Abstract 11159: Prolonged QRS Duration Predicts Outcomes in Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jacob Joseph ◽  
Brian L Claggett ◽  
Inder S Anand ◽  
Jerome L Fleg ◽  
Thao Huynh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Primary Outcome ◽  
Statistical Significance ◽  
Study Cohort ◽  
Preserved Ejection Fraction ◽  
Entire Study ◽  
Increased Risk ◽  
Qrs Duration ◽  
Entire Study Cohort

Introduction: QRS widening on the surface electrocardiogram (ECG) is a marker of disease progression in heart failure (HF) with reduced ejection fraction. We hypothesized that prolonged QRS duration would similarly identify patients with HF with preserved ejection fraction (HFPEF) at high risk for cardiovascular (CV) events. Methods: We examined the relationship of baseline QRS duration to primary outcome [composite of CV death, aborted cardiac arrest, or HF hospitalization (HFH)] and HFH alone in TOPCAT, a multicenter, randomized, placebo-controlled trial of spironolactone in HFPEF. QRS duration was analyzed as a dichotomous variable (≥ 120 ms or < 120 ms). Multivariable analyses were conducted including variables that were significantly associated with QRS duration ≥ 120 ms (Table 1). Analyses were conducted in the entire study cohort as well as in separate analyses for only subjects enrolled from the Americas or from Russia/Georgia independently. Results: QRS duration was known in 3426 of 3445 TOPCAT patients. Compared to those with QRS duration < 120ms, 613 (17.9%) subjects had a QRS duration ≥ 120 ms and were older (72.9 years vs. 67.8 years; p < 0.0001) and more likely to be men (62% vs. 45%; p<0.0001). A QRS duration ≥ 120 ms was independently associated with an increased risk of primary outcome and HFH in the entire study cohort and in the subset of patients enrolled in the Americas but was of borderline statistical significance in Russia/Georgia (Table 1). No statistical interaction was observed between treatment with spironolactone and QRS duration (p value for interaction= 0.33). Conclusions: QRS duration identifies HFPEF subjects at a higher risk of adverse clinical outcomes; spironolactone had a similar effect on outcomes independent of QRS duration. This easily obtainable marker may be an important component of risk stratification in this syndrome.

scholarly journals Serum uric acid, influence of sacubitril/valsartan, and cardiovascular outcomes in heart failure with preserved ejection fraction: PARAGON-HF

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Selvaraj ◽  
B.L Claggett ◽  
D.V Veldhuisen ◽  
I.S Anand ◽  
B Pieske ◽  
...  
Keyword(s):  
Heart Failure ◽  
Uric Acid ◽  
Ejection Fraction ◽  
Serum Uric Acid ◽  
Primary Outcome ◽  
Adverse Outcomes ◽  
Funding Source ◽  
Preserved Ejection Fraction ◽  
Private Company ◽  
Increased Risk

Abstract Background Serum uric acid (SUA) is a biomarker of several pathobiologies relevant to the pathogenesis of heart failure with preserved ejection fraction (HFpEF), though by itself may also worsen outcomes. In HF with reduced EF, SUA is independently associated with adverse outcomes and sacubitril/valsartan reduces SUA compared to enalapril. These effects in HFpEF have not been delineated. Purpose To determine the prognostic value of SUA, relationship of change in SUA to quality of life and outcomes, and influence of sacubitril/valsartan on SUA in HFpEF. Methods We analyzed 4,795 participants from the Prospective Comparison of ARNI with ARB Global Outcomes in HF with Preserved Ejection Fraction (PARAGON-HF) trial. We related baseline hyperuricemia to the primary outcome (CV death and total HF hospitalization), its components, myocardial infarction or stroke, and a renal composite outcome. At the 4-month visit, the relationship between SUA change and Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS) and several biomarkers including N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also assessed. We simultaneously adjusted for baseline and time-updated SUA to determine whether lowering SUA was associated with clinical benefit. Results Average age was 73±8 years and 52% were women. After multivariable adjustment, hyperuricemia was associated with increased risk for most outcomes (primary outcome HR 1.61, 95% CI 1.37, 1.90, Fig 1A). The treatment effect of sacubitril/valsartan for the primary outcome was not modified by baseline SUA (interaction p=0.11). Sacubitril/valsartan reduced SUA −0.38 mg/dL (95% CI: −0.45, −0.31) compared with valsartan (Fig 1B), with greater effect in those with baseline hyperuricemia (−0.50 mg/dL) (interaction p=0.013). Change in SUA was independently and inversely associated with change in KCCQ-OSS (p=0.019) and eGFR (p&lt;0.001), but not NT-proBNP (p=0.52). Time-updated SUA was a stronger predictor of adverse outcomes over baseline SUA. Conclusions SUA independently predicts adverse outcomes in HFpEF. Sacubitril/valsartan significantly reduces SUA compared to valsartan, an effect that was stronger in those with higher baseline SUA, and reducing SUA was associated with improved outcomes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Novartis

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.

Association of Hyper-Polypharmacy With Clinical Outcomes in Heart Failure With Preserved Ejection Fraction

2021 ◽  
Author(s):  
Masatoshi Minamisawa ◽  
Brian Claggett ◽  
Kota Suzuki ◽  
Sheila M. Hegde ◽  
Amil M. Shah ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adverse Events ◽  
Ejection Fraction ◽  
Primary Outcome ◽  
Hazard Ratio ◽  
Preserved Ejection Fraction ◽  
Serious Adverse Events ◽  
Increased Risk ◽  
Patients With Heart Failure ◽  
The Relationship

Background: Polypharmacy is associated with a poor prognosis in the elderly, however, information on the association of polypharmacy with cardiovascular outcomes in heart failure with preserved ejection fraction is sparse. This study sought to investigate the relationship between polypharmacy and adverse cardiovascular events in patients with heart failure with preserved ejection fraction. Methods: Baseline total number of medications was determined in 1758 patients with heart failure with preserved ejection fraction enrolled in the Americas regions of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist), by 3 categories: nonpolypharmacy (<5 medications), polypharmacy (5–9), and hyper-polypharmacy (≥10). We examined the relationship of polypharmacy status with the primary outcome (cardiovascular death, HF hospitalization, or aborted cardiac arrest), hospitalizations for any reason, and serious adverse events. Results: The proportion of patients taking 5 or more medications was 92.5% (inclusive of polypharmacy [38.7%] and hyper-polypharmacy [53.8%]). Over a 2.9-year median follow-up, compared with patients with polypharmacy, hyper-polypharmacy was associated with an increased risk for the primary outcome, hospitalization for any reason and any serious adverse events in the univariable analysis, but not significantly associated with mortality. After multivariable adjustment for demographic and comorbidities, hyper-polypharmacy remained significantly associated with an increased risk for hospitalization for any reason (hazard ratio, 1.22 [95% CI, 1.05–1.41]; P =0.009) and any serious adverse events (hazard ratio, 1.23 [95% CI, 1.07–1.42]; P =0.005), whereas the primary outcome was no longer statistically significant. Conclusions: Hyper-polypharmacy was common and associated with an elevated risk of hospitalization for any reason and any serious adverse events in patients with heart failure with preserved ejection fraction. There were no significant associations between polypharmacy status and mortality.

Abstract 12936: Impact of Mitral Regurgitation on Heart Failure Hospitalization and Mortality in Older Age Adults With a Preserved Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ginger Y Jiang ◽  
Warren J Manning ◽  
Lawrence Markson ◽  
A. R Garan ◽  
Marwa A Sabe ◽  
...  
Keyword(s):  
Heart Failure ◽  
Mitral Regurgitation ◽  
Ejection Fraction ◽  
Primary Outcome ◽  
Secondary Outcome ◽  
P Value ◽  
Preserved Ejection Fraction ◽  
Risk Of Death ◽  
Increased Risk ◽  
All Cause Mortality

Background: The effect of mitral regurgitation (MR) severity on heart failure (HF) hospitalization and mortality in individuals with a preserved ejection fraction (LVEF) and no prior HF history is uncertain. Methods: Transthoracic echocardiogram (TTE) reports from patients with an LVEF > 50% at our institution were linked to complete Medicare inpatient claims, 2003-2017. Patients with HF hospitalization within the 12 months prior to TTE were excluded. We evaluated the relationship of baseline MR severity and time to the composite of all-cause mortality or HF hospitalization using the Kaplan-Meier technique. Secondary outcomes included the individual components of all-cause mortality and HF hospitalization, adjusting for the competing risk of death with Fine-Gray methods. Results: A total of 18,315 individuals met inclusion criteria (77.6 ±7.7 years, 54.3% female). Over a median follow-up time of 6.5 (IQR 3.0 to 10.2) years, the primary endpoint occurred in 7566 individuals (50.6%) of whom 6,927 (37.8%) died and 1703 (13.9%) were admitted for HF at a median of 1.4 (IQR 0.2 to 4.3) years and 1.6 (IQR 0.2 to 4.3) years respectively ( Figure ). After multivariable adjustment, MR severity was not associated with the primary or secondary outcome at 1-, 3-, 5-, or 10-years after TTE (p > 0.05 for all). Mitral valve prolapse (MVP) was associated with decreased risk of the primary outcome at 1-year and 3-years (interaction p-value = 0.04 for both). Jet eccentricity did not impact the observed relationship (interaction p-value > 0.05). Conclusions: In this large, single institution echocardiographic study of individuals with preserved ejection fraction and no prior history of HF, MR severity was not associated with an increased risk of all-cause mortality or HF hospitalization. Presence of MVP was associated with decreased risk of the primary outcome with increasing MR severity.

Prevalence and prognostic significance of heart failure with preserved ejection fraction in systemic sclerosis

2021 ◽  
Author(s):  
Marta Fontes Oliveira ◽  
Ana Leonor Rei ◽  
Maria Isilda Oliveira ◽  
Isabel Almeida ◽  
Mário Santos
Keyword(s):  
Heart Failure ◽  
Systemic Sclerosis ◽  
Ejection Fraction ◽  
Statistical Significance ◽  
Prognostic Significance ◽  
Left Ventricular ◽  
Preserved Ejection Fraction ◽  
Increased Risk ◽  
Atrial Enlargement

Aim: Heart failure with preserved ejection fraction (HFpEF) is a clinically relevant complication of systemic sclerosis (SSc). We aimed to examine the prevalence, correlates and prognostic significance of HFpEF in an SSc population. Materials & methods: HFpEF was defined by the presence of exertional dyspnoea, abnormal cardiac structure (left ventricular hypertrophy or left atrial enlargement) and NT-proBN (>125 pg/ml). Results: Of the 155 studied patients, 27% had HFpEF criteria. These patients were older, had more cardiovascular risk factors, and were more likely to have atrial fibrillation or interstitial lung disease. Conclusion: Over a median follow-up of 9 years, SSc patients with HFpEF had a 3.4-fold increased risk of dying (HR: 3.37, 95% CI: 1.21–9.31), although this association has lost statistical significance after adjusting for age. On the contrary, NT-proBNP was an independent predictor of a worse prognosis.

scholarly journals Prognostic Implication of Liver Function Tests in Heart Failure With Preserved Ejection Fraction Without Chronic Hepatic Diseases: Insight From TOPCAT Trial

2021 ◽  
Vol 8 ◽  
Author(s):  
Weihao Liang ◽  
Xin He ◽  
Dexi Wu ◽  
Ruicong Xue ◽  
Bin Dong ◽  
...  
Keyword(s):  
Heart Failure ◽  
Liver Function ◽  
Ejection Fraction ◽  
Cardiovascular Mortality ◽  
Primary Outcome ◽  
Prognostic Significance ◽  
Liver Function Tests ◽  
Preserved Ejection Fraction ◽  
Hepatic Diseases ◽  
Function Tests

Background: Liver dysfunction is prevalent in patients with heart failure (HF), but the prognostic significance of liver function tests (LFTs) remains controversial. Heart failure with preserved ejection fraction (HFpEF) had been introduced for some time, but no previous study had focused on LFTs in HFpEF. Thus, we aim to evaluate the prognostic significance of LFTs in well-defined HFpEF patients.Methods and Results: We conveyed a post-hoc analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT). The primary outcome was the composite of cardiovascular mortality, HF hospitalization, and aborted cardiac arrest, and the secondary outcomes were cardiovascular mortality and HF hospitalization. In Cox proportional hazards models, aspartate transaminase (AST) and alanine transaminase (ALT) were not associated with any of the outcomes. On the contrary, increases in total bilirubin (TBIL) and alkaline phosphatase (ALP) were associated with increased risks of the primary outcome [TBIL: adjusted hazard ratio (HR), 1.17; 95% confidence interval (CI) 1.08–1.26; ALP: adjusted HR, 1.12; 95% CI 1.04–1.21], cardiovascular mortality (TBIL: adjusted HR, 1.16; 95% CI 1.02–1.31; ALP: adjusted HR, 1.16; 95% CI 1.05–1.28), and HF hospitalization (TBIL: adjusted HR, 1.22; 95% CI 1.12–1.33; ALP: adjusted HR, 1.12; 95% CI 1.03–1.23).Conclusion: Elevated serum cholestasis markers TBIL and ALP were significantly associated with a poor outcome in HFpEF patients without chronic hepatic diseases, while elevated ALT and AST were not.

scholarly journals 216-70: QRS duration and bundle branch block pattern - Prevalence in heart failure with preserved ejection fraction

EP Europace ◽  
2016 ◽  
Vol 18 (suppl_1) ◽  
pp. i159-i159
Author(s):  
Liam Toner ◽  
Alex Voskoboinik ◽  
Michelle Ord ◽  
Andrew Teh ◽  
Han Lim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Preserved Ejection Fraction ◽  
Bundle Branch Block ◽  
Qrs Duration ◽  
Block Pattern

scholarly journals MR-proANP and incident cardiovascular disease in patients with type 2 diabetes with and without heart failure with preserved ejection fraction

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jesper Jensen ◽  
Morten Schou ◽  
Caroline Kistorp ◽  
Jens Faber ◽  
Tine W. Hansen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Natriuretic Peptides ◽  
Continuous Variable ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
Definition Of

Abstract Background Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D. Methods We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6–17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP. Results A total of 126 CV events occurred (median follow-up 4.8 [4.1–5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89–202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64–4.00] and 3.32 [1.64–6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32–56] pmol/l) did not have an increased risk (HR 2.18 [0.78–6.14]). Conclusions Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.

scholarly journals Cardiac Tissue Factor Regulates Inflammation, Hypertrophy and Heart Failure in Mouse Model of Type 1 Diabetes

2021 ◽  
Author(s):  
Dasan Mary Cibi ◽  
Reddemma Sandireddy ◽  
Hanumakumar Bogireddy ◽  
Nicole Tee ◽  
Siti Aishah Binte Abdul Ghani ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Tissue Factor ◽  
Cardiac Tissue ◽  
Immune Cell ◽  
Preserved Ejection Fraction ◽  
Cardiac Inflammation ◽  
Protein Levels ◽  
Increased Risk

Diabetes patients have an increased risk of heart failure (HF). Diabetes is highly prevalent in HF with preserved ejection fraction (HFpEF), which is on the rise worldwide. The role of diabetes in HF is less established and available treatments of HF are not effective in HFpEF patients. Tissue factor (TF), a transmembrane receptor, plays an important role in immune-cell inflammation and atherothrombosis in diabetes. However, its role in diabetes-induced cardiac inflammation, hypertrophy, and HF has not been studied. Here, we have utilized Wildtype (WT), heterozygous, and Low-TF (with 1% human TF) mice to determine TF’s role in <i>Type1 diabetes</i>-induced HF. We found significant upregulation of cardiac TF mRNA and protein levels in diabetic WT hearts compared to non-diabetic controls. WT diabetic hearts also exhibited increased inflammation and cardiac hypertrophy versus controls. However, these changes in cardiac inflammation and hypertrophy were not found in diabetic Low-TF mice compared to their non-diabetic controls. TF deficiency was also associated with improved cardiac function parameters suggestive of HFpEF, which was evident in diabetic WT mice. The TF regulation of inflammation and cardiac remodeling was further dependent on downstream ERK1/2 and STAT3 pathways. In summary, our study demonstrated an important role of TF in regulating diabetes-induced inflammation, hypertrophy, and remodeling of the heart leading to HF with preserved ejection fraction.

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