scholarly journals Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus

2020 ◽  
Vol 7 ◽  
Author(s):  
Mausam Patel ◽  
Daniela Rodriguez ◽  
Keyvan Yousefi ◽  
Krista John-Williams ◽  
Armando J. Mendez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Ejection Fraction ◽  
Cardiac Death ◽  
Density Lipoprotein ◽  
Molecular Pathways ◽  
Preserved Ejection Fraction ◽  
Control Subjects ◽  
Increased Risk

Background: Diabetes mellitus (DM) is associated with increased risk of sudden cardiac death (SCD), particularly in patients with heart failure with preserved ejection fraction (HFpEF). However, there are no known biomarkers in the population with DM and HFpEF to predict SCD risk.Objectives: This study was designed to test the hypothesis that osteopontin (OPN) and some proteins previously correlated with OPN, low-density lipoprotein receptor (LDLR), dynamin 2 (DNM2), fibronectin-1 (FN1), and 2-oxoglutarate dehydrogenase-like (OGDHL), are potential risk markers for SCD, and may reflect modifiable molecular pathways in patients with DM and HFpEF.Methods: Heart tissues were obtained at autopsy from 9 SCD victims with DM and HFpEF and 10 age and gender-matched accidental death control subjects from a Finnish SCD registry and analyzed for the expression of OPN and correlated proteins, including LDLR, DNM2, FN1, and OGDHL by immunohistochemistry.Results: We observed a significant upregulation in the expression of OPN, LDLR, and FN1, and a marked downregulation of DNM2 in heart tissues of SCD victims with DM and HFpEF as compared to control subjects (p < 0.01).Conclusions: The dysregulated protein expression of OPN, LDLR, FN1, and DNM2 in patients with DM and HFpEF who experienced SCD provides novel potential modifiable molecular pathways that may be implicated in the pathogenesis of SCD in these patients. Since secreted OPN and soluble LDLR can be measured in plasma, these results support the value of further prospective studies to assess the predictive value of these plasma biomarkers and to determine whether tuning expression levels of OPN and LDLR alters SCD risk in patients with DM and HFpEF.

Abstract 572: Hyperglycemia and Poor Outcomes in Patients without Diabetes Mellitus in the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS): A Propensity Matched Analysis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Prakash C Deedwania ◽  
Bertram Pitt ◽  
Enrique V Carbajal ◽  
Ali Ahmed
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Acute Myocardial Infarction ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Propensity Scores ◽  
Cox Regression ◽  
Baseline Serum ◽  
Increased Risk

Background: The effect of hyperglycemia on outcomes in patients with acute MI (AMI) and low LVEF without diabetes mellitus is not well known. Methods: In the EPHESUS trial, of the 4411 non-DM patients, 554 had baseline hyperglycemia (≥140 mg/dL). Propensity scores for hyperglycemia were calculated for each of the 4411 patients based on 63 baseline covariates, and a greedy 1:8 matching protocol was used to match 400 and 2542 patients respectively with and without hyperglycemia. Matched Cox regression models were used to estimate associations between hyperglycemia and outcomes during 16 months of follow up. Results: Patients with hyperglycemia were more likely to be older, have higher heart rate, lower LVEF, and receive nitrates, statins, digoxin, loop diuretics, and PTCA during index admission. Unadjusted hazard ratios {HR} and 95% confidence intervals {CI} for hyperglycemia were: all-cause death (1.51; 1.22–1.87; P<0.001), cardiovascular (CV) death (1.52; 1.21–1.90; P<0.001), heart failure (HF) death (2.19, 1.46–3.29; P<0.001), all-cause hospitalization (1.23; 1.08–1.40; P=0.002), CV hospitalization (1.51, 1.24–1.84; P<0.001) and HF hospitalization (1.75; 1.37–2.25; P<0.001). In the matched cohort, hyperglycemia was significantly associated with CV death (HR=1.25, 95%CI=1.01–1.54; P=0.039), sudden cardiac death (HR=1.33; 95%CI=1.02–1.73, P=0.035) and fatal/nonfatal AMI (HR=1.53, 95%CI=1.07–2.19; P=0.04; Figure ). Conclusions: In non-diabetic post-AMI HF patients, hyperglycemia is a poor prognosticator and is associated with increased risk of fatal and non-fatal AMI, CV death, HF deaths, sudden cardiac death, and CV hospitalization. Figure Fatal or non fatal acute myocardial infarction (AMI) by baseline serum glucose in post-AMI patients with no known history of diabetes mellitus

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.

Sudden Cardiac Death in Heart Failure Patients With Preserved Ejection Fraction

2012 ◽  
Vol 18 (10) ◽  
pp. 749-754 ◽  
Author(s):  
Selcuk Adabag ◽  
Lindsay G. Smith ◽  
Inder S. Anand ◽  
Alan K. Berger ◽  
Russell V. Luepker
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Ejection Fraction ◽  
Cardiac Death ◽  
Preserved Ejection Fraction ◽  
Heart Failure Patients

scholarly journals A prediction model for sudden cardiac death in patients with heart failure and preserved ejection fraction

2014 ◽  
Vol 16 (11) ◽  
pp. 1175-1182 ◽  
Author(s):  
Selcuk Adabag ◽  
Thomas S. Rector ◽  
Inder S. Anand ◽  
John J. McMurray ◽  
Michael Zile ◽  
...  
Keyword(s):  
Heart Failure ◽  
Sudden Cardiac Death ◽  
Ejection Fraction ◽  
Prediction Model ◽  
Cardiac Death ◽  
Preserved Ejection Fraction ◽  
Patients With Heart Failure

Abstract P308: Lower Neighborhood Socioeconomic Status is Associated with Higher BNP and Prolonged QTc Intervals among Heart Failure Patients with Preserved Ejection Fraction

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Norrina B Allen ◽  
Sylvia Badon ◽  
Sanjiv J Shah
Keyword(s):  
Heart Failure ◽  
Socioeconomic Status ◽  
Sudden Cardiac Death ◽  
Ejection Fraction ◽  
Census Tract ◽  
Cardiac Death ◽  
Nyha Class ◽  
Qtc Interval ◽  
Preserved Ejection Fraction ◽  
Neighborhood Socioeconomic Status

Background: Prior studies have shown that high B-type natriuretic peptide (BNP) levels and prolonged QTc intervals are associated with increased mortality, particularly sudden cardiac death, among heart failure (HF) patients. Whether neighborhood socioeconomic status (nSES) impacts BNP or QTc remains unknown. Methods: This study included consecutive patients enrolled from the outpatient clinic of the Northwestern Heart Failure with Preserved Ejection Fraction (HFpEF) Program from June 2007 to November 2010 after hospitalization for HF and followed through May 2011. Patients’ residential addresses were geocoded to identify their census tract of residence. Census 2000 data were used to create a single, summary score of nSES based on residential income, education and employment for each census tract and was divided into tertiles. Outcomes included post-discharge BNP and QTc, obtained within 1 month after HF hospitalization during the outpatient HFpEF clinic visit GEE models were used to examine the association between nSES and BNP and QTc adjusting for age, race, gender, NYHA class, blood pressure, obesity, smoking, glucose, eGFR, and comorbidities. Results: Among the 368 HFpEF patients, 37.0% were female, 50.5% White, avg. age was 64.8 yrs and 45.9% had NYHA class 3+. Higher nSES was significantly associated with lower BNP levels and shorter QTc intervals (Table). The adjusted BNP levels per nSES tertile were 718 pg/mL (±101.4) for the lowest nSES tertile, 508 pg/mL (± 75.3) for the intermediate nSES tertile and 454.2 pg/mL for the highest nSES tertile. Simlarly, QTc interval decreased with increasing tertile of nSES from 464.1 ms (± 5.7) in the lowest nSES tertile to 457.2 ms (± 5.8) and 448.9 ms (± 5.4) for the intermediate and highest tertiles, respectively. Conclusion: Low nSES is associated with increased BNP levels and a longer QTc interval in HFpEF patients. These findings may explain the association of nSES with higher rates of sudden cardiac death and worse outcomes among HF patients in disadvantaged neighborhoods.

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