Left ventricular three-dimensional quadripolar lead acute clinical study: the LILAC study.

AIMS: This multicenter acute clinical study was designed to verify novel three-dimensional (3D) quadripolar lead designs that can achieve ≤2.5 V average pacing capture threshold (PCT) not only at the apex, but also at the base of the left ventricle with phrenic nerve stimulation (PNS) avoidance for cardiac resynchronization. METHODS: During the implant procedure, up to two different left ventricular investigational leads were introduced and tested in the same target coronary vein based on the coronary sinus venogram in a wedged and unwedged position. Adverse events were collected in 30 days following the procedure. RESULTS: Eighty-seven leads were tested in 50 patients. When the best performing spiral electrode was chosen from each lead testing, the average of the best PCT on spiral in a wedged position was similar to the unwedged position (1.7 ± 1.5 V vs 1.9 ± 1.5 V, P = ns) and was similar to the wedged tip electrode average PCT (1.7 ± 1.5 V vs 1.6 ± 1.6 V, P = ns). In the majority of patients (89-96%), pacing was achievable in a mid-basal ventricular location without PNS. CONCLUSIONS: This acute study demonstrated that a 3D quadripolar spiral lead design can achieve acceptable PCTs and avoid PNS without repositioning the lead at implant in the vast majority of patients. It also demonstrated that this lead design can achieve mid-basal ventricular stimulation with low PCT and good acute stability.

Biventricular pacing is superior to right ventricular pacing in bradycardia patients with preserved systolic function: 2-year results of the PACE trial.

AIMS: The Pacing to Avoid Cardiac Enlargement (PACE) trial is a prospective, double-blinded, randomized, multicentre study that reported the superiority of biventricular (BiV) pacing to right ventricular apical (RVA) pacing in the prevention of left ventricular (LV) adverse remodelling and deterioration of systolic function at 1 year. In the current analysis, we report the results at extended 2-year follow-up for changes in LV function and remodelling. METHODS AND RESULTS: Patients (n = 177) with bradycardia and preserved LV ejection fraction (EF ≥45%) were randomized to receive RVA or BiV pacing. The co-primary endpoints were LVEF and LV end-systolic volume (LVESV). Eighty-one (92%) of 88 in the RVA pacing group and 82 (92%) of 89 patients in the BiV pacing group completed 2-year follow-up with a valid echocardiography. In the RVA pacing group, LVEF further decreased from the first to the second year, but it remained unchanged in the BiV pacing group, leading to a significant difference of 9.9 percentage points between groups at 2-year follow-up (P < 0.001). Similarly, LVESV continues to enlarge from the first to the second year in the RVA pacing group, leading to a difference of 13.0 mL (P < 0.001) between groups. Predefined subgroup analysis showed consistent results with the whole study population for both co-primary endpoints, which included patients with pre-existing LV diastolic dysfunction. Eighteen patients in the BiV pacing group (20.2%) and 55 in the RVA pacing group (62.5%) had a significant reduction of LVEF (of ≥5%, P < 0.001). CONCLUSION: Left ventricular adverse remodelling and deterioration of systolic function continues at the second year after RVA pacing. This deterioration is prevented by BiV pacing.

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.

Different determinants of improvement of early and late systolic mitral regurgitation contributed after cardiac resynchronization therapy.

BACKGROUND: Functional mitral regurgitation (MR) at different phases of the regurgitant period may respond differently to cardiac resynchronization therapy (CRT). The aims of this study were to examine the impact of CRT on the phasic changes of MR (early vs late systole) and to explore the mechanisms of such changes. METHODS: Instantaneous MR flow rate and total MR volume were evaluated in 60 patients who had more than mild functional MR before and 3 months after CRT. In addition, indices of global left ventricular (LV) remodeling, mitral deformation, and LV systolic dyssynchrony were assessed. RESULTS: CRT diminished MR volume (38 ± 18 vs 32 ± 20 mL) by reducing both the early (72 ± 47 vs 58 ± 48 mL/sec) and late (48 ± 42 vs 40 ± 42 mL/sec) systolic components (all p values < .01). In patients with ≥10% reductions in total MR volume but not in patients without this improvement, there were significant reductions in LV end-systolic volume, increases in LV +dP/dt, decreases in mitral valvular tenting, and improvements of systolic dyssynchrony at 3 months (all P values < .05). By multivariate regression, the reductions in LV end-systolic volume and tenting area were independent determinants of a reduction in total MR volume: the reductions in LV end-systolic volume and global dyssynchrony determined the reduction in early systolic MR, and the reductions in tenting area and global dyssynchrony determined reduction in late systolic MR. CONCLUSIONS: CRT decreases MR volume by reducing both early and late systolic MR. The determinants of the phasic improvement in functional MR are different.

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.

Prevalence and determinants of left ventricular systolic dyssynchrony in patients with normal ejection fraction received right ventricular apical pacing: a real-time three-dimensional echocardiographic study.

AIMS: Right ventricular apical (RVA) pacing may induce mechanical dyssynchrony. However, its impact on patients with normal ejection fraction (EF) is not fully understood. This study examined the prevalence and predictors of RVA pacing-induced systolic dyssynchrony by real-time three-dimensional echocardiography (RT3DE), and evaluated its impact on left ventricular (LV) function. METHODS AND RESULTS: Ninety-three patients with sinus node dysfunction and normal EF (>50%) received RVA-based dual-chamber pacing were assessed by RT3DE during RVA pacing (V-pace) and intrinsic conduction (V-sense). Systolic dyssynchrony was evaluated using the standard deviation of the time to minimal regional volume of 16 LV segments (Tmsv-16SD), and a cutoff value of 16 ms was determined from 93 normal controls. Systolic dyssynchrony was induced in 49.5% of patients at V-pace with significant increase in LV end-systolic volume (LVESV), decrease in EF, and worsening of Tmsv-16SD (all P < 0.001). Furthermore, patients who developed dyssynchrony had larger LVESV (P < 0.001), lower EF (P < 0.001) at V-pace mode, and higher cumulative percentage of RVA pacing in the past 6 months (P < 0.001) than those without systolic dyssynchrony. In multivariate logistic regression analysis, independent predictors of developing LV systolic dyssynchrony during V-pace included a low normal EF at V-sense, pre-existing LV hypertrophy, and cumulative RVA pacing >40% in the past 6 months. CONCLUSION: For patients with preserved EF received RVA pacing, half of them would develop systolic dyssynchrony which was associated with EF deterioration and LV enlargement. A low normal EF, a high cumulative percentage of RVA pacing, and pre-existing LV hypertrophy were predictors of developing dyssynchrony.

Biventricular pacing in patients with bradycardia and normal ejection fraction.

BACKGROUND: Observational studies suggest that conventional right ventricular apical pacing may have a deleterious effect on left ventricular function. In this study, we examined whether biventricular pacing is superior to right ventricular apical pacing in preventing deterioration of left ventricular systolic function and cardiac remodeling in patients with bradycardia and a normal ejection fraction. METHODS: In this prospective, double-blind, multicenter study, we randomly assigned 177 patients in whom a biventricular pacemaker had been successfully implanted to receive biventricular pacing (89 patients) or right ventricular apical pacing (88 patients). The primary end points were the left ventricular ejection fraction and left ventricular end-systolic volume at 12 months. RESULTS: At 12 months, the mean left ventricular ejection fraction was significantly lower in the right-ventricular-pacing group than in the biventricular-pacing group (54.8+/-9.1% vs. 62.2+/-7.0%, P<0.001), with an absolute difference of 7.4 percentage points, whereas the left ventricular end-systolic volume was significantly higher in the right-ventricular-pacing group than in the biventricular-pacing group (35.7+/-16.3 ml vs. 27.6+/-10.4 ml, P<0.001), with a relative difference between the groups in the change from baseline of 25% (P<0.001). The deleterious effect of right ventricular apical pacing occurred in prespecified subgroups, including patients with and patients without preexisting left ventricular diastolic dysfunction. Eight patients in the right-ventricular-pacing group (9%) and one in the biventricular-pacing group (1%) had ejection fractions of less than 45% (P=0.02). There was one death in the right-ventricular-pacing group, and six patients in the right-ventricular-pacing group and five in the biventricular-pacing group were hospitalized for heart failure (P=0.74). CONCLUSIONS: In patients with normal systolic function, conventional right ventricular apical pacing resulted in adverse left ventricular remodeling and in a reduction in the left ventricular ejection fraction; these effects were prevented by biventricular pacing. (Centre for Clinical Trials number, CUHK_CCT00037.)

Changes in global left ventricular function by multidirectional strain assessment in heart failure patients undergoing cardiac resynchronization therapy.

BACKGROUND: The aim of this study was to evaluate the acute and late effects of cardiac resynchronization therapy (CRT) on multidirectional left ventricular (LV) strain assessed by two-dimensional speckle-tracking imaging and automated function imaging (AFI). METHODS: Multidirectional LV strain (global radial strain [GRS Avg], global circumferential strain [GCS Avg], and global longitudinal peak systolic strain [GLPSS Avg]) were measured in 141 patients with heart failure before CRT implantation, immediately afterward, and after 3 to 6 months of follow-up. Moreover, the acute effects on multidirectional LV strain were evaluated after interrupting CRT at follow-up. Response to CRT was defined as a decrease in LV end-systolic volume > or = 15%. RESULTS: Responders (57%) and nonresponders (43%) showed similar baseline values for GRS Avg, GCS Avg, and GLPSS Avg. At follow-up, significant improvement in multidirectional LV strain, combined with significant reverse LV remodeling and improvement in LV ejection fraction, was noted only in responders. Importantly, no significant changes in multidirectional LV strain were observed immediately after CRT device implantation or after device interruption at follow-up. CONCLUSIONS: Two-dimensional speckle-tracking imaging and AFI enable the quantification of multidirectional LV mechanics. Improvement in LV strain in the 3 orthogonal directions after CRT appears to be a long-term effect and is related to the extent of reverse LV remodeling after CRT.

Impact of cardiac contractility modulation on left ventricular global and regional function and remodeling.

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 + or - 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 + or - 10.5% and a gain in ejection fraction by 4.8 + or - 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 + or - 0.6 cm/s vs. 2.5 + or - 0.7 cm/s) or 6 basal LV segments (2.5 + or - 0.6 cm/s vs. 3.0 + or - 0.7 cm/s) were increased significantly (both p < 0.001). In contrast, CCM had no impact on regional or global Em (2.9 + or - 1.3 cm/s vs. 2.9 + or - 1.1 cm/s), whereas Ts-SD (28.2 + or - 11.2 ms vs. 27.9 + or - 12.7 ms) and Te-SD (30.0 + or - 18.3 ms vs. 30.1 + or - 20.7 ms) remained unchanged (all p = NS). Mitral regurgitation was reduced (22 + or - 14% vs. 17 + or - 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.

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.

Leveraging cardiac resynchronization therapy devices to monitor patients with heart failure.

Cardiac resynchronization therapy is a standard therapy for heart failure patients with cardiac dyssynchrony. The implantable device provides a convenient and continuous platform for heart failure monitoring. Information such as heart rate variability and activity status retrieved from the device allows physicians to more comprehensively evaluate these high-risk patients. Several registries and prospective observational studies have evaluated the value of intrathoracic impedance monitoring in predicting exacerbation of heart failure. With its sensitivity and positive predictive power, the fluid index--derived from the raw intrathoracic impedance--may alert clinicians to subclinical or clinical heart failure deterioration. Uncertainty remains as to whether the additional device-derived information will translate into clinical benefit by reducing the number of hospitalizations for heart failure. An ongoing randomized controlled clinical trial is expected to clarify the role of the device-based pulmonary fluid index in the management of heart failure.

Comparison of angiotensin-converting enzyme inhibitor alone and in combination with irbesartan for the treatment of heart failure.

OBJECTIVE: Angiotensin-converting enzyme inhibitor (ACEI) is beneficial in patients with congestive heart failure (CHF). Some, but not all, angiotensin receptor blocker (ARB) was demonstrated to be effective as "add-on" therapy. We investigated whether irbesartan is useful as an add-on therapy in CHF. DESIGN: Randomized control trial. SETTING: Single center. PATIENTS: 50 CHF patients on stable doses of ACEI. INTERVENTIONS: Add-on therapy with irbesartan (300 mg/day) or continuation of conventional therapy (control group) for 1 year. MAIN OUTCOME MEASURES: Serial clinical and echocardiographic assessment were performed as baseline, 3 months and 1 year after therapy. RESULTS: There was no difference in clinical characteristics between 2 groups. Patients in the add-on therapy group had significant increase in 6-Minute Hall-Walk distance (351+/-89 to 392+/-84 m, P<0.01), achieved higher METs exercise time on treadmill test (3.9+/-1.1 to 4.6+/-1.3 METs, P=0.01), reduction of NYHA Class (2.4+/-0.5 to 2.0+/-0.8, P<0.005) and improvement of QOL score (28+/-19 to 17+/-18, P<0.05). These parameters were not improved in the control group and a worsening of exercise capacity was observed (P<0.05). A reduction of left ventricular end-systolic diameter (4.94+/-0.85 vs 4.30+/-1.17 cm, P<0.05) was observed in the add-on group. At the end of 1 year, more patients have normal or abnormal relaxation pattern in the add-on group than the control group (82% vs 53% chi(2)=7.1, P=0.02). Blood pressure and renal function were unchanged in both groups. CONCLUSION: The addition of irbesartan to conventional ACEI therapy in CHF further improves symptoms, exercise capacity and quality of life without adverse effects on hemodynamics and renal function.

The role of repeating optimization of atrioventricular interval during interim and long-term follow-up after cardiac resynchronization therapy.

BACKGROUND: Cardiac resynchronization therapy (CRT) is an effective therapy for heart failure patients with electromechanical delay. Optimization of atrioventricular interval (AVI) is a cardinal component for the benefits. However, it is unknown if the AVI needs to be re-optimized during long-term follow-up. METHODS: Thirty-one patients (66+/-11 years, 20 males) with sinus rhythm who received CRT underwent serial optimization of AVI at day 1, 3-month and during long-term follow-up by pulse Doppler echocardiography (PDE). At long-term follow-up, the optimal AVI and cardiac output (CO) estimated by non-invasive impedance cardiography (ICG) were compared with those by PDE. RESULTS: The follow-up was 16+/-11 months. There was no significant difference in the mean optimal AVI when compared between any 2 time points among day 1 (99+/-30 ms), 3-month (97+/-28 ms) and long-term follow-up (94+/-28 ms). However, in individual patient, the optimal AVI remained unchanged only in 14 patients (44%), and was shortened in 12 (38%) and lengthened in 6 patients (18%). During long-term follow-up, although the mean optimal AVIs obtained by PDE or ICG (94+/-28 vs. 92+/-29 ms) were not different, a discrepancy was found in 14 patients (45%). For the same AVI, the CO measured by ICG was systematically higher than that by PDE (3.5+/-0.8 Vs. 2.7+/-0.6 L/min, p<0.001). CONCLUSION: Optimization of AVI after CRT appears necessary during follow-up as it was readjusted in 55% of patients. Although AVI optimization by ICG was feasible, further studies are needed to confirm its role in optimizing AVI after CRT.

Usefulness of tissue Doppler velocity and strain dyssynchrony for predicting left ventricular reverse remodeling response after cardiac resynchronization therapy.

The assessment of systolic dyssynchrony by echocardiography is useful in predicting a favorable response to cardiac resynchronization therapy (CRT). Tissue Doppler velocity and tissue Doppler longitudinal strain have been suggested for this purpose. This study compared parameters of systolic dyssynchrony derived from these 2 imaging modalities for their predictive values of CRT response. Two hundred fifty-six patients from 3 different centers who received CRT were followed for 6 +/- 3 months. Parameters of systolic dyssynchrony based on tissue Doppler velocity and strain imaging were assessed for the prediction of left ventricular (LV) reverse remodeling (reduction of LV end-systolic volume > or =15%). These included time to peak systolic velocity (or peak strain) of 12 LV segments to calculate the SD (Ts-SD or Tepsilon-SD), maximal difference in delay (Ts-Diff or Tepsilon-Diff), and opposite wall delay (Ts-OW or Tepsilon-OW). The septal-to-lateral delay (Ts-Sep-Lat or Tepsilon-Sep-Lat) was also measured. LV reverse remodeling, defined as improvement in end-systolic volume > or =15%, was observed in 141 patients (55%). All 4 tissue velocity parameters predicted LV reverse remodeling, and the areas under the receiver-operating characteristic curves were 0.86, 0.85, 0.84, and 0.79 for Ts-SD, Ts-Diff, Ts-OW, and Ts-Sep-Lat, respectively (all p <0.001). The cut-off values derived from receiver-operating characteristic curve analysis were 33 ms for Ts-SD, 100 ms for Ts-Diff, 90 ms for Ts-OW, and 60 ms for Ts-Sep-Lat, and their sensitivities were 93%, 92%, 81%, and 70%, with specificities of 78%, 68%, 80%, and 76%, respectively. In contrast, none of the longitudinal strain parameters predicted LV reverse remodeling. The areas under the receiver-operating characteristic curves ranged from 0.49 to 0.53 (all p = NS). The same conclusions were obtained in subgroup analyses of QRS duration (120 to 150 vs >150 ms) and ischemic or nonischemic cause of heart failure. In conclusion, parameters of tissue Doppler longitudinal velocity, but not longitudinal strain, predicted LV reverse remodeling after CRT.

Improvement of atrial function and atrial reverse remodeling after cardiac resynchronization therapy for heart failure.

OBJECTIVES: We sought to examine whether cardiac resynchronization therapy (CRT) improves atrial function and induces atrial reverse remodeling. BACKGROUND: Cardiac resynchronization therapy is an established therapy for advanced heart failure with prolonged QRS duration, which improves left ventricle (LV) function and is associated with LV reverse remodeling. METHODS: A total of 107 heart failure patients (66 +/- 11 years) who received CRT and were followed up for 3 months were studied. Atrial function was assessed by M-mode, 2-dimensional echocardiography, transmitral Doppler, tissue Doppler velocity, and strain (epsilon) imaging. Left atrial (LA) emptying fraction based on the change in areas (LAA-EF) and volumes (LAV-EF) were calculated. The LV reverse remodeling was defined by a reduction of LV end-systolic volume >10%. RESULTS: In the responders of LV reverse remodeling (n = 62), LAA-EF and LAV-EF were significantly increased (p < 0.001). Responders also had significant decrease in LA size area and volumetric measurements, both before (p < 0.05) and after atrial systole (p < 0.001). However, these parameters were unchanged in the nonresponders (n = 45, p = NS). In the responders, tissue Doppler velocity analysis showed improvement of contraction velocity in both left (p = 0.005) and right atria (p = 0.018), whereas epsilon in both atria were increased in all the phases of cardiac cycle, namely ventricular end-systole (p < 0.001), early diastole (p < 0.001), and late diastole (p = 0.007). CONCLUSIONS: Cardiac resynchronization therapy improves both left and right atrial pump function. The increase in atrial epsilon throughout the cardiac cycle is likely reflecting the improvement of atrial compliance. These changes lead to LA reverse remodeling with reduction of LA size before and after atrial systole.

The Pacing to Avoid Cardiac Enlargement (PACE) trial: clinical background, rationale, design, and implementation.

BACKGROUND: Deleterious effect on left ventricular (LV) function was observed with conventional right ventricular apical (RVA) pacing. Preliminary data suggested that biventricular pacing (BiV) may be superior to RVA pacing in patients with LV systolic dysfunction. However, the optimal pacing mode and site(s) for patients with normal LV systolic function remain controversial. METHODS: The Pacing to Avoid Cardiac Enlargement (PACE) trial is a prospective, multicenter, randomized, double blinded, parallel, controlled study aiming to determine if BiV pacing is better than conventional RVA pacing in preserving LV systolic function and preventing remodeling in patients with LV ejection fraction (EF) > or = 45% indicated for pacing. This study targets to recruit 200 patients from various centers in Asia, all of whom will receive BiV pacemaker implantation before being randomized to either atrial-based RVA or BiV pacing for 1 year. Their echocardiographic parameters including LV volumes, left ventricular ejection fraction (LVEF), and dyssynchrony index by tissue Doppler imaging, exercise capacity, quality of life assessment, neurohormone levels, and clinical events will be assessed before and after pacing. The primary endpoints are changes in LV end-systolic volume and LVEF 1 year after pacing. It is designed with 90% power to detect a 5% difference in the LVEF after 1 year of pacing. The enrollment began in 2006. It is expected to conclude at the end of 2008. CONCLUSION: The PACE trial will determine whether atrial-based BiV pacing can preserve LV systolic function and prevent LV adverse remodeling induced by conventional RVA pacing in patients with normal LV systolic function and standard pacing indication.

Comparison of intensive and low-dose atorvastatin therapy in the reduction of carotid intimal-medial thickness in patients with coronary heart disease.

BACKGROUND: Intensive statin therapy has been shown to improve prognosis in patients with coronary heart disease (CHD). It is unknown whether such benefit is mediated through the reduction of atherosclerotic plaque burden. AIM: To examine the efficacy of high-dose atorvastatin in the reduction of carotid intimal-medial thickness (IMT) and inflammatory markers in patients with CHD. DESIGN: Randomised trial. SETTING: Single centre. PATIENTS: 112 patients with angiographic evidence of CHD. INTERVENTIONS: A high dose (80 mg daily) or low dose (10 mg daily) of atorvastatin was given for 26 weeks. MAIN OUTCOME MEASURES: Carotid IMT, C-reactive protein (CRP) and proinflammatory cytokine levels were assessed before and after therapy. RESULTS: The carotid IMT was reduced significantly in the high-dose group (left: mean (SD), 1.24 (0.48) vs 1.15 (0.35) mm, p = 0.02; right: 1.12 (0.41) vs 1.01 (0.26) mm, p = 0.01), but was unchanged in the low-dose group (left: 1.25 (0.55) vs 1.20 (0.51) mm, p = NS; right: 1.18 (0.54) vs 1.15 (0.41) mm, p = NS). The CRP levels were reduced only in the high-dose group (from 3.92 (6.59) to 1.35 (1.83) mg/l, p = 0.01), but not in the low-dose group (from 2.25 (1.84) to 3.36 (6.15) mg/l, p = NS). A modest correlation was observed between the changes in carotid IMT and CRP (r = 0.21, p = 0.03). CONCLUSIONS: In patients with CHD, intensive atorvastatin therapy results in regression of carotid atherosclerotic disease, which is associated with reduction in CRP levels. On the other hand, a low-dose regimen only prevents progression of the disease.

Implantable cardiac resynchronization therapy devices to monitor heart failure clinical status.

Cardiac resynchronization therapy is a standard therapy for selected patients with heart failure. With advances in technology and storage capacity, the device acts as a convenient platform to provide valuable information about heart failure status in these high-risk patients. Unlike other modalities of investigation which may only allow one-off evaluation, heart failure status can be monitored by device diagnostics including heart rate variability, activity status, and intrathoracic impedance in a continuous basis. These parameters do not just provide long-term prognostic information but also may be useful to predict upcoming heart failure exacerbation. Prompt and early intervention may abort decompensation, prevent hospitalization, improve quality of life, and reduce health care cost. Moreover, this information may be applied to titrate the dosage of medication and monitor response to heart failure treatment. This review will focus on the prognostic and predictive values of heart failure status monitoring provided by these devices.

Diastolic and systolic asynchrony in patients with diastolic heart failure: a common but ignored condition.

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.