Figure 4 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Calibrated integrated backscatter (IBS) of the basal anteroseptal and basal posterior walls in each group: controls, mutation carriers without phenotype expression (Mut+/Phen−) and mutation carriers with phenotype expression (Mut+/Phen+). Structural alterations of the basal anteroseptum are the greatest in the Mut+/Phen+ group, followed by Mut+/Phen− group and by controls. Similarly, structural alterations of the basal posterior wall are the greatest in the Mut+/Phen+ group, but are similar between the Mut+/Phen− group and controls.
Source publication
To evaluate the presence of myocardial structural alterations and subtle myocardial dysfunction during familial screening in asymptomatic mutation carriers without hypertrophic cardiomyopathy (HCM) phenotype.
Sixteen HCM families with pathogenic mutation were studied and 46 patients with phenotype expression (Mut+/Phen+) and 47 patients without phe...
Similar publications
Background:
Early detection of subclinical left ventricular (LV) systolic dysfunction in hypertensive patients is important for the prevention of progression of hypertensive heart disease.
Methods:
We studied 60 hypertensive patients (age ranged from 21 to 49 years, the duration of hypertension ranged from 1 to 18 years) and 30 healthy controls,...
Background
Our study aimed to demonstrate the short-term impacts of right ventricular apical pacing (RVAP) and right ventricular septal pacing (RVSP) on left ventricular (LV) regional longitudinal strain (RLS) and global longitudinal strain (GLS) in patients with preserved ejection fraction (EF). LV strain and functions may be altered by RVAP. RVSP...
Background
Global longitudinal strain (GLS) is a sensitive marker of myocardial dysfunction and atrial reservoir function. We sought to evaluate its value for predicting atrial fibrillation (AF) in the general population.Methods
Participants from the Copenhagen City Heart Study examined with echocardiography, including speckle tracking analyses, we...
Anomalous left coronary artery from the pulmonary artery (ALCAPA) is a reversible cause of left ventricular (LV) dysfunction in infants. The LV function is expected to improve serially and return to normal by 1 year after surgical repair. The pattern of improvement in LV function has not been serially analyzed after ALCAPA repair. We report our pre...
Background: Mitral regurgitation (MR) is a common heart valve disease, causing many serious complications in several organ systems, especially the cardiovascular system. The 2D speckle tracking echocardiography (STE) is a new technique for detecting potential cardiac dysfunction when only tissue function abnormalities are present. The study aimed t...
Citations
... Echocardiographic findings include normal WT/borderline hypertrophy (12-14 mm), mitral valve leaflet elongation, myocardial crypts and myocardial apical trabeculations (the latter are better seen at cardiac magnetic resonance, CMR), while the LA is usually normal or only mildly dilated [19,40]. TDI-derived myocardial velocities and 2D strain analysis can be useful since even patients with normal WT can have reduced myocardial velocities and mild segmental longitudinal dysfunction [42]. Moreover, exercise echocardiography can be performed to look for exercise-induced intraventricular gradients due to SAM, an additional finding suggestive of HCM [39]. ...
Hypertrophic cardiomyopathy (HCM) is the most frequent cardiac disease with genetic substrate, affecting about 0.2–0.5% of the population. While most of the patients with HCM have a relatively good prognosis, some are at increased risk of adverse events. Identifying such patients at risk is important for optimal treatment and follow-up. While clinical and electrocardiographic information plays an important role, echocardiography remains the cornerstone in assessing patients with HCM. In this review, we discuss the role of echocardiography in diagnosing HCM, the key features that differentiate HCM from other diseases and the use of echocardiography for risk stratification in this setting (risk of sudden cardiac death, heart failure, atrial fibrillation and stroke). The use of modern echocardiographic techniques (deformation imaging, 3D echocardiography) refines the diagnosis and prognostic assessment of patients with HCM. The echocardiographic data need to be integrated with clinical data and other information, including cardiac magnetic resonance, especially in challenging cases or when there is incomplete information, for the optimal management of these patients.
... We observed that regional longitudinal strain, but not global longitudinal strain, was significantly reduced at an early stage of HCM, before the development of left ventricular hypertrophy. This finding is consistent with previous reports (22)(23)(24), but not with another ! 12 one (25). ...
... In our study, we were also able to define a cut-off for early strain abnormalities and we have deliberately chosen to set the criteria with an optimal specificity and PPV since this could be more useful for clinical applications. Only one study previously proposed a threshold for segmental strain abnormality at the preclinical stage (24), and there was no validation cohort. In this study by Yiu et al., the segment of interest was also the basal anteroseptal segment, and the threshold was associated with high sensitivity but limited specificity (24). ...
... Only one study previously proposed a threshold for segmental strain abnormality at the preclinical stage (24), and there was no validation cohort. In this study by Yiu et al., the segment of interest was also the basal anteroseptal segment, and the threshold was associated with high sensitivity but limited specificity (24). In the present study, we identified two new criteria (absolute basal anteroseptal strain value and ratio between basal inferoseptal and basal anterolateral (BIS/BAL) strain) to detect mutation ! 13 carriers at the preclinical stage with excellent specificity and the diagnostic accuracy was confirmed in a validation cohort. ...
Aims:
Hypertrophic cardiomyopathy (HCM) is a genetic disease with delayed cardiac expression. Our objective was to characterize left ventricular (LV) myocardial strain by two-dimensional echocardiography in sarcomeric mutation carriers before the hypertrophic stage.
Methods and results:
We studied 140 adults [derivation cohort (n = 79), validation cohort (n = 61)]. The derivation cohort comprised 38 confirmed HCM patients with hypertrophy (LVH+/Gen+), 20 mutation carriers without LV hypertrophy (LVH-/Gen+), and 21 healthy controls. LV global longitudinal strain was not different in LVH-/Gen+ compared with controls [20.6%, interquartile (IQ): 18.3/24.2 vs. 22.9%, IQ: 20.9/26.8] but was reduced in LVH+/Gen+ patients (14.1%, IQ: 11.8/18.5, P < 0.001). Regional peak longitudinal strain was significantly decreased in LVH-/Gen+ when compared with controls in four segments: basal anteroseptal (BAS) wall (P = 0.018), basal inferoseptal wall (P = 0.047), basal inferior wall (P = 0.006), and mid anteroseptal wall (P = 0.022). Receiver operating characteristic analysis identified that BAS strain <16.5% had a sensitivity (Se), specificity (Sp), positive and negative predictive values (PPV, NPV) of 57%, 90%, 82%, and 67%, respectively, to differentiate LVH-/G+ patients from controls. Similarly, the accuracy of a ratio between basal inferoseptal/basal anterolateral (BIS/BAL) strain <0.76 was 73%, 92%, 82%, and 64%, respectively (Se/Sp/PPV/NPV). In the validation cohort, the accuracy of BAS and BIS/BAL was 39%/93%/87%/57% and 55%/96%/95%/64% (Se/Sp/PPV/NPV), respectively, to differentiate the LVH-/Gen+ group from controls.
Conclusion:
Regional longitudinal strain, but not global strain, was significantly reduced at the early stage of HCM before LV hypertrophy. This suggests that the inclusion of strain (BAS < 16.5%; BIS/BAL < 0.76) in the evaluation of HCM relatives would help identify mutation carriers and early LV abnormalities.
... When we analyzed separately the basal Previous studies showed impairment of radial strain in HCM patients compared to controls [10][11][12][13], while none of these presented data on mutation carriers. In this latter group only five focused previous studies were published [9,[18][19][20][21]. Among these, all found similar values between mutation carriers and controls in the global longitudinal strain while four of them found regional longitudinal strain impairment. ...
... Among these, all found similar values between mutation carriers and controls in the global longitudinal strain while four of them found regional longitudinal strain impairment. These latter four studies found alterations in different segments but principally in the basal segment of the septum [9, [18][19][20]. ...
Treatment of overt form of hypertrophic cardiomyopathy (HCM) is often unsuccessful. Efforts are focused on a possible early identification in order to prevent or delaying the development of hypertrophy. Our aim was to find an echocardiographic marker able to distinguish mutation carriers without left ventricular hypertrophy (LVH) from healthy subjects. We evaluated 28 patients, members of eight families. Three types of mutation were recognized: MYBPC3 (five families), MYH7 (two families) and TNNT2 (one family). According to genetic (G) and phenotypic (Ph) features, patients were divided in three groups: Group A (10 patients), mutation carriers with LVH (G+/Ph+); Group B (9 patients), mutation carriers without LVH (G+/Ph−); Group C (9 patients), healthy subjects (G−/Ph−). Echocardiography examination was performed acquiring standard 2D, DTI and 2D-strain imaging. Global longitudinal strain (GLS) and global radial strain (GRS) at basal and mid-level were measured. GRS was significantly different between group B and C at basal level (32.18% ± 9.6 vs. 44.59% ± 12.67 respectively; p-value < 0.0001). In basal posterior and basal inferior segments this difference was particularly evident. ROC curves showed for both the involved segments good AUCs (0.931 and 0.861 for basal posterior and inferior GRS respectively) with the best predictive cut-off for basal posterior GRS at 43.65%, while it was 38.4% for basal inferior GRS. Conversely, GLS values were similar in the three group. 2D longitudinal strain is a valid technique to study HCM. Radial strain and particularly basal posterior and inferior segmental reduction could be able to identify mutation carriers in a pre-clinical phase of disease.
... We further quantified the degree of disarray by image analysis of the H&E nuclear orientation and MTR fiber orientation. Significantly different alignment indexes were observed between the mutant and WT native tissue for both the nuclear alignment (p ¼ 0.0001) and the fiber alignment (p < 0.0001); furthermore, the effect was similar for both (0.32 and 0.50, respectively), indicating a tight coupling between nuclear and fiber alignment in native cardiac tissue (18).We quantified the degree of interstitial fibrosis and found significantly different fibrosis fraction between mutant and WT native tissues in both the MTR (p < 0.0001) and SR (p < 0.0001) stains (Figure 2) with a very similar average fibrosis fraction (13%) via both staining methods, indicative of moderate fibrosis(19).No overt cardiac hypertrophy was observed in these tissues; however, the occurrence of tissue remodeling and concomitant cardiac dysfunction before the development of myocardial hypertrophy and increased left ventricular wall thickness is consistent with both a previous study in this large animal model(10) and in human studies(9,(20)(21)(22)(23)(24)(25). We hypothesized that the moderate interstitial fibrosis and modestfiber disarray discerned through histological analysis of the mutant tissues would result in alterations of the passive properties of the mutant myocardium. ...
Hypertrophic cardiomyopathy (HCM) is often caused by single sarcomeric gene mutations that affect muscle contraction. Pharmacological correction of mutation effects prevents but does not reverse disease in mouse models. Suspecting that diseased extracellular matrix is to blame, we obtained myocardium from a miniature swine model of HCM, decellularized thin slices of the tissue, and re-seeded them with healthy human induced pluripotent stem cell-derived cardiomyocytes. Compared with cardiomyocytes grown on healthy extracellular matrix, those grown on the diseased matrix exhibited prolonged contractions and poor relaxation. This outcome suggests that extracellular matrix abnormalities must be addressed in therapies targeting established HCM.
... As shown in Fig. 1, the link(s) between the biophysical insult (trigger) and the initial compensatory response are proximal and thus both likely represent important therapeutic targets before the onset of Birreversible^cascades of pathogenic remodeling. This molecular compensatory phase correlates to patients with Bpreclinical disease^who are defined as carrying a pathogenic gene mutation (phenotype) yet remain in the preclinical state (phenotype) or G(+) P (-) [35,47,92]. Given the early stage of remodeling, these patients have the greatest potential benefit from novel therapeutic interventions. ...
The classic clinical definition of hypertrophic cardiomyopathy (HCM) as originally described by Teare is deceptively simple, “left ventricular hypertrophy in the absence of any identifiable cause.” Longitudinal studies, however, including a seminal study performed by Frank and Braunwald in 1968, clearly described the disorder much as we know it today, a complex, progressive, and highly variable cardiomyopathy affecting ~ 1/500 individuals worldwide. Subsequent genetic linkage studies in the early 1990s identified mutations in virtually all of the protein components of the cardiac sarcomere as the primary molecular cause of HCM. In addition, a substantial proportion of inherited dilated cardiomyopathy (DCM) has also been linked to sarcomeric protein mutations. Despite our deep understanding of the overall function of the sarcomere as the primary driver of cardiac contractility, the ability to use genotype in patient management remains elusive. A persistent challenge in the field from both the biophysical and clinical standpoints is how to rigorously link high-resolution protein dynamics and mechanics to the long-term cardiovascular remodeling process that characterizes these complex disorders. In this review, we will explore the depth of the problem from both the standpoint of a multi-subunit, highly conserved and dynamic “machine” to the resultant clinical and structural human phenotype with an emphasis on new, integrative approaches that can be widely applied to identify both novel disease mechanisms and new therapeutic targets for these primary biophysical disorders of the cardiac sarcomere.
... Pri bolnikih s hipertrofično kardiomiopatijo (HCM) in ohranjenim EF v zgodnji fazi bolezni okvaro miokarda dokažemo z znižanim GLS (39), dodatno pa so v hipertrofičnih segmentih znižane tudi sistolične vrednosti longitudinalne deformacije (Slika 5B) (40). Znižane vrednosti longitudinalne deformacije opisujejo tudi pri bolnikih s pozitivno mutacijo gena za HCM, ki pa klinično še nimajo izražene hipertrofije (41). V zadnjih evropskih priporočilih za obravnavno bolnikov s HCM (42) je STI omenjena kot ena od metod za zgodnjo prepoznavo sistolične okvare pri tej skupini bolnikov. ...
Slikovna preiskava deformacije miokarda s sledenjem ultrazvočnega vzorca (ang. speckle tracking imaging-STI) je novejša metoda v ehokardiografiji, ki omogoča vpogled v mehaniko delovanja srčne mišice in se vse pogosteje uporablja pri vsakdanjem kliničnem delu. S to metodo se je uveljavil tudi nov globalni kazalec deformacije levega prekata v longitudinalni smeri (angl. global longitudinal strain-GLS), ki se je izkazal kot bolj občutljiv kazalec za odkrivanje zgodnje okvare miokarda kot klasični ehokardiografski kazalci sistolične funkcije. Kazalci deformacije imajo tako diagnostično kot prognostično vrednost pri številnih bolezenskih stanjih. Značilne spremembe, ki jih lahko zaznamo s STI pri ishemični bolezni srca so znižanje deformacije v sistoli, raztezanje miokarda v zgodnji sistoli in skrajšanje miokarda po koncu sistole. Metoda STI nam je v pomoč pri odkrivanju zgodnje okvare sistolične funkcije pri bolnikih s hipertrofijo miokarda in pri razlikovanju vzrokov hipertrofij. S STI lahko prepoznamo subklinično okvaro miokarda po kemoterapiji, zato ji dajejo evropska priporočila prednost pred klasičnimi ehokardiografskimi kazalci pri nadaljnjem kliničnem odločanju. Pri asimptomatičnih bolnikih z zmerno do hudo boleznijo srčnih zaklopk znižane vrednosti GLS kažejo na prikrito okvaro miokarda in napovedujejo večje tveganje za po-operativne zaplete. Pri bolnikih z miokarditisom s STI zaznamo znižane vrednosti segmentne deformacije in odražajo fokalno prizadetost levega prekata. Prav tako pa kazalniki deformacije miokarda tudi dobro napovedujejo uspešnost zdravljenja pri bolnikih z resinhronizacijskim spodbujevalnikom.
V prispevku želimo predstaviti osnove analizo GLS po posameznih korakih, ki veljajo ne glede na vrsto ultrazvočnega aparata ali programske opreme, ter predstaviti primere uporabe STI pri posameznih bolezenskih stanjih, za katere obstaja največ dokazov klinične uporabnosti.
... Several HCM cohort studies have shown that GLS is predictive of outcome [5][6][7]. Data regarding GLS in HCM gene mutation carriers without hypertrophic changes are limited [8][9][10][11]. Our aim was to assess GLS in mutation carriers and healthy controls and to determine its predictive value for the development of HCM during long-term followup. ...
... In patients with HCM, multiple strain imaging studies have demonstrated an impaired longitudinal systolic function while LVEF is normal [4,9,11,16,17]. In mutation carriers without hypertrophy, results are contradictory. Some tissue Doppler and strain imaging studies reported lower myocardial longitudinal velocities and deformation in mutation carriers [8,18,19] while other studies observed no difference [9-11, 20, 21]. ...
... However, the clinical relevance of this difference is not sufficient in order to use GLS as a discriminating parameter, because the difference was small (~1%) and there was a large overlap of the measurements. Similar to the conclusion of Yiu et al. [9], this suggests that the assessment of GLS is not helpful for the identification of mutation carriers when genetic testing is not available. ...
Background
Previous studies have reported that global longitudinal strain (GLS) is reduced in patients with hypertrophic cardiomyopathy (HCM) while left ventricular ejection fraction (LVEF) is normal. Our aim was to assess GLS in individuals with HCM mutations without hypertrophic changes and to determine its prognostic value for the development of HCM.
Methods and results
This retrospective case-control and cohort study included 120 HCM mutation carriers and 110 controls. GLS and LVEF were assessed with Tomtec Imaging software. Age, gender, and body surface area were similar in mutation carriers and controls. Compared to controls, mutation carriers had a higher maximal wall thickness (9 ± 2 vs 8 ± 2 mm, p < 0.001), higher LVEF (60 ± 5 vs 58 ± 4%, p < 0.001) and higher GLS (−21.4 ± 2.3% vs −20.3 ± 2.2%, p < 0.001). The GLS difference was observed in the mid-left ventricle (−21.5 ± 2.5% vs −19.9 ± 2.5%, p < 0.001) and the apex (−24.1 ± 3.5% vs −22.1 ± 3.4%, p < 0.001), but not in the base of the left ventricle (−20.0 ± 3.3% vs −20.0 ± 2.6%, p = 0.9). Echocardiographic follow-up was performed in 80 mutation carriers. During 5.6 ± 2.9 years’ follow-up, 13 (16%) mutation carriers developed HCM. Cox regression analysis showed age (hazard ratio (HR) 1.08, p = 0.01), pathological Q wave (HR 8.56; p = 0.01), and maximal wall thickness (HR 1.94; p = 0.01) to be independent predictors of the development of HCM. GLS was not predictive of the development of HCM (HR 0.78, p = 0.07).
Conclusion
GLS is increased in HCM mutation carriers without hypertrophic changes. GLS was of no clear prognostic value for the development of HCM during follow-up, in contrast to age, pathological Q waves and maximal wall thickness.
... In this study, we also noted a significant negative correlation between ECV and segmental systolic and diastolic function as assessed by circumferential strain and early and late diastolic strain rate. While the negative correlation is significant, the overall association is rather weak, likely due to intrinsic myocardial abnormalities which have been observed in animal models and in patients with HCM [36][37][38][39][40][41]. We view these correlations as providing insights into factors that affect cardiac function in HCM. ...
We sought to determine the relation between myocardial extracellular volume (ECV), left ventricular (LV) diastolic function, and exercise tolerance in patients with hypertrophic cardiomyopathy (HCM). Forty five HCM patients with an ejection fraction >50% and no previous septal reduction therapy underwent imaging by CMR and transthoracic echocardiography. CMR was used to quantify LV volumes, mass, EF, LA volumes, scar burden, pre and post contrast T1 relaxation times and ECV. Echocardiography was used to measure outflow tract gradients, mitral inflow and annular velocities, circumferential strain, systolic, early and late diastolic strain rates. Exercise duration and peak oxygen consumption were noted. HCM patients had increased native T1 relaxation time and ECV vs. controls [ECV controls: 24.7 (23.2–26.4) vs. HCM: 26.8 (24.6–31.3)%, P = 0.014]. Both parameters were significantly associated with LV diastolic dysfunction, circumferential strain, diastolic strain rate and peak oxygen consumption (r = −0.73, P < 0.001). Compared to controls, HCM patients have significantly longer native T1 relaxation time and higher ECV. These structural changes lead to worse LV global and segmental diastolic function and in turn reduced exercise tolerance.
... The 12 included studies for meta-analysis [16][17][18][19][24][25][26][27][28][29][30][31][32][33] covered years 2001 to 2015, regions including America, Europe and Asia, and mean age from 9.8 to 55.0. The G1/LVH2 and control groups contained 302 and 349 subjects, respectively. ...
Objectives:
To evaluate whether diastolic dysfunction derived by tissue Doppler imaging (TDI) would be an earlier manifestation in genotype-positive hypertrophic cardiomyopathy (HCM) subjects without left ventricular hypertrophy (LVH).
Methods:
We systematically searched Pubmed, Medline, and Web of Science with an upper date limit of June 2016 for studies evaluating the diastolic function of HCM genotype-positive subjects without hypertrophy (G+/LVH-). Based on the inclusion criteria, eligible studies were selected. The quality of selected studies was assessed by the Newcastle-Ottawa Scale before being included in the meta-analysis. The statistic data such as weighted mean difference (WMD) and 95% confidence interval (CI) were calculated by Stata 12.0 software.
Results:
Seventeen studies were included in the systematic review, and 12 were finally involved in the meta-analysis. The G+/LVH- subjects showed decreased Ea derived by TDI on both the interventricular septum (WMD [95% CI] = -1.822 [-3.104, -0.541]) and lateral wall (WMD [95% CI] = -2.269 [-3.820, -0.719]), and increased E/Ea on both interventricular septum (WMD [95% CI] = 1.363 [0.552, 2.174]) and lateral (WMD [95% CI] = 1.339 [0.386, 2.293]) wall.
Conclusions:
Tissue Doppler imaging-derived diastolic dysfunction can be found in HCM genotype-positive subjects without hypertrophy.
... The approach that concerns the textural analysis of echocardiographic images is recent [4,7]. Studies to differentiate sarcomeric HCM from amyloidosis on functional bases, such as 3D speckle tracking [8], septal strain [9], the «septal cyclic integrated backscatter (SCIB)» and septal entropy [10] did not prove to be conclusive. ...
Cardiac hypertrophy is a risk factor of cardiovascular mortality and is rou- tinely examined using ultrasound (US) imaging. This imaging modality does not allow the differentiation of the types of hypertrophy, such as the infiltrative caused by amyloidosis and the sarcomeric type resulting from hypertrophic cardiomyopathy. This leads to errors in this disease’s prognosis and treatment.
The myocardial tissue undergoes modifications specific to every disease ex- pressed in ultrasound by changes in texture difficult to be perceived by the naked eye. Our work is focused on the detection and quantification of speckle texture from the ultrasound image database of different types of cardiac hyper- trophy.
The images undergo texture characterization using Gabor filters of different orientations, sizes, and decomposition levels. The first and second-order statis- tical features are then determined from the resulting images. Next, Principal Component Analysis (PCA) is used for feature reduction followed by Linear Discriminant Analysis (LDA) for supervised clustering. This work gives good classification results differentiating the two main classes of cardiac hypertro- phy in addition to the three sub-classes of cardiac amyloidosis. This serves as a good basis for further studies of amyloidosis and its diagnosis in clinical practice.
We also performed rigid and local registrations of dynamic cardiac models with ultrasound patient-specific data. Such modeling complements our texture characterization approach in order to provide non-invasive clinical healthcare for the different stages of this pathology’s detection and treatment.
