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.     

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)     

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.     

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.     

Long-Term Survival in Patients Treated with Cardiac Resynchronization Therapy: A 3-Year Follow-Up Study from the InSync/InSync ICD Italian Registry

Background: Studies reporting the long-term survival of patients treated with cardiac resynchronization therapy (CRT) outside the realm of randomized controlled trials are still lacking. The aim of this study was to quantify the survival of patients treated with CRT in clinical practice and to investigate the long-term effects of CRT on clinical status and echocardiographic parameters.
Methods: The study population consisted of 317 consecutive patients with implanted CRT devices from eight Italian University/Teaching Hospitals. The patients were enrolled in a national observational registry and had a minimum follow-up of 2 years. A visit was performed in surviving patients and mortality data were obtained by hospital file review or direct telephone contact.
Results: During the study period, 83 (26%) patients died. The rate of all-cause mortality was significantly higher in ischemic than nonischemic patients (14% vs 8%, P = 0.002). Multivariate analysis showed that ischemic etiology (HR 1.72, CI 1.06–2.79; P = 0.028) and New York Heart Association (NYHA) class IV (HR 2.87, CI 1.24–6.64; P = 0.014) were the strongest predictors of all-cause mortality. The effects of CRT persisted at long-term follow-up (for at least 2 years) in terms of NYHA class improvement, increase of left ventricular ejection fraction, decrease of QRS duration (all P = 0.0001), and reduction of left ventricular end-diastolic and end-systolic diameters (P = 0.024 and P = 0.011, respectively).
Conclusions: During long-term (3 years) follow-up after CRT, total mortality rate was 10%/year. The outcome of ischemic patients was worse mainly due to a higher rate of death from progressive heart failure. Ischemic etiology along with NYHA class IV was identified as predictors of death. Benefits of CRT in terms of clinical function and echocardiographic parameters persisted at the time of long-term follow-up.     

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.     

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)     

Technical Aspects of Implantation of LV Lead for Cardiac Resynchronization Therapy in Chronic Heart Failure

The goal of this study was to analyze total procedural and fluoroscopic time during initial experience with implantation of LV lead in a single center, and to assess the performance of electrophysiologically-guided approach for cannulation of the coronary sinus (CS) in a subsequent period. Over an initial period of 29 months, a total of 46 attempts to implant biventricular pacing system were revised. During the first phase, only one type of LV electrode was available for three implanters (11 attempts). The second phase covered their early experience with other stylet-controlled LV leads (10 attempts). Additional LV leads including the over-the-wire design were available in the third phase and 25 attempts were done by he most experienced implanter. In a period of advanced experience, 92 implant procedures performed by four implanters using an electrophysiologically-guided approach to CS cannulation were revised. In the first period, success rates for different phases reached 70%, 90%, and 96%, respectively. Significant decrease in both procedural and fluoroscopic times was achieved with increased experience (Phase I: 247.1 ± 104.5 minutes and 31.2 ± 34.3 minutes, Phase II: 219.4 ± 85.6 minutes, and 22.9 ± 19.1 minutes, Phase III: 116.4 ± 89.9 minutes and 6.6 ± 4.4 minutes, respectively, P < 0.05). Advanced experience with electrophysiologically-guided approach to CS cannulation allowed achievement of this target within a reasonable amount of time (15.4 ± 16.3 minutes) and with minimum fluoroscopic time (2.1 ± 2.9 minutes). In conclusion, both individual learning curve and technical advances significantly influence success rate, procedural, and fluoroscopic times for biventricular system implantation. Electrophysiologically-guided approach makes cannulation of the CS a highly reproducible procedure that requires minimum fluoroscopic time. (PACE 2004; 27[Pt. I]:783–790)     

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)     

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 .     

Response to Cardiac Resynchronization Therapy in Patients with Heart Failure and Renal Insufficiency

Background: Renal insufficiency (RI) adversely impacts prognosis in heart failure (HF) patients, partly because renal and cardiac dysfunction are intertwined, yet few cardiac resynchronization therapy (CRT) studies have examined patients with moderate‐to‐severe RI. Methods: We analyzed 787 CRT‐defibrillator (CRT‐D) recipients with a glomerular filtration rate (GFR) measured prior to implant. Patients were grouped by GFR (in mL/min/1.73 m²): ≥60 (n = 376), 30–59 (n = 347), and <30 (n = 64). Overall survival, changes in left ventricular (LV) ejection fraction and LV end‐systolic diameter, and GFR change at 3–6 months were compared among CRT‐D groups and with a control cohort (n = 88), also stratified by GFR, in whom LV lead implant was unsuccessful and a standard defibrillator (SD) was placed. All patients met clinical criteria for CRT‐D. Results: Among CRT‐D recipients, overall survival improved incrementally with higher baseline GFR (for each 10 mL/min/1.73 m² increase, corrected hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.13–1.30, P < 0.0001). Survival among SD and CRT‐D patients within GFR < 30 and GFR ≥ 60 groups was similar, whereas CRT‐D recipients with GFR 30–59 had significantly better survival compared to SD counterparts (HR 2.23, 95% CI 1.34–3.70; P = 0.002). This survival benefit was associated with improved renal and cardiac function. CRT recipients with GFR ≥ 60 derived significant echocardiographic benefit but experienced a GFR decline, whereas those with GFR < 30 had no echocardiographic benefit but did improve GFR. Conclusions: CRT may provide the largest survival benefit in HF patients with moderate RI, perhaps by improving GFR and LV function. Severe baseline RI predicts poor survival and limited echocardiographic improvement despite a modest GFR increase, such that CRT may not benefit those with GFR < 30 mL/min/1.73 m². CRT recipients with normal renal function derive echocardiographic benefit but no overall survival advantage. (PACE 2010; 850–859)     

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)