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Objectives: This study aimed to evaluate the impact of cardiac contractility modulation (CCM) on left ventricular (LV) size and myocardial function. Background: CCM is a device-based therapy for patients with advanced heart failure. Previous studies showed that CCM improved symptoms and exercise capacity; however, comprehensive assessment of LV structure, function, and reverse remodeling is not available. Methods: Thirty patients (60 ± 11 years, 80% male) with New York Heart Association (NYHA) functional class III heart failure, ejection fraction <35%, and QRS <120 ms were assessed at baseline and 3 months. LV reverse remodeling was measured by real-time 3-dimensional echocardiography. Using tissue Doppler imaging, the peak systolic velocity (Sm) and peak early diastolic velocity (Em) were calculated for LV function, while the standard deviation of the time to peak systolic velocity (Ts-SD) and the time to peak early diastolic velocity (Te-SD) were calculated for mechanical dyssynchrony. Results: LV reverse remodeling was evident, with a reduction in LV end-systolic volume by −11.5 ± 10.5% and a gain in ejection fraction by 4.8 ± 3.6% (both p < 0.001). Myocardial contraction was improved in all LV walls, including sites remote from CCM delivery (all p < 0.05); hence, the mean Sm of 12 (2.2 ± 0.6 cm/s vs. 2.5 ± 0.7 cm/s) or 6 basal LV segments (2.5 ± 0.6 cm/s vs. 3.0 ± 0.7 cm/s) were increased significantly (both p < 0.001). In contrast, CCM had no impact on regional or global Em (2.9 ± 1.3 cm/s vs. 2.9 ± 1.1 cm/s), whereas Ts-SD (28.2 ± 11.2 ms vs. 27.9 ± 12.7 ms) and Te-SD (30.0 ± 18.3 ms vs. 30.1 ± 20.7 ms) remained unchanged (all p = NS). Mitral regurgitation was reduced (22 ± 14% vs. 17 ± 15%, p = 0.02). Clinically, there was improvement of NYHA functional class (p < 0.001) and 6-min hall walk distance (p = 0.015). A 24-h Holter monitor showed that premature ventricular contractions were not increased during CCM. Conclusions: CCM improves both global and regional LV contractility, including regions remote from the impulse delivery, and may contribute to LV reverse remodeling and gain in systolic function. Such improvement is unrelated to diastolic function or mechanical dyssynchrony. [Copyright &y& Elsevier]

Efficacy of CRT for Mildly Prolonged QRS.. Introduction:Cardiac resynchronization therapy (CRT) has been shown to reverse left ventricular (LV) remodeling and improve symptoms in heart failure patients with wide QRS complexes; however, its role in patients with mildly prolonged QRS complexes is unclear. This study investigated if CRT benefited patients with mildly prolonged QRS complexes>120 to 150 ms and explored if the severity of systolic asynchrony determined such a response.Methods and Results:Fifty-eight patients (age 66± 11 years, 66% male) who had undergone CRT were studied prospectively. Of these patients, 27 had QRS duration between 120 and 150 ms (group A), and 31 had QRS duration>150 ms (group B). Tissue Doppler echocardiography and clinical assessment were performed at baseline and 3 months after CRT. Both groups had significant reduction of LV volume and increased ejection fraction,+dP/dt, and sphericity index (all P<0.05). These improvements were greater in group B and were explained by the higher prevalence of systolic intraventricular asynchrony. Significant reverse remodeling (reduction of LV end-systolic volume>15%) was evident in 46% of group A patients and 68% of group B patients. Improvement in clinical endpoints was observed in both groups (all P<0.01), although the changes in metabolic equivalent and New York Heart Association functional class were greater in group B. In both groups, systolic asynchrony index (TS-SD) was the most important predictor of reverse remodeling (r=−0.78, P<0.001) and was the only independent predictor in the multivariate model (β=−1.80, confidence interval=−2.18 to−1.42, P<0.001); QRS duration was not. A predefined TS-SD value>32.6 ms had a sensitivity of 94% and specificity of 83% to predict reverse remodeling. Improvement of intraventricular asynchrony after CRT was evident only in responders (P= 0.01).Conclusion:Improvement of LV remodeling and clinical status is evident after CRT in heart failure patients with QRS duration>120 to 150 ms. These responders are closely predicted by the severity of prepacing intraventricular asynchrony but not QRS duration.(J Cardiovasc Electrophysiol, Vol. 15, pp. 1-8, September 2004) [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Objectives: The present study aimed to examine whether diastolic and systolic asynchrony exist in diastolic heart failure (DHF) and their prevalence and relationship to systolic heart failure (SHF) patients. Background: Few data exist on mechanical asynchrony in DHF. Methods: Tissue Doppler echocardiography was performed in 373 heart failure patients (281 with SHF and 92 with DHF) and 100 normal subjects. Diastolic and systolic asynchrony was determined by measuring the standard deviation of time to peak myocardial systolic (Ts-SD) and peak early diastolic (Te-SD) velocity using a 6-basal, 6-mid-segmental model, respectively. Results: Both heart failure groups had prolonged Te-SD (DHF vs. SHF vs. controls subjects: 32.2 ± 18.0 ms vs. 38.0 ± 25.2 ms vs. 19.5 ± 7.1 ms) and Ts-SD (31.8 ± 17.0 ms vs. 36.7 ± 15.2 ms vs. 17.6 ± 7.9 ms) compared with the control group (all p < 0.001 vs. control subjects). Based on normal values, the DHF group had comparable diastolic (35.9% vs. 43.1%; chi-square = 1.48, p = NS), but less systolic asynchrony than the SHF group (39.1% vs. 56.9%; chi-square = 8.82, p = 0.003). Normal synchrony, isolated systolic, isolated diastolic, and combined asynchrony were observed in 39.1%, 25.0%, 21.7%, and 14.1% of DHF patients, respectively, and these were 25.6%, 31.3%, 17.4%, and 25.6%, correspondingly, in SHF (chi-square = 10.01, p = 0.019). The correlation between systolic and diastolic asynchrony, and between the myocardial velocities and corresponding mechanical asynchrony appeared weak. A wide QRS duration (>120 ms) was rare in DHF (10.9% vs. 37.7% in SHF) (chi-square = 16.69, p < 0.001). Conclusions: Diastolic and/or systolic asynchrony was common in 61% of DHF patients despite narrow QRS complex. The presence of asynchrony was not related to myocardial systolic or diastolic function. Systolic and diastolic asynchrony were not tightly coupled, implying distinct mechanisms. [Copyright &y& Elsevier]

Cardiac resynchronization therapy (CRT) has been shown to reduce symptoms and reverse left ventricular (LV) remodeling. It is not known, however, whether diastolic function will improve after CRT and diastolic asynchrony will predict LV reverse remodeling. Seventy-six patients (mean age 65 ± 12 years, 74% men) who received CRT were studied at baseline and after 3 months. Diastolic function was assessed by transmitral Doppler and tissue Doppler imaging. LV systolic and diastolic asynchrony were assessed by the time to peak myocardial contraction (Ts) and early diastolic relaxation (Te) using the 6 basal, 6 mid-segmental model. There were 42 responders (55%) with LV reverse remodeling (defined as a reduction of LV end-systolic volume ≥15%). Parameters of systolic function were significantly improved only in the responders. For diastolic function, there were reductions of transmitral E velocity in the 2 groups, without any change in atrial velocity or the E/A ratio. Tissue Doppler imaging revealed that myocardial early diastolic velocity was unchanged in responders but was significantly worsened in nonresponders. The systolic asynchrony index (the SD of Ts of 12 LV segments) correlated significantly with LV reverse remodeling (r = −0.64, p <0.001) but not the diastolic asynchrony index (the SD of Te of 12 LV segments) (r = −0.10, p = NS). The systolic asynchrony index was the only independent predictor of reverse remodeling (β = −0.99, 95% confidence interval −1.41 to −0.58, p <0.001). In conclusion, CRT improves systolic function and systolic asynchrony but has a neutral effect on diastolic function and diastolic asynchrony. LV reverse remodeling response is determined by the severity of prepacing systolic asynchrony but not diastolic asynchrony or the diastolic filling pattern. [Copyright &y& Elsevier]