scholarly journals Left atrial coupling index versus left atrial function index in heart failure with reduced ejection fraction and iron deficiency

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Tsarouchas ◽  
C Bakogiannis ◽  
D Mouselimis ◽  
E.D Pagourelias ◽  
I Kelemanis ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Cox Regression ◽  
Relevant Literature ◽  
Reduced Ejection Fraction ◽  
Function Index ◽  
Coupling Index ◽  
Increased Risk

Abstract Background Left atrial (LA) form and function has been the focus of extensive research in heart failure with reduced ejection fraction (HFrEF). The LA coupling index (LACI, see Picture 1 for definition) and the LA function Index (LAFI) have both been proposed as potent predictors of morbidity and mortality in HFrEF. Albeit promising, both parameters have drawbacks that could limit their usefulness in clinical settings - LACI can only be measured during sinus rhythm (SR), while LAFI calculation is arguably more involved. A side-by-side comparison of the two indices has not yet been performed. Purpose Investigate and compare the feasibility and efficacy of using LACI and LAFI as prognostic factors in HFrEF. Methods HFrEF patients that visited our outpatient HF clinic were invited to participate in the study. Clinical examination, 6-minute walk testing, and a full echocardiographic study were performed, the latter enabling quantification of LACI, LAFI, as well as most traditional echocardiographic predictors of HF prognosis (Picture 1). LACI and LAFI cut-offs of 6 and 25 respectively were defined in accordance with the relevant literature. Cox regression was performed to assess each parameter's correlation with risk of HF-related hospitalization and mortality over a 6-month follow-up period. Results In the end, 63 patients were included in the study (aged 69.3±9.7 years, 84% male). LACI could not be measured in 19 patients due to atrial tachycardia. The median LACI was 6.2 (8.7) while the median LAFI of the entire sample was 24.8 (44.5). LACI and LAFI correlated strongly (r=−0.813, p<0.001). Neither correlated significantly with the risk of HF-related hospitalization (Picture 1) or death in our sample (Picture 2). 6MWD was the only parameter to independently correlate with increased risk of hospitalization (HR=0.39, p<0.001) or death (HR=0.42, p=0.02). Conclusions The collinearity detected between LACI and LAFI indicate that both quantify similar aspects of left atrial (dys)function. That said, neither index had significant capability to predict hospitalization or death in our sample of HFrEF patients. Although a non-significant trend for higher LACI in patients with poorer prognosis was detected in our sample, it was also incalculable in 30% of patients, who were not in SR during echocardiography. Extended follow-up of an expanded sample size will enable more refined investigation of LACI's and LAFI's prognostic capacity. FUNDunding Acknowledgement Type of funding sources: None. Hospitalization Cox regression results LACI and LAFI survival curves

Prevalence and prognostic impact of somatic mutations in patients with heart failure and reduced ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D.J Vazquez Andres ◽  
A Hernandez Vicente ◽  
M Diez Diez ◽  
M Gomez Molina ◽  
A Quintas ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Somatic Mutations ◽  
Myocardial Dysfunction ◽  
Study Endpoint ◽  
Prognostic Impact ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
Patients With Heart Failure

Abstract Introduction Somatic mutations in hematopoietic cells are associated with age and have been associated with higher mortality in apparently healthy adults, especially due to atherosclerotic disease. In animal models, somatic mutations are associated with atherosclerosis progression and myocardial dysfunction, especially when gene TET2 is affected. Preliminary clinical data, referred to ischemic heart failure (HF), have associate the presence of these acquired mutations with impaired prognosis. Purpose To study the prevalence of somatic mutations in patients with heart failure with reduced ejection fraction (HFrEF) and their impact on long-term prognosis. Methods We studied a cohort of elderly patients (more than 60 years old) hospitalized with HFrEF (LVEF<45%). The presence of somatic mutations was assessed using next generation sequencing (Illumina HiSeq 2500), with a mutated allelic fraction of at least 2% and a panel of 55 genes related with clonal hematopoiesis. Patients were followed-up for a median of three years. The study endpoint was a composite of death or readmission for worsening HF. Kaplan-Meier analysis (log-rank test) and Cox proportional hazards regression models were performed adjusting for age, sex and LVEF. Results A total of 62 patients (46 males (74.2%), age 74±7.5 years) with HFrEF (LVEF 29.7±7.8%) were enrolled in the study. The ischemic etiology was present in 54% of patients. Somatic mutations in Dnmt3a or Tet2 were present in 11 patients (17.7%). No differences existed in baseline characteristics except for a higher prevalence of atrial fibrillation in patients with somatic mutations (70% vs. 40%, p=0.007). During the follow-up period, 40 patients (64.5%) died and 38 (61.3%) had HF re-admission. The KM survival analysis for the combined event is shown in Figure 1. Compared with patients without somatic mutations and after adjusting for covariates, there was an increased risk of adverse outcomes when the somatic mutations were present (HR 3.6, 95% CI [1.6, 7.8], p=0.0014). This results remains considering death as a competing risk (Gray's test p=0.0097) and adjusting for covariates (HR = 2.21 95% CI [0.98, 5], p=0.0556). Conclusions Somatic mutation are present in patients with HFrEF and determine a higher risk of adverse events in the follow-up. Further studies are needed to assess the clinical implications of these findings. Figure 1 Funding Acknowledgement Type of funding source: None

P1663The impact of highest doses of ACEi/ARB therapy on mortality of patients suffering from heart failure with reduced ejection fraction: a long-term follow-up, propensity-matched cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
B Muk ◽  
M Vamos ◽  
P Bogyi ◽  
Z S Majoros ◽  
D Vagany ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Nearest Neighbor ◽  
Cox Regression ◽  
Converting Enzyme Inhibitors ◽  
Mortality And Morbidity ◽  
Cox Regression Analysis ◽  
Reduced Ejection Fraction ◽  
Total Cohort

Abstract The angiotensin-converting enzyme inhibitors (ACEi) as cornerstone of neurohormonal drug regime reduce mortality and morbidity in heart failure with reduced ejection fraction (HFrEF) hence these drugs are recommended for every HFrEF patients without presence of contraindication or intolerance. However, there are controversial results regarding the incremental survival benefit of higher doses of these drugs used in HFrEF. In addition, achieving the highest doses (TD1) (20 mg < enalapril daily dose≤40 mg, or dose equivalent ACEi/ARB), of these drugs often accompanies side effects related to the uptitration, which may make it impossible to start other therapies proven to result in undoubtful mortality benefit (i.e. sacubitril/valsartan). Aim To assess the effect of TD1 of ACEi/ARB on mortality of HFrEF patients followed at a heart failure outpatient clinic (HFOC). Methods Data of 579 consecutive HFrEF patients, who hadn't been treated with an ACEi/ARB or were receiving ≤50% of doses equivalent with 20mg enalapril daily (TD2) at the time of initiation of care (NYHA: 3.1±0.8; LVEF: 27.5±6.6%; age: 61.1±13.0 years; male: 76.1%; ischemic: 46.8%; atrial fibrillation: 27.6%; diabetes: 34.9%; hypertension: 72.5%), followed at our HFOC was analysed. After therapy optimization (TO) ACEis/ARBs were applied in 96.5% and at least TD2 was reached in 55.9% of the total cohort, while TD1 of an ACEi/ARB was applied in 111 patients (19.2% of total cohort). BBs in 88.4%, target doses of BBs in 46.8%, MRAs in 57.0% of total cohort were used. To adjust for possible confounders, patients were matched based on the ACEi/ARB doses reached during TO applying propensity score matching (PSM) using the nearest neighbor matching (caliper: 0.2). All-cause mortality (ACM) was assessed using the Kaplan-Meier method and compared with the Cox proportional hazard model. Results After 7.1±4.7 years follow-up ACM of patients treated with TD1 of ACEis/ARBs was significantly lower than those treated with lower doses in the total cohort (HR=0.67; 95% CI=0.50–0.89; p=0.005). Applying multivariate Cox regression analysis the use of TD1 of an ACEi/ARB didn't remain independent predictor of survival; creatinine, NYHA f.c., age, sex, ischemic etiology were proved to be significant predictor of mortality. After PSM the survival of patients receiving TD1 of an ACEi/ARB didn't differ from those treated with lower doses (HR=0.84; 95% CI=0.61–1.14; p=0.27). Conclusions The current ESC guidelines recommend the use of target doses or maximal tolerated doses of ACEis or ARBs in HFrEF. In a real-world patient cohort whom all the effort was made to reach the target doses, ACM of patients treated with TD1 of an ACEi/ARB was significantly lower than those treated with lower doses, however this result wasn't independent from the patient characteristics. Beside that, after PSM the survival of patients treated with TD1 or with lower doses of an ACEi/ARB did not differ significantly.

scholarly journals Impact of atrial fibrillation in patients with heart failure and reduced, mid-range or preserved ejection fraction

Heart ◽  
2020 ◽  
Vol 106 (15) ◽  
pp. 1160-1168 ◽  
Author(s):  
Mi Kyoung Son ◽  
Jin Joo Park ◽  
Nam-Kyoo Lim ◽  
Won-Ho Kim ◽  
Dong-Ju Choi
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Propensity Score Matching Analysis ◽  
Increased Risk ◽  
Multicentre Cohort Study ◽  
Patients With Heart Failure ◽  
Registration Number

ObjectiveTo determine the prognostic value of atrial fibrillation (AF) in patients with heart failure (HF) and preserved, mid-range or reduced ejection fraction (EF).MethodsPatients hospitalised for acute HF were enrolled in the Korean Acute Heart Failure registry, a prospective, observational, multicentre cohort study, between March 2011 and February 2014. HF types were defined as reduced EF (HFrEF, LVEF <40%), mid-range EF (HFmrEF, LVEF 40%–49%) or preserved EF (HFpEF, LVEF ≥50%).ResultsOf 5414 patients enrolled, HFrEF, HFmrEF and HFpEF were seen in 3182 (58.8%), 875 (16.2%) and 1357 (25.1%) patients, respectively. The prevalence of AF significantly increased with increasing EF (HFrEF 28.9%, HFmrEF 39.8%, HFpEF 45.2%; p for trend <0.001). During follow-up (median, 4.03 years; IQR, 1.39–5.58 years), 2806 (51.8%) patients died. The adjusted HR of AF for all-cause death was 1.06 (0.93–1.21) in the HFrEF, 1.10 (0.87–1.39) in the HFmrEF and 1.22 (1.02–1.46) in the HFpEF groups. The HR for the composite of all-cause death or readmission was 0.97 (0.87–1.07), 1.14 (0.93–1.38) and 1.03 (0.88–1.19) in the HFrEF, HFmrEF and HFpEF groups, respectively, and the HR for stroke was 1.53 (1.03–2.29), 1.04 (0.57–1.91) and 1.90 (1.13–3.20), respectively. Similar results were observed after propensity score matching analysis.ConclusionsAF was more common with increasing EF. AF was seen to be associated with increased mortality only in patients with HFpEF and was associated with an increased risk of stroke in patients with HFrEF or HFpEF.Trial registration numberNCT01389843

Late mortality with a 3-year follow-up of hospitalized patients with heart failure with normal, mid-range or reduced ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
G Dutra ◽  
B Ferraz De Oliveira Gomes ◽  
T Moreira Curcio ◽  
L De Oliveira Pereira ◽  
B Ferreira Da Silva Mendes ◽  
...  
Keyword(s):  
Heart Failure ◽  
Multivariate Analysis ◽  
Ejection Fraction ◽  
Cox Regression ◽  
Clinical Laboratory ◽  
Categorical Variables ◽  
Post Discharge ◽  
Late Mortality ◽  
Reduced Ejection Fraction

Abstract Introduction In 2016, the European Society of Cardiology published a new concept of heart failure (HF) inbetween HF with reduced ejection fraction (EF) (HFrEF; EF&lt;40%) and HF with preserved EF (HFpEF; EF&gt;50%), the HF with mid-range EF (HFmrEF; EF between 40% and 49%). There are few studies evaluating its distinct clinical characteristics, especially in Latin America. Objective To compare clinical, laboratory and mortality characteristics in individuals with HFpEF, HFmrEF and HFrEF. Method Retrospective analysis in a prospective database of Brazilian coronary care unit admissions of patients clinically diagnosed with decompensated HF associated with serum cerebral natriuretic peptide (BNP) levels above 400 mg/dL, between September 2011 and June 2019. The clinical and laboratory characteristics of the patients, as well as the HF classification into HFpEF, HFmrEF and HFrEF, were evaluated with the first echocardiogram of the hospitalization. Analysis of variance (ANOVA) to compare means, the chi-square test for categorical variables, and the Cox regression for survival analysis were performed, with a significance level of 5%. Results The analysis included 519 patients (mean age, 74.46±12.75 years; men, 59.6%). Post-discharge follow-up was 2.94±2.55 years. Late mortality according to EF did not statistically differ between groups (53.8% x 52.1% x 57.9%, p=0.5). Multivariate analysis with Cox regression showed the following main predictors of late mortality: age (aHR 1.03; 95% CI: 1.02–1.04) and dementia (aHR 1.85; 95% CI: 1.31–2.62). The HFpEF group (aHR 1.63; 95% CI: 1.08–2.94) had higher mortality as compared to the HFmrEF (aHR 0.59; 95% CI: 0.36–0.97) and the HFrEF (aHR 0.63; 95% CI: 0.32–1.2) groups. Conclusion Factors associated with aging, such as dementia, were predictors of higher late mortality. The multivariate analysis of survival, regardless of the risk factors studied, showed a higher 3-year mortality in the HFpEF group as compared to that of the HFmrEF and HFrEF groups. Funding Acknowledgement Type of funding source: None

scholarly journals Nonalcoholic Fatty Liver Disease and Risk of Heart Failure Among Medicare Beneficiaries

2021 ◽  
Author(s):  
Marat Fudim ◽  
Lin Zhong ◽  
Kershaw V. Patel ◽  
Rohan Khera ◽  
Manal F. Abdelmalek ◽  
...  
Keyword(s):  
Heart Failure ◽  
Liver Disease ◽  
Ejection Fraction ◽  
Fatty Liver Disease ◽  
Preserved Ejection Fraction ◽  
Medicare Beneficiaries ◽  
Nonalcoholic Fatty Liver ◽  
Reduced Ejection Fraction ◽  
Increased Risk

Background Nonalcoholic fatty liver disease (NAFLD) and heart failure (HF) are increasing in prevalence. The independent association between NAFLD and downstream risk of HF and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection fraction) is not well established. Methods and Results This was a retrospective, cohort study among Medicare beneficiaries. We selected Medicare beneficiaries without known prior diagnosis of HF. NAFLD was defined using presence of 1 inpatient or 2 outpatient claims using International Classification of Diseases, Ninth Revision, Clinical Modification ( ICD‐9‐CM ), claims codes. Incident HF was defined using at least 1 inpatient or at least 2 outpatient HF claims during the follow‐up period (October 2015–December 2016). Among 870 535 Medicare patients, 3.2% (N=27 919) had a clinical diagnosis of NAFLD. Patients with NAFLD were more commonly women, were less commonly Black patients, and had a higher burden of comorbidities, such as diabetes, obesity, and kidney disease. Over a mean 14.3 months of follow‐up, patients with (versus without) baseline NAFLD had a significantly higher risk of new‐onset HF in unadjusted (6.4% versus 5.0%; P <0.001) and adjusted (adjusted hazard ratio [HR] [95% CI], 1.23 [1.18–1.29]) analyses. Among HF subtypes, the association of NAFLD with downstream risk of HF was stronger for HF with preserved ejection fraction (adjusted HR [95% CI], 1.24 [1.14–1.34]) compared with HF with reduced ejection fraction (adjusted HR [95% CI], 1.09 [0.98–1.2]). Conclusions Patients with NAFLD are at an increased risk of incident HF, with a higher risk of developing HF with preserved ejection fraction versus HF with reduced ejection fraction. The persistence of an increased risk after adjustment for clinical and demographic factors suggests an epidemiological link between NAFLD and HF beyond the basis of shared risk factors that requires further investigation.

scholarly journals Predictors of all-cause mortality among patients with implantable cardiac defibrillators for nonischemic heart failure with reduced ejection fraction

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
G Cinier ◽  
MI Hayiroglu ◽  
AC Yumurtas ◽  
Z Kolak ◽  
T Cetin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cox Regression ◽  
Icd Implantation ◽  
Reduced Ejection Fraction ◽  
All Cause Mortality ◽  
Long Term Follow Up ◽  
Implantable Cardiac Defibrillators

Abstract Funding Acknowledgements Type of funding sources: None. Background Implantable cardiac defibrillators (ICD’s) are recommended in patients with heart failure with reduced ejection fraction (HFrEF) of nonischemic etiology. Determining patients who are at high risk despite ICD implantation is of clinical value. Methods Between 2009-2019 patients who were implanted ICD due to nonischemic HFrEF were included to the present analysis. Baseline characteristics, laboratory parameters and echocardiographic findings were obtained from the electronic database. The primary outcome was all-cause mortality. Appropriate and inappropriate device therapies were also extracted from the database and was confirmed with patients’ reports. Predictors for long term all-cause mortality was determined by using Cox regression analysis. Results Overall, 1199 patients were screened and 238 were eligible for the analysis. ICD’s were implanted for primary and secondary prevention in 68 (28.6%) and 170 (71.4%) of patients respectively. Multivariate analysis revealed that increased pro-BNP [Hazard ratio (HR): 1.001, 95% Confidence interval (CI): 1.000 – 1.001, p = 0.024] and reduced left ventricle ejection fraction (HR: 0.950, 95% CI: 0.907 – 0.994, p: 0.026) predicted all-cause mortality during long term follow up. Pro-BNP &gt; 425 pg/ml has sensitivity and specificity of 74% for each in predicting all-cause mortality. Conclusion Among patients who were implanted ICD for HFrEF of nonischemic etiology, higher pro-BNP prior to the implantation and lower LVEF predicted all-cause mortality during long term follow up. Table 1Univariate analysisP valueHR (95% CI)Multivariate analysisP valueHR (95% CI)Diabetes mellitus0.0062.587 (1.315 - 5.090)Diabetes mellitus0.1441.837 (0.812 - 4.153)Atrial fibrillation0.0023.080 (1.531 - 6.195)Atrial fibrillation0.1811.738 (0.774 - 3.903)NYHA &gt; 20.0172.394 (1.168 - 4.908)NYHA &gt; 20.2531.642 (0.701 - 3.847)RDW0.0441.191 (1.005 - 1.412)RDW0.6461.046 (0.862 - 1.270)Lymphocytes0.0220.616 (0.408- 0.932)Lymphocytes0.1650.683 (0.399 - 1.170)Blood urea nitrogen0.0381.015 (1.001- 1.030)Blood urea nitrogen0.1521.015 (0.995 - 1.036)Pro-BNP&lt;0.0011.001 (1.000 - 1.001)Pro-BNP0.0241.001 (1.000 - 1.001)Albumin&lt;0.0010.252 (0.143 - 0.444)Albumin0.0790.525 (0.256 - 1.079)Ejection fraction&lt;0.0010.921 (0.885 - 0.959)Ejection fraction0.0260.950 (0.907 - 0.994)LVEDD0.0011.408 (1.017 - 1.079)LVEDD0.1521.078 (0.973 - 1.194)LVESD0.0041.038 (1.012 - 1.065)LVESD0.2890.957 (0.883 - 1.038)Appropriate shock in follow-up0.0102.407 (1.237 - 4.684)Appropriate shock in follow-up0.1561.768 (0.805 - 3.883)Univariate and multivariate Cox regression analyses for long-term mortality after ICD implantation Abstract Figure 1

scholarly journals Sacubitril/Valsartan Induces Global Cardiac Reverse Remodeling in Long-Lasting Heart Failure with Reduced Ejection Fraction: Standard and Advanced Echocardiographic Evidences

2020 ◽  
Vol 9 (4) ◽  
pp. 906 ◽  
Author(s):  
Matteo Castrichini ◽  
Paolo Manca ◽  
Vincenzo Nuzzi ◽  
Giulia Barbati ◽  
Antonio De Luca ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
Reverse Remodeling ◽  
Prognostic Impact ◽  
Reduced Ejection Fraction

Sacubitril/valsartan reduces mortality in heart failure with reduced ejection fraction (HFrEF) patients, partially due to cardiac reverse remodeling (RR). Little is known about the RR rate in long-lasting HFrEF and the evolution of advanced echocardiographic parameters, despite their known prognostic impact in this setting. We sought to evaluate the rates of left ventricle (LV) and left atrial (LA) RR through standard and advanced echocardiographic imaging in a cohort of HFrEF patients, after the introduction of sacubitril/valsartan. A multi-parametric standard and advanced echocardiographic evaluation was performed at the moment of introduction of sacubitril/valsartan and at 3 to 18 months subsequent follow-up. LVRR was defined as an increase in the LV ejection fraction ≥10 points associated with a decrease ≥10% in indexed LV end-diastolic diameter; LARR was defined as a decrease >15% in the left atrium end-systolic volume. We analyzed 77 patients (65 ± 11 years old, 78% males, 40% ischemic etiology) with 76 (28–165) months since HFrEF diagnosis. After a median follow-up of 9 (interquartile range 6–14) months from the beginning of sacubitril/valsartan, LVRR occurred in 20 patients (26%) and LARR in 33 patients (43%). Moreover, left ventricular global longitudinal strain (LVGLS) improved from −8.3 ± 4% to −12 ± 4.7% (p < 0.001), total left atrial emptying fraction (TLAEF) from 28.2 ± 14.4% to 32.6 ± 13.7% (p = 0.01) and peak atrial longitudinal strain (PALS) from 10.3 ± 6.9% to 13.7 ± 7.6% (p < 0.001). In HFrEF patients, despite a long history of the disease, the introduction of sacubitril/valsartan provides a rapid global (i.e., LV and LA) RR in >25% of cases, both at standard and advanced echocardiographic evaluations.

scholarly journals Refining the Role of Left Atrial Strain in Heart Failure with Reduced Ejection Fraction

2021 ◽  
Author(s):  
Alessandro Malagoli ◽  
Luca Rossi ◽  
Alessia Zanni ◽  
Concetta Sticozzi ◽  
Massimo Francesco Piepoli ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Left Atrial ◽  
Left Atrial Strain ◽  
Reduced Ejection Fraction ◽  
Atrial Strain

Abstract 14922: Prognostic Value of Baseline BNP and NT-ProBNP and its Interaction With Spironolactone in Patients With Heart Failure and Preserved Ejection Fraction in the TOPCAT Trial

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Inder S Anand ◽  
Scott D Solomon ◽  
Brian Claggett ◽  
Sanjiv J Shah ◽  
Eileen O’Meara ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Primary Outcome ◽  
Cox Regression ◽  
Selection Criterion ◽  
Adverse Outcomes ◽  
Preserved Ejection Fraction ◽  
Patient Selection Criterion ◽  
Increased Risk ◽  
Patients With Heart Failure

Background: Plasma natriuretic peptides (NP) are helpful in the diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) and predict adverse outcomes. Levels of NP beyond a certain cut-off level are often used as inclusion criteria in clinical trials to ensure that the patients have HF, and to select patients at higher risk. Whether treatments have a differential effect on outcomes across the spectrum of NP levels is unclear. In the I-Preserve trial a benefit of irbesartan on all outcomes was only seen in HFpEF patients with low but not high NP levels. We hypothesized that in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial, spironolactone might have a greater benefit in patients with lower NP levels. Methods and Results: BNP (n=468) or NT-proBNP (n=400) levels were available at baseline in 868 patients with HFpEF enrolled in the natriuretic peptide stratum (BNP ≥100 pg/mL or an NT- proBNP ≥360 pg/mL) of the TOPCAT trial. In a multi-variable Cox regression model, that included age, gender, region (Americas vs. Russia/Georgia), atrial fibrillation, diabetes, eGFR, BMI and heart rate, higher BNP or NT-proBNP as a continuous, standardized log-transformed variable or grouped by terciles (see Figure for BNP & NT-proBNP tercile values) was independently associated with an increased risk of the primary endpoint of cardiovascular mortality, aborted cardiac arrest, or hospitalization for heart failure (Figure-1). There was a significant interaction between the effect of spironolactone and baseline BNP or NT-proBNP terciles for the primary outcome (P=0.02, Figure-2), with greater benefit of the drug in the lower compared to higher NP terciles. Conclusions: The benefit of spironolactone in lower risk HFpEF patients may indicate effects of the drug on early, but not late higher-risk stage of the disease. These findings question the strategy of using elevated NP as a patient selection criterion in HFpEF trials.

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