Cardiac resynchronization therapy optimization using noninvasive cardiac output measurement

Aims: Noninvasive cardiac output (CO) measurement (NICOM) is a novel method to assess ventricular function and offers a potential alternative for optimization of cardiac resynchronization therapy (CRT) devices. We compared the effect of NICOM‐based optimization to no optimization (empiric settings) on CRT outcomes. Methods: Two hundred and three patients undergoing CRT were assessed in two consecutive nonrandomized groups; an empiric group (n = 54) was programmed to “out of the box” settings with a fixed AV delay of 120 ms and a VV delay of 0 ms; and the optimization group (n = 149) underwent adjustments of both the AV and VV delays according to the greatest improvement in resting CO. The primary endpoints were improvements in left ventricular (LV) volumes and function from baseline at 6 months. Secondary endpoints were change in New York Heart Association (NYHA) class, quality of life score, and 6‐minute walk test (6 MWT) performance. Results: After 6 months of CRT, the optimization group had a better clinical response with lower NYHA class (2.1±0.8 vs 2.4 ± 0.8, P = 0.048) and quality of life scores (35 ± 18 vs 42 ± 20, P = 0.045) but no differences in 6‐MWT performance (269 ± 110 vs 277 ± 114 m, P = 0.81). Echocardiographic response was also better in the optimization group with lower LV end systolic volume (108 ± 51 vs 126 ± 60 mL, P = 0.048) and higher ejection fraction (30 ± 7 vs 27 ± 8, P = 0.01) compared to empiric settings. Conclusion: Device optimization using noninvasive measures of CO is associated with better clinical and echocardiographic response compared to empiric settings. (PACE 2011; 34:1527–1536)     

Long‐Term Effects of Upgrading to Biventricular Pacing: Differences with Cardiac Resynchronization Therapy as Primary Indication

Background: Few studies have assessed the long‐term effects of cardiac resynchronization therapy (CRT) in patients with advanced heart failure (HF) and previously right ventricular apical pacing (RVAP). Aims: To assess the clinical and hemodynamic impact of upgrading to biventricular pacing in patients with severe HF and permanent RVAP in comparison with patients who had CRT implantation as initial therapy. Methods and Results: Thirty‐nine patients with RVAP, advanced HF (New York Heart Association [NYHA] III–IV), and severe depression of left ventricular ejection fraction (LVEF) were upgraded to biventricular pacing (group A). Mean duration of RVAP before upgrading was 41.8 ± 13.3 months. Clinical and echocardiographic results were compared to those obtained in a group of 43 patients with left bundle branch block and similar clinical characteristics undergoing “primary” CRT (group B). Mean follow‐up was 35 ± 10 months in patients of group A and 38 ± 12 months in group B. NYHA class significantly improved in groups A and B. LVEF increased from 0.23 ± 0.07 to 0.36 ± 0.09 (P < 0.001) and from 0.26 ± 0.02 to 0.34 ± 0.10 (P < 0.001), respectively. Hospitalizations were reduced by 81% and 77% (P < 0.001). Similar improvements in echocardiographic signs of ventricular desynchronization were also observed. Conclusion: Patients upgraded to CRT exhibit long‐term clinical and hemodynamic benefits that are similar to those observed in patients treated with CRT as initial strategy. (PACE 2010; 841–849)     

Site‐Specific Differences in Latency Intervals during Biventricular Pacing: Impact on Paced QRS Morphology and Echo‐Optimized V‐V Interval

Objective: To investigate differences in latency intervals during right ventricular (RV) pacing and left ventricular (LV) pacing from the (postero‐)lateral cardiac vein in cardiac resynchronization therapy (CRT) patients and their relationship to echo‐optimized interventricular (V‐V) intervals and paced QRS morphology. Methods: We recorded digital 12‐lead electrocardiograms in 40 CRT patients during RV, LV, and biventricular pacing at three output settings. Stimulus‐to‐earliest QRS deflection (latency) intervals were measured in all leads. Echocardiographic atrioventricular (AV) and V‐V optimization was performed using aortic velocity time integrals. Results: Latency intervals were longer during LV (34 ± 17, 29 ± 15, 28 ± 15 ms) versus RV apical pacing (17 ± 8, 15 ± 8, 13 ± 7 ms) for threshold, threshold ×3, and maximal output, respectively (P < 0.001), and shortened with increased stimulus strength (P < 0.05). The echo‐optimized V‐V interval was 58 ± 31 ms in five of 40 (12%) patients with LV latency ≥ 40 ms compared to 29 ± 20 ms in 35 patients with LV latency < 40 ms (P < 0.01). During simultaneous biventricular pacing, four of five (80%) patients with LV latency ≥ 40 ms exhibited a left bundle branch block (LBBB) pattern in lead V₁ compared to three of 35 (9%) patients with LV latency < 40 ms (P < 0.01). After optimization, all five patients with LV latency ≥ 40 ms registered a dominant R wave in lead V₁. Conclusions: LV pacing from the lateral cardiac vein is associated with longer latency intervals than endocardial RV pacing. LV latency causes delayed LV activation and requires V‐V interval adjustment to improve hemodynamic response to CRT. Patients with LV latency ≥ 40 ms most often display an LBBB pattern in lead V₁ during simultaneous biventricular pacing, but a right bundle branch block after V‐V interval optimization. (PACE 2010; 1382–1391)     

Cardiac Resynchronization Therapy Device Implantation in Patients with Therapeutic International Normalized Ratios

Background: Many patients who need cardiac resynchronization therapy (CRT) require chronic anticoagulation. Current guidelines recommend discontinuation of warfarin and the initiation of anticoagulant “bridging” therapy during these procedures. We evaluated the safety of CRT‐device (CRT‐D) implantation without interruption of warfarin therapy. Methods: A total of 123 consecutive patients requiring CRT‐D therapy were enrolled, 49 identified as high risk for thromboembolic events who received either intravenous heparin, low molecular weight heparin, or warfarin therapy. The control group comprised 74 patients with low risk of thromboembolic events who required only cessation of warfarin perioperatively. Patients were evaluated at discharge and 15 and 30 days postoperatively for pocket hematomas, thromboembolic events, and bleeding. Patients’ length of stay was also catalogued. Results: Patients in the bridging arm had a significant increase in the rate of pocket hematomas (4.1%[control] vs 5.0%[warfarin] vs 20.7%[bridging], P = 0.03) and subsequent longer length of stay (1.6 ± 1.6 [control] vs 2.9 ± 2.7 [warfarin] vs 3.7 ± 3.2 [bridging], P < 0.001). Hematoma formation postoperatively was not different among patients undergoing an upgrade procedure versus those without preexisting cardiac rhythm devices (12% vs 6.2%, P = NS). Patients with a prosthetic mechanical mitral valve had a higher incidence of pocket hematoma formation (1.8% vs 20%, P = 0.03). Conclusions: Our findings suggest that implantation of CRT‐Ds without interruption of warfarin therapy in patients at high risk of thromboembolic events is a safe alternative to routine bridging therapy. This strategy is associated with reduced risk of pocket hematomas and shorter length of hospital stay. (PACE 2010; 400–406)     

Greater three-dimensional ventricular lead tip separation is associated with improved outcome after cardiac resynchronization therapy

Background: Effective cardiac resynchronization therapy (CRT) is more likely with widely separated left ventricular (LV) and right ventricular (RV) pacing leads tips. We hypothesized that lead separation is an important factor in determining the clinical response to CRT. Methods: A retrospective study of 86 consecutive patients age 71 ± 10 years, male (74%), coronary disease (71%), atrial fibrillation (23%), LV ejection fraction (22 ± 9%), QRS duration (160 ± 27 ms), New York Heart Association (NYHA) class III (81%), NYHA class IV (19%) undergoing CRT from January 2006 to September 2008. The median follow‐up was 12 months and clinical response to CRT was defined as reduction of NYHA class by one or more. The three‐dimensional separation between RV and LV pacing lead tips was calculated using measurements obtained from orthogonal posteroanterior and lateral chest radiographs performed the day after implantation. Results: Fifty‐nine patients (69%) responded to CRT. There was a statistically significant association between increased three‐dimensional lead separation and clinical response to CRT (P= 0.005). Stronger association was obtained when lead separation was corrected for cardiac size (P= 0.001). A significantly higher response rate of 88% was achieved in patients with QRS duration of 160 ms or more, and lead separation of 100 mm or more compared with 60% when lead separation was less than 100 mm and QRS duration remained the same (P = 0.027). Conclusions: Greater three‐dimensional separation of LV‐to‐RV leads is associated with improved response to CRT. A prospective multicenter trial is needed to assess lead separation as a predictor for response. (PACE 2010; 33:1490–1496)     

Advantage of Optimizing V‐V Timing in Cardiac Resynchronization Therapy Devices

Background: There is little consensus as to the benefits of interventricular (V‐V) timing optimization in cardiac resynchronization therapy (CRT). A variety of parameters are currently used to optimize device timing. This study was designed to investigate the potential advantage of using 3D ejection fraction (EF) and aortic velocity‐time integral (VTI) as measures of global left ventricular (LV) function to optimize ventricular activation in CRT devices. Methods: Seventy‐four patients seen in the Optimization Clinic with adequate echocardiographic images were included. Three aortic VTI and two 3D EF values were recorded at five V‐V settings and the average value used. Aortic VTI and 3D EF were classified as the best, worst, and simultaneous setting values. Data were analyzed using a two‐tailed paired t‐test. Results: Comparing the best to worst V‐V timing settings, VTI improved by 4.7 ± 7.5 cm (P < 0.0001) and 3D EF by 9.9%± 5.7% (P < 0.0001). Comparing the simultaneous setting to the best V‐V timing setting, VTI improved by 2.4 ± 2.1 cm (P < 0.0001) and 3D EF by 3.8%± 4.9% (P < 0.0001). Aortic VTI improved in 85% of patients and 3D EF improved in 72%. However, only 26% of the patients had the same optimal setting using aortic VTI and 3D EF yielding an r² value of 0.003. Conclusions: Individualized echocardiographic V‐V optimization of CRT devices improves global LV function as measured by aortic VTI and 3D EF. Substantial differences in function were seen over an 80‐ms range of V‐V timing and optimization resulted in improved LV function in the majority of patients. (PACE 2010; 33:1161–1168)     

Adrenomedullin Plasma Levels Predict Left Ventricular Reverse Remodeling after Cardiac Resynchronization Therapy

Background: Increase in adrenomedullin (ADM) plasma levels in congestive heart failure (HF) patients is due to many cardiac and systemic factors, particularly to greater fluid retention and to activation of sympathetic nervous system. Aim of this study was to assess the role of plasma ADM levels in HF patients treated by cardiac resynchronization therapy (CRT). Methods: 50 patients, mean age 70 years, 34 male, New York Heart Association (NYHA) Class III–IV HF, left ventricular ejection fraction (LVEF) < 35%, underwent CRT. All patients were in sinus rhythm and with complete left bundle branch block (QRS duration 138 ± 6 msec). A complete echoDoppler exam, blood samples for brain natriuretic peptide (BNP), and ADM were obtained from 2 to 7 days before implantation. Results: At 16 ± 6 months follow‐up, ≥1 NYHA Class improvement was observed in 38 patients. However, a >10% reduction in end‐systolic dimensions (ESD) was reported in 21 patients (Group I): ?16.6 ± 1.8%; in the remaining 29 patients ESD change was almost negligible: ?2.0 ± 1.03% (Group II), P < 0.0001. The two groups were comparable for age, sex, cause of LV dysfunction, therapy, QRS duration at baseline, preimplantation ESD, LVEF%, and BNP. Significantly higher pre implantation ADM levels were present in Group I than in Group II (27.2 ± 1.8 pmol/l vs 17.9 ± 1.4, P = 0.0003). Conclusions: Significantly higher ADM levels indicate a subgroup of patients in whom reverse remodeling can be observed after CRT. Patients with lower ADM basal values before CRT could represent a group in whom the dysfunction is so advanced that no improvement can be expected. (PACE 2010; 865–872)     

Continuously adjusting CRT therapy: clinical impact of adaptive cardiac resynchronization therapy

Cardiac resynchronization therapy (CRT) is a well-established therapy to reduce morbidity and mortality in patients with moderate and severe symptomatic congestive heart failure. Left ventricular (LV) pacing that fuses with intrinsic right ventricular (RV) conduction results in similar or even better cardiac performance compared to biventricular (Biv) pacing. Optimal programming of the atrio-ventricular (AV) and inter-ventricular (VV) delays is crucial to improve LV performance since suboptimal programming of AV and VV delays affect LV filling as well as cardiac output. CRT optimization using echocardiogram is resource-dependent and time consuming. Adaptive CRT (aCRT) algorithm provides a dynamic, automatic, ambulatory adjustment of CRT pacing configuration (Biv or LV pacing) and optimization of AV and VV delays. aCRT algorithm is safe and efficacious for CRT-indicated patients without permanent atrial fibrillation. It has been shown to improve CRT response and reduce morbidity and mortality for patients with normal AV conduction.     

Comparison of hemodynamic versus dyssynchrony assessment for interventricular delay optimization with echocardiography in cardiac resynchronization therapy

Background: Best practice for cardiac resynchronization therapy (CRT) device optimization is not established. This study compared Tissue Doppler Imaging (TDI) to study left ventricular (LV) synchrony and left ventricular outflow tract velocity‐time integral (LVOT VTI) to assess hemodynamic performance. Methods: LVOT VTI and LV synchrony were tested in 50 patients at three interventricular (VV) delays (LV preactivation at ?30 ms, simultaneous biventricular pacing, and right ventricular preactivation at +30 ms), selecting the highest VTI and the greatest degree of superposition of the displacement curves, respectively, as the optimum VV delay. Results: In 39 patients (81%), both techniques agreed (Kappa = 0.65, p < 0.0001) on the optimum VV delay. LV preactivation (VV ? 30) was the interval most frequently chosen. Conclusions: Both TDI and LVOT VTI are useful CRT programming methods for VV optimization. The best hemodynamic response correlates with the best synchrony. In most patients, the optimum VV interval is LV preactivation. (PACE 2011; 34:984–990)     

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

Background: 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. Methods and Results: This was a randomized study of 72 patients with high risk of sudden cardiac death, ejection fraction (EF) ≤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 (ΔESV =?7 ± 52 mL), and CRT OFF group (ΔESV =?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. Conclusion: 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.     

The hemodynamic effect of right ventricle (RV), RT3DE targeted left ventricle (LV) and biventricular (BIV) pacing in the early postoperative period after cardiac surgery

Background: Congestive heart failure negatively impacts the prognosis in patients after cardiac surgery. The aim of our study was to assess the value of targeted cardiac resynchronization therapy (CRT) within 72 hours after cardiac surgery in patients with mechanical dyssynchrony, who had an ejection fraction ≤ 35%, QRS ≥150 ms or between 120 and 150 ms. Methods: A prospective randomized trial based on three‐dimensional echocardiography (RT3DE) and optimized sequential dual‐chamber (DDD ) pacing in patients after cardiac surgery. DDD epicardial pacing (Medtronic coaxial epicardial leads 6495) was provided by a modified Medtronic INSYNC III Pacemaker (Medtronic Inc., Minneapolis, MN, USA). Summary of results: The study included 21 patients with ischemic heart disease (HD) or valvular HD (16 men, 5 women, average age 69 years) with left ventricle (LV) dysfunction after cardiac surgery . Patients with biventricular (BIV) (CO 6.7 ± 1.7 L/min, CI 3.5 ± 0.8 L/min/m²) and LV (CO 6.2 ± 1.5 L/min, CI 3.2 ± 0.7 L/min/m²) pacing had statistically significantly higher CO and CI than patients with right ventricular (RV) (CO 5.4 ± 1.4 L/min, CI 2.8 ± 0.6 L/min/m²) pacing (BIV vs RV P ≤ 0.001; LV vs RV P ≤ 0.05; BIV vs LV P ≤ 0.05). Conclusions: RT3DE targeted and optimized CRT in the early postperative period after cardiac surgery provided better hemodynamic results than RV pacing. (PACE 2011; 34:1231–1240)     

Female gender is associated with a better outcome after cardiac resynchronization therapy

Background: Some studies have suggested that women respond differently to cardiac resynchronization therapy (CRT). We sought to determine whether female gender influences long‐term clinical outcome, symptomatic response as well as echocardiographic response after CRT. Methods and Results: A total of 550 patients (age 70.4 ± 10.7 yrs [mean ± standard deviation]) were followed up for a maximum of 9.1 years (median: 36.2 months) after CRT‐pacing (CRT‐P) or CRT‐defibrillation (CRT‐D) device implantation. Outcome measure included mortality as well as unplanned hospitalizations for heart failure or major adverse cardiovascular events (MACE). Female gender predicted survival from cardiovascular death (hazard ratio [HR]: 0.52, P = 0.0051), death from any cause (HR: 0.52, P = 0.0022), the composite endpoints of cardiovascular death /heart failure hospitalizations (HR: 0.56, P = 0.0036) and death from any cause/hospitalizations for MACE (HR: 0.67, P = 0.0214). Female gender predicted death from pump failure (HR: 0.55, P = 0.0330) but not sudden cardiac death. Amongst the 322 patients with follow‐up echocardiography, left ventricular (LV) reverse remodelling (≥15% reduction in LV end‐systolic volume) was more pronounced in women (62% vs 44%, P = 0.0051). In multivariable Cox proportional hazards analyses, the association between female gender and cardiovascular survival was independent of age, LV ejection fraction, atrial rhythm, QRS duration, CRT device type, New York Heart Association (NYHA) class, and LV reverse remodelling (adjusted HR: 0.48, P = 0.0086). At one year, the symptomatic response rate (improvement by ≥1 NYHA classes or ≥25% increase in walking distance) was 78% for both women and men. Conclusions: Female gender is independently associated with a lower mortality and morbidity after CRT. (PACE 2011; 82–88)     

Long term effects of cardiac resynchronization therapy in non-ambulatory NYHA IV heart failure patients

Background: We aimed at evaluating the long‐term effects of cardiac resynchronization therapy (CRT) in nonambulatory New York Heart Association (NYHA) IV heart failure patients (NAIVHFP). Methods: Eighteen patients, 15 men and three women, eight with ischemic and 10 with nonischemic cardiomyopathy, who underwent biventricular pacemaker implantation while they were in nonambulatory NYHA IV class, were studied. Patients’ age was 58 ± 9 years and left ventricular ejection fraction (LVEF) 18 ± 3 %. Follow‐up data were obtained through review of follow‐up visits notes, stored echocardiographic studies, device interrogation data, and death certificates. Results: After a mean duration of 1223 ± 846 days, 11 patients were alive, including five patients who underwent heart transplantation (OCT) and seven dead. Three of 11 patients who received a CRT‐defibrillator, experienced at least one appropriate discharge, but eventually they either died or received an OCT during follow‐up. Sustained improvements in NYHA class (Z = 2.4, P = 0.015) and 6‐minute walk distance (0 vs 212 ± 95 m, P ? 0.001) were documented after a median duration of 855 days postimplantation. Cumulative proportion of death or OCT at 18 months—when full follow‐up data were available—was 18%, which compared favorably with historical controls. Full echocardiographic and clinical follow‐up data at 12‐months postimplantation were available for 10 patients, documenting a significant reduction in end‐systolic volume (248 ± 82 vs 269 ± 97 mL, P = 0.039). Conclusions: CRT can be safely applied in this subset of extreme severity heart failure patients, achieving encouraging survival rates and reverse remodeling effects. These observations can form an evidence‐based rationale for including NAIVHFP in randomized CRT trials. (PACE 2011; 34:1553–1560)     

Hemodynamics and prognosis after primary cardiac resynchronization system implantation compared to "upgrade" procedures

Introduction: Left bundle brunch block (LBBB) and right ventricular stimulation (RVS) may be associated with asynchrony and heart failure. Differences between these two entities and their response to cardiac resynchronization therapy (CRT) are not well defined. Methods: Patients receiving CRT from 1999 to 2006 were analyzed for cardiac events and prognosis separated between primary implants for LBBB (n = 221) and upgrades from RVS (n = 107). A subgroup of 105 patients (LBBB = 69; RVS = 36) was studied in more detail (New York Heart Association [NYHA], quality of life, brain natriuretic peptide, peakVO2, left ventricular ejection fraction [LVEF], wedge pressure, Cardiac Index, QRS, left‐right preejection period using pulsed wave doppler, septum‐lateral wall motion delay using tissue doppler imaging) at baseline and after 1 year. Results: Age (68.4 ± 11 years vs 68.7 ± 15 years, n. s.), NYHA class (3.1 vs 3.1, n. s.), LVEF (26.4 vs 28.1, n. s.), and clinical parameters were comparable between LBBB and RVS. The latter group consisted of more patients with chronic atrial fibrillation (14% vs 37%, P = 0.03). After 1 year, NYHA class (?0.8 ± 0.8 vs ?0.6 ± 0.8, n. s.), LVEF (+13.7 ± 14% vs +8.7 ± 10%, n. s.), and clinical parameters improved similarly. After a median follow‐up of 2.33 ± 1.8 years in the LBBB versus 2.43 ± 1.9 years in the RVS group, there was no difference in long‐term prognosis or cardiac events in the total cohort (5‐year event rate, 53% vs 55%, P = n. s.). Conclusion: Upgrade patients showed similar baseline parameters and response to CRT as to primary implants. No difference in events or long‐term prognosis could be observed.     

Selection of patient for cardiac resynchronization therapy: role of QT corrected dispersion

Aims : About 30 to 50% of patients undergoing cardiac resynchronization therapy (CRT) may not show clinical or echocardiographic improvement, despite fulfilling guidelines recommendations for CRT. For this reason, we need a more accurate method to assess CRT eligibility. The aims of this study were to verify, on a 12‐month follow‐up, the usefulness of QT corrected dispersion (QTcD) in a patient's selection for CRT. Methods : We stratified 53 patients who underwent CRT, into two groups based on the estimation of QTcD, that is, QTcD > 60 ms and QTcD ≤ 60 ms. In all patients were performed New York Heart Association (NYHA) class determination, six‐minute walking test, QtcD, and QRS measurements, and complete echocardiographic assessment at 1, 3, 6, and 12 months after implantation. Results : At baseline, there were no significant differences in clinical, echocardiographic, and electrocardiographic parameters duration between two groups. At 12‐month follow‐up between the two groups, there were significant differences in NYHA (1.2 ± 0.4 vs 2 ± 0.6; P < 0.01), six‐minute walking distance (422 ± 68 vs 364 ± 68; P < 0.01), left ventricular (LV) ejection fraction (34 ± 7% vs 28 ± 6%; P < 0.01), LV end‐diastolic diameter (57 ± 7 vs 63 ± 8; P < 0.01), and LV intraventricular dyssynchrony (24 ± 14 vs 39 ± 23; P < 0.01). Conclusion: This study suggests that QTc dispersion in addition to QRS duration could improve the sensitivity of electrocardiogram in a patient's selection for CRT. (PACE 2012;1–6)     

Cardiac Resynchronization Therapy in Non‐Left Bundle Branch Block Morphologies

Introduction: In select patients with systolic heart failure, cardiac resynchronization therapy (CRT) has been shown to improve quality of life, exercise capacity, ejection fraction (EF), and survival. Little is known about the response to CRT in patients with right bundle branch block (RBBB) or non‐specific intraventricular conduction delay (IVCD) compared with traditionally studied patients with left bundle branch block (LBBB). Methods: We assessed 542 consecutive patients presenting for the new implantation of a CRT device. Patients were placed into one of three groups based on the preimplantation electrocardiogram morphology: LBBB, RBBB, or IVCD. Patients with a narrow QRS or paced ventricular rhythm were excluded. The primary endpoint was long‐term survival. Secondary endpoints were changes in EF, left ventricular end‐diastolic and systolic diameter, mitral regurgitation, and New York Heart Association (NYHA) functional class. Results: Three hundred and thirty‐five patients met inclusion criteria of which 204 had LBBB, 38 RBBB, and 93 IVCD. There were 32 deaths in the LBBB group, 10 in the RBBB, and 27 in the IVCD group over a mean follow up of 3.4 ± 1.2 years. In multivariate analysis, no mortality difference amongst the three groups was noted. Patients with LBBB had greater improvements in most echocardiographic endpoints and NYHA functional class than those with IVCD and RBBB. Conclusion: There is no difference in 3‐year survival in patients undergoing CRT based on baseline native QRS morphology. Patients with RBBB and IVCD derive less reverse cardiac remodeling and symptomatic benefit from CRT compared with those with a native LBBB. (PACE 2010; 590–595)     

Stretch‐Activated Receptors Mediate Cardiac Memory

Background: Cardiac memory refers to long‐lasting T‐wave changes that follow an episode of altered ventricular activation sequence. Memory‐induced alterations in repolarizing ion channel activity have been characterized. However, the mechanism by which changes in activation sequence produce these effects is unknown. We hypothesized that cardiac memory is mediated by the response of stretch‐activated receptors (SARs) to a change in mechanical activation sequence. Methods: In anesthetized, closed‐chest dogs, coronary sinus leads were used to pace the posterolateral left ventricle (LV) continuously for 1 hour at a rate of 120 bpm. The surface vectorcardiogram was used to quantify cardiac memory by measuring T‐wave displacement after pacing. Streptomycin, which has been shown to block SARs, was given at a dose of 4 g intramuscularly 1 hour before experimental LV pacing sessions. T‐wave displacement after control sessions of LV pacing in the absence of drug (n = 12) was compared to that produced by pacing after streptomycin administration (n = 10 sessions). Results: There was a distinct and consistent cardiac memory seen after 1 hour of LV pacing under control conditions, with T‐wave displacement of 1.28 ± 0.43 mV (P < 0.001 vs baseline). Pretreatment with streptomycin had no direct effect on the electrocardiogram or hemodynamics, but decreased pacing‐induced T‐wave displacement to 0.50 ± 0.28 mV (P < 0.001 vs control sessions). Conclusions: Streptomycin, a SAR blocker, dramatically attenuated the development of cardiac memory following epicardial pacing. These data suggest that SARs are a critical link between mechanical sequence of activation and regional modulation of action potential duration that is responsible for cardiac memory.     

Interatrial conduction correlates with optimal atrioventricular timing in cardiac resynchronization therapy devices

Background: Echocardiographic optimization of the atrioventricular delay (AV) may result in improvement in cardiac resynchronization therapy (CRT) outcome. Optimal AV has been shown to correlate with interatrial conduction time (IACT) during right atrial pacing. This study aimed to prospectively validate the correlation at different paced heart rates and examine it during sinus rhythm (Sinus). Methods: An electrophysiology catheter was placed in the coronary sinus (CS) during CRT implant (n = 33). IACT was measured during Sinus and atrial pacing at 5 beats per minute (bpm) and 20 bpm above the sinus rate as the interval from atrial sensing or pacing to the beginning of the left atrial activation in the CS electrogram. P‐wave duration (PWd) was measured from 12‐lead surface electrocardiogram, and the interval from the right atrial to intrinsic right ventricular activation (RA‐RV) was measured from device electrograms. Within 3 weeks after the implant patients underwent echocardiographic optimization of the sensed and paced AVs by the mitral inflow method. Results: Optimal sensed and paced AVs were 129 ± 19 ms and 175 ± 24 ms, respectively, and correlated with IACT during Sinus (R = 0.76, P < 0.0001) and atrial pacing (R = 0.75, P < 0.0001), respectively. They also moderately correlated with PWd (R = 0.60, P = 0.0003 during Sinus and R = 0.66, P < 0.0001 during atrial pacing) and RA‐RV interval (R = 0.47, P = 0.009 during Sinus and R = 0.66, P < 0.0001 during atrial pacing). The electrical intervals were prolonged by the increased atrial pacing rate. Conclusion: IACT is a critical determinant of the optimal AV for CRT programming. Heart rate‐dependent AV shortening may not be appropriate for CRT patients during atrial pacing. (PACE 2011; 34:443–449)     

Acute Left Ventricular Dyssynchrony Improvement Predicts Long-Term Benefit from Cardiac Resynchronization Therapy

Study Objective: To evaluate the relationship between acute response to cardiac resynchronization therapy (CRT) and long-term clinical outcome in patients with drug refractory heart failure.
Methods and Results: In 28 patients undergoing CRT implant, left ventricular (LV) dyssynchrony was evaluated by tissue Doppler imaging (TDI)-derived longitudinal strain by mean of septum-lateral basal asynchrony index (S-Li) and basal delayed longitudinal contraction (DLC). TDI measurements were made before, and 30 minutes and 1 year after implant. Baseline and 1-year follow-up New York Heart Association (NYHA) functional class, 6-minute walking test (6-MWT) distance, and quality of life (QoL) score were measured. Responders (n = 22) were defined by a ≥ 1 decrease in NYHA functional class and 6-MWT ≥25% at 1 year. At baseline, no differences were observed between responders and nonresponders in clinical and echocardiographic measurements. LV dyssynchrony acutely recovered only in responders 30 minutes after implantation, with a significant reduction in S-Li and DLC. Moreover, the percent decreases in S-Li and DLC were highly correlated with those observed in NYHA class (r = 0.70, and r = 0.81, respectively, P < 0.001), 6-MWT (r = 0.59, and r = 0.57, respectively, P < 0.001 and P < 0.01), and QoL score (r = 0.71, and r = 0.83, respectively, p < 0.001) at 1-year follow-up.
Conclusions: Acute recovery of LV intraventricular dyssynchrony is a major discriminator between responders and nonresponders to CRT, which strongly correlates with a favorable long-term clinical outcome.     

A Prospective Randomized Evaluation of VV Delay Optimization in CRT-D Recipients: Echocardiographic Observations from the RHYTHM II ICD Study

Background: All current cardiac resynchronization therapy (CRT) devices allow the programming of the atrioventricular (AV/PV) delays and the sequential stimulation of the ventricles via the inter ventricular (VV) delay.
Aim: This post hoc analysis of the RHYTHM II study was conducted to compare the reverse remodeling associated with VV delay optimization in patients randomly assigned to simultaneous (SIM) biventricular stimulation versus patients assigned to optimized VV delay programming (OPT) (1:3 randomization scheme).
Methods: The analysis included 14 patients assigned to the SIM group and 34 patients to the OPT group who completed the 6-month follow-up period with paired echocardiographic recordings.
Results: In both study groups, changes consistent with left ventricular (LV) remodeling were observed between baseline and 6 months, with significant improvements in LV function and decrease in LV dimensions. In the OPT group, there was also a decrease in left atrial diameter and mitral valve closure to opening time. At 6 months, the overall proportion of echocardiographic responders (≥10% decrease in LV end-systolic volume or ≥5% absolute increase in LV ejection fraction) was similar in both groups. The optimal AV/VV delays, evaluated by maximization of LV outflow tract velocity time integral, changed over time.
Conclusions: Ventriculo-ventricular delay optimization was associated with better immediate hemodynamic function than simultaneous biventricular stimulation, though did not promote additional reverse remodeling at 6 months and did not increase the proportion of echocardiographic responders to CRT. Optimization of both the AV and VV intervals was patient-specific and optimal values changed over time.