Determination of sensed and paced atrial-ventricular delay in cardiac resynchronization therapy.

BACKGROUND: Optimization of atrial-ventricular delay (AVD) during atrial sensing (SAVD) and pacing (PAVD) provides the most effective cardiac resynchronization therapy (CRT). We demonstrate a novel electrocardiographic methodology for quantifying electrical synchrony and optimizing SAVD/PAVD. METHODS: We studied 40 CRT patients with LV activation delay. Atrial-sensed to RV-sensed (As-RVs) and atrial-paced to RV-sensed (Ap-RVs) intervals were measured from intracardiac electrograms (IEGM). LV-only pacing was performed over a range of SAVD/PAVD settings. Electrical dyssynchrony (cardiac resynchronization index; CRI) was measured at each setting using a multilead ECG system placed over the anterior and posterior torso. Biventricular pacing, which included multiple interventricular delays, was also conducted in a subset of 10 patients. RESULTS: When paced LV-only, peak CRI was similar (93 ± 5% vs. 92 ± 5%) during atrial sensing or pacing but optimal PAVD was 61 ± 31 ms greater than optimal SAVD. The difference between As-RVs and Ap-RVs intervals on IEGMs (62 ± 31 ms) was nearly identical. The slope of the correlation line (0.98) and the correlation coefficient r (0.99) comparing the 2 methods of assessing SAVD-PAVD offset were nearly 1 and the y-intercept (0.63 ms) was near 0. During simultaneous biventricular (BiV) pacing at short AVD, SAVD and PAVD programming did not affect CRI, but CRI was significantly (p < .05) lower during atrial sensing at long AVD. CONCLUSIONS: A novel methodology for measuring electrical dyssynchrony was used to determine electrically optimal SAVD/PAVD during LV-only pacing. When BiV pacing, shorter AVDs produce better electrical synchrony.

Relationship between QRS duration and resynchronization window for CRT optimization: Implications for CRT in narrow QRS patients.

AIMS: Cardiac resynchronization therapy (CRT) response is proportional to QRS duration (QRSd). We hypothesize that this is, in part, due to slower conduction velocity and hence wider range of programmed device settings that produce adequate electrical wavefront fusion and resynchronization in wider QRSd patients. METHODS: CRT patients (n = 122) with left ventricular (LV) conduction delay, sinus rhythm and intact atrioventricular node conduction were studied. Patients were categorized by QRSd: narrow (<120 ms; n = 20); moderate (120-150 ms, n = 37); and prolonged (≥150 ms; n = 65). Electrocardiographic data was acquired during native rhythm and LV-only pacing at varying atrioventricular delays (AVDs). Electrical synchrony was quantified as cardiac resynchronization index (CRI) using multi­lead electrocardiographic systems and a proprietary algorithm that quantified wavefront fusion. A Gaussian distribution equation was fitted to CRI response. RESULTS: Peak CRI was high (87.6 ± 6.3%) and similar (p = 0.716) across QRSd groups. The standard deviation of the Gaussian distribution significantly correlated with QRSd (R = 0.614, p < 0.001), and progressively and significantly (p < 0.001) increased as QRSd increased from narrow (34.8 ± 10.0 ms), to moderate (50.6 ± 8.4 ms), to prolonged (67.6 ± 18.3 ms). At AVDs 20 and 40 ms from optimal, CRI differed significantly (p < 0.001) between groups, with progressively higher CRI values as native QRSd increased. CONCLUSION: Electrical resynchronization with optimally programmed LV-only pacing was similar between patients with varying QRSd, including patients with narrow QRSd. The resynchronization window that corresponded with optimal electrical resynchronization decreased as native QRSd decreased. This finding provides one potential explanation for the lack of significant benefit of CRT in narrow QRSd patients in previous studies.

Electrical dyssynchrony mapping and cardiac resynchronization therapy.

PURPOSE: There is no clinical methodology for quantification or display of electrical dyssynchrony over a wide range of atrial-ventricular delays (AVD) and ventricular-ventricular delays (VVD) in patients with cardiac resynchronization therapy (CRT). This study aimed to develop a new methodology, based on wavefront fusion, for mapping electrical synchrony. METHODS: A cardiac resynchronization index (CRI) was measured at multiple device settings in 90 patients. Electrical dyssynchrony maps (EDM) were constructed for each patient to display CRI at any combination of AVD and VVD. An optimal synchrony line (OSL) depicted the AVD/VVD combinations producing the highest CRIs. Fusion of right ventricular paced (RVp), left ventricular paced (LVp), and native wavefront offsets were calculated. RESULTS: CRI significantly increased (p < 0.0001) from 58.0 ± 28.1% at baseline to 98.3 ± 1.7% at optimized settings. EDMs in patients with high-grade heart block (n = 20) had an OSL parallel to the simultaneous biventricular pacing (BiVPVV-SIM) line with leftward shift across all AVDs (RVp-LVpOFFSET = 50.5 ± 29.8 ms). EDMs in patients with intact AV node conduction (n = 64) had an OSL parallel to the BiVPVV-SIM line with leftward shift at short AVDs (RVp-LVpOFFSET = 33.4 ± 23.3 ms), curvilinear at intermediate AVDs (triple fusion), and vertical at long AVDs (native-LVpOFFSET = 85.2 ± 22.8 ms) in all patients except those with poor LV lead position (n = 6). CONCLUSION: A new methodology is described for quantifying and graphing electrical dyssynchrony over a physiologic range of AVDs/VVDs. This methodology offers a noninvasive, practical, clinical approach for measuring electrical synchrony that could be applied to optimization of CRT devices.

The ECG Belt for CRT response trial: Design and clinical protocol.

The ECG Belt for CRT response trial is designed to test the hypothesis that in patients traditionally less likely to respond to cardiac resynchronization therapy (CRT), an individualized approach utilizing the electrocardiogram (ECG) Belt to guide lead placement, vector selection, and device programming is superior to current standard of care. The ECG Belt is a noninvasive mapping technology designed to measure beat by beat electrical activation of the left ventricle by utilizing unipolar measurements from multiple ECG electrodes on the body surface. The ECG Belt for CRT response trial is a multicenter, prospective, randomized, investigational pre-market research study conducted at 48 centers in the United States, Canada, and Europe and will randomize approximately 400 subjects. The trial has three arms (enrollment will be 2:1:1, respectively): utilization of the Belt to guide implant as well as postimplant programming, utilizing the Belt to guide postimplant programming alone, and a non-Belt control arm. AdaptivCRT will be an option in the treatment arm but not the control arms. The primary endpoint is change in left ventricular end-systolic volume between preimplant and at 6 months. This paper describes the design and analytic plan for the trial.

Electrical wavefront fusion in heart failure patients with left bundle branch block and cardiac resynchronization therapy: Implications for optimization.

BACKGROUND: Novel metrics of electrical dyssynchrony based on multi-electrode mapping and ECG-based markers of fusion are better predictors of cardiac resynchronization therapy (CRT) response than QRS duration. OBJECTIVE: To describe a new methodology for measuring electrical synchrony based on wavefront fusion and electrocardiographic cancellation in patients with CRT and its potential for CRT optimization. METHODS: Patients with left bundle branch block (LBBB) type conduction and CRT (n = 84) were studied at multiple device settings using an ECG belt (53 anterior and posterior electrodes). The area between combinations of anterior and posterior curves (AUC) was calculated and cardiac resynchronization index (CRI) defined as percent change in AUC compared to LBBB. RESULTS: In 14 patients with complete heart block or atrial fibrillation, CRI at optimal ventriculo-ventricular delay (VVD) (40 ± 19 ms) was significantly higher than with simultaneous biventricular pacing (BiVp) (90 ± 8.6% vs. 54.2 ± 24.2%, p < 0.001). In all 70 patients paced LV-only, LV-paced wavefront was ahead of native wavefront at short atrio-ventricular delay (AVD) and CRI increased with increase in AVD, peaked, and then decreased. Optimal CRI during LV-only pacing was significantly better than optimal CRI with simultaneous BiVp (89.6 ± 8% vs. 64.4 ± 22%, p < 0.001), and occurred at AVD 68 ± 22 ms less than the atrial-RV sensed interval. With sequential BiVp, best CRI was 83.9 ± 13% (with LV preactivation of 40 ± 20 ms). Best CRI at any setting was markedly better than CRI at standard setting (91.6 ± 7.7% vs. 52.7 ± 23.3, p < 0.001). CONCLUSION: We describe a novel non-invasive investigational tool that quantifies wavefront fusion and electrical dyssynchrony, and may allow for individualized CRT optimization.

Body surface activation mapping of electrical dyssynchrony in cardiac resynchronization therapy patients: Potential for optimization.

BACKGROUND: Electrical synchronization is likely improved by cardiac resynchronization therapy (CRT), but is difficult to quantify with 12-lead ECG. We aimed to quantify changes in electrical synchrony and potential for optimization with CRT using a body-surface activation mapping (BSAM) system. METHODS: Standard deviation of activation times (SDAT) was calculated in 94 patients using BSAM at baseline CRT (CRTbl), native, and different CRT configurations. RESULTS: SDAT decreased 20% from native to CRTbl (p<0.01) and an additional 26% (p<0.01) at optimal CRT (CRTopt), the minimal SDAT setting. Patients with LBBB and patients with QRS duration ≥150ms had higher native SDAT and greater decrease with CRTbl (p<0.01); however, the improvement from CRTbl to CRTopt was similar in all four groups (range: 24-28%). CRTopt was achieved with biventricular pacing in 52% and LV-only pacing in 44%. We propose that improved wavefront fusion demonstrated by BSAMs contributed substantially to the improved electrical synchrony. CONCLUSION: Optimization potential is similar regardless of pre-CRT QRS morphology or duration. BSAM could possibly improve CRT response by individualizing device programming to minimize electrical dyssynchrony.

On the underutilization of cardiac resynchronization therapy.

Cardiac resynchronization therapy (CRT) is an exciting therapy that can treat patients with systolic heart failure and left ventricular dysfunction who have a wide QRS complex. Indications for its use have been refined and expanded based on recent clinical data and guidelines, yet the rate of new CRT implants in the United States has not changed much over the past 8 years. Many patients receiving implantable cardioverter-defibrillators can benefit from, but are not receiving, appropriately-indicated CRT devices. We summarize data on CRT use, discuss reasons for probable underutilization, and provide recommendations for augmenting proper and effective use of this highly beneficial therapy.

Causes and clinical consequences of inappropriate shocks experienced by patients wearing a cardioverter-defibrillator.

BACKGROUND: The LifeVest® wearable cardioverter-defibrillator (WCD) prevents sudden cardiac death in at-risk patients who are not candidates for an implantable defibrillator. The safety and efficacy of the WCD may be impacted by inappropriate shocks (IAS). OBJECTIVE: The purpose of this study was to assess the causes and clinical consequences of WCD IAS in survivors of IAS events. METHODS: The Food and Drug Administration's Manufacturers and User Facility Device Experience database was searched for IAS adverse events (AE) that were reported during 2021 and 2022. RESULTS: A total of 2568 IAS-AE were found (average number of IAS per event: 1.5 ± 1.9; range 1-48). IAS were caused by tachycardias (1255 [48.9%]), motion artifacts (840 [32.7%]), and oversensing (OS) of low-level electrical signals (473 [18.4%]) (P <.001). Tachycardias included atrial fibrillation (AF) (828 [32.2%]), supraventricular tachycardia (SVT) (333 [13.0%]), and nonsustained ventricular tachycardia/fibrillation (NSVT/VF) (87 [3.4%]). Activities responsible for motion-induced IAS included riding a motorcycle, lawnmower, or tractor (n = 128). In 19 patients, IAS induced sustained ventricular tachycardia or ventricular fibrillation that subsequently were terminated by appropriate WCD shocks. Thirty patients fell and suffered physical injuries. Conscious patients (n = 1905) did not use the response buttons to abort shocks (47.9%) or used them improperly (20.2%). IAS resulted in 1190 emergency room visits or hospitalizations, and 17.3% of patients (421/2440) discontinued the WCD after experiencing IAS, especially multiple IAS. CONCLUSIONS: The LifeVest WCD may deliver IAS caused by AF, SVT, NSVT/VF, motion artifacts, and oversensing of electrical signals. These shocks may be arrhythmogenic, result in injuries, precipitate WCD discontinuation, and consume medical resources. Improved WCD sensing, rhythm discrimination, and methods to abort IAS are needed.

Post-Shock Asystole in Patients Dying Out of Hospital While Wearing a Cardioverter Defibrillator.

BACKGROUND: The wearable cardioverter-defibrillator (WCD) prevents sudden cardiac death due to ventricular tachycardia (VT) or ventricular fibrillation (VF) but does not pace for post-shock asystole (PS-A) or bradycardia (PS-B;<50 beats/ min). OBJECTIVES: The purpose of this study was to assess PS-A and PS-B in patients dying out of hospital (OOH) while wearing a WCD. METHODS: The database of the U.S. Food and Drug Administration Manufacturers and User Facility Device Experience (MAUDE) was queried for manufacturers' reports of OOH deaths while patients were wearing a WCD. Excluded were patients who did not receive a shock or were initially shocked for asystole or during resuscitation. RESULTS: From January 2017 to March 2022, 313 patients received an initial WCD shock for VF (n = 150), VT (n = 90), and non-VF/VT rhythms (n = 73). PS-A occurred in 204 patients (65.2%), and PS-B occurred in 111 (35.5%); 85 (41.7%) PS-A patients also had PS-B. Most PS-A patients (n = 185; 90.7%) had an initial shocked rhythm of VF or VT, but 19 patients (9.3%) were initially inappropriately shocked for atrial fibrillation/supraventricular tachycardia (n = 7) and idioventricular (n = 8) or sinus (n = 4) rhythm. PS-A occurred after the first WCD shock in 118 (63.8%) and after the first, second, or third shocks in 159 patients (85.9%). Seven patients had post-shock heart block. Eight patients had permanent pacemakers; 1 became nonfunctional after 1 shock, and 7 showed noncapture and/or asystole after 1 to 4 shocks. CONCLUSIONS: Post-shock asystole appears to be common in patients who die OOH after being shocked by a WCD for VF or VT. PS-A also occurs after inappropriate WCD shocks for non-VF/VT rhythms. Implanted pacemakers may not prevent PS-A after a WCD shock. WCD backup pacing should be explored.

Comparison of cardiac resynchronization therapy outcomes in patients with New York Heart Association functional class I/II versus III/IV heart failure.

BACKGROUND: Several randomized trials have shown that cardiac resynchronization therapy (CRT) benefits New York Heart Association (NYHA) functional class I/II heart failure (HF) patients, but it is unknown if similar outcomes occur in the real-world. METHODS AND RESULTS: All patients receiving CRT between 2003 and 2008 with ejection fraction (EF) ≤35% and QRS duration ≥120 ms were included. Outcomes assessed were subjective clinical response, echocardiographic response, and survival free of cardiovascular (CV) hospitalization. Baseline demographics in functional class I/II (n = 155) and functional class III/IV (n = 512) were similar, except for differences in age and several comorbidities. Clinical response was similar in both groups. The functional class I/II group had a greater decrease in left ventricular (LV) end-diastolic dimension (P = .031), and trended toward greater improvements in LV end-systolic dimension (P = .056) and EF (P = .059). The functional class I/II group had a better 5-year survival rate (79 vs 54%; P < .0001) and survival free of CV hospitalization (45% vs 26%; P < .0001). CONCLUSIONS: In this real-world clinical scenario, NYHA functional class I/II CRT patients improved clinical status, and LV function and size as good as or better than those in NYHA functional class III/IV patients. These observations provide further support for the use of CRT in patients with mild symptoms of HF.

Cardiac resynchronization therapy in the real world: comparison with the COMPANION study.

BACKGROUND: Several clinical trials have confirmed that cardiac resynchronization therapy (CRT) improves outcomes in well defined patient populations. It is uncertain, however, whether outcomes are similar in real-world clinical settings. This study compared outcomes after CRT with defibrillator (CRT-D) in a large real-world private-practice cardiology setting with those in the COMPANION multicenter trial. METHODS AND RESULTS: A total of 429 consecutive patients who received CRT-D for standard indications (group 1) were retrospectively compared with the 595 patients (group 3) in the COMPANION CRT-D cohort regarding survival and survival free of cardiovascular (CV) hospitalization. A subgroup of the group 1 patients who met the COMPANION entrance criteria (group 2) was also compared with the COMPANION cohort (group 3) both with and without propensity-matching statistical analysis. Survival and survival free of CV hospitalization was better in group 1 than in group 3. Survival in group 2 with and without propensity matching was similar to group 3. However, survival free of CV hospitalization was better in the real-world patients (group 2) even after adjustment for differences in baseline characteristics. CONCLUSIONS: Survival and CV hospitalization outcomes in a real-world clinical setting are as good as, or better than, those demonstrated in the COMPANION research trial.

Prospective evaluation of elastic restraint to lessen the effects of heart failure (PEERLESS-HF) trial.

BACKGROUND: Left ventricular (LV) remodeling predicts poor outcomes in heart failure (HF) patients. The HeartNet(®) cardiac restraint device (Paracor Medical Inc., Sunnyvale, CA) may reduce LV remodeling and improve functional capacity, quality of life, and outcomes in HF patients. To evaluate the safety and efficacy of the HeartNet Ventricular Support System in HF patients receiving optimal medical therapy. METHODS AND RESULTS: Prospective, randomized, controlled, multicenter trial in patients with symptomatic HF and LV ejection fraction ≤35% on optimal medical and device therapy. The primary efficacy end points were changes in peak VO(2), 6-minute walk (6MW) distance, and Minnesota Living with Heart Failure (MLWHF) quality of life score at 6 months. The primary safety end point was all-cause mortality at 12 months. Because the planned adaptive interim analysis of the first 122 subjects with a completed 6-month follow-up indicated futility to reach the peak VO(2) end point, trial enrollment was suspended. Hence, the results on the 96 treatment and 114 control subjects are reported. Groups were similar at baseline. At 6 months, responder frequency for a prespecified improvement was similar between groups for peak VO(2) (P = .502) and MLWHF score (P = .184) but borderline higher for improvement in 6MW distance in the treatment compared with the control group (33 [38%] vs. 25 [25%]; P = .044). At 6 months, the treatment group had a significantly greater improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) (P < .001) and decrease in LV mass (P = .032), LV end-diastolic diameter (P = .015), LV end-systolic diameter (P = .032), and LV end-diastolic volume (P = .031) as compared with controls. At 12 months, all-cause mortality and responder rates were similar in the 2 groups. Success rate for the HeartNet implantation was 99%. CONCLUSION: Enrollment in the trial was stopped because an interim analysis showed futility of reaching the peak VO(2) end point. However, because of the device safety and favorable signals for LV remodeling and quality of life, further investigation of this device is warranted.

Effects of exenatide vs. metformin on endothelial function in obese patients with pre-diabetes: a randomized trial.

BACKGROUND: Glucagon like peptide-1 (GLP-1) receptor agonist treatment may improve endothelial function via direct and indirect mechanisms. We compared the acute and chronic effects of the GLP-1 receptor agonist exenatide vs. metformin on endothelial function in patients with obesity and pre-diabetes. METHODS: We performed a randomized, open-label, clinical trial in 50 non-diabetic individuals (mean age 58.5 ± 10.0; 38 females) with abdominal obesity and either impaired fasting glucose, elevated HbA1c, or impaired glucose tolerance (IGT) who were randomized to receive 3-months of exenatide or metformin. Microvascular endothelial function, assessed by digital reactive hyperemia (reactive hyperemic index: RHI), C-reactive protein (CRP), circulating oxidized LDL (oxLDL), and vascular cell adhesion molecule-1 (VCAM-1) were measured at baseline and 3-months. Seven subjects with IGT participated in a sub-study comparing the effects of pre-administration of exenatide and metformin on postprandial endothelial function. RESULTS: There were no differences for the change in RHI (Δ exenatide: 0.01 ± 0.68 vs. Δ metformin: -0.17 ± 0.72, P = 0.348), CRP, oxLDL, or VCAM-1 between exenatide and metformin treatment. Triglycerides were reduced more with exenatide compared to metformin (Δ exenatide: -25.5 ± 45.7 mg/dL vs. Δ metformin: -2.9 ± 22.8 mg/dL, P = 0.032). In the sub-study, there was no difference in postprandial RHI between exenatide and metformin. CONCLUSIONS: Three months of exenatide therapy had similar effects on microvascular endothelial function, markers of inflammation, oxidative stress, and vascular activation, as metformin, in patients with obesity and pre-diabetes. CLINICAL TRIALS REGISTRATION: This study is registered on http://www.clinicaltrials.gov/: NCT00546728.

Pacemaker optimization in nonresponders to cardiac resynchronization therapy: left ventricular pacing as an available option.

BACKGROUND: Echocardiographic (ECHO)-guided pacemaker optimization (PMO) in cardiac resynchronization therapy (CRT) nonresponders acutely improves left ventricular (LV) function. However, the chronic results of LV pacing in this group are less understood. METHODS: We retrospectively studied 28 CRT nonresponders optimized based on ECHO to LV pacing and compared them to 28 age- and gender-matched patients optimized to biventricular (BiV) pacing. ECHOs with tissue Doppler imaging assessed LV hemodynamics before, immediately after, and 29 ± 16 months after PMO. Also, 56 age- and gender-matched CRT responders were included for comparison of clinical outcomes. RESULTS: PMO resulted in acute improvements in longitudinal LV systolic function and several measures of dyssynchrony, with greater improvements in the LV paced group. Chronic improvements in ejection fraction (EF) (3.2 ± 7.7%), and left ventricle end-systolic volume (LVESV) (-11 ± 36 mL) and one dyssynchrony measure were seen in the combined group. Chronically, both LV and BiV paced patients improved some measures of systolic function and dyssynchrony although response varied between the groups. Survival at 3.5 years was similar (P = 0.973) between the PMO (58%) and nonoptimized groups (58%) but survival free of cardiovascular hospitalization was significantly (P = 0.037) better in the nonoptimized group. CONCLUSIONS: CRT nonresponders undergoing PMO to either LV or BiV pacing have acute improvements in longitudinal systolic function and some measures of dyssynchrony. Some benefits are sustained chronically, with improvements in EF, LVESV, and dyssynchrony. A strategy of ECHO-guided PMO results in survival for CRT nonresponders similar to that of CRT patients not referred for PMO.

Cardiac resynchronization therapy optimization in nonresponders and incomplete responders using electrical dyssynchrony mapping.

BACKGROUND: Nonresponse to cardiac resynchronization therapy (CRT) occurs in ∼30%-50% of patients. There are no well-accepted clinical approaches for optimizing CRT in nonresponders. OBJECTIVE: The purpose of this study was to demonstrate the effect of CRT optimization using electrical dyssynchrony mapping on left ventricular (LV) function, size, and dyssynchrony in selected patients with nonresponse/incomplete response to CRT. METHODS: We studied 39 patients with underlying left bundle branch block or interventricular conduction delay who had an LV ejection fraction of ≤40% after receiving CRT and had significant electrical dyssynchrony. Electrical dyssynchrony was measured at multiple atrioventricular delays and interventricular delays. The QRS area between combinations of 9 anterior and 9 posterior electrograms (QRS area under the curve) was calculated, and cardiac resynchronization index (CRI) was defined as the percent change in QRS area under the curve compared to native conduction. Electrical dyssynchrony maps depicted CRI over the wide range of settings tested. Patients were programmed to an optimal device setting, and echocardiograms were recorded 5.9 ± 3.7 months postoptimization. RESULTS: CRI increased from 49.4% ± 24.0% to 90.8% ± 10.5%. CRT optimization significantly improved LV ejection fraction from 31.8% ± 4.7% to 36.3% ± 5.9% (P < .001) and LV end-systolic volume from 108.5 ± 37.6 to 98.0 ± 37.5 mL (P = .009). Speckle-tracking measures of LV strain significantly improved by 2.4% ± 4.5% (transverse; P = .002) and 1.0% ± 2.6% (longitudinal; P = .017). Aortic to pulmonic valve opening time, a measure of interventricular dyssynchrony, significantly (P = .040) decreased by 14.9 ± 39.4 ms. CONCLUSION: CRT optimization of electrical dyssynchrony using a novel electrical dyssynchrony mapping technology significantly improves LV systolic function, LV end-systolic volume, and mechanical dyssynchrony. This methodology offers a noninvasive, practical clinical approach to treating nonresponders and incomplete responders to CRT.

Leadless left ventricular stimulation with WiSE-CRT System - Initial experience and results from phase I of SOLVE-CRT Study (nonrandomized, roll-in phase).

BACKGROUND: Left ventricular (LV) endocardial pacing is a promising method to deliver cardiac resynchronization therapy (CRT). WiSE-CRT is a wireless LV endocardial pacing system, and delivers ultrasonic energy to an LV electrode. OBJECTIVE: The purpose of this study was to present short-term outcomes with the WiSE-CRT system in centers with no prior implanting experience. METHODS: Data were prospectively collected from 19 centers where WiSE-CRT systems were implanted during the roll-in phase of the SOLVE-CRT trial. Patients were followed at 1, 3, and 6 months, including transthoracic echo (TTE) at 6 months. RESULTS: The WiSE-CRT was successfully implanted in all 31 attempted cases, and 30 patients completed the 6-month follow-up. One patient underwent heart transplantation 1 month after implantation, and was excluded. Fourteen (46.7%) patients demonstrated ≥1 NYHA class improvement. TTE data were available in 29 patients. LV ejection fraction, LV end-systolic volume, and LV end-diastolic volume improved from 28.3% ± 6.7% to 33.5% ± 6.9% (P < .001), 134.9 ± 51.3 mL to 111.1 ± 40.3 mL (P = .0004), and 185.4 ± 58.8 mL to 164.9 ± 50.6 mL (P = .0017), respectively. There were 3 (9.7%) device-related type 1 complications: 1 insufficient LV pacing, 1 embolization of an unanchored LV electrode, and 1 skin infection. CONCLUSIONS: We demonstrated a high success rate of LV endocardial electrode placement in centers with no prior implanting experience. Favorable clinical responses in heart failure symptoms and significant LV reverse remodeling were noted.

Torsion and dyssynchrony differences between chronically paced and non-paced heart failure patients.

BACKGROUND: Chronic right ventricular pacing may lead to left ventricular dyssynchrony, systolic dysfunction, remodeling, and heart failure. Cardiac mechanics may differ between paced and nonpaced heart failure patients, and their optimal treatment may also differ. METHODS AND RESULTS: Echocardiograms were analyzed using tissue Doppler imaging and speckle tracking echocardiography in 20 patients with chronic right ventricular pacing for complete heart block (RVP group), 29 nonpaced patients with different heart failure etiologies but ejection fractions similar to the RVP group (HF group), and 25 control subjects without pacemakers or heart failure (control group). Left ventricle volumes were smaller in RVP than HF (end-diastolic volume = 93.6 ± 25.1 mL vs. 112.1 ± 22.8 mL), but intraventricular longitudinal and radial dyssynchrony were similar. Dyssynchrony within the septum was greater (number of segments lengthening during systole = 1.9 ± 1.7 vs. 0.9 ± 1.8), systolic torsion was lower (6.2 ± 7.3° vs. 10.6 ± 4.2°), untwisting was delayed (time from peak torsion to peak untwist rate = 188 ± 141 ms vs. 102 ± 73 ms), and apical rotation was reversed in more subjects (35% vs 0%) in RVP than HF groups (P < .05 for all). CONCLUSIONS: Intraventricular dyssynchrony was similar between RVP and HF groups with similar ejection fraction. However, RVP subjects had smaller ventricles, greater dyssynchrony within the septum, lower torsion, altered apical rotation, and delayed untwisting.

Minimizing ventricular pacing to reduce atrial fibrillation in sinus-node disease.

BACKGROUND: Conventional dual-chamber pacing maintains atrioventricular synchrony but results in high percentages of ventricular pacing, which causes ventricular desynchronization and has been linked to an increased risk of atrial fibrillation in patients with sinus-node disease. METHODS: We randomly assigned 1065 patients with sinus-node disease, intact atrioventricular conduction, and a normal QRS interval to receive conventional dual-chamber pacing (535 patients) or dual-chamber minimal ventricular pacing with the use of new pacemaker features designed to promote atrioventricular conduction, preserve ventricular conduction, and prevent ventricular desynchronization (530 patients). The primary end point was time to persistent atrial fibrillation. RESULTS: The mean (+/-SD) follow-up period was 1.7+/-1.0 years when the trial was stopped because it had met the primary end point. The median percentage of ventricular beats that were paced was lower in dual-chamber minimal ventricular pacing than in conventional dual-chamber pacing (9.1% vs. 99.0%, P<0.001), whereas the percentage of atrial beats that were paced was similar in the two groups (71.4% vs. 70.4%, P=0.96). Persistent atrial fibrillation developed in 110 patients, 68 (12.7%) in the group assigned to conventional dual-chamber pacing and 42 (7.9%) in the group assigned to dual-chamber minimal ventricular pacing. The hazard ratio for development of persistent atrial fibrillation in patients with dual-chamber minimal ventricular pacing as compared with those with conventional dual-chamber pacing was 0.60 (95% confidence interval, 0.41 to 0.88; P=0.009), indicating a 40% reduction in relative risk. The absolute reduction in risk was 4.8%. The mortality rate was similar in the two groups (4.9% in the group receiving dual-chamber minimal ventricular pacing vs. 5.4% in the group receiving conventional dual-chamber pacing, P=0.54). CONCLUSIONS: Dual-chamber minimal ventricular pacing, as compared with conventional dual-chamber pacing, prevents ventricular desynchronization and moderately reduces the risk of persistent atrial fibrillation in patients with sinus-node disease. (ClinicalTrials.gov number, NCT00284830 [ClinicalTrials.gov].).

Results of the Prospective Minnesota Study of ECHO/TDI in Cardiac Resynchronization Therapy (PROMISE-CRT) study.

BACKGROUND: Retrospective single-center studies have shown that measures of mechanical dyssynchrony before cardiac resynchronization therapy (CRT), or acute changes after CRT, predict response better than QRS duration. The Prospective Minnesota Study of Echocardiographic/TDI in Cardiac Resynchronization Therapy (PROMISE-CRT) study was a prospective multicenter study designed to determine whether acute (1 week) changes in mechanical dyssynchrony were associated with response to CRT. METHODS AND RESULTS: Nine Minnesota Heart Failure Consortium centers enrolled 71 patients with standard indications for CRT. Left ventricular (LV) size, function, and mechanical dyssynchrony (echocardiography [ECHO], tissue Doppler imaging [TDI], speckle-tracking echocardiography [STE]) as well as 6-minute walk distance and Minnesota Living with Heart Failure Questionnaire scores were measured at baseline and 3 and 6 months after CRT. Acute change in mechanical dyssynchrony was not associated with clinical response to CRT. Acute change in STE radial dyssynchrony explained 73% of the individual variation in reverse remodeling. Baseline measures of mechanical dyssynchrony were associated with reverse remodeling (but not clinical) response, with 4 measures each explaining 12% to 30% of individual variation. CONCLUSIONS: Acute changes in radial mechanical dyssynchrony, as measured by STE, and other baseline mechanical dyssynchrony measures were associated with CRT reverse remodeling. These data support the hypothesis that acute improvement in LV mechanical dyssynchrony is an important mechanism contributing to LV reverse remodeling with CRT.

QRS Complex Detection and Measurement Algorithms for Multichannel ECGs in Cardiac Resynchronization Therapy Patients.

We developed an automated approach for QRS complex detection and QRS duration (QRSd) measurement that can effectively analyze multichannel electrocardiograms (MECGs) acquired during abnormal conduction and pacing in heart failure and cardiac resynchronization therapy (CRT) patients to enable the use of MECGs to characterize cardiac activation in such patients. The algorithms use MECGs acquired with a custom 53-electrode investigational body surface mapping system and were validated using previously collected data from 58 CRT patients. An expert cohort analyzed the same data to determine algorithm accuracy and error. The algorithms: 1) detect QRS complexes; 2) identify complexes of the most prevalent morphology and morphologic outliers; and 3) determine the array-specific (i.e., anterior and posterior) and global QRS complex onsets, offsets, and durations for the detected complexes. The QRS complex detection algorithm had a positive predictivity and sensitivity of ≥96% for complex detection and classification. The absolute QRSd error was 17 ± 14 ms, or 12%, for array-specific QRSd and 12 ± 10 ms, or 8%, for global QRSd. The absolute global QRSd error (12 ms) was less than the interobserver variation in that measurement (15 ± 10 ms). The sensitivity, positive predictivity, and error of the algorithms were similar to the values reported for current state-of-the-art algorithms designed for and limited to simpler data sets and conduction patterns and within the variation found in clinical 12-lead ECG QRSd measurement techniques. These new algorithms permit accurate, real-time analysis of QRS complex features in MECGs in patients with conduction disorders and/or pacing.