Incident Heart Failure Hospitalization Research Articles

Early Aortic Valve Replacement in Symptomatic Normal-Flow, Low-Gradient Severe Aortic Stenosis: A Propensity Score-Matched Retrospective Cohort Study.

Aortic valve replacement (AVR) is considered a class I indication for symptomatic severe aortic stenosis (AS). However, there is little evidence regarding the potential benefits of early AVR in symptomatic patients diagnosed with normal-flow, low-gradient (NFLG) severe AS. Two-hundred eighty-one patients diagnosed with symptomatic NFLG severe AS (stroke volume index ≥35 mL/m², mean transaortic pressure gradient <40 mmHg, peak transaortic velocity <4 m/s, and aortic valve area <1.0 cm²) between January 2010 and December 2020 were included in this retrospective study. After performing 1:1 propensity score matching, 121 patients aged 75.1±9.8 years (including 63 women) who underwent early AVR within 3 months after index echocardiography, were compared with 121 patients who received conservative care. The primary outcome was a composite of all-cause death and heart failure (HF) hospitalization. During a median follow-up of 21.9 months, 48 primary outcomes (18 in the early AVR group and 30 in the conservative care group) occurred. The early AVR group demonstrated a significantly lower incidence of primary outcomes (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.29-0.93; p=0.028); specifically, there was no significant difference in all-cause death (HR, 0.51; 95% CI, 0.23-1.16; p=0.110), although the early AVR group showed a significantly lower incidence of hospitalization for HF (HR, 0.43; 95% CI, 0.19-0.95, p=0.037). Subgroup analyses supported the main findings. An early AVR strategy may be beneficial in reducing the risk of a composite outcome of death or hospitalization for HF in symptomatic patients with NFLG severe AS. Future randomized studies are required to validate and confirm our findings.

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

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

Protein biomarkers of cardiac remodeling and inflammation associated with HFpEF and incident events

There is increasing evidence that HFpEF is a heterogeneous clinical entity and distinct molecular pathways may contribute to pathophysiology. Leveraging unbiased proteomics to identify novel biomarkers, this study seeks to understand the underlying molecular mechanisms of HFpEF. The discovery cohort consisted of HFpEF cases and non-HF controls from the CATHGEN study (N = 176); the validation cohort consisted of participants from the TECOS trial of patients with diabetes (N = 109). Proteins associated with HFpEF were included in a LASSO model to create a discriminative multi-protein model and assessed in the validation cohort. Survival models and meta-analysis were used to test the association of proteins with incident clinical outcomes, including HF hospitalization, mortality and HFpEF hospitalization in CATHGEN, TECOS and the Jackson Heart Study. In the derivation set, 190 proteins were associated with HFpEF in univariate analysis, of which 65 remained significant in the multivariate model. Twenty (30.8%) of these proteins validated in TECOS, including LCN2, U-PAR, IL-1ra, KIM1, CSTB and Gal-9 (OR 1.93–2.77, p < 0.01). LASSO regression yielded a 13-protein model which, when added to a clinical model inclusive of NT-proBNP, improved the AUC from 0.82 to 0.92 (p = 1.5 × 10–4). Five proteins were associated with incident HF hospitalization, four with HFpEF hospitalization and eleven with mortality (p < 0.05). We identified and validated multiple circulating biomarkers associated with HFpEF as well as HF outcomes. These biomarkers added incremental discriminative capabilities beyond clinical factors and NT-proBNP.

Abstract 10755: Association Between Weight Loss and Prognosis in Patients With Atrial Fibrillation: The Fushimi AF Registry

Background: Weight loss is one of the key factors of frailty, and we previously reported that low body weight (≤50 kg) was associated with higher mortality and morbidity in patients with atrial fibrillation (AF). However, the association of weight loss with prognosis in AF patients is unclear. Methods: From the Fushimi AF registry, 2,523 patients with data on changes in body weight at 1 year after enrollment and follow-up data after 1 year were included in the analysis. We defined weight loss as changes in body weight ≤-4.5 kg based on the frailty-defining criteria in the Cardiovascular Health Study. Results: At 1 year after enrollment, 273 (10.8%) patients had weight loss. Mean body weight (changes) at 1 year in patients with and without weight loss were 58.8±14.1 (-8.7±5.8) and 60.7±13.1 (0.7±3.4) kg, respectively (P=0.03). Patients with weight loss were more likely to be male, and had more heart failure, diabetes and chronic kidney disease at baseline. Age and prevalence of prior stroke/systemic embolisms (SE) were similar between the groups, but patients with weight loss had higher incidence of heart failure hospitalization (12.5% and 4.7%) and stroke/SE (4.8% and 2.2%) before 1-year follow-up. Landmark analysis after 1 year revealed that patients with weight loss showed significantly higher incidence of all-cause death and cardiac death (Figure A), but not stroke/SE or major bleeding. Incidence of heart failure hospitalization tended to be higher in patients with weight loss, but not statistically significant. Patients with weight loss also showed higher all-cause and cardiac mortality even in those without low body weight (Figure B). After adjustment for clinical confounders, weight loss was significantly associated with the incidence of all-cause death (hazard ratio, 1.79; 95% confidence interval, 1.43-2.21). Conclusion: In AF patients, weight loss was significantly and independently associated with higher 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.

Abstract 13166: Proteomic Pathways Across Ejection Fraction Categories in Heart Failure: An Exscel Substudy

Background: Ejection fraction (EF) is a key component of heart failure (HF) categorization, including the newly-proposed HF with mildly reduced EF (HFmrEF) category. The biologic basis of HFmrEF, as an entity distinct from HF with preserved EF (HFpEF) and reduced EF (HFrEF), has not been substantiated. Methods: The EXSCEL trial randomized participants with type 2 diabetes to once-weekly exenatide (EQW) vs. placebo. In participants with prevalent HF, we profiled ~5000 serum proteins. Principal component analysis (PCA) and ANOVA (FDR p&lt;0.1) were used to determine differences in factors and individual proteins between three EF groups, as documented in EXSCEL (EF&gt;55% [HFpEF], EF 40-55% [HFmrEF], EF&lt;40% [HFrEF]). Cox proportional hazards was used to assess relationships between baseline proteins and changes in protein level with incident HF hospitalization. Results: Of 1199 EXSCEL participants with prevalent HF, 284 (24%), 704 (59%) and 211 (18%) had HFpEF, HFmrEF and HFrEF, respectively. Eight PCA protein factors and 221 individual proteins within these factors differed significantly across the 3 groups. Levels of the majority of proteins (83.3%) demonstrated concordance between HFmrEF and HFpEF, but higher levels in HFrEF, including the domain of extracellular matrix, e.g. COL28A1, tenascin C [TNC]; p&lt;0.0001. A minority of proteins (1%) were concordant between HFmrEF and HFrEF including matrix metalloproteinase-9 (p&lt;0.0001). Baseline levels of 94% of the 221 significant proteins were associated with incident HF including domains of extracellular matrix (COL28A1, TNC), angiogenesis (ANG2, VEGFa, VEGFd), myocyte stretch (NTpro-BNP), and renal function (cystatin-C). Change in levels of 18 of these proteins from baseline to 12 months (including increase in TNC) predicted subsequent HF (p&lt;0.05). TNC levels were reduced by EQW compared with placebo (p&lt;0.0001). Conclusions: In this large clinical trial, we found that most proteins were similar between HFmrEF and HFpEF. A key ECM protein, tenascin C, showed this relationship, and baseline level and change in tenascin C predicted HF and changed beneficially with EQW. These results suggest that HFmrEF is more biologically similar to HFpEF and highlight prognostic and modifiable biomarkers that vary by EF.

Abstract 13149: Mental Stress-Induced Hemodynamic Changes and Cardiovascular Outcomes

Introduction: Hemodynamic responses to mental stress (MS) have been associated with adverse CV outcomes. We investigated if hemodynamic responses during laboratory MS testing are predictive of outcomes. Hypothesis: Lower rate pressure product (RPP) changes during MS testing are predictive of adverse CV events. Methods: Patients recruited into the Mental Stress Ischemia Prognosis Study and Myocardial Infarction and Mental Stress Study 2 studies underwent MS testing with a standardized public speaking stressor and followed for incident CV death, MI rates (primary endpoint) and heart failure hospitalizations (secondary endpoint). Maximum changes in the RPP during MS were calculated. A generalized linear mixed model determined predictors of RPP change, and Prentice, Williams, Peterson model gap time approach was used for analysis of recurrent events after adjustment for demographic and clinical variables. Results: In 919 patients (mean 59.6 years; 65.6% men), the median change in RPP was 5,112 mmHg x beats/minute (IQR, 3,666 - 7,120). Patients with lower RPP changes (&lt;median) during MS were more likely to have a lower resting RPP, be male, and have a history of smoking, obesity, and heart failure. Serum epinephrine levels (22.5 ± 37.3 pg/mL; p&lt;0.001) increased after MS and correlated with RPP changes (r = 0.32; p &lt; 0.001). During a mean follow-up of 4.6 years, there were 135 CV death and MI events (3.2/100 patient-years) and 279 events including HF hospitalizations (6.7 events/100 patient-years). After adjusting for the baseline RPP, demographics, clinical factors, and medication, patients with lower change in RPP during MS had higher primary [HR, 1.7 (95% CI, 1.1 - 2.5); p = 0.009] and secondary events [HR, 1.5 (95% CI, 1.1 - 2.0); p = 0.006]. Conclusions: A reduced change in RPP during MS is independently associated with worse outcomes in patients with CAD. Whether hemodynamic reactivity during MS can be clinically used to identify residual risk needs further evaluation.

Prospective associations of circulating thrombospondin-2 level with heart failure hospitalization, left ventricular remodeling and diastolic function in type 2 diabetes

BackgroundCirculating thrombospondin-2 (TSP2) levels were associated with the development of heart failure (HF) in recent studies. However, these studies included only a minority of patients with type 2 diabetes, which is associated with an increased HF risk. As hyperglycemia induces TSP2 expression and its tissue expression increases in type 2 diabetes, we investigated the prospective association of circulating TSP2 with incident HF hospitalization (HHF), and its associations with longitudinal changes of echocardiographic parameters in type 2 diabetes.MethodsBaseline serum TSP2 levels were measured in 4949 patients with type 2 diabetes to determine its association with incident HHF using multivariable Cox regression analysis. In the echocardiographic study, baseline serum TSP2 levels were measured in another 146 patients with type 2 diabetes but without cardiovascular diseases who underwent detailed transthoracic echocardiography at baseline and after 1 year.ResultsOver a median follow-up of 7.8 years, 330 of 4949 patients (6.7%) developed incident HHF. Baseline serum TSP2 levels were independently associated with the development of HHF (HR 1.31, 95%CI 1.06–1.62, p = 0.014) after adjustments for baseline conventional cardiovascular risk factors, atrial fibrillation, estimated glomerular filtration rate, albuminuria and high-sensitivity C-reactive protein level, use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, loop-diuretics, aspirin, insulin, metformin and sodium-glucose co-transporter 2 inhibitors. Moreover, baseline serum TSP2 levels were independently associated with increase in average E/e’ and left atrial volume index (p = 0.04 and < 0.01, respectively).ConclusionSerum TSP2 levels were independently associated with both incident HHF and deterioration in diastolic function in type 2 diabetes.Trial registrationNot Applicable

PSUN156 Circulating thrombospondin-2 level as a novel biomarker of heart failure in type 2 diabetes

Abstract Introduction Circulating thrombospondin-2 (TSP2) has been associated with adverse cardiovascular outcomes in patients with heart failure (HF). Type 2 diabetes (T2D) increases HF risk and induces TSP2 tissue expression. Here, we investigated prospectively the role of circulating TSP2 as a novel biomarker of incident HF hospitalization (HHF), and its associations with longitudinal changes of echocardiographic parameters in T2D. Methods Baseline serum TSP2 level was measured in 4949 T2D patients from the Hong Kong West Diabetes Registry to determine its association with incident HHF using multivariable Cox regression analysis. In the echocardiographic study, baseline serum TSP2 level was measured in another 146 T2D patients without cardiovascular diseases who underwent detailed transthoracic echocardiography at baseline and after 1 year. Results Over a median follow-up of 7.8 years, 330 of 4949 patients (6.7%) developed incident HHF. Baseline serum TSP2 level was independently associated with the development of HHF (HR 1.31, 95%CI 1.06–1.62, p=0.014) after adjustments for conventional cardiovascular risk factors, atrial fibrillation, estimated glomerular filtration rate, albuminuria and high-sensitivity C-reactive protein level at baseline, as well as use of medications including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, frusemide, aspirin, insulin, metformin and sodium-glucose co-transporter 2 inhibitors. In the echocardiographic study, baseline serum TSP2 level was independently associated with increase in average E/e' and left atrial volume index (p=0.04 and &amp;lt;0.01, respectively). Conclusion Serum TSP2 level was independently associated with both incident HHF and deterioration in diastolic function in T2D, suggesting its potential to be developed as a novel HF biomarker in T2D. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

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.

Vascular endothelial factor C and D in patients with heart failure with preserved, mildly reduced, and reduced ejection fraction: the PREHOSP-CHF study

Abstract Background The lymphatic system has been suggested to play an important role in cardiovascular diseases including heart failure (HF). Vascular endothelial growth factor C (VEGF-C) and D (VEGF-D) are key regulators of lymphangiogenesis, and we recently reported the association of low VEGF-C with the risk of all-cause death and high VEGF-D with the risk of HF hospitalization in patients with HF. Purpose To investigate the association of VEGF-C and VEGF-D with prognosis in patients with HF with preserved ejection fraction (EF) (HFpEF: EF≥50%), mildly reduced EF (HFmrEF: EF, 40–49%), and reduced EF (HFrEF: EF&amp;lt;40%). Methods The PREHOSP-CHF study is a multicenter prospective cohort study to determine the predictive value of angiogenesis-related biomarkers in HF. A total of 1,024 patients (mean age 75.5±12.6 years; 58.7% male) admitted to acute decompensated HF were included in the analyses. Serum levels of VEGF-C and VEGF-D, as well as N-terminal pro B-type natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin-I (hs-cTnI), high sensitivity C reactive protein, were measured at the time of discharge. Patients were followed-up over two years. Results The numbers of HFpEF, HFmrEF, and HFrEF were 429 (41.9%), 186 (18.2%), and 409 (39.9%), respectively. HFpEF patients were older, more likely to be female, and had more hypertension, atrial fibrillation, and anemia, but less coronary artery disease. NT-proBNP and hs-cTnI levels increased with decreasing EF. VEGF-C levels decreased with increasing EF (median [interquartile range]: HFpEF, 4508 [3318–5919] pg/ml; HFmrEF, 4719 [3663–6203] pg/ml; HFrEF, 5023 [3804–6382] pg/ml), whereas VEGF-D levels were comparable among the three EF groups (HFpEF, 404.6 [293.1–560.3] pg/ml; HFmrEF, 386.0 [298.5–556.3] pg/ml; HFrEF, 414.2 [296.1–557.3] pg/ml). In multivariate stepwise logistic regression analyses, anemia and high NT-proBNP were independently associated with low VEGF-C levels, and high NT-proBNP was independently associated with high VEGF-D levels, across all the EF groups. During the follow-up, incidences of all-cause death and HF hospitalizations were similar among the three EF groups (log-rank P=0.6 for all-cause death, and log-rank P=0.3 for HF hospitalization). On multivariate Cox proportional hazard analyses including established risk factors and cardiovascular biomarkers, VEGF-C levels tended to be inversely associated with the incidence of all-cause death in patients with HFpEF and HFrEF (Figure). On the contrary, VEGF-D levels were significantly and positively associated with the incidence of HF hospitalization in patients with HFpEF, and tended to be positively associated with it in patients with HFmrEF and HFrEF (Figure). Conclusions Low VEGF-C was associated with the risk of all-cause death in patients with HFpEF and HFrEF, while high VEGF-D was associated with the risk of HF hospitalization especially in HFpEF. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Grant-in-Aid for Clinical Research from the National Hospital Organization

Ultra-sensitive troponin-I and incident coronary heart disease, stroke, heart failure, cardiac arrhythmias, arterial aneurysms and venous thromboembolism hospitalizations

Abstract Background Cardiac troponin I (cTnI) as measured by high-sensitive assays has been related to incident cardiovascular disease events (CVD) in the community. With the advent of ultra-sensitive assays, it is now possible to detect troponin I at very low concentration, far below the classical threshold of 1.9 pg/mL. However, the clinical relevance of these low concentrations for predicting CVD is largely unknown. Purpose To examine the association of cTnI as low as 0.013 pg/mL with incident cardiovascular disease events (CVDs) in the primary prevention setting. Methods cTnI was analyzed in the baseline plasma (2008–2012) of CVD free volunteers from the Paris Prospective Study III using for the first time a novel ultra-sensitive immunoassay (Simoa Troponin-I 2.0 Kit, Quanterix, Lexington) with a limit of detection (LOD) of 0.013 pg/mL. Incident CVD hospitalizations for coronary heart disease, stroke, arrhythmias, venous thromboembolism, arterial aneurysms and heart failure were validated by critical review of the hospital records. Hazard ratios were estimated per log-transformed standard deviation (SD) increase of cTnI in Cox models using age as the time scale. The added value (gain in discriminatory capacity) of cTnI for CVD risk prediction was examined by calculating the Harell's C-index boostraped difference of the SCORE 2 risk model with and without cTnI. Results There were 9503 CVD free participants (40% women) aged 59.6 (6.3) years at baseline. cTnI was detected in 99.6% of the participants (median value = 0.63 pg/mL, interquartile range [IQR] 0.39–1.09). After a median follow-up of 8.34 years (IQR, 8.0–10.07), 516 participants suffered 612 events. In fully-adjusted analysis, higher cTnI (per 1 SD increase of log cTnI) was significantly associated with CVD events combined (n=516, HR= 1.21; 1.06; 1.39). In univariate Cox analysis and compared to each single established risk factor, cTnI had the highest discrimination capacity for incident CVD events (C-index=0.6349) (Figure 1). Adding log cTnI to the SCORE 2 algorithm increased significantly albeit moderately discriminatory capacity (C-index 0.698 vs. 0.685; boostraped C index difference: 0.0135 (95% CI: 0.0131; 0.0138)). Conclusion cTnI concentrations as measured by a novel ultra-sensitive immunoassay is associated with a significant increased risk of incident CVD events in the primary prevention setting. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): ANR: French National Research AgencyEurope: Horizon 2020

Quantitative technetium pyrophosphate and cardiovascular magnetic resonance in patients with suspected cardiac amyloidosis

BackgroundQuantitation of myocardial 99m Tc-pyrophosphate activity may have high diagnostic accuracy, but its correlation with disease burden is unknown. We examined the relationship between 99m Tc-pyrophosphate quantitation and cardiac magnetic resonance (CMR) measures in patients with suspected transthyretin cardiac amyloidosis (ATTR-CM) or light chain cardiac amyloidosis (AL-CM). MethodsConsecutive patients who underwent 99mTc-pyrophosphate imaging and CMR were included. ATTR-CM and AL-CM were diagnosed using standard criteria. 99mTc-pyrophosphate images were assessed with standard parameters and quantified with cardiac pyrophosphate activity (CPA) and volume of involvement (VOI). We assessed the association between 99mTc-pyrophosphate image interpretation and CMR tissue characteristics. ResultsSeventy patients were identified, mean age 70.4 ± 11.4 years, with ATTR-CM and AL-CM diagnosed in 22 (31%) and 11 (16%) patients, respectively. In patients with ATTR-CM, there were significant correlations between CPA (r2 = 0.509, P < 0.001) and VOI (r2 = 0.586, P < 0.001) with native myocardial T1 mapping values. Additionally, CPA (adjusted hazard ratio (aHR) 1.04, P = 0.016), VOI (aHR 1.12, P = 0.034), and average myocardial T1 (aHR 1.12, P = 0.025) were associated with incidence of heart failure hospitalization or death. ConclusionCPA and VOI were correlated with CMR measures of myocardial fibrosis in patients with ATTR-CM. 99mTc-pyrophosphate quantitation may have a role in ATTR-CM disease staging, guiding treatment, or following response to therapy.

Effectiveness and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in type 2 diabetes: an Italian cohort study

BackgroundGLP-1 receptor agonists (GLP-1 RA) and SGLT-2 inhibitors (SGLT-2i) have shown to reduce the risk of major adverse cardiovascular events (MACE), death and worsening nephropathy when added to standard of care. However, these two dug classes differ in efficacy and safety. We compared the effectiveness and safety profile of GLP-1 RA and SGLT-2i in a large and unselected cohort of patients with type 2 diabetes resident in Lombardy from 2015 to 2020.MethodsUsing linkable administrative health databases, we included patients aged 50 years and older initiating GLP-1 RA or SGLT-2i. Clinical events were: death, hospital admission for myocardial infarction (MI), stroke, heart failure (HF), and renal disease as individual and composite outcomes (MACE-3: all cause-death, non-fatal MI, non-fatal stroke; MACE-4: MACE-3 plus unstable angina). Outcomes were evaluated separately in subjects with and without previous cardiovascular (CV) diseases. Treatments were compared using Cox proportional hazards regression model after Propensity Score Matching (PSM) in both intention-to-treat (ITT) and per protocol (PP) analyses. Serious adverse events were also evaluated.ResultsThe analysis comprised 20,762 patients per cohort. The ITT analysis showed a significant risk reduction for non-fatal MI (HR 0.77; CI 95% 0.66–0.90), MACE-3 (HR 0.91; CI 95% 0.84–0.98), and MACE-4 (HR 0.92; CI 95% 0.86–0.99) in GLP-1RA compared with SGLT-2i users, while no difference was reported in the incidence of HF hospitalization and stroke between the two cohorts. Similar benefits were found in the subgroup of patients without previous CV diseases only. PP analysis largely confirmed the main results. The incidence of serious adverse events was low in both cohorts (< 1%).ConclusionsGLP-1RA showed to be equally safe and more effective than SGLT-2i in reducing the risk of MACE-3, MACE-4 and MI. This study adds to the growing body of real-world evidence addressing the specific clinical properties of GLP-1RA and SGLT-2i in everyday practice to tailor treatment to the individual patient.

Use of Guideline-Directed Medical Therapy in Patients Aged ≥ 65 Years After the Diagnosis of Heart Failure: A Canadian Population-Based Study

BackgroundGuideline-directed medical therapy (GDMT) improves clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Despite its proven efficacy, GDMT is underutilized in clinical practice. The current study examines GDMT utilization after incident hospitalization for HF to promote medication initiation, and titration to target dosing within a reasonable time period. MethodsThis observational study identified 66,372 patients with HFrEF who were aged ≥ 65 years and had an incident HF hospitalization, using administrative health data (2013-2018). GDMT (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors, β-blockers (BB), and mineralocorticoid receptor antagonists ) received within the 6 months after hospitalization was evaluated by monitoring therapy combinations, optimal dosing (proportion receiving ≥ 50% of the target dose for these inhibitors and blockers, and any dose of MRA), and maximal and last dose assessed, and by use of a GDMT intensity score. ResultsAmong patients with HFrEF, 4768 (7.2%) were on no therapy, 17,184 (25.9%), were on monotherapy, 30,912 (46.6%) were on dual therapy, and 13,508 (20.4%) were on triple therapy. Only 8747 (13.2%) and 5484 (8.3%) achieved optimal GDMT based on the maximum dose and the last dispensed dose, respectively, within 6 months postdischarge. Finally, 38,869 (58.6%) achieved < 50% of the maximum intensity score, 23,006 (34.7%) achieved between 50% and 74% of the maximum intensity score, and 4497 (6.8%) achieved a score that was ≥ 75% of the maximum intensity score. ConclusionsCurrent pharmacologic management for patients with HFrEF does not align with the Canadian guidelines. Given this gap in care, innovative strategies to optimize care in patients with HFrEF are needed.

Vitamin D Levels in Black Americans and the Association With Left Ventricular Remodeling and Incident Heart Failure With Preserved Ejectin Fraction: The Jackson Heart Study

BackgroundIn observational studies, a lower serum vitamin D3 concentration has been associated with an increased risk of cardiovascular disease. However, the associations between serum vitamin D3 levels and left ventricular (LV) structure and heart failure with preserved ejection fraction (HFpEF) have not been well-characterized among Black Americans. The prevalence of vitamin D3 deficiency is higher among Black Americans than in other race/ethnicity groups. We hypothesized that serum vitamin D3 levels are associated with LV concentric remodeling and incident HFpEF in Black Americans. Methods and ResultsAmong 5306 Black Americans in the Jackson Heart Study cohort, we investigated the relationships between serum vitamin D3 levels and LV structure and function, evaluated with echocardiography, and incident HF hospitalization, categorized as either HF with reduced EF (HFrEF; an EF of <50%) or HFpEF (an EF of ≥50%). After adjustment for possible confounding factors, lower vitamin D3 levels were associated with greater relative wall thickness (β for 1 standard deviation [SD] increase –0.003, 95% confidence interval –0.005 to –0.000). Over a median follow-up period of 11 years (range 10.2–11.0 years), 340 participants developed incident HF (7.88 cases per 1000 person-years), including 146 (43%) HFrEF and 194 (57%) HFpEF cases. After adjustment, higher serum vitamin D3 levels were associated with decreased hazard for HF overall (hazard ratio for 1 SD increase 0.88, 95% confidence interval 0.78–0.99) driven by a significant association with HFpEF (hazard ratio for 1 SD increase 0.84, 95% confidence interval 0.71–0.99). ConclusionsIn this community-based Black American cohort, lower serum vitamin D3 levels were associated with LV concentric remodeling and an increased hazard for HF, mainly HFpEF. Further investigation is required to examine whether supplementation with vitamin D3 can prevent LV concentric remodeling and incident HFpEF in Black Americans.

Association of Intra-individual Differences in Estimated GFR by Creatinine Versus Cystatin C With Incident Heart Failure

Lower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFRcys) and creatinine (eGFRcr) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidney disease (CKD) are unknown. Prospective cohort study. 4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. Difference in GFR estimates (eGFRdiff; ie, eGFRcys minus eGFRcr). Incident HF hospitalization. Fine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFRdiff with incident HF. Of 4,512 participants, one-third had eGFRcys and eGFRcr values that differed by over 15 mL/min/1.73 m2. In multivariable-adjusted models, each 15 mL/min/1.73 m2 lower baseline eGFRdiff was associated with higher risk of incident HF hospitalization (hazard ratio [HR], 1.20 [95% CI, 1.07-1.34]). In time-updated analyses, those with eGFRdiff less than-15 mL/min/1.73 m2 had higher risk of incident HF hospitalization (HR, 1.99 [95% CI, 1.39-2.86]), and those with eGFRdiff≥15 mL/min/1.73 m2 had lower risk of incident HF hospitalization (HR, 0.67 [95% CI, 0.49-0.91]) compared with participants with similar eGFRcys and eGFRcr. Participants with faster declines in eGFRcys relative to eGFRcr had higher risk of incident HF (HR, 1.49 [95% CI, 1.19-1.85]) compared with those in whom eGFRcys and eGFRcr declined in parallel. Entry into the CRIC Study was determined by eGFRcr, which constrained the range of baseline eGFRcr-but not eGFRcys-values. Among persons with CKD who have large differences between eGFRcys and eGFRcr, risk for incident HF is more strongly associated with eGFRcys. Diverging slopes between eGFRcys and eGFRcr over time are also independently associated with risk of incident HF.

Post-operative atrial fibrillation and risk of heart failure hospitalization.

Post-operative atrial fibrillation (POAF) is associated with stroke and mortality. It is unknown if POAF is associated with subsequent heart failure (HF) hospitalization. This study aims to examine the association between POAF and incident HF hospitalization among patients undergoing cardiac and non-cardiac surgeries. A retrospective cohort study was conducted using all-payer administrative claims data that included all non-federal emergency department visits and acute care hospitalizations across 11 states in the USA. The study population included adults aged at least 18 years hospitalized for surgery without a prior diagnosis of HF. Cox proportional hazards regression models were used to examine the association between POAF and incident HF hospitalization after making adjustment for socio-demographics and comorbid conditions. Among 76 536 patients who underwent cardiac surgery, 14 365 (18.8%) developed incident POAF. In an adjusted Cox model, POAF was associated with incident HF hospitalization [hazard ratio (HR) 1.33; 95% confidence interval (CI) 1.25-1.41]. In a sensitivity analysis excluding HF within 1 year of surgery, POAF remained associated with incident HF hospitalization (HR 1.15; 95% CI 1.01-1.31). Among 2 929 854 patients who underwent non-cardiac surgery, 23 763 (0.8%) developed incident POAF. In an adjusted Cox model, POAF was again associated with incident HF hospitalization (HR 2.02; 95% CI 1.94-2.10), including in a sensitivity analysis excluding HF within 1 year of surgery (HR 1.49; 95% CI 1.38-1.61). Post-operative atrial fibrillation is associated with incident HF hospitalization among patients without prior history of HF undergoing both cardiac and non-cardiac surgeries. These findings reinforce the adverse prognostic impact of POAF and suggest that POAF may be a marker for identifying patients with subclinical HF and those at elevated risk for HF.

Longitudinal Changes in Cardiac Troponin and Risk of Heart Failure Among Black Adults

BackgroundAmong Black adults, high-sensitivity cardiac troponin I (hs-cTnI) is associated with heart failure (HF) risk. The association of longitudinal changes in hs-cTnI with risk of incident HF, HF with reduced and preserved ejection fraction (HFrEF and HFpEF, respectively), among Black adults is not well-established. Methods and ResultsThis study included Black participants from the Jackson Heart Study with available hs-cTnI data at visits 1 (2000–2004) and 2 (2005–2008) and no history of cardiovascular disease. Cox models were used to evaluate associations of categories of longitudinal change in hs-cTnI with incident HF risk. Among 2423 participants, 11.6% had incident elevation in hs-cTnI at visit 2, and 16.9% had stable or improved elevation (≤50% increase in hs-cTnI), and 4.0% had worsened hs-cTnI elevation (>50% increase). Over a median follow-up of 12.0 years, there were 139 incident HF hospitalizations (64 HFrEF, 58 HFpEF). Compared with participants without an elevated hs-cTnI, those with incident, stable or improved, or worsened hs-cTnI elevation had higher HF risk (adjusted hazard ratio 3.20 [95% confidence interval, 1.92–5.33]; adjusted hazard ratio 2.40, [95% confidence interval, 1.47–3.92]; and adjusted hazard ratio 8.10, [95% confidence interval, 4.74–13.83], respectively). Similar patterns of association were observed for risk of HFrEF and HFpEF. ConclusionsAmong Black adults, an increase in hs-cTnI levels on follow-up was associated with a higher HF risk. Lay SummaryThe present study included 2423 Black adults from the Jackson Heart Study with available biomarkers of cardiac injury and no history of cardiovascular disease at visits 1 and 2. The majority of participants did not have evidence of cardiac injury at both visits (67.5%), 11.6% had evidence of cardiac injury only on follow-up, 14.5% had stable elevations, 4.0% had worsened elevations, and 2.4% had improved elevations of cardiac injury biomarkers during follow-up. Compared with participants without evidence of cardiac injury, those with new, stable, and worsened levels of cardiac injury had a higher risk of developing heart failure. TweetAmong Black adults, persistent or worsening subclinical myocardial injury is associated with an elevated risk of HF.

1148-P: Risk Factor Control and Risk of Hospitalization for Heart Failure in Diabetic Patients

Both diabetes and ischemic heart disease (IHD) are important risk factors for heart failure hospitalization. We investigated the association between the degree of risk-factor control and risk of heart failure in diabetic patients with and without IHD. A total of 20,9diabetic patients from UK Biobank were included, and matched with 82,582 controls based on age, sex, the presence of IHD, and assessment center. Risk-factor control was evaluated by 3 factors: glycated hemoglobin &amp;lt;53 mol/mol, blood pressure &amp;lt;140/90 mm/Hg and non-HDL-cholesterol &amp;lt;130 mg/dl. The Cox regression model was used to assess the association between the number of risk-factor control and the risk of heart failure. During a mean follow-up of 8.7 years, 1,139 incident heart failure hospitalization were documented. Higher degree of risk-factor control was significantly associated with a lower risk of heart failure in diabetic patients without IHD, but not in diabetic patients with IHD (P-interaction=0.008) . Moreover, as compared with non-diabetic controls, the diabetes-related excess risk of heart failure became diminished when all the three risk factors were under control in diabetic patients without IHD; the hazard ratio for heart failure was 1. (95%, CI, 0.85-1.49) . Our findings highlight the importance of early intervention for controlling cardiovascular risk factors in preventing heart failure, especially before the onset of IHD. Disclosure H.Ma: None. X.Wang: None. Y.Heianza: None. L.Qi: None.