Patients with Ischemic Cardiomyopathy Have Higher Degrees of Dyssynchrony Than Patients with Non-Ischemic Cardiomyopathy as Measured by Phase Analysis of Gated SPECT Perfusion Imaging

The 11th Annual Scientific Meeting independent samples t-test for continuous variables and Fishers Exact Test for categorical variables. Spearman correlation was calculated between select variables and both post-diagnosis/post-ICD implant survival time. Results: ICDs were placed predominantly for secondary prevention following aborted sudden death or in patients otherwise deemed to be at high risk for ventricular arrhythmias. Among the total sample size of 24 patients, 19 patients died during the follow-up period. Mean time from diagnosis to death was 505 days and mean time from ICD implantation to death was 450 days in these patients. Baseline clinical parameters of the group included left ventricular (LV) ejection fraction of 0.55 6 0.09, posterior wall thickness of 15 6 3 mm, LV mass of 243 6 101g, LV end-diastolic dimension of 42 6 9mm, PR interval of 191 6 28ms, QRS duration of 102 6 29ms and corrected QT interval of 451 6 29ms. Comparison of means between survivors and non-survivors across variables did not show significant differences. Conclusions: The prognosis of patients with cardiac amyloidosis remains very poor despite ICD implantation, with little predictive insight provided by standard clinical measures. The potential survival benefit of such therapy appears to be lower when compared to patients with other causes of nonischemic cardiomyopathy. Further evaluation of ICD implantation in cardiac amyloidosis by a randomized prospective study is warranted.

180 Mortality Outcomes According to Frequency of Right Ventricular Pacing (RVP): Does More RVP Shorten Survival? Brent Lampert1, Hans Moore2, Steven Singh2, Brian Lewis2, Ross Fletcher2, Pamela Karasik2; 1Georgetown University Hospital, Washington, DC; 2Veterens Affairs Medical Center, Washington, DC Introduction: Right ventricular pacing (RVP) has been associated with adverse outcomes, such as congestive heart failure and death. Despite the lack of conclusive randomized clinical trials, minimizing RVP has become a therapeutic goal. The Eastern Pacemaker Surveillance Center (EPSC) maintains a large database of transtelephonic monitoring records (TTMs) and outcomes. It provides the opportunity to retrospectively address the question ‘‘Does more RVP shorten survival?’’ Methods: Patients with permanent pacemakers implanted between January 1, 1995 and December 31, 2005 were analyzed. Average frequency of RVP on TTMs was validated using regression analysis as a satisfactory surrogate for overall frequency of RVP measured by direct pacemaker interrogation. Patients with less than 20% RVP and those with greater than 80% RVP were compared. Mortality outcomes were analyzed as average time to death following pacemaker insertion. Results: From the EPSC registry, 7198 patients were identified with six or more TTMs (Mean 5 21 TTMs). When at least six TTMs were available there was a strong correlation (R2 5 0.75) between average frequency RVP compared to logged overall frequency RVP obtained from pacemaker interrogations. The average follow-up was 5.3 years. The average age at time of pacemaker implant was significantly higher in the group with O 80% RVP (72 vs. 67 years; p ! 0.0001). There were an equal proportion of deaths in each group: 1113 deaths (22%) in 4968 patients with O 80% RVP, and 126 deaths (22%) in 565 patients with ! 20% RVP. However the duration of survival, measured as average time to death following pacemaker implantation, was 4.7 years with O 80% RVP, and only 4.3 years with ! 20% RVP (p ! 0.0001). Conclusions: Following pacemaker implantation, survival with O 80% RVP was longer than with ! 20% RVP, in this unselected population. Review of this large clinical database suggests that more frequent RVP does not shorten survival. Prospective studies would be needed to validate these findings.



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CHF 6 weeks after termination of pacing, transmural endocardial-to-epicardial conduction time shortened compared to CHF (10 6 9 vs. 39 6 1 ms, p 5 0.006). Conclusions: Electrical intramural dyssynchrony develops as a consequence of pacing-induced CHF. Additionally, there is evidence of reversal of electrical intramural dyssynchrony upon recovery of cardiac function. This novel finding suggests another aspect of overall ventricular dyssynchrony that may not be reflected on surface ECG or by routine noninvasive modalities. The benefit of cardiac resynchronization therapy for intramural dyssynchrony is unclear and yet to be defined.

182 Comparison of CRT-D Device Diagnostics in HF Patients with and without Diabetes Mellitus Andrew Kaplan1, Haresh Sachanandani2, Jon Peterson2, Chris Mullin2, Kellie Berg2; 1 Cardiovascular Associates of Mesa, Mesa, AZ; 2Boston Scientific CRM, St. Paul, MN Introduction: Diabetes Mellitus (DM) is an independent predictor of heart failure (HF) and a prevalent co-morbidity. DM patients with HF (DM-HF) have worse outcomes than non-diabetics with HF (ND-HF). BSC CRM RENEWALÔ cardiac resynchronization (CRT) devices measure patient activity, minimum heart rate, and heart rate variability (HRV), an indicator of autonomic tone. While HF and DM are known to reduce HRV, measures of autonomic tone have rarely been studied in the DM-HF population. Methods: 1232 patients were enrolled in the Cardiac Resynchronization Therapy Registry Evaluating Patient Response with RENEWAL Family Devices (CRT RENEWAL) study. 959 patients having sufficient device baseline clinical data were analyzed. Two-sided Student’s t-test and Chi-Squared test were used to analyze differences between groups and interactions of variables and repeated measures regression models were used to compare diagnostics between groups over time. Results: DM was reported in 33.7% of the study patients. An increased prevalence of ischemic cardiomyopathy and hypertension besides significantly increased BMI and systolic BP was observed in the DM-HF group, while LVEF, NYHA class and diastolic BP were not different. The DM-HF group had a higher number of HF decompensation events (16.1% vs. 8.2%, p ! 0.001). Minimum HR (D 5 2.9, p ! 0.001) was higher, while SDANN (D 5 10.3, p ! 0.001), Foot% (D 5 4.1, p ! 0.001) and Activity Log (D 5 0.8, p ! 0.001) were lower in the DM-HF group compared to the ND-HF group after adjusting for baseline factors. These diagnostics were not significantly different between the Type I and Type II DM-HF patients, although Type I patients tended towards higher minimum HR and Activity and lower SDANN and Foot%. Conclusions: CRT device-based measures of HRV and Activity differ significantly between DM-HF and ND-HF subjects. Further analysis is required to determine how these differences may be useful in evaluating relative risk of DM-HF and ND-HF patients, and differentiating diabetic therapy.

CRT RENEWAL Baseline Characteristics Variable Ischemic (%) BMI Systolic BP Hypertension (%)

Diabetics (N 5 323)

Non-Diabetics (N 5 636)

P value

213 (65.9%) 30.6 6 6.6 125.2 6 19.1 247 (76.5%)

331 (52%) 28.1 6 6.1 122.3 6 19.1 367 (57.7%)

! 0.001 ! 0.001 0.03 ! 0.001

181 Intramural Electrical Dyssynchrony in Pacing-Induced Congestive Heart Failure Nilesh Mathuria1, Jianwen Wang2, Robert L. Hood2, April L. Gilbert2, Daryl G. Schulz2, Liyun Rao2, Jeff Siou3, Mihir Naware3, Dorin Panescu3, Hue-Te Shih2, Sherif F. Nagueh2, Dirar S. Khoury2; 1Cardiology, Baylor College of Medicine, Houston, TX; 2Cardiology, Methodist Hospital Research Institute, Houston, TX; 3 CRMD, St. Jude Medical, Sylmar, CA Introduction: Inter and intra-ventricular dyssynchrony can develop as a consequence of congestive heart failure (CHF). The purpose of this study was to investigate intramural electrical conduction properties within the left ventricular (LV) wall during CHF. Hypothesis: Electrical dyssynchrony develops within the LV wall in pacinginduced CHF. Methods: Biventricular pacemakers were implanted in 8 normal mongrel dogs (mean weight: 38 kg), and continuous rapid right ventricular pacing (rate: 230 bpm) was initiated to induce CHF. Echocardiography and catheterization were performed biweekly while pacing was temporarily stopped. At each catheterization, an intracardiac electrode-catheter was placed at the LV endocardium precisely opposite to the pacemaker coronary sinus lead tip located at the LV epicardium. Intrinsic transmural electrical conduction delay was assessed by recording endocardial electrograms via the electrode catheter and epicardial electrograms via the pacemaker coronary sinus lead, both in posterolateral LV. After inducing CHF, pacing was stopped in 4 dogs to allow for recovery of systolic function. All times were corrected for heart rate. Results: All dogs developed CHF within 2-4 weeks of pacing from baseline (EF: 27 6 8 vs. 49 6 4%; LV end-diastolic pressure: 20 6 9 vs. 6 6 3 mmHg; QRS: 98 6 8 vs. 70 6 14 msec with no LBBB). Transmural endocardialto-epicardial intrinsic electrical conduction time lengthened during CHF compared to baseline (35 6 13 vs. 10 6 5 ms, p ! 0.001). In four dogs recovering from

183 Patients with Ischemic Cardiomyopathy Have Higher Degrees of Dyssynchrony Than Patients with Non-Ischemic Cardiomyopathy as Measured by Phase Analysis of Gated SPECT Perfusion Imaging Mark A. Trimble1,4, Salvador Borges-Neto1,4, Emily F. Honeycutt4, Ji Chen2, Ernest V. Garcia2, Ami E. Iskandrian3, Eric J. Velazquez1,4; 1Duke University Medical Center, Durham, NC; 2Emory University Medical Center, Atlanta, GA; 3The University of Alabama at Birmingham, Birmingham, AL; 4Duke Clinical Research Institute, Durham, NC Introduction: Cardiac resynchronization therapy (CRT) is used for the treatment of patients with severe heart failure. Approximately 30% of patients do not respond to CRT when QRS duration is used to measure dyssynchrony. We compared the degree of dyssynchrony as measured by phase analysis of gated SPECT perfusion imaging in subjects with ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM), and we describe the relationship between resting perfusion defects and myocardial ischemia and the quantification of dyssynchrony. Hypothesis: Subjects with ICM have higher levels of dyssynchrony than subjects with NICM. Methods: We developed a Fourier analysis method which converts regional myocardial counts from the discrete frames per cardiac cycle into a continuous thickening function which allows fine temporal resolution of the phase of the onset of myocardial thickening and its corresponding amplitude. Phase SD, the standard deviation of the distribution of the phase angles, and histogram bandwidth are indices used to quantify mechanical dyssynchrony. We compared these indices in 125 subjects with left ventricular dysfunction (ICM, n 5 98 and NICM, n 5 27), and we evaluated the relationship between the sum rest and sum difference perfusion scores and mechanical

S128 Journal of Cardiac Failure Vol. 13 No. 6 Suppl. 2007 dyssynchrony. Results: The degree of dyssynchrony was significantly higher in subjects with ICM when compared with subjects with NICM as measured by the Phase SD (49.3  vs. 28.0  , p ! .0001) and bandwidth (138.7  vs. 88.9  , p ! .0001). The sum rest perfusion score demonstrated moderate correlation with the degree of mechanical dyssynchrony as measured by the phase SD (r 5 0.54) and bandwidth (r 5 0.51). There was no correlation between myocardial ischemia as described by the sum difference score and the degree of dyssynchrony as measured by the phase SD (r 5 0.07) and bandwidth (r 5 0.07). Conclusions: A novel technique to quantify mechanical dyssynchrony has been developed. Subjects with ICM have higher degrees of dyssynchrony than subjects with NICM. There is a moderate correlation between myocardial perfusion defects and ventricular dyssynchrony. There is no relationship between myocardial ischemia and ventricular dyssynchrony.

184 Heart Failure Patients with Prolonged QRS Duration Have Higher Degrees of Mechanical Dyssynchrony as Measured by Phase Analysis of Gated SPECT Perfusion Imaging Than Patients with Normal QRS Duration Mark A. Trimble1,4, Eric J. Velazquez1,4, Emily F. Honeycutt4, Ji Chen2, Ernest V. Garcia2, Ami E. Iskandrian3, Salvador Borges-Neto1,4; 1Duke University Medical Center, Durham, NC; 2Emory University Medical Center, Atlanta, GA; 3The University of Alabama at Birmingham, Birmingham, AL; 4Duke Clinical Research Institute, Durham, NC Introduction: Cardiac resynchronization therapy (CRT) is approved for treatment of patients with advanced heart failure and a prolonged QRS duration. Approximately 30% of patients do not benefit from CRT. QRS duration may not reflect the degree of mechanical dyssynchrony. A new method to quantify dyssynchrony has been developed using phase analysis of gated SPECT perfusion imaging. We compared the degrees of dyssynchrony in heart failure patients with prolonged and normal QRS duration and evaluated the correlation between QRS duration and mechanical dyssynchrony. Hypothesis: Subjects with prolonged QRS duration have higher degrees of dyssynchrony than subjects with normal QRS duration. Methods: We developed a Fourier analysis method to convert the regional myocardial counts from discrete frames per cardiac cycle into a continuous thickening function which allows fine temporal resolution of the phase of the onset of myocardial thickening and its corresponding amplitude. Five indices describe the dispersion of the regional left ventricular timing of the onset of mechanical contraction including peak phase, phase standard deviation (SD), bandwidth, skewness, and kurtosis. We compared these indices in subjects with left ventricular dysfunction and QRS ! 120msec (n 5 77) and QRS $ 120msec (n 5 48) and evaluated the correlation of these indices with QRS duration. Results: The degree of dyssynchrony was higher in subjects with prolonged QRS duration as measured by phase SD (57.2  vs. 36.9  , p ! .001), bandwidth (154.8  vs. 111.2  , p 5 0.0005), skewness (2.6 vs. 3.1, p 5 0.0005), and kurtosis (9.5 vs. 11.6, p 5 0.003). Peak phase did not differ between these cohorts (141.2  vs. 130.0  , p 5 0.68). Peak phase, phase SD, bandwidth, skewness, and kurtosis demonstrated weak correlations with QRS duration (r 5 0.12, 0.50, 0.40, -0.26, and -0.09 respectively). Conclusions: A novel method to quantify left ventricular dyssynchrony has been developed. There are higher amounts of dyssynchrony in heart failure patients with prolonged QRS durations, but the degree of mechanical dyssynchrony does not correlate strongly with QRS duration. More precise measurement of dyssynchrony may improve patient selection for CRT.

demonstrated moderate correlation with left ventricular mass with correlation coefficients of 0.66, 0.62, -0.67, and -0.56 respectively. Peak phase did not correlate with LVEF, ESV, or left ventricular mass with correlation coefficients of -.03, -.05, and -0.07 respectively. Conclusions: The degree of dyssynchrony is negatively correlated with LVEF and positively correlated with ESV and mass. Phase SD, bandwidth, skewness, and kurtosis used to quantify dyssynchrony have moderately strong correlations with left ventricular ejection fraction, end-systolic volume, and mass.

186 Cardiac Resynchronization Therapy Improves Renal Function in Heart Failure Patients with Reduced Glomerular Filtration Rate Guido Boerrigter1, Lisa C. Costello-Boerrigter1, William T. Abraham2, Martin G. St. John-Sutton3, Denise M. Heublein1, Kristin M. Kruger4, Michael R.S. Hill4, Peter A. McCullough5, John C. Burnett1; 1Mayo Clinic and Mayo Clinic College of Medicine, Rochester, MN; 2Ohio State University, Columbus, OH; 3University of Pennsylvania Medical Center, Philadelphia, PA; 4Medtronic, Inc., Minneapolis, MN; 5William Beaumont Hospital, Royal Oak, MI Background: Renal dysfunction has emerged as an important independent prognostic factor in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves functional status and left ventricular (LV) function in HF patients with ventricular dyssynchrony. We hypothesized that CRT would also improve glomerular filtration rate as estimated by the abbreviated MDRD equation (eGFR) in patients with reduced eGFR. Methods: This is a retrospective analysis of the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study, which evaluated CRT in HF patients with NYHA class III-IV, ejection fraction # 35%, QRS $ 130 ms, and stable medical regimen. Patients were evaluated before implantation and 6 months after randomization to control (CRT device OFF, n 5 225) or CRT (n 5 228). Patients were categorized according to their baseline eGFR: $ 90 (category A), 60 # eGFR ! 90 (category B), and 30 # eGFR ! 60 (category C) mL/min per 1.73m2. Results: At baseline, reduced eGFR was associated with ischemic etiology, increased age, mitral regurgitation, and neurohumoral activation. CRT increased LV ejection fraction and decreased LV volumes and mitral regurgitation in all categories. Importantly, CRT improved eGFR (p 5 0.003) and reduced blood urea nitrogen (p 5 0.008) compared to control in category C, but not A and B (Figure). In addition, only in category C did atrial natriuretic peptide decrease, suggesting reduced atrial distention and filling pressures with CRT in this group with impaired eGFR. Conclusions: CRT increased eGFR and reduced blood urea nitrogen in HF patients with reduced baseline eGFR. By improving cardiac function, CRT can indirectly improve renal function, underscoring the importance of cardiorenal interaction and providing another mechanism for the beneficial effects of CRT.

185 Relationship between Mechanical Dyssynchrony as Measured by Phase Analysis of Gated SPECT Perfusion Imaging and Cardiac Structure and Function Mark A. Trimble1,4, Salvador Borges-Neto1,4, Ji Chen2, Ernest V. Garcia2, Ami E. Iskandrian3, Eric J. Velazquez1,4; 1Duke University Medical Center, Durham, NC; 2 Emory University Medical Center, Atlanta, GA; 3The University of Alabama at Birmingham, Birmingham, AL; 4Duke Clinical Research Institute, Durham, NC Introduction: Cardiac resynchronization therapy (CRT) is used for the treatment of patients with advanced heart failure. However, 30% of patients fail to benefit. More precise measurements of dyssynchrony may improve patient selection for CRT. A new method to quantify dyssynchrony has been described using phase analysis of gated SPECT perfusion imaging. The objective of this study is to describe the relationship between the phase analysis indices used to quantify dyssynchrony and left ventricular ejection fraction (LVEF), end-systolic volume (ESV), and mass. Hypothesis: The degreee of dyssynchrony will negatively correlate with LVEF and positively correlate with ESV and mass. Methods: We developed a Fourier analysis method to convert the regional myocardial counts from the discrete frames per cardiac cycle into a continuous thickening function which allows fine temporal resolution of the phase of the onset of myocardial thickening and its corresponding amplitude. Five indices are used to describe the dispersion of the regional left ventricular timing of the onset of mechanical contraction including peak phase, phase standard deviation (SD), bandwidth, skewness, and kurtosis. We evaluated the correlation of these indices with LVEF, ESV, and mass in 200 subjects (left ventricular dysfunction, n 5 125; normal controls, n 5 75) Results: Phase SD, bandwidth, skewness, and kurtosis demonstrated moderate correlation with LVEF with correlation coefficients of -0.71, -0.69, 0.74, and 0.62 respectively. Phase SD, bandwidth, skewness, and kurtosis demonstrated moderate correlation with ESV with correlation coefficients of 0.71, 0.66, -0.67, and -0.54 respectively. Phase SD, bandwidth, skewness, and kurtosis

187 Impact of Permanent Pacing in Patients with Cardiac Amyloidosis: A Single Center Experience Tracy Webster1, Grace Lin1, Traci Jurrens1, Angela Dispenzieri1, Robert Kyle1, Martha Grogan1, Peter A. Brady1; 1Cardiovascular Diseases, Mayo Clinic, Rochester, MN Background: Cardiac involvement occurs in subtypes of amyloidosis may result in bradyarrhythmias. Whether differences in sinus node function or conduction system disease exist in patients with primary systemic (AL) or transthyretin (senile or familial) amyloidosis is unknown. In addition, it is not clear whether the presence of sinus node function or conduction system disease or pacemaker implantation alter outcomes in cardiac amyloidosis (CA) in this population. Objectives: To determine the impact of permanent pacemaker implantation on outcomes from CA. Methods: We reviewed our single center experience at Mayo Clinic with pacemakers in CA patients between 2000 and 2005. All clinical, pathological, and echocardiographic data were prospectively obtained and retrospectively analyzed. Survival of CA patients