Regular issue: ClinicalDeviceCardiac resynchronization therapy and the relationship of percent biventricular pacing to symptoms and survival
Introduction
Heart failure (HF) currently affects an estimated 5.8 million Americans and is one of the leading causes for hospitalization and deaths in the United States.1, 2, 3 Cardiac resynchronization therapy (CRT) has been shown to improve outcomes in patients with reduced left ventricular function in association with bundle branch block.4, 5, 6 The highest response rates to CRT correlate with maintaining a high percentage of biventricular pacing.7 Effective delivery of continuous CRT may be hindered in the presence of native ventricular condition, due to long AV delay programming, atrial tachycardia, or atrial fibrillation (AF).8, 9, 10 Although AF itself is associated with worsened outcomes in HF patients, CRT seems to improve outcomes in AF.11, 12, 13, 14, 15
No clinical trial has evaluated overall mortality and HF symptoms after device implantation in relation to percent biventricular pacing in large numbers of patients with CRT devices that regularly transmit device data and health status information over a network. Earlier studies of CRT therapy in normal sinus rhythm and in the presence of AF have suggested that a greater degree of biventricular pacing may be required to realize all of the benefits of CRT.13, 16
Technology advances now enable remote transmission of data collected and stored in CRT devices to be transmitted to protected networks. In the United States, an estimated 13,000 newly implanted implantable cardioverter-defibrillator (ICD) and CRT device patients are added to a remote network per month and over 350,000 patients transmit data regularly. These transmitted data are accessible to the physicians and provide a unique opportunity to assess device-related data in large patient cohorts.2
The ALTITUDE study was designed to address prospectively defined questions utilizing de-identified data obtained from the LATITUDE remote monitoring system (Boston Scientific Corp., Natick, Massachusetts). We sought to investigate the impact of percent biventricular pacing on mortality.
Section snippets
Methods
The LATITUDE project is an independent clinical science initiative launched in 2008 that was formed to prospectively analyze data from implanted ICD and cardiac resynchronization therapy with defibrillation (CRT-D) devices manufactured by Boston Scientific that regularly transmit information remotely. The system, LATITUDE, gained U.S. Food and Drug Administration approval in 2005 and was market released in 2006 for CRT-D and then ICD devices. Compatible devices implanted before system
Survival status
Survival status was obtained by cross-reference to the Social Security Death Index provided to Boston Scientific for implanted patients on a quarterly schedule. Follow-up for vital status data was continued for 6 months after collection of study data was closed to allow for lag time in reporting. Patients without Social Security numbers were excluded from the analysis and totaled 10% of the total population.
Percent pacing and AF burden
Percent biventricular pacing and AF burden were calculated using pacing and sensing histograms. biventricular pacing was calculated as the percent of ventricular beats paced. The burden of AF was estimated as the percent of atrial sensed beats occurring at rates greater than 180 beats/min.18, 19 Patients with an average daily burden of >0.5% were considered to have paroxysmal AF.
Symptom status
A subset of patients (n = 10,344) completed weekly patient HF symptom status questions that were transmitted as part of the weekly device remote follow-up. The questions are displayed on the remote communicator, and patients answer the same questions weekly (Table 1). Symptom data were compared with percent biventricular pacing and AF burden for each week in which symptoms were reported (Table 2).
Statistical analyses
Percent biventricular pacing and percent AF at the first remote transmission were included as baseline predictors of subsequent mortality in a Cox regression model. Paroxysmal AF at first transmission was used for stratification of patients for Kaplan-Meier mortality analysis. Percent biventricular pacing was analyzed as quartiles because this demonstrated the best fit to the data using Akaike information criterion.20 A cut-point value dividing the population into 2 pacing groups with a
Results
Patient characteristics and device programmed parameters are shown in Table 3. Patients were grouped according to the percent of biventricular pacing and AF burden, expressed as percent of daily atrial beat, >180 beats/min. The median and mean biventricular pacing at the first remote follow-up were 98.5% and 94.4%, respectively.
In the multivariate Cox regression model adjusting for estimated AF burden, age, and gender, percent biventricular pacing above the median was significantly associated
Discussion
Consistent with results from significantly smaller patient populations, in this cohort of >30,000 patients from the ALTITUDE study, mortality was inversely associated with the percentage of biventricular pacing both in the presence of normal sinus or paced atrial rhythm and when the atrial rhythm is fibrillation.7, 8, 10 A novel finding of this study is that the greatest magnitude of reduction in mortality was observed with a biventricular pacing cutoff in excess of 98%. Prior registry and
Study limitations
The analysis was performed in a retrospective patient cohort. Fusion/pseudofusion beats could not be evaluated in this study, and effective pacing may be underreported by device measures.18 Prospective studies that allow a beat-by-beat analysis of biventricular capture are required to confirm our findings.
Premature ventricular contractions may also be responsible for a reduction in biventricular pacing. Although premature ventricular contraction counters are included and reported upon device
Conclusion
In this large cohort analyzed from the ALTITUDE study, mortality was inversely associated with the percentage of biventricular pacing, and small gains in the percentage of biventricular pacing are clinically important. Further prospective studies are needed to determine whether mortality can be reduced by specific programming strategies that further increase biventricular pacing.
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Cited by (0)
Conflicts of interest: D.L.H. has received consulting fees from Medtronic Inc., St. Jude Medical, Biotronik Inc., Wiley Publishing, Sorin Medical, and Boston Scientific Corp. and royalty fees from Wiley Publishing; L.A.S. has received institutional grant support and institutional fellowship support from Boston Scientific Corp., St. Jude Medical, and Medtronic Inc. and consultant fees from Boston Scientific Corp. and St. Jude Medical; J.D.D. has received consulting fees and lecture honoraria from Boston Scientific Corp. and St. Jude Medical; F.R.G. has received consulting fees from Boston Scientific Corp.; P.A.H. has received consulting fees from Boston Scientific Corp.; J.P.B. has received consulting fees and institutional grant support from Boston Scientific Corp.; M.S. and P.W.J. are employees of Boston Scientific Corp.