Left Ventricular Stiffness Research Articles

Abstract 4141497: Left ventricular diastolic function by echocardiography is related to extracellular volume and is an independent predictor of mortality in patients with aortic regurgitation

Background: Cardiac catheterization along with cardiac biopsy studies have shown the presence of abnormally increased left ventricular (LV) chamber stiffness in patients with severe aortic regurgitation (AR) and its significant correlation with interstitial fibrosis. LV diastolic dysfunction (DD) is associated with increased mortality in several patient populations. However, there is a paucity of data on the association of DD with mortality in patients with AR. Hypotheses: 1 - LV DD is related to extracellular volume (ECV), imaging marker of interstitial fibrosis, by cardiac magnetic resonance imaging (CMR) 2 - LV DD by echocardiography is associated with mortality in patients with AR Methods: We studied patients with moderate or greater AR who underwent echocardiographic and CMR imaging within 12 months. We excluded patients with concomitant valve disease, prior valve intervention, cardiomyopathy deemed unrelated to AR, congenital heart disease and terminal conditions. The primary outcome was all-cause death. CMR was used to obtain LV volumes, EF and mass, AR severity, scar extent by delayed hyperenhancement, and ECV. DD was assessed by comprehensive echocardiography. Results: The study included 323 patients. Mean age was 61.9 ± 16.0 years and 22% were female. Median follow-up was 3.8 years, during which 65 patients died and 172 had aortic valve replacement. Median LV EF was 56 (47-65) %, AR volume on CMR was 40 (30-61) mL, and AR fraction was 40 (33-47) %. ECV progressively increased with higher grades of LV DD (Figure 1). Table 1 shows the univariate associations with mortality in the study. On multivariable analysis based on the Lasso variable selection process, Euroscore, Charlson comorbidity index, DD grade, and RAP were associated with total mortality. Conclusion: ECV by CMR progressively increases with higher grades of DD by echocardiography, and DD is independently associated with mortality in patients with AR.

RV-PA uncoupling is a strong predictor of 3-year all-cause mortality in transthyretin amyloid cardiomyopathy

Abstract Background Right ventricle to pulmonary artery coupling (RV-PAc) describes the right ventricle's ability to adjust to an increased afterload which, in case of transthyretin amyloid cardiomyopathy (ATTR-CM), can result from increased left ventricular diastolic stiffness due to fibril deposition. While RV-PAc is a validated prognostic parameter in pulmonary arterial hypertension (PAH), its prognostic relevance in ATTR-CM remains unclear. This study sought to evaluate the prognostic implications of impaired RV-PAc on survival in ATTR-CM. Methods In this two-centre study, RV-PAc was investigated by the echocardiographic surrogate of ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP) in 418 ATTR-CM patients, all treated with TTR stabilizer. The primary outcome was all-cause mortality. Receiver operation curves and Youden’s J analysis were applied to identify an optimal cut-off value of RV-PAc ratio. Results Within a median time of 631 (IQR 361-983) days after diagnosis, 14.4% of patients died. RV-PAc ratio at first presentation emerged as a robust marker for risk stratification with a determined optimal cut-off of 0.382mm/mmHg (area under the curve (AUC) 0.746, 95% CI 0.68-0.82). Patients with RV-PAc ratio ≤0.382mm/mmHg (impaired RV-PAc, n=158) exhibited significantly lower survival (HR 4.07, 95% CI 2.26-7.33, p<0.001) within 3 years of follow up than those with RV-PAc ratio > 0.382mm/mmHg. In multivariate Cox regression analysis, incorporating a range of known prognostic variables, reduced RV-PAc was a strong echocardiographic predictor of mortality (Hazard Ratio (HR) 2.99, 95% Confidence Interval (CI) 1.63-5.51, p <0.001). Conclusion Impaired adaption of the RV to increased afterload is associated with worse outcome in ATTR-CM patients. RV-PAc ratio can serve as an echocardiographic predictor for all-cause mortality within three years after diagnosis. Therefore, determination of RV-PAc could improve risk stratification for ATTR-CM patients.Figure_1_Kaplan-Meier curves

Diagnosing heart failure with preserved ejection fraction in patients with unexplained dyspnoea using left ventricular pressure-volume loops at rest and on exertion

Abstract Background To date, diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging, especially in euvolaemic patients presenting with unexplained dyspnoea on exertion and reduced exercise capacity. A stepwise approach was introduced with the HFA-PEFF diagnostic algorithm*, in which a relevant number of patients has to undergo invasive workup for a final judgement. Purpose The present study aimed to examine a population of patients with unexplained dyspnoea on exertion, using the diagnostic methods endorsed by the HFA-PEFF algorithm as well as left ventricular (LV) pressure-volume loops at rest, on exertion, and during caval occlusion, in order to identify and describe different phenotypes of HFpEF. Methods We prospectively included patients with unexplained dyspnoea on exertion, a left ventricular ejection fraction (LVEF) of ≥ 50%, and without an obvious cause of the dyspnoea. All patients underwent a comprehensive invasive haemodynamic workup. After invasive rule-out of a haemodynamically relevant coronary artery stenosis, we performed a right heart catheterization at rest (R) and on exertion (E) with an arm ergometer. Real-time continuous pressure-volume loops were obtained using a 7-French conductance catheter at rest, on exertion, and under temporal preload reduction via partial occlusion of the vena cava inferior. Results Thirty patients were included. Two patients had to be excluded from further analysis (one due to a technical failure of the conductance catheter and one with severe hypertension (systolic blood pressure > 200 mmHg) during the assessment). The 28 patients in this analysis had a mean age of 64.4±9.7 years and 57% were female. Eleven patients fulfilled invasively easily obtainable diagnostic criteria of HFpEF (mean pulmonary capillary wedge pressure (mPCWP) at rest ≥ 15 mmHg, exertional mPCWP ≥ 25 mmHg, LV end-diastolic pressure (LVEDP) at rest ≥ 16 mmHg, or exertional LVEDP ≥ 25 mmHg) according to the current guideline*. An additional 15 patients had a normal mPCWP and LVEDP, but fulfilled diagnostic criteria for HFpEF measured by the conductance catheter (time constant of LV relaxation tau > 48 ms and/ or chamber stiffness b > 0.27). We referred to this group as "early HFpEF". Patients with early HFpEF had a significantly higher systolic blood pressure, a worse LV relaxation time, and were more likely to exhibit chronotropic insufficiency compared to the HFpEF group (Table 1). HFpEF patients were characterised by significantly higher natriuretic peptides, LVEDP on exertion, and LV stiffness compared to patients with early HFpEF (pressure-volume loops are depicted in Figure 1). Conclusion Invasive haemodynamic testing for HFpEF in patients with unexplained dyspnoea on exertion via right heart catheterization without obtaining LV pressure-volume loops had a false negative rate of 58%. Better detection, the prognosis, and treatment of this "early HFpEF" population warrants further research.Table 1Figure 1

Reproducibility of Cardiac Multifrequency MR Elastography in Assessing Left Ventricular Stiffness and Viscosity.

Cardiac magnetic resonance elastography (MRE) shows promise in assessing the mechanofunctional properties of the heart but faces clinical challenges, mainly synchronization with cardiac cycle, breathing, and external harmonic stimulation. To determine the reproducibility of in vivo cardiac multifrequency MRE (MMRE) for assessing diastolic left ventricular (LV) stiffness and viscosity. Prospective. This single-center study included a total of 28 participants (mean age, 56.6 ± 23.0 years; 16 male) consisting of randomly selected healthy participants (mean age, 44.6 ± 20.1 years; 9 male) and patients with aortic stenosis (mean age, 78.3 ± 3.8 years; 7 male). 3 T, 3D multifrequency MRE with a single-shot spin-echo planar imaging sequence. Each participant underwent two cardiac MMRE examinations on the same day. Full 3D wave fields were acquired in diastole at frequencies of 80, 90, and 100 Hz during a total of three breath-holds. Shear wave speed (SWS) and penetration rate (PR) were reconstructed as a surrogate for tissue stiffness and inverse viscous loss. Epicardial and endocardial ROIs were manually drawn by two independent readers to segment the LV myocardium. Shapiro-Wilk test, Bland-Altman analysis and intraclass correlation coefficient (ICC). P-value <0.05 were considered statistically significant. Bland-Altman analyses and intraclass correlation coefficients (ICC = 0.96 for myocardial stiffness and ICC = 0.93 for viscosity) indicated near-perfect test-retest repeatability among examinations on the same day. The mean SWS for scan and re-scan diastolic LV myocardium were 2.42 ± 0.24 m/s and 2.39 ± 0.23 m/s; the mean PR were 1.24 ± 0.17 m/s and 1.22 ± 0.14 m/s. Inter-reader variability showed good to excellent agreement for myocardial stiffness (ICC = 0.92) and viscosity (ICC = 0.85). Cardiac MMRE is a promising and reproducible method for noninvasive assessment of diastolic LV stiffness and viscosity. 2 TECHNICAL EFFICACY: 1.

Sacubitril/valsartan improves diastolic left ventricular stiffness with increased titin phosphorylation via cGMP-PKG activation in diabetic mice

Titin, a giant sarcomeric protein, regulates diastolic left ventricular (LV) passive stiffness as a molecular spring and could be a therapeutic target for diastolic dysfunction. Sacubitril/valsartan (Sac/Val), an angiotensin receptor neprilysin inhibitor, has been shown to benefit patients with heart failure with preserved ejection fraction. The effect of Sac/Val is thought to be due to the enhancement of the cGMP/PKG pathway via natriuretic peptide. In this study, the effects of Sac/Val on LV diastolic dysfunction are demonstrated in a mouse diabetic cardiomyopathy model focusing on titin phosphorylation. Sac/Val-treated diabetic mice showed a greater increase in myocardial levels of cGMP-PKG than Val-treated and control mice. Conductance catheter analysis showed a significant reduction in LV stiffness in diabetic mice, but not in non-diabetic mice. Notably, diastolic LV stiffness was significantly reduced in Sac/Val-treated diabetic hearts compared with Val-treated or vehicle-treated diabetic mice. The phosphorylation level of titin (N2B), which determines passive stiffness and modulates active contraction, was higher in Sac/Val-treated hearts compared with Val-treated hearts in diabetic mice. Given that alteration of titin phosphorylation through PKG contributes to myocardial stiffness, the beneficial effects of Sac/Val in heart failure might be partly attributed to the induction of titin phosphorylation.

Diabetes induces modifications in costameric proteins and increases cardiomyocyte stiffness.

Several studies have demonstrated that Diabetes mellitus can increase the risk of cardiovascular disease and remains the principal cause of death in these patients. Costameres connect the sarcolemma with the cytoskeleton and extracellular matrix, facilitating the transmission of mechanical forces and cell signaling. They are related to cardiac physiology because individual cardiac cells are connected by intercalated discs that synchronize muscle contraction. Diabetes impacts the nano-mechanical properties of cardiomyocytes, resulting in increased cellular and left ventricular stiffness, as evidenced in clinical studies of these patients. The question of whether costameric proteins are affected by diabetes in the heart has not been studied. This work analyzes whether T1DM modifies the costameric proteins and coincidentally changes the cellular mechanics in the same cardiomyocytes. The samples were analyzed by immunotechniques using laser confocal microscopy. Significant statistical differences were found in the spatial arrangement of the costameric proteins. However, these differences are not due to their expression. Atomic force microscopy was used to compare intrinsic cellular stiffness between diabetic and normal cardiomyocytes and obtain the first elasticity map sections of diabetic living cardiomyocytes. Data obtained demonstrated that diabetic cardiomyocytes had higher stiffness than control. The present work shows experimental evidence that intracellular changes related to cell-cell and cell-extracellular matrix communication occur, which could be related to cardiac pathogenic mechanisms. These changes could contribute to alterations in the mechanical and electrical properties of cardiomyocytes and consequently, to diabetic cardiomyopathy.

Evaluation of diastolic wall strain in patients with mitral valve regurgitation

Background: Diastolic wall strain (DWS) is a non invasive, easy, echocardiographic parameter that has been used to determine left ventricular diastolic stiffness. The relationship between left ventricle functions and diastolic wall strain is previously revealed but we don’t know if this method correlates with mitral regurgitation (MR) severity or not. In this study, we sought to determine the relationship between DWS and MR. Methods: This study included 107 subjects with primary mitral regurgitation, divided in two groups as mild-to-moderate and severe mitral regurgitation, and 54 control subjects. We calculated the DWS from the M-mode echocardiographic measurements of the LV posterior wall thickness at end-systole and end-diastole during sinus rhythm. Results: MR group had lower values of DWS than control subjects and severe MR group had the lowest ones (0.38 ± 0.06; 0.27 ± 0.07; 0.15 ± 0.035 respectively and p

Abstract P325: Additive effect of nighttime blood pressure on left ventricular strain in patients with primary aldosteronism evaluated via cardiac magnetic resonance tissue tracking

Background: Primary aldosteronism (PA) induces left ventricular (LV) remodeling and increases the risk of high nighttime blood pressure (BP), which causes further heart damage. This study aimed to investigate whether nighttime BP aggravates LV deformation dysfunction and to identify independent factors affecting the global peak strain (PS) of LV remodeling in patients with PA compared to patients with essential hypertension (EH). Methods: A total of 280 patients with PA and 280 age- and sex-matched patients with EH who underwent cardiac magnetic resonance examination at the First Affiliated Hospital of Chengdu Medical College were included. According to the results of adrenal computed tomography and/or adrenal venous sampling, there were 154 patients with aldosterone-producing adenoma (APA) and 126 patients with idiopathic hyperaldosteronism (IHA). Twenty-four-hour ambulatory BP monitoring (ABPM), LV function, global strain parameters, and other clinical medical data were compared, and multivariate analysis was performed to identify the independent indicators of the LV PS. Results: No differences in age, sex, body mass index, clinical BP, 24-h mean BP, daytime BP, or duration of hypertension were found between the groups. Nighttime systolic BP (132 ± 17 vs. 126 ± 18 mm Hg, P &lt; 0.05) and diastolic BP (85 ± 11 vs. 80 ±10 mm Hg, P &lt; 0.05) were greater in PA patients than in EH patients. Compared with the EH controls, the PA patients had a lower LV global PS and peak diastolic strain rate (PDSR) in three directions. No significant differences were found in the PS (radial or longitudinal) or PDSR in the three directions between the APA and IHA groups. Furthermore, nighttime BP was an independent predictor of LV global radial, circumferential, and longitudinal PS. Conclusions: High nighttime BP may aggravate LV stiffness in patients with PA, resulting in decreased LV strain and function. Nighttime BP was independently correlated with LV global PS in patients with PA.

Randomized Crossover Trial of 2-Week Ketone Ester Treatment in Patients With Type 2 Diabetes and Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) is a major cause of morbidity and mortality in patients with type 2 diabetes (T2DM). Acute increases in circulating levels of ketone body 3-hydroxybutyrate have beneficial acute hemodynamic effects in patients without T2DM with chronic heart failure with reduced ejection fraction. However, the cardiovascular effects of prolonged oral ketone ester (KE) treatment in patients with T2DM and HFpEF remain unknown. A total of 24 patients with T2DM and HFpEF completed a 6-week randomized, double-blind crossover study. All patients received 2 weeks of KE treatment (25 g D-ß-hydroxybutyrate-(R)-1,3-butanediol × 4 daily) and isocaloric and isovolumic placebo, separated by a 2-week washout period. At the end of each treatment period, patients underwent right heart catheterization, echocardiography, and blood samples at trough levels of intervention, and then during a 4-hour resting period after a single dose. A subsequent second dose was administered, followed by an exercise test. The primary end point was cardiac output during the 4-hour rest period. During the 4-hour resting period, circulating 3-hydroxybutyrate levels were 10-fold higher after KE treatment (1010±56 µmol/L; P<0.001) compared with placebo (91±55 µmol/L). Compared with placebo, KE treatment increased cardiac output by 0.2 L/min (95% CI, 0.1 to 0.3) during the 4-hour period and decreased pulmonary capillary wedge pressure at rest by 1 mm Hg (95% CI, -2 to 0) and at peak exercise by 5 mm Hg (95% CI, -9 to -1). KE treatment decreased the pressure-flow relationship (∆ pulmonary capillary wedge pressure/∆ cardiac output) significantly during exercise (P<0.001) and increased stroke volume by 10 mL (95% CI, 0 to 20) at peak exercise. KE right-shifted the left ventricular end-diastolic pressure-volume relationship, suggestive of reduced left ventricular stiffness and improved compliance. Favorable hemodynamic responses of KE treatment were also observed in patients treated with sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogs. In patients with T2DM and HFpEF, a 2-week oral KE treatment increased cardiac output and reduced cardiac filling pressures and ventricular stiffness. At peak exercise, KE treatment markedly decreased pulmonary capillary wedge pressure and improved pressure-flow relationship. Modulation of circulating ketone levels is a potential new treatment modality for patients with T2DM and HFpEF. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT05236335.

Racial Differences of Cardiac Structure and Function in Heart Failure With Preserved Ejection Fraction

Potential race differences in cardiac structure and function among patients with heart failure with preserved ejection fraction (HFpEF) are not well-understood, but may have pathophysiological and treatment implications. In this study, patients with HFpEF who self-identified as Asian (n = 360), White (n = 787), and Black (n = 171) from 3 institutions underwent comprehensive transthoracic echocardiography to evaluate for potential differences. The Asian HFpEF group was oldest and the Black HFpEF group was youngest (75 ± 12 years vs 73 ± 13 years vs 62 ± 12 years; P < .0001). Women constituted the lowest proportion of patients with HFpEF among Asian individuals, but were the largest among Black patients (49% vs 56% vs 73%; P < .0001). Body mass index and obesity prevalence were highest in Black patients with HFpEF and were lowest in Asian patients. Black individuals with HFpEF had greater left ventricular (LV) wall thickening and concentricity, smaller LV chamber size, leftward-shifted LV end-diastolic pressure-volume relationship, indicating greater LV stiffening, smallest left atrial volumes, and the most right ventricular dilatation. Asian individuals with HFpEF had greater LV and left atrial dilation, more rightward shifted LV end-diastolic pressure-volume relationship, and the highest arterial stiffness. In summary, we show that patients with HFpEF of Asian, Black, and White race display key differences in clinical, anthropometric, and cardiac structure-function indices, indicating that consideration of race-related differences might important to individualize treatment strategies in HFpEF.

Additive effect of admission hyperglycemia on left ventricular stiffness in patients following acute myocardial infarction verified by CMR tissue tracking

BackgroundStress hyperglycemia occurs frequently in patients following acute myocardial infarction (AMI) and may aggravate myocardial stiffness, but relevant evidence is still lacking. Accordingly, this study aimed to examine the impact of admission stress hyperglycemia on left ventricular (LV) myocardial deformation in patients following AMI.MethodsA total of 171 patients with first AMI (96 with normoglycemia and 75 with hyperglycemia) underwent cardiac magnetic resonance (CMR) examination were included. AMI patients were classified according to admission blood glucose level (aBGL): < 7.8 mmol/L (n = 96), 7.8–11.1 mmol/L (n = 41) and ≥ 11.1 mmol/L (n = 34). LV strains, including global radial/circumferential/longitudinal peak strain (PS)/peak systolic strain rate (PSSR)/peak diastolic strain rate (PDSR), were measured and compared between groups. Further, subgroup analyses were separately conducted for AMI patients with and without diabetes. Multivariate analysis was employed to assess the independent association between aBGL and LV global PS in AMI patients.ResultsLV global PS, PSSR and PDSR were decreased in radial, circumferential and longitudinal directions in hyperglycemic AMI patients compared with normoglycemic AMI patients (all P < 0.05). These differences were more obvious in patients with diabetes than those without diabetes. AMI patients with aBGL between 7.8 and 11.1 mmol/L demonstrated significant decreased radial and longitudinal PS, radial PSSR, and radial and longitudinal PDSR than those with aBGL < 7.8 mmol/L (all P < 0.05). AMI patients with aBGL ≥ 11.1 mmol/L showed significantly decreased PS, PSSR and PDSR in all three directions than those with aBGL < 7.8 mmol/L, and decreased longitudinal PSSR than those with aBGL between 7.8 and 11.1 (all P < 0.05). Further, aBGL was significantly and independently associated with radial (β = − 0.166, P = 0.003) and longitudinal (β = 0.143, P = 0.008) PS.ConclusionsHyperglycemia may exacerbate LV myocardial stiffness in patients experienced first AMI, leading to reduction in LV strains. aBGL was an independent indicator of impaired LV global PS in AMI patients. Blood glucose monitoring is more valuable for AMI patients with diabetes.

Sex Differences in Aging-related Myocardial Stiffening Quantitatively Measured with MR Elastography.

Purpose To investigate the feasibility of using quantitative MR elastography (MRE) to characterize the influence of aging and sex on left ventricular (LV) shear stiffness. Materials and Methods In this prospective study, LV myocardial shear stiffness was measured in 109 healthy volunteers (age range: 18-84 years; mean age, 40 years ± 18 [SD]; 57 women, 52 men) enrolled between November 2018 and September 2019, using a 5-minute MRE acquisition added to a clinical MRI protocol. Linear regression models were used to estimate the association of cardiac MRI and MRE characteristics with age and sex; models were also fit to assess potential age-sex interaction. Results Myocardial shear stiffness significantly increased with age in female (age slope = 0.03 kPa/year ± 0.01, P = .009) but not male (age slope = 0.008 kPa/year ± 0.009, P = .38) volunteers. LV ejection fraction (LVEF) increased significantly with age in female volunteers (0.23% ± 0.08 per year, P = .005). LV end-systolic volume (LVESV) decreased with age in female volunteers (-0.20 mL/m2 ± 0.07, P = .003). MRI parameters, including T1, strain, and LV mass, did not demonstrate this interaction (P > .05). Myocardial shear stiffness was not significantly correlated with LVEF, LV stroke volume, body mass index, or any MRI strain metrics (P > .05) but showed significant correlations with LV end-diastolic volume/body surface area (BSA) (slope = -3 kPa/mL/m2 ± 1, P = .004, r2 = 0.08) and LVESV/BSA (-1.6 kPa/mL/m2 ± 0.5, P = .003, r2 = 0.08). Conclusion This study demonstrates that female, but not male, individuals experience disproportionate LV stiffening with natural aging, and these changes can be noninvasively measured with MRE. Keywords: Cardiac, Elastography, Biological Effects, Experimental Investigations, Sexual Dimorphisms, MR Elastography, Myocardial Shear Stiffness, Quantitative Stiffness Imaging, Aging Heart, Myocardial Biomechanics, Cardiac MRE Supplemental material is available for this article. Published under a CC BY 4.0 license.

Evaluation of the relationship between left atrial stiffness, left ventricular stiffness, and left atrioventricular coupling index in type 2 diabetes patients: a speckle tracking echocardiography study.

Cardiovascular complications are a leading cause of mortality and disability in individuals with diabetes mellitus (DM). Moreover, DM can directly impact the structure and function of cardiac muscle. We conducted a study to evaluate cardiac stiffness in DM patients in both the left atrium (LA) and left ventricle (LV), as well as to assess the impact of DM on the synchronization of the LA and LV, particularly within the Vietnamese population, utilizing speckle tracking echocardiography (STE). We studied 111 research subjects divided into two groups comprising 52 patients with DM and 59 healthy individuals. All the subjects provided relevant clinical information, and echocardiography was performed to assess the indices of LA stiffness, LV stiffness, and left atrioventricular coupling index (LACI). Our study indicated that DM patients exhibited greater LA and LV stiffness than control patients. The LACI (%) in the DM group was also greater than that in the control group (17.12% ± 6.72% vs. 12.28% ± 3.96%, respectively; p < 0.001). The LACI was positively correlated with the LA and LV stiffness indices. Decreased levels of LV GLS, adjusted for age, sex, blood pressure, and BMI, have emerged as identified risk factors for DM. LA stiffness, LV stiffness, and the LACI are greater in DM patients than in normal individuals.

Comparative effects of canagliflozin and sitagliptin in chronically ischemic myocardium.

Recent studies demonstrate that sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP4i), two classes of antidiabetic drugs, are cardioprotective. However, the mechanisms of these benefits and their comparative efficacy remain unclear. We aimed to compare the effects of these antidiabetic agents on cardiac function, perfusion, and microvascular density using a swine model of chronic myocardial ischemia. Chronic myocardial ischemia was induced in Yorkshire swine by ameroid constrictor placement to the left circumflex artery. Two weeks later, pigs were administered vehicle ("CON", 8 pigs), 300 mg SGLT2i canagliflozin, ("CANA", 8 pigs), or 100 mg DPP4i sitagliptin ("SIT", 5 pigs) daily. Five weeks later, pigs were euthanized. Cardiac function, perfusion, collateralization, and protein expression were determined by pressure-volume catheter, microsphere analysis, immunofluorescence, and immunoblotting, respectively. Compared with SIT, CANA was associated with improved stroke volume and cardiac output, with a trend towards reduced left ventricular stiffness. Both CANA and SIT trended towards improved perfusion compared to CON, but there were no differences between the two treatment groups. SIT was associated with improved capillary density with a trend towards improved arteriolar density compared to CANA. Both CANA and SIT were associated with increased expression of vascular endothelial cadherin compared to CON, without differences in treatment groups. SIT pigs had decreased 5' adenosine monophosphate-activated protein kinase activation compared to CON and CANA. There was a trend towards increased endothelial nitric oxide synthase activation in the SIT group compared to CON. There were no differences in activation of extracellular signal-regulated kinase 1/2 across groups. In the setting of chronic myocardial ischemia, canagliflozin is associated with improved cardiac function compared to sitagliptin, with similar effects on perfusion despite differences in microvascular collateralization.

Evaluation of left ventricular stiffness with echocardiography.

Half of patients with heart failure are presented with preserved ejection fraction (HFpEF). The pathophysiology of these patients is complex, but increased left ventricular (LV) stiffness has been proven to play a key role. However, the application of this parameter is limited due to the requirement for invasive catheterization for its measurement. With advances in ultrasound technology, significant progress has been made in the noninvasive assessment of LV chamber or myocardial stiffness using echocardiography. Therefore, this review aims to summarize the pathophysiological mechanisms, correlations with invasive LV stiffness constants, applications in different populations, as well as the limitations of echocardiography-derived indices for the assessment of both LV chamber and myocardial stiffness. Indices of LV chamber stiffness, such as the ratio of E/e' divided by left ventricular end-diastolic volume (E/e'/LVEDV), the ratio of E/SRe (early diastolic strain rates)/LVEDV, and diastolic pressure-volume quotient (DPVQ), are derived from the relationship between echocardiographic parameters of LV filling pressure (LVFP) and LV size. However, these methods are surrogate and lumped measurements, relying on E/e' or E/SRe for evaluating LVFP. The limitations of E/e' or E/SRe in the assessment of LVFP may contribute to the moderate correlation between E/e'/LVEDV or E/SRe/LVEDV and LV stiffness constants. Even the most validated measurement (DPVQ) is considered unreliable in individual patients. In comparison to E/e'/LVEDV and E/SRe/LVEDV, indices like time-velocity integral (TVI) measurements of pulmonary venous and transmitral flows may demonstrate better performance in assessing LV chamber stiffness, as evidenced by their higher correlation with LV stiffness constants. However, only one study has been conducted on the exploration and application of TVI in the literature, and the accuracy of assessing LV chamber stiffness remains to be confirmed. Regarding echocardiographic indices for LV myocardial stiffness evaluation, parameters such as epicardial movement index (EMI)/ diastolic wall strain (DWS), intrinsic velocity propagation of myocardial stretch (iVP), and shear wave imaging (SWI) have been proposed. While the alteration of DWS and its predictive value for adverse outcomes in various populations have been widely validated, it has been found that DWS may be better considered as an overall marker of cardiac function performance rather than pure myocardial stiffness. Although the effectiveness of iVP and SWI in assessing left ventricular myocardial stiffness has been demonstrated in animal models and clinical studies, both indices have their limitations. Overall, it seems that currently no echocardiography-derived indices can reliably and accurately assess LV stiffness, despite the development of several parameters. Therefore, a comprehensive evaluation of LV stiffness using all available parameters may be more accurate and enable earlier detection of alterations in LV stiffness.

Persistent Interstitial Fibrosis and Left Ventricular Stiffening Despite Cessation of Repetitive Pressure Overload in Swine

Persistent Interstitial Fibrosis and Left Ventricular Stiffening Despite Cessation of Repetitive Pressure Overload in Swine

Porcine Model of Hypertrophy-Independent Left Ventricular Stiffening via Repetitive Pressure Overload.

Diastolic dysfunction arising from alterations in myocardial structure and/or function is a central component of several cardiovascular disorders, including heart failure with preserved ejection fraction (HFpEF). Basic research aimed at understanding underlying mechanisms contributing to the development of diastolic dysfunction has generally centered upon models of left ventricular (LV) hypertrophy arising from persistent and severe elevations in myocardial afterload (e.g., aortic banding). Mechanisms of hypertrophy-independent diastolic dysfunction, on the other hand, have received less attention, even though overt anatomic LV hypertrophy is absent in many HFpEF patients. Here, we describe the development of a novel porcine model of repetitive pressure overload (RPO) in which chronic, intermittent exposure to transient episodes of hypertension produces an increase in LV stiffness, interstitial fibrosis, cardiomyocyte hypertrophy, and capillary rarefaction without significant changes in LV mass. This model offers important insight into how diastolic dysfunction and HFpEF may develop in the absence of comorbidities, sustained hypertension, or LV hypertrophy, while also providing a useful translational research tool for investigation of novel therapeutic approaches to restore myocardial compliance and improve diastolic function.

Kiosk 6R-FB-10 - Non-invasive Prediction of Increased Left Ventricular Chamber Stiffness Using Echocardiography and Cardiac Magnetic Resonance Imaging

Kiosk 6R-FB-10 - Non-invasive Prediction of Increased Left Ventricular Chamber Stiffness Using Echocardiography and Cardiac Magnetic Resonance Imaging

Left Ventricular Dysfunction in Hypertensive Patients and Inter-arm Pressure Difference

Background: Systolic inter-arm pressure difference (SIAD) is considered as cardiovascular risk. We aimed to ascertain whether the presence of (SIAD) is associated with impaired left ventricular (LV) functions or not. Methods: Blood pressure (BP) was measured on both arms of 81 participants, echocardiographic parameters of LV functions; ejection fraction, mitral E, A, eˋ, aˋand tricuspid regurgitant velocities, left atrial volume index, E/A and E/eˋ ratio, LV stiffness index and myocardial performance index (MPI) were measured, and global longitudinal strain (GLS) was assessed. Results: Higher SIAD level had good positive correlations with age, body mass index (BMI), duration of hypertension (HTN), MPI, and LV end-systolic volume. SIAD had good negative correlations with mitral E wave velocity, E/A ratio, eˋ and sˋ wave velocities, and with the average GLS. Impaired LV average GLS is independently associated with: Years from HTN discovery followed by BMI, gender, and age. Conclusion: BP reading in both arms on the first visit is not sufficient; hypertensive patients need evaluation of the SIAD on follow up. We need to consider the SIAD on risk stratification and BP control. This will be simple to follow in primary care and areas with low resources.

Intrinsic Wave Velocity Propagation: A Novel Parameter for Assessing the Effect of Anthracycline Chemotherapy Agents on Cardiac Diastolic Function in Breast Cancer Patients.

Anthracycline chemotherapeutic agents have significant cardiotoxicity. The present study emphasized the effect of anthracycline chemotherapy drugs on left ventricular (LV) myocardial stiffness in breast cancer patients by measuring the intrinsic wave velocity propagation (IVP), and evaluating the potential clinical value of IVP in detecting early LV diastolic function impairment. A total of 68 newly diagnosed breast cancer patients, who were treated with anthracycline-based chemotherapy, were analyzed. Transthoracic echocardiography was performed at baseline (T0), and after 1, 2, 3, 4 and 8 chemotherapeutic cycles (T1, T2, T3, T4 and T5, respectively). Then, the IVP, LV strain parameters [global longitudinal strain (GLS), longitudinal peak strain rate at systole (LSRs), longitudinal peak strain rate at early diastole (LSRe), longitudinal peak strain rate at late diastole (LSRa), and the E/LSRe ratio], and conventional echocardiographic parameters were obtained and further analyzed. A relative reduction of >15% in GLS was considered a marker of early LV subclinical dysfunction. Compared to the T0 stage, IVP significantly increased at the T1 stage. However, there were no significant changes in GLS, LSRs, or LSRe between the T0 and T1 stages. These parameters significantly decreased from the T2 stage. LSRa started to significantly decrease at the T5 stage, and the E/LSRe ratio started to significantly increase at the T3 stage (all P<0.05). At the T0 stage, IVP (AUC=0.752, P<0.001) had a good predictive value for LV subclinical dysfunction after chemotherapy. IVP is a potentially sensitive parameter for the early clinical assessment of anthracycline-related cardiac diastolic impairment.