Predictor Of Heart Failure Hospitalization Research Articles

Dynamic risk stratification of worsening heart failure using a deep learning-enabled implanted ambulatory single-lead electrocardiogram.

Implantable loop recorders (ILRs) provide continuous single-lead ambulatory electrocardiogram (aECG) monitoring. Whether these aECGs could be used to identify worsening heart failure (HF) is unknown. We linked ILR aECG from Medtronic device database to the left ventricular ejection fraction (LVEF) measurements in Optum® de-identified electronic health record dataset. We trained an artificial intelligence (AI) algorithm [aECG-convolutional neural network (CNN)] on a dataset of 35 741 aECGs from 2247 patients to identify LVEF ≤ 40% and assessed its performance using the area under the receiver operating characteristic curve. Ambulatory electrocardiogram-CNN was then used to identify patients with increasing risk of HF hospitalization in a real-world cohort of 909 patients with prior HF diagnosis. This dataset provided 12 467 follow-up monthly evaluations, with 201 HF hospitalizations. For every month, time-series features from these predictions were used to categorize patients into high- and low-risk groups and predict HF hospitalization in the next month. The risk of HF hospitalization in the next 30 days was significantly higher in the cohort that aECG-CNN identified as high risk [hazard ratio (HR) 1.89; 95% confidence interval (CI) 1.28-2.79; P = 0.001] compared with low risk, even after adjusting patient demographics (HR 1.88; 95% CI 1.27-2.79 P = 0.002). An AI algorithm trained to detect LVEF ≤40% using ILR aECGs can also readily identify patients at increased risk of HF hospitalizations by monitoring changes in the probability of HF over 30 days.

Association between sodium-to-potassium ratio in spot urine and hospitalization due to heart failure in high-risk Japanese patients

BackgroundIn Japanese cardiovascular (CV) high-risk patients, the ESPRIT (Evaluation of Sodium Intake for the Prediction of Cardiovascular Events in Japanese High-risk Patients) study showed that high sodium excretion (≥4.0 g/day) was associated with a composite CV events of heart failure (HF) hospitalization, acute coronary syndrome, cerebrovascular events, and CV deaths. In this context, the sodium-to-creatinine (Na/Cr) ratio in spot urine was found to be significantly associated with HF hospitalizations. Since a stable potassium balance plays a particularly relevant role for CV patients, this post-hoc study was designed to investigate the extent to which consideration of the sodium-to-potassium (Na/K) ratio represents a better predictor of HF hospitalizations in the ESPRIT study population. MethodsThis is a post-hoc analysis of a previously reported ESPRIT study (n = 520, 60 HF hospitalizations). ResultsReceiver operating curve analysis yielded optimal Na/K ratio cut-off value of 2.9 for detecting HF hospitalization. Kaplan–Meier curve showed that high Na/K ratio in spot urine was associated with increased HF hospitalization (p < 0.001). Cox proportional hazards model analysis revealed that high Na/K ratio was associated with HF hospitalization with a hazard ratio of 2.97 (confidence interval: 1.67–5.61). An association between high Na/K ratio and HF hospitalization remained after adjustments for Na/Cr ratio in spot urine or the use of diuretics. ConclusionThe Na/K ratio in spot urine is associated with HF hospitalization in high-risk Japanese patients.

Impact of C-reactive protein levels and role of anakinra in patients with ST-elevation myocardial infarction

BackgroundInterleukin-1 blockade with anakinra reduces C-reactive protein (CRP) levels and prevents heart failure (HF) events after ST-segment myocardial infarction (STEMI). The effectiveness of anakinra according to the degree of systemic inflammation in STEMI has not been addressed. MethodsWe analyzed 139 patients from three Virginia Commonwealth University Anakinra Response Trial randomized clinical trials to assess whether CRP levels predicted HF hospitalization or death in patients with STEMI, and if CRP levels influenced the effects of treatment with anakinra. ResultsCRP cut-off levels for prediction of the composite of death or HF hospitalization for CRP at admission, 3 and 14 days were, respectively 6.45 mg/L (100% of sensitivity and 66.1% specificity), 26 mg/L (100% of sensitivity and 78% specificity) and 9.56 mg/L (100% of sensitivity and 80% specificity). More patients with elevated CRP levels died or had a HF hospitalization (5/47 [11%] vs 0/82 [0%], p = 0.004 for CRP at admission; 5/32 [15.6%] vs 0/92 [0%], p < 0.001 for day 3 and 5/26 [19%] vs 0/89 [0%], p < 0.001 for day 14). A greater number of patients treated with anakinra had low CRP levels at 3 and 14 days compared to placebo (Odds Ratio 0.11 [95% IC 0.04–0.28], p < 0.0001 and OR 0.35 [95% CI 0.14–0.86], p = 0.02, respectively). Anakinra significantly prevented death or HF hospitalization in patients with high inflammatory burden (p = 0.04 for admission, p = 0.24 for day 3, and p = 0.05 for day 14). ConclusionPatients with elevated CRP had higher incidence of HF hospitalization or death. Anakinra reduced the number of patients with elevated CRP levels and prevented death or HF hospitalization in patients with elevated CRP levels.

Sex Differences in Clinical Outcomes after Aortic Valve Intervention for Isolated Severe Aortic Stenosis.

There are known pathophysiologic and clinical differences according to sex in patients with aortic stenosis (AS). To evaluate if these differences persist after valve replacement, we conducted an observational study including 451 patients with symptomatic AS who survived aortic valve intervention (AVI) in two centers. Clinical data and mortality were evaluated at a mean follow-up of 5 years. 56% of patients were women. At baseline, women were older (80.6 vs. 78 years, p = 0.013), presented higher mean gradient (48 vs. 45 mmHg, p = 0.023), lower aortic valve area (0.70 vs. 0.74 cm2, p = 0.002) and higher systolic pulmonary artery pressure (36 vs. 33 mmHg, p = 0.016). They underwent percutaneous aortic valve replacement more frequently than men (47 vs. 35.9%, p = 0.017). At 5 years follow-up, women required more admissions due to heart failure (23 vs. 9%, p = 0.046) but they did not present higher cardiovascular nor overall mortality (27.7% vs. 29.8%, p = 0.741; 11.1 vs. 10.1%, p = 0.619, respectively). Female sex was an independent predictor of heart failure hospitalization at follow-up (HR 95% 1.16-4.22, p = 0.016). Women undergo AVI at a more advanced stage than men, resulting in a higher frequency of readmissions due to heart failure during the follow-up period, but not in higher mortality.

Role of fragmented QRS complex in the prognosis of patients undergoing cardiac resynchronization therapy. A new red flag to look for?

Abstract Introduction Cardiac resynchronization therapy (CRT) has demonstrated to reduce mortality and hospitalization for heart failure in selected patients with heart failure with reduced ejection fraction (HFrEF). However, there is a significant percentage of readmissions for heart failure (HF) after implantation. In the recent years, several biomarkers and electrocardiographic findings possibly related with prognosis in this group of patients have been identified. Fragmentation of QRS complex (fQRS) has been related with worse prognosis in various cardiac diseases, but the evidence in patients undergoing CRT is limited. Purpose The objective of this study is to evaluate if the presence of pre-implantation fragmented QRS complex has a prognostic role in patients undergoing cardiac resynchronization therapy in terms of hospitalization for HF. Methods Consecutive patients undergoing CRT were prospectively included from October 2009 to December 2022. Demographic clinical, electrocardiographic and echocardiographic variables were recorded. Prospective follow-up variables were collected from electronic clinical records and telephone interview. Fragmentation of the QRS complex was defined by the presence of different RSR′ patterns including an additional R-wave (R′), notching of the R-wave and S-wave or the presence of more than 1R′ in two contiguous leads corresponding to a main coronary artery territory. Results 244 patients were included. Mean age at the implantation of the device was 71.8 years (standard deviation, SD ±9.8 years), 79.5% were male and 40.2% were diabetic. Mean LVEF was 24.9% (SD ±8.9) and the aetiology was non-ischaemic in 50.8% of the patients and ischaemic in 49.2%. 40.2% had prior history of acute myocardial infarction. Pre-implantation fragmented QRS complex was found in 58.6% of the patients and mostly in inferior leads of the surface ECG. Mean QRS duration was 157.9ms and 82.0% had left-bundle branch block morphology. CRT with defibrillator implantation was performed in 71.4% of the patients. The median follow-up time was 27.4 month. After device implantation, mean LVEF was 33.2% and 76.6% presented NYHA class I-II. During this period, 28.7% of the patients died. Additionally, 29.1% of the patients presented at least one hospitalization for heart failure (HF), 22.5% with fQRS and 6.6% without fQRS. A multivariate survival study using Cox regression showed that the presence of pre-implantation fQRS was an independent predictor of HF hospitalization events (HR 2.24; 95% CI 1.20-4.18). Figure 1 presents Kaplan-Meier curves for hospitalization for HF. Conclusions According to our results, pre-implantation fQRS is a strong independent predictor of hospitalization for HF after CRT implantation. Thus, patients with fQRS could benefit from a more rigorous follow-up as they present higher risk of decompensation. Further research is needed to confirm our findings.Figure 1.Kaplan-Meier curves

Abstract 17139: Angiopoietin 2 Independently Predicts Heart Failure Hospitalization and is Beneficially Modified by GLP1RA: Results From the EXSCEL Trial

Background: Higher plasma concentrations of angiopoietin 2 (ANGPT2) are associated with higher risk for hospitalization for heart failure (HF) and death in univariate analyses. However, the independent association of this ANGPT2 after adjustment for clinical factors or clinically available biomarkers is not known. Methods: High throughput proteomic profiling was performed using the SomaLogic SomaScan platform in 5473 patients with type 2 diabetes enrolled in the EXSCEL clinical trial of the GLP1RA exenatide vs. placebo who had available biospecimens at baseline. The association between ANGPT2 with time-to-HF hospitalization, MACE, and death was assessed using univariable and multivariable Cox modeling, with adjustment for age, sex, HbA1c, NT-proBNP, hs-TnT, left ventricular ejection fraction, HF etiology and study treatment. These analyses were also performed in the subset of participants living with obesity (BMI &gt;30 kg/m 2 ), and those with CKD (CrCl &lt;60ml/min). Results: In 5473 EXSCEL trial participants included in this biomarker sub-study, 215 (3.9%) experienced a hospitalization for heart failure, 813 (14.9%) a MACE event and 528 (9.7%) died during a median follow-up of 3.2 years. Relative ANGPT2 concentration was significantly associated with HF hospitalization (aHR 1.70 [95% CI 1.39 to 2.08]), MACE (1.20 [1.07 to 1.35]), and death (aHR 1.21 [1.05 to 1.39]) in univariable and multivariable analyses, including after adjustment for NT-proBNP and TnT (Figure). Exenatide use resulted in significant changes from baseline in ANGPT2 concentrations (p interaction&lt;0.001) (Figure). Conclusion: ANGPT2 is predictive of hospitalization for HF, MACE, and death independent of clinical factors including traditional biomarkers of NT-proBNP and TnT. ANGPT2 was beneficially modified by exenatide, a GLP1RA, suggesting a potential role for this biomarker in optimizing HF therapy.

Development and validation of a multivariate model for predicting heart failure hospitalization and mortality in patients receiving maintenance hemodialysis

Background Heart failure (HF) in patients undergoing maintenance hemodialysis (MHD) increases their hospitalization rates, mortality, and economic burden significantly. We aimed to develop and validate a predictive model utilizing contemporary deep phenotyping for individual risk assessment of all-cause mortality or HF hospitalization in patients on MHD. Materials and Methods A retrospective review was conducted from January 2017 to October 2022, including 348 patients receiving MHD from four centers. The variables were adjusted by Cox regression analysis, and the clinical prediction model was constructed and verified. Results The median follow-up durations were 14 months (interquartile range [IQR] 9–21) for the modeling set and 14 months (9–20) for the validation set. The composite outcome occurred in 72 (29.63%) of 243 patients in the modeling set and 39 (37.14%) of 105 patients in the validation set. The model predictors included age, albumin, history of cerebral hemorrhage, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers/“sacubitril/valsartan”, left ventricular ejection fraction, urea reduction ratio, N-terminal prohormone of brain natriuretic peptide, and right atrial size. The C-index was 0.834 (95% CI 0.784–0.883) for the modeling set and 0.853 (0.798, 0.908) for the validation set. The model exhibited excellent calibration across the complete risk profile, and the decision curve analysis (DCA) suggested its ability to maximize patient benefits. Conclusion The developed prediction model offered an accurate and personalized assessment of HF hospitalization risk and all-cause mortality in patients with MHD. It can be employed to identify high-risk patients and guide treatment and follow-up.

Significance of effective cardiac resynchronization therapy pacing for clinical responses: An analysis based on the effective cardiac resynchronization therapy algorithm

High percent ventricular pacing maximizes cardiac resynchronization therapy (CRT) response. An effective CRT algorithm classifies each left ventricular (LV) pace as effective or ineffective on the basis of the detection of QS or QS-r morphology on the electrogram; however, the relationship between percent effective CRT pacing (%e-CRT) and responses is unclear. We aimed to clarify the association between %e-CRT and clinical outcomes. Of the 136 consecutive CRT patients, 49 using the adaptive and effective CRT algorithm with percent ventricular pacing > 90% were evaluated. The primary and secondary outcomes were heart failure (HF) hospitalization and prevalence of CRT responders, defined as patients with an improvement in LV ejection fraction of ≥10% or a reduction in LV end-systolic volume of ≥15% after CRT device implantation, respectively. We divided the patients into the effective group (n = 25) and the less effective group (n = 24) by the median value of %e-CRT (97.4%). During the median follow-up period of 507 days (interquartile range 335-730 days), the effective group had a significantly lower risk of HF hospitalization than did the less effective group as revealed by Kaplan-Meier analysis (log-rank, P = .016). Univariate analysis revealed %e-CRT ≥ 97.4% (hazard ratio 0.12; 95% confidence interval 0.01-0.95; P = .045) as a predictor of HF hospitalization. The effective group had a higher prevalence of CRT responders than did the less effective group (23 [92%] vs 9 [38%]; P < .001). Univariate analysis revealed that %e-CRT ≥ 97.4% (odds ratio 19.20; 95% confidence interval 3.63-101.00; P < .001) was a predictor of CRT response. High %e-CRT is associated with high CRT responder prevalence and low HF hospitalization risk.

Prognostic value of left ventricular global constructive work in patients with cardiac amyloidosis.

The aim of the present study was to evaluate the role of ejection fraction (EF), left ventricular (LV) global longitudinal strain (LVGLS) and global constructive work (GCW) as prognostic variables in patients with cardiac amyloidosis (CA). CA patients were retrospectively identified between 2015 and 2021 at a tertiary care hospital. Comprehensive clinical, biochemical, and imaging evaluation including two-dimensional (2D) echocardiography with myocardial work (MW) analysis was performed. A clinical combined endpoint was defined as all-cause mortality and heart failure readmission. 70 patients were followed for 16 (7-37) months and 37 (52.9%) reached the combined endpoint. Patient with versus without clinical events had a significantly lower LVEF (40.71% vs. 48.01%, p = 0.039), LVGLS (-9.26 vs. -11.32, p = 0.034) and GCW (1034.47mmHg% vs. 1424.86mmHg%, p = 0.011). Multivariable analysis showed that LVEF ( odds ratio (OR): 0.904; 95% confidence interval (CI): 0.839-0.973, p = 0.007), LVGLS ( OR: 0.620; 95% CI: 0.415-0.926, p = 0.020) and GCW ( OR: 0.995; 95% CI: 0.990-0.999, p = 0.016) were significant predictors of outcome, but the model including GCW had the best discriminative ability to predict the combined endpoint (C-index = 0.888). A GCW less than 1443mmHg% was able to predict the clinical endpoint with a sensitivity of 94% and a specificity of 64% (Area under the curve (AUC): 0.771 (95% CI: 0.581-0.961; p = 0.005)). In CA patients, GCW may be of additional prognostic value to LVEF and GLS in predicting heart failure hospitalization and all-cause mortality.

Abstract 10619: Pericoronary Fat Attenuation Index on Coronary Computed Tomography Angiography Predicts Hospitalization for Heart Failure in Patients With Suspected Coronary Artery Disease

Introduction: Chronic inflammation is focused as a cause of heart failure (HF). Pericoronary fat attenuation index (FAI) assessed on coronary CT angiography (CCTA), a maker of vascular inflammation, is reported to associate with risk of cardiac mortality. However, relationship between pericoronary FAI and development of HF has not been fully elucidated. Hypothesis: Pericoronary FAI predicts hospitalization for HF. Methods: A total of 1196 consecutive patients who underwent clinically indicated CCTA and transthoracic echocardiography for suspected CAD were enrolled. Patients with a history of CAD, hospitalization for HF, left ventricular ejection fraction (LVEF) &lt;40%, and hemodialysis were excluded. We assessed pericoronary FAI of proximal 40 mm segments for three major coronary arteries. Association between pericoronary FAI and incidence of hospitalization for HF was analyzed by Cox regression analysis. Results: During a median follow-up of 4.3 years, 29 hospitalizations for HF occurred. Pericoronary FAI of three major coronary arteries were significantly corelated each other. Pericoronary FAI of left anterior descending artery (LAD) was higher in patients with hospitalization for HF than in patients without hospitalization for HF (-61.4 ± 7.8 HU and -67.4 ± 7.2 HU, p&lt;0.001). Optimal cut-off value of pericoronary FAI of LAD for predicting hospitalization for HF was -64.8 HU. Pericoronary FAI of LAD (&gt;-64.8 HU) was significantly associated with hospitalization for HF after adjusted by age and gender (HR 4.77, 95%CI 2.10-10.81). In addition, these analyses were performed in 885 patients without significant stenosis (16 hospitalizations for HF occurred). In this cohort, pericoronary FAI of LAD in patients with hospitalization for HF was higher than that in patients without hospitalization for HF (-60.8 ± 7.2 HU and -67.3 ± 7.2 HU, p&lt;0.001), and association of FAI of LAD with hospitalization for HF remained significant. Pericoronary FAI of LAD was significantly correlated with left atrial volume index, left ventricular mass index, LVEF and E/e’, respectively (p&lt;0.001). Conclusions: Pericoronary FAI of LAD on CCTA may be a useful clinical predictor of hospitalization for HF in patients suspected CAD without history of CAD and hospitalization for HF.

An electrocardiography score predicts heart failure hospitalization or death beyond that of cardiovascular magnetic resonance imaging

The electrocardiogram (ECG) and cardiovascular magnetic resonance imaging (CMR) provide powerful prognostic information. The aim was to determine their relative prognostic value. Patients (n = 783) undergoing CMR and 12-lead ECG with a QRS duration < 120 ms were included. Prognosis scores for one-year event-free survival from hospitalization for heart failure or death were derived using continuous ECG or CMR measures, and multivariable logistic regression, and compared. Patients (median [interquartile range] age 55 [43–64] years, 44% female) had 155 events during 5.7 [4.4–6.6] years. The ECG prognosis score included (1) frontal plane QRS-T angle, and (2) heart rate corrected QT duration (QTc) (log-rank 55). The CMR prognosis score included (1) global longitudinal strain, and (2) extracellular volume fraction (log-rank 85). The combination of positive scores for both ECG and CMR yielded the highest prognostic value (log-rank 105). Multivariable analysis showed an association with outcomes for both the ECG prognosis score (log-rank 8.4, hazard ratio [95% confidence interval] 1.29 [1.09–1.54]) and the CMR prognosis score (log-rank 47, hazard ratio 1.90 [1.58–2.28]). An ECG prognosis score predicted outcomes independently of CMR. Combining the results of ECG and CMR using both prognosis scores improved the overall prognostic performance.

IncidenCe and predictOrs of heaRt fAiLure after acute coronarY Syndrome: The CORALYS registry

BackgroundPrevious studies investigating predictors of Heart Failure (HF) after acute coronary syndrome (ACS) were mostly conducted during fibrinolytic era or restricted to baseline characteristics and diagnoses prior to admission. We assessed the incidence and predictors of HF hospitalizations among patients treated with percutaneous coronary intervention (PCI) for ACS. Methods and resultsCORALYS is a multicenter, retrospective, observational registry including consecutive patients treated with PCI for ACS. Patients with known history of HF or reduced left ventricular ejection fraction (LVEF) were excluded. Incidence of HF hospitalizations was the primary endpoint. The composite of HF hospitalization or cardiovascular death, and cardiovascular and all-cause death were the secondary endpoints. Predictors of HF hospitalizations and the impact of HF hospitalization on cardiovascular and all-cause death were assessed by means of multivariable Cox proportional hazards model.14699 patients were included. After 2.9 ± 1.8 years, the incidence of HF hospitalizations was 12.7%. Multivariable analysis identified age, diabetes, chronic kidney disease, previous myocardial infarction, atrial fibrillation, pulmonary disease, GRACE risk-score ≥ 141, peripheral artery disease, cardiogenic shock at admission and LVEF ≤40% as independently associated with HF hospitalizations. Complete revascularization was associated with a lower risk of HF (HR 0.46,95%CI 0.39–0.55). HF hospitalization was associated with higher risk of CV and all-cause death (HR 1.89,95%CI 1.5–2.39 and HR 1.85,95%CI 1.6–2.14, respectively). ConclusionsIncidence of HF hospitalizations among patients treated with PCI for ACS is not negligible and is associated with detrimental impact on patients' prognosis. Several variables may help to assess the risk of HF after ACS.

Serum microRNAs are key predictors of long-term heart failure and cardiovascular death after myocardial infarction.

Patients with acute myocardial infarction (MI) are at high risk of upcoming events, in particular heart failure (HF), but reliable stratification methods are lacking. Our goal was to evaluate the potential role of circulating miRNAs as prognostic biomarkers in patients presenting with MI. We conducted a prospective study among 311 consecutive patients hospitalized with MI (65% ST-segment elevation MI & median age of 55years) with long-term follow-up. An initial screening was conducted to select candidate miRNAs, with subsequent study of 14 candidate miRNAs. The primary outcome was the composite of hospital admission for HF or cardiovascular death. During a mean follow-up of 2.1years miR-21-5p, miR-23a-3p, miR27b-3p, miR-122-5p, miR210-3p, and miR-221-3p reliably predicted the primary outcome. Multivariate Cox regression analyses highlighted that miR-210-3p [hazard ratio (HR) 2.65 per 1 SD increase, P<0.001], miR-23a-3p (HR 2.11 per 1 SD increase, P<0.001), and miR-221-3p (HR 2.03 per 1 SD increase, P<0.001) were able to accurately predict the primary outcome, as well as cardiovascular death, HF hospitalizations, and long-term New York Heart Association (NYHA) functional class. These three miRNAs clearly improved the performance of multivariate clinical models: ΔC-statistic=0.10 [95% confidence interval (CI), 0.03-0.17], continuous net reclassification index=34.8% (95%CI, 5.8-57.4%), and integrated discrimination improvement (P<0.001). This is the largest study evaluating the prognostic value of circulating miRNAs for HF-related events among patients with MI. We show that several miRNAs predict HF hospitalizations, cardiovascular mortality, and poor long-term NYHA status and improve current risk prediction methods.

P363 HIGH–SENSITIVITY TROPONINS FOR OUTCOME PREDICTION IN THE GENERAL POPULATION: A SYSTEMATIC REVIEW AND META–ANALYSIS

Abstract Background High–sensitivity (hs) assays allow to measure cardiac troponin T and I (cTnT/I) even in healthy individuals. The higher hs–cTn values, the higher the ongoing cardiomyocyte damage, and then reasonably the risk of developing symptomatic cardiac disease. Methods We retrieved all studies evaluating the prognostic value of hs–cTnT or I in the general population. We calculated pooled hazard ratio (HR) values for all–cause and cardiovascular death, cardiovascular events and heart failure (HF) hospitalization. Results We included 24 studies for a total of 203,202 subjects; 11 studies assessed hs–cTnT and 14 hs–cTnI. One standard deviation (SD) increase in baseline hs–cTn was associated with a 23% higher risk of all–cause death (HR 1.226, 95% CI 1.083–1.388, p &amp;lt; 0.001, I2=88.5%); all these studies measured hs–cTnI. In an exploratory analysis on 3 studies with 25,760 subjects, hs–cTn predicted cardiovascular death (HR 1.822, 95% CI 1.241–2.674, p = 0.002, I2=87.2%). After synthesizing 9 studies with 58,565 subjects, hs–cTn predicted cardiovascular events (HR 1.328, 95% CI 1.167–1.513, p &amp;lt; 0.001, I2=93.8%). Both hs–cTnT (HR 1.627, 95% CI 1.145–2.311, p &amp;lt; 0.001) and hs–cTnI (HR 1.260, 95% CI 1.115–1.423, p &amp;lt; 0.001; p for interaction &amp;lt;0.001). Furthermore, in 10 studies with 61,467 subjects, hs–cTn predicted HF hospitalization (HR 1.493, 95% CI 1.368–1.630, p &amp;lt; 0.001, I2=76.6%). Both hs–cTnT (HR 1.566, 95% CI 1.303–1.883, p &amp;lt; 0.001) and hs–cTnI (HR 1.467, 95% CI 1.321–1.628, p &amp;lt; 0.001) were associated with HF hospitalization (p for interaction &amp;lt;0.001). Conclusions Hs–cTn values hold strong prognostic value in subjects from the general population, predicting the risk of all–cause and cardiovascular mortality, cardiovascular events, and HF hospitalization.

High-sensitivity troponins for outcome prediction in the general population: a systematic review and meta-analysis

BackgroundHigh-sensitivity (hs) assays allow to measure cardiac troponin T and I (cTnT/I) even in healthy individuals. The higher hs-cTn values, the higher the ongoing cardiomyocyte damage, and then reasonably the risk of developing symptomatic cardiac disease. MethodsWe retrieved all studies evaluating the prognostic value of hs-cTnT or I in the general population. We calculated pooled hazard ratio (HR) values for all-cause and cardiovascular death, cardiovascular events and heart failure (HF) hospitalization. ResultsWe included 24 studies for a total of 203,202 subjects; 11 studies assessed hs-cTnT and 14 hs-cTnI. One standard deviation (SD) increase in baseline hs-cTn was associated with a 23% higher risk of all-cause death (HR 1.226, 95% CI 1.083-1.388, p<0.001, I2=88.5%); all these studies measured hs-cTnI. In an exploratory analysis on 3 studies with 25,760 subjects, hs-cTn predicted cardiovascular death (HR 1.822, 95% CI 1.241-2.674, p=0.002, I2=87.2%). After synthesizing 9 studies with 58,565 subjects, hs-cTn predicted cardiovascular events (HR 1.328, 95% CI 1.167-1.513, p<0.001, I2=93.8%). Both hs-cTnT (HR 1.627, 95% CI 1.145-2.311, p<0.001) and hs-cTnI (HR 1.260, 95% CI 1.115-1.423, p<0.001; p for interaction <0.001). Furthermore, in 10 studies with 61,467 subjects, hs-cTn predicted HF hospitalization (HR 1.493, 95% CI 1.368-1.630, p<0.001, I2=76.6%). Both hs-cTnT (HR 1.566, 95% CI 1.303-1.883, p<0.001) and hs-cTnI (HR 1.467, 95% CI 1.321-1.628, p<0.001) were associated with HF hospitalization (p for interaction <0.001). Conclusionshs-cTn values hold strong prognostic value in subjects from the general population, predicting the risk of all-cause and cardiovascular mortality, cardiovascular events, and HF hospitalization.

419 High-sensitivity troponins for outcome prediction in the general population: a systematic review and meta-analysis

Abstract Aims High-sensitivity (hs) assays allow to measure cardiac troponin T and I (cTnT/I) even in healthy individuals. The higher hs-cTn values, the higher the ongoing cardiomyocyte damage, and then reasonably the risk of developing symptomatic cardiac disease. Methods and results We retrieved all studies evaluating the prognostic value of hs-cTnT or I in the general population. We calculated pooled hazard ratio (HR) values for all-cause and cardiovascular death, cardiovascular events and heart failure (HF) hospitalization. We included 24 studies for a total of 203 202 subjects; 11 studies assessed hs-cTnT and 14 hs-cTnI. One standard deviation (SD) increase in baseline hs-cTn was associated with a 23% higher risk of all-cause death (HR: 1.226, 95% CI: 1.083–1.388, P &amp;lt; 0.001, I2 = 88.5%); all these studies dosed hs-cTnI. In an exploratory analysis on three studies with 25 760 subjects, hs-cTn predicted cardiovascular death (HR: 1.822, 95% CI: 1.241–2.674, P = 0.002, I2 = 87.2%). After synthesizing nine studies with 58 565 subjects, hs-cTn predicted cardiovascular events (HR: 1.328, 95% CI: 1.167–1.513, P &amp;lt; 0.001, I2 = 93.8%). Both hs-cTnT (HR: 1.627, 95% CI: 1.145–2.311, P &amp;lt; 0.001) and hs-cTnI (HR: 1.260, 95% CI: 1.115–1.423, P &amp;lt; 0.001; p for interaction &amp;lt;0.001). Furthermore, in 10 studies with 61 467 subjects, hs-cTn predicted HF hospitalization (HR: 1.493, 95% CI: 1.368–1.630, P &amp;lt; 0.001, I2 = 76.6%). Both hs-cTnT (HR: 1.566, 95% CI: 1.303–1.883, P &amp;lt; 0.001) and hs-cTnI (HR: 1.467, 95% CI: 1.321–1.628, P &amp;lt; 0.001) were associated with HF ho (p for interaction &amp;lt;0.001). Conclusions hs-cTn values hold strong prognostic value in subjects from the general population, predicting the risk of all-cause and cardiovascular mortality, cardiovascular events, and HF hospitalization.

Abstract 13846: Prognostic Value of Echocardiographic Markers of Diastolic Dysfunction for Heart Failure in Overweight and Obese Patients in CAMELLIA-TIMI 61

Background: Recent guidelines have outlined echo markers of diastolic dysfunction (DD); evidence is limited for their prognostic value for hospitalization for heart failure (HHF) in overweight and obese pts. Methods: CAMELLIA-TIMI 61 was a randomized placebo-controlled trial of the weight loss agent lorcaserin in 12,000 pts with BMI ≥27 with or at risk for CV disease (median follow-up, 3.3 yrs). Echo with core lab interpretation was performed on a subset of pts. Established DD parameters were measured, including the ratio of the peak early transmitral diastolic flow velocity over the early diastolic mitral annulus velocity (average E/e’), left atrium volume index (LAVi), and tricuspid regurgitation jet velocity (TRV). These were analyzed continuously, using the standard cutpoints of &gt;14, &gt;34 mL/m 2 , and &gt;2.8 m/s, respectively, and separately to determine the optimal cutpoints. The primary outcome for this analysis was HHF. Results: In 3,972 pts with baseline ejection fraction ≥50%, all 3 variables on a continuous scale predicted increased risk of HHF; using standard cutpoints, only E/e’&gt;14 remained independently associated with HHF after adjustment for the other 2 echo parameters and clinical variables ( Panel A ). In an analysis of optimal cutpoints in these overweight and obese pts, &gt;13 was optimal for E/e’, &gt;2.5 m/s for TRV, and &gt;58 mL/m 2 for LAVi. In a model with all 3 echo parameters, all remained significant predictors of HHF. After incorporation of clinical variables, E/e’ (HR 2.15, 95%CI 1.24-3.72) and LAVi (HR 2.41, 1.33-4.36) remained independent predictors of HHF ( Panel A ). Rates of HHF were 0.6, 3.3, and 10.1% (p-trend&lt;0.0001) in pts with none, one, or both measures of DD ( Panel B ). Conclusions: Several echocardiographic markers of diastolic dysfunction used in current guidelines predict increased risk of HHF events in the understudied obese and overweight population. A higher LAVi (&gt; 58 ml/m 2 ) cutpoint should be considered in these pts to prognosticate risk of HHF.

Abstract 12189: The Ratio of Cyclic Guanosine Monophosphate to Brain Natriuretic Peptide (cGMP/BNP) Stratifies The Risk of Heart Failure Hospitalization in Cardiac Resynchronization Therapy (CRT) Patients

Background: Cardiac Resynchronization Therapy (CRT) is established treatment for patients with heart failure, however, there are various predictors of prognosis. Although CRT responder is reported to have a better prognosis than CRT non-responder, some cases have poor clinical outcomes even among CRT responders. Meanwhile, brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP) are associated with the severity of heart failure. Little is known about the efficacy of prognostic value of BNP and cGMP in CRT patients especially among CRT responders. Methods: Among 246 consecutive CRT patients, we retrospectively analyzed 86 patients whose biomarkers were measured at the time of implantation. The patients were divided into two groups by the median value of cGMP/BNP (0.26). The endpoint was heart failure hospitalization, and the CRT responder was defined as an improvement of end-systolic volume (ESV) ≥ 15% or ejection fraction (EF) ≥ 10% at 6 months after CRT implantation. Results: The patients were 65.4 ± 13.6 years old, 64 (74%) patients were male, 17 (20%) patients were ischemic cardiomyopathy, and 47 (55%) patients were CRT responders. During a median follow-up period of 830 (interquartile range: 482-1246) days, 27 patients (31%) had heart failure hospitalization (high cGMP/BNP group: 8 vs low cGMP/BNP group 19, p = 0.016). Kaplan-Meier analysis revealed the risk of heart failure hospitalization was higher in high cGMP/BNP group than in low group (log-rank p = 0.0025), and the same result was observed even among CRT responders (log-rank p=0.018). cGMP/BNP increased in responders (p = 0.0045) but not in non-responders (p = 0.23) at 6 months after CRT implantation in Wilcoxon signed-rank test. Univariate analysis showed that BMI, chronic kidney disease, diabetes mellitus, hemoglobin, CRT responder, and cGMP/BNP were predictors of heart failure hospitalization. Conclusion: cGMP/BNP is useful for the heart failure risk stratification in CRT patients.

Abstract 13991: Angiopoietin-2 in Patients With Atrial Fibrillation - Associations With Clinical Characteristics and Outcomes

Introduction: Natriuretic peptides and cardiac troponin are associated with clinical outcomes in patients with atrial fibrillation (AF) but the search for disease-specific biomarkers is ongoing. We evaluated a novel candidate biomarker of endothelial remodeling and vascular growth, Angiopoietin-2 (Ang2), and its associations with clinical characteristics and outcomes in patients with AF not receiving oral anticoagulation. Methods: We used a prototype electroimmunoassay (Roche Diagnostics) to measure levels of Ang2 in plasma samples obtained at baseline from patients with AF randomized to aspirin monotherapy in two clinical trials. Associations of Ang2 with clinical characteristics and outcomes were explored using linear and Cox regression models. Results: A total of 2,987 patients were included (median age 71 years, 58% male and 13% with prior stroke). Median (25th-75th percentile) Ang2 plasma level was 3.12 (2.15-4.88) ng/mL. In adjusted analyses, Ang2 showed significant associations with AF-rhythm on the baseline ECG, age, heart failure, non-paroxysmal AF, female sex, active smoking, higher body mass index, creatinine and diabetes. Adjusting for age and other clinical characteristics, Ang2 was associated with subsequent ischemic stroke (third vs. first quartile, hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.19-2.61), heart failure hospitalization (HR 1.75, 95% CI 1.27-2.41), cardiovascular (HR 2.01, 95% CI 1.36-2.97) and all-cause death (HR 1.24, 95% CI 1.01-1.53), but not major bleeding. The association with heart failure remained after additional adjustment for N-terminal pro-B-type natriuretic peptide (p=0.002). There was no interaction with cardiac rhythm at baseline for any of the outcomes. Conclusions: Plasma levels of circulating Ang2 were associated with clinical characteristics and outcomes in patients with AF not receiving oral anticoagulation. Ang2 was a particularly strong predictor of heart failure hospitalization.

Readmissions, Death and Its Associated Predictors in Heart Failure With Preserved Versus Reduced Ejection Fraction.

BackgroundData on rehospitalizations for heart failure (HF) in Asia are scarce. We sought to determine the burden and predictors of HF (first and recurrent) rehospitalizations and all‐cause mortality in patients with HF and preserved versus reduced ejection fraction (preserved EF, ≥50%; reduced EF, <40%), in the multinational ASIAN‐HF (Asian Sudden Cardiac Death in Heart Failure) registry.Methods and ResultsPatients with symptomatic (stage C) chronic HF were followed up for death and recurrent HF hospitalizations for 1 year. Predictors of HF hospitalizations or all‐cause mortality were examined with Cox regression for time to first event and other methods for recurrent events analyses. Among 1666 patients with HF with preserved EF (mean age, 68±12 years; 50% women), and 4479 with HF with reduced EF (mean age, 61±13 years; 22% women), there were 642 and 2302 readmissions, with 28% and 45% attributed to HF, respectively. The 1‐year composite event rate for first HF hospitalization or all‐cause death was 11% and 21%, and for total HF hospitalization and all‐cause death was 17.7 and 38.7 per 100 patient‐years in HF with preserved EF and HF with reduced EF, respectively. In HF with preserved EF, consistent independent predictors of these clinical end points included enrollment as an inpatient, Southeast Asian location, and comorbid chronic kidney disease or atrial fibrillation. The same variables were predictive of outcomes in HF with reduced EF except atrial fibrillation, and also included Northeast Asian location, older age, elevated heart rate, decreased systolic blood pressure, diabetes, smoking, and non‐usage of beta blockers.ConclusionsOne‐year HF rehospitalization and mortality rates were high among Asian patients with HF. Predictors of outcomes identified in this study could aid in risk stratification and timely interventions.RegistrationURL: https://www.clinicaltrials.gov; Unique identifier: NCT01633398.