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Aims: Neuroendocrine neoplasms (NNs) range from well to poorly differentiated and indolent to highly aggressive. The site of origin in metastatic NNs has therapeutic and prognostic implications. SATB2 is a transcriptional regulator involved in osteoblastic and neuronal differentiation and is a sensitive and specific marker of colorectal epithelium. This study aimed to evaluate the expression of SATB2 in NNs from various primary sites and its utility as a marker in determining the site of origin of these neoplasms. Methods and results: SATB2 immunohistochemistry was performed on 266 NNs, including lung small cell carcinomas (n = 39) and carcinoids (n = 30), bladder (n = 21) and prostate (n = 31) small cell carcinomas, and gastrointestinal (GI)/pancreatic NNs of various primary sites (n = 145) consisting of well‐differentiated neuroendocrine tumours (WDNET)s (n = 124) and poorly differentiated neuroendocrine carcinomas (PDNEC)s (n = 21). SATB2 was expressed in prostatic (10 of 31, 32%) and bladder (eight of 21, 38%) small cell carcinomas, lung carcinoid tumours (one of 30, 3%), and lung small cell carcinomas (eight of 39, 21%). Among primary GI NNs, SATB2 was expressed in 37 of 124 (30%) WDNETs and four of 21 (19%) PDNECs. Of the former, 15 of 15 (100%) rectal/rectosigmoid and 22 of 22 (100%) appendiceal neoplasms expressed SATB2. Using receiver operator characteristic analysis, SATB2 was a sensitive and specific marker for rectal (100.0%, 80.0%) and appendiceal (100.0%, 84.5%) WDNETs, respectively. Conclusions: In summary, SATB2 is a sensitive and specific marker for rectal/rectosigmoid and appendiceal WDNETs, and may represent a useful diagnostic tool when these sites of origin are considered in the differential diagnosis. [ABSTRACT FROM AUTHOR]

Objectives: Immunohistochemistry (IHC) staining of core biopsy sections often plays an essential role in the diagnosis of acute megakaryoblastic leukemia (AMKL). The goal of this study was to define the relative sensitivities of commonly used stains for markers of megakaryocytic differentiation.Methods: The sensitivities of IHC stains for CD42b, CD61, and von Willebrand factor (vWF) were compared in 32 cases of pediatric AMKL.Results: The sensitivities of CD42b, CD61, and vWF were 90.6%, 78.1% and 62.5%, respectively. When CD42b and CD61 were used together, the combined sensitivity increased to 93.6%. There were no cases in which vWF was positive when both CD42b and CD61 were negative.Conclusions: CD42b can reliably be used as a solitary first-line marker for blasts of megakaryocytic lineage, whereas CD61 may be reserved for infrequent cases that are CD42b negative. There is no role for the routine use of vWF when CD42b and CD61 are available. [ABSTRACT FROM AUTHOR]

Few data exist regarding predictors of rapid aortic root dilation and referral for aortic surgery in Marfan syndrome (MFS). To identify independent predictors of the rate of aortic root (AoR) dilation and referral for aortic surgery, we investigated the data from the Pediatric Heart Network randomized trial of atenolol versus losartan in young patients with MFS. Data were analyzed from the echocardiograms at 0, 12, 24, and 36 months read in the core laboratory of 608 trial subjects, aged 6 months to 25 years, who met original Ghent criteria and had an AoR z-score (AoRz) > 3. Repeated measures linear and logistic regressions were used to determine multivariable predictors of AoR dilation. Receiver operator characteristic curves were used to determine cut-points in AoR dilation predicting referral for aortic surgery. Multivariable analysis showed rapid AoR dilation as defined by change in AoRz/year > 90th percentile was associated with older age, higher sinotubular junction z-score, and atenolol use (R2 = 0.01) or by change in AoR diameter (AoRd)/year > 90th percentile with higher sinotubular junction z-score and non-white race (R2 = 0.02). Referral for aortic root surgery was associated with higher AoRd, higher ascending aorta z-score, and higher sinotubular junction diameter:ascending aorta diameter ratio (R2 = 0.17). Change in AoRz of 0.72 SD units/year had 42% sensitivity and 92% specificity and change in AoRd of 0.34 cm/year had 38% sensitivity and 95% specificity for predicting referral for aortic surgery. In this cohort of young patients with MFS, no new robust predictors of rapid AoR dilation or referral for aortic root surgery were identified. Further investigation may determine whether generalized proximal aortic dilation and effacement of the sinotubular junction will allow for better risk stratification. Rate of AoR dilation cut-points had high specificity, but low sensitivity for predicting referral for aortic surgery, limiting their clinical use. Clinical Trial Number ClinicalTrials.gov number, NCT00429364. [ABSTRACT FROM AUTHOR]

Lymphoma of the urinary tract is relatively rare and comprises of < 5% of all primary extra nodal lymphoma. Diagnoses of these lesions at anearly stage is important as they can disseminate or transform into high grade lesion if there is a delay in the diagnoses. There are only few case series and case reports on the malignant lymphoma of the urinary tract. The aim of this study was to characterize lymphoma involving the urinary bladder and prostate. We retrospectively reviewed the clinical data and histologic findings of the malignant lymphoma involving urinary bladder and prostate at our institution. Lymphoma involving the lower urinary tract clinically presented with lower urinary tract symptoms and usually with concurrent associated urinary bladder cancer or prostatic cancer in our series. Lymphoma should be included in the differential diagnoses especially in patients with prior history of lymphoid disorders. There should be a high index of suspicion when there is any atypical lymphoid infiltrate in routine urinary bladder and prostate surgical specimens. [ABSTRACT FROM AUTHOR]

This study proposes a computational method for estimating in vivo mechanical properties of tissues using clinical imaging data. In particular, a new level-set-based objective functional to compare a target and estimated shape of a tissue structure is introduced, along with its integration into an optimization-based approach for inverse material parameter estimation. The approach employs a continuous shape comparison metric using signed distance functions and combines the adjoint method for efficient gradient-based optimization. Simulated inverse problems based upon estimating cardiac ventricular wall stiffness from untagged imaging and hemodynamic data are used to assess the capability of the proposed approach. The results show that the proposed method is able to consistently and effectively minimize the shape-based objective functional to estimate material parameters. The minimization of this shape difference is capable of providing relatively accurate estimates of material parameters, although naturally depending on the sensitivity of the shape change to the particular parameters, and the process is tolerant to the inclusion of model error. Thus, the approach has the potential capability to provide estimates of in vivo mechanical properties of tissues from the shape of the tissue structure as can be directly estimated from imaging data. [ABSTRACT FROM AUTHOR]

Introduction: Our objective is to describe the rate of intracranial aneurysm (ICA) detection by MRI/MRA/CTA in patients with a history of coarctation of the aorta. Hypothesis: A 10% prevalence of ICAs in patients with coarctation of the aorta has been described in a few small studies. This has led to a recommendation to screen all patients with a history of coarctation for ICA with MRA or CTA although no age for this screening is specified. We hypothesize that, with earlier detection and coarctation intervention, the rate of ICA is lower and screening brain imaging may only be warranted in older patients or patients with certain risk factors. Methods: We retrospectively reviewed charts of patients with coarctation of the aorta who had undergone MRI/MRA/CTA imaging ages 13 years and older from the years 2000 to 2018. Results: We identified a cohort of 102 patients and there were no reported ICAs. The median age of coarctation repair was 4.4 months (range 2 days-47 years) and the initial repair was primarily surgical (90.2%). There were 35 (34.3%) patients with recurrent coarctation requiring re-intervention. One patient had CAD, 11 patients were smokers, 4 had a history of DM and 41 (40.2%) had history of HTN following coarctation repair. Imaging modalities included CTA (13.7%), MRI (41.2%) and MRA (46.1%) with 52.9% of those studies being performed for history of coarctation and the remainder performed for neurologic symptoms. The median age of CTA was 33.3 years, of MRI was 22.4 years and of MRA was 25 years. Conclusions: Patients with a history of coarctation of the aorta have been consistently reported to have a 10% risk for ICA, however we have not documented any ICAs by MRI/MRA/CTA in this reviewed patient population. We feel this may reflect the varying age at which patients undergo these imaging studies as well as earlier detection and repair of coarctation. These results suggest that the rate of ICA may be lower than previously reported and that the age of screening should be more clearly described. [ABSTRACT FROM AUTHOR]

Transcatheter pulmonary valve replacement (TPVR) with the self-expanding Harmony valve (Medtronic) is an emerging treatment for patients with native or surgically repaired right ventricular outflow tract (RVOT) pulmonary regurgitation (PR). Limited data are available since U.S. Food and Drug Administration approval in 2021. In this study, the authors sought to evaluate the safety and short-term effectiveness of self-expanding TPVR in a real-world experience. This was a multicenter registry study of consecutive patients with native RVOT PR who underwent TPVR through April 30, 2022, at 11 U.S. centers. The primary outcome was a composite of hemodynamic dysfunction (PR greater than mild and RVOT mean gradient >30 mm Hg) and RVOT reintervention. A total of 243 patients underwent TPVR at a median age of 31 years (Q1-Q3: 19-45 years). Cardiac diagnoses were tetralogy of Fallot (71%), valvular pulmonary stenosis (21%), and other (8%). Acute technical success was achieved in all but 1 case. Procedural serious adverse events occurred in 4% of cases, with no device embolization or death. Hospital length of stay was 1 day in 86% of patients. Ventricular arrhythmia prompting treatment occurred in 19% of cases. At a median follow-up of 13 months (Q1-Q3: 8-19 months), 98% of patients had acceptable hemodynamic function. Estimated freedom from the composite clinical outcome was 99% at 1 year and 96% at 2 years. Freedom from TPVR-related endocarditis was 98% at 1 year. Five patients died from COVID-19 (n = 1), unknown causes (n = 2), and bloodstream infection (n = 2). In this large multicenter real-world experience, short-term clinical and hemodynamic outcomes of self-expanding TPVR therapy were excellent. Ongoing follow-up of this cohort will provide important insights into long-term outcomes. [Display omitted] [ABSTRACT FROM AUTHOR]

There is currently no clear consensus on screening techniques to evaluate the presence or severity of Fontan-associated liver disease (FALD). Cardiac MRI (CMR) is used routinely for post-Fontan surveillance, but CMR-derived measures that relate to the severity of FALD are not yet defined. This was a cross-sectional single-center study of post-Fontan patients who underwent a CMR. CMR exams were re-analyzed by a single pediatric cardiologist. Surrogates of FALD included Gamma-Glutamyl Transferase (GGT), Fibrosis-4 laboratory score (FIB-4), and imaging findings. Findings consistent with cirrhosis on liver ultrasound included increased liver echogenicity and/or nodularity. Statistical analyses were performed to investigate potential relationships between CMR parameters and markers of FALD. Sixty-one patients were included. A larger inferior vena cava cross-sectional area (IVC-CSA) indexed to height was significantly associated with a higher FIB-4 score (Spearman's ρ = 0.28, p = 0.04), a higher GGT level (Spearman's ρ = 0.40, p = 0.02), and findings consistent with cirrhosis on liver ultrasound (OR 1.17, 95% CI: (1.01, 1.35), p = 0.04). None of the other CMR parameters were associated with markers of FALD. A larger indexed IVC-CSA was associated with higher systemic ventricle end-diastolic pressure (EDP) on cardiac catheterization (Spearman's ρ = 0.39, p = 0.018) as well as older age (Spearman's ρ = 0.46, p = < 0.001). Indexed IVC-CSA was the only CMR parameter that was associated with markers of FALD. This measure has the potential to serve as an additional non-invasive tool to improve screening strategies for FALD. Visual abstract summarizing the primary findings of this paper [ABSTRACT FROM AUTHOR]

Clinical Context and History: This 65-year-old white male patient presented to the VA Medical Center in 2013 with a chief complaint of memory loss. Past medical history included hypothyroidism and depression, and diagnoses of Alzheimer disease (AD) and posterior cortical atrophy were made at ages 55 and 62 years, respectively. The patient continued to work as an HVAC technician after the diagnosis of AD but was compelled to retire secondary to progressive cognitive decline. History was negative for cerebrovascular accident, seizures, lightheadedness, balance difficulties, hallucinations, and substance abuse. The patient's mother had been diagnosed with AD. Neuropsychological evaluation revealed deterioration of short-term memory and constructional apraxia with clinical progression over the ensuing three years. MRI studies done in 2012, 2014, and 2016 were interpreted as stable and within normal limits. Sleep studies were unremarkable. Cerebrospinal fluid (CSF) glucose, IgG/albumin index, oligoclonal bands, VDRL, anti Yo and anti-Hu antibodies and taw, 14-3-3 and prion proteins were all non-contributory. CSF total protein was borderline elevated (45 mg/dL). Non-contributory serum/plasma assays included FT-4, TT-3, TSH, myeloperoxidase and anti-proteinase antibodies, homocysteine, vitamin B-12, ANA, C and p-ANCA, atypical p-ANCA, and HIV and RPR serologies. Thyroid microsomal, anti-thyroglobulin, and anti-TPO antibodies were, however, all strongly positive. Results/Discussion: Review of the lab and imaging data suggested to neurology that the likely diagnosis was Hashimoto encephalopathy (HE) rather than AD. This rare entity is hypothesized to be of autoimmune etiology, has a strong female predominance, and is not related to thyroid function. Age of onset is generally 45–55 years old with pleiotropic presenting complaints frequently including cognitive decline. The patient was placed on high-dose prednisone with improvement of cognition. Conclusion: Although rare the diagnosis of HE is consequential as, in contrast to AD, HE irresponsive to immunosuppressive therapy. [ABSTRACT FROM AUTHOR]

Background: Adult congenital heart disease (ACHD) patients pose unique challenges in identifying the time for transplantation and factors influencing outcomes. Objective: To identify hemodynamic, functional, and laboratory parameters that correlate with 1‐ and 10‐year outcomes in ACHD patients considered for transplantation. Methods: A retrospective chart review of long‐term outcomes in adult patients with congenital heart disease (CHD) evaluated for heart or heart + additional organ transplant between 2004 and 2014 at our center was performed. A machine learning decision tree model was used to evaluate multiple clinical parameters correlating with 1‐ and 10‐year survival. Results: We identified 58 patients meeting criteria. D‐transposition of the great arteries (D‐TGA) with atrial switch operation (20.7%), tetralogy of Fallot/pulmonary atresia (15.5%), and tricuspid atresia (13.8%) were the most common diagnosis for transplant. Single ventricle patients were most likely to be listed for transplantation (39.8% of evaluated patients). Among a comprehensive list of clinical factors, invasive hemodynamic parameters (pulmonary capillary wedge pressure (PCWP), systemic vascular pressure (SVP), and end diastolic pressures (EDP) most correlated with 1‐ and 10‐year outcomes. Transplanted patients with SVP < 14 and non‐ transplanted patients with PCWP < 15 had 100% survival 1‐year post‐transplantation. Conclusion: For the first time, our study identifies that hemodynamic parameters most strongly correlate with 1‐ and 10‐year outcomes in ACHD patients considered for transplantation, using a data‐driven machine learning model. [ABSTRACT FROM AUTHOR]

Stimulated Raman histology can be interpreted by humans and artificial intelligence. Stimulated Raman histology can provide procedural tumoral mapping during cryosurgical ablation of prostate cancer. Stimulated Raman histology can identify prostate cancer in a prostate biopsy in approximately 1 minute. Identification of clinically significant prostate cancer radial to a MRI predicted margin during cryosurgical ablation is at high risk for recurrence. In-field or in-margin recurrence after partial gland cryosurgical ablation (PGCA) of prostate cancer (PCa) remains a limitation of the paradigm. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real time, label-free, high-resolution microscopic images of unprocessed, un-sectioned tissue which can be interpreted by humans or artificial intelligence (AI). We evaluated surgical team and AI interpretation of SRH for real-time pathologic feedback in the planning and treatment of PCa with PGCA. About 12 participants underwent prostate mapping biopsies during PGCA of their PCa between January and June 2022. Prostate biopsies were immediately scanned in a SRH microscope at 20 microns depth using 2 Raman shifts to create SRH images which were interpreted by the surgical team intraoperatively to guide PGCA, and retrospectively assessed by AI. The cores were then processed, hematoxylin and eosin stained as per normal pathologic protocols and used for ground truth pathologic assessment. Surgical team interpretation of SRH intraoperatively revealed 98.1% accuracy, 100% sensitivity, 97.3% specificity for identification of PCa, while AI showed a 97.9% accuracy, 100% sensitivity and 97.5% specificity for identification of clinically significant PCa. 3 participants' PGCA treatments were modified after SRH visualized PCa adjacent to an expected MRI predicted tumor margin or at an untreated cryosurgical margin. SRH allows for accurate rapid identification of PCa in PB by a surgical team interpretation or AI. PCa tumor mapping and margin assessment during PGCA appears to be feasible and accurate. Further studies evaluating impact on clinical outcomes are warranted. [ABSTRACT FROM AUTHOR]

Due to medical advances, women with congenital heart disease (CHD) are living longer, healthier lives and many are considering pregnancy. The hemodynamic changes of pregnancy present high risks of morbidity and mortality for many women with CHD. As little is known about these women's reproductive health experiences, this study explores their perceptions of pregnancy and family planning care as related to CHD. Women ages 18-45 years with a diagnosis of CHD associated with a World Health Organization (WHO) classification II–IV for pregnancy morbidity and mortality participated in individual, semi-structured interviews exploring their experiences, attitudes, and preferences toward parenthood, pregnancy, contraception and family planning care provision. Interviews were audio-recorded, transcribed verbatim. Two independent coders performed analysis using deductive and inductive coding approaches. Twenty women with CHD participated in interviews (average age 30.1 years, SD 5.85). Nine women had a prior pregnancy and 14 considered becoming a parent in the future. We identified 5 key themes among the women: (1) CHD impacted their reproductive health goals and decisions; (2) Women with CHD perceived a lack of safe contraceptive methods for their condition; (3) Women desired tailored, disease-specific sexual and reproductive health (SRH) information; (4) Women viewed their cardiologist as the primary source for SRH information and prefer provider-initiated discussions starting in adolescence; and (5) Women desire coordinated pre-pregnancy and intrapartum care between their cardiologists and women's health providers. These results provide a foundation for interventions to improve patient-centered interdisciplinary reproductive healthcare for this population. [ABSTRACT FROM AUTHOR]

The optimal strategy for thromboprophylaxis in patients with a Fontan circulation is unknown. The aim of this study was to compare the efficacy and safety of aspirin, warfarin, and nonvitamin K oral anticoagulants (NOACs) in a network meta-analysis. Relevant studies published by February 2022 were included. The primary efficacy outcome was thromboembolic events; major bleeding was a secondary safety outcome. Frequentist network meta-analyses were conducted to estimate the incidence rate ratios (IRRs) of both outcomes. Ranking of treatments was performed based on probability (P) score. A total of 21 studies were included (26,546 patient-years). When compared with no thromboprophylaxis, NOAC (IRR: 0.11; 95% CI: 0.03-0.40), warfarin (IRR: 0.23; 95% CI: 0.14-0.37), and aspirin (IRR: 0.24; 95% CI: 0.15-0.39) were all associated with significantly lower rates of thromboembolic events. However, the network meta-analysis revealed no significant differences in the rates of major bleeding (NOAC: IRR: 1.45 [95% CI: 0.28-7.43]; warfarin: IRR: 1.38 [95% CI: 0.41-4.69]; and aspirin: IRR: 0.72 [95% CI: 0.20-2.58]). Rankings, which simultaneously analyze competing interventions, suggested that NOACs have the highest P score to prevent thromboembolic events (P score 0.921), followed by warfarin (P score 0.582), aspirin (P score 0.498), and no thromboprophylaxis (P score 0.001). Aspirin tended to have the most favorable overall profile. Aspirin, warfarin, and NOAC are associated with lower risk of thromboembolic events. Recognizing the limited number of patients and heterogeneity of studies using NOACs, the results support the safety and efficacy of NOACs in patients with a Fontan circulation. [Display omitted] [ABSTRACT FROM AUTHOR]

Ebstein anomaly is the most common form of tricuspid valve congenital anomalies. The tricuspid valve is abnormal with different degrees of displacement of the septal leaflet and abnormal rotation of the valve towards the right ventricular outflow tract. In severe forms, it results in significant tricuspid regurgitation and requires surgical repair. There is an increased interest in understanding the anatomy of the tricuspid valve in this lesion as the surgical repair has evolved with the invention and wide adoption of the cone operation. Multimodality imaging plays an important role in diagnosis, follow-up, surgical planning and post-operative care. This review provides anatomical tips for the cardiac imagers caring for patients with Ebstein anomaly and will help provide image-based personalized medicine. [ABSTRACT FROM AUTHOR]

Introduction: Connective tissue disorders predispose patients to earlier aortic dissections and aneurysms. However, there is limited large cohort data given its low incidence.Methods: The National Inpatient Sample was searched for all adults with Marfans (MFS) and Ehlers Danlos (EDS) disease between 2010 and 2017. ICD codes were used to select those with a type A aortic dissection or aneurysm.Results: There was a total of 19,567 cases, giving the estimated incidence of MFS and EDS of 18 and 22.4 per 100k people, respectively. After inclusion criteria, there were 2553 MF and 180 EDS patients. There was no statistical difference in mortality between the MFS and EDS cohorts (4.6% vs. 2.8%, p = .26). EDS patients were more likely to undergo a TEVAR procedure (2.8% vs. 1.0%, p = .03). MF patients were more likely to have a complication of acute kidney injury (p = .02). EDS patients were more likely older (50 vs. 42, p < .001) and female (47% vs. 33%, p < .001). MFS patients were more likely to have a type A aortic dissection (44% vs. 31%, p < .001). The majority (89%) of patients were treated at urban teaching hospitals. On univariable logistic regression, aortic dissection was a predictor for mortality (odds ratio 7.31, p < .001). The type of connective tissue disease was not a significant predictor.Conclusions: National level estimates show low mortality for patients with MF or ED presenting to the hospital with aortic dissection or aneurysm. The differences in age and gender can guide surveillance for these patient populations, leading to more elective admissions and reduced hospital mortality. [ABSTRACT FROM AUTHOR]

The Child Opportunity Index (COI) is a validated measurement that uses a composite index of 29 indicators of social determinants of health linked to the US Census. Patients post-Fontan palliation for single ventricle physiology often have reduced exercise capacity compared to the general population. Our hypothesis is that COI levels are directly associated with exercise capacity and inversely with late outcomes. A retrospective, single-center study was performed, including 99 patients post-Fontan procedure who had cardiac magnetic resonance imaging at our institution from January 2010 to July 2023, of which 78 had undergone an exercise test. Univariate analysis was performed with Pearson correlational testing and multivariable linear regression was then used to evaluate independent predictors of % predicted VO2. The mean age and sex were not different between the low and high COI groups (24.1 ± 8.5 y vs 22.5 ± 9.7 y; 34.5% vs 29.3% female). Patients with low COI had lower peak VO2 (25.7 vs 31.0 L/min/kg, p = 0.002) and % predicted peak VO2 (61.9 vs 71.4%, p = 0.003). At follow-up post-Fontan (mean of 17.9 ± 7.4 y) there was one mortality and two heart transplants. There were more interventions in the low COI group (1.5 vs 0.9 intervention occurrence/patient, p = 0.038). There was no difference in hospital admissions or significant comorbidities between COI groups. Lower COI was associated with worse exercise capacity in Fontan patients and may negatively impact the need for late interventions. This highlights the need for efforts to provide community resources to promote equity in cardiac outcomes.Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary.Confirmed as correct. Thank you! [ABSTRACT FROM AUTHOR]

Guideline-directed heart failure therapy with angiotensin receptor blocker/neprilysin inhibitor (ARNi) and sodium-glucose transporter inhibitors (SGLT2i) has been incrementally beneficial in improving outcomes in heart failure patients. Evaluate the feasibility and efficacy of guideline-directed medical therapy (GDMT) in adults congenital heart disease (ACHD) patients. In a retrospective cohort study, ACHD patients with either New York Heart Association (NYHA) Class II symptoms or systemic ejection fraction (EF) <45%, optimized on a combination of beta-blocker (BB), ARNi, mineralocorticoid receptor antagonist (MRA) and SGLT2i were evaluated. Forty-six patients with a mean age 42.6 ± 12.1 years prescribed GDMT were identified. Twenty-eight (61%) were male, 20 (43%) had a systemic right ventricle (RV) and 9 (20%) had single-ventricle physiology. Over the optimization period, 20 (43%) were sustained on ARNi and 42 (91%) on SGLT2i in addition to treatment with BB and MRA. Over a period of 45 weeks, echocardiography parameters for left ventricle (LV) ejection fraction (EF) (+7.5%, p = 0.006), systemic ventricle (SV) velocity time integral (VTI) (+1.9 cm, p = 0.012) and LV global longitudinal strain (GLS) (−2.5%, p = 0.005) improved when 3–4 medications were used versus 1–2 medications alone. The use of either ARNi or SGLT2i (+8.1%, p = 0.017) or in combination (+7.0%, p = 0.043) increased LVEF compared to the use of neither medication. Combination GDMT is beneficial in improving myocardial characteristics in ACHD patients with systemic RV and LV. • The efficacy of GDMT in ACHD patients is unknown. • Study showed feasibility of use of β-blocker, ARNi, MRA and SGLT2i with close monitoring of vitals and serum chemistry. • Patients showed improvement in myocardial function with 3-4 GDMT medications versus 1-2 GDMT medications. [ABSTRACT FROM AUTHOR]

A patent foramen ovale (PFO) is a frequent incidental finding during echocardiography in otherwise healthy children. In most healthy children with a diagnosis of isolated incidental PFO, no further follow-up or intervention is necessary. In some children, PFO is associated with certain clinical syndromes such as cryptogenic stroke, decompression sickness, migraine, and platypnea-orthodeoxia syndrome. This review discusses PFO anatomy, diagnostic imaging, PFO-associated clinical situations, management options, and the role of PFO in certain congenital heart disease. This review also highlights the current deficiency of pediatric data guiding management of these uncommon but important PFO-associated conditions. Future multicenter randomized controlled studies are necessary to guide the management of these unique and challenging PFO-associated conditions. [ABSTRACT FROM AUTHOR]

After the Fontan procedure, patients require lifelong follow-up due to significant late morbidity and mortality. Thrombocytopenia is seen frequently post-Fontan, likely due to secondary hypersplenism from elevated Fontan pressure. We investigated platelet counts in patients with a Fontan circulation and assessed associations with catheterization data and clinical outcomes. This retrospective study included 92 patients (33% female) post-Fontan who had a complete blood count performed between January 2011 and July 2023. The age at evaluation was 24.0 ± 8.9 years. Outcomes measured included elevated Fontan pressure (≥ 15 mmHg), Fontan-associated liver disease (FALD), unscheduled admissions, transplant, and death. Participants with thrombocytopenia (≤ 150,000/µL) had significantly higher rates of elevated Fontan pressure (OR 8.1, 95% CI 1.3–52.7, p = 0.03), FALD (OR 4.1, 95% CI 1.6–10.6, p = 0.004), and unscheduled admissions (362 ± 577 versus 115 ± 185 admissions per 1000 patient-years, p = 0.02). Thrombocytopenia post-Fontan is associated with elevated Fontan pressure, FALD, and increased morbidity. Platelet count could serve as a non-invasive factor in identifying patients at risk of decompensation. [ABSTRACT FROM AUTHOR]

Fontan-associated liver disease (FALD) is universal in patients with a Fontan circulation. Hepatocellular carcinoma (HCC) is one of its severe expressions, and, though rare, frequently fatal. The purpose of this study was to describe the clinical presentation, risk factors, and outcomes of HCC in patients with a Fontan circulation. A multicenter case series of Fontan patients with a diagnosis of HCC formed the basis of this study. The case series was extended by published cases and case reports. Clinical presentation, tumor characteristics, laboratory and hemodynamic findings as well as treatment types and outcomes, were described. Fifty-four Fontan patients (50% female) with a diagnosis of HCC were included. Mean age at HCC diagnosis was 30 ± 9.4 years and mean duration from Fontan surgery to HCC diagnosis was 21.6 ± 7.4 years. Median HCC size at the time of diagnosis was 4 cm with a range of 1 to 22 cm. The tumor was located in the right hepatic lobe in 65% of the patients. Fifty-one percent had liver cirrhosis at the time of HCC diagnosis. Fifty percent of the patients had no symptoms related to HCC and alpha-fetoprotein was normal in 26% of the cases. Twenty-six patients (48%) died during a median follow-up duration of 10.6 (range 1–50) months. HCC in Fontan patients occurs at a young age with a 1-year survival rate of only 50%. Meticulous liver surveillance is crucial to detect small tumors in the early stage. • HCC is asymptomatic at the time of diagnosis in 50% of Fontan patients. • 26% of Fontan patients with HCC have a normal alpha-fetoprotein. • 1-year survival after HCC diagnosis in patients with a Fontan circulation is 50%. • Meticulous liver surveillance is important in patients with a Fontan circulation. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) symptoms of SARS-CoV-2/COVID-19 in the form of anorexia, nausea, vomiting, abdominal pain and diarrhea are usually preceded by respiratory manifestations and are associated with a poor prognosis. Hematochezia is an uncommon clinical presentation of COVID-19, and we hypothesize that older patients with significant comorbidities (obesity and cardiovascular) and prolonged hospitalization are susceptible to ischemic injury to the bowel. We reviewed the clinical course, key laboratory data including acute-phase reactants, and drug/medication history in 2 elderly male patients admitted for COVID-19 respiratory failure. Both patients had a complicated clinical course and suffered from hematochezia, acute blood loss, and anemia which led to hemodynamic instability requiring blood transfusion around day 40 of their hospitalization. Colonoscopic impressions were correlated with the histopathological findings in the colonic biopsies that included changes compatible with ischemia and nonspecific acute inflammation, edema, and increased eosinophils in the lamina propria. Both patients were hemodynamically stable, on prophylactic anticoagulants, multiple antibiotics, and antifungal agents due to respiratory infections at the time of lower GI bleeding. Hematochezia resolved spontaneously with supportive care. Both patients eventually recovered and were discharged. Elderly patients with significant comorbid conditions are uniquely at risk for ischemic injury to the bowel. This case report highlights hematochezia as an uncommon GI manifestation of spectrum of COVID-19 complications. The causes of bleeding in these COVID-19 associated cases are likely multifactorial and can be attributed to concomitant etiologies based on their age, multiple comorbid conditions, prolonged hospitalization compounded by lung injury, and hypoxia precipitated by the virus. We hypothesize that rather than a direct viral cytopathic effect, ischemia and hypoperfusion may be unleashed due to the cytokine storm orchestrated by the virus that leads to abnormal coagulation profile. Additional factors that may contribute to ischemic injury are prophylactic use of anticoagulants and polypharmacy. There were no other causes to explain the brisk lower GI bleeding. Presentation of hematochezia was followed by hemodynamic instability that may further increase the mortality and morbidity of COVID-19 patients, and prompt consultation and management by gastroenterology is therefore warranted. [ABSTRACT FROM AUTHOR]

We performed a secondary analysis of the Pediatric Heart Network (PHN) Marfan Trial public-use database to evaluate associations between extracardiac features and cardiac and aortic phenotypes in study participants. Aortic aneurysm phenotype was defined as aortic root Z-score ≥4.5, aortic root growth rate ≥75th percentile, aortic dissection, and aortic surgery. Severe cardiac phenotype was defined as aortic dissection, aortic Z-score ≥4.5, aortic valve surgery, at least moderate mitral regurgitation, mitral valve surgery, left ventricular dysfunction, or death. Extracardiac manifestations were characterized by specific organ system involvement and by a novel aggregate extracardiac score (AES) that was created for this study based on the original Ghent nosology. Mixed effects logistic regression analysis compared AES and systems involvement to outcomes. Of 608 participants (60% male), the median age at enrollment was 10.8 years (interquartile range: 6, 15.4). Aortic aneurysm phenotype was observed in 71% of participants and 64% had severe cardiac phenotype. On univariable analysis, skeletal (OR: 1.95, 95% CI: 1.01, 3.72; p = 0.05), skin manifestation (OR: 1.62, 95% CI: 1.13, 2.34; p = 0.01) and AES (OR: 1.17, 95% CI: 1.02, 1.34; p = 0.02) were associated with aortic aneurysm phenotype but were not significant in multivariable analysis. There was no association between extracardiac manifestations and severe cardiac phenotype. Thus, the severity of cardiac manifestations in Marfan syndrome (MFS) was independent of extracardiac phenotype and AES. Severity of extracardiac involvement did not appear to be a useful clinical marker for cardiovascular risk-stratification in this cohort of children and young adults with MFS. [ABSTRACT FROM AUTHOR]

Studies in adult HT have demonstrated improved cardiac function in the recipient following administration of T3 to the donor. The purpose of this experiment was to assess the effects of T3 on the function of the immature donor heart following HT in a piglet model. A total of 32 piglets were divided into 16 donors and 16 recipients. Following creation of brain death, half of the donor piglets were randomized to receive three doses of T3 (0.2 μg/kg) along with hydrocortisone (1 mg/kg). The donor hearts were then transplanted into the recipient piglets on CPB. Duration of survival off CPB, inotrope score, and EF of heart following CPB were evaluated. There were no differences between the two groups in age, weight, pre-brain death EF, T3 levels, and CPB times. Post- CPB survival times were inversely related to the ischemic times in both groups (Pearson r=−0.80, P<.001), and this relationship was not influenced by T3. There was no difference in inotrope score, EF, or biochemical assessment between the two groups. Administration of T3 in combination with hydrocortisone to the brain-dead donor confers no beneficial effect on myocardial function or survival following HT in a piglet model. [ABSTRACT FROM AUTHOR]

The article offers information on hepatocellular carcinoma (HCC) which is a recognized long-term complication following the Fontan operation. Topics discussed include information on symptoms of HCC which involves abdominal pain, jaundice, ascites, dyspnea, and fever; an observation that patients undergoing the Fontan operation are at risk of developing HCC from a young age; and information on medical therapy with sorafenib in HCC.

Purpose For adolescents and young adults, receiving a heart transplant is a profoundly challenging experience. This pilot study examined the burden of psychiatric co-morbidities and resiliency factors in post-transplant patients using patient-reported outcomes (PRO). Methods Patients transplanted between ages 15-25 years at one of three tertiary care centers were asked to complete six PRO measures—PROMIS® measures to assess depression, anxiety, satisfaction with social roles (SSR), and physical functioning (PF); Posttraumatic Stress Diagnostic Scale for DSM-5 (PDS-5) for Posttraumatic Stress Disorder (PTSD); and the Connor-Davidson Resilience Scale-10 for resiliency. Formal psychiatric diagnoses and demographics were collected retrospectively from chart review. Comparisons were made between PRO measures and formal diagnoses, with further comparison between those transplanted for congenital heart disease (CHD) and cardiomyopathy (CM). PROMIS® scores were dichotomized at their literature-reported cutoffs for depression and anxiety. Fisher's exact test, McNemar's test for paired samples, and Wilcoxon rank-sum test were used as appropriate. Results We enrolled 14 patients (median age at transplant 17.9 years [IQR 16.5, 20.7 yr]; 86% male and 64% with CM). Of 13 with complete data, 8/13 patients (62%) had at least mild PTSD symptoms and 3/13 (23%) had PDS-5 scores indicating probable PTSD diagnosis. Only one patient carried a formal diagnosis of PTSD. 5/13 (39%) patients had probable depression by PROMIS®. Compared to CM patients, CHD patients had more severe PTSD symptoms (p = 0.035), higher depression scores (p = 0.018) and lower PF and SSR PROMIS® scores (p = 0.017 and 0.003, respectively). Conversely, CM patients had higher resiliency scores (p = 0.021). Conclusion In this pilot study, we found high prevalence of PTSD and depression symptoms with discordant formal psychiatric diagnoses. This suggests that these disorders may be underrecognized in the adolescent and young adult heart transplant population. The routine use of PRO measures should be tested in an expanded prospective study to further evaluate their screening utility for psychiatric co-morbidities among members of this vulnerable population. [ABSTRACT FROM AUTHOR]