cardiac resynchronization therapy for various …...ardiac resynchronization therapy (crt) has been...

Circulation Journal Vol.79, March 2015

Circulation JournalOfficial Journal of the Japanese Circulation Societyhttp://www.j-circ.or.jp

hancement (LGE) cardiovascular magnetic resonance imaging (cMRI), might occur in patients with a systemic RV.12 More-over, the extent of the LGE correlates with the age, ventricular dysfunction, and electrophysiological parameters. These fea-tures are analogous to those of ischemic heart disease. Hence, the effectiveness of CRT for patients with CHD, especially a systemic RV, is not conclusive.

MethodsStudy DesignThe Ethics Committee of the National Cerebral and Cardio-vascular Center approved our retrospective study. Our strategy for CRT implantations was based on an acute hemodynamic study, which we performed prior to the device implantation in order to evaluate the acute effect of the CRT and to determine the optimal pacing sites; that is, the acute hemodynamic study

ardiac resynchronization therapy (CRT) has been shown to benefit patients with congestive heart failure.1–5 However, limited data are available on CRT in pa-

tients with congenital heart disease (CHD).6–10 Some studies on the use of CRT for CHD have shown that the efficacy of CRT pacing for patients with a systemic right ventricle (RV) or univentricular heart is not conclusive.

Editorial p 519

In an adult congestive heart failure series, ischemic heart disease has been found to be a significant predictor of the lack of a response to CRT.11 Furthermore, a higher overall scar burden, large number of severely scarred segments, and great-er scar density near the left ventricle (LV) leads to an unfavor-able response to CRT in ischemic cardiomyopathy patients. Myocardial fibrosis, as determined via late gadolinium en-

C

Received April 4, 2014; revised manuscript received December 2, 2014; accepted December 3, 2014; released online January 9, 2015 Time for primary review: 27 days

Department of Pediatric Cardiology (H.S., A.M., O.Y., H.O.), Department of Pediatric Cardiovascular Surgery (K.K., T.H., H.I.), National Cerebral and Cardiovascular Center, Suita, Japan

Mailing address: Heima Sakaguchi, MD, PhD, Department of Pediatrics, National Cerebral and Cardiovascular Center, 5-7-1 Fujishiro-dai, Suita 565-8565, Japan. E-mail: [email protected]

ISSN-1346-9843 doi: 10.1253/circj.CJ-14-0395All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: [email protected]

Cardiac Resynchronization Therapy for Various Systemic Ventricular Morphologies in Patients With

Congenital Heart DiseaseHeima Sakaguchi, MD, PhD; Aya Miyazaki, MD; Osamu Yamada, MD; Koji Kagisaki, MD;

Takaya Hoashi, MD, PhD; Hajime Ichikawa, MD, PhD; Hideo Ohuchi, MD, PhD

Background: Cardiac resynchronization therapy (CRT) can result in functional improvement and reduced mortal-ity in patients with medically refractory heart failure. Although CRT is reportedly effective in patients with congenital heart disease (CHD), it is still controversial in patients who have systemic right ventricle.

Methods and Results: Twenty CHD patients treated with CRT since 2006 were divided into 3 groups based on systemic ventricular (sysV) morphology (7 with left ventricle [sLV], 7 with right ventricle [sRV], and 6 with unbalanced 2 ventricles as a single-ventricular physiology [sBV]). The acute effects of CRT on hemodynamics and sysV function before device implantation was retrospectively evaluated and the chronic (≥6 months) effects of CRT on late out-comes was assessed. In our CHD populations, sysV volume index was reduced from 139±41 to 118±33 ml/m2 (P=0.04) after CRT, and there was significant improvement in B-type natriuretic peptide levels (from 341±384 to 160±152 pg/ml, P=0.01) and New York Heart Association (NYHA) functional class (from 2.1±0.6 to 1.8±0.7, P=0.02) on a late outcome. The sRV group did not show a late sysV volume reduction despite significant QRS shortening, and an increase of sysV peak dP/dt in the acute study differed from that of other groups.

Conclusions: CRT improves late hemodynamic and functional status in sLV and sBV CHD patients with a dys-synchronized sysV. However, an acute CRT effect cannot guarantee long-term benefit in sRV patients. (Circ J 2015; 79: 649 – 655)

Key Words: Cardiac resynchronization therapy; Congenital heart disease; Dyssynchrony; Reverse remodeling; Systemic right ventricle

ORIGINAL ARTICLEPediatric Cardiology and Adult Congenital Heart Disease


650 SAKAGUCHI H et al.

who could not undergo conventional bi-ventricular surgical correction, which included various complex morphologies (Table). The sLV patients had a morphological LV as a sysV, and in contrast, the sRV patients did not have a morphological LV or a pulmonary ventricle. The sBV patients had 2 unbal-anced ventricles that were unsuitable for conventional bi-ventricular surgical repair on the grounds of various inadequa-cies such as unilateral ventricular hypoplasia and structural disturbances of the atrio-ventricular valve. We evaluated the acute effect of CRT on the hemodynamics and sysV function before the device implantation, and then assessed the chronic (≥6 months) impact of CRT, including the plasma B-type na-triuretic peptide (BNP) level and New York Heart Association (NYHA) functional class.

Acute Hemodynamic StudyWe performed an electrophysiology study before the introduc-tion of CRT pacing to evaluate the efficacy of the CRT. We evaluated the hemodynamics and sysV function, such as the QRS duration, peak +dP/dt, ejection fraction (EF), end-dia-stolic pressure (EDP), and central venous pressure (CVP)

was followed by a device implantation, and 6 months after the implantation, the chronic effects of the CRT were evaluated. In this study, dyssynchrony was defined as the presence of electrical dyssynchrony that was confirmed by electrocardio-grams with a QRS duration of greater than 130 ms. A retro-spective review was performed of all available clinical data, electrocardiograms, cardiac catheterizations, and clinical out-comes in those patients who underwent a CRT at the National Cerebral and Cardiovascular Center between January 2006 and December 2012.

PatientsThe study population consisted of 20 CHD patients (mean age, 22±13 years) who had been treated with CRT at our institu-tion. We divided the patients into 3 groups based on the type of systemic ventricle (sysV), including 7 patients with a sys-temic LV (sLV), which included a double-inlet LV after a ventricular septation and tetralogy of Fallot; 7 with a systemic RV (sRV), which included a congenitally or surgically cor-rected transposition of the great arteries; and 6 with 2 extreme-ly unbalanced ventricles as an univentricular physiology (sBV)

Table. Patient Characteristics

Age Previous PM NYHA Baseline QRS duration sysV-EF Type of

deviceDirection of the dual site pacing

sLV

DILV s/p VS 26 + 2 240 29 CRT-P Horizon

DILV s/p VS 28 − 2 180 25 CRT-P Horizon

DILV s/p VS 20 + 2 190 36 CRT-P Horizon

TOF s/p 12 + 1 192 34 DDD Horizon

TOF s/p 10 − 2 180 48 CRT-P Horizon

cPS s/p 25 − 3 157 31 CRT-P Horizon

AVSD s/p chronic AF 46 − 2 146 47 CRT-D Horizon

Mean 23.9 183.6 35.7

sBV

cTGA s/p PAB 4 + 1 133 57 CRT-P Horizon

Riso CAVC s/p BDG 38 − 2 200 26 CRT-P Long

Liso hypo LV s/p BDG 7 − 2 172 13 CRT-P Long

Liso CAVC s/p Fontan (ECG) 10 + 2 156 35 CRT-P Horizon

Liso DORV PA MAPCA s/p UF and palliative RVOTR

4 + 3 180 22 CRT-P Long

DORV s/p Fontan (APC) 17 + 2 174 21 CRT-P Horizon

Mean 13.3 169.2 29.0

sRV

cTGA s/p FR 9 + 1 200 50 DDD Long

cTGA s/p TVR 36 − 3 190 30 CRT-D Horizon

cTGA s/p FR 31 − 3 160 31 DDD Horizon

cTGA s/p TVR 47 + 2 176 43 CRT-P Long

TGA s/p Mustard 28 + 2 236 24 CRT-P Horizon

Riso hypo LVs/p Fontan 11 + 3 177 36 CRT-P Long

DIRV PA s/p BTS 38 + 2 225 46 CRT-P Long

Mean 28.6 194.9 37.1

Total (n=20) 22±13 183±27 34±11

AF, atrial fibrillation; APC, atriopulmonary connection; AVSD, atrioventricular septal defect; BDG, bidirectional Glenn; BTS, Blalock-Taussig shunt; CAVC, common atrioventricular canal; cPS, critical pulmonary stenosis; CRT-D, cardiac resynchronization therapy (CRT) defibrillator; CRT-P, CRT pacemaker; cTGA, corrected transposition of the great arteries; DDD, conventional dual chamber pacemaker; DILV, double inlet left ventricle; DIRV, double inlet right ventricle; DORV, double outlet right ventricle; ECG, extra-cardiac conduit; FR, functional repair; Liso, left atrial isomerism; LV, left ventricle; MAPCA, major aortopulmonary collateral arteries; NYHA, New York Heart Association; PA, pulmonary atresia; PAB, pulmonary arterial banding; PM, pacemaker; Riso, right atrial isomerism; RVOTR, right ventricular outflow tract reconstruction; sBV, unbalanced 2 ventricles as a single ventricular physiology; sLV, left ventricle systemic ventricle; s/p, status of post; sRV, right ventricle systemic ventricle; sysV-EF, systemic ventricle-ejection fraction; TCPC, total cavopulmonary connection; TGA, transposition of the great arter-ies; TOF, tetralogy of Fallot; TVR, tricuspid valve replacement; UF, unifocalization; VS, ventricular septation.


651CRT for the Various Systemic Ventricular Morphologies

hemodynamic study, and 6 months after the CRT. The QRS was measured in leads II, V1, and V5 for consistency, at a paper speed of 100 mm/s by a digital caliper using an EP-WorkMate an EP-WorkMate® (EP MedSystems Inc, West Berlin, NJ, USA) (EP MedSystems Inc, West Berlin, NJ, USA). All ECGs also underwent a secondary blinded review by a single investigator.

Statistical AnalysisContinuous data are expressed as the mean ± standard devia-tion. Comparisons between groups were made using a 2-tailed, unpaired Student’s t-test or Fisher’s exact test, as appropriate. A value of P<0.05 was considered statistically significant. The mean of the 3 groups were compared by a one-way ANOVA. For the post-hoc analysis, the Tukey HSD test was used to determine pairwise differences between groups, and the Dunnett’s test was used to determine significant differences between a given data set and the control values of the data set.

ResultsPatient CharacteristicsThere were no significant differences between the groups in the baseline characteristics, which consisted of age, NYHA functional class, QRS duration before the CRT, and sysV-EF measured on cine-angiograms in the acute hemodynamic study. All patients also had electrical dyssynchrony (QRS duration ≥130 ms); of those, 11 had already undergone a pace-maker implantation and 2 patients in the sLV group were in-dicated for a pacemaker implantation because of advanced atrio-ventricular block. The other 6 patients were indicated for a device implantation for dyssynchronized ventricular move-ment rather than for bradycardia.

There were 3 patients in the sLV group with a double inlet LV after a ventricular septation who had already been im-planted with, or indicated for, a permanent pacemaker. In those cases, the inter-ventricular septum could not actively contract but contracted passively. In the sBV group, 4 out of 6 cases had heterotaxy syndrome and were not indicated for a bi-ventricular surgical correction. In the sRV group, 5 out of 7 cases had a congenitally or surgically corrected transposition of great arteries with a systemic RV.

All our patients were taking medications for heart failure at the time of the CRT initiation. The most common medications were diuretics and were used in 19 (95%) patients, followed by angiotensin-converting enzyme inhibitors/angiotensin re-ceptor blockers (18 patients; 90%), β-blockers (14 patients; 70%) and digoxin (10 patients; 50%).

Electrical DyssynchronyTwelve patients (60%) had electrical dyssynchrony during ventricular pacing, owing to having a permanent ventricular pacing system prior to the CRT initiation. We placed an ad-ditional ventricular lead to upgrade to CRT pacing in these patients. In 2 cases, we upgraded to CRT pacing using a con-ventional DDD pacemaker and used the occasion to re-im-plant the ventricular leads due to a lead failure. The other 8 patients had electrical dyssynchrony during intrinsic conduc-tion. Of those, 3 patients who were included in the sLV group had right bundle branch block with a pulmonary ventricle. The other 5 patients had right bundle branch block with a systemic RV (sRV group) or an inadequate atrio-ventricular conduction disturbance with heterotaxy syndrome with an unbalanced systemic bi-ventricle (sBV). The majority of our patients (60%) had ventricular dyssynchrony associated with single-site ven-

during dual-site pacing and intrinsic beats. At first, we rough-ly mapped the sysV to determine the electrical delay using a multi-polar catheter. Basically, among the sLV and sBV pa-tients, we placed the pacing catheter at an opposite site to synchronize the sysV in the horizontal direction. In the sRV patients, we assumed the ideal pacing sites in the longitudinal direction. We paced the systemic RV between the RV inferior wall and outflow practically, if at all possible. The optimal pacing sites were determined in a comprehensive manner to consider the electrical conduction delay, ideal pacing direc-tion, and shortening of the QRS duration. Basically, dual-site ventricular pacing was performed completely simultaneously. Furthermore, the atrio-ventricular pacing delay was adjusted before the acute study by echocardiography, as advocated by Ishikawa et al,13 in patients who were previously implanted with a permanent pacemaker, and determined at just the same timing as the intrinsic atrio-ventricular conduction.

We used Simpson’s rule to estimate the right and left ven-tricular volumes and divided the end-diastolic ventricular vol-ume by the body surface area to obtain the end-diastolic vol-ume index (EDVI). We also calculated the sysV-EF. The sysV peak +dP/dt was measured using a Pressure Wire® Certus (St. Jude Medical, St. Paul, MN, USA). Optimal pacing sites were chosen from among several pacing sites based on the improve-ment in the sysV peak +dP/dt and shortening of the QRS dura-tion. In the acute hemodynamic study, the heart rates under both conditions were carefully adjusted. Moreover, young children underwent the acute study under general anesthesia to help minimize the impact of anxiety or body movement, which could cause unstable hemodynamics.

Device ImplantationConventional resynchronization therapy involves implantation of a transvenous pacing lead into the RV and a left ventricular lead placed transvenously into a coronary sinus branch. How-ever, in our CHD series, this route was rarely feasible. There-fore, we had to implant the CRT system epicardially via a thoracotomy, depending on the ideal pacing sites that were chosen during the acute hemodynamic study.

In patients for whom a transvenous lead implantation was not recommended (eg, small body size, single-ventricle phys-iology, corrected transposition of great arteries, or uncorrected cardiac defects), an epicardial lead placement was performed via a median sternotomy or lateral thoracotomy. In patients undergoing a transvenous lead placement, a left ventricular lead insertion was attempted using conventional techniques. In one case, 1 atrial and 2 ventricular leads were placed for a combined transvenous and epicardial approach.

Evaluation of the Chronic Effects of CRTApproximately 6 months after the implantation of the CRT device, we recorded the BNP level and NYHA functional class in all patients. We also evaluated the sysV function, including the sysV-EDVI, sysV-EF, and QRS duration to determine the effect on the late outcomes. The sysV-EDVI and -EF were calculated by cine-angiograms based on a multiple-slice meth-od. Biplane radiographic equipment, including cine-fluoro-graphic units with filming speeds of 30 frames · s–1, were used. To ensure valid measurements, ectopic or post-ectopic beats were avoided.

Electrocardiogram (ECG) AnalysisECGs were reviewed to compare the QRS duration to age-based normal values. An analysis was performed on the ECG data obtained before the CRT implantation, during an acute



Figure 1. Two unbalanced ventricles were synchronized in order to place both ventricles in the horizontal direction (A) in the sBV group. In 3 of the sBV patients who had a large RV as the main chamber, dual site pacing was performed between the RV apex and RV outflow beneath the aorta and in the (B) longitudinal direction. In the sRV group, dual site pacing was performed between the RV apex and RV outflow (C). sBV, unbalanced 2 ventricles as a single ventricular physiology; RV, right ventricle.

Figure 2. Acute impact of the cardiac resynchronization therapy (CRT). In the acute hemodynamic study, the QRS dura-tion (A), peak +dP/dt (B) and central ve-nous pressure (CVP) (C) significantly improved with the dual site pacing. End-diastolic pressure (EDP) (D).



had a QRS duration that did not shorten and the sysV peak +dP/dt improved with dual site ventricular pacing. We then implanted the CRT device system based on the findings of this acute hemodynamic study. Subsequently, dual site pacing had a beneficial effect on the heart rates and shortened the QRS duration in this patient with atrial fibrillation.

Chronic Impact of CRTFifteen patients treated with CRT pacing underwent cardiac catheterization to evaluate the chronic impact on the sysV volume reduction. Before the catheterization, we adjusted the atrio-ventricular pacing delay using echocardiography, as ad-vocated by Ishikawa et al.13 The CRT treatment settings, such as the pacing interval between 2 ventricular pacing sites, were concurrently optimized. Figure 3 shows the chronic impact of CRT on the sysV volume, BNP level, and NYHA functional class. The ventricular volume index decreased significantly from 139±41 to 118±33 ml/m2 (P=0.04) after CRT pacing, and there was a significant improvement in the BNP level (from 341±384 to 160±152 pg/ml, P=0.01) and NYHA functional class (from 2.1±0.6 to 1.8±0.7, P=0.02) at approximately 6 months after the device implantation. Moreover, the ventricu-lar volume decreased as a chronic effect of the CRT pacing in patients with CHD.

Impact of the sysV Morphology on the Chronic Effects of CRTWe also evaluated the influence of the ventricular morpholo-gies on the chronic effect. The QRS duration was significantly shortened, both in the acute hemodynamic study and 6 months after the CRT, compared to the baseline values in all 3 groups (Figure 4A). However, although the EDVI and sysV-EF sig-nificantly improved in the sLV and sBV groups, no improve-ment was observed in the patients with an sRV despite a sig-nificant QRS shortening (from 195±27 to 145±25 ms, P<0.01; Figures 4B,C). To compare the chronic impact of CRT among the 3 different sysV morphologies, we performed mul-tiple comparisons on the values of the QRS duration ratio (post QRS/pre QRS), EDVI ratio (post EDVI/pre EDVI), and

tricular pacing. All the patients underwent an evaluation of their mechanical dyssynchrony with conventional echocardiography. We confirmed the wall motion delay between the different distinct sites of the systemic ventricular wall and any systemic ventricular shuffle or swinging motion by eyeballing it.

Acute Hemodynamic StudyIn the sLV group, dual site pacing was performed between the RV apex and LV free wall according to the conventional method in adults with heat failure. Basically, we synchronized the 2 unbalanced ventricles to pace both ventricles in the horizontal direction (Figure 1A) in the sBV group. In 3 of the sBV patients who had a large RV as the main chamber, dual site pacing was performed between the RV apex and RV out-flow beneath the aorta (Figure 1B) based on our philosophy to synchronize the ‘RV’ in the longitudinal direction. In the sRV group, in 3 patients who were enrolled in the early peri-od, dual site pacing was performed between the LV apex and RV free wall, and in another 4 patients, between the RV apex and RV outflow (Figure 1C).

Figure 2 shows the acute impact of CRT on the QRS dura-tion and hemodynamics in all patients. Four patients did not undergo an acute hemodynamic study before the CRT device implantation because they had stable hemodynamics. In those 4 patients, we implanted an additional ventricular lead for bi-ventricular pacing concomitantly with the generator or lead exchange or re-do operation, such as a RV outflow tract recon-struction. During the acute hemodynamic study, dual site pac-ing resulted in a significantly shortened QRS duration (from 183±27 to 132±18 ms, P<0.01), significantly increased sysV peak +dP/dt (from 697±190 to 814±242 mmHg/s, P<0.01), and significantly decreased CVP (from 10.2±4.9 to 9.5±4.8 mmHg, P=0.01; Figures 2A–C). No significant improvement was noted in the sysV-EDP during dual site pacing (Figure 2D). However, a significant shortening of the QRS duration was achieved with dual site ventricular pacing (P<0.01), with im-provement in the systolic properties of the sysV as an acute effect (P<0.01). Only 1 patient with chronic atrial fibrillation

Figure 3. Chronic (≥6-month) impact of CRT. The systemic ventricular end-diastolic volume index (EDVI), plasma B-type natri-uretic peptide (BNP) levels, and New York Heart Association (NYHA) functional status significantly improved 6 months after the CRT pacing therapy (Post). Two NYHA class 2 patients died after a concomitant surgery.



point was not a ventricular volume reduction but an improve-ment in the functional status. In our series, the functional sta-tus improved even in the sRV group. We believe that there may be differences in the response to CRT treatment among CHD patients in various hemodynamic settings, particularly those with systemic ventricular morphologies. Our data showed that the sLV patients responded better to the CRT than the sRV patients within the meaning of a ventricular volume reduction.

These different responses of the sLV and sRV to CRT are due to the multifactorial mechanisms of sRV failure. First, the sRV patients have myocardial damage caused by repeated surgeries. Second, the morphological aspects, including the geometry of the RV, make it more suited to handle a volume overload and less suited to handle the constant pressure over-load of the systemic circulation.15 Furthermore, physiological processes are very important; a RV pressure overload causes ventricular hypertrophy, which reduces the myocardial capil-lary density and flow reserve. This creates demand ischemia, which further deteriorates the function of the systemic RV. Such mechanisms of sRV failure eventually lead to myocar-dial fibrosis, to which late sRV dysfunction is related, and the extent of fibrosis correlates with the electrophysiological pa-rameters.16 These features of sRV failure are similar to those of ischemic cardiomyopathy or end-stage cardiomyopathy. In fact, the MIRACLE study showed that the benefits of CRT with respect to the EF and reverse remodeling were greater in patients with non-ischemic heart failure than ischemic heart failure.17,18 Moreover, as Vidal et al described, CRT non-re-sponder patients have a more advanced stage of cardiomy-opathy.

Although therapeutic options for patients with LV failure are well-established, their role in the treatment of patients with sRV failure is unclear. Results of studies on the effects of angiotensin-converting enzyme inhibitors, angiotensin recep-tor blockers and β-blockers have been mixed; some have dem-onstrated a significant improvement and others have not.19–27 Our data on the poor response to CRT pacing for sRV patients are analogous to the effect of medical treatments for conges-tive heart failure in sRV patients. We do not yet know the pacing sites that are optimal for a systemic RV. Resynchroni-

EF ratio (post EF/pre EF). Although, there was a significant difference between the sLV and sRV on the values of the EDVI ratio by the post-hoc analysis, there was no significant difference between the sBV and sRV. There was no significant difference in either the QRS duration ratio or EF ratio among the 3 groups.

MortalityTwo of the 19 (10%) patients died during the follow up after the CRT device implantation. The cause of death was periop-erative mortality in 1 case (conversion to total cavopulmonary connection; TCPC). In this case, the CRT device system was implanted at the time of the TCPC conversion. The indication for this surgery was mainly a low cardiac output due to ven-tricular dyssynchrony between the LV and RV as a systemic bi-ventricle. In the other case, death was due to interstitial pneumonitis associated with the use of amiodarone for fre-quent episodes of supraventricular tachycardia and syncope.

DiscussionWe have described the acute and chronic impact of CRT in patients with CHD. We implanted a CRT pacing system based on shortening of the QRS duration with improved sysV per-formance during the acute hemodynamic study. A ventricular volume reduction was achieved with CRT pacing in the sLV group. CRT pacing using conventional methods did not result in a favorable response in patients with a sRV despite signifi-cant shortening of the QRS duration. In cases with a sBV, the 2 unbalanced ventricles have a systemic ventricular function. Therefore, anatomic interventricular dyssynchrony also results in functional intra-ventricular dyssynchrony, and biventricular pacing could greatly improve the dyssynchrony and hemody-namics in such cases. The sLV group responded well to CRT, similar to the patients with chronic heart failure with a struc-turally normal heart. However, CRT pacing did not result in a favorable response in patients with a sRV despite significant shortening of the QRS duration.

Several studies have reported on the efficacy of CRT for CHD patients.6–10,14 However, in these studies, the primary end-

Figure 4. Impact of the cardiac resynchronization therapy (CRT) on the QRS duration and systemic ventricle (sysV) function among the 3 sysV morphologies. The rectangle indicates the left ventricle sysV (sLV), the circle indicates the unbalanced sysV single ventricle physiology (sBV), and the triangle indicates the right ventricle sysV (sRV) group. (A) QRS duration before the CRT with dual site pacing and ≥6 months after the CRT treatment; (B,C) The sysV end-diastolic volume index (EDVI) and ejection frac-tion (EF) before and after the CRT treatment in the 3 groups.



ME, Triedman JK, et al. Cardiac resynchronization therapy (and multisite pacing) in pediatrics and congenital heart disease: Five years experience in a single institution. J Cardiovasc Electrophysiol 2009; 20: 58 – 65.

9. Suzuki T, Sumitomo N, Yoshimoto J, Miyazaki A, Hinokiyama K, Ushinohama H, et al. Current trends in use of implantable cardio-verter defibrillator and cardiac resynchronization therapy with a pacemaker or defibrillator in Japanese pediatric patients: Results from a nationwide questionnaire survey. Circ J 2014; 78: 1710 – 1716.

10. Sakaguchi H, Miyazaki A, Ohuchi H, Kagisaki K. Interventricular dyssynchrony due to unilateral atrioventricular conduction block in a patient with right atrial isomerism and twin atrioventricular nodes. Heart Rhythm 2011; 8: 1072 – 1075.

11. Reuter S, Garrigue S, Bordachar P, Hocini M, Jaïs P, Haïssaguerre M, et al. Intermediate-term results of biventricular pacing in heart failure: Correlation between clinical and hemodynamic data. Pacing Clin Electrophysiol 2000; 23: 1713 – 1717.

12. Babu-Narayan SV, Goktekin O, Moon JC, Broberg CS, Pantely GA, Pennell DJ, et al. Late gadolinium enhancement cardiovascular mag-netic resonance of the systemic right ventricle in adults with previous atrial redirection surgery for transposition of the great arteries. Cir-culation 2005; 111: 2091 – 2098.

13. Ishikawa T, Sumita S, Kimura K, Kikuchi M, Kosuge M, Kuji N, et al. Prediction of optimal atrioventricular delay in patients with im-planted DDD pacemakers. Pacing Clin Electrophysiol 1999; 22: 1365 – 1371.

14. Fang F, Sanderson JE, Yu CM. Potential role of biventricular pacing beyond advanced systolic heart failure. Circ J 2013; 77: 1364 – 1369.

15. Sheehan F, Redington A. The right ventricle: Anatomy, physiology and clinical imaging. Heart 2008; 94: 1510 – 1515.

16. Winter MM, Bouma BJ, Groenink M, Konings TC, Tijssen JG, van Veldhuisen DJ, et al. Latest insights in therapeutic options for sys-temic right ventricular failure: A comparison with left ventricular failure. Heart 2009; 95: 960 – 963.

17. Woo GW, Petersen-Stejskal S, Johnson JW, Conti JB, Aranda JA Jr, Curtis AB. Ventricular reverse remodeling and 6-month outcomes in patients receiving cardiac resynchronization therapy: Analysis of the MIRACLE study. J Interv Card Electrophysiol 2005; 12: 107 – 113.

18. Vidal B, Delgado V, Mont L, Poyatos S, Silva E, Angeles Castel M, et al. Decreased likelihood of response to cardiac resynchronization in patients with severe heart failure. Eur J Heart Fail 2010; 12: 283 – 287.

19. Doughan AR, McConnell ME, Book WM. Effect of beta blockers (carvedilol or metoprolol XL) in patients with transposition of great arteries and dysfunction of the systemic right ventricle. Am J Car-diol 2007; 99: 704 – 706.

20. Josephson CB, Howlett JG, Jackson SD, Finley J, Kells CM. A case series of systemic right ventricular dysfunction post atrial switch for simple D-transposition of the great arteries: The impact of beta-blockade. Can J Cardiol 2006; 22: 769 – 772.

21. Lindenfeld J, Keller K, Campbell DN, Wolfe RR, Quaife RA. Im-proved systemic ventricular function after carvedilol administration in a patient with congenitally corrected transposition of the great arteries. J Heart Lung Transplant 2003; 22: 198 – 201.

22. Giardini A, Lovato L, Donti A, Formigari R, Gargiulo G, Picchio FM, et al. A pilot study on the effects of carvedilol on right ventricu-lar remodelling and exercise tolerance in patients with systemic right ventricle. Int J Cardiol 2007; 114: 241 – 246.

23. Hechter SJ, Fredriksen PM, Liu P, Veldtman G, Merchant N, Freeman M, et al. Angiotensin-converting enzyme inhibitors in adults after the Mustard procedure. Am J Cardiol 2001; 87: 660 – 663, A11.

24. Robinson B, Heise CT, Moore JW, Anella J, Sokoloski M, Eshaghpour E. Afterload reduction therapy in patients following intraatrial baffle operation for transposition of the great arteries. Pediatr Cardiol 2002; 23: 618 – 623.

25. Therrien J, Provost Y, Harrison J, Connelly M, Kaemmerer H, Webb GD. Effect of angiotensin receptor blockade on systemic right ven-tricular function and size: A small, randomized, placebo-controlled study. Int J Cardiol 2008; 129: 187 – 192.

26. Lester SJ, McElhinney DB, Viloria E, Reddy GP, Ryan E, Tworetzky W, et al. Effects of losartan in patients with a systemically function-ing morphologic right ventricle after atrial repair of transposition of the great arteries. Am J Cardiol 2001; 88: 1314 – 1316.

27. Pérez-Calvo J, Civeira F, Ferrando J, Martínez-Rodés P, Torralba MA, Banzo J, et al. The effects of enalapril on exercise capacity and right ventricular function in patients with chronic cor pulmonale. An Med Interna 2000; 17: 527 – 532.

zation of the systemic RV while considering the degeneration of the myocardium, geometry and mechanism of contraction, is a direction for future study. The evaluation of fibrosis using cMRI might help us to avoid placing epicardial ventricular leads on highly degenerated areas. With regard to the geom-etry of the RV, resynchronization of the sRV might have to be performed in a longitudinal (apex to outflow) rather than a horizontal direction.

Study LimitationsOne limitation to this study was the small number of patients. In addition, the heterogeneity of the ventricular morphology did not facilitate the evaluation of accurate echocardiographic parameters that would suggest ventricular dyssynchrony; in the present study, dyssynchrony was defined based on the presence of a QRS duration ≥130 ms and dyssynchronized ventricular motion, as viewed in cine-angiography and echo-cardiography. The third limitation was the inaccurate assess-ment of the cardiac function and ventricular volume, espe-cially of a non-LV-type systemic ventricle, in terms of the EDVI and EF; other modalities, such as cMRI, would have improved the accuracy; however, the technique was contrain-dicated in patients who had undergone a device implantation.

ConclusionsCRT pacing improved the electrical dyssynchrony in patients with CHD. In patients with a sLV and sBV, a ventricular vol-ume reduction was achieved by CRT pacing. However, pa-tients with a sRV did not respond as well as the sLV/sBV patients to CRT pacing. Although CRT pacing might be able to correct one of the exacerbating factors of heart failure in CHD patients, resynchronization of the sRV will require a new approach.

AcknowledgmentsThe authors thank all the fellows in our department for their contribution to the medical care of the patients.

The present study was supported by the Intramural Research Fund (22-6-6) for Cardiovascular Diseases from the National Cerebral and Cardio-vascular Center.

References 1. Cazeau S, Ritter P, Lazarus A, Gras D, Backdach H, Mundler O, et

al. Multisite pacing for end-stage heart failure: Early experience. Pacing Clin Electrophysiol 1996; 19: 1748 – 1757.

2. Cazeau S, Leclercq C, Lavergne T, Walker S, Varma C, Linde C, et al. Effects of multisite biventricular pacing in patients with heart failure and intraventricular conduction delay. N Engl J Med 2001; 344: 873 – 880.

3. Sakamaki F, Seo Y, Ishizu T, Yanaka S, Atsumi A, Yamamoto M, et al. Tissue Doppler imaging dyssynchrony parameter derived from the myocardial active wall motion improves prediction of responders for cardiac resynchronization therapy. Circ J 2012; 76: 689 – 697.

4. Fujimoto S. Cardiac sympathetic activity and left ventricular dys-synchrony: An old and new issue. Circ J 2012; 76: 295 – 296.

5. Cua CL, Feltes TF. Echocardiographic evaluation of the single right ventricle in congenital heart disease: Results of new techniques. Circ J 2012; 76: 22 – 31.

6. Dubin AM, Janousek J, Rhee E, Strieper MJ, Cecchin F, Law IH, et al. Resynchronization therapy in pediatric and congenital heart dis-ease patients: An international multicenter study. J Am Coll Cardiol 2005; 46: 2277 – 2283.

7. Janousek J, Gebauer RA, Abdul-Khaliq H, Turner M, Kornyei L, Grollmuss O, et al. Cardiac resynchronisation therapy in paediatric and congenital heart disease: Differential effects in various ana-tomical and functional substrates. Heart 2009; 95: 1165 – 1171.

8. Cecchin F, Frangini PA, Brown DW, Fynn-Thompson F, Alexander

cardiac resynchronization therapy for various …...ardiac resynchronization therapy (crt) has been...

Documents