P2604Clinical features associated with the development of diastolic dysfunction

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S H Bots ◽  
G B Verschoor ◽  
F H Rutten ◽  
N C Onland-Moret ◽  
L Hofstra ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Clinical Features ◽  
Blood Lipid ◽  
Stepwise Logistic Regression ◽  
Men And Women ◽  
Adjusted Risk ◽  
Increased Risk ◽  
Pressure Lowering

Abstract Background/Introduction Treatment for heart failure with preserved ejection fraction (HFpEF) is still elusive, which is a serious problem given the fact that it affects approximately 8 million people in Europe. Diastolic dysfunction (DD) is considered a precursor of HFpEF and could serve as a target for prevention. However, it is yet unclear which clinical features are associated with the development of diastolic dysfunction in men and women. Purpose To determine which clinical features are associated with the development of diastolic dysfunction in men and women visiting a cardiology outpatient clinic. Methods All individuals who visited one of the 13 Cardiology Centers Netherlands locations at least twice between April and 2007 and February 2018 for an echocardiographic evaluation were eligible for inclusion. Participants with incomplete data on diastolic function parameters or diastolic dysfunction at baseline were excluded. Information on age, sex, body mass index (BMI), systolic blood pressure (SBP), blood lipid levels, kidney function, cardiac history, co-morbidities and cardiovascular drug use was obtained for all participants. Diastolic function was scored based on E/e', relative wall thickness (RWT) and left-atrial dimension indexed by body surface area (LAD/BSA). The score allotted zero points for E/e' ≤8, RWT ≤0.41 and LAD/BSA ≤2.3, one point for E/e' between 9–14, RWT >0.42 and LAD/BSA >2.3, and two points for E/e' ≥15. Development of DD was defined as an increase in diastolic function score between the first and second echo. Missing data on determinants (max 26%) was imputed using multiple imputation. A stepwise logistic regression based on AIC was applied to evaluate the association between selected clinical features and DD. All analyses were performed in R. Results The study population comprised 1301 patients with a mean age of 56 (± 11) years and 46% were women. The median time between echo appointments was 631 (IQR: 381–1132) days and 549 patients developed DD (42%). After stepwise regression, the final model included age, sex, BMI, SBP, triglycerides and hypertension. DD was less likely to occur in men compared with women (OR=0.62, 95% CI: 0.57–0.67), and more likely in patients with hypertension (OR=1.29, 95% CI: 1.18–1.42) after adjustment. The adjusted risk for DD increased with triglyceride level (OR=1.24, 95% CI: 1.19–1.29), age (OR=1.04 per year, 95% CI: 1.03–1.04), BMI (OR=1.03 per kg/m2, 95% CI: 1.01–1.04) and SBP (OR=1.01 per 1 mmHg, 95% CI: 1.006–1.011) (Figure 1). Figure 1 Conclusion(s) Women and those with hypertension were at higher risk of developing DD compared to their male or normotensive counterparts. Age, triglyceride levels, BMI and SBP were also independently associated with an increased risk for DD. Prevention efforts focussing on life style changed and possibly lipid and blood pressure lowering drugs may reduce the risk of developing DD.

scholarly journals A Sex-Specific Role of Endothelial Sirtuin 3 on Blood Pressure and Diastolic Dysfunction in Female Mice

2020 ◽  
Vol 21 (24) ◽  
pp. 9744
Author(s):  
Heng Zeng ◽  
Xiaochen He ◽  
Jian-Xiong Chen
Keyword(s):  
Blood Pressure ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Normal Diet ◽  
Specific Role ◽  
Sirtuin 3 ◽  
Control Female ◽  
Female Mice ◽  
Flow Reserve

Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by a diastolic dysfunction and is highly prevalent in aged women. Our study showed that ablation of endothelial Sirtuin 3 (SIRT3) led to diastolic dysfunction in male mice. However, the sex-specific role of endothelial SIRT3 deficiency on blood pressure and diastolic function in female mice remains to be investigated. Methods and Results: In this study, we demonstrate that the ablation of endothelial SIRT3 in females elevated blood pressure as compared with control female mice. Diastolic function measurement also showed that the isovolumic relaxation time (IVRT) and myocardial performance index (MPI) were significantly increased, whereas the E’ velocity/A’ velocity (E’/A’) ratio was reduced in the endothelial-specific SIRT3 knockout (SIRT3 ECKO) female mice. To further investigate the regulatory role of endothelial SIRT3 on blood pressure and diastolic dysfunction in metabolic stress, SIRT3 ECKO female mice were fed a normal diet and high-fat diet (HFD) for 20 weeks. The knockout of endothelial SIRT3 resulted in an increased blood pressure in female mice fed with an HFD. Intriguingly, SIRT3 ECKO female mice + HFD exhibited impaired coronary flow reserve (CFR) and more severe diastolic dysfunction as evidenced by an elevated IVRT as compared with control female mice + HFD. In addition, female SIRT3 ECKO mice had higher blood pressure and diastolic dysfunction as compared to male SIRT3 ECKO mice. Moreover, female SIRT3 ECKO mice + HFD had an impaired CFR and diastolic dysfunction as compared to male SIRT3 ECKO mice + HFD. Conclusions: These results implicate a sex-specific role of endothelial SIRT3 in regulating blood pressure and diastolic function in mice. Deficiency of endothelial SIRT3 may be responsible for a diastolic dysfunction in aged female.

scholarly journals Features of heart failure with preserved ejection fraction (HFpEF) in diabetic patients with resistant hypertension

2021 ◽  
Vol 24 (4) ◽  
pp. 304-314
Author(s):  
M. A. Manukyan ◽  
A. Y. Falkovskaya ◽  
V. F. Mordovin ◽  
T. R. Ryabova ◽  
I. V. Zyubanova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Blood Pressure ◽  
Blood Flow ◽  
Ejection Fraction ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Resistant Hypertension ◽  
Diabetic Patients ◽  
Preserved Ejection Fraction

BACKGROUND: It is expected that a steady increase in the incidence of diabetes and resistant hypertension (RHTN), along with an increase in life expectancy, will lead to a noticeable increase in the proportion of patients with heart failure with preserved ejection fraction (HFpEF). At the same time, data on the frequency of HFpEF in a selective group of patients with RHTN in combination with diabetes are still lacking, and the pathophysiological and molecular mechanisms of its formation have not been yet studied sufficiently.AIM: To assess the features of the development HFpEF in diabetic and non-diabetic patients with RHTN, as well as to determine the factors associated with HFpEF.MATERIALS AND METHODS: In the study were included 36 patients with RHTN and type 2 diabetes mellitus (DM) (mean age 61.4 ± 6.4 years, 14 men) and 33 patients with RHTN without diabetes, matched by sex, age and level of systolic blood pressure (BP). All patients underwent baseline office and 24-hour BP measurement, echocardiography with assess diastolic function, lab tests (basal glycemia, HbA1c, creatinine, aldosterone, TNF-alpha, hsCRP, brain naturetic peptide, metalloproteinases of types 2, 9 (MMP-2, MMP-9) and tissue inhibitor of MMP type 1 (TIMP-1)). HFpEF was diagnosed according to the 2019 AHA/ESC guidelines.RESULTS: The frequency of HFpEF was significantly higher in patients with RHTN with DM than those without DM (89% and 70%, respectively, p=0.045). This difference was due to a higher frequency of such major functional criterion of HFpEF as E/e’≥15 (p=0.042), as well as a tendency towards a higher frequency of an increase in left atrial volumes (p=0.081) and an increase in BNP (p=0.110). Despite the comparable frequency of diastolic dysfunction in patients with and without diabetes (100% and 97%, respectively), disturbance of the transmitral blood flow in patients with DM were more pronounced than in those without diabetes. Deterioration of transmitral blood flow and pseudo-normalization of diastolic function in diabetic patients with RHTN have relationship not only with signs of carbohydrate metabolism disturbance, but also with level of pulse blood pressure, TNF-alfa, TIMP-1 and TIMP-1 / MMP-2 ratio, which, along with the incidence of atherosclerosis, were higher in patients with DM than in those without diabetes.CONCLUSIONS: Thus, HFpEF occurs in the majority of diabetic patients with RHTN. The frequency of HFpEF in patients with DN is significantly higher than in patients without it, which is associated with more pronounced impairments of diastolic function. The progressive development of diastolic dysfunction in patients with diabetes mellitus is associated not only with metabolic disorders, but also with increased activity of chronic subclinical inflammation, profibrotic state and high severity of vascular changes.

Abstract 14648: Interleukin-18 Blockade Prevents Diastolic Dysfunction in a Mouse Model of Heart Failure With Preserved Ejection Fraction

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jessica A Regan ◽  
Adolofo G Mauro ◽  
Salvatore Carbone ◽  
Carlo Marchetti ◽  
Eleonora Mezzaroma ◽  
...  
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Ejection Fraction ◽  
Mouse Model ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Low Dose ◽  
Preserved Ejection Fraction ◽  
Interleukin 18 ◽  
Lv Diastolic Function

Background: Heart failure with preserved ejection fraction (HFpEF) is characterized by elevated left ventricular (LV) filling pressures due to impaired LV diastolic function. Low-dose infusion of angiotensin 2 (AT2) in the mouse induces a HFpEF phenotype without increasing blood pressure. AT2 infusion induces expression of Interleukin-18 (IL-18) in the heart. We therefore tested whether IL-18 mediated AT2-induced LV diastolic dysfunction in this model. Methods: We infused subcutaneously AT2 (0.2 mg/Kg/day) or a matching volume of vehicle via osmotic pumps surgically implanted in the interscapular space in adult wild-type (WT) male mice and IL-18 knock-out mice (IL-18KO). We also treated WT mice with daily intraperitoneal injections of recombinant murine IL-18 binding protein (IL-18bp, a naturally occurring IL-18 blocker) at 3 different doses (0.1, 0.3 and 1.0 mg/kg) or vehicle for 25 days starting on day 3. We performed a Doppler-echocardiography study before implantation and at 28 days to measure LV dimensions, mass, and systolic and diastolic function in all mice. LV catheterization was performed prior to sacrifice to measure LV end-diastolic pressure (LVEDP) using a Millar catheter. Results: AT2 induces a significant increase in isovolumetric relaxation time (IRT) and myocardial performance index (MPI) at Doppler echocardiography and elevation of LVEDP at catheterization, indicative of impaired LV diastolic function, in absence of any measurable effects on systolic blood pressure nor LV dimensions, mass, or systolic function. Mice with genetic deletion of IL-18 (IL-18 KO) or WT mice treated with IL-18bp had no significant increase in IRT, MPI or LVEDP with AT2 infusion. Conclusion: Genetic or pharmacologic IL-18 blockade prevent diastolic dysfunction in a mouse model of HFpEF induced by low dose AT2 infusion, suggesting a critical role of IL-18 in the pathophysiology of HFpEF.

Abstract 2280: Urine Albumin/creatinine Ratio, Cardiac Structure And Diastolic Function In Patients With Hypertension And Diastolic Dysfunction: The Validd Study

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Anil Verma ◽  
Rajesh Janardhanan ◽  
William L Daley ◽  
Susan Ritter ◽  
William A Kaye ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Organ Damage ◽  
Left Ventricular ◽  
Creatinine Ratio ◽  
Albumin Creatinine Ratio ◽  
End Organ Damage ◽  
Urine Albumin ◽  
Urine Albumin Creatinine Ratio

Background: Increasing urine albumin/creatinine ratio (ACR) is associated with systemic microvascular damage and increased cardiovascular morbidity and mortality. However, the relationship between albuminuria and left ventricular (LV) diastolic function, an early measure of myocardial end-organ damage in hypertension, has not been well defined. Methods: Urine ACR and echocardiographic measures of LV structure and function were assessed in 384 patients enrolled in the VALsartan In Diastolic Dysfunction (VALIDD) trial with mild hypertension and no heart failure and evidence of diastolic dysfunction based on Doppler assessment of myocardial relaxation velocities. Results: Urine ACR was undetected in 151 (39.3%) subjects, between 1 to 30 mg/g in 194 (50.5%), and > 30mg/g in 39 (10.2%). The mean blood pressure in the cohort was 143.8 ± 16.1/86.2 ± 10.3 mmHg and LV hypertrophy was present in < 4% of enrolled patients. Higher urine ACR was associated with lower annular relaxation velocity (E′), higher E/E′ (Figure ), higher prevalence of concentric LV remodeling and higher NT-ProBNP even after adjusting for age, diabetes, systolic BP, eGFR and LV mass index (LVMi) (p < 0.02 for all associations). Conclusion: Albuminuria is associated with worsening diastolic function in patients with hypertension, and both measures may represent important and modifiable markers of early end-organ damage even in patients with mild blood pressure elevation. E′ stratified by urine albumin creatinine ratio E/E′ stratified by urine albumin creatinine ratio

Abstract WP218: Increased Systolic Blood Pressure Variability Among Diabetic Patients is Associated With Higher Risk of Incident Stroke: A Secondary Analysis of ACCORDION

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Adam H de Havenon ◽  
Ka-Ho Wong ◽  
Eva Mistry ◽  
Mohammad Anadani ◽  
Shadi Yaghi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Variability ◽  
Proportional Hazards ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Diabetic Patients ◽  
Adjusted Risk ◽  
Cox Proportional Hazards Models ◽  
Increased Risk

Background: Increased blood pressure variability (BPV) has been associated with stroke risk, but never specifically in patients with diabetes. Methods: This is a secondary analysis of the Action to Control Cardiovascular Risk in Diabetes Follow-On Study (ACCORDION), the long term follow-up extension of ACCORD. Visit-to-visit BPV was analyzed using all BP readings during the first 36 months. The primary outcome was incident ischemic or hemorrhagic stroke after 36 months. Differences in mean BPV was tested with Student’s t-test. We fit Cox proportional hazards models to estimate the adjusted risk of stroke across lowest vs. highest quintile of BPV and report hazard ratios along with 95% confidence intervals (CI). Results: Our analysis included 9,241 patients, with a mean (SD) age of 62.7 (6.6) years and 61.7% were male. Mean (SD) follow-up was 5.7 (2.4) years and number of BP readings per patient was 12.0 (4.3). Systolic, but not diastolic, BPV was higher in patients who developed stroke (Table 1). The highest quintile of SBP SD was associated with increased risk of incident stroke, independent of mean blood pressure or other potential confounders. (Table 2, Figure 1). There was no interaction between SBP SD and treatment arm assignment, although the interaction for glucose approached significance (Table 2). Conclusion: Higher systolic BPV was associated with incident stroke in a large cohort of diabetic patients. Future trials of stroke prevention may benefit from interventions targeting BPV reduction.

scholarly journals Diastolic dysfunction and mortality in 436  360 men and women: the National Echo Database Australia (NEDA)

2020 ◽  
Author(s):  
David Playford ◽  
Geoff Strange ◽  
David S Celermajer ◽  
Geoffrey Evans ◽  
Gregory M Scalia ◽  
...  
Keyword(s):  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Cardiovascular Imaging ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Prognostic Impact ◽  
Ventricular Ejection Fraction ◽  
Increased Risk ◽  
American Society ◽  
Related Mortality

Abstract Aims  To examine the characteristics/prognostic impact of diastolic dysfunction (DD) according to 2016 American Society of Echocardiography (ASE) and European Society of Cardiovascular Imaging (ESCVI) guidelines, and individual parameters of DD. Methods and results  Data were derived from a large multicentre mortality-linked echocardiographic registry comprising 436 360 adults with ≥1 diastolic function measurement linked to 100 597 deaths during 2.2 million person-years follow-up. ASE/European Association of Cardiovascular Imaging (EACVI) algorithms could be applied in 392 009 (89.8%) cases; comprising 11.4% of cases with ‘reduced’ left ventricular ejection fraction (LVEF &lt; 50%) and 88.6% with ‘preserved’ LVEF (≥50%). Diastolic function was indeterminate in 21.5% and 62.2% of ‘preserved’ and ‘reduced’ LVEF cases, respectively. Among preserved LVEF cases, the risk of adjusted 5-year cardiovascular-related mortality was elevated in both DD [odds ratio (OR) 1.31, 95% confidence interval (CI) 1.22–1.42; P &lt; 0.001] and indeterminate status cases (OR 1.11, 95% CI 1.04–1.18; P &lt; 0.001) vs. no DD. Among impaired LVEF cases, the equivalent risk of cardiovascular-related mortality was 1.51 (95% CI 1.15–1.98, P &lt; 0.001) for increased filling pressure vs. 1.25 (95% CI 0.96–1.64, P = 0.06) for indeterminate status. Mitral E velocity, septal e’ velocity, E:e’ ratio, and LAVi all correlated with mortality. On adjusted basis, pivot-points of increased risk for cardiovascular-related mortality occurred at 90 cm/s for E wave velocity, 9 cm/s for septal e’ velocity, an E:e’ ratio of 9, and an LAVi of 32 mL/m2. Conclusion  ASE/EACVI-classified DD is correlated with increased mortality. However, many cases remain ‘indeterminate’. Importantly, when analysed individually, mitral E velocity, septal e’ velocity, E:e’ ratio, and LAVi revealed clear pivot-points of increased risk of cardiovascular-related mortality.

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