Carey, Patricia

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

Purpose. Spontaneous coronary artery dissection (SCAD) has emerged as an important cause of acute coronary syndrome predominantly affecting women. Although the knowledge of SCAD has expanded over the past 2 decades, limited evidence exists to guide post-event management and prevention of future adverse events. This review aims to synthesize the current understanding of SCAD and outline considerations for exercise prescription and cardiac rehabilitation (CR) in this unique population. Review Methods. A comprehensive literature review was conducted, incorporating original research articles, systematic reviews, meta-analyses, and current clinical guidelines related to SCAD and CR. Summary. Current literature demonstrates that CR is safe in this population and is associated with improvement in measures of physical and mental health. Expert consensus supports reintroduction of exercise and an individualized multidisciplinary CR framework.This review highlights current evidence and expert recommendations for the multidisciplinary outpatient management of patients with SCAD.

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.

A 63-year-old female with mixed connective tissue disease on long-term immunosuppression (prednisone, azathioprine, hydroxychloroquine (HCQ)) was referred to a tertiary care center for evaluation of progressive dyspnea and exertional chest discomfort. Cardiac history included transient complete heart block and ventricular tachycardia with dual-chamber AICD, and severe aortic stenosis with bicuspid aortic valve. Laboratory evaluation was notable for NT pro-BNP > 5000 pg/mL and elevated but adynamic troponin (300-500 ng/L). Electrocardiogram revealed atrial pacing with first degree atrioventricular block. Echocardiogram confirmed severe aortic stenosis, elevated filling pressures, abnormal left ventricular longitudinal strain and LV hypertrophy. Cardiac MRI, sarcoid PET, and PYP SPECT/CT were without any evidence of edema, scar, inflammation or amyloid deposition. Catheterization revealed severe pulmonary hypertension and elevated filling pressures, without significant coronary disease. Medical treatment included empagliflozin (discontinued due to urosepsis), bumetanide, spironolactone, and metoprolol succinate. Neither TAVR nor transition to biventricular pacing improved LV function. Ultimately, endomyocardial biopsy was performed, revealing histologic features of HCQ-induced cardiotoxicity, including myocyte hypertrophy and interstitial fibrosis. HCQ was discontinued. She was referred to Rheumatology for alternative treatments. HCQ induced cardiomyopathy represents <2% of adverse events of patients treated with HCQ, presenting as hypertrophic or restrictive cardiomyopathy with conduction abnormalities. Mean treatment duration in HCQ cardiomyopathies is approximately 12.7 years. Confirmation of diagnosis requires endomyocardial biopsy, as imaging findings are often non-specific. Management involves discontinuing the offending agent and optimizing heart failure therapy. Around 45% of patients with HCQ cardiomyopathy exhibit resolution of cardiac function following medication discontinuation. This case emphasizes the importance of a systematic approach to unexplained heart failure, particularly in patients with long-term HCQ use. Infiltrative or toxic cardiomyopathies should be considered when imaging suggests myocardial dysfunction. Multimodal imaging and biopsy are crucial for diagnosis. Early recognition is essential to prevent irreversible myocardial damage and improve long-term outcomes.

Background: There is a lack of data regarding the current state of lactation accommodations at continuing medical education (CME) events to guide best practice recommendations. Objective: To evaluate CME attendee attitudes, experiences, and preferences as it pertains to lactation support accommodations at CME events. Design: A cross-sectional study utilizing an electronic-based survey. Methods: Surveys were administered electronically to attendees of seven CME courses from August 2022 to October 2023, and de-identified data were collected to a secure database. Attitudes regarding lactation accommodations, personal preferences for lactation accommodations, and experiences with lactation at CME events were analyzed. Results: Of the 337 survey respondents, 169 had personal experience with lactation and 47 had experience with lactation at a CME course within the past 10 years. The majority of respondents agreed that lactation accommodations should be a priority ( n = 264, 83%) and are a medical need ( n = 285, 89%). Of those with recent experience lactating at a CME course, only 19% ( n = 9) indicated adequate lactation accommodations were provided. Due to inadequate accommodations, 77% ( n = 36) of respondents experienced decreased participation in the CME course content, 70% ( n = 33) claimed fewer hours of CME credit, and 74% ( n = 35) experienced decreased satisfaction in the CME course. Preferences for lactation accommodations included proximity to the meeting, audio–visual streaming of content, privacy, security, and signage supporting lactation in addition to an adequate designated space with access to an electrical plug and water supply. Conclusions: The current state of lactation accommodations at CME courses is inadequate and contributes to inequitable experiences for lactating participants. Course participants are supportive of lactating healthcare professionals at CME courses and recognize lactation accommodations as a priority. Further work is needed to inform and institute changes to lactation accommodations for healthcare professionals.

Background Conventional thrombosis risk stratification in polycythemia vera (PV) considers age &gt; 60 years and thrombosis history for assignment to low (no risk factor) or high (at least 1 risk factor) risk category (J Clin Oncol.2011;29(6):761-70). The current study exclusively focused on low-risk PV with the following objectives: i) estimate the incidence of arterial and venous thrombosis; ii) examine the prognostic relevance of clinical and genetic risk factors for thrombosis; and iii) assess the impact of treatment on thrombosis risk. Methods Patients were retrospectively recruited from the Mayo Clinic, USA, and University of Florence, Italy, PV databases. Diagnosis was according to the International Consensus Classification criteria (Blood 2022;140:1200). Only first major arterial (AT) and unprovoked venous thrombosis (VT) were considered. Conventional statistical methods were applied (JMP Pro 17.0.0, SAS Institute, Cary, NC, USA). Results Mayo Clinic cohort A total of 346 patients with low-risk PV were considered: median age 49 years; males 54%; median hemoglobin 17.7 g/dl; median leukocyte count 10.9 x 109/L; leukocyte count &gt;11 x 109/L 49%; median platelet count 471 x 109/L; cardiovascular (CV) risk factors 47%; hypertension 29%; hyperlipidemia 20%; smoking history 12%; diabetes mellitus 5%. Most frequent mutations, other than JAK2, were ASXL1 (13%) and TET2 (13%). Median follow-up was 13.4 years (1-52) (4,636 patient-years) during which 25 (7%) AT and 20 (6%) VT were documented. The corresponding incidence rates were 5.4 and 4.3 per 1,000 patient-years. In multivariable logistic regression analysis, baseline hemoglobin &gt;17.5 g/dl in women or &gt;20 g/dl in men (15% vs 4%; OR 5.1; p&lt;0.01) and absence of leukocytosis &gt;11 x 109/L (10% vs 4%; OR 2.9; p=0.02) were associated with increased risk of AT; in addition, diabetes mellitus (19% vs 7%; OR 3.9; p=0.06), showed borderline significance; overall incidence of AT was 20% in the presence of ≥2 risk factors (n=61), 7% in the presence of one risk factor (n=177), and 1% in the absence of all three risk factors (n=108; p&lt;0.01). Multivariable analysis for arterial thrombosis-free survival (TFS) confirmed the predictive performance of these risk factors: hemoglobin thresholds (HR 4.4; p&lt;0.01); absence of leukocytosis &gt;11 x 109/L (HR 2.7; p=0.03); and diabetes (HR 2.8; p=0.09); 20-year cumulative incidence of AT was 32% in the presence of ≥2 risk factors and 7% otherwise (p&lt;0.01). In multivariable analysis, smoking history was found to be surprisingly protective against VT (0% vs. 7%; p=0.02) while female gender was associated with a borderline higher risk (8% vs 4%; OR 2.2; p=0.09); VT incidence rates were 9% in the presence of both risk factors (n=144), 4% with one risk factor (n=172), and 0% in the absence of both risk factors (n=40; p=0.02); 20-year cumulative incidence of VT was 10% in the presence of both risk factors and 3% otherwise (p=0.03). ASXL1 and TET2 mutations did not appear to modify the risk of either VT (p=0.59) or AT (p=0.66). Treatment at diagnosis included aspirin and cytoreductive therapy in 63% and 24% of patients, respectively. Aspirin but not cytoreductive therapy was associated with a lower incidence of AT (5% vs 11%; 2.3 vs 3.0 per 1,000 patient-years; p=0.04) and VT (4% vs 10%; 1.9 vs 2.8 per 1,000 patient-years; p=0.03). Thrombosis-free survival was not influenced by documented treatment at diagnosis or at the time of event (p&gt;0.1). University of Florence cohort A total of 284 low-risk PV patients were followed for a median of 9.1 years (1-38) with 19 (7%) AT and 24 (8%) VT events recorded; the corresponding incidence rates were 7.4 and 9.3 per 1,000 patient-years. In this Florence cohort, risk factors for AT were diabetes mellitus (HR 3.9), hyperlipidemia (HR 3.8) and advanced age, with only age remaining significant during multivariable analysis (p=0.03). Predictors of VT included hyperlipidemia (HR 4.2) and hypertension (HR 2.1). Treatment with aspirin or cytoreductive therapy did not impact thrombosis-free survival (p&gt;0.1). Conclusion The current study confirms the infrequent occurrence of AT and VT in low-risk PV but also exposes the challenges in identifying risk factors that are reproducible in different but otherwise well-characterized patient cohorts. Discrepancies were also apparent in retrospective comparison of treatment effects on thrombosis, which reinforces the need for prospective studies.

Background: Treatment of symptomatic splenomegaly in myelofibrosis (MF) was revolutionized by JAK2 inhibitors (JAKi), with ruxolitinib inducing a &gt;35% spleen volume reduction in 42% of patients at 24 weeks (N Engl J Med 2012;366). However, the benefit is often transient with a median duration of spleen response of three years (N Engl J Med. 2011;365). Treatment modalities for the management of MF-associated splenomegaly resistant to JAKi treatment includes surgical resection and involved-field radiotherapy. In the current study, we describe our experience with the former. Methods: Study patients were retrospectively recruited from Mayo Clinic (USA) databases based on the following criteria: i) diagnosis according to the International Consensus Classification (Blood 2022;140:1200); ii) documentation of JAKi therapy exposure followed by splenectomy; iii) availability of information before and after splenectomy. Splenectomy was performed as an open (n=29) or laparoscopic (n=5) surgery. Conventional statistical methods were employed for data analysis (JMP Pro 17.0.0, SAS Institute, Cary, NC, USA). Results: A total of 34 patients (median age 62.5 years, range 43-79; 59% males) were identified with splenectomies performed between 2011-2024. Mutation distribution included JAK2 62%, CALR 26%, MPL 3%, and triple negative 9%. ASXL1 mutation was present in 37% and SRSF2 mutation was present in 26% of 19 informative cases. Karyotype was very high risk in 15% and unfavorable in 12%. Median time from diagnosis to JAKi initiation was 7.5 years (0-31). Majority (76%) were treated with one JAKi; 18% had been exposed to 2 different JAKi and 6% with three JAKi. JAKi included ruxolitinib (n=27), momelotinib (n=5), pacritinib (n=3), fedratinib (n=3), and BMS-911543 JAKi (n=5). Two patients underwent allogeneic stem cell transplant (ASCT) three and six months prior to splenectomy. Prior treatment included splenic radiation in 4 patients (median 0.6 years (0.2-1.2)). Pre-operative splenic embolization was performed in 4 patients on same day of splenectomy; one patient had embolization 10 months prior to splenectomy. Median interval from diagnosis to splenectomy was 10.3 years (1.0-35.4) and from initiation of JAKi therapy to splenectomy 1.8 years (0.03-12.1). Most patients had multiple indications for splenectomy including 76% with symptomatic splenomegaly, 50% with significant cytopenia, and 18% in preparation of ASCT. At time of splenectomy, median spleen size on imaging was 25.1 cm (14.7-36) and 55% were red cell transfusion-dependent (Revised international working group criteria). Postoperative complications were reported in 22 (65%) of patients. Major bleeding occurred in 11 (32%) (of which 7 (64%) required repeat surgical exploration) and thrombosis in 9 (26%); 5 patients experienced both major bleeding and thrombosis. Other complications included infection (n=5), renal injury (n=3), and pneumothorax (n=2). At a median follow up of 1.7 years (0.01-10.2) post-splenectomy, 12 (35%) ASCT were documented at a median of 2.3 years (1.5-26.4) post-procedure. Median post-splenectomy survival was 4.3 years (5-year survival 44%) and significantly longer in transplanted patients (median not reached vs 2.6 years; 5-year survival 65% vs 22%; p=0.02). Among patients without post-splenectomy ASCT (n=22), 12 (55%) deaths (including 2 from post-operative complications) and 3 leukemic transformations were recorded. Additionally, 13 of the 22 had transfusion-dependent anemia at splenectomy and subsequently 6 (46%) became transfusion-independent (TI) (≥12 weeks without transfusion) with median TI response duration of 2.8 years (0.3-7.1). In addition, among 5 non-transplanted patients with baseline thrombocytopenia (&lt; 50 x 109/L (16-42 x 109/L)), 4 (80%) had platelet count &gt; 100 x 109/L (median; 170 x 109/L, range: 119-279 x 109/L) within 3 months post-procedure. Conclusions: Splenectomy following JAKi-resistant or intolerant MF is associated with improvement of transfusion-dependent anemia (46% response), resolution of severe thrombocytopenia (80%), and may allow for successful transition to ASCT (35%). However, the procedure is associated with significant perioperative complications occurring in the majority of patients and underscores the need for future collaborative studies to develop selection criteria and evaluate alternative treatment modalities.