Cardiac Resynchronization Therapy in Pediatric and Congenital Heart Disease

Cardiac resynchronization therapy (CRT) is an emerging option for treating dyssynchrony-associated heart failure in patients with pediatric or congenital heart disease. CRT has proved beneficial for both the acute manipulation of cardiac output after surgery for congenital heart defects and for the management of chronic systemic ventricular failure. Although there are no prospective and randomized trial data, retrospective series show that CRT is similarly effective for managing dyssynchrony-associated heart failure in this younger population as it is for treating adults with ischemic and idiopathic dilated cardiomyopathy. The heterogeneity of anatomical and functional substrates in which CRT shows efficacy calls for further studies defining the usefulness of CRT in specific subgroups of patients.     

Effects of Cardiac Resynchronization Therapy on Diastolic Function: Evaluation by Radionuclide Angiography

While the beneficial effects of cardiac resynchronization therapy (CRT) on left ventricular (LV) systolic function have been demonstrated, no information is available regarding its effects on LV diastolic function during exercise. Using radionuclide angiography, we prospectively evaluated the effects of CRT on diastolic function at rest and during exercise in 15 patients consecutively referred for CRT. All patients underwent equilibrium Tc⁹⁹ radionuclide angiography with bicycle exercise performed (1) at baseline; (2) immediately after CRT implantation, in spontaneous rhythm and during CRT; and (3) after 3 months of biventricular stimulation. Diastolic function was assessed by measurements of peak filling rate (PFR). At baseline, activation of biventricular stimulation influenced PFR neither at rest (1.06 ± 0.34 vs 1.07 ± 0.50 mL/s during spontaneous rhythm, P = 0.9) nor during exercise (1.45 ± 0.62 vs 1.33 ± 0.48 mL/s, P = 0.3). At 3 months, improvements were observed in New York Heart Association functional class and systolic function. By contrast, no improvement in diastolic function was observed either at rest (PFR = 1.11 ± 0.45 vs 1.07 ± 0.50 mL/s in spontaneous rhythm at baseline, P = 0.6) or during exercise (1.23 ± 0.50 vs 1.33 ± 0.48 mL/s, P = 0.2). These observations indicate that the intermediate benefits conferred by CRT on LV systolic function at rest and during exercise were not accompanied by similar improvements in diastolic function .     

Proportion of Candidates for Cardiac Resynchronization Therapy

ERDOGAN, A., et al. : Proportion of Candidates for Cardiac Resynchronization Therapy. Biventricular pacing has been used as an adjunct to standard heart failure therapy in symptomatic patients with left bundle branch block (LBBB). Estimates of the number of patients for whom this treatment is appropriate are unavailable, but are of clinical and socioeconomic importance. LBBB combined with a low (<0.35) ejection fraction was found in 7,121 consecutive patients referred for elective diagnostic angiography in 1996 through 2000 from a total population of about 125,000 residents. Patients with LBBB (n = 289, 4%) had lower ejection fractions (0.53 ± 0.23) in comparison with patients without LBBB (P < 0.0001). The ejection fraction was <0.35 in 558 (8%) patients. LBBB was combined with a low ejection fraction in 96 (1.4%) patients (i.e., 19 patients per year and about 15 patients per year per 100,000 residents). Of these 96 patients, 80 had normal sinus rhythm, 82 had mitral regurgitation (grade > II), 86 were <75 years of age, and 68 had coronary artery disease. Holter recordings performed in 47 of 96 patients showed nonsustained VT in 28 (60%). LBBB, low ejection fraction, sinus rhythm, and age <75 years were found in 71 (1%) patients (i.e., 11 patients per year per 100,000 residents). The prevalence of LBBB combined with severely impaired left ventricular ejection function is about 1–2% in patients who undergo cardiac catheterization. The authors estimate that biventricular pacing might be considered as an adjunct to standard heart failure therapy in five to ten patients per year per 100,000 residents in industrial countries. About half of these patients are potential candidates for implantation of cardioverter defibrillators combined with permanent pacing. (PACE 2003; 26[Pt. II]:152–154)     

Adrenomedullin Plasma Levels Predict Left Ventricular Reverse Remodeling after Cardiac Resynchronization Therapy

Background: Increase in adrenomedullin (ADM) plasma levels in congestive heart failure (HF) patients is due to many cardiac and systemic factors, particularly to greater fluid retention and to activation of sympathetic nervous system. Aim of this study was to assess the role of plasma ADM levels in HF patients treated by cardiac resynchronization therapy (CRT). Methods: 50 patients, mean age 70 years, 34 male, New York Heart Association (NYHA) Class III–IV HF, left ventricular ejection fraction (LVEF) < 35%, underwent CRT. All patients were in sinus rhythm and with complete left bundle branch block (QRS duration 138 ± 6 msec). A complete echoDoppler exam, blood samples for brain natriuretic peptide (BNP), and ADM were obtained from 2 to 7 days before implantation. Results: At 16 ± 6 months follow‐up, ≥1 NYHA Class improvement was observed in 38 patients. However, a >10% reduction in end‐systolic dimensions (ESD) was reported in 21 patients (Group I): ?16.6 ± 1.8%; in the remaining 29 patients ESD change was almost negligible: ?2.0 ± 1.03% (Group II), P < 0.0001. The two groups were comparable for age, sex, cause of LV dysfunction, therapy, QRS duration at baseline, preimplantation ESD, LVEF%, and BNP. Significantly higher pre implantation ADM levels were present in Group I than in Group II (27.2 ± 1.8 pmol/l vs 17.9 ± 1.4, P = 0.0003). Conclusions: Significantly higher ADM levels indicate a subgroup of patients in whom reverse remodeling can be observed after CRT. Patients with lower ADM basal values before CRT could represent a group in whom the dysfunction is so advanced that no improvement can be expected. (PACE 2010; 865–872)     

Is the Left Ventricular Lateral Wall the Best Lead Implantation Site for Cardiac Resynchronization Therapy?

GASPARINI, M., et al .: Is the Left Ventricular Lateral Wall the Best Lead Implantation Site for Cardiac Resynchronization Therapy? Short-term hemodynamic studies consistently report greater effects of cardiac resynchronization therapy (CRT) in patients stimulated from a LV lateral coronary sinus tributary (CST) compared to a septal site. The aim of the study was to compare the long-term efficacy of CRT when performed from different LV stimulation sites. From October 1999 to April 2002, 158 patients (mean age 65 years, mean LVEF 0.29, mean QRS width 174 ms) underwent successful CRT, from the anterior (A) CST in 21 patients, the anterolateral (AL) CST in 37 patients, the lateral (L) CST in 57 patients, the posterolateral (PL) CST in 40 patients, and the middle cardiac vein (MCV) CST in 3 patients. NYHA functional class, 6-minute walk test, and echocardiographic measurements were examined at baseline, and at 3, 6, and 12 months. Comparisons were made among all pacing sites or between lateral and septal sites by grouping AL + L + PL CST as lateral site (134 patients, 85%) and A + MC CST as septal site (24 patients, 15%). In patients stimulated from lateral sites, LVEF increased from 0.30 to 0.39   (P < 0.0001)   , 6-minute walk test from 323 to 458 m   (P < 0.0001)   , and the proportion of NYHA Class III–IV patients decreased from 82% to 10%   (P < 0.0001)   . In patients stimulated from septal sites, LVEF increased from 0.28 to 0.41   (P < 0.0001)   , 6-minute walk test from 314 to 494 m   (P < 0.0001)   , and the proportion of NYHA Class III–IV patients decreased from 75% to 23%   (P < 0.0001)   . A significant improvement in cardiac function and increase in exercise capacity were observed over time regardless of the LV stimulation sites, either considered singly or grouped as lateral versus septal sites. (PACE 2003; 26[Pt. II]:162–168)     

Influence of Different Atrioventricular and Interventricular Delays on Cardiac Output During Cardiac Resynchronization Therapy

Restoration of the atrioventricular (AVD) and interventricular (VVD) delays increases the hemodynamic benefit conferred by biventricular (BiV) stimulation. This study compared the effects of different AVD and VVD on cardiac output (CO) during three stimulation modes: BiV-LV = left ventricle (LV) preceding right ventricle (RV) by 4 ms; BiV-RV = RV preceding LV by 4 ms; LVP = single-site LV pacing. We studied 19 patients with chronic heart failure due to ischemic or idiopathic dilated cardiomyopathy, QRS ≥ 150 ms, mean LV end-diastolic diameter = 78 ± 7 mm, and mean LV ejection fraction = 21 ± 3%. CO was estimated by Doppler echocardiographic velocity time integral formula with sample volume placed in the LV outflow tract. Sets of sensed-AVDs (S-AVD) 90–160 ms, paced-AVDs (P-AVD) 120–160 ms, and VVDs 4–20 ms were used. BiV-RV resulted in lower CO than BiV-LV. S-AVD 120 ms and P-AVD 140 ms caused the most significant increase in CO for all three pacing modes. LVP produced a similar increase in CO as BiV stimulation; however, AV sequential pacing was associated with a nonsignificantly higher CO during LVP than with BiV stimulation. CO during BiV stimulation was the highest when LV preceded RV, and VVD ranged between 4 and 12 ms. The most negative effect on CO was observed when RV preceded LV by 4 ms. Hemodynamic improvement during BiV stimulation was dependent both on optimized AVD and VVD. LV preceding RV by 4–12 ms was the most optimal. Advancement of the RV was not beneficial in the majority of patients.     

Cardiac Resynchronization Therapy:

In patients with heart failure and wide QRS complex, cardiac resynchronization therapy (CRT) is associated with improvement of symptoms and cardiac function. This study examined the effects of a 3-month period of CRT on left ventricular (LV) and right ventricular (RV) ejection fraction (EF) and on LV volumes, both at rest and during exercise. A CRT system was implanted in 15 patients with severe heart failure and wide QRS. Before implant and 3 months later, all patients underwent assessment of cardiac performance with equilibrium Tc⁹⁹ radionuclide angiography with imaging in the best septal left anterior oblique view. Exercise was performed on a bicycle ergometer. At 3 months, a significant improvement in New York Heart Association functional class was observed, and radionuclide angiography showed a significant decrease in LV volumes and a significant increase in LVEF at rest, as well as a significant increase in LVEF during exercise. The remodeling processes associated with CRT did not appear to include RV function, since RVEF did not improve, and changes in RVEF did not correlate with changes in LVEF, neither at rest nor during exercise.     

心力衰竭患者血清心肌肌钙蛋白与心功能的相关性研究

目的:观察充血性心力衰竭(CHF)患者血清心肌肌钙蛋白I(CTn-I)水平及其与心功能的相关性。方法:选择160例CHF患者,应用微粒子化学发光法测定血清CTn-I水平。采用NYHA心功能分级法及左室射血分数(LVEF)值进行分类,并进行组间均数t检验及相关性分析。结果:心功能(NYHA)为Ⅰ、Ⅱ、Ⅲ、Ⅳ级者,其血清CTn-I水平分别为(0.04±0.01)μg/L,(0.09±0.02)μg/L,(0.20±0.11)μg/L,(0.35±0.21)μg/L。160例患者中LVEF≤35%者,CTn-I水平为(0.24±0.15)μg/L;LVEF>35%者CTn-I为(0.08±0.03)μg/L。LVEF值与CTn-I呈负相关(r=-0.590,P<0.01)。结论:CHF患者血清CTn-I水平升高,其升高程度与心力衰竭严重程度相平行。     

Long-Term Variations in Optimal Programming of Cardiac Resynchronization Therapy Devices

The optimal follow-up and long-term programming of cardiac resynchronization therapy (CRT) devices are uncertain. The aim of this study was to quantify the temporal variations in programming parameters to optimize the follow-up of these devices. Before, during, and at specified intervals over 9 months after implant, 40 recipients of CRT devices were studied. At each visit, the patients were tested with a fixed sequence of stimulation parameters during echocardiographic and electrocardiographic (ECG) recordings. The optimal AV delay and inter-ventricular delays (V-V) were determined according to echocardiographic criteria. The echocardiographic data were, in turn, compared with the ECG recordings. Among the 40 patients, the optimal stimulation parameters remained unchanged throughout the follow-up in only three patients. In 18 patients, adjustments were required at each follow-up sessions. There was a trend toward reduction in the left ventricular (LV) predominance of the optimal V-V delay and an increase in the AV delay during follow-up. The mean optimal V-V delay at implant was 22 ms (−12 to +32 ms) with the LV activated first, versus 12 ms (−16 to +32 ms) at 9 months. The mean AV delay at implant was 115 ms versus 137 ms at 9 months. Individual changes could not be accurately predicted. The optimal stimulation parameters for CRT vary over time. Detailed, regular reevaluations, and reprogramming of optimal parameters may be appropriate.     

Cardiac Resynchronization Therapy in Patients with Right Ventricular Pacing-Induced Cardiomyopathy

Background: It is not known whether patients with normal baseline left ventricular (LV) function who develop right ventricular (RV) pacing-induced cardiomyopathy as a result of dual-chamber pacing can benefit from cardiac resynchronization therapy (CRT). We retrospectively assessed the effect of a CRT upgrade on RV pacing-induced cardiomyopathy.
Methods and Results: We reviewed the charts of patients who received a CRT device for RV pacing-induced cardiomyopathy. We assessed the effects of CRT on LV function, recovery, and other response parameters. From September 2005 through February 2009, 21 patients (13 men; aged 63 ± 9 years) underwent a treatment upgrade to a CRT system. Before the dual-chamber pacemaker was implanted, the LV ejection fraction (LVEF) was 53 ± 2.3%. After pacing, the LVEF was 31.2 ± 3.8%, the LV end-diastolic dimension (LVEDD) was 5.8 ± 0.5 cm, and B-type natriuretic peptide (BNP) levels were 426 ± 149 pg/mL. The duration of pacing before documentation of pacing-induced cardiomyopathy was 3.8 ± 1.5 months. All the patients had been on a stable medical regimen for at least 2 months. After the upgrade to CRT, the follow-up time was 4.9 ± 0.9 months. Sixteen patients (76%) reported a significant improvement in their symptoms. After the CRT upgrade, the LVEF increased to 37.4 ± 9.0% (P < 0.01 vs pre-CRT). The LVEDD decreased to 5.0 ± 1.0 cm (P = 0.03 vs pre-CRT), and BNP levels decreased to 139 ± 92 pg/mL (P = 0.08 vs pre-CRT).
Conclusion: A CRT upgrade is an effective treatment for RV pacing-induced cardiomyopathy and should be implemented as soon as the diagnosis is established. Unfortunately, about 24% of our patients did not respond to the upgrade. (PACE 2010; 37–40)     

Long-Term Effectiveness of Dual Site Left Ventricular Cardiac Resynchronization Therapy in a Patient with Congestive Heart Failure

This article describes a case of cardiac resynchronization therapy (CRT) performed with dual site left ventricular pacing. The main clinical and functional long-term results are in agreement with the most recent data regarding traditional CRT. Furthermore, this innovative pacing modality allowed optimal inter- and intraventricular resynchronization. (PACE 2004; 27[Pt. I]:805–807)     

How Many Patients with Dilated Cardiomyopathy May Potentially Benefit from Cardiac Resynchronization Therapy?

GRIMM, W., et al .: How Many Patients with Dilated Cardiomyopathy May Potentially Benefit from Cardiac Resynchronization Therapy? The clinical and electrocardiographic Marburg Cardiomyopathy database was analyzed to identify potential candidates for cardiac resynchronization therapy (CRT) with biventricular or left ventricular pacing among 566 patients with dilated cardiomyopathy (DCM). All of the following restrictive selection criteria were fulfilled by 38 patients (7%): NYHA functional class ≥ 3 (   n = 193   , 34%), left ventricular ejection fraction (LVEF) <30% (n = 238, 42%), sinus rhythm (   n = 437   , 77%), left bundle branch block (LBBB,   n = 142   , 25%), and QRS duration ≥ 150 ms (   n = 136   , 24%). In 78 of the 566 patients (14%) all of the following less restrictive selection criteria were fulfilled: NYHA functional class ≥3 (   n = 193   , 34%), LVEF < 35% in presence of any underlying rhythm (n = 326, 58%), QRS duration ≥ 120 ms with right or left bundle branch block (   n = 223   , 39%). Thus, between 7% and 14% of patients with DCM were candidates for CRT depending on the application of strict versus less restrictive selection criteria.(PACE 2003; 26[Pt. II]:155–157)     

Advantage of Optimizing V‐V Timing in Cardiac Resynchronization Therapy Devices

Background: There is little consensus as to the benefits of interventricular (V‐V) timing optimization in cardiac resynchronization therapy (CRT). A variety of parameters are currently used to optimize device timing. This study was designed to investigate the potential advantage of using 3D ejection fraction (EF) and aortic velocity‐time integral (VTI) as measures of global left ventricular (LV) function to optimize ventricular activation in CRT devices. Methods: Seventy‐four patients seen in the Optimization Clinic with adequate echocardiographic images were included. Three aortic VTI and two 3D EF values were recorded at five V‐V settings and the average value used. Aortic VTI and 3D EF were classified as the best, worst, and simultaneous setting values. Data were analyzed using a two‐tailed paired t‐test. Results: Comparing the best to worst V‐V timing settings, VTI improved by 4.7 ± 7.5 cm (P < 0.0001) and 3D EF by 9.9%± 5.7% (P < 0.0001). Comparing the simultaneous setting to the best V‐V timing setting, VTI improved by 2.4 ± 2.1 cm (P < 0.0001) and 3D EF by 3.8%± 4.9% (P < 0.0001). Aortic VTI improved in 85% of patients and 3D EF improved in 72%. However, only 26% of the patients had the same optimal setting using aortic VTI and 3D EF yielding an r² value of 0.003. Conclusions: Individualized echocardiographic V‐V optimization of CRT devices improves global LV function as measured by aortic VTI and 3D EF. Substantial differences in function were seen over an 80‐ms range of V‐V timing and optimization resulted in improved LV function in the majority of patients. (PACE 2010; 33:1161–1168)