Maja Cikes

Velocity and deformation imaging for the assessment of myocardial dysfunction

Recent developments in echocardiographic imaging technology and processing enabled the quantification of myocardial motion and deformation in a clinical setting. Echocardiographic strain (-rate) imaging provides a relatively easy way to study myocardial deformation. However, although (local) deformation is clearly linked to cardiac (dys-) function, it is important to understand how this information can be used in clinical practice and how specific deformation patterns should be interpreted. This review paper first discusses which issues are important to address when assessing cardiac function and how (regional) deformation and myocardial contractility are related. The use and interpretation of deformation profiles is further illustrated for some typical cardiac pathologies. The observed deformation patterns are discussed in light of the changes in regional contractility (ischemia), timing of contractile force development (LBBB and heart failure), pressure/volume overload, and assessing diastolic function.

Effect of Combined Systolic and Diastolic Functional Parameter Assessment for Differentiation of Cardiac Amyloidosis From Other Causes of Concentric Left Ventricular Hypertrophy

Background—Differentiation of cardiac amyloidosis (CA) from other causes of concentric left ventricular hypertrophy remains a clinical challenge, especially in patients with preserved ejection fraction at the early disease stages. Methods and Results—Consecutive hypertrophic patients with CA, isolated arterial hypertension, Fabry disease, and Friedreich ataxia (n=25 per group) were investigated; 25 healthy volunteers served as a control group. Standard echocardiography was performed, and segmental longitudinal peak systolic strain (LSsys) in the septum was assessed by 2-dimensional speckle tracking imaging. Indices of left ventricular hypertrophy and ejection fraction were similar among all patient groups. Deceleration time of early filling was significantly lower in patients with CA (147±46 milliseconds) compared with those with isolated arterial hypertension, Fabry disease, or control subjects (all P<0.0125). Septal basal LSsys (−6±2%) was significantly lower in patients with CA compared with those with isolated arterial hypertension (−14±6%), Fabry disease (−12±5%), Friedreich ataxia (−16±2%), or control subjects (−17±3%; all P<0.001), whereas septal apical LSsys was similar among all patient groups and control subjects (all P>0.05). A data-driven cutoff value for the ratio of septal apical to basal LSsys ratio >2.1 differentiated CA from other causes of left ventricular hypertrophy (sensitivity, 88%; specificity, 85%; positive predictive value, 67%; negative predictive value, 96%). The prevalence of septal apical to basal LSsys ratio >2.1 plus deceleration time of early filling <200 milliseconds was 88% in CA but 0% in all other groups. Conclusions—A systolic septal longitudinal base-to-apex strain gradient (septal apical to basal LSsys ratio >2.1), combined with a shortened diastolic deceleration time of early filling (deceleration time of early filling <200 milliseconds), aids in differentiating CA from other causes of concentric left ventricular hypertrophy.

The role of echocardiographic deformation imaging in hypertrophic myopathies

Echocardiography has a leading role in the routine assessment and diagnosis of hypertrophic ventricles. However, the use of M-mode echocardiography and measurement of global left ventricular function may be misleading. Traditionally, systolic function was thought to be preserved in patients with hypertrophic myopathies until the late stages of the disease, and hypertrophic myopathies were thought to affect the myocardium more diffusely than ischemic heart disease. Ultrasound deformation imaging, either by Doppler myocardial imaging or speckle tracking, provides more-sensitive detection of regional myocardial motion and deformation than standard echocardiography. Basic and clinical studies that apply these techniques have revealed early, often subclinical impairment in systolic function. This information allows the detection and treatment of myocardial dysfunction at an early stage, which is of high clinical importance. Physiological hypertrophic remodeling seen in athletes differs from pathological myocardial hypertrophy, which can be caused by compensatory reactive hypertrophy owing to pressure overload in patients with aortic stenosis or hypertension, as well as amyloidosis, Fabry disease or Friedreich ataxia. Each of the etiologies associated with hypertrophy demonstrate distinct regional changes in myocardial deformation, which allows identification of the underlying processes, and will improve the assessment and follow-up of patients with hypertrophic myopathies.

Echocardiographic quantification of regional deformation helps to distinguish isolated left ventricular non‐compaction from dilated cardiomyopathy

Pronounced trabeculation is presented in both left ventricular non‐compaction (LVNC) and dilated cardiomyopathy (DCM), which sometimes makes the differentiation difficult. We hypothesized that echocardiographic deformation analysis would help to differentiate these two cardiomyopathies.

Atrial apoptosis and fibrosis adversely affect atrial conduit, reservoir and contractile functions †

OBJECTIVES Chronic atrial volume overload and atrial fibrillation (AF) induce structural changes within atrial myocardium. The aim of this study was to evaluate the effect of adverse cellular remodelling on echocardiographic strain rate (SR) deformation indices of atrial contractile, conduit and reservoir functions. METHODS Forty-four consecutive patients with organic mitral regurgitation were analysed. Twenty-eight patients had long-standing persistent AF (AF group), while 16 were in normal sinus rhythm (NSR group). Left atrial (LA) samples were harvested from all the patients for histological analysis. Postoperative echocardiographic data acquisition was performed exclusively during organized atrial electrical activity in order to assess the contractile reserve of patients from both groups. RESULTS Fibrotic atria had inferior conduit (SR-E: r = -0.36, P = 0.017), reservoir (SR-S: r = -0.31, P = 0.041) and contractile functions (SR-A: r = -0.33, P = 0.027). Analogously, atria with greater apoptotic burdens showed a negative correlation with multiple indices of left atrial functions (SR-E: r = -0.38, P = 0.010; SR-S: r = -0.33, P = 0.028; SR-A: r = -0.28, P = 0.067). The efficiency of atrial contractility was significantly reduced among AF-group patients after conversion to sinus rhythm, when compared with patients in the NSR group (LA active emptying fraction: 20 ± 12 vs 30 ± 10%, P = 0.004; SR-A: 1.1 ± 1.0 vs 2.8 ± 1.9 s(-1), P < 0.001). Superior strain-rate indices of atrial conduit and reservoir functions were noted in the NSR group (SR-E: 3.5 ± 2.3 vs 1.3 ± 1.0 s(-1), P < 0.001; LA expansion index: 86 ± 31 vs 60 ± 42%, P = 0.004). Fibrosis was evident in 7.2 [3.3;9.4]% of the LA tissue sample in the AF group, while it accounted for 3.4 [1.2;8.1]% of atrial tissue in the NSR group (P = 0.054). Apoptosis was documented in 13 (46%) patients in the AF group, whereas none of the patients in the NSR group exhibited signs of programmed cell death (P = 0.001). Myocyte degeneration was more prevalent in the AF group (odds ratio: 7.0, 95% confidence interval: 1.3-36.7, P = 0.021). Age showed a positive correlation with worsening degrees of atrial fibrosis and apoptosis (r = 0.41, P = 0.006; r = 0.49, P = 0.001, respectively). Multiple regression analysis identified SR-S (β = -1.263, P = 0.036) and age (β = 0.144, P = 0.057) as independent predictors of fibrosis. Independent determinants of apoptosis were preoperative AF (β = 4.539, P = 0.007), age (β = 0.188, P = 0.009) and SR-S (β = -1.780, P = 0.002). CONCLUSIONS Atria exhibiting greater fibrotic and apoptotic burdens had impaired conduit, reservoir and contractile function, as evaluated by deformation imaging. Among patients with chronic LA volume overload, exposure to long-standing persistent AF induced more pronounced degrees of adverse atrial cellular remodelling. Strain-rate descriptors of atrial reservoir function harboured potential to predict atrial fibrosis and apoptosis.

Impact of Regional Left Ventricular Function on Outcome for Patients with AL Amyloidosis

Objectives The aim of this study was to explore the left ventricular (LV) deformation changes and the potential impact of deformation on outcome in patients with proven light-chain (AL) amyloidosis and LV hypertrophy. Background Cardiac involvement in AL amyloidosis patients is associated with poor outcome. Detecting regional cardiac function by advanced non-invasive techniques might be favorable for predicting outcome. Methods LV longitudinal, circumferential and radial peak systolic strains (Ssys) were assessed by speckle tracking imaging (STI) in 44 biopsy-proven systemic AL amyloidosis patients with LV hypertrophy (CA) and in 30 normal controls. Patients were divided into compensated (n = 18) and decompensated (n = 26) group based on clinical assessment and followed-up for a median period of 345 days. Results Ejection fraction (EF) was preserved while longitudinal Ssys (LSsys) was significantly reduced in both compensated and decompensated groups. Survival was significantly reduced in decompensated group (35% vs. compensated 78%, P = 0.001). LSsys were similar in apical segments and significantly reduced in basal segments between two patient groups. LSsys at mid-segments were significantly reduced in all LV walls of decompensated group. Patients were further divided into 4 subgroups according to the presence or absence of reduced LSsys in no (normal), only basal (mild), basal and mid (intermediate) and all segments of the septum (severe). This staging revealed continuously worse prognosis in proportion to increasing number of segments with reduced LSsys (mortality: normal 14%, mild 27%, intermediate 67%, and severe 64%). Mid-septum LSsys<11% suggested a 4.8-fold mortality risk than mid-septum LSsys≥11%. Multivariate regression analysis showed NYHA class and mid-septum LSsys were independent predictors for survival. Conclusions Reduced deformation at mid-septum is associated with worse prognosis in systemic amyloidosis patients with LV hypertrophy.

Predictive Value of Assessing Diastolic Strain Rate on Survival in Cardiac Amyloidosis Patients with Preserved Ejection Fraction

Objectives Since diastolic abnormalities are typical findings of cardiac amyloidosis (CA), we hypothesized that speckle-tracking-imaging (STI) derived longitudinal early diastolic strain rate (LSRdias) could predict outcome in CA patients with preserved left ventricular ejection fraction (LVEF >50%). Background Diastolic abnormalities including altered early filling are typical findings and are related to outcome in CA patients. Reduced longitudinal systolic strain (LSsys) assessed by STI predicts increased mortality in CA patients. It remains unknown if LSRdias also related to outcome in these patients. Methods Conventional echocardiography and STI were performed in 41 CA patients with preserved LVEF (25 male; mean age 65±9 years). Global and segmental LSsys and LSRdias were obtained in six LV segments from apical 4-chamber views. Results Nineteen (46%) out of 41 CA patients died during a median of 16 months (quartiles 5–35 months) follow-up. Baseline mitral annular plane systolic excursion (MAPSE, 6±2 vs. 8±3 mm), global LSRdias and basal-septal LSRdias were significantly lower in non-survivors than in survivors (all p<0.05). NYHA class, number of non-cardiac organs involved, MAPSE, mid-septal LSsys, global LSRdias, basal-septal LSRdias and E/LSRdias were the univariable predictors of all-cause death. Multivariable analysis showed that number of non-cardiac organs involved (hazard ratio [HR]  = 1.96, 95% confidence interval [CI] 1.17–3.26, P = 0.010), global LSRdias (HR = 7.30, 95% CI 2.08–25.65, P = 0.002), and E/LSRdias (HR = 2.98, 95% CI 1.54–5.79, P = 0.001) remained independently predictive of increased mortality risk. The prognostic performance of global LSRdias was optimal at a cutoff value of 0.85 S−1 (sensitivity 68%, specificity 67%). Global LSRdias <0.85 S−1 predicted a 4-fold increased mortality in CA patients with preserved LVEF. Conclusions STI-derived early diastolic strain rate is a powerful independent predictor of survival in CA patients with preserved LVEF.

The shape of the aortic outflow velocity profile revisited: is there a relation between its asymmetry and ventricular function in coronary artery disease?

AIMS Myocardium contracts in the beginning of ejection causing outflow acceleration, resulting in asymmetric outflow velocity profiles peaking around one-third of ejection and declining when force development declines. This article aimed to demonstrate that decreased contractility in coronary artery disease (CAD) changes outflow timing and profile symmetry. METHODS AND RESULTS Seventy-nine patients undergoing routine full dose dobutamine stress-echo (DSE) were divided into two groups based on resting wall motion and DSE response: DSE negative (DSE(neg)) (35 of 79 patients) and positive (DSE(pos)) (44 of 79 patients) which were compared with 32 healthy volunteers. Aortic CW-Doppler traces at rest were analysed semi-automatically; time-to-peak (T(mod)), ejection-time (ET(mod)), rise-time (t(rise)), and fall-time (t(fall)) were quantified. Asymmetry (asymm) was calculated as the normalized difference of left and right half of the spectrum. Normal curves were triangular, early-peaking, whereas patients showed more rounded shapes and later peaks. T(rise) was longest in DSE(pos). T(fall) was shortest in DSE(pos), followed by controls and DSE(neg). Asymm was lowest in DSE(pos), followed by controls and DSE(neg). Abnormally symmetric profiles (asymm <0.25) were found in none of the controls, 2.9% DSE(neg), and 27.3% DSE(pos). A good correlation was found between assym and ejection fraction (EF) and T(mod)/ET(mod) and EF. Notably, an LV dynamic gradient was induced in 71.4% DSE(neg) and in 18.2% DSE(pos), associated with LV hypertrophy and supernormal (very asymmetric) traces. CONCLUSION Decreased myocardial function results in a more symmetrical outflow, while very asymmetrical traces suggest increased contractility, potentially inducing intra-cavity gradients during DSE. Therefore, including outflow symmetry as a clinical measurement provides additional information on patients with CAD.

Analysis of Doppler Ultrasound Outflow Profiles for the Detection of changes in Cardiac Function

Detecting changes in the contractility of the heart muscle, especially in the presence of coronary artery disease, is an important medical task. From isolated myocytes, it was suggested that chronic ischemia decreases but prolongs contraction. Additionally, severe aortic stenosis shows higher but often prolonged outflow velocities. From this, we hypothesize that there is a correlation between the morphology of the aortic outflow velocity profile and myocardial function. To test this hypothesis, we (semi-) automatically analyzed continuous wave Doppler aortic outflow traces from 112 individuals. The traces were segmented and a set of morphology features were extracted. Areas under ROC curve were used as a measure of quality of each feature for detecting changes in cardiac function related to coronary artery disease. Signal analysis has shown that the probabilistic distributions of the various features are different for normal individuals and patients with ongoing disease. This result shows that aortic outflow profiles provide information on cardiac function and that the presented signal analysis and feature extraction method might be used to provide additional diagnostic information in the clinical management of coronary artery disease.

An integrated framework for the assessment of cardiac function - Description and illustrated applications

Assessing myocardial function is a difficult task in clinical practice. Routinely, (systolic) cardiac function is mostly quantified based on ejection fraction, a measure of the volume fraction of the left ventricle being ejected with each cardiac cycle. However, this approach has a lot of limitations since normal ejection fraction can occur while there are clearly functional abnormalities, while a reduced value does not say anything about what is wrong with the heart muscle. Recently, echocardiographic strain (-rate) imaging has been introduced, enabling the regional quantification of myocardial deformation. However, local deformation is also influenced by a number of factors and therefore does not necessarily represent local contractile force development. In this paper, we present an integrated framework, describing intrinsic cardiac function in its relationship with the boundary conditions. To illustrate how this framework can be used to study and understand cardiac function, two applications are discussed (regional ischemia and left bundle branch block). These applications are illustrated with simulations of regional deformation profiles.