Assessing myocardial perfusion in suspected coronary artery disease: rationale and design of the second phase 3, open-label multi-center study of flurpiridaz (F-18) injection for positron emission tomography (PET) imaging.

BACKGROUND: Positron emission tomography (PET) myocardial perfusion imaging (MPI) with the novel radiopharmaceutical Fluorine-18 Flurpiridaz has been shown in Phase 1, 2, and first Phase 3 clinical studies to be safe and effective in diagnosing coronary artery disease (CAD). We describe the methodology of the second FDA-mandated phase 3 prospective, open-label, international, multi-center trial of F-18 Flurpiridaz PET MPI. METHODS: The primary study end point is to assess the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD [≥ 50% by quantitative invasive coronary angiography (ICA)] in patients with suspected CAD. The secondary endpoints are to evaluate the diagnostic efficacy of F-18 Flurpiridaz PET MPI compared to Tc-99 m-labeled SPECT MPI in the detection of CAD in all patients and in the following subgroups: (1) females; (2) patients with body mass index ≥ 30 kg/m2; and (3) diabetic patients. This trial's design differs from the first phase 3 trial in that (1) comparison to SPECT is now a secondary end point; (2) patients with known CAD are excluded; and (3) both SPECT and PET MPI are performed before ICA. CONCLUSIONS: This second phase 3 study will provide additional evidence on the diagnostic efficacy of F-18 Flurpiridaz PET MPI in the detection of significant CAD. TRIAL REGISTRATION NUMBER: NCT03354273.

Coronary risk equivalence of diabetes assessed by SPECT-MPI.

BACKGROUND: Several publications and guidelines designate diabetes mellitus (DM) as a coronary artery disease (CAD) risk equivalent. The aim of this investigation was to examine DM cardiac risk equivalence from the perspective of stress SPECT myocardial perfusion imaging (MPI). METHODS AND RESULTS: We examined cardiovascular outcomes (cardiac death or nonfatal MI) of 17,499 patients referred for stress SPECT-MPI. Patients were stratified into four categories: non-DM without CAD, non-DM with CAD, DM without CAD, and DM with CAD, and normal or abnormal perfusion. Cardiac events occurred in 872 (5%), with event-free survival best among non-DM without CAD, worst in DM with CAD, and intermediate in DM without CAD, and non-DM with CAD. After multivariate adjustment, risk remained comparable between DM without CAD and non-DM with CAD [AHR 1.0 (95% CI 0.84-1.28), P =0.74]. Annualized event rates for normal subjects were 1.4% and 1.6% for non-DM with CAD and DM without CAD, respectively (P = 0.48) and 3.5% (P = 0.95) for both abnormal groups. After multivariate adjustment, outcomes were comparable within normal [AHR 1.4 (95% CI 0.98-1.96) P = 0.06] and abnormal [AHR 1.1 (95% CI 0.83-1.50) P = 0.49] MPI. CONCLUSIONS: Diabetic patients without CAD have comparable risk of cardiovascular events as non-diabetic patients with CAD after stratification by MPI results. These findings support diabetes as a CAD equivalent and suggest that MPI provides additional prognostic information in such patients.

Correction to: Clinical Quantification of Myocardial Blood Flow Using PET: Joint Position Paper of the SNMMI Cardiovascular Council and the ASNC.

The above position statement originally published containing errors in the author metadata; specifically, the Expert Content Reviewers-Andrew Einstein, Raymond Russell and James R. Corbett-were tagged as full authors of the paper. The article metadata has now been corrected to remove Drs. Einstein, Russell and Corbett from the author line, and the PubMed record has been updated accordingly.

Status of cardiovascular PET radiation exposure and strategies for reduction: An Information Statement from the Cardiovascular PET Task Force.

Cardiovascular positron emission tomography (PET) imaging provides high-quality visual and quantitative myocardial perfusion and function images. In addition, cardiovascular PET can assess myocardial viability, myocardial inflammatory disorders such as cardiac sarcoid, and infections of implanted devices including pacemakers, ventricular assist devices, and prosthetic heart valves. As with all nuclear cardiology procedures, the benefits need to be considered in relation to the risks of exposure to radiation. When performed properly, these assessments can be obtained while simultaneously minimizing radiation exposure. The purpose of this information statement is to present current concepts to minimize patient and staff radiation exposure while ensuring high image quality.

Myocardial perfusion imaging in women for the evaluation of stable ischemic heart disease-state-of-the-evidence and clinical recommendations.

This document from the American Society of Nuclear Cardiology represents an updated consensus statement on the evidence base of stress myocardial perfusion imaging (MPI), emphasizing new developments in single-photon emission tomography (SPECT) and positron emission tomography (PET) in the clinical evaluation of women presenting with symptoms of stable ischemic heart disease (SIHD). The clinical evaluation of symptomatic women is challenging due to their varying clinical presentation, clinical risk factor burden, high degree of comorbidity, and increased risk of major ischemic heart disease events. Evidence is substantial that both SPECT and PET MPI effectively risk stratify women with SIHD. The addition of coronary flow reserve (CFR) with PET improves risk detection, including for women with nonobstructive coronary artery disease and coronary microvascular dysfunction. With the advent of PET with computed tomography (CT), multiparametric imaging approaches may enable integration of MPI and CFR with CT visualization of anatomical atherosclerotic plaque to uniquely identify at-risk women. Radiation dose-reduction strategies, including the use of ultra-low-dose protocols involving stress-only imaging, solid-state detector SPECT, and PET, should be uniformly applied whenever possible to all women undergoing MPI. Appropriate candidate selection for stress MPI and for post-MPI indications for guideline-directed medical therapy and/or invasive coronary angiography are discussed in this statement. The critical need for randomized and comparative trial data in female patients is also emphasized.

Intersocietal Accreditation Commission Accreditation Status of Outpatient Cerebrovascular Testing Facilities Among Medicare Beneficiaries: The VALUE Study.

OBJECTIVES: Accreditation of cerebrovascular ultrasound laboratories by the Intersocietal Accreditation Commission (IAC) and equivalent organizations is supported by the Joint Commission certification of stroke centers. Limited information exists on the accreditation status and geographic distribution of cerebrovascular testing facilities in the United States. Our study objectives were to identify the proportion of IAC-accredited outpatient cerebrovascular testing facilities used by Medicare beneficiaries, describe their geographic distribution, and identify variations in cerebrovascular testing procedure types and volumes by accreditation status. METHODS: As part of the VALUE (Vascular Accreditation, Location, and Utilization Evaluation) Study, we examined the proportion of IAC-accredited facilities that conducted cerebrovascular testing in a 5% Centers for Medicare and Medicaid Services random Outpatient Limited Data Set in 2011 and investigated their geographic distribution using geocoding. RESULTS: Among 7327 outpatient facilities billing Medicare for cerebrovascular testing, only 22% (1640) were IAC accredited. The proportion of IAC-accredited cerebrovascular testing facilities varied by region (χ(2)[3] = 177.1; P < .0001), with 29%, 15%, 13%, and 10% located in the Northeast, South, Midwest, and West, respectively. However, of the total number of cerebrovascular outpatient procedures conducted in 2011 (38,555), 40% (15,410) were conducted in IAC-accredited facilities. Most cerebrovascular testing procedures were carotid duplex, with 40% of them conducted in IAC-accredited facilities. CONCLUSIONS: The proportion of facilities conducting outpatient cerebrovascular testing accredited by the IAC is low and varies by region. The growing number of certified stroke centers should be accompanied by more accredited outpatient vascular testing facilities, which could potentially improve the quality of stroke care.

Does risk for major adverse cardiac events in patients undergoing vasodilator stress with adjunctive exercise differ from patients undergoing either standard exercise or vasodilator stress with myocardial perfusion imaging?

BACKGROUND: In patients with functional limitations, the use of adjunctive exercise with vasodilator stress has advantages over vasodilator stress alone in single photon emission computed tomography myocardial perfusion imaging (MPI) for technical reasons and with regards to more effective cardiac risk stratification. Whether patients who undergo vasodilator with adjunctive exercise stress MPI possess clinical characteristics and cardiac risk that differs from those who undergo standard exercise or vasodilator stress MPI is unknown. METHODS: Prospectively collected data on 19,367 consecutive patients referred for stress MPI to a tertiary care center (9,331 [48%] underwent exercise-only, 3,793 [20%] underwent vasodilator plus exercise, and 6,243 [32%] underwent vasodilator-only) were analyzed. Perfusion data were scored using the ASNC 17-segment with a summed stress score (SSS) < 4 = normal, 4-8 = mildly abnormal, and > 8 = moderate to severely abnormal. Patients were followed a mean of 1.96 ± 0.95 years. Demographics, clinical characteristics, and the occurrence of major adverse cardiac events (cardiac death or nonfatal myocardial infarction) were compared between the three stress modality groups. RESULTS: Comparison of demographics and clinical characteristics revealed significant differences in gender, age, cardiac risk factors, and stress MPI between the three stress modality groups (P < .001). In follow-up, cardiac event-free survival of patients in the vasodilator plus exercise stress group was significantly higher than those in the vasodilator-only group but lower than those in the exercise-only group (P < .001). Annualized cardiac event rates of patients in the vasodilator plus exercise stress group were significantly lower than those in the vasodilator-only group for all three categories of the SSS (P < .001). After multivariable adjustment, with exercise-only as reference category, vasodilator plus exercise and vasodilator-only stress emerged as independent predictors (more likely occurrence) of cardiac death, while vasodilator-only stress emerged as an independent predictor (more likely occurrence) of cardiac death or nonfatal myocardial infarction. With vasodilator-only as the reference category, exercise-only and vasodilator plus exercise stress emerged as independent predictors (less likely occurrence) of cardiac death as well as of cardiac death or nonfatal myocardial infarction. CONCLUSIONS: Patients undergoing vasodilator plus exercise stress MPI possess clinical characteristics and cardiac risk that differs significantly from those undergoing either standard exercise or vasodilator stress MPI and places them in a lower risk category compared to vasodilator stress alone.

Facility perception of nuclear cardiology accreditation: Results of an Intersocietal Accreditation Commission (IAC) survey.

BACKGROUND: The Medicare Improvements for Patients and Providers Act requires accreditation for all non-hospital suppliers of nuclear cardiology, nuclear medicine, and positron emission tomography (PET) studies as a condition of reimbursement. The perceptions of these facilities regarding the value and impact of the accreditation process are unknown. We conducted an electronic survey to assess the value of nuclear cardiology accreditation. METHODS: A request to participate in an electronic survey was sent to the medical and technical directors (n = 5,721) of all facilities who had received Intersocietal Accreditation Commission (IAC) Nuclear/PET accreditation. Demographic information, as well as, opinions on the value of accreditation as it relates to 16 quality metrics was obtained. RESULTS: There were 664 (11.6%) respondents familiar with the accreditation process of which 26% were hospital-based and 74% were nonhospital-based. Of the quality metrics examined, the process was perceived as leading to improvements by a majority of all respondents for 10 (59%) metrics including report standardization, report completeness, guideline adherence, deficiency identification, report timeliness, staff knowledge, facility distinction, deficiency correction, acquisition standardization, and image quality. Overall, the global perceived improvement was greater for hospital-based facilities (63% vs 57%; P < .001). Ninety-five percent of respondents felt that accreditation was important. Hospital-based facilities were more likely to feel that accreditation demonstrates a commitment to quality (43% vs 33%, P = .029), while nonhospital-based facilities were more likely to feel accreditation is important for reimbursement (50% vs 29%, P≤ .001). CONCLUSION: Although the accreditation process is demanding, the results of the IAC survey indicate that the accreditation process has a positive perceived impact for the majority of examined quality metrics, suggesting the facilities find the process to be valuable.

Relationship between quantitative cardiac neuronal imaging with ¹²³I-meta-iodobenzylguanidine and hospitalization in patients with heart failure.

PURPOSE: Hospitalization in patients with systolic heart failure is associated with morbidity, mortality, and cost. Myocardial sympathetic innervation, imaged by (123)I-meta-iodobenzylguanidine ((123)I-mIBG), has been associated with cardiac events in a recent multicenter study. The present analysis explored the relationship between (123)I-mIBG imaging findings and hospitalization. METHODS: Source documents from the ADMIRE-HF trial were reviewed to identify hospitalization events in patients with systolic heart failure following cardiac neuronal imaging using (123)I-mIBG. Time to hospitalization was analyzed with the Kaplan-Meier method and compared to the mIBG heart-to-mediastinum (H/M) ratio using multiple-failure Cox regression. RESULTS: During 1.4 years of median follow-up, 362 end-point hospitalizations occurred in 207 of 961 subjects, 79 % of whom had H/M ratio <1.6. Among subjects hospitalized for any cause, 88 % had H/M ratio <1.6 and subjects with H/M ratio <1.6 experienced hospitalization earlier than subjects with higher H/M ratios (log-rank p = 0.003). After adjusting for elevated brain natriuretic peptide (BNP) and time since heart failure diagnosis, a low mIBG H/M ratio was associated with cardiac-related hospitalization (HR 1.48, 95 % CI 1.05 - 2.0; p = 0.02). CONCLUSION: The mIBG H/M ratio may risk-stratify patients with heart failure for cardiac-related hospitalization, especially when used in conjunction with BNP. Further studies are warranted to examine these relationships.

Stress-only SPECT myocardial perfusion imaging: a review.

Myocardial perfusion imaging (MPI) has enjoyed considerable success for decades due to its diagnostic accuracy and wealth of prognostic data. Despite this success several limitations such as lengthy protocols and radiation exposure remain. Advancements to address these shortcomings include abbreviated stress-only MPI (SO MPI) protocols, PET and both hardware and software methods to reduce radiation exposure and time. SO MPI has advantages in protocol time and radiation reduction with a wealth of supporting data in terms of diagnostic validity and prognostic value. Newer technologies such as attenuation correction, and advanced camera technologies have enabled SO MPI to be more efficient in reducing the time of acquisition and radiation dose and improving accuracy. This review examines the literature available, regarding accuracy, patient outcomes, implementation strategies, and newer developments associated with SO MPI.

Cardiovascular risk stratification in diabetic patients following stress single-photon emission-computed tomography myocardial perfusion imaging: the impact of achieved exercise level.

BACKGROUND: Previous studies have demonstrated that diabetic patients undergoing exercise stress single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI) have significantly lower cardiac events when compared to the diabetic patients undergoing pharmacologic stress SPECT MPI across all perfusion categories. However, there are limited data on the level of exercise achieved during exercise SPECT MPI among diabetic patients and its impact on cardiovascular outcomes. METHODS: We retrospectively analyzed 14,849 consecutive patients (3,654 diabetics and 11,195 non-diabetics) undergoing exercise stress, combined exercise and pharmacologic stress, and pharmacologic stress SPECT MPI from 1996 to 2005 at a single tertiary care center. Diabetic and non-diabetic patients were categorized into 3 groups based on the metabolic equivalents (METs) achieved: ≥5 METs, <5 METs, and pharmacologic stress groups. All studies were interpreted using the 17-segment ASNC model. The presence, extent, severity of perfusion defects were calculated using the summed stress score (SSS), and patients were classified into normal (SSS < 4), mildly abnormal (SSS 4-8), and moderate-severely abnormal (SSS > 8) categories. Annualized event rates (AER) for the composite end point of non-fatal myocardial infarction and cardiac death were calculated over a mean follow-up period of 2.4 ± 1.4 years with a maximum of 6 years. RESULTS: In moderate-severe perfusion abnormality (SSS > 8) category, diabetic patients who were able to achieve ≥5 METs had significantly lower AER compared to diabetic patients who were unable to achieve ≥5 METs (3% vs 5.5%, P = .04), and non-diabetic patients unable to achieve ≥5 METs (3% vs 4.8%, P < .001). Diabetic patients who achieved a high workload of ≥10 METs had a very low AER of 0.9%. Diabetic patients, who attempted exercise but were unable to achieve ≥5 METs, still had significantly lower AER than diabetics undergoing pharmacologic stress MPI across all perfusion categories [1.5% vs 3.2%, P = .006 (SSS < 4); 2.5% vs 4.9%, P = .032 (SSS 4-8); 5.5% vs 10.3%, P = .003 (SSS > 8)]. After adjustment for cardiovascular risk factors, the percentage decrease in cardiac event rate for every 1-MET increment in exercise capacity was 10% in the overall cohort, 12% in diabetic group, and 8% in non-diabetic group. CONCLUSIONS: Despite significant perfusion defects, diabetic patients who achieve ≥5 METs during stress SPECT MPI have significantly reduced risk for future cardiac events. Diabetic patients who achieve ≥10 METs have a very low annualized event rate. These findings support that exercise capacity obtained during SPECT MPI is a surrogate for outcomes among diabetic patients undergoing nuclear stress testing.

Risk stratification using line source attenuation correction with rest/stress Tc-99m sestamibi SPECT myocardial perfusion imaging.

BACKGROUND: Although line source attenuation correction (AC) in SPECT MPI studies improves diagnostic accuracy, its prognostic value is less understood. METHODS: Consecutive patients (n = 6,513) who underwent rest/stress AC ECG-gated SPECT MPI were followed for cardiac death or non-fatal myocardial infarction (MI). A 17-segment model and AC summed stress score (SSS) were used to classify images. RESULTS: Of the 6,513 patients, cardiac death or non-fatal MI occurred in 267 (4.1%), over 2.0 ± 1.4 years. The AC-SSS in patients with a cardiac event (5.6 ± 7.8) was significantly higher than in those without (1.9 ± 4.6, P < .001). The annualized cardiac event rate in patients with an AC-SSS 1-3 (3.6%) was significantly higher than in those with an AC-SSS = 0 (1.1%, P < .001) but similar to that in those with an AC-SSS 4-8 (2.9%, P = .4). Accordingly, patients were classified to AC-SSS = 0, 1-8, and >8 with annualized cardiac event rates of 1.1%, 3.2%, and 8.5%, respectively (P < .0001). In multivariate analysis, an AC-SSS 1-8 and >8 emerged as independent predictors of cardiac events (P < .02 and P < .0001, respectively). CONCLUSION: Rest/stress ECG-gated SPECT MPI with line source AC provides highly effective and incremental risk stratification for future cardiac events.

Diagnostic accuracy of high-resolution attenuation-corrected Anger-camera SPECT in the detection of coronary artery disease.

BACKGROUND: There is limited data on diagnostic accuracy of recently introduced high-resolution Anger (HRA) SPECT incorporating attenuation correction (AC), noise reduction, and resolution recovery algorithms. We therefore studied 54 consecutive patients (excluding those with prior MI or cardiomyopathy) who had HRA-AC SPECT and coronary angiography (CA) ≤ 30 days and no change in symptoms. METHODS: The HRA-AC studies were acquired in 128 × 128 matrix (3.2 mm pixel) format with simultaneous Gd-153 line-source AC. Measured variables were image quality, interpretive certainty, sensitivity and specificity for any CAD, sensitivity for single- and multivessel CAD, and the influence of gender, body mass index (BMI), and stress modality. RESULTS: The mean age of the patients was 66 ± 11 years with a BMI of 32 ± 7 kg·m(-2). Mean interpretive certainty score was 2.7 on a 3-point scale and mean image quality score was 3.3 on a 4-point scale. Stress perfusion defects were detected in 34 of 38 patients with obstructive CAD [sensitivity 89%, 95% confidence interval (CI) 76%-95%]. The specificity was 75% (CI 51%-90%) and overall diagnostic accuracy was 85% (CI 73%-92%). Accuracy did not differ for females vs males, for BMI ≤30 vs >30, or for pharmacologic vs exercise SPECT. Sensitivity for single-vessel disease was 88% (CI 69%-96%) and for multivessel disease was 93% (CI 69%-99%). CONCLUSION: New Anger technology incorporating innovative improvements results in high image quality with excellent interpretive certainty and high diagnostic accuracy.

Accreditation status and geographic location of outpatient vascular testing facilities among Medicare beneficiaries: the VALUE (Vascular Accreditation, Location & Utilization Evaluation) study.

OBJECTIVE: There is limited information on the accreditation status and geographic distribution of vascular testing facilities in the US. The Centers for Medicare & Medicaid Services (CMS) provide reimbursement to facilities regardless of accreditation status. The aims were to: (1) identify the proportion of Intersocietal Accreditation Commission (IAC) accredited vascular testing facilities in a 5% random national sample of Medicare beneficiaries receiving outpatient vascular testing services; (2) describe the geographic distribution of these facilities. METHODS: The VALUE (Vascular Accreditation, Location & Utilization Evaluation) Study examines the proportion of IAC accredited facilities providing vascular testing procedures nationally, and the geographic distribution and utilization of these facilities. The data set containing all facilities that billed Medicare for outpatient vascular testing services in 2011 (5% CMS Outpatient Limited Data Set (LDS) file) was examined, and locations of outpatient vascular testing facilities were obtained from the 2011 CMS/Medicare Provider of Services (POS) file. RESULTS: Of 13,462 total vascular testing facilities billing Medicare for vascular testing procedures in a 5% random Outpatient LDS for the US in 2011, 13% (n=1730) of facilities were IAC accredited. The percentage of IAC accredited vascular testing facilities in the LDS file varied significantly by US region, p<0.0001: 26%, 12%, 11%, and 7% for the Northeast, South, Midwest, and Western regions, respectively. CONCLUSIONS: Findings suggest that the proportion of outpatient vascular testing facilities that are IAC accredited is low and varies by region. Increasing the number of accredited vascular testing facilities to improve test quality is a hypothesis that should be tested in future research.

The role of radionuclide imaging in heart failure.

The incidence of heart failure (HF) is increasing and it remains the only area in cardiovascular disease wherein hospitalization rates and mortalities have worsened in the past 25 years. This review is provided to assess the role of radionuclide imaging in HF. The focus is on three aspects: the value of nuclear imaging to distinguish ischemic from non-ischemic etiologies; risk stratification of patients with HF with evaluation of candidates for specific treatment strategies; and the role of cardiac neuronal imaging in patients with HF. Distinguishing ischemic from non-ischemic cardiomyopathy is important because patients with ischemic cardiomyopathy can potentially have dramatic improvement with revascularization. Single photon emission computed tomography (SPECT) has excellent reported sensitivity and negative predictive value in the detection of coronary artery disease in HF patients. SPECT imaging is also useful in establishing treatment strategies in patients with HF, including those with new onset CHF. Cardiac neuronal imaging of mIBG is particularly helpful in risk stratification of patients with HF. The modality can be used to monitor the response to therapy as dysfunctional mIBG uptake may show improvement with pharmacological treatment.