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His bundle pacing (HBP) is the most physiologic form of pacing and has been associated with reduced risk for heart failure hospitalization (HFH) and mortality compared to right ventricular pacing. Left bundle branch area pacing (LBBAP) is a safe and effective alternative option for patients needing ventricular pacing. The aim of this study was to compare the clinical outcomes between LBBAP and HBP among a large cohort of patients undergoing permanent pacemaker implantation.This observational registry included consecutive patients with AV block/AV node ablation who underwent de novo permanent pacemaker implantations with successful LBBAP or HBP between April 2018 and October 2020. The primary outcome was the composite endpoint of time to death from any cause or HFH. Secondary outcomes included the composite endpoint among patients with prespecified ventricular pacing burden and individual outcomes.The study population included 359 patients who met the inclusion criteria (163 in the HBP and 196 in the LBBAP group). Paced QRSd during LBBAP was similar to HBP (125 ± 20.2 vs. 126 ± 23.5 ms, p = .643). There were no statistically significant differences in the primary composite outcome in LBBAP (17.3%) compared to HBP (24.5%) (hazard ratio [HR]: 1.15, 95% CI: 0.72-1.82, p = .552). Secondary outcomes of death (10% vs. 17%; HR: 1.3, 95% CI: 0.73-2.33, p = .38) and HFH (10% vs. 12%; HR: 1.02, 95% CI: 0.54-1.94, p = .94) were not different among both groups.There were no statistically significant differences in the clinical outcomes of death or HFH in LBBAP when compared to HBP.

The field of pacing in Africa has evolved in an uncoordinated way across the continent with significant variation in local expertise, cost, and utilization. There are many countries where pacemaker services do not meet one-hundredth of the national demand. Regional, national, and institutional standards for pacemaker qualification and credentials are lacking. This paper reviews the current needs for bradycardia pacing and evaluates what standards should be set to develop pacemaker services in a resource-constrained continent, including the challenges and opportunities of capacity building and training as well as standards for training programs (training prerequisites, case volumes, program content, and evaluation).

Traditional right ventricular (RV) pacing for the management of bradyarrhythmias has been pursued successfully for decades, although there remains debate regarding optimal pacing site with respect to both hemodynamic and clinical outcomes. The deleterious effects of long-term RV apical pacing have been well recognized. This has generated interest in approaches providing more physiological stimulation, namely, His bundle pacing (HBP). This paper reviews the anatomy of the His bundle, early clinical observations, and current approaches to permanent HBP. By stimulating the His-Purkinje network, HBP engages electrical activation of both ventricles and may avoid marked dyssynchrony. Recent studies have also demonstrated the potential of HBP in patients with underlying left bundle branch block and cardiomyopathy. HBP holds promise as an attractive mode to achieve physiological pacing. Widespread adaptation of this technique is dependent on enhancements in technology, as well as further validation of efficacy in large randomized clinical trials.

Background The incidence of permanent pacemaker (PPM) implantation is higher following mitral valve surgery (MVS) with ablation for atrial fibrillation (AF) compared with MVS alone. Objectives This study identified risk factors and outcomes associated with PPM implantation in a randomized trial that evaluated ablation for AF in patients who underwent MVS. Methods A total of 243 patients with AF and without previous PPM placement were randomly assigned to MVS alone (n = 117) or MVS + ablation (n = 126). Patients in the ablation group were further randomized to pulmonary vein isolation (PVI) (n = 62) or the biatrial maze procedure (n = 64). Using competing risk models, this study examined the association among PPM and baseline and operative risk factors, and the effect of PPM on time to discharge, readmissions, and 1-year mortality. Results Thirty-five patients received a PPM within the first year (14.4%), 29 (83%) underwent implantation during the index hospitalization. The frequency of PPM implantation was 7.7% in patients randomized to MVS alone, 16.1% in MVS + PVI, and 25% in MVS + biatrial maze. The indications for PPM were similar among patients who underwent MVS with and without ablation. Ablation, multivalve surgery, and New York Heart Association functional (NYHA) functional class III/IV were independent risk factors for PPM implantation. Length of stay post-surgery was longer in patients who received PPMs, but it was not significant when adjusted for randomization assignment (MVS vs. ablation) and age (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.61 to 1.08; p = 0.14). PPM implantation did not increase 30-day readmission rate (HR: 1.43; 95% CI: 0.50 to 4.05; p = 0.50). The need for PPM was associated with a higher risk of 1-year mortality (HR: 3.21; 95% CI: 1.01 to 10.17; p = 0.05) after adjustment for randomization assignment, age, and NYHA functional class. Conclusions AF ablation, multivalve surgery, and NYHA functional class III/IV were associated with an increased risk for permanent pacing. PPM implantation following MVS was associated with a significant increase in 1-year mortality. (Surgical Ablation Versus No Surgical Ablation for Patients With Atrial Fibrillation Undergoing Mitral Valve Surgery; NCT00903370)

Background The aldosterone inhibitor eplerenone (EPL) has been shown to reduce the incidence of atrial fibrillation (AF) in patients with systolic heart failure, but the mechanism is unknown. Objectives This study hypothesized that by reducing atrial dilation and fibrosis in the absence of heart failure, EPL also reduces AF burden and prevents AF perpetuation. Methods The authors conducted a randomized controlled study in 34 sheep that were atrially tachypaced (13 ± 1 week). They compared daily oral EPL (n = 19) versus sugar pill (SP) treatment (n = 15) from the start of tachypacing. The endpoint was a continuous 7-day stretch of persistent AF (n = 29) or completion of 23 weeks tachypacing (n = 5). Results EPL significantly reduced the rate of left atrial dilation increase during AF progression. Atria from EPL-treated sheep had less smooth muscle actin protein, collagen-III expression, interstitial atrial fibrosis, and cell hypertrophy than SP-treated sheep atria did. However, EPL did not modify the AF-induced increase in the rate of dominant frequency and ion channel densities seen under SP treatment, but rather prolonged the time to persistent AF in 26% of animals. It also reduced the degree of fibrillatory conduction, AF inducibility, and AF burden. Conclusions In the sheep model, EPL mitigates fibrosis and atrial dilation, modifies AF inducibility and AF complexity, and prolongs the transition to persistent AF in 26% of animals, but it does not prevent AF-induced electrical remodeling or AF persistence. The results highlight structural remodeling as a central upstream target to reduce AF burden, and the need to prevent electrical remodeling to avert AF perpetuation.

Cardiac pacing is an effective treatment for patients with bradycardia due to sinus node dysfunction or atrioventricular block. Despite decades of technological advances, the optimal ventricular pacing site to mimic normal human ventricular physiology and best hemodynamic response remains elusive. Beginning with atrial synchronous right ventricular (RV) apical pacing, the search has continued through alternate RV pacing sites, minimizing RV pacing, biventricular pacing, left ventricular (LV) pacing, and His-bundle pacing. Understanding the deleterious effects of long-term RV apical pacing in vulnerable populations has created tremendous interest in alternate pacing options. This paper reviews the current status of available pacing options, with particular focus on His-bundle pacing. Permanent His-bundle pacing has emerged as the leading candidate for physiological pacing because it provides nearly normal electrical activation of both ventricles and thereby avoids ventricular dyssynchrony. Synchronized LV pacing, multisite LV pacing, and LV endocardial pacing offer promise as novel pacing options in select patients.

ObjectivesThis study sought to assess the effects of tranilast on atrial remodeling in a canine atrial fibrillation (AF) model.BackgroundTranilast inhibits transforming growth factor (TGF)-β1 and prevents fibrosis in many pathophysiological settings. However, the effects of tranilast on atrial remodeling remain unclear.MethodsBeagles were subjected to atrial tachypacing (400 beats/min) for 4 weeks while treated with placebo (control dogs, n = 8) or tranilast (tranilast dogs, n = 10). Sham dogs (n = 6) did not receive atrial tachypacing. Atrioventricular conduction was preserved. Ventricular dysfunction developed in the control and tranilast dogs due to rapid ventricular responses.ResultsAtrial fibrillation duration (211 ± 57 s) increased, and AF cycle length and atrial effective refractory period shortened in controls, but these changes were suppressed in tranilast dogs (AF duration, 18 ± 10 s, p < 0.01 vs. control). The L-type calcium channel α1c (Cav1.2) micro ribonucleic acid expression decreased in control dogs (sham 1.38 ± 0.24 vs. control 0.65 ± 0.12, p < 0.01), but not in tranilast dogs (0.97 ± 0.14, p = not significant vs. sham). Prominent atrial fibrosis (fibrous tissue area, sham 0.8 ± 0.1 vs. control 9.3 ± 1.3%, p < 0.01) and increased expression of tissue inhibitor of metalloproteinase protein 1 were observed in control dogs but not in tranilast dogs (fibrous tissue area, 1.4 ± 0.2%, p < 0.01 vs. control). The TGF-β1 (sham 1.00 ± 0.07 vs. control 3.06 ± 0.87, p < 0.05) and Rac1 proteins were overexpressed in control dogs, but their overexpression was inhibited in tranilast dogs (TGF-β1, 1.28 ± 0.20, p < 0.05 vs. control).ConclusionsTranilast prevented atrial remodeling and suppressed AF development in a canine model. Its inhibition of TGF-β1 and Rac1 overexpression may contribute to its antiremodeling effects.

Transcatheter aortic valve replacement (TAVR) is an established therapy for patients with aortic stenosis [(1)][1]. Rapid pacing (RP), to ablate left ventricular (LV) ejection, stabilizes deployment and is necessary for balloon-expandable TAVR although it is less important for repositionable, self

ObjectivesWe hypothesized that autonomic atrial remodeling can be reversed by low-level (LL) vagosympathetic nerve stimulation (VNS).BackgroundPreviously, we showed that VNS can be antiarrhythmogenic.MethodsThirty-three dogs were subjected to electrical stimulation (20 Hz) applied to both vagosympathetic trunks at voltages 10% to 50% below the threshold that slowed sinus rate or AV conduction. Group 1 (n = 7): Programmed stimulation (PS) was performed at baseline and during 6-h rapid atrial pacing (RAP). PS allowed determination of effective refractory period (ERP) and AF inducibility measured by window of vulnerability (WOV). LL-VNS was continuously applied from the 4th to 6th hours. Group 2 (n = 4): After baseline ERP and WOV determinations, 6-h concomitant RAP+LL-VNS was applied. Sustained AF was induced by injecting acetylcholine (ACh) 10 mM into the anterior right ganglionated plexus (Group 3, n = 10) or applying ACh 10 mM to right atrial appendage (Group 4, n = 9).ResultsGroup 1: The ERP progressively shortened and the ΣWOV (sum of WOV from all tested sites) progressively increased (p < 0.05) during 3-h RAP then returned toward baseline during 3-h RAP+LL-VNS (p < 0.05). Group 2: 6-h concomitant RAP+LL-VNS did not induce any significant change in ERP and ΣWOV. Group 3 and Group 4: AF duration (AF-D) and cycle length (AF-CL) were markedly altered by 3-h LL-VNS (Group 3: baseline: AF-D = 389 ± 90 s, AF-CL = 45.1 ± 7.8 ms; LL-VNS: AF-D = 50 ± 15 s, AF-CL = 82.0 ± 13.7 ms [both p < 0.001]; Group 4: baseline: AF-D = 505 ± 162 s, AF-CL = 48.8 ± 6.6 ms; LL-VNS: AF-D = 71 ± 21 s, AF-CL = 101.3 ± 20.9 ms [both p < 0.001]).ConclusionsLL-VNS can prevent and reverse atrial remodeling induced by RAP as well as suppress AF induced by strong cholinergic stimulation. Inhibition of the intrinsic cardiac autonomic nervous system by LL-VNS may be responsible for these salutary results.

To the Editor: It is known that a transient change in the sequence of ventricular depolarization may be followed by inverted T waves that become apparent once ventricular activation normalizes. In 1982, Rosenbaum et al. [(1)][1] coined this cumulative phenomenon “cardiac memory,” as it occurs

Objectives We sought to confirm our hypothesis that the human sinoatrial node (SAN) is functionally insulated from the surrounding atrial myocardium except for several exit pathways that electrically bridge the nodal tissue and atrial myocardium. Background The site of origin and pattern of excitation within the human SAN has not been directly mapped. Methods The SAN was optically mapped in coronary-perfused preparations from nonfailing human hearts (n = 4, age 54 ± 15 years) using the dye Di-4-ANBDQBS and blebbistatin. The SAN 3-dimensional structure was reconstructed using histology. Results Optical recordings from the SAN had diastolic depolarization and multiple upstroke components, which corresponded to the separate excitations of the SAN and atrial layers. Excitation originated in the middle of the SAN (66 ± 17 beats/min), and then spread slowly (1 to 18 cm/s) and anisotropically. After a 82 ± 17 ms conduction delay within the SAN, the atrial myocardium was excited via superior, middle, and/or inferior sinoatrial conduction pathways. Atrial excitation was initiated 9.4 ± 4.2 mm from the leading pacemaker site. The oval 14.3 ± 1.5 mm × 6.7 ± 1.6 mm × 1.0 ± 0.2 mm SAN structure was functionally insulated from the atrium by connective tissue, fat, and coronary arteries, except for these pathways. Conclusions These data demonstrated for the first time, to our knowledge, the location of the leading SAN pacemaker site, the pattern of excitation within the human SAN, and the conduction pathways into the right atrium. The existence of these pathways explains why, even during normal sinus rhythm, atrial breakthroughs could arise from a region parallel to the crista terminalis that is significantly larger (26.1 ± 7.9 mm) than the area of the anatomically defined SAN.

Cardiac resynchronization therapy (CRT) is an effective treatment for patients with drug-refractory, chronic heart failure. Multiple single-center and multicenter studies have shown significant reductions in left ventricular (LV) volumes and an increase in LV systolic function. More importantly, CRT reduces mortality and morbidity during long-term follow-up. Current guidelines consider CRT as a Class I indication for heart failure patients in New York Heart Association (NYHA) functional class III to IV with depressed LV ejection fractionor=35% and a wide QRS complex (or=120 ms). However, the benefits of this therapy could possibly be extended to selected subgroups of patients who do not fulfill these criteria. These subgroups include patients with mildly symptomatic heart failure and patients with a narrow QRS complex (120 ms). Results from recent multicenter controlled clinical trials including heart failure patients in NYHA functional class I to II or with a narrow QRS complex are equivocal. Although expanding CRT to patients with a narrow QRS complex seems currently not likely, the benefits of CRT in mildly symptomatic patients are more evident. Perhaps attenuation of disease progression will prove to be a successful new treatment strategy in heart failure patients in the future. In addition, multimodality cardiac imaging will allow optimizing responder rate in patients undergoing CRT according to current guidelines.

ObjectivesWe sought to investigate the impact of left ventricular (LV) pacing site on mechanical response to cardiac resynchronization therapy (CRT) in patients with ischemic cardiomyopathy (ICM).BackgroundCRT reduces morbidity and mortality in patients with dyssynchronous LV failure; however, variability in response, particularly in ICM patients, poses ongoing challenges. Endocardial biventricular (BiV) stimulation may provide more flexibility in LV site selection and yield more natural transmural activation patterns. Whether this applies to ICM and whether optimal LV endocardial pacing locations vary among ICM patients remain unknown.MethodsPeak rate of LV pressure increase (dP/dtmax) was measured at baseline, during VDD pacing at the right ventricular apex, and during BiV pacing from the right ventricular apex and 51 ± 14 different LV endocardial sites in patients with ICM (n = 11). Seven patients already had an epicardial LV lead (CRT) in place, allowing comparison of epicardial BiV stimulation with that using an endocardial site directly transmural to the CRT-coronary sinus lead tip. Electroanatomic 3-dimensional maps with color-coded dP/dtmaxresponse defined optimal pacing regions delivering ≥85% of maximal increase in dP/dtmax.ResultsEndocardial BiV pacing improved dP/dtmaxover right ventricular apex pacing in all patients (mean increase 241 ± 38 mm Hg/s; p < 0.0001). In patients with pre-existing CRT leads, LV endocardial versus epicardial pacing at transmural sites yielded equivalent dP/dtmaxvalues. However, dP/dtmaxat the best endocardial site exceeded that achieved with the pre-implanted CRT device (mean increase 111 ± 25 mm Hg/s; p = 0.004). An average of ∼2 optimal endocardial sites were identified for each patient, located at the extreme basal lateral wall (8 of 11 patients) and other regions (9 of 11). Standard mid-LV free wall pacing yielded suboptimal LV function in 73% of patients. Optimal pacing sites were typically located in LV territories remote (9.3 ± 3.6 cm) from the infarct zone.ConclusionsCRT delivered at best LV endocardial sites is more effective than via pre-implanted coronary sinus lead pacing. The location of optimal LV endocardial pacing varies among patients with ICM, and individual tailoring may improve CRT efficacy in such patients.

ObjectivesThe purpose of the study was to define the extent and nature of cardiac resynchronization therapy (CRT) device usage outside consensus guidelines using national data.BackgroundRecent literature has shown that the application of CRT in clinical practice frequently does not adhere to evidence-based consensus guidelines. Factors underlying these practices have not been fully explored.MethodsFrom the National Cardiovascular Data Registry's Implantable Cardiac-Defibrillator Registry, we defined a cohort of 45,392 cardiac resynchronization therapy-defibrillator (CRT-D) implants between January 2006 and June 2008 with a primary prevention indication. We defined “off-label” implants as those in which the ejection fraction was >35%, the New York Heart Association functional class was below III, or the QRS interval duration was

The year in echocardiography has been marked by incremental progress in our understanding of the methodology and potential applications of techniques introduced in the last few years, such as speckle tracking (STE), real-time 3-dimensional echocardiography (RT3DE), and Doppler tissue imaging (DTI).

ObjectivesThis study sought to determine the incidence of ineffective capture using 12-lead Holter monitoring and to assess whether this affects response to cardiac resynchronization therapy (CRT).BackgroundCardiac resynchronization therapy is used in patients with atrial fibrillation (AF), prolonged QRS duration, and heart failure in the setting of ventricular dysfunction. The percentage of ventricular pacing is used as an indicator of adequate biventricular (BiV) pacing. Although device counters show a high pacing percentage, there may be ineffective capture because of underlying fusion and pseudo-fusion beats.MethodsWe identified 19 patients (age 72 ± 8 years, ejection fraction 18 ± 5%), with permanent AF who underwent CRT. All patients received digoxin, beta-blockers, and amiodarone for rate control; device interrogation showed >90% BiV pacing. Patients had a 12-lead Holter monitor to assess the presence of effective (>90% fully paced beats/24 h) pacing. At 12 months post-CRT, the New York Heart Association functional class was reassessed and an echocardiogram was obtained and compared with pre-CRT.ResultsOnly 9 (47%) patients had effective pacing. The other 10 (53%) patients had 16.4 ± 4.6% fusion and 23.5 ± 8.7% pseudo-fusion beats. Long-term responders (≥1 New York Heart Association functional class improvement) to CRT had a significantly higher percentage of fully paced beats (86.4 ± 17.1% vs. 66.8 ± 19.1%; p = 0.03) than nonresponders.ConclusionsPacing counters overestimate the degree of effective BiV pacing in patients with permanent AF undergoing CRT therapy. Only patients with complete capture responded clinically to CRT. These findings have important implications for the application of CRT to patients with permanent AF and heart failure.

Objectives Our aim was to determine the feasibility and value of a protocol-driven approach to patients with cardiac resynchronization therapy (CRT) who did not exhibit a positive response long after implant. Background Up to one-third of patients with advanced heart failure do not exhibit a positive response to CRT. Methods A total of 75 consecutive ambulatory patients with persistent advanced heart failure symptoms and/or adverse reverse remodeling and CRT implanted >6 months underwent a comprehensive protocol-driven evaluation to determine the potential reasons for a suboptimal response. Recommendations were made to maximize the potential of CRT, and adverse events were documented. Results All patients ( mean left ventricular [LV] ejection fraction 23 +/- 9%, LV end-diastolic volume 275 +/- 127 ml) underwent evaluation. Eighty-eight percent of patients had significantly better echocardiographic indexes of LV filling and LV ejection with optimal setting of their CRT compared with a temporary VVI back-up setting. Most patients had identifiable reasons for suboptimal response, including inadequate device settings (47%), suboptimal medical treatment (32%), arrhythmias ( 32%), inappropriate lead position (21%), or lack of baseline dyssynchrony ( 9%). Multidisciplinary recommendations led to changes in device settings and/or other therapy modifications in 74% of patients and were associated with fewer adverse events (13% vs. 50%, odds ratio: 0.2 [95% confidence interval: 0.07 to 0.56], p = 0.002) compared with those in which no recommendation could be made. Conclusions Routine protocol-driven approach to evaluate ambulatory CRT patients who did not exhibit a positive response is feasible, and changes in device settings and/or other therapies after multidisciplinary evaluation may be associated with fewer adverse events.

Objectives Our aim was to determine the potential hemodynamic contributions of cardiac resynchronization therapy (CRT) in patients admitted for advanced decompensated heart failure. Background CRT restores synchrony of the heart resulting in hemodynamic support that can facilitate the reversal of left ventricular (LV) remodeling in some patients. Methods A total of 40 consecutive patients with advanced decompensated heart failure and CRT implanted >3 months, admitted due to hemodynamic derangements, underwent simultaneous comprehensive echocardiographic and invasive hemodynamic evaluation under different CRT settings. Results All patients (mean LV ejection fraction 22 +/- 7%, LV end-diastolic volume 323 +/- 140 ml, 40% ischemic) had experienced progressive cardiac remodeling despite adequate LV lead positions and continuous biventricular pacing. A significant worsening of hemodynamics was observed immediately when CRT was programmed OFF in the majority (88%) of patients (systolic blood pressure: 105 +/- 12 mm Hg to 98 +/- 13 mm Hg; pulmonary capillary wedge pressure: 17 +/- 6 mm Hg to 21 +/- 7 mm Hg; cardiac output: 4.6 +/- 1.4 l/min/m(2) to 4.0 +/- 1.1 l/min/m(2); all p < 0.001). Worsening of hemodynamics coincided with reappearance of significant electrical (QRS width 161 +/- 29 ms to 202 +/- 39 ms, p < 0.001) and intraventricular mechanical dyssynchrony (15 +/- 26 ms to 57 +/- 41 ms, p < 0.001), together with a significant reduction in diastolic filling time (377 +/- 138 ms to 300 +/- 118 ms, p < 0.001). Conclusions Despite progressive cardiac remodeling and decompensation, chronic CRT continues to provide hemodynamic augmentation in the failing heart in most patients. Our data suggest that disease progression may not be explained by diminished beneficial hemodynamic contributions of successful resynchronization.

Objectives The purpose of this study was to differentiate non–re-entrant junctional tachycardia (JT) and typical atrioventricular node re-entry tachycardia (AVNRT). Background JT may mimic AVNRT. Ablation of JT is associated with a lower success rate and a higher incidence of heart block. Electrophysiologic differentiation of these tachycardias is often difficult. Methods We hypothesized that JT can be distinguished from AVNRT based on specific responses to premature atrial complexes (PACs) delivered at different phases of the tachycardia cycle: when a PAC is timed to His refractoriness, any perturbation of the subsequent His indicates that anterograde slow pathway conduction is involved and confirms a diagnosis of AVNRT. A PAC that advances the His potential immediately after it without terminating tachycardia indicates that retrograde fast pathway is not essential for the circuit and confirms a diagnosis of JT. This protocol was tested in 39 patients with 44 tachycardias suggesting either JT or AVNRT based on a short ventriculo-atrial interval and apparent AV node dependence. Tachycardias were divided into 3 groups: clinically obvious AVNRT, clinically obvious JT, and clinically indeterminate rhythm. Results In the 26 cases of clinically obvious AVNRT, the sensitivity and specificity of the test were 61% and 100%, respectively. In the 9 cases of clinically obvious JT, the sensitivity and specificity were 100% and 100%, respectively. In the 9 cases of clinically indeterminate rhythm, the technique indicated AVNRT in 1 patient and JT in 7 patients, and the test was indeterminate in 1 patient. Conclusions The response to PACs during tachycardia can distinguish JT and AVNRT with 100% specificity in adult patients.

Objectives The aim of the current study was to evaluate echocardiographic parameters after 6 months of cardiac resynchronization therapy (CRT) as well as long-term outcome in patients with the left ventricular (LV) lead positioned at the site of latest activation (concordant LV lead position) as compared with that seen in patients with a discordant LV lead position. Background A nonoptimal LV pacing lead position may be a potential cause for nonresponse to CRT. Methods The site of latest mechanical activation was determined by speckle tracking radial strain analysis and related to the LV lead position on chest X-ray in 244 CRT candidates. Echocardiographic evaluation was performed after 6 months. Long-term follow-up included all-cause mortality and hospitalizations for heart failure. Results Significant LV reverse remodeling (reduction in LV end-systolic volume from 189 +/- 83 ml to 134 +/- 71 ml, p < 0.001) was noted in the group of patients with a concordant LV lead position (n = 153, 63%), whereas patients with a discordant lead position showed no significant improvements. In addition, during long-term follow-up (32 +/- 16 months), less events (combined for heart failure hospitalizations and death) were reported in patients with a concordant LV lead position. Moreover, a concordant LV lead position appeared to be an independent predictor of hospitalization-free survival after long-term CRT (hazard ratio: 0.22, p = 0.004). Conclusions Pacing at the site of latest mechanical activation, as determined by speckle tracking radial strain analysis, resulted in superior echocardiographic response after 6 months of CRT and better prognosis during long-term follow-up. (J Am Coll Cardiol 2008; 52: 1402 -9) (C) 2008 by the American College of Cardiology Foundation

ObjectivesOur aim was to study the relationship between T-wave alternans (TWA) and rate-response (restitution) of repolarization in subjects with and without ventricular systolic dysfunction.BackgroundT-wave alternans is a promising predictor of sudden death, yet the mechanisms linking it with human ventricular arrhythmias are unclear. From theoretic considerations, we hypothesized that abnormal TWA is linked with steep restitution of action potential duration (APD) and that both predict arrhythmic outcome.MethodsWe studied 53 subjects with left ventricular ejection fraction (LVEF) ≤40% and 18 control subjects. At electrophysiologic study, we recorded APD at 90% repolarization (APD90) in the right (n = 62) or left (n = 9) ventricle during pacing while measuring TWA from the body surface.ResultsAs expected, TWA (at 1; 58% vs. 67%). T-wave alternans and simultaneous APD alternans always occurred at diastolic intervals where APD restitution was not steep (p < 0.001), and there was no relationship between maximum restitution slope and TWA magnitude. Over 829 ± 473 days, TWA (p = 0.02), but not restitution slope >1, predicted ventricular arrhythmias in subjects with LVEF ≤40%.ConclusionsThe mechanism by which TWA predicts arrhythmic mortality does not reflect the maximum slope of ventricular APD restitution. Better understanding of the mechanisms underlying TWA may enable improved prediction and prevention of ventricular arrhythmias.

ObjectivesThe purpose of this study was to evaluate the relationship between dyssynchrony involving the mitral valve apparatus and the acute improvement in mitral regurgitation (MR) after cardiac resynchronization therapy (CRT). The effect of interruption of CRT at 6 months’ follow-up on dyssynchrony and MR was also evaluated.BackgroundMitral regurgitation may improve acutely after CRT, but the precise mechanism is not fully understood.MethodsOut of 63 consecutive patients with baseline MR, 25 patients showed an acute reduction in MR severity immediately after CRT. This selected group of 25 patients (age 68 ± 10 years, left ventricular ejection fraction 23 ± 8%) was evaluated in the current study. Echocardiography including speckle tracking strain analysis was performed at baseline, after CRT initiation, and during interruption of CRT at 6 months’ follow-up to study the relationship between dyssynchrony between the papillary muscles and severity of MR.ResultsAccording to the inclusion criteria, all patients showed an immediate improvement in MR after CRT (vena contracta width decreased from 0.54 ± 0.15 cm to 0.39 ± 0.13 cm; p < 0.001), accompanied by an improvement in mitral deformation indexes. Furthermore, dyssynchrony between the papillary muscles decreased from 169 ± 69 ms to 25 ± 26 ms (p < 0.001). Importantly, these beneficial effects were maintained at 6 months’ follow-up, but acute loss of resynchronization (from 26 ± 28 ms to 134 ± 51 ms; p < 0.001) was observed after interruption of CRT, with an acute recurrence of MR and worsening in mitral deformation indexes.ConclusionsCardiac resynchronization therapy can acutely reduce MR in patients with dyssynchrony involving the papillary muscles; interruption of CRT at 6 months’ follow-up, however, resulted in acute loss of resynchronization with recurrence of MR.

ObjectivesThe purpose of this study was to test the hypothesis that a combined echocardiographic assessment of longitudinal dyssynchrony by tissue Doppler imaging (TDI) and radial dyssynchrony by speckle-tracking strain may predict left ventricular (LV) functional response to cardiac resynchronization therapy (CRT).BackgroundMechanical LV dyssynchrony is associated with response to CRT; however, complex patterns may exist.MethodsWe studied 190 heart failure patients (ejection fraction [EF] 23 ± 6%, QRS duration 168 ± 27 ms) before and after CRT. Longitudinal dyssynchrony was assessed by color TDI for time to peak velocity (2 sites in all and 12 sites in a subgroup of 67). Radial dyssynchrony was assessed by speckle-tracking radial strain. The LV response was defined as ≥15% increase in EF.ResultsOne hundred seventy-six patients (93%) had technically sufficient baseline and follow-up data available. Overall, 34% were EF nonresponders at 6 ± 3 months after CRT. When both longitudinal dyssynchrony by 2-site TDI (≥60 ms) and radial dyssynchrony (≥130 ms) were positive, 95% of patients had an EF response; when both were negative, 21% had an EF response (p < 0.001 vs. both positive). The EF response rate was lowest (10%) when dyssynchrony was negative using 12-site TDI and radial strain (p < 0.001 vs. both positive). When either longitudinal or radial dyssynchrony was positive (but not both), 59% had an EF response. Combined longitudinal and radial dyssynchrony predicted EF response with 88% sensitivity and 80% specificity, which was significantly better than either technique alone (p < 0.0001).ConclusionsCombined patterns of longitudinal and radial dyssynchrony can be predictive of LV functional response after CRT.

ObjectivesWe compared mechanical dyssynchrony and the impact of cardiac resynchronization therapy (CRT) in failing hearts with a pure right (RBBB) versus left bundle branch block (LBBB).BackgroundCardiac resynchronization therapy is effective for treating failing hearts with conduction delay and discoordinate contraction. Most data pertain to LBBB delays. With RBBB, the lateral wall contracts early so that biventricular (BiV) pre-excitation may not be needed. Furthermore, the magnitude of dyssynchrony and impact of CRT in pure RBBB versus LBBB remains largely unknown.MethodsDogs with tachypacing-induced heart failure combined with right or left bundle branch radiofrequency ablation were studied. Basal dyssynchrony and effects of single and BiV CRT on left ventricular (LV) function were assessed by pressure-volume catheter and tagged magnetic resonance imaging, respectively.ResultsLeft bundle branch block and RBBB induced similar QRS widening, and LV function (ejection fraction, maximum time derivative of LV pressure [dP/dtmax]) was similarly depressed in failing hearts with both conduction delays. Despite this, mechanical dyssynchrony was less in RBBB (circumferential uniformity ratio estimate [CURE] index: 0.80 ± 0.03 vs. 0.58 ± 0.09 for LBBB, p < 0.04; CURE 0→1 is dyssynchronous→synchronous). Cardiac resynchronization therapy had correspondingly less effect on hearts with RBBB than those with LBBB (i.e., 5.5 ± 1.1% vs. 29.5 ± 5.0% increase in dP/dtmax, p < 0.005), despite similar baselines. Furthermore, right ventricular-only pacing enhanced function and synchrony in RBBB as well or better than did BiV, whereas LV-only pacing worsened function.ConclusionsLess mechanical dyssynchrony is induced by RBBB than LBBB in failing hearts, and the corresponding impact of CRT on the former is reduced. Right ventricular-only pacing may be equally efficacious as BiV CRT in hearts with pure right bundle branch conduction delay.

ObjectivesThis study was designed to analyze the relevance of ventricular activation patterns for ventricular electrical remodeling after atrioventricular (AV) block in dogs.BackgroundBradycardia is thought to be the main contributor to ventricular electrical remodeling after complete AV block. However, an altered ventricular activation pattern or AV dyssynchrony may also contribute.MethodsFor 4 weeks, AV block dogs were either paced from the high-ventricular septum near the His bundle at lowest captured rate (n = 9, high-septal pacing [HSP]) or kept at idioventricular rate without controlled activation (n = 14, chronic AV block [CAVB]). Multiple electrocardiographic and electrophysiological parameters were measured under anesthesia at 0 and 4 weeks. Proarrhythmia was tested at 4 weeks by IKrblock (25 μg/kg dofetilide intravenous).ResultsAt 0 weeks, the 2 groups were comparable, whereas after 4 weeks of similar bradycardia, QT duration at unpaced conditions had increased from 300 ± 5 to 395 ± 18 ms in CAVB (+32 ± 6%) and from 307 ± 8 ms to 357 ± 11 ms in HSP (+17 ± 4%; p < 0.05). Frequency dependency of repolarization was less steep in HSP compared to CAVB dogs after 4 weeks remodeling. Beat-to-beat variability of repolarization, a proarrhythmic parameter, increased only in CAVB from 0 to 4 weeks. Torsades de pointes arrhythmias were induced at 4 weeks in 44% HSP versus 78% CAVB dogs (p = 0.17). Cumulative duration of arrhythmias per inducible dog was 87 ± 36 s in CAVB and 30 ± 21 s in HSP (p < 0.05).ConclusionsHigh-septal pacing reduces the magnitude of ventricular electrical remodeling and proarrhythmia in AV block dogs, suggesting a larger role for altered ventricular activation pattern in the generation of ventricular electrical remodeling than previously assumed.

Several important studies related to the treatment of atrial fibrillation (AF) were published in the past year. In addition, building on recent data, the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA), and the Heart Rhythm Society (HRS) provided updates to the

ObjectivesThe purpose of this study was to compare left ventricular (LV) dyssynchrony assessment by gated myocardial perfusion single-photon emission computed tomography (SPECT) (GMPS) and tissue Doppler imaging (TDI).BackgroundRecently, it has been suggested that LV dyssynchrony is an important predictor of response to cardiac resynchronization therapy (CRT); dyssynchrony is predominantly assessed by TDI with echocardiography. Information on LV dyssynchrony can also be provided by GMPS with phase analysis of regional LV maximal count changes throughout the cardiac cycle, which tracks the onset of LV thickening.MethodsIn 75 patients with heart failure, depressed LV function, and wide QRS complex, GMPS and 2-dimensional echocardiography, including TDI, were performed as part of clinical screening for eligibility for CRT. Clinical status was evaluated with New York Heart Association functional classification, 6-min walk distance, and quality-of-life score. Different parameters (histogram bandwidth, phase SD, histogram skewness, and histogram kurtosis) of LV dyssynchrony were assessed from GMPS and compared with LV dyssynchrony on TDI with Pearson’s correlation analyses.ResultsHistogram bandwidth and phase SD correlated well with LV dyssynchrony assessed with TDI (r = 0.89, p < 0.0001 and r = 0.80, p < 0.0001, respectively). Histogram skewness and kurtosis correlated less well with LV dyssynchrony on TDI (r = −0.52, p < 0.0001 and r = −0.45, p < 0.0001, respectively).ConclusionsThe LV dyssynchrony assessed from GMPS correlated well with dyssynchrony assessed by TDI; histogram bandwidth and phase SD showed the best correlation with LV dyssynchrony on TDI. These parameters seem most optimal for assessment of LV dyssynchrony with gated SPECT. Outcome studies after CRT are needed to further validate the use of GMPS for assessment of LV dyssynchrony.

Objectives Speckle-tracking strain analysis was used to assess the effects of permanent right ventricular (RV) pacing on the heterogeneity in timing of regional wall strain and left ventricular (LV) dyssynchrony. Background Recent studies have shown detrimental effects of RV pacing, possibly related to the induction of LV dyssynchrony. Methods Fifty-eight patients treated with His bundle ablation and pacemaker implantation were studied. To assess the effect of RV pacing on time-to-peak radial strain of different LV segments, we applied speckle-tracking analysis to standard LV short-axis images. In addition, New York Heart Association (NYHA) functional class, LV volumes, and systolic function were assessed at baseline and after long-term RV pacing. Results At baseline, similar time-to-peak strain for the 6 segments was observed (mean 371 ± 114 ms). In contrast, after a mean of 3.8 ± 2.0 years of RV pacing, there was a marked heterogeneity in time-to-peak strain of the 6 segments. In 33 patients (57%), LV dyssynchrony, represented by a time difference ≥130 ms between the time-to-peak strain of the (antero)septal and the posterolateral segments, was present. In these patients, a deterioration of LV systolic function and NYHA functional class was observed. In 11 patients, an “upgrade” of the conventional pacemaker to a biventricular pacemaker resulted in partial reversal of the detrimental effects of RV pacing. Conclusions Speckle-tracking analysis revealed that permanent RV pacing induced heterogeneity in time-to-peak strain, resulting in LV dyssynchrony in 57% of patients, associated with deterioration of LV systolic function and NYHA functional class. Biventricular pacing may reverse these adverse effects of RV pacing.

Despite significant advances in battery longevity, lead performance, and programming features since the first implanted permanent pacemaker was developed, the basic design of cardiac pacemakers has remained relatively unchanged over the past 50 years. Because of inherent limitations in their design, conventional (transvenous) pacemakers are prone to multiple potential short- and long-term complications. Accordingly, there has been intense interest in a system able to provide the symptomatic and potentially lifesaving therapies of cardiac pacemakers while mitigating many of the risks associated with their weakest link-the transvenous lead. Leadless cardiac pacing represents the future of cardiac pacing systems, similar to the transition that occurred from the use of epicardial pacing systems to the familiar transvenous systems of today. This review summarizes the current evidence and potential benefits of leadless pacing systems, which are either commercially available (in Europe) or under clinical investigation.

1.1 Document Development Process #### 1.1.1 Writing Committee Organization The writing committee was selected to represent the American College of Cardiology (ACC) and the Heart Rhythm Society (HRS) and included a cardiovascular training program director, an electrophysiology (EP) program

Heart failure (HF) has been the subject of a number of important published clinical and translational investigations over the past year. We also anticipate that updates of the American professional societies' major clinical guidelines will be published later this year. In this article, we summarize

The purpose of this study was to evaluate the effects of cardiac resynchronization therapy (CRT) in heart failure patients with narrow QRS complex (120 ms) and evidence of left ventricular (LV) dyssynchrony on tissue Doppler imaging (TDI).Cardiac resynchronization therapy is beneficial in selected heart failure patients with wide QRS complex (or =120 ms). Patients with narrow QRS complex are currently not eligible for CRT, and the potential effects of CRT are not well studied.Thirty-three consecutive patients with narrow QRS complex and 33 consecutive patients with wide QRS complex (control group) were prospectively included. All patients needed to have LV dyssynchronyor =65 ms on TDI, New York Heart Association (NYHA) functional class III/IV heart failure, and LV ejection fractionor =35%.Baseline characteristics, particularly LV dyssynchrony, were comparable between patients with narrow and wide QRS complex (110 +/- 8 ms vs. 175 +/- 22 ms; p = NS). No significant relationship was observed between baseline QRS duration and LV dyssynchrony (r = 0.21; p = NS). The improvement in clinical symptoms and LV reverse remodeling was comparable between patients with narrow and wide QRS complex (mean NYHA functional class reduction 0.9 +/- 0.6 vs. 1.1 +/- 0.6 [p = NS] and mean LV end-systolic volume reduction 39 +/- 34 ml vs. 44 +/- 46 ml [p = NS]).Cardiac resynchronization therapy appears to be beneficial in patients with narrow QRS complex and severe LV dyssynchrony on TDI, with similar improvement in symptoms and comparable LV reverse remodeling to patients with wide QRS complex. The current results need confirmation in larger patient cohorts.

Objectives We evaluated the ability of delayed enhancement magnetic resonance imaging (DE-MRI) to predict clinical response to cardiac resynchronization therapy (CRT). Background Cardiac resynchronization therapy reduces morbidity and mortality in selected heart failure patients. However, up to 30% of patients do not have a response. We hypothesized that scar burden on DE-MRI predicts response to CRT. Methods The DE-MRI was performed on 28 heart failure patients undergoing CRT. Patients with QRS ≥120 ms, left ventricular ejection fraction ≤35%, New York Heart Association functional class II to IV, and dyssynchrony ≥60 ms were studied. Baseline and 3-month clinical follow-up, wall motion, 6-min walk, and quality of life assessment were performed. The DE-MRI was performed 10 min after 0.20 mmol/kg intravenous gadolinium. Scar measured by planimetry was correlated with response criteria. Results Twenty-three patients completed the protocol (mean age 64.9 ± 11.7 years), with 12 (52%) having a history of myocardial infarction. Thirteen (57%) patients met response criteria. Percent total scar was significantly higher in the nonresponse versus response group (median and interquartile range of 24.7% [18.1 to 48.7] vs. 1.0% [0.0 to 8.7], p = 0.0022) and predicted nonresponse by receiver-operating characteristic analysis (area = 0.94). At a cutoff value of 15%, percent total scar provided a sensitivity and specificity of 85% and 90%, respectively, for clinical response to CRT. Similarly, septal scar ≤40% provided a 100% sensitivity and specificity for response. Regression analysis showed linear correlations between percent total scar and change in each of the individual response criteria. Conclusions The DE-MRI accurately predicted clinical response to CRT. This technique offers unique information in the assessment of patients referred for CRT.

ObjectivesThe purpose of this study was to test the hypothesis that cardiac-directed expression of adenylyl cyclase VI (ACVI) facilitates atrioventricular (AV) nodal conduction.BackgroundCardiac-directed expression of ACVI, unlike other strategies to increase cyclic adenosine monophosphate generation, reduces mortality in murine cardiomyopathy. Recent reports suggest that ACVIexpression may also protect against lethal bradycardia.MethodsWe performed immunofluorescence staining for ACVIin the AV node of transgenic mice. We then performed electrophysiologic studies (EPSs) using a 1.7-F octapolar catheter at the AV junction in 11 transgenic ACVImice and 14 control mice.ResultsImmunofluorescence staining revealed increased ACVIexpression in the AV node of transgenic mice versus controls. During EPS, AV intervals approximated PR intervals (R2= 0.99) and related linearly to atrial-to-His intervals (R2= 0.98; both p < 0.0001). Thus, we studied AV intervals to avoid electrocardiogram pacing artifacts and inconsistent inscription of His bundle electrograms. At baseline, ACVImice had shorter AV intervals (47 ± 9 ms) than controls (57 ± 11 ms; p = 0.02), despite similar sinus rates. In pacing, AV intervals were shorter in ACVImice than controls for a wide cycle-length range (p < 0.01). The ACVImice also had shorter AV Wenckebach cycle lengths (ACVI: 114 ± 12 ms; control: 131 ± 28 ms; p = 0.05) and ventriculo-atrial effective refractory periods (ACVI: 97 ± 21 ms; control: 127 ± 15 ms; p = 0.05). We observed no differences between groups in sinus node function, and ventricular arrhythmias were not inducible.ConclusionsCardiac-directed expression of ACVIfacilitates AV nodal conduction without altering sinus node function. These results suggest the need to define a role for ACVIgene transfer in treating diseases of AV conduction.

ObjectivesWe attempted to assess the efficacy of combined cardiac resynchronization therapy-implantable cardioverter-defibrillator (CRT-ICD) in heart failure patients with and without ventricular arrhythmias.BackgroundBecause CRT and ICDs both lower all-cause mortality in patients with advanced heart failure, combination of both therapies in a single device is challenging.MethodsA total of 191 consecutive patients with advanced heart failure, left ventricular ejection fraction 120 ms received CRT-ICD. Seventy-one patients had a history of ventricular arrhythmias (secondary prevention); 120 patients did not have prior ventricular arrhythmias (primary prevention). During follow-up, ICD therapy rate, clinical improvement after 6 months, and mortality rate were evaluated.ResultsDuring follow-up (18 ± 4 months), primary prevention patients experienced less appropriate ICD therapies than secondary prevention patients (21% vs. 35%, p < 0.05). Multivariate analysis revealed, however, no predictors of ICD therapy. Furthermore, a similar, significant, improvement in clinical parameters was observed at 6 months in both groups. Also, the mortality rate in the primary prevention group was lower than in the secondary prevention group (3% vs. 18%, p < 0.05).ConclusionsAs 21% of the primary prevention patients and 35% of the secondary prevention patients experienced appropriate ICD therapy within 2 years after implant, and no predictors of ICD therapy could be identified, implantation of a CRT-ICD device should be considered in all patients eligible for CRT.

ObjectivesThis study was designed to determine whether cardiac resynchronization therapy (CRT) by means of biventricular pacing (BiVP) alters the QT interval (QTc) and QT dispersion (QTD), and whether such changes relate to the risk of developing major arrhythmic events (MAE).BackgroundProlonged QTcis associated with MAE. Left ventricular pacing and BiVP alter QTc.MethodsA total of 75 patients with drug-resistant heart failure (New York Heart Association functional class III/IV) and QRS duration ≥120 ms underwent CRT. The QTcand QTD were measured before and 48 days after BiVP.ResultsOver 807 days (range 93 to 1,543 days), 11 patients had a MAE. Compared to baseline, at 48 days after CRT, QTD increased in 47% of patients and QTcdecreased in 53%. The QTcat follow-up was higher in MAE patients compared with no-MAE patients (35.9 ± 14.2 ms vs. 0.52 ± 6.0 ms; p = 0.0323). Similar differential responses for QTD were observed (46.4 ± 13.5 ms in MAE vs. −5.1 ± 4.1 ms in no MAE, p < 0.0001). The MAE occurred in 29% of patients exhibiting an increase in QTD and in 3% of those exhibiting a decrease (p = 0.0017). In multiple regression analyses, change in QTD from baseline (ΔQTD) strongly predicted MAE, independent of ΔQTc, QRS duration, and left ventricular ejection fraction and end-diastolic volume (p < 0.001). Differences in survival curves were observed when patients were dichotomized according to whether QTD increased or decreased in relation to baseline values (p < 0.0001).ConclusionsThe MAE in patients with BiVP are related to pacing-induced increases in QTD. Measures of ventricular repolarization at the time of pacemaker implantation may guide selection of patients for combined CRT and defibrillator therapy.

Clinical trials in patients with pacemakers for sinus node dysfunction or atrioventricular block (AVB) and implantable cardioverter-defibrillators provide increasing evidence showing that desynchronization of ventricular electrical activation and contraction, induced by conventional right ventricular apex (RVA) pacing, is a serious threat for long-term cardiac morbidity and mortality. The risk of heart failure is increased even in hearts with initially normal pump function and in case of part-time ventricular pacing. These epidemiologic data fit with knowledge from decades of pathophysiological research, indicating that right ventricular (RV) pacing creates abnormal contraction, reduced pump function, hypertrophy, and ultrastructural abnormalities. This paper presents a new paradigm that aims to tailor ventricular pacing to the individual patient to achieve a way of pacing that is as physiologic as possible. In patients without AVB and no intraventricular conduction abnormalities, ventricular pacing should be avoided as much as possible, using atrial-based pacing. In patients with AVB, alternate single-site RV or left ventricular pacing or biventricular pacing may be superior to RVA pacing. Efforts to optimize the pacing mode or site should be greater in patients with a longer expected duration of pacing, poorer cardiac function, and larger mechanical asynchrony. Awareness of the problem of desynchronization should also lead to more regular monitoring of cardiac pump function and mechanical asynchrony in any patient with ventricular pacing.

A leadless cardiac pacemaker (LCP) system was recently introduced to overcome lead-related complications of conventional pacing systems. To date, long-term results of an LCP system are unknown.The aim of this study was to assess the complication incidence, electrical performance, and rate response characteristics within the first year of follow-up of patients implanted with an LCP.We retrospectively assessed intermediate-term follow-up data for 31 of 33 patients from the LEADLESS trial cohort who had an indication for single-chamber pacing and received an LCP between December 2012 and April 2013.The mean age of the cohort was 76 ± 8 years, and 65% were male. Between 3 and 12 months of follow-up, there were no pacemaker-related adverse events reported. The pacing performance results at 6- and 12-month follow-up were, respectively, as follows: mean pacing threshold (at a 0.4-ms pulse width), 0.40 ± 0.26 V and 0.43 ± 0.30 V; R-wave amplitude 10.6 ± 2.6 mV and 10.3 ± 2.2 mV; and impedance 625 ± 205 Ω and 627 ± 209 Ω. At the 12-month follow-up in 61% of the patients (n = 19 of 31), the rate response sensor was activated, and an adequate rate response was observed in all patients.The LCP demonstrates very stable performance and reassuring safety results during intermediate-term follow-up. These results support the use of the LCP as a promising alternative to conventional pacemaker systems. Continued evaluation is warranted to further characterize this system. (Evaluation of a New Cardiac Pacemaker; NCT01700244).

Prolongation of QRS (or =120 ms) occurs in 14% to 47% of heart failure (HF) patients. Left bundle branch block is far more common than right bundle branch block. Left-sided intraventricular conduction delay is associated with more advanced myocardial disease, worse left ventricular (LV) function, poorer prognosis, and a higher all-cause mortality rate compared with narrow QRS complex. It also predisposes heart failure patients to an increased risk of ventricular tachyarrhythmias, but the incidence of cardiac or sudden death remains unclear because of limited observations. A progressive increase in QRS duration worsens the prognosis. No electrocardiographic measure is specific enough to provide subgroup risk categorization for excluding or selecting HF patients for prophylactic implantable cardioverter-defibrillator (ICD) therapy. In ICD patients with HF, a wide underlying QRS complex more than doubles the cardiac mortality compared with a narrow QRS complex. There is a high incidence of an elevated defibrillation threshold at the time of ICD implantation in patients with QRSor =200 ms. Mechanical LV dyssynchrony potentially treatable by ventricular resynchronization occurs in about 70% of HF patients with left-sided intraventricular conduction delay, a fact that would explain the lack of therapeutic response in about 30% of patients subjected to ventricular resynchronization according to standard criteria relying on QRS duration. The duration of the basal QRS complex does not reliably predict the clinical response to ventricular resynchronization, and QRS narrowing after cardiac resynchronization therapy does not correlate with hemodynamic and clinical improvement. Mechanical LV dyssynchrony is best shown by evolving echocardiographic techniques (predominantly tissue Doppler imaging) currently in the process of standardization.

Resynchronization therapy involving right ventricular endocardial and left ventricular epicardial pacing improves cardiac output, quality of life, and New York Heart Association functional class in patients with congestive heart failure. Although a great deal of attention has been directed at showing the mechanical benefits and in fine-tuning the biventricular pacing configuration and protocol, little attention has been focused on the consequences of reversing the direction of activation of the left ventricular wall. Recent basic science and clinical studies have shown a proarrhythmic effect of reversing the direction of activation of the left ventricular wall. Reversal of the normal activation sequence prolongs the QT interval and increases the existing transmural dispersion of repolarization, creating the substrate and trigger for re-entrant arrhythmias under long QT conditions. A number of case reports of R-on-T extrasystoles and ventricular tachyarrhythmia induction as a result of biventricular pacing support this observation, and raise concern that biventricular pacing may be proarrhythmic in select cases, particularly when associated with a prolonged QT interval. Our focus in this review is on current understanding of transmural heterogeneity of repolarization that exists across the left ventricular wall, how this dispersion of repolarization is amplified as a consequence of reversal of the normal activation sequence, and how these basic experimental findings may apply to patients receiving cardiac resynchronization therapy.

ObjectivesThe InSync III study evaluated sequential cardiac resynchronization therapy (CRT) in patients with moderate-to-severe heart failure and prolonged QRS.BackgroundSimultaneous CRT improves hemodynamic and clinical performance in patients with moderate-to-severe heart failure (HF) and a wide QRS. Recent evidence suggests that sequentially stimulating the ventricles might provide additional benefit.MethodsThis multicenter, prospective, nonrandomized, six-month trial enrolled a total of 422 patients to determine the effectiveness of sequential CRT in patients with New York Heart Association (NYHA) functional class III or IV HF and a prolonged QRS. The study evaluated: whether patients receiving sequential CRT for six months experienced improvement in 6-min hall walk (6MHW) distance, NYHA functional class, and quality of life (QoL) over control group patients from the reported Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial; whether sequential CRT increased stroke volume compared to simultaneous CRT; and whether an increase in stroke volume translated into greater clinical improvements compared to patients receiving simultaneous CRT.ResultsInSync III patients experienced greater improvement in 6MHW, NYHA functional class, and QoL at six months compared to control (all p < 0.0001). Optimization of the sequential pacing increased (median 7.3%) stroke volume in 77% of patients. No additional improvement in NYHA functional class or QoL was seen compared to the simultaneous CRT group; however, InSync III patients demonstrated greater exercise capacity.ConclusionsSequential CRT provided most patients with a modest increase in stroke volume above that achieved during simultaneous CRT. Patients receiving sequential CRT had improved exercise capacity, but no change in functional status or QoL.

Objectives We sought to evaluate the effects of biventricular (BDOO) pacing compared with conventional (CDOO) atrioventricular (AV) sequential and atrial (AOO) pacing in children and infants in the early postoperative period after open heart surgery for congenital heart disease (CHD). Background Biventricular pacing using right ventricular (RV) and left ventricular (LV) leads can improve hemodynamics in patients with CHD, but it is unclear whether this occurs in early postoperative children with CHD. Methods Nineteen children (age, 5 days to 5.4 years; median, 5.5 months) with a definitive biventricular repair for CHD underwent AOO, CDOO, and BDOO pacing with temporary epicardial leads for 10 min each. The AV delay was 80% of the PR interval for the CDOO and BDOO modes. Lead placement was two right atrial, two RV, and one LV. Blood samples for cardiac index (arterial and venous) and tissue Doppler (TDI) traces were obtained in each pacing mode with a Vivid 7 BT04 digital ultrasound system (GE/VingMed, Horten, Norway) from an apical four-chamber view and analyzed with EchoPac software. Results The QRS duration was significantly shorter for BDOO compared with CDOO, and the cardiac index was higher with BDOO compared with CDOO. Systemic blood pressure was not different between the three modes of pacing (AOO, CDOO, BDOO). The TDI-derived strain rate showed minimal dyssynchrony in AOO as seen by isovolumic tensing (IVT) and peak systolic contraction (PSC) timing differences between RV and LV. The CDOO worsened dyssynchrony with prolonged ΔIVT and PSC. The BDOO showed improved synchrony as seen by ΔIVT and PSC. Conclusions The TDI-derived strain rate showed worsened ventricular dyssynchrony with CDOO and improvement with BDOO. Cardiac index and QRS duration were improved by BDOO compared with CDOO. This suggests that short-term pacing with BDOO may benefit children with CHD needing pacing in the postoperative period.