Stuart W. Adler

Impact of atrial prevention pacing on atrial fibrillation burden: Primary results of the Study of Atrial Fibrillation Reduction (SAFARI) trial

BACKGROUND The role of atrial-based pacing algorithms in preventing atrial fibrillation (AF) remains controversial. The inconsistent results noted in previous trials may be due in part to differences in endpoints, pacing algorithms, and study design. SAFARI, a worldwide, prospective, randomized clinical trial, was designed to address these issues and to evaluate the safety and efficacy of a suite of prevention pacing therapies (PPTs) among patients with paroxysmal AF. METHODS AND RESULTS Patients who met standard pacemaker indications and documented symptomatic AF were implanted with a pacemaker (Vitatron Selection 9000). At 4 months, only patients with documented AF despite dual-chamber pacing were randomized to PPTs ON or PPTs OFF and followed for 6 months. Incidence of permanent AF and change in AF burden were compared between the two groups. Among the 555 patients enrolled, 240 had AF burden at 4 months and were randomized. The risk of developing permanent AF was similar in both groups (0 in the PPTs ON group vs. 3 in the OFF group). However, there was a significant reduction in AF burden between baseline and 10-month follow-up in the ON group compared with the OFF group (median decrease of 0.08 hours/day vs no change, P = .03). CONCLUSION Among patients with paroxysmal AF and standard bradycardia indications, PPTs are safe and associated with less AF burden compared with conventional pacing.

Results of the PROspective MInnesota Study of ECHO/TDI in Cardiac Resynchronization Therapy (PROMISE-CRT) Study

BACKGROUND Retrospective single-center studies have shown that measures of mechanical dyssynchrony before cardiac resynchronization therapy (CRT), or acute changes after CRT, predict response better than QRS duration. The Prospective Minnesota Study of Echocardiographic/TDI in Cardiac Resynchronization Therapy (PROMISE-CRT) study was a prospective multicenter study designed to determine whether acute (1 week) changes in mechanical dyssynchrony were associated with response to CRT. METHODS AND RESULTS Nine Minnesota Heart Failure Consortium centers enrolled 71 patients with standard indications for CRT. Left ventricular (LV) size, function, and mechanical dyssynchrony (echocardiography [ECHO], tissue Doppler imaging [TDI], speckle-tracking echocardiography [STE]) as well as 6-minute walk distance and Minnesota Living with Heart Failure Questionnaire scores were measured at baseline and 3 and 6 months after CRT. Acute change in mechanical dyssynchrony was not associated with clinical response to CRT. Acute change in STE radial dyssynchrony explained 73% of the individual variation in reverse remodeling. Baseline measures of mechanical dyssynchrony were associated with reverse remodeling (but not clinical) response, with 4 measures each explaining 12% to 30% of individual variation. CONCLUSIONS Acute changes in radial mechanical dyssynchrony, as measured by STE, and other baseline mechanical dyssynchrony measures were associated with CRT reverse remodeling. These data support the hypothesis that acute improvement in LV mechanical dyssynchrony is an important mechanism contributing to LV reverse remodeling with CRT.

Chronic performance of an active fixation coronary sinus lead

BACKGROUND Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in appropriately selected patients with heart failure. Optimal left ventricular (LV) lead placement is useful in enhancing response from CRT. Three significant obstacles to LV lead placement are patient-specific variations in coronary venous anatomy, phrenic nerve stimulation, and a significant rate of LV lead dislodgement or microdislodgement. OBJECTIVE The primary objective of this study was to determine the safety and effectiveness of the Medtronic StarFix active fixation LV lead. Secondary objectives evaluated implant success, lead placement and procedure time, lead handling and lobe deployment, additional electrical performance, and all adverse events reported in the study. METHODS There were 441 patients enrolled in this multicenter study. Standard cardiac resynchronization therapy (CRT) inclusion criteria were used. Patients were followed up for a mean of 23 months. Implant data, success with CRT, LV lead performance, clinical outcomes, and experience with LV lead revisions were prospectively evaluated. RESULTS The mean LV stimulation threshold at implant was 1.3 +/- 1 volts and was stable over time. Sensing was also excellent. In 96.3% of the implantations in this study, the physician was able to place the lead in a nonanterior position. Extracardiac (phrenic nerve) stimulation required invasive intervention in 11 subjects (2.5%). Only 3 dislodgements (0.7%) were observed. Two occurred in the first 5 implants and were attributed to inadequate engagement of the venous subbranch. CONCLUSION The Medtronic 4195 is safe and highly efficacious. It affords the physician more choices in lead placement location and has a remarkably low dislodgement rate.

Correlation of impedance minute ventilation with measured minute ventilation in a rate responsive pacemaker.

COLE, C.R., et al.: Correlation of Impedance Minute Ventilation with Measured Minute Ventilation in a Rate Responsive Pacemaker. Although rate responsive pacing based on impedance minute ventilation (IMV) is now standard, there is almost no data confirming the relationship between IMV from an implanted pacemaker and measured minute ventilation (VE) during exercise. Nineteen completely paced adults implanted with Medtronic Kappa 400 pacemakers underwent symptom‐limited maximal metabolic treadmill testing using a modified Minnesota Pacemaker Response Protocol. Minute ventilation (VE, L/min) was simultaneously measured using the flowmeter of a respiratory metabolic gas analysis system and the transthoracic impedance minute ventilation circuitry of the pacemaker. Correlation coefficients (r) were used to find the best fit line to describe the relationship between the two measurements. Mean (± SD) r values for the first, second, and third order polynomial equations and for log and exponential equations were: 0.92 ± 0.08, 0.94 ± 0.04, 0.95 ± 0.04, 0.91 ± 0.06, and 0.91 ± 0.07, respectively. None of the r values were statistically different from the first order equation. Transthoracic IMV as measured by the Medtronic Kappa 400 is closely correlated to measured minute ventilation and is represented well by a first order (linear) equation.

Intramural dyssynchrony from acute right ventricular apical pacing in human subjects with normal left ventricular function.

Ventricular pacing causes early myocardial shortening at the pacing site and pre-stretch at the opposing ventricular wall. This contraction pattern is energetically inefficient and may lead to decreased cardiac function. This study was designed to describe the acute effects of right ventricular apical (RVa) pacing on dyssynchrony and systolic function in human subjects with normal left ventricular (LV) function and compare these effects to pacing from alternate ventricular sites. Patients (n = 26) undergoing an electrophysiology evaluation were studied during atrial pacing (AAI) and dual chamber pacing from the RVa, left ventricular free wall (LVfw), and the combination of RVa and LVfw (BiV). Tissue Doppler imaging was used to measure intramural dyssynchrony by utilizing an integrated cross-correlation synchrony index (CCSI) from the apical 4-chamber view. RVa and BiV pacing significantly reduced systolic function as measured by longitudinal systolic contraction amplitude (SCAlong) (p < 0.05) and LV velocity time integral (VTI) (p < 0.05) compared to AAI and LVfw pacing. RVa (and to a lesser extent BiV) pacing resulted in septal and lateral intramural dyssynchrony as indicated by significantly (p < 0.05) lower CCSI values as compared to AAI. CCSI was significantly (p < 0.05) worse during RVa than LVfw pacing. In patients with normal LV function, acute ventricular pacing in the RVa alone, or in conjunction with LVfw pacing (BiV), results in impaired regional and global LV systolic function and intramural dyssynchrony as compared to LVfw pacing alone.

Influence of Posture, Breathing Pattern, and Type of Exercise on Minute Ventilation Estimation by a Pacemaker Transthoracic Impedance Sensor

Previous studies have shown a high correlation between transthoracic impedance minute ventilation (IMV) determined by a pacemaker sensor and actual minute ventilation (VĖ) measured by standard methods. We hypothesized that several factors (e.g., posture, breathing pattern, and exercise type) could potentially affect the calibration between IMV and VĖ. In patients with Medtronic Kappa 400 pacemakers, VĖ (L/min) was monitored using a standard cardiopulmonary metabolic gas analysis system with simultaneous recording of IMV (ohms/min) using DR‐180 extended telemetry monitors. Effects of posture and of breathing pattern at rest (19 patients; age 60 ± 13 years) were evaluated by monitoring each patient under three conditions: (a) slow breathing, supine, (b) slow breathing, sitting, and (c) shallow breathing, supine. Calibration at rest was defined as the ratio of IMV to VĖ. Effect of type of exercise on calibration compared treadmill versus graded bicycle ergometer exercise (18 patients; age 62 ± 14 years). Calibration during exercise was defined as: (a) “Begin” (the IMV to VĖ ratio at VĖ =10 L/min, the typical VĖ value at beginning of exercise), and (b) slope of the IMV/VĖ regression line. Calibration of IMV/VĖ was significantly smaller for sitting versus supine position (0.7130.177, P ≤ 0.001) and for shallow versus slow breathing (0.7210.373, P < 0.001), and larger for treadmill versus bicycle exercise (Begin: 1.240.43, P = 0.018; Slope: 1.260.42, P = 0.013). In conclusion, posture, breathing pattern, and type of exercise affect the IMV estimation of the actual VĖ, possibly by altering the static or dynamic geometry (thus, the impedance) of the intrathoracic viscera.

Rate Responsive Pacing Using Transthoracic Impedance Minute Ventilation Sensors: A Multicenter Study on Calibration Stability

DURU, F., et al.: Rate Responsive Pacing Using Transthoracic Impedance Minute Ventilation Sensors: A Multicenter Study on Calibration Stability. Previous studies showed that transthoracic impedance. Previous studies showed that transthoracic impedance minute ventilation (IMV), as measured by a pacemaker sensor, is closely correlated to actual minute ventilation (VE·) determined by standard methods. The aim of this study was to analyze the changes in the calibration between IMV and VE· at rest and during exercise over time. Fifteen patients (age 60 ± 13 years) with Medtronic Kappa 400 pacemakers completed a baseline visit followed by two visits separated by 1 month and 1 week, respectively. In each patient, VE· (L/min) was monitored at rest in the supine and sitting positions and during graded bicycle ergometer exercise using a standard cardiopulmonary metabolic gas analysis system with simultaneous recording of IMV (Ω/min) using DR‐180 extended telemetry monitors. Calibration at rest was defined as the ratio of IMV to VE·, calculated from 1‐minute average values in the supine and sitting positions. Calibration during bicycle exercise was defined as intercept (IMV value at VE·= 10 L/min‐typical VE· value at beginning of exercise), and slope of the IMV/VE· regression line. The calibration of IMV showed individual variability over time. The magnitude (absolute value) of observed fractional changes in calibration at 1 month was 0.23 ± 0.20 (rest‐supine), 0.20 ± 0.15 (rest‐sitting), 0.18 ± 0.19 (exercise‐intercept), 0.28 ± 0.35 (exercise‐slope), and 0.18 ± 0.15, 0.15 ± 0.09, 0.28 ± 0.39, and 0.27 ± 0.15, respectively, at 1 week. The magnitude of change at 1 month was not statistically different from the magnitude of change at 1 week. In conclusion, the calibration of IMV, as measured by a pacemaker sensor, versus actual VE· may demonstrate variability. However, this study also suggests that the observed changes are not cumulative over time. These results have implications for patient monitoring applications using these sensors and for development of future pacemaker rate response algorithms.

Echocardiographic Improvements with Pacemaker Optimization in the Chronic Post Cardiac Resynchronization Therapy Setting

The current study assessed the acute effects of pacemaker optimization (PMO) on cardiac function using echocardiographic (ECHO) tissue Doppler imaging (TDI) in the post CRT setting. Data were analyzed from 50 consecutive patients clinically referred for PMO. Patients underwent a sequential ECHO/TDI-guided PMO study to determine optimal pacemaker settings. In 34 of 50 patients a change in pacemaker settings was made because of an objective improvement in ECHO/TDI findings. Overall, significant improvements were observed for ECHO/TDI measures of systolic function (global systolic contraction score, p < 0.001; ejection time, p < 0.05), diastolic function (diastolic filling period, p < 0.01; mitral velocity-time integral, p < 0.05) and left ventricular (LV) dyssynchrony (standard deviation of time to peak displacement, p < 0.05). In most patients referred for chronic PMO, ECHO/TDI-guided PMO can be used to objectively improve cardiac systolic function, diastolic function and/or LV dyssynchrony.

Cardiac resynchronization therapy in the real world: comparison with the COMPANION study.

BACKGROUND Several clinical trials have confirmed that cardiac resynchronization therapy (CRT) improves outcomes in well defined patient populations. It is uncertain, however, whether outcomes are similar in real-world clinical settings. This study compared outcomes after CRT with defibrillator (CRT-D) in a large real-world private-practice cardiology setting with those in the COMPANION multicenter trial. METHODS AND RESULTS A total of 429 consecutive patients who received CRT-D for standard indications (group 1) were retrospectively compared with the 595 patients (group 3) in the COMPANION CRT-D cohort regarding survival and survival free of cardiovascular (CV) hospitalization. A subgroup of the group 1 patients who met the COMPANION entrance criteria (group 2) was also compared with the COMPANION cohort (group 3) both with and without propensity-matching statistical analysis. Survival and survival free of CV hospitalization was better in group 1 than in group 3. Survival in group 2 with and without propensity matching was similar to group 3. However, survival free of CV hospitalization was better in the real-world patients (group 2) even after adjustment for differences in baseline characteristics. CONCLUSIONS Survival and CV hospitalization outcomes in a real-world clinical setting are as good as, or better than, those demonstrated in the COMPANION research trial.

Extraction of chronically implanted coronary sinus leads active fixation vs passive fixation leads

BACKGROUND The Medtronic model 4195 (StarFix) left ventricular lead is an active fixation lead that provides additional support within the coronary sinus (CS) via deployable lobes. While this lead has been shown to have excellent stability within the CS, concerns about its extractability have been raised. OBJECTIVE The aim of this study was to compare the safety and efficacy of the extraction of the model 4195 lead vs other Medtronic CS leads in a prospective cohort study. METHODS Patients undergoing extraction of this and other CS leads for standard indications were prospectively enrolled and studied. The primary outcomes of interest were the removal success rates and associated complication rates. Patients were followed for a month postprocedure. RESULTS The overall left ventricular lead extraction success rate was 97.6% (n = 205). Among 40 patients with chronic model 4195 leads, there were 37 successful extractions (92.5%) as compared to 98.8% for the 165 non-4195 leads. However, in 2 of the 3 StarFix lead extraction failures, standard extraction techniques were not used. All 10 of the model 4195 leads that had been implanted for less than 6 months were extracted without incident. CONCLUSION In this largest study of CS lead extractions published to date, the overall success rate of the extraction of chronically implanted CS leads is high and the complication rate is similar in these lead models. The extraction of the model 4195 lead is clearly more challenging, but it can be accomplished in high-volume extraction centers with experienced operators. It is recommended that the model 4195 lead be extracted by experienced operators.