Risultati per: Il ruolo dell’imaging nel sanguinamento gastrointestinale: linea guida

Circulation, Volume 150, Issue Suppl_1, Page A4136597-A4136597, November 12, 2024. Background:Collagen is the major extracellular matrix that imparts mechanical strength to fibrous caps covering fibroatheromas. Intracoronary polarimetry with polarization-sensitive (PS) optical frequency domain imaging (OFDI) measures polarization properties, such as birefringence and depolarization (Figure 1). Birefringence is elevated in collagen and collagen-synthesizing smooth muscle cells, while depolarization is increased by the presence of macrophages and lipid/necrotic cores.Purpose:This study aimed to investigate polarimetric signatures of coronary lesions with healed coronary plaques (HCP) in patients with ACS and chronic coronary syndrome (CCS). Furthermore, we aimed to investigate diagnostic value for birefringence and depolarization of ACS culprit lesions discriminating from CCS target lesions.Methods:We conducted a single center prospective registry of intracoronary PS-OFDI imaging in patients with coronary artery disease (n = 50). A total of 862 OFDI frames selected from culprit or target lesions were analyzed. Coronary plaque phenotypes were assessed using conventional OFDI imaging. HCP was defined as plaques with one or more layers of different optical density and a clear demarcation from underlying components on intensity images. Birefringence and depolarization of the newer intima was measured in cross-sectional images. Birefringence and depolarization of ACS- and CCS-lesions were compared using a generalized estimating equation model. Receiver operating characteristic (ROC) analysis was used to investigate the diagnostic performance of polarimetric signatures for identifying ACS-lesions.Results:Compared to CCS-lesions, ACS-lesions featured significantly higher lipid-burden index and maximum lipid arc (both p < 0.05). Compared to the CCS-lesions, ACS-lesions exhibited significantly lower birefringence (p < 0.05) and higher depolarization (p < 0.05). In the ROC analysis for differentiating ACS-lesions from CCS-lesions, area under the curves (AUC) for birefringence and depolarization were 0.712 and 0.672, respectively. In the multivariable ROC analysis in diagnosing ACS lesions, combination of birefringence with depolarization improved the AUC to 0.755 (p ＝ 0.025).Conclusions:Intracoronary polarimetry provides quantitative assessment of plaque composition in patients. Further research is warranted to investigate whether birefringence can serve as a marker of healing failure following plaque rupture and erosion.

Circulation, Volume 150, Issue Suppl_1, Page A4142247-A4142247, November 12, 2024. Background:Cardiac transplantation remains the single most effective treatment for end-stage heart failure. Despite the routine use of anti-rejection drugs in clinical practice, approximately 40% of cardiac transplant patients still experience unavoidable rejection. Timely diagnosis of early acute rejection (AR) is essential to prevent further tissue damage. Transplant rejection and graft damage is primarily mediated by recipient cytotoxic CD8+T cells, which attack allografts by releasing perforin and granzyme B (GzmB).Aim:This study aimed to evaluate whether GzmB-targeted positron emission tomography (PET) imaging agent (68Ga-grazytracer) can characterize T lymphocyte infiltration in AR.Method:Mice were subjected to GzmB-targeted PET/CT on POD 3, 5, and 7. Autoradiography, Masson staining, immunohistochemistry, and flow cytometry were performed to verify the inflammatory infiltration and graft damage . Allograft-bearing mice were intraperitoneally administered with tacrolimus (2 mg kg−1) daily from operative day to post-operative day (POD) 7.Result:The uptake of68Ga-grazytracer was observed increased with the extension of rejection time(SUVmax:0.54 ± 0.07 vs. 0.19 ± 0.05 at POD 7 days, P

Circulation, Volume 150, Issue Suppl_1, Page A4124722-A4124722, November 12, 2024. Background:Cardiovascular magnetic resonance (CMR) derived T1 parametric mapping offers quantitative, regional assessments of myocardial edema and fibrosis. Pediatric cardiac allografts are subject to fibrosis due to rejection inflammation, coronary vasculopathy, cardiopulmonary bypass and graft failure. The role of CMR parametric mapping in identifying clinically important myocardial fibrosis in this population remains unknown. Thus, the aim of this study was to correlate endomyocardial biopsy (EMB)-derived fibrosis measurements with local T1 values in PHTx patients.Methods:PHTx pts undergoing EMB also underwent simultaneous cardiac MRI including T1 parametric mapping in 6 short axis slices at 1.5 T. Segmental T1 values were measured and the segments corresponding to EMB sites were noted from overlay registration. Trichrome-stained EMBs were digitally scanned and analyzed for fibrosis content. Encounters were divided into low and high fibrosis groups, and clinical variables from echocardiography, clinical treatment, and cardiac catheterization were compared using student’s t-test and linear regression.Results:Thirty-three PHTx pts (age of 12.8+4.9 years) underwent 94 surveillance encounters, for a total of 283 EMB samples. 75 encounters had no active rejection and 19 encounters had active rejection requiring treatment. Average T1 was significantly higher in active rejection group (1056 vs 1018 ms, p

Circulation, Volume 150, Issue Suppl_1, Page A4137891-A4137891, November 12, 2024. Background:Inflammation and immune dysregulation are thought to drive residual cardiovascular disease risk among persons living with HIV (PLWH) despite effective viral suppression with antiretroviral therapy (ART).Question:We investigated differences in carotid vascular inflammation and atherosclerosis in a longitudinal cohort of virally suppressed PLWH (n = 50; on stable ART with CD4 >250 cells/mm3, viral load 6 months) and HIV-uninfected controls (n = 51) matched for age, sex, hypertension, diabetes, smoking, hyperlipidemia, and family history of premature coronary artery disease.Methods&Results:Participants were >40 years old at enrollment, 8% female, and had a high prevalence of cardiovascular risk factors (Table 1). Measures of carotid inflammation and capillary permeability (Ktrans), neovascularization (Vp), and wall thickness were assessed at baseline, 1 year, and change over 1 year by dynamic contrast-enhanced magnetic resonance imaging. Both PLWH and controls demonstrated a reduction in systolic and diastolic blood pressures and total cholesterol over 1 year; however, the difference was not significant by HIV status. PLWH had a significant reduction in triglycerides compared with controls (-48.8 mg/dL vs 12.8 mg/dL; p = 0.026). HIV was not associated with baseline, follow-up, or change in markers of systemic inflammation assessed by plasma cytokines (C-reactive protein, interleukin-6, interleukin-1ß), nor vascular inflammation or plaque as assessed byKtrans,Vp, carotid wall thickness, or percent wall volume (Tables 2&3).Conclusions:In contrast to other studies of chronically treated and virally suppressed PLWH, HIV infection was not associated with carotid inflammation or plaque.

Circulation, Volume 150, Issue Suppl_1, Page A4146885-A4146885, November 12, 2024. Background:Mitral annular disjunction (MAD) is identified by a displacement of the posterior mitral valve annulus into the left atrial wall and is commonly coexisting with mitral valve prolapse (MVP). MAD and MVP are both associated with a high prevalence of premature ventricular complexes (PVCs); however, the underlying mechanisms of increased PVC burden in these patients are unknown. We sought to determine the association between PVC burden, structural heart changes, and late gadolinium enhancement (LGE) in patients with MVP, with and without MAD.Methods:We analyzed patients with MVP who underwent cardiac magnetic resonance (CMR) imaging and 24-48hr Holter monitoring from 2020 to 2024. Patients with prior myocardial infarction or ischemic pattern LGE were excluded. LGE was characterized dichotomously as present or absent. Multivariate logistic regression was performed to assess significant independent associations with PVC burden > 5%.Results:The study included 107 patients (mean age 53.2 ± 17.6 years old, female (65%), mean LVEDVi 99cc/m2, mean LVEF 58±8%, mean mitral regurgitant fraction 23±16%). There were 56 patients with MAD + MVP and 51 with MVP – MAD. PVCs > 5% were noted in 26% of the cohort, and LGE was present in 32%. MAD was present in 52%, and 14% had mitral regurgitant fraction >40%. Multivariate analysis identified MAD and sex-specific LV dilation as independent predictors of significant PVC burden. Mitral regurgitant fraction showed a trend towards significance, while LGE was not significantly associated with PVC burden >5% (Figure 1).Conclusions:PVC burden > 5%, MAD, and LGE were prevalent in patients with MVP referred for CMR evaluation. MAD and left ventricular (LV) dilation were independently associated and more strongly predictive of high PVC burden than LGE. Future studies are needed to investigate further structural mechanisms and potential interactions with myocardial fibrosis impacting electrical activity in patients with MVP.

Circulation, Volume 150, Issue Suppl_1, Page A4123370-A4123370, November 12, 2024. Background:Cardiovascular imaging is critical for the diagnosis and management of cardiovascular disease. Whether geographic distance to a cardiovascular imaging center (CVIC) impacts access to care is unknown.Methods:We evaluated all Medicare beneficiaries (Fee-for-service and Medicare Advantage) from 2018-2022, excluding those < 65, without continuous Medicare enrollment in the previous year, individuals missing zip code of residence, or CVICs missing zip codes. We estimated distance from the centroid of an individual’s zip code of residence to the centroid of the zip code with the nearest CVIC (defined as > 10 imaging procedures/year). Multivariable regression models were used to estimate likelihood of imaging receipt by distance.Results/Data:A total of 64,260,530 individuals (age 73.0 ± 8 years, 54.6% female, 80.1% White) received care at 3,886 CVICS. The vast majority (95%) lived within 16 miles of a CVIC, but varied considerably by modality with substantially greater distances for cardiac CT, cardiac MRI, and PET (Median [IQR] distance in miles to CVIC, Echo: 3.4 [0.4-7.0]; SPECT: 3.8 [1.3-7.9]; cardiac CT: 8.1 [3.7-21.3]; cardiac MRI: 17.4 [7.3-43.3]; PET: 88.9 [26.2-194.6]). CVICs performing cardiac CT, cardiac MRI, or PET were nearly all in metropolitan locations. Likelihood of imaging receipt was triphasic: lowest within 0-10 miles of a CVIC (mainly metropolitan locations), greater within 10-15 miles, and then increasingly lower beyond 15 miles (Figure 1). Sites beyond the 16-mile threshold were predominantly in the Midwest and West (Figure 2).Conclusions:In this study of 64 million Medicare beneficiaries, 2018-2022, 95% of the US population was found to live within 16 miles of a CVIC, though varied by modality. While those living > 16 miles from a CVIC received less imaging, the lowest use was identified among individuals living in the same zip code as a CVIC, suggesting a possible disconnect between access to imaging care and proximity.

Circulation, Volume 150, Issue Suppl_1, Page A4115015-A4115015, November 12, 2024. Background:Coronary Artery Disease (CAD) is a significant global health issue, necessitating improved diagnostic tools for visualizing cardiac energetics. Traditional imaging methods such as PET and dobutamine stress echocardiography do not directly assess mitochondrial metabolism. Hyperpolarized Carbon-13 metabolic magnetic resonance imaging (HP-13C MRI) offers a promising non-invasive method for investigating mitochondrial function in CAD. This study utilizes HP-13C MRI to detect changes in mitochondrial metabolism in patients undergoing Coronary Artery Bypass Graft (CABG) surgery (Fig.1).Methods:We conducted HP-13C MRI examinations on two patients with advanced CAD before and (~4-6 months after CABG surgery and one healthy subject (Fig. 2 A,B). Participating subjects provided informed consent according to a protocol approved by the Institutional Review Board and Protocol Review Committee. Baseline blood samples were analyzed for pyruvate, triglycerides, free fatty acids, and insulin levels. Post-glucose load, patients received an intravenous injection of an IND-approved metabolic probe, [1-13C] pyruvic acid, prepared under Good Manufacturing Practice regulations. The HP solution was administered after polarization in a clinical polarizer (SPINlab™, GE Healthcare). Imaging was performed using a GE MR750 MR system with a Helmholtz loop-pair13C coil (PulseTeq Limited, UK). Data were reconstructed and analyzed with MATLAB scripts.Results and Discussion:Baseline blood measurements were normal for the healthy subject, but those with advanced CAD showed variable and abnormal values (Fig. 2C). HP-13C MRI safely assessed cardiac metabolism in patients with advanced CAD. Patients with advanced CAD exhibited reduced pyruvate metabolism compared to healthy controls, shown by lower myocardial bicarbonate/(bicarbonate+lactate) ratios (Bic/(Bic+Lac)). Following CABG, only Patient 2 showed improved Bic/(Bic+Lac), while Patient 1 did not (Fig. 3A-B). This variability may be influenced by differences in nutrition, hormonal status, medication regimens, or other factors. Changes in % Bic/(Bic+Lac) across different coronary artery segments were observed post-CABG in CAD patients (Fig. 3C).Conclusion:HP-13C MRI non-invasively assesses cardiac metabolism in CAD patients, demonstrating the potential to evaluate post-CABG metabolic changes. Our efforts continue to recruit large cohort to understand individual variability.

Circulation, Volume 150, Issue Suppl_1, Page A4142430-A4142430, November 12, 2024. Background:Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (OHT). Noninvasive methods to detect CAV and risk stratify OHT patients are needed. The value of fully quantitative stress cardiac magnetic resonance imaging has been recently validated and may be a promising technique for OHT surveillance. We aimed to evaluate the feasibility of quantitative stress CMR after OHT.Methods:We enrolled asymptomatic OHT recipients without coronary artery disease to undergo regadenoson stress CMR (1.5T GE HealthCare) with cine imaging, tissue mapping, and late gadolinium enhancement (LGE) imaging for routine CAV surveillance. Using the dual sequence technique, quantitative perfusion values were determined using Fermi deconvolution. Myocardial perfusion reserve (MPR) was calculated as the ratio of stress to rest myocardial blood flow (MBF).Results:Fifty-three subjects (mean age 47.06 ± 17.14 years) were included. OHT recipients (n=11, mean 6.77 ± 4.34 years post-transplant) were compared with healthy controls (n=43). No life-threatening adverse events, brief or prolonged atrioventricular block or other arrhythmias occurred with regadenoson. Coronary angiography was performed in 9 OHT patients before CMR, with an average of 1.99 ± 2.05 years between studies. No visual inducible ischemia was reported. Post OHT, rest MBF was significantly higher (1.69 ± 0.52 mL/g/min vs 1.01 ± 0.24 mL/g/min, p=0.004) and stress MBF was lower (2.33 ± 0.69 mL/g/min vs 2.95 ± 0.88 mL/g/min, p=0.02) compared to controls. MPR was significantly lower in OHT recipients compared to controls (1.46 ± 0.51 vs 3.11 ± 1.12, p

Circulation, Volume 150, Issue Suppl_1, Page A4139718-A4139718, November 12, 2024. Background:Paclitaxel-coated balloon (PCB) has been used for the treatment of coronary artery disease in the small native coronary artery and its safety and efficacy have been reported in clinical trials.Research Questions:The real-word long-term outcomes after intravascular imaging device-guided percutaneous coronary intervention (PCI) with PCB have not fully elucidated.Aims:To elucidate the long-term outcome after PCB treatment.Methods:This was a single-center, retrospective and observational study. We enrolled 1226 lesions from 713 patients which were treated by intravascular imaging device-guided PCI with PCB (342 lesions from 211 patients) or durable-polymer everolimus-eluting stent (DP-EES, 784 lesions from 502 patients) which diameter was less than 3.0 mm in the native coronary arteries. Long-term clinical outcomes were compared between PCB and DP-EES. Primary outcome was major adverse cardiac event (MACE) defined as a composite of cardiac death (CD), myocardial infarction (MI), target vessel revascularization (TVR) and device thrombosis. Secondary outcomes were all-cause death, CD, MI, target lesion revascularization (TLR), TVR and device thrombosis. Cumulative incidences of clinical outcomes were estimated by the Kaplan-Meier method and compared by the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (CIs) of PCB relative to DP-EES for MACE were estimated through a multivariable Cox model and an inverse probability weighted (IPW).Results:Cumulative 5-year incidence of MACE was similar between PCB and DP-EES (18.5% vs. 20.7%, P=0.78, Figure). Cumulative 5-year incidences of all-cause death (23.2% vs. 16.8%, P=0.12), CD (8.0% vs. 7.0%, P=0.81), MI (2.2% vs. 2.5%, P=0.97), TLR (5.9% vs. 8.9%, P=0.35), TVR (12.6% vs. 14.4%, P=0.90) and device thrombosis (0% vs. 0.6%, P=0.20) were also similar between PCB and DP-EES. Even after adjustment for baseline characteristics, cumulative 5-year incidence of MACE was similar between PCB and DP-EES (multivariate and IPW adjusted HRs 0.72 [95% CI: 0.37-1.39], P=0.33 and 0.67 [95% CI: 0.21-2.07], P=0.48, respectively).Conclusion:PCB demonstrated comparable 5-year clinical outcomes with intravascular imaging device-guided PCI compared to DP-EES.

Circulation, Volume 150, Issue Suppl_1, Page A4144186-A4144186, November 12, 2024. Background:Right atrial pressure (RAP) is estimated noninvasively by sonographic evaluation of inferior vena cava (IVC) size and collapsibility. We evaluated a new internal jugular vein (IJV) based approach for RAP estimation.Methods:Sixty-nine patients underwent right heart catheterization and sonographic evaluation of IVC and right IJV. Both IVC long axis (LA) –IVC(LA)and short axis (SA) -IVC(SA)images were analyzed for RAP. SA images of right IJV were obtained at the clavicular level at 0°and clavicular and mandibular levels at 45°&90° (60° if the patient is unable to sit upright) (Figure 1). Cine images were recorded during free breathing, sniff, and valsalva maneuvers at each location, in each posture. IJV was classified as distended (D), pulsatile (P), or collapsed (C). Models were developed to grade noninvasive RAP (niRAP) based on IJV classification in these images –IJV(c)and combined IJV&IVC imaging –IJV+IVC(Figure 2). A simple modelIJV(s)using only 45° posture was also analyzed. The invasive RAP (iRAP) was categorized as 3 (10 mm Hg) and compared with the niRAP fromIJV(c),IJV(s),IVC(LA),IVC(SA)andIJV+IVC.Results:IVC(LA)was nondiagnostic in 3 patients andIVC(SA)in 8 patients. In comparison, bothIJV(c)andIJV(s)were diagnostic in all patients. The correct niRAP category was identified in more patients by IJV (c-54%, s-54%) than by IVC imaging (LA-39%, SA-46%).IVC(SA)performed better than the traditionalIVC(LA). While bothIJV(c)andIJV(s)had an overall similar performance,IJV(c)was better when iRAP >10 and theIJV(s)was better when iRAP ≤10. CombinedIJV+IVCidentified RAP category correctly in most patients (64% overall, 84% if iRAP >10) (Table 1).Discussion:While IJV was diagnostic in all patients, IVC imaging was nondiagnostic in some. IJV correctly identified the RAP category more often than IVC and combined IJV and IVC had the best performance. IJV imaging was easier to perform and more comfortable for patients. A simpler 45° only evaluation of IJV had a performance similar to comprehensive IJV imaging. WhileIVC(SA)was nondiagnostic in more patients, its classification was more accurate thanIVC(LA).Conclusion:Sonographic imaging of IJV is potentially better than IVC imaging in noninvasive evaluation of RAP. Combined IJV and IVC imaging is better than IJV or IVC alone. When IVC only imaging is done, short axis or biplane imaging is preferable to long axis alone.

Circulation, Volume 150, Issue Suppl_1, Page A4147215-A4147215, November 12, 2024. Background:Patients with ischemic heart failure (IHF) often undergo myocardial viability assessment to help determine the appropriate treatment strategy, whether revascularization or medical therapy. However, there is a lack of evidence regarding the optimal imaging modality for this purpose. The present study aimed to compare the clinical outcomes of IHF patients undergoing cardiac magnetic resonance (CMR) versus positron emission tomography (PET) for myocardial viability assessment.Methods:We enrolled patients >18 years with IHF and ejection fraction (EF)

Circulation, Volume 150, Issue Suppl_1, Page A4113716-A4113716, November 12, 2024. Background:Current conventional echocardiographic assessment of diastolic function relies on predicting left ventricular (LV) filling pressure as a surrogate of diastolic function. High frame rate (HFR) Shear wave (SW) imaging is emerging as an innovative parameter for assessing myocardial stiffness, a key determinant of diastolic function. Natural SW are induced by valve closure (i.e. mitral valve closure (MVC)). Little is known so far, to which extent SWs could reflect changes in diastolic LV filling pressures.Purpose:We aimed at investigating the relationship between natural SW after MVC and LV diastolic pressures in an attempt to set up a cut-off value beyond which, elevated LV pressure can be suspected indicating diastolic dysfunction.Methods:Thirty patients (mean age 68.4±9.9 years) scheduled for clinically indicated left heart catheterization were prospectively recruited. Left ventricular end-diastolic pressure (LVEDP) was measured during the catheterization. Immediately afterwards, conventional as well as HFR (1167 ±86 Hz) echocardiography was performed. We drew an anatomical M-mode along the anteroseptal wall in the parasternal long axis view from base to apex and the display was colour coded for tissue acceleration. SWs appeared immediately after MVC as tilted green bands and their propagation velocity was measured semi-automatically(Figure 1).Results:LVEDP in our cohort ranged from 7.5 to 29.5 mmHg. From conventional echocardiographic parameters, only mitral inflow to mitral relaxation velocity ratio (E/e’) correlated moderately with LVEDP (r=0.51, p=0.006). SW velocities after MVC showed strong positive correlation with LVEDP (r=0.78, p

Circulation, Volume 150, Issue Suppl_1, Page A4146142-A4146142, November 12, 2024. Clinical Presentation:A 62-year-old male with a complex medical history, including pulmonary sarcoidosis, diabetes, constrictive pericarditis post partial pericardial stripping, cirrhosis, and congestive heart failure, presented with signs and symptoms of volume overload. Despite increasing diuretics and previous paracentesis, his condition continued to deteriorate. There were raising concerns for constrictive pericarditis due to cardiac sarcoidos. Echocardiography (TEE) showed pericardial thickening and calcification adjacent to the left ventricle and dilated IVC 2.4 cm (TTE). Cardiac magnetic resonance imaging (CMR) demonstrated conical deformity of the ventricles, thickened pericardium with signal void suggestive of calcification. Computed Tomography (CT) showed significant near circumferential pericardial calcifications. Subsequent catheterization confirmed constriction and identified a right coronary artery lesion. Following this, the patient underwent a redo pericardiectomy and coronary artery bypass grafting, at the Cleveland Clinic. However, his post-operative course was marked by complex challenges, including multi-organ dysfunction, the need for tracheostomy, feeding tube, renal replacement therapy, and recurrent ascites. Despite intensive care, his condition did not improve, leading to a transition to comfort care and eventually the patient passed away in December 2023.Discussion:This case highlights the intricate management of a patient with a myriad of underlying health issues. While multimodality imaging is pivotal in ensuring accurate preoperative diagnosis and guiding surgical interventions, it is important to acknowledge that challenges may persist in the postoperative phase. This case study underscores the vital role of multimodality imaging, irrespective of post-surgical outcomes, in facilitating precise diagnosis and delivering optimal patient care. The subsequent referral to the Cleveland Clinic for redo surgery, followed by a challenging and ultimately palliative care journey, shows the complexity of her clinical course and the importance of multimodality imaging and comprehensive care strategies.

Circulation, Volume 150, Issue Suppl_1, Page A4143721-A4143721, November 12, 2024. Background:People with established cardiovascular disease (CVD) are at risk of early cognitive decline, and neurodegenerative diseases such as dementia. White matter hyperintensities (WMH) of presumed vascular origin are associated with progressive cerebrovascular disease and risk factors for CVD. The shared risk factors include blood pressure, sedentary lifestyle, genomic risk factors likeAPOE4mutations. The extent to which common risk factors explain the co-occurrence of CVD and neurological diseases is unclear.Purpose:To determine the extent of which CMR measurements associated with WMH independent of known cerebrovascular risk factors.Methods:Cardiac and brain MRI images were analysed for 33,198 UK biobank participants. WMH analysis included 5 brain regions (Frontal, Parietal, Temporal, Occipital, Basal Ganglia and Thalami) and total brain WMH volume. Cardiac traits included stroke volumes, atrial volumes, ejection fractions (EF) of right and left chambers, left ventricular (LV) strain, LV wall thickness and aortic areas.Multivariable regression analysis was carried out, where each cardiac trait was regressed on each brain region and adjusted for demographics, cardiac risk factors, family history of disease and socioeconomic factors. Results were evaluated against a multiple testing correct p-value threshold of 0.05, reflecting the number of principle components(n=10) necessary to explain at least 90% of the cardiac trait variability.Results:Higher values of 7 cardiac traits (LV end stroke volume, aortic areas, mid and basal wall thickness) associated with higher WMH volumes for all brain regions. Conversely three traits (LV ejection fraction, descending aorta distensibility and RV ejection fraction) associated positively with lower WMH volumes for all brain regions. LV cardiac output and maximum LAV only associated with frontal lobe WMH volumes. Associations onAPOE- ε4 carriership, a known risk factor of Alzheimer’s disease, showed negative association in homozygous carriers between aortic distensibility of the ascending and descending aorta and higher WMH volumes in the frontal and occipital lobes.Conclusions:This study offers insight into WMH burden in a large population of adults. Using cardiac traits as surrogate markers of different cardiac disease could explain how cardiac functionality defines WMH volume distribution and subsequently the wider relationship between cardiovascular and cerebrovascular disease.

Circulation, Volume 150, Issue Suppl_1, Page A4139471-A4139471, November 12, 2024. Heart disease continues to be the leading cause of death globally, even with the development and implementation of numerous pharmacological and surgical treatments. Transplanting cardiomyocytes derived from human-induced pluripotent stem cells (hiPSC-CMs) shows potential for repairing heart damage. However, tracking and quantifying these cells after transplantation in large animals remains challenging. This study aimed to develop a hiPSC line that overexpresses ferritin heavy chain (FHC) to enable tracking of transplanted hiPSC-CMs via magnetic resonance imaging (MRI). Using the CRISPR/dCas9 activation system, we increased FHC expression in hiPSCs and hiPSC-CMs. Both mRNA and protein levels of FHC were significantly elevated following transfection. Cell viability was unaffected by iron chloride concentrations between 0 μM and 2000 μM. hiPSCs and hiPSC-CMs overexpressing FHC (hiPSC-FHCOEand hiPSC-CM-FHCOE) showed enhanced iron chloride uptake without changes in their electrophysiological properties compared to control hiPSC-CMs. Additionally, hiPSC-CM-FHCOE cells provided strong contrast and lower T2* values, indicating their effectiveness for cardiac MRI. When hiPSC-CM-FHCOE cells were injected into mouse hearts and imaged three days later, MRI revealed distinct signals from these cells with lower T2* values and rapid signal decay. Overall, endogenous FHC labeling in hiPSC-CMs could significantly improve the precision of cardiac MRI, marking a crucial advancement in assessing the success of hiPSC-CM transplantation in large animal models and enhancing cardiac regenerative therapies.

Circulation, Volume 150, Issue Suppl_1, Page A4144999-A4144999, November 12, 2024. Obesity is associated with increased cardiovascular risk and adverse cardiac changes such as left ventricular hypertrophy (LVH) and in TOF higher body mass index (BMI) contributed to increase risk. Previous multicenter study concluded that right ventricular (RV) dysfunction contributed to cardiovascular event. Current recommendations for pulmonary valve replacement (PVR) in TOF patients use indexed RV endiastolic volume (RVEDVi) to determine timing of PVR. In the presence of obesity, RVEDVi may underestimate the severity of RV volume load. We sought to determine both diastolic (RVEDV) and systolic (REVSV) volume in obese and non-obese patients and the impact of the volume on right ventricular ejection fraction (RVEF).We conducted a retrospective study of adult TOF patients > 18 years age in obese (BMI ≥ 30 kg/m2) and non-obese (BMI < 30 kg/m2) patients with a cardiac magnetic resonance imaging (CMR) prior to PVR for pulmonary regurgitation (PR). CMR database and electronic records were reviewed to compare anthropometric, demographic, and CMR variables between obese and non-obese patients.Table 1 shows demographic and CMR results between non-obese (n = 57) and obese (n = 32) patients. Indexed ventricular volume were smaller in obese compared to non-obese patients (LVEDVi 78.7±12.1 vs 84.3±14.9 mL/m2, p=0.04; RVEDVi 157.4±21.5 vs 169.4±32.7 mL/m2, p=0.03), in contrast the non-indexed volume were significantly larger (LVEDV, 166.7±32.9 vs 148.8±30.5 mL, p=0.006; RVEDV 333.1±61.3 vs RVEDV 297.6±56.6 mL, p=0.004). There is an association with ventricular volume with lower RVEF. In both groups the mean RVEF was abnormal but not different (43.2±8.7 vs 43.8±8.4%, P=NS). Patients with lower RVEF trended towards a lower LVEF especially in the obese group (Figure 1A-F).Our study showed that indexed ventricular volume was smaller in obese patients and may lead to false reassurance suggesting underestimation of the volume load from the PR. Our patients have lower RVEF which correlated with larger volume and evidence of ventricular-ventricular interaction with lower LVEF in patients with lower RVEF. When assessing timing of PVR in asymptomatic TOF patients, other parameters beyond indexed volume in those with elevated BMI should be considered including ejection fraction and different methods of indexing RV volume similar to LVM. Future larger and longitudinal studies are needed to determine if delayed repair in obese patients lead worse remodeling and outcomes.