Stress-First Myocardial Perfusion Imaging.

Stress-first approaches to myocardial perfusion imaging provide diagnostically and prognostically accurate perfusion data equivalent to a full rest-stress study while saving time in the imaging laboratory and reducing the radiation exposure to patients and laboratory staff. Unfortunately, implementing a stress-first approach in a nuclear cardiology laboratory involves significant challenges such as the need for attenuation correction, triage of patients to an appropriate protocol, real-time review of stress images, and consideration of differential reimbursement. Despite it being best practice for both the patient and the laboratory, these impediments have kept the proportions of studies performed stress-first relatively unchanged in North America and world-wide in the last 10 years.

Buccal caffeine strips for reversal of adverse symptoms of vasodilator stress.

BACKGROUND: Due to recurrent shortages of aminophylline, intravenous caffeine has emerged as a commonly used, safe and reliable method to treat adverse effects of vasodilator stress agents. We sought to evaluate the safety and effectiveness of buccal caffeine strips which are rapidly absorbed, inexpensive, readily available, and simplify caffeine administration. METHODS: Consecutive patients undergoing regadenoson stress SPECT MPI were assessed for the occurrence of symptoms during testing over an 11-week period at a single metropolitan hospital. Adverse symptoms, including their severity and duration, were recorded at the time of testing. Patient satisfaction was rated on a scale of 1 to 5 (5 being the most satisfied). Patients received reversal with caffeine if symptoms were felt to be significant enough by the patient and physician performing the test. The treatment received alternated week to week between IV caffeine (60 mg) or 100 mg buccal caffeine strips. Caffeine was given at least 3 minutes after tracer injection. A rescue dose of IV caffeine was offered 10 minutes later if indicated. RESULTS: Of the 122 patients enrolled in the study, 70 (57%) were included during buccal caffeine weeks and 52 (43%) during IV caffeine weeks, and only 28 (24%) received reversal with a caffeine agent. Seven (6%) received IV caffeine and 21 (17%) received buccal caffeine. There was no significant difference in symptom duration between IV and buccal caffeine after treatment (152.8 vs 163.4 seconds, P = 0.87). There was no significant difference in initial and final symptom severity between groups. Only 2 patients in the buccal group required rescue IV caffeine for ongoing symptoms and emesis. None of the IV group required a rescue dose. There was no significant difference in patient satisfaction between the groups (2.8 vs 3.2, P = 0.38). CONCLUSION: Buccal caffeine strips are a safe, well tolerated, and effective initial strategy to reverse adverse effects of vasodilator stress in the minority of patients who request it. Buccal caffeine alone or with IV rescue caffeine was highly effective in reversing adverse effects and was free of major adverse clinical events.

The safety of carotid stenosis during vasodilator pharmacologic stress testing.

BACKGROUND: While thousands of patients undergo stress testing annually, the risk of exercise and pharmacologic stress in patients with carotid artery disease has not been fully defined but is of concern as patients are at risk for cerebrovascular accidents and transient ischemic attacks. METHODS: All patients with either ultrasound or CTA evaluation of their carotid arteries from over a 10 year period who underwent stress testing within 180 days without intervening carotid intervention were reviewed for any adverse events within 24 hours of their stress test. The primary end point was any cerebrovascular event or syncope while the secondary endpoints included death, myocardial infarction, urgent angiography, urgent revascularization, or exaggerated hemodynamic response (systolic BP drop > 20 mmHg or systolic BP > 180 mmHg at peak stress). Patients were stratified into categories based on their level of carotid disease. Patients with severe carotid stenosis were propensity matched to those with mild or no stenosis. RESULTS: A total of 4457 patients underwent carotid ultrasound, 10,644 CTA, and 16,011 had stress testing during this time period with 514 having both a carotid evaluation and a stress test within 6 months. After propensity matching, 62 patients with severe carotid stenosis were matched to 170 patients with mild or no carotid stenosis. Incidentally, all patients with severe carotid stenosis underwent pharmacologic stress. There were no primary endpoints and only three secondary endpoints in two patients in the mild or no carotid stenosis group. The proportion of exaggerated hemodynamic response to stress was similar in both groups-21.0% in the carotid stenosis group vs 31.2% without (P = .17) having a significant drop in systolic BP, and 3.2% vs 4.7% (P = 1.0) having a significantly elevated systolic BP. CONCLUSION: In this study cohort there were few primary and secondary outcome events with no events occurring in patients with significant carotid stenosis. Additionally, there was no difference in exaggerated hemodynamic responses. While these results suggest that stress testing entails no demonstrable increased risk in patients with significant carotid stenosis, continued care should be taken given the limitations of the small size of this study.

Non-traditional factors affecting referral for coronary angiography following SPECT myocardial perfusion imaging.

BACKGROUND: The use of myocardial perfusion imaging (MPI) in the management of coronary artery disease (CAD) is well established. Although prior studies have shown disparities in the use of invasive angiography in patients with acute MI, data on factors affecting referral to angiography post-MPI are lacking. We sought to evaluate the primary determinants of referral to invasive angiography post-MPI and specifically assess the role of non-traditional non-clinical factors such as race/ethnicity, socioeconomic factors, insurance status, and marital status. METHODS: All patients without known CAD who underwent stress SPECT MPI over 15 years were reviewed and the performance of coronary angiography within 90 days of their MPI was recorded. Multiple factors were analyzed for an association with referral to angiography, including exercise and MPI results, baseline demographics, traditional cardiac risk factors, and non-traditional factors such as ethnicity, insurance, marital and socioeconomic status. In a secondary analysis, these factors were assessed with regard to abnormal MPI results. RESULTS: Out of 27,895 total patients, 2,150 (7.7%) underwent invasive coronary angiography. On multivariate analysis, inpatient location, positive ECG response, and abnormal MPI results were the strongest predictors of angiography. Non-traditional factors such as race/ethnicity and insurance status had a significant association with referral to angiography with Caucasians (OR 1.42, 95% CI 1.18-1.71, P < .0001) and those with private insurance (OR 1.35, 95% CI 1.13-1.62, P = .001) or Medicare (OR 1.30, 95% CI 1.08-1.56, P = .006) having higher rates of angiography despite controlling for traditional risk factors and test results. CONCLUSION: Our study results indicate that non-traditional factors such as race/ethnicity and insurance status influence patient management decisions and impact the performance of downstream cardiac invasive testing after stress MPI. Higher rates of angiography in Caucasians, privately insured and Medicare patients were seen despite controlling for traditional risk factors and abnormal test results. Further research is needed to better understand these disparities, especially in the current healthcare environment.

Hemiplegic migraine episode triggered by regadenoson.

SPECT and PET myocardial perfusion imaging (MPI) are widely used to evaluate patients for coronary artery disease. Regadenoson (a selective A2A adenosine receptor agonist) is a commonly used vasodilator agent for stress MPI because of its safety profile and ease of use. Common adverse reactions such as headache, shortness of breath, flushing, and chest and abdominal discomfort are typically mild and can be effectively reversed using methylxanthines such as aminophylline and caffeine. Neurological adverse reactions such as seizure and stroke have rarely been reported with the use of regadenoson. The hemodynamic changes associated with regadenoson administration, such as an exaggerated hypotensive or hypertensive response, may be the cause for the reported cerebrovascular accidents. Activation of central nervous system A2A adenosine receptors is thought to be responsible for seizure episodes in patients with or without known histories of seizure. A2A adenosine receptors activation is also believed to play a role in headaches and migraine. This patient reported who has a history of hemiplegic migraine developed left side weakness and headache following the administration of regadenoson during a PET MPI study. Imaging work-up to rule out cerebrovascular accident was normal. After 1 hour from the onset of his symptoms, his weakness and headache significantly improved with complete resolution within 24 hours. We concluded that regadenoson triggered a hemiplegic migraine episode in this patient, which has not been previously reported in the literature. It may be prudent to avoid regadenoson and adenosine use in patients with a history of hemiplegic migraine.

Impact of Gd-153 scanning line source attenuation correction on downstream invasive testing.

BACKGROUND: Attenuation correction (AC) using hardware and software solutions has been shown to increase the specificity of SPECT MPI by decreasing false positive results and improving prognostic ability. Theoretically this should reduce downstream testing and unnecessary costs. We sought to assess the consequences of the use of Gd-153 scanning line source attenuation correction during SPECT myocardial perfusion imaging (MPI) on downstream invasive testing. METHODS: All patients who underwent a clinically indicated Tc-99m stress SPECT MPI study from 2013 to 2015 at five hospitals (2 with AC and 3 without) were retrospectively reviewed. Patient demographics, results of testing, subsequent coronary angiography within 3 months, and revascularization were recorded. The results of the MPI studies, downstream angiogram utilization, and results of angiography were compared and a propensity matched subgroup analysis was performed. RESULTS: A total of 9968 patients underwent SPECT MPI during the study time period (6106 performed with AC and 3862 without). Out of 3928 patients included in the propensity matched cohort, there was no difference in the proportion of abnormal MPI results between the two groups (31.5% vs 30.4%, P = 0.47), however, more patients underwent coronary angiography within 90 days in the AC group (10.6% vs 8.7%, P = 0.05). There was no significant difference in the proportion of patients with angiographically significant obstructive disease (53.4% vs 56.1%, P = 0.19), however, fewer patients in the AC group with obstructive coronary disease were revascularized (36.1% vs 46.8%, P = 0.04). The findings remained consistent after sub-group analysis in patients without known coronary disease. CONCLUSION: The use of scanning line source AC did not meaningfully influence the rate of abnormal MPI results or downstream invasive testing in this cohort. The clinical utility of scanning line source AC may be limited to facilitating stress-first imaging protocols.

Efficiency of tetrofosmin versus sestamibi achieved through shorter injection-to-imaging times: A systematic review of the literature.

Based on superior image quality, more accurate gated images, and lower radiation exposure to patients, Technetium-99m (Tc-99m) based tracers are preferred over Thallium-201 for SPECT myocardial perfusion imaging. The two Tc-99m tracers, sestamibi and tetrofosmin, have many similar characteristics but there are differences in blood and liver clearance rates, as well as the recommended time after injection for imaging to achieve optimal image quality. Because published peer-reviewed studies examining optimal times between injection and imaging are limited, it can be difficult to identify evidence-based opportunities to optimize imaging protocols. Using systematic literature review methods, this study was designed to identify and consolidate the available evidence on the use of sestamibi compared to tetrofosmin for variable injection to imaging times in regard to test efficiency, including test length and re-scan rates, and image quality, including overall quality and cardiac to extra-cardiac ratios. The composite of this data shows that earlier imaging with tetrofosmin is equivalent to later imaging with sestamibi when assessing subjective image quality or when quantifying heart-to-extra-cardiac ratios. Image quality and heart-to-extra-cardiac ratios comparing early versus later imaging with tetrofosmin were comparable if not equivalent to each other. The equivalency of the imaging quality occurs with 15 minutes (on average) earlier imaging compared to sestamibi and 30 minutes compared to standard time tetrofosmin. The subjective findings of equivalent image quality are also shown with objective measurements of heart-to-extra-cardiac ratios. In this review, the significantly shorter injection-to-acquisition times with tetrofosmin compared to sestamibi resulted in better efficiency and less waiting times for patients; in addition, significantly higher re-scan rates with sestamibi compared to tetrofosmin due to hepatic activity contributed to better throughput with tetrofosmin.

Comparison of Benefit of Transcatheter Aortic Valve Implantation in Patients With Low Gradient Versus High Gradient Aortic Stenosis and Left Ventricular Dysfunction.

Patients with low gradient severe aortic stenosis (LG-AS) often exhibit significant limitations in functional status and quality of life. We aimed to evaluate the clinical effect of transcatheter aortic valve implantation (TAVI) on LG-AS patients compared to those with high transvalvular gradients and similar left ventricular dysfunction. Retrospective analysis of records for all patients with a left ventricular ejection fraction <50% who underwent TAVI at our institution was performed. Patients were grouped according to their transvalvular gradient. Data were collected from The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Clinical benefit endpoints included improvements in left ventricular ejection fraction and changes in the Kansas City Cardiomyopathy Questionnaire. Additional outcomes analyzed included 1-year all-cause mortality, stroke rates, rates of rehospitalization, need for a permanent pacemaker, and hospital length of stay. Two hundred three patients met our inclusion criteria. one hundred one LG-AS patients (mean transvalvular gradient <40 mm Hg) were compared to 102 patients with high transvalvular gradients (mean transvalvular gradient >40 mm Hg). LG-AS patients yielded similar improvements in left ventricular ejection fraction (43.5% ± 63.7 vs 37.7% ± 58.7; p = 0.525) and Kansas City Cardiomyopathy Questionnaire scores (423.51% ± 1257.02 vs 266.56% ± 822.81; p = 0.352). There were no differences between the groups with respect to 1-year mortality (16.8% vs 12.7%; p = 0.412), stroke rates, hospital length of stay, need for permanent pacemaker implantation or hospital readmissions. In conclusion, we found that TAVI is associated with comparable improvement in clinical and echocardiographic outcomes in LG-AS patients as compared to those with high gradient severe aortic stenosis.

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.

Clinical effectiveness of an outpatient pathway for low-risk chest pain emergency department visits.

BACKGROUND: Studies suggest that patients who present with atypical chest pain and are low or low-intermediate risk can safely undergo a rapid rule-out for cardiac ischemia with serial ECGs and cardiac biomarkers followed by additional testing as needed. We sought to evaluate a novel Emergency Department (ED) protocol for patients to undergo their additional functional testing as an outpatient. METHODS: Patients presenting to the ED with atypical chest pain, normal ECG, and negative cardiac troponin felt to be low risk were referred for outpatient stress testing within 72 hours of presentation as part of a pilot program. We analyzed test characteristics, length of stay, and 30-day return visits to ED in the pilot group and compared results to a similar cohort assessed in the ED by a traditional chest pain observation protocol. RESULTS: A total of 156 patients were included over a 5-month period with 29.5% not returning for testing. There was a 70% reduction in length of stay for outpatient stress test protocol patients. All-cause and cardiac return visits to the ED were not significantly different between the outpatient cohort and the traditional chest pain unit group and were reduced by 47 and 75%, respectively, in patients who completed their outpatient testing. The provisional injection protocol resulted in a 81% reduction in radiation exposure when compared to traditional MPI stress protocols due to a greater utilization of exercise treadmill tests without imaging. CONCLUSION: Outpatient stress testing is a reliable alternative to traditional chest pain observation with a significantly shorter length of stay, reduced healthcare costs, and improved radiation safety profile for patients when compared to traditional inpatient observation.

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.

Clinical predictors of antitachycardia pacing response in implantable cardioverter defibrillator patients.

BACKGROUND: Antitachycardia pacing (ATP) provides safe and painless termination of reentrant ventricular arrhythmias in patients with implantable cardioverter defibrillator (ICDs), improving their quality of life. Established predictors of ATP responsiveness are not well known; only longer ventricular tachycardia (VT) cycle length and higher ejection fraction have been found to predict ATP success. OBJECTIVE: To investigate clinical and ECG predictors of ATP response in ICD patients with monomorphic VT. METHODS: The ICD clinic database was searched for monomorphic VT events requiring ICD therapy in patients with ischemic or non-ischemic cardiomyopathy. Each patient's first ICD encounter for VT was assessed. Patient demographics, clinical characteristics, VT rate, and ATP responsiveness (always, sometimes, and never successful) were recorded. An ECG was analyzed for QRS morphology and duration. Data was assessed for predictors of ATP responsiveness. RESULTS: In 527 patients, characteristics associated with always successful ATP included ACE-I/ARB therapy and slower VT rate (never successful ATP 197 ± 28 bpm, sometimes successful ATP 190 ± 27 bpm, always successful ATP 183 ± 22 bpm, P < .0001). Secondary prevention indication, amiodarone therapy, and longer QRS duration were associated with ATP failure. After multivariate analysis, only faster VT rate and amiodarone therapy were predictive of ATP failure. CONCLUSIONS: Neither QRS morphology nor duration was predictive of ATP success. Slower VT rate was predictive of repeated ATP responsiveness. Amiodarone therapy, which is known to increase VT cycle length, interestingly was associated with ATP failure for unclear reasons. More individualized and possibly more aggressive ATP programming may be warranted in patients on amiodarone.

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.