BACKGROUND:A novel method to quantify dyssynchrony using phase analysis of single-photon emission computed tomography (SPECT) myocardial perfusion imaging has been developed. We sought to determine the prevalence of SPECT-derived mechanical dyssynchrony, and we report clinical variables which predict mechanical dyssynchrony in patients with left ventricular dysfunction. METHODS:We used a count-based Fourier analysis method to convert the regional myocardial counts from discrete frames per cardiac cycle into a continuous thickening function which allows resolution of the phase of the onset of myocardial contraction. The standard deviation of left ventricular phases (Phase SD) describes the regional phase dispersion as a measure of dyssynchrony. Significant dyssynchrony was defined as Phase SD ≥ 43°. 260 patients with left ventricular ejection fraction ≤ 35% were examined. RESULTS:The prevalence of mechanical dyssynchrony in the entire cohort of patients studied was 52%. Univariate predictors of Phase SD were age (P = .03), black race (P = .0005), QRS duration, EF, EDV, summed stress score (SSS), and summed rest score (SRS) (all P = <.0001). Black race, male gender, QRS EF, and SRS were independent predictors of SPECT-based mechanical dyssynchrony. CONCLUSIONS:Significant SPECT-based mechanical dyssynchrony is relatively common among patients with left ventricular dysfunction. In a population of patients with predominantly ischemic heart disease referred for SPECT, a reduced EF, increasing QRS duration, severity and extent of myocardial scar on SPECT imaging are independent predictors of mechanical dyssynchrony and may serve to identify patients for dyssynchrony screening.

CRT has been shown to be beneficial in the majority of patients with NYHA class III-IV symptoms, prolonged QRS duration, and an EF ≤35%. The use of imaging modalities to quantify dyssynchrony may help identify patients who may benefit from CRT, but do not meet current selection criteria. We hypothesize that patients with mild-to-moderate LV dysfunction have significant degrees of mechanical dyssynchrony.

Left ventricular (LV) dyssynchrony is an increasingly important consideration in the evaluation and management of patients with LV systolic dysfunction. Improvements in clinical status, LV remodeling, and survival have been demonstrated with the use of cardiac resynchronization therapy (CRT). The current selection criteria for patients who undergo CRT include the presence of severe LV dysfunction, significant heart failure symptoms, and electrical dyssynchrony on surface electrocardiography (wide QRS interval). However, up to 40% of patients who undergo CRT do not experience reductions in symptoms or LV functional improvement. Because electrical dyssynchrony is not synonymous with contractile or mechanical dyssynchrony, efforts have been made to more accurately quantify mechanical dyssynchrony in the hope of improving the selection of patients for CRT. These efforts have focused largely on echocardiographic measures of mechanical dyssynchrony. A novel method to quantify LV mechanical dyssynchrony has been developed using phase analysis of gated single photon-emission computed tomographic myocardial perfusion imaging. In conclusion, this report describes potential advantages, compared with other methods, of using myocardial perfusion imaging to evaluate patients for CRT; reviews the method of the phase analysis technique to quantify dyssynchrony; reviews the available evidence of its utility; and describes future directions in research.

Background . Using phase analysis of gated single photon emission computed tomography (SPECT) imaging, we examined the relation between myocardial perfusion, degree of electrical dyssynchrony, and degree of SPECT-derived mechanical dyssynchrony in patients with left ventricular (LV) dysfunction. Methods and Results . We retrospectively examined 125 patients with LV dysfunction and ejection fraction of 35% or lower. Fourier analysis converts regional myocardial counts into a continuous thickening function, allowing resolution of phase of onset of myocardial thickening. The SD of LV phase distribution (phase SD) and histogram bandwidth describe LV phase dispersion as a measure of dyssynchrony. Heart failure (HF) patients with perfusion abnormalities have higher degrees of dyssynchrony measured by median phase SD (45.5° vs 27.7°, P <.0001) and bandwidth (117.0° vs 73.0°, P =.0006). HF patients with prolonged QRS durations have higher degrees of dyssynchrony measured by median phase SD (54.1° vs 34.7°, P <.0001) and bandwidth (136.5° vs 99.0°, P =.0005). Mild to moderate correlations exist between QRS duration and phase analysis indices of phase SD ( r =0.50) and bandwidth ( r =0.40). Mechanical dyssynchrony (phase SD >43°) was 43.2%. Conclusions . HF patients with perfusion abnormalities or prolonged QRS durations have higher degrees of mechanical dyssynchrony. Gated SPECT myocardial perfusion imaging can quantify myocardial function, perfusion, and dyssynchrony and may help in evaluating patients for cardiac resynchronization therapy. (J Nucl Cardiol 2008;15:663-70.)

Cardiac resynchronization therapy (CRT) has shown benefits in patients with severe heart failure. However, at least 30% of patients selected for CRT by use of traditional criteria (New York Heart Association class III or IV, depressed left ventricular [LV] ejection fraction, and prolonged QRS duration) do not respond to CRT. Recent studies with tissue Doppler imaging have shown that the presence of LV dyssynchrony is an important predictor of response to CRT. Phase analysis has been developed to allow assessment of LV dyssynchrony by gated single photon emission computed tomography myocardial perfusion imaging. This technique uses Fourier harmonic functions to approximate regional wall thickness changes over the cardiac cycle and to calculate the regional onset-of-mechanical contraction phase. Once the onset-of-mechanical contraction phases are obtained 3-dimensionally over the left ventricle, a phase distribution map is formed that represents the degree of LV dyssynchrony. This technique has been compared with other methods of measuring LV dyssynchrony and shown promising results in clinical evaluations. In this review the phase analysis methodology is described, and its up-to-date validations are summarized.

Introduction: Diastolic dysfunction causes heart failure and decreased exercise tolerance, yet its assessment remains imperfect. We hypothesized that a novel application of two-dimensional speckle tracking echocardiography, which directly measures myocardial strain tissue mechanics, may more accurately quantify diastolic function than currently used measures. Therefore it may more sensitively detect exercise training-induced improvements in diastolic function in subjects enrolled in the NHLBI funded Peripheral Effects of Exercise on Cardiovascular Health Study (STRRIDE II). Methods: Fifteen overweight, sedentary subjects without cardiovascular disease had comprehensive echocardiograms performed before and after an eight-month exercise program. Two-dimensional speckle tracking methods were used to extract left ventricular global longitudinal strain throughout the cardiac cycle, which was analyzed for measures of diastolic function. Changes in strain derived variables were compared to conventional Doppler measures including the ratio of peak early (E) and late (A) diastolic mitral inflow velocities, early inflow to annular velocity ratio (E/e'), and isovolumic relaxation time (IVRT). Results: After exercise training, strain-based variables were unchanged (data not shown), but there were significant improvements in its first derivative, including peak longitudinal early diastolic strain rate (17.4% increase, p=0.03) and early longitudinal peak diastolic strain rate deceleration time (22.3% shorter, p=0.01). In contrast, traditional Doppler variables were unchanged, including E/A ratio (7.2% increase, p=0.29), E/e' (12.2% increase, p=0.13) and IVRT (2.3% shorter, p=0.74). Conclusions: Diastolic function can be assessed using strain analysis of speckle tracking echocardiography. Further, the data obtained are more sensitive in quantifying exercise training-induced improvements in diastolic function than traditional measures. Refinement and application of this novel methodology will enhance our understanding of diastolic function and the positive effects of exercise training.

Background Coronary artery disease is a leading cause of morbidity and mortality. Multiple imaging modalities are used to screen for significant coronary artery disease. We report the concordance between coronary computed tomography angiography (CTA) and stress cardiac positron emission tomography (CPET) to detect significant coronary artery disease, the feasibility of combining CTA and CPET in one diagnostic test, and the ability of CTA and CPET to detect significant coronary artery disease by comparison with cardiac catheterization. Methods Forty patients were prospectively enrolled and imaged with a hybrid PET/CT scanner. Eighteen patients had cardiac catheterization data for comparison. Concordance of findings between diagnostic tests was assessed by examining overall percentage in agreement, area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values. Results The overall agreement between CTA and CPET for detecting significant coronary artery disease was 76.3% with a sensitivity and specificity of 91.7 and 69.2%, respectively. The overall agreement between CTA and cardiac catheterization for detecting significant coronary artery disease was 81.3% with a sensitivity and specificity of 81.8 and 80.0%, respectively. The overall agreement between CPET and cardiac catheterization for detecting significant coronary artery disease was 77.8% with a sensitivity and specificity of 76.9 and 80.0%, respectively. Conclusion CTA and CPET can be performed in a single diagnostic test interval to simultaneously assess the extent of coronary artery disease and its hemodynamic significance. The sensitivity and specificity of CTA and CPET are similar to existing noninvasive screening tests.

Background A novel method to quantify dyssynchrony has been developed using phase analysis of gated single-photon emission computed tomography perfusion imaging. We report on the effect of variability in image reconstruction on the phase analysis results (repeatability) and on the interobserver and intraobserver reproducibility of the technique. Methods Phase standard deviation (SD) and bandwidth are phase indices that quantify dyssynchrony. To evaluate repeatability, raw data sets were processed twice in 50 patients with left ventricular dysfunction and 50 normal controls. To determine the optimal processing method, two replicated phase analysis results were obtained using automated and manual base parameter placement. Reproducibility of the phase analysis was determined using the data from 20 patients. Results In normal controls, manual base parameter placement improves repeatability of the phase analysis as measured by the mean absolute difference between two reads for phase SD (12.0° vs. 1.2°, P<0.0001) and bandwidth (33.7° vs. 3.6°, P<0.0001). Repeatability is better for normal controls than for patients with left ventricular dysfunction for phase SD (1.2° vs. 6.0°, P<0.0001) and bandwidth (3.6° vs. 26.5°, P<0.0001). Reproducibility of the phase analysis is high as measured by the intraclass correlation coefficients for phase SD and bandwidth of 0.99 and 0.99 for the interobserver comparisons and 1.00 and 1.00 for the intraobserver comparisons. Conclusion A novel method to quantify dyssynchrony has been developed using gated single-photon emission computed tomography perfusion imaging. Manual base parameter placement reduces the effect that variability in image reconstruction has on phase analysis. A high degree of reproducibility of phase analysis is observed.

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 = 98 and NICM, n = 27), and we evaluated the relationship between the sum rest and sum difference perfusion scores and mechanical 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 = 0.54) and bandwidth (r = 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 = −0.07) and bandwidth (r = −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.

Background Technetium Tc 99m gated single photon emission computed tomography (SPECT) has become the cornerstone of noninvasive risk stratification in patients with ischemic heart disease, but its role in patients with heart failure is not as well established.Study Design This study is a substudy of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) trial-a National Institutes of Health/National Heart, Lung, and Blood Institute-funded randomized controlled trial-designed to evaluate the role of exercise training in patients with heart failure due to left ventricular dysfunction. For this substudy, a total of 300 patients distributed on an approximately I : I basis between the exercise training and usual care'arms of HF-ACTION will undergo resting technetium Tc 99m gated SPECT at baseline and 12 months to compare changes in left ventricular function with exercise training. These changes, along with baseline data, will be correlated with changes in exercise parameters, inflammatory markers, and clinical outcomes: death, cardiovascular hospitalization, and quality of life scores. In a subset of patients, first-pass radionuclide ventriculography will be obtained to assess the relationship between ventricular dyssynchrony, ejection fraction, changes in exercise parameters, and outcomes.Conclusion The role of nuclear imaging in patients with heart failure remains poorly defined. This substudy aims to harness the power of a large heart failure trial (HF-ACTION) to further delineate the utility of fechnetium Tc 99m gated SPECT imaging and first-pass radionuclide ventriculography for predicting important clinical outcomes in this population.

Background. Cardiac resynchronization therapy (CRT) is approved for the treatment of patients with advanced systolic heart failure and evidence of dyssynchrony on electrocardiograms. However, a significant percentage of patients do not demonstrate improvement with CRT. Echocardiographic techniques have been used for more accurate determination of dyssynchrony. Single photon emission computed tomography (SPECT) myocardial perfusion imaging has not previously been used to evaluate cardiac dyssynchrony. The objective of this study is to evaluate mechanical dyssynchrony as described by phase analysis of gated SPECT images in patients with left ventricular dysfunction, conduction delays, and ventricular paced rhythms.Methods and Results. A novel count-based method is used to extract regional systolic wall thickening amplitude and phase from gated SPECT images. Five indices describing the phase dispersion of the onset of mechanical contraction are determined: peak phase, phase SD, bandwidth, skewness, and kurtosis. These indices were determined in consecutive patients with left ventricular dysfunction (n = 120), left bundle branch block (n = 33), right bundle branch block (n = 19), and ventricular paced rhythms (n = 23) and were compared with normal control subjects (n = 157). Phase SD, bandwidth, skewness, and kurtosis were significantly different between patients with left ventricular dysfunction, left bundle branch block, right bundle branch block, and ventricular paced rhythms and normal control subjects (all P <.001) Peak phase was significantly different between patients with right ventricular paced rhythms and normal control subjects (P =.001).Conclusions. A novel SPECT technique for describing left ventricular mechanical dyssynchrony has been developed and may prove useful in the evaluation of patients for CRT.

Captopril was the first oral angiotensin-converting enzyme (ACE) inhibitor available and, as such, has been extensively studied and in clinical use for many years. Several studies have defined captopril's efficacy in the treatment of congestive heart failure (CHF) as well as determined its safety profile. The most common adverse hematologic reactions associated with captopril use include neutropenia and agranulocytosis. This paper describes an uncommon and a potentially serious hematologic side effect associated with captopril-hemolytic anemia.

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 = 77) and QRS ≥ 120msec (n = 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 = 0.0005), skewness (2.6 vs. 3.1, p = 0.0005), and kurtosis (9.5 vs. 11.6, p = 0.003). Peak phase did not differ between these cohorts (141.2° vs. 130.0°, p = 0.68). Peak phase, phase SD, bandwidth, skewness, and kurtosis demonstrated weak correlations with QRS duration (r = 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.

Captopril was the first oral angiotensin-converting enzyme (ACE) inhibitor available and, as such, has been extensively studied and in clinical use for many years. Several studies have defined captopril's efficacy in the treatment of congestive heart failure (CHF) as well as determined its safety profile. The most common adverse hematologic reactions associated with captopril use include neutropenia and agranulocytosis. This paper describes an uncommon and a potentially serious hematologic side effect associated with captopril-hemolytic anemia.

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 = 125; normal controls, n = 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 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.