Background: Intramyocardial delivery of autologous bone marrow mononuclear cells (MNCs) reduce fibrosis and increase capillary density in ischemic heart failure with reduced ejection fraction (HFrEF) models. Initial clinical studies suggest beneficial effects in patients who received high doses of cells with favorable characteristics. We hypothesized that ischemic HFrEF patients selected for favorable MNC characteristics will have improved HF outcomes. Methods: This Phase III, multicenter, double-blind, 3:2 randomized trial enrolled NYHA II/III, refractory ischemic HFrEF patients with LVEF 20-40% and marrow CD34+ cell populations >140K/ml at 18 USA hospitals. Patients (n=115) received transendocardial delivery of concentrated cells or sham control procedure. Outcomes on all randomized participants over 24 months included 3-tier hierarchical composites of 1) all-cause death, heart transplant or LVAD, 2) non-fatal MACE and 3) six-minute walk distance (6MWD) or quality-of-life (QoL) scores analyzed by Finkelstein Schoenfeld test statistic and Win Ratio (WR), echocardiography, and pre-specified subgroups assessment. Findings: Participants were enrolled from 2018 through 2023. The primary endpoint was not met (WR=0̰·99, 95% CI: 0·63-1·56) due to improvements in tier-3 6MWD seen in the control group. The treatment group (n=74) had fewer tier 1 events (-3·6%, 95% CI: -17·5%, 10·3%), tier 2 events (-8·7%, 95% CI: -22·7%, 5·3%) and improved tier-3 QoL scores than controls (n=41; WR=1·42, 95% CI: 0·91, 2·22). Significant treatment effects were seen with the composite endpoint including tier-3 QoL for subgroups with NTproBNP/BNP >median of 506 pg/ml (WR=2·12, 95% CI: 1·05, 4·27), LVEF

We present the case of a 62-year-old man with severe coronary artery disease who presented to the hospital in refractory ventricular fibrillation cardiac arrest. He showed signs of life despite prolonged resuscitation. We thus decided to initiate extracorporeal cardiopulmonary resuscitation (ECPR). The patient had a known total occlusion of his infrarenal aorta that had been surgically bypassed with a bifemoral-axillary graft. We successfully initiated ECPR via the surgical graft, establishing blood flow to the central circulation through the axillary artery in a peripheral configuration while ensuring blood flow to the left leg via the femoral-femoral graft. The patient was extubated neurologically intact the following day and subsequently underwent coronary artery bypass graft surgery while on extracorporeal membrane oxygenation (ECMO) support. He was subsequently weaned off inotropic support and decannulated from ECMO. He was discharged home neurologically intact and independent in his activities of daily living. This case demonstrates that cannulation for ECPR via a surgical vascular graft is possible and that a total occlusion of the infrarenal aorta in the presence of a surgical bypass is not an absolute contraindication to ECMO.

Background There is increasing recognition that the pathophysiology of coronary microvascular dysfunction (CMD) plays a pivotal role in the development of heart failure with preserved ejection fraction (HFpEF). However, the mechanisms underlying this role are not known. Study design and methods The Women's Ischemia Syndrome Evaluation Mechanisms of Coronary Microvascular Dysfunction Leading to Pre-Heart Failure With Preserved Ejection Fraction (WISE Pre-HFpEF) is a prospective cohort study enrolling 180 women and men undergoing clinically indicated invasive coronary angiography for suspected ischemia with no obstructive coronary artery disease. The study aims to investigate (1) CMD-related ischemia contribution to myocellular damage and impaired left ventricular (LV) relaxation as determined invasively by ultra-high sensitivity cardiac troponin I (u-hscTnI) measurements in the coronary sinus/great cardiac vein and LV pressure-volume loops, respectively, during provocative stress testing with isometric handgrip, and (2) CMD-related ischemic myocellular damage contribution to LV diastolic dysfunction progression as assessed using cardiac magnetic resonance imaging obtained at enrollment and 1-2 years later, along with prospectively repeated ambulatory u-hs-cTnI measurements. Conclusions The WISE pre-HFpEF study is designed to investigate whether ischemic myocardial damage secondary to CMD contributes to the progression of LV diastolic dysfunction. The findings from this study will provide new understanding of the role of CMD in HFpEF development as well as the potential benefits of CMD-directed therapies for the prevention and treatment of HFpEF. Trial registration ClilicalTrial.gov, NCT03876223 (Am HeartJ 2025;284:47-56.)

BACKGROUND:Intra-aortic balloon pumps (IABP) are commonly used as a bridge to heart transplant (Htx). Although IABPs were designed for transfemoral arterial placement, axillary IABPs (axIABP) allow for continued ambulation and rehabilitation. However, increased rates of device complications with axillary compared to femoral insertion suggest anatomic variations that predispose patients to device failure. METHODS:We conducted a single-center retrospective study of patients who received axIABP as a bridge to HTx between February 2018 and July 2022. Pre-axIABP computed tomography (CT) images were reviewed for all patients, and anatomic features of the axillary and central arteries were measured and correlated with mechanical axIABP complications. RESULTS:A total of 48 patients underwent successful axIABP placement with available pre-insertion CT images, of whom 35 (72.9%) were male. Out of 48 patients, 26 (54.2%) experienced 34 complications, including axIABP rupture (n = 10, 29%), infection (n = 8, 23%), and thrombosis (n = 6, 18%). CTs showed an average axillary artery diameter and depth of 6.79 and 55.6 mm, respectively. The average subclavian artery takeoff angle from the aortic arch was 95.4°. CONCLUSION:Of the 10 vascular anatomic features measured, there was no association between any single measurement and axIABP complications. However, there may be other structural features not measured by routine CT, technical issues with insertion, and device factors not accounted for in this study that drive axIABP complications. Nonetheless, our findings suggest that normal variations in the measured vascular anatomy should not preclude axIABP use.

Objectives:To evaluate the utility of higher dose intracoronary acetylcholine (ACh) during invasive coronary function testing (CFT) in women with suspected ischemia and no obstructive coronary artery disease (INOCA) for detection of epicardial vasospasm, relation to quality of life (QoL) and the presence of scar by late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMRI). Background:CFT is an established method for diagnosis of coronary microvascular dysfunction (CMD). The utility of epicardial vasospasm provocation testing with higher dose ACh infusion is not fully understood. Methods:Women with suspected INOCA undergoing invasive CFT were enrolled in the Women's Ischemia Syndrome Evaluation-Pre-Heart Failure with Preserved Ejection Fraction (WISE Pre-HFpEF) study (NCT03876223). Incremental infusions of 0.364, 36.4 μg and 108 μg ACh were used for vasospasm provocation. Vasospasm was defined as ≥75 % artery diameter reduction compared to post-nitroglycerin diameter and related to QoL and LGE on CMRI. Results:Among 73 women (56 ± 11 years), epicardial vasospasm was detected in 17 (23 %). Among women with vasospasm, the vast majority (94 %) had coronary endothelial dysfunction and few (12 %) had other abnormal CFT measures. Those with vasospasm had more nocturnal angina symptoms, calcium channel blocker use, poorer QoL (all p = 0.001) and disease perception (p = 0.02) than those without. LGE scar by CMRI was not associated with vasospasm (p = 0.22). Conclusions:Among women with suspected INOCA, intracoronary Ach spasm testing provoked epicardial vasospasm in one fourth. Women with epicardial vasospasm overwhelmingly had concomitant endothelial dysfunction, worse QoL but not more frequent myocardial scar on CMRI.

Background: Patients with diabetes mellitus and concomitant atheterosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. Methods: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this pre-specified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome. Results: Of 15,076 patients, 5,676 (39%) had DM of which 2,820 (49.7%) were assigned to 81 mg and 2,856 (50.3%) to 325 mg of aspirin. Patients with vs. without DM had higher rates of the composite cardiovascular outcome (9.6% vs 5.9%, p < 0.001) and bleeding events (0.78% vs 0.50%, p < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs 10.0%; HR 0.98; 95% CI 0.83-1.16, p = 0.265) or safety outcome (0.87% vs 0.69%; subdistribution HR 1.25; 95% CI 0.72 – 2.16, p = 0.772). Conclusions: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest higher dose of aspirin yields no added clinical benefit even in a more vulnerable population

Saphenous vein graft (SVG) pseudoaneurysms are an infrequent, but life-threatening complication of coronary artery bypass grafting (CABG) surgery if left untreated. Here, we discuss the case of a 77-year-old patient, with a prior history of CABG and transcatheter aortic valve implantation (TAVI), who was incidentally found on computed tomography angiography (CTA) to have a pseudoaneurysm of his SVG with an initial chief complaint of dizziness. Despite increasing reports of SVG pseudoaneurysm, there is no consensus on definitive treatment. Due to the high mortality risk of this patient with surgical intervention, a minimally invasive percutaneous coronary intervention was performed. The patient was effectively treated with two overlapping Viabahn-covered stents, which completely excluded the pseudoaneurysm. Follow-up imaging at two months showed two well-positioned overlapping self-expanding stents with total occlusion of the pseudoaneurysm.

Background:Women have smaller coronary size than men independent of body surface area. Female to male heart transplantation demonstrates coronary lumen enlargement. Purpose:To investigate relationships between endogenous androgens and coronary luminal size in women with suspected ischemic heart disease (IHD). Methods:We analyzed 69 women with available androgen levels. Results:Group mean age was 54 ± 10 years with 64 % post-menopausal. Lumen cross-sectional area (CSA) and external elastic membrane (EEM) CSA positively correlated with free testosterone (FT) (r = 0.29, p = 0.049; r = 0.29, p = 0.01), respectively, and negatively correlated with SHBG (r = -0.26, p = 0.03; r = -0.29, p = 0.02), respectively. Atheroma CSA positively correlated with FT (r = 0.24. p = 0.05). These correlations became non-significant after adjusting for waist circumference. Conclusions:In women with suspected ischemic heart disease, endogenous androgens, coronary atheroma and luminal size are related, and may be moderated by waist circumference.

Background: Transcatheter aortic valve replacement (TAVR) is a commonly used treatment for severe aortic stenosis. As degenerative aortic stenosis is primarily a disease afflicting older adults, a frailty assessment is essential to patient selection and optimal periprocedural outcomes. Objective: This study aimed to enhance frailty assessments of TAVR candidates by integrating real-world structured and unstructured data. Methods: This study analyzed data from 14,000 patients between January 2018 and December 2019 to assess frailty in TAVR patients at the University of Florida. Frailty was identified using the Fried criteria, which includes weight loss, exhaustion, walking speed, grip strength, and physical activity. Latent Dirichlet allocation for topic modeling and Extreme Gradient Boosting for frailty prediction were applied to unstructured clinical notes and structured electronic health record (EHR) data. We also used least absolute shrinkage and selection operator regression for feature selection. Model performance was rigorously evaluated using nested cross-validation, ensuring the generalizability of the findings. Results: Model performance was significantly improved by combining unstructured clinical notes with structured EHR data, achieving an area under the receiver operating characteristic curve of 0.82 (SD 0.07), which surpassed the EHR-only model's area under the receiver operating characteristic curve of 0.64 (SD 0.08). The Shapley Additive Explanations analysis found that congestive heart failure management, back problems, and atrial fibrillation were the top frailty predictors. Additionally, the latent Dirichlet allocation topic modeling identified 7 key topics, highlighting the role of specific medical treatments in predicting frailty. Conclusions: Integrating unstructured clinical notes and structured EHR data led to a notable enhancement in predicting frailty. This method shows great potential for standardizing frailty assessments using real-world data and improving patient selection for TAVR.

Heart failure with preserved ejection fraction (HFpEF) is the most common cardiac complication in patients with coronary microvascular dysfunction (CMD), yet its underlying pathways remain unclear. Aortic pulse-wave velocity (aPWV) is an indicator of large artery stiffness and a predictor for cardiovascular disease. However, aPWV in CMD and HFpEF is not well characterized and may provide understanding of disease progression. Among participants without obstructive coronary artery disease, we evaluated 51 women with suspected CMD and 20 women and men with evidence of HFpEF. All participants underwent aPWV measurement (SphygmoCor, Atcor Medical) with higher aPWV indicating greater vascular stiffness. Cardiac magnetic resonance imaging (CMRI) assessed left ventricular (LV) ejection fraction, CMD via myocardial perfusion reserve index (MPRI), and ventricular remodeling via LV mass-volume ratio. . Statistical analysis was performed using Wilcoxon rank sum tests, Pearson correlations and linear regression analysis. Compared to the suspected CMD group, the HFpEF participants were older (65 ± 12 vs 56 ± 11 yrs., p = 0.002) had higher BMI (31.0 ± 4.3 vs 27.8 ± 6.7 kg/m2, p = 0.013), higher aPWV (10.5 ± 2.0 vs 8.0 ± 1.6 m/s, p = 0.05) and lower MPRI (1.5 ± 0.3 vs1.8 ± 0.3, p = 0.02), but not remodeling. In a model adjusted for cardiovascular risk factors, the HFpEF group had a lower LVEF (estimate −4.78, p = 0.0437) than the suspected CMD group. HFpEF participants exhibit greater arterial stiffness and lower myocardial perfusion reserve, with lower LVEF albeit not remodeling, compared to suspected CMD participants. These findings suggest arterial stiffness may contribute to progression from CMD to HFpEF. Prospective work is needed and ongoing.

Alterations in the dynamic pulsatility and elastic function of the aorta are thought to contribute to the development of coronary microvascular dysfunction, via their impact on small vessel function as well as on left ventricular remodeling.( 1 Mitchell GF. Aortic stiffness, pressure and flow pulsatility, and target organ damage. J Appl Physiol (1985) 2018;125:1871-1880. Google Scholar ) We previously showed that invasively measured aortic stiffness is correlated with coronary flow reserve (CFR) in women with suspected ischemia and no obstructive coronary arteries (INOCA).( 2 Nichols W.W. Denardo S.J. Davidson J.B. Huo T. Bairey Merz C.N. Pepine C.J. Association of aortic stiffness and wave reflections with coronary flow reserve in women without obstructive coronary artery disease: An ancillary study from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE). Am Heart J. 2015; 170: 1243-1254 Google Scholar ) This study aimed to explore the relationship between extended parameters of aortic health and coronary physiology from a contemporary cohort of women with suspected INOCA.

Background Cytochrome P450 2C19 (CYP2C19) intermediate and poor metabolizer patients exhibit diminished clopidogrel clinical effectiveness after percutaneous coronary intervention (PCI). However, outcome studies to date have lacked racial diversity. Thus, the impact of CYP2C19 genotype on cardiovascular outcomes in patients treated with clopidogrel who identify as Black or African American remains unclear. Methods and Results Adults among 5 institutions who self‐identified as Black or African American, underwent PCI and clinical CYP2C19 genotyping, and were treated with clopidogrel were included. Data were abstracted from health records. Major atherothrombotic (composite of death, myocardial infarction, ischemic stroke, stent thrombosis, or revascularization for unstable angina) and bleeding event rates within 1 year after PCI were compared across CYP2C19 metabolizer groups using multivariable Cox regression adjusted for potential confounders and baseline variables meeting a threshold of P <0.10. The population included 567 Black patients treated with clopidogrel (median age, 62 years; 46% women; 70% with an acute coronary syndrome indication for PCI). Major atherothrombotic events rates were significantly higher among clopidogrel‐treated intermediate and poor metabolizers (24 of 125 [19.2%]) versus patients treated with clopidogrel without a no function allele (43 of 442 [9.7%]; 35.1 versus 15.9 events per 100 person‐years; adjusted hazard ratio, 2.00 [95% CI, 1.20–3.33], P =0.008). Bleeding event rates were low overall (23 of 567 [4.1%]) and did not differ among the metabolizer groups. Conclusions Black patients with CYP2C19 intermediate and poor metabolizer phenotypes who are treated with clopidogrel exhibit increased risk of adverse cardiovascular outcomes after PCI in a real‐world clinical setting. Bleeding outcomes should be interpreted cautiously. Prospective studies are needed to determine whether genotype‐guided use of prasugrel or ticagrelor in intermediate and poor metabolizers improves outcomes in Black patients undergoing PCI.