Change In Left Ventricular End-systolic Volume Research Articles

SmartDelay Determined AV Optimization: A Comparison of AV Delay Methods Used in Cardiac Resynchronization Therapy (SMART-AV): Rationale and Design

The clinical benefit of cardiac resynchronization therapy (CRT) for patients with moderate-to-severely symptomatic heart failure, left ventricular systolic dysfunction, and ventricular conduction delay is established. However, some patients do not demonstrate clinical improvement following CRT. It is unclear whether systematic optimization of the programmed atrioventricular (AV) delay improves the rate of clinical response. SMART-AV is a randomized, multicenter, double-blinded, three-armed trial that will investigate the effects of optimizing AV delay timing in heart failure patients receiving CRT + defibrillator (CRT-D) therapy. A minimum of 950 patients will be randomized in a 1:1:1 ratio using randomly permuted blocks within each center programmed to either DDD or DDDR with a lower rate of 60. The study will include echocardiographic measurements of volumes and function [e.g., left ventricular end-systolic volume (LVESV)], biochemical measurements of plasma biomarker profiles, and functional measurements (e.g., 6-minute hall walk) in CRT-D patients who are enrolled and randomized to fixed AV delay (i.e., 120 ms), AV delay determined by electrogram-based SmartDelay, or an AV delay determined by echocardiography (i.e., mitral inflow). Patients will be evaluated prior to initiation of CRT, 3 and 6 months post-implant. The primary endpoint is the relative change in LVESV at 6 months between the groups. Patient enrollment commenced in May 2008 and the study is registered at clinicaltrials.gov. SMART-AV is a randomized, clinical trial designed to evaluate three different methods of AV delay optimization to determine whether systematic AV optimization is beneficial for patients receiving CRT for 6 months post-implant.

Effect of repeated intracoronary injection of bone marrow cells in patients with ischaemic heart failure☆ The Danish Stem Cell study—Congestive Heart Failure trial (DanCell‐CHF)

It has been suggested that myocardial regeneration may be achieved by a single intracoronary bone marrow derived stem cell infusion in selected patients with ischaemic heart disease. The effect is uncertain in patients with chronic ischaemic heart failure and it is not known whether repeated infusions would have additional positive effects. To assess whether two treatments of intracoronary infusion of bone marrow stem cells, administered 4 months apart, could improve left ventricular (LV) systolic function in patients with chronic ischaemic heart failure. The study was prospective and non-randomised, comprising an observational baseline period of 4 months followed by an interventional period of 12 months. Intracoronary bone marrow cell infusion was performed at the end of the baseline period and repeated 4 months later. 32 patients were included. LV ejection fraction remained unchanged (33+/-9% vs. 34+/-10% after 8 months, p=0.30). Likewise, there was no significant change in LV end-systolic volume, wall motion score index (WMSI) or contractile reserve. At 12 months, a decrease in target vessel WMSI was seen (2.17+/-0.34 vs. 2.06+/-0.46, p=0.02). Furthermore, NYHA class improved (p<0.0001). No deaths were observed. In this non-randomised study, no change in LV ejection fraction could be demonstrated after repeated intracoronary bone marrow stem cell treatment in patients with chronic ischaemic heart failure.

The Pacing to Avoid Cardiac Enlargement (PACE) Trial: Clinical Background, Rationale, Design, and Implementation

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. 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. 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.

Effect of Total Scar Burden on Contrast-Enhanced Magnetic Resonance Imaging on Response to Cardiac Resynchronization Therapy

It was shown that improvement in left ventricular (LV) function and reverse remodeling after cardiac resynchronization therapy (CRT) were greater in patients with nonischemic cardiomyopathy than in those with ischemic cardiomyopathy. The aim of this study is to evaluate the influence of scar burden on response to CRT. We included 34 patients with ischemic cardiomyopathy (New York Heart Association class 3.1 +/- 0.4, LV ejection fraction 23 +/- 7%). Contrast-enhanced magnetic resonance imaging was used to determine total scar burden, using a 17-segment model with a 5-point hyperenhancement scale (from score 0 = no hyperenhancement, indicating no scar, to score 4 = hyperenhancement >76%, transmural scar). Linear regression analysis showed a significant correlation (r = -0.91, p <0.05) between total scar burden at baseline and change in LV end-systolic volume after 6 months of CRT. Also, patients not responding to CRT had significantly more scar tissue than responders. A scar burden >1.20 resulted in complete functional nonresponse. In conclusion, total scar burden, assessed using contrast-enhanced magnetic resonance imaging, is an important factor influencing response to CRT and may be included in the selection process for CRT candidates.

Impact of Chronotropic Effect of Cilostazol After Acute Myocardial Infarction Insights From Change in Left Ventricular Volume and Function

Cilostazol, a phosphodiesterase inhibitor, is an antiplatelet agent with positive chronotropic effect, the impact of which on left ventricular (LV) volume and function in acute myocardial infarction (AMI) was evaluated in the present study. In 56 patients with AMI treated with primary coronary stenting, serial echocardiographic studies within 24 h and at 6 months were performed. Patients received a conventional antiplatelet regimen either without cilostazol (group 1, n=29) or with cilostazol (group 2, n=27). At 6 months, the difference in the change in heart rate between group 1 and group 2 was statistically significant (9.9 beats/min; p=0.04). However, changes in LV end-systolic volume (LVESV) (7.1+/-8.2 vs 10.0+/-21.7 ml, p=0.60), LV ejection fraction (EF) (8.2+/-9.9 vs 9.0+/-12.6%, p=0.85) and the ratio of early mitral inflow velocity to the mitral annular velocity (E/E') (0.6+/-3.7 vs -1.7+/-3.2) were not different between the 2 groups. Cardiac event rate was similar between the 2 groups. On multivariate regression analyses, cilostazol therapy had no significant influence on the changes in LVESV, LVEF or E/E'. In this study, the addition of cilostazol on conventional drug therapy had no adverse influence on LV remodeling or LV function after AMI.

Differential change in left ventricular mass and regional wall thickness after cardiac resynchronization therapy for heart failure

LV reverse remodelling has been shown to be a favourable response after cardiac resynchronization therapy (CRT) in many clinical trials. This study investigated whether left ventricular (LV) reverse remodelling after CRT has any structural benefit, which include the improvement of LV mass or regional wall thickness. Fifty patients (66 +/- 11 years) receiving CRT were followed up for at least 3 months. Echocardiography with tissue Doppler imaging was performed serially before and at day 1 and 3 months after CRT. Although LV end-systolic volume (LVESV) was decreased at day 1 after CRT (141 +/- 74 vs. 129 +/- 71 cm(3), P < 0.001), further LV reverse remodelling was observed at 3 months (110 +/- 67 cm(3), P < 0.001 vs. day 1). LV ejection fraction increased at day 1 (26.5 +/- 9.3 vs. 28.5 +/- 9.1%, P < 0.005) and was further improved at 3 months (34.2 +/- 10.5%, P < 0.001 vs. day 1). However, reduction of LV mass (231 +/- 67 vs. 213 +/- 59 g, P < 0.001) and regional wall thickness was only observed at 3 months, but not at day 1. The improvement of LV mass correlated with the change in LVESV (r = 0.66, P < 0.001) and the baseline systolic asynchrony index (Ts-SD) (r = -0.52, P < 0.001). LV mass was only decreased significantly in responders of LV reverse remodelling (245 +/- 66 vs. 207 +/- 61 g, P < 0.001), but increased in non-responders (209 +/- 64 vs. 223 +/- 56 g, P = 0.02). Responders had significant decrease in thickness of all the four walls for -6 to -11% (all P < or =0.02), whereas non-responders had increased thickness in septal and lateral walls for +11% (both P < 0.05). The acute reduction in LV volume after CRT is mediated by haemodynamic and geometric benefits without actual changes in LV mass. However, at 3-month follow-up, reduction in LV mass and regional wall thickness was demonstrated, which represents structural reverse remodelling. Such benefit was only observed in volumetric responders but was worsened in non-responders.

Left Ventricular Reverse Remodeling but Not Clinical Improvement Predicts Long-Term Survival After Cardiac Resynchronization Therapy

In patients with severe heart failure and dilated cardiomyopathy, cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function associated with LV reverse remodeling and favorable 1-year survival. However, it is unknown whether LV reverse remodeling translates into a better long-term prognosis and what extent of reverse remodeling is clinically relevant, which were investigated in this study. Patients (n=141) with advanced heart failure (mean+/-SD age, 64+/-11 years; 73% men) who received CRT were followed up for a mean (+/-SD) of 695+/-491 days. The extent of reduction in LV end-systolic volume (LVESV) at 3 to 6 months relative to baseline was examined for its predictive value on long-term clinical outcome. The cutoff value for LV reverse remodeling in predicting mortality was derived from the receiver operating characteristic curve. Then the relation between potential predictors of mortality and heart failure hospitalizations were compared by Kaplan-Meier survival analysis, followed by Cox regression analysis. There were 22 (15.6%) deaths, mostly due to heart failure or sudden cardiac death. The receiver operating characteristic curve found that a reduction in LVESV of > or =9.5% had a sensitivity of 70% and specificity of 70% in predicting all-cause mortality and of 87% and 69%, respectively, for cardiovascular mortality. With this cutoff value, there were 87 (61.7%) responders to reverse remodeling. In Kaplan-Meier survival analysis, responders had significantly lower all-cause morality (6.9% versus 30.6%, log-rank chi2=13.26, P=0.0003), cardiovascular mortality (2.3% versus 24.1%, log-rank chi2=17.1, P<0.0001), and heart failure events (11.5% versus 33.3%, log-rank chi2=8.71, P=0.0032) than nonresponders. In the Cox regression analysis model, the change in LVESV was the single most important predictor of all-cause (beta=1.048, 95% confidence interval=1.019 to 1.078, P=0.001) and cardiovascular (beta=1.072, 95% confidence interval=1.033 to 1.112, P<0.001) mortality. Clinical parameters were unable to predict any outcome event. A reduction in LVESV of 10% signifies clinically relevant reverse remodeling, which is a strong predictor of lower long-term mortality and heart failure events. This study suggests that assessing volumetric changes after an intervention in patients with heart failure provides information predictive of natural history outcomes.

Long-term effects of darusentan on left-ventricular remodelling and clinical outcomes in the EndothelinA Receptor Antagonist Trial in Heart Failure (EARTH): randomised, double-blind, placebo-controlled trial

Endothelin-receptor blockade provides haemodynamic benefit in experimental and clinical heart failure. We aimed to measure the effects of long-term endothelin-blockade on left-ventricular (LV) remodelling and clinical outcomes in patients with chronic heart failure. 642 patients with chronic heart failure were assigned the oral endothelin(A)-antagonist darusentan at 10, 25, 50, 100, or 300 mg daily or placebo for 24 weeks in addition to standard therapy in a randomised, double-blind, placebo-controlled trial. In the 50-300 mg groups, darusentan was uptitrated over 6 weeks. Primary endpoint was change in LV end-systolic volume (LVESV) at 24 weeks from baseline, measured by MRI. All patients for whom assessable MRI scans were available at baseline and follow-up were included in the analysis. Darusentan was well tolerated. LVESV could be assessed in 485 (76%) patients with paired MRI data at baseline and 6 months. The change in LVESV was not significantly different from that with placebo at any dose (mean difference from placebo 1.27 mL [95% CI -9.9 to 12.4] with 10 mg dose, -1.84 mL [-13.0 to 9.3] with 25 mg, -5.68 mL [-16.9 to 5.6] with 50 mg, -4.05 mL [-15.5 to 7.4] with 100 mg, and -4.34 mL [-15.7 to 7.0] with 300 mg). Heart failure worsened in 71 (11.1%) patients, and 30 (4.7%) died during the study with no difference between groups. Endothelin(A) blockade with darusentan did not improve cardiac remodelling or clinical symptoms or outcomes in patients with chronic heart failure receiving an angiotensin-converting-enzyme inhibitor, beta blocker, or aldosterone antagonist. Thus, endothelin(A) blockade is unlikely to be useful as an add-on treatment in such patients.

Effect of revascularization on left ventricular remodeling in patients with heart failure from severe chronic ischemic left ventricular dysfunction

Few data exist regarding the effect of revascularization on left ventricular (LV) geometry in patients with severe LV systolic dysfunction and viable myocardium. We hypothesized that patients with chronic ischemic LV dysfunction but viable myocardium will have improved LV geometry after revascularization, which in turn will improve long-term outcome. Accordingly, 70 patients with severe ischemic LV dysfunction (LV ejection fraction <0.35) were studied at rest. They then either underwent revascularization (n = 36) or were treated medically (n = 34). Fifty-four patients had viable myocardium, and 16 did not. They were evaluated for change in LV function and geometry (size and shape) a mean of 21 months later. Further follow-up was performed for a mean of 3.5 years to determine outcome. Patients with viable myocardium had improvement not only in regional and global function, but also in LV geometry (shape and size), which was independent of and incremental to the improvement in function. On long-term follow-up, change in LV end-systolic volume was the only multivariate discriminator between 15 patients who died and 55 who did not, irrespective of whether they had undergone revascularization. Thus, measurement of the effect of revascularization of viable myocardium in chronic ischemic heart disease should not only include improvement in resting regional and global LV function, but also LV geometry. Improvement in LV geometry contributes to better LV systolic function, which in turn is the best predictor of survival after revascularization.

Cardiac sympathetic dysfunction contributes to left ventricular remodeling after acute myocardial infarction.

To investigate the role of the cardiac sympathetic nervous system in left ventricular remodelling, 50 patients with first-time acute myocardial infarction (AMI) and patency of the infarct-related artery after reperfusion underwent quantitative iodine-123 metaiodobenzylguanidine (MIBG) imaging at 4 days and 4 weeks (n=42), and quantitative technetium-99m tetrofosmin imaging at 2 days after AMI. They also underwent both ventriculography and coronary angiography on admission and about 4 weeks after AMI. On the basis of left ventricular end-systolic volume (LVESV), patients were divided into two groups. Patients with LVESV dilatation (n=20) had a significantly lower ejection fraction (P<0.003) and a significantly higher severity score of 99mTc-tetrofosmin (P<0.04), and total severity (P<0.01), delta extent (P<0.007) and delta severity (P<0.0008) scores of MIBG than patients without LVESV dilatation (n=30). delta severity score of MIBG was directly correlated with change in LVESV at 4 weeks (r=0.63, P<0.0001). Stepwise linear discriminant function analysis showed that delta severity score of MIBG (P<0.0002) was the only discriminator of LVESV dilatation. Patients with LVESV dilatation had higher regional washout rates in both the infarct and the non-infarct zones than patients without such dilatation. Furthermore, no MIBG parameters changed significantly between 4 days and 4 weeks after AMI. In reperfused AMI, delta severity score of MIBG was related to the degree of ventricular dilatation and was the only powerful discriminator of ventricular dilatation. These results suggest that cardiac sympathetic nervous abnormality might contribute to left ventricular remodelling in reperfused AMI. MIBG imaging may allow identification of reperfused AMI patients at high risk for left ventricular remodelling.

Serial assessment of left ventricular function after myocardial infarction

Left ventricular (LV) function is an important predictor of morbidity and mortality after myocardial infarction (MI). Changes in LV function have been examined during the early and late phases after MI, but serial measurements of LV function during the subacute period have not been performed. To assess sequential changes in LV function during the subacute period after MI, we used quantitative two-dimensional echocardiography to examine 22 patients over a 1-year period. Twenty-one of the 22 patients had a Q-wave MI. Eleven had an anterior MI and 10 had an inferior MI; their peak creatine phosphokinase (CPK) was 1213 mlU/ml ± 14. Three weeks after acute MI, LV ejection fraction (LVEF) had increased from 45% to 52%. Seven of 19 patients showed an LVEF <43% at baseline. In five of these patients, LVEF improved, but in two patients, LVEF was still <43% in week 3. There was a significant enlargement of LV end-diastolic volume (LVEDV) (94 ml to 112 ml, p < 0.05) across the four observations but no change in LV end-systolic volume (LVESV; 54 ml to 56 ml, p = n.s.). When two groups (G1 [depressed], LVEF ≤43%; G2 [preserved], LVEF >43%) were compared, the group with depressed LVEF demonstrated a higher probability of improvement in LVEF (34% to 47%, p < 0.001) and stroke volume (38 ml to 65 ml, p < 0.01).

Effect of the pericardium on systolic ventricular interdependence in the dog

Systolic ventricular interdependence, whereby changes in left ventricular (LV) ejection alter right ventricular (RV) ejection, has been described. It is unclear, however, whether this interaction is influenced by pericardial volume constraint or by myocardial mechanical coupling. We hypothesized that if mechanical coupling were the primary factor determining systolic ventricular interdependence then it should be unaltered by the presence or absence of an intact pericardium, but affected by changes in LV end-systolic volume. We tested this hypothesis by observing the changes in RV stroke volume (SV rv) and peak systolic pressure (PSP rv) during a single LV isovolumic contraction under conditions of normal or increased (1.3 × normal) RV end-diastolic volume with and without an intact pericardium. In 10 anesthetized, open-chested dogs SV rv was derived from the integrated pulmonary arterial flow probe signal and RV ejection fraction (EF rv) was derived from the thermodilution plateau method and a rapidly responsive thermistor in the pulmonary artery. Right ventricular end-diastolic volume was considered to be the ratio of SV rv to EF rv. Left ventricular isovolumic contraction increased SV rv and PSP rv during all conditions P <.01). However, PSP rv increased more when the pericardium was intact ( P <.05). These data suggest that LV ejection can enhance SV rv and that this interaction is not appreciably altered by volume loading or the presence of an intact pericardium. Pericardial interactions may alter PSP rv but do not affect SV rv.

Assessment of left ventricular function before and after Fontan's operation for the correction of tricuspid atresia. Changes in left ventricular function determined by left ventricular volume change.

Functional change in the left ventricle was studied in the light of changes in the left ventricular (LV) volume preload before and after Fontan's operation. Six cases with tricuspid atresia (TA) were studied, and they had either types Ib or IIb. The preoperative LV end-diastolic volume index (LVEDVI) was 123 +/- 44 ml/m2, which corresponds to 166% +/- 45% of normal values. This suggests that in TA the preload of the LV volume is increased because of its peculiar hemodynamic situation. After Fontan's operation, the LVEDV decreased by 24.6% to 119.6 +/- 87.7 ml (P = 0.01), which corresponds to 120% +/- 50.9% of normal values. Presenting a striking contrast to the decrease in LVEDV, the postoperative reduction in LV end-systolic volume (LVESV) was approximately 8%. Preoperative and postoperative values for LVESV were 67.1 +/- 50.8 ml and 62 +/- 45.6 ml, thus, the systolic volume was decreased. Because of the small change in LVESV, the ejection fraction (EF) of the left ventricle significantly decreased from 0.61 +/- 0.1 preoperatively to 0.48 +/- 0.1 postoperatively. The cardiac index (CI) remained in the range of 1.9-2.5 l/min/m2 with a mean of 2.2 +/- 0.2 l/min/m2 at 1 month after operation. But, later, improvement in EF was observed in one case, in which the CI increased from 2.5 to 3.2 l/min/m2.(ABSTRACT TRUNCATED AT 250 WORDS)