Young, Kathleen A.

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.

Background: Syncope is a common presenting complaint in the outpatient setting and requires a thoughtful and meticulous approach to history-taking skills. This is crucial in discerning cardiac versus non-cardiac etiologies, underscoring the pivotal role of healthcare professionals in the diagnostic process. Case Report: This is a case of a 76-year-old male who presented to the primary care clinic following an episode of syncope with abrupt loss of consciousness. Given the presentation, there was a high suspicion of cardiac etiology, and further testing was pursued. An electrocardiogram (ECG) demonstrated normal sinus rhythm with a pre-existing first-degree atrioventricular (AV) block. The Holter monitor was without sustained arrhythmias. A dobutamine stress echocardiogram was negative for myocardial ischemia, though a resting transthoracic echocardiogram demonstrated findings consistent with cardiac amyloidosis. Further evaluation with cardiology confirmed the diagnosis of transthyretin (ATTR) cardiac amyloidosis. He was initiated on appropriate treatment and underwent a dual chamber implantable cardioverter defibrillator (ICD) given his presentation. The patient ultimately succumbed to his disease 5 years after his diagnosis. Conclusion: If the cardiac etiology of syncope is suspected, further cardiac structural evaluation is necessary. Cardiac amyloidosis, although rare, is a cause of cardiogenic syncope that should not be overlooked. It should be considered in the differential diagnosis in the appropriate clinical setting, highlighting the need for a broad and comprehensive approach to diagnosis.

Background A multidisciplinary approach improves guideline‐directed medical therapy in systolic heart failure (HF), but its efficacy in patients with HF due to cardiac sarcoidosis is unreported. Methods and Results In a retrospective cohort study, we reviewed 848 patients from our institutional cardiac sarcoidosis clinics, identifying those with a cardiac sarcoidosis diagnosis, HF (left ventricular ejection fraction <50%) at index evaluation, and echocardiograms within 90 days and 11 to 36 months. Patients were stratified by participation in a pharmacist‐led medication therapy management (MTM) program for guideline‐directed medical therapy optimization (MTM versus non‐MTM [NMTM]) without randomization. Demographics, left ventricular ejection fraction, guideline‐directed medical therapy (quantified by Kansas City Medical Optimization score), and immunosuppressive therapy were assessed. Primary outcomes included changes in Kansas City Medical Optimization score, left ventricular ejection fraction, and cardiovascular event–free survival (unplanned HF hospitalization, left ventricular assist device /heart transplant, or death). The final cohort included 111 patients (median age, 57 years; 34% women; 64% New York Heart Association class I–II); 43 (39%) were MTM and 68 (61%) were NMTM. Mean Kansas City Medical Optimization score was similar at index evaluation (MTM, 23.2; NMTM, 29.6; P =0.83). At follow‐up (median, 16 months), the Kansas City Medical Optimization score increased significantly in both groups (MTM, 23.2 to 74.8; P <0.001; NMTM, 29.6 to 58.7; P <0.001) but was higher in MTM ( P =0.001). Mean left ventricular ejection fraction trended toward higher values in MTM (44.4% versus 40.0%, P =0.05). The primary clinical outcome occurred in 1 MTM (2.3%) and 16 NMTM (23.5%) patients, with higher risk in NMTM (hazard ratio, 11.97 [95% CI, 1.58–90.54]; P =0.002). Conclusions In this retrospective cohort study, a pharmacist‐led MTM program was associated with favorable guideline‐directed medical therapy optimization and lower risk of adverse cardiovascular outcomes in patients with cardiac sarcoidosis with HF.

Introduction: Cardiac sarcoidosis (CS) often results in systolic heart failure (HF) and responds favorably to guideline directed medical therapy (GDMT). A multidisciplinary team approach to HF care is recommended but few published examples exist in CS patients. Methods: We queried an institutional registry of 599 CS patients (2000-2023) for patients with index LVEF < 50% (within 90 d of index CS evaluation) and follow-up TTE within 11-36 months. In our CS medication therapy management (MTM) program (started 1/8/2019), pharmacists conduct independent visits with CS patients (in person or remote), discuss GDMT tolerance and symptoms, review monitoring laboratory studies, and adjust GDMT (ACEi/ARB/ARNi, beta-blocker, MRA, and/or SGLT2i) via collaborative practice agreement with the CS cardiologists. Patients were classified as MTM (≥1 MTM encounter) or NMTM patients (0 encounters). We compared (1) GDMT, (2) cardiac remodeling, and (3) clinical outcomes (event free survival to first heart failure hospitalization, LVAD, heart transplant, or death). Results: Nineteen percent (113/599) CS patients met inclusion criteria (34% female, 92% white, median age 57 y, 19% definite CS, 58% probable CS, 31% presumed CS), with 44 MTM (median 11.5 encounters, IQR 11) and 69 NMTM patients. Both MTM and NMTM patients were on a median 2 GDMT agents at index evaluation (p=0.21). At follow-up (median 19 mo MTM, 15 mo NMTM, p=0.05), MTM patients were on more GDMT agents than NMTM (median 3.0 vs 2.0, p<0.001), with higher % target dose of ACEi/ARB/ARNi (98% vs 71%, p=0.009), beta-blocker (87% vs 57%, p=0.004), and SGLT2i use (30% vs 9%, p=0.004), but similar MRA use (48% vs 32%, p=0.09). Immunosuppressive therapy was used in 88% patients (89% MTM vs 87% NMTM, p=0.79). Index LVEF was similar (MTM 36%, NMTM 32%, p=0.07). Mean change in LVEF (excluding LVAD/transplant patients) demonstrated a non-significant trend towards improved remodeling in MTM (+8.6%) vs NMTM patients (+5.5%; p=0.39). MTM patients exhibited lower risk of the clinical outcome (1/44 MTM vs 16/69 MTM patients; univariable HR 0.08 [95%CI 0.01 - 0.63], log-rank p=0.016). Conclusions: A pharmacist MTM program for CS patients with HF is associated with improved GDMT uptitration and clinical outcomes, emphasizing the value of collaborative multidisciplinary CS care.

Abstract Aims Women with congenital heart disease (CHD) are at risk of pregnancy-related adverse outcomes (PRAO). The purpose of this study was to assess temporal changes in cardiac structure and function (cardiac remodelling) during pregnancy, and the association with PRAO in women with CHD. Methods and results Retrospective study of pregnant women with CHD and serial echocardiograms (2003–2021). Cardiac structure and function were assessed at pre-specified time points: prepregnancy, early pregnancy, late pregnancy, and postnatal period. PRAO was defined as the composite of maternal cardiovascular, obstetric, and neonatal complications. The study comprised 81 women with CHD (age, 29 ± 5 years). Compared to the baseline echocardiogram, there was a relative increase in right ventricular systolic pressure (RVSP) (relative change 13 ± 5%, P &lt; 0.001, in early pregnancy; and 18 ± 5%, P &lt; 0.001, in late pregnancy). There was a relative decrease in right ventricle free wall strain (RVFWS) (relative change −11 ± 3%, P &lt; 0.001, in late pregnancy; and −11 ± 4%, P = 0.003, in postnatal period), and a relative decrease in RVFWS/RVSP (relative change, −10 ± 5%, P = 0.02 in early pregnancy, −26 ± 7%, P &lt; 0.001, in late pregnancy, and −14 ± 5%, P &lt; 0.001, in postnatal period). Baseline right ventricular to pulmonary arterial (RV–PA) coupling, and temporal change in RV–PA coupling were associated with PRAO, after adjustment for maternal age and severity of cardiovascular disease. Conclusion Women with CHD had a temporal decrease in RV systolic function and RV–PA coupling, and these changes were associated with PRAO. Further studies are required to delineate the aetiology of deterioration in RV–PA coupling during pregnancy, and the long-term implications of right heart dysfunction observed in the postnatal period.

Introduction: In patients with heart failure, preferences for end-of-life (EOL) care and involvement in advance care planning can vary over their illness trajectory. The aim of this study was to compare EOL preferences by prognosis, assessed using the validated Meta-analysis Global Group in Chronic Heart Failure (MAGGIC) risk score, in patients hospitalized with acute decompensated heart failure (ADHF). Hypothesis: EOL preferences and planning vary by prognosis. Methods: Between January 2014 and January 2016, Southeastern Minnesota residents hospitalized with ADHF at Mayo Clinic hospitals in Rochester, MN were prospectively recruited into an observational cohort study. Information on EOL preferences and advance care planning were assessed by patient questionnaire. MAGGIC risk scores and associated 1-year mortality estimates were calculated using patient characteristics at the time of hospital admission and stratified by quartile. The associations of EOL preferences/ planning and prognosis were examined using two sample t-tests and linear regression. Results: Among 400 patients (mean age 77.7 years, 46% female), predicted 1-year mortality ranged from 3.9-72.5% (median 22.5%). Patients with higher estimated mortality (worse prognosis) more often elected Do Not Resuscitate (DNR) status (p=0.001) and more often had an advanced directive (p<0.001, Table). No other differences in EOL preferences or planning by prognosis were observed. Conclusions: In community patients hospitalized with ADHF, resuscitation preferences and rates of completion of advance care planning documents varied with prognosis, though patient-clinician EOL discussions and awareness and attitudes about EOL options did not.

Introduction: Although national guidelines call on physicians to conduct regular conversations about end-of-life (EOL) care and planning with patients with heart failure (HF), research suggests that physicians often avoid these discussions. The aim of this study was to evaluate whether patients hospitalized with acute decompensated HF (ADHF) reported ever discussing their preferences for EOL care with their physicians. Methods: Between January 2014 and January 2016, Southeastern Minnesota residents hospitalized with ADHF at Mayo Clinic hospitals in Rochester, MN were prospectively recruited into an observational cohort study that included the administration of face-to-face questionnaires. Patients were asked questions regarding details of EOL discussions with their physicians, their preference for prognostic information, whether they had an advanced directive, attitudes about dying and hospice, and familiarity with palliative care and hospice. Results: Among 400 patients (mean age 77.7 years, 46% female, 48% preserved ejection fraction), only 68 (17.5%) reported previously discussing EOL wishes with their physician. Most patients (62.2%) indicated a preference to discuss their prognosis with their physician. Patients reporting prior EOL discussions were more often anemic (82.6% vs. 68.9%, p=0.022), hyponatremic (28.6% vs. 12.5%, p=0.002), and married (68.1% vs. 51.5%, p=0.012). They more often recognized the term ‘hospice’ (95.7% vs. 87.3%, p=0.045), had more favorable attitudes of dying and hospice (p=0.030), and more often had an advanced directive (83.6% vs. 67.7%, p=0.010). No other differences in demographics, comorbidity burden, HF characteristics, or in-hospital and 30-day outcomes were observed. Conclusions: Only 17.5% of patients hospitalized with ADHF reported previously discussing their preferences for EOL care with their physician. Patients reporting EOL discussions were more knowledgeable about EOL options and more likely to have completed advance care planning documents. Despite increasing recognition of the importance of these conversations, they are still occurring infrequently, and represent an important modifiable gap in the optimal longitudinal care of patients with HF.

Abstract Cardiac sarcoidosis (CS), with either extracardiac involvement or in isolation, is increasingly recognized. Complications from cardiac involvement are the leading cause of death in patients with sarcoidosis, rendering early detection extremely important given the significant therapeutic and prognostic implications. However, the diagnosis of CS remains challenging due to the lack of a reliable gold standard, largely due to the low sensitivity of traditional endomyocardial biopsy and patchy myocardial involvement. Recent advances in cardiac imaging with [18F] fluoro-deoxyglucose positron emission tomography-computed tomography ([18F]FDG PET/CT) and cardiac magnetic resonance (CMR) have provided unprecedented information on the prevalence of CS and have revolutionized the diagnosis and management of CS patients. Abnormal PET/CMR findings are now major criteria in societal guidelines to establish a probabilistic diagnosis of CS. This review provides a brief introduction to CS and a summary of current diagnostic criteria, followed by a review on the current use and strengths of PET/CT and CMR for diagnosis, risk stratification and treatment response evaluation. CMR is the most robust technique to assess left ventricular function, to detect myocardial fibrosis and differentiate CS from other cardiomyopathies and has an excellent negative predictive value. On the other hand, [18F]FDG PET/CT is the modality of choice to assess active myocardial inflammation which may be amenable to immunosuppressive treatment as well as to detect extracardiac involvement, to identify potential biopsy sites and to monitor treatment efficacy. Understanding the complementary value of both techniques is crucial to the optimal utilization of advanced imaging in patients with CS. Lastly, some gaps are identified for future research.

Abstract Background Pregnancy related cardiomyopathy is a significant cause of maternal morbidity and mortality globally. A presumed overlap between normal pregnancy-associated symptoms and clinical symptoms of cardiomyopathy contributes to delays in diagnosis and increased risk of maternal mortality. Purpose We sought to evaluate the association between patient-reported cardiovascular symptoms and the presence of cardiomyopathy among pregnant and postpartum patients. We hypothesize that individual cardiovascular symptoms are unrelated to the presence of cardiomyopathy. We also evaluated the use of a novel adaptation of a validated health status questionnaire in relation to cardiomyopathy. Methods We enrolled 48 pregnant (&gt;13 weeks) and postpartum (up to 12 months) participants in a prospective study between October 2021 and February 2022. All study participants completed a baseline questionnaire, which included current cardiovascular symptoms, an assessment of health status using an adapted version of the Kansas City Cardiomyopathy Questionnaire (KCCQ-12), followed by a resting transthoracic echocardiogram on the same day. We defined cardiomyopathy as a left ventricular ejection fraction (LVEF) &lt;50% based on 2-D echocardiography. Fisher's exact and Wilcoxon rank-sum tests were employed to evaluate the association between reported cardiovascular symptoms, the adapted KCCQ-12 (KCC-A) score, and cardiomyopathy. Results At the time of enrollment, 67% were pregnant and 33% postpartum. Forty-eight percent identified as White, 31% as Black, 10% as Asian, and 10% as other race. The median age was 31 years (Q1: 28, Q3: 35) and 6% had an LVEF &lt;50%. We found no statistically significant association between four reported cardiovascular symptoms (shortness of breath, orthopnea, fast breathing, and episodes of “asthma” that did not improve with inhalers or other treatment) and cardiomyopathy or medial E/e' ratio. KCC-A scores were low in the study population overall (median 52; Q1:40, Q3: 61). We demonstrated a significantly lower KCC-A score among women with LVEF &lt;50% (median 24; Q1: 15, Q3: 44) compared to women with LVEF ≥50% (median 54; Q1: 44, Q3: 61) p=0.02. Conclusions We showed no significant association between individual cardiovascular symptoms and cardiomyopathy in an obstetric population. However, we demonstrate for the first time that an adapted KCCQ-12 questionnaire for health status assessment could potentially identify women with a high-likelihood of cardiomyopathy during the peripartum period who may benefit from additional evaluation including echocardiography. Larger studies are needed to validate this finding. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This study was funded by a research grant from the Miami Heart Research Institute, Florida Heart Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health