Association between Impaired Renal Function and Subclinical Myocardial Dysfunction in Patients with Heart Failure with Preserved Ejection Fraction: Assessment Using Noninvasive Pressure-Strain Loop.

INTRODUCTION: The objective of this study was to evaluate the abnormal myocardial function in HFpEF patients with renal dysfunction (RD) and investigate the relationship between renal function and myocardial mechanical characteristics in patients with HFpEF. METHODS: 134 patients with HFpEF and 32 control subjects were enrolled in our study. Clinical and echocardiography data were collected for offline analysis. Global work index (GWI), global constructive work (GCW), global waste work (GWW), and global work efficiency (GWE) were measured after noninvasive pressure-strain loop analysis. Univariate and multivariate analyses were used to determine the correlation between renal function and myocardial function in patients with HFpEF. RESULTS: In comparison to control subjects, patients with HFpEF tend to have higher GWW (78 [50-115] vs. 108 [65-160] mm Hg%, p < 0.05) and lower GWE (96 [95-97] vs. 95 [92-96] %, p < 0.05), while left ventricular ejection fraction (65.5 ± 3.3 vs. 64.3 ± 4.6%, p < 0.05) was comparable between them. Besides, increased GWW (86 [58-152] vs. 125 [94-187] mm Hg%, p < 0.05) and decreased GWE (96 [93-97] vs. 94 [92-96] %, p < 0.05) were detected in patients with RD compared to those with normal renal function. An independent correlation was found between estimated glomerular filtration rate and GWW after multivariate analysis. DISCUSSION/CONCLUSION: More severely impaired myocardial function was detected in HFpEF patients with RD compared to those with normal renal function. Estimated glomerular filtration rate was independently correlated to GWW in patients with HFpEF.

Parameter subset reduction for imaging-based digital twin generation of patients with left ventricular mechanical discoordination.

BACKGROUND: Integration of a patient's non-invasive imaging data in a digital twin (DT) of the heart can provide valuable insight into the myocardial disease substrates underlying left ventricular (LV) mechanical discoordination. However, when generating a DT, model parameters should be identifiable to obtain robust parameter estimations. In this study, we used the CircAdapt model of the human heart and circulation to find a subset of parameters which were identifiable from LV cavity volume and regional strain measurements of patients with different substrates of left bundle branch block (LBBB) and myocardial infarction (MI). To this end, we included seven patients with heart failure with reduced ejection fraction (HFrEF) and LBBB (study ID: 2018-0863, registration date: 2019-10-07), of which four were non-ischemic (LBBB-only) and three had previous MI (LBBB-MI), and six narrow QRS patients with MI (MI-only) (study ID: NL45241.041.13, registration date: 2013-11-12). Morris screening method (MSM) was applied first to find parameters which were important for LV volume, regional strain, and strain rate indices. Second, this parameter subset was iteratively reduced based on parameter identifiability and reproducibility. Parameter identifiability was based on the diaphony calculated from quasi-Monte Carlo simulations and reproducibility was based on the intraclass correlation coefficient ( ICC ) obtained from repeated parameter estimation using dynamic multi-swarm particle swarm optimization. Goodness-of-fit was defined as the mean squared error ( χ 2 ) of LV myocardial strain, strain rate, and cavity volume. RESULTS: A subset of 270 parameters remained after MSM which produced high-quality DTs of all patients ( χ 2 < 1.6), but minimum parameter reproducibility was poor ( ICC min = 0.01). Iterative reduction yielded a reproducible ( ICC min = 0.83) subset of 75 parameters, including cardiac output, global LV activation duration, regional mechanical activation delay, and regional LV myocardial constitutive properties. This reduced subset produced patient-resembling DTs ( χ 2 < 2.2), while septal-to-lateral wall workload imbalance was higher for the LBBB-only DTs than for the MI-only DTs (p < 0.05). CONCLUSIONS: By applying sensitivity and identifiability analysis, we successfully determined a parameter subset of the CircAdapt model which can be used to generate imaging-based DTs of patients with LV mechanical discoordination. Parameters were reproducibly estimated using particle swarm optimization, and derived LV myocardial work distribution was representative for the patient's underlying disease substrate. This DT technology enables patient-specific substrate characterization and can potentially be used to support clinical decision making.

Targeting subclinical ventricular dysfunction in atrial fibrillation: What can myocardial work add?

Atrial fibrillation (AF) could impact on left ventricular function leading to a sublinical myocardial dysfunction, as identified by myocardial work parameters in a population-based cohort of AF patients compared with healthy individuals; factors associated with these parameters are also shown. SBP: systolic blood pressure; LAVI: left atrial volume index.

Quantitative assessment of left ventricular myocardial work in patients with different types of atrial fibrillation by non-invasive pressure-strain loop technique.

OBJECTIVE: This study aimed to analyze myocardial work in patients with atrial fibrillation (AF) using a noninvasive pressure strain loop (PSL) technique to provide a basis for the quantitative assessment of left ventricular (LV) systolic function. METHODS: LV myocardial work of 107 AF patients (56 with paroxysmal atrial fibrillation and 51 with persistent atrial fibrillation) and 55 healthy individuals were assessed by the noninvasive PSL and then compared. RESULTS: Global longitudinal strain (GLS) in absolute values, global work index (GWI), global constructive work (GCW), and global work efficiency (GWE) were significantly lower in the AF group than control group, whereas peak strain dispersion (PSD) and global wasted work (GWW) were significantly higher (P < .05). Further subdivision according to the AF type revealed that, compared with the controls, GLS in absolute values and GWE decreased significantly; PSD and GWW increased significantly in the paroxysmal AF group (P < .05). Nevertheless, GWI and GCW were not significantly different between paroxysmal AF and control groups (P > .05). Compared to paroxysmal AF, persistent AF induced a further decrease in absolute GLS and GWE and a further increase in GWW (P < .05), but PSD did not increase further (P > .05). Multiple linear regression analysis showed that GWI and GCW were independently associated with systolic blood pressure. GWW was associated with types of AF and left atrial volume index (LAVI). GWE was correlated with age, types of AF, disease duration, and LAVI. Receiver operating characteristic curve analysis showed that the area under the curve predicting myocardial injury was higher for GWE and GWW than for GLS (area under the curve:  .880,  .846, and  .821, respectively). CONCLUSIONS: Non-invasive PSL can quantitatively assess LV systolic function in patients with different kinds of AF and detect early subclinical myocardial injury in patients with paroxysmal AF. GWE and GWW outperform GLS and LV ejection fraction when assessing myocardial injury. Systolic blood pressure, type of AF, LVAI, disease duration, and age may be associated with myocardial injury in patients with AF.

From ejection fraction, to myocardial strain, and myocardial work in echocardiography: Clinical impact and controversies.

Enhancing an echocardiographic tool, aimed to detect even subtle left ventricular (LV) systolic function abnormalities, capable of obtaining both early diagnosis and risk prediction of heart disease, represents an ambitious, attractive, and arduous purpose in the modern era of cardiovascular imaging. Ideally, that tool should be simple, reliable, and reproducible, in order to be concretely applied in routine clinical practice. Importantly, that technique should be physiologically plausible and useful both at the population-level, as well as in the individual subject. For a long time, LV ejection fraction (EF) has been considered the first-line parameter for assessing LV global systolic function, strictly related to the prognosis, at least in some settings. However, LV EF limitations are well-known, even though frequently overemphasized, including its load-dependency. Therefore, myocardial strain techniques have been proposed, deemed able to disclose even subtle early LV function anomalies. Nevertheless, many disadvantages of myocardial strain have been reported as well. More recently, myocardial work (MW) analysis has been introduced as a new echocardiographic tool for the evaluation of LV global systolic function, attempting to overcome EF and strain disadvantages. However, MW has shown many limits as well. Notwithstanding, LV EF still remains a landmark functional classification marker for heart failure and cardiac oncology, allowing reliable fast reassessment of LV function changes during patient management, in order to guide treatment in individual cases as well. Notably, global longitudinal strain and MW parameters seem to show better meaningful results at the population-level, but controversial clinical impact, major limitations, wide cut-offs spread and overlap, when the single value needs to be applied to the single case. Taking into account the recent literature-based evidence, the scope of the present narrative critical review is trying to delineate the different types of information given by the described LV global systolic function parameters, both at the population-level and in the individual case, in order to trace a comparative analysis of advantages and limitations in clinical practice.

Study of stress-strain loops on cardiotoxicity related to immune checkpoint inhibitors.

OBJECTIVE: To evaluate the effect of immune checkpoint inhibitors (ICIs) on left ventricular myocardial work by pressure-strain loop (PSL). METHODS: Forty-three immunotherapy patients were enrolled in the case group, and another 43 healthy volunteers were enrolled in the control group. They were examined by echocardiography before immunotherapy (T0 phase), after three cycles of treatment (T3 phase) and after six cycles of treatment (T6 phase). Conventional echocardiographic parameters, left ventricular global longitudinal strain (GLS), and myocardial work indices, including global work index (GWI), global constructive work (GCW), global work waste (GWW), and global work efficiency (GWE), were collected for analysis to compare the results of the different immunotherapy cycles. RESULTS: There were no statistically significant differences of baseline characteristics, conventional echocardiographic parameters, left ventricular strain, and myocardial work indices between T0 phase and control group (all p > .05). There were no statistically significant differences in LVEF between T0, T3, and T6 phase (all p > .05). GLS, GWI, GCW, and GWE were decreased and GWW was increased in T3 and T6 phase. There were no statistically significant difference between GLS in T3 and T0 phase (q = .9057, p > .05). The difference was statistically significant between GLS in T6 and T0 phase (q = 5.5651, p < .01). The difference was statistically significant between GLS in T3 and T6phase(q = 4.6594, p < .01). There were statistically significant difference in GWI, GCW, GWE, and GWW in the T3 and T6 phase compared with the T0 phase (p < .01). CONCLUSION: PSL can effectively evaluate the effect of ICIs on left ventricular myocardial work, to provide a new method for the early clinical detection of ICIs-related cardiotoxicity.

Quantitative evaluation of right ventricular myocardial function changes in patients with atrial septal defect before and after occlusion by noninvasive right ventricular pressure-strain loop.

OBJECTIVE: The noninvasive right ventricular pressure-strain loop (PSL) represents a novel method for the quantitative assessment of right ventricular myocardial function. Given that atrial septal defect (ASD) is a prevalent congenital heart anomaly associated with right ventricular volume overload, this study aimed to quantitatively assess the myocardial function of the right ventricle in ASD patients pre- and post-occlusion by noninvasive right ventricular PSL. METHODS: This study included 36 patients diagnosed with secundum ASD group and 30 healthy adults (control group). We compared conventional right ventricular echocardiographic parameters, right ventricular strain, and myocardial work in the ASD group before occlusion, two days post-occlusion, and three months post-occlusion, with those in the control group. RESULTS: Prior to and two days following occlusion, the ASD group exhibited higher right ventricular global work index (RVGWI), right ventricular global wasted work (RVGWW), and right ventricular global constructive work (RVGCW) compared to the control group (P < .05). Within the ASD group, post-occlusion, RVGWI, RVGCW, and RVGWW values were significantly reduced compared to pre-occlusion values (P < .001). Furthermore, RVGWI and RVGCW showed a significant decrease three months after occlusion compared to two days post-occlusion (P < .05). Multivariate regression analysis identified ASD diameter and pulmonary artery systolic pressure (PASP) as independent predictors of RVGWI (ß = .405, P < .001; ß = 2.307, P = .037) and RVGCW(ß = .350, P<.001; ß = 1.967, P = .023). CONCLUSIONS: The noninvasive right ventricular PSL effectively demonstrates the alterations in right ventricular myocardial function in ASD patients, pre- and post-occlusion. The metrics of right ventricular myocardial work (RVMW) offer a novel indicator for evaluating right ventricular myocardial function in these patients. Moreover, ASD diameter and PASP emerge as independent determinants of RVGWI and RVGCW.

Effect of Ciprofol on Left Ventricular Myocardial Strain and Myocardial Work in Children Undergoing Cardiac Surgery: A Single-center Double-blind Randomized Noninferiority Study.

OBJECTIVE: The current work was designed to compare the effects of ciprofol and propofol on left ventricular systolic function and myocardial work by noninvasive speckle-tracking echocardiography in children undergoing surgical repair of atrial septal or ventricular septal defects. DESIGN: A single-center double-blind randomized noninferiority study was conducted. SETTING: The research occurred at a tertiary care center affiliated with Shanghai Jiao Tong University, China. PARTICIPANTS: One hundred and twelve children aged 1 month to 16 years undergoing atrial septal or ventricular septal defect surgery with cardiopulmonary bypass were included. INTERVENTIONS: One hundred and twelve children were allocated randomly to receive ciprofol (n = 67) or propofol (n = 45) in a 1.5:1 ratio. Ciprofol or propofol were intravenously infused at loading doses of 0.4 mg/kg or 2.0 mg/kg, respectively, over 30 seconds, depending on the physical condition of each patient. When the bispectral index was maintained between 45 and 55 after induction, transthoracic echocardiography, including apical two-chamber, three-chamber, and four-chamber views, were collected bedside. MEASUREMENTS AND MAIN RESULTS: Of the 112 patients enrolled, 104 completed the study. Global longitudinal strain in the ciprofol and propofol groups after anesthesia was -17.3% (95% confidence interval [CI] -18.0% to -16.6%) and -17.8% (95% CI -18.7 to -17.0%) in the full analysis set and -17.5% (95% CI -18.2% to -16.9%) and -17.8% (95% CI -18.7% to -17.0%) in the per-protocol set, respectively. The noninferiority margin was set at 2% and confirmed with a lower limit of two-sided 95% CI for the intergroup difference of 1.58% in the full analysis set and 1.34% in the per-protocol set. There were no significant differences between the groups in left ventricular systolic and diastolic function and myocardial work indices. Postoperative vasoactive-inotropic score, NT-proBNP, duration of mechanical ventilation, and the length of stay in the cardiac intensive care unit and hospital were also comparable between the two groups (all p > 0.05). CONCLUSIONS: Ciprofol did not show different effects on myocardial function and postoperative outcomes from propofol. Further, on the sensitive cardiac systole marker global longitudinal strain, ciprofol demonstrated noninferiority to propofol. Ciprofol might be an alternative solution for cardiac anesthesia in children with congestive heart disease with mild lesion.

Evaluation the Effect of Anthracyclines on Cardiac Function in Children Lymphoma Survivors by Left Ventricular Myocardial Work.

Anthracycline chemotherapy is associated with the left ventricular (LV) dysfunction, but the conventional echocardiographic parameter is insensitive in detecting subclinical cardiac dysfunction, and the role of echocardiography in children cancer survivors (CCSs) has not been well established. Here, the myocardial work (MW) was employed to evaluate the early effect of the anthracyclines on LV function in children lymphoma survivors, as well as to explore the clinical application value of this modality. 51 children lymphoma survivors treated with anthracyclines were included. During the treatments, the echocardiography was performed at baseline (T0 phase), the 3rd (T1 phase) and 6th (T2 phase) chemotherapeutic cycle, respectively. After that, the conventional echocardiographic parameters, LV global longitudinal strain (GLS), and global myocardial work (GMW) parameters were obtained. Finally, these echocardiographic parameters were compared to distinguish the differences among three groups, and correlation analysis was used to identify relationship between GMW parameters and LV GLS. Compared with the baseline, we found that there are no significant differences for LVEF and other conventional echocardiographic parameters after chemotherapy, but the value of LV lateral E/E' increased at T1 and T2 group. The GLS, global work index, global constructed work, and global work efficiency were decreased, while the global wasted work was increased after chemotherapy (all P < 0.05). The correlation analysis showed that the GLS has significant correlation with GMW parameters (all P < 0.001). The MW, as a new noninvasive echocardiography modality, could be used to quantitatively evaluate the LV MW in children lymphoma survivors treated with anthracyclines, which providing a sensitive method to early detect the children's LV dysfunction after the chemotherapy.

Impaired Myocardial Work in Children with Hypertrophic Cardiomyopathy and Left Ventricular Fibrosis on Cardiac Magnetic Resonance Imaging.

Echocardiography is pivotal for diagnosis and monitoring of hypertrophic cardiomyopathy (HCM) and can evaluate myocardial function using myocardial work (MW) calculations. Echocardiography is often supplemented by cardiovascular magnetic resonance (CMR) imaging, which can detect myocardial fibrosis using late gadolinium enhancement (LGE). We sought to study the relationship between baseline LGE and MW at baseline and during follow-up in pediatric HCM patients. During the study period (2008-2023), 75 patients were followed up for HCM. In 14 patients (age 14.2 ± 2.8 years, 50.0% male, 6.4 ± 2.9 years follow-up), both LGE-CMR and echocardiography were performed. Global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency (GWE) were measured, and myocardial fibrosis was estimated by qualitative assessment of LGE. Patients with LGE (n = 7) exhibited significantly impaired baseline MW, including GWI (mean difference, MD - 487.4 mmHg %, 95% CI [- 866.8 mmHg % to - 108.3 mmHg %], p = 0.027), GCW (MD - 536.8 mmHg %, 95% CI [- 929.8 mmHg % to - 144.4 mmHg %], p = 0.020), and GWE (MD - 4.4%, 95% CI [- 8.1% to - 0.7%], p = 0.039). Regional analysis revealed impaired MW indices in segments with LGE, notably basal and mid septal segments. GWI demonstrated high diagnostic performance for LGE presence (sensitivity 93%, specificity 88%, and area under receiver operating characteristic curve 0.85). Baseline LGE presence had no significant impact on MW deterioration during follow-up. MW is significantly impaired in HCM patients with myocardial fibrosis, highlighting potential utility of echocardiography-derived MW analysis as a valuable tool.

Global left ventricular myocardial work: A novel method to assess left ventricular myocardial function and predict major adverse cardiovascular events in maintenance hemodialysis patients.

BACKGROUND: The application value of myocardial work (MW) in evaluating myocardial function and predicting major adverse cardiovascular events (MACE) in maintenance hemodialysis (MHD) patients has not been fully explored. PURPOSE: Comparing noninvasive MW parameters between MHD patients and healthy controls, and further determining its value in predicting MACE in MHD patients. METHODS: A prospective single-institution study included 92 MHD patients without prior cardiovascular disease and 40 age- and sex-matched healthy controls. Conventional echocardiographic data, global longitudinal strain (GLS), and MW parameters (global work index [GWI], global constructive work [GCW], global work efficiency [GWE], global wasted work [GWW]) were derived and compared between MHD and the control. Logistic regression was used to determine the predictive value of these parameters for MACE. The receiver operating characteristic curve was utilized to compare the predictive differences of MACE between GWE and GLS. RESULTS: Compared with healthy individuals, MHD patients had significantly reduced GWE, GLS and elevated LVMI, GWW (all p < 0.001), while there was no significant difference in left ventricular ejection fraction. Twenty eight (30%) MHD patients experienced MACE. Two nested models adding GWE and GLS, respectively, showed that age (p < 0.005), GWE (p = 0.034), and GLS (p = 0.014) were independent predictors of MACE. The AUC derived from GWE for predicting MACE was significantly higher than that derived from GLS (0.836 vs. 0.743, p = 0.039). CONCLUSIONS: Myocardial work is a novel tool for assessing left ventricular myocardial performance in MHD patients. GWE is an independent predictor of MACE.

A novel method for the evaluation of right ventricular dysfunction in acute pulmonary embolism: Myocardial work indices.

PURPOSE: The presence of right ventricular dysfunction indicates a higher risk status in patients with pulmonary embolism (PE). The RV strain evaluated by speckle-tracking echocardiography seems to be more reliable method in the evaluation of RV dysfunction as compared to standard echocardiographic measures. In this study, we aimed to determine the value of myocardial-work indices in evaluating serial changes of RV function in acute PE. METHODS: Our study comprised 83 consecutive acute PE patients who admitted to our tertiary cardiovascular hospital. Echocardiography was performed within the first 24-hours of hospitalization, and RV and LV myocardial-work parameters were obtained along with standard echocardiographic parameters. The change in the RV/LVr detected on tomography was selected as the primary outcome measure, and its' predictors were analyzed with classical linear regression and a generalized additive model (GAM). RESULTS: Among the LV-RV strain and myocardial work parameters, the RV global longitudinal strain (GLS) has borderline statistical significance in predicting the RV/LVr change whereas the RV global work efficiency (RV-GWE) strongly predicted RV/LVr change (p: 0.049 and <0.001, respectively). CONCLUSION: In this study, classical linear regression and GAM analyses showed that RV-GWE seems to offer a better prediction of RV/LVr change in patients with acute PE.

Usability of myocardial work parameters in demonstrating myocardial involvement in INOCA patients.

BACKGROUND: Myocardial work (MW) is a novel echocardiographic modality, which has been shown to have diagnostic and prognostic values in patients with cardiovascular diseases, patients with obstructive coronary artery disease, in particular. However, only a handful of studies have examined the MW analysis in ischemia with nonobstructive coronary artery (INOCA) disease. This study, therefore, aimed to detect the early left ventricular involvement in INOCA patients diagnosed by an invasive coronary angiography performing the MW analysis. METHODS: This study included a total of 119 patients with nonobstructive coronary artery disease diagnosed by invasive coronary angiography, who were checked for prior ischemia tests performing myocardial perfusion scintigraphy. Out of these 119 patients, 49 patients developed ischemia (i.e., ischemic group) diagnosed using cardiac single-photon emission computed tomography, whereas 70 patients did not (i.e., nonischemic group). The subjects were divided into three groups based on the global MW tertiles. The groups were compared in terms of the conventional, longitudinal strain, and MW findings by conducting echocardiographic examinations. RESULTS: The study subjects were divided into three groups based on the global constrictive work (GCW) value. The three groups were not statistically different in terms of the mean age of the patients (53.0 ± 12 vs. 52.4 ± 13.3 vs. 52.1 ± 12.3; p = 0.96). Furthermore, the three groups were not statistically different regarding the gender, height, weight, and laboratory parameters of the patients except albumin. There was no statistically difference among the tertiles of GCW groups in the measurements of cardiac chambers, LA diameter, interventricular septum, E wave, and A wave. Also, there was no statistical difference in tissue Doppler recordings. The parameters associated with MW were examined, three groups were not statistically different in terms of the global waste work (GWW) (116 ± 92, 122 ± 73, 135 ± 62, p = 0.52, respectively). In contrast, the three groups were different regarding the Global work index (GWI) (1716 ± 300, 1999 ± 130, 2253 ± 195, p < 0.001, respectively), GCW (1888 ± 206, 2298 ± 75, 2614 ± 155, p < 0.001, respectively), and Global work efficiency parameters (92.8 ± 3.6, 94.4 ± 3.2, 95.1 ± 1.8 p = 0.004, respectively). CONCLUSION: It was concluded that the MW parameters GCW and GWI may have been used for predicting INOCA in patients.

Echocardiographic Myocardial Work: A Novel Method to Assess Left Ventricular Function in Patients with Coronary Artery Disease and Diabetes Mellitus.

Myocardial ischemia caused by coronary artery disease (CAD) and the presence of metabolic abnormalities and microvascular impairments detected in patients with diabetes mellitus (DM) are a common cause of left ventricular (LV) dysfunction. Transthoracic echocardiography is the most-used, non-invasive imaging method for the assessment of myocardial contractility. The accurate evaluation of LV function is crucial for identifying patients who are at high risk or may have worse outcomes. Myocardial work (MW) is emerging as an alternative tool for the evaluation of LV systolic function, providing additional information on cardiac performance when compared to conventional parameters such as left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) because it incorporates deformation and load into its analysis. The potential of MW in various conditions is promising and it has gained increased attention. However, larger studies are necessary to further investigate its role and application before giving an answer to the question of whether it can have widespread implementation into clinical practice. The aim of this review is to summarize the actual knowledge of MW for the analysis of LV dysfunction caused by myocardial ischemia and hyperglycemia.

Multiaxial pressure-strain analysis of regional myocardial work in the setting of graded coronary stenoses and dobutamine stress.

We present a detailed analysis of regional myocardial blood flow and work to better understand the effects of coronary stenoses and low-dose dobutamine stress. Our analysis is based on a unique open-chest model in anesthetized canines that features invasive hemodynamic monitoring, microsphere-based blood flow analysis, and an extensive three-dimensional (3-D) sonomicrometer array that provides multiaxial deformational assessments in the ischemic, border, and remote vascular territories. We use this model to construct regional pressure-strain loops for each territory and quantify the loop subcomponent areas that reflect myocardial work contributing to the ejection of blood and wasted work that does not. We demonstrate that reductions in coronary blood flow markedly alter the shapes and temporal relationships of pressure-strain loops, as well as the magnitudes of their total and subcomponent areas. Specifically, we show that moderate stenoses in the mid-left anterior descending coronary artery decrease regional midventricle myocardial work indices and substantially increase indices of wasted work. In the midventricle, these effects are most pronounced along the radial and longitudinal axes, with more modest effects along the circumferential axis. We further demonstrate that low-dose dobutamine can help to restore or even improve function, but often at the cost of increased wasted work. This detailed, multiaxial analysis provides unique insight into the physiology and mechanics of the heart in the presence of ischemia and low-dose dobutamine, with potential implications in many areas, including the detection and characterization of ischemic heart disease and the use of inotropic support for low cardiac output.NEW & NOTEWORTHY Our unique experimental model assesses cardiac pressure-strain relationships along multiple axes in multiple regions. We demonstrate that moderate coronary stenoses decrease regional myocardial work and increase wasted work and that low-dose dobutamine can help to restore myocardial function, but often with further increases in wasted work. Our findings highlight the significant directional variation of cardiac mechanics and demonstrate potential advantages of pressure-strain analyses over traditional, purely deformational measures, especially in characterizing physiological changes related to dobutamine.

Virtual pacing of a patient's digital twin to predict left ventricular reverse remodelling after cardiac resynchronization therapy.

AIMS: Identifying heart failure (HF) patients who will benefit from cardiac resynchronization therapy (CRT) remains challenging. We evaluated whether virtual pacing in a digital twin (DT) of the patient's heart could be used to predict the degree of left ventricular (LV) reverse remodelling post-CRT. METHODS AND RESULTS: Forty-five HF patients with wide QRS complex (≥130 ms) and reduced LV ejection fraction (≤35%) receiving CRT were retrospectively enrolled. Echocardiography was performed before (baseline) and 6 months after CRT implantation to obtain LV volumes and 18-segment longitudinal strain. A previously developed algorithm was used to generate 45 DTs by personalizing the CircAdapt model to each patient's baseline measurements. From each DT, baseline septal-to-lateral myocardial work difference (MWLW-S,DT) and maximum rate of LV systolic pressure rise (dP/dtmax,DT) were derived. Biventricular pacing was then simulated using patient-specific atrioventricular delay and lead location. Virtual pacing-induced changes ΔMWLW-S,DT and ΔdP/dtmax,DT were correlated with real-world LV end-systolic volume change at 6-month follow-up (ΔLVESV). The DT's baseline MWLW-S,DT and virtual pacing-induced ΔMWLW-S,DT were both significantly associated with the real patient's reverse remodelling ΔLVESV (r = -0.60, P < 0.001 and r = 0.62, P < 0.001, respectively), while correlation between ΔdP/dtmax,DT and ΔLVESV was considerably weaker (r = -0.34, P = 0.02). CONCLUSION: Our results suggest that the reduction of septal-to-lateral work imbalance by virtual pacing in the DT can predict real-world post-CRT LV reverse remodelling. This DT approach could prove to be an additional tool in selecting HF patients for CRT and has the potential to provide valuable insights in optimization of CRT delivery.

Noninvasive assessment of myocardial work during left ventricular isovolumic relaxation in patients with diastolic dysfunction.

BACKGROUND: This study aims to investigate the value of myocardial work (MW) parameters during the isovolumic relaxation (IVR) period in patients with left ventricular diastolic dysfunction (LVDD). METHODS: This study prospectively recruited 448 patients with risks for LVDD and 95 healthy subjects. An additional 42 patients with invasive measurements of left ventricular (LV) diastolic function were prospectively included. The MW parameters during IVR were noninvasively measured using EchoPAC. RESULTS: The total myocardial work during IVR (MWIVR), myocardial constructive work during IVR (MCWIVR), myocardial wasted work during IVR (MWWIVR), and myocardial work efficiency during IVR (MWEIVR) of these patients were 122.5 ± 60.1 mmHg%, 85.7 ± 47.8 mmHg%, 36.7 ± 30.6 mmHg%, and 69.4 ± 17.8%, respectively. The MW during IVR was significantly different between patients and healthy subjects. For patients, MWEIVR and MCWIVR were significantly correlated with the LV E/e' ratio and left atrial volume index, MWEIVR exhibited a significant correlation with the maximal rate of decrease in LV pressure (dp/dt per min) and tau, and the MWEIVR corrected by IVRT also exhibited a significant correlation with tau. CONCLUSIONS: MW during IVR significantly changes in patients with risks for LVDD, and is correlated to LV conventional diastolic indices, including dp/dt min and tau. Noninvasive MW during IVR may be a promising tool to evaluate the LV diastolic function.

Myocardial function including estimates of myocardial work in young adults born very preterm or with extremely low birthweight - a cohort study.

BACKGROUND: Preterm birth and low birthweight have been associated with increased risk of heart failure and cardiovascular disease in young adulthood. However, results from clinical studies of myocardial function are not consistent. Echocardiographic strain analyses allow detection of early stages of cardiac dysfunction, and non-invasive estimates of myocardial work can provide additional information on cardiac function. We aimed to evaluate left ventricular (LV) myocardial function including measures of myocardial work in young adults born very preterm (gestational age < 29 weeks) or with extremely low birthweight (< 1000 g) (PB/ELBW), compared with term-born age- and sex matched controls. METHODS: 63 PB/ELBW and 64 controls born in Norway in the periods 1982-1985, 1991-1992, and 1999-2000 were examined with echocardiography. LV ejection fraction (EF) and LV global longitudinal strain (GLS) were measured. Myocardial work was estimated from LV pressure-strain loops after determination of GLS and construction of a LV pressure curve. Diastolic function was evaluated by determination of the presence or absence of elevated LV filling pressure, including measures of left atrial longitudinal strain. RESULTS: The PB/ELBW with mean birthweight 945 (standard deviation (SD) 217) grams, mean gestational age 27 (SD 2) weeks, and mean age 27 (SD 6) years had LV systolic function mainly within normal range. Only 6% had EF < 50% or impaired GLS >-16%, but 22% had borderline impaired GLS between - 16% and - 18%. Mean GLS in PB/ELBW (-19.4% (95% confidence interval (CI) -20.0, -18.9)) was impaired compared to controls (-20.6% (95% CI -21.1, -20.1)), p = 0.003. Lower birthweight was associated to more impaired GLS (Pearson correlation coefficient - 0.2). Means of EF, measures of diastolic function including left atrial reservoir strain, global constructive and wasted work, global work index and global work efficiency was similar in PB/ELBW and controls. CONCLUSION: The young adults born very preterm or with extremely low birthweight had impaired LV-GLS compared to controls, although systolic function mainly within normal range. Lower birthweight was associated with more impaired LV-GLS. These findings could indicate an elevated lifetime risk of developing heart failure in preterm born individuals. Measures of diastolic function and myocardial work were similar compared to controls.

Evaluation of global and regional myocardial work in hypertrophic cardiomyopathy patients by left ventricular pressure-strain loop.

OBJECTIVE: This study aimed to investigate the value of left ventricular (LV) press-strain loop (PSL) in evaluating global and regional myocardial work (MW) in hypertrophic cardiomyopathy (HCM) patients. METHODS: A total of 30 HCM patients with interventricular septum hypertrophy (HCM group) and 35 healthy subjects (control group) were selected from First Hospital of Qinhuangdao. The general clinical data and conventional ultrasound parameters of two groups were acquired. The MW parameters were analyzed using LV PSL. The regional MW parameters in the HCM group were compared between ventricular septum and the free walls of left ventricle. RESULTS: The epicardial adipose tissue thickness of the HCM group was significantly greater than that of the control group (P < 0.05). Global work efficiency was significantly reduced, while global wasted work was increased in patients with HCM compared with controls (all P < 0.05). The HCM group was compared in the group, to be specific, in the HCM group, the work index, the work efficiency, and the longitudinal strain on the interventricular septum were lower than those on the free wall (all P < 0.05). CONCLUSION: PSL is more effective than LVEF in assessing left ventricular systolic function in HCM and is able to quantify regional myocardial work in the ventricular septum in HCM patients with preserved LVEF, suggesting a novel idea for clinical diagnosis and assessment.

Abnormal inter-ventricular diastolic mechanical delay in patients with ST-segment elevation myocardial infarction.

BACKGROUND: This study aimed to investigate the ventricular mechanical relaxation pattern and its clinical influence in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Echocardiography was performed to measure mitral and tricuspid diastolic opening times. Left ventricular diastolic mechanical delay (LVMDd) was defined as diastolic filling of the right ventricle earlier than that of the left ventricle, and right ventricular diastolic mechanical delay (RVMDd) was defined as the right ventricular diastolic filling later than left ventricular filling. RESULTS: Among 152 patients with STEMI, 100 (65.8%) had LVMDd, and 47 (30.9%) had RVMDd. In-hospital complications were significantly increased in patients with RVMDd (61.6% vs. 41.0%, P = 0.017). Those with RVMDd exhibited significantly lower left ventricular global longitudinal strain (11.7 ± 4.1% vs. 13.2 ± 4.0%, P = 0.035), global work index (913.8 ± 365.9 vs. 1098.9 ± 358.8 mmHg%, P = 0.005) and global constructive work (1218.6 ± 392.8 vs. 1393.7 ± 432.7 mmHg%, P = 0.021). Mitral deceleration time significantly decreased (127.4 ± 33.5 vs. 145.6 ± 41.7 ms, P = 0.012), and the ratio of early mitral inflow to early mitral annular velocity (E/E') significantly increased [13.0(11.0-20.0) vs. 11.9(9.3-14.3), P = 0.006] in the RVMDd group. Logistic regression analysis showed that age (odds ratio [OR]:0.920; P = 0.001), brain natriuretic peptide level (OR: 1.1002; P = 0.036) and mitral E/E' (OR: 1.187; P = 0.003) were independently associated with RVMDd. CONCLUSIONS: Delayed right ventricular filling is related to more severe left ventricular systolic and diastolic dysfunction in STEMI patients. More attention should be paid to patients with RVMDd to prevent adverse events during hospitalization.