Ray, Jordan

Abstract 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 18 F-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 18 F-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.

BACKGROUND: Publicly reported 30-day acute myocardial infarction (AMI) mortality rates are widely used to benchmark hospital performance. However, these measures may lack validity when they include deaths among patients with do-not-resuscitate (DNR) orders or those receiving palliative care—groups for whom mortality may be expected and goal-concordant. METHODS: We analyzed the national 100% Medicare Inpatient Standard Analytic File and Medicare Beneficiary Summary file to assess 30-day AMI mortality rates stratified by DNR status (absent, present-on-admission, and postadmission) and palliative care involvement. We then conducted a retrospective chart review of all 30-day AMI mortalities at a single academic medical center (2019–2025), applying Global Registry of Acute Coronary Events and a Palliative Performance Scale scores to identify unpreventable deaths, which we defined as a Global Registry of Acute Coronary Events >190.5 or Palliative Performance Scale ≤40%. Global Registry of Acute Coronary Events is a risk-stratification tool using clinical and laboratory variables whereas the Palliative Performance Scale is a bedside functional status and palliative care assessment quantifying patient’s self-care ability. RESULTS: Across n=467 259 total AMI encounters, mean (SD) age was 75.1 (10.5), and the population was 44% female. Thirty-day mortality was 10.4% (39 112/376 062) among patients without DNRs, 43.1% (26 181/60 719) in those with present-on-admission DNR, and 72.1% (21 984/30 478) in those with postadmission DNR. Among 9.2% (43 090/467 259) of encounters with palliative care, there was a 76.9% mortality rate (33 151/43 090). Hazard ratios for mortality were 5.25 (95% CI, 5.17–5.33) for present-on-admission DNR and 10.73 (95% CI, 10.55–10.91) for postadmission DNR as compared with encounters without DNRs. Among n=24 AMI mortalities at our institution, 71% (17/24) had DNRs, and 33% (8/24) met the unpreventable death criteria. CONCLUSIONS: The validity of 30-day AMI mortality metrics may be undermined by their inclusion of high-acuity, end-of-life patients, which may disincentivize hospitals from delivering appropriate, patient-centered care. Removal of DNR or palliative cases from performance measures should be explored to better identify opportunities for reducing preventable deaths.

Background: Coronary artery disease (CAD) is common among liver transplantation (LT) candidates, yet whether pre-transplant percutaneous coronary intervention (PCI) improves post-LT outcomes remains uncertain. Methods: We conducted a single-center, Institutional Review Board-approved cohort study of adults undergoing LT from 2005 to 2025. Asymptomatic candidates with significant stenosis on invasive angiography were included; prior coronary artery bypass grafting was excluded. The primary endpoint was major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke/transient ischemic attack, new systolic dysfunction, post-LT coronary revascularization, or all-cause death). Results: Among 111 patients (median age 65 years; 84% male), 66 (59%) underwent PCI and 45 (41%) were managed medically. Over a median 32 months of follow-up, 61 patients (55%) experienced MACE. Composite MACE did not differ between PCI and non-PCI groups (52% vs. 60%, p = 0.40; log-rank p = 0.59). Fine–Gray modeling showed no association of PCI with MACE; independent predictors were prior MI (HR 1.81, 95% CI 1.01–3.24) and pre-transplant dialysis (HR 2.13, 95% CI 1.07–4.24). Major bleeding occurred in 7%. Matched and era-stratified analyses were concordant. Conclusions: In asymptomatic LT candidates with angiographically severe CAD, pre-LT PCI was not associated with a lower incidence of post-LT MACE.

Background Aortic valve calcium score is associated with hemodynamic severity of aortic stenosis. Whether this association is present in calcific mitral stenosis remains unknown. Methods and Results This study was a retrospective analysis of consecutive patients with mitral stenosis secondary to mitral annular calcification (MAC) undergoing transseptal catheterization. All patients underwent invasive mitral valve assessment via direct left atrial and left ventricular pressure measurement. Computed tomography within 1 year of cardiac catheterization and with adequate visualization of the mitral annulus was included. MAC calcium score quantification by Agatston method was obtained offline using dedicated software (Aquarius, TeraRecon, V.4). Median patient age was 66.9±11.2 years, 47% of patients were women, 50% had coronary artery disease, 40% had atrial fibrillation, 47% had prior cardiac surgery, and 33% had prior chest radiation. Median diastolic mitral valve gradient was 9.4±3.4 mm Hg on echocardiography and 8.5±4 mm Hg invasively. Invasive median mitral valve area using the Gorlin formula was 1.87±0.9 cm 2 . Median MAC calcium score for the cohort was 7280±7937 Hounsfield units. MAC calcium score correlated with the presence of atrial fibrillation ( P =0.02) but was not associated with other comorbidities. There was no correlation between MAC calcium score and mitral valve area ( r =0.07; P =0.6) or mitral valve gradient ( r =−0.03; P =0.8). Conclusions MAC calcium score did not correlate with invasively measured mitral valve gradient and mitral valve area in patients with MAC‐related mitral stenosis, suggesting that calcium score should not be used as a surrogate for invasive hemodynamic parameters.

Abstract Cardiovascular disease is a major cause of mortality among oncologic patients. As cancer therapies continue to evolve and advance, cancer survival rates have been increasing and so has the burden of cardiovascular disease within this population. For this reason, cardio-oncology plays an important role in promoting multidisciplinary care with the primary care provider, oncology, and cardiology. In this review, we discuss the roles of different providers, strategies to monitor patients receiving cardiotoxic therapies, and summarize cancer therapy class-specific toxicities. Continued collaboration among providers and ongoing research related to cardiotoxic cancer therapies will enable patients to receive maximal, evidence-based, comprehensive care.

As survival in breast cancer patients from newer therapies increases, concerns for chemotherapy-induced cardiotoxicity (CIC) have offset some of these benefits, manifesting as a decline in left ventricular ejection fraction (LVEF). Patients receiving anthracycline-based chemotherapy followed by trastuzumab are at risk for CIC. Previous research evaluating whether clinical biomarkers predict cardiotoxicity has been inconsistent. Recently, angiotensin II type 1 receptor (ATR1) and endothelin 1 (ET1) have been shown to play a role in breast tumor growth. We evaluated ATR1 and ET1 expression in breast cancer tissue and its association with CIC. A total of 33 paraffin-embedded breast tissue specimens from women with breast cancer treated with anthracycline-based chemotherapy and trastuzumab were analyzed by immunohistochemistry (IHC) and qRT-PCR. We found that ET1 expression was increased in patients with an LVEF ≤ 50% (p = 0.032) with a lower LVEF correlating with higher ET1 expression (r = 0.377, p = 0.031). In patients with a change in LVEF of greater than 10%, greater ET1 expression was noted compared to those without a change in LVEF (p = 0.017). Increased ET1 expression in breast tumor tissue is associated with reduced LVEF. Future studies need to examine whether ET1 may be a tissue biomarker that helps predict the risk of developing CIC in women with breast cancer.

Introduction: Pulmonary arterial hypertension (PAH) is a fatal disease and vasodilators are the mainstay for its therapy. However, they offer restricted advancement opportunities for the control and treatment of PAH. Thus, the PAH field needs a paradigm-shifting strategy for its successful management and control. Objective: To test the hypothesis that gut microbial dysbiosis and its increased permeability are associated with PAH. Methods: Healthy control subjects and patients with PAH were recruited from two hospitals in the Americas to ascertain the wider applicability of our hypothesis. Fecal samples of PAH patients (n=19) and control, reference subjects (n=16) were obtained at the Hospital de Clinicas de Porto Alegre, Brazil, for microbiota analysis. Plasma/serum samples were collected from PAH patients (n=22) and control, reference subjects (n=19) at the Mayo Clinic, Jacksonville, Florida, USA, for analysis of gut leakiness and inflammatory biomarkers. Results: In PAH patients, a significant decrease in abundance, diversity and evenness of gut microbial population was observed as measured by 16S ribosomal DNA analyses of fecal samples. Analysis of fecal bacteria populations also demonstrated significant increases in gram-positive, facultative-anaerobic genera, such as Actinomyces, Bifidobacterium Slackia, and Streptococcus in PAH patients. Further, plasma zonulin and iFABP, the biomarkers for gut leakiness increased by 40.3% (p=0.0018) and 81% (p=0.0012), respectively in PAH patients. High plasma LPS, HMGB1, and TIMP1 levels are involved in increased gut inflammation and gut mucosal injury. We also observed LPS, HMGB1, and TIMP1 levels were increased by 363% (p=0.0096), 20.5% (p=0.0027), and 213% (p<0.0001), respectively in PAH patients. Conclusions: PAH patients demonstrate profound gut microbial dysbiosis and increased permeability and inflammation. Further characterization of PAH specific microbial species holds novel management potential with the use of pre- and probiotics, designer antibiotics, appropriate fecal/bacterial transplantation, on top of background proven therapies.

Abstract Introduction Doxorubicin is an anthracycline used as a chemotherapeutic drug for the treatment of a wide range of adult and pediatric cancers. Doxorubicin is associated with an increased risk of cardiomyopathy and heart failure with up to 10% of patients developing cardiac complications. A GWAS conducted of 1,191 patients from the N9831 clinical trial identified that cardiac gene expression and genetic variants of TRPC6 were associated with a decline in left ventricular ejection fraction (LVEF) (p=0.005 and p=1.6x10–6, respectively). TRPC6 is a non-selective cation channel expressed in heart and vascular tissue. TRPC6 participates in the pathogenesis of cardiac hypertrophy as a pathological response to chronic mechanical stress. Chronic activation has been found to promote cardiac fibrosis leading to heart failure. Purpose TRPC6 variants could be associated with increased risk of doxorubicin-induced cardiotoxicity. Data/tests to determine which patients may progress to cardiomyopathy and heart failure are currently lacking and there are no targeted treatments to prevent cardiomyopathy in these patients. Methods In preliminary in vivo data, B6.129 wild-type mice or TRPC6 knockout mice were treated with either 6x intraperitoneal saline or 4mg/kg doxorubicin injections (cumulative dose of 24mg/kg). Results We found doxorubicin increased cardiac vacuolation (male, p≤0.001 and female, p≤0.05) in WT mice compared to controls. Higher HW/BW ratio was observed in male TRPC6 knock out mice compared to wild-type mice when both were treated with doxorubicin (males, p=0.005 and females, p=0.19). Additionally, we found that doxorubicin-induced cardiac injury was significantly reduced in TRPC6 knock-out mice compared to wild-type mice based on reduced vacuolation (p=0.0004 males, p=0.03 females), with the effect being greater in male mice than female mice. Furthermore, a significant decrease in stroke volume (p=0.007), diastolic volume (p=0.01) and cardiac output (p=0.004) in wild-type male mice treated with doxorubicin compared to control and TRPC6 knock-out mice. Our in vitro preliminary data show that inhibition of TRPC6 using the TRPC6 inhibitor GsMTx-4 in human iPSC-derived cardiomyocytes significantly reduced doxorubicin-induced apoptosis (p&lt;0.0001). Further we treated male mice with the TRPC6 inhibitor, GsMTx4, and found that they had less global longitudinal cardiac strain (p=0.04) and higher ejection fraction (p=0.01) compared to mice who were only treated with doxorubicin. Histologically we found that mice given the TRPC6 inhibitor had less fibrosis as measured by Trichrome stained heart sections (p=0.004) which could account for improvements in cardiac function. Conclusion TRPC6 could be a novel therapeutic target in the prevention of chemotherapy-induced cardiomyopathy and heart failure. Additionally genetic mapping of TRCP6 functional variants may provide a new screening tool to determine increased risk of developing heart failure. Funding Acknowledgement Type of funding sources: Private hospital(s). Main funding source(s): Mayo Clinic

Abstract Background: Cardiac toxicity (CT) in the form of left ventricular systolic dysfunction is a well-known complication of anti-HER2 therapy. Prior clinical trial data has suggested potential factors associated with increased risk for CT. We sought to develop a clinical risk prediction model from real world patients to better identify patients who may be at higher risk for CT. Methods: Patients treated with anti-HER2 agents at all Mayo Clinic sites from Jan 2008 to July 2015 were reviewed. Patient data including age, race, body mass index, comorbidities, smoking history, baseline ejection fraction (EF), presence of left ventricular hypertrophy (LVH), prior cancer treatments, number of anti-HER2 agents used, and cardiac medication use were recorded. Factors were compared in patients with and without development of CT. Cox regression models were used to identify univariate and multivariate predictors of CT. A risk score was then assigned based on the final multivariable model. Results: 604 patients were included in final analysis. Median follow-up 2.9 yrs; median age: 57 yr; baseline EF: 64%. One yr CT rate was 7%. Independent predictors of CT were age, baseline EF, LVH, and anthracycline use (C index=0.74). Based on model coefficient, scores of 1, 1, 2 and 3 were assigned to age&gt;55, EF &lt;60%, anthracycline exposure and LVH, respectively. Two random samples of 300 patients were created out of the original cohort for internal validation of the risk score model. In each, the risk score was found to be a highly significant predictor for CT with C index of 0.72 {HR 2.13 (95% CI 1.57-2.90), p &lt;0.001} and 0.77 {HR 2.45 (95% CI 1.74-3.44), p &lt;0.001}. Conclusions: Patients with risk factors of older age, lower baseline EF, anthracycline use and LVH are at increased risk for CT when treated with anti-HER2 agents. Using a risk prediction model at therapy initiation may enhance identification of patients who benefit from cardiology referral, closer cardiac monitoring, and/or prophylactic treatment while on anti-HER2 targeted therapy. Table 1. Multivariable Cox regression model predicting cardiac dysfunctionParameterParameter EstimateHR (95%CI)p valueScoreAge &gt;550.909552.48(1.27, 4.84)0.00751EF&lt;600.634361.89(1.01, 3.53)0.04751Anthracycline Exposure1.046132.85(1.48, 5.46)0.00162Baseline LVH1.633565.12(2.04,12.85)&lt;0.0013 Citation Format: Pooja P Advani, Lauren Cornell, Zhuo Li, Jordan Ray, Catalina Sanchez, Armando Villanueva, Taryn Smith, Alvaro Moreno-Aspitia. A validated clinical risk prediction model for cardiac toxicity in patients treated with antiHER2 agents [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-14.

A 61-year-old male presented for an annual exam and received a transthoracic echocardiogram (TTE) which revealed a mobile mass arising from a subaortic membrane. Further investigations with a transesophageal echocardiogram (TEE) and cardiac computerized tomography angiography (CTA) confirmed the presence of a mobile 9 mm×3 mm mass on a subaortic membrane. Cardiothoracic surgery was performed with an open operation removing the mass and subaortic membrane. Upon visual inspection, the mass was likened to a sea anemone and immunohistochemical staining performed pathologically confirmed the diagnosis of cardiac papillary fibroelastoma. This case represents the first reported example of a cardiac papillary fibroelastoma (PFE) arising from a subaortic membrane. Although PFEs are benign cardiac tumors, proper identification and consideration for excision of these lesions may be indicated to prevent thromboembolic complications.