Faculty Bibliography

Cardiometabolic risk factors, obesity, diabetes and hyperlipidemia contribute to cardiovascular disease (CVD). While platelets are involved in CVD pathogenesis, the relationship between risk factor burden on platelet indices and the platelet transcriptome remains uncertain. Blood was collected from CVD-free adults, measuring platelet count, mean platelet volume (MPV), immature platelet fraction (IPF), and absolute immature platelet fraction (AIPF) by hemogram. Platelets were isolated and analyzed via RNA sequencing. Participants were stratified by number of cardiometabolic risk factors (diabetes, obesity, hyperlipidemia). We calculated median (IQR) values of platelet indices and p-for-trend via linear regression across risk factor burden. To evaluate the association between risk factor burden and platelet transcripts, we performed multivariable linear regression adjusting for age, sex, and race/ethnicity. Among 141 participants, (50.5 ± 14.8 years, 42% male, 26% Black) risk factor burden was associated with increasing platelet size, IPF, and AIPF but not platelet count. Platelet RNA sequencing identified 100 differentially expressed transcripts (p < .01; 66 upregulated, 34 downregulated). Gene ontology enrichment analysis demonstrated upregulated pathways of secondary metabolic processes (NES = 1.96, p < .01), and hematopoietic stem cell proliferation (NES = 1.95, p < .01). Greater cardiometabolic risk factor burden is associated with increased platelet size and immaturity and suggesting novel platelet-mediated mechanisms linking risk factor burden with CVD.

While weight loss is highly recommended for those with obesity, >60% will regain their lost weight. This weight cycling is associated with elevated risk of cardiovascular disease, relative to never having lost weight. How weight loss/regain directly influence atherosclerotic inflammation is unknown. Thus, we studied short-term caloric restriction (stCR) in obese hypercholesterolemic mice, without confounding effects from changes in diet composition. Weight loss was found to promote atherosclerosis resolution independent of plasma cholesterol. From single-cell RNA-sequencing and subsequent mechanistic studies, this can be partly attributed to a unique subset of macrophages accumulating with stCR in epididymal white adipose tissue (eWAT) and atherosclerotic plaques. These macrophages, distinguished by high expression of Fcgr4, help to clear necrotic cores in atherosclerotic plaques. Conversely, weight regain (WR) following stCR accelerated atherosclerosis progression with disappearance of Fcgr4+ macrophages from eWAT and plaques. Furthermore, WR caused reprogramming of immune progenitors, sustaining hyper-inflammatory responsiveness. In summary, we have developed a model to investigate the inflammatory effects of weight cycling on atherosclerosis and the interplay between adipose tissue, bone marrow, and plaques. The findings suggest potential approaches to promote atherosclerosis resolution in obesity and weight cycling through induction of Fcgr4+ macrophages and inhibition of immune progenitor reprogramming.

BACKGROUND:Pulmonary embolism (PE) is can present with cardiac arrest. Catheter-based therapies (CBT) provide rapid reperfusion for patients with PE, though their effect on outcomes of patients with PE and cardiac arrest are not well known. AIMS/OBJECTIVE:To evaluate the effect of CBT on outcomes among patients with PE and cardiac arrest. METHODS:This was a retrospective cohort study of patients with PE and cardiac arrest from 2017 to 2020, using the National Readmission Database (NRD). We compared patients who underwent CBT versus no CBT and patients managed with CBT alone versus systemic thrombolysis alone. The primary endpoint was in-hospital death; exploratory outcomes were 90-day death and readmissions. Multivariable logistic and Cox proportional hazards modeling were used. RESULTS:Nine hundred and seventy-three patients were included (111 with CBT). CBT was associated with a lower risk of in-hospital death (36.9% vs. 49.3%, p = 0.015; aOR 0.44, 95% CI 0.23-0.85) with no difference in 90-day readmission (11.3% vs. 18.7%, p = 0.19; aHR 0.63, 95% CI 0.27-1.47). Among the 390 patients with either CBT or systemic thrombolysis alone in-hospital death (34.4% vs. 48.5%, p = 0.023; aOR 0.51, 95% CI 0.21-1.25) and 90-day readmissions (13.3% vs. 11.8%, p = 0.79; aHR 1.04, 95% CI 0.39-2.76) were similar. Ninety-day survival was higher with CBT when compared with no CBT or systemic thrombolytic alone (log-rank p = 0.050 and 0.020, respectively). CONCLUSIONS:Among patients with PE and cardiac arrest, CBT was associated with decreased risk of in-hospital death and 90-day survival compared with no CBT. Further prospective study on utility of CBT in PE and cardiac arrest is needed.

The Predicting Risk of Cardiovascular EVENTS (PREVENT) equations, created and endorsed by the American Heart Association, provide cardiovascular risk estimates for the general population, but have not yet been tested in multiethnic populations. In the present study, in a large nationwide multiethnic sample of US veterans, the utility of PREVENT to predict the risk of total cardiovascular disease (CVD: fatal and nonfatal myocardial infarction, stroke or heart failure; PREVENT-CVD), atherosclerotic cardiovascular disease (ASCVD: fatal and nonfatal myocardial infarction or stroke; PREVENT ASCVD) and heart failure was evaluated. We assessed the discrimination and calibration performance of ASCVD prediction with PREVENT ASCVD compared with a previous risk-prediction score, pooled cohort equations (PCEs). Among 2,500,291 veterans aged 30-79 years (93.9% men and 6.1% women), 407,342 total CVD events occurred over a median (interquartile range (IQR)) follow-up of 5.8 (IQR = 3.1-8.3) years. The Concordance index (C-index) (95% confidence interval (CI)) for PREVENT-CVD was 0.65 (95% CI = 0.65-0.65) in the overall sample and was similar across different race and ethnic groups (Asian, Native Hawaiian or Pacific Islander, 0.70 (95% CI = 0.69-0.71); Hispanic, 0.70 (95% CI = 0.69-0.70); non-Hispanic Black. 0.68 (95% CI = 0.68-0.69) and non-Hispanic White, 0.65 (95% CI = 0.64-0.65)). C-indices were similar between PREVENT ASCVD and PCEs and ranged from 0.61 to 0.63. Calibration slopes for PREVENT-CVD and -ASCVD in the overall sample were 1.09 (s.e. = 0.04) and 1.15 (s.e. = 0.04), respectively. In contrast, PCEs demonstrated overprediction for ASCVD with a calibration slope of 0.51 (s.e. = 0.06). Calibration slopes for PREVENT and PCEs were similar across race and ethnic groups. Among US veterans, the PREVENT equations accurately estimated CVD and ASCVD risk with some variability across race and ethnicity groups and outperformed PCEs for ASCVD risk prediction.

BACKGROUND:Inclusion of patients, caregivers, and community members in scientific research should be essential for patient-centered care. Patients’ lived experiences can propose new areas of focus that may not have previously been considered, ensure that potentially sensitive topics are addressed thoughtfully, contribute to the interpretation of findings, and identify future directions of research. Further, their inclusion in the drafting of manuscripts can ensure that research findings are translatable to real-world practice. To achieve this goal, the Researching COVID to Enhance Recovery (RECOVER) consortium developed a Representative Authorship system for development of scientific manuscripts that report RECOVER data. This paper describes a Quality Improvement (QI) project that was conducted to identify system strengths and improvement opportunities. METHODS:An online QI survey was distributed to RECOVER’s Representative Authors about a year into the implementation of the Representative Authorship System. The survey focused on several key aspects, including the clarity regarding the authorship process, training opportunities, the matching process, communication within writing groups, and the perceived impact of the representative engagement on the quality and applicability of research. The survey also explored participants’ satisfaction with compensation, support, and involvement in the system, as well as areas for improvement. RESULTS:The survey was sent to 49 representative authors with 17 respondents (35%). Most respondents reported positive experiences, highlighting the effective matching to manuscripts based on their expertise and the perceived positive impact of their involvement on research outcomes. Additionally, participants felt that including diverse voices enhanced the relevance of research for clinical practice. Several areas for improvement were identified, including communication challenges within writing groups, the utility of manuscript orientation calls, and the fairness of compensation. Respondents also indicated a need for more training opportunities and logistical support. CONCLUSIONS:RECOVER’s Representative Authorship system is effective in fostering collaboration and improving the inclusivity of scientific research. The survey findings indicate that there are logistical changes around communication, training, and compensation that could enhance the experience for all collaborators. Based on these findings, we plan to implement changes to improve awareness, understanding, and collaboration. Additional work is needed to solicit feedback from investigators and administrative staff to obtain a more holistic understanding of the system. SUPPLEMENTARY INFORMATION:The online version contains supplementary material available at 10.1186/s12913-025-12914-3.

BACKGROUND:Limited contemporary evidence exists on risk prediction by stress imaging and exercise electrocardiography (ECG) among patients with chronic coronary syndromes (CCS). Objectives From the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) study, prognosis was examined by core laboratory-defined stress imaging and exercise ECG findings in CCS patients. METHODS:A total of 5,179 patients (qualifying by stress nuclear imaging [n = 2,567], echocardiography [n = 1,085], cardiac magnetic resonance [CMR] [n = 257], and ECG [n = 1,270]) were randomized. Cox models assessed associations between trial endpoints and the number of scarred and ischemic segments, rest/stress left ventricular ejection fraction (LVEF), and ST-segment depression. HRs and 95% CIs were calculated per millimeter, segment, or 5% of LVEF. We examined prognostic models for the following trial endpoints: 1) the trial's primary endpoint of cardiovascular (CV) death, myocardial infarction (MI), resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure; 2) CV death; 3) spontaneous MI; 4) procedural MI; and 5) type 2 MI. RESULTS:The number of scarred segments (HR: 1.07 [95% CI: 1.02-1.13]; P = 0.0209), rest LVEF (HR: 0.88 [95% CI: 0.83-0.93]; P < 0.001), and stress LVEF (HR: 0.87 [95% CI: 0.83-0.91]; P < 0.001) predicted the trial's primary endpoint of CV death, MI, resuscitated cardiac arrest, or hospitalization for unstable angina or heart failure. The extent of scar and rest/stress LVEF on echocardiography and nuclear imaging predicted several trial endpoints. The number of ischemic segments predicted spontaneous (HR: 1.08 [95% CI: 1.03-1.14]; P = 0.0104) and procedural MI (HR: 1.14 [95% CI: 1.03-1.25]; P = 0.0015) but was of borderline significance for the trial's primary endpoint (P = 0.0746). Ischemia extent by CMR predicted the trial's primary endpoint (P = 0.0068) and spontaneous MI (P = 0.0042). CONCLUSIONS:ISCHEMIA trial findings from 320 worldwide centers revealed that stress imaging and exercise ECG measures exhibited a variable association with key trial endpoints delineating risk patterns for ischemia and infarction. Stress CMR ischemia predicted several trial endpoints, supporting an expanded role in the evaluation of patients with CCS (ISCHEMIA [International Study of Comparative Health Effectiveness With Medical and Invasive Approaches]; NCT01471522).

BACKGROUND:Pulmonary vein (PV) isolation is the cornerstone of radiofrequency (RF) ablation for atrial fibrillation (AF) and PV reconnection is a common cause of recurrent AF. The relationship between PV ostial wall thickness (WT) and durable PV isolation is a matter of ongoing investigation. Additionally, the relationship between catheter impedance and WT is not well understood. We studied the relationship between PV ostial WT, ablation lesion metrics, and PV reconnection. METHODS:16 patients were identified who underwent an initial and redo AF ablation procedure and had a cardiac CTA analyzed using ADAS-3D imaging software performed prior to the initial ablation. Ablation lesion metrics from the initial ablation procedure were collected from the electroanatomic mapping software. Reconnected and isolated PV were identified based on electroanatomic mapping data collected at the redo AF ablation procedure. Patients with reconnected PV exhibited thicker left atrial walls (1.4 mm vs 1.2 mm, P < 0.05) and reconnected veins exhibited thicker ostial walls (1.7 mm, vs 1.5 mm, P < 0.05). LA volume, number of ablation lesions, and ablation lesion time were not significantly different between reconnected and isolated PV. Impedance drop during ablation was greater in patients with reconnected PV compared to patients with isolated PV (- 9.0 Ω vs - 6.6 Ω, P < 0.05). There was no correlation between PV ostial WT and ablation lesion impedance drop. CONCLUSION/CONCLUSIONS:PV reconnection was associated with thicker LA and PV ostial WT. Future studies will examine whether targeting thicker PV ostial tissue with more aggressive lesion metrics or different ablation technology can improve PV isolation and ablationoutcomes.

BACKGROUND:Long-term safety and efficacy data for aficamten in symptomatic obstructive hypertrophic cardiomyopathy are needed. OBJECTIVES/OBJECTIVE:This study aims to evaluate 48-week experience from the ongoing FOREST-HCM (A Follow-Up, Open-Label, Research Evaluation of Sustained Treatment With Aficamten [CK-3773274] in Hypertrophic Cardiomyopathy) study. METHODS:Obstructive hypertrophic cardiomyopathy participants in an aficamten study (REDWOOD-HCM [Dose-finding Study to Evaluate the Safety, Tolerability, PK, and PD of CK-3773274 in Adults With HCM; NCT04219826]; SEQUOIA-HCM [Aficamten vs Placebo in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT05186818]) could enroll in this phase 2/3, open-label, extension study. Participants received aficamten 5 mg once daily titrated ≤20 mg based on site-read echocardiographic assessments of Valsalva left ventricular outflow tract gradient and left ventricular ejection fraction. RESULTS:; P = 0.0008), lateral E/e' (-2.2 ± 6.1; P = 0.02), and cardiac biomarkers (P ≤ 0.0031). Aficamten was well tolerated with 2 (4.3%) asymptomatic and transient instances of left ventricular ejection fraction <50% (range: 47%-49%), neither resulting in drug discontinuation, and no new-onset atrial fibrillation. CONCLUSIONS:Aficamten treatment over 48 weeks was well tolerated and associated with substantial and durable relief of obstruction and symptom burden, lower cardiac biomarker levels, and cardiac phenotypic changes, which may indicate favorable cardiac remodeling. (A Follow-Up, Open-Label, Research Evaluation of Sustained Treatment With Aficamten [CK-3773274] in Hypertrophic Cardiomyopathy [FOREST-HCM]; NCT04848506).

BACKGROUND:In patients with diabetes mellitus (DM) and high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI), the optimal duration of dual antiplatelet therapy (DAPT) remains uncertain. AIMS/OBJECTIVE:We sought to compare early DAPT discontinuation in DM and non-DM patients enrolled in the prospective XIENCE Short DAPT programme. METHODS:The effects of 1- versus 3-month DAPT on ischaemic and bleeding outcomes were compared using propensity score stratification. The primary endpoint was a composite of all-cause death or myocardial infarction (MI) at 1 year. The incidence of Bleeding Academic Research Consortium (BARC) Type 2 to 5 bleeding was the key secondary endpoint. RESULTS:Out of 3,352 included patients, 1,299 (38.8%) had DM; diabetic patients had a higher 1-year incidence of death or MI (DM vs non-DM: 10.1% vs 6.6%) and similar BARC 2-5 bleeding (DM vs non-DM: 9.5% vs 9.2%). With 1- versus 3-month DAPT, the incidence of death or MI did not statistically differ in DM patients (adjusted hazard ratio [adjHR] 0.70, 95% confidence interval [CI]: 0.47-1.05) and non-DM patients (adjHR 1.26, 95% CI: 0.87-1.81), although heterogeneity by DM status was evident (p for interaction=0.015). BARC 2-5 bleeding was numerically lower with 1-month DAPT in both groups (DM: adjHR 0.67, 95% CI: 0.45-1.01; non-DM: adjHR 0.78, 95% CI: 0.56-1.07; p for interaction=0.973). CONCLUSIONS:Among HBR patients with DM undergoing PCI, 1-month DAPT, as compared to 3-month DAPT, was not associated with an excess of fatal or non-fatal MI and even reduced the occurrence of bleeding. These findings should be interpreted in the context of a predominantly stable patient population with low procedural complexity and may not be generalisable to higher-risk cases.