Patients Undergoing Cardiac Resynchronization Therapy Implantation Research Articles

The rationale and design of the SMART CRT trial.

The SMART CRT study will assess the efficacy of an atrioventricular optimization algorithm to improve reverse remodeling among patients undergoing cardiac resynchronization therapy (CRT) in the presence of interventricular electrical delay. The SMART CRT study is a global, multicenter, prospective, randomized study of patients undergoing CRT implantation. The primary endpoint of this trial is response rate to CRT, defined as decrease in left ventricular end-systolic volume (LVESV) ≥15% at 6months compared to preimplant baseline. Additional prespecified analyses are: (1) clinical composite endpoint combining all-cause mortality, heart failure events, New York Heart Association class, and Quality of Life (using a patient global assessment instrument); (2) the individual components of the clinical composite endpoint; (3) 6-minute walk distance; (4) Kansas City Cardiomyopathy Questionnaire; (5) LVESV as a continuous variable; and (6) absolute left-ventricular ejection fraction. Subjects with intraventricular delay ≥ 70ms measured between the right ventricular and left ventricular pacing leads will be randomized in a 1:1 ratio to have either an AV Delay and pacing chamber determined by SmartDelay™ or a Fixed AV Delay of 120ms with biventricular pacing. Enrollment of an estimated 726 of subjects from up to 100 centers worldwide is planned to achieve 436 randomized subjects and 370 complete data sets required to power the primary endpoint. This trial will provide important data regarding the importance of AV Delay programming in patients with prolonged interventricular delay at the pacing sites.

Clinical outcomes after upgrading from pacemakers to cardiac resynchronization therapy.

Right ventricular pacing may lead to heart failure (HF). Upgrades from pacemakers to cardiac resynchronization therapy (CRT) were excluded from most randomized, controlled trials. We sought to determine the long-term outcomes of upgrading from pacemakers to CRT with (CRT-D) or without (CRT-P) defibrillation in patients with no history of sustained ventricular arrhythmias. In this observational study, clinical events were quantified in relation to the type of implant (de novo or upgrade) and device type at upgrade (CRT-P or CRT-D). Patients underwent CRT implantation (n=1,545; 1,314 [85%] de novo implants and 231 [15%] upgrades) over a median of 4.6 years [interquartile range: 2.4-7.0]. In analyses of crude event rates, upgrades had a higher total mortality (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI] 0.10-1.61), a higher total mortality or HF hospitalization (aHR: 1.26; 95% CI 1.05-1.51), but similar mortality or hospitalization for major adverse cardiac events (MACEs, aHR: 1.15; 95% CI 0.96-1.38). No group differences emerged in any of these endpoints after propensity score matching. After inverse probability weighting in upgrades, total mortality (HR: 0.55; 95% CI 0.36-0.73), total mortality or HF hospitalization (HR: 0.56; 95% CI 0.34-0.79), and total mortality or hospitalization for MACEs (HR: 0.61; 95% CI 0.40-0.82) were lower after CRT-D than after CRT-P. Upgrading from pacemakers to CRT was associated with a similar long-term risk of mortality and morbidity to de novo CRT. After upgrade, CRT-D was associated with a lower mortality than CRT-P.

Guidewire Method for Measuring Local Left Ventricular Electrical Activation Time During Cardiac Resynchronization Implantation.

The timing of local activation at left ventricular (LV) pacing leads is measured from the onset of the QRS complex to the peak of the LV electrogram (QLV). Pacing from the sites of late activation is associated with higher response rates to cardiac resynchronization therapy (CRT). Prior studies have measured QLV from permanent pacing leads, or have used electroanatomic mapping systems. The current study compares QLV measurements made with a guidewire to those collected from permanent LV pacing leads positioned at the same venous site without the use of electroanatomic mapping systems. In this study, 20 patients undergoing CRT implantation (14 males, mean QRS: 164.0 ms) had QLV measurements taken using a guidewire. QLV and LV electrogram duration measurements were made at LV pacing sites, and were repeated after positioning the permanent LV pacing lead at the same site. There was no difference in QLV measurements obtained using a guidewire and those obtained using the permanent pacing lead placed at the same site (p = 0.569). QLV measurements obtained with a guidewire and the permanent LV pacing lead at the same site, respectively, were strongly correlated (r = 0.965; p < 0.001). The median absolute difference in electrogram duration was 7.0 ms (p = 0.55). The average time required to make QLV measurements using the guidewire was 11.7 minutes [standard deviation (SD): 6.8]. The average total fluoroscopy time for the entire CRT implant procedure was 10.9 minutes (SD: 5.1). In light of these results, it can be suggested that a guidewire can be used to prospectively measure LV prior to selection or placement of a permanent pacing lead without the use of an electroanatomic mapping system.

Profound differences in prognostic impact of left ventricular reverse remodeling after cardiac resynchronization therapy relate to heart failure etiology

An ischemic etiology of heart failure (HF) has been associated with reduced left ventricular reverse remodeling after cardiac resynchronization therapy (CRT). The purpose of this study was to assess the relationship between the etiology of HF and reverse remodeling and outcome after CRT. Consecutive patients undergoing CRT implantation between October 1, 2008 and August 14, 2015 were retrospectively evaluated. Coronary angiography classified ischemic vs nonischemic etiology. Reverse remodeling was defined as the changes in left ventricular ejection fraction (LVEF) after 6 months. Clinical outcome was assessed 1 year after implantation using a combined end point of all-cause mortality and HF readmission. A total of 685 patients were included (300/385 for ischemic/nonischemic etiology). Compared with patients with ischemic cardiomyopathy, patients with nonischemic cardiomyopathy exhibited a greater degree of improvement in LVEF (8.4% ± 10.4% vs 15.8% ± 12.3%; P < .001). After correcting for differences, an ischemic etiology of HF predicted less reverse remodeling (P < .001) and a higher rate of mortality or HF readmission (hazard ratio 1.63; 95% confidence interval [CI] 1.12-2.73; P = .011). Nevertheless, in comparison to a greater degree of improvement in LVEF, a lesser degree of improvement in LVEF (0%-5%) was associated with a higher risk of all-cause mortality and HF hospitalization in patients with nonischemic cardiomyopathy (odds ratio 9.78; 95% CI 1.95-49.04; P = .006) but not in patients with ischemic cardiomyopathy (odds ratio 3.58; 95% CI 0.85-15.18; P= .083). The most accurate cutoff for improvement in LVEF predicting good clinical outcome was 5.5% in ischemic cardiomyopathy vs 10.5% in nonischemic cardiomyopathy. CRT results in reverse remodeling in both patients with ischemic and nonischemic cardiomyopathy, but to a lesser extent in the former. Patients with an ischemic etiology are at an intrinsically higher risk of mortality and HF hospitalization, but derive benefit on outcome at a lesser degree of reverse remodeling.

The concept of triple wavefront fusion during biventricular pacing: Using the EGM to produce the best acute hemodynamic improvement in CRT.

Previous reports suggest that biventricular pacing (BiVp) fused with intrinsic conduction (BiVp-fusion, triple wavefront fusion) is associated with improved resynchronization compared to pure-BiVp in cardiac resynchronization therapy (CRT). This study aimed to assess the association between acute hemodynamic benefit of CRT and signs of BiVp-fusion by using a novel electrogram (EGM)-based method. In 17 patients undergoing CRT implantation, 28 combinations of atrioventricular (AV) and interventricular (VV) delays were applied while invasively measuring acute hemodynamic response based on maximum rate of left ventricular (LV) pressure rise (LV dP/dtmax ) to assess optimal BiVp settings. BiVp-fusion was noted if farfield signal (caused by first intrinsic ventricular depolarization) was seen prior to right ventricular (RV) pacing (RVp) artifact on integrated bipolar RV EGM, or QRS morphology changed compared to pure-BiVp (short AV-delay) as seen on electrocardiogram (ECG). Mean optimal RVp timing was at 98 ± 17% of intrinsic right atrial (RA)-RVfarfield (interval from right atrial pace or sense to RV farfield signal) interval, while preactivating the LV at 50 ± 11% of RA-RVsense (interval from right atrial pace or sense to RV sense interval) interval. BiVp-fusion was noted in 16 of 17 (94%) patients on ECG during optimal BiVp. Eight of these patients showed intrinsic farfield signal prior to RVp artifact on RV EGM. In the remaining eight, the RVp was paced just within the RA-RVfarfield interval with a mean of 25 ± 14 ms prior to the onset; therefore, the intrinsic farfield was masked. Optimal hemodynamic BiVp facilitates triple wavefront fusion, by pacing the RV around the onset of intrinsic farfield signal on RV EGM, while preactivating the LV. Aiming at BiVp-fusion could be a target for noninvasive EGM-based CRT device setting optimization.

Mid-regional pro-atrial natriuretic peptide to predict clinical course in heart failure patients undergoing cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) induces reverse cardiac remodelling in heart failure (HF), but many patients receiving CRT remain non-responders. This study assessed the role of amino-terminal-pro-B-type natriuretic peptide (NT-proBNP), mid-regional-pro-atrial natriuretic peptide (MR-proANP), and mid-regional-pro-adrenomedullin (MR-proADM) at the time of device implantation to predict favourable clinical course (CRT response and/or risk of MACE) in HF patients receiving CRT. A total of 137 HF patients were prospectively included. Blood was drawn from the coronary sinus (CS) at CRT implantation, and from a peripheral vein (PV) simultaneously and after 6 months. Clinical CRT response at 6 months and major adverse cardiovascular events (MACE) at 2 years were assessed. Baseline PV-levels of MR-proANP (202 vs. 318 pmol/L, P = 0.009) and MR-proADM (843 vs. 1112 pmol/L, P = 0.02) were lower in CRT responders compared with non-responders. At 6 months, CRT responders showed a decrease in MR-proANP levels, compared with an increase in non-responders (-32 vs. +7 pmol/L, P = 0.02). During the same period, NT-proBNP decreased by a similar way in responders and non-responders, while MR-proADM was unchanged in both groups. High baseline MR-proANP, either in PV (OR 0.41, 95% CI 0.24-0.71, P = 0.002) or CS (OR 0.32, 95% CI 0.15-0.70, P = 0.005) was associated with reduced likelihood of CRT response. Furthermore, PV and CS levels of NT-proBNP, MR-proANP, and MR-proADM were all associated with increased risk of 2-year MACE (all P < 0.01). Mid-regional-pro-atrial natriuretic peptide may assist prediction of clinical course in HF patients undergoing CRT implantation. Low circulating MR-proANP at the time of device implantation is associated with CRT response and more favourable outcome.

Increasing sex differences in the use of cardiac resynchronization therapy with or without implantable cardioverter-defibrillator

Previous studies have identified sex disparities in the use of cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators (ICD), although the basis of underutilization in women remains poorly understood. The aim of this study was to assess sex differences in patterns of CRT use with our without ICD. In this cross-sectional study using the National Inpatient Sample database we identified 311 009 patients undergoing CRT implantation in the United States between 2006 and 2012. Demographic and clinical characteristics were compared between men and women undergoing CRT implantation, with special attention to clinical predictors of left ventricular reverse remodelling (CRT response, score range: 0-4) and reduced ICD efficacy (score range: 0-7). When compared to men, women undergoing CRT implantation were significantly more likely to have ≥ 3 predictors of CRT response (47.3 vs. 33.2%, P < 0.001) and less likely to have ≥3 predictors of reduced ICD efficacy (27.0 vs. 37.3%, P < 0.001). Despite this, men were significantly more likely to undergo CRT with ICD (CRT-D) as the type of CRT (88.6 vs. 80.1% of all CRT implants). Compared to those with the greatest likelihood of CRT response (score ≥ 3), those with the least likelihood of CRT response had a significant decreased odds of CRT-D implant (adj odds ratio 0.27 [0.24-0.31], P < 0.001), with a greater decreased odds in women compared to men (P, for sex interaction <0.001). The difference in the % of CRT-D implant in men vs. women increased over the study period (P, sex Δ time trend = 0.012). In this large, contemporary cohort, sex differences in CRT-D implantation were inversely related to predicted CRT efficacy and have increased over time. Future efforts to narrow the gap in CRT-D implantation in men and women may help better align device selection with those most likely to benefit.

Left ventricular scar impact on left ventricular synchronization parameters and outcomes of cardiac resynchronization therapy

BackgroundLeft ventricular scar, including global scar and lateral wall, plays an important role in predicting response to cardiac resynchronization therapy (CRT). Materials and methodsThirty patients underwent CRT implantation. Assessment of left ventricular (LV) dyssynchrony was done through Gated SPECT LV phase analysis. Pre-implantation cardiac magnetic resonance (CMR) with late gadolinium enhancement technique to examine LV scar burden. Echocardiographic examination of LV end-systolic volume (LVES) prior to CRT and 6 months later. ResultsThirty patients received CRT (mean age 58.7±9.0, 24 males). Reverse LV remodeling (decline ≥15% from baseline VES) was documented in 19 patients. Temporal changes in LV dyssynchrony parameters were correlated to LV reverse remodeling. Applying ROC for predicting CRT non-response showed a cutoff 36.5% of global LV scar burden had a sensitivity of 81.8% and specificity of 68.4%. A cutoff for lateral wall scar burden 40.5% of whole lateral wall had a sensitivity of 72.7% and specificity of 68.4%. ConclusionReverse LV remodeling is associated with temporal improvements in LV dyssynchrony parameters. LV scar had an unfavorable impact on CRT response. Both global and lateral wall scar burden could predict CRT nonresponse status.

ECG parameters predict left ventricular conduction delay in patients with left ventricular dysfunction

Estimating left ventricular electrical delay (Q-LV) from a 12-lead ECG may be important in evaluating cardiac resynchronization therapy (CRT). The purpose of this study was to assess the impact of Q-LV interval on ECG configuration. One hundred ninety-two consecutive patients undergoing CRT implantation were divided electrocardiographically into 3 groups: left bundle branch block (LBBB), right bundle branch block (RBBB), and nonspecific intraventricular conduction delay (IVCD). The IVCD group was further subdivided into 81 patients with left (L)-IVCD and 15 patients with right (R)-IVCD (resembling RBBB, but without S wave in leads I and aVL). The Q-LV interval in the different groups and the relationship between ECG parameters and the maximum Q-LV interval were analyzed. Patients with LBBB presented a long Q-LV interval (147.7 ± 14.6 ms, all exceeding cutoff value of 110 ms), whereas RBBB patients presented a very short Q-LV interval (75.2 ± 16.3 ms, all <110 ms). Patients with an IVCD displayed a wide range of Q-LV intervals. In L-IVCD, mid-QRS notching/slurring showed the strongest correlation with a longer Q-LV interval, followed, in decreasing order, by QRS duration >150 ms and intrinsicoid deflection >60 ms. Isolated mid-QRS notching/slurring predicted Q-LV interval >110 ms in 68% of patients. The R-IVCD group presented an unexpectedly longer Q-LV interval (127.0 ± 12.5 ms; 13/15 patients had Q-LV >110 ms). Patients with LBBB have a very prolonged Q-LV interval. Mid-QRS notching in lateral leads strongly predicts a longer Q-LV interval in L-IVCD patients. Patients with R-IVCD constitute a subgroup of patients with a long Q-LV interval.

16-76: Assessing the value of novel biomarkers in the prediction of clinical outcomes after cardiac resynchronization therapy

Purpose: Cardiac resynchronization therapy (CRT) improves mortality in chronic heart failure (HF) patients with ventricular dyssynchrony, although some patients do not improve clinically and pass away unexpectedly despite correct CRT indications. In this study we investigated a set of novel heart failure biomarkers associated with various pathways of heart failure pathophysiology, our purpose was to assess their ability to predict clinical outcomes after CRT. Methods: We enrolled 136 consecutive chronic HF patients undergoing CRT implantation to our prospective single-center observational study. We measured the plasma levels of fractalkine, pentraxin-3, hepatocyte growth factor, CA-125 and MMP-9 before and six months after CRT with commercially available assays. The primary endpoint of the study was five year all-cause mortality, we considered six month reverse remodelling defined as at least 15% decrease in end systolic volume as secondary end-point. Results: During five years of follow-up 58 patients (43%) deceased, 66 were considered as non-responder. From the investigated baseline clinical variables age, NYHA class III-IV and NT-proBNP were predictive of reverse remodelling. Five years all-cause mortality was significantly related to left brundle branch block, beta blocker therapy and increasing NT-proBNP levels. After adjusting to all significant baseline parameters HGF was the only independent predictor of reverse remodelling (OR: 0.54, CI for OR: 0.32-0.90, p = 0.01) and 5-year mortality (HR: 1.35, CI for HR: 1.11-1.64, p = 0.003). The reclassification analyses revealed that HGF reached a reclassification improvement of 39 % [NRI= 0.39 (0.07-0-71), p = 0.01] in reverse remodeling and 69 % [NRI= 0.69 (0.39-0.99), p < 0.0001] in 5-year mortality prediction. Moreover, discrimination development was 3 % [IDI= 0.03 (0.00-0.06), p = 0.02] in reverse remodelling and 6% [IDI = 0.06 (0.02-0.11) in 5-year mortality prediction. Conclusion: Of all studied biomarkers HGF, the pleiotropic cardioprotective agent was the only independent predictor of clinical outcomes in HF patients undergoing CRT, reclassification analyses showed that it may be useful in refining patient selection.

Temporal changes of left ventricular synchronization parameters and outcomes of cardiac resynchronization therapy

BackgroundLeft ventricular dyssynchrony plays an important role in predicting response to cardiac resynchronization therapy (CRT). MethodsThirty patients underwent CRT implantation. Assessment of left ventricular (LV) dyssynchrony was done through Gated SPECT LV phase analysis. ResultsThirty patients received CRT (mean age 58.7±9.0, 24 males). CRT implantation had a favorable prognosis on cardiac functions (LVEF preimplantation: 26.8±4.7% versus 29.1±6.4% post-implantation; P=0.002). Reverse LV remodeling (⩾15%) was documented in 19 patients. Temporal changes in LV dyssynchrony parameters were correlated to LV reverse remodeling. Applying ROC curve for LV phase analysis showed that a cutoff value of 152° for histogram bandwidth had a sensitivity of 72.7% and specificity of 63.2% for predicting CRT non-response status. Also, a cutoff value of 54° for histogram standard deviation had a sensitivity of 81.8% and specificity of 63.2%. ConclusionResponders of CRT showed improved LV dyssynchrony profiles. Utilizing Gated SPECT LV analysis could provide predictors for CRT non-response. Reverse LV remodeling is associated with temporal improvements in LV dyssynchrony parameters.

Zero x-ray cardiac resynchronization therapy device implantation guided by a nonfluoroscopic mapping system: A pilot study

Fluoroscopic guidance is the standard tool used in device implantation. This means that both the patient and the operator are exposed to radiation, which may sometimes be high. The possibility of single-lead permanent pacemaker implantation without fluoroscopy has already been demonstrated. The aim of our study was to investigate the feasibility and reliability of biventricular device implantation guided only by an electroanatomic navigation system. Sixty-one patients with heart failure underwent implantation of a cardiac resynchronization therapy (CRT) device with or without defibrillator (CRT-D; CRT-P). The procedure was performed with or without fluoroscopy guidance (Rx+; Rx0). In the latter case, the EnSite Velocity system was used; this system is able to reconstruct the anatomy and activation of the cardiac chambers by simultaneously collecting a "cloud" of anatomical points from multiple electrodes. Lead positioning was achieved in 24 of 26 patients undergoing CRT implantation without fluoroscopy (92% success). No complications were observed during the procedure and no catheter dislodgment occurred the day after the implantation or during 1-month follow-up. Procedure time progressively decreased from 136 minutes in the first case to 59 minutes in the last one, suggesting that operators gradually gained confidence while using the new technique. Our study demonstrates the feasibility, efficacy, and safety of lead positioning guided only by the nonfluoroscopic EnSite Velocity mapping system without the use of fluoroscopy in CRT-P or CRT-D implantation. The benefits in terms of significantly reduced fluoroscopy exposure are associated with technical and clinical advantages.

Comparison of Conventional versus Steerable-Catheter Guided Coronary Sinus Lead Positioning in Patients Undergoing Cardiac Resynchronization Device Implantation

ObjectivesThe aim of this study was to compare conventional versus steerable catheter guided coronary sinus (CS) cannulation in patients with advanced heart failure undergoing cardiac resynchronization therapy (CRT).BackgroundSteerable catheter guided coronary sinus cannulation could reduce fluoroscopy time and contrast medium use during CRT implantation.Methods176 consecutive patients with ischemic and non-ischemic heart failure undergoing CRT implantation from January 2008 to December 2012 at the University Hospital of Cologne were identified. During the study period two concurrent CS cannulation techniques were used: standard CS cannulation technique (standard-group, n = 113) and CS cannulation using a steerable electrophysiology (EP) catheter (EPCath-group, n = 63). Propensity-score matched pairs of conventional and EP-catheter guided CS cannulation made up the study population (n = 59 pairs). Primary endpoints were total fluoroscopy time and contrast medium amount used during procedure.ResultsThe total fluoroscopy time was 30.9 min (interquartile range (IQR), 19.9–44.0 min) in the standard-group and 23.4 min (IQR, 14.2-34-2 min) in the EPCath-group (p = 0.011). More contrast medium was used in the standard-group (60.0 ml, IQR, 30.0–100 ml) compared to 25.0 ml (IQR, 20.0–50.0 ml) in the EPCath-group (P<0.001).ConclusionsUse of steerable EP catheter was associated with significant reduction of fluoroscopy time and contrast medium use in patients undergoing CRT implantation.

Longer right to left ventricular activation delay at cardiac resynchronization therapy implantation is associated with improved clinical outcome in left bundle branch block patients

AimsData on longer right to left ventricular activation delay (RV-LV AD) predicting clinical outcome after cardiac resynchronization therapy (CRT) by left bundle branch block (LBBB) are limited. We aimed to evaluate the impact of RV-LV AD on N-terminal pro–B-type natriuretic peptide (NT-proBNP), ejection fraction (EF), and clinical outcome in patients implanted with CRT, stratified by LBBB at baseline.Methods and resultsHeart failure (HF) patients undergoing CRT implantation with EF ≤ 35% and QRS ≥ 120 ms were evaluated based on their RV-LV AD at implantation. Baseline and 6-month clinical parameters, EF, and NT-proBNP values were assessed. The primary endpoint was HF or death, the secondary endpoint was all-cause mortality. A total of 125 patients with CRT were studied, 62% had LBBB. During the median follow-up of 2.2 years, 44 (35%) patients had HF/death, 36 (29%) patients died. Patients with RV-LV AD ≥ 86 ms (lower quartile) had significantly lower risk of HF/death [hazard ratio (HR): 0.44; 95% confidence interval (95% CI): 0.23–0.82; P = 0.001] and all-cause mortality (HR: 0.48; 95% CI: 0.23–1.00; P = 0.05), compared with those with RV-LV AD < 86 ms. Patients with RV-LV AD ≥ 86 ms and LBBB showed the greatest improvement in EF (28–36%; P<0.001), NT-proBNP (2771–1216 ng/mL; P < 0.001), and they had better HF-free survival (HR: 0.23, 95% CI: 0.11–0.49, P < 0.001) and overall survival (HR: 0.35, 95% CI: 0.16–0.75; P = 0.007). There was no difference in outcome by RV-LV AD in non-LBBB patients.ConclusionLeft bundle branch block patients with longer RV-LV activation delay at CRT implantation had greater improvement in NT-proBNP, EF, and significantly better clinical outcome.

Cardiac resynchronization therapy acutely improves ventricular-arterial coupling by reducing the arterial load: assessment by pressure-volume loops.

Cardiac resynchronization therapy (CRT) has been demonstrated to improve ventricular-arterial coupling by reducing effective arterial elastance (Ea) on long-term follow-up. Detailed invasive studies showing possible acute peripheral effects of CRT are not available. We evaluated the hemodynamic effects of CRT in patients with systolic dysfunction, in order to investigate the impact on ventricular-arterial coupling and, in particular, on Ea immediately after the initiation of pacing. We studied 37 heart failure patients undergoing CRT implantation based on conventional criteria. On implantation, left ventricular (LV) pressure and volume data were determined via a conductance catheter. Twelve patients with a standard indication for electrophysiologic study and preserved LV function served as a control group. In comparison with the control group, heart failure patients showed reduced systolic and diastolic function. LV end-systolic elastance (Ees: end-systolic pressure/volume) was impaired (0.79 ± 0.33 mm Hg/mL vs 1.84 ± 0.89 mm Hg/mL, P = 0.012) and Ees/Ea reduced (0.36 ± 0.17 vs 1.19 ± 1.81, P = 0.022). In heart failure patients, CRT immediately improved systolic function, increasing stroke work from 3.9 ± 1.8 L*mm Hg to 6.9 ± 3.3 L*mm Hg (P < 0.001) and Ees to 1.02 ± 0.62 mm Hg/mL (P = 0.001). Ea decreased from 2.59 ± 1.35 mm Hg/mL to 1.68 ± 0.91 mm Hg/mL (P < 0.001), leading to an increase in Ees/Ea to 0.70 ± 0.38 (P < 0.001). Our data indicate that switching CRT on induces an immediate reduction in arterial load, conceivably as a consequence of restored autonomic balance.

Impact of Using a Telescoping‐Support Catheter System for Left Ventricular Lead Placement on Implant Success and Procedure Time of Cardiac Resynchronization Therapy

Proper positioning of the left ventricular (LV) lead improves clinical outcomes and survival in patients receiving cardiac resynchronization therapy (CRT). Techniques of LV lead insertion using contrast injection and a telescoping system of delivery catheters to support advancement of the lead into the target branch may allow more efficient, targeted lead placement. We sought to evaluate the impact of an LV lead implant approach using telescoping-support catheters (group TS) on success rate, lead location, and procedural time compared to standard over-the-wire implant techniques (group OTW). Four hundred thirty-seven consecutive patients undergoing CRT implantation were divided into group TS (n = 105) or group OTW (n = 332) based upon a review of the operative technique used for LV lead implantation. The primary outcome was success of LV lead implantation at the index procedure. Secondary endpoints included optimal positioning of the LV lead and reduction in procedural fluoroscopy time. Failed LV lead placement was lower (1.9% vs 8.1%, P = 0.02) and optimal lead positioning was achieved more often for group TS than group OTW (87% vs 75%, P = 0.01). In addition, there were significantly shorter fluoroscopy times for group TS versus group OTW (29.6 minutes vs 41.9 minutes, P < 0.01). A CRT-implant approach using contrast injection and a telescoping-support catheter system results in fewer failed LV lead implants, improved LV lead location, and shorter procedure times.

The anatomic and electrical location of the left ventricular lead predicts ventricular arrhythmia in cardiac resynchronization therapy

Both anatomic and electrical locations of the left ventricular (LV) lead have been identified as important predictors of clinical outcomes in cardiac resynchronization therapy (CRT). The impact of LV lead location on incident device-treated ventricular arrhythmia (VA), however, is not well understood. To assess the relationship between electrical and anatomic LV lead location and device treated VAs in CRT. Sixty-nine patients undergoing CRT implantation for standard indications were evaluated. Anatomic LV lead location was assessed by means of coronary venography and chest radiography and categorized as apical or nonapical. Electrical LV lead location was assessed by LV electrical delay (LVLED) and was calculated as the time between the onset of the native QRS on the surface electrocardiogram and sensed signal on the LV lead during implantation and corrected for native QRS. Incident appropriate device-treated VA was assessed via device interrogation. Apical lead placement was an independent predictor of VAs (hazard ratio 5.29; 95% confidence interval 1.69-16.5; P = .004). Among patients with a nonapical lead, LVLED<50% native QRS was an independent predictor of VAs (hazard ratio 6.90; 95% confidence interval 1.53-31.1; P = .012). Those with a nonapical lead and LVLED ≥ 50% native QRS were at substantially lower risk for first incident and recurrent VAs when compared to all other patients. The apical lead position is associated with an increased risk of VAs in CRT patients. Among patients with a nonapical lead position, an LVLED of<50% of the native QRS is associated with an increased risk of VAs.

Short-spaced dipole for managing phrenic nerve stimulation in patients with CRT: The “phrenic nerve mapping and stimulation EP” catheter study

Phrenic nerve stimulation (PNS), occurring in 33%-37% of the patients with cardiac resynchronization therapy (CRT), is a limiting factor when implanting left ventricular (LV) leads from coronary veins. To test the hypothesis that PNS occurrence is related to bipolar electrode spacing. During standard CRT defibrillator implant procedures, a 5-F diagnostic electrophysiology catheter with 10 electrodes, spaced 2-5-2 mm, was positioned in a cardiac vein suitable for permanent LV lead placement. Pacing in the unipolar configuration identified the site with the lowest PNS threshold. PNS and left ventricular pacing (LVP) thresholds were then measured in different configurations at 0.5 ms: unipolar, each LV electrode served as the cathode in turn; and bipolar with different electrode spacing, cathode being the electrode with the lowest unipolar PNS threshold. From February to September 2010, 40 patients undergoing CRT implantation were enrolled in 4 centers in Italy. It was possible to identify PNS and perform a complete set of measurements in 23 patients. A bipolar electrode spacing of 2 mm resulted in higher PNS thresholds in bipolar configurations han did a bipolar electrode spacing of ≥ 5 mm. However, no significant increase in the LVP threshold was observed (P = ns). This experience suggests that LVP with a bipolar electrode spacing of 2 mm significantly increases the PNS threshold without affecting the LVP threshold, thereby increasing the possibility of delivering CRT when the LV lead is placed in proximity to the phrenic nerve.

Disparity in Left Ventricular Stimulation Among Different Pacing Configurations in Cardiac Resynchronization Therapy

Cardiac resynchronization therapy (CRT) demands high energy utilization due to continuous biventricular pacing. Current technology allows 6 pacing configurations for a bipolar left ventricular (LV) lead. Understanding the energy requirements for each configuration will allow optimization of pacing output. Pacing impedance, LV voltage threshold at 1.5 ms (rheobase) and 0.4 ms and chronaxie were obtained in 6 LV configurations in 49 consecutive patients undergoing CRT implantation or replacement. Strength-duration curves were derived using the Lapicque formula. Pacing impedances and voltage thresholds at 1.5 and 0.4 ms, calculated minimum threshold energy at chronaxie, current drain, energy thresholds at 0.4 ms, and strength-duration curves were statistically different between LV configurations (P<0.05). The lowest threshold energy requirements were found in Tip→right ventricular (RV) coil and Tip→Can configuration. Energy strength-duration curves involving the ring as the cathode (Ring→RV, Ring→Can, and Ring→Tip) had the highest LV thresholds. The pacing configuration with the lowest energy threshold correlated 89% of the time with the lowest voltage threshold at 0.4 ms. The probability to reach LV thresholds <1.5 V at 0.4 ms was increased from 51% with 2 LV configurations to 67% with 6 LV configurations. Pacing impedance, LV thresholds, minimum threshold energy at chronaxie, current drain, voltage, and energy strength-duration curves were statistically different between LV pacing configurations. LV pacing configuration with the lowest voltage threshold does not always reflects the lowest energy threshold, particularly in the presence of a low impedance configuration. The availability of 6 LV configurations increases the probability of optimizing LV pacing output.

Abstract 18008: The Burden and Morphology of Premature Ventricular Contractions in Patients Undergoing Cardiac Resynchronization Therapy

Introduction: Frequent premature ventricular contractions (PVC's) limit effective delivery of cardiac resynchronization therapy (CRT). However, neither the burden nor morphology of PVC's is well defined in patients with ischemic (ICM) and non-ischemic (NICM) cardiomyopathy. Methods: In MADIT-CRT, 947 patients enrolled in the CRT-D arm underwent 24-hour 12-lead Holter monitoring. Patients with &gt;5000 PVC's were identified and the morphology of PVC's in each of these patients was assessed. Based on previously published ECG criteria, we characterized PVC's to originate from the RV or LV outflow tract, sinus of Valsalva, or a non-outflow tract location. Results: A total of 146 (15%) patients were identified, of whom 88 (60%) had ICM and 58 (40%) had NICM. The median total PVC count in ICM patients was 8807 as compared to 8950 in NICM patients, p=NS. PVC's with a LBBB morphology occurred in 34 (39%) ICM patients and 33 (57%) of NICM patients, p=0.03. In addition, RVOT appearing PVC's were significantly more frequent in NICM patients (19 (33%) vs. 11 (13%) in ICM patients, p=0.003). There was no difference in the number of PVC's that appeared to originate from the LVOT [ICM vs. NICM, 15 (17%) vs. 9 (16%), p=NS] or from the sinus of Valsalva [ICM vs. NICM 9 (10%) vs. 8 (14%), p=NS]. Non-outflow tract appearing PVC's were significantly more common in patients with ICM when compared to patients with NICM, 53 (60%) vs. 22 (38%), p=0.008. Conclusions: In 15% of patients undergoing CRT implantation, &gt;5000 PVCs were observed. While there was no difference in the burden of PVC between ICM and NICM patients, there were significant differences in morphology (and thus site of origin) of PVC's in the 2 groups of patients. These data may have implications, especially in patients in whom catheter ablation is necessary to eliminate PVC's in order to maximize CRT.