Diabetes is associated with increased risk of CV events in heart failure with preserved ejection fraction: findings from the Irbesartan in Heart Failure with Preserved Systolic Function Trial

2008 ◽  
Vol 7 ◽  
pp. 2-2
Author(s):  
R MCKELVIE ◽  
M KOMAJDA ◽  
B MASSIE ◽  
J MCMURRAY ◽  
M ZILE ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Systolic Function ◽  
Preserved Ejection Fraction ◽  
Increased Risk

Abstract 3640: Diabetes Mellitus is Associated with Increased Risk of Fatal and Non-Fatal Cardiovascular Events in Heart Failure Patients with Preserved Ejection Fraction - Findings From the Irbesartan in Heart Failure with Preserved Systolic Function Trial

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Robert S McKelvie ◽  
Michel Komajda ◽  
Barry M Massie ◽  
John J McMurray ◽  
Michael R Zile ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Systolic Function ◽  
Clinical History ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
History Of ◽  
One Year

Background: Diabetes mellitus (DM), present in about a quarter of heart failure (HF) patients with reduced ejection fraction (HF-REF), is associated with increased risk of fatal and non-fatal cardiovascular (CV) events. Less is known about the prevalence and impact of DM in HF patients with preserved ejection fraction (HF-PEF). The prevalence and effect of DM on clinical outcomes were examined in patients enrolled in the Irbesartan in Heart Failure with Preserved Systolic Function Trial (I-PRESERVE). Methods: The I-PRESERVE trial randomized 4128 HF-PEF patients (EF≥45%) to receive irbesartan or placebo. The primary outcome of time to all-cause mortality or CV hospitalization (myocardial infarction [MI], stroke, worsening HF, atrial or ventricular arrhythmia or unstable angina) was compared between patients with and without DM over one year of follow-up. A combined HF endpoint (HF mortality and hospitalization) was also evaluated. Comparison of the outcomes between patients with and without DM was expressed as a hazard ratio (HR). The independent predictive role of DM was examined in a multivariable model (which included symptoms, signs, clinical history, CV examination, biochemical, and hematological findings). Results: In I-PRESERVE 27% had a history of DM at baseline. DM patients more often had a body mass index ≥30 (51% vs 38%), history of stroke (12% vs 9%), history of MI (28% vs 22%), estimated glomerular filtration rate <60 ml/min/1.73m 2 (34% vs 29%), and pulmonary congestion on chest x-ray (46% vs 38%). In patients with DM, 17% and 11% had primary and HF events, respectively within 1 year; for patients without DM, 11% and 6% had primary and HF events. In a multivariate analysis DM remained a significant predictor of primary events (HR 1.48; 95% CI 1.22, 1.79) or HF events (HR 1.67; 95% CI 1.32, 2.12). Conclusions: The prevalence of DM in HF-PEF is similar to that reported in HF-REF. HF-PEF patients with DM have a significantly worse outcome than those without DM and this increased risk is independent of other factors associated with a worse prognosis.

scholarly journals Central and obstructive apneas prevalence in heart failure with reduced, mid-range and preserved ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Borrelli ◽  
P Sciarrone ◽  
F Gentile ◽  
N Ghionzoli ◽  
G Mirizzi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Function ◽  
Systolic Dysfunction ◽  
Cardiopulmonary Exercise Testing ◽  
Left Ventricular ◽  
Apnea Hypopnea Index ◽  
Preserved Ejection Fraction ◽  
2D Echocardiography

Abstract Background Central apneas (CA) and obstructive apneas (OA) are highly prevalent in heart failure (HF) both with reduced and preserved systolic function. However, a comprehensive evaluation of apnea prevalence across HF according to ejection fraction (i.e HF with patients with reduced, mid-range and preserved ejection fraction- HFrEf, HFmrEF and HFpEF, respectively) throughout the 24 hours has never been done before. Materials and methods 700 HF patients were prospectively enrolled and then divided according to left ventricular EF (408 HFrEF, 117 HFmrEF, 175 HFpEF). All patients underwent a thorough evaluation including: 2D echocardiography; 24-h Holter-ECG monitoring; cardiopulmonary exercise testing; neuro-hormonal assessment and 24-h cardiorespiratory monitoring. Results In the whole population, prevalence of normal breathing (NB), CA and OA at daytime was 40%, 51%, and 9%, respectively, while at nighttime 15%, 55%, and 30%, respectively. When stratified according to left ventricular EF, CA prevalence decreased from HFrEF to HFmrEF and HFpEF: (daytime CA: 57% vs. 43% vs. 42%, respectively, p=0.001; nighttime CA: 66% vs. 48% vs. 34%, respectively, p&lt;0.0001), while OA prevalence increased (daytime OA: 5% vs. 8% vs. 18%, respectively, p&lt;0.0001; nighttime OA: 20 vs. 29 vs. 53%, respectively, p&lt;0.0001). When assessing moderte-severe apneas, defined with an apnea/hypopnea index &gt;15 events/hour, prevalence of CA was again higher in HFrEF than HFmrEF and HFpEF both at daytime (daytime moderate-severe CA: 28% vs. 19% and 23%, respectively, p&lt;0.05) and at nighttime (nighttime moderate-severe CA: 50% vs. 39% and 28%, respectively, p&lt;0.05). Conversely, moderate-severe OA decreased from HFrEF to HFmrEF to HFpEF both at daytime (daytime moderate-severe OA: 1% vs. 3% and 8%, respectively, p&lt;0.05) and nighttime (noghttime moderate-severe OA: 10% vs. 11% and 30%, respectively, p&lt;0.05). Conclusions Daytime and nighttime apneas, both central and obstructive in nature, are highly prevalent in HF regardless of EF. Across the whole spectrum of HF, CA prevalence increases and OA decreases as left ventricular systolic dysfunction progresses, both during daytime and nighttime. Funding Acknowledgement Type of funding source: None

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.

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 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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