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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.

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.

Abstract Aims Radiation therapy (RT) is an integral component of cancer therapy but associated with adverse events. Our goal was to establish risk prediction models for major adverse cardiovascular and cerebrovascular events (MACCE) after chest RT. Methods and results A retrospective study of lung/breast cancer patients who had chest RT with planning CT at Mayo Clinic between 01/2010 and 01/2014. Predictive models were developed based on weighted independent predictors using a derivation (406 lung and 711 breast cancer) and validation cohort (179 lung and 234 breast cancer). Patient characteristics, pre-RT CT for coronary artery calcification (CAC), and post-RT MACCE data were reviewed. Post-RT MACCE occurred in 6.1 and 5.6% in the derivation and validation cohort over a mean follow-up of 42 ± 13 months. Post-therapy model (C2AD2) included CAC (two points), MACCE history (two points), age ≥74 (three points), DM (two points), and mean heart radiation dose ≥ 850 mGy (two points), and pre-therapy model (C2AD) included post-therapy model parameters minus mean heart radiation dose. Both models stratified patients into three risk groups: low (0–2), intermediate (3–5), and high (≥6). Post-RT MACCE across these groups were 2.7, 8.9, and 19.8% in the derivation, and 3.9, 6.6, and 16.4% in the validation cohort for post-therapy model (C2AD2) and 2.8, 9.2, and 20.4% in the derivation and 3.7, 9.2, and 13.2% in the validation cohort for pre-therapy model. Both models showed statistically significant graded survival outcome. Conclusion Post-therapy (C2AD2) and pre-therapy (C2AD) models are simple, easy to use and effective tools to stratify breast and lung cancer patients undergoing chest radiation for post-RT MACCE.

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) is known to cause dilation in both the mitral (MA) and the tricuspid (TA) annuli. Few studies have investigated MA dynamics and function in AF compared to sinus rhythm (SR). However, no study addressed this issue in TA. Hence, we set forth to describe TA dynamics in AF and SR and its relationship with severity of tricuspid regurgitation (TR). Methods 3D echocardiographic imaging data were acquired from adult patients in AF or SR with varying degrees of TR between 2018 and 2020. TA was automatically tracked throughout the cardiac cycle using a commercially available software (TomTec 4MV software; Figure 1) over 4-6 cardiac cycles per patient. Time to minimal area as percentage of the R-R interval was recorded in each of the cycles. Absolute change in TA area was calculated as the difference between maximal and minimal TA area in each cardiac cycle and was averaged over 4-6 cycles per patient. This measurement was used to reflect the dynamic range of TA deformation during the cardiac cycle. Right atrial (RA) and right ventricular (RV) volumes and longitudinal strain were also measured (speckle tracking, 4-ch view). Results A total of 70 patients were studied (35 AF; 35 SR; 54% males in each group). Patients with AF were older [median (IQR) of 81 (72-86) years vs. 69 (59-78) years in SR, p &lt; 0.001], had larger maximal TA area and circumference (p &lt; 0.001 for both), larger RA size (p &lt; 0.001), lower RA reservoir strain (p &lt; 0.001) and RV free-wall strain (p &lt; 0.001). Absolute change in TA area was significantly decreased in AF [2.3 (1.7-2.7) cm2] vs. 3.1 (2.3-3.5) cm2 in SR, p = 0.002. Patients with ≥ moderate TR (n = 41, 59%) had lower absolute change in TA area [2.4 (1.7-3.1) cm2 vs. 2.8 (2.2-3.5) cm2 in &lt; moderate TR, p = 0.05]. Female sex was associated with lower absolute change in TA area [2.3 (1.7-3.2) cm2 vs. 2.7 (2.2-3.6) cm2 in males, p = 0.02] on univariate analysis. AF patients had more frequently ≥ moderate TR [28 AF vs. 13 SR, p &lt; 0.001]. On multivariate analysis including sex, rhythm, TR severity, RA and RV strains, and averaged maximal TA area, independent factors associated with lower absolute change in TA area were AF, ≥ moderate TR, and larger maximal TA area (p &lt; 0.05 for all). Time to minimal TA size was achieved in (0-40%) of the R-R interval in 70% of patients in SR compared to only 41% of patients in AF (Figure 2) and in 73% in patients with &lt; moderate TR compared to 43% in patients with ≥ moderate TR. Conclusion AF is associated with blunted TA dynamics resulting in lower decrease in TA size and with a heterogenous timing of minimal TA size throughout the cardiac cycle. The blunted and discoordinated annular contraction may reduce systolic tricuspid valve competence and be involved in the pathophysiology of functional TR. Future studies are needed to confirm this hypothesis and evaluate the effect of restoration of SR on TA dynamics and time to minimal TA size. Abstract Figure 1Abstract Figure 2

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: Perceived personal control (PPC) represents the belief that a person can alter his/her own situation or state. Higher PPC has been associated with increased health-related quality of life and helps facilitate healthy behavioral changes. We investigated whether disclosure of coronary heart disease (CHD) genetic risk influences PPC and genetic counseling satisfaction (GCS) in the myocardial infarction genes (MI-GENES) study, a randomized controlled trial of disclosing genetic risk of CHD. Methods: Participants (40-65 year-old, at intermediate 10-year CHD risk, and not on statins) were randomized to receive estimated 10-year risk of CHD based on their Framingham Risk Score (FRS) or FRS plus a 28 SNP genetic risk score (FRS*GRS). CHD risk was disclosed in each arm by a genetic counselor during a 30-minute scripted session that included a discussion of the impact of family history on CHD risk. For FRS*GRS participants, the genetic counselor also reviewed how their genetic risk score altered their FRS. Each participant then met with a physician to engage in shared-decision making regarding the need for statin therapy. Afterwards, study participants were asked to complete validated surveys to assess PPC and GCS. The 9-item PPC questionnaire was scored 0-9, with higher scores indicating greater control beliefs. The 5-item GCS questionnaire was scored 0-10, with greater scores indicating greater satisfaction with the disclosure session. Results: 207 patients (mean age 58.8±5 years, 46.7% males) were randomized to receive either FRS or FRS*GRS. Patients randomized to receive FRS*GRS had higher PPC compared to FRS although the absolute difference was small (8.85±0.77 vs. 8.54±1.31, P=0.016). Patients randomized to receive FRS*GRS also had a higher GCS score than FRS patients (9.08±2.67 vs. 8.3±3.67, P=0.050]. Conclusions: Disclosure of genetic risk for CHD did not adversely affect PPC or GCS. In fact, patients who received CHD genetic risk information had higher PPC and GCS. Our findings suggest that disclosure of CHD genetic risk is appreciated by patients and may empower them to improve health-related behaviors.

Background: Whether disclosing genetic risk for coronary heart disease (CHD) to individuals influences information seeking and information sharing is not known. Methods: The myocardial infarction genes (MI-GENES) trial randomized participants aged 45-65 years who were at intermediate risk for CHD based on conventional risk factors and not on statins, to receive their conventional risk score (CRS) or their CRS plus a genetic risk score (GRS) based on 28 susceptibility variants. CHD risk was disclosed by a genetic counselor and then discussed with a physician. Surveys to assess information seeking (including internet use and accessing electronic health records (EHR)) were completed before and three and six months after risk disclosure. Information sharing parameters were assessed after risk disclosure. We assessed whether these behaviors differed by GRS disclosure, or by high (≥1.1) or low (<1.1) GRS. Adjustments were made for age, sex, family history of CHD, baseline CRS and GRS, and education. Results were reported as the mean difference (and standard error) in the score for each survey response between the GRS and CRS participants, with significance determined by regression analysis. Results: GRS participants accessed their EHR to obtain information related to their CHD risk more than CRS participants (0.14 ± 0.06, p=0.03). Overall internet use (0.61 ± 0.23, p=0.01), as well as internet use to seek information about heart disease (0.14 ± 0.06, p=0.02) and how genetic factors affect risk of having a heart attack (0.23 ± 0.07, p=0.002), was significantly higher in the GRS participants. GRS participants shared information about heart attack risk with others (0.35 ± 0.13, p=0.007), particularly family members (0.1 ± 0.04, p=0.02), (V4: 0.10 ± 0.05, p=0.05), and their primary care provider (V4: 0.15 ± 0.07, p=0.03) more than CRS participants. Internet use, EHR access, and information sharing did not differ significantly between the high and low GRS groups. Conclusions: Disclosure of GRS for CHD resulted in greater information seeking (including internet use and EHR access) and information sharing by study participants. Disclosure of genetic risk for CHD may help advance patient engagement in precision medicine.

Abstract Aims Beat-to-beat variability in cycle length is well-known in atrial fibrillation (Afib); whether this also translates to variability in annulus size remains unknown. Defining annulus maximal size in Afib is critical for accurate selection of percutaneous devices given the frequent association with mitral and tricuspid valve diseases. Methods and results Images were obtained from 170 patients undergoing 3D echocardiography [100 (50 sinus rhythm (SR) and 50 Afib) for mitral annulus (MA) and 70 (35 SR and 35 Afib) for tricuspid annulus (TA)]. Images were analysed for differences in annular dynamics with a commercially available software. Number of cardiac cycles analysed was 567 in mitral valve and 346 in tricuspid valve. Median absolute difference in maximal MA area over four to six cycles was 1.8 cm2 (range 0.5–5.2 cm2) in Afib vs. 0.8 cm2 (range 0.1–2.9 cm2) in SR, P &lt; 0.001. Maximal MA area was observed within 30–70% of the R-R interval in 81% of cardiac cycles in SR and in 73% of cycles in Afib. Median absolute difference in maximal TA area over four to six cycles was 1.4 cm2 (range 0.5–3.6 cm2) in Afib vs. 0.7 cm2 (range 0.3–1.7 cm2) in SR, P &lt; 0.001. Maximal TA area was observed within 60–100% of the R-R interval in 81% of cardiac cycles in SR, but only in 49% of cycles in Afib. Conclusion MA and TA reach maximal size within a broad time interval centred around end-systole and end-diastole, respectively, with significant beat-to-beat variability. Afib leads to a larger beat-to-beat variability in both timing of occurrence and values of annulus size than in SR.