Changes In Dyssynchrony Research Articles

Acute deterioration in dyssynchrony and systolic function from Lot-CRT to LBBB pacing

Abstract Background Better electrical synchronization and left ventricular (LV) systolic function was recently reported in left bundle branch–optimized cardiac resynchronization therapy ( Lot-CRT ) when compared with conventional CRT. The implantation of left bundle branch pacing (LBBP) is less expensive, easier to operate and has shorter exposure time to X-ray than Lot-CRT. Purpose To observe whether there are negative changes in dyssynchrony and LV systolic function when switched from Lot-CRT to LBBP. determine whether LBBP pacing alone can replace CRT therapy. Methods 30 patients (21 males, 64.4±9.5 years, 43% with persistent atrial fibrillation) who fulfilled the criteria of CRT implantation received Lot-CRT. The right atrial electrode of the patients with atrial fibrillation or the right ventricular electrode of those with sinus rhythm was implanted into the left bundle branch area. After six months, 20 patients whose LV ejection fraction (LVEF) increased by more than 5% and New York Heart Association functional class increased by at least 1 grade were selected for further investigation. Right and left ventricular pacemaker electrodes were programmed to shut off, leaving only the left bundle branch area pacing for one month. The LV size, systolic function, interventricular mechanical delay (IVMD), and LV mechanical dyssynchrony (LVMD) were compared by using two-dimensional speckle tracking echocardiography. Results It was found that QRS duration slightly widened, the LA size increased, the LV size slightly increased and LVEF decreased, p<0.05. There was no statistical significance in the IVMD (p=0.064). The LV mechanical dyssynchrony increased significantly, p<0.001. Conclusions Deteriotation of LV dyssynchrony and systolic function was recorded when Lot-CRT to LBBP for a short period in recovering patients with systolic dysfunction. It indicates that LBBP may not yet maintain the benefits of Lot-CRT in this group of patients.The comparison between Lot-CRT and LBBP

The influence of afterload on left ventricular contractility: 2D-strain and dyssynchrony in stress echocardiography

Abstract Funding Acknowledgements Type of funding sources: None. Background Hypertensive response to exercise (HRE) has negative prognostic value but its impact on the left ventricle (LV) contractility and on stress echocardiography (SE) results remains controversial. The global longitudinal strain (GLS) and LV dyssynchrony changes in response to afterload increase were shown even in patients with narrow QRS at rest, but not on exertion. Purpose We aimed to analyze the relation between the blood pressure (BP) during SE and LV GLS and dyssynchrony changes. Methods We performed exercise SE on treadmill in 96 patients without coronary artery stenosis (invasive or CT coronary angiography). Patients divided into two groups: HRE (n = 41) and normal response to exercise (NRE) (n = 55). We analyzed GLS and standard deviation of time between the onset of QRS and segmental longitudinal strain peaks (STE-TIME SD) using speckle tracking and 3d-ejection fraction (EF) at rest and on exertion. Results 2D-EF increase was higher in patients with NRE, but 3D-EF did not differ between groups. Wall motion abnormalities (WMA) on peak stress were detected more often in patients with HRE who had higher wall motion score index (WMSI). GLS on exertion and its increment were lower in HRE group (Fig. 1 - "Bull’s eye" diagrams of GLS at rest and on exertion in patient with NRE (upper panel) and HRE (lower panel)). Among dyssynchrony markers we revealed higher values of STE-TIME SD on exertion in HRE group (Table 1). Moreover the analysis showed positive correlations between BP level on exertion and peak GLS (r = 0.56, p < 0.0001), GLS increase (r = 0.54, p < 0.0001) and STE-TIME SD on exertion (r = 0.27, p < 0.02) Conclusions HRE is associated with less increment in GLS and 2D-EF on exertion. Besides LV dyssynchrony signs can appear in response to exaggerated afterload increase even in patients with narrow QRS complexes. Patients with HRE more often show stress-induced WMA and have greater WMSI on exertion in absence of coronary artery lesions, thus HRE can alter the specificity of the test in transient ischemia detection. Table 1 HRE NRE p Δ-2D ejection fraction 5.0 (4.0; 7.0) 10.0 (8.0; 12.5) <0.0000001 Δ-3D ejection fraction 8.25 (4.0; 8.25) 8.24 (8.15; 11.65) 0.09 Wall motion abnormalities on exertion 46.34% 1.8% <0.00001 Wall motion score index 1.0 (1.0; 1.18) 1.0 (1.0; 1.0) 0.00013 GLS on exertion -21.0 (-22.0; -19.0) -24.0 (-26.5; -23.0) <0.0000001 ΔGLS 0.0 (-1.0; 2.0) 4.0 (2.0; 6.0) <0.0000001 STE-TIME SD-IMPOST 42.0 (35.0; 53.0) 35.0 (27.5; 45.0) 0.012 Left ventricle systolic function and dyssynchrony in two groups. Abstract Figure 1.

Global longitudinal strain and left ventricle dyssynchrony changes during stress echocardiography in response to antihypertensive treatment optimization

Abstract Funding Acknowledgements Type of funding sources: None. Background. The positive effect of blood pressure (BP) lowering medications on global longitudinal strain (GLS) and left ventricle (LV) dyssynchrony even in patients with narrow QRS complexes at rest has been established at rest. The dynamic changes of GLS and dyssynchrony markers on exertion are still remain underinvestigated, especially in patients with hypertensive response to exercise (HRE). Purpose. The aim of the study was to define if any changes in GLS and dyssynchrony markers assessed during exercise stress echocardiography (SE) can occur after the optimization of antihypertensive treatment. Methods. 18 patients without coronary artery stenosis on coronary angiography, underwent exercise SE on treadmill. All patients had arterial hypertension and HRE, defined as elevation of systolic BP ≥190 mmHg in women and ≥210 mmHg in men or ≥180 mmHg from the second stage of standard Bruce protocol. After optimization of BP lowering medications (addition/dose correction of ACEI/ARB, CCB or diuretics) we repeated SE within 138.5 ± 85.1 days. GLS and dyssynchrony markers at rest and on exertion from both tests were subsequently analyzed with the QLab and 3D-Q Advanced software. Results. The target systolic BP at rest was reached in all 18 patients (145.8 ± 21.8 mmHg vs. 126.1 ± 14.5 mmHg, p = 0.03), moreover exercise BP on exercise decreased significantly (209.4 ± 15.4 mmHg vs. 170.8 ± 14.4 mmHg, p = 0.003). We observed improvement in tolerance to exertion (7.2 ± 2.4 METs vs. 8.7 ± 3.0 METs, p = 0.0004), 2D and 3D-ejection fraction increase (4.7 ± 2.2% vs. 8.8 ± 2.1%, p = 0.0002 and 3.9 ± 4.9% vs. 10.8 ± 8.5, p = 0.03) and significant reduction of wall motion score index (1.21 ± 0.24 vs. 1.03 ± 0.11, p = 0.001). The speckle tracking analysis revealed increase in GLS on exertion (-20.4 ± 3.5 vs. -23.78 ± 3.2, p = 0.001) and its increment (-0.28 ± 2.1 vs. 3.17 ± 1.89, p = 0.0006), while the level of rest GLS remained unchanged (-20.61 ± 2.9 vs. -20.61 ± 2.6, p = 0.9) (Fig. 1). The dyssynchrony marker STE-TIME SD-IMPOST (standard deviation of time from QRS onset to peak segmental longitudinal strain on exertion) has also diminished (47.3 ± 18.4 vs. 33.8 ± 12.2, p = 0.005). Conclusions. Stress-induced wall motion abnormalities and poor increase/decrease in GLS observed in patients with HRE even in absence of coronary artery stenosis can resolve or diminish after antihypertensive treatment optimization. Speckle tracking LV-dyssynchrony markers in patients with narrow QRS complexes can also decrease in response to BP-lowering medications. Abstract Figure 1.

Dynamic Left Ventricular Dyssynchrony Assessed on 3-Dimensional Speckle-Tracking Area Strain During Dobutamine Stress Has a Negative Impact on Cardiovascular Events in Patients With Idiopathic Dilated Cardiomyopathy

Left ventricular (LV) dyssynchrony is not a stable phenomenon, but rather, changes dynamically. Given that the prognostic impact of dynamic dyssynchrony has not yet been elucidated, the objective was to investigate the clinical impact of dynamic dyssynchrony on patients with dilated cardiomyopathy (DCM). Seventy DCM patients with ejection fraction 32±9% were retrospectively recruited, and 3-dimensional speckle-tracking area strain was used to measure both contractile reserve and changes in dyssynchrony during dobutamine stress. The standard deviation of time-to-peak area strain was adopted as the systolic dyssynchrony index. Event-free survival was then tracked over a 13-month period. A ≥7.55% increase in systolic dyssynchrony index during dobutamine stress (Δsystolic dyssynchrony index) was the best predictor of cardiovascular events with 77% sensitivity and 88% specificity. Multivariate Cox analysis indicated that not only the absence of contractile reserve (Δglobal area strain ≤21.1%: hazard ratio [HR], 15.29; P=0.01), but the presence of dynamic dyssynchrony (ΔLV dyssynchrony ≥7.55%: HR: 7.591; P=0.003) was an independent predictor of cardiovascular events. Importantly, absence of dynamic dyssynchrony and presence of contractile reserve were associated with the most favorable outcome (98%), whereas the reverse condition was associated with the worst outcome (20%, P<0.001). Dynamic dyssynchrony is a potential predictor of cardiovascular events in patients with DCM, while assessment of dynamic dyssynchrony in combination with contractile reserve may further improve prognostic risk stratification.

Abstract 9449: Dynamic Left Ventricular Dyssynchrony Assessed by Three Dimensional Speckle-Tracking Area Strain during Dobutamine Stress Has a Negative Impact on Cardiovascular Events in Patients with Idiopathic Dilated Cardiomyopathy

Background: Left ventricular (LV) dyssynchrony is not a stable phenomenon, but rather, changes dynamically with changes in hemodynamic conditions. Since the prognostic impact of dynamic dyssynchrony has not yet been elucidated, our objective was to investigate, by using novel three-dimensional (3-D) speckle-tracking area strain, the clinical impact of dynamic dyssynchrony on patients with idiopathic dilated cardiomyopathy (DCM). Methods: Forty-eight DCM patients with ejection fractions of 33±9% (all &lt;45%) were prospectively recruited, and 3-D speckle-tracking area strain was used to measure both contractile reserve and changes in dyssynchrony during dobutamine stress (20μ g/kg/min). The standard deviation of time-to-peak area strain from 16 LV segments was adopted as the LV dyssynchrony index. Event-free survival was then tracked over a 12-month period. Results: A ≥6.94% increase in the dyssynchrony index during dobutamine stress (Δdyssynchrony index) was the best predictor of cardiovascular events with 90% sensitivity and 82% specificity. Multivariate Cox analysis indicated that not only the absence of contractile reserve ([[Unable to Display Character: &amp;#8710;]]global area strain ≤3.89%, p=0.03), but also the presence of dynamic dyssynchrony ([[Unable to Display Character: &amp;#8710;]]LV dyssynchrony ≥6.94%, p=0.04) was an independent predictors of cardiovascular events. Patients with dynamic dyssynchrony had a significantly poorer prognosis than those without (log rank p&lt;0.001). Importantly, absence of dynamic dyssynchrony and presence of contractile reserve during dobutamine stress were associated with the most favorable outcome (100%), whereas the reverse condition was associated with the worst outcome (20%, p&lt;0.001). Conclusions: Dynamic dyssynchrony during dobutamine stress constitutes a potential predictor of cardiovascular events in patients with DCM, while assessment of dynamic dyssynchrony in combination with contractile reserve may further improve prognostic risk stratification.

Assessment of mechanical dyssynchrony in fulminant myocarditis.

It is often difficult to assess ventricular synchrony in patients with fulminant myocarditis. We report a pediatric case of fulminant myocarditis where clinical course and changes in dyssynchrony were followed with speckle tracking echocardiography. Dyssynchrony of the left ventricle changed day by day. It was useful to assess the progression of ventricular damage and its recovery.

The role of pacing-induced dyssynchrony in left ventricular remodeling associated with long-term right ventricular pacing for atrioventricular block

AimsPatients with atrioventricular (AV) block can develop left ventricular (LV) dysfunction with long-term right ventricular pacing (RVP). We investigated the role of RVP-induced LV dyssynchrony in this adverse remodeling. Methods and ResultsNineteen patients with normal LV function undergoing pacemaker implantation for AV block were included. Right ventricular pacing leads were positioned at the apex. Two-dimensional and tissue Doppler echocardiography was performed before and immediately after implantation and at the end of follow-up. The maximal delay between peak velocities of opposing basal LV walls was measured using tissue Doppler echocardiography, as an index of LV dyssynchrony. With the initiation of RVP, LV dyssynchrony increased in some patients and decreased in others, as compared with intrinsic rhythm. The RVP-induced change in dyssynchrony inversely correlated with baseline dyssynchrony (r = −0.686, P = .010). After 28 ± 3.6 months, LV end-systolic volume (ESV) increased, and ejection fraction decreased (from 34 ± 12 to 40 ± 20 mL, P = .010 and from 65% ± 6% to 56% ± 11%, P < .001, respectively). The change in LV ESV was greater in patients with 60% or greater cumulative RVP (9.9 vs 0.08 mL, P = .027). Within this frequently paced group, the RVP-induced change in dyssynchrony correlated with the increase in LV ESV (r = 0.727, P = .026). Patients who had a 15% or greater increase in LV ESV had greater RVP-induced change in dyssynchrony (28.4 vs −7.8 milliseconds, P = .037). ConclusionSome patients with AV block experience an increase in LV dyssynchrony with RVP. Increased LV dyssynchrony predicts adverse LV remodeling during long-term follow-up.

Cardiac Resynchronization by Cardiosphere-Derived Stem Cell Transplantation in an Experimental Model of Myocardial Infarction

Cardiosphere-derived stem cell (CDC) transplantation can improve global left ventricular ejection fraction (LVEF) after myocardial infarction (MI). The aim of this study was to examine the effects of CDC transplantation on regional function and dyssynchrony after MI. Two million rat CDCs (n= 7) or phosphate-buffered saline (n= 7) was injected into the infarct regions of Wistar Kyoto rats. Infarct size and CDC localization were evaluated by positron emission tomography (n= 7). Two-dimensional and strain echocardiography were performed at 1 and 4 weeks after MI. LVEF, circumferential strain, and time to peak circumferential strain were measured in the basal and apical short-axis views. Dyssynchrony was defined as the maximal difference of time to peak circumferential strain of opposing segments in each short-axis view. Engraftment was measured by quantitative polymerase chain reaction. Positron emission tomography revealed that infarct size was 15.4 ± 3.6% of the left ventricle and that CDCs were localized to the infarct and border zone. CDC transplantation improved mean LVEF (45 ± 8% to 52 ± 7%, P= .02), mean circumferential strain (-7 ± 2% to -10 ± 1%, P= .02), and mean dyssynchrony (45 ± 10 to 28 ± 11 m sec, P= .04) of the infarct/peri-infarct zone from 1 to 4 weeks after MI, despite CDC engraftment of only 2.4 ± 3%. In contrast, mean LVEF (48 ± 5% to 40 ± 4%, P= .03) and mean circumferential strain (-8 ± 2% to -7 ± 1%, P= .02) of the infarcted region deteriorated, with no significant change in dyssynchrony (42 ± 12 vs 46 ± 13 m sec, P= .60) in the saline group during the same time period. Change in LVEF was correlated with change in circumferential strain (r= -0.8, P= .002) and dyssynchrony (r= 0.6, P= .02) of the infarct/peri-infarct region at 4 weeks after MI. CDC therapy enhanced LVEF by improving circumferential strain and decreasing dyssynchrony of the infarct/peri-infarct region at 4 weeks, but not 1 week, after MI. Cellular resynchronization therapy using CDCs may be an alternative to traditional electrical cellular resynchronization therapy in post-MI dyssynchrony.

Left ventricular systolic torsion correlates global cardiac performance during dyssynchrony and cardiac resynchronization therapy

Left ventricular (LV) systolic torsion is a primary mechanism contributing to stroke volume (SV). We hypothesized that change in LV torsion parallels changes in global systolic performance during dyssynchrony and cardiac resynchronization therapy (CRT). Seven anesthetized open chest dogs had LV pressure-volume relationship. Apical, basal, and mid-LV cross-sectional echocardiographic images were studied by speckle tracking analysis. Right atrial (RA) pacing served as control. Right ventricular (RV) pacing simulated left bundle branch block. Simultaneous RV-LV free wall and RV-LV apex pacing (CRTfw and CRTa, respectively) modeled CRT. Dyssynchrony was defined as the time difference in peak strain between earliest and latest segments. Torsion was calculated as the maximum difference between the apical and basal rotation. RA pacing had minimal dyssynchrony (52 ± 36 ms). RV pacing induced dyssynchrony (189 ± 61 ms, P < 0.05). CRTa decreased dyssynchrony (46 ± 36 ms, P < 0.05 vs. RV pacing), whereas CRTfw did not (110 ± 96 ms). Torsion during baseline RA was 6.6 ± 3.7°. RV pacing decreased torsion (5.1 ± 3.6°, P < 0.05 vs. control), and reduced SV, stroke work (SW), and dP/dt(max) compared with RA (21 ± 5 vs. 17 ± 5 ml, 252 ± 61 vs. 151 ± 64 mJ, and 2,063 ± 456 vs. 1,603 ± 424 mmHg/s, respectively, P < 0.05). CRTa improved torsion, SV, SW, and dP/dt(max) compared with RV pacing (7.7 ± 4.7°, 23 ± 3 ml, 240 ± 50 mJ, and 1,947 ± 647 mmHg/s, respectively, P < 0.05), whereas CRTfw did not (5.1 ± 3.6°, 18 ± 5 ml, 175 ± 48 mJ, and 1,699 ± 432 mmHg/s, respectively, P < 0.05). LV torsion changes covaried across conditions with SW (y = 0.94x+12.27, r = 0.81, P < 0.0001) and SV (y = 0.66x+0.91, r = 0.81, P < 0.0001). LV dyssynchrony changes did not correlate with SW or SV (r = -0.12, P = 0.61 and r = 0.08, P = 0.73, respectively). Thus, we conclude that LV torsion is primarily altered by dyssynchrony, and CRT that restores LV performance also restores torsion.

Mechanism of decrease in mitral regurgitation after cardiac resynchronization therapy: optimization of the force-balance relationship.

Cardiac resynchronization therapy (CRT) has been shown to reduce functional mitral regurgitation (MR). It has been proposed that the mechanism of MR reduction relates to geometric change or, alternatively, changes in left ventricular (LV) contractile function. Normal mitral valve (MV) function relies on a balance between tethering and closing forces on the MV leaflets. Functional MR results from a derangement of this force-balance relationship, and CRT may be an important modulator of MV function by its ability to enhance the force-balance relationship on the MV. We hypothesized that CRT improves the comprehensive force balance acting on the valve, including favorable changes in both geometry and LV contractile function. We examined the effect of CRT on 34 patients with functional MR before and after CRT (209+/-81 days). MR regurgitant volume, closing forces on MV (derived from Doppler transmitral pressure gradients), including dP/dt and a factor (closing pressure ratio) expressing how long the peak closing gradient is maintained over systole (closing pressure ratio=velocity time integral/MR peak velocityxmitral regurgitation time), and dyssynchrony by tissue Doppler were measured. End-diastolic volume, end-systolic volume, mitral valve annular area (MAA) and contraction (percent change in MAA from end-diastole to midsystole), leaflet closing area (leaflet area during valve closure), and tenting volume (volume under leaflets to annular plane) were measured by 3D echocardiography. After CRT, end-diastolic volume (253+/-111 versus 221+/-110 mL, P<0.001) and end-systolic volume (206+/-97 versus 167+/-91 mL, P<0.001) decreased and ejection fraction (19+/-6 versus 27+/-9%, P<0.001) increased. MR regurgitant volume decreased from 35+/-17 to 23+/-14 mL (P<0.001), MAA from 11.6+/-3.5 to 10.5+/-3.1 cm(2) (P<0.001), leaflet closing area from 15.4+/-5 to 13.7+/-3.8 cm(2) (P<0.001), and tenting volume from 5.7+/-2.6 to 4.6+/-2.2 mL (P<0.001). Peak velocity (and therefore transmitral closing pressure) was more sustained throughout systole, as reflected by the increase in the closing pressure ratio (0.77+/-0.1 versus 0.84+/-0.1 before CRT versus after CRT, P=0.01); dP/dt also improved after CRT. There was no change in dyssynchrony or MAA contraction. Reduction in MR after CRT is associated with favorable changes in MV geometry and closing forces on the MV. It does so by favorably affecting the force balance acting on the MV in 2 ways: reducing tethering through reversal of LV remodeling and increasing the systolic duration of peak transmitral closing pressures.

Left ventricular mechanical dyssynchrony is load independent at rest and during endotoxaemia in a porcine model

In diseased or injured states, the left ventricle displays higher degrees of mechanical dyssynchrony. We aimed at assessing mechanical dyssynchrony ranges in health related to variation in load as well as during acute endotoxin-induced ventricular injury. In 16 juvenile anaesthetized pigs, a five-segment conductance catheter was placed in the left ventricle as well as a balloon-tipped catheter in the inferior vena cava. Mechanical dyssynchrony during systole, including dyssynchrony time in per cent during systole and internal flow fraction during systole, were measured at rest and during controlled pre-load reduction sequences, as well as during 3 h of endotoxin infusion (0.25 microg kg(-)1 h(-1)). Systolic dyssynchrony and internal flow fraction did not change during the course of acute beat-to-beat pre-load alteration. Endotoxin-produced acute pulmonary hypertension by left ventricular dyssynchrony measures was not changed during the early peak of pulmonary hypertension. Endotoxin ventricular injury led to progressive increases in systolic mechanical segmental dyssynchrony (7.9 +/- 1.2-13.0 +/- 1.3%) and ventricular systolic internal flow fraction (7.1 +/- 2.4-16.6 +/- 2.8%), respectively for baseline and then at hour 3. There was no localization of dyssynchrony changes to segment or region in the ventricular long axis during endotoxin infusion. These results suggest that systolic mechanical dyssynchrony measures may be load independent in health and during acute global ventricular injury by endotoxin. More study is needed to validate ranges in health and disease for parameters of mechanical dyssynchrony.

Coherent Averaging Improves the Evaluation of Left Ventricular Dyssynchrony by Conductance Catheter

Coherent averaging is a technique to recover the response to repetitively applied stimuli when that response is embedded in random noise. We derived novel indices for left ventricular dyssynchrony estimation from volume-catheter signals using coherent averaging procedure: mechanical dyssynchrony (DYSCoh) internal flow fraction (IFFCoh) and mechanical dispersion (DISPCoh). The percentage power of non-repetitive components in the volume signals (ResTotAvg) was also estimated. The aims of the study were to evaluate the indices, characterizing repetitive and non-recurrent components of the conductance-volume signals, and to assess the ability of these indices to detect the changes in dyssynchrony induced by biventricular pacing (BIV). We compared the results obtained in 20 heart failure patients indicated to BIV (HF Group) during spontaneous conduction with the results from 12 patients with preserved ventricular function (non-HF Group), and with those obtained during BIV. DISPCoh and ResTotAvg were significantly different in HF compared to non-HF group, and identified HF patients with high accuracy (area under curve at ROC analysis > 0.8). These indices also demonstrated significant differences after BIV (p = 0.047 and p = 0.037 respectively) and their baseline values correlated with the acute increase of stroke volume (r = 0.64 and r = 0.78, both with p < 0.005). Coherent averaging-based indices permit independent quantification and differentiation of repetitive components of ventricular dyssynchrony from non-recurrent mechanical non-uniformities, which seem associated with HF and conduction disturbances. These indices identified HF patients with high accuracy, and were able to describe the reversal of dyssynchrony caused by BIV and to predict the acute hemodynamic improvement.

Left Ventricular Dyssynchrony in Patients with Normal Ventricular Systolic Function Referred for Exercise Echocardiography

Exercise testing is often normal despite the presence of exertional symptoms. We hypothesized that left ventricular (LV) dyssynchrony might occur in some patients in the absence of ischemia, LV dysfunction, or wide QRS, and might contribute to exertional symptoms and diminished exercise capacity. Echocardiographic parameters were assessed before and with exercise in 40 patients (age 62 +/- 8 years, 27 with exertional symptoms). All had normal clinically indicated exercise echocardiograms and narrow QRS. The time to peak systolic velocity (Ts) was measured in 12 segments to calculate the standard deviation (Ts-SD) and the maximal difference (Ts-diff). At rest, 25 patients (63%) had dyssynchrony by Ts-SD. With exercise, mean Ts-SD did not increase significantly (34.9 +/- 19.3 ms vs 39.5 +/- 27.2 ms, P = .28). However, Ts-SD increased by greater than 40% in 15 patients (37.5%), remained stable in 19 patients (47.5%), and decreased by greater than 40% in 6 patients (15%). Similar responses were observed for Ts-diff. Patients with exercise-induced dyssynchrony were not more likely to have symptoms. Exercise capacity was inversely correlated with resting Ts-SD (r = -0.37, P = .02) and resting Ts-diff (r = -0.38, P = .02), but not with exercise-induced changes in dyssynchrony. Patients with resting dyssynchrony had higher resting heart rate (73 +/- 12 vs 63 +/- 11 beats/min, P = .02). LV dyssynchrony may occur more frequently than previously thought and may develop with exercise in the absence of ischemia. Exercise-induced LV dyssynchrony was not related to exertional symptoms or exercise capacity. Patients with dyssynchrony at rest had a higher resting heart rate and achieved a lower workload; this may indicate early myocardial impairment.

The Impact of Exercise-Induced Changes in Intraventricular Dyssynchrony on Functional Improvement in Patients with Nonischemic Cardiomyopathy

The assessment of dynamic intraventricular dyssynchrony has been reported to be feasible in a clinical setting. However, its prognostic implication in functional improvement has not yet been investigated. Symptom-limited, supine bicycle exercise was performed on 41 patients with nonischemic cardiomyopathy (52 +/- 12 years, ejection fraction < 40%). Using Doppler tissue imaging, the average of peak systolic velocities at 6 basal segments was obtained at rest and peak exercise. Dyssynchrony index (Ts-SD12) was defined as the SD of the time to peak systolic velocities at 12 left ventricular segments. The percent change of end-systolic volume (%Delta ESV) was calculated at follow-up. A 15% or greater reduction in end-systolic volume (%Delta ESV < -15%) was considered as functional improvement. During exercise, changes in dyssynchrony (Delta Ts-SD12) were individually variable. Average of peak systolic velocities (V) at 6 basal segments at peak exercise independently correlated with Ts-SD12 at peak exercise (beta = -0.541, P < .001). Follow-up echocardiography was performed on 35 patients after medical treatment for 13.0 +/- 4.9 months. There was significant association of %Delta ESV with the change in mitral regurgitation (r = 0.434, P = .009), disease duration (r = 0.343, P = .045), QRS interval (r = 0.347, P = .041), and Delta Ts-SD12 (r = 0.511, P = .002). Multivariate analysis identified Ts-SD12 measured at peak exercise as the strongest predictor for functional improvement (%Delta ESV: beta = 0.577, P < .001; and Delta ejection fraction: beta = -0.563, P < .001). In patients with heart failure, dynamic dyssynchrony can be assessed during exercise. Ts-SD12 at peak exercise may be an independent predictor for reverse remodeling with medical treatment.

Systolic and Diastolic Dyssynchrony are Unaffected by Revascularization of Viable, Dysfunctional Myocardium

There is little information about change in dyssynchrony with stress or after revascularization. Subjects were recruited to this study if they were referred for revascularization of viable, dysfunctional myocardium. The inclusion criteria were ejection fraction of < or = 35%, sinus rhythm, and QRS duration < or = 120 msec. Tissue Doppler echocardiography with dobutamine stress was performed at baseline and 6 months after revascularization, and dyssynchrony indices (T-sd(c)) were calculated. A total of 25 patients completed a 6-month follow-up. The mean (standard deviation) resting systolic and diastolic T-sd(c) at baseline were 49.3 (18.2) msec and 41.0 (29.4) msec, respectively, with little change during dobutamine stress. After revascularization, there were no significant differences in mean T-sd(c) although there was a modest effect on systolic T-sd(c) at recovery (46.0 [23.1] msec baseline, 34.2 [20.1] msec follow-up, mean difference 11.8 msec, 95% confidence interval 0.3-23.4 msec, P = .046). Resting dyssynchrony in ischemic left ventricular dysfunction does not seem to be altered by dobutamine stress or revascularization.

Abstract 2817: The Impact of Exercise-Induced Changes in Intraventricular Dyssynchrony on the Functional Improvement in Patients with Non-Ischemic Cardiomyopathy

Background: We studied whether dynamic changes in LV asynchrony may affect the functional improvement of LV in medically treated patients with non-ischemic cardiomyopathy (CMP). Methods: Supine bicycle exercise was performed in 41 patients (age 51±12 years, EF 33±8%). Using tissue Doppler imaging, the average of peak systolic velocities of 6 basal LV segments were obtained at rest (V b ) and peak exercise (V p ). ΔV was calculated by [V p -V b ], reflecting the contractile reserve. Dyssynchrony index (SD 4 ) was defined as the standard deviation of the time to peak systolic velocities at 4 basal &amp; mid segments of septum and lateral wall on apical 4 chamber view. ΔSD 4 was calculated as [peak exercise SD 4 - resting SD 4 ]. Follow-up echocardiography was done in 35 patients after medication for 11.2±4.2 months. Functional changes of LV was assessed by ΔEF FU and %change of ESV (ΔESV FU ). Results: Baseline SD 4 was 24±17 ms. During exercise, SD 4 increased in 24 patients (ΔSD 4 =+14±12 ms), whereas decreased in 17 patients (ΔSD 4 =-17±14 ms). ΔSD 4 correlated with ΔV (r=-0.36, p=0.021) and exercise-induced increase in MR (ΔJet/LA area (%); r=0.31, p=0.05 and ΔPISA radius at 40cm/s of aliasing v; r=0.46, p=0.003). ΔV and ΔPISA were related to the follow-up change of LV function. Especially, ΔSD 4 independently correlated with ΔEF FU (β= -0.82, p&lt;0.001) and also with ΔESV FU (β= 0.40, p=0.021)(Fig ). However, baseline SD 4 didn’t affect ΔEF FU . On ROC curve analysis, sensitivity and specificity of ΔSD 4 &lt;4.0 ms were 82% and 78% for predicting ΔEF FU &gt;+5% and 70% and 63% for predicting ΔESV FU &lt;-15%. Conclusion : Exercise-induced changes in dyssynchrony (ΔSD 4 ) can predict the functional improvement in non-ischemic CMP.

Abstract 1604: Response to Cardiac Resynchronization Therapy Differs Between Patients With and Without Previous Right Ventricular Pacing

Background: Previous large studies on the effects of cardiac resynchronization therapy (CRT) in patients with heart failure have generally excluded patients previously paced from the right ventricle (RV). Previously RV paced patients (RVp) can exhibit an iatrogenic cause of dyssynchrony and reduced systolic function and thus, may respond differently to CRT than patients not previously RV paced (nRVp). The purpose of this study was to test the hypothesis that RVp patients have greater improvements in left ventricular systolic function, volumes, and dyssynchrony in response to CRT than nRVp. Methods: Standard echocardiograms with tissue Doppler imaging were performed before and after chronic CRT in RVp (n = 21, 16 male) and nRVp (n = 70, 54 male) heart failure patients. Ejection fraction (EF), left ventricular end diastolic (LVEDV) and systolic (LVESV) volumes were calculated using the biplane Simpson’s method. Longitudinal dyssynchrony was calculated as the standard deviation of time to peak displacement (TT-12) of 12 segments in the apical views. Using mid-ventricular short axis views and speckle-tracking methods, radial dyssynchrony (Rad dys ) was calculated as the maximal time difference between six myocardial segments for peak radial strain. Echo response was defined as ≥ 15% reduction in LVESV. Results are reported as mean ± SD. Results: Significant baseline differences (p &lt; 0.05) were observed between groups (RVp vs. nRVp) for age (74 ± 13 vs. 67 ± 13 year), follow-up time (6.1 ± 1.8 vs. 4.6 ± 2.1 months), LVEDV (154.3±50.8 vs.185.3±56.9 mL), and a trend for LVESV (112.4 ± 40.6 vs. 134.9 ± 47 mL, p = 0 .05). No differences were observed for EF, etiology of heart failure, and dyssynchrony measures between groups at baseline. Echo response rate was significantly ( p &lt; 0.05) greater in RVp (76%) than nRVp (57%). After adjusting for baseline differences, RVp had greater improvement in EF (14 ± 9 vs. 8 ± 7%, p &lt; 0.05) and LVESV (−33 ± 18 vs. −20 ± 21%, p &lt; 0.05). After adjustment for follow-up time, no difference was observed for change in dyssynchrony between groups. Conclusion: RVp patients upgraded to CRT exhibit greater improvements in systolic function and ventricular remodeling as compared to nRVp patients.

Prognostic Value of Intraventricular Dyssynchrony According to Clinical Stage of Left Ventricular Impairment

Intraventricular dyssynchrony has prognostic implications in patients who have severe functional limitation and decreased ejection fraction. Patients with less advanced cardiac disease often exhibit intraventricular dyssynchrony, but there is little available information about its prognostic relevance in such patients. We investigated the prognostic effect of intraventricular dyssynchrony on outcome in 318 patients with known or suspected coronary artery disease who were classified according to the presence or absence of left ventricular dysfunction and heart failure symptoms. Mortality was considered the primary end point over a median follow-up of 56 months, and a Cox proportional hazards model was used for survival analysis. Despite a low prevalence (8%) of left bundle branch block, there was a high prevalence of intraventricular dyssynchrony even in patients without symptomatic heart failure. The magnitude of intraventricular dyssynchrony correlated poorly with QRS duration (r = 0.25), end-systolic volume index (r = 0.27), and number of scar segments (r = 0.25). There were 58 deaths during follow-up. Ventricular volume, ischemic burden, and magnitude of intraventricular dyssynchrony predicted outcome, but magnitude of intraventricular dyssynchrony was an independent predictor of survival only in patients with asymptomatic left ventricular dysfunction. In conclusion, patients with known or suspected coronary artery disease have a high prevalence of intraventricular dyssynchrony. Although ventricular volume, ischemic burden, and intraventricular dyssynchrony are potentially important prognostic markers, the relative importance of intraventricular dyssynchrony changes with the clinical setting and may be greatest in patients with preclinical disease.

Dynamic Ventricular Dyssynchrony: An Exercise-Echocardiography Study

We sought to assess the effects of exercise on ventricular dyssynchrony in patients with normal and depressed left ventricular (LV) function. Asynchronous myocardial contraction adversely influences ventricular function and is associated with a poor prognosis in heart failure. Exercise-induced changes in ventricular dyssynchrony may be an important determinant of dynamic changes in cardiac output and mitral regurgitation. A total of 65 consecutive heart failure patients and 50 matched healthy control patients underwent exercise echocardiography. Conventional and tissue Doppler parameters were measured before and during symptom-limited exercise. Left ventricular dyssynchrony was defined as the standard deviation of 12 LV segmental electromechanical delays. Analysis of the control group allowed delimitation of normal cutoff values. In patients with normal left ventricular function, exercise did not modify the extent of LV asynchrony. In contrast, in heart failure patients, LV dyssynchrony increased by at least 20% in 34%, remained stable in 37%, and decreased by at least 20% in 29%. Moreover, 26% of heart failure patients had either exercise induction or normalization of ventricular dyssynchrony. A significant association was found between exercise-induced changes in dyssynchrony and the presence of ischemic cardiomyopathy (p < 0.05). Rest-exercise differences in ventricular dyssynchrony were correlated with changes in cardiac output and mitral regurgitation (r = -0.63 and 0.56, respectively). In heart failure patients, exercise can alter the magnitude of ventricular dyssynchrony. Some patients have a response to exertion with induction of ventricular dyssynchrony, whereas others show normalization. Changes in ventricular dyssynchrony during exercise correlate with alterations in cardiac output and mitral regurgitation.