Irene E. van Geldorp

Left ventricular endocardial pacing improves resynchronization therapy in canine left bundle-branch hearts.

Background—We investigated the benefits of the more physiological activation achieved by left ventricular (LV) endocardial pacing (ENDO) as compared with conventional epicardial (EPI) LV pacing in cardiac resynchronization therapy. Methods and Results—In 8 anesthetized dogs with experimental left bundle-branch block, pacing leads were positioned in the right atrium, right ventricle, and at 8 paired (EPI and ENDO) LV sites. Systolic LV pump function was assessed as LVdP/dtmax and stroke work and diastolic function as LVdP/dtmin. Electrical activation and dispersion of repolarization were determined from 122 epicardial and endocardial electrodes and from analysis of the surface ECG. Overall, ENDO-biventricular (BiV) pacing more than doubled the degree of electrical resynchronization and increased the benefit on LVdP/dtmax and stroke work by 90% and 50%, respectively, as compared with EPI-BiV pacing. During single-site LV pacing, the range of AV intervals with a >10% increase in LV resynchronization (79±31 versus 32±24 ms, P<0.05) and LVdP/dtmax (92±29 versus 63±39 ms) was significantly longer for ENDO than for EPI pacing. EPI-BiV but not ENDO-BiV pacing created a significant (40±21 ms) transmural dispersion of repolarization. Conclusions—Data from this acute animal study indicate that the use of an endocardial LV pacing electrode may increase the efficacy of resynchronization therapy as compared with conventional epicardial resynchronization therapy.

LV Endocardial Pacing Improves Resynchronization Therapy in Canine LBBB Hearts

Background—We investigated the benefits of the more physiological activation achieved by left ventricular (LV) endocardial pacing (ENDO) as compared with conventional epicardial (EPI) LV pacing in cardiac resynchronization therapy. Methods and Results—In 8 anesthetized dogs with experimental left bundle-branch block, pacing leads were positioned in the right atrium, right ventricle, and at 8 paired (EPI and ENDO) LV sites. Systolic LV pump function was assessed as LVdP/dtmax and stroke work and diastolic function as LVdP/dtmin. Electrical activation and dispersion of repolarization were determined from 122 epicardial and endocardial electrodes and from analysis of the surface ECG. Overall, ENDO-biventricular (BiV) pacing more than doubled the degree of electrical resynchronization and increased the benefit on LVdP/dtmax and stroke work by 90% and 50%, respectively, as compared with EPI-BiV pacing. During single-site LV pacing, the range of AV intervals with a >10% increase in LV resynchronization (79±31 versus 32±24 ms, P<0.05) and LVdP/dtmax (92±29 versus 63±39 ms) was significantly longer for ENDO than for EPI pacing. EPI-BiV but not ENDO-BiV pacing created a significant (40±21 ms) transmural dispersion of repolarization. Conclusions—Data from this acute animal study indicate that the use of an endocardial LV pacing electrode may increase the efficacy of resynchronization therapy as compared with conventional epicardial resynchronization therapy.

Beneficial effects of biventricular pacing in chronically right ventricular paced patients with mild cardiomyopathy

AIMS To investigate whether cardiac resynchronization therapy (CRT) by means of biventricular (BiV) pacing can improve left ventricular (LV) function, remodelling and clinical status in chronically right ventricular (RV) paced patients with mild cardiomyopathy. METHODS AND RESULTS Thirty-six chronically (10 +/- 7 years) RV paced patients with left ventricular ejection fraction (LVEF) < 40% or LVEDD > 55 mm, without an established indication for CRT, were subjected to 6 months RV and BiV pacing in a patient-blinded, randomized crossover design. Treatment-effects of BiV pacing were evaluated for LV function, LV remodelling and clinical status. As compared with RV pacing, BiV pacing significantly improved LV function (LVEF 46 +/- 12 vs. 39 +/- 12% and LVFS 24 +/- 7 vs. 21 +/- 7%) and reduced LV end-diastolic and end-systolic diameters and volumes (LVEDD 56 +/- 8 vs. 59 +/- 8 mm, LVESD 43 +/- 8 vs. 47 +/- 9 mm, LVEDV 132 +/- 65 vs.144 +/- 62 mL and LVESV 77 +/- 56 vs. 92 +/- 55 mL, respectively). In 19 patients (53%) response to BiV pacing was clinically relevant, defined as LVESV reduction >15%. BiV pacing also significantly improved NYHA classification. CONCLUSION BiV pacing following chronic RV pacing may improve LV function and reverse LV remodelling in patients with relatively mild LV dysfunction or remodelling. Hence, upgrade to BiV pacing might be considered in chronically RV paced patients with mild cardiomyopathy.

Permanent Cardiac Pacing in Children: Choosing the Optimal Pacing Site A Multicenter Study

Background— We evaluated the effects of the site of ventricular pacing on left ventricular (LV) synchrony and function in children requiring permanent pacing. Methods and Results— One hundred seventy-eight children (aged <18 years) from 21 centers with atrioventricular block and a structurally normal heart undergoing permanent pacing were studied cross-sectionally. Median age at evaluation was 11.2 (interquartile range, 6.3–15.0) years. Median pacing duration was 5.4 (interquartile range, 3.1–8.8) years. Pacing sites were the free wall of the right ventricular (RV) outflow tract (n=8), lateral RV (n=44), RV apex (n=61), RV septum (n=29), LV apex (n=12), LV midlateral wall (n=17), and LV base (n=7). LV synchrony, pump function, and contraction efficiency were significantly affected by pacing site and were superior in children paced at the LV apex/LV midlateral wall. LV dyssynchrony correlated inversely with LV ejection fraction (R=0.80, P=0.031). Pacing from the RV outflow tract/lateral RV predicted significantly decreased LV function (LV ejection fraction <45%; odds ratio, 10.72; confidence interval, 2.07–55.60; P=0.005), whereas LV apex/LV midlateral wall pacing was associated with preserved LV function (LV ejection fraction ≥55%; odds ratio, 8.26; confidence interval, 1.46–47.62; P=0.018). Presence of maternal autoantibodies, gender, age at implantation, duration of pacing, DDD mode, and QRS duration had no significant impact on LV ejection fraction. Conclusions— The site of ventricular pacing has a major impact on LV mechanical synchrony, efficiency, and pump function in children who require lifelong pacing. Of the sites studied, LV apex/LV midlateral wall pacing has the greatest potential to prevent pacing-induced reduction of cardiac pump function.

Impact of the permanent ventricular pacing site on left ventricular function in children: a retrospective multicentre survey.

Background Chronic right ventricular (RV) pacing is associated with deleterious effects on cardiac function. Objective In an observational multicentre study in children with isolated atrioventricular (AV) block receiving chronic ventricular pacing, the importance of the ventricular pacing site on left ventricular (LV) function was investigated. Methods Demographics, maternal autoantibody status and echocardiographic measurements on LV end-diastolic and end-systolic dimensions and volumes at age <18 years were retrospectively collected from patients undergoing chronic ventricular pacing (>1 year) for isolated AV block. LV fractional shortening (LVFS) and, if possible LV ejection fraction (LVEF) were calculated. Linear regression analyses were adjusted for patient characteristics. Results From 27 centres, 297 children were included, in whom pacing was applied at the RV epicardium (RVepi, n=147), RV endocardium (RVendo, n=113) or LV epicardium (LVepi, n=37). LVFS was significantly affected by pacing site (p=0.001), and not by maternal autoantibody status (p=0.266). LVFS in LVepi (39±5%) was significantly higher than in RVendo (33±7%, p<0.001) and RVepi (35±8%, p=0.001; no significant difference between RV-paced groups, p=0.275). Subnormal LVFS (LVFS<28%) was seen in 16/113 (14%) RVendo-paced and 21/147 (14%) RVepi-paced children, while LVFS was normal (LVFS≥28%) in all LVepi-paced children (p=0.049). These results are supported by the findings for LVEF (n=122): LVEF was <50% in 17/69 (25%) RVendo- and in 10/35 (29%) RVepi-paced patients, while LVEF was ≥50% in 17/18 (94%) LVepi-paced patients. Conclusion In children with isolated AV block, permanent ventricular pacing site is an important determinant of LV function, with LVFS being significantly higher with LV pacing than with RV pacing.

Comparison of a non-invasive arterial pulse contour technique and echo Doppler aorta velocity-time integral on stroke volume changes in optimization of cardiac resynchronization therapy

AIMS We investigated the accuracy and feasibility of a non-invasive arterial pulse contour technique for continuous measurement of stroke volume (SV) in optimization of atrioventricular (AV) delay in cardiac resynchronization therapy (CRT), by comparing SV changes assessed by Nexfin CO-Trek® (Nexfin) and echo Doppler aortic velocity-time integral (VTIao). Furthermore, we investigated whether AV-delay optimization increases the effect of CRT when compared with a default AV delay (120 ms). METHODS AND RESULTS In 23 CRT patients, biventricular pacing (BiVP) was applied at various AV delays, while recording 10 beats preceding BiVP (baseline) and the first 10 BiVP beats, for both methods in parallel. Agreement between Nexfin and VTIao measurements was evaluated (Bland-Altman) on beat-to-beat changes in SV, as well as on effects of BiVP (averaged over 8 beats) at various AV delays. Individual optimal AV delays, for Nexfin (AVopt-n) and VTIao (AVopt-ao), were derived from the second-order polynomial fitted to the effect measurements of 20 patients. In 252 episodes assessed, the difference between measurements (= Nexfin - VTIao) was -0.6 ± 8.1% for beat-to-beat SV changes and -1.3 ± 7.3% for effects of BiVP. Optimal AV delays for Nexfin were well related to AVopt-ao (R(2) = 0.69). The effect (%) of BiVP at the optimal AV delay was significantly larger than at the default AV delay: median difference (range) being +6.3% (0.1-14.4%; P < 0.001) for VTIao and +4.7% (0.0-14.0%; P < 0.001) for Nexfin. CONCLUSION Individual AV optimization increases the effect of CRT. Nexfin is a promising tool in individual CRT optimization, as Nexfin agrees with VTIao on measuring beat-to-beat SV changes and on assessing relative effects of BiVP on SV at various AV delays.

Comparison of different invasive hemodynamic methods for AV delay optimization in patients with cardiac resynchronization therapy: Implications for clinical trial design and clinical practice

Background Reproducibility and hemodynamic efficacy of optimization of AV delay (AVD) of cardiac resynchronization therapy (CRT) using invasive LV dp/dtmax are unknown. Method and results 25 patients underwent AV delay (AVD) optimisation twice, using continuous left ventricular (LV) dp/dtmax, systolic blood pressure (SBP) and pulse pressure (PP). We compared 4 protocols for comparing dp/dtmax between AV delays: Immediate absolute: mean of 10 s recording of dp/dtmax acquired immediately after programming the tested AVD, Delayed absolute: mean of 10 s recording acquired 30 s after programming AVD, Single relative: relative difference between reference AVD and the tested AVD, Multiple relative: averaged difference, from multiple alternations between reference and tested AVD. We assessed for dp/dtmax, LVSBP and LVPP, test–retest reproducibility of the optimum. Optimization using immediate absolute dp/dtmax had poor reproducibility (SDD of replicate optima = 41 ms; R2 = 0.45) as did delayed absolute (SDD 39 ms; R2 = 0.50). Multiple relative had better reproducibility: SDD 23 ms, R2 = 0.76, and (p < 0.01 by F test). Compared with AAI pacing, the hemodynamic increment from CRT, with the nominal AV delay was LVSBP 2% and LVdp/dtmax 5%, while CRT with pre-determined optimal AVD gave 6% and 9% respectively. Conclusions Because of inevitable background fluctuations, optimization by absolute dp/dtmax has poor same-day reproducibility, unsuitable for clinical or research purposes. Reproducibility is improved by comparing to a reference AVD and making multiple consecutive measurements. More than 6 measurements would be required for even more precise optimization — and might be advisable for future study designs. With optimal AVD, instead of nominal, the hemodynamic increment of CRT is approximately doubled.

Chronic ventricular pacing in children: toward prevention of pacing-induced heart disease

In children with congenital or acquired complete atrioventricular (AV) block, ventricular pacing is indicated to increase heart rate. Ventricular pacing is highly beneficial in these patients, but an important side effect is that it induces abnormal electrical activation patterns. Traditionally, ventricular pacemaker leads are positioned at the right ventricle (RV). The dyssynchronous pattern of ventricular activation due to RV pacing is associated with an acute and chronic impairment of left ventricular (LV) function, structural remodeling of the LV, and increased risk of heart failure. Since the degree of pacing-induced dyssynchrony varies between the different pacing sites, ‘optimal-site pacing’ should aim at the prevention of mechanical dyssynchrony. Especially in children, generally paced from a very early age and having a perspective of life-long pacing, the preservation of cardiac function during chronic ventricular pacing should take high priority. In the perspective of the (patho)physiology of ventricular pacing and the importance of the sequence of activation, this paper provides an overview of the current knowledge regarding possible alternative sites for chronic ventricular pacing. Furthermore, clinical implications and practical concerns of the various pacing sites are discussed. The review concludes with recommendations for optimal-site pacing in children.

Acute hemodynamic benefits of biventricular and single-site systemic ventricular pacing in patients with a systemic right ventricle

BACKGROUND Patients treated by atrial redirection surgery (Senning or Mustard procedure) for transposition of the great arteries (TGA) have an important risk for heart failure caused by dysfunction of the systemic right ventricle. Conventional nonsystemic ventricular pacing (non-systVP) may even further increase this risk. OBJECTIVE We investigated the effects of endocardial non-systVP, biventricular pacing (BiVP), and single-site systemic ventricular pacing (systVP) on systolic cardiac pump function in patients with TGA and status post atrial redirection surgery (SenningMustardTGA). METHODS During clinically indicated catheterization in 9 patients with SenningMustardTGA, endocardial ventricular stimulation (overdrive DDD mode; 80-90 beats/min) was applied with temporary pacing leads at the nonsystemic and the systemic ventricle. Acute changes in the maximal rate of pressure rise (dP/dtmax) and systolic pressure of the systemic ventricle, as induced by non-systVP, systVP, and BiVP compared to reference, were assessed with a pressure wire within the systemic ventricle. Reference was AAI pacing with a similar heart rate (n = 7) or non-systVP at a lower heart rate than that during stimulation at experimental sites (85 beats/min vs 90 beats/min; n = 2). RESULTS Systemic dP/dtmax and systolic ventricular pressure were significantly higher during systVP (+15.6% and +5.1%, respectively) and BiVP (+14.3% and +4.9%, respectively, compared with non-systVP). In 6 of 7 patients, systemic dP/dtmax was higher during BiVP and systVP than during AAI pacing. CONCLUSIONS In a population of patients with SenningMustardTGA, acute hemodynamic effects of endocardial systVP and BiVP were significantly and equally better than those of non-systVP. In some patients, systVP and BiVP might even be better than ventricular activation by the intrinsic conduction system.

Late recovery of atrioventricular conduction after postsurgical chronic atrioventricular block is not exceptional.

OBJECTIVE Postsurgical atrioventricular block may complicate surgery for congenital heart defects and is generally considered permanent when persisting longer than 14 days after surgery. In this study, we evaluate the occurrence of spontaneous late recovery of atrioventricular conduction in postsurgical chronic atrioventricular block and discuss its clinical implications. METHODS We retrospectively reviewed all cardiac surgical procedures on cardiopulmonary bypass between January 1993 and November 2010 in subjects younger than 18 years. Patients with postsurgical advanced second- or third-degree atrioventricular block persisting longer than 14 days after surgery were included. RESULTS Of a total of 2850 cardiac surgical procedures on cardiopulmonary bypass, 59 (2.1%) were immediately complicated by chronic postsurgical atrioventricular block of advanced second (n = 4) or third degree (n = 55). In another 6 patients (0.2%), late occurrence of chronic advanced second- (n = 3) or third-degree (n = 3) atrioventricular block, without signs of any etiology other than previous surgery, was seen 0.4 to 10 years after surgery (median, 5.7 years). Late (>2 weeks) regression to either completely normal atrioventricular conduction or asymptomatic first-degree atrioventricular block occurred 3 weeks to 7 years (median, 3.1 years) after surgery in 7 (12%) patients with immediate postsurgical chronic atrioventricular block. CONCLUSIONS Complete recovery of atrioventricular conduction or regression to asymptomatic first-degree atrioventricular block occurred in 12% of patients with postsurgical chronic second- or third-degree atrioventricular block. To prevent unnecessary adverse side effects of chronic ventricular pacing and to prolong battery longevity, ventricular pacing should be minimized in patients with recovered normal atrioventricular conduction.