Global longitudinal active strain energy density (GLASED): age and sex differences between young and veteran athletes.

BACKGROUND: Global longitudinal active strain energy density (GLASED) is an innovative method for assessing myocardial function and quantifies the work performed per unit volume of the left ventricular myocardium. The GLASED, measured using MRI, is the best prognostic marker currently available. This study aimed to evaluate the feasibility of measuring the GLASED using echocardiography and to investigate potential differences in the GLASED among athletes based on age and sex. METHODS: An echocardiographic study was conducted with male controls, male and female young athletes, and male and female veteran athletes. GLASED was calculated from the myocardial stress and strain. RESULTS: The mean age (in years) of the young athletes was 21.6 for males and 21.4 for females, while the mean age of the veteran athletes was 53.5 for males and 54.2 for females. GLASED was found to be highest in young male athletes (2.40 kJ/m3) and lowest in female veterans (1.96 kJ/m3). Veteran males exhibited lower values (1.96 kJ/m3) than young male athletes did (P < 0.001). Young females demonstrated greater GLASED (2.28 kJ/m3) than did veteran females (P < 0.01). However, no significant difference in the GLASED was observed between male and female veterans. CONCLUSION: Our findings demonstrated the feasibility of measuring GLASED using echocardiography. GLASED values were greater in young male athletes than in female athletes and decreased with age, suggesting possible physiological differences in their myocardium. The sex-related differences observed in GLASED values among young athletes were no longer present in veteran athletes. We postulate that measuring the GLASED may serve as a useful additional screening tool for cardiac diseases in athletes, particularly for those with borderline phenotypes of hypertrophic and dilated cardiomyopathies.

Global Longitudinal Active Strain Energy Density (GLASED): A Powerful Prognostic Marker in a Community-Based Cohort.

BACKGROUND: Identifying the imaging method that best predicts all-cause mortality, cardiovascular adverse events and heart failure risk is crucial for tailoring optimal management. Potential prognostic markers include left ventricular myocardial mass, ejection fraction, myocardial strain, stroke work, contraction fraction, pressure-strain product and a new measurement called global longitudinal active strain density (GLASED). OBJECTIVES: This study sought to compare the utility of 23 potential left ventricular prognostic markers of structure and contractile function in a community-based cohort. METHODS: The impact of cardiovascular magnetic resonance image-derived markers extracted by machine learning algorithms was compared to the future risk of adverse events in a group of 44,957 UK Biobank participants. RESULTS: Most markers, including the left ventricular ejection fraction, have limited prognostic value. GLASED was significantly associated with all-cause mortality and major adverse cardiovascular events, with the largest hazard ratio, highest ranking and differentiated risk in all three tertiles (P ≤ 0.0003). CONCLUSIONS: GLASED predicted all-cause mortality and major cardiovascular adverse events better than conventional markers of risk and is recommended for assessing patient prognosis.

Quantifying myocardial active strain energy density: A comparative analysis of analytic and finite element methods for estimating left ventricular wall stress and strain.

AIMS: This study compared commonly used methods for calculating left ventricular wall stress with the finite element analysis and evaluated different approaches to strain estimation. We sought to improve the accuracy of contractance estimation by developing a novel stress equation. BACKGROUND: Multiple methods for calculating LV contractile stress and strain exist. Contractance is derived from stress and strain information and is a measure of myocardial work per unit volume of muscle. Precise stress and strain information are essential for its accurate evaluation. METHODS AND RESULTS: We compared widely used methods for stress and strain calculations across diverse clinical scenarios representing distinct types of left ventricular myocardial disease. Our analysis revealed significant discrepancies in both the stress and strain values obtained with different methods. However, a newly developed modified version of the Mirsky equation demonstrated close agreement with the finite element analysis results for circumferential stress, while the Lamé method produced results close to those of finite element analysis for longitudinal stress and improved contractance accuracy. CONCLUSION: This study highlights significant inconsistencies in stress and strain values calculated using different methods, emphasising the potential impact on contractance calculations and subsequent clinical interpretation. We recommend adopting the Lamé method for longitudinal stress assessment and the modified Mirsky equation for circumferential stress analysis. These methods offer a balance between accuracy and feasibility, making them advantageous for clinical practice. By adopting these recommendations, we can improve the accuracy of LV wall stress and strain estimates, leading to more dependable contractance calculations, better prognostication and improved clinical decisions. CLINICAL AND TRANSLATIONAL IMPACT STATEMENT: Accurately estimating myocardial stress and strain is of paramount significance in clinical practice because the calculation of the contractance, defined and quantified by myocardial active strain energy density, necessitates correct stress and strain data. Contractance, which assesses myocardial work per unit muscle volume, has emerged as a promising indicator of contractile function and a predictor of future risk. The new recommendations for calculating myocardial stress improve the reliability of calculating contractance and enhance the understanding of myocardial diseases.

Left ventricular contractance: A new measure of contractile function.

AIMS: Myocardial contractility is poorly defined and difficult to compare between studies. Contractance or myocardial active strain energy density (MASED) measures the mechanical work done per unit volume (with units of kJ/m3) by any cardiac tissue during contraction. Contractance is an ideal candidate for measuring contractile function as it combines information from both stress and strain. METHODS AND RESULTS: Data obtained from three previously published experimental studies using trabecular tissue was used to provide contemporaneous nominal stress and strain data in 18 different scenarios with different loading conditions. Contractance varied in the differing loading conditions with values of 1.16 (low preload), 2.02 (high afterload) and 3.76 kJ/m3 (normal). Contractance varied between 0 with isometric loading and 2.14 kJ/m3 with an isotonic and moderate afterload. Increasing inotropy increased contractance to 4.7 kJ/m3. CONCLUSION: We showed that calculating MASED was feasible and provided a measure of energy production (work done) per unit volume of myocardium during contraction. The new term for contractile function, contractance, can be defined and quantified by MASED. Contractance measures contractile function in differing preload, afterload and inotropic settings. The method of measuring contractance is transferable to the assessment of global and regional systolic function.

Left ventricular active strain energy density is a promising new measure of systolic function.

The left ventricular ejection fraction does not accurately predict exercise capacity or symptom severity and has a limited role in predicting prognosis in heart failure. A better method of assessing ventricular performance is needed to aid understanding of the pathophysiological mechanisms and guide management in conditions such as heart failure. In this study, we propose two novel measures to quantify myocardial performance, the global longitudinal active strain energy (GLASE) and its density (GLASED) and compare them to existing measures in normal and diseased left ventricles. GLASED calculates the work done per unit volume of muscle (energy density) by combining information from myocardial strain and wall stress (contractile force per unit cross sectional area). Magnetic resonance images were obtained from 183 individuals forming four cohorts (normal, hypertension, dilated cardiomyopathy, and cardiac amyloidosis). GLASE and GLASED were compared with the standard ejection fraction, the corrected ejection fraction, myocardial strains, stroke work and myocardial forces. Myocardial shortening was decreased in all disease cohorts. Longitudinal stress was normal in hypertension, increased in dilated cardiomyopathy and severely decreased in amyloid heart disease. GLASE was increased in hypertension. GLASED was mildly reduced in hypertension (1.39 ± 0.65 kJ/m3), moderately reduced in dilated cardiomyopathy (0.86 ± 0.45 kJ/m3) and severely reduced in amyloid heart disease (0.42 ± 0.28 kJ/m3) compared to the control cohort (1.94 ± 0.49 kJ/m3). GLASED progressively decreased in the hypertension, dilated cardiomyopathy and cardiac amyloid cohorts indicating that mechanical work done and systolic performance is severely reduced in cardiac amyloid despite the relatively preserved ejection fraction. GLASED provides a new technique for assessing left ventricular myocardial health and contractile function.

The corrected left ventricular ejection fraction: a potential new measure of ventricular function.

Left ventricular ejection fraction (LVEF) has a limited role in predicting outlook in heart diseases including heart failure. We quantified the independent geometric factors that determine LVEF using cardiac MRI and sought to provide an improved measure of ventricular function by adjusting for such independent variables. A mathematical model was used to analyse the independent effects of structural variables and myocardial shortening on LVEF. These results informed analysis of cardiac MRI data from 183 patients (53 idiopathic dilated cardiomyopathy (DCM), 36 amyloidosis, 55 hypertensives and 39 healthy controls). Left ventricular volumes, LVEF, wall thickness, internal dimensions and longitudinal and midwall fractional shortening were measured. The modelling demonstrated LVEF increased in a curvilinear manner with increasing mFS and longitudinal shortening and wall thickness but decreased with increasing internal diameter. Controls in the clinical cohort had a mean LVEF 64  ±  7%, hypertensives 66  ±  8%, amyloid 49 ±  16% and DCM 30  ±  11%. The mean end-diastolic wall thickness in controls was 8  ±  1 mm, DCM 8  ±  1 mm, hypertensives 11  ±  3 mm and amyloid 14  ±  3 mm, P < 0.0001). LVEF correlated with absolute wall thickening relative to ventricular size (R2 = 0.766). A regression equation was derived from raw MRI data (R2 = 0.856) and used to 'correct' LVEF (EFc) by adjusting the wall thickness and ventricular size to the mean of the control group. Improved quantification of the effects of geometric changes and strain significantly enhances understanding the myocardial mechanics. The EFc resulted in reclassification of a 'ventricular function' in some individuals and may provide an improved measure of myocardial performance especially in thick-walled, low-volume ventricles.

The central nervous system and heart failure.

The view that chronic heart failure was exclusively a disease of the heart dominated the cardiovascular literature until relatively recently. However, over the last 40 years it has increasingly come to be seen as a multisystem disease. Aside from changes in the sympathetic and parasympathetic nervous systems and the renin-angiotensin-aldosterone system, adaptations to the lungs, muscles and gastrointestinal tract have been clearly documented. It is clear that the brain and CNS are also affected in patients with heart failure, although this is often under recognized. The purpose of this review is to summarize the changes in the structure and biochemical function of the CNS in patients with chronic heart failure and to discuss their potential importance.

The end of the unique myocardial band: Part I. Anatomical considerations.

The concept of the 'unique myocardial band', which proposes that the ventricular myocardial cone is arranged like skeletal muscle, provides an attractive framework for understanding haemodynamics. The original idea was developed by Francisco Torrent-Guasp. Using boiled hearts and blunt dissection, Torrent-Guasp created a single band of ventricular myocardium extending from the pulmonary trunk to the aortic root, with the band thus constructed encircling both ventricular cavities. Cooked hearts can, however, be dissected in many ways. In this review, we show that the band does not exist as an anatomical entity with defined borders. On the contrary, the ventricular cardiomyocytes are aggregated end to end and by their branching produce an intricate meshwork. Across the thickness of the left ventricular wall, the chains of cardiomyocytes exhibit a gradually changing helical angle, with a circumferential zone formed in the middle. There is no abrupt change in helical angle, as could be expected if the wall was constructed of opposing limbs of a single wrapped band, nor does the long axis of the cardiomyocytes consistently match with the long axis of the unique myocardial band. There are, furthermore, no connective tissue structures that could be considered to demarcate its purported boundaries. The unique myocardial band should be consistent with evolution, and although the ventricular wall of fish and reptiles has one or several distinct layers, a single band is not found. In 1965, Lev and Simpkins cautioned that the ventricular muscle mass of a cooked heart can be dissected almost at the whim of the anatomist. We suggest that the unique myocardial band should have ended there.

The end of the unique myocardial band: Part II. Clinical and functional considerations.

Two of the leading concepts of mural ventricular architecture are the unique myocardial band and the myocardial mesh model. We have described, in an accompanying article published in this journal, how the anatomical, histological and high-resolution computed tomographic studies strongly favour the latter concept. We now extend the argument to describe the linkage between mural architecture and ventricular function in both health and disease. We show that clinical imaging by echocardiography and magnetic resonance imaging, and electrophysiological studies, all support the myocardial mesh model. We also provide evidence that the unique myocardial band model is not compatible with much of scientific research.

Key Questions Relating to Left Ventricular Noncompaction Cardiomyopathy: Is the Emperor Still Wearing Any Clothes?

The evidence is increasing that left ventricular noncompaction cardiomyopathy as it is currently defined does not represent a failure of compaction of pre-existing trabecular myocardium found during embryonic development to form the compact component of the ventricular walls. Neither is there evidence of which we are aware to favour the notion that the entity is a return to a phenotype seen in cold-blooded animals. It is also known that when seen in adults, the presence of excessive ventricular trabeculations does not portend a poor prognosis when the ejection fraction is normal, with the risks of complications such as arrhythmia and stroke being rare in this setting. It is also the case that images of "noncompaction" as provided from children or autopsy studies are quite different from the features observed clinically in asymptomatic adults with excessive trabeculation. Our review suggests that the presence of an excessively trabeculated left ventricular wall is not in itself a clinical entity. It is equally possible that the excessive trabeculation is no more than a bystander in the presence of additional lesions such as dilated cardiomyopathy, with the additional lesions being responsible for the reduced ejection fraction bringing a given patient to clinical attention. We, therefore, argue that the term "noncompaction cardiomyopathy" is misleading, because there is neither failure of compaction nor a cardiomyopathic process in most individuals that fulfill widely used diagnostic criteria.

Cardiovascular Mechanisms of Extravascular Lung Water Accumulation in Divers.

This study assessed the relation between altered cardiac function and the development of interstitial pulmonary edema in scuba divers. Fifteen healthy men performed a 30-minute scuba dive in open sea. They were instructed to fin for 30 minutes and were wearing wet suits. Before and immediately after immersion, cardiac indexes and extravascular lung water were measured using echocardiography and lung ultrasound, respectively. The mean ultrasound lung comet score increased from 0 to 4.6 ± 3.4. The diameter of the inferior caval vein increased by 47 ± 5.2%, systolic pulmonary artery pressure by 105 ± 8.6%, left atrial volume by 18.0 ± 3.3%, and left ventricle end-diastolic volume by 10 ± 2.4% suggesting that both right and left ventricular (LV) filling pressures were elevated. Doppler studies showed an increased mitral E peak (+2.5 ± 0.3%) and E/A ratio (+22.5 ± 3.4%) with a decreased mitral A peak (-16.4 ± 2.7%), E peak deceleration time (-14.5 ± 2.4%) consistent with rapid early LV filling but without a change in LV stroke volume. There was an increase in right/left ventricle diameter ratio (+33.6 ± 4.8%) suggesting a relative increase in right-sided heart output compared with the left. Furthermore, the lung comet score correlated significantly with inferior caval vein diameter, systolic pulmonary artery pressure, right/left ventricle diameter ratio, and E-wave deceleration time. In conclusion, the altered right/left heart stroke volume balance could play an essential role in the development of immersion pulmonary edema. Our findings have important implications for the pathogenesis of cardiogenic pulmonary edema.

Insights from echocardiography, magnetic resonance imaging, and microcomputed tomography relative to the mid-myocardial left ventricular echogenic zone.

BACKGROUND: The anatomical substrate for the mid-mural ventricular hyperechogenic zone remains uncertain, but it may represent no more than ultrasound reflected from cardiomyocytes orientated orthogonally to the ultrasonic beam. We sought to ascertain the relationship between the echogenic zone and the orientation of the cardiomyocytes. METHODS: We used 3D echocardiography, diffusion tensor imaging, and microcomputed tomography to analyze the location and orientation of cardiomyocytes within the echogenic zone. RESULTS: We demonstrated that visualization of the echogenic zone is dependent on the position of the transducer and is most clearly seen from the apical window. Diffusion tensor imaging and microcomputed tomography show that the echogenic zone seen from the apical window corresponds to the position of the circumferentially orientated cardiomyocytes. An oblique band seen in the parasternal view relates to cardiomyocytes orientated orthogonally to the ultrasonic beam. CONCLUSIONS: The mid-mural ventricular hyperechogenic zone represents reflected ultrasound from cardiomyocytes aligned orthogonal to the ultrasonic beam. The echogenic zone does not represent a space, a connective tissue sheet, a boundary between ascending and descending limbs of a hypothetical helical ventricular myocardial band, nor an abrupt change in cardiomyocyte orientation.

Physiological mechanisms of pulmonary hypertension.

Pulmonary hypertension is usually related to obstruction of pulmonary blood flow at the level of the pulmonary arteries (eg, pulmonary embolus), pulmonary arterioles (idiopathic pulmonary hypertension), pulmonary veins (pulmonary venoocclusive disease) or mitral valve (mitral stenosis and regurgitation). Pulmonary hypertension is also observed in heart failure due to left ventricle myocardial diseases regardless of the ejection fraction. Pulmonary hypertension is often regarded as a passive response to the obstruction to pulmonary flow. We review established fluid dynamics and physiology and discuss the mechanisms underlying pulmonary hypertension. The important role that the right ventricle plays in the development and maintenance of pulmonary hypertension is discussed. We use principles of thermodynamics and discuss a potential common mechanism for a number of disease states, including pulmonary edema, through adding pressure energy to the pulmonary circulation.

The Relationship Between Left Ventricular Wall Thickness, Myocardial Shortening, and Ejection Fraction in Hypertensive Heart Disease: Insights From Cardiac Magnetic Resonance Imaging.

Hypertensive heart disease is often associated with a preserved left ventricular ejection fraction despite impaired myocardial shortening. The authors investigated this paradox in 55 hypertensive patients (52±13 years, 58% male) and 32 age- and sex-matched normotensive control patients (49±11 years, 56% male) who underwent cardiac magnetic resonance imaging at 1.5T. Long-axis shortening (R=0.62), midwall fractional shortening (R=0.68), and radial strain (R=0.48) all decreased (P<.001) as end-diastolic wall thickness increased. However, absolute wall thickening (defined as end-systolic minus end-diastolic wall thickness) was maintained, despite the reduced myocardial shortening. Absolute wall thickening correlated with ejection fraction (R=0.70, P<.0001). In multiple linear regression analysis, increasing wall thickness by 1 mm independently increased ejection fraction by 3.43 percentage points (adjusted ß-coefficient: 3.43 [2.60-4.26], P<.0001). Increasing end-diastolic wall thickness augments ejection fraction through preservation of absolute wall thickening. Left ventricular ejection fraction should not be used in patients with hypertensive heart disease without correction for degree of hypertrophy.

Thoracic aortic aneurysms due to giant cell aortitis.

We present three cases of thoracic aortic aneurysms caused by giant cell aortitis. Thoracic aortic aneurysms are common and usually related to hypertension, a bicuspid aortic valve or connective tissue diseases such as Marfan syndrome. Our report serves as a reminder that giant cell aortitis is an unusual yet very important cause of thoracic aortic aneurysm.

Contractile Dysfunction in Sarcomeric Hypertrophic Cardiomyopathy.

The pathophysiological mechanisms underlying the clinical phenotype of sarcomeric hypertrophic cardiomyopathy are controversial. The development of cardiac hypertrophy in hypertension and aortic stenosis is usually described as a compensatory mechanism that normalizes wall stress. We suggest that an important abnormality in hypertrophic cardiomyopathy is reduced contractile stress (the force per unit area) generated by myocardial tissue secondary to abnormalities such as cardiomyocyte disarray. In turn, a progressive deterioration in contractile stress provokes worsening hypertrophy and disarray. A maintained or even exaggerated ejection fraction is explained by the increased end-diastolic wall thickness producing augmented thickening. We propose that the nature of the hemodynamic load in an individual with hypertrophic cardiomyopathy could determine its phenotype. Hypertensive patients with hypertrophic cardiomyopathy are more likely to develop exaggerated concentric hypertrophy; athletic individuals an asymmetric pattern; and inactive individuals a more apical hypertrophy. The development of a left ventricular outflow tract gradient and mitral regurgitation may be explained by differential regional strain resulting in mitral annular rotation.

Effects of Persistent Atrial Fibrillation-Induced Electrical Remodeling on Atrial Electro-Mechanics - Insights from a 3D Model of the Human Atria.

AIMS: Atrial stunning, a loss of atrial mechanical contraction, can occur following a successful cardioversion. It is hypothesized that persistent atrial fibrillation-induced electrical remodeling (AFER) on atrial electrophysiology may be responsible for such impaired atrial mechanics. This simulation study aimed to investigate the effects of AFER on atrial electro-mechanics. METHODS AND RESULTS: A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4 states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2-3 months after cardioversion (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodeled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+ content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+ transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished. CONCLUSIONS: This study provides novel insights into understanding atrial electro-mechanics illustrating that AFER impairs atrial contraction due to reduced intracellular Ca2+ transients.