Worse Diastolic Function Research Articles

Obesity accelerates cardiac senescence in heart failure with preserved ejection fraction

Abstract Background Diastolic reserve decreases with aging. A recently developed artificial intelligence (AI) algorithm can predict age based on 12-lead electrocardiogram (ECG) analysis. Purpose This study aims to use a validated AI algorithm to assess cardiac senescence and investigate the impact of obesity on cardiac aging in heart failure with preserved ejection fraction (HFpEF). Methods This retrospective cohort study includes 403 patients with HFpEF, admitted for treatment with intravenous diuretics. ECG age was assessed by a convolutional neural network as previously validated. Patients were stratified according to the presence of obesity (body mass index >30 kg/m2) and ECG age was compared between groups. The relationship between ECG versus calendar age and structural/functional alterations on echocardiography, as well as the risk of atrial fibrillation (AF) development, was evaluated. Results In 253 (63%) obese patients with HFpEF, calendar age was 8 years younger compared with their non-obese counterparts, but ECG age was only 3 years younger. ECG minus calendar age was higher in obese patients (P-value <0.001; figure) and correlated moderately strong with weight, fat free, and fat mass (r=0.35–0.41; P-value <0.001). Older ECG age was correlated with worse diastolic function, but not with left ventricular afterload (table). Calendar age correlated less strongly with diastolic dysfunction (table). ECG age did predict AF development, independently of calendar age, gender, and presence of obesity [HR (95% CI) = 1.31 (1.06–1.63) per 5-year; P-value=0.015]. Conclusions Obesity accelerates cardiac senescence in HFpEF as reflected by more pronounced diastolic dysfunction and a higher AF risk, which was identified from ECG analysis by a validated AI algorithm. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Belgian American Educational Foundation (B.A.E.F.); Special Research Fund (BOF) of Hasselt University (Hasselt, Belgium).

Abstract P044: Intensity Of Hypertensive Exposure In Young Adulthood And Myocardial Structure And Function In Middle Age

Background and aims: To measure the association between intensity of hypertensive exposure and myocardial structure and function during a 25-year period in young adulthood. Methods: The Coronary Artery Risk Development in Young Adults (CARDIA) Study enrolled 5,115 healthy black and white American aged 18-30 years at baseline (March 1985 to May 2011). Intensity of hypertensive exposure was estimated based on their durations of hypertension over 25 years. Myocardial structure and function was identified by echocardiogram at year 25. Results: Of 2027 participants, 1315 were women (64.9%) and 906 were black (44.7%); mean (SD) age was 24.9 (3.6) at baseline. Duration of stage 1 hypertension was associated with higher left ventricular (LV) structure: LV mass (β [SE], 3.69 [1.80], P < 0.001), relative wall thickness (β [SE], 0.009 [0.003], P = 0.001), worse longitudinal strain (β [SE], 0.27 [0.008], P < 0.001), worse diastolic function: e’ (β [SE], -0.25 [0.07], P < 0.001), E/e’ (β [SE], 0.23 [0.007], P < 0.001). Duration of stage 2 hypertension was associated with higher left ventricular (LV) structure: LV mass (β [SE], 7.30 [2.23], P = 0.001), worse longitudinal strain (β [SE], 0.44 [0.13], P = 0.001), worse diastolic function: e’ (β [SE], -0.77 [0.12], P < 0.001), E/e’ (β [SE], 0.48 [0.13], P < 0.001). Conclusions: In early adulthood, more severe intensity of hypertensive exposure is associated with myocardial structure and diastolic dysfunction in middle age. Key Words: cardiac structure, cardiac dysfunction, hypertension, young adult

Abstract 545: Sex Difference in Right Ventricular Response to Pressure Overload is Associated With Differential Fibrotic Remodeling and Cyclic Guanosine Monophosphate Signaling

Background: In HFpEF and PAH, men are more likely than women to develop right ventricular dysfunction (RVD) and die. Mechanisms underlying these sex differences are not well understood. In advanced HF patients, RVD is associated with RV fibrosis. Sex differences in cGMP anti-fibrotic cardioprotection have been reported. Hypothesis: Sex differences in RV response to pressure overload may be due to differential anti-fibrotic cGMP signaling in the RV. Methods: Adult male and female C57BL6/J mice underwent pulmonary artery banding (PAB, 25g) vs. thoracotomy (Sham). RV remodeling was assessed by echocardiography, pressure-volume loop recordings, morphometrics, and histology. Expression of transcripts encoding various cGMP signaling proteins ( Nppa, Nppb, Npr1, Npr2, Npr3, Gucy1a3, Gucy1b3, Pde5, Pde9a, Pkg1a ), the fetal gene program, tissue fibrosis and ECM remodeling ( Ace, Tgfβs, Smads, Ctgf, αSma, Postn, Col1α1, Lum, Igfbp5, Mmp2-3, Timp1-2) were assessed at 9wks. Results: Post-PAB survival rate did not differ between sexes (log-rank HR 1.02, 95% CI 0.30-3.48, P=NS), but median time-to-death was 20 days (IQR 15-32) for M-PAB vs. 35.5 days (IQR 10.8-41.5) for F-PAB. PAB increased RV mass in both sexes (Fulton’s index 0.45±0.07 M-PAB vs 0.21±0.01 M-Sham, P<0.01; 0.49±0.06 F-PAB vs 0.22±0.01 F-Sham, P<0.01). RV myocyte hypertrophy was greater in M-PAB (cardiomyocyte area 592.7±6μm 2 vs 397.7±21.6μm 2 F-PAB, P<0.01). RV dilation and decreased TAPSE and RV S’ were present in all PAB mice. Only M-PAB had depressed RV FAC (29.9±1.9% vs. 38.1±2.4% F-PAB, P=0.02). M-PAB had worse diastolic function than F-PAB (Tau 32.8±2.9ms M-PAB vs 14.2±2.1ms M-Sham, P<0.01; 25.6±5.3ms F-PAB vs 15.0±2.1ms M-Sham, P=NS). In male but not female mice, PAB induced upregulation of Nppa, Nppb, Npr1, Npr2, Npr3, Gucy1a3, Gucy1b3, Pde5 and Pkg1a in the RV. RV transcript levels of Ace, Col1α1, Ctgf, Igfbp5, Mmp2, and Timp2 were also higher in M-PAB than F-PAB. Conclusions: Males have worse RV functional response to PAB than do females. This sex difference was also associated with increased mRNA levels of cGMP signaling mediators and upregulation of pro-hypertrophic and pro-fibrotic genes in male PAB mice. Further studies are needed to elucidate sex-dependent regulation of RV remodeling.

Factors Associated With Cognitive Impairment in Heart Failure With Preserved Ejection Fraction.

Cognitive impairment is prevalent in heart failure and is associated with higher mortality rates. The mechanism behind cognitive impairment in heart failure with preserved ejection fraction (HFpEF) has not been established. The aim of this study was to evaluate associations between abnormal cardiac hemodynamics and cognitive impairment in individuals with HFpEF. A secondary analysis of Atherosclerosis Risk in Communities (Atherosclerosis Risk in Communities) study data was performed. Participants free of stroke or dementia who completed in-person assessments at visit 5 were included. Neurocognitive test scores among participants with HFpEF, heart failure with reduced ejection fraction (HFrEF), and no heart failure were compared. Sociodemographics, comorbid illnesses, medications, and echocardiographic measures of cardiac function that demonstrated significant (P < .10) bivariate associations with neurocognitive test scores were included in multivariate models to identify predictors of neurocognitive test scores among those with HFpEF. Multiple imputation by chained equations was used to account for missing values. Scores on tests of attention, language, executive function, and global cognitive function were worse among individuals with HFpEF than those with no heart failure. Neurocognitive test scores were not significantly different among participants with HFpEF and HFrEF. Worse diastolic function was weakly associated with worse performance in memory, attention, and language. Higher cardiac index was associated with worse performance on 1 test of attention. Cognitive impairment is prevalent in HFpEF and affects several cognitive domains. The current study supports the importance of cognitive screening in patients with heart failure. An association between abnormal cardiac hemodynamics and cognitive impairment was observed, but other factors are likely involved.

Alterations in plasma triglycerides and ceramides: links with cardiac function in humans with type 2 diabetes

Cardiac dysfunction in T2D is associated with excessive FA uptake, oxidation, and generation of toxic lipid species by the heart. It is not known whether decreasing lipid delivery to the heart can effect improvement in cardiac function in humans with T2D. Thus, our objective was to test the hypothesis that lowering lipid delivery to the heart would result in evidence of decreased "lipotoxicity," improved cardiac function, and salutary effects on plasma biomarkers of cardiovascular risk. Thus, we performed a double-blind randomized placebo-controlled parallel design study of the effects of 12 weeks of fenofibrate-induced lipid lowering on cardiac function, inflammation, and oxidation biomarkers, and on the ratio of two plasma ceramides, Cer d18:1 (4E) (1OH, 3OH)/24:0 and Cer d18:1 (4E) (1OH, 3OH)/16:0 (i.e., "C24:0/C16:0"), which is associated with decreased risk of cardiac dysfunction and heart failure. Fenofibrate lowered plasma TG and cholesterol but did not improve heart systolic or diastolic function. Fenofibrate treatment lowered the plasma C24:0/C16:0 ceramide ratio and minimally altered oxidative stress markers but did not alter measures of inflammation. Overall, plasma TG lowering correlated with improvement of cardiac relaxation (diastolic function) as measured by tissue Doppler-derived parameter e'. Moreover, lowering the plasma C24:0/C16:0 ceramide ratio was correlated with worse diastolic function. These findings indicate that fenofibrate treatment per se is not sufficient to effect changes in cardiac function; however, decreases in plasma TG may be linked to improved diastolic function. In contrast, decreases in plasma C24:0/C16:0 are linked with worsening cardiac function.

P1285ACTIVE FLUID MANAGEMENT IMPROVES LEFT VENTRICULAR FUNCTION AND MECHANICS IN HEMODIALYSIS PATIENTS: A RANDOMIZED TRIAL

Abstract Background and Aims Relative hypervolemia or overhydration (ROH) above 15% of the normally hydrated body extracellular volume (ECV), assessed by bioimpedance spectroscopy (BIS), puts chronic hemodialysis (HD) patients at an increased risk of cardiovascular (CV) incidents and death, as numerous studies have shown. It has also been reported that the reduction of ROH to the value below 15% of ECV can positively affect hypertension and some aspects of the left ventricle (LV) function and morphology. The concept of Active Fluid Management (AFM) has been developed and it hypothesized that maintaining average (weekly) predialysis overhydration (AWOH) below 15% of ECV will preserve heart function and structure and thus lead to fewer CV complications. The purpose of this study was to investigate the effects of AFM concept guided by BIS on cardiac morphology, mechanics and function in chronic HD patients. Methods Randomized prospective single-center study lasted 9 months and included BIS naive HD patients from the Dialysis unit of Zvezdara University Medical Center in Belgrade with HD vintage greater of 3 months. BIS was performed by Body Composition Monitor (BCM). In accordance with the AFM concept, BIS was applied to patients in the Active group every time their average weekly ROH (AWOH) exceeded 15% of their normal ECV and their dry weight (DW) was time-adjusted according to the findings along with clinical assessment. In the Control group, patients were treated in accordance with the standard clinical practice. Cardiac structural and functional characteristics were obtained at the beginning and the end of the study by using 2-dimensional Doppler echocardiography and spackle tracking modality. Cardiac markers (high-sensitivity C-reactive protein, Troponin T and N-terminal pro-brain natriuretic peptide) were measured at the same time. Results The study included 42 patients (25 M) in the Active group and 41 patients (23 M) in the Control group. Patients from both groups were of similar age (56.1 ± 11.5 vs. 57.5 ± 13.2 years, p = 0.6) and HD vintage (79.9 ± 59.2 months vs. 95.3 ± 80.0 months, p = 0.6). 73 patients completed the 9 months study, 38 in the Active group and 35 in Control group. Within the Active group, recommended AWOH lower than 15% ECV has 55% at start and 76% of patients at the end of study (p&amp;lt; 0.01). In parallel, there were improvements in their LV ejection fraction (LVEF), from 41.3 ± 9.3% to 44.0 ± 8.8% (p &amp;lt; 0.01), LV end systolic volume index, from 40.2 ± 12.5 to 35.8 ± 13.5 ml/m2 (p &amp;lt; 0.05), LV mass indexed at height at 2.7 (LVMI2.7) from 62.8 ± 19.7 g / m2.7 to 57.7 ± 16.9 g/m2.7 (p &amp;lt;0.01) and Global radial strain (GRS) - from 18.6 ± 10.2% to 21.8 ± 12.2% (p &amp;lt;0.05). In the Control group, there were signs of LV diastolic function worsening at the end of the study: E/A ratio increased from 1.0 ± 0.3 to 1.2 ± 0.6 (p &amp;lt; 0.01), as well as E/e’ lateral ratio from 10.6 ± 5.0 to 11.1 ±4.1 (p &amp;lt;0.01) and right ventricle systolic pressure (RVSP) from 34.8 ± 10.2 mmHg to 38.8 ± 8.3 mmHg (p &amp;lt;0.05). This worsening of LV diastolic function in the Control group correlated with the increased level of one of the cardiac markers, N-terminal pro-brain natriuretic peptide (NT-proBNP) - from 5810.0 (3339.0-15627.0) pg/ml to 8024.0 (4433.0-17467.0) pg/ml (p &amp;lt;0.04). Conclusion Active Fluid Management leads to the improvement of left ventricle systolic function and prevents worsening of diastolic function in the observed hemodialysis patients. This concept implemented could favourably affect the clinical course of hemodialysis patients in daily clinical practice.

58-OR: Diastolic Dysfunction, a Precursor for Heart Failure in Young Adults with Youth-Onset Type 1 and Type 2 Diabetes: The SEARCH for Diabetes in Youth Study

Individuals with diabetes are at high risk for heart failure with preserved ejection fraction due to diabetic cardiomyopathy (DCM), defined as abnormal myocardial structure and function in the absence of overt coronary artery disease. DCM leads to myocardial fibrosis and remodeling with one of the first signs being left ventricular (LV) diastolic dysfunction. The objective was to compare the prevalence of diastolic dysfunction among young adults with type 1 diabetes (T1D) vs. type 2 diabetes (T2D) with diabetes diagnosed in childhood. Participants had T1D or T2D and were enrolled in the SEARCH for Diabetes in Youth Study. Cardiovascular risk factors and diastolic function via echocardiography were measured at an in-person visit, after an average disease duration of 10.9 years (both groups). Unadjusted means were compared between those with T1D and T2D, p &amp;lt;0.05 indicating significance. Diastolic dysfunction was defined as abnormal LV filling volume, LV pressure, or transmitral velocity, based on published norms for age. Of 458 eligible participants, 255 had T1D (mean age 21.2±5.2 years, 60.8% non-Hispanic white, 54.1% female, mean A1c 9.0±1.9%), and 203 had T2D (mean age 24.3±4.3 years, 24.1% non-Hispanic white, 75.4% female, mean A1c 9.6±3.0%). Participants with T2D had a worse cardiovascular risk profile (higher BMI, systolic and diastolic BP, triglycerides, LDL-C, A1c and lower HDL-C) than those with T1D, all p&amp;lt;0.05. Participants with T2D also had lower LV filling volume, transmitral velocity and higher LV pressure, all p&amp;lt;0.05, than those with T1D, suggesting worse diastolic function. The unadjusted prevalence of diastolic dysfunction was high in both groups (57.7% in T2D vs. 47.2% in T1D; p&amp;lt;0.05). Diastolic function is worse in individuals with T2D compared to T1D, but diastolic dysfunction is high in both groups. These findings support monitoring of young adults with diabetes for development of heart-related complications. Disclosure A.S. Shah: None. D. Dabelea: None. L.M. Dolan: None. S. Isom: None. R. Dagostino: Consultant; Self; Amgen, AstraZeneca, Celgene, Daiichi Sankyo. L.E. Wagenknecht: None. G. Imperatore: None. S. Saydah: None. A.D. Liese: None. J.M. Lawrence: None. C. Pihoker: None. E.M. Urbina: None. Funding Centers for Disease Control and Prevention (1U18DP006131, U18DP006133, U18DP006134, U18DP006136, U18DP006138, U18DP006139); National Institutes of Health (1UC4DK108173)

Abstract 24: Amyloidogenic V122I Transthyretin Variant is Associated With Progression of Adverse Cardiac Mechanics in Middle-aged African American Adults: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Introduction: Direct-to-consumer testing (e.g. 23andme) reports now include common pathogenic variants in the transthyretin (TTR) gene, such as V122I. TTR cardiac amyloidosis due to V122I is an autosomal dominant disease known to be of variable penetrance in elderly African Americans. However, the association of carrier status for V122I with echocardiographic measures of cardiac mechanics in middle-age African Americans is not known. Hypothesis: Presence of V122I TTR mutation is associated with adverse cardiac mechanics in middle-aged African Americans. Methods: All African Americans from the CARDIA study with imputed genetic data (R 2 = 0.98) and echocardiography at year 25 (Y25) were included. Echo parameters at Y25 and change from Y25 to Y30 were compared between V122I heterozygote carriers and controls using linear regression models. The analysis was adjusted for age, sex, and top 3 principal components of ancestry. Analysis for change from Y25 to Y30 was adjusted for baseline Y25 echo parameters. Results: Of 874 included participants, mean age was 50.2 (3.6) years at Y25. There were 843 controls and 31 carriers for the V122I genotype (3.5% prevalence). There was no difference in age, sex, or clinical characteristics. Carriers of the V122I variant had worse diastolic function as measured by early diastolic tissue Doppler velocity (e’) at Y25 (9.2 [2.1] vs. 10.2 [2.4], p=0.048). From Y25 to Y30, V122I carriers had greater progression of left ventricular (LV) volume and mass as well as greater decline in subclinical LV systolic function as measured by circumferential strain (Table). Conclusions: Prevalence of the carrier status of the V122I genotype in CARDIA is relatively high and consistent with prior studies. Our findings suggest that the V122I mutation may be a unique risk enhancer for heart failure in middle-aged African Americans. Further data are needed for clarity on risk associated with carrier status of V122I and implications for cascade screening given emerging therapies for TTR cardiac amyloidosis.

March 2020 at a glance: heart failure with preserved ejection fraction, left atrial myopathy, atrial fibrillation and cardiac amyloidosis.

Diagnosis of heart failure (HF) with preserved ejection fraction (HFpEF) remains challenging.1 The algorithm developed by the Heart Failure Association (HFA) and the validation of its second step in two independent study groups are reported in this issue. The positive and negative predictive values of a high and a low HFA-PEFF score were 98% and 73%, respectively. However, 36% of patients were classified in the intermediate-likelihood category, where additional testing, e.g. diastolic stress testing, is advised.2 Coronary microvascular function may concur to the pathogenesis of HFpEF.3 Yang et al.4 analysed it in HFpEF patients. Coronary microvascular function was abnormal in 117 patients (72%). Isolated endothelium-dependent and independent microvascular dysfunction were present in 29% and 33% of patients, respectively. Combined microvascular dysfunction was found in 10%. Endothelium-independent microvascular dysfunction was associated with worse diastolic function and higher mortality.4 Epicardial fat may contribute to diastolic dysfunction.3, 5 Wu et al.6 showed that also the amount of intramyocardial fat, measured by cardiac magnetic resonance, is higher in HFpEF compared to patients with HF and reduced ejection fraction (HFrEF) and to patients without HF. Intramyocardial fat was independently related with diastolic dysfunction in HFpEF. Left atrial (LA) function is associated with an increased risk of HF in patients with atrial fibrillation (AF).7 Khan et al.8 conducted a meta-analysis of 22 studies and showed worse LA function in HFpEF patients compared to controls. Decreased LA reservoir strain was associated with more clinical events. Cardiopulmonary exercise test (CPET) is useful for the risk stratification of HFpEF patients.9, 10 Pugliese et al.11 evaluated patients with hypertension with and without HFpEF by CPET and exercise stress echocardiography. Reduced peak oxygen consumption, low cardiac output, high E/e' and B-lines were found more frequently in patients with HFpEF and hypertension compared to the others. Severe functional mitral regurgitation (FMR) is associated with poor outcomes and may be a target for treatment of HFrEF.12-14 Tamargo et al.15 compared HFpEF patients with or without mild/moderate FMR. They found that HFpEF patients with FMR have larger and less compliant atria, worse pulmonary haemodynamics and reduced cardiac output compared to non-FMR-HFpEF patients, regardless of AF. Inciardi et al.,16 evaluating patients undergoing echocardiography, observed a significant association between FMR (even mild), LA function and pulmonary pressure. Kloosterman et al.17 calculated an AF genetic risk score in 3759 HF patients. It was an independent predictor of AF prevalence, regardless of HF phenotypes, and improved AF prediction when added to clinical risk factors. The role of heart rate in patients with AF and HF is still controversial.14, 18 Docherty et al.19 demonstrated that, independently of natriuretic peptides, high heart rate is associated with poor outcomes in patients with HFrEF and sinus rhythm, but not in those with HFrEF and AF. Telemonitoring may have a crucial role for HF management.14, 20 Previous studies suggested that it may be more useful in patients with AF and HF. However, these findings were not confirmed in an analysis of the Remote Management of Heart Failure Using Implanted Electronic Devices (REM-HF) trial.21 The two most common types of cardiac amyloidosis are transthyretin (TTR)-related and light-chain amyloidosis (AL).22 Milandri et al.23 evaluated the prevalence and impact of carpal tunnel syndrome (CTS) in patients with TTR and AL amyloidosis, compared to the general population. CTS was most common in male, elderly patients with TTR amyloidosis and cardiac involvement. It was an independent predictor of mortality and was associated with an increased risk of cardiomyopathy development.

Клініко-гемодинамічні предиктори когнітивної дисфункції в пацієнтів з ішемічною хворобою серця

Мета роботи – визначити клінічні та гемодинамічні чинники ризику розвитку когнітивної дисфункції в пацієнтів з ішемічною хворобою серця.Матеріали і методи. У дослідження залучено 110 хворих із хронічною ішемічною хворобою серця – із наявністю в анамнезі гострого інфаркту міокарда, нестабільної стенокардії або процедури реваскуляризації коронарних артерій. Залежно від стану діастолічної функції пацієнтів розділили на три групи: І група – нормальна діастолічна функція; ІІ – порушення релаксації; ІІІ – псевдонормалізація або рестрикція. Когнітивну функцію оцінювали за допомогою шкал MMSE, MoCA, батареї тестів на лобну дисфункцію, Trial Making Test та аудіовербального тесту Рея.Результати та обговорення. Середня кількість балів за шкалою MMSE зі збільшенням ступеня вираження діастолічної дисфункції (ДД) зменшувалася і становила в І групі 25,40±2,58, в ІІ – 24,95±2,69, ІІІ – 22,30±3,17 (p1,3&lt;0,0001, p2,3=0,001); за шкалою МоСА – 23,47±3,41 в І групі, 22,09±3,48 в ІІ групі і 19,85±5,19 в ІІІ групі (p1,2=0,039, p1,3=0,004, p2,3&gt;0,05). Між показниками за MMSE та типом ДД виявлено від’ємну кореляцію середнього ступеня (r=–0,35; p&lt;0,05), а між кількістю балів за MMSE та тиском наповнення лівого шлуночка (ТНЛШ) – від’ємну кореляцію сильного ступеня (r=–0,50; p&lt;0,00001). Для шкали МоСА відзначено кореляцію середнього ступеня (r=–0,30; p=0,0018) з ДД і від’ємну кореляцію сильного ступеня (r=–0,41; p&lt;0,05) з ТНЛШ. Також зафіксовано від’ємну кореляцію слабкого ступеня між показником батареї тестів на лобну дисфункцію та ТНЛШ (r=–0,24; p&lt;0,05). Виявлено, що кількість балів за шкалою MMSE статистично значуще корелює зі статусом куріння, індексом об’єму лівого передсердя та індексом маси міокарда лівого шлуночка (відповідно r=0,23, r=–0,25, r=–0,25). З показником за шкалою МоСА корелювали показники індексу об’єму лівого передсердя та індексу маси міокарда лівого шлуночка (r=–0,25, r=–0,18). Ймовірність розвитку когнітивної дисфункції підвищувалася при збільшенні рівня глікованого гемоглобіну (відношення шансів (ВШ) 2,65; 95 % довірчий інтервал (ДІ) 1,08–6,48; р=0,033), погіршанні стану діастолічної функції (ВШ 3,18; 95 % ДІ 1,18–8,59; p=0,023) і збільшенні ТНЛШ (ВШ 6,03; 95 % ДІ 2,32–15,69; p=0,0002) – за шкалою MMSE, і при погіршанні стану діастолічної функції (ВШ 2,86; 95 % ДІ 1,18–6,94; p=0,020) – за шкалою МоСА. За результатами прямої множинної логістичної регресії виявлено, що серед усіх показників лише ТНЛШ статистично значуще впливав на загальну кількість балів за шкалою MMSE (ВШ 1,28; 95 % ДІ 1,11–1,47; р=0,0007).Висновки. Виявлено, що показник діастолічної функції має статистично значущий вплив на стан когнітивної функції. Відзначено від’ємну кореляцію між типом ДД, показником ТНЛШ і показниками за шкалами когнітивних функцій. Ймовірність когнітивної дисфункції за шкалою MMSE підвищувалася при збільшенні рівня глікованого гемоглобіну, погіршанні стану діастолічної функції, збільшенні ТНЛШ; за шкалою МоСА – при погіршанні стану діастолічної функції. За результатами множинної регресії лише ТНЛШ статистично значуще впливав на загальну кількість балів за шкалою MMSE.

Temporal Changes in Resting Heart Rate, Left Ventricular Dysfunction, Heart Failure and Cardiovascular Disease: CARDIA Study

The prognostic significance of temporal changes in resting heart rate in young adults for premature heart failure and cardiovascular disease is unclear. We investigated the association between temporal changes in resting heart rate in young adults and early adult risk factors, subsequent cardiac function, and the risk of heart failure and cardiovascular by middle age. We examined 4343 Coronary Artery Risk Development in Young Adults (CARDIA) study participants (mean [SD] age was 29.9 [3.6] years at the CARDIA Year-5 examination [1990-1991], 49% of participants were men, and 45% were African-American). Adjusted linear regression models were used to assess the association between temporal changes in resting heart rate, early life cardiovascular disease risk factors, and midlife cardiac function. Cox proportional hazard regression models were used to relate temporal changes in resting heart rate to heart failure and cardiovascular disease. Outcomes were followed up until August 31, 2017. Higher alcohol consumption (β=0.03, P <0.001), lower physical activity (β=0.002, P=001), smoking (β=1.58, P <0.001), men (P <0.001), African Americans (P <0.001), impaired left ventricular relaxation (e´,β=-0.13, P=0.002), and worse diastolic function (E/e´, β=0.1, P=0.01) were associated with longitudinal increases in resting heart rate. We observed 268 cardiovascular disease and 74 heart failure events over a median of 26 years. In Cox models, baseline and temporal changes in resting heart rate were associated with higher risk of heart failure (hazard ratio [HR] =1.37 95% confidence interval [CI] [1.05-1.79] and HR=1.38 95% CI [1.02-1.86]) and a higher risk cardiovascular disease (HR=1.23 95% CI [1.07-1.42] and HR=1.23 95% CI [1.05-1.44]). Baseline and temporal changes in resting heart rate in young adults were associated with incident heart failure and cardiovascular disease by midlife. Contributory factors were associations between temporal increases in resting heart rate and early adult risk factors and subsequent cardiac dysfunction.

Renal Dysfunction in Heart Failure With Preserved Ejection Fraction: Insights From the RELAX Trial

Patients with heart failure with preserved ejection fraction (HFpEF) and chronic kidney disease (CKD) represent a high-risk phenotype. The Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction (RELAX) trial enrolled a high proportion of CKD participants, allowing investigation into differences in HFpEF by CKD status. Among 212 participants, we investigated the associations of CKD with biomarkers, cardiac structure, and exercise capacity, and identified predictors of change in estimated glomerular filtration rate (eGFR) over trial follow-up. CKD participants (eGFR ≤60 mL/min/1.73m2) were older, had more comorbidities, and had worse diastolic function. Lower eGFR was associated with higher levels of endothelin-1, N-terminal pro-B-type natriuretic peptide, aldosterone, uric acid, and biomarkers of fibrosis (P < .05 for all). Whereas lower eGFR was associated with worse peak oxygen consumption (VO2) after adjustment for demographics, clinical comorbidities, exercise modality, ejection fraction, and chronotropic index (β coefficient per 1 SD decrease in eGFR: -0.61, 95% CI: -1.01, -0.22, P = .002), this association was attenuated after further adjustment for hemoglobin (β coefficient: -0.26, 95% CI: -0.68, 0.16, P = .22). Hemoglobin mediated 35% of the association between eGFR and peak VO2. Sildenafil therapy was independently associated with worsening eGFR over the trial (β coefficient: -2.79, 95% CI: -5.34, -0.24, P = .03). Renal dysfunction in HFpEF is characterized by echocardiographic and biomarker profiles indicative of more advanced disease, and reduced hemoglobin is a strong mediator of the association between renal dysfunction and low exercise capacity. Sildenafil therapy was associated with worsening of renal function in RELAX.

101 Semi-automated volume-strain loops: a new tool in TTE to assess diastolic dysfunction

Abstract AIM This work aims to evaluate a novel semi-automatic tool for the assessment of volume-strain loops by transthoracic echocardiography (TTE). METHOD 17 patients with proved cardiac amyloidosis and 18 patients with heart failure with preserved ejection fraction (HFpEF) were compared to 19 controls, from a local database. All TTE were performed using Vivid E95 ultrasound system (General Electrics Healthcare, Horten, Norway). The complete method includes several steps: 1) extraction of LV strain full traces from apical 4 and 2 cavities views, 2) estimation of LV volume from these two traces by spline interpolations, 3) resampling of LV strain curves, determined for the same cardiac beat, (in apical 4-, 2- and 3- cavities views) as a function of pre-defined percentage increments of LV-volume and 4) calculation of the LV volume-strain loop area. (Figure 1, panel A) RESULTS (Table 1): LVEF was similar between all groups whereas global longitudinal strain was significantly lower in amyloidosis group than controls (-14.4 vs -20.5%; p &amp;lt; 0.001). HFpEF and amyloidosis groups had a worse diastolic function than controls with a greater left atrial volume index , a faster tricuspid regurgitation, a greater E/e’ ratio with a p &amp;lt; 0.001 for all these indices. Simultaneously, the global area of volume-strain loop was significantly lower in HFpEF and amyloidosis group than controls (72 vs 36 vs 120.0 %.mL, respectively, p &amp;lt; 0.0001) with an intermediate profile of HFpEF(Figure 1, panel B, HFpEF in green). This area was better correlated with mean e’ (r = 0.650, p &amp;lt; 0.001) than all other indices. CONCLUSION LV volume-strain loop area appears a very promising new tool to assess semi-automatically diastolic function. Main echocardiographic results Controls n = 19 HFpEF n = 18 Amyloidosis n = 17 p-value LVEDV (mL) 105 ± 15 103 ± 30 95 ± 93 0.476 LVEF (%) 65 ± 5 62 ± 7 62 ± 7 0.196 GLS (%) -20.5 ± 1.8 -18.4 ± 4.3 -14.4 ± 3.8 &amp;lt;0.0001 LAVi (ml.m-2) 22 ± 5 51 ± 14 51 ± 22 &amp;lt;0.0001 E/A ratio 2.1 ± 0.4 1.2 ± 0.7 1.7 ± 1.0 0.005 Mitral E/Ea average 5.9 ± 1.4 13.7 ± 5.8 17.3 ± 5.4 &amp;lt;0.0001 Vmax TR (m/s) 2.0 ± 0.3 3.1 ± 0.4 2.7 ± 0.5 &amp;lt;0.0001 V-S loop area (ml.%) 120 ± 54 72 ± 45 37 ± 21 &amp;lt;0.0001 Abstract 101 Figure 1

Semi-automated volume-strain loops: A new tool in TTE to assess diastolic dysfunction

This work aims to evaluate a novel semi-automatic tool for the assessment of volume-strain loops by transthoracic echocardiography (TTE). The proposed method was evaluated on a typical model of left ventricular (LV) diastolic dysfunction: the cardiac amyloidosis. Seventeen patients with proved cardiac amyloidosis and 18 patients with heart failure with preserved ejection fraction (HFpEF) were compared to 19 controls, from a local database. All TTE were performed using Vivid E9 or E95 ultrasound system (General Electrics Healthcare, Horten, Norway). The complete method includes several steps: 1) extraction of LV strain full traces from apical 4 and 2 cavities views, 2) estimation of LV volume from these two traces by spline interpolations, 3) resampling of LV strain curves, determined for the same cardiac beat, (in apical 4-, 2- and 3- cavities views) as a function of pre-defined percentage increments of LV-volume and 4) calculation of the LV volume-strain loop area. ( Fig. 1 , panel A) ( Table 1 ): LVEF was similar between all groups whereas global longitudinal strain was significantly lower in amyloidosis group than controls (−14.4 vs. −20.5%; P < 0.001). HFpEF and amyloidosis groups had a worse diastolic function than controls with a greater left atrial volume index (51 vs. 22 mL/m 2 ), a faster tricuspid regurgitation (3.1 and 2.7 vs. 2.0 m/s), a greater E/e’ ratio (13.7 and 17.3 vs. 5.9) with a P < 0.001 for all these indices. Simultaneously, the global area of volume-strain loop was significantly lower in HFpEF and amyloidosis group than controls (72 vs. 36 vs. 120.0% mL, respectively, P < 0.0001). HFpEF has an intermediate profile between controls and amyloidosis ( Fig. 1 , panel B, HFpEF in green). This area was better correlated with mean e’ ( r = 0.650, P < 0.001) than all other indices. LV volume-strain loop area appears a very promising new tool to assess semi-automatically diastolic function.

Left Ventricular Dysfunction in Patients With Primary Aldosteronism: A Propensity Score-Matching Follow-Up Study With Tissue Doppler Imaging.

BackgroundPrimary aldosteronism is the most common cause of secondary hypertension and is associated with left ventricular hypertrophy. However, whether aldosterone excess is responsible for left ventricular (LV) diastolic dysfunction is unknown.Methods and ResultsWe prospectively enrolled 129 patients with aldosterone‐producing adenoma and 120 patients with essential hypertension, and analyzed their clinical, biochemical, and echocardiographic data, including tissue Doppler images. The patients with aldosterone‐producing adenoma were reevaluated 1 year after adrenalectomy. After propensity score matching, there were 105 patients in each group. The patients with aldosterone‐producing adenoma had worse diastolic function than the patients with essential hypertension, as reflected by lower e′ (P<0.001) and higher E/e′ (P=0.003). Multivariate analysis showed that LV diastolic function was significantly correlated with age (P<0.001), sex (P<0.001), body mass index (P=0.002), systolic blood pressure (P=0.004), creatinine (P=0.008), and log‐transformed aldosterone‐renin ratio (P=0.003). After adrenalectomy, the patients with aldosterone‐producing adenoma had significant improvements in LV diastolic function as reflected by an increase in e′ (P=0.003) and decrease in E/e′ (P=0.002). The change in E/e′ was independently correlated with baseline E/e′ (P<0.001) and change in LV mass index (P=0.006).ConclusionsThe patients with primary aldosteronism had worse LV diastolic function than the patients with essential hypertension after propensity score matching, and this could be reversed after adrenalectomy, suggesting that aldosterone excess may induce LV diastolic dysfunction.

P1244Survival after septal myectomy in male and female patients with hypertrophic obstructive cardiomyopathy

Abstract In recent years, studies have debated the impact of gender on the presentation and clinical course of HCM, with research showing that at time of myectomy, women are older, have worse diastolic function and more advanced cardiac remodeling. The clinical impact of these differences is unknown. We included 221 HCM patients (57% men) who underwent septal myectomy and are followed in our center. Time to treatment was calculated in relation to symptom onset. Pre- and post-operative clinical and echocardiographic data were collected. Gender differences were assessed at baseline and in survival analyses for the composite endpoint of all-cause mortality, cardiac transplantation, re-intervention and aborted sudden cardiac death. Women were older at time of myectomy, but time until treatment was similar (table). Pre-operative echocardiographic indices were comparable among groups, but were significantly higher in women when correcting for body surface area. At three months, no differences were found in clinical and echocardiographic results. After 6.1 [2.9–10.1] years, 24% of women and 23% of men had reached the composite endpoint (p=0.30, figure). Gender comparison pre- and post-myectomy Men (n=125) Women (n=96) p value Age 49±14 54±17 0.02 Maximal wall thickness, mm 19.9±4.7 19.8±5.8 0.97 Indexed maximal wall thickness, mm/m2 9.8±2.5 11.5±4.5 0.001 Left atrial diameter, mm 48.1±7.3 45.9±7.3 0.06 Indexed left atrial diameter, mm/m2 23.5±3.5 26.5±7.5 0.002 LV end-diastolic diameter, mm 45.4±7.6 42.8±5.6 0.04 Indexed LV end-diastolic diameter, mm/m2 22.1±3.7 23.6±3.0 0.02 Gradient reduction, %* 75.1±25.0 72.9±28.6 0.63 Improvement in symptoms*† 97 (95%) 64 (89%) 0.34 MWT = maximal wall thickness; LV = left ventricle. *At three months follow-up; †Defined as a reduction of ≥1 NYHA class, measured in 102 men and 72 women. Survival after myectomy Although women present later in life and seem to have more advanced disease at time of myectomy, time to treatment is similar and survival after myectomy is excellent for both men and women.

P1486Semi-automated volume-strain loops: a new tool in TTE to assess diastolic dysfunction

Abstract Aim This work aims to evaluate a novel semi-automatic tool for the assessment of volume-strain loops by transthoracic echocardiography (TTE). The proposed method was evaluated on a typical model of left ventricular (LV) diastolic dysfunction: the cardiac amyloidosis. Method 18 patients with proved cardiac amyloidosis were compared to 19 controls, from a local database. All TTE were performed using Vivid E9 or E95 ultrasound system. The complete method includes several steps: 1) extraction of LV strain full traces from apical 4 and 2 cavities views, 2) estimation of LV volume from these two traces by spline interpolations, 3) resampling of LV strain curves, determined for the same cardiac beat, (in apical 4-, 2- and 3- cavities views) as a function of pre-defined percentage increments of LV-volume and 4) calculation of the LV volume-strain loop area. (Figure 1, panel B) Results (Table 1): LVEF was similar between both groups whereas global longitudinal strain was significantly lower in amyloidosis group (−14.4 vs −20.5%; p&lt;0.001). Amyloidosis group had a worse diastolic function with a greater left atrial volume index (51 vs 22ml/m2), a faster tricuspid regurgitation (2.7 vs 2.0 m/s), a greater E/e' ratio (17.3 vs 5.9) with a p&lt;0.001 for all these indices. Simultaneously, the global area of volume-strain loop was significantly lower in amyloidosis group (36.5 vs 120.0%.mL). This area was better correlated with mean e' with r=0.734 (p&lt;0.001) than all other indices (Figure 1, panel A). Table 1 Amyloidosis (N=18) Controls (N=19) p Global strain-volume loop area (%.mL) 36.5±21.3 120.0±54.2 &lt;0.001 Global longitudinal strain (%) −14.4±3.8 −20.5±1.8 &lt;0.001 Left ventricular ejection fraction (%) 62±7 65±5 0.08 Left atrial volume index (ml/m2) 51±22 22±5 &lt;0.001 E/A 1.72±0.97 2.07±0.45 0.17 Mean e' 5.5±1.3 14.4±2.8 &lt;0.001 Mean E/e' 17.3±5.4 5.9±1.4 &lt;0.001 Tricuspid regurgitation velocity (m/s) 2.7±3.8 2.0±0.3 &lt;0.001 Figure 1 Conclusion LV volume-strain loop area appears a very promising new tool to assess semi-automatically diastolic function. Future applications will concern the integration of LV volume-strain loop area as novel feature in machine-learning approach.

P2603Impaired right ventricular force-frequency relationship in patients with heart failure is associated with diastolic dysfunction and worse functional capacity

Abstract Background The force-frequency relationship (FFR) is an important intrinsic regulatory mechanism of cardiac contractility, related to changes in Ca2+ availability within the myocardial cell. In normal hearts this relationship is positive, so that an increase in contractile force is induced by elevation of the stimulation frequency. In heart failure (HF), the force-frequency relationship can be markedly depressed, but most studies focused their attention on left ventricular function and little is known about the right ventricle (RV). Purpose We aimed at performing a comprehensive analysis of HF phenotypes based on the right ventricular force-frequency relationship. To this purpose we stratified a large cohort of HF patients using the relationship between RV function (assessed by tricuspid annular plane systolic excursion, TAPSE) and heart rate (HR) during a symptom-limited cardiopulmonary exercise test (CPET). Material and methods We prospectively enrolled 184 HF patients, irrespective of their LV ejection fraction. We performed a stress echocardiographic evaluation using a tiltable cycle ergometer, recording standard images to assess LV systolic, diastolic, and valvular function. We divided patients in 2 groups using the slope of the linear relationship between TAPSE and HR at rest and at peak exercise, as follows: slope ≥0,01 for “positive” FFR, slope &lt;0,01 for “flat or negative” FFR. Differences between groups were tested using unpaired t-tests for continuous variables (or Mann-Whitney U tests, when appropriate) and chi-square tests for categorical variables. Results 55 patients had a “flat or negative” FFR: they were slighty older (age 70±10 vs. 66±12; p=0,036), but the 2 groups had similar clinical characteristics such as hypertension, diabetes or COPD rate. Patients with a “flat or negative” FFR had a worse diastolic function, with higher left ventricular filling pressures (E/e' ratio 24±10 vs. 19±11 p=0,022) and left atrial volume (LAVi 55±29 ml/m2 vs. 44±20 ml/m2; p=0,009). No differences in LV ejection fraction, mitral regurgitation and pulmonary artery systolic pressure were observed between the groups. TAPSE at rest was similar between the groups (18±5 mm vs. 18±4 mm; p=0,553) but significantly different at peak exercise (16±4 mm vs. 22±5 mm; p&lt;0,001). Average peak heart rate was similar in the 2 groups. Patients with a “flat or negative” FFR exhibited a significantly lower peak VO2 (11,6±3,0 ml/min/kg vs. 13,5±4,4 ml/min/kg; p=0,003), whereas they had a higher VE/VCO2 slope (35,1±9,6 vs. 32,3±8,2 p=0,05). RV Force-Frequency relationship Conclusion The “flat or negative” right ventricular force-frequency relationship identifies a peculiar phenotype, with a higher grade of diastolic dysfunction and an impaired exercise capacity. The inability to adapt right ventricular contractility with increasing heart rate seems not related to RV afterload (similar PASP increase) but rather to an intrinsic failure of the right heart.

P2258Pulse wave velocity, total arterial compliance, and cardiac structure and function in late life

Abstract Background Coupled abnormalities in arterial and left ventricular (LV) stiffness characterize aging and heart failure with preserved ejection fraction. We hypothesized that two measures of aortic stiffness, pulse wave velocity (PWV; reflecting segmental arterial wall stress in late systole) and total arterial compliance (TAC; reflecting distensibility of entire arterial system) differentially relate to cardiac structure and function in the elderly. Methods Among participants in the Atherosclerosis Risk In Community (ARIC) study, we assessed the cross-sectional relationship of carotid-femoral PWV (cfPWV) and TAC with echocardiographic measures of cardiac structure and function using multivariable linear regression adjusting for demographics and co-morbidities. TAC defined as stroke volume over pulse pressure [mL/mmHg]. Exclusions were LVEF &lt;50%, prevalent HF, ≥moderate valvular disease. Results Of the 4,141 participants included in this study, mean age was 75±5 years, 41% were male, and 80% were white. Mean values were: cfPWV: 11.7±3.4 m/sec; TAC: 1.1±0.3 mL/mmHg. Greater cfPWV was associated with greater LV mass, worse systolic function, and worse diastolic function (Table). In contrast, worse TAC was not related to LV structure and did not demonstrate consistent relationships with measures of LV diastolic function, but was associated with worse LV longitudinal strain. Echo measures cfPWV (1SD increase) TAC (1SD decrease) β Coefficient p-value β Coefficient p-value Cardiac structure Mean wall thickness, cm 0.10 &lt;0.001 -0.01 0.499 LVMI, g/m2 0.04 0.016 0.02 0.299 LVEDVI, ml/m2 -0.07 &lt;0.001 -0.02 0.332 LV systolic function LVEF (Simpson's), % -0.04 0.01 -0.16 &lt;0.001 Longitudinal strain, % 0.14 &lt;0.001 0.19 &lt;0.001 LV diastolic function Septal e', cm/sec -0.08 &lt;0.001 -0.02 0.169 E/e' septal 0.04 0.005 -0.02 0.138 LAVI, ml/m2 -0.05 0.003 -0.04 0.026 Conclusion Two non-invasive measures of aortic stiffness, cfPWV and TAC, demonstrate differential associations with LV structure and function in late life. Greater cfPWV is more robustly associated with LV structure and function than TAC.

P3434Galectin-3 identifies healthy subjects at risk of developing (pre-)diastolic dysfunction

Abstract Background/Introduction Biomarkers might be useful to identify healthy subjects who are at risk of developing diastolic dysfunction. Cardiac remodeling, in particular fibrosis, is a hallmark of diastolic dysfunction. Previous (pre)clinical studies have linked galectin-3 to fibrogenesis. Therefore, we aimed to evaluate whether galectin-3 would be able to identify apparently healthy individuals who are at risk of developing pre-clinical diastolic dysfunction. Purpose To study whether galectin-3 is able to identify healthy subjects who are at risk of developing pre-clinical diastolic dysfunction over time. Methods We measured both galectin-3 and B-type natriuretic peptide (BNP) in 1.500 participants of the population study LifeLines. Based upon the biomarker profile, we selected 88 subjects with elevated galectin-3 (&gt;14.3 ng/mL; n=42) and with low galectin-3 (&lt;9.8 ng/mL; n=46) values, while all participants demonstrated low BNP. We matched these groups so other confounding variables like age, sex, kidney function (creatinine), body weight (BMI) and blood pressure were comparable between both groups. After approximately five years follow up, we invited those 88 participants to determine the level of diastolic dysfunction using echocardiography. Statistical analyses were performed in IBM SPSS Statistics 25 and StataMP 13. Results We included 88 participants at a median age of 50 years (standard deviation ± 11 years) in this case-control study. Besides the galectin-3 levels, all other variables were adequately matched and fully comparable between both groups. Obviously, galectin-3 levels (median, IQR) were markedly different between the groups (galectin-3 levels 7.35 ng/L (6.9 - 8.6) vs 16.4 ng/L (15.1- 17.8), P&lt;0.001). Subjects with elevated galectin-3 demonstrated signs of structural cardiac remodeling: enlarged left atrial diameter (35.3 mm vs. 37.3 mm P=0.034), and larger diastolic interventricular septum thickness (IVS) (9.4 mm vs. 10.1 mm P=0.038), and a smaller left ventricular end-diastolic internal dimension index (LVIDd Index) (2.3 cm/m2 vs. 2.2 cm/m2 P=0.026), a smaller left ventricular end diastolic volume (LVEDV) (98.9 mL vs. 89.9 mL P=0.025). In addition, they exhibited several indicators of worse diastolic function, such as a higher E/e' ratio (5.2 vs. 5.9, P=0.046), while there was no significant difference in the left ventricular ejection fraction (60.8% vs. 59.9%, P=0.110). Conclusion Elevated galectin-3, when fully matched for confounding factors, is associated with the development of preclinical-diastolic dysfunction before onset of clinical symptoms. Our data suggest that substantial elevations of galectin-3 in apparently healthy subjects hint towards preclinical cardiac dysfunction. Acknowledgement/Funding Dutch Heart Foundation 2015T034; NWO VIDI, grant 917.13.350; ERC CoG 818715, SECRETE-HF