Cardiac Mechanics Modeling: Recent Developments and Current Challenges

Exercise guidelines recommend incorporating resistance exercise (RE) into a regular aerobic training program during pregnancy. However, few women do so because of uncertainties about the safety of prenatal RE, particularly regarding the Valsalva maneuver (VM). The aim of this study was to determine the acute cardiovascular responses to prenatal RE at different intensities, with and without VM. Healthy pregnant (n = 15; 22.9 ± 5.9 wk of gestation) and nonpregnant women (n = 15) were recruited. Maximal strength over 10 repetitions (10RM) for semireclined leg press was determined. Women underwent standardized assessments of cardiac structure, function and mechanics (echocardiography), heart rate (ECG), and blood pressure (photoplethysmography) at baseline, during RE at 20%, 40%, and 60% 10RM while free-breathing, and at 40% 10RM with VM. Significant differences were identified between subjects at baseline (independent t-tests), between and within subjects during free-breathing RE (general linear model, baseline as a covariate), and between and within subjects for 40% 10RM free-breathing versus VM (mixed-effects model). Resting cardiac output, heart rate, and stroke volume were greater in pregnant women, without differences in blood pressure, ejection fraction, or cardiac mechanics. During free-breathing RE, pregnant women had a greater ejection fraction compared with nonpregnant women; however, all other hemodynamic variables were not different between groups. Cardiac mechanics during free-breathing RE across all intensities were not different between groups, with the exception that pregnant women had a lower apical circumferential strain that did not affect global cardiac function. No differences were observed between groups during 40% 10RM RE with and without VM. Pregnant women have proportionate cardiac responses to light-moderate RE, both with and without the VM. These findings reinforce the safety of RE in healthy pregnancy.

BackgroundCentral artery dilation and remodeling are associated with higher heart failure and cardiovascular risks. However, data regarding carotid artery diameter from hypertension to heart failure have remained elusive. We sought to investigate this issue by examining the association between carotid artery diameter and surrogates of ventricular dysfunction.Methods and ResultsTwo hundred thirteen consecutive patients including 49 with heart failure and preserved ejection fraction (HFpEF), 116 with hypertension, and an additional 48 healthy participants underwent comprehensive echocardiography and tissue Doppler imaging. Ultrasonography of the common carotid arteries was performed for measurement of intima‐media thickness and diameter (CCAD). Cardiac mechanics, including LV twist, were assessed by novel speckle‐tracking software. A substantial graded enlargement of CCAD was observed across all 3 groups (6.8±0.6, 7.7±0.73, and 8.7±0.95 mm for normal, hypertension, and HFpEF groups, respectively; ANOVA P<0.001) and correlated with serum brain natriuretic peptide level (R2=0.31, P<0.001). Multivariable models showed that CCAD was associated with increased LV mass, LV mass‐to‐volume ratio (β‐coefficient=10.9 and 0.11, both P<0.001), reduced LV longitudinal and radial strain (β‐coeffficient=0.81 and −3.1, both P<0.05), and twist (β‐coefficient=−0.84, P<0.05). CCAD set at 8.07 mm as a cut‐off had a 77.6% sensitivity, 82.3% specificity, and area under the receiver operating characteristic curves (AUROC) of 0.86 (95% CI 0.80 to 0.92) in discriminating HFpEF. In addition, CCAD superimposed on myocardial deformation significantly expanded AUROC (for longitudinal strain, from 0.84 to 0.90, P of ΔAUROC=0.02) in heart failure discrimination models.ConclusionsIncreased carotid artery diameter is associated with worse LV geometry, higher brain natriuretic peptide level, and reduced contractile mechanics in individuals with HFpEF.

Funding Acknowledgements No financial support Background Chronic exercise training leads to cardiac remodelling; the so-called Athlete’s Heart. Previous studies are often limited by a cross-sectional design whilst longitudinal training studies are often constrained to the assessment of non-athletes. Echocardiography provides comprehensive assessment of mechanics and may give additional insight into short-term changes in training volume in the elite athlete. Purpose To examine the impact of a short-term (9 months) increase in training volume on cardiac structure and mechanics in elite international competing rowers. Methods As part of the work-up to the 2012 Olympic Games, twenty-seven elite rowers (26.4 ± 3.7 years, 19 male) underwent baseline echocardiography prior to and post (9-months) a planned increase in training volume. Conventional echocardiographic indices including mechanics of all cardiac chambers were assessed. Results In response to increased training volume, there was a significant increase in left ventricular (LV) size (IVSd 9.2 ± 1.2 to 9.7 ± 1.1 mm, p = 0.001; PWd 8.3 ± 1.3 to 8.7 ± 1.4 mm, p = 0.013), LVIDd (56.5 ± 4.6 to 57.9 ± 4.2 mm, p = 0.001), and LVMi (90.2 ± 17.8 to 100.8 ± 17.1 g/m2, p = 0.000), see table. There was a significant increase in LV twist (9.2 ± 4.5 to 11.2 ± 4.7 °, p = 0.04; basal rotation -4.4 ± 3.1 to -4.5 ± 3.4 °, p = 0.84; apical rotation 5.8 ± 3.4 to 7.1 ± 3.7 °, p = 0.011), see figure, however, there were no changes in any other conventional indices of function or any other cardiac mechanics. There was a significant increase in left atrial (LA) volume (58.8 ± 15.2 to 65.3 ± 17.6 mm, p = 0.01) whilst no changes were observed in right heart structure. Conclusion An increase in exercise training volume in elite rowers across 9-months induced mild balanced structural remodelling of the LV and LA with a concomitant increase in LV twist. Contradictory to findings in non-athletes, there was no increase in right ventricular or atrial structure or function which may be representative of the elite athlete status and possibly already at threshold for physiological adaptation. Abstract P784 Figure.

Cardiac mechanical contraction is triggered by electrical activation via an intracellular calcium-dependent process known as excitation-contraction coupling. Dysregulation of cardiac myocyte intracellular calcium handling is a common feature of heart failure. At the organ scale, electrical dyssynchrony leads to mechanical alterations and exacerbates pump dysfunction in heart failure. A reverse coupling between cardiac mechanics and electrophysiology is also well established. It is commonly referred as cardiac mechanoelectric feedback and thought to be an important contributor to the increased risk of arrhythmia during pathological conditions that alter regional cardiac wall mechanics, including heart failure. At the cellular scale, most investigations of myocyte mechanoelectric feedback have focused on the roles of stretch-activated ion channels, though mechanisms that are independent of ionic currents have also been described. Here we review excitation-contraction coupling and mechanoelectric feedback at the cellular and organ scales, and we identify the need for new multicellular tissue-scale model systems and experiments that can help us to obtain a better understanding of how interactions between electrophysiological and mechanical processes at the cell scale affect ventricular electromechanical interactions at the organ scale in the normal and diseased heart.

A modular framework for implicit 3D–0D coupling in cardiac mechanics

BackgroundComorbidities are common in heart failure (HF), and the number of comorbidities has been associated with poor outcomes in HF patients. However, little is known about the effect of multiple comorbidities on cardiac mechanics, which could impact the pathogenesis of HF. We sought to determine the relationship between comorbidity burden and adverse cardiac mechanics.Methods and ResultsWe performed speckle‐tracking analysis on echocardiograms from the HyperGEN study (n=2150). Global longitudinal, circumferential, and radial strain, and early diastolic (e') tissue velocities were measured. We evaluated the association between comorbidity number and cardiac mechanics using linear mixed effects models to account for relatedness among subjects. The mean age was 51±14 years, 58% were female, and 47% were African American. Dyslipidemia and hypertension were the most common comorbidities (61% and 58%, respectively). After adjusting for left ventricular (LV) mass index, ejection fraction, and several potential confounders, the number of comorbidities remained associated with all indices of cardiac mechanics except global circumferential strain (eg, β=−0.32 [95% CI −0.44, −0.20] per 1‐unit increase in number of comorbidities for global longitudinal strain; β=−0.16 [95% CI −0.20, −0.11] for e' velocity; P≤0.0001 for both comparisons). Results were similar after excluding participants with abnormal LV geometry (P<0.05 for all comparisons).ConclusionsHigher comorbidity burden is associated with worse cardiac mechanics, even in the presence of normal LV geometry. The deleterious effect of multiple comorbidities on cardiac mechanics may explain both the high comorbidity burden and adverse outcomes in patients who ultimately develop HF.

Hypoxic exposure increases right ventricular (RV) afterload by triggering pulmonary hypertension, with consequent effects on the structure and function of the RV. Improved myocardial contractility is a critical circulatory adaptation to exercise training. However, the types of exercise that enhance right cardiac mechanics during hypoxic stress have not yet been identified. This study investigated how high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) influence right cardiac mechanics during hypoxic exercise A total of 54 young and healthy sedentary males were randomly selected to engage in either HIIT (3-min intervals at 40% and 80% of oxygen uptake reserve, n = 18) or MICT (sustained 60% of oxygen uptake reserve, n = 18) for 30 min/day and 5 days/week for 6 weeks or were included in a control group (CTL, n = 18) that did not engage in any exercise. The primary outcome was the change in right cardiac mechanics during semiupright bicycle exercise under hypoxic conditions (i.e., 50 watts under 12% FiO2 for 3 min) as measured by two-dimensional speckle tracking echocardiography.: After 6 weeks of training, HIIT was superior to MICT in improving maximal oxygen consumption (VO2max). Furthermore, the HIIT group showed reduced pulmonary vascular resistance (PVR, pre-HIIT:1.16 ± 0.05 WU; post-HIIT:1.05 ± 0.05 WU, p < 0.05) as well as an elevated right ventricular ejection fraction (RVEF, pre-HIIT: 59.5 ± 6.0%; post-HIIT: 69.1 ± 2.8%, p < 0.05) during hypoxic exercise, coupled with a significant enhancement of the right atrial (RA) reservoir and conduit functions. HIIT is superior to MICT in dilating RV chamber and reducing radial strain but ameliorating radial strain rate in either systole (post-HIIT: 2.78 ± 0.14 s-1; post-MICT: 2.27 ± 0.12 s-1, p < 0.05) or diastole (post-HIIT: − 2.63 ± 0.12 s-1; post-MICT: − 2.36 ± 0.18 s-1, p < 0.05). In the correlation analysis, the changes in RVEF were directly associated with improved RA reservoir (r = 0.60, p < 0.05) and conduit functions (r = 0.64, p < 0.01) but inversely associated with the change in RV radial strain (r = − 0.70, p < 0.01) and PVR (r = − 0.70, p < 0.01) caused by HIIT. HIIT is superior to MICT in improving right cardiac mechanics by simultaneously increasing RA reservoir and conduit functions and decreasing PVR during hypoxic exercise.

Strain imaging provides an accessible, feasible and non-invasive technique to assess cardiac mechanics. Speckle tracking echocardiography (STE) is the primary modality with the utility for detection of subclinical ventricular dysfunction. Investigation and adoption of this technique has increased significantly in both the research and clinical environment. It is therefore important to provide information to guide the sonographer on the production of valid and reproducible data. The focus of this review is to (1) describe cardiac physiology and mechanics relevant to strain imaging, (2) discuss the concepts of strain imaging and STE and (3) provide a practical guide for the investigation and interpretation of cardiac mechanics using STE.

The arterial switch operation (ASO) has become the standard surgical treatment for patients with d-transposition of the great arteries. While ASO has significantly improved survival rates, a subset of patients develop a unique anatomical anomaly known as the gothic aortic arch (GAA). Understanding cardiac mechanics in this population is crucial, as altered mechanics can have profound consequences for cardiac function and exercise capacity. The GAA has been associated with changes in ventricular function, hemodynamics, and exercise capacity. Studies have shown a correlation between the GAA and decreased ascending aorta distensibility, loss of systolic wave amplitude across the aortic arch, and adverse cardiovascular outcomes. Various imaging techniques, including echocardiography, cardiac magnetic resonance imaging, and cardiac computed tomography, play a crucial role in assessing cardiac mechanics and evaluating the GAA anomaly. Despite significant advancements, gaps in knowledge regarding the prognostic implications and underlying mechanisms of the GAA anomaly remain. This review aims to explore the implications of the GAA anomaly on cardiac mechanics and its impact on clinical outcomes in young patients after ASO. Advancements in imaging techniques, such as computational modeling, offer promising avenues to enhance our understanding of cardiac mechanics and improve clinical management.

The main objective of this study was to model the left ventricle (LV) based on 2D echocardiography imaging technique to assess the cardiac mechanics for group of patients affected by heart failure. A prospective study has been made at Ibn Al-Bitar center for cardiac surgery, for 13 patients with heart failure (HF), 9 patients were males (69%) and 4 females (31%). The mean age was 54±7 years. Those patients were supposed to undergo a CRT-D (Cardiac Resynchronization Therapy Defibrillator) implant as they didn’t respond to drug therapy. Before CRT-D implantation, 2D echocardiography was performed for all the patients, to model the left ventricle and to measure indices that were used to evaluate cardiac mechanics which are LV pressure, wall stresses, global longitudinal strain, and cardiac output. After 3-months of follow-up, 2D echocardiography was re-assessed and the left ventricular mechanics has been re-measured. Post CRT-D implantation, significant improvement in the cardiac mechanics was observed in 54% of the patients which were called responders (patients that respond to CRT-D device) and the other patients were called non-responders. It has been seen that, the circumferential wall stresses were decreased in responder’s group while increased or remain unchanged in non-responders. Global longitudinal strain for the responder’s group were increased while remain unchanged in the non-responders. So, patients were divided into responders and non-responders, based on improvement of the cardiac mechanics after 3-moths of follow up. It has been concluded that the modelling of the left ventricle based on images obtained from 2D echocardiography imaging techniques, was an important computational tool that was used to enhance understanding and support the evaluation, surgical guidance and treatment management of basic biophysics underlying cardiac mechanics.

Functional Cardiac Recovery and Hematologic Response to Chemotherapy in Patients With Light-Chain Amyloidosis (from the Stanford University Amyloidosis Registry)

Comparing Cardiac Mechanics and Myocardial Fibrosis in DBD and DCD Heart Transplant Recipients

Food restriction (FR) is the only known intervention capable of increasing mammalian life span. It not only increases longevity, but reduces the incidence of a broad spectrum of age-related pathologies, including cardiomyopathy, and retards the physiological decline associated with aging. Previous work from this laboratory has shown that long-term FR affects the contractile machinery of the heart, shifting the cardiac myosin profile from the fast, V1 isoform to the slow, V3 isoform. The aim of the present study was to determine whether FR also induces changes in cardiac mechanics. Isolated, isovolumically beating hearts were examined from four groups of rats: 1) ad libitum-fed rats killed at 10-13 mo of age, 2) FR rats offered only 60% of the calories consumed by ad libitum-fed rats and killed at the same age, 3) young ad libitum-fed rats having the same heart weights as the FR rats, and 4) ad libitum-fed rats subjected to short-term FR, i.e., for the last 3 wk of life, and also killed at 10-13 mo of age. Both short- and long-term FR profoundly and to approximately the same extent affected cardiac mechanics. Hearts from FR rats developed much higher pressures than hearts from the ad libitum-fed rats under conditions of low-calcium perfusate. This difference disappeared, however, when contractility was enhanced by either calcium or isoproterenol. FR prolonged both contraction and relaxation times. Long-term ad libitum-fed rats (adult, 10-13 mo of age) had a lower isoproterenol sensitivity than the young ad libitum-fed rats (10 wk of age). Both short- and long-term FR restored the sensitivity to isoproterenol. In summary, FR profoundly affects many aspects of cardiac mechanics, enhancing some age-related changes (prolongation of the contraction and relaxation times), attenuating another (increasing the isoproterenol sensitivity), and, finally, inducing some unique changes unrelated to age (increased pressure development under low-calcium perfusate).

Seismocardiogram, SCG, is the measure of precordial vibrations produced by the beating heart, from which cardiac mechanics may be explored on a beat-to-beat basis. We recently collected a large amount of SCG data (>69 recording hours) from an astronaut to investigate cardiac mechanics during sleep aboard the International Space Station and on Earth. SCG sleep recordings are characterized by a prolonged duration and wide heart rate swings, thus a specific algorithm was developed for their analysis. In this article we describe the new algorithm and its performance. The algorithm is composed of three parts: 1) artifacts removal, 2) identification in each SCG waveform of four fiducial points associated with the opening and closure of the aortic and mitral valves, 3) beat-to-beat computation of indexes of cardiac mechanics from the SCG fiducial points. The algorithm was tested on two sleep recordings and yielded the identification of the fiducial points in more than 36,000 beats with a precision, quantified by the Positive Predictive Value, ≥99.2%. These positive findings provide the first evidence that cardiac mechanics may be explored by the automatic analysis of SCG long-lasting recordings, taken out of the laboratory setting, and in presence of significant heart rate modulations.

Introduction: A genetic predisposition to abnormal cardiac mechanics may explain the familial predisposition to heart failure (HF). We hypothesized that indices of cardiac mechanics (speckle-tracking strain parameters and tissue velocities) are heritable traits. Methods: We performed speckle-tracking analysis on echocardiograms and measured global longitudinal, circumferential, and radial strain (GLS, GCS, GRS), early diastolic strain rate, and e’ velocities in the HyperGEN study, a family- and population-based study of hypertension (N=2058 [54% African American (AA)]). Additive genetic heritability estimates for cardiac mechanics were calculated by maximizing the likelihood variance components in SOLAR (ver.6) adjusted for age, sex, race, height, weight, systolic blood pressure (SBP), left ventricular (LV) mass, ejection fraction, reader, image quality, and institution. Results: Mean age was 51±14 years and HF risk factors were common: hypertension (56%), obesity (47%), and diabetes (16%). Clinical and conventional echocardiographic characteristics, including male gender, hypertension, elevated fasting glucose, higher body-mass index, and LV hypertrophy were all significantly associated with increased absolute GLS and septal e’ velocity (P&lt;0.05). After adjustment for covariates (and correlation within the same families), genetic contributions remained significant in GLS and septal e’ velocity in all participants, a finding which persisted in race-stratified analyses (Table). Conclusions: Echocardiographic measures of cardiac mechanics, particularly GLS and e’ velocity, are heritable traits, even after adjustment for clinical and cardiac structural factors (e.g., SBP and LV mass, respectively) that are known to be heritable and associated with cardiac mechanics. These data support the exploration of genetics of cardiac mechanics, which may provide insight into the molecular pathogenesis of LV dysfunction and HF.