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Experimental design and contractility data for cardiac muscle. Shown on the left is a schematic of a left ventricular trabecular muscle stretched between a stationary bottom hook and a top hook attached to a force transducer. The muscle is stimulated to contract by direct‐contact electrodes located behind the muscle. Shown on the right is a recording of a single cardiac muscle contraction. Resting tension (RT) is reflective of the muscle's innate stiffness. Developed tension (DT) is the amount of force generated by the muscle upon stimulation.
Source publication
Background
Hypertrophic cardiomyopathy (HCM) is a primary myopathic process in which regional left ventricular dysfunction may exist without overt global left ventricular dysfunction. In obstructive HCM patients who underwent surgical myectomy (SM), we sought to determine if there is a significant association between echocardiographic longitudinal...
Context in source publication
Context 1
... thin trabecular muscles were dissected from the LV surface of the septum. Isometric muscle contraction studies were performed as we have previously described at 37°C, stimulation rate 1.0 Hz, duration 5 ms, and voltage 20% above threshold 24,25 (Figure 2). When the muscle was initially mounted in the bath, it was mounted at a slack length, adjusted to a resting tension of %0.5 g. ...
Citations
... Multiple studies have noted a clear association between impaired regional strain and GLS with histopathological changes, myocardial fibrosis and myocardial performance in patients with HCM [37][38][39]. Additionally, there are studies suggesting LV-GLS maybe more sensitive than late gadolinium enhancement by CMR [40]. Although the majority of the studies showed that the presence of worse LV-GLS is associated with worse outcomes, a consensus regarding at what value of LV-GLS a clinician should be concerned has not been determined [41]. ...
... Multiple studies have noted a clear association between impaired regional strain and GLS with histopathological changes, myocardial fibrosis and myocardial performance in patients with HCM [37][38][39]. Additionally, there are studies suggesting LV-GLS maybe more sensitive than late gadolinium enhancement by CMR [40]. Although the majority of the studies showed that the presence of worse LV-GLS is associated with worse outcomes, a consensus regarding at what value of LV-GLS a clinician should be concerned has not been determined [41]. ...
Hypertrophic cardiomyopathy (HCM) is a relatively common inherited cardiomyopathy, which is occasionally challenging to differentiate from hypertensive heart disease and athletes heart on the basis of morphologic or functional abnormalities alone. Imaging studies provide solution for majority of clinical presentations. Generally, transthoracic echocardiography (TTE) is employed as a first line imaging tool and contrast enhanced echocardiography (CEE), contrast tuned imaging echocardiography (CTIE), cardiac magnetic resonance (CMR), cardiac computed tomography (CCT), cardiac nuclear imaging and speckle tracking echocardiography (STE) are encouraged for either suboptimal studies because of poor visualization of left ventricular (LV) cavity or for comprehensive delineation of the cardiac anatomy, its widespread left and right ventricular involvement, associations and complications. We are reporting a case of 48-year old male presenting to us with atypical chest pain and a history of suspicious solitary episode of syncope. His routine ECG was indicative of left ventricular hypertrophy with strain pattern, and his TTE was substandard and inadequate in the apical four chamber (4CH) and five chamber (5CH) views, hence CTIE was performed without the application of intravenous contrast agents, to produce a remarkable illustration of HCM. Keywords: Hypertrophic cardiomyopathy, contrast echocardiography, contrast tuned imaging, speckle tracking echocardiography, 4Dimensional XStrain, Non obstructive HCM
... In a comprehensive study of patients with HOCM undergoing surgical myectomy, the reduced longitudinal strain was found to correlate with disarray and fibrosis rather than with septal thickness [18]. We could not assess the association between fibrosis and the effect of disopyramide as only one patient underwent a cardiac magnetic resonance (CMR) study to assess fibrosis. ...
Background:
Disopyramide is a class Ia antiarrhythmic drug that has been used for the second-line treatment of symptomatic hypertrophic obstructive cardiomyopathy (HOCM). The aim of the study was to assess the impact of short-acting disopyramide in patients with hypertrophic obstructive cardiomyopathy (HOCM) using two-dimensional speckle-tracking echocardiography.
Methods:
This prospective study included patients with HOCM on chronic treatment with short-acting disopyramide. Two sequential comprehensive echocardiographic examinations were performed: after temporary disopyramide suspension and 2.5 h after disopyramide intake.
Results:
19 patients were included in the study. The effect of disopyramide on the left ventricle was not uniform. After the intake of disopyramide, the mean global strain peak was -17 ± 2% before disopyramide intake and -14 ± 2% after (p < 0.0001). There was a significant reduction in strain in the basal septal (p = 0.015), basal inferior (p = 0.019), basal posterior (p = 0.05), apical anterior (p = 0.0001), and apical lateral segments (p = 0.021). In all other segments, there was no significant change. Disopyramide also caused a significant accentuation of the base-apex strain gradients (p = 0.036). No change was noted in circumferential and left atrial strain. While the left ventricular ejection fraction and outflow gradients did not change, the significant reduction in global and segmental longitudinal strain demonstrated the acute negative inotropic effect of disopyramide on the myocardium in patients with HOCM.
Conclusion:
A strain analysis may be a useful tool to assess the negative inotropic effect of cardiovascular medication on the left ventricle in patients with HOCM.
... Unlike CMRI, which defines tissue characteristics through direct observation of the changes in the acquired myocardial tissue images [65], 2D-STE analysis should be considered only indirectly as related to MF, by assessing the impact of the underlying pathology on tissue function [66]. A number of histological and pathophysiological changes affecting the extracellular matrix may impact myocardial mechanics by increasing myocardial stiffness [67][68][69][70]. These changes in cardiomyocyte mechanics are reflected as global or regional impairment in deformation parameters assessed by 2D-STE analysis [71][72][73]. ...
The pathological remodeling of myocardial tissue is the main cause of heart diseases. Several processes are involved in the onset of heart failure, and the comprehension of the mechanisms underlying the pathological phenotype deserves special attention to find novel procedures to identify the site of injury and develop novel strategies, as well as molecular druggable pathways, to counteract the high degree of morbidity associated with it. Myocardial fibrosis (MF) is recognized as a critical trigger for disruption of heart functionality due to the excessive accumulation of extracellular matrix proteins, in response to an injury. Its diagnosis remains focalized on invasive techniques, such as endomyocardial biopsy (EMB), or may be noninvasively detected by cardiac magnetic resonance imaging (CMRI). The detection of MF by non-canonical markers remains a challenge in clinical practice. During the last two decades, two-dimensional (2D) speckle tracking echocardiography (STE) has emerged as a new non-invasive imaging modality, able to detect myocardial tissue abnormalities without specifying the causes of the underlying histopathological changes. In this review, we highlighted the clinical utility of 2D-STE deformation imaging for tissue characterization, and its main technical limitations and criticisms. Moreover, we focalized on the importance of coupling 2D-STE examination with the molecular approaches in the clinical decision-making processes, in particular when the 2D-STE does not reflect myocardial dysfunction directly. We also attempted to examine the roles of epigenetic markers of MF and hypothesized microRNA-based mechanisms aiming to understand how they match with the clinical utility of echocardiographic deformation imaging for tissue characterization and MF assessment.
... The restoration in lateral strains shown in our results indicated reversed regional myocardial function, even similar to controls. The lateral wall was the region with the least frequency of LV hypertrophy (23) and was less involved with myocyte disarray or fibrosis (24) that impaired myocardial performance (25,26); the sensitivity to the reduced load (21) and a compensatory effect followed by the septum dysfunction may contribute to the lateral wall restoration. The deterioration of septal CS that we observed was in accordance with previous studies (9,12). ...
Purpose:
To investigate myocardial remodeling using cardiac MRI (CMR) feature tracking (FT) and to explore the relationship between CMR parameters with outcomes in hypertrophic obstructive cardiomyopathy (HOCM) after myectomy.
Materials and methods:
In this single-center retrospective study, patients with HOCM undergoing myectomy between 2011 and 2019 were included. Pre- and postmyectomy global and regional strains were compared. Healthy participants were included for comparison. Composite events were recorded at follow-up performed after a minimum of 12 months. The paired-samples t test was utilized to compare pre- and postmyectomy variables.
Results:
A total of 73 patients (44 years ± 14 [SD]; 45 men) were evaluated. Compared with preoperative parameters, global circumferential strain (CS) (-17.6% ± 4.4 vs -16.7% ± 3.9, P = .02) was impaired, but global longitudinal strain (LS) was improved (-9.3% ± 2.8 vs -10.8% ± 3.3, P < .001). Septal CS (-14.2% ± 4.0 vs -11.0% ± 4.4, P < .001) and septal radial strain (RS) (16.4% ± 10.6 vs 13.7% ± 9.5, P = .007) worsened, while septal LS (-8.1% ± 3.5 vs -10.2% ± 3.4, P < .001), lateral RS (40.1% ± 16.6 vs 54.4% ± 22.6, P < .001), lateral CS (-20.2% ± 4.1 vs -23.1% ± 4.8, P < .001), and lateral LS (-5.6% ± 5.6 vs -8.4% ± 5.2, P = .001) were improved. Sixteen of 73 patients (22%) experienced composite events after median follow-up of 39.1 months. Postoperative global CS provided the highest discrimination for composite event occurrence (area under the receiver operating characteristic curve, 0.73; 95% CI: 0.61, 0.83) with a cutoff of -16.7%. Patients with postoperative global CS greater than -16.7% had reduced event-free survival compared with those with postoperative global CS less than or equal to -16.7% (log-rank P = .002).
Conclusion:
CMR-FT analysis demonstrated longitudinal and lateral restorations, but impaired global CS, after myectomy in patients with HOCM; furthermore, increased global CS was associated with poorer outcomes.Keywords: MR Imaging, Cardiac, Outcomes Analysis, Comparative Studies, Surgery© RSNA, 2022 Supplemental material is available for this article.
... A transgenic HCM mouse model demonstrated decreased sarcomere length and impaired systolic shortening in regions of myocardial hypertrophy (23). In human hearts noninvasive imaging, histology, and in vitro experiments suggested an association between disarray, fibrosis, active contraction in vitro, and STE-derived deformation in vivo (24,25). Similarly, diffusion tensor CMR and CMR-derived strain rate imaging inferred intramural disarray correlated with both active and passive myocardial function (26). ...
... All imaged tissue samples were derived from surgical myectomy; therefore, the sample size was limited and potentially not representative of the heart as a whole. However, septal tissue has consistently demonstrated structural abnormalities in prior studies (22,24,25,52). ...
Background: Distinguishing the etiology of left ventricular hypertrophy (LVH) is clinically relevant due to patient outcomes and management. Easily obtained, echocardiography-based myocardial deformation patterns may improve standard non-invasive phenotyping, however, the relationship between deformation phenotypes and etiology-related, microstructural cardiac remodeling has not been reported. Synchrotron radiation-based X-ray phase-contrast imaging (X-PCI) can provide high resolution, three-dimensional (3D) information on myocardial microstructure. The aim of this pilot study is to apply a multiscale, multimodality protocol in LVH patients undergoing septal myectomy to visualize in vivo and ex vivo myocardial tissue and relate non-invasive LVH imaging phenotypes to the underlying synchrotron-assessed microstructure.
Methods and findings: Three patients (P1-3) undergoing septal myectomy were comprehensively studied. Medical history was collected, and patients were imaged with echocardiography/cardiac magnetic resonance prior to the procedure. Myocardial tissue samples obtained during the myectomy were imaged with X-PCI generating high spatial resolution images (0.65 μm) to assess myocyte organization, 3D connective tissue distribution and vasculature remodeling. Etiology-centered non-invasive imaging phenotypes, based on findings of hypertrophy and late gadolinium enhancement (LGE) distribution, and enriched by speckle-tracking and tissue Doppler echocardiography deformation patterns, identified a clear phenotype of hypertensive heart disease (HTN) in P1, and hypertrophic cardiomyopathy (HCM) in P2/P3. X-PCI showed extensive interstitial fibrosis with normal 3D myocyte and collagen organization in P1. In comparison, in P2/P3, X-PCI showed 3D myocyte and collagen disarray, as well as arterial wall hypertrophy with increased perivascular collagen, compatible with sarcomere-mutation HCM in both patients. The results of this pilot study suggest the association of non-invasive deformation phenotypes with etiology-related myocyte and connective tissue matrix disorganization. A larger patient cohort could enable statistical analysis of group characteristics and the assessment of deformation pattern reproducibility.
Conclusion: High-resolution, 3D X-PCI provides novel ways to visualize myocardial remodeling in LVH, and illustrates the correspondence of macrostructural and functional non-invasive phenotypes with invasive microstructural phenotypes, suggesting the potential clinical utility of non-invasive myocardial deformation patterns in phenotyping LVH in everyday clinical practice.
... Previously, the role of the extracellular matrix (ECM) in myocardial contraction and stiffness has been highlighted [8,9], and changes in the ECM increase myocardial stiffness even after preventing myocyte hypertrophy in preclinical models [10]. On the cellular level, the changes affecting contractile and regulatory proteins have been shown to impact cardiomyocyte mechanics [11,12]. These changes in cardiomyocyte mechanics are reflected in the deformation parameters assessed by STE, which can detect and quantify the amount as well as the rate of deformation of myocardial segments and is linked to a particular pattern of change in the myocardial tissue [13][14][15]. ...
... The same group correlated STE deformation parameters with in vitro mechanics of isolated trabecular muscle in 122 HCM patients [12], and showed that resting tension (the tension measured when the muscle was mounted on the measurement instrument) and developed tension (the maximum tension developed after lengthening the muscle) were significantly correlated with longitudinal systolic strain and early diastolic SR. In multivariate analysis (which included degree of myocyte disarray and interstitial fibrosis), both systolic strain and early diastolic SR were independently associated with both Similarly, in a separate study of 46 HCM patients, longitudinal strain in the basal septum was modestly correlated with maximal tension developed by single cardiomyocytes isolated from resected septal myocardium [11]. ...
Myocardial pathology results in significant morbidity and mortality, whether due to primary cardiomyopathic processes or secondary to other conditions such as ischemic heart disease. Cardiac imaging techniques characterise the underlying tissue directly, by assessing a signal from the tissue itself, or indirectly, by inferring tissue characteristics from global or regional function. Cardiac magnetic resonance imaging is currently the most investigated imaging modality for tissue characterisation, but, due to its accessibility, advanced echocardiography represents an attractive alternative. Speckle tracking echocardiography (STE) is a reproducible technique used to assess myocardial deformation at both segmental and global levels. Since distinct myocardial pathologies affect deformation differently, information about the underlying tissue can be inferred by STE. In this review, the current available studies correlating STE deformation parameters with underlying tissue characteristics in humans are examined, with separate emphasis on global and segmental analysis. The current knowledge is placed in the context of integrated backscatter and the future of echocardiographic based tissue characterisation is discussed. The use of these imaging techniques to more precisely phenotype myocardial pathology more precisely will allow the design of translational cardiac research studies and, potentially, tailored management strategies.
... Septal and lateral EDWT were higher than controls ( Table 5, p < 0.001). Septal wall thickening and septal circumferential strain were significantly reduced compared with controls ( [9,33] vs. 36 [26,39] % s −1 , p = 0.02, resp.). Lateral systolic and diastolic strain rate were comparable to controls (Table 5). ...
... In our HOCM population scar is not responsible for the functional deterioration after myectomy. This implies that other mechanisms may be responsible for this loss in function, such as loss of myocyte integrity or progression of myocyte disarray [33]. ...
Surgical therapies in aortic valve stenosis (AVS) and hypertrophic obstructive cardiomyopathy (HOCM) aim to relief intraventricular pressure overload and improve clinical outcome. It is currently unknown to what extent myocardial adaptation concurs with restoration of intraventricular pressures, and whether this is similar in both patient groups. The aim of this study was to investigate changes in myocardial adaptation after surgical therapies for AVS and HOCM. Ten AVS and ten HOCM patients were enrolled and underwent cardiac magnetic resonance cine imaging and myocardial tagging prior to, and 4 months after aortic valve replacement (AVR) and septal myectomy, respectively. Global left ventricular (LV) analyses were derived from cine images. Circumferential strain was assessed from myocardial tagging images at the septal and lateral wall of the mid ventricle. Pressure gradients significantly decreased in both AVS and HOCM after surgery (p < 0.01), with a concomitant decrease in left atrial volume (p < 0.05) suggesting lower diastolic filling pressures. Also, LV volumes, mass and septal wall thickness decreased in both, but to a larger extent in AVS than in HOCM patients. AVR improved wall thickening (p < 0.05) and did not change systolic strain rate. Myectomy did not affect wall thickening and reduced septal systolic strain rate (p = 0.03). Both AVR and myectomy induced positive structural remodeling in line with a reduction of pressure overload. A concomitant recovery in systolic function however was found in AVR only. The systolic functional deterioration in HOCM patients seems to be inherent to myectomy and the ongoing and irreversible disease.
... In fact, the association between FWRVLS and central venous pressure has already been reported in these patients [14]. Also, RVLS evaluates longitudinal myocardial tissue, which accounts for 80% of RV stroke volume [6], and longitudinal strain is associated with myocardial contractile performance and worse RV systolic dysfunction in patients with RV MI affecting the proximal right coronary artery [15,16]. In the same way, RVLS has been shown to be a predictor of adverse cardiovascular outcomes in patients with reduced and preserved LVEF in the long term [12]. ...
Right ventricular (RV) systolic dysfunction due to acute myocardial infarction is associated with serious complications in the short-term. Acute kidney injury (AKI) is a frequent and unrecognized complication. This study aimed to assess whether RV longitudinal strain predicts AKI and short-term prognosis in patients with RV infarction. Prospective cohort of patients with RV infarction. RV function was evaluated with global and free wall right ventricular longitudinal strain (GRVLS and FWRVLS), tricuspid annular plane systolic excursion, and tricuspid S′ wave. The primary endpoint was AKI defined as an increase ≥ 50% in serum creatinine and/or a decrease ≥ 25% in glomerular filtration rate during follow-up at 7 days. The secondary endpoint was death from any cause at 30 days. We included 101 patients with RV infarction (male 67%, age 66 ± 11 years). During follow-up at 7 days, 40% of patients developed AKI. At 30 days, 8% of patients died. At univariate analysis, FWRVLS was significantly associated with AKI (Hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.03–1.20, p = 0.006). At multivariate analysis, only age, temporary pacemaker implant, and FWRVLS remained as independent predictors of AKI (HR 1.05, 95% CI 1.02–1.08, p = 0.002; HR 2.12, 95% CI 1.11–4.07, p = 0.023; HR 1.10, 95% CI 1.02–1.19, p = 0.018, respectively). At 30 days, patients with FWRVLS ≥ − 15.5% showed a lower survival rate than those with lower strain (84 ± 6 vs. 97 ± 2%, p = 0.021). In patients with RV infarction, FWRVLS was an independent predictor of AKI and was associated with higher mortality in the short-term.
... 13 In HCM, LV-GLS is associated with histopathological changes, in vitro myocardial performance, and myocardial fibrosis. [14][15][16] Although it is intuitive to think that LV-GLS could potentially offer incremental utility in HCM patients, prognostic data regarding the role of LV-GLS in HCM patients are limited. [17][18][19][20][21][22] We sought to study whether LV-GLS provides incremental prognostic utility for long-term events in patients with obstructive HCM. ...
... LV-GLS was analyzed offline using Velocity Vector Imaging (VVI; Siemens Medical Solutions, Mountain View, CA). 14,16,24 All raw data were stored in DICOM format without compression. The frame rate was ≥30 frames/sec. ...
... 14 In another proof-of-concept study, we demonstrated a significant association between basal septal strain rate and in vitro myocardial performance (resting tension and developed tension) of the same segment removed during myectomy. 16 It appears that myocyte disarray, a hallmark of HCM histopathology, may predispose to worsening regional LV mechanics, preceding overt LV systolic dysfunction. Indeed past similar efforts in transgenic mice have demonstrated an association between myocardial fibrosis, strain, and actual myocardial performance. ...
Background
In obstructive hypertrophic cardiomyopathy patients with preserved left ventricular (LV) ejection fraction, we sought to determine whether LV global longitudinal strain (LV‐GLS) provided incremental prognostic utility.
Methods and Results
We studied 1019 patients with documented hypertrophic cardiomyopathy (mean age, 50±12 years; 63% men) evaluated at our center between 2001 and 2011. We excluded age <18 years, maximal LV outflow tract gradient <30 mm Hg, bundle branch block or atrial fibrillation, past pacemaker/cardiac surgery, including myectomy/alcohol ablation, and obstructive coronary artery disease. Average resting LV‐GLS was measured offline on 2‐, 3‐, 4‐chamber views using Velocity Vector Imaging (Siemens, Malvern, PA). Outcome was a composite of cardiac death and appropriate internal defibrillator (implantable cardioverter defibrillator) discharge. Maximal LV thickness, LV ejection fraction, indexed left atrial dimension, rest and maximal LV outflow tract gradient, and LV‐GLS were 2.0±0.2 cm, 62±4%, 2.2±4 cm/m², 52±42 mm Hg, 103±36 mm Hg, and −13.6±4%. During 9.4±3 years of follow‐up, 668 (66%), 166 (16%), and 122 (20%), respectively, had myectomy, atrial fibrillation, and implantable cardioverter defibrillator implantation, whereas 69 (7%) had composite events (62 cardiac deaths). Multivariable competing risk regression analysis revealed that higher age (subhazard ratio, 1.04 [1.02–1.07]), AF during follow‐up (subhazard ratio, 1.39 [1.11–1.69]), and worsening LV‐GLS (subhazard ratio, 1.11 [1.05–1.22]) were associated with worse outcomes, whereas myectomy (subhazard ratio, 0.44 [0.25–0.72]) was associated with improved outcomes (all P<0.01). Sixty‐one percent of events occurred in patients with LV‐GLS worse than median (−13.7%).
Conclusions
In obstructive hypertrophic cardiomyopathy patients with preserved LV ejection fraction, abnormal LV‐GLS was independently associated with higher events, whereas myectomy was associated with improved outcomes.
