Yu-Jia Liang

Resting global and regional left ventricular contractility in patients with heart failure and normal ejection fraction: insights from speckle-tracking echocardiography

Obejctive To compare left ventricular (LV) systolic performance and contractility in patients with heart failure and normal ejection fraction (HFNEF), compared with patients with heart failure and reduced ejection fraction (HFREF) and healthy subjects using newer echocardiographic techniques. Design A case–control trial. Setting University teaching hospital (tertiary referral centre). Patients Sixty healthy control subjects (53±10 years), 112 patients with HFNEF (74±12 years) and 175 patients with HFREF (67±13 years). Interventions All underwent standard two-dimensional, Doppler and speckle-tracking echocardiography. Main outcome measures Effective arterial (Ea) and LV end-systolic elastance (Ees), stress-corrected mid-wall shortening, preload recruitable stroke work, two-dimensional strain and torsion. Comparisons were adjusted for age, gender and body size. Results Besides diastolic dysfunction, patients with HFNEF had impaired load-independent ventricular contractility with a progressive decrease of the corrected Ees from controls (2.9±0.8 mm Hg/g) to HFNEF (2.2±0.9 mm Hg/g) followed by HFREF (0.8±0.3 mm Hg/g; all p<0.001). Ventricular-arterial coupling ratio was preserved in the HFNEF subgroup (normal 0.48±0.09 vs 0.65±0.16; p=NS) at the expense of both increased LV systolic stiffness and Ea. In addition, there was progressive decrease of global 2D circumferential, radial and longitudinal strain as well as torsion from normal, HFNEF to HFREF groups, even after adjustment for LV end-systolic wall stress or end-diastolic volume (all p<0.01). About 50% of patients with HFNEF had ≥1 global strain or torsion parameter depressed below normal after correction for LV end-systolic wall stress, with >85% falling below their corresponding stress-corrected mean. Conclusions Impaired myocardial contractility is evident in many patients with HFNEF and this may contribute towards pathophysiology of HFNEF more than previously thought.

Tissue Doppler velocity is superior to strain imaging in predicting long-term cardiovascular events after cardiac resynchronisation therapy

Objective: To examine the predictive value of systolic dyssynchrony measured by tissue Doppler velocity versus tissue Doppler strain imaging on long-term outcome after cardiac resynchronisation therapy (CRT). Design: Cohort study. Setting: Two university hospitals. Patients: Two hundred and thirty-nine patients (65 (SD 12) years, 76% males) who underwent CRT. Interventions: Baseline echocardiography with tissue Doppler imaging (TDI) and clinical follow-up for 37 (20) months. Main outcome measures: The time to peak systolic velocity during ejection phase (Ts) and the time to peak systolic strain (Tϵ) were assessed for dyssynchrony, that is the maximal delay in Ts and the maximal delay in Tϵ among the four left ventricular basal segments. Occurrence of cardiovascular endpoints between patients with and without dyssynchrony was compared by Kaplan–Meier curves, followed by Cox regression analysis for potential predictor(s). Results: There were 78 (33%) deaths, with cardiovascular causes in 64 (27%) patients, while 136 (57%) patients were hospitalised for cardiovascular events, including decompensated heart failure in 87 (36%) patients. Patients with the maximal delay in Ts of ⩾65 ms showed a lower event rate for cardiovascular mortality (19% vs 38%, logrank χ2 = 7.803, p = 0.005) and other prognostic endpoints. In Cox regression analysis, the maximal delay in Ts (hazard ratio (HR) 0.463, 95% CI 0.270 to 0.792, p = 0.005) and ischaemic aetiology (HR 2.716, 95% CI 1.505 to 4.901, p = 0.001) were independent predictors of cardiovascular mortality. In contrast, the maximal delay in Tϵ of ⩾80 ms failed to predict any cardiovascular event. Conclusions: Echocardiographic evidence of prepacing systolic dyssynchrony measured by TDI velocity, but not TDI strain, predicted lower long-term cardiovascular events after CRT.

Impact of reduction in early- and late-systolic functional mitral regurgitation on reverse remodelling after cardiac resynchronization therapy

AIMS To examine whether the presence of pre-pacing functional mitral regurgitation (MR) and its improvement would affect the extent of left ventricular (LV) reverse remodelling after cardiac resynchronization therapy (CRT). METHODS AND RESULTS Echocardiographic assessment was performed in 83 patients before and 3 months after CRT. Total MR volume and the early- and late-systolic MR flow rate were assessed. At 3 months, there was reduction in total MR volume (38 ± 20 vs. 33 ± 21 mL) with decrease in both early- (71 ± 52 vs. 60 ± 51 mL/s) and late-systolic (49 ± 46 vs. 42 ± 46 mL/s) MR flow rate (all P < 0.05). Receiver-operating characteristic curve found that an 11% decrease in total MR volume was associated with LV reverse remodelling [defined by the reduction in LV end-systolic volume (LVESV) of ≥15%] [sensitivity, 90%; specificity, 80%; area under the curve (AUC), 0.85; P < 0.001]. The improvement in early- and late-systolic MR was also associated with LV reverse remodelling, in which improvement in early-systolic MR had higher sensitivity, specificity, and AUC than late-systolic MR. The extent of reverse remodelling with gain in LV ejection fraction and forward stroke volume was greatest in patients with improvement in total MR, intermediate in those with mild or no MR at baseline, and the least in those without improvement in total MR (LVESV, -29.8 ± 12.0 vs. -18.6 ± 16.6 vs. -5.5 ± 8.6%; ejection fraction, 11.8 ± 6.2 vs. 7.0 ± 6.8 vs. 3.0 ± 5.0%; forward stroke volume, 43.1 ± 37.9 vs. 21.1 ± 26.1 vs. 6.8 ± 34.6%; all P < 0.05). CONCLUSION Improvement of functional MR contributes to LV reverse remodelling after CRT, whereas reduction of early-systolic MR is more powerful than late-systolic MR.

Difference in prevalence and pattern of mechanical dyssynchrony in left bundle branch block occurring in right ventricular apical pacing versus systolic heart failure.

BACKGROUND This study compared the prevalence and pattern of mechanical dyssynchrony in patients with normal heart and right ventricular apical (RVA) pacing versus patients with systolic heart failure (SHF) and spontaneous left bundle branch block (LBBB). METHODS A total of 112 patients having LBBB pattern on surface electrocardiogram were included (57 with ejection fraction>50% received RVA pacing; 55 had SHF with ejection fraction<35%). Using tissue Doppler imaging, systolic and diastolic dyssynchrony was defined by the standard deviation of the time to peak systolic and peak early diastolic velocity, respectively. RESULTS Despite comparable QRS duration and LBBB pattern, the prevalence of electromechanical dyssynchrony was significantly lower in the patients with RVA pacing (systolic: 54% vs 73%, chi2=4.058, P=.044; diastolic: 32% vs 61%, chi2=9.738, P=.002). The presence of coexisting systolic and diastolic dyssynchrony, isolated systolic dyssynchrony, isolated diastolic dyssynchrony, and no dyssynchrony also showed a different distribution between the 2 groups (RVA pacing: 14%, 40%, 18%, and 28%; SHF: 51%, 22%, 11%, and 16%; chi2=17.498, P=.001). Furthermore, the SHF group had a higher prevalence of medial wall (ie, septal, anteroseptal, and inferior) delay (56% vs 30%), whereas RVA pacing resulted in more free wall (ie, lateral, posterior and anterior) delay (44% vs 70%) (chi2=8.050, P=.005). CONCLUSIONS The prevalence of mechanical dyssynchrony is lower in patients with normal ejection fraction and RVA pacing when compared with patients with SHF and spontaneous LBBB. The pattern of delay in contraction also appears to be different between the 2 groups.

A novel multi-layer approach of measuring myocardial strain and torsion by 2D speckle tracking imaging in normal subjects and patients with heart diseases

BACKGROUND This study adopted a new multi-layer approach of measuring myocardial deformation by two-dimensional (2D) speckle tracking imaging to examine whether a transmural gradient exists in normal subjects and cardiac diseases. METHODS Eighty patients were included with 20 in each group: (1) normal control; (2) acute coronary syndrome (ACS) with ejection fraction (EF) >45%; (3) right ventricular apical (RVA) pacing with EF>45%; (4) systolic heart failure (SHF) with EF<45%. Circumferential strain (ε-circum), torsion (Tor) and systolic dyssynchrony defined as the maximal difference in the time to peak circumferential strain were measured in the subendocardial and subepicardial myocardium layers (QLab 6.0, Philips). RESULTS In all the 4 groups, a subendocardial to subepicardial gradient was present in both ε-circum (-20.7 ± 7.6 vs. -14.9 ± 5.6%, p<0.001) and Tor (12.0 ± 6.0 vs. 9.3 ± 4.7°, p<0.05), with higher values in the subendocardial layer. However, it was significantly narrowed for ε-circum (2.7 ± 1.2%) and Tor (0.8 ± 0.9°) in SHF patients (all p ≤ 0.001 vs. other groups). On the contrary, systolic dyssynchrony measured in the 2 layers showed no difference (264 ± 107 vs. 273 ± 110 ms, p = NS) and a homogenous distribution in ε-circum was observed from basal to apical planes (-17.0 ± 6.8 vs. -18.1 ± 7.4 vs. -18.1 ± 7.8%, all p = NS). CONCLUSIONS A transmural gradient exists in circumferential strain and torsion, with higher values in the subendocardial layer. It might be reduced when systolic function is impaired. Therefore, the multi-layer approach of 2D speckle tracking imaging provides further information on assessment of myocardial diseases.

LV Mechanical Dyssynchrony in Heart Failure With Preserved Ejection Fraction Complicating Acute Coronary Syndrome

OBJECTIVES The aim of this study was to evaluate the role of left ventricular (LV) mechanical dyssynchrony in heart failure with preserved ejection fraction (HFPEF) complicating acute coronary syndrome (ACS). BACKGROUND In systolic heart failure, LV mechanical dyssynchrony worsens cardiac function and cardiac resynchronization therapy improves clinical outcome. The role of LV mechanical dyssynchrony in HFPEF complicating ACS is unknown. METHODS One hundred two patients presenting with ACS (ejection fraction ≥50%) and 104 healthy controls were studied using tissue Doppler imaging: group 1 (n = 55) had HFPEF on presentation and group 2 (n = 47) had no clinical HFPEF. The SD of time to peak systolic myocardial velocity and the SD of early diastolic (Te-SD) myocardial velocity of 12 LV segments were obtained for evaluation of dyssynchrony. Longitudinal mean myocardial ejection systolic velocity (mean Sm) and mean early diastolic velocity (mean Em) were measured. RESULTS Te-SD was greater in group 1 (33 ± 13 ms) than group 2 (21 ± 9 ms) (p < 0.001), and diastolic mechanical dyssynchrony was evident in 35% of patients in group 1 but in only 9% in group 2 (p < 0.001). Conversely, the SD of time to peak systolic myocardial velocity was similar in the 2 ACS groups (34 ± 16 ms vs. 32 ± 18 ms; p = NS), showing a similar prevalence of systolic mechanical dyssynchrony (47% vs. 43%; p = NS). Worsening of the diastolic dysfunction grade was associated with a parallel increase in Te-SD (grades 0, 1, 2, and 3: 16 ± 3 ms, 21 ± 5 ms, 28 ± 9 ms, and 41 ± 17 ms, respectively; p < 0.001). Te-SD correlated negatively with mean Em (r = -0.56, p < 0.001) and positively with peak mitral inflow velocity of the early rapid-filling wave/Em (r = 0.69, p < 0.001); mean myocardial ejection systolic velocity correlated significantly with mean Em (r = 0.56, p < 0.001), SD of time to peak systolic myocardial velocity (r = -0.42, p < 0.001) and Te-SD (r = -0.23, p = 0.001). Multivariate analysis identified peak mitral inflow velocity of the early rapid-filling wave/Em as the only variable independently associated with HFPEF (odds ratio: 1.48, p = 0.001). When peak mitral inflow velocity of the early rapid-filling wave/Em was excluded from the model, Te-SD (odds ratio: 1.13, p < 0.001) and mean Em (odds ratio: 0.37, p < 0.001) became independently associated with HFPEF. CONCLUSIONS LV diastolic mechanical dyssynchrony may impair diastolic function and contribute to the pathophysiology of HFPEF, complicating ACS.

Incremental value of global systolic dyssynchrony in determining the occurrence of functional mitral regurgitation in patients with left ventricular systolic dysfunction

AIMS The aim of this study was to assess the contribution of left ventricular (LV) systolic dyssynchrony to functional mitral regurgitation (MR). METHODS AND RESULTS Patients (n = 136) with LV systolic dysfunction (ejection fraction <50%) and at least mild MR were prospectively recruited. The effective regurgitant orifice area (EROA) was assessed by the proximal isovelocity surface area method. Left ventricular global systolic dyssynchrony [the maximal difference in time to peak systolic velocity among the 12 LV segments (Ts-Dif)] and regional systolic dyssynchrony (the delay between the anterolateral and posteromedial papillary muscle attaching sites) were assessed by tissue Doppler imaging. Left ventricular global and regional remodelling, systolic function, indices of mitral valvular and annular deformation were also measured. The size of the EROA correlated with the degrees of mitral deformation, LV remodelling, systolic function, and systolic dyssynchrony. By multivariate logistic regression analysis, the mitral valve tenting area (OR = 1.020, P < 0.001) and the Ts-Dif (OR = 1.011, P = 0.034) were independent determinants of significant functional MR (defined by EROA ≥20 mm(2)). From the receiver-operating characteristic curve, the tenting area of 2.7 cm(2) (sensitivity 83%, specificity 82%, AUC 0.86, P < 0.001) and the Ts-Dif of 85 ms (sensitivity 66%, specificity 72%, AUC 0.74, P < 0.001) were associated with significant functional MR. The assessment of Ts-Dif showed an incremental value over the mitral valve tenting area for determining functional MR (χ(2) = 53.92 vs.49.11, P = 0.028). CONCLUSION This cross-sectional study showed that LV global, but not regional systolic dyssynchrony, is a determinant of significant functional MR in patients with LV systolic dysfunction, and is incremental to the tenting area that is otherwise the strongest factor for mitral valve deformation.

Relation of Left Ventricular Systolic Dyssynchrony in Patients With Heart Failure to Left Ventricular Ejection Fraction and to QRS Duration

Left ventricular (LV) systolic dyssynchrony is an important pathologic mechanism in patients with heart failure (HF). However, the prevalence of intraventricular dyssynchrony in patients with different LV ejection fractions (EFs) is unknown. This study evaluated 402 consecutive patients with HF (mean age 64.99 +/- 13.15 years, 72.4% men) and 120 healthy controls. Dyssynchrony indexes included the SD of the time to peak systolic velocity (Ts) in ejection phase in the 12-segmental model (Ts-SD) and the difference in Ts between basal septal and basal lateral segments (Ts-Septal-Lateral) using tissue Doppler imaging. Patients were divided into 3 groups according to LVEF (LVEF <20%, >20% to 35%, and >35% to 50%) and compared with healthy controls. Both indexes were significantly higher in all 3 LVEF groups compared with controls (p <0.0001). Based on the established cut-off values, systolic dyssynchrony was equally prevalent in all 3 LVEF groups and was 67%, 62%, and 55% using Ts-SD and 38%, 36%, and 35% using Ts-Septal-Lateral, respectively. However, the prevalence of systolic dyssynchrony was higher using Ts-SD than Ts-Septal-Lateral (chi-square = 94.43, p <0.001). Conversely, the prevalence of electrical dyssynchrony, defined as a >120-ms QRS duration, decreased significantly with increasing LVEF (44%, 35%, and 16%; chi-square 5.60, p <0.001). In conclusion, the prevalence of mechanical systolic dyssynchrony was independent of severity of LV systolic dysfunction. This may implicate the potential role of cardiac resynchronization therapy for those with LVEF of 35% to 50%, in particular when systolic dyssynchrony is present.

Comparison of left ventricular reverse remodeling induced by cardiac contractility modulation and cardiac resynchronization therapy in heart failure patients with different QRS durations.

BACKGROUND Cardiac contractility modulation (CCM) is a new device-based therapy for advanced systolic heart failure with normal QRS duration and therefore not suitable for cardiac resynchronization therapy (CRT). Left ventricular (LV) reverse remodeling was reported in patients treated with CCM or CRT, however, the extent of response was not compared. METHODS This observational study consisted of three groups of patients with symptomatic heart failure and LV ejection fraction <35% despite optimal medical therapy. Group 1 included those received CCM with a QRS duration <120 ms (n=33), Group 2 included those received CRT with a QRS duration of 120-150 ms (n=43), and Group 3 included those received CRT with a QRS duration >150 ms (n=56). LV end-systolic volume (LVESV) was measured at baseline and 3 months later. RESULTS Age, gender, etiology of heart failure and baseline ejection fraction were comparable. A significant LV reverse remodeling was observed in each group. The degree of LVESV reduction was similar between Group 1 and Group 2 (-11.3 ± 1 1.8 vs. -13.6 ± 18.3%, p=0.833), however, it was greater in Group 3 (-25.0 ± 18.0%, both p<0.01). By using the reduction ≥ 15%, the responder rate was not different between Group 1 (39%) and Group 2 (42%), but significantly higher in Group 3 (68%) (χ(2)=9.514, p=0.009). CONCLUSION CCM exhibited a similar LV reverse remodeling response to CRT for patients with a mildly prolonged QRS, though the effect was less strong when compared to CRT for patients with a very wide QRS.

Impact of a Dedicated Training Program on the Reproducibility of Systolic Dyssynchrony Measures Using Tissue Doppler Imaging

BACKGROUND The reproducibility of the measurement of mechanical dyssynchrony by echocardiography including Doppler tissue imaging has recently been questioned. The aim of this study was to ascertain the role of a dedicated training program to improve skills and the reproducibility of dyssynchrony assessment. METHODS In 70 patients with heart failure, color Doppler tissue images were acquired, and the time to peak systolic velocity of each segment and several dyssynchrony indices, including the standard deviation of time to peak systolic velocity, were measured by an expert to constitute a reference standard. The same images were then assessed by two beginners, who had only basic knowledge of dyssynchrony analysis after a 1-hour lecture, and two graduates, who had received a structured hands-on training program. Both sets of results were compared with the standard. RESULTS For the standard deviation of time to peak systolic velocity, the linear correlations between the standard and beginner 1 (r = 0.643) and beginner 2 (r = 0.532) were only modest (P < .001 for both). When referenced to the standard, interobserver variability was 18% for beginner 1 and 19% for beginner 2. Measurements with differences of ≥10 msec were found in 24% and 22% of cases by beginners 1 and 2, respectively. In contrast, the assessments made by graduates 1 and 2 were significantly improved. The correlation coefficients were 0.935 and 0.929 (P < .001 for both), and interobserver variability values were 8% and 7%. The prevalence rates of measurements with differences ≥ 10 msec were 1.5% and 3%, respectively. CONCLUSIONS There is a learning curve for the measurement of systolic dyssynchrony using Doppler tissue imaging, but good reproducibility can be achieved by the use of a dedicated training program.