Cardiac Resynchronization Therapy Off Research Articles

Adaptive CRT algorithm and electrical synchrony

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): United Hospital Medical Education and Research Committee, United Hospital Foundation. Background We have previously shown that optimization of cardiac resynchronization therapy (CRT) nonresponders using a novel electrical dyssynchrony mapping (EDM) system significantly improves electrical dyssynchrony, left ventricle (LV) size and systolic function. Whether this methodology can improve electrical dyssynchrony (and potentially LV function) in nonresponder patients programmed with the adaptive CRT (aCRT) algorithm is not known. Purpose To quantify electrical dyssynchrony in CRT nonresponders programmed using aCRT and determine if it can be improved using EDM. Methods We studied 97 patients programmed with the aCRT algorithm at multiple device settings with an ECG system of 9 anterior and 9 posterior electrodes. We quantified electrical dyssynchrony using a measure of wavefront fusion, cardiac resynchronization index (CRI), calculated as % change in area under the curve between all combinations of anterior and posterior electrodes as compared to native LBBB (CRT off). CRI results were displayed on an electrical dyssynchrony map (EDM) showing atrial-to-right ventricle-paced intervals (A-RVp) on the y-axis and atrial-to-left ventricle-paced intervals (A-LVp) on the x-axis. Results Figure 1 shows an EDM for a typical patient with CRI values marked at different programmed settings. Figure 2 shows CRI for 58 patients programmed LV-only by aCRT at baseline (red bars) and 39 patients programmed biventricular (BiV) by aCRT at baseline (blue bars). CRI at baseline was significantly (p≤0.001) higher in patients programmed LV-only vs. those programmed BiV. In both groups programming to LV-only at the optimal atrial-ventricular delay (AVD) and to sequential BiV pacing at the optimal ventricular-ventricular delay (VVD) produced significantly and markedly better CRI as compared to CRI at aCRT baseline settings. In the patients programmed by aCRT at baseline to LV-only, BiV VV=0 at standard device setting (SAV 120 ms) had significantly worse CRI than baseline. Conclusions Electrical dyssynchrony as measured by CRI is better in patients programmed aCRT LV-only than those programmed aCRT BiV. CRI can be improved by 20% or more by using EDM to program patients to LV-only pacing at the optimal AVD or to BiV pacing at the optimal VVD. EDM technology offers the possibility of substantially improving electrical synchrony in nonresponder patients programmed with aCRT.

Cardiac Resynchronization Therapy in continuous flow Left Ventricular Assist Device Recipients: A Systematic Review and Meta-analysis from ELECTRAM Investigators.

Whether cardiac resynchronization therapy (CRT) continues to augment left ventricular remodeling in patients with the continuous-flow left ventricular assist device (cf-LVAD) remains unclear. We performed a systematic review and meta-analysis of all clinical studies examining the role of continued CRT in end-stage heart failure patients with cf-LVAD reporting all-cause mortality, ventricular arrhythmias, and ICD shocks. Mantel-Haenszel risk ratio (RR) random-effects model was used to summarize data. Eight studies (7 retrospective and 1 randomized) with a total of 1,208 unique patients met inclusion criteria. There was no difference in all-cause mortality (RR 1.08, 95% CI 0.86 - 1.35, p = 0.51, I2=0%), all-cause hospitalization (RR 1.01, 95% CI 0.76-1.34, p = 0.95, I2=11%), ventricular arrhythmias (RR 1.08, 95% CI 0.83 - 1.39, p = 0.58, I2 =50%) and ICD shocks (RR 0.87, 95% CI 0.57 - 1.33, p = 0.52, I2 =65%) comparing CRT versus non-CRT. Subgroup analysis demonstrated significant reduction in ventricular arrhythmias (RR 0.76, 95% CI 0.64 - 0.90, p = 0.001) and ICD shocks (RR 0.65, 95% CI 0.44 - 0.97, p = 0.04) in "CRT on" group versus "CRT off" group. CRT was not associated with a reduction in all-cause mortality or increased risk of ventricular arrhythmias and ICD shocks compared to non-CRT in cf-LVAD patients. It remains to be determined which subgroup of cf-LVAD patients benefit from CRT. The findings of our study are intriguing, and therefore, larger studies in a randomized prospective manner should be undertaken to address this specifically.

Continued versus Suspended Cardiac Resynchronization Therapy after Left Ventricular Assist Device Implantation

Cardiac resynchronization therapy (CRT) improves outcomes in heart failure patients with wide QRS complex. However, CRT management following continuous flow Left Ventricular Assist Device (LVAD) implant vary: some centers continue CRT while others turn off the left ventricular (LV) lead at LVAD implant. We sought to study the effect of continued CRT versus turning off CRT pacing following continuous flow LVAD implantation. A comprehensive retrospective multicenter cohort of 295 patients with LVAD and pre-existing CRT was studied. CRT was programmed off after LVAD implant in 44 patients. We compared their outcomes to the rest of the cohort using univariate and multivariate models. Mean age was 60 ± 12 years, 83% were males, 52% had ischemic cardiomyopathy and 54% were destination therapy. Mean follow-up was 2.4 ± 2.0 years, and mean LVAD support time was 1.7 ± 1.4 years. Patients with CRT OFF had a higher Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) mean profile (3.9 vs 3.3, p = 0.01), more secondary prevention indication for a defibrillator (64.9% vs 44.5%, p = 0.023), and more pre-LVAD ventricular arrhythmias (VA) (77% vs 60%, p = 0.048). There were no differences between the CRT OFF and CRT ON groups in overall mortality (Log rank p = 0.32, adjusted HR = 1.14 [0.54–2.22], p = 0.71), heart transplantation, cardiac and noncardiac mortality, all cause hospitalizations, hospitalizations for ICD shocks, and number and frequency of ICD shocks or anti-tachycardia pacing therapy. There were no differences in post LVAD atrial arrhythmias (AA) (Adjusted OR = 0.45 [0.18–1.06], p = 0.31) and ventricular arrhythmias (OR = 0.65 [0.41–1.78], p = 0.41). There was no difference in change in LVEF, LV end diastolic and end systolic diameters between the 2 groups. Our study suggests that turning off CRT pacing after LVAD implantation in patients with previous CRT pacing did not affect mortality, heart transplantation, device therapies or arrhythmia burden. A prospective study is needed to confirm these findings.

Improvement of abnormal systolic motion of the interventricular septum with cardiac resynchronization therapy.

There is no consensus in the literature regarding what is the responsible mechanism of left ventricular dyssynchrony; septal dyskinesia or late movement of left ventricle (LV) lateral wall. We aim to evaluate the abnormal systolic motion in each myocardial segment and the improvement of LV systolic function with pulsed tissue Doppler imaging (TDI) in patients undergoing cardiac resynchronization therapy (CRT) with left bundle branch block (LBBB). A total of 26 patients undergoing CRT implantation with LBBB, wide QRS duration (≥120ms), and low ejection fraction (EF) (<35%) were included. Pulsed TDI was taken from apical 4-chamber view and parasternal short axis view (PSAX). All echocardiographic parameters were measured when CRT is on and off. Systolic ejection time (ET) of anteroseptal and posterolateral wall of LV in PSAX was statistically significantly longer in CRT on group (321.6±62.7vs 237.5±59.3 ms, P<.001; 323.9±58.0vs 289.4±43.7 ms, P=.015, respectively). In apical 4-chamber view, septal annulus systolic ET is significantly longer in CRT on group than CRT off group (315.8±57.2vs 287.3 ± 42.2, P=.014). Also, there was a strong correlation between systolic ET of the septum in PSAX with aortic velocity time integral (VTI), QRS duration and EF (r=.587, P=.002; r=.479, P=.013; r=.440, P=.025; respectively). Circumferential contraction of septal myocardial fibers is improved with CRT and it is strongly correlated with increase of aortic VTI and shortening of QRS duration. These findings predict the deterioration of septal contraction as the main mechanism in patients with LBBB pattern and, CRT may improves myocardial contraction by correcting septal systolic motion.

Bipolar active fixation left ventricular lead or quadripolar passive fixation lead? An Italian multicenter experience.

About one-third of patients receiving cardiac resynchronization therapy (CRT) are not responders, due to either patient selection or technical issues. Left ventricular quadripolar passive fixation leads (QPL) and bipolar active fixation (BAF) leads have been designed to ensure a targeted left ventricular stimulation area, minimizing lead dislodgments and phrenic nerve stimulation (PNS). The aim was to compare real-world safety and efficacy of BAF (Attain Stability, Medtronic Plc.) and QPL (Attain Performa, Medtronic Plc.). We performed a retrospective analysis examining procedural and follow-up data of 261 BAF and 124 QPL (programmed to single-site left ventricular pacing), included in the ClinicalService project from 16 Italian hospitals. At median follow-up of 12 months, no difference in left ventricular pacing threshold was recorded between BAF and QPL (1.3 ± 0.9 V @0.4 ms vs. 1.3 ± 1.0 V @0.4 ms; P = 0.749). Total left ventricular lead dislodgement rate was 1.43/100 patient-years in BAF vs. 2.9/100 patient-years in QPL (P = 0.583). However, no dislodgements occurred among BAF after hospital discharge. Events requiring repeated surgery or permanently turning CRT off occurred in 0.8% of BAF, as compared with 4.0% of QPL (P = 0.025). There was no difference between groups in the echo CRT responders' rate (70% of BAF and 66% of QPL; P = 0.589) or in the annual rate of heart failure hospitalization (P = 0.513). BAF resulted in noninferior clinical outcome and CRT responders' rate in comparison to QPL. Moreover, BAF ensured more precise and stable placement in cardiac veins, with comparable electrical performance and less than 1% patients with unsolved PNS.

Prospective Randomized Evaluation of Implantable Cardioverter‐Defibrillator Programming in Patients With a Left Ventricular Assist Device

BackgroundVentricular arrhythmias are common in patients with left ventricular assist devices (LVADs) but are often hemodynamically tolerated. Optimal implantable cardioverter defibrillator (ICD) tachy‐programming strategies in patients with LVAD have not been determined. We sought to determine if an ultra‐conservative ICD programming strategy in patients with LVAD affects ICD shocks.Methods and ResultsAdult patients with an existing ICD undergoing continuous flow LVAD implantation were randomized to standard ICD programming by their treating physician or an ultra‐conservative ICD programming strategy utilizing maximal allowable intervals to detection in the ventricular fibrillation and ventricular tachycardia zones with use of ATP. Patients with cardiac resynchronization therapy (CRT) devices were also randomized to CRT ON or OFF. Patients were followed a minimum of 6 months. The primary outcome was time to first ICD shock. Among the 83 patients studied, we found no statistically significant difference in time to first ICD shock or total ICD shocks between groups. In the ultra‐conservative group 16% of patients experienced at least one shock compared with 21% in the control group (P=0.66). There was no difference in mortality, arrhythmic hospitalization, or hospitalization for heart failure. In the 41 patients with CRT ICDs fewer shocks were observed with CRT‐ON but this was not statistically significant: 10% of patients with CRT‐ON (n=21) versus 38% with CRT‐OFF (n=20) received shocks (P=0.08).ConclusionsAn ultra‐conservative programming strategy did not reduce ICD shocks. Programming restrictions on ventricular tachycardia and ventricular fibrillation zone therapy should be reconsidered for the LVAD population. The role of CRT in patients with LVAD warrants further investigation.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01977703.

Effect of Continued Cardiac Resynchronization Therapy on Ventricular Arrhythmias After Left Ventricular Assist Device Implantation

Cardiac resynchronization therapy (CRT) reduces ventricular arrhythmia (VA) burden in some patients with heart failure, but its effect after left ventricular assist device (LVAD) implantation is unknown. We compared VA burden in patients with CRT devices in situ who underwent LVAD implantation and continued CRT (n= 39) to those who had CRT turned off before discharge (n= 26). Implantable cardioverter-defibrillator (ICD) shocks were significantly reduced in patients with continued CRT (1.5 ± 2.7 shocks per patient vs 5.5 ± 9.3 with CRT off, p= 0.014). There was a nonsignificant reduction in cumulative VA episodes per patient with CRT continued at discharge (42 ± 105 VA per patient vs 82 ± 198 with CRT off, p= 0.29). On-treatment analysis by whether CRT was on or off identified a significantly lower burden of VA (17 ± 1 per patient-year CRT on vs 37 ± 1 per patient-year CRT off, p <0.0001) and ICD shocks (1.2 ± 0.3 per patient-year CRT on vs 1.7 ± 0.3 per patient-year CRT off, p= 0.018). In conclusion, continued CRT is associated with significantly reduced ICD shocks and VA burden after LVAD implantation.

Comparison of Left Ventricular Torsion and Strain With Biventricular Pacing in Patients With Underlying Right Bundle Branch Block Versus Those With Left Bundle Branch Block

The benefits of biventricular pacing in patients with cardiac resynchronization therapy (CRT) remain poorly understood in those with right bundle branch block (RBBB). The aim of this study was to examine the differences in several speckle tracking-derived parameters, including left ventricular torsion and longitudinal strain with CRT on and off for patients with underlying left bundle branch block (LBBB) and RBBB. Twelve patients with CRT and RBBB were compared with a similar group of patients with underlying LBBB who were sent for evaluation and atrioventricular optimization. Echocardiographic images were acquired with biventricular pacing on and off. The 2 groups had similar baseline characteristics, including age, the ejection fraction, and QRS duration. During intrinsic conduction (CRT off), patients with LBBB had lower torsion angles than those with RBBB (2.3 ± 1.0° in those with LBBB vs 6.3 ± 1.0° in those with RBBB, p = 0.03) but trended toward improvements in torsional parameters, including torsional angle and peak untwisting velocity with CRT on, whereas these parameters worsened in patients with RBBB. Compared with CRT off, analyses of septal and lateral strain curves showed significant improvements in septal strain during 100% and 200% of systole with CRT on in patients with LBBB, whereas biventricular pacing resulted in a trend toward worsening of septal strain in patients with RBBB. Negligible changes were noted in lateral strain values. In conclusion, CRT favorably improves regional mechanics in patients with LBBB primarily involving the ventricular septum, with a negligible positive impact on cardiac function in patients with underlying RBBB.

Impact of Ejection Fraction on the Clinical Response to Cardiac Resynchronization Therapy in Mild Heart Failure

Current guidelines recommend cardiac resynchronization therapy (CRT) in mild heart failure (HF) patients with QRS prolongation and ejection fraction (EF) ≤30%. To assess the effect of CRT in less severe systolic dysfunction, outcomes in the REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study were evaluated in which patients with left ventricular (LV) ejection fraction (LVEF) >30% were included. The results of patients with baseline EF >30% (n=177) and those with EF ≤30% (n=431), as determined by a blinded core laboratory, were compared. In the LVEF >30% subgroup, there was a trend for improvement in the clinical composite response with CRT ON versus CRT OFF (P=0.06) and significant reductions in LV end systolic volume index (-6.7 ± 21.1 versus 2.1 ± 17.6 mL/m(2); P=0.01) and LV mass (-20.6 ± 50.5 versus 5.0 ± 42.4 g; P=0.04) after 12 months. The time to death or first HF hospitalization was significantly prolonged with CRT (hazard ratio, 0.26; P=0.012). In the LVEF <30% subgroup, significant improvements in clinical composite response (P=0.02), reverse remodeling parameters, and time to death or first HF hospitalization (hazard ratio, 0.58; P=0.047) were observed. After adjusting for important covariates, the CRT ON assignment remained independently associated with improved time to death or first HF hospitalization (hazard ratio, 0.54; P=0.035), whereas there was no significant interaction with LVEF. Among subjects with mild HF, QRS prolongation, and LVEF >30%, CRT produced reverse remodeling and similar clinical benefit compared with subjects with more severe LV systolic dysfunction. http://www.clinicaltrials.gov. Unique identifier: NCT00271154.

ACUTE NON-INVASIVE CARDIAC OUTPUT MEASUREMENTS FOLLOWING CARDIAC RESYNCHRONIZATION THERAPY PREDICT LEFT VENTRICULAR REVERSE REMODELING AT 6 MONTHS AND LONG TERM SURVIVAL

Abstract Category: 28. Cardiac PacingSession-Poster Board Number: 1089-397Authors: Fakhar Z. Khan, Munmohan S. Virdee, David Begley, John Hutchinson, Beverley Smith, Philip A. Read, Peter J. Pugh, Simon P. Fynn, David P. Dutka, Addenbrooke’s Hospital, Cambridge, United Kingdom, Papworth Hospital, Cambridge, United Kingdom Background: We aimed to assess to what extent acute changes in non invasive cardiac output measurements (NICOM) are related to longer term outcomes following cardiac resynchronization therapy (CRT).Methods: In 196 patients (69±9yrs, EF 23±7%, QRS 154±12ms, NYHA III/IV 183/13) CO recordings were made within 1 day of CRT at baseline (CRT OFF) and during optimized settings (CRT ON). Response was defined by >15% reduction in left ventricular end systolic volume (LVESV) at 6 months.Results: There was a significant difference in CO readings during CRT between responders (n=112) and non responders (6.23±1.21 vs 5.19±0.96L/min, p 20% in CO, 1 day after CRT implant had greater survival than those patients with <20% improvement (figure).Conclusions: NICOM recordings following CRT accurately predict LV reverse remodeling and long term survival. This validation study suggests potential use in either the optimization of CRT devices or in the guidance of LV lead placement.

The impact of cardiac resynchronization therapy on the incidence of ventricular arrhythmias in mild heart failure

Cardiac resynchronization therapy (CRT) decreases mortality, improves functional status, and induces reverse left ventricular (LV) remodeling in selected populations. However, the effect of CRT on ventricular arrhythmias is controversial. This is particularly important among patients with mild heart failure (HF), in whom sudden death is a leading cause of mortality. This study sought to assess the impact of CRT on ventricular arrhythmias in mild HF. The REsynchronization reVErses Remodeling in Systolic left vEntricular dysfunction (REVERSE) study is a multicenter randomized, double-blind trial of CRT among patients with mild systolic HF. The time to first appropriate, treated ventricular tachycardia/ventricular fibrillation (VT/VF) episode or spontaneous sustained VT in cardiac resynchronization therapy plus defibrillation device (CRT-D) patients was compared between groups, as were predictors of VT/VF. The study randomized 508 patients who received CRT-D devices. There were no significant demographic differences between groups. There were no differences in VT/VF episodes or VT storm between groups. Specifically, in the CRT ON group, the estimated event rate was 18.7% at 2 years, compared with 21.9% in the CRT OFF group (hazard ratio 1.05, P = .84). However, among CRT ON patients, those with reverse remodeling had a reduced incidence of VT/VF compared with those without remodeling (5.6% vs. 16.3%, hazard ratio 0.31, P = .001). CRT for up to 2 years does not impact VT/VF in mild HF despite marked clinical and remodeling effects of pacing. This neutral effect may be attributable to competing antiarrhythmic effects of reverse remodeling and proarrhythmic effect of pacing. http://www.clinicaltrials.gov/ct2/show/NCT00271154.

Cardiac resynchronization therapy; the importance of evaluating cardiac metabolism

Cardiac resynchronization therapy; the importance of evaluating cardiac metabolism

Assessment of Resynchronization Therapy on Functional Status and Quality of Life in Patients Requiring an Implantable Defibrillator

The effect of cardiac resynchronization therapy (CRT) on physical function and Quality of Life (QoL) in patients who require an implantable defibrillator but do not meet guideline criteria for CRT has not been studied in detail. This was a randomized study of 72 patients with high risk of sudden cardiac death, ejection fraction (EF) < or =35%, mild-to-moderate heart failure symptoms, and QRS > 120 ms. Patients received a CRT defibrillator and were randomized to CRT turned ON or OFF. Objective and subjective measures were performed at baseline and after 6 months. There was no difference in change in left ventricular end-systolic volume (ESV) by radionuclid angiogram scan, the primary endpoint, between the CRT ON group (DeltaESV =-7 +/- 52 mL), and CRT OFF group (DeltaESV =-30 +/- 47 mL). Similarly, echocardiogram measures of ESV and EF showed no difference between the two groups. In the CRT ON group, selected measures of QoL and subjective exercise tolerance but not heart failure symptoms improved significantly. Six-minute walk distance prolonged in the CRT ON group (baseline 313.6 +/- 114.4 m, 6-month 365.0 +/- 122.5 m, P = 0.01), but the difference in change in walk distance between the two groups was not significant. Further studies with larger sample size and longer follow-up will be required to allow definite conclusions regarding the potential benefit of CRT in this patient population.

Cardiac Resynchronization Induces Major Structural and Functional Reverse Remodeling in Patients With New York Heart Association Class I/II Heart Failure

Cardiac resynchronization therapy (CRT) improves LV structure, function, and clinical outcomes in New York Heart Association class III/IV heart failure with prolonged QRS. It is not known whether patients with New York Heart Association class I/II systolic heart failure exhibit left ventricular (LV) reverse remodeling with CRT or whether reverse remodeling is modified by the cause of heart failure. Six hundred ten patients with New York Heart Association class I/II heart failure, QRS duration > or =120 ms, LV end-diastolic dimension > or =55 mm, and LV ejection fraction < or =40% were randomized to active therapy (CRT on; n=419) or control (CRT off; n=191) for 12 months. Doppler echocardiograms were recorded at baseline, before hospital discharge, and at 6 and 12 months. When CRT was turned on initially, immediate changes occurred in LV volumes and ejection fraction; however, these changes did not correlate with the long-term changes (12 months) in LV end-systolic (r=0.11, P=0.31) or end-diastolic (r=0.10, P=0.38) volume indexes or LV ejection fraction (r=0.07, P=0.72). LV end-diastolic and end-systolic volume indexes decreased in patients with CRT turned on (both P<0.001 compared with CRT off), whereas LV ejection fraction in CRT-on patients increased (P<0.0001 compared with CRT off) from baseline through 12 months. LV mass, mitral regurgitation, and LV diastolic function did not change in either group by 12 months; however, there was a 3-fold greater reduction in LV end-diastolic and end-systolic volume indexes and a 3-fold greater increase in LV ejection fraction in patients with nonischemic causes of heart failure. CRT in patients with New York Heart Association I/II resulted in major structural and functional reverse remodeling at 1 year, with the greatest changes occurring in patients with a nonischemic cause of heart failure. CRT may interrupt the natural disease progression in these patients. Clinical Trial Registration- Clinicaltrials.gov Identifier: NCT00271154.

Prevention of Disease Progression by Cardiac Resynchronization Therapy in Patients With Asymptomatic or Mildly Symptomatic Left Ventricular Dysfunction: Insights From the European Cohort of the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) Trial

The aim of this study was to determine the long-term effects of cardiac resynchronization therapy (CRT) in the European cohort of patients enrolled in the REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial. Previous data suggest that CRT slows disease progression and improves the outcomes of asymptomatic or mildly symptomatic patients with left ventricular (LV) dysfunction and a wide QRS complex. We randomly assigned 262 recipients of CRT pacemakers or defibrillators, with QRS > or =120 ms and LV ejection fraction < or =40% to active (CRT ON; n = 180) versus control (CRT OFF; n = 82) treatment, for 24 months. Mean baseline LV ejection fraction was 28.0%. All patients were in sinus rhythm and receiving optimal medical therapy. The primary study end point was the proportion worsened by the heart failure (HF) clinical composite response. The main secondary study end point was left ventricular end-systolic volume index (LVESVi). In the CRT ON group, 19% of patients were worsened versus 34% in the CRT OFF group (p = 0.01). The LVESVi decreased by a mean of 27.5 +/- 31.8 ml/m(2) in the CRT ON group versus 2.7 +/- 25.8 ml/m(2) in the CRT OFF group (p < 0.0001). Time to first HF hospital stay or death (hazard ratio: 0.38; p = 0.003) was significantly delayed by CRT. After 24 months of CRT, and compared with those of control subjects, clinical outcomes and LV function were improved and LV dimensions were decreased in this patient population in New York Heart Association functional classes I or II. These observations suggest that CRT prevents the progression of disease in patients with asymptomatic or mildly symptomatic LV dysfunction. (REsynchronization reVErses Remodeling in Systolic Left vEntricular Dysfunction [REVERSE]; NCT00271154).

Functional Mitral Regurgitation at Rest Determines the Acute Hemodynamic Response to Cardiac Resynchronization Therapy During Exercise: An Acute Exercise Echocardiographic Study

Cardiac resynchronization therapy (CRT) acutely enhances forward stroke volume (FSV) during exercise by reducing the severity of functional mitral regurgitation (MR) in patients with systolic chronic heart failure. Whether CRT increases FSV in patients without functional MR at rest is unknown. Accordingly, the aim of the study was to compare the effect of CRT on exercise-induced increase in FSV in patients with chronic heart failure with or without functional MR at rest. Forty-one patients with systolic chronic heart failure who had recently undergone CRT performed 2 exercise stress echocardiography tests, the first with CRT On and the second with CRT Off. Twenty-six patients had more than trivial MR (effective regurgitant orifice [ERO] < 10 mm2 in 16 patients, < 20 mm2 in 8 patients, and > or = 20 mm2 in 2 patients), and 15 patients had no MR at rest. Mean exercise-induced change (Delta) in mitral ERO was reduced by CRT (8 +/- 7 mm2 vs 1 +/- 4 mm2, P < .00001). In patients with functional MR at rest, Delta FSV during dynamic exercise was greater with CRT On than CRT Off (4 +/- 8 vs -2 +/- 7 mL, P = .0002), whereas CRT did not significantly affect Delta FSV in patients without MR at rest (9 +/- 9 mL vs 9 +/- 9 mL, P = .93). Similarly, Delta cardiac output was greater with CRT On than CRT Off (1.6 +/- 1.2 L/min vs 1.1 +/- 1.2 L/min, P = .002) in patients with functional MR at rest, whereas Delta cardiac output was similar with CRT On and CRT Off in patients without MR at rest (1.9 +/- 1.4 L/min vs 2.0 +/- 1.2 L/min, P = .59). Severity of functional MR decreased or failed to increase, whereas cardiac output improved during exercise in 9 of 26 patients (34%) with CRT On and in only 2 of 26 patients (8%) with CRT Off (P = .039). Functional MR at rest may be an important determinant of the acute hemodynamic response to CRT during exercise.

Abstract 4852: Changes In Left Ventricular Structure And Function Over 12 Months In Patients With Mild Or Asymptomatic Heart Failure With Previous Symptoms In The Resynchronization Reverses Remodelling In Systolic Left Ventricular Dysfunction (reverse) Study

Background: Cardiac Resynchronization Therapy (CRT) induces LV reverse remodeling that translates into symptom relief and improved survival in New York Heart Association (NYHA) symptom class III/IV heart failure (HF). We hypothesized that CRT would also result in LV reverse remodeling in NYHA class I/II (asymptomatic or minimally symptomatic) HF and slow disease progression. Method: All patients in the RE synchronization re VE rses R emodeling in S ystolic left v Entricular dysfunction (REVERSE) study had an EF&lt;40% and a QRS&gt;120ms and had optimal HF therapy for at least 1 month. Echograms were obtained at baseline, pre-hospital discharge (PHD), 6 and 12 months. At the PHD visit two limited echos were performed (one with CRT OFF and one with CRT ON), to assess the acute mechanical effect of pacing. LV volume indices, EF, LV mass and severity of mitral regurgitation (MR) were quantified at all time points by a Core Echo lab. Results: Of 610 patients, 82% had NYHA class II and 18% had class I HF. Patients were randomized 2:1 to CRT ON (n=419) or CRT OFF (n=191). LV volume indices at end-systole and end-diastole decreased and EF increased significantly from baseline to 12 months in CRT ON, but did not change in CRT OFF. LV mass and severity of MR did not change in either group at 12 months (Table ). When CRT ON was switched to CRT OFF at PHD, there were no significant acute changes in LV size or function. Conclusion: CRT results in major structural and functional LV reverse remodeling in patients with NYHA class I/II HF that may delay the natural disease progression. The progressive reverse LV remodeling is demonstrated on top of the attenuation seen with optimal medical therapy in NYHA class I/II (CRT OFF group). The echo findings in REVERSE may have important clinical implications for use of CRT in the optimal therapy of patients with NYHA class I/II heart failure. Table. Mean ± S.D. (n) Echocardiographic Parameters: CRT ON vs. CRT OFF

Short-term Effects of Cardiac Resynchronization Therapy on Sleep-Disordered Breathing in Patients With Systolic Heart Failure

We evaluated the short-term effect of cardiac resynchronization therapy (CRT) on sleep apnea in patients with systolic heart failure. Sleep-disordered breathing is common in patients with left ventricular systolic dysfunction. Twelve patients (mean [+/-SE] age, 59.6+/-7.8 years; mean left ventricular ejection fraction, 28.0+/-2.8%) with an implanted atrial-synchronized biventricular pacemaker for the treatment of left ventricular systolic dysfunction were selected and studied. Each subject underwent polysomnography on 3 consecutive nights with CRT on the first night, CRT off the second night, and CRT on the third night. Echocardiography was performed prior to each polysomnogram. The central sleep event index (ie, the number of central sleep apneas [CSAs] and hypopneas per hour of sleep) score was lower with CRT compared to that without CRT (mean central sleep event index score with CRT on, 6.9+/-1.7 events per hour of sleep; mean central sleep event index score with CRT off, 14.3+/-2.9 events per hour of sleep; mean central sleep event index score with CRT on, 8.1+/-1.5 events per hour of sleep; p<0.001). Similarly, the cumulative duration of central sleep events (the number of minutes per hour of sleep during CRT) was one half that observed without CRT (CRT on, 2.8+/-0.7 min per hour of sleep; CRT OFF 6.2+/-1.2 min per hour of sleep; CRT ON 3.1+/-0.7 min per hour of sleep; p<0.001). There was a significant correlation between mitral regurgitant volume and central sleep event index on all three nights (r>or=0.77; p<0.01). CRT reduces CSA severity in the short term. This reduction correlated significantly with the CRT-mediated reduction of mitral regurgitation.

Importance of contractile reserve for CRT

To assess whether response to cardiac resynchronization therapy (CRT) is related to myocardial viability in the paced left ventricular (LV) region, evaluated by contractile reserve (CR). Non-response to CRT may partly be due to inefficient pacing by the LV lead located in a fibrotic area. Nineteen patients (64 +/- 13 years, 14 men, 9 ischaemic) with severe heart failure (EF = 27 +/- 8%, QRS = 154 +/- 25 ms) were included in the week after device implantation. Stroke volume (SV) and LV dyssynchrony (by Tissue Doppler Imaging) were successively assessed with CRT on and CRT off. Afterwards, CRT device was maintained off during dobutamine infusion to assess CR in the LV-pacing region. LV end-systolic volume (ESV) was assessed after 6 months to quantify reverse remodelling. CR in the paced LV region (n = 10, 5/9 ischaemic and 5/10 non-ischaemic) was correlated to a reduction in LV dyssynchrony under CRT (120 +/- 76 vs. 78 +/- 64 ms, P = 0.02). Conversely, LV dyssynchrony was unchanged (161 +/- 100 vs. 163 +/- 80 ms) without CR. In desynchronized patients (>65 ms, n = 15), increase in SV under CRT and changes in ESV at 6 months were +22 and -18%, respectively, when CR was present and 0% and +9%, respectively, when absent. Acute haemodynamic response and reverse remodelling under CRT require viability in the target region of LV lead.

Effects of Cardiac Resynchronization on Disease Progression in Patients With Left Ventricular Systolic Dysfunction, an Indication for an Implantable Cardioverter-Defibrillator, and Mildly Symptomatic Chronic Heart Failure

The effects of cardiac resynchronization therapy (CRT) in patients with mildly symptomatic heart failure have not been fully elucidated. The Multicenter InSync ICD Randomized Clinical Evaluation II (MIRACLE ICD II) was a randomized, double-blind, parallel-controlled clinical trial of CRT in NYHA class II heart failure patients on optimal medical therapy with a left ventricular (LV) ejection fraction < or =35%, a QRS > or =130 ms, and a class I indication for an ICD. One hundred eighty-six patients were randomized: 101 to the control group (ICD activated, CRT off) and 85 to the CRT group (ICD activated, CRT on). End points included peak VO2, VE/CO2, NYHA class, quality of life, 6-minute walk distance, LV volumes and ejection fraction, and composite clinical response. Compared with the control group at 6 months, no significant improvement was noted in peak VO2, yet there were significant improvements in ventricular remodeling indexes, specifically LV diastolic and systolic volumes (P=0.04 and P=0.01, respectively), and LV ejection fraction (P=0.02). CRT patients showed statistically significant improvement in VE/CO2 (P=0.01), NYHA class (P=0.05), and clinical composite response (P=0.01). No significant differences were noted in 6-minute walk distance or quality of life scores. In patients with mild heart failure symptoms on optimal medical therapy with a wide QRS complex and an ICD indication, CRT did not alter exercise capacity but did result in significant improvement in cardiac structure and function and composite clinical response over 6 months.