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)     

Utilization of Defibrillators and Resynchronization Therapy at the Time of Evaluation at a Heart Failure and Cardiac Transplantation Center

Background: Internal cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT) reduce mortality, but are underutilized in routine clinical practice. The use of these devices in patients at the time of an initial evaluation at an advanced heart failure and cardiac transplantation center is unknown. Methods: We retrospectively analyzed consecutive patients who were enrolled in a database examining parameters of cardiopulmonary exercise testing in chronic heart failure (CHF) patients at the time of an initial outpatient evaluation at a tertiary care center. Rates of ICD and CRT use in eligible patients were determined. Results: Two hundred two patients had an average age of 54 ± 13 years and an average peak oxygen consumption (pVO₂) of 12.5 ± 4.5 mL/kg/min. Of 97 patients eligible for an ICD only, 57% had an ICD at the time of evaluation. Sixty‐four percent of ICD‐eligible male patients had an ICD compared to 36% of ICD‐eligible female patients (P = 0.015). Of 105 patients meeting criteria for CRT, 54% had a CRT device. There was no difference between CRT use in eligible male and female patients. Conclusions: ICDs and CRT are underutilized in patients with severe CHF at the time of evaluation at a tertiary care center despite young age, objective functional limitation, and active consideration for advanced CHF therapies. Female patients have lower rates of ICD use than male patients. (PACE 2010; 988–993)     

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)     

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.     

Long-Term Follow-Up of Patients with Refractory Heart Failure and Myocardial Ischemia Treated with Cardiac Resynchronization Therapy

Studies in patients without coronary artery disease have shown the restoration of glucose metabolism by cardiac resynchronization therapy (CRT) without changes in myocardial perfusion. We report on the long-term outcome of CRT in 24 patients with severe heart failure (HF) and advanced coronary artery disease not amenable for revascularization. All patients had documented myocardial ischemia on stress ⁹⁹Tc-sestamibi single-photon emission computed tomography, and all underwent successful implantations of CRT systems. The mean left ventricular ejection fraction was 21%± 4%, 19 patients (79%) had anginal complaints and 20 (83%) had diffuse three-vessel disease. During a follow-up of 13 ± 0.7 months, two patients died suddenly and one died of progressive HF. Among survivors, functional capacity decreased from New York Heart Association class 3.2 ± 1.4 to 2.1 ± 1.0 (P < 0.01), and the Minnesota questionnaire quality-of-life scores decreased from 43 ± 15 to 28 ± 13 (P < 0.01). Despite an increase from 264 ± 104 to 385 ± 121 m in distance walked in 6 minutes (P < 0.01), the number of anginal attacks/week remained unchanged (4.7 ± 0.7 to 4.5 ± 0.6). Patients with advanced HF, stable angina, and documented myocardial ischemia may undergo safe and successful implantations of CRT systems.     

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)     

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)     

Long-Term Outcomes of CRT-PM Versus CRT-D Recipients

Objective: To compare the rates of all-cause mortality in recipients of cardiac resynchronization therapy devices without (CRT-PM) versus with defibrillator (CRT-D).
Methods: Between February 1999 and July 2004, 233 patients (mean age = 69 ± 8 years, 180 men) underwent implantation of CRT-PM or CRT-D devices. New York Heart Association (NYHA) heart failure functional class II was present in 11%, class III in 69%, and class IV in 20% of patients; mean left ventricle ejection fraction (LVEF) was 26.5 ± 6.5 %, 48% presented with idiopathic dilated cardiomyopathy and 49% with ischemic heart disease. Cox multiple variable regression analysis was performed in search of predictors of death.
Results: The clinical characteristics of the 117 CRT-PM and 116 CRT-D recipients were similar, except for LVEF (28.2 ± 6.2% vs 25.0 ± 6.5%, respectively; P < 0.001), and ischemic versus nonischemic etiology of heart failure (41% vs 56%, respectively P = 0.02). Over a mean follow-up of 58 ± 15 months, no significance difference in overall mortality rate was observed between the two study groups. Male sex, NYHA functional class IV, and atrial fibrillation at implant were significant predictors of death.
Conclusions: There was no difference in long-term survival rate among patients with CRT-D versus CRT-PM, although CRT-D more effectively lowered the sudden death rate. Male sex, NYHA functional class IV, and atrial fibrillation predicted the worst prognosis.     

Understanding the Timing Cycles of a Cardiac Resynchronization Device Designed with Left Ventricular Sensing

Some devices used for cardiac resynchronization therapy (CRT) can sense from the left ventricular (LV) lead as in Biotronik CRT devices (Biotronik GmbH, Berlin, Germany), whose special LV timing cycles form the basis of this report. LV sensing (LVs) was designed to prevent competitive pacing outside the LV myocardial absolute refractory period. LVs works by inhibiting the release of an LV pacemaker stimulus (LVp) in the vulnerable period of the LV during a programmable period. LVs with stored LV electrograms may also provide recordings of diagnostic value in tachyarrhythmias. LVs has added a new dimension to the evaluation of the function of CRT devices, because it is manifested by unfamiliar timing cycles. In this respect, Biotronik devices can initiate an LV upper rate interval (URI) upon sensing a right‐sided event when LVs is turned off. An inhibited LVp can also initiate an LVURI. The LVURI should generally be programmed to a relatively short duration and shorter than the right ventricular URI to prevent a special form of desynchronization arrhythmia sustained by LVs. This arrhythmia is characterized by recurring delayed LVs events in sequences associated with RV pacing followed by LVs events with loss of LVp.     

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.     

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.     

Effects of Cardiac Resynchronization Therapy on Heart Rate Turbulence

Background: Cardiac resynchronization therapy (CRT) improves the clinical status of patients with heart failure (HF), though its effects on heart rate turbulence (HRT) are unknown.
Methods: We measured HRT indices in 58 recipients of CRT systems (mean age = 56 ± 9 years, 41 men) in New York Heart Association HF functional class III–IV, and with a left ventricular (LV) ejection fraction ≤35%. At 6 months of follow-up, 42 patients were responders and 13 nonresponders to CRT, and three patients died suddenly. The HRT indices turbulence onset (TO%) and turbulence slope (TS ms/RR interval) were calculated from digital 24-hour electrocardiogram before and after 6 months of CRT. TO ≥ 0% and TS ≤ 2.5 ms/RR interval were considered abnormal.
Results: Mean TO in the entire population was 0.4 ± 1.5 before CRT, and decreased to −0.8 ± 7.0 during the 6 months of CRT (ns). TS increased significantly from 2.0 ± 1.7 at baseline, to 3.9 ± 3.1 (P < 0.05), and a significantly lower proportion of patients had abnormal HRT indices at 6 months. In contrast to the significant increase observed in responders, not significant change in TS was observed among the nonresponders.
Conclusions: During 6 months of CRT, improvements in HRT indices and a decrease in the proportion of patients with abnormal HRT were observed. CRT may have beneficial effects on baroreflex sensitivity.     

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)