Robert Pagnanelli

Myocardial perfusion changes in patients irradiated for left-sided breast cancer and correlation with coronary artery distribution

PURPOSE To evaluate postradiation regional heart perfusion changes with single photon emission tomography (SPECT) myocardial perfusion imaging in 69 patients treated with tangential photon beams radiation therapy (RT) for left-sided breast cancer. To correlate SPECT changes with percent irradiated left ventricle (LV) volume and risk factors for coronary artery disease (CAD). METHODS AND MATERIALS Rest SPECT of the LV was acquired pre-RT and at 6-month intervals post-RT. The extent of defects (%) with a severity > 1.5 standard deviations below the mean was quantitatively analyzed for the distributions of the left anterior descending (LAD) artery, left circumflex (LCX) artery, and right coronary artery (RCA) based on computer assisted polar map reconstruction (i.e., bulls-eye-view). Changes in perfusion were correlated with percent irradiated LV receiving > 25 Gy (range 0-32%). Data on patient- and treatment-related factors were collected prospectively (e.g., cardiac premorbidity, risk factors for CAD, chemotherapy, and hormonal treatment). RESULTS In the LAD distribution, there were increased perfusion defects at 6 months (median 11%; interquartile range 2-23) compared with baseline (median 5%; interquartile range 1-14) (p < 0.001). There were no increases in perfusion defects in the LCX or RCA distributions. In multivariate analysis, the SPECT perfusion changes in the LAD distribution at 6 months were independently associated with percent irradiated LV (p < 0.001), hormonal therapy (p = 0.005), and pre-RT hypercholesterolemia (p = 0.006). The SPECT defects in the LAD distribution at 12 and 18 months were not statistically different from those at 6 months. The perfusion defects in the LAD distribution were limited essentially to the regions of irradiated myocardium. CONCLUSION Tangential photon beam RT in patients with left-sided breast cancer was associated with short-term SPECT defects in the vascular distribution corresponding to the radiation portals. Factors related to the extent of perfusion defects included the percent irradiated LV, hormonal treatment, and pre-RT hypercholesterolemia.

Repeatability and reproducibility of phase analysis of gated single-photon emission computed tomography myocardial perfusion imaging used to quantify cardiac dyssynchrony.

BackgroundA 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. MethodsPhase 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. ResultsIn 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. ConclusionA 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.

Evaluation of mechanical dyssynchrony and myocardial perfusion using phase analysis of gated SPECT imaging in patients with left ventricular dysfunction

AbstractBackground. 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.)

Myocardial Perfusion Imaging with 201Tl

The object of this review is to provide information about 201Tl-thallous chloride in radionuclide myocardial perfusion imaging. This technique has experienced a recent resurgence because of the shortage of 99mTc. After reading this article, the technologist will be able to describe the properties and uptake mechanism of 201Tl, the procedure for myocardial perfusion imaging with this agent, and the advantages and disadvantages of thallium, compared with the technetium agents.

Emerging Role of Myocardial Perfusion Imaging to Evaluate Patients for Cardiac Resynchronization Therapy

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.

Cardiovascular nuclear imaging: Balancing proven clinical value and potential radiation risk

The debate on the potential risk of radiation exposure from diagnostic imaging tests highlights the importance of balancing the demonstrated clinical benefit and the theoretic risk of cardiovascular imaging studies. The Cardiovascular Council of the Society of Nuclear Medicine upholds the responsible application of imaging studies that use radiotracers associated with relatively small amounts of ionizing radiation. Radionuclide-based cardiac imaging studies, including myocardial perfusion imaging (MPI), provide accurate diagnostic and prognostic information about patients with suspected or known heart disease. There is a large body of scientific evidence on the clinical value of MPI, based on studies performed on many thousands of patients. On the basis of this information, appropriate-use criteria and guidelines were developed and endorsed by the Society of Nuclear Medicine and other professional societies, including the American College of Cardiology, American Heart Association, and American Society of Nuclear Cardiology (1). Cardiovascular nuclear medicine studies provide highly sensitive and specific tests that may be indicated for the evaluation of diagnosis, prognosis, and treatment response of coronary artery disease, as well as for selection of patients who benefit from revascularization. The value and justification of MPI for risk assessment is based on large observational outcome studies that demonstrate accurate risk stratification with radionuclide-based MPI in populations with an intermediate pretest risk. The incremental prognostic value of SPECT MPI is greater than that of the exercise electrocardiography stress test or coronary angiography. The cost effectiveness of MPI as a gatekeeper to coronary angiography has been established after being carefully and extensively studied. Several recent publications have raised concern about the potential harmful effects of ionizing radiation associated with cardiac imaging. Review of the measurement of radiation and associated biologic effects can help put this issue into reasonable perspective. Radiation effective dose is a measure used to estimate the biologic effects of radiation. Measuring the radiation effective dose associated with diagnostic imaging is complex and imprecise and often results in varying estimates among experts (2). A typical effective dose for a rest–stress same-day SPECT scan using 99mTclabeled agents (1,110 MBq [30 mCi] stress, 370 MBq [10 mCi] rest), the most commonly used MPI protocol, is approximately 10 mSv. Other agents and protocols are associated with a wide range of radiation exposure (2). In comparison, exposure to radiation from natural sources amounts to approximately 3 mSv annually. The risk of a fatal malignancy from medical imaging–related radiation is difficult to estimate precisely but is likely small and difficult to discern from the background risk of natural malignancies. The theoretic lifetime attributable risk of cancer from a rest and stress 99mTc-based MPI study for individuals age 35 y or older is less than 1.5 in 1,000 (3). This risk is less in older patients, who constitute most patients evaluated for coronary artery disease. The estimated risk of fatal malignancy from a typical MPI study is 0.5 per 1,000 individuals, compared with a risk of death from natural cancer of 212 per 1,000 (4). The potential risk of cancer must be balanced against the risk of death, myocardial infarction, or other morbid vascular events in an appropriately referred population. This risk ranges from 1% to 10% or more per year and is orders of magnitude greater than the potential lifetime risk of cancer and death from cancer attributable to cardiovascular nuclear medicine studies. Assessment of risk-to-benefit ratio mandates a good understanding of the clinical characteristics of the patient, including risk factors for coronary artery disease, prior history of coronary artery disease, and left ventricular function. For example, given the substantially higher risk of morbid coronary events or heart failure in patients with left ventricular dysfunction, higher radiation exposure associated with 201Tl or 18F-FDG for radionuclide assessment of viability is readily justifiable. In this context, one must not fail to take into account the risks of missing important diagnostic information by not performing a test (which could potentially influence near-term management and outcomes) because of a theoretic concern about a long-term small risk of malignancy. Similarly, assessment of the significance of radiation exposure risk in population-based studies would be challenging without information on the overall pool from which the patients are selected and how representative they are of the total patient population. While the potential long-term radiation risk associated with cardiovascular nuclear medicine studies is debated (5), Received Mar. 17, 2011; revision accepted Mar. 24, 2011. For correspondence or reprints contact: Mehran M. Sadeghi, Yale University School of Medicine, 950 Campbell Ave., West Haven, CT 06516. E-mail: mehran.sadeghi@yale.edu COPYRIGHT a 2011 by the Society of Nuclear Medicine, Inc. DOI: 10.2967/jnumed.111.090654

Myocardial perfusion, function, and dyssynchrony in patients with heart failure: baseline results from the single-photon emission computed tomography imaging ancillary study of the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) Trial.

BACKGROUND There are currently limited data on the relationships between resting perfusion abnormalities, left ventricular ejection fraction (LVEF), New York Heart Association (NYHA) functional class, and exercise capacity as defined by peak VO(2) and 6-minute walk test in patients with heart failure (HF) and reduced LVEF. Furthermore, the association between resting perfusion abnormalities and left ventricular dyssynchrony is currently unknown. This article addresses the Heart Failure and A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) gated SPECT imaging (gSPECT) substudy baseline results. METHODS HF-ACTION was a multicenter, randomized controlled trial of aerobic exercise training versus usual care in 2,331 stable patients with LVEF of < or = 35% and NYHA class II to IV HF symptoms treated with optimal medical therapy. Subjects enrolled in the HF-ACTION substudy underwent resting Tc-99m tetrofosmin gSPECT at baseline (n = 240). Images were evaluated for extent and severity of perfusion abnormalities using a 17-segment and a 5-degree gradation severity score (summed rest score [SRS]). Left ventricular function and dyssynchrony were assessed using validated available commercial software. RESULTS The average age of patients enrolled was 59, 69% were male, 63% were white, and 33% were African American. Of the 240 participants, 129 (54%) were ischemic and 111 (46%) were nonischemic in etiology. The median LVEF by gSPECT for the entire cohort was 26%. Among the nuclear variables, there was a modest correlation between LVEF and SRS (r = -0.31, P < .0001) and there were stronger correlations between phase SD and SRS (r = 0.66, P < .0001) as well as phase SD and LVEF (r = -0.50, P < .0001). Patients with NYHA class III symptoms had more severe and significant degrees of dyssynchrony (median phase SD 54 degrees ) than those with NYHA class II symptoms (median phase SD 39 degrees, P = .001). Patients with an ischemic etiology had a higher SRS (P < .0001) and significantly more dyssynchrony (P < .0001) than those who were nonischemic. However, there was no difference in LVEF or objective measures of exercise capacity between these groups. With respect to peak VO(2), there was a weak correlation with LVEF (r = 0.18, P = .006) and no correlation with SRS (r = -0.04, P = 0.59) or with dyssynchrony (r = -0.13, P = .09). A weak but statistically significant correlation between SRS and 6-minute walk was observed (r = -0.15, P = .047). CONCLUSIONS Gated SPECT imaging can provide important information in patients with HF due to severe LV dysfunction including quantitative measures of global systolic function, perfusion, and dyssynchrony. These measurements are modestly but significantly related to symptom severity and objective measures of exercise capacity.

Efficiency comparison between 99mTc-tetrofosmin and 99mTc-sestamibi myocardial perfusion studies

The purpose of this investigation was to compare the efficiency of two different imaging protocols using two different clinically available 99mTc labelled myocardial perfusion tracers. One thousand one hundred and thirty-four imaging studies were performed prospectively, using either 99mTc-tetrofosmin or 99mTc-sestamibi, alternating the use of each tracer for a total period of 8 months. 99mTc-tetrofosmin rest studies were performed with injections of 259 MBq-370 MBq and imaging 30 min later. Exercise studies were performed with injections of 777 MBq-1.11 GBq and imaging 20 min later. 99mTc-sestamibi studies used doses similar to those in the 99mTc-tetrofosmin studies. Imaging followed a standard procedure, at 60 min after rest injection, and 30 min after exercise. For patients undergoing pharmacological stress testing,99mTc-sestamibi was imaged 45 min after injection and 99mTc-tetrofosmin was imaged 30 min after injection. Variables analysed were (1) injection-to-imaging time for the procedure, and (2) the number of repeated scans because of extra cardiac activity. The completion time for the rest study was significantly shorter for 99mTc-tetrofosmin compared to 99mTc-sestamibi (47.7±21.7 min vs 74.3±25.8 min P<0.0001). Likewise, the total study time was shorter for 99mTc-tetrofosmin compared to 99mTc-sestamibi (90±32.7 min vs 124±37 min, P<0.0001). More importantly, the number of repeated scans was higher with 99mTc-sestamibi compared to 99mTc-tetrofosmin, 21.4% vs 10%, P = 0.001 for rest studies and 19.7% vs 7.9% P = 0.1 for rest and stress. It was concluded that, using a same day rest/stress protocol, 99mTc-tetrofosmin provided higher patient throughput with fewer repeat scans. These factors may be considered for efficiency improvement in nuclear cardiology laboratories using 99mTc perfusion tracers.

Hiatal hernia depicted on Tc-99m sestamibi images: myocardial perfusion imaging.

A 68-year-old obese, hypertensive, diabetic woman with a history of intermittent bleeding from a hiatal hernia was examined and found to have anemia and exertional chest discomfort and dyspnea. After treatment of her anemia, she was referred for assessment of myocardial ischemia. The results of Tc-99m sestamibi rest and exercise stress myocardial perfusion images were normal. Extracardiac tracer accumulation was identified near the base of the heart on the rest study, which correlated in location to a large hiatal hernia on radiographs. Localization of Tc-99m sestamibi within the stomach likely represented reflux of tracer from the duodenum. Other considerations include free pertechnetate secretion from the gastric mucosa or gastric bleeding during tracer injection.

Relationship of technetium-99m tetrofosmin-gated rest single-photon emission computed tomography myocardial perfusion imaging to death and hospitalization in heart failure patients: results from the nuclear ancillary study of the HF-ACTION trial.

BACKGROUND We hypothesized that the severity of resting perfusion abnormalities assessed by the summed rest score (SRS) would be associated with a higher rate of adverse outcomes in patients with heart failure (HF) and reduced left ventricular (LV) ejection fraction (EF). METHODS A subset of 240 subjects from HF-ACTION underwent resting technetium-99m tetrofosmin-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). Images were evaluated using a 17-segment model to derive the SRS and additional nuclear variables. RESULTS After adjusting for prespecified covariates, SRS was significantly associated with the primary end point (hazard ratio 0.98, 95% confidence interval [CI] 0.97-1.00, P = .04), with a higher SRS corresponding to lower risk of an event. This association was not present in the unadjusted analysis. The relationship between SRS and the primary outcome was likely due to a higher event ratein patients with ischemic HF and a low SRS. The LV phase SD was not predictive of the primary outcome (hazard ratio 1.00, 95% confidence interval 0.99-1.01, P = .49). In a post hoc analysis, nuclear variables provided incremental prognostic information when added to clinical information (P = .006). CONCLUSIONS Gated SPECT MPI provides important information in patients with HF and reduced LVEF. In the adjusted analysis, SRS has an unexpected relationship with the primary end point. Phase SD was not associated with the primary end point. Rest-gated SPECT MPI provides incrementally greater prognostic information than clinical information alone.