid-binding protein (A-FABP), a cytokine implicated in the cardiometabolic syndrome, might play an important part in mediating the association between EAT and cardiac structure/function in preserved ejection fraction heart failure (HFpEF). We conducted a prospective cohort study comprising 252 prospectively enrolled study participants classified as healthy (n = 40), high-risk (n = 161), or HFpEF (n = 51). EAT was assessed using echocardiography and compared between the three groups and related to A-FABP, cardiac structural/functional assessment utilizing myocardial deformations (strain/strain rates) and HF outcomes. EAT thickness was highest in participants with HFpEF (9.7 ± 1.7 mm) and those at high-risk (8.2 ± 1.5 mm) and lowest in healthy controls (6.4 ± 1.9 mm, p < 0.001). Higher EAT correlated with the presence of cardiometabolic syndrome, diabetes and renal insufficiency independent of BMI and waist circumference (pinteraction for all > 0.1), and was associated with reduced LV global longitudinal strain (GLS) and LV mass-independent systolic/diastolic strain rates (SRs/SRe) (all p < 0.05). Higher A-FABP levels were associated with greater EAT thickness (pinteraction > 0.1). Importantly, in the combined control cohort, A-FABP levels mediated the association between EAT and new onset HF. Excessive EAT is independently associated with the metabolic syndrome, renal insufficiency, and higher A-FABP levels. The association between EAT and new onset HF is mediated by A-FABP, suggesting a metabolic link between EAT and HF.

Association of Kidney and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus: Insights From the EMPA-REG OUTCOME Trial

In EMPA-REG OUTCOME, empagliflozin (10 or 25mg once daily) reduced the risk of hospitalisation for heart failure (HHF) and kidney events in patients with type 2 diabetes and established cardiovascular (CV) disease. We evaluated the bi-directional relationship between kidney and HF outcomes.

Abstract 16784: Under-Enrollment of Real-World Heart Failure With Preserved Ejection Fraction Patients in Major HFpEF Clinical Trials

Introduction: Inclusion criteria for enrollment in HFpEF clinical trials vary considerably and often exclude patients with co-morbidities such as obesity. We tested the hypotheses that: 1) a large number of patients with clinical and hemodynamic evidence of HFpEF are excluded from major HFpEF clinical trials; and 2) there is no difference in clinical outcomes between patients excluded versus those who met enrollment criteria by evaluating reasons for exclusion from HFpEF clinical trials and comparing clinical outcomes in a real-world HFpEF cohort. Methods: Patients referred to the Johns Hopkins HFpEF Clinic with clinical and hemodynamic evidence of HFpEF (pulmonary capillary wedge pressure [PCWP] ≥ 12 mmHg on a loop diuretic or PCWP ≥ 15 mmHg) were assessed for inclusion into 4 major HFpEF trials (TOPCAT, I-PRESERVE, PARAGON-HF, and RELAX). Cumulative hazard of HF hospitalization or death at 2 years from index clinic visit was compared between patients included and excluded by each trial. Results: Of 132 HFpEF patients, the median PCWP was 19 mmHg (IQR: 15-22 mmHg). Forty-four (33%) of patients met enrollment criteria for TOPCAT, 39 (29%) for I-PRESERVE, 21 (16%) for PARAGON-HF, and 50 (38%) for RELAX. The top 5 criteria that would have excluded patients included low natriuretic peptide level, obesity, elevated blood pressure, young age, and low hemoglobin (Figure 1A) . There was no difference in HF burden (hospitalizations, diuretic dosing, or NYHA class), or in clinical outcomes including HF hospitalization or death between patients who did or did not meet inclusion criteria for each clinical trial (Figure 1B ). Conclusion: We demonstrate that in a real-world cohort of hemodynamically-proven HFpEF few patients would have met criteria for enrollment in major HFpEF clinical trials, yet HF burden and outcomes were no different. Given the lack of proven therapies in HFpEF, consideration should be given to unifying and broadening enrollment criteria in HFpEF clinical trials.

Impact of arterial stiffness on diastolic function and outcomes of heart failure in patients presenting with acute myocardial infarction

Abstract Background Relation of arterial stiffness and cardiovascular disease is well-known. However, there is no data on association between diastolic function and brachial-ankle pulse wave velocity (baPWV) and influence on heart failure outcomes in patients with acute myocardial infarction (AMI). Methods Among patients presenting with AMI, all subjects underwent baPWV and echocardiography were recruited. Diastolic function was categorized by 2016 guideline of ASE/EACVI left ventricular diastolic function. Heart failure outcomes were defined 1) hospitalization for heart failure, 2) cardiac death and 3) sudden cardiac arrest. Results Totally 1,016 subjects were enrolled (FU duration; 3.5±2.0 years, mean age 65±13, predominant male 71.3% and STEMI 40.8%) from 2012 to 2015 in the our University Hospital. Elderly, female, low BMI, higher PWV, HTN, DM and stroke were associated with higher baPWV. Increased arterial stiffness (defined as baPWV ≥1700) had higher prevalence of diastolic dysfunction compared with baPWV &amp;lt;1700 (98.3% vs 86.2%). HF outcomes of 69 events were identified (HF; n=48, cardiac death; n=16, sudden cardiac arrest; n=2, death d/t HF; n=3). In the multivariate analysis, baPWV ≥1700, HTN and low BMI (23 kg/m2) were independent predictors for HF outcomes after adjustment with age, LVEF, DM and stroke (Table 1). Furthermore, KM curve showed that increased arterial stiffness was associated with higher prevalence of diastolic dysfunction and poor outcomes of heart failure (Figure 1). Conclusions In patients with AMI, arterial stiffness was associated with higher prevalence of diastolic dysfunction an independent predictor for heart failure hospitalization and cardiac death. Figure 1. Diastolic dysfunction and HF in AMI Funding Acknowledgement Type of funding source: None

Impact of polyvascular disease and renal dysfunction on cardiovascular outcomes in diabetes: post hoc analyses from EMPA-REG OUTCOME

Abstract Background Individuals with polyvascular disease and impaired renal function are at high risk of cardiovascular (CV) events, but this relationship is not well investigated in people with type 2 diabetes (T2D). Furthermore, the impact of polyvascular disease plus renal dysfunction on the risk for hospitalisation for heart failure (HHF) remains unclear. Purpose We investigated this in a post hoc analysis of the EMPA-REG OUTCOME trial in which empagliflozin reduced risk of CV death and HHF versus placebo in people with T2D and vascular disease. In addition, we explored the treatment effect of empagliflozin on CV, HF and mortality outcomes across the spectrum of baseline polyvascular disease and impaired renal function. Methods Patients with T2D, CV disease and estimated glomerular filtration rate (eGFR) of ≥30 ml/min/1.73 m2 received empagliflozin 10 mg, 25 mg, or placebo. Vascular beds (VBs) were defined as coronary artery disease, peripheral artery disease, and cerebrovascular disease (Fig). By use of Cox regression, we explored the association between baseline eGFR &amp;lt; or ≥60 ml/min/1.73 m2, with or without polyvascular disease (1 vs ≥2 VBs involved), and CV death, HHF, CV death (excl. fatal stroke)/HHF, and all-cause mortality (ACM), as well as the treatment effect of empagliflozin versus placebo on these outcomes. Results Patients with ≥2 VBs involved and eGFR &amp;lt;60 ml/min/1.73 m2 [n=463], were slightly older (mean age 68.2 vs. 64.3 or 62.6 years), had T2D duration &amp;gt;10 years more often (73.4% vs. 63.2% or 54.9%), and a higher HF prevalence at baseline (19.4% vs. 11.1% or 9.2%) versus those with ≥2 VBs involved and eGFR ≥60 ml/min/1.73 m2 [n=866], or those with only 1 VB involved regardless of eGFR [n=5630], respectively. However, characteristics were generally balanced between treatment groups. Notably, co-existing polyvascular disease and eGFR &amp;lt;60 ml/min/1.73 m2 was strongly associated with increased risk of all outcomes. The placebo incidence rates per 1000 patient-years for CV death were 14.4 (95% CI 10.9, 18.3) and 19.6 (12.8, 27.8) in those with 1 VB involved and eGFR ≥60 or eGFR &amp;lt;60, respectively, and 32.7 (21.7, 45.8), and 52.4 (32.9, 76.5) in those with 2 VBs and eGFR ≥60 or eGFR &amp;lt;60 ml/min/1.73 m2, respectively. Importantly, empagliflozin reduced the risk for all outcomes regardless of number of VBs affected and kidney function (Fig). Conclusions Co-existing polyvascular disease and eGFR &amp;lt;60 ml/min/1.73 m2 confer an extremely high risk of CV and all-cause mortality, and HHF. Empagliflozin lowered this risk consistently compared with placebo, regardless of polyvascular disease and impaired kidney function. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance