bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4136023: Eligibility and Barriers of Mavacamten Therapy in Patients with Hypertrophic Cardiomyopathy: A Retrospective Analysis
Authors: Jiang Sarah , Sardesai Krish , Yousaf Abdulrehman , Norgard Nicholas , ASIF TALAL
Published: November 2024

Background:
Hypertrophic Cardiomyopathy (HCM) is a common genetic heart disorder characterized by the thickening of the myocardium. Mavacamten has emerged as a novel medication for targeted therapy in HCM patients, but its adoption faces multiple hurdles. This study aims to evaluate the eligibility of HCM patients for Mavacamten treatment based on certain clinical criteria and to promote consideration of potential barriers patients face in obtaining this medication.

Methods:
We conducted a retrospective analysis of 115 HCM patients at Truman Medical Center that included demographic data, clinical characteristics, and treatment histories. Patient eligibility for Mavacamten was determined based on ejection fraction (EF) > 55%, symptomatic obstructive HCM, and intolerance to first-line therapy (beta-blockers, calcium channel blockers). Statistical analysis was performed using standard deviation and mean comparisons to estimate the proportion of eligible patients.

Results:
Out of 115 patients, 96 patients have an EF>55%. 76 patients (66.1%) have a clinical heart failure diagnosis. 94 patients (81.7%) are taking beta-blockers. 49 patients (42.6%) have uncontrolled hypertension indicated by blood pressure >140. Considering these factors, 49 (42.6%) met the clinical criteria for Mavacamten treatment. Of these patients eligible to receive Mavacamten treatment, only one patient was actively taking Mavacamten. The most common obstacles to receiving the drug included lack of insurance coverage, high medication cost, and limited awareness among healthcare providers regarding new treatment options.

Conclusion:
While a considerable proportion of HCM patients qualify for Mavacamten based on clinical criteria, external factors significantly impede access to this potentially life-altering treatment. Efforts should address this treatment gap through raising awareness to healthcare professionals and improving insurance coverage. This will enhance patient access to Mavacamten, ultimately improving outcomes in HCM management. This study summarizes the eligibility and obstacles to Mavacamten in a sample of HCM patients, emphasizing the need for systemic changes to facilitate access to advanced therapies.
Abstract 4136032: Digital Biomarkers Associated With Coronary Artery Calcium And Traditional Risk Factors Extracted From Facial Photos Through Multi-Label Deep Learning For Detecting Coronary Artery Disease
Authors: Zeng Juntong , Lin Shen , Sun Runchen , Li Zhongchen , Zheng Zhe
Published: November 2024

Background:
Biomarkers like coronary artery calcium (CAC) and traditional risk factors are well-validated for coronary artery disease (CAD) assessment but not always available, and with limited workup efficiency and potential radiation risk. Facial features contain biological information related to atherosclerosis.

Aims:
We aim to extract CAC and traditional risk factor-associated digital biomarkers from facial images and evaluate their value in predicting CAD status compared with conventional clinical approaches.

Methods:
Suspected individuals referred for confirmatory CAD evaluation across nine centers were included. Participants in one center constituted the derivation set. External validation included one dataset of participants from a different time period in the derivation center and the other dataset from the other eight centers. We developed a multi-label deep-learning model to extract digital biomarkers from facial photos based on a multi-dimensional label of CAC score and eight traditional risk factors to comprehensively represent coronary atherosclerosis risk profile. The extracted digital biomarkers were evaluated for both effectiveness in reflecting components of the multi-dimensional label and clinical value in predicting obstructive CAD.

Results:
A total of 13248 facial photos from 3312 eligible participants (mean age, 58.5 years; 517 [25.9%] female) were included. In external validation, a set of digital biomarkers (FacialCAD) were extracted, effectively reflecting components of the multi-dimensional label, especially for CAC stratification (CAC>0, AUC 0.919 [0.885 – 0.949]; CAC≥100, AUC 0.906 [0.876 – 0.933]) and nearly perfect prediction for the age and sex. The performance of the FacialCAD in predicting obstructive CAD (AUC 0.721 [0.694–0.748]) significantly outperformed two guideline-recommended CAD models (0.721 vs. 0.653, P<0.001; 0.721 vs. 0.686, P=0.032), with further significant improvement when combined with these models (△AUC= +0.085, P<0.001; △AUC= +0.068, P<0.001).

Conclusion:
FacialCAD, a set of CAC and risk factors-associated novel digital biomarkers extracted from facial images, exhibited superior and incremental value to conventional clinical approaches in predicting CAD status.
Abstract 4136036: Five-year Outcomes of Heart-Kidney Transplant Recipients Bridged with Durable Mechanical Circulatory Support: Less AMR Better Survival?
Authors: Manla Yosef , Patel Jignesh , Kittleson Michelle , Nikolova Andriana , Chang David , Kransdorf Evan , Stern Lily , Czer Lawrence , Lee Mason , Kobashigawa Jon
Published: November 2024

Introduction:
Despite the increased risk of sensitization in patients receiving pre-transplant durable mechanical circulatory support (D-MCS), it has been suggested that removing D-MCS at the time of transplant may lead to a drop in HLA-antibody levels. Whether this may reduce rejection rates and improve long-term outcomes in patients undergoing heart-kidney transplantation (HKTx) has not been widely investigated. Therefore, we aim to investigate the impact of pre-transplant D-MCS on 5-year clinical outcomes of patients undergoing HKTx.

Methods:
We included 98 patients undergoing HKTx between 2010 and 2018 at a single center. Recipient pre-transplant characteristics and clinical outcomes were compared between patients receiving D-MCS (n=24) versus non-D-MCS patients (n=74). The D-MCS cohort included those who received total artificial heart (n=13), left ventricular assist device (n=8), and biventricular assist devices (n=3). Endpoints included 1- and 5-year survival, 1-year-freedom from acute cellular rejection (defined as grade 2R or 3R), 1-year-freedom from antibody-mediated rejection (AMR, defined as pathologic AMR of grade ≥1), 5-year freedom from cardiac allograft vasculopathy (CAV, stenosis ≥30% by angiography), 5-year freedom from non-fatal major adverse cardiac events (NF-MACE including myocardial infarction, new congestive heart failure, percutaneous coronary intervention, implantable cardioverter defibrillator/pacemaker implant, stroke), and 5-year freedom from left ventricular dysfunction (LVEF ≤40).

Results:
At 1 year, freedom for AMR was numerically higher in the D-MCS group (100 vs. 90.2%, P=0.12). Additionally, the 5-year post-transplant survival rate was higher in the D-MCS group (95.8% vs. 80.8%), but it did not reach statistical significance (P=0.091). Comparable outcomes were noted for other outcomes, including 5-year freedom from CAV, NF-MACE, or LVD (Table
1
).

Conclusion:
The current study hints at better 5-year survival in HTKx recipients receiving pre-transplant D-MCS, which could be attributed to lower rates of AMR in this population. Future larger studies are warranted to further validate these findings.
Abstract 4136159: Determinants of Exercise Intolerance in Postural Orthostatic Tachycardia Syndrome: a Systematic Review
Authors: Abbate Gerardina , Hogwood Austin , Thomas Georgia , MARKLEY ROSHANAK , Priday Anna , Arena Ross , Abbate Antonio , Canada Justin
Published: November 2024

Background:
Postural Orthostatic Tachycardia Syndrome (POTS) is a syndrome of an exaggerated heart rate (HR) response with standing, disproportionately affecting young women associated with exercise intolerance due to dizziness, palpitations, and/or chest pain.

Research question:
How does the exaggerated increase in HR with standing translate into impaired exercise tolerance in subjects with POTS?

Aims:
To systematically analyze determinants of exercise intolerance in subjects with POTS.

Methods:
We searched the National Library of Science and identifed 11 cohorts with a diagnosis of POTS and an assessment of exercise capacity. We abstracted the information including type of exercise testing, hemodynamics and gas exchange parameters (peak oxygen consumption [VO
2
]) with exercise, and effect of interventions (if present).

Results:
We identified 849 subjects with POTS, female:male ratio of 8.5:1, 25±8 years, and 365 age-and sex-matched controls. A cycle ergometer was used in 8 studies (574 subjects, 68%) and a treadmill in 3 (275 subjects, 32%). Peak VO
2
was measured in 10 studies (836 subjects, 98%), and exercise hemodynamics in 9 (593 subjects, 70%). All 11 (100%) studies described a higher HR at rest and during submaximal exercise in subjects with POTS, with a similar slope of HR/load, and shorter time to peak HR. Of the 9 studies with hemodynamics, 6 (67%) reported a reduction in stroke volume (SV) with standing and with exercise, but only 1 (11%) documented a reduction in cardiac output (CO). Two studies (22%) enrolling teenagers showed a variable increase in SV and CO in POTS. Peak VO
2
was reduced in 8 (80%) studies when compared with predicted values, but only in 4

(40%) when compared with controls matched for deconditioning. Intravenous fluid administration in two studies did not affect HR, SV, CO or peak VO
2
. Exercise training in one study (19 subjects) and propranolol 20 mg in another study (11 subjects) led to improving peak VO
2
.

Conclusions:
An exaggerated HR response with standing and with exercise is a hallmark of POTS, a mechanism by which subjects reach a higher HR at lower workloads. While the increase in HR is associated with a reduction in SV, CO is typically maintained and occasionally increased, therefore making it an unlikely mechanism responsible for the peculiar exertional symptoms of POTS. Strategies that result in a reduction in HR may, on the other hand, translate in improved exercise capacity in subjects with POTS.
Abstract 4136182: Usefulness of Lymphocyte-to-Monocyte Ratio in Predicting Late Recurrence of Atrial Fibrillation after Catheter Ablation and its Association With the Type of Atrial Fibrillation
Authors: Tamaki Shunsuke , Kawakami Hiroshi , Fujisawa Tomoki , Miyabe Ryo , Nakao Yasuhisa , Miyazaki Shigehiro , Akazawa Yusuke , Miyoshi Toru , Higaki Akinori , Seike Fumiyasu , Higashi Haruhiko , Nishimura Kazuhisa , Inoue Katsuji , Ikeda Shuntaro , Yamaguchi Osamu
Published: November 2024

Introduction:
Leukocyte activation is reported to be an important inflammatory pathway underlying atrial fibrillation (AF). The lymphocyte-to-monocyte ratio (LMR) is a novel, cost-effective, and widely available marker of inflammation.

Research Questions:
The usefulness of LMR in predicting late recurrence of AF (LRAF) after catheter ablation (CA), and the impact of AF type on its usefulness, have not yet been elucidated.

Goals:
We aimed to elucidate the association between LMR measured just before CA and the risk of LRAF in patients who underwent CA for AF, and to investigate whether the type of AF impacts the predictability of LMR for LRAF.

Methods:
We enrolled 597 consecutive patients with AF (median age, 65 years; 32% female; 334 patients with paroxysmal AF [PAF] and 263 patients with persistent AF [PeAF]) who underwent initial radiofrequency CA. LMR was measured within 3 days prior to the date of CA, and calculated by dividing the absolute lymphocyte count by the absolute monocyte count using the same blood samples. Any detectable atrial tachyarrhythmia lasting for longer than 30 s beyond a 3-month blanking period after the procedure was considered as LRAF. Patients were followed-up for a maximum of 3 years.

Results:
During a median follow-up of 24 months, LRAF occurred in 215 patients (96 with PAF and 119 with PeAF). Although there was no significant difference in LMR between patients with and without LRAF in PAF (5.3 [4.1–6.7] vs 5.2 [4.0–6.6], p=0.403), LMR in patients with LRAF was significantly lower than those without LRAF in PeAF (4.7 [3.9–6.4] vs 5.6 [4.5–6.8], p=0.015). Multivariate Cox analysis showed that LMR was an independent predictor of LRAF in PeAF (p=0.008), but not in PAF (p=0.662). Receiver operating characteristic curve analysis revealed that an LMR of 4.8 was a fair discriminator for LRAF in PeAF. Although there was no significant difference in the risk of LRAF between the patients with lower (LMR<4.8) and higher LMR (LMR≥4.8) in PAF, patients with lower LMR had a significantly higher risk of LRAF than those with higher LMR in PeAF (Figure).

Conclusions:
Pre-ablation LMR was shown to be useful for predicting LRAF in patients with PeAF who underwent CA for AF, while not in patients with PAF.
Abstract 4136202: Incident Hypertension and Survival Outcomes After Immune Checkpoint Inhibitor Initiation
Authors: Balinski Alexander , Royfman Rachel , Patel Prem , Khan Sarah , Wieschhaus Keaton , Kola-Kehinde Onaopepo , Ghazi Sanam , Ferdousi Mussammat , Ruz Patrick , Gatti-Mays Margaret , Adesanya T.M. Ayodele , Addison Daniel
Published: November 2024

Introduction:
Immune checkpoint inhibitors (ICIs) are commonly used as anticancer agents linked with dramatic antitumor response but are associated with cardiotoxicity. Recent isolated reports have suggested ICIs may link with hypertension (HTN) after years of treatment. Yet, the timing and long-term ramifications of this HTN are unknown.

Methods:
From a large cohort of well-phenotyped cancer patients treated with ICIs from 2011-2022, we assessed the incidence of new or worsened HTN [systolic blood pressure (SBP) ≥130 mmHg (or in a higher HTN stage) on two occasions within a three-month period or addition of an antihypertensive medication] after ICI initiation. Secondary endpoints included major cardiovascular events (MACE), defined as symptomatic arrhythmia, myocardial infarction, stroke, heart failure, or cardiac death. Observed incident HTN rates were compared to Framingham-predicted rates, using JNC 8 cutoffs of 140/90 mmHg. Landmark analysis, excluding patients who were observed to have new HTN but had SBPs ≥130 mmHg on two occasions within six-months prior to ICI initiation, identified patients with possible undiagnosed HTN. Multivariable regression and survival analysis were used to define factors associated with new worsened HTN and MACE and the relationship between SBP increase and MACE risk. Further, the effect of standard antihypertensive classes on the prevention of ICI-related HTN will be assessed.

Results:
Overall, from 312 patients treated with ICIs (mean age 63.5 years, 67.4% baseline HTN, 11.0% on dual ICI-therapy), 50.0% (156/312) developed new or worsened HTN over a mean of 27 months follow-up. Cumulative incidence of new HTN by 1-year was 50.0% wherein the mean peak increase in SBP was 12 mmHg. In landmark analysis, excluding those with undiagnosed HTN and applying the JNC 8 cutoff of ≥140/90 mmHg, the observed new HTN rate was 21.4% at 1 year, >2-fold higher than the Framingham-predicted rate of 9.3% (RR 2.3,
P
<0.0001). In those with preexisting HTN, 49% developed worsened HTN. In multivariate analysis, only time on ICI treatment, ECOG status, and autoimmune disease history were associated with new or worsened HTN after ICI-initiation (
P
<0.05 for all). Further, only prior autoimmune disease and ECOG status associated with MACE; while beyond traditional cancer factors, only new or worsening HTN associated with lower mortality.

Conclusions:
Collectively, these data suggest that HTN may be common with ICIs, and prognosticates survival.
Abstract 4136204: Clearing Senescent Cells Improves Mouse Survival Rate Post Myocardial Infarction through Alteration of Cardiomyocyte and Immune Cell Subpopulations
Authors: Mehdizadeh Mozhdeh , leblanc francis , naud patrice , Lettre Guillaume , Thorin Eric , Ferbeyre Gerardo , Nattel Stanley
Published: November 2024

Introduction:
Cellular senescence often involves a p16-pathway, and p16 overexpression is a hallmark of senescent cells. The role of cellular senescence in myocardial infarction (MI) and any mediating mechanisms remain unclear.

Aims:
To investigate the effect of p16
+
cell clearance on survival post MI and elucidate underlying mechanisms.

Methods:
We utilized INK-ATTAC transgenic mice, in which p16
+
cells undergo targeted apoptosis upon exposure to AP20187 (AP). Sham and MI mice were treated with AP or vehicle (V) twice-weekly for one month, starting 3-4 hours post-MI. Survival rate improvement post MI in the AP group (Fig A, P<0.001) prompted us to evaluate effects of senescent cell clearance at the cardiac cellular level and its involvement in MI-associated pathways at 3 days post-MI. The infarct and peri-infarct areas were collected and snap-frozen. Nuclei were extracted with modified gentleMACS methods; libraries were constructed using 10X Genomics. Standard software (CellRanger, Seurat) were employed for single-nuclei-RNA-seq data analysis.

Results:
Cardiomyocytes (CMs) showed 5 distinct subsets. CM subclusters 1 and 2 showed enrichments of genes characteristic of infarct boarder zones, while most sham CMs were found in subcluster 0, reflecting healthy-CMs. AP-treated mice exhibited a higher proportion of healthy CMs (Fig B). Differentially expressed genes (DEGs) between V and AP group were enriched in the healthy CMs, suggesting that clearance of p16
+
cells improves the status of CMs post MI (Fig C). Immune-cell profiling showed that by far the largest number of DEG for AP vs vehicle were expressed in the (arginase-1) Arg1 macrophage subgroup (Fig D). The percentage of Arg1 macrophages decreased in the AP group (FDR=0.059) (Fig E). We noted significant enrichment in the hypoxia and cardiac rupture pathways in Arg1 macrophages (Fig F), correlating with the high death rate from myocardial rupture in V-mice.

Conclusion:
These results suggest a significant role of p16
+
senescent cells in post-MI mortality, potentially through effects on cardiomyocytes and a specific macrophage subpopulation, Arg1 macrophages.
Abstract 4136273: A Machine Learning Approach to Simplify Risk Stratification of Patients with Atherosclerotic Cardiovascular Disease
Authors: Li Hsin Fang , Nute Andrew , Weerasinghe Roshanthi , Wendt Staci , Wilson Eleni , Sidelnikov Eduard , Kathe Niranjan , Swihart Charissa , Jones Laney , Gluckman Ty
Published: November 2024

Introduction:
The 2018 AHA/ACC/Multisociety Blood Cholesterol Guideline recommends that patients with atherosclerotic cardiovascular disease (ASCVD) be classified as very high-risk (VHR) or not very high-risk (NVHR). This designation is based on the presence of
>
2 major ASCVD events (recent acute coronary syndrome [ACS], history of myocardial infarction [MI], history of ischemic stroke, symptomatic peripheral artery disease [PAD]) or 1 major ASCVD event and
>
2 high-risk conditions (age ≥65 years, heterozygous familial hypercholesterolemia, history of coronary revascularization, diabetes, hypertension, chronic kidney disease, current smoking, persistently elevated LDL-cholesterol [LDL-C], history of heart failure). While this approach was initially instituted to better predict future ASCVD events alone, more intensive LDL-C lowering is now recommended for those at VHR (LDL-C treatment threshold of 55 mg/dL for VHR patients vs 70 mg/dL for NVHR patients). We aimed to simplify ASCVD risk stratification in patients with clinical ASCVD using machine learning models.

Methods:
We used electronic health record data (Providence Health system) from 2022 to identify patients with ASCVD based on ICD-10 codes. Patient demographics, comorbidities, and laboratory data stratified patients as VHR or NVHR. Then, a classification and regression tree analysis was performed, with the outcome being VHR classification. Patients were randomly assigned to either the testing or training dataset in equal proportion. Variables in the model included age, sex, race, ethnicity, and the Guideline criteria. Model performance was assessed using misclassification rate and area under the receiver operative curve (AUC).

Results:
A total of 491,514 patients with ASCVD were included, of which 56% were male, 77% were white, and the mean (SD) age was 72.5 (13.0) years. Over half of patients (59%) were VHR. Those with recent ACS, history of MI, history of ischemic stroke, or PAD were classified as VHR 93%, 92%, 84%, and 91%, respectively. Presence of hypertension in these patients increased the likelihood of being VHR to 97%, 97%, 94%, and 98%, respectively. The misclassification rate and AUC for the testing set were 6.8% and 96.2%, respectively.

Conclusions:
Most patients with a major ASCVD event and hypertension were found to be VHR. Relying on these two factors alone can help simplify risk assessment. This approach may also help increase use of guideline-recommended LDL-C lowering therapy.
Abstract 4136277: The Lay Public Misconceives Characteristics of Acute Coronary Syndrome-Related Chest Pain
Authors: Blakeman John , Eckhardt Ann , Kim MyoungJin
Published: November 2024

Introduction:
The most common acute coronary syndrome (ACS) symptom is chest pain. Chest pain is an umbrella term more precisely described using words like pressure or tightness. Previous studies have not explored the lay public’s conceptions of ACS-related chest pain. Misconceptions about chest pain make it difficult for individuals to recognize this symptom if they were to experience it, delaying care seeking.

Research Question:
How does the lay public conceive of ACS-related chest pain?

Methods:
Participants from across the U.S. were recruited in May and June 2023. Participants completed an online survey including the Chest Pain Conception Questionnaire. Descriptive statistics were used to characterize conceptions of chest pain quality, timing, intensity, and distress. Conceptions of men and women were compared using the independent-samples
t
-test and Chi-square test.

Results:
Participants (n=597) were mostly women (n=355; 59.5%) with a mean age of 54.0 years (SD = 11.5). The sample was diverse: White (n=414, 69.2%), Black (n=101; 16.9%), Hispanic or Latina/o/e/x (n=96; 16.1%), and Asian (n=67; 11.2%). Participants often thought of pressure (78.9%), tightness (77.4%), squeezing (75.5%), gripping (72.9%), and heaviness (72.5%) as possible descriptors of ACS-related chest pain. They less often thought of discomfort (48.7%), fullness (16.8%), and indigestion (13.4%). Participants expected ACS-related chest pain to be “intense” and to bother them “a lot,” both with median scores of 4.0 on a 5-point Likert scale. Participants felt that ACS-related chest pain would “often” (median 4.0) occur with activity and “sometimes” (median 3.0) occur at rest. Women were more likely to rate specific descriptors of chest pain (i.e., pressure, tightness) and general descriptors of chest pain (i.e., discomfort, pain) as more likely ACS-related chest pain descriptors than men, (all
ps
≤ .05). Women (n=58; 16.3%) were about twice as likely as men (n=22; 9.2%) to endorse indigestion as a possible descriptor of ACS-related chest pain, (
p
= .013, OR = 0.52 [95% CI = 0.31-0.87]).

Conclusions:
As many as 1 in 5 participants did not endorse common descriptors such as pressure and tightness as potentially characterizing ACS-related chest pain. Most believed this symptom would be intense and bother them a lot. They also more often associated ACS-related chest pain with activity than with rest. Clinical and research interventions can target the misconceptions identified in this study.
Abstract 4136286: Safety Events with a Large-Bore Aspiration Thrombectomy Device for Pulmonary Embolism: An analysis of the U.S. Food and Drug Administration Manufacturer and User Facility Device Experiences from 2018 to 2024
Authors: Lee Shannon , Schwarzman Logan , Megowan Nichelle , THOMAS JOSEPH
Published: November 2024

Introduction:
Large bore thrombectomy is increasingly used to treat acute PE. Post-market surveillance using the U.S. FDA Manufacturer and User Facility Device Experience (MAUDE) database may capture serious device adverse events (AE) not described in small pre-market clinical trials. We aim to analyze serious AE associated with use of the Inari Medical (Irvine, California) large bore thrombectomy system to treat PE.

Methods:
All MAUDE events between January 1, 2018 and May 1, 2024 involving PE treatment with Triever and Flowtriever devices were reviewed and categorized based on device type, incident year, and clinical event. Based on narrative description, AE were placed into categories of cardiac, pulmonary, device malfunction, anemia, and other.

Results:
A total of 58 AE reports representing 50 unique clinical episodes were included. MAUDE event types were death (n=32), injury (n=23) and malfunction (n=3), and the majority (45/58) involved the larger aspiration catheters (Table 1). Death occurred in 27 of 50 unique episodes. Cardiac injury (n=19) and pulmonary injury (n=18) were most common and included 25 serious perforations. Serious AEs are listed in Table 2. Device malfunction/improper use was rare (n=7) and was not associated with death. Paradoxical embolism was described causing stroke and coronary occlusion. 3 of 4 blood loss AEs occurred prior to 2021.

Conclusion:
This report includes the largest description of reported AEs with large bore aspiration thrombectomy systems used to treat PE. This report describes serious events, often associated with death, that are likely infrequent and were not detected in pivotal studies or registries. Understanding these AEs may guide future technique and device refinement, and the current findings demonstrate the importance of large post-approval studies.
Abstract 4136330: It’s ‘Tachy’ To Be Fooled - Adenosine Use During Leadless Pacemaker Placement to Ensure Reliable Threshold Assessment in the Setting of Tachycardia
Authors: Arvind Shreya , Kolluri Madhumita , Palle Sindhuja , Moskowitz Craig
Published: November 2024

Introduction:
Accurate assessment of pacing thresholds during permanent pacemaker implantation is critical to ensure device function and longevity. A few reports have described rate-related threshold variability during Micra
TM
leadless pacemaker (Medtronic Inc, Minneapolis, MN) procedures. Postulated mechanisms for this phenomenon include variable myocardial contact or micro-dislodgment, and inflammation-induced phase IV block. In this case series, we demonstrate the use of adenosine to induce transient heart block for accurate threshold assessment in patients with tachycardia during leadless pacemaker placement.

Cases:
A 69-year-old male with a history of atrial flutter presented with complete atrioventricular (AV) block requiring emergent transvenous pacing. A Micra placement was performed. During the procedure, the patient was tachycardic in rapid atrial flutter despite multiple doses of metoprolol. It was noted that with rapid pacing from the pacemaker at 120 pulses per minute (ppm) the threshold was ≤1V at 0.24 ms. An adequate “tug-test” was performed and at least 2 of 4 tines were noted to be fixated based on fluoroscopic motion. To confirm the capture threshold before final deployment, 12 mg of adenosine was given to induce heart block. However, at a rate of 60 ppm, there was no ventricular capture at 3V at 0.24ms. The device was repositioned and repeat threshold testing with adenosine at 60 ppm was 0.38V at 0.24ms. Pacing parameters were assessed the next day and remained stable.

Similarly, a 75-year-old female with ischemic cardiomyopathy was admitted with new atrial fibrillation (AF). She then developed pauses prompting Micra placement. During initial threshold testing, she was in rapid AF despite receiving multiple doses of metoprolol. Heart block was induced with 12mg adenosine to assess the threshold at a lower pacing rate of 60 ppm. The capture threshold achieved was 0.5V at 0.24ms.

Discussion:
Nusbickel et al., Yoshiyama et al., and Sano et al. have reported rate dependent discrepancies in capture thresholds after Micra implantation. Our cases highlight the importance of capture threshold assessment at lower pacing rates during implantation. In patients who are tachycardic at the time of the procedure, adenosine may be useful to more reliably assess device capture threshold and determine the need for repositioning.
Abstract 4136358: Diagnostic accuracy of Apple Watch Electrocardiogram for Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Shahid Sufyan , Iqbal Minahil , Saeed Humza , Hira Sara , Batool Amna , Goyal Aman
Published: November 2024

Background:
Electrocardiography (ECG) stands as the gold standard for the evaluation of cardiac arrhythmias. Recent smartwatches aim to promptly detect rhythm abnormalities enhancing user experience. However, the accuracy of these devices remains controversial. Our purpose was to perform a systematic review and meta-analysis evaluating the diagnostic performance of the Apple Watch electrocardiogram in detecting atrial fibrillation (AF).

Methods:
The literature search was conducted on PubMed, Embase, and Cochrane through April, 2024 for studies comparing the diagnostic accuracy of Apple Watch to standard 12 Lead ECG. Statistical analysis was performed using R Software version 4.4.0. Pooled analyses of sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were determined along with their 95% confidence intervals (CI). The quality of studies was analyzed using the QUADAS-2 tool.

Results:
The meta-analysis included 11 studies comprising 13,490 participants. Their mean age was 62.56 ± 3.92 years and 28% of the population were females. The pooled sensitivity and specificity of Apple Watch for detecting AF was 94.8% (95% CI 91.7 - 96.8%) and 95% (95% CI 88.6 - 97.8%) respectively. The AUC was 0.96 (95% CI 0.92 - 0.97; Figure 1). Sensitivity analysis for heterogeneity revealed no significant change in values for sensitivity 94.8% (95% CI 91.7-96.8%) and specificity 94.9% (95% CI 88.6-97.8%). The studies had a low risk of bias in Index test and reference standard domains, but a high risk of bias in patient selection and Flow and timing domains.

Conclusion:
The Apple Watch ECG shows a high accuracy in detecting atrial fibrillation, providing a convenient and timely option for such patients.
Abstract 4136398: Gender Disparities Absent in Citation Metrics and Online Attention Across Thoracic Surgery Publications
Authors: Sato Alyssa , Karlsberg Ronald , Quesada Carlos
Published: November 2024

Introduction:
A recent study by Women As One highlighted the prevalence of “MANuscripts” (publications authored solely by men) and their potential impact on equity in academic promotions within cardiology. The study revealed notable differences in citation rates and online attention between publications in cardiology journals led by male and female authors. To further explore these disparities, we examined publications in prominent thoracic surgery journals.

Hypothesis:
Thoracic surgery publications where women hold key authorship roles (primary and senior) receive lower citations and online attention compared to those with men as leading authors.

Methods:
We analyzed data from peer-reviewed publications in 2019 from two high-impact thoracic surgery journals: The Annals of Thoracic Surgery and The Journal of Thoracic and Cardiovascular Surgery. Citation metrics and Altmetric Attention Scores (AAS) were sourced from Google Scholar paired with the Altmetric Google Chrome extension. Citation rates, AAS, and names of primary and senior authors were manually collected between September 22, 2023 and December 21, 2023. The genders of key authors were determined using Genderize, a gender-determination software, supplemented by manual searches for authors not detected by the software. A minimal number of publications were excluded if either their AAS or citation metrics were unavailable. Significant differences in the data were analyzed using one-sided Mann-Whitney U-tests.

Results:
Of the 1,482 authors included in the analysis, 18.4% were females in primary or senior roles. Our analysis found no significant differences in citation rates or AAS between male and female primary authors (p=0.09 and p=0.31, respectively), or between male and female senior authors (p=0.48 and p=0.38, respectively). Furthermore, after combining the data of male primary and senior authors and comparing it to the combined data of female primary and senior authors, no significant discrepancies were found for both citations (p=0.13) and AAS (p=0.28).

Conclusion:
Contrary to analyses of cardiology journals, our data from thoracic surgery articles does not indicate a gender disparity between male and female authors in terms of citations and online attention. While this does not definitively rule out the presence of inequity in thoracic surgery research, it suggests that male-authored manuscripts may not be a primary source of gender disparity in this field.
Abstract 4136412: Quantitative Cardiac Magnetic Resonance Standardized Signal Intensity Comparison in Dilated Cardiomyopathy versus Cardiac Sarcoidosis
Authors: Liao Ting-Wei Ernie , Xu Lingyu , Khoshknab MirMilad , Mather Paul , Bravo Paco , Desjardins Benoit , Nazarian Saman
Published: November 2024

Introduction/Background:
Dilated cardiomyopathy (DCM) and cardiac sarcoidosis (CS) manifest unique late gadolinium enhancement (LGE) patterns on cardiac magnetic resonance (CMR), indicative of differing distributions of myocardial scar tissue. Nevertheless, these LGE patterns lack specificity, leading to significant overlap between the two conditions.

Goals/Aims:
This study seeks to introduce a novel quantitative method employing z-score analysis of LGE-CMR signal intensity to objectively evaluate and compare the spatial distribution of LGE intensity between DCM and CS.

Methods/Approach:
The retrospective cohort included 22 NICM patients (13 DCM, 9 CS) that underwent pre-procedural CMR prior to ventricular tachycardia (VT) ablation between November 2018 to May 2023. LGE images were delineated into sub-endocardial, mid-myocardial, and sub-epicardial layers, categorized into anterior, lateral, inferior, and septal walls based on the AHA 17 segment model for LV myocardial segmentation. CMR signal intensities were standardized as z-scores: z = (x−μ)/σ, where x is the MRI signal intensity for a specific myocardial segment and layer, and μ and σ are the mean and standard deviation across all myocardial segments and layers of the LV, to characterize regional intensity variations.

Results/Data:
Compared to patients with DCM, those with CS exhibited significantly higher CMR signal intensity z-scores in the septum (β=0.32, p=0.009), particularly in the endocardial third of the right ventricular side (β=0.56, p=0.001). A z-score greater than 0.40 in this area was associated with a CS diagnosis, with an area under the ROC curve of 0.692 in 5-fold cross-validation.

Conclusions:
Patients with CS exhibit higher affinity for contrast in the septum, particularly on the RV endocardium. Standardized analysis of CMR signal intensities provides a novel, quantitative method for distinguishing CS from DCM, with the former exhibiting higher CMR signal intensity z-scores in the septum.
Abstract 4136442: Efficacy and Safety of Paclitaxel-coated balloons versus Uncoated balloons in the Management of Coronary in-stent restenosis: a Meta Analysis of Randomized Controlled Trials
Authors: Najeeb Hala , Malik Javeria , Christina Carol , Aquil Sakina , Aamir Muhammad , Aslam Mutiba , Rasheed Ayesha , Khalid Muhammad , Butt Malaika , Gul Wajiha , Kashif Hamna , Nasir Beena Muntaha , Moeed Abdul , Alam Mahboob , Bennett Courtney
Published: November 2024

Introduction:
Coronary in-stent restenosis (ISR) remains challenging despite stent technology advancements. Paclitaxel-coated balloons (PCB) offer a promising non-implant approach to deliver antiproliferative agents directly to the vessel wall. This meta-analysis aims to evaluate the comparative effectiveness of PCB versus uncoated balloons (UCB) in managing coronary ISR to address emerging safety concerns.

Methodology:
Medline, Scopus and Embase were searched until April 2024 for randomized controlled trials (RCTs) comparing PCB versus UCB in patients undergoing coronary ISR. Primary outcomes were in-segment late lumen loss (LLL), binary restenosis, target lesion revascularization (TLR), major adverse cardiac events (MACE), and mortality. Secondary outcomes included in-stent LLL, in-stent binary restenosis, myocardial infarction (MI), cardiac death, target vessel MI, and target vessel revascularization (TVR).

Results:
This meta-analysis includes seven RCTs with 1,408 patients (PCB = 864, UCB = 544). PCB significantly reduced in-segment LLL (MD= -0.50, 95% CI [-0.67, -0.33]; P < 0.00001), in-segment binary restenosis (RR= 0.25, 95% CI [0.14, 0.45]; P < 0.00001), target lesion revascularization (RR= 0.43, 95% CI [0.32, 0.58]; P < 0.00001), mortality (RR=0.56, 95% CI [0.39, 0.80]; P=0.001), and MACE (RR= 0.36, 95% CI [0.25, 0.51]; P < 0.00001). PCB also significantly decreased in-stent LLL (MD= -0.52, 95% CI [-0.72, -0.32]; P < 0.00001), in-stent binary restenosis (RR = 0.19, 95% CI [0.11, 0.35]; P < 0.00001), and TVR (RR = 0.45, 95% CI [0.29, 0.70]; P = 0.0003). PCB showed a short-term reduction in MACE and target lesion revascularization at 6 months, 1 year and 3 years of followup. No difference was observed in MI, cardiac death, or target vessel MI.

Conclusion:
In patients with coronary ISR, PCB are associated with reduced in-segment LLL, in-segment binary restenosis events, target lesion revascularization, mortality, MACE, in-stent LLL, in-stent binary restenosis and target vessel revascularization.
Abstract 4136459: Machine Learning in Time-to-Event Prediction of Ventricular Arrhythmias among Older Adults with Type 2 Diabetes and Coronary Artery Disease
Authors: Jeon Yein , Payne Thomas
Published: November 2024

Introduction:
Patients with Type 2 diabetes mellitus (T2DM) have an increased risk for coronary artery disease (CAD) compared to patients without T2DM. Ventricular arrhythmias (VA), such as ventricular fibrillation and ventricular tachycardia, are the major causes of mortality among patients with CAD. Thus, T2DM patients with CAD, especially older adults, have a higher risk of VA compared to patients without T2DM. The time-to-event prediction can contribute to decreasing mortality due to VA in older adults with T2DM and CAD by providing an estimated time and probability of diagnosis at specific time points. However, the limited number of older T2DM patients with CAD, who are diagnosed with ventricular arrhythmias, lowers the performance of a traditional time-to-event analysis model.

Hypothesis:
We hypothesize that machine learning can improve performance in time-to-event prediction.

Methods:
This study includes 3975 participants aged >65 years, diagnosed with T2DM and CAD in the All of US database. The baseline time was the earliest date when the patients were older than 65 years and diagnosed with T2DM and CAD. Of all participants, 379 were diagnosed with VA within 5 years from baseline. We compared the machine learning–based time-to-event analysis models to the Cox Proportional Hazards model to explore the potential of machine learning in time-to-event analysis. Additionally, the Synthetic Minority Oversampling Technique was applied to resolve the imbalanced data issue. The model performance was evaluated based on the concordance index, which calculates the correlation between predicted risk scores and actual observations, after 5-fold cross-validation.

Results:
The average concordance index of the Gradient Boosting Machines model was the highest among the five models, including the Cox Proportional Hazards model, with balanced data (Table).

Conclusion:
We identified that machine learning could improve the performance of prediction models in time-to-event analysis. The Synthetic Minority Oversampling Technique could mitigate the issue of imbalanced data. In addition, machine learning-based survival models showed higher concordance index values compared to the Cox Proportional Hazards model.
Abstract 4136463: Novel Systemic Inflammatory Biomarkers Can Predict Significant Coronary Disease in High Risk Patients
Authors: Bani Hani Dania , Alshraideh Jafar , Alduraidi Hamzah , Al-Zaiti Salah
Published: November 2024

Background:
Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Chronic inflammation is a known risk factor for atherosclerosis, plaque formation, disease progression, and plaque instability. Novel inflammatory biomarkers have been recently linked to excess risk of adverse cardiovascular events, including incident myocardial infarction. Elevated inflammatory biomarkers may help identify patients at higher risk for severe CAD.

Aim:
This study aimed to evaluate the use of novel systemic inflammatory markers in predicting the pretest probability of severe CAD in patients referred to diagnostic coronary angiography in a single tertiary care center.

Methods:
This was a prospective observational cohort study enrolling consecutive patients referred to diagnostic coronary angiography in a tertiary care center. Preprocedural laboratory results were obtained from medical charts, including complete blood counts with differentials. Three novel systemic inflammatory markers were computed using existing mathematical formulas: systemic immune-inflammation index (SII = neutrophil count*platelet/lymphocyte); systemic inflammation response index (SIRI = neutrophil*monocyte/lymphocyte); and systemic immune inflammatory response index (SIIRI = neutrophil*monocyte*platelet/lymphocyte). The primary study outcome was severe CAD defined as the presence of ≥70% stenosis in one of three main coronary arteries requiring percutaneous coronary intervention). The outcome was adjudicated by an independent reviewers blinded to computations of biomarkers.

Result:
The sample included 264 patients (age 59.3±10.8, 47% Females). Overall, 84 patients (32%) met the primary study outcomes. In univariate analysis, those with severe CAD had significantly higher SIRI (2.9±0.7 vs. 2.6±0.6, p = 0.001) and SIIRI (8.4±0.8 vs. 8.1±0.7, p = 0.015) compared to their counterparts. In multivariate analysis adjusted for age and sex, only SIRI was an independent predictor of severe CAD. Using SIRI > 20.8 (upper quartile) was associated with nearly three-fold excess risk of severe CAD (OR = 2.72, 95% CI 1.45-5.09).

Conclusion:
Elevated SIRI, a marker of ongoing systemic inflammatory response, could be indicative of severe CAD. As an inexpensive biomarker based exclusively on complete blood count, SIRI can be used to prioritize patients referred for diagnostic angiography and potentially expedite treatments in those at higher risk for coronary events.
Abstract 4136480: A Rare Cause of a Classic Presentation of NSTEMI: Case of 39-Year-Old Female with Hypothyroidism Induced Myocarditis
Authors: Quadri Fayz , Qazi Mariam , Teague Taylor
Published: November 2024

Background:
Myocarditis is a cause of non-ischemic cardiomyopathy (NICM) and troponin elevation. There are many causes including uncontrolled thyroid disorder (TD). A thorough history, cardiac MRI (cMRI) followed by an endomyocardial biopsy (EMB) is necessary for diagnosis. This case illustrates a classic presentation of NSTEMI with a rare cause of myocarditis due to uncontrolled hypothyroidism.

Description of Case:
A 39-year-old female with history of congenital hypothyroidism and tobacco use disorder presented to the Emergency Department with sudden onset of unprovoked sub-sternal chest pain. She stated she had stopped taking her levothyroxine years ago due to side effects such as abdominal discomfort. On admission, work up included high sensitivity troponin (Hs-cTn), EKG, urine drug screen (UDS), and thyroid panel. There was no evidence of ischemic changes on EKG, Hs-cTn was 3600 (normal: 3-54) which up-trended to 43,742, and UDS was negative. She was placed on appropriate medical therapy for NSTEMI and taken for urgent coronary angiography wbich showed normal epicardial arteries. A transthoracic echocardiogram (TTE) was unremarkable with a normal ejection fraction (EF). However, she continued to complain of chest discomfort and palpitations. Her vital signs remained stable but her thyroid panel revealed a TSH of 127 (normal: 0.27-4.2), T4 of 0.18 (normal: 0.92 – 1.6) and T3 of 1.0 (normal: 2.3-4.2). Inflammatory markers were also elevated. A cMRI was obtained revealing gadolinium enhancement in the anterior septal wall with extension into the subepicardium of the inferior wall suggestive of possible myocarditis. An EMB was performed to elucidate etiology. Pathology results were only remarkable for edema but newly reduced EF of 30-35% was noted on TTE at time of biopsy. Endocrinology was consulted for untreated hypothyroidism and patient was initiated on levothyroxine leading to improvement of her symptoms.

Discussion:
Our patient's history and work up were consistent with myocarditis induced by severe hypothyroidism. TD is a rare cause of reversible NICM and symptoms improve once TD is controlled. While there are several cases reported on hyperthyroidism associated myocarditis, there are only a few cases of myocarditis associated with uncontrolled hypothyroidism. Clinicians should maintain a broad differential to ensure a thorough work up in a patient presenting with NSTEMI, and a thyroid panel should be included especially if myocarditis is suspected.