A simplified wall-based model for regional innervation/perfusion mismatch assessed by cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT to predict arrhythmic events in ischaemic heart failure.

AIMS: Cardiac 123iodine-meta-iodobenzylguanidine (123I-mIBG) single-photon emission computed tomography (SPECT) imaging provides information on regional myocardial innervation. However, the value of the commonly used 17-segment summed defect score (SDS) as a prognostic marker is uncertain. The present study examined whether a simpler regional scoring approach for evaluation of 123I-mIBG SPECT combined with rest 99mTc-tetrofosmin SPECT myocardial perfusion imaging could improve prediction of arrhythmic events (AEs) in patients with ischaemic heart failure (HF). METHODS AND RESULTS: Five hundred and two ischaemic HF subjects of the ADMIRE-HF study with complete cardiac 123I-mIBG and rest 99mTc-tetrofosmin SPECT studies were included. Both SPECT image sets were read together by two experienced nuclear imagers and scored by consensus. In addition to standard 17-segment scoring, the readers classified walls (i.e. anterior, lateral, inferior, septum and apex) as normal, matched defect, mismatched (innervation defect > perfusion defect), or reverse mismatched (perfusion defect > innervation defect). Cox proportional hazards ratios (HRs) were used to determine if age, body mass index, functional class, left ventricular ejection fraction (LVEF), B-type natriuretic peptide (BNP), norepinephrine, 123I-mIBG SDS, 99mTc-tetrofosmin SDS, innervation/perfusion mismatch SDS, and our simplified visual innervation/perfusion wall classification were associated with occurrence of AEs (i.e. sudden cardiac death, sustained ventricular tachycardia, resuscitated cardiac arrest, appropriate implantable cardioverter-defibrillator therapy). At 2-year median follow-up, 52 subjects (10.4%) had AEs. Subjects with 1 or 2 mismatched walls were twice as likely to have AEs compared with subjects with either 0 or 3-5 mismatched walls (16.3% vs. 8.3%, P = 0.010). Cox regression analyses showed that patients with a visual mismatch in 1-2 walls had an almost two times higher risk of AEs [HR 2.084 (1.109-3.914), P = 0.001]. None of the other innervation, perfusion and mismatch scores using standard 17 segments were associated with AEs. BNP (ng/L) was the only non-imaging parameter associated with AEs. CONCLUSION: A visual left ventricular wall-level based scoring method identified highest AE risk in ischaemic HF subjects with intermediate levels of innervation/perfusion mismatches. This simple technique for the evaluation of SPECT studies, which are often challenging in HF subjects, seems to be superior to the 17-segment scoring method.

SPECT myocardial perfusion imaging in liver transplantation candidates.

BACKGROUND: The optimal cardiovascular evaluation prior to liver transplantation remains controversial and includes stress echocardiography, stress MPI, cardiac CTA, and coronary angiography. This study summarizes our experience of the past decade using SPECT MPI in patients with end-stage liver disease, including patient characteristics, stress testing protocols, test results, the need for repeat testing, and downstream testing. METHODS: All patients who underwent a clinically indicated stress SPECT MPI study as part of their pre-liver transplant evaluation from 2004 to 2014 were reviewed from the Nuclear Cardiology database. Results of perfusion imaging, repeat testing, subsequent angiography, and need for revascularization were reviewed. RESULTS: A total of 2500 patients were referred for SPECT MPI, of those 111 had known CAD and 271 underwent more than one MPI study. Compared to other patients undergoing stress MPI, pre-liver transplant patients were younger, had fewer cardiac risk factors and lower prevalence of prior cardiac history, and used pharmacologic stress more often. During the study decade, patient age increased, prevalence of hypertension increased and smoking decreased, prevalence of known CAD increased, and the number of abnormal studies decreased. Abnormal perfusion results were present in 7.8% of pre-liver transplant patients compared to 34.3% of all other patients. In a multivariate model, age and lower ejection fraction were associated with an abnormal MPI result. Of the 64 patients who underwent subsequent invasive or non-invasive coronary angiography after an abnormal MPI, obstructive CAD was diagnosed in 25 patients (1.0%), non-obstructive CAD was diagnosed in 23 patients (0.9%), and normal coronaries found in 16 patients (0.6%); a total of 18 (0.7%) of these underwent coronary revascularization. The average time to repeat testing was 27.2 ± 17.9 months. In a multivariate model, younger age and exercise stress were associated with repeat testing. In only 17 patients out of 271 with a normal initial perfusion, the repeat study became abnormal. The use of stress-first imaging was successful in 80% of patients with a reduction in Tc-99m dose from 39.1 to 18.3 mCi. CONCLUSION: Abnormal SPECT MPI results in candidates for liver transplantation are infrequent compared to non-liver transplant patients and the incidence of obstructive CAD on subsequent angiography even less. Repeat testing in those on the transplant waiting list after initial normal test results appears to be of limited value. Stress-first protocols may be considered for the majority of these patients to reduce testing time and radiation exposure.

Risk stratification with vasodilator stress SPECT myocardial perfusion imaging in patients with elevated cardiac biomarkers.

BACKGROUND: Although the diagnostic accuracy and prognostic utility of vasodilator stress MPI have been well established in the non-acute setting, the efficacy of all of the vasodilator stressors in risk stratifying post-MI patients as well as the evaluation of cardiac troponin elevation of unclear etiology is not established. Accordingly, the aim of the present study was to investigate the prognostic efficacy of vasodilator stress MPI in the setting of elevated cardiac troponin to accurately risk stratify these higher-risk patients. METHODS: All patients from two tertiary centers, from 1/1/2010 through 12/31/2012, with elevated cardiac biomarkers within < 7 days and undergoing stress SPECT MPI testing were studied. Results of stress MPI were scored using a 17-segment model based on semiquantitative scoring as normal or abnormal (mild, moderate, or severe) using a total perfusion defect (TPD) of 0%, 1-10%, 10-20%, and > 20%. Mortality data through the year 2014 were obtained from the National Death Index, and survival analyses were performed. The primary endpoint was all-cause mortality with the secondary endpoint being cardiac mortality. RESULTS: A total of 503 patients were followed for an average of 33.6 ± 16.2 months, with a mean age of 69.3 years; 53.7% male; and a majority (88.7%) of them undergoing vasodilator stress. A significant increase in all-cause mortality was seen based on the severity of TPD results for all vasodilators (P < .0001) and regadenoson (P < .0001). Similar prognostic ability was seen for all-cause mortality. This association was maintained even after adjustment for cardiac risk factors, previous coronary disease, and troponin quartiles. MPI results (stress TPD and LVEF) added to traditional cardiac risk factors, and troponin values resulted in a significant incremental increase in the ability to predict all-cause and cardiac mortality, and stress TPD remained independently predictive for both all-cause and cardiac mortality in a multivariate model. CONCLUSION: Vasodilator stress (including regadenoson) MPI effectively risk stratifies patients with recently elevated cardiac biomarkers, with the increasing risk of mortality with the increasing severity of perfusion defects. It provides incremental prognostic value, in addition to clinical factors and degree of troponin elevation.

Correction to: Risk stratification with vasodilator stress SPECT myocardial perfusion imaging in patients with elevated cardiac biomarkers.

The following error (highlighted in bold below) appears in the Results section of the Abstract: A total of 503 patients were followed for an average of 33.6 ± 16.2 months, with a mean age of 69.3 years; 53.7% male; and a majority (88.7%) of them undergoing vasodilator stress. A significant increase in all-cause mortality was seen based on the severity of TPD results for all vasodilators (P < .0001) and regadenoson (P < .0001). Similar prognostic ability was seen for all-cause (this should actually be cardiac) mortality. This association was maintained even after adjustment for cardiac risk factors, previous coronary disease, and troponin quartiles. MPI results (stress TPD and LVEF) added to traditional cardiac risk factors, and troponin values resulted in a significant incremental increase in the ability to predict all-cause and cardiac mortality, and stress TPD remained independently predictive for both all-cause and cardiac mortality in a multivariate model.

Aminophylline shortage and current recommendations for reversal of vasodilator stress: An ASNC information statement endorsed by SCMR.

Pharmacologic reversal of serious or intolerable side effects (SISEs) from vasodilator stress is an important safety and comfort measure for patients experiencing such effects. While typically performed using intravenous aminophylline, recurrent shortages of this agent have led to a greater need to limit its use and consider alternative agents. This information statement provides background and recommendations addressing indications for vasodilator reversal, timing of a reversal agent, incidence of observed SISE with vasodilator stress, clinical and logistical considerations for aminophylline-based reversal, and alternative non-aminophylline based reversal protocols.

Aminophylline shortage and current recommendations for reversal of vasodilator stress: an ASNC information statement endorsed by SCMR.

Pharmacologic reversal of serious or intolerable side effects (SISE) from vasodilator stress is an important safety and comfort measure for patients experiencing such effects. While typically performed using intravenous aminophylline, recurrent shortages of this agent have led to a greater need to limit its use and consider alternative agents. This information statement provides background and recommendations addressing indications for vasodilator reversal, timing of a reversal agent, incidence of observed SISE with vasodilator stress, clinical and logistical considerations for aminophylline-based reversal, and alternative non-aminophylline based reversal protocols.

Triage of patients for attenuation-corrected stress-first Tc-99m SPECT MPI using a simplified clinical pre-test scoring model.

BACKGROUND: Stress-only Tc-99m SPECT MPI saves time and reduces radiation exposure while a normal study has a benign prognosis. However, no guidelines exist as to which patients should undergo stress-first MPI. The purpose of this study was to validate a previously published pre-test prediction scoring model and refine the stress-first triage process further if possible. METHODS: We retrospectively reviewed all patients who underwent an attenuation-corrected Tc-99m SPECT MPI over a 39-month period. Based on 17-segment model semi-quantitative scoring, a successful stress-first MPI was defined as a summed stress attenuation-corrected score ≤ 1. Based on results from multivariate analysis, the previously published prediction score (comprised eight clinical and demographic variables) was compared to triage based on coronary artery disease (CAD) status alone and with the addition of other highly associated variables. Logistic regression and Chi-squared analyses were used to determine the magnitude of variable effect and to compare model results. RESULTS: A total of 2,277 patients were included, and the prediction score successfully stratified patients into low-risk (91.1% successful stress-first), intermediate-risk (79.4%), and high-risk (50.7%) groups. Comparing the use of the prediction score to the use of a history of CAD as the only triage factor, 69.0% of patients would be accurately triaged using the prediction score with a cutoff of 7 (maximized sensitivity and specificity), while 78.6% were correctly triaged with CAD status alone (P < .0001). The addition of variables highly associated with a successful stress-first protocol (congestive heart failure [OR 3.4] and an abnormal resting ECG [OR 2.1]) to CAD status further enhanced triage accuracy to 81% (P < .0001). CONCLUSIONS: While the previously described prediction score effectively identifies patients who can successfully undergo stress-first MPI, it is cumbersome. Triaging based solely on CAD status and with the addition of other key variables is practical and provides improved predictive accuracy for successful stress-first MPI. Utilizing this simplified pre-test scoring model may allow for wider adoption of stress-first imaging protocols which have clear advantages over traditional rest-stress protocols.

Assessment of 123I-mIBG and 99mTc-tetrofosmin single-photon emission computed tomographic images for the prediction of arrhythmic events in patients with ischemic heart failure: Intermediate severity innervation defects are associated with higher arrhythmic risk.

RATIONALE: 123I-mIBG planar image heart-to-mediastinum ratios effectively risk-stratify heart failure (HF) patients. The value of single-photon emission computed tomographic (SPECT) imaging for identifying increased risk of ventricular arrhythmias is less clear. This study sought to determine if findings from simultaneous interpretation of 123I-mIBG and 99mTc-tetrofosmin SPECT are predictive of arrhythmic events (ArEs). METHODS: 123I-mIBG SPECT images from 622 patients with ischemic HF were presented in standard displays alongside 99mTc-tetrofosmin images. Consensus interpretations using a 17-segment model produced summed scores. Cox proportional hazards analyses related findings to adjudicated ArEs over 2 years. RESULTS: 471 patients had images adequate for total 17-segment scoring. There were 48 ArEs (10.2%). Neither 123I-mIBG nor 99mTc-tetrofosmin SPECT summed scores were univariate predictors. On multivariate proportional hazards analysis, the 123I-mIBG SPECT score was independently predictive of ArEs (HR: 0.975, 95% CI 0.951-0.999, P = 0.042), but HR<1 indicated that risk decreased with increasing score. This occurred because patients with intermediately abnormal SPECT studies had a higher likelihood of ArEs compared to patients with extensive abnormalities. CONCLUSIONS: The presumption of a monotonic increase in ArE risk with increasing summed 123I-mIBG SPECT score may not be correct as ischemic HF patients with abnormalities of intermediate extent appear at highest risk.

Multicenter evaluation of stress-first myocardial perfusion image triage by nuclear technologists and automated quantification.

BACKGROUND: A stress-first myocardial perfusion imaging (MPI) protocol saves time, is cost effective, and decreases radiation exposure. A limitation of this protocol is the requirement for physician review of the stress images to determine the need for rest images. This hurdle could be eliminated if an experienced technologist and/or automated computer quantification could make this determination. METHODS: Images from consecutive patients who were undergoing a stress-first MPI with attenuation correction at two tertiary care medical centers were prospectively reviewed independently by a technologist and cardiologist blinded to clinical and stress test data. Their decision on the need for rest imaging along with automated computer quantification of perfusion results was compared with the clinical reference standard of an assessment of perfusion images by a board-certified nuclear cardiologist that included clinical and stress test data. RESULTS: A total of 250 patients (mean age 61 years and 55% female) who underwent a stress-first MPI were studied. According to the clinical reference standard, 42 (16.8%) and 208 (83.2%) stress-first images were interpreted as "needing" and "not needing" rest images, respectively. The technologists correctly classified 229 (91.6%) stress-first images as either "needing" (n = 28) or "not needing" (n = 201) rest images. Their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 66.7%, 96.6%, 80.0%, and 93.5%, respectively. An automated stress TPD score ≥1.2 was associated with optimal sensitivity and specificity and correctly classified 179 (71.6%) stress-first images as either "needing" (n = 31) or "not needing" (n = 148) rest images. Its sensitivity, specificity, PPV, and NPV were 73.8%, 71.2%, 34.1%, and 93.1%, respectively. In a model whereby the computer or technologist could correct for the other's incorrect classification, 242 (96.8%) stress-first images were correctly classified. The composite sensitivity, specificity, PPV, and NPV were 83.3%, 99.5%, 97.2%, and 96.7%, respectively. CONCLUSION: Technologists and automated quantification software had a high degree of agreement with the clinical reference standard for determining the need for rest images in a stress-first imaging protocol. Utilizing an experienced technologist and automated systems to screen stress-first images could expand the use of stress-first MPI to sites where the cardiologist is not immediately available for interpretation.

An assessment of the safety, hemodynamic response, and diagnostic accuracy of commonly used vasodilator stressors in patients with severe aortic stenosis.

BACKGROUND: Increasing numbers of patients are undergoing transcatheter aortic valve replacement, which often involves assessment of coronary artery disease ischemic burden. The safety and diagnostic accuracy of vasodilator stress agents in patients with severe aortic stenosis (AS) undergoing SPECT myocardial perfusion imaging (MPI) has not been established. METHODS: Patients with severe AS (valve area <1 cm2) on echocardiography who underwent vasodilator stress SPECT MPI at two centers were identified. Patients with aortic valve intervention prior to MPI or who underwent concurrent exercise during stress testing were excluded. AS patients were matched to controls without AS based on age, gender, BMI, ejection fraction, and stress agent. Symptoms, serious adverse events, hemodynamic response, and correlation to invasive angiography were assessed. RESULTS: A total of 95 cases were identified with 45% undergoing regadenoson, 31% dipyridamole, and 24% adenosine stress. A significant change in systolic blood pressure (BP), cases vs controls, was observed with adenosine [-17.9 ± 20.1 vs -2.6 ± 24.9 P = .03)], with a trend toward significance with regadenoson [-16.8 ± 20.3 vs -9.4 ± 17.9 (P = .08)] and dipyridamole [-17.8 ± 20.6 vs -9.0 ± 12.1 (P = .05)]. The change in heart rate was significantly different only for adenosine [5.3 ± 16.8 vs 14.2 ± 10.8 (P = .04)]. Overall, 45% of cases vs 24% of controls (P = .004) had a >20 mmHg decrease in systolic BP. Age, BMI, and resting systolic BP were related to a >20 mmHg decrease in systolic BP on univariate analysis, although only higher resting systolic BP was a predictor on multivariate analysis. In 33 patients who underwent angiography, the sensitivity, specificity, and diagnostic accuracy of vasodilator stress MPI was 77%, 69%, and 73%, respectively. No serious adverse events occurred in the severe AS patients. CONCLUSION: Severe AS patients are more likely to have a hemodynamically significant decrease in systolic BP with vasodilator stress. There were no serious adverse events in this severe AS cohort with good diagnostic performance of MPI compared to angiography.

Safety of vasodilator stress myocardial perfusion imaging in patients with elevated cardiac biomarkers.

BACKGROUND: While adenosine and dipyridamole as myocardial perfusion imaging (MPI) stress agents have literature supporting their safety in the setting of myocardial infarction (MI), regadenoson does not. Studying a high risk cohort of patients with elevated cardiac biomarkers may shed light on potential safety issues of these agents which might also affect lower risk cohorts. METHODS: All patients who had undergone a clinically indicated stress MPI study at two academic centers from 1/1/2010 through 12/31/2012 with elevated troponin ≤7 days prior to testing were included. The primary endpoint was a composite of death, non-fatal MI, congestive heart failure (CHF), stroke, ventricular arrhythmias, atrial fibrillation/flutter, or atrioventricular block requiring intervention within 24 h of testing. RESULTS: Of the 703 stress MPI studies that met inclusion criteria, 360 (51.2%), 199 (28.3%), 74 (10.5%), 9 (1.3%), and 61 (8.7%) underwent regadenoson, dipyridamole, adenosine, dobutamine, and exercise stress, respectively. The primary endpoint occurred in 11 (1.6%) patients with an incidence of 1.4% (n = 5), 1.0% (n = 2), 1.4% (n = 1), 11.1% (n = 1), and 3.3% (n = 2) following regadenoson, dipyridamole, adenosine, dobutamine, and exercise stress, respectively (P = 0.137). The adverse events included non-fatal MI in 7 (1.0%) patients, death in 1 (0.1%) patient, CHF in 1 (0.1%) patient, ventricular arrhythmia in 1 (0.1%) patient, and atrial arrhythmia in 1 (0.1%) patient. CONCLUSION: In the setting of elevated troponin, serious complications associated with either exercise or vasodilator stress testing appear to be relatively rare with no increased risk attributable to a particular vasodilator agent.