Echocardiographic Markers Of Diastolic Dysfunction Research Articles

Abstract 14281: Association of Sleep Apnea Prevalence and Severity With H 2 FPEF Score and Echocardiographic Markers of Heart Failure With Preserved Ejection Fraction

Background: While heart failure with preserved ejection fraction (HFpEF) is highly associated with the presence of sleep apnea, few studies have examined the association between diagnostic scoring systems used to predict HFpEF risk, such as the H 2 FPEF score, and OSA prevalence and severity. Methods: We performed a retrospective chart review on all patients (N = 434) who underwent both an echocardiogram and a sleep study at the University of Pennsylvania between July 1, 2020, and June 30, 2022. Associations between echocardiographic parameters and OSA severity, as well as between H 2 FPEF score and OSA severity, were examined using linear tests of trend. The association between H 2 FPEF score categorization and odds of prevalent OSA was examined with logistic regression. Results: OSA severity was associated with echocardiographic markers of diastolic dysfunction including greater LV mass index (p = 0.04), left atrial volume index (p = 0.03), and LV relative thickness (p = 0.008). Patients with intermediate H 2 FPEF risk scores had 4.3 times greater odds of prevalent OSA compared with those patients with low risk H 2 FPEF scores (95% CI 2.2, 8.7, p < 0.001). Patients with high H2FPEF risk scores had over 17-fold higher odds of prevalent OSA compared to those with low-risk scores (17.7, 95% CI 4.3, 120.7, p < 0.001) (Figure 1). Increasing risk of HFpEF according to H 2 FPEF categorization was strongly correlated with OSA severity as measured by apnea-hypopnea index (p < 0.001) and oxygen desaturation index (p = 0.002). Conclusions: In an ambulatory population referred for both sleep study and echocardiogram, markers of diastolic dysfunction were associated with OSA severity. OSA prevalence and severity were strongly associated with increased H 2 FPEF scores. Clinicians should have a low threshold for referring OSA patients with dyspnea for cardiac workup, as well as a low threshold for referring HFpEF patients for sleep study.

Abstract 13846: Prognostic Value of Echocardiographic Markers of Diastolic Dysfunction for Heart Failure in Overweight and Obese Patients in CAMELLIA-TIMI 61

Background: Recent guidelines have outlined echo markers of diastolic dysfunction (DD); evidence is limited for their prognostic value for hospitalization for heart failure (HHF) in overweight and obese pts. Methods: CAMELLIA-TIMI 61 was a randomized placebo-controlled trial of the weight loss agent lorcaserin in 12,000 pts with BMI ≥27 with or at risk for CV disease (median follow-up, 3.3 yrs). Echo with core lab interpretation was performed on a subset of pts. Established DD parameters were measured, including the ratio of the peak early transmitral diastolic flow velocity over the early diastolic mitral annulus velocity (average E/e’), left atrium volume index (LAVi), and tricuspid regurgitation jet velocity (TRV). These were analyzed continuously, using the standard cutpoints of >14, >34 mL/m 2 , and >2.8 m/s, respectively, and separately to determine the optimal cutpoints. The primary outcome for this analysis was HHF. Results: In 3,972 pts with baseline ejection fraction ≥50%, all 3 variables on a continuous scale predicted increased risk of HHF; using standard cutpoints, only E/e’>14 remained independently associated with HHF after adjustment for the other 2 echo parameters and clinical variables ( Panel A ). In an analysis of optimal cutpoints in these overweight and obese pts, >13 was optimal for E/e’, >2.5 m/s for TRV, and >58 mL/m 2 for LAVi. In a model with all 3 echo parameters, all remained significant predictors of HHF. After incorporation of clinical variables, E/e’ (HR 2.15, 95%CI 1.24-3.72) and LAVi (HR 2.41, 1.33-4.36) remained independent predictors of HHF ( Panel A ). Rates of HHF were 0.6, 3.3, and 10.1% (p-trend<0.0001) in pts with none, one, or both measures of DD ( Panel B ). Conclusions: Several echocardiographic markers of diastolic dysfunction used in current guidelines predict increased risk of HHF events in the understudied obese and overweight population. A higher LAVi (> 58 ml/m 2 ) cutpoint should be considered in these pts to prognosticate risk of HHF.

Association between retinal arterial narrowing and left ventricular diastolic dysfunction in masked hypertensives.

Morphological change in retinal vessel diameters has been reported to be associated with negative cardiovascular outcomes, but its association with left ventricular diastolic dysfunction (LVDD) is not clear. This study aimed to examine the association between echocardiographic markers of LVDD and retinal vascular diameters, in untreated masked hypertension (MH). In this observational study, 105 MH patients without other cardiovascular risks were included (mean age 48.4±5.7, female 72.4%). All individuals underwent extensive clinical and laboratory investigations, including echocardiography, ambulatory blood pressure monitoring, and retinal vascular diameters measured by optical coherence tomography. In the group, LVDD was diagnosed in 36 participants evaluated by left ventricular volume index, E/A and E/e' ratio. Compared to non-LVDD, LVDD subjects displayed narrower retinal arteriolar diameter (139.1±33.8 vs 165.1±29.1; adjusted P=.007) and wider retinal venular diameter (237.9±42.2 vs 214.9±44.8; adjusted P=.045). Significant and independent associations were demonstrated for retinal arteriolar narrowing and E/A ratio (adjusted β=0.744, P=.031) and for retinal arteriolar diameter and E/e' ratio (adjusted β=-0.158, P=.001) after controlling for age, gender, body mass index, ambulatory systolic blood pressure, low-density lipoprotein cholesterol, and retinal venular diameter. In untreated MH subjects, retinal arteriolar diameter, a marker of microvascular damage, was independently associated with echocardiographic markers of diastolic dysfunction. These findings might underscore the hypothesis that microvascular disease could contribute to cardiac remodeling.

Subclinical cardiac stiffness is associated with arterial stiffness in healthy young nulligravid women: Potential links to preeclampsia.

Preeclampsia is an independent risk factor for subsequent cardiovascular disease and diastolic dysfunction and has been linked to arterial stiffness. We hypothesized that arterial stiffness would be associated with echocardiographic markers of diastolic dysfunction in healthy nulligravid women. 31 healthy nulligravid women underwent assessment of peripheral arterial stiffness via aorto-femoral pulse wave velocity, popliteal distensibility and β stiffness measures as well as hemodynamic response to volume challenge. 22 underwent cardiac assessment via conventional and stress echocardiography with a focus on diastolic function utilizing tissue/pulse wave Doppler imaging and 3D speckle tracking. Bivariate associations between variables were evaluated using correlation coefficients (Pearson r) and Student's t-tests. No participants had echocardiographic values meeting criteria for overt diastolic dysfunction. Baseline global circumferential strain was significantly correlated with distensibility and β stiffness (n = 18, r = -0.61, p = 0.007, n = 18, r = 0.56, p = 0.01). Peak deceleration time was correlated with βstiffness (n = 9; r = 0.80, p = 0.01). Pulse wave velocity was not significantly correlated with cardiac measures (p > 0.05). Family history of a first or second degree relative with myocardial infarction or hypertension was associated with decreased popliteal artery distensibility (p = 0.02 and p = 0.03, respectively). In healthy nulligravid women there is evidence that markers of decreased left ventricular relaxation are associated with increased peripheral vascular stiffness as is a family history of myocardial infarction or hypertension. These findings raise the possibility that the diastolic dysfunction and arterial stiffness observed in the setting of preeclampsia are driven by underlying properties present prior to pregnancy and contribute to lifetime cardiovascular risk.

127 Relationship between plasma concentrations of b-type natriuretic peptide and exercise capacity in hypertrophic cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) is characterised by increased left ventricular wall thickness leading to exercise intolerance and heart failure. Peak oxygen consumption (peak VO2) on cardiopulmonary exercise testing (CPET) is often...

Low adiponectin is associated with diastolic dysfunction in women: a cross-sectional study from the Troms\xf8 Study

BackgroundHeart failure with preserved ejection fraction is closely associated with diastolic dysfunction and related to obesity and female sex. We investigated whether adiponectin, an adipocyte-secreted protein hormone with cardioprotective effects, was associated with indices of diastolic dysfunction, and whether the association was sex dependent.MethodsWe conducted a cross-sectional study on 1165 women and 896 men without diabetes. We stratified the multivariable adjusted logistic regression analyses and the fractional polynomial regression analyses according to sex, with echocardiographic markers of diastolic dysfunction as dependent variables, and adiponectin as the independent variable of interest.ResultsDecreased adiponectin was associated with higher odds of average tissue Doppler e’ < 9 in women (odds ratio [OR] 1.17 per 1 μg/mL adiponectin decrease, 95% confidence interval [CI] 1.04–1.30), but not in men (p for interaction with sex 0.04). Women, but not men, had higher odds of E/e’ ratio ≥ 8 with lower adiponectin (OR 1.12 per 1 μg/mL adiponectin decrease, 95% CI 1.02–1.24, p for interaction with sex 0.04). Adiponectin in the lower sex-specific tertile was associated with increased odds of concentric left ventricular hypertrophy in women (OR 2.44, 95% CI 1.03–5.77), but with decreased odds in men (OR 0.32, 95% CI 0.11–0.88, p for interaction with sex 0.002), and decreased odds of eccentric hypertrophy in men only (OR 0.53, 95% CI 0.33–0.88, p for interaction with sex 0.02). Adiponectin in the lower sex-specific tertile was associated with moderately enlarged left atria in women only (OR 1.43, 95% CI 1.01–2.03, p for interaction with sex 0.04). Finally, adiponectin had a non-linear relationship with left ventricular mass in women only, with exponentially increasing left ventricular mass with lower adiponectin levels (p for interaction with sex 0.01).ConclusionsLow adiponectin was associated with higher odds of indices of diastolic dysfunction in women, but lower odds of indices of diastolic dysfunction in men. Lower adiponectin was associated with increased left ventricular mass in women only.

Uric acid predicts mortality and ischaemic stroke in subjects with diastolic dysfunction: the Tromsø Study 1994-2013.

AimsTo investigate whether serum uric acid predicts adverse outcomes in persons with indices of diastolic dysfunction in a general population.Methods and resultsWe performed a prospective cohort study among 1460 women and 1480 men from 1994 to 2013. Endpoints were all‐cause mortality, incident myocardial infarction, and incident ischaemic stroke. We stratified the analyses by echocardiographic markers of diastolic dysfunction, and uric acid was the independent variable of interest. Hazard ratios (HR) were estimated per 59 μmol/L increase in baseline uric acid. Multivariable adjusted Cox proportional hazards models showed that uric acid predicted all‐cause mortality in subjects with E/A ratio <0.75 (HR 1.12, 95% confidence interval [CI] 1.00–1.25) or E/A ratio >1.5 (HR 1.51, 95% CI 1.09–2.09, P for interaction between E/A ratio category and uric acid = 0.02). Elevated uric acid increased mortality risk in persons with E‐wave deceleration time <140 ms or >220 ms (HR 1.46, 95% CI 1.01–2.12 and HR 1.13, 95% CI 1.02–1.26, respectively; P for interaction = 0.04). Furthermore, in participants with isovolumetric relaxation time ≤60 ms, mortality risk was higher with increasing uric acid (HR 4.98, 95% CI 2.02–12.26, P for interaction = 0.004). Finally, elevated uric acid predicted ischaemic stroke in subjects with severely enlarged left atria (HR 1.62, 95% CI 1.03–2.53, P for interaction = 0.047).ConclusionsIncreased uric acid was associated with higher all‐cause mortality risk in subjects with echocardiographic indices of diastolic dysfunction, and with higher ischaemic stroke risk in persons with severely enlarged left atria.

Endothelin-1 in the Human Myocardium and Circulating Plasma: Evaluation before, during and after Correction of Aortic Stenosis with Aortic Valve Replacement

Objectives: Due to the pathological effects of endothelin-1 (ET-1) on cardiomyocytes and the extracellular matrix, ET-1 levels may impact on the prognosis of aortic stenosis (AS) patients operated with aortic valve replacement (AVR). We examined ET-1 levels in AS patients throughout the whole AVR process, thus exposing potential therapeutic windows of opportunity. Methods: Plasma ET-1 levels were measured before and 2 days, 6 and 12 months after AVR in 22 patients with AS. Myocardial ET-1 was measured in biopsies from 7 patients undergoing AVR. Peroperatively, plasma ET-1 was analyzed in the coronary sinus and radial artery before aortic cross-clamp and at 5 and 20 min of reperfusion, in a second group of 30 patients. Results: Circulating ET-1 levels were transiently increased 2.6-fold 2 days following AVR. Myocardial ET-1 protein was 2.1-fold higher in patients with AS compared to controls. Plasma levels of ET-1 correlated to echocardiographic markers of diastolic dysfunction postoperatively. There was no increase in plasma ET-1 during early reperfusion, but veno-arterial differences indicated potential cardiac ET-1 extraction. Conclusions: Plasma ET-1 increases 2 days following AVR and myocardial ET-1 protein levels are increased in patients with AS before AVR. Peroperatively, no plasma ET-1 augmentation or release from the heart was observed in AS patients.

Diastolic Electromechanical Coupling

Background— Electromechanical coupling, a well-described phenomenon in systolic dysfunction, has not been well studied in diastole. We hypothesized that the ECG T-peak to T-end (TpTe) interval, representing transmural dispersion of repolarization, is associated with echocardiographic markers of diastolic dysfunction (DD). Methods and Results— We performed a prospective, cross-sectional study of the association between TpTe and markers of DD in 84 consecutive, unselected patients referred for exercise echocardiography. We systematically measured TpTe on the resting ECG, and we performed comprehensive assessment of DD at rest and at peak stress. ECGs and echocardiograms were analyzed independently, blinded to each other and to all clinical data. By univariable analysis, increased TpTe was associated with older age, increased E/e’ ratio, and DD ( P &lt;0.05 for all associations after correcting for multiple comparisons). Increased TpTe was inversely associated with reduced tissue Doppler e’ velocity, a marker of DD ( R = −0.66, P &lt;0.0001). This association persisted after adjusting for age, QTc, exercise-induced wall motion abnormalities, and left ventricular mass index (β= −0.41 [95% confidence interval, −0.70 to −0.12] cm/s per 10-ms increase in TpTe; P =0.006). Baseline TpTe was also independently associated with resting DD (adjusted odds ratio, 3.9 [95% confidence interval, 1.4–10.7]; P =0.009) and peak exercise E/e’ ratio ( P &lt;0.0001). Conclusions— Increased TpTe is associated with both resting and exercise-induced DD. Electromechanical coupling may represent a pathophysiologic link between electrical transmural dispersion of repolarization and abnormal myocardial relaxation, and may be a novel therapeutic target.

Fator de diferenciação de crescimento 15: um novo biomarcador em pacientes com disfunção diastólica?

Growth differentiation factor-15 (GDF-15), a stress-responsive transforming growth factor-ß-related cytokine, is elevated and independently related to an adverse prognosis in systolic heart failure.This study aimed to investigate plasma levels of GDF-15 in patients with preclinical diastolic dysfunction or heart failure with normal ejection fraction (HFnEF).We evaluated 119 patients with normal ejection fraction referred for an elective coronary angiography, 75 (63%) of whom had coronary artery disease. Subjects were classified as having either mild left ventricular diastolic dysfunction (LVDD grade I, n = 61), HFnEF (LVDD grade II or III, n = 38) or normal diastolic function (controls, n = 20). In a subgroup of 20 subjects, changes in cardiac output (CO) were measured by inert gas rebreathing (InnocorTM) in response to an orthostatic hemodynamic test.Growth differentiation factor-15 levels in HFnEF [median 1.08, interquartile range (0.88-1.30) ng/ml] were significantly higher than in controls [0.60 (0.50-0.71) ng/ml, p = 0.003] and in patients with LVDD grade I [0.78 (0.62-1.04) ng/ml, p < 0.001]. In addition, GDF-15 was significantly elevated in patients with LVDD grade I compared to controls (p = 0.003). Furthermore, GDF-15 was correlated with echocardiographic markers of diastolic dysfunction and was correlated with the magnitude of CO response to the change in body position from standing to supine (r = -0.67, p = 0.005).Growth differentiation factor-15 levels are elevated in subjects with HFnEF and can differentiate normal diastolic function from asymptomatic LVDD. In addition, GDF-15 is associated with a reduced cardiac output response in the orthostatic hemodynamic test.