Left Ventricular Diastolic Stiffness Research Articles

Abstract 11417: Elevated Serum Osteoprotegerin is Associated With Increased Left Ventricular Mass Index and Left Ventricular Diastolic Stiffness in African Americans: Insights From the Genetic Epidemiology Network of Arteriopathy (GENOA) Study

Background: Osteoprotegerin (OPG) associates with a poor prognosis in patients that have already developed heart failure with preserved ejection fraction (HFpEF). OPG also associates with fibrosis and collagen cross-linking which increase diastolic stiffness in the left ventricle (LV). Little is known about the relationship of OPG and LV structure and function in African Americans who are disproportionately affected by HFpEF. We hypothesized that OPG may serve as an early indicator of developing LV hypertrophy and stiffening which are prominent precursors to HFpEF. Methods and Results: Our analysis included 1172 participants with preserved LV ejection fraction (EF >50%) from the African American (Jackson) cohort of the Genetic Epidemiology Network of Arteriopathy (GENOA) Study (mean age 62.9 years, 72% female). LV diastolic stiffness was assessed by echocardiography using the recently developed diastolic wall strain (DWS) indicator calculated as (LV posterior wall thickness at end-systole - LV posterior wall thickness at end-diastole) / LV posterior wall thickness at end-systole. Associations between serum OPG levels and indices of LV structure and function were evaluated using a generalized linear mixed models (GLMM) accounting for clustering in siblings, and adjusted for possible confounders including age, gender, past history of hypertension and diabetes, current smoking status and estimated glomerular filtration rate (eGFR). OPG levels correlated with age, female sex, presence of hypertension and diabetes, lower eGFR, and higher N-terminal prohormone brain natriuretic peptide levels (p <0.05 for all). Thus, higher OPG levels were associated with characteristics common in patients with HFpEF. Multivariable linear regression analysis revealed that after adjustment for covariates, higher OPG levels were associated with greater LV mass index and increased LV diastolic stiffness (p <0.05, for all). Conclusions: Higher OPG levels associated with characteristics common in patients with HFpEF in African Americans. The serum OPG levels also significantly associated with known precursors to HFpEF, indicating a potential pathophysiologic role for OPG in the development of HFpEF in African Americans.

Abstract 12230: Increased Left Ventricular Myocardial Stiffness is Associated With Incident Heart Failure in African Americans: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Increased left ventricular (LV) myocardial stiffness may be associated with future deterioration of LV hemodynamics and incident heart failure (HF). Diastolic wall strain (DWS) is a recently developed echocardiographic indicator of LV myocardial stiffness. We hypothesized that increased LV myocardial stiffness evaluated by DWS is associated with incident HF in a community-based African American cohort in the ARIC. Methods and Results: We investigated the association between LV myocardial stiffness and incident HF among 1553 African American participants (mean age 58.5 years, 66% women) without a history of cardiovascular diseases or LV wall motion abnormalities in the ARIC Study. Echocardiography was performed at Visit 3 in the African American cohort in Jackson, MS. DWS was calculated as (posterior wall thickness at end-systole - posterior wall thickness at end-diastole) / posterior wall thickness at end-systole. DWS quartiles were generated and used to make the Kaplan-Meier survival curves for incident HF with log-rank test. Cox proportional hazards models were used to evaluate the association between baseline DWS and incident HF. Over a median follow-up of 15.6 years, there were 251 HF events (incidence rate: 10.9 per 1,000 person-years). Participants with lower DWS (increased LV diastolic stiffness) had a higher incidence of HF than those with higher DWS (unadjusted hazard ratio 1.86, 95%CI 1.28-2.71 in 1 st quartile vs 4 th quartile, p=0.001). After adjustment for traditional risk factors and incident coronary heart disease during the course, DWS was independently associated with incident HF (hazard ratio 1.62, 95%CI 1.10-2.38 in 1 st quartile vs 4 th quartile, p=0.015). Conclusions: Increased LV myocardial stiffness evaluated by DWS was associated with an increased risk of HF in a community-based African American cohort in the ARIC. Increased LV myocardial stiffness may lead to future deterioration of LV hemodynamics and incident HF.

Oral treatment with a zinc complex of acetylsalicylic acid prevents diabetic cardiomyopathy in a rat model of type-2 diabetes: activation of the Akt pathway.

BackgroundType-2 diabetics have an increased risk of cardiomyopathy, and heart failure is a major cause of death among these patients. Growing evidence indicates that proinflammatory cytokines may induce the development of insulin resistance, and that anti-inflammatory medications may reverse this process. We investigated the effects of the oral administration of zinc and acetylsalicylic acid, in the form of bis(aspirinato)zinc(II)-complex Zn(ASA)2, on different aspects of cardiac damage in Zucker diabetic fatty (ZDF) rats, an experimental model of type-2 diabetic cardiomyopathy.MethodsNondiabetic control (ZL) and ZDF rats were treated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 29–30 weeks, the electrical activities, left-ventricular functional parameters and left-ventricular wall thicknesses were assessed. Nitrotyrosine immunohistochemistry, TUNEL-assay, and hematoxylin-eosin staining were performed. The protein expression of the insulin-receptor and PI3K/AKT pathway were quantified by Western blot.ResultsZn(ASA)2-treatment significantly decreased plasma glucose concentration in ZDF rats (39.0 ± 3.6 vs 49.4 ± 2.8 mM, P < 0.05) while serum insulin-levels were similar among the groups. Data from cardiac catheterization showed that Zn(ASA)2 normalized the increased left-ventricular diastolic stiffness (end-diastolic pressure–volume relationship: 0.064 ± 0.008 vs 0.084 ± 0.014 mmHg/µl; end-diastolic pressure: 6.5 ± 0.6 vs 7.9 ± 0.7 mmHg, P < 0.05). Furthermore, ECG-recordings revealed a restoration of prolonged QT-intervals (63 ± 3 vs 83 ± 4 ms, P < 0.05) with Zn(ASA)2. Left-ventricular wall thickness, assessed by echocardiography, did not differ among the groups. However histological examination revealed an increase in the cardiomyocytes’ transverse cross-section area in ZDF compared to the ZL rats, which was significantly decreased after Zn(ASA)2-treatment. Additionally, a significant fibrotic remodeling was observed in the diabetic rats compared to ZL rats, and Zn(ASA)2-administered ZDF rats showed a similar collagen content as ZL animals. In diabetic hearts Zn(ASA)2 significantly decreased DNA-fragmentation, and nitro-oxidative stress, and up-regulated myocardial phosphorylated-AKT/AKT protein expression. Zn(ASA)2 reduced cardiomyocyte death in a cellular model of oxidative stress. Zn(ASA)2 had no effects on altered myocardial CD36, GLUT-4, and PI3K protein expression.ConclusionsWe demonstrated that treatment of type-2 diabetic rats with Zn(ASA)2 reduced plasma glucose-levels and prevented diabetic cardiomyopathy. The increased myocardial AKT activation could, in part, help to explain the cardioprotective effects of Zn(ASA)2. The oral administration of Zn(ASA)2 may have therapeutic potential, aiming to prevent/treat cardiac complications in type-2 diabetic patients.

The hemodynamic effects of acute aortic regurgitation into a stiffened left ventricle resulting from chronic aortic stenosis.

Acute aortic regurgitation (AR) post-chronic aortic stenosis is a prevalent phenomenon occurring in patients who undergo transcatheter aortic valve replacement (TAVR) surgery. The objective of this work was to characterize the effects of left ventricular diastolic stiffness (LVDS) and AR severity on LV performance. Three LVDS models were inserted into a physiological left heart simulator. AR severity was parametrically varied through four levels (ranging from trace to moderate) and compared with a competent aortic valve. Hemodynamic metrics such as average diastolic pressures (DP) and reduction in transmitral flow were measured. AR index was calculated as a function of AR severity and LVDS, and the work required to make up for lost volume due to AR was estimated. In the presence of trace AR, higher LVDS had up to a threefold reduction in transmitral flow (13% compared with 3.5%) and a significant increase in DP (2-fold). The AR index ranged from ∼42 to 16 (no AR to moderate AR), with stiffer LVs having lower values. To compensate for lost volume due to AR, the low, medium, and high LVDS models were found to require 5.1, 5.5, and 6.6 times more work, respectively. This work shows that the LVDS has a significant effect on the LV performance in the presence of AR. Therefore, the LVDS of potential TAVR patients should be assessed to gain an initial indication of their ability to tolerate post-procedural AR.

Doppler indexes of left ventricular systolic and diastolic function in relation to the arterial stiffness in a general population.

Late-systolic loading of the left ventricular (LV) is determined by arterial wave reflections and central vascular stiffening. We, therefore, investigated the relationship between various Doppler indexes reflecting LV systolic and diastolic function and arterial stiffness in the framework of a large population study of randomly recruited study participants. In 1233 study participants (51.7% women; mean age, 48 years; 41.5% hypertensive), using conventional and tissue Doppler imaging, we measured: the transmitral early (E) and late (A) diastolic velocities; tissue Doppler imaging systolic and early (e') and late diastolic mitral annular velocities; and end-systolic longitudinal and radial strain. Using applanation tonometry, we assessed central pulse pressure (cPP), augmentation pressure and carotid-femoral pulse wave velocity. After full adjustment, transmitral E and A peaks increased with augmentation pressure and cPP (P less than 0.0001) and e' was positively associated with cPP (P = 0.013). The E/e' ratio increased significantly with augmentation pressure (P less than 0.0001), cPP (P less than 0.0001) and pulse wave velocity (P = 0.048). Although accounting for covariables, all arterial indexes were on average significantly higher in the diastolic dysfunction group with elevated filling pressure (n = 171) when compared to participants with normal diastolic function (n = 961; P ≤ 0.0004) or with impaired relaxation (n = 101; P ≤ 0.008). Longitudinal strain decreased independently with mean arterial pressure (P = 0.03). The correlation between radial strain and the arterial indexes shifted from positive at middle age (50-60 years) to negative at older (P less than 0.0001 for interaction). Our study underscored the importance of arterial characteristics as a mediator of LV systolic and diastolic dysfunction. We demonstrated an age-dependent relationship between radial strain and indexes of arterial stiffness.

Arterial Stiffness Is Significantly Associated With Left Ventricular Diastolic Dysfunction in Patients With Cardiovascular Disease.

Left ventricular (LV) diastolic dysfunction is considered the main cause of heart failure with preserved ejection fraction (HFpEF). There have been few reports on the correlation between LV diastolic dysfunction and arterial stiffness in patients with clinical cardiovascular disease.This cross-sectional study enrolled 100 patients (67 men, 33 women; mean age, 70 years). All participants were diagnosed with cardiovascular disease. A total of 89 (89%) patients had coronary artery disease or HF. Patients with reduced EF and valvular disease were excluded. Arterial stiffness was assessed by the cardio-ankle vascular index (CAVI), and LV diastolic dysfunction was estimated using echocardiography. The patients were divided into two groups based on the median value of CAVI. In all patients the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e') was significantly higher in the high CAVI group than in the low CAVI group (15.5 ± 6.4 versus 12.5 ± 2.9, P = 0.003). In the HF subgroup, E/e' was also significantly higher in the high CAVI group than in the low CAVI group (17.2 ± 5.9 versus 13.0 ± 3.1, P = 0.026). In univariate regression analysis, CAVI was significantly associated with E/e' in all patients (β = 0.28, P = 0.004) and in HF patients (β = 0.4, P = 0.028). Also in multivariate analysis, CAVI remained as an independent predictive factor of E/e' (β = 0.252, P = 0.037).A high CAVI was independently associated with LV diastolic dysfunction in patients with clinical cardiovascular disease. These results suggested that arterial stiffness contributed to the development of LV diastolic dysfunction.

Abstract 17895: Complementary Prognostic Value of Cardiac Metaiodobenzylguanidine Imaging and Diastolic Wall Strain in Patients With Preserved Left Ventricular Ejection Fraction Admitted for Acute Decompensated Heart Failure

Introduction: Cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging has been reported to provide prognostic information in patients with heart failure with preserved ejection fraction (HFpEF). On the other hand, diastolic wall strain (DWS) has been recently introduced as a simple and feasible echocardiographic index in assessing left ventricular (LV) diastolic stiffness, and has been shown to be associated with poor outcome in patients with HFpEF. Hypothesis: We assessed the hypothesis that cardiac MIBG imaging and DWS might have a complementary prognostic value in HFpEF patients admitted for acute decompensated heart failure (ADHF). Methods: We studied 70 consecutive patients admitted for ADHF and discharged with survival whose LV ejection fraction measured by echocardiography was ≧40% (age: 77±12 years, male: 49%, NYHA class at discharge: 2.2±0.8). Cardiac MIBG imaging and echocardiography were performed just before discharge. The cardiac MIBG heart-to-mediastinum ratio (H/M) and washout rate were calculated from the chest anterior view images obtained at 20 and 200min after isotope injection. DWS was determined in the LV M-mode echocardiogram using a validated formula. The endpoints were unplanned hospitalization for worsening heart failure (WHF) and pump failure death (PFD). Results: During a follow-up period of 2.0±0.8 years, 20 patients had WHF and 7 patients had PFD. At multivariate Cox analysis, out of the variables including clinical, hemodynamic, biochemical, MIBG and echocardiographic parameters, H/M on delayed image (late H/M) and DWS were significantly independently associated with WHF (p=0.0058) and PFD (p=0.0160), respectively. Kaplan-Meier analysis showed that the patients with late H/M &lt;1.73 (mean value) and those with DWS &lt;0.292 (mean value) had a significantly higher risk of WHF and PFD, respectively (Figure). Conclusions: Cardiac MIBG imaging and DWS had a complementary prognostic value in HFpEF patients admitted for ADHF.

Abstract 17219: Increased Aortic Stiffness Following Intrauterine Exposure to Chronic Hypoxia in Rats

Background: We have previously demonstrated in rats that fetal hypoxia is associated with altered left ventricular (LV) diastolic function beginning in early postnatal life (2 weeks). In the present study we hypothesized that intrauterine hypoxia exposure alters aortic stiffness which may contribute to the evolution of myocardial dysfunction after birth. Methods: Six pregnant rats were exposed to hypoxic conditions (11.5% FiO2) from E15-21and 3 were maintained in normoxic conditions. After delivery, 4 neonatal rats from each group were examined longitudinally at day 1, 3, and week 1, 2, 4, 8 for changes in aortic stiffness. Pups were anesthetized by face mask with 1.5% isoflurane. Aortic stiffness was assessed by measuring the pulse wave velocity (PWV) in the ascending aorta at 3 points: 1. Proximal to the branch of the first brachiocephalic artery 2. At the level of the diaphragm and 3. Just above the aortic bifurcation into the iliac arteries. T1 was the time interval from the peak of the R wave by ECG to onset of flow in the ascending aorta and T2 from peak of the R wave to onset of flow in either the mid aorta or distal aorta. The distance from the suprasternal notch to the subxiphoid process and to the anterior superior iliac spine was measured in each animal. The PWV was calculated using the following equation: [distance/(T2-T1)]. Three consecutive tracings were assessed and the PWV averaged for each study. Statistical analysis was performed using a 2-way ANOVA. Results: In pups exposed to fetal hypoxia, PWV was significantly increased (p≤0.001) compared to controls at day 1 (4.8±1.5 vs. 2.3±0.2 m/s), day 3 (5.5±0.3 vs. 2.6±0.1 m/s) and week 1 (4.4±0.4 vs. 2.8±0.1 m/s). Interestingly, there was an interaction of time and fetal exposure (p=0.006) whereby PWV values converged from weeks 2 - 8 such that fetal exposure to hypoxia no longer had an effect. No correlation was found between LV diastolic function parameters and aortic PWV in the fetal hypoxia rats at any postnatal age. Conclusion: Prenatal exposure to hypoxia was associated with increased aortic stiffness during early development. The lack of a relationship between LV diastolic function and aortic stiffness could suggest these represent independent effects of fetal hypoxia exposure.

Abstract 12002: Increasing Heart Rate in Left Bundle Branch Block Results in Incomplete Relaxation and Increases Left Ventricular Diastolic Stiffness

Introduction: Left bundle branch block (LBBB) slows LV pressure decay and shortens diastole. At low heart rates (HR) this may not compromise filling as diastolic duration is sufficient for complete relaxation. Purpose: We investigated if further abbreviation of diastole at increased HR could cause incomplete relaxation, particularly in the late activated LV lateral wall; thereby increasing diastolic LV stiffness, which may cause increased filling pressure. Methods: We analyzed data from a study of 10 canines where HR was increased from 120 to 140 by atrial pacing before and after induction of LBBB. Ventricular and pericardial pressures, LV volume and regional segment lengths (SL) were measured. Global diastolic stiffness was calculated from end diastolic (ED) transmural LV pressure-volume (PV) relations and regional stiffness from pressure-SL relations in septum and lateral wall. A mathematical model was used to estimate the increase in filling pressure due to incomplete relaxation at HR 160 and 180. Results: In LBBB, tau was prolonged and diastole abbreviated at both HR 120 and 140, compared to baseline (Fig. 1). Increased HR during LBBB stiffened the ventricle, seen as an upward shift of the ED PV relation by 1.4±1.7 mmHg (±SD), (p=0.03) whereas no shift (-0.9±1.5 mmHg) (NS) was seen at baseline (Fig. 2). Regional ED P-SL relations showed a larger upward shift of the lateral wall (1.1±1.8 mmHg) and hence a more pronounced stiffening compared to the septum (0.6±1.5 mmHg) (p&lt;0.05), indicating more delayed lateral wall relaxation. Mathematical estimation showed an increase in filling pressure of 7 and 16 mmHg due to further diastolic abbreviation at HR 160 and 180, respectively. Conclusions: LV diastolic stiffness is increased at high heart rates in LBBB due to incomplete relaxation, particularly of the late activated LV lateral wall. Diastolic stiffening by increased HR may lead to exercise intolerance and dyspnoea in LBBB patients due to elevated filling pressure.

Abstract 499: Lower Diastolic Wall Strain Is Associated With Percutaneous Coronary Intervention in Patients With Normal Left Ventricular Systolic Function

Background: Left ventricular (LV) diastolic dysfunction occurs before LV systolic dysfunction and electrocardiographic changes in ischemic cascade. Diastolic wall strain (DWS) has been proposed as a marker of LV diastolic stiffness. Therefore, the objectives of this study were to defined the relationship between DWS and percutaneous coronary intervention (PCI) and see other echocardiographic parameters in patients who undergoing coronary angiography (CAG). Methods: 254 patients (mean age: 61 ± 10, 136 (54%) men) undergoing CAG and normal left ventricular systolic function without regional wall motion abnormalities were enrolled, and among them, 68 (27%) patients performed PCI. All patients performed echocardiography before CAG and DWS defined using posterior wall thickness (PWT) measurements from standard echocardiographic images (DWS =[PWT(systole)-PWTdiastole)]/PWT(systole)). Results: Patients who performed PCI showed significantly lower DWS (0.27 ± 0.09 vs. 0.39 ± 0.08, p &lt; 0.001). Age did not differ between the two groups (61.6 ± 10.6 vs. 60.9 ± 10.4, p = 0.623), and LV ejection fraction was also similar (62.8 ± 4.6 vs. 63.5 ± 5.2%, p = 0.380). Other echocardiographic parameters did not show significance differences but E/E’ ratio was slightly but significantly elevated in patients performed PCI (10.9 ± 4.8 vs 9.2 ± 3.3, p = 0.011). In multiple regression analysis, lower DWS was an independent predictor for PCI (Cut-off value: 0.34, sensitivity: 89%, AUC: 0.870, SE: 0.025, p &lt; 0.001). Conclusion: DWS, a simple parameter that can be calculated from routine 2D echocardiography, is inversely associated with presence of coronary artery disease and PCI.

The impact of arterial load on left ventricular performance: an invasive haemodynamic study in severe mitral stenosis.

A hallmark of mitral stenosis (MS) is the markedly altered left ventricular (LV) loading. As most of the methods used to determine LV performance in MS patients are influenced by loading conditions, previous studies have shown conflicting results. The present study calculated LV elastance, which is a robust method to quantify LV function. We demonstrate that LV loading in MS patients is elevated but normalizes after valve repair and might be a result of reflex pathways. Additionally, we show that the LV in MS is less compliant than normal due to a combination of right ventricular loading and the valvular disease itself. Immediately after valve dilatation the increase in blood inflow into the LV results in even greater LV stiffness. Our findings enrich our understanding of heart function in MS patients and provide a simple reproducible way of assessing LV performance in MS. Left ventricular (LV) function in rheumatic mitral stenosis (MS) remains an issue of controversy, due to load dependency of previously employed assessment methods. We investigated LV performance in MS employing relatively load-independent indices robust to the altered loading state. We studied 106subjects (32±8years, 72% female) with severe MS (0.8±0.2 cm(2) ) and 40age-matched controls. MS subjects underwent simultaneous bi-ventricular catheterization and transthoracic echocardiography (TTE) before and immediately after percutaneous transvenous mitral commisurotomy (PTMC). Sphygmomanometric brachial artery pressures and TTE recordings were simultaneously acquired in controls. Single-beat LV elastance (Ees ) was employed for LV contractility measurements. Effective arterial elastance (Ea ) and LV diastolic stiffness were measured. MS patients demonstrated significantly elevated afterload (Ea : 3.0±1.3 vs. 1.5±0.3mmHgml(-1) ; P<0.001) and LV contractility (Ees : 4.1±1.6 vs. 2.4±0.5mmHgml(-1) ; P<0.001) as compared to controls, with higher Ea in subjects with smaller mitral valve area (≤ 0.8cm(2) ) and pronounced subvalvular fusion. Stroke volume (49±16 to 57±17ml; P<0.001) and indexed LV end-diastolic volume (LVEDVindex : 57±16 to 64±16mlm(-2) ; P<0.001) increased following PTMC while Ees and Ea returned to more normal levels. Elevated LV stiffness was demonstrated at baseline and increased further following PTMC. Our findings provide evidence of elevated LV contractility, increased arterial load and increased diastolic stiffness in severe MS. Following PTMC, both LV contractility and afterload tend to normalize.

Left ventricular diastolic dysfunction and myocardial stiffness in diabetic mice is attenuated by inhibition of dipeptidyl peptidase 4.

Obesity and Type 2 diabetes mellitus (DM) induce left ventricular (LV) diastolic dysfunction, which contributes to an increasing prevalence of heart failure with a preserved LV ejection fraction. We investigated the effects of sitagliptin (SITA), an inhibitor of dipeptidylpeptidase-4 (DPP-4) and anti-diabetic drug, on LV structure and function of obese mice with Type 2 DM. Obese Type 2 diabetic mice (Lepr(db/db), BKS.Cg-Dock7(m)+/+ Lepr(db)/J), displaying increased cardiomyocyte and LV stiffness at the age of 16 weeks, were treated with SITA (300 mg/kg/day) or vehicle for 8 weeks. SITA severely impaired serum DPP-4 activity, but had no effect on glycaemia. Invasive haemodynamic recordings showed that SITA reduced LV passive stiffness and increased LV stroke volume; LV end-systolic elastance remained unchanged. In addition, SITA reduced resting tension of isolated single cardiomyocytes and intensified phosphorylation of the sarcomeric protein titin. SITA also increased LV concentrations of cGMP and increased activity of protein kinase G (PKG). In vitro activation of PKG decreased resting tension of cardiomyocytes from vehicle-treated mice, but had no effect on resting tension of cardiomyocytes from SITA-treated mice. In obese Type 2 diabetic mice, in the absence of hypoglycaemic effects, inhibition of DPP-4 decreases LV passive stiffness and improves global LV performance. These effects seem at least partially mediated by stimulatory effects on the myocardial cGMP-PKG pathway and, hence, on the phosphorylation status of titin and the hereto coupled cardiomyocyte stiffness modulus.

Diastolic wall strain: a simple marker of abnormal cardiac mechanics.

BackgroundDiastolic wall strain (DWS), defined using posterior wall thickness (PWT) measurements from standard echocardiographic images (DWS = [PWT(systole)-PWT(diastole)]/PWT(systole)), has been proposed as a marker of left ventricular (LV) diastolic stiffness. However, the equation for DWS is closely related to systolic radial strain, and whether DWS is associated with abnormal cardiac mechanics (reduced systolic strains and diastolic tissue velocities) is unknown. We sought to determine the relationship between DWS and systolic and diastolic cardiac mechanics.MethodsWe calculated DWS and performed speckle-tracking analysis in a large population- and family-based study (Hypertension Genetic Epidemiology Network [HyperGEN]; N = 1907 after excluding patients with ejection fraction [EF] < 50% or posterior wall motion abnormalities). We measured global longitudinal, circumferential, and radial strain (GLS, GCS, and GRS, respectively) and early diastolic (e’) tissue velocities, and we determined the independent association of DWS with cardiac mechanics using linear mixed effects models to account for relatedness among study participants. We also prospectively performed receiver-operating characteristic (ROC) analysis of DWS for the detection of abnormal cardiac mechanics in a separate, prospective validation study (N = 35).ResultsIn HyperGEN (age 51 ± 14 years, 59% female, 45% African-American, 57% hypertensive), mean DWS was 0.38 ± 0.05. DWS decreased with increasing comorbidity burden (β-coefficient -0.013 [95% CI -0.015, -0.011]; P < 0.0001). DWS was independently associated with GLS, GCS, GRS, and e’ velocity (adjusted P < 0.05) but not LV chamber compliance (EDV20, P = 0.97). On prospective speckle-tracking analysis, DWS correlated well with GLS, GCS, and GRS (R = 0.61, 0.57, and 0.73, respectively; P < 0.001 for all comparisons). C-statistics for DWS as a diagnostic test for abnormal GLS, GCS, and GRS were: 0.78, 0.79, and 0.84, respectively.ConclusionsDWS, a simple parameter than can be calculated from routine 2D echocardiography, is closely associated with systolic strain parameters and early diastolic (e’) tissue velocities but not LV chamber compliance.

Patient-specific finite element modeling of the Cardiokinetix Parachute(®) device: effects on left ventricular wall stress and function.

The Parachute(®) (Cardiokinetix, Inc., Menlo Park, California) is a catheter-based device intended to reverse left ventricular (LV) remodeling after antero-apical myocardial infarction. When deployed, the device partitions the LV into upper and lower chambers. To simulate its mechanical effects, we created a finite element LV model based on computed tomography (CT) images from a patient before and 6 months after Parachute(®) implantation. Acute mechanical effects were determined by in silico device implantation (VIRTUAL-Parachute). Chronic effects of the device were determined by adjusting the diastolic and systolic material parameters to better match the 6-month post-implantation CT data and LV pressure data at end-diastole (ED) (POST-OP). Regional myofiber stress and pump function were calculated in each case. The principal finding is that VIRTUAL-Parachute was associated with a 61.2 % reduction in the lower chamber myofiber stress at ED. The POST-OP model was associated with a decrease in LV diastolic stiffness and a larger reduction in myofiber stress at the upper (27.1%) and lower chamber (78.4%) at ED. Myofiber stress at end-systole and stroke volume was little changed in the POST-OP case. These results suggest that the primary mechanism of Parachute(®) is a reduction in ED myofiber stress, which may reverse eccentric post-infarct LV hypertrophy.

Left ventricular diastolic dysfunction is associated with cerebral white matter lesions (leukoaraiosis) in elderly patients without ischemic heart disease and stroke

Cerebral white matter lesions (WML) are known to increase with age, as is left ventricular (LV) diastolic dysfunction with normal contraction. Although aging is a common risk factor, the link between these diseases is not fully understood. The aim was to clarify this relationship, using the ratio between early diastolic mitral inflow and early diastolic mitral annular tissue velocity (E/E'). E/E' measured by tissue Doppler echocardiography offers an indicator of the severity of LV diastolic dysfunction, reflecting both diastolic LV stiffness and diastolic LV filling pressure. Participants comprised 75 patients aged between 65 and 75 years with normal LV contraction and no signs or history of symptomatic heart failure, ischemic heart diseases, atrial fibrillation, stroke, or cognitive dysfunction. The volume of WML was quantified on brain magnetic resonance imaging. The participants were classified into three groups: Low E/E', E/E' ≤ 8; Middle E/E', 8 < E/E' < 15; and High E/E', E/E' ≥ 15. WML volume was 3.6 ± 3.0 mL in Low E/E', 5.4 ± 6.5 mL in Middle E/E' and 12.0 ± 11.0 mL in High E/E', increasing significantly with increased diastolic LV stiffness (Low vs High, P = 0.034; Middle vs High, P = 0.016). Linear regression analysis showed the positive association between the volume of WML and E/E' ratio (r = 0.377, P = 0.0009). This investigation identified an association between LV diastolic dysfunction and WML. Further investigations are required to clarify whether there is a direct association between the two diseases.

Sex‐specific cardiovascular structure and function in heart failure with preserved ejection fraction

Women are more likely to develop heart failure with preserved ejection fraction (HFpEF) than men. We studied the relationship between sex and cardiovascular structure and function in patients with HFpEF. The study included 279 participants from the PARAMOUNT study (57% women) with analysable baseline echocardiograms (mean age 71 years, 94% hypertensive, 38% diabetic). We assessed sex-based differences in baseline clinical characteristics and measures of cardiovascular structure/function. Coronary artery disease was less common in women than in men. Women were more obese and symptomatic, and less likely to have albuminuria. Women had higher indexed left ventricular (LV) wall thicknesses, worse diastolic function (lower E', P = 0.002; higher E/E', P < 0.001), while LV mass and LV volumes indexed for height(2.7) were similar. Nonetheless, female sex was associated with a trend towards higher prevalence of abnormal LV geometry (defined as concentric hypertrophy, or eccentric hypertrophy, or concentric remodelling) at baseline (unadjusted P = 0.028, adjusted P = 0.056) and 12 weeks' follow up (unadjusted P = 0.001, adjusted P = 0.006), but not at 36 weeks' follow up (unadjusted P = 0.81, adjusted P = 0.99). Despite higher LV ejection fraction in women, global LV strain was similar between the sexes, while Tissue Doppler Imaging S' mitral velocity was lower in women. Both LV diastolic and systolic stiffness were higher in women than men (P < 0.001), even adjusting for LV concentricity and clinical covariates. We observed no sex differences in systolic arterial-LV coupling, as women also had higher absolute arterial elastance compared with men, although this difference was not significant after adjusting for height(2.7) . More pronounced diastolic dysfunction may contribute to the greater predisposition for HFpEF in women compared with men.

Systolic and Diastolic Mechanics in Stress Cardiomyopathy

Stress cardiomyopathy (SCM) is a peculiar form of reversible left ventricular dysfunction seen predominantly in women and occurs in response to emotional or physical stress. Because dysfunction in SCM is reversible and that of acute myocardial infarction (MI) is not, we hypothesized that these fundamental mechanistic differences between SCM and MI would be associated with different systolic and diastolic properties. We examined 3 groups, all women: patients with SCM (n=24; mean age, 63±12 years), those with left anterior (LAD) ST-segment-elevation MI (n=36; mean age, 63±10 years), and referent control subjects (n=30; mean age, 62±8 years). All underwent angiography, ventriculography, and pressure measurements within 48 hours of presentation. Left ventricular volumes, diastolic pressures, and diastolic stiffness were higher in SCM and LAD MI patients than in control subjects but no different from each other. Similarly, left ventricular diastolic pressures and diastolic stiffness were elevated in the SCM and LAD MI groups compared with the control group. Left ventricular ejection fraction in SCM and LAD MI were 40.8±12.3% and 49.6±5.6%, respectively, versus 70.4±9.4% in control subjects (P<0.001), and stroke work less than half the value of control subjects. Indexes of contractility and ventricular-arterial coupling were similarly abnormal in SCM and LAD MI. SCM and LAD MI show severe diastolic dysfunction. At similar left ventricular volumes, their diastolic pressures are more than twice as high as in control subjects, and systolic dysfunction is equally reduced in SCM and LAD MI. Despite a completely different pathophysiology in terms of systolic and diastolic function, SCM is indistinguishable from acute LAD-territory MI.

Impact of Comorbidities on Myocardial Remodeling and Dysfunction In Heart Failure with Preserved Ejection Fraction

Heart failure (HF) with preserved ejection (HFpEF) is widely prevalent and associated with poor outcome and incompletely understood pathophysiology. In contrast to HF with reduced EF (HFrEF), modern HF pharmacotherapy did not improve outcome in HFpEF, which emphasizes the urgent need to elucidate responsible pathogenetic mechanisms in HFpEF. Over the last decennium, myocardial structure, cardiomyocyte function and intramyocardial signaling were shown to be specifically altered in HFpEF. Myocardial remodelling and dysfunction in HFpEF comprises myocardial hypertrophy and fibrosis and increased cardiomyocyte stiffness. Increased cardiomyocyte stiffness in HFpEF importantly contributes to high left ventricular (LV) diastolic stiffness and results from specific changes in transcriptional and posttranslational modifications of the giant elastic sarcomeric protein, titin. Increased systemic vascular inflammation, endothelial dysfunction and oxidative stress resulting in reduced nitric oxide (NO) bioavailability appear importantly involved in increased diastolic LV stiffness and adverse remodelling in HFpEF. Recently, a new paradigm for HFpEF was proposed, which suggests that prevalent comorbidities, such as overweight/obesity, diabetes, hypertension, chronic pulmonary obstructive disease, anemia and chronic kidney dysfunction drive myocardial dysfunction and remodelling through coronary microvascular endothelial inflammation. Additional demographic characteristics in HFpEF are older age and female predominance, which could contribute to maladaptive cardiovascular structural and functional changes in a synergistic manner with the prevalent comorbidities. Although HFpEF is associated with more impaired cardiovascular abnormalities and worse outcome beyond the level explainable by comorbidities alone, the rationale for an important involvement of noncardiac comorbidities in myocardial dysfunction and remodeling in HFpEF seems plausible. In the following review, this rationale of an important involvement of comorbidities in HFpEF pathophysiology is further addressed in light of the proposed new HFpEF paradigm.

Aortic Stiffness Is Associated With Left Ventricular Diastolic Dysfunction in Systemic Lupus Erythematosus: A Controlled Transesophageal Echocardiographic Study

Aortic stiffness and left ventricular (LV) diastolic dysfunction are common and associated with increased morbidity and mortality in systemic lupus erythematosus (SLE). In SLE, aortic stiffness and LV diastolic dysfunction may be associated. This 6-year-duration, cross-sectional, and controlled study was conducted in 76 SLE patients (69 women; mean age, 37 ± 12 years) and 26 age- and sex-matched healthy controls. All subjects underwent clinical and laboratory evaluations and transesophageal echocardiography (TEE) to assess LV diastolic function and stiffness of the descending thoracic aorta using the pressure-strain elastic modulus (PSEM). To validate results using PSEM, aortic strain, stiffness, and distensibility were assessed. Patients as compared with controls had higher PSEM (8.14 ± 4.25 vs 5.97 ± 2.31 U, P < 0.001) and had lower mitral inflow E/A and septal and lateral mitral annulus tissue Doppler E'/A' velocity ratios, longer isovolumic relaxation time, lower septal and lateral mitral annulus E' velocities, and higher mitral E/septal E' and mitral E/lateral E' velocity ratios (all P ≤ 0.03), all indicative of LV diastolic dysfunction. In patients, PSEM was correlated with parameters of LV diastolic dysfunction (all P < 0.05), was independently negatively associated with E/A and E'/A' ratios and E' velocities, and was positively associated with E/E' ratios (P ≤ 0.02 for each parameter and P < 0.001 for all parameters as a profile). Aortic strain, stiffness, and distensibility were also worse in patients than in controls (all P < 0.05) and were correlated with parameters of LV diastolic dysfunction (all P ≤ 0.03). Aortic stiffness is independently associated with LV diastolic dysfunction in young adult patients with SLE.

Relation Between Left Ventricular Diastolic Function and Arterial Stiffness in Patients with Bicuspid Aortic Valve

PP-234 Bicuspid aortic valve (BAV) is the result of abnormal aortic leaflet formation during valvulogenesis. Recently, it has been shown that BAV is associated with abnormal aortic stiffness, which has a negative impact on left ventricular (LV) diastolic function. The purpose of this study was to