Background. Cardiovascular disease is a leading cause of death among women with breast cancer, and the 2026 ACC/AHA dyslipidemia guideline endorses coronary artery calcium (CAC) scoring to guide statin therapy before cardiotoxic treatment. Breast cancer patients routinely undergo staging 18F-fluorodeoxyglucose PET/CT, whose low-dose CT visualizes the coronary arteries, thus enabling CAC quantification at no additional cost or radiation. Methods. In this single-center retrospective study, consecutive women with newly diagnosed breast cancer undergoing staging 18F-FDG PET/CT (2009?2021) had semi-automated Agatston CAC scoring performed on the low-dose CT and were stratified by CAC presence (CAC-P) versus absence (CAC-A). We assessed a composite of cardiac diagnostic testing (stress testing, coronary CT angiography, invasive angiography), clinical events, and reclassification of statin eligibility per ACC/AHA guideline thresholds in a prevention-eligible subgroup. Results. Among 276 women (mean age 55.5 years; median follow-up 7.1 years), CAC was present in 68 (25%) but was clinically reported in only 5.4%. CAC-P was associated with more cardiac testing (34% vs 12%; age-adjusted hazard ratio 2.75, 95% CI 1.43?5.28) and, though underpowered, with more atherosclerotic events (7.4% vs 1.4%), but not with the all-cause composite. In the prevention-eligible subgroup (n=39), CAC scoring would have changed statin eligibility in 64%, initiating therapy in 62% of CAC-P women and supporting de-prescribing in 67% of CAC-A women. Conclusions. CAC can be feasibly quantified from staging PET/CT in women with breast cancer and would frequently reclassify statin eligibility at no additional cost or radiation, yet is rarely reported.

Introduction The evaluation of diastolic function in diabesity patients undergoing incretin-based therapy could facilitate early detection and help prevent progression to heart failure. Methodology A group of 15 diabesity cases with chest x-ray examinations (< 1 month) before and after ≥ 12 months of incretin-based therapy (absent ventricular/valvular dysfunction) were identified. Standard diabesity descriptors and predictions of pulmonary venous hypertension (aka “pulmonary congestion”) [None; Stage 1: vascular distention/redistribution but minimal interstitial edema; or Stage ≥ 2: vascular congestion with ≥ mild interstitial or alveolar edema] by validated AI-enabled chest x-ray staging, representing mean left atrial pressure in diastolic dysfunction, were evaluated pre- and post-therapy. Results By weight loss, cases clustered into equal-sized subgroups: 1. Significant Responders (9–30% decreases); 2. Insignificant Responders (0–2% decreases); and 3. Non-Responders (2–12% increases). Regarding hemoglobin A1c changes: 1. Significant Responders collectively decreased; 2. Insignificant Responders varied; and 3. Non-Responders were largely stable. Pre-therapy, all 15 cases demonstrated AI-enabled chest x-ray evidence of diastolic dysfunction; post-therapy, 4 improved (especially cases of greatest weight loss or hemoglobin A1c reduction), 5 were stable, and 6 worsened. Per subgroup, AI-enabled chest x-ray indications therapeutic response were: 1. Significant Responders (all demonstrating unequivocally decreased obesity and improved diabetes) collectively showed stable-decreased dysfunction; 2. Insignificant Responders (all demonstrating minimally decreased obesity but stable-worsening diabetes in most) reflected stable-increased dysfunction in 60%; and 3. Non-Responders (all demonstrating increased obesity but stable-improved diabetes) showed increased dysfunction in 80%. Conclusion AI-enabled CXR staging detects background subclinical diastolic dysfunction in diabesity and monitors its response to incretin-based therapy.

Idiopathic pulmonary fibrosis (IPF) is a lethal progressive lung disease urgently needing new therapies. Current treatments only delay disease progression, leaving lung transplant as the sole remaining option. Recent studies support a model whereby IPF arises because alveolar epithelial type II (AT2) cells, which normally mediate distal lung regeneration, acquire airway and/or mesenchymal characteristics, preventing proper repair. Mechanisms driving this abnormal differentiation remain unclear. We performed integrated transcriptomic and epigenomic analysis of purified AT2 cells which revealed genome-wide alterations in IPF lungs. The most prominent epigenetic alteration was activation of an enhancer in thyroid receptor interactor 13 (TRIP13), although TRIP13 was not the most significantly transcriptionally upregulated gene. TRIP13 is broadly implicated in epithelial-mesenchymal plasticity. In cultured human AT2 cells and lung slices, small molecule TRIP13 inhibitor DCZ0415 prevented acquisition of the mesenchymal gene signature characteristic of IPF, suggesting TRIP13 inhibition as a potential therapeutic approach to fibrotic disease.

BACKGROUND:Surveillance donor-specific antibody (DSA) and pathologic antibody-mediated rejection (pAMR) testing is recommended in the first year after heart transplantation (HTx) in adult patients. Whether pAMR testing adds prognostic information to contemporary DSA testing has not been fully studied. METHODS:This was a single-center study of consecutive endomyocardial biopsies (EMB) performed between November 2010 and February 2023 in adult HTx patients. The primary objective was to evaluate whether pAMR testing contributes additional information to DSA testing to better predict overall survival. Secondary end-points included cardiac survival and allograft dysfunction. RESULTS:A total of 6,033 EMBs from 544 HTx patients were reviewed for the study. The pAMR+/DSA+ patients had significantly lower overall (pc = 0.013) and cardiac survival (pc = 0.002), while the pAMR+/DSA- and pAMR-/DSA+ patients showed no difference in either outcome compared to the pAMR-/DSA- group. We found significantly lower overall survival in pAMR+/DSA+ patients with allograft dysfunction (pc < 0.001) but not in pAMR+/DSA+ patients without allograft dysfunction (pc = 0.569), when compared to the pAMR-/DSA- without allograft dysfunction group. The pAMR+/DSA+ patients with cardiac allograft dysfunction accounted for 18% of deaths or cardiac retransplants while only representing 4% of the HTx cohort. Moderate or severe primary graft dysfunction (PGD) also was a novel risk factor for the development of de novo DSAs (dnDSA) by 4 weeks post-HTx (p = 0.025). CONCLUSIONS:Surveillance DSA testing may effectively identify high-risk pAMR+ patients. Earlier DSA testing at 10 to 14 days post-HTx should also be considered in moderate or severe PGD patients.

Background Heart failure with reduced ejection fraction (HFrEF) is progressive and pervasive. Guidelines provide evidence-based recommendations to manage HFrEF, yet adherence to Guideline Directed Medical Therapy (GDMT) is low. An opportunity exists to improve adherence by delivering actionable data, reducing clinician information overload, and enhancing patient care. A Pragmatic Trial Evaluating the Impact of the Anumana Clinical Decision Support Tool for Guideline-Directed Management of Heart Failure (ACT-HF) will evaluate a clinical decision support software (CDSS) that integrates in electronic health records (EHR), automates chart review, and identifies care gaps. Methods Anumana's Guideline Navigator is an innovative, multi-module AI-enabled CDSS with automated chart review to rapidly analyze EHR data, detect care gaps, and provide alerts for eligible patients not receiving optimal GDMT. ACT-HF, a multi-center cluster pragmatic trial, will recruit and randomize clinician participants (≤250) from 2 health systems to receive intervention software or provide usual care. The trial will evaluate outpatient care for adults with documented HFrEF and not on optimal GDMT (>2148). Outcomes will be evaluated at 90 days. Clinician participants may discuss results with patients, but patients will not have access to the CDSS. Results Primary outcome is change in GDMT medications; exploratory endpoints include clinical outcomes, resource utilization, and usability. Subgroup analyses include health system, clinician, and patient-level characteristics associated with outcomes. Conclusion Building on efforts to improve GDMT adherence, ACT-HF will test Anumana's Guideline Navigator in a multicenter study to evaluate outcomes and further refine the CDSS EHR integration EHR for improved clinical utility, workflow integration, and patient outcomes.

Light chain amyloidosis and transthyretin amyloidosis are rare protein misfolding disorders characterized by amyloid deposition in organs, varied clinical manifestations, and poor outcomes. Amyloid fibrils trigger various signaling pathways that initiate cellular, metabolic, structural, and functional changes in the heart and other organs. Imaging modalities have advanced to enable detection of amyloid deposits in involved organs and to assess organ dysfunction, disease stage, prognosis, and treatment response. The Amyloidosis Forum hosted a hybrid meeting to focus on the use of imaging endpoints in clinical trials for systemic immunoglobulin light chain amyloidosis and transthyretin amyloidosis. Stakeholders from academia and industry, together with representatives from multiple regulatory agencies reviewed the use of imaging biomarkers with a focus on cardiac amyloidosis, described applications and limitations of imaging in clinical trials, and discussed qualification of imaging as a surrogate clinical outcome. Survey results provided important patient perspectives. This review summarizes the proceedings of the Amyloidosis Forum.

Lipoprotein(a) [Lp(a)] has been established as an independent risk factor for cardiovascular diseases. However, its role in cardiac allograft vasculopathy (CAV) development remains controversial. In a retrospective cohort study of 385 patients who underwent heart transplant between 2001 and 2023, Lp(a) concentrations were compared between patients with and without clinically significant CAV (grade 01 vs 2-3). Preoperative Lp(a) concentrations were not significantly different between patients with and without CAV (14.0vs 12.0 mg/dL, P = . 42). High ( >= 50 mg/dL) Lp(a) values were not associated with CAV development on univariable or multivariable analysis (hazard ratio [HR] 1.009, 95% CI: 0.47-2.14, P = . 9). A history of graft rejection was the only independent factor associated with CAV (HR 2.88, 95 % CI: 1.50-5.52, P = . 001). Elevated Lp(a) levels were not associated with increased risk of CAV. The lack of a significant association between traditional risk factors and CAV underscores that CAV is not purely an atherosclerotic process and different pathophysiological mechanisms are involved. (c) 2024 National Lipid Association. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

AbstractAimsWe aim to determine if our previously validated, diagnostic artificial intelligence (AI) electrocardiogram (ECG) model is prognostic for survival among patients with cardiac amyloidosis (CA).MethodsA total of 2533 patients with CA (1834 with light chain amyloidosis (AL), 530 with wild‐type transthyretin amyloid protein (ATTRwt) and 169 with hereditary transthyretin amyloid (ATTRv)] were included. An amyloid AI ECG (A2E) score was calculated for each patient reflecting the likelihood of CA. CA stage was calculated using the European modification of the Mayo 2004 criteria for AL and Mayo stage for transthyretin amyloid (ATTR). Risk of death was modelled using Cox proportional hazards, and Kaplan–Meier was used to estimate survival.ResultsMedian age of the cohort was 67 [inter‐quartile ratio (IQR) 59, 74], and 71.6% were male. The median overall survival for the cohort was 35.6 months [95% confidence interval (CI) 32.3, 39.5]. For AL, ATTRwt and ATTRv, respectively, median survival was 22.9 (95% CI 19.2, 28.2), 47.2 (95% CI 43.4, 52.3) and 61.4 (95% CI 48.7, 75.9) months. On univariate analysis, an increasing A2E score was associated with more than a two‐fold risk of all‐cause death. On multivariable analysis, the A2E score retained its importance with a risk ratio of 2.0 (95% CI 1.58, 2.55) in the AL group and 2.7 (95% CI 1.81, 4.24) in the ATTR group.ConclusionsAmong patients with AL and ATTR amyloidosis, the A2E model helps to stratify risk of CA and adds another dimension of prognostication.

Cardiac sarcoidosis (CS), an increasingly recognized disease of unknown etiology, is associated with significant morbidity and mortality. Given the limited diagnostic yield of traditional endomyocardial biopsy (EMB), there is increasing reliance on multimodality cardiovascular imaging in the diagnosis and management of CS, with EMB being largely supplanted by the use of 18F-fluorodeoxyglucose (FDG-PET) and cardiac magnetic resonance imaging (CMR). This article aims to provide a comprehensive review of imaging modalities currently utilized in the screening, diagnosis, and monitoring of CS, while highlighting the latest developments in each area.

Abstract Although uncommon, it is important to recognize that many systemic diseases can affect the heart. Cardiac involvement may in fact be the first sign of an underlying systemic disease. The presence or absence of a concomitant cardiac abnormality in the setting of a systemic disease may affect treatment options and prognosis.

Rationale: Inhibition of aromatase with anastrozole reduces pulmonary hypertension in experimental models. Objectives: We aimed to determine whether anastrozole improved the 6-minute-walk distance (6MWD) at 6 months in pulmonary arterial hypertension (PAH). Methods: We performed a randomized, double-blind, placebo-controlled phase II clinical trial of anastrozole in subjects with PAH at seven centers. Eighty-four postmenopausal women with PAH and men with PAH were randomized in a 1:1 ratio to receive anastrozole 1 mg or placebo by mouth daily, stratified by sex using permuted blocks of variable sizes. All subjects and study staff were masked. The primary outcome was the change from baseline in 6MWD at 6 months. By intention-to-treat analysis, we estimated the treatment effect of anastrozole using linear regression models adjusted for sex and baseline 6MWD. Assuming 10% loss to follow-up, we anticipated having 80% power to detect a difference in the change in 6MWD of 22 meters. Measurements and Main Results: Forty-one subjects were randomized to placebo and 43 to anastrozole, and all received the allocated treatment. Three subjects in the placebo group and two in the anastrozole group discontinued the study drug. There was no significant difference in the change in 6MWD at 6 months (placebo-corrected treatment effect, -7.9 m; 95% confidence interval, -32.7 to 16.9; P = 0.53). There was no difference in adverse events between the groups. Conclusions: Anastrozole did not show a significant effect on 6MWD compared with placebo in postmenopausal women with PAH and in men with PAH. Anastrozole was safe and did not have adverse effects. Clinical trial registered with www.clincialtrials.gov (NCT03229499).

Severe tricuspid regurgitation (TR) is a progressive condition associated with substantial morbidity, poor quality of life, and increased mortality. Patients with TR commonly have coexisting conditions including congestive heart failure, pulmonary hypertension, chronic lung disease, atrial fibrillation, and cardiovascular implantable electronic devices, which can increase the complexity of medical and surgical TR management. As such, the optimal timing of referral for isolated tricuspid valve (TV) intervention is undefined, and TV surgery has been associated with elevated risk of morbidity and mortality. More recently, an unprecedented growth in TR treatment options, namely the development of a wide range of transcatheter TV interventions (TTVI) is stimulating increased interest and referral for TV intervention across the entire medical community. However, there are no stepwise algorithms for the optimal management of symptomatic severe TR before TTVI. This article reviews the contemporary assessment and management of TR with addition of a medical framework to optimize TR before referral for TTVI.

Background An artificial intelligence (AI)-based electrocardiogram (ECG) model identifies patients with a higher likelihood of low ejection fraction (EF). Patients with an abnormal AI-ECG score but normal EF (false positives; FP) more often developed future low EF. Objective The purpose of this study was to evaluate echocardiographic characteristics and all-cause mortality risk in FP patients. Methods Patients with transthoracic echocardiography and ECG were classified retrospectively into FP, true negatives (TN) (EF ≥50%, normal AI-ECG), true positives (TP) (EF <50%, abnormal AI-ECG), or false negatives (FN) (EF <50%, normal AI-ECG). Echocardiographic abnormalities included systolic and diastolic left ventricular function, valve disease, estimated pulmonary pressures, and right heart parameters. Cox regression was used to assess factors associated with all-cause mortality. Results Of 100,586 patients (median age 63 years; 45.5% females), 79% were TN, 7% FP, 5% FN, and 8% TP. FPs had more echocardiographic abnormalities than TN but less than FN or TP patients. An echocardiographic abnormality was present in 97% of FPs. Over median 2.7 years, FPs had increased mortality risk (age and sex-adjusted HR: 1.64 [95% CI: 1.55-1.73]) vs TN. Age and sex-adjusted mortality was higher in FP with abnormal echocardiography than FP with normal echocardiography and to TN regardless of echocardiography result; FP with normal echocardiography had comparable mortality risk to TN with abnormal echocardiography. Conclusions FP patients were more likely than TNs to have echocardiographic abnormalities with 97% of exams showing an abnormality. FP patients had higher mortality rates, especially when their echocardiograms also had an abnormality; the concomitant use of AI ECG and echocardiography helps in stratifying risk in patients with normal LVEF.

Whipple disease is a rare systemic illness associated with weight loss, diarrhea, and arthralgia. Asymptomatic carriage is common, but the disease can be complicated by cardiac involvement and may result in culture-negative endocarditis. Cardiac manifestations of the disease can lead to death. This report presents the case of a 66-year-old man with Whipple disease and biventricular heart failure with cardiogenic shock. Medical therapy followed by successful replacement of the aortic and mitral valves resulted in substantial improvement.

Breast cancer (BC) survivors are at increased risk for cardiovascular disease (CVD) and require their primary care physicians to manage their long-term general medical care, including cardiovascular (CV) health. Yet, evidence exists that some primary care physicians possess insufficient knowledge about survivorship care. With the goal of bridging these knowledge gaps, a PubMed review was conducted from July 7, 2020, through October 2, 2020, with an updated PubMed review from January 3, 2024, through April 28, 2024, focusing on CV health considerations in the primary care of BC survivors. Search terms included variations of “breast cancer survivors” and “cardiovascular.” In total, 152 publications were included. Breasts cancer survivors may have increased CVD risk because some anticancer therapies are cardiotoxic and risk factors for BC often also increase the risk for CVD. Multiple risk factors overlap for BC and CVD such as older age, Western diet, early menarche, physical inactivity, high body mass index, and smoking. In this review, results are summarized from studies that report the presence of CV risk factors and CVD in BC survivors. Also described are the CV effects of BC therapies (chemotherapy, hormonal agents, targeted therapies, and radiotherapy) and the type of CV evaluation (cardiac imaging and measurement of biomarkers) that these patients may need. Primary care physicians have an important role in managing the CV health of BC survivors from preventing, assessing, and managing CV risk factors to referring patients to appropriate specialists when needed.