Citations

Abstract Background Contemporary prevalence and penetrance of familial hypercholesterolemia (FH) and the associated coronary heart disease (CHD) risk across diverse genetic ancestries in the United States are unclear. Purpose To estimate prevalence of individuals harboring pathogenic/likely pathogenic (P/LP) variants in LDLR, APOB, and PCSK9, distribution of low-density-lipoprotein cholesterol (LDL-C) levels, and associated CHD risk for carriers in an ancestrally diverse cohort. Methods In 242,167 All of Us (AoU) participants with available whole-genome sequencing data, we obtained LDL-C measurements, statin prescriptions, and ascertained P/LP variants in FH-related genes and presence of CHD based on electronic-health record data. P/LP variants in LDLR, APOB, and PCSK9 were identified in AoU data by filtering for high-impact (frameshift, canonical splice site, indels, and stop gain) and predicted-deleterious missense variants, then selecting those classified as P/LP in ClinVar. Untreated LDL-C levels were estimated assuming a 30% reduction if there was a record of a statin prescription in the preceding 12 months and the highest value among multiple measurements for each individual were selected. Penetrance was defined as LDL-C>155 mg/dl. CHD was determined using a validated phenotyping algorithm based on diagnostic and procedural billing codes. Logistic regression models were used to obtain prevalence and penetrance estimates and odds ratios for CHD, along with associated 95% confidence intervals (95% CI). Results We identified 221 FH-related P/LP variants (LDLR=169, APOB=50, PCSK9=2) in the study cohort. Of 125,841 European (EUR), 53,367 African (AFR), 40,189 admixed American (AMR), and 22,770 other ancestry individuals, 1:218 (0.46%, 95% CI 0.42%-0.50%), 1:307 (0.33%,0.28%-0.38%), 1:350 (0.29%, 0.24%-0.34%), and 1:201 (0.50%, 0.41%-0.59%) were carriers of a P/LP variant. In 92,616 individuals with at least one LDL-C measurement, carriers of a P/LP variant had a higher distribution of LDL-C across all ancestries with similarly high penetrance (Figure 1). Harboring a P/LP variant in LDLR, APOB, and PCSK9 was associated with similarly increased odds of CHD across all the different ancestry groups (Figure 2). Conclusions Monogenic FH was prevalent, penetrant, and significantly associated with CHD similarly across diverse ancestry groups in the AoU cohort. These findings support a ‘genotype first’ approach to detection of FH to enable early intervention across diverse ancestry groups.Figure 1 Figure 2

Abstract Background The extravascular implantable cardioverter defibrillator (EV-ICD) was designed to avoid lead-related complications associated with transvenous systems and deliver features such as anti-tachycardia pacing (ATP) and reduced generator size that provide an advantage over a subcutaneous ICD (S-ICD). As such, the EV-ICD is an attractive alternative for younger patients with genetic heart diseases (GHDs) who are not in need of permanent pacing. Objective To examine the indications, complications, and the clinical outcomes of patients with GHDs who received an EV-ICD. Methods A retrospective review of the electronic record was done for all GHD patients evaluated in genetic heart rhythm and/or cardiomyopathy clinics who had an EV-ICD implanted between 1/2021 and 2/2025. Basic demographic, ICD indications, complications, and therapy data were then extracted for all study patients. Results Overall, 23 patients (35% female; mean age 39 ± 16 years; 61% with a disease-causative genetic variant; mean LVEF 57%) with an underlying GHD (hypertrophic cardiomyopathy in 9, arrhythmogenic cardiomyopathy in 8, idiopathic ventricular fibrillation in 3, dilated cardiomyopathy in 2, and long QT syndrome in 1) had an EV-ICD implanted. For the majority, an EV-ICD was implanted for primary prevention (15/23; 65%) and represented their first ICD system (21/23; 91%). The success rate of the procedure was 96% with only one abandoned procedure because of poor R-wave sensing. Inadvertent intraprocedural lead placement in the pericardial space occurred in 1 patient with previous thoracotomy and surgically placed epicardial lead without sequelae or need for revision. Over a mean follow-up of 8±9 months, the rate of complications was low (1/23; 4%) with one electrode displacement and this patient underwent defibrillation threshold testing (DFT), the device properly detected VF and emitted a successful shock 30 J. Thus far, 2 patients have received appropriate VT/VF-terminating therapies (3 ICD shocks, 0 ATP) with successful conversion to sinus rhythm. One patient died following an electrical storm. One patient had 3 inappropriate ICD shock for sinus tachycardia while exercising followed by 1 successful shock for VF. Conclusion In this early experience, EV-ICDs appear to be safe and effective in younger patients with genetic arrhythmogenic and hypertrophic cardiomyopathies. Future studies are needed to better understand the utility of EV-ICDs in patients with cardiac channelopathies and advantages of EV-ICDs over transvenous and S-ICD systems in patients with an array of sudden death-predisposing GHDs.

Abstract Background/Introduction Patients with transthyretin cardiac amyloidosis (ATTR-CA) and atrial fibrillation (AF) have increased risk for left atrial thrombi, necessitating anticoagulation therapy if bleeding risk is not prohibitive. Limited data is available comparing the use of direct oral anticoagulants (DOACs) to warfarin in this population. Purpose To evaluate and compare clinical efficacy and safety outcomes of DOACs versus warfarin in patients with ATTR-CA and AF. Methods We conducted a retrospective cohort study using the TriNetX Network, which includes data from over 140 million patients, between 2014 and 2022. Adults (aged ≥18 years) with ATTR-CA and AF were identified. These patients were further categorized into two groups: one cohort which utilized DOACs for oral anticoagulation and the other cohort on warfarin. 1:1 propensity score matching (PSM) was utilized to balance baseline characteristics between the two cohorts. The primary outcome was rate of stroke, with secondary outcomes including all-cause death, all-cause hospitalizations, and acute heart failure exacerbations. Safety outcomes included intracranial hemorrhage, gastrointestinal hemorrhage, and hematuria. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated. Results Among 8,214 adults with ATTR-CA and AF, 5,774 patients were on a DOAC while 2,440 patients were on warfarin. After PSM, 2,425 patients were included in each group. The use of DOACs for AF in patients with ATTR-CA was associated with a significantly lower risk of ischemic stroke compared to warfarin (5.7% versus 7.3%, aOR 0.771 [95% CI, 0.612-0.971]) by the end of the one year follow up. There were no differences in all-cause mortality (19.8% versus 21%, aOR 0.927 [95% CI, 0.806-1.066]), all-cause hospitalizations (19.2% versus 21.6%, aOR 0.863 [95% CI, 0.624-1.195]) or heart failure exacerbations (43.6% versus 46%, aOR 0.906 [95% CI, 0.809-1.015]). Safety outcomes favored DOACs over warfarin, with a lower risk of intracranial hemorrhage (4.5% versus 7.8%, aOR 0.565 [95% CI, 0.444-0.720]), and comparable rates of GI hemorrhage and hematuria. Conclusions DOACs may be safely used in ATTR-CA patients with AF, offering a lower risk of stroke compared to warfarin and a more favorable safety profile. These findings emphasize the potential advantages of DOACs in this population and underline the need for prospective studies to validate these results.

Abstract Background Cancer therapies have prolonged survival in lymphoma. However, lymphoma patients may develop significant coronary artery disease (CAD), which may be treated by percutaneous coronary intervention (PCI). The characteristics and outcomes of lymphoma patients treated by PCI are not well studied. Methods We reviewed lymphoma patients undergoing PCI at our institution between 2010 and 2020 and compared them to a cohort without cancer. Patient characteristics and predictors of long-term mortality and major adverse cardiac events (MACE) (death, myocardial infarction, target lesion revascularization) were studied using descriptive statistics and survival analysis utilizing a Cox proportional hazards model. Results Of the 11,953 patients in the study cohort, 83 had a history of lymphoma meeting study criteria. Lymphoma patients, as compared to non-lymphoma patients were similar with respect to age, sex, hypertension, diabetes, hyperlipidemia, prior MI, and prior PCI (all p=ns). Over a median follow-up of 3.9 (1.0, 5.0) years, the mortality at 5 years was higher in lymphoma versus non-lymphoma patients (47.5% vs 29.8%) (P=0.005) (Figure). After adjusting for age, sex, hypertension, diabetes, shock, smoking status, heart failure, and chronic renal disease, lymphoma was an independent predictor of mortality (OR 1.59; 95% CI 1.07-2.36, p=0.02). Lymphoma was not independently associated with MACE. Discussion Lymphoma patients undergoing PCI have significantly lower survival rates than non-cancer controls. After accounting for important cardiac risk factors, lymphoma was independently associated with higher long term mortality.

Abstract Background Acute myocardial infarction (AMI) patients face a substantial risk of cardiovascular events and rehospitalization. The impact of the SmartHeart 12-lead ECG telemedicine device on healthcare utilization has not been tested in a US randomized trial. Methods Patients with AMI were randomized at discharge to standard of care without (control group) or with the SmartHeart 12-lead ECG device (intervention group). The primary endpoint was the rate of emergency department (ED) visits, hospital readmissions, and any cardiovascular testing from discharge to 90 days of follow-up. Results The primary endpoint was reached in 57/96 patients (59.4%) in the control group and 53/84 patients (63.1%) in the intervention group (p = 0.61). However, in the intervention group, only 24.7% of patients complied with 2 follow-up training SmartHeart 12-lead ECG transmissions after discharge, and only 21.6% used the device thereafter. In patients who did use the device after training, 38.2% were advised by the study team to refer to the ED, each time with a significant clinical presentation: 7 patients had chest pain (3 AMI); 2 atrial flutter/fibrillation; 1 ventricular fibrillation. Among device users, ED presentations were lower in the intervention (2/25, 8.0%) than in the control (28/96, 29.2%) group (p = 0.04, Figure 1). Conclusion In this US-based trial, the utilization of the SmartHeart 12-lead ECG device was low, which compromised the primary outcome analysis. Decreased compliances resulted in more ED visits. Figure 1: Cumulative incidence of ED visits in controls and per protocol device use compliant patients.Cumulative incidence of ED visits in con

BACKGROUND AND OBJECTIVES: External ventricular drain (EVD) placement is the most commonly performed bedside emergent neurosurgical procedure. However, catheter misplacement occurs in approximately 25% of cases, potentially resulting in neurological injury or the need for repositioning, highlighting the need for safer and more accurate placement techniques. This review aims to (1) summarize technological innovations developed to enhance the accuracy and safety of bedside EVD placement, (2) evaluate their reported benefits and limitations, and (3) identify key barriers to their clinical implementation in critical care settings. METHODS: We conducted a systematic review of PubMed, Embase, and Scopus combining terms related to EVD placement and assistive technologies. All the studies evaluated EVD placement using simulations, phantoms, cadavers, and patient procedures conducted at the bedside and in the operating room. RESULTS: We identified 3898 records, and 76 studies met the inclusion criteria. Of these, 30 studies compared stereotactic systems, ultrasound guidance, frameless neuronavigation, and augmented or mixed reality technologies to the freehand technique. These studies consistently reported improved accuracy with advanced systems although complication rates and procedural times were variably reported. An additional 35 and 12 studies evaluated nonimmersive and immersive technologies, respectively, in noncomparative settings. Most of these demonstrated high first-pass success and mean tip deviations under 3 mm. Variability in the definitions of accuracy and procedural metrics limited data synthesis, but the overall findings suggest a promising trajectory for technology-assisted EVD placement. CONCLUSION: Assistive technologies for EVD placement show potential to improve accuracy and safety over the freehand technique. These early successes signal potential to improve bedside neurosurgical care. Realizing this promise will require future studies to standardize accuracy metrics, report time, and safety outcomes consistently and validate performance in real-world critical care settings.

Objective: Orthobiologics are increasingly sought-after interventions in sports medicine for treatment of musculoskeletal injuries and conditions. Despite this trend, differences exist across sports medicine fellowship programs regarding foundational knowledge, educational curricula, and practical experience with orthobiologic therapies (eg, platelet-rich plasma, bone marrow aspirate concentrate, microfragmented adipose tissue). This represents an important educational gap for those training in sports medicine fellowships. To address this gap, an educational toolkit was envisioned with the sports medicine fellowship director and trainee in mind. Data Sources: Collective observations from physician experts in sports medicine education established the variations in curricula and expertise of graduating fellows. A literature review was conducted to source English-language peer reviewed articles from the online PubMed database. The scope of this project did not include an independent systematic analysis or statistical assessments. Main Results: An educational toolkit consisting of 12 adaptable modules was developed, each with a suggested reading list from the published literature. The modules may be rearranged to support each program's learning schedule. The information and lessons contained herein may be valuable to all healthcare providers interested in the evidence-based application of orthobiologics and insightful interpretation of related research. Conclusions: By implementing an educational toolkit, sports medicine fellowships may improve the quality of education on orthobiologics. This is intended to improve the knowledge and skill set of fellowship graduates, thus promoting the scientific, responsible use of orthobiologic interventions.