Bifocal Right Ventricular Cardiac Resynchronization Therapies in Patients with Unsuccessful Percutaneous Lateral Left Ventricular Venous Access

Biventricular cardiac resynchronization therapy (CRT) with a lateral left ventricular (LV) lead cannot always be achieved. We report a single center experience of CRT utilizing a protocol that specifically required the implantation of a bifocal right ventricular (RV) lead system when lateral LV pacing could not be achieved. Consecutive candidates for CRT were included in the study. If strict criteria for lateral LV pacing were not met, they underwent implantation of a bifocal RV lead system with two 7F, active fixation leads, one placed septally at the apex, and the other in the high septal outflow tract. All patients were followed for 12 months and the two groups were compared. A biventricular (BiV) stimulation system was implanted in 44 patients, and a bifocal RV system in six. The demographic characteristics of the two groups were similar. Both groups experienced a similar improvement in functional capacity, increase in 6 minutes walking distance, and decreased need for hospitalizations. The mean increase in LV ejection fraction was 11% in the bifocal RV group versus 10% in the BiV group. Though the tissue Doppler indices of LV synchrony improved earlier in the BiV group, (19% vs 10%) the improvement was similar in both groups at 6 months (23% vs 20%). The clinical improvements conferred by CRT can be matched by a bifocal RV system in selected patients. This alternate approach should be considered when implantation of a LV lateral lead was unsuccessful.     

Relevance of Echocardiographic Evaluation of Right Ventricular Function in Patients Undergoing Cardiac Resynchronization Therapy

Aims: Right ventricular (RV) dysfunction is a marker of poor prognosis in heart failure (HF) patients. It is still unclear whether RV function might influence response to cardiac resynchronization therapy (CRT).
Methods: Forty-four consecutive patients with HF, large QRS, and either intraventricular or interventricular dyssynchrony underwent echocardiographic evaluation before, 1 month after, and 6 months after CRT. Response to CRT was considered in case of significant LV reverse remodeling, defined as the occurrence of LV end-systolic volume (LVESV) reduction ≥15% at 6 months.
Results: All echocardiographic indexes of baseline RV function and dimensions were significantly more impaired in nonresponders versus responders to CRT: tricuspid annular plane systolic excursion (TAPSE 15 ± 4 mm vs 20 ± 5 mm, P = 0.001), RV systolic pulmonary artery pressure (RVSP 39 ± 14 mmHg vs 27 ± 8 mmHg, P = 0.02), RV end-diastolic area (RVEDA 23 ± 6 cm² vs 16 ± 3 cm² P < 0.001), RV end-systolic area (RVESA 16 ± 6 cm² vs 8 ± 2 cm², P = 0.001), and RV fractional area change (30 ± 12% vs 48 ± 8%, P < 0.001). All the indexes of RV function significantly correlated with the percentage of LVESV reduction after CRT. Severe RV dysfunction was defined as TAPSE ≤14 mm and the population was stratified into two groups based on baseline TAPSE ≤ or > 14 mm. As compared to those with high TAPSE (n = 30), patients with low TAPSE (n = 14) were less likely to show LV reverse remodeling after CRT (76% vs 14%, P < 0.001).
Conclusions: Our study suggests that RV function significantly affects response to CRT. Poor LV reverse remodeling occurs after CRT in patients with HF having severe RV dysfunction at baseline.     

右室双部位及双室起搏对心衰犬急性心功能及心室同步的影响

【目的】探讨右室5X部位及双室起搏心衰模型犬急性心功能及心室同步的影响。【方法】选取12只左束支传导阻滞的心衰模型犬,采用自身对照方法随机行右心房一右室双部位（或双室）起搏,起搏频率180次／分钟,每种方式起搏前及起搏稳定15min后行彩色多普勒超声心动图检查,测定左心室舒张末期内径（LVEDd）、左室射血分数（LVEF）、室间机械延迟（IVMD）、室间隔与左室后壁运动延迟（SPWMD）、左心室12个节段达峰时间的标准差（Ts—SD）。【结果】右室双部位起搏：与起搏前相比,LVEDd、IvMD、SPWMD、Ts—SD减小,LVEF增加,差异有显著性（P〈O．05）;与双室起搏相比,SPWMD、Ts—SD增加,差异有显著性（P〈0．05）,LVEDd、IVMD、LVEF差异无显著性（P〉0．05）。【结论】在改善室间不同步及心功能方面,右室双部位与双室起搏有近似效果,但改善左室内不同步前者不及后者。     

Right Ventricular Myocardial Function in Patients with Either Idiopathic or Ischemic Dilated Cardiomyopathy Without Clinical Sign of Right Heart Failure: Effects of Cardiac Resynchronization Therapy

Objective: In dilated cardiomyopathy (DCM), right ventricular (RV) dysfunction has been reported and attributed both to altered loading conditions and to RV involvement in the myopathic process. The aim of the study was to detect RV myocardial function in DCM using two‐dimensional (2D) strain echocardiography and to assess the effects of cardiac resynchronization therapy (CRT) on RV myocardial strain during a 6‐month follow‐up. Methods and Results: A total of 110 patients (mean age: 55.4 ± 11.2 years) with either idiopathic (n = 60) or ischemic (n = 50) DCM, without overt clinical signs of RV failure, underwent standard echo and 2D strain analysis of RV longitudinal strain in RV septal and lateral walls. The two groups were comparable for clinical variables (New York Heart Association class III in 81.8%). Left ventricular volumes, ejection fraction, stroke volume, and mitral valve effective regurgitant orifice were similar between the two groups. No significant differences were evidenced in Doppler mitral and tricuspid inflow measurements. RV diameters were mildly increased in patients with idiopathic DCM, while RV tricuspid annulus systolic excursion and Tei‐index were comparable between the two groups. RV global longitudinal strain and regional peak myocardial strain were significantly impaired in patients with idiopathic DCM compared with those having ischemic DCM (all P < 0.001). Using left ventricular end‐systolic volume as marker for response to CRT, 70 patients (63.3%) were long‐term responders. Ischemic DCM patient responders to CRT showed a significant improvement in RV peak systolic strain. Conversely, in patients with idiopathic DCM and in ischemic patients nonresponders to CRT, no improvement in RV function was evidenced. By multivariable analysis, in the overall population, ischemic etiology of DCM (P < 0.0001), positive response to CRT (P < 0.001), and longitudinal intraventricular dyssynchrony (P <0.01) emerged as the only independent determinants of RV global longitudinal strain after CRT. Conclusions: Two‐dimensional strain represents a promising noninvasive technique to assess RV myocardial function in patients with DCM. RV myocardial deformation at baseline and after CRT are more impaired in idiopathic compared with ischemic DCM patients. Future longitudinal studies are warranted to understand the natural history of RV myocardial function, the extent of reversibility of RV dysfunction with CRT, and the possible prognostic impact of such indexes in patients with congestive heart failure.     

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)     

Similar Long-Term Benefits Conferred by Apical Versus Mid-Septal Implantation of the Right Ventricular Lead in Recipients of Cardiac Resynchronization Therapy Systems

Introduction: The benefits conferred by cardiac resynchronization therapy (CRT) are markedly influenced by the left ventricular (LV) lead placement. Little is known regarding the optimal right ventricular (RV) stimulation site.
Study Objective: To compare the long-term outcomes of CRT in patients with RV leads placed in the mid-septal region versus the apex.
Methods and Results: This nonrandomized, observational study included 117 patients with standard indications for CRT. The LV lead was implanted on the postero-lateral or lateral LV wall, while the RV lead was implanted at the apex (n = 82) or in the mid-septum (n = 35). Both groups were similar with respect to baseline clinical, demographic, and echocardiographic characteristics. After 12 months of CRT, the rates of clinical response to CRT were similar in both groups (63% vs. 66%), and similar degrees of reverse LV remodeling and LV resynchronization were observed on echocardiography and color tissue Doppler imaging. A ≥30% relative increase in LV ejection fraction (EF) occurred in 76% of patients in the RV apex group, versus 49% of patients in the RV mid-septum group (P = 0.05). A ≥45% left ventricular ejection fraction (LVEF) was measured at 12 months in 40% of patients in the RV apex group, versus 31% in the RV mid-septum group (ns).
Conclusions: RV mid-septal stimulation was not associated with a higher rate of response to CRT or greater improvement in LV function compared to RV apical stimulation.     

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)     

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)     

Interlead Distance and Left Ventricular Lead Electrical Delay Predict Reverse Remodeling During Cardiac Resynchronization Therapy

Background: Both anatomic interlead separation and left ventricle lead electrical delay (LVLED) have been associated with outcomes following cardiac resynchronization therapy (CRT). However, the relationship between interlead distance and electrical delay in predicting CRT outcomes has not been defined. Methods: We studied 61 consecutive patients undergoing CRT for standard clinical indications. All patients underwent intraprocedural measurement of LVLED. Interlead distances in the horizontal (HD), vertical (VD), and direct (DD) dimensions were measured from postprocedure chest radiographs (CXR). Remodeling indices [percent change in left ventricle (LV) ejection fraction, end‐diastolic, end‐systolic dimensions] were assessed by transthoracic echocardiogram. Results: There was a positive correlation between corrected LVLED and HD on lateral CXR (r = 0.361, P = 0.004) and a negative correlation between LVLED and VD on posteroanterior (PA) CXR (r =?0.281, P = 0.028). To account for this inverse relationship, we developed a composite anatomic distance (defined as: lateral HD—PA VD), which correlated most closely with LVLED (r = 0.404, P = 0.001). Follow‐up was available for 48 patients. At a mean of 4.1 ± 3.2 months, patients with optimal values for both corrected LVLED (≥75%) and composite anatomic distance (≥15 cm) demonstrated greater reverse LV remodeling than patients with either one or neither of these optimized values. Conclusions: We identified a significant correlation between LV–right ventricular interlead distance and LVLED; additionally, both parameters act synergistically in predicting LV anatomic reverse remodeling. Efforts to optimize both interlead distance and electrical delay may improve CRT outcomes. (PACE 2010; 575–582)     

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)     

Segmental Wall Motion Abnormality Analyzed by Equilibrium Radionuclide Angiography and Improvement in Ventricular Function by Cardiac Resynchronization Therapy

Introduction: The purpose of this study was to determine the impact of the left ventricular (LV) segmental wall motion abnormalities detected by equilibrium radionuclide angiography (ERNA) on the improvement in LV and right ventricular (RV) function during biventricular (BIV) stimulation .
Results: We studied 28 patients in NYHA functional classes III or IV and QRS duration >150 ms on resting electrocardiogram. ERNA was performed before and during BIV stimulation at a 6-month follow-up. A significant shortening of QRS duration was observed during BIV stimulation (165 ± 5 ms before vs 133 ± 6 ms during, P < 0.01). Wall motion abnormalities (WMA) were observed in 16 patients (10 with nonischemic cardiomyopathies). In this group, LV and RV ejection fractions (EF) did not increase during BIV stimulation (LVEF = 22 ± 2% vs 20 ± 1.6%, ns; RVEF = 34 ± 3% vs 37 ± 3.8%, ns). Significant increases in RVEF (23 ± 3.2 %→ 38 ± 2.9%, P = 0.001) and LVEF (20 ± 2.5 %→ 30 ± 3%, P = 0.01) were observed in the group of patients without segmental WMA and with global hypokinesia (GH). In this group, a significant decrease in the dispersion in the phase of RV contraction was observed (SD = 39 ± 5 vs 26 ± 2 ms; P < 0.01). WMA predicted an increase in LVEF, in contrast to a baseline 6-minute-walk test, maximal oxygen consumption and LVEF, or amount of QRS shortening.
Conclusions: BIV stimulation increased in LV and RV EF in patients with ventricular dyssynchrony in absence of segmental WMA. ERNA was reliable in the selection of candidates for CRT.     

Acute Left Ventricular Dyssynchrony Improvement Predicts Long-Term Benefit from Cardiac Resynchronization Therapy

Study Objective: To evaluate the relationship between acute response to cardiac resynchronization therapy (CRT) and long-term clinical outcome in patients with drug refractory heart failure.
Methods and Results: In 28 patients undergoing CRT implant, left ventricular (LV) dyssynchrony was evaluated by tissue Doppler imaging (TDI)-derived longitudinal strain by mean of septum-lateral basal asynchrony index (S-Li) and basal delayed longitudinal contraction (DLC). TDI measurements were made before, and 30 minutes and 1 year after implant. Baseline and 1-year follow-up New York Heart Association (NYHA) functional class, 6-minute walking test (6-MWT) distance, and quality of life (QoL) score were measured. Responders (n = 22) were defined by a ≥ 1 decrease in NYHA functional class and 6-MWT ≥25% at 1 year. At baseline, no differences were observed between responders and nonresponders in clinical and echocardiographic measurements. LV dyssynchrony acutely recovered only in responders 30 minutes after implantation, with a significant reduction in S-Li and DLC. Moreover, the percent decreases in S-Li and DLC were highly correlated with those observed in NYHA class (r = 0.70, and r = 0.81, respectively, P < 0.001), 6-MWT (r = 0.59, and r = 0.57, respectively, P < 0.001 and P < 0.01), and QoL score (r = 0.71, and r = 0.83, respectively, p < 0.001) at 1-year follow-up.
Conclusions: Acute recovery of LV intraventricular dyssynchrony is a major discriminator between responders and nonresponders to CRT, which strongly correlates with a favorable long-term clinical outcome.     

Marked Improvement in Left Ventricular Function and Significant Reverse Left Ventricular Remodeling within 3 Months of Cardiac Resynchronization Therapy in Patients with Dilated Cardiomyopathy

We monitored reverse left ventricular (LV) remodeling and LV function during the first 6 months of cardiac resynchronization therapy (CRT) in 34 patients (mean age = 55.3 ± 13.6 years, 28 men) with dilated cardiomyopathy (DCM), left bundle branch block, in stable New York Heart Association class III, and on fixed drug regimen who underwent implantation of CRT systems with or without cardioverter defibrillator back-up. QRS-complex duration was reduced from 169.69 ± 19.6 ms (SD) to 144.1 ± 23.4 ms during CRT. Parasternal M-mode and apical 2D-echocardiography was performed before and 3 and 6 months after device implantation. LV enddiastolic (EDD) and endsystolic (ESD) diameters were measured, and biplane LV enddiastolic (EDV), and endsystolic (ESV) volumes and ejection fractions (EF) were calculated using a modified Simpson formula. Significant decreases in LVEDD (P = 0.0064 at 3 months and P = 0.021 at 6 months), LVESD (P = 0.023 at 3 months, and P = 0.003 at 6 months), and LVESV (P = 0.006 resp. P = 0.007), and increases in LVEF (P = 0.003 at 3 months and P < 0.001 at 6 months) were observed. Mean LVEF increased from 23% at baseline to 39% at 6 months. CRT induced prominent reverse LV remodeling and significantly increased LVEF within a few months in patients with DCM.     

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.