Askew, J. Wells

BACKGROUND: Technetium-based cardiac amyloid radionuclide imaging enables noninvasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM), but conventional planar and visual semiquantitative approaches have important limitations. We developed the quantitative 3-dimensional Mayo 3D Score, defined as the ratio of mean left ventricular myocardial radiotracer uptake to right atrial blood-pool uptake using computed tomography (CT)-fused single-photon emission CT (SPECT) volumes of interest, and sought to validate its diagnostic performance against myocardial pathology. METHODS: Consecutive patients who underwent 99m Tc-pyrophosphate SPECT/CT at Mayo Clinic for suspected ATTR-CM between June 2017 and January 2025 with archived myocardial tissue were included. Baseline characteristics, including demographics, echocardiogram, biomarkers, visual semiquantitative, and Mayo 3D Score metrics, were collected. Myocardial specimens underwent histopathologic confirmation of amyloid, with amyloid subtype determination and further semiquantitative grading of amyloid burden and deposition patterns. RESULTS: Among 230 patients (median age, 72 years; 78% male), 107 (47%) had ATTR-CM, of whom 9 had hereditary ATTR-CM. The Mayo 3D Score showed excellent discrimination against pathology (area under the receiver operating characteristic curve, 0.92 [0.88–0.96]), exceeding planar Perugini (0.87 [0.83–0.92]; P =0.006), and heart-to-contralateral lung ratio (0.86 [0.81–0.91]; P =0.004) and comparable to SPECT Perugini (0.90 [0.86–0.94]; P =0.12). A cutoff ≥1.0 yielded 86.0% sensitivity, 92.7% specificity, 91.1% positive predictive value, and 88.4% negative predictive value. Among ATTR-positive cases, the Mayo 3D Score correlated strongly with semiquantitative amyloid burden (Spearman ρ=0.69), was higher in pericellular than nodular deposition patterns ( P <0.001), and was not associated with vascular involvement ( P =0.42). CONCLUSIONS: In patients with suspected ATTR-CM undergoing 99m Tc-pyrophosphate SPECT/CT, the Mayo 3D Score demonstrated superior diagnostic performance compared with planar metrics and comparable to SPECT Perugini, while correlating with myocardial ATTR burden and deposition patterns on pathology. These findings support its integration as a quantitative adjunct within clinical diagnostic ATTR-CM workflows.

Abstract Background 99mTc-labelled cardiac scintigraphy enables noninvasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM). Guidelines recommend using planar semiquantitative (heart to contralateral ratio, H/CL) and single photon emission computed tomography (SPECT) qualitative visual grading for diagnostic interpretation. However, planar imaging has inherent limitations, and visual grading is prone to interobserver variability, underscoring the need for standardized quantitative assessment. We developed a 3D volumetric quantitative score (3D Score) and assessed its diagnostic performance compared to myocardial tissue, the gold standard for ATTR-CM diagnosis. Methods At a single, tertiary referral center, we retrospectively identified consecutive patients from 06/2017 to 06/2024 who underwent 3-hour 99mTc-pyrophosphate or 99mTc-hydroxymethylene diphosphonate planar and SPECT/CT for suspected ATTR-CM and had archived myocardial tissue (biopsy or myectomy). On planar imaging, H/CL was calculated. On SPECT/CT, volumes of interest were drawn around the entire left ventricle (LV), avoiding calcifications, and within the right atrium (RA) blood pool. Mean uptake values were used to calculate the 3D Score (LVmean:RAmean), Fig 1A. Myocardial tissue was stained via sulfated Alcian blue and/or Congo red histochemistry. Once histologically confirmed, amyloid deposits were subtyped by liquid chromatography tandem mass spectrometry. The diagnostic performance of H/CL and 3D Score was assessed using receiver operating characteristic (ROC) curve analysis and predictive characteristics were defined. ROC areas under the curve (AUC) were compared using Delong test. Optimal cutoffs were determined using Youden’s J statistic. Baseline characteristics (demographics, echocardiogram, biomarkers) and H/CL were compared between patients above and below 3D Score cutoff. Results 239 patients were identified (median age 72 [65-78], 78% male, 46% ATTR positive). Median time between cardiac scintigraphy and myocardial tissue collection was 22 (6-65) days. Distribution of the 3D Score stratified by ATTR-CM status is illustrated in Fig 1B-C. The discriminative ability of the 3D Score was excellent (AUC 0.92) and superior to H/CL (0.87, p =0.006, Fig 1D-E). The optimal 3D Score cutoff for identifying ATTR-CM was ≥1.0 with sensitivity of 86%, specificity of 92%, positive predictive value (PPV) 90%, and negative predictive value (NPV) 89%. The optimal H/CL ratio cutoff for identifying ATTR-CM was ≥1.4 with sensitivity of 72%, specificity of 86%, PPV 81%, NPV 78%. Baseline characteristics of the overall cohort stratified by 3D Score are displayed in Table 1. Conclusions The 3D Score demonstrated excellent diagnostic performance for detecting ATTR-CM and was superior to current quantitative metrics. Future studies are needed to externally validate its performance across diverse patient cohorts and imaging centers and to investigate correlation with myocardial amyloid burden. Figure 1

BACKGROUND: Guidelines recommend 3-hour cardiac amyloid radionuclide imaging (CARI) for transthyretin amyloid cardiomyopathy. Citing rapid blood clearance of 99m Tc-hydroxymethylene-diphosphonate (HMDP) and efficient laboratory throughput, 1-hour imaging is increasingly practiced despite limited supporting evidence. We sought to compare diagnostic performance and interpreter experience of 1-hour versus 3-hour HMDP-CARI. METHODS: Consecutive patients with suspected transthyretin amyloid cardiomyopathy (n=114) underwent both 1-hour and 3-hour HMDP single photon emission computed tomography (CT)/CT. Two cardiologist-radiologist reader teams, blinded to imaging timepoint (1 versus 3 hours), assessed overall interpretation, single photon emission CT–based Perugini grade, interpretation difficulty, interpreter confidence, and need for CT-fused images for anatomic localization. Discordant, equivocal, and difficult cases were arbitrated by a third tie-breaking team. The myocardial-to-blood-pool radiotracer uptake ratio (3-dimensional Score) was measured as a surrogate of contrast resolution. RESULTS: Interinterpreter agreement was high at both time points (κ≥0.81), with more cases requiring arbitration at 3 hours versus 1 hour (22% versus 13%; P =0.049). Overall interpretation and Perugini grades were concordant between time points in 111/114 (97%) and 106/114 (93%) patients, respectively. Three patients (3%) were negative at 1 hour but equivocal at 3 hours, all of which were clinically ruled out for transthyretin amyloid cardiomyopathy. Interpreter confidence was comparable at both timepoints (97% versus 95%; P =0.317). Compared with 3-hour imaging, contrast resolution was inferior (lower 3-dimensional score, P <0.001) and CT fusion was more frequently needed (57% versus 31%, P <0.001) at 1-hour imaging. CONCLUSIONS: In a prospective, blinded comparison of 1-hour versus 3-hour HMDP-CARI, diagnostic performance and interpreter experience were similar, with readers requesting CT fusion more frequently at 1 hour to optimize myocardial-to-blood pool discrimination.

The Impact of Ordering Provider Specialty on Appropriateness Classification In prior studies, our laboratory applied the ACCF/ASNC AUC for SPECT MPI to several cohorts of patients in Mayo Clinic Rochester. The purpose of this study was to re-examine our data to test the hypothesis that the specialty of the ordering provider affected the appropriateness. We compared the ordering providers specialty with appropriateness determined in prior studies. The study group consisted of 281 patients who underwent stress SPECT MPI studies in May 2005 and 282 patients in October 2006 (before any quality improvement initiatives were begun at Mayo). Appropriateness categories were assigned by 2 experienced nurses from the CV Research Studies Unit not affiliated with the nuclear laboratory. Patients who were studied for pre-operative evaluation (n = 20) or post myocardial infarction (n = 7) were excluded because they comprised less than 5 percent of the patients. Pre-operative testing in our institution is done primarily by stress echocardiography. The final study group consisted of 526 patients. Excluding the 64 unclassified patients, AUE categories were appropriate (75 %), uncertain (13 %), inappropriate (12%). Results by ordering provider are shown in the figure, where CV = Cardiovascular MDs, ED = Emergency Department MDs, IM = General and Internal Medicine MDs, RN = Registered Nurses, and SP = other Specialty MDs. There was no significant association (p = 0.19); Chi-square analysis between appropriateness and specialty groups. In a clinical practice where pre-operative testing using SPECT is infrequent, the rate of inappropriate studies was similar for all ordering providers. Quality improvement efforts in similar practices will likely require a broad focus on all ordering physicians/nurses.

Background: Between 1990-2006, there was a tremendous increase in utilization of single photon emission computed tomography myocardial perfusion imaging (SPECT). Characteristics of the observed increase of SPECT utilization have never been studied. Methods: Using the Mayo Clinic nuclear cardiology database, we examined all SPECT tests performed between 1/1/1991-12/31/2007 in patients without prior coronary artery disease (CAD). Patients with history of CAD, left bundle branch block, paced rhythm, bicycle/ rest-only tests, cardiomyopathy, valvular heart disease, and technically unsatisfactory studies were excluded. The study cohort was divided into 4 time periods: 1991-5, 1996-2000, 2001-5, and 2006-7. Results: There were 29255 eligible SPECT tests (mean age 62.4 ± 12y, 54% men). Annual utilization of SPECT studies increased from 682 in 1992 to a peak of 2738 in 2002, and then decreased to 2134 in 2007, Fig 1. There were very modest changes in CAD risk factors over time. Testing of asymptomatic patients nearly doubled (21.9% in 1991-5 to 42.7% in 2006-7). Tests on patients with typical angina decreased dramatically (18.3% in 1991-5 to 5.3% in 2006-7), Fig 2. Summed stress score, summed difference score, and high risk SPECT tests decreased over time, Fig 3. Normal SPECT studies and negative study ECG increased for both pharmacologic and exercise tests. Conclusions: In Mayo Clinic Rochester, annual SPECT utilization in patients without prior CAD increased between 1992 and 2002, but then decreased in advance of national trends. Normal tests increased, while summed stress score, summed difference score, and high risk tests all decreased. These data suggest that SPECT was increasingly utilized in patients with a lower prevalence of CAD.

Background: Over the past 20 years, there has been an increasing decline in the prevalence of abnormal stress single-photon emission computed tomography myocardial perfusion imaging (SPECT) studies among patients with no history of coronary artery disease (CAD). The trend of SPECT studies among patients with known CAD has not been evaluated before. Methods: Using the Mayo Clinic nuclear cardiology database, we examined all stress SPECT tests performed between 1/1991-12/2012 in patients with prior history of CAD defined as having prior myocardial infarction, percutaneous coronary intervention, and/or coronary artery bypass grafting. Patients with left bundle branch block, paced rhythm, bicycle or rest-only tests, cardiomyopathy, valvular heart disease, and technically unsatisfactory studies were excluded. The study cohort was divided into 5 time periods: 1991-5, 1996-2000, 2001-5, 2006-10, and 2011-12. Results: There were 19373 eligible SPECT tests (mean age 66.2 ± 10.9y, 75.4% men). Annual utilization of SPECT studies in patients with history of CAD increased from an average of 495 tests per year between 1991-1995 to a peak of 1425 in 2003; and then decreased to 552 tests in 2012. Asymptomatic patients comprised 33% in 1991-1995, peaked at 48% in 2006, and then decreased back to 31% in 2012. Over time, patients with typical angina decreased while patients with dyspnea increased, P <0.001 (Fig 1). The percentage of high risk SPECT tests significantly decreased, and the percentage of low-risk SPECT tests significantly increased despite the overall decline of SPECT utilization between 2003 and 2012. Almost 80% of all tests performed in 2012 had a low risk summed stress score compared to 29% in 1991, P <0.001 (Fig 2). Conclusions: In Mayo Clinic Rochester, annual SPECT utilization in patients with prior CAD increased between 1992 and 2003, but then decreased significantly after 2003. Fewer patients had typical angina while patients with dyspnea increased over time. High risk SPECT tests declined while low risk tests increased dramatically. These data suggest that stress SPECT was being increasingly utilized in CAD patients without typical angina who are at low risk.

Background: Transthoracic echocardiography is the mainstay of cardiac imaging and is highly dependent upon cardiac sonographers for whom image acquisition can be physically demanding and associated with musculoskeletal pain. Prior studies are limited by the absence of adequate control groups and a lack of adjustment for potential confounders. Objectives: The purpose of this study was to determine the prevalence and impact of work-related musculoskeletal pain in cardiac sonographers as compared to a large control group of non-invasive healthcare professionals with similar demographics. Methods: An electronic survey was administered to Mayo Clinic employees identified by human resources at six major patient care facilities in four different states. Results: There were 2682 employees within the departments of cardiology and radiology who were contacted and 1532 (57%) completed the survey. After exclusion of those who wear protective lead aprons, 517 employees comprised the control group and 66 cardiac sonographers made up the study group. Cardiac sonographers and the control group were similar in age, sex, BMI, length of employment and history of prior musculoskeletal pain. Cardiac sonographers reported work-related musculoskeletal pain more frequently than the control group (88% vs 40%; p<0.001). This association persisted after multivariable adjustment for age, sex, body mass index, length of current employment and history of pre-existing musculoskeletal pain (OR 11.6; (95% CI 5.32, 25.5); p<0.001). Cardiac sonographers were more likely to seek medical care for their work-related pain (55% vs 21%; p<0.001) and to have missed work due to pain (35% vs 12%, p<0.001). Conclusions: In this multi-site case control study, cardiac sonographers experienced significantly more work-related pain and missed more work due to pain than a large control group of non-invasive healthcare professionals with similar demographics.

Abstract Background Several high-sensitivity cardiac troponin (cTn) assays have been cleared by the United States (US) Food and Drug Administration (FDA) for clinical use. Although some of them have been used outside the US for some time, there is limited experience thus far across US sites. Following FDA clearance of the Roche 5th Gen cTnT assay in January 2017, a multicenter US regional healthcare system introduced this more sensitive cTnT assay into clinical practice in September 2018. Purpose To examine cTn testing patterns, incidence of acute myocardial infarction (MI), and resource utilization before and after implementation of the 5th Gen cTnT assay across a large US healthcare system. Methods Using electronic-health records reporting software (Cogito SlicerDicer, EPIC), administrative data was examined to evaluate the transition (4-months before and after implementation) from the 4th to 5th Gen cTnT assays across 16 hospitals but not the major hub hospital of the system that transitioned at a separate time. Adult patient visits (emergency and hospital encounters), cTnT testing, incidence of chest discomfort and acute MI, and resource utilization, including hospital admissions, were examined during the transition period. Results 98,558 adult ED patient visits occurred during an 8-month period across 16 hospitals, including 50,485 and 48,073 patient visits before (5/12/18 – 9/11/18) and after (9/12/18 – 1/11/19) implementation of the 5th Gen cTnT assay respectively. cTnT testing occurred in 20% (range 8.9–34.8%) of all ED visits, with testing performed in the absence of chest pain in 54% (range 37–67%) of cases. Acute MI was diagnosed in 5.6% (n=561) of cases using the 4th Gen cTnT assay as compared to 6.6% (n=608) of cases using the 5th Gen cTnT assay (absolute difference 1.0%, 95% CI: 0.32–1.68, p=0.004). Much of the increase in MI diagnoses were in women (2.2% vs. 2.8%, p=0.008). The proportion of ED patients requiring hospital admission did not differ between pre- and post-implementation periods (24.1% vs. 23.6%, p=0.4); however, among the subset of patients with chest pain, fewer admissions occurred post-implementation (17.9% vs. 15.8%, p=0.006). There was no increase in echocardiography (9.3% vs. 8.4%), coronary angiography (2.9% vs. 3.1%), or cardiac consultations (7.3% vs. 7.3%) utilization post-implementation. Conclusions Cardiac troponin testing occurs in nearly 20% of ED visits in a large multicenter regional healthcare system. About half of all tests are ordered in the absence of chest pain, with a low MI rate observed among the patients undergoing testing. Following implementation of the 5th Gen cTnT assay, testing rates/patterns remained unchanged, with a small but significant increase in MI diagnoses, primarily due to more women being diagnosed with MI. Fewer ED patients with chest pain required admission. Despite using a more sensitive cTn assay, hospital admissions and resource utilization did not increase post-implementation.