Risk Of Subsequent Heart Failure Research Articles

The association of NT-proBNP levels in atrial fibrillation patients and 3-year risk of heart hospitalization and death

Abstract Background NT-proBNP-levels are often elevated in patients with atrial fibrillation (AF), but their clinical use and interpretation for predicting subsequent cardiovascular events has not been explored in an all-comers setting. Aim To determine whether NT-proBNP levels are associated with the risk of subsequent heart failure (CHF) and/or death in patients with AF and its relation to prior CHF diagnosis Method All patients with new-onset AF (defined by ICD-code I48) who had an NT-proBNP-level within +/- 14 days of the date of the AF date measured in a regional laboratory repository between 2000-2021 were included in the analysis cohort. Patients were categorized into NT-proBNP level (pg/mL) <1000, 1000-1999, ≥2000. If several NT-proBNP-levels were measured, the maximal value was used. The association between NT-proBNP level and the outcome CHF hospitalization and/or death within 3 years of diagnosis was assessed in Cox regression analyses adjusted for baseline characteristic and medications. Since there was an interaction (p<0.001) between Nt-proBNP-level and prior/new-onset CHF at time of AF diagnosis and no known CHF, two separate analyses were performed in patients with or new-onset CHF and those without prior CHF. Results There were 10559 patients with AF and no CHF, and 11 257 with AF and CHF. There were 14% of patients with new-onset CHF at time of new-onset AF diagnosis. These were grouped together with patients with known CHF. Patients with no prior CHF were younger (76 years (95% CI 68-83) vs 80 (72-87), p<0.001), and healthier with less often diabetes (18.4% vs 24.5%, p<0.001), prior myocardial infarction (12.0% vs 24.3%), a lower CHA2DS2-VASc score (3.0 vs 5.0, p<0.001) and a lower median NT-proBNP level (1650 pg/mL (95% CI 702-3549) vs 4240 pg/mL (2160-8860), p<0.001). Among patients with AF and no prior CHF, the incidence rate in the lowest NT-proBNP level was low, but increased with higher levels (Table). Adjusting for covariates and medications, the risk of both CHF hospitalization and CHF/death compared to the reference category NTproBNP< 1000 pg/mL was nearly 2 and 3 times higher among those who with initial NT-proBNP level 1000-1999 and ≥ 2000. Among patients with AF and known CHF, the incidence rate of CHF hospitalization or CHF hospitalization/death at the same NT-proBNP-strata was several times higher compared to patients without known CHF. Adjusting for covariates, the risk increased for CHF hospitalization or CHF/hospitalization similarly for each strata as for patients without known CHF. AF patients without known HF but with the highest elevation of NTproBNP-level had a risk of subsequent hospitalization of heart failure which was higher than those with known heart failure and lowest NTproBNP-level. Conclusion A higher NTproBNP-level in patients with AF identifies patients at higher risk of CHF hospitalization and/or death in both patients with no and prior CHF.Table

Clinical significance of ST-segment depression during atrial fibrillation rhythm for subsequent heart failure events.

The clinical significance of ST-segment depression during atrial fibrillation (AF) rhythm has not been fully evaluated. The aim of the present study was to explore the association of ST-segment depression during AF rhythm with subsequent heart failure (HF) events. The study enrolled 2718 AF patients whose baseline electrocardiography (ECG) was available from a Japanese community-based prospective survey. We assessed the association of ST-segment depression in baseline ECG during AF rhythm with clinical outcomes. The primary ednpoint was a composite HF endpoint: cardiac death or hospitalization due to HF. The prevalence of ST-segment depression was 25.4% (upsloping 6.6%, horizontal 18.8%, downsloping 10.1%). Patients with ST-segment depression were older and had more comorbidities than those without. During the median follow-up of 6.0 years, the incidence rate of the composite HF endpoint was significantly higher in patients with ST-segment depression than those without (5.3% vs. 3.6% per patient-year, log-rank P < 0.01). The higher risk was present in horizontal or downsloping ST-segment depression, but not in upsloping one. By multivariable analysis, ST-segment depression was an independent predictor for the composite HF endpoint (hazard ratio 1.23, 95% confidence interval 1.03-1.49, P = 0.03). In addition, ST-segment depression at anterior leads, unlike inferior or lateral leads, was not associated with higher risk for the composite HF endpoint. ST-segment depression during AF rhythm was associated with subsequent HF risk; however, the association was affected by type and distribution of ST-segment depression.

The Risk of Heart Failure Progression in Patients With Patent Foramen Ovale: Differential Risk Associated With Device Closure

A patent foramen ovale (PFO) can unload left atrial pressure via an interatrial shunt. We investigated whether device closure of PFO is associated with a subsequent risk of heart failure (HF), particularly in patients with structural heart disease or atrial fibrillation (AF). We enrolled 4,804 consecutive patients who underwent transesophageal echocardiography at tertiary medical centers in Korea between 2007 and 2019. The primary outcome was the 4-year risk of HF hospitalization. Underlying structural heart disease was determined by echocardiography. A PFO was observed in 981 (20.4%) patients, where 161 underwent device closure. During follow-up (median, 3.5 [1.4-6.4] years), the primary outcome was lower in patients with PFO than in those without (2.6% vs 4.0%; adjusted hazard ratio [aHR], 0.65; 95% CI, 0.45-0.94; P=.021). Among the patients with PFO, the primary outcome was higher in the device closure group than in the no-closure group (5.5% vs 1.2%; aHR, 5.59; 95% CI, 4.26-7.34; P<.001). A consistent result was found in patients with structural heart disease or AF (9.6% vs 3.9%; aHR, 2.55; 95% CI, 1.95-3.33; P<.001), demonstrating an increased risk of the primary outcome proportionate to the number of combined structural abnormalities. However, no significant association was observed between the primary outcome and PFO closure in those without structural heart disease or AF (1.7% vs 1.5%; aHR, 1.22; 95% CI, 0.99-1.50; P=.054). Patients with underlying structural heart disease or AF may be predisposed to symptomatic HF progression after PFO closure. Therefore, careful medical surveillance with optimal risk management is needed in these patients.

Abstract 9538: Impact of Device Closure on Heart Failure Progression in Patients With Patent Foramen Ovale

Background: Patent foramen ovale (PFO) can unload left atrial pressure via interatrial shunt. We evaluated whether device occlusion of PFO is associated with subsequent risk of heart failure (HF). Methods: We enrolled 4,804 consecutive patients (median age: 68 years, 62.4% male) who underwent transesophageal echocardiography at tertiary medical centers in Korea between 2007 and 2019. The primary outcome was the 4-year risk of HF. The independent association of PFO closure with HF was evaluated using the Cox regression hazard model after multivariate adjustment for demographics, clinical risk factors, and echocardiographic parameters. Additional subgroup analysis was performed according to the presence structural heart disease defined as left ventricular (LV) ejection fraction &lt; 55%, left atrial (LA) size &gt; 35ml or LA volume ≥ 40ml/m 2 , LV mass index ≥ 115g/m 2 , E/e' ≥ 15, or presence of atrial fibrillation. Results: In total, PFO was observed in 981 (20.4%) patients, where 161 (16.4%) of them underwent device closure. Patients with PFO showed a lower risk of HF than those without (2.6 vs. 4.0%, adjusted hazard ratio [HR]: 0.65, 95% confidence interval [CI] 0.45-0.94, p=0.021). PFO closure group showed a significantly higher risk of HF than no closure group (5.5 vs. 1.2%, adjusted HR: 5.59, 95% CI 4.26-7.34, p&lt;0.001) (Figure). In subgroup analysis, PFO closure was significantly associated with HF risk in patients with underlying structural heart disease (9.6 vs. 3.9%, adjusted HR: 2.55, 95% CI 1.95-3.33, p&lt;0.001), demonstrating an increasing trend in proportion to the number of structural abnormalities. However, PFO closure showed no significant association with HF risk in patients without structural heart disease (1.7 vs. 1.5%, adjusted HR: 1.22, 95% CI 0.99-1.50, p=0.054). Conclusion: PFO closure may increase the risk of HF. Therefore, careful patient selection is needed, especially among those with underlying structural heart disease.

Stress related neural activity: potential mechanism contributing to benefit of physical activity on heart failure incidence

Abstract Background We previously observed that: 1) physical activity (PA) decreases stress-related neural activity (SNA) in a dose-dependent manner and 2) resting SNA predicts incident heart failure (HF). Thus, we hypothesize that PA may decrease the risk of incident HF in part through its beneficial effect on SNA. Methods Self-reported PA data were acquired from Partners Biobank participants. Metabolic equivalent of task-minutes per week (MET*minutes/week) were calculated and participants were categorized according to their adherence to current PA recommendations (&amp;lt;500 and ≥500 MET-min/wk). In a subset with clinically indicated 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging (n=744), SNA was measured as a ratio of amygdalar to ventromedial prefrontal cortical activity. Subsequent HF and baseline CVD risk factor data were obtained using International Classification of Diseases Codes. Kaplan-Meier and Cox regression analyses were used to evaluate the relationship between PA vs HF risk. Mediation analysis was used to test whether PA's impact on SNA significantly mediated the association between PA and HF. Results Among 50,363 participants (median age 59 years [IQR 42, 70], 40% male), 13,850 (11.6%) were diagnosed with HF over a median period of 3.1 years. PA within recommendations was associated with lower risk of subsequent HF (hazard ratio (HR) [95% confidence interval (CI)]: 0.849 [0.760, 0.948], p=0.004, Figure 1) in a model adjusted for CVD risk factors and history of myocardial infarction. As noted previously, higher SNA associated with higher risk of subsequent HF (HR [95% CI]: 1.34 [1.08, 1.66], p=0.007); and PA within guideline recommendations (vs.below) associated with lower SNA (Zscore ± SD: −0.14±0.92 vs 0.02±1, p=0.037). Moreover, mediation analysis shows that exercise reduces HF risk in part via reductions in SNA, accounting for 9% of the total relationship between exercise and HF risk (p&amp;lt;0.05, Figure 2). Conclusion PA associates with reductions in: A) stress-associated neural activity and B) subsequent HF risk. Moreover, the mechanism by which PA reduces HF risk may involve salutary effects on stress-related neural pathways. Funding Acknowledgement Type of funding sources: None.

Effects of DPP4 Inhibitor in Platelet Reactivity and Other Cardiac Risk Markers in Patients with Type 2 Diabetes and Acute Myocardial Infarction.

Background: The management of acute myocardial infarction (AMI) presents several challenges in patients with diabetes, among them the higher rate of recurrent thrombotic events, hyperglycemia and risk of subsequent heart failure (HF). The objective of our study was to evaluate effects of DPP-4 inhibitors (DPP-4i) on platelet reactivity (main objective) and cardiac risk markers. Methods: We performed a single-center double-blind randomized trial. A total of 70 patients with type 2 diabetes (T2DM) with AMI Killip ≤2 on dual-antiplatelet therapy (aspirin plus clopidogrel) were randomized to receive sitagliptin 100 mg or saxagliptin 5 mg daily or matching placebo. Platelet reactivity was assessed at baseline, 4 days (primary endpoint) and 30 days (secondary endpoint) after randomization, using VerifyNow Aspirin™ assay, expressed as aspirin reaction units (ARUs); B-type natriuretic peptide (BNP) in pg/mL was assessed at baseline and 30 days after (secondary endpoint). Results: Mean age was 62.6 ± 8.8 years, 45 (64.3%) male, and 52 (74.3%) of patients presented with ST-segment elevation MI. For primary endpoint, there were no differences in mean platelet reactivity (p = 0.51) between the DPP-4i (8.00 {−65.00; 63.00}) and placebo (−14.00 {−77.00; 52.00}) groups, as well in mean BNP levels (p = 0.14) between DPP-4i (−36.00 {−110.00; 15.00}) and placebo (−13.00 {−50.00; 27.00}). There was no difference between groups in cardiac adverse events. Conclusions: DPP4 inhibitor did not reduce platelet aggregation among patients with type 2 diabetes hospitalized with AMI. Moreover, the use of DPP-4i did not show an increase in BNP levels or in the incidence of cardiac adverse events. These findings suggests that DPP-4i could be an option for management of T2DM patients with acute MI.

Clinical utility of simple subjective gait speed for the risk stratification of heart failure in a primary prevention setting

Little is known regarding the relationship between self-reported gait speed and the subsequent risk of heart failure (HF) and cardiovascular disease (CVD). We sought to clarify the clinical utility of self-reported gait speed in primary CVD prevention settings. This is an observational cohort study using the JMDC Claims Database, which is an administrative health claims database. Data were collected between January 2005 and April 2020. Medical records of 2,655,359 participants without a prior history of CVD were extracted from the JMDC Claims Database. Gait speed was assessed using information from questionnaires provided at health check-ups, and study participants were categorized into fast or slow gait speed groups. The primary outcome was HF. The secondary outcomes included myocardial infarction (MI), angina pectoris (AP), and stroke. The median age was 45.0 years, and 55.3% of participants were men. 46.1% reported a fast gait speed. The mean follow-up period was 1180 ± 906 days. HF, MI, AP, and stroke occurred in 1.9%, 0.2%, 1.9%, and 1.0% of participants, respectively. Multivariable Cox regression analyses showed that, compared with slow gait speed, fast gait speed was associated with a lower incidence of HF, MI, AP, and stroke. The discriminative predictive ability for HF significantly improved by adding self-reported gait speeds to traditional risk factors (net reclassification improvement 0.0347, p < 0.001). In conclusion, our analysis demonstrated that subjective gait speed could be a simple method to stratify the risk of HF and other CVD events in the general population. Further investigations are required to clarify the underlying mechanism of our results and to develop a novel approach for primary CVD prevention.

Biomarker changes as surrogate endpoints in early-phase trials in heart failure with reduced ejection fraction.

AimsNo biomarker has achieved widespread acceptance as a surrogate endpoint for early‐phase heart failure (HF) trials. We assessed whether changes over time in a panel of plasma biomarkers were associated with subsequent morbidity/mortality in HF with reduced ejection fraction (HFrEF).Methods and resultsIn 1040 patients with HFrEF from the BIOSTAT‐CHF cohort, we investigated the associations between changes in the plasma concentrations of 30 biomarkers, before (baseline) and after (9 months) attempted optimization of guideline‐recommended therapy, on top of the BIOSTAT risk score and the subsequent risk of HF hospitalization/all‐cause mortality using Cox regression models. C‐statistics were calculated to assess discriminatory power of biomarker changes/month‐nine assessment. Changes in N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and WAP four‐disulphide core domain protein HE4 (WAP‐4C) were the only independent predictors of the outcome after adjusting for their baseline plasma concentration, 28 other biomarkers (both baseline and changes), and BIOSTAT risk score at baseline. When adjusting for month‐nine rather than baseline biomarkers concentrations, only changes in NT‐proBNP were independently associated with the outcome. The C‐statistic of the model including the BIOSTAT risk score and NT‐proBNP increased by 4% when changes were considered on top of baseline concentrations and by 1% when changes in NT‐proBNP were considered on top of its month‐nine concentrations and the BIOSTAT risk score.ConclusionsAmong 30 relevant biomarkers, a change over time was significantly and independently associated with HF hospitalization/all‐cause death only for NT‐proBNP. Changes over time were modestly more prognostic than baseline or end‐values alone. Changes in biomarkers should be further explored as potential surrogate endpoints in early phase HF trials.

Effect of monthly vitamin D supplementation on cardiac biomarkers: A post-hoc analysis of a randomized controlled trial

The effects of vitamin D supplementation on cardiovascular diseases are controversial. Data on effects of vitamin D upon cardiac biomarkers, as surrogate endpoints of cardiovascular diseases, are limited and inconclusive. Therefore, we carried out a post-hoc analysis of sub-samples of a randomized, double-blinded, placebo-controlled trial with community-based older adults who were randomized to receive monthly 100,000-IU vitamin D or placebo, to determine effect of monthly vitamin D supplementation on high-sensitivity cardiac troponin I (hs-cTnI), troponin T (hs-cTnT) and N-terminal-pro-B-type natriuretic peptide (NT-proBNP). Adjusted relative difference (aRD) of follow-up geometric mean of biomarkers and adjusted relative risk (aRR) of elevated biomarkers between two groups were calculated. A total of 779 participants aged 50–84 y, randomized to vitamin D (n = 395) or placebo (n = 384) groups underwent sampling for measurement of plasma biomarkers at baseline and after one or two years treatment. Over a mean follow-up of 1.6 years, we did not find significant relative difference of geometric mean levels of three biomarkers at follow-up between vitamin D and placebo groups: hs-cTnI (aRD=1.03, 95%CI=0.97–1.09), hs-cTnT (aRD=0.99, 95%CI=0.95–1.04), and NT-proBNP (aRD=1.01, 95%CI=0.92–1.10). No significant differences were found in likelihood of clinically elevated biomarkers between two groups: hs-cTnI (aRR=0.92, 95%CI=0.51–1.69), hs-cTnT (aRR=1.11, 95%CI=0.86–1.42), and NT-proBNP (aRR=1.03,95%CI=0.89–1.20). However, among participants with initial low vitamin D status (<50 nmol/L, n = 200), follow-up NT-proBNP were significantly lower in the vitamin D group compared to placebo (geometric mean 75.9 vs 94.5 pg/mL, respectively; aRD=0.84, 95%CI=0.71-<1.00). The same results were observed for the NT-proBNP levels change from baseline between two groups. Overall, in older adults, monthly vitamin D supplementation did not reduce concentrations of hs-cTnI, hs-cTnT, and NT-proBNP. In those with low vitamin D status, vitamin D treatment was associated, on follow up and change from baseline, with lower plasma NT-proBNP compared with placebo. This potentially signals reduced risk of subsequent heart failure within this sub-group. However, we acknowledge that these findings need to be considered exploratory. Further research is required to replicate them.

Association of primary Sjögren’s syndrome with incident heart failure: a secondary analysis of health claims data in Taiwan

Objective:Mounting evidence has demonstrated that various chronic inflammatory diseases are associated with incident heart failure (HF). However, there is scarce evidence about the association between primary Sjögren’s syndrome (pSS) and HF. We aimed to explore this association using a nationwide database in Taiwan.Methods:We selected patients with incident pSS and no history of HF. Using propensity score matching based on age, sex, cohort entry time, comorbidities, and concomitant medications, cohorts of patients with and without pSS (as controls) were created in a 1:1 ratio and the groups were compared. The cumulative incidence of HF was calculated using Kaplan–Meier estimation. Cox proportional hazard regression analysis was used to measure the hazard ratio (HR) of HF-related hospitalization for the pSS cohort compared with the comparison group.Results:A total of 16,466 pairs of patients with pSS and those without pSS were identified. The cumulative incidence of HF-related hospitalization at 3, 5, and 10 years in patients with pSS was 1.05%, 1.89%, and 4.33%, respectively. The risk of HF-related hospitalization was not higher in patients with pSS than in the general population (HR: 0.98, 95% confidence interval [CI]: 0.84–1.14). There was no difference in survival probability after the first episode of HF-related hospitalization between pSS and non-pSS groups.Conclusion:Our results suggest that distinct inflammatory spectrums in each chronic inflammatory disease might have differential impacts on cardiac function and subsequent risk of HF. Future studies are needed to elucidate the complex and diverse mechanisms of HF in various chronic autoimmune diseases.

Chronic kidney disease and risk of atrial fibrillation and heart failure in general population-based cohorts – the BiomarCaRE project

Abstract Background Chronic kidney disease (CKD) has a complicated relationship with the heart, leading to many adverse outcomes. Purpose The aim of the study was to evaluate the relationship between CKD and the incidence of atrial fibrillation (AF) and heart failure (HF) along with mortality as a competing risk in general population cohorts. Methods This study was conducted as part of the BiomarCaRE project using harmonised data from 12 population-based cohorts (n=40,212) from Europe. Cox proportional hazards models were used to determine hazard ratios (HRs) for the incidence of AF and HF in CKD and with competing mortality risk after adjusting for covariates. Results Mean age at baseline was 51.1 (standard deviation 11.9) years, and 49.3% were men. Overall, 3.5% had CKD at baseline. The rate for incident AF was 3.9 per 1000 person-years during follow-up. The HR for AF for those with CKD compared with those without was 1.23 (95% CI 1.00–1.52, p=0.0465) after adjustment for covariates. The rate for incident HF was 3.9 per 1000 person-years and the associated risk in the presence of CKD was HR 1.67 (95% CI 1.39–2.01). In subjects with CKD, N-terminal pro-B-type natriuretic peptide (NT-proBNP) showed an association with AF, while NT-proBNP and C-reactive protein (CRP) showed an association with HF. Conclusion CKD is an independent risk factor for subsequent AF and even more so for HF. In patients with CKD, NT-proBNP was clearly associated with subsequent risk of AF. In addition to this marker, hs-CRP was also associated with risk of subsequent HF. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): 7th framework programme collaborative project, grant agreement no. HEALTH-F2-2011_278913. Atrial Fibrillation and HF in CKD

Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart.

Coronary heart disease is a leading cause of mortality and morbidity. Those that survive acute myocardial infarction are at significant risk of subsequent heart failure due to fibrotic remodelling of the infarcted myocardium. By applying knowledge from the study of embryonic cardiovascular development, modern medicine offers hope for treatment of this condition through regeneration of the myocardium by direct reprogramming of fibrotic scar tissue. Here, we will review mechanisms of cell fate specification leading to the generation of cardiovascular cell types in the embryo and use this as a framework in which to understand direct reprogramming. Driving expression of a network of transcription factors, micro RNA or small molecule epigenetic modifiers can reverse epigenetic silencing, reverting differentiated cells to a state of induced pluripotency. The pluripotent state can be bypassed by direct reprogramming in which one differentiated cell type can be transdifferentiated into another. Transdifferentiating cardiac fibroblasts to cardiomyocytes requires a network of transcription factors similar to that observed in embryonic multipotent cardiac progenitors. There is some flexibility in the composition of this network. These studies raise the possibility that the failing heart could one day be regenerated by directly reprogramming cardiac fibroblasts within post-infarct scar tissue.

980-P: Existing Microvascular Complications and Risk of Subsequent Heart Failure (HF) in Type 1 Diabetes (T1D)

We aimed to quantify the association between existing microvascular diseases and risk of subsequent HF in adults with T1D. Participants from Pittsburgh Epidemiology of Diabetes Complication (EDC) Study without known baseline HF (n=655) were classified into 4 groups based on the number (n=0-3) of existing microvascular diseases, i.e., overt nephropathy, proliferative retinopathy, and confirmed distal symmetric polyneuropathy (CDSP). Overt nephropathy was defined as an AER &amp;gt;300mg/24h in ≥ 2 of three validated timed biennial urine collections. Proliferative retinopathy was based on stereoscopic fundus photographs or a history of receiving laser therapy for proliferative diabetes retinopathy. CDSP was identified by following the Michigan Neuropathy Screening Instrument and the Michigan Diabetes Neuropathy Score. HF was determined by hospitalization, cause-of-death records, clinic exams, and/or self-reports of physician diagnosis. We applied Cox PH models to quantify the association between the number of existing microvascular diseases and risk of subsequent HF over 25 years follow-up controlling for diabetes duration (or age), sex, HbA1c, and CAD comorbidity. Mean baseline age and T1D duration were 27 years and 19 years. The 25-year cumulative incidence of HF was 6.6% (43/655). Over half didn’t have any microvascular disease at baseline; 19.7%, 16.7% and 10.8% had 1, 2 and 3 microvascular diseases, respectively. In participants with 1, 2, and 3 microvascular diseases, the adjusted HR (95%CI) of any clinically defined HF was 3.1 (1.3, 7.6), 2.5 (0.9, 6.9), and 4.0 (1.3, 11.9), compared with those without any microvascular disease. The HR (95%CI) of hospitalization or death for HF was 2.0 (0.6, 7.3), 2.2 (0.6, 8.7), and 4.1 (1.0, 16.4). As microvascular disease burden increases so does the risk of HF, independently of diabetes duration, sex, HbA1c, and CAD among adults with long-duration childhood-onset T1D. Disclosure J. Guo: None. T. Costacou: None. R. G. Miller: None. T. J. Orchard: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK034818)

Change in global longitudinal strain following acute coronary syndrome and subsequent risk of heart failure.

Global Longitudinal Strain (GLS) is a well-established predictor of heart failure (HF) following acute coronary syndrome (ACS). We aim to investigate the prognostic value of GLS obtained at a follow-up consultation, as well as the change in GLS for long-term risk of incident HF. A total of 235 ACS patients had an echocardiogram performed immediately after percutaneous coronary intervention (PCI) and a follow-up echocardiogram (FUE) median 215 (IQR: 71; 878) days after the first echocardiogram. Endpoint was incident HF. Follow-up time after FUE was median 4.8 (IQR: 3.7; 5.6) years. Patients diagnosed with HF before FUE were excluded. Mean age was 63 ± 11years and 77% were male. Baseline GLS was on average 12.7 ± 3.9%, FUE GLS was on average 13.5 ± 3.9% and mean improvement in GLS was 0.73 ± 3.68% between the 2 echocardiograms. A total of 57 (24%) patients suffered incident HF following the FUE. FUE GLS provided significantly higher prognostic information for risk of incident HF than ∆GLS when assessed by the C-statistics (C-statistics: 0.71 vs. 0.61, P = 0.021). Furthermore, after multivariable adjustments only FUE GLS [HR = 1.15, 95% CI (1.02; 1.29), P = 0.018, per 1% decrease] remained an independent predictor of incident HF. In patients with ACS, who do not develop HF before FUE, FUE GLS was an independent predictor of long-term risk of incident HF while ∆GLS was not.

Abstract P007: Ankle-brachial Index And Cardiovascular Outcomes In Older Adults: The Atherosclerosis Risk In Communities Study

Introduction: The ankle-brachial index (ABI) is a representative diagnostic indicator of peripheral artery disease (PAD) and recognized as a risk enhancer in the ACC/AHA guidelines for primary prevention of atherosclerotic cardiovascular disease (ASCVD). However, our understanding of the association between ABI and cardiovascular (CVD) risk in older adults is limited. Additionally, the prognostic value of ABI among individuals with prior ASCVD is not well understood. Hypothesis: In a contemporary cohort of older adults, low ABI is independently associated with higher risk of CVD events, regardless of prevalent ASCVD at baseline (coronary heart disease [CHD], stroke, and/or symptomatic PAD). Methods: At ARIC Visit 5 (2011-2013), we studied 5,005 participants (4,160 without prior ASCVD [median age 74 years, 38% male], and 843 with ASCVD [median age 76 years, 65% male]). We quantified the association between ABI categories and subsequent risk of heart failure (HF) and composite CHD/stroke using multivariable Cox proportional hazards models. Results: Over a median follow-up of 5.5 years, we observed 400 CHD/stroke and 338 HF cases (242 CHD/stroke and 199 HF cases in those without prior ASCVD). After adjustment for CVD risk factors, in those without ASCVD history, ABI ≤0.9 was associated with a higher risk of both CHD/stroke and HF ( Table ). In those with a history of ASCVD, low ABI was not significantly associated with CHD/stroke, but was associated with HF (hazard ratio 7.1, 95% CI: 2.5-20.5); ABI categories of 0.9-1.1 and &gt;1.3 were also significantly associated with HF. Addition of ABI to traditional risk factors improved prediction of CHD/stroke risk in those without prior ASCVD and prediction of HF, regardless of baseline ASCVD ( Table ). Conclusions: Low ABI (≤0.9) was associated with incident CHD/stroke in those without prior ASCVD and HF regardless of baseline ASCVD status. These results support ABI as a risk enhancer for guiding primary prevention of ASCVD and suggest its potential value in HF risk assessment for older adults.

Apabetalone and hospitalization for heart failure in patients following an acute coronary syndrome: a prespecified analysis of the BETonMACE study

BackgroundPatients with diabetes and acute coronary syndrome (ACS) are at high risk for subsequent heart failure. Apabetalone is a selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. Preclinical data suggest that apabetalone exerts favorable effects on pathways related to myocardial structure and function and therefore could impact subsequent heart failure events. The effect of apabetalone on heart failure events after an ACS is not currently known.MethodsThe phase 3 BETonMACE trial was a double-blind, randomized comparison of apabetalone versus placebo on the incidence of major adverse cardiovascular events (MACE) in 2425 patients with a recent ACS and diabetes. This prespecified secondary analysis investigated the impact of apabetalone on hospitalization for congestive heart failure, not previously studied.ResultsPatients (age 62 years, 74.4% males, 90% high-intensity statin use, LDL-C 70.3 mg/dL, HDL-C 33.3 mg/dL and HbA1c 7.3%) were followed for an average 26 months. Apabetalone treated patients experienced the nominal finding of a lower rate of first hospitalization for heart failure (2.4% vs. 4.0%, HR 0.59 [95%CI 0.38–0.94], P = 0.03), total number of hospitalizations for heart failure (35 vs. 70, HR 0.47 [95%CI 0.27–0.83], P = 0.01) and the combination of cardiovascular death or hospitalization for heart failure (5.7% vs. 7.8%, HR 0.72 [95%CI 0.53–0.98], P = 0.04).ConclusionApabetalone treatment was associated with fewer hospitalizations for heart failure in patients with type 2 diabetes and recent ACS. Future studies are warranted to define the potential for BET inhibition with apabetalone to prevent heart failure in patients with diabetes and ACS.

Human pluripotent stem cell-derived cardiomyocytes as a target platform for paracrine protection by cardiac mesenchymal stromal cells

Ischemic heart disease remains the foremost cause of death globally, with survivors at risk for subsequent heart failure. Paradoxically, cell therapies to offset cardiomyocyte loss after ischemic injury improve long-term cardiac function despite a lack of durable engraftment. An evolving consensus, inferred preponderantly from non-human models, is that transplanted cells benefit the heart via early paracrine signals. Here, we tested the impact of paracrine signals on human cardiomyocytes, using human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) as the target of mouse and human cardiac mesenchymal stromal cells (cMSC) with progenitor-like features. In co-culture and conditioned medium studies, cMSCs markedly inhibited human cardiomyocyte death. Little or no protection was conferred by mouse tail tip or human skin fibroblasts. Consistent with the results of transcriptomic profiling, functional analyses showed that the cMSC secretome suppressed apoptosis and preserved cardiac mitochondrial transmembrane potential. Protection was independent of exosomes under the conditions tested. In mice, injecting cMSC-conditioned media into the infarct border zone reduced apoptotic cardiomyocytes > 70% locally. Thus, hPSC-CMs provide an auspicious, relevant human platform to investigate extracellular signals for cardiac muscle survival, substantiating human cardioprotection by cMSCs, and suggesting the cMSC secretome or its components as potential cell-free therapeutic products.

Stopping renin-angiotensin system blockers after acute kidney injury and risk of adverse outcomes: parallel population-based cohort studies in English and Swedish routine care

BackgroundThe safety of restarting angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB) after acute kidney injury (AKI) is unclear. There is concern that previous users do not restart ACEI/ARB despite ongoing indications. We sought to determine the risk of adverse events after an episode of AKI, comparing prior ACEI/ARB users who stop treatment to those who continue.MethodsWe conducted two parallel cohort studies in English and Swedish primary and secondary care, 2006–2016. We used multivariable Cox regression to estimate hazard ratios (HR) for hospital admission with heart failure (primary analysis), AKI, stroke, or death within 2 years after hospital discharge following a first AKI episode. We compared risks of admission between people who stopped ACEI/ARB treatment to those who were prescribed ACEI/ARB within 30 days of AKI discharge. We undertook sensitivity analyses, including propensity score-matched samples, to explore the robustness of our results.ResultsIn England, we included 7303 people with AKI hospitalisation following recent ACEI/ARB therapy for the primary analysis. Four thousand three (55%) were classified as stopping ACEI/ARB based on no prescription within 30 days of discharge. In Sweden, we included 1790 people, of whom 1235 (69%) stopped treatment. In England, no differences were seen in subsequent risk of heart failure (HR 1.10; 95% confidence intervals (CI) 0.93–1.30), AKI (HR 0.90; 95% CI 0.77–1.05), or stroke (HR 0.99; 95% CI 0.71–1.38), but there was an increased risk of death (HR 1.27; 95% CI 1.15–1.41) in those who stopped ACEI/ARB compared to those who continued. Results were similar in Sweden: no differences were seen in risk of heart failure (HR 0.91; 95% CI 0.73–1.13) or AKI (HR 0.81; 95% CI 0.54–1.21). However, no increased risk of death was seen (HR 0.94; 95% CI 0.78–1.13) and stroke was less common in people who stopped ACEI/ARB (HR 0.56; 95% CI 0.34–0.93). Results were similar across all sensitivity analyses.ConclusionsPrevious ACEI/ARB users who continued treatment after an episode of AKI did not have an increased risk of heart failure or subsequent AKI compared to those who stopped the drugs.

Utility of 6-Minute Walk Test to Predict Response to Cardiac Resynchronization Therapy in Patients With Mild Heart Failure

Clinical studies of heart failure (HF) generally utilize the 6-minute walk test (6MWT) for functional capacity (FC) assessment. However, data on the impact of cardiac resynchronization therapy (CRT) on 6MWT and its role to predict long-term outcomes in mild HF patients with CRT are lacking. We studied 1,381 subjects with mild HF enrolled in Multicenter Automatic Defibrillator Implantation Trial - Cardiac Resynchronization Therapy with 6MWT data at baseline and 1 year. We assessed the effects of CRT-D on percent change in 6MWT at 1 year by left bundle branch block (LBBB) status, identified independent predictors of 6MWT at 1 year, and evaluated the association between changes in 6MWT and risk for HF or death. Treatment with CRT-D versus implantable cardiac defibrillator (ICD) was not associated with a significant improvement in 6MWT at 1-year in LBBB subjects (2.2 % vs 0.0%, p = 0.428, but it was associated with a deterioration in 6MWT in non-LBBB subjects (4.1% vs 0.0%, p = 0.308). Multivariate analysis showed that each 5% reduction in 6MWT was independently associated with a corresponding 3% increase in the risk of subsequent HF or death (p = 0.014). In conclusion, our findings suggest that 6MWT has limited utility to identify CRT response in mild HF subjects with LBBB. However, 6MWT showed a signal toward deterioration in mild HF subjects with non-LBBB, and this was predictive of subsequent increased risk of HF or death.

Association of Long-term Change and Variability in Glycemia With Risk of Incident Heart Failure Among Patients With Type 2 Diabetes: A Secondary Analysis of the ACCORD Trial.

To evaluate the associations between long-term change and variability in glycemia with risk of heart failure (HF) among patients with type 2 diabetes mellitus (T2DM). Among participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, variability in HbA1c was assessed from stabilization of HbA1c following enrollment (8 months) to 3 years of follow-up as follows: average successive variability (ASV) (average absolute difference between successive values), coefficient of variation (SD/mean), and SD. Participants with HF at baseline or within 3 years of enrollment were excluded. Adjusted Cox models were used to evaluate the association of percent change (from baseline to 3 years of follow-up) and variability in HbA1c over the first 3 years of enrollment and subsequent risk of HF. The study included 8,576 patients. Over a median follow-up of 6.4 years from the end of variability measurements at year 3, 388 patients had an incident HF hospitalization. Substantial changes in HbA1c were significantly associated with higher risk of HF (hazard ratio [HR] for ≥10% decrease 1.32 [95% CI 1.08-1.75] and for ≥10% increase 1.55 [1.19-2.04]; reference <10% change in HbA1c). Greater long-term variability in HbA1c was significantly associated with higher risk of HF (HR per 1 SD of ASV 1.34 [95% CI 1.17-1.54]) independent of baseline risk factors and interval changes in cardiometabolic parameters. Consistent patterns of association were observed with use of alternative measures of glycemic variability. Substantial long-term changes and variability in HbA1c were independently associated with risk of HF among patients with T2DM.