Sex-and age-related variations in myocardial tissue composition of the healthy heart: A native T1 mapping cohort study.

AIMS: Cardiovascular diseases manifest differently in males and females, potentially influenced by inherent sex- and age-related differences in myocardial tissue composition. Such inherent differences are not well-established in the literature. With this study using cardiac magnetic resonance (CMR) native T1 mapping, we aim to determine the effect of sex and age on myocardial tissue composition in healthy individuals. METHODS AND RESULTS: CMR native T1 mapping was performed in 276 healthy individuals (55% male, age 8---84 years) on a 1.5 Tesla scanner using a MOLLI 5(3)3 acquisition scheme. Additionally, 30 healthy participants (47% male, age 24-68 years) underwent a 1-year follow-up CMR to assess the longitudinal changes of native T1. Mean native T1 values were 1000±22 ms in males and 1022±23 ms in females (mean difference [MD]=22 ms, 95% CI [17, 27]). Female sex was associated with higher native T1 in multivariable linear regression adjusting for age, heart rate, left ventricular mass index, and blood T1 (ß=10 ms, 95% CI [3.4, 15.8]). There was no significant interaction between sex and age (p=0.27). Further, age was not associated with native T1 (ß=0.1 ms, 95% CI [-0.02, 0.2]), and native T1 did not change during a 1-year period (MD -4 ms, 95% CI [-11, 3]). CONCLUSION: Female sex was associated with higher native T1; however, there was no association between age and native T1. Additionally, there was no evidence of an interaction between sex and age. Our findings indicate intrinsic sex-based disparities in myocardial tissue composition.

The Influence of Food Intake and Preload Augmentation on Cardiac Functional Parameters: A Study Using Both Cardiac Magnetic Resonance and Echocardiography.

(1) Background: To investigate how food intake and preload augmentation affect the cardiac output (CO) and volumes of the left ventricle (LV) and right ventricle (RV) assessed using cardiac magnetic resonance (CMR) and trans-thoracic echocardiography (TTE). (2) Methods: Eighty-two subjects with (n = 40) and without (n = 42) cardiac disease were assessed using both CMR and TTE immediately before and after a fast infusion of 2 L isotonic saline. Half of the population had a meal during saline infusion (food/fluid), and the other half were kept fasting (fasting/fluid). We analyzed end-diastolic (EDV) and end-systolic (ESV) volumes and feature tracking (FT) using CMR, LV global longitudinal strain (GLS), and RV longitudinal strain (LS) using TTE. (3) Results: CO assessed using CMR increased significantly in both groups, and the increase was significantly higher in the food/fluid group: LV-CO (ΔLV-CO: +2.6 ± 1.3 vs. +0.7 ± 1.0 p < 0.001), followed by increased heart rate (HR) (ΔHR: +12 ± 8 vs. +1 ± 6 p < 0.001). LV and RV achieved increased stroke volume (SV) through different mechanisms. For the LV, through increased contractility, increased LV-EDV, decreased LV-ESV, increased LV-FT, and GLS were observed. For the RV, increased volumes, increased RV-EDV, increased RV-ESV, and at least for the fasting/fluid group, unchanged RV-FT and RV-LS were reported. (4) Conclusions: Preload augmentation and food intake have a significant impact on hemodynamic and cardiac functional parameters. This advocates for standardized recommendations regarding oral intake of fluid and food before cardiac assessment, for example, TTE, CMR, and right heart catheterization. We also demonstrate different approaches for the LV and RV to increase SV: for the LV by increased contractility, and for the RV by volume expansion.

A new method to quantify left ventricular mass by 2D echocardiography.

Increased left ventricular mass (LVM) is a strong independent predictor for adverse cardiovascular events, but conventional echocardiographic methods are limited by poor reproducibility and accuracy. We developed a novel method based on adding the mean wall thickness from the parasternal short axis view, to the left ventricular end-diastolic volume acquired using the biplane model of discs. The participants (n = 85) had various left ventricular geometries and were assessed using echocardiography followed immediately by cardiac magnetic resonance, as reference. We compared our novel two-dimensional (2D) method to various conventional one-dimensional (1D) and other 2D methods as well as the three-dimensional (3D) method. Our novel method had better reproducibility in intra-examiner [coefficients of variation (CV) 9% vs. 11-14%] and inter-examiner analysis (CV 9% vs. 10-20%). Accuracy was similar to the 3D method (mean difference ± 95% limits of agreement, CV): Novel: 2 ± 50 g, 15% vs. 3D: 2 ± 51 g, 16%; and better than the "linear" 1D method by Devereux (7 ± 76 g, 23%). Our novel method is simple, has considerable better reproducibility and accuracy than conventional "linear" 1D methods, and similar accuracy as the 3D-method. As the biplane model forms part of the standard echocardiographic protocol, it does not require specific training and provides a supplement to the modern echocardiographic report.

Necropsy Validation of a Novel Method for Left Ventricular Mass Quantification in Porcine Transthoracic and Transdiaphragmal Echocardiography.

Introduction: Increased left ventricular mass (LVM) is one of the most powerful predictors of adverse cardiovascular events. Clinical evaluation requires reliable, accurate and reproducible echocardiographic LVM-quantification to manage patients. For this purpose, we have developed a novel two-dimensional (2D) method based on adding the mean wall thickness to the left ventricular volume acquired by the biplane method of disks, which has recently been validated in humans using cardiac magnetic resonance as reference value. We assessed the hypothesis that the novel method has better accuracy than conventional one-dimensional (1D) methods, when compared to necropsy LVM in pigs. Materials and Methods: Echocardiography was performed during anesthesia in 34 Danish Landrace pigs, weight 47-59 kg. All pigs were euthanized, cardiac necropsy was performed and the left ventricle was trimmed and weighed for necropsy LVM. Trans-thoracic echocardiography was applied for parasternal images. Transdiaphragmal echocardiography was applied for the apical images, which are otherwise difficult to obtain in pigs. We compared the conventional 1D- and 2D-methods and the novel 2D-method to the LVM from cardiac necropsy. Results: Necropsy LVM was 132 ± 11 g (mean ± SD). The novel method had better accuracy than other methods (mean difference ± 95% limits of agreement; coefficients of variation; standard error of the estimate, Pearson's correlation). Novel (-1 ± 20 g; 8%; 11 g; r = 0.70), Devereux (+26 ± 37 g; 15%; 33 g; r = 0.52), Area-Length (+27 ± 34 g; 13 %; 33 g; r = 0.63), Truncated Ellipsoid (+10 ± 30 g; 12%; 19 g; r = 0.63), biplane endo-/epicardial tracing (-3 ± 2 g; 10%; 14 g; r = 0.57). No proportional bias in linear regression was detected for any method, when compared to necropsy LVM. Conclusion: We confirm high accuracy of the novel 2D-based method compared to conventional 1D/2D-methods.

Layer-specific longitudinal strain detects transmural dysfunction in chronic severe aortic regurgitation before and after aortic valve surgery.

To assess if layer-specific longitudinal strain (LS) provides incremental diagnostic and prognostic value compared to global longitudinal strain (GLS) in patients with chronic severe aortic regurgitation (AR) scheduled for aortic valve surgery. Forty-one patients were examined with speckle tracking echocardiography before surgery along with 15 healthy age-matched controls. Paired strain analyses before and after surgery were available in 31 patients. Layer-specific LS analysis enabled assessment of epicardial GLS (GLSepi), endocardial GLS (GLSendo), and conventional GLS. Strain parameters were indexed to end-diastolic volume (EDV; GLS/EDV) to account for increased preload. The prognostic value of layer-specific LS was evaluated using the primary outcome of persistent LV dilatation (LVEDV ≥ 175 mL) three months after surgery. Absolute (GLS, GLSepi, GLSendo) and EDV-indexed layer-specific LS (GLS/EDV, GLSepi/EDV, GLSendo/EDV) were impaired in severe AR compared to controls at baseline (GLS:17.0 ± 3.2 vs. 20.6 ± 2.0; GLSepi:14.6 ± 2.8 vs. 18.1 ± 1.9; GLSendo:20.2 ± 3.7 vs. 23.8 ± 2.2%; GLS/EDV:0.09 ± 0.05 vs. 0.21 ± 0.05; GLSepi/EDV:0.08 ± 0.04 vs. 0.18 ± 0.04; GLSendo/EDV:0.11 ± 0.06 vs. 0.24 ± 0.05%/mL; all p < 0.001). In severe AR, GLS, GLSepi and GLSendo decreased after surgery whereas GLS/EDV, GLSepi/EDV and GLSendo/EDV increased (all p < 0.001). Impaired absolute and EDV-indexed layer-specific LS were all associated with the primary outcome (all p ≤ 0.01). Area under the curve analysis revealed similar prognostic value of GLSepi, GLSendo and GLS (GLS:0.86; GLSepi:0.87; GLSendo:0.86; p = n.s.). EDV-indexed LS did not improve the predictive value significantly (GLS/EDV:0.93; GLSepi/EDV: 0.93; GLSendo/EDV:0.92; p = n.s.). Layer-specific LS detects transmural dysfunction in chronic severe AR and predicts persistent LV dilation after surgery. Layer-specific LS or EDV-indexed LS does not provide incremental prognostic value compared to conventional GLS.

Layer-Specific Strain Is Preload Dependent: Comparison between Speckle-Tracking Echocardiography and Cardiac Magnetic Resonance Feature-Tracking.

BACKGROUND: Speckle-tracking echocardiographic (STE) imaging and cardiac magnetic resonance feature-tracking (CMR-FT) are novel imaging techniques enabling layer-specific quantification of myocardial deformation. Conventional echocardiographic parameters are load dependent, but few studies have investigated the effects of loading conditions on STE and CMR-FT layer-specific strain and the interchangeability of the two modalities. The aim of this study was to evaluate the effects of acute preload augmentation by saline infusion on STE and CMR-FT longitudinal and circumferential layer-specific strain parameters and their intermodal agreement. METHODS: A total of 80 subjects, including 41 control subjects (mean age, 40 ± 12 years; 49% men) and 39 patients with cardiac disease (mean age, 47 ± 15 years; 92% men) were examined using STE and CMR-FT layer-specific strain analysis before and after saline infusion (median, 2.0 L) with quantification of transmural global longitudinal strain (GLS), epicardial GLS, endocardial GLS, transmural global circumferential strain (GCS), epicardial GCS, and endocardial GCS in addition to epicardial-endocardial gradients. Bland-Altman plots and Pearson correlation coefficients were used to evaluate agreement between the two modalities across all strain parameters. RESULTS: Acute saline infusion increased all STE and CMR-FT layer-specific strain parameters in both groups. STE and CMR-FT GLS increased by 1.4 ± 1.5% and 1.5 ± 2.0% (P < .001) in control subjects and by 0.9 ± 1.8% and 0.9 ± 1.9% (P < .001) in patients with cardiac disease. STE and CMR-FT GCS increased by 2.0 ± 2.2% and 1.8 ± 2.3% (P < .001) in control subjects and by 1.8 ± 2.3% and 1.7 ± 3.6% in patients with cardiac disease (P < .001 and P = .03). STE longitudinal strain correlated strongly with corresponding CMR-FT longitudinal strain (GLS, epicardial GLS, and endocardial GLS: r = 0.81, r = 0.82, and r = 0.81, respectively) despite poor intermodal agreement (bias ± limits of agreement, -2.84 ± 4.06%, 0.16 ± 3.68%, and 2.33 ± 3.52%, respectively) whereas GCS, epicardial GCS, and endocardial GCS correlated weakly between the two modalities (r = 0.28, r = 0.19, and r = 0.34, respectively) and displayed poor intermodal agreement (bias ± limits of agreement, -1.33 ± 6.86%, 4.43 ± 6.49%, and -9.92 ± 8.55%, respectively). CONCLUSIONS: STE and CMR-FT longitudinal and circumferential layer-specific strain parameters are preload dependent in both control subjects and patients with cardiac disease. STE and CMR-FT longitudinal layer-specific strain parameters are strongly correlated, whereas circumferential layer-specific strain parameters are weakly correlated. STE and CMR-FT longitudinal and circumferential strain should not be used interchangeably, because of poor intermodal agreement.

Left Ventricular Mass Assessment by 1- and 2-Dimensional Echocardiographic Methods in Hemodialysis Patients: Changes in Left Ventricular Volume Using Echocardiography Before and After a Hemodialysis Session.

RATIONALE & OBJECTIVE: Left ventricular (LV) mass (LVM) is a predictor of cardiovascular morbidity and mortality and commonly calculated using 1-dimensional (1D) echocardiographic methods. These methods are vulnerable to small measurement errors and LVM may wrongly change according to changes in LV volume (LVV). Less commonly used 2-dimensional (2D) methods can accommodate to the changes in LVV and may be a better alternative among patients receiving hemodialysis (HD) with large fluid fluctuations. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: Patients with end-stage kidney disease receiving HD. EXPOSURE: One HD session. ANALYTICAL APPROACH: Transthoracic echocardiography was performed right before and after HD. LVM was calculated using 1D (Devereux, Penn, and Teichholz) and 2D methods (truncated ellipsoid and area-length). OUTCOMES: Significant differences in LVM after HD. RESULTS: We compared dimensions, LVV and LVM, in 53 patients (mean age, 63 ± 15 years; 66% men). For each 1-L increase in ultrafiltration volume (UFV), LV internal diameter decreased 1.1 mm (95% CI, 0.5-1.7 mm; P = 0.001). Patients were divided into 2 groups by the median UFV of 1.6 L. Patients with UFV > 1.6 L had significant smaller LVV and LV internal diameter after HD. LVM calculated using 1D methods decreased according to changes in LVV. Conversely, LVM calculated using 2D methods was not significantly different after HD. No significant change in differences between diastolic - systolic myocardial thickness or LVM as assessed using 1D and 2D methods was observed before and after HD, indicating that LVM remained constant despite HD. LIMITATIONS: We did not use contrast enhancement, 3-dimensional methods, or cardiac magnetic resonance. CONCLUSIONS: LVM calculated using 2D methods, truncated ellipsoid and area-length, is less affected by fluctuations in fluid and LVV, in contrast to 1D methods. Complementary LVM calculation using 2D methods is encouraged, especially in patients with large fluid fluctuations in which increased LVM using a 1D method has been detected.

Assessment of left ventricular outflow tract and aortic root: comparison of 2D and 3D transthoracic echocardiography with multidetector computed tomography.

AIMS: Accurate echocardiographic assessment of left ventricular outflow tract (LVOT) and the aortic root is necessary for risk stratification and choice of appropriate treatment in patients with pathologies of the aortic valve and aortic root. Conventional 2D transthoracic echocardiographic (TTE) assessment is based on the assumption of a circular shaped LVOT and aortic root, although previous studies have indicated a more ellipsoid shape. 3D TTE and multidetector computed tomography (MDCT) applies planimetry and are not dependent on geometrical assumptions. The aim was to test accuracy, feasibility, and reproducibility of 3D TTE compared to 2D TTE assessment of LVOT and aortic root areas, with MDCT as reference. METHODS AND RESULTS: We examined 51 patients with 2D/3D TTE and MDCT at the same day. All patients were re-examined with 2D/3D TTE on a different day to evaluate 2D and 3D re-test variability. Areas of LVOT, aortic annulus, and sinus were assessed using 2D, 3D TTE, and MDCT. Both 2D/3D TTE underestimated the areas compared to MDCT; however, 3D TTE areas were significantly closer to MDCT-areas. 2D vs. 3D mean MDCT-differences: LVOT 1.61 vs. 1.15 cm2, P = 0.019; aortic annulus 1.96 vs. 1.06 cm2, P < 0.001; aortic sinus 1.66 vs. 1.08 cm2, P = 0.015. Feasibility was 3D 76-79% and 2D 88-90%. LVOT and aortic annulus areas by 3D TTE had lowest variabilities; intraobserver coefficient of variation (CV) 9%, re-test variation CV 18-20%. CONCLUSION: Estimation of LVOT and aortic root areas using 3D TTE is feasible, more precise and more accurate than 2D TTE.

Right Ventricular and Pulmonary Vascular Function are Influenced by Age and Volume Expansion in Healthy Humans.

BACKGROUND: Patients with heart failure (HF) often show signs of right ventricular (RV) dysfunction. The RV function of coupled with the pulmonary circulation (tricuspid annular plane systolic excursion [TAPSE]/pulmonary arterial systolic pressure [PASP]) has been shown to divide HF patients into distinct prognostic strata, but less is known about which factors influence this prognostic marker, and whether those factors can be modified. We sought to obtain normative values and discern the individual effects of age, sex, and fluid overload on RV function. METHODS AND RESULTS: Sixty healthy subjects aged 20-80 years were enrolled in this prospective study. Right heart catheterization with hemodynamic measurements were performed at rest after a rapid saline solution infusion (10 mL/kg, 150 mL/min). Linear regression and Spearman correlation models were used to estimate associations between TAPSE/PASP and relevant variables. In healthy persons of all ages, the median (5th-95th percentiles) normative TASPE-PASP ratio was 1.25 (0.81-1.78) mm/mm Hg. The correlation between progressive age and declining TAPSE/PASP was significant (r = -0.35; P = .006). Sex did not influence TAPSE/PASP (P = .30). Rapid fluid expansion increased central venous pressure from 5 ± 2 mm Hg to 11 ± 4 mm Hg after fluid infusion (P < .0001). This resulted in a 32% decrease in the TAPSE-PASP ratio after fluid infusion, compared to baseline (P < .0001). CONCLUSIONS: The TAPSE-PASP ratio was affected by age, but not sex. TAPSE/PASP is not only a reflection of intrinsic RV function and pulmonary vascular coupling, but fluid status also dynamically affects this index of RV function. Normative values with invasive measurements were obtained for future assessment of HF patients.

Tissue Velocities and Myocardial Deformation in Asymptomatic and Symptomatic Aortic Stenosis.

BACKGROUND: Assessment of myocardial longitudinal function has proved to be a sensitive marker of deteriorating myocardial function in aortic stenosis, demonstrated by both color Doppler tissue imaging and recently by two-dimensional speckle-tracking echocardiography. The aim of this study was to compare velocity (color Doppler tissue imaging) and deformation (two-dimensional speckle-tracking echocardiography) in relation to global and regional longitudinal function in asymptomatic and severe symptomatic aortic stenosis. METHODS: In a cross-sectional design, 231 patients with aortic stenosis were divided into four groups: asymptomatic moderate aortic stenosis (aortic valve area, 1.0-1.5 cm(2); n = 38), asymptomatic severe aortic stenosis (aortic valve area < 1.0 cm(2); n = 66), and symptomatic severe aortic stenosis with preserved (n = 68) and reduced (<50%) left ventricular ejection fraction (n = 59). RESULTS: Among all global (peak systolic s', diastolic e' and a', longitudinal displacement, and global longitudinal strain and strain rate) and regional longitudinal (basal, middle, and apical longitudinal strain and strain rate) parameters, only diastolic e', longitudinal displacement, and basal longitudinal strain (BLS) remained significantly associated with symptomatic status, independent of age, gender, heart rate, aortic valve area, stroke volume index, left ventricular mass index, left atrial volume index, and tricuspid annular systolic plane excursion. Furthermore, in a model with the aforementioned parameters, including e', longitudinal displacement, and BLS, only BLS remained significantly associated with symptomatic status in the entire study population (BLS per one-unit decrease: odds ratio, 1.23; 95% CI, 1.04-1.46; P = .017). Furthermore, patients with BLS < 13% were more likely to be symptomatic (odds ratio, 4.97; 95% CI, 2.6-9.4; P < .001), and no patients with asymptomatic severe aortic stenosis with BLS ≥ 13% were admitted with myocardial infarction or heart failure during follow-up of 1,462 days. CONCLUSIONS: Among the many echocardiographic measures of longitudinal velocity and deformation, BLS has the strongest association with symptomatic status in aortic stenosis, and BLS < 13% is related to adverse outcomes in severe asymptomatic aortic stenosis.