Citations

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that increases risk for premature coronary artery disease and has accessible and effective interventions. The Dutch lipid clinic network is currently the most used diagnostic criterion; however, genetic sequencing provides a definitive diagnosis of FH. The goals of this study were to determine whether germline genetic screening using exome sequencing could be used to efficiently identify individuals who were genotype positive for FH. METHODS: Participants were recruited from 3 geographically and racially diverse sites in the United States (Rochester, MN; Phoenix, AZ; and Jacksonville, FL). Participants underwent Exome+ sequencing (dba Helix, San Mateo, CA) and return of results for specific genetic findings in APOB , LDLR , or PCSK9 . A chart review was performed to collect demographics, personal, and family cardiovascular history. RESULTS: At the time of the study, 84 413 participants were enrolled in the Tapestry study. Annotation and interpretation of all variants in genes for FH resulted in the identification of 419 likely pathogenic and pathogenic variants (prevalence, 0.50%), which included 116 APOB , 298 LDLR , and 5 PCSK9 . Sixty-six percent were female, the mean body mass index was 27.3, with 12.3% reporting a history of diabetes. Hypertriglyceridemia (≥150 mg/dL) was present in 39.5% and reduced HDL (<50 mg/dL) was present in 56.7% of patients. 27.5% of patients were not on cholesterol-lowering medications, and only 10% of FH carriers were at goal low-density lipoprotein cholesterol levels. A history of coronary artery disease was reported in 22.4% of the cohort. Nearly 90% of these participants were newly diagnosed carriers of FH. Only 30.8% of confirmed genetic diagnoses of FH satisfied clinical (Dutch lipid clinic network) criteria for a diagnosis. CONCLUSIONS: Our results emphasize the need for wider utilization of germline genetic sequencing for enhanced screening and detection of individuals who have familial hypercholesterolemia. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT05212428.

Background: Ventricular tachycardia (VT) is a major contributor to death among ischemic heart disease (IHD) patients. In this systematic review and meta-analysis, we evaluate the efficacy of catheter ablation in patients with ischemic cardiomyopathy. Methods: We conducted a meta-analysis by searching the electronic database up to April 2025. Seven studies, including 1192 patients, were identified. A random-effect model was used to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs). Trial sequential analysis was conducted to assess sample size adequacy. Results: Among Ischemic heart disease patients with ICDs, VT ablation was associated with a significant reduction in ICD shocks (RR = 0.50, 95% CI [0.34–0.74]), a trend toward reduced VT storm (RR = 0.64, 95% CI [0.40–1.04], p = 0.07), and lower rates of cardiovascular hospitalization (RR = 0.73, 95% CI [0.53–1.01], p = 0.06) compared to ICD alone. However, no significant differences were observed when compared to patients receiving ICD plus antiarrhythmic drugs (AADs). Additionally, VT ablation showed no significant impact on mortality or VT/VF recurrence compared to either ICD alone or ICD with AADs. Trial Sequential Analysis provided conclusive evidence for VT/VF recurrence outcomes, while further data are required for other outcomes. Conclusion: Among ischemic heart disease patients with ICD, VT ablation reduces ICD shocks, VT storm, and cardiovascular hospitalizations compared to ICD-only, but offers no significant advantage over ICD combined with antiarrhythmic drugs. VT ablation does not impact mortality or the recurrence of VT/VF. Trial Sequential Analysis confirmed conclusive evidence for VT/VF recurrence, while additional data is needed for other outcomes.

Background: Glucagon-like peptide-1 (GLP-1) agonists have been shown to improve outcomes across various cardiovascular diseases. However, data regarding the effects of GLP-1 agonists in obstructive hypertrophic cardiomyopathy (HCM) is limited. Objective: This study aimed to evaluate the 5-year outcomes of GLP-1 agonists in patients with HCM. Methods: Using TriNetX Analytics Network, we identified patients aged ≥18 years with a diagnosis of obstructive hypertrophic cardiomyopathy between 1/1/2014 and 1/1/2019. Patients were divided into two groups: those treated with GLP-1 agonists for ≥ 1 year and those who were not. Propensity score matching (PSM) was performed using demographics, cardiac medications, and comorbidities. The study outcomes were 5-year all-cause mortality and cardiac adverse events. Results: A total of 52,978 patients with HCM were identified, including 2,654 (5.0%) patients treated with GLP-1 agonists. After PSM, 2,588 patients in each group were analyzed. Patients on GLP-1 agonists were associated with lower odds of all-cause mortality (5.0% vs. 15.6%, p<0.01), all-cause hospitalization (46.3% vs. 67.8%, p<0.01), acute decompensated heart failure ((9.4% vs. 21.4%, p<0.01), cardiac arrest (3.6% vs. 5.4%, p<0.01), cerebrovascular accidents (9.5% vs. 14.1%, p<0.01), and cardiogenic shock (1.4% vs. 3.6%, p<0.01). Additionally, reduced rates of new ICD implantation (3.5% vs. 7.9%, p<0.01) and septal reduction therapy (1.7% vs. 3.5%, p<0.01) were observed in the GLP-1 agonists group. Conclusion: The use of GLP-1 agonists in HCM was associated with improved cardiovascular outcomes. Future clinical trials are needed to validate these potential benefits.

Background: Leadless pacemaker has emerged as a promising alternative to traditional transvenous pacemaker (PM) among elderly patients who are at high risk of complications. Objective: This study aims to assess and compare 5-year clinical outcomes of leadless PM versus transvenous single-chamber PM in elderly patients using a multi-national dataset. Methods: Using the TriNetX Analytics Research Network, we included patients aged ≥65 years who underwent leadless versus transvenous single-chamber PM implantation between 1/1/2014 and 1/1/2020. Propensity score matching (PSM) was performed by using patient’s demographic, LVEF, cardiac comorbidities, and medications. The study outcomes included all-cause mortality and adverse cardiovascular events over a 5-year follow-up period. Results: After PSM, 7,501 patients in each group were analyzed. Leadless PM was associated with a significantly lower odds of 5-year all-cause mortality (odds ratio [OR]: 0.534; 95% confidence interval [CI]: 0.497-0.575), heart failure exacerbation (OR: 0.779, 95% CI: 0.721-0.841), major bleeding (OR: 0.666, 95% CI: 0.604-0.734), cardiac arrest (OR: 0.747, 95% CI: 0.646-0.864) and stroke (OR: 0.825, 95% CI: 0.750-0.908) compared to transvenous single-chamber PM. No significant difference was observed between the two groups in all-cause hospitalization (OR: 1.006, 95%CI: 0.938-1.079), cardiac thrombus (OR: 1.077, 95%CI: 0.791-1.465) or venous thromboembolism (OR: 1.028, 95%CI: 0.916-1.153). Conclusion: Leadless PM was associated with significantly improved mortality and cardiovascular outcomes compared to transvenous single-chamber PM in elderly patients. These findings support the strong consideration of leadless pacing as a strategy to reduce mortality and improve clinical outcomes in this high-risk population.

Background: Transvenous lead extraction (TLE) is the standard of care for cardiac implantable electronic device (CIED) infections. Data regarding the optimal timing of CIED reimplantation after TLE are not well established. Objective: This study aims to assess the 5-year outcomes of early (≤7 days) versus non-early (>7 days) CIED reimplantation following TLE for CIED infection using a multi-national database. Methods: Using the TriNetX Analytics Research Network, we included patients aged ≥18 years who underwent TLE for CIED infection between 1/1/2014 and 1/1/2020. Patients were further categorized into two groups: early CIED reimplantation (≤7 days from TLE) and non-early CIED reimplantation. Propensity score matching (PSM) was performed by including patient demographics, LVEF, cardiac comorbidities and medications. The study outcomes included all-cause mortality and cardiac adverse events during a 5-year study period. Results: A total of 1668 patients in the early CIED reimplantation group and 1550 in the non-early group were identified. After PSM, 1327 patients in each group were analyzed. Compared to non-early group, early CIED reimplantation group was associated with significantly higher odds of all-cause hospitalization (odds ratio [OR]: 1.837, 95% confidence interval [CI]: 1.532-2.203) and repeated device infection (OR: 1.569, 95% CI: 1.314-1.873) at 5-year follow-up. However, no significant differences were observed in all-cause mortality (OR: 0.927, 95% CI: 0.778-1.104), HF exacerbation (OR: 1.021, 95% CI: 0.855-1.218), cardiac arrest (OR:0.924, 95% CI: 0.739-1.157), stroke (OR: 1.169, 95% CI: 0.915-1.494), cardiac thrombus (OR: 1.163, 95% CI: 0.749-1.808), major bleeding (OR: 1.079, 95% CI: 0.857-1.358) and venous thromboembolism (OR: 0.923, 95% CI: 0.759-1.123) between the two groups. Conclusion: Early reimplantation of CIED following TLE of infected devices was associated with worse outcomes in all-cause hospitalization and repeated device infection. Further large prospective studies are needed to define the optimal timing of device reimplantation.

Background: Spontaneous coronary artery dissection (SCAD) is increasingly recognized as a cause of acute coronary syndrome, particularly in young to middle-aged women. While most presentations are associated with preserved left ventricular ejection fraction (LVEF), a subset of patients present with acute systolic dysfunction. The characteristics of patients who recover their LVEF are not clearly defined. Methods: We retrospectively analyzed 495 patients with angiographically confirmed SCAD treated at three Mayo Clinic sites (Arizona, Rochester, and Florida) from 1994 to 2023. Patients with a prior history of myocardial infarction, coronary artery disease, and congenital heart disease were excluded. Baseline LVEF at SCAD presentation was categorized into <35%, 35–39%, 40–49%, and ≥50%. Follow-up LVEF was assessed by echocardiography performed between 30 days and 1 year post-SCAD. The primary outcome was improvement in LVEF to ≥50% at follow-up. Results: A total of 495 SCAD patients were included. At presentation, 26% had reduced LVEF: 6% had LVEF <35%, 5% had LVEF between 35–39%, and 15% had LVEF between 40–49%. Patients who did not normalize their EF at follow-up were slightly younger (45 vs. 48 years, p=0.04), were more likely to have had an in-hospital cardiac arrest (13% vs. 4%, p=0.01), required mechanical circulatory support during their care, and had SCAD involving the left main artery (11% vs. 2%, p=0.01). Predictors of EF normalization included SCAD which involved the obtuse marginals (15% vs. 4%, p<0.05). The group with the lowest EF at presentation had the highest probability of persistent EF <50% at follow-up (32% for those with LVEF <35%) while patients who had normal EF at presentation had a 6% chance of having EF <50% at follow-up (Figure 1). Conclusions: Our study shows that the majority of SCAD patients have normal EF at presentation. 80% of those with reduced EF at presentation will normalize at follow-up. Predictors of low EF at follow-up included dissection involving the left main artery, lower EF at SCAD presentation, in-hospital arrest and use of mechanical circulatory support.

Abstract Background Carbon ion radiotherapy (CIRT), characterized by its Bragg peak and a reduced lateral scattering compared to proton radiotherapy (PT), offers excellent dose conformity in radiation treatment. Meanwhile, compared to PT, CIRT causes more complex and severe DNA damage in tumor cells, which results in a higher relative biological effectiveness (RBE), making it particularly advantageous in treating radioresistant and hypoxia tissues than conventional radiotherapy. However, CIRT's high RBE and the nuclear fragmentation dose tail outside the target presents challenges in sparing organ at risk (OARs). Combining PT and CIRT offers a potential hybrid modality that leverages the biological effectiveness of carbon ions while minimizing normal tissue toxicity with high biological damage. Purpose Despite the potential of combining PT and CIRT, balancing their respective advantages while mitigating disadvantages remains a significant challenge. This study aims to develop an optimized treatment approach that automatically adjusts the relative contributions of protons and carbon ions, improving target dose conformity while minimizing biological impact on OARs. Methods We propose a biological optimization framework for multi‐modality combining PT and CIRT (CCIPRT). The biological dose is modeled as the product of the physical dose and RBE. Through iterative Jacobian‐based linearization, the biological dose of carbon ion is expressed in a linear model, enabling the formulation of a linear least‐square objective. The biological dose of proton is formulated as a linear model using the physical dose and dose‐averaged linear energy transfer (LET). The joint optimization problem is then solved using iterative convex relaxation and the alternating direction method of multipliers. For comparison, single‐modality PT and CIRT were also implemented. Results When the target dose of CCIPRT is prescribed in terms of the physical dose, compared to PT, CCIPRT increased the mean biological dose in the target by 37.7%, 29.6%, and 31.1% for brain, lung, and abdomen, respectively; compared to CIRT, CCIPRT reduced the biological dose in CTV1cm (ring surrounding CTV with 1 cm width) by 47.2%, 32.3%, and 40.4% for brain, lung, and abdomen, respectively. When the target dose of CCIPRT is prescribed in terms of the biological dose, compared to PT, CCIPRT achieved higher conformity index (CCIPRT: 0.96 and 0.97; PT: 0.93 and 0.96 for brain and liver cases, respectively) and reduced the dose in CTV1cm by 9.5% and 7.0% for brain and liver cases, respectively; compared to CIRT, CCIPRT enhanced healthy tissue sparing, reducing the dose to the body by 7.5% and 9.2% for brain and liver cases, respectively. Conclusions A novel multi‐modality CCIPRT treatment planning is developed with demonstrated superior performance over single‐modality PT or CIRT, with enhanced biological effectiveness and dose conformity compared to PT and reduced OAR dose compared to CIRT.

Abstract Background Dystonia and Parkinson's disease (PD) exhibit clinical and genetic overlap, but the relevance of dystonia gene variants in PD remains unclear. Objective The aim was to assess the frequency of dystonia‐linked pathogenic variants in PD. Methods We screened sequencing data from 15,684 individuals (8272 PD, 3200 atypical parkinsonism, and 4212 unaffected) from the Global Parkinson's Genetics Program (GP2) and Accelerating Medicines Partnership‐Parkinson's Disease (AMP‐PD) for variants in genes linked to isolated dystonia, dystonia‐parkinsonism, and myoclonus‐dystonia. Results Pathogenic variants were identified only in PD patients. Forty‐five PD individuals (0.54%) carried 26 distinct (likely) pathogenic variants in nine dystonia‐linked genes, most frequently in GCH1 , followed by VPS16 . Conclusion Though rare, pathogenic variants in dystonia‐linked genes are present in clinically and pathologically diagnosed PD. Our results reinforce GCH1 as a PD‐relevant gene with clinical implications, whereas variants identified in other genes are rare and of uncertain relation to the PD phenotype. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.