bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4140255: DIAGNOSIS TO RECOVERY: PSYCHOLOGICAL DISTRESS IN PULMONARY EMBOLISM
Authors: Rajasekar Bhairavi , Hurley Karen , Cameron Scott , Tefera Leben
Published: November 2024

Pulmonary embolism (PE) is the third leading cause of cardiovascular death. It has been shown to be accompanied by significant psychological distress. The prevalence and longitudinal trends of anxiety and depression in PE patients largely remains unknown. We conducted a prospective observational study examining 188 PE patients attending a dedicated Pulmonary Embolism Response Team (PERT) Clinic. Participants completed standardized assessments using the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire (PHQ-9) to measure anxiety and depression, respectively, following their PE diagnosis and ensuing treatment. Our findings revealed noteworthy gender disparities in the psychological impact of PE on survivors. Among women, 41% reported anxiety and 44% reported depression. Among men, 17% reported anxiety and 20% reported depression. Women more likely to experience depression post-PE and were twice as likely than men to experience anxiety. Furthermore, regardless of gender, we observed a decrease in the prevalence of anxiety and depression over time from the date of initial diagnosis. Younger patients exhibited higher levels of anxiety and depression compared to older counterparts. Additionally, patients with recurrent PE had higher levels of anxiety and depression compared to those with a single thrombotic episode. This study represents the largest dedicated prospective study to date to examine the psychological impact of PE on patients' psyche. It underscores the significant psychological toll of PE on patients' recovery. We noted women experienced higher rates of anxiety and depression compared to men. Younger patients and those were recurrent PE were more likely to experience psychological distress. Regardless of age and sex, the prevalence of anxiety and depression decreased with time. These findings highlight the importance of tailored psychosocial support strategies to address the unique emotional needs of patients following a PE diagnosis. Disparities in anxiety and depression prevalence following PE diagnosis and treatment exist. This study highlights the importance of implementing tailored psychosocial support strategies to address the unique emotional needs of PE patients, particularly among women, younger patients, and those with recurrent PE.
Abstract 4140257:
CDCP1
’s Role in Cardiac Fibrosis: Unveiling Potential Mechanisms in a Pressure Over-Load Mouse Model
Authors: Wang Li , Wang Min , Vyas Hridyanshu , Roos Carolyn , Huang Runqing , Liu Duan , Ghazal Rachad , Lambert Laura , Weinshilboum Richard , Miller Jordan , Pereira Naveen
Published: November 2024

Background:
CDCP1
has been associated with reverse remodeling in human dilated cardiomyopathy (DCM) mediating its effect by reducing cardiac fibrosis which has been demonstrated in-vitro using human cardiac fibroblasts (CF) and in-vivo histologically in mice. However, the role of and the molecular mechanisms by which
CDCP1
attenuates cardiac fibrosis in-vivo is unknown.

Methods:
To characterize the transcriptomic profiles of
CDCP1
in cardiac fibrosis,
Cdcp1
KO FVB/NJ mice were generated, and implanted with osmotic minipumps containing angiotensin II and phenylephrine (Ang II/PE) or saline at age of 10 weeks. There were 4 experimental groups (6 mice each), Saline_WT, Saline_KO, AngII/PE_WT, and AngII/PE_KO. After 4 weeks of AngII/PE induction, mice were euthanized, RNA was extracted from their heart tissue followed by RNA-seq to explore transcriptomic profiles. Fibrosis was histologically determined using picosirius (PSR) staining and was quantified by percentage of fibrosis area.

Results:
Histological analysis demonstrated that
Cdcp1
KO attenuated severe cardiac fibrosis by 32.7% determined by quantification of percentage of fibrosis area. When comparing the transcriptome-wide gene expression in WT mice hearts from Saline to AngII/PE induction, a total of 316 differentially expressed genes (DEGs) were identified (
Fig. 1A
). Expression of
Nppb
(encodes ProBNP), a marker for heart failure, was significantly upregulated. The most significantly upregulated DEG after AngII/PE induction was
Crlf1
(
Fig. 1A
), a gene predominantly expressed in CF, consistent with previous findings. We next compared transcriptomic profiles of AngII/PE induction WT and
Cdcp1
KO mice hearts, to explore the role of CDCP1 in cardiac fibrosis. A total of 163 DEGs were identified (
Fig. 1B
). Notably,
Cdcp1
-mediated DEGs enriched GO Pathways associated with extracellular matrix organization (Biological Process) and collagen-containing extracellular matrix (Cellular Component) (
Figs. 1C, 1D
), pivotal processes in cardiac fibrosis. In addition,
Cdcp1
KO resulted in several “top” DEGs (including
Rnase1, Ccl7, Ccl12 Il21r
, and
Il6
) which have known function in inflammation, suggesting that
CDCP1
might attenuate cardiac fibrosis through immune regulation .

Conclusion:
Our findings underscore the pivotal role of
CDCP1
in modulating cardiac fibrosis in-vivo, potentially through immune regulation. Targeting
CDCP1
may offer promising therapeutic avenues for mitigating myocardial fibrosis.
Abstract 4140272: Prevalence, Clinical Correlates, and Outcomes of Tricuspid Regurgitation Among Older Adults: The Atherosclerosis Risk in Communities Study
Authors: Kharidia Khush , Giugni Fernando , Lamberson Victoria , Yang Yimin , Claggett Brian , Van't Hof Jeremy , Wagenknecht Lynne , Mosley Thomas , Skali Hicham , Shah Amil
Published: November 2024

Introduction:
Tricuspid regurgitation (TR) prevalence increases with age and is associated with higher mortality. Limited data exist regarding the prognostic relevance of TR among older adults in the general population.

Objective:
To estimate the prevalence of TR in late life, identify cardiac structural and functional measures associated with TR severity, and determine the prognostic relevance of TR severity.

Methods:
In the community-based Atherosclerosis Risk in Communities (ARIC) study, 3,046 participants underwent protocol echocardiography at the 7
th
study visit (2018-2019). TR severity was assessed qualitatively as none/trace, mild, moderate, or severe by a board-certified cardiologist. Dyspnea was assessed using the modified Medical Research Council questionnaire and post-Visit 7 mortality was ascertained through the National Death Index. Cross-sectional associations of TR severity with clinical characteristics, echocardiographic measures, and dyspnea were assessed using multivariable linear and logistic regression models. Associations with death were assessed using Cox proportional hazard models adjusted for demographics.

Results:
Mean age was 81±4 years, 58% were women, 25% reported Black race, and mean LVEF was 63±8%. TR prevalence was 30% mild, 9% moderate, and 1% severe. Greater TR severity was associated with older age, female sex, higher HF prevalence, and loop diuretic use. Greater TR severity was also associated with lower LVEF, worse LV diastolic function (higher LAVi, E/A, E/e’ septal), higher NT-proBNP, higher prevalence of moderate-severe mitral regurgitation, greater pulmonary artery systolic pressure, and larger RV size. Severe TR was associated with higher odds of moderate-severe dyspnea (OR:2.3 [1.2-4.5], p=0.012). During follow-up (median 2.1 years [IQR 1.7-2.5]), 192 participants died. Higher TR severity was associated with greater mortality (Figure). Compared to participants with none/trace TR, even mild TR was associated with a 64% greater mortality risk.

Conclusion:
TR is common in late life and is associated with greater left heart disease despite generally preserved LVEF. Greater TR severity, even when mild, is a marker of increased mortality. Longer follow-up is needed to determine whether this risk is independent of concomitant left heart dysfunction.
Abstract 4140276: Safety, Efficacy and Cardiovascular Benefits of Combination Therapy with Sodium-Glucose Co-Transporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists in Patients with Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Mousavi Asma , Shojaei Shayan , Soleimani Hamidreza , Semirani-Nezhad Davood , Ebrahimi Pouya , Zafari Ali , Ebrahimi Rasoul , Roozbehi Khatere , Harrison Anil , Syed Mushabbar , Kampaktsis Polydoros , Kuno Toshiki , Heffron Sean , Samsky Marc , Khorsand Askari Mani , Hosseini Kaveh
Published: November 2024

Background:
The potential benefits and risks of combination sodium-glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) therapy versus (vs.) monotherapy, remain a subject of debate to reduce metabolic and cardiovascular outcomes in patients with diabetes mellitus. This study aims to systematically review and meta-analyze the available evidence from randomized controlled trials (RCTs).

Methods:
A comprehensive search identified relevant RCTs comparing combination therapy with SGLT-2i and GLP-1RA to monotherapy or placebo. The primary outcome was the incidence of major adverse cardiovascular events (MACE) (all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, and hospitalization for heart failure (hHF)). Secondary outcomes included changes in metabolic parameters and adverse events. Random-effects meta-analysis estimated risk ratios, mean difference, and 95% confidence intervals (CI).

Results:
The meta-analysis included 11 RCTs with 42,851 participants, of which 2,870 on combination therapy, and the rest on SGLT-2i (37.1%), GLP-1RA (20.1%) monotherapies or placebo (42.8%). Combination therapy had a significantly lower risk of MACE vs. GLP-1RA monotherapy (RR=0.81, 95% CI 0.65;1.00) and placebo (RR=0.73, 95% CI 0.61;0.88). Combination therapy also had a lower risk of hHF vs. GLP-1RA, SGLT-2, and placebo monotherapies (RR=0.37, 95% CI 0.22;0.65), (RR=0.37, 95% CI 0.19;0.75), and (RR=0.43, 95% CI 0.24;0.75), respectively. Combination therapy was showed greater weight loss and HbA1c reduction vs. SGLT-2i monotherapy (MD=-2.03, 95% CI -2.85;-1.21 and MD=-0.74, 95% CI -1.21;-0.27), respectively, while no difference vs. GLP-1RA monotherapy. Incidence of nausea and diarrhea was higher with combination therapy vs. SGLT-2i monotherapy (MD=3.34, 95% CI 1.74;6.43 and MD=1.75, 95% CI 1.10;2.77), respectively.

Conclusion:
Combination SGLT-2i and GLP-1RA therapy may provide superior cardiovascular, weight, and HbA1c outcomes vs. monotherapy, despite higher gastrointestinal adverse events. These results impact the management of patients with metabolic and cardiovascular diseases, and highlighting the need for further research to optimize combination therapy.
Abstract 4140290: Long Term Remote Patient Monitoring Reduces Blood Pressure in Patients with Stage II Hypertension
Authors: Subramanian Ajan , Huang Yong , Nagesh Nitish , Wang Li , Liu Zhiyu , Hou Weiyi , Azimi Iman , Stafford Randall , Rahmani Amir
Published: November 2024

Background:
We evaluated the efficacy of a digital health program integrating self-measured blood pressure (BP) monitoring and lifestyle coaching in managing hypertension (HTN). Conducted from 2019 to 2022 across 39 healthcare facilities in 10 US states, using Bluetooth-enabled devices, mobile apps, and a care coordination platform, longitudinal BP data was collected.

Methods:
Linear mixed models with patient-specific random intercepts assessed within-subject BP changes. Causal modeling evaluated BP improvement by adherence level, measured by the regularity and frequency of BP measurements in the first 6 months, adjusting for covariates including age, gender, BMI, and medication compliance. To assess the patient adherence to the impact on BP outcomes in the long term we also analyzed those with data at baseline and endpoints from 6 to 24 months.

Results:
We analyzed 5520 patients with baseline HTN II (SBP/DBP: 152.6 ± 12.7 / 87.6 ± 10.5 mmHg, mean± SD), 51.3% female, 43.3% in 65-80yr and 34.9% in 46-65yr. BP change at 6 months was -12.5 ± 16.9 / -6.9 ± 10.0 (N = 4171, p<0.001); at 12 months, -13.1 ± 17.3 / -7.5 ± 10.0 (N = 2625, p<0.001); and at 24 months, -14.1 ± 17.8 / -8.0 ± 10.4 (N = 1424, p<0.001). Regression analysis accounting for covariates showed steep initial reductions (-0.4 mmHg/week, p<0.001 for 0-6 months) with continued reductions of diminished magnitude with further follow-up (-0.07 mmHg/week, p<0.001 for 7-24 months). Causal modeling demonstrated that higher program adherence was linked to significantly greater reductions in SBP. Those with the highest adherence had greater reductions in SBP vs. those with the lowest adherence at both 6 months (-16.3 vs. -6.1, p<0.001) and 24 months (-17.1 vs. -11.4, p<0.001). Patients in the lowest adherence group (N = 1145, 3.7 ± 2.3 BP measurements/week with 3.0 weeks of gap between measurement weeks) also showed significant reductions in BP with 24.0% and 41.4% controlled (<140/90 mmHg) at 6 and 24 months respectively.

Conclusions:
The digital BP monitoring program significantly improved self-measured BP control in HTN stage II patients. Causal modeling showed that longer-term remote monitoring was linked to greater reductions in BP. Greater adherence to self-measurement led to greater reductions in BP, while the minimal adherence group also showed significant improvement, underscoring the program's effectiveness in long-term cardiovascular health management in a population with diverse engagement levels.
Abstract 4140323: Barriers and Facilitators to Outpatient Cardiac Rehabilitation Attendance Among Patients with Low Socioeconomic Status: A Qualitative Study
Authors: Mathews Lena , Okonkwo Miriam Chiamaka , Tolefree Tionna , Stewart Kerry , Benz Scott Lisa , Cooper Lisa , Ndumele Chiadi , Matsushita Kunihiro , RIEKERT KRISTIN
Published: November 2024

Introduction:
Individuals with low socioeconomic status (SES) have a higher risk of CVD events yet are less likely to utilize outpatient cardiac rehabilitation (OCR), which is an evidence-based secondary prevention strategy. Understanding barriers and facilitators to the implementation of OCR among individuals with low SES is critical to design targeted interventions to improve attendance.

Aims:
To identify barriers and facilitators to OCR attendance among individuals with low SES using the Capability, Opportunity, Motivation, and Behavior (COM-B) theoretical model.

Methods:
We purposefully recruited patients for in-depth interviews who had: a recent CVD event (≤ 3 months); documented referral to OCR; low SES (Medicaid eligible, or in the top quartile of area deprivation index); those who attended ≥ 1 session of OCR and those who did not. Semi-structured interviews were recorded and transcribed verbatim. Codes were identified using a phenomenological approach guided by the COM-B model.

Results:
Participants (N=26) were 54% women, 58% Black, with mean age of 67.1 (12.7 years). Barriers and facilitators identified fit the COM-B model.
Capability
themes included knowledge and awareness of OCR. OCR attendees (n=12) recalled discussing OCR, the benefits, and their physicians encouraging participation pre-discharge. Non-attendees (N=14) reported no, or very little knowledge about OCR, or weak recommendations by their physician.
Opportunity
themes included social support from caregivers/family, peers, and their healthcare team. OCR attendees described a strong support network of caregivers who helped with logistics and motivation to participate, wanting to be with peers, and outreach of the healthcare team after discharge. Non-attendees described lack of social support, logistical barriers, and no outreach.
Motivation
themes reflected the strong belief in the benefits of CR to improve physical and mental health, quality of life, and prevent future events among attendees. Non-attendees generally lacked a perceived need for OCR particularly if they had returned to baseline after their CVD event.

Conclusions:
Non-attenders of CR were distinguishable from attendees using the COM-B model, which can be used to guide intervention development. Our findings support a multi-level strategy that includes tailored education, social support, motivational enhancement, implemented by a trained health navigator, to overcome barriers to CR attendance among patients with low SES.
Abstract 4140337: Resting Heart Rate and Chronotropic Incompetence are Linked
Authors: Li Anita , Samuels Summer , Meyer Markus
Published: November 2024

Background:
Cardiac output reserve and exercise capacity are strong predictors of life expectancy. Chronotropic incompetence (CI) is the inability to reach an age appropriate maximum heart rate with exercise. CI reduces cardiac output reserve and exercise capacity, both of which increase all-cause mortality risk. Sinus node dysfunction may manifest as CI and abnormally low resting heart rate (RHR). The relationship between low RHR and CI has yet to be described.

Purpose:
We hypothesize that resting sinus bradycardia (low RHR) could be a predictor of chronotropic incompetence and reduced exercise capacity.

Methods:
The derivation cohort consists of 201 patients with normal Bruce protocol treadmill stress echocardiogram. Patients with ejection fractions <50%, baseline or stress induced wall motion abnormalities, and valvular diseases were excluded. The confirmation cohort, which was obtained from the National Institute of Health, consisted of 3315 patients with normal Bruce protocol treadmill stress test results in the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) Trial. RHR and peak exercise heart rates (PHR) were tabulated. All patients were categorized based on whether their PHR reached 85% of age-predicted maximum heart rates (APMHR) by the Astrand formula (220 - age in years) and the Tanaka formula (208 - 0.7 x age in years).

Results:
The mean(SD) age in the derivation cohort was 60(±11) years old and 45% were female. 46/201 (23%) did not reach their APMHR. The mean(SD) RHR in CI patients was 65.6(±12) beats per minute (BPM), while it was 69.2 (±12) BPM without CI (p =0.04).

In the confirmation cohort, the mean age was 60(±6.9) years old and 48% were female. 427/3315 (13%) did not reach their APMHR. The mean RHR in CI patients was 68.9(±12) BPM versus 74.0 (±13) BPM in the patients that reached APMHR (p <0.001). The Tanaka formula revealed similar results (p <0.001).

Patients with RHR below or equal to 60 BPM were almost twice as likely to have CI (20%) when compared to patients with RHR over 60 BPM (11%), with a statistical significance of p < 0.001. Patients with CI had a greater cumulative hazard ratio for death and hospitalizations due to myocardial infarction or unstable angina (Image 1).

Conclusion:
These results demonstrate that CI is linked to lower RHR. Below 60 BPM RHR may therefore be an indicator of sinus node dysfunction and CI, both of which predict a reduced exercise capacity and increase all-cause mortality risk.
Abstract 4140387: Evaluating the Mental Health of Adolescent Patients with Cardiac Implantable Electronic Devices
Authors: Gakenheimer-Smith Lindsey , Ou Zhining , Presson Angela , Etheridge Susan , Pilcher Thomas , Asaki S Yukiko , Hammond Benjamin , Bennett Murphy Laura , Wood Laura , Cunningham Sean , Niu Mary
Published: November 2024

Background:
Adolescents with cardiac implantable electronic devices (CIEDs) face greater psychological distress than their peers. Fluctuations over time and mitigating factors remain unclear.

Objectives:
We assessed the mental health symptom burden among adolescents with CIEDs over time, measured its impact on health-related quality of life (QoL) and executive functioning (ExF), and identified factors associated with mental health distress.

Methods:
In a single center, prospective study from 1/2023 – 5/2024, 41 CIED patients, median 18 years (range 12-21) completed serial validated mental health measures of anxiety, depression, post-traumatic stress disorder (PTSD), cardiac QoL, and ExF. Primary outcome: abnormal mental health screen in any of the domains. Secondary outcome: clinically significant change in anxiety or depression scores, defined as ≥6 and ≥5, between baseline and 3-month follow-up. Univariable linear regression model assessed association between QoL score and select variables.

Results:
Fifty-four percent of patients had abnormal baseline mental health screens (39% poor cardiac QoL, 36% trauma history, 28% anxiety, 17% depression, 13% abnormal ExF, 5% PTSD). At follow-up, 34% of anxiety or depression scores were clinically significant (Figure). Higher anxiety and depression scores, male sex, and higher PTSD scores were associated with lower cardiac QoL (coefficients: -2.00, p<0.001; -2.23, p<0.001; -10.53, p=0.007; and -0.75, p=0.002). Higher resilience score correlated with increased overall QoL (coefficient: 1.06, p=0.004) but not cardiac QoL (coefficient: 0.54, p=0.11). Mental health scores were not associated with cardiac diagnosis, CIED type or date of implant, or number of ICD shocks.

Conclusion:
Over 50% of adolescents with CIEDs had abnormal mental health screens. Anxiety and depression scores fluctuated significantly over 3 months. Higher baseline anxiety, depression, and PTSD scores and male sex were linked to lower cardiac QoL. Higher resilience improved overall QoL. Mental health measures showed no association with cardiac diagnosis type, CIED type or duration, or ICD shocks. Routine mental health screening is crucial for improving mental health and quality of life in this population.
Abstract 4140400: Risk of Atherosclerotic Cardiovascular Disease after Cancer Diagnosis: Findings from Three Prospective Cohort Studies
Authors: Liu Qiang , Wang Qiaoli , Wang Molin , Wang Jing , Song Mingyang , Giovannucci Edward
Published: November 2024

Background:
Evidence linking cancer diagnosis to risk of incident atherosclerotic cardiovascular disease (ASCVD) remains inconclusive.

Research Questions:
Do cancer patients experience a higher risk of ASCVD independent of shared risk factors? How does the risk of ASCVD evolve over time following a cancer diagnosis?

Aims:
To determine the association between cancer diagnosis and subsequent risk of ASCVD (coronary heart disease and stroke), and its trajectory over time after cancer diagnosis.

Methods:
We prospectively followed 108,689 women in the Nurses’ Health Study (NHS) (1984-2020), 113,608 women in the NHSII (1991-2019) and 45,327 men from the Health Professionals Follow-up Study (HPFS) (1986-2016) who were free of ASCVD and cancer at baseline. We conducted multivariable-adjusted time-varying Cox proportional hazards models to assess ASCVD risk following individual cancer diagnosis. We conducted restricted cubic spline analyses to assess the varied ASCVD risk over time after cancer diagnosis.

Results:
During up to 36 years of follow-up, 48,069 incident cancer cases and 32,592 ASCVD cases were documented. After adjusting for shared risk factors, ASCVD risk was significantly elevated after diagnosis of cervical cancer (HR: 1.63; 95%CI: 1.10-2.42) and Hodgkin lymphoma (HR: 2.17; 95%CI: 1.42-3.30) compared with non-cancer participants. Prostate cancer diagnosis was associated with a lower ASCVD risk (HR: 0.91; 95% CI: 0.85-0.97). Breast cancer diagnosis was associated with decreased ASCVD risk during the first 15 years after diagnosis, but this risk gradually increased afterward (P =0.02). Bladder cancer was associated with increased ASCVD risk during the first 10 years and attenuated afterward (P=0.03). The risk of ASCVD increased over time after cancer diagnosis among patients with cancers of colorectum (P=0.003), lung (P=0.007), and endometrium (P=0.05). No significant association with ASCVD risk was observed for cancers of oral cavity and pharynx, sarcoma, melanoma, kidney, thyroid, leukemia, or ovary. Results were consistent across sensitivity analyses.

Conclusions:
Increased ASCVD risk was observed for patients diagnosed with cervical cancer or Hodgkin lymphoma, independent of shared risk factors. ASCVD risk trajectories varied over time after diagnosis according to different cancer types. These findings support a need for tailored ASCVD screening among cancer survivors based on specific cancer types and post-diagnosis durations.
Abstract 4140424: Early Insights on Mavacamten Usage in Canada: A Retrospective Cohort Study of the Patient Support Program
Authors: Ong Kevin Chun , Crean Andrew , Garceau Patrick , Moeller Andrew , Brellier Florence , Corriveau Stephanie , Ward Michael
Published: November 2024

Introduction:
Mavacamten is a first-in-class cardiac myosin inhibitor initially approved in the US for treating obstructive hypertrophic cardiomyopathy (oHCM) under the FDA-mandated Risk Evaluation Mitigation Strategy (REMS). Subsequently, mavacamten was approved in Canada with less restrictions. A patient support program (PSP) was implemented, offering a unique opportunity to generate data on mavacamten utilization in the Canadian population.

Aims:
The objective of the study was to obtain real-world insights into the demographic and clinical characteristics, including dosing and treatment duration of patients treated with mavacamten for oHCM in Canada.

Methods:
This was an observational retrospective study of 683 adult patients with symptomatic oHCM enrolled in the Canadian mavacamten PSP between January 4, 2023 to April 12, 2024. Baseline demographic and clinical data were collected for age, gender, NYHA class, vLVOT gradient, LVEF and change in mavacamten dose.

Results:
The baseline clinical characteristics of the 683 patients are summarized in Table 1. Patients were distributed across several provinces with a median age of 65 years and a similar distribution between the male and female populations. The majority (N=458: 67.1%) were classified as NYHA class II. Nearly all patients were initiated at 5 mg of mavacamten as per the Canadian product monograph. Most (63.7%) of patients were on β-blockers alone (Table 1). The median follow-up time was 27.4 weeks (range 1.6-70.1). Notably, at the time of data cut off, 13.2% of patients were receiving mavacamten alone compared to 10.5% at initiation. The median treatment duration was 24.6 weeks, censored at data cut-off, with a discontinuation rate of 7.9%, primarily due to adverse events (2.5%) and lack of efficacy (0.9%).

Conclusions:
Mavacamten has been widely adopted across Canada with low discontinuation rates indicating good tolerability. The current risk management strategies in Canada are sufficient and obviate the need for a stricter approach. These early results provide the largest dataset on mavacamten utilization in the Canadian HCM population, adding to the accruing evidence of its safe and effective use in the real world.
Abstract 4140452: Impact of Beta-Blocker Dosage on All-Cause Mortality Post-Myocardial Infarction in Patients with Ejection Fraction ≥50%
Authors: Zaatari Ghaith , Mitrani Raul , Goldberger Jeffrey
Published: November 2024

Background:
The recent REDUCE-AMI trial showed no benefit to beta-blockers (BB) for patients post-myocardial infarction (MI) with preserved ejection fraction (EF≥50%). Target doses were metoprolol 100 mg and bisoprolol 5 mg daily (50% of the target doses used in the initial randomized clinical trials [RCTs] of BB post-MI).

Research question:
Do lower BB doses improve survival in post-MI patients with EF≥50%?

Aims:
To compare the effect of BB dose on all-cause mortality post-MI in patients with EF≥50%.

Methods:
This is a sub-study from the OBTAIN prospective multi-center registry. Of 7057 patients enrolled with acute MI, 3402 with EF≥50% were discharged alive (age:62.5±13.4 years, 67% male, 28% diabetics, length of stay 6.1±6.0 days). Discharge BB dose was indexed to the target daily BB dose used in RCTs, reported as %. Dosage groups were >0-12.5%, >12.5-25%, >25-50%, and >50% of the target dose. Follow-up vital status was obtained by chart review, Social Security Death Index, or direct contact up to 3 years post-MI. Kaplan-Meier (KM) method was used to calculate three-year survival. Cox proportional hazard regression model was used to identify significant predictors and conduct univariate and multivariate analysis.

Results:
The KM 3 year survival estimates were 89.0% and 84.3% for patients on and off BB, respectively (unadjusted hazard ratio (HR)=0.66, p=0.012; adjusted HR=0.52, p=0.18). The KM 3 year survival estimates(figure) were 89.8%, 91.0%, 87.9%, and 83.1% for patients on >0-12.5%, >12.5-25%, >25- 50%, and >50% of the BB target dose (unadjusted HR of 0.58, p=0.007; 0.58, p=0.003; 0.70; p=0.066; and 0.98, p=0.93), respectively, compared to no BB. After multivariate analysis, BB target dose showed similar trend, but not statistically significant (adjusted HR=0.65, p=0.46; 0.42, p=0.13; 0.53, p=0.31; 1.01, p=0.92).

Conclusion:
In OBTAIN, patients treated with low dose BB (≤25% of the target dose) had improved survival post-MI. As this dose was not studied in REDUCE-AMI, these findings are complementary and confirm only that high dose BB therapy provides no benefit post-MI in patients with preserved EF. RCTs to assess the benefit of low dose BB therapy post-MI with preserved EF are needed.
Abstract 4140462: Effects of Right Ventricular vs. Conduction System Pacing on Left Ventricular Systolic and Diastolic Function Reserve and Pulmonary Gas Exchange During Exercise Stress in Pacemaker Dependent Patients with Normal Left Ventricular Ejection Fraction
Authors: Wen Songnan , Wheatley-Guy Courtney , Parks Jordan , Wingler Catherine T. , Simpson Rose A. , Silva Monique , El Masry Hicham , Naqvi Tasneem
Published: November 2024

Background:
Right ventricular pacing (RVP) can have adverse cardiac effects and cause pacing induced cardiomyopathy (PiCM). His bundle pacing (HBP)&Left Bundle Branch area pacing (LBBAP) mimic physiologic conduction (PhysioP) and maintain biventricular synchrony.
Hypothesis and Aims:
Reduced left ventricular (LV) systolic function reserve in the presence of normal baseline LV ejection fraction (EF) could precede development of RV PiCM. Our aim was to compare the effects of RVP vs. PhysioP on bicycle exercise cardiopulmonary performance in patients with normal LVEF who required pacing for bradyarrhythmias.

Methods:
Patients with sinus rhythm and RVP or PhysioP&ventricular pacing burden of >70% who completed cardiopulmonary exercise test and simultaneous stress echocardiography (SE) were included. Pulmonary gas exchange was calculated using Ventilation/CO2 production at rest and during exercise. Changes in LV size, EF, longitudinal strain and diastolic function and gas exchange parameters were compared post and pre exercise in the 2 groups.

Results:
25 of 29 patients completed the study [68 ± 23 yrs, 48% M; LVEF 56±5%, 11 RVP, 14 PhysioP]. There was no difference in baseline demographic&clinical variables, exercise duration, rest and peak heart rate and blood pressure between 2 groups. Pacing duration was 2.61±1.48 yrs in RVP vs. 0.84±0.67 yrs (p=0.003) in the Physio group. Resting echocardiographic parameters (
Table 1A)
were comparable. Compared to RVP, reduction in LV end-diastolic volume (EDV) 3.4±14.1 ml vs. -23.1±18.1ml, p=0.006)&LV end-systolic volume (ESV -5.7±11.6 ml vs. -18.0±9.5ml, p=0.01) was more pronounced in the PhysioP group. Changes in LVEF, LV strain&diastolic function were not different between the 2 groups (
Table 1B
). There were no significant differences in changes in pulmonary gas exchange parameters in the 2 groups.

Conclusions:
In patients with normal LVEF and pacemaker dependent, RVP is associated with impaired but PhysioP with preserved LV systolic function reserve, which can be detected by exercise SE. SE may help identify patients at risk for RV PiCM. Benefit of PhysioP needs to be determined by larger studies with longer follow-up.
Abstract 4140466: Time Interval from Right Atrium to Coronary Sinus Predicts Atrial Fibrillation Recurrence After Catheter Ablation
Authors: Yamashita Daiki , Fujimoto Naoki , Sugiura Shinya , Kagawa Yoshihiko , Fujita Satoshi , Dohi Kaoru
Published: November 2024

Background:
Atrial fibrillation (AF) recurrence after catheter ablation may occur in patients with atrial remodeling progression. Atrial conduction time has been proposed as a marker of atrial remodeling. This study aimed to investigate whether atrial conduction time, measured during an electrophysiological study, is related to AF recurrence.

Methods:
Overall, 441 patients with AF (mean age, 67 years; female, 144 years; paroxysmal AF (PAF)/non-PAF, 233/208) who underwent initial radiofrequency catheter ablation at Mie University Hospital between January 2018 and December 2022 were enrolled. We measured the interval from the earliest potential in the right atrium (RA) to the latest potential in the coronary sinus (CS) (RA-CS interval time) using a BeeAT catheter during sinus rhythm after ablation (Figure 1). The primary endpoint was the recurrence of AF or other atrial tachycardia lasting > 30 s from 3 months to 1 year postoperatively.

Results:
During the 1-year follow-up, AF recurrence was observed in 44 patients. Patients were categorized into two groups according to AF recurrence. RA-CS interval times were significantly prolonged in the recurrence group (122.5±17.7 vs. 98.5±17.7 ms, p<0.001). In Cox regression analysis, after adjustment for confounders, RA-CS interval time was an independent factor associated with AF recurrence (Hazard ratio 1.05; 95% CI 1.03–1.07, p<0.001). The cut-off value of the RA-CS interval time using the ROC curve was 111 ms (Figure 2, AUC 0.845, 95% CI 0.785–0.905). Patients with RA-CS interval time ≥111 msec had a significantly higher recurrence rate rather than <111 ms (Figure 3).

Conclusions:
The RA-CS interval was an independent predictor of AF recurrence in the first year after catheter ablation.
Abstract 4140467: The Effect of PCSK9 Inhibition With Alirocumab in Patients With Probable Familial Hypercholesterolemia or Type III Hyperlipoproteinemia: Results from the ODYSSEY OUTCOMES Trial
Authors: Geba Gregory , Mohammadi Kusha , DAMASK AMY , Paulding Charles , Lotta Luca , Hindy George , Pordy Robert , Manvelian Garen , Shapiro Michael , Bittner Vera , Bhatt Deepak , Szarek Michael , Schwartz Gregory , Steg Philippe , Fazio Sergio
Published: November 2024

Background:
Patients with acute coronary syndrome (ACS) and elevated LDL-C levels despite statin therapy may have genetic dyslipidemias, such as heterozygous familial hypercholesterolemia (HeFH) or type III hyperlipoproteinemia (T3HLP), which convey heightened cardiovascular (CV) risk due to lifelong exposure. In this post hoc analysis of the ODYSSEY OUTCOMES trial, we identified patients likely affected by HeFH or T3HLP and evaluated the lipid-lowering and CV efficacy of alirocumab.

Methods:
Clinical HeFH was based upon ACS at age <55 (males) or <60 (females) with back-calculated untreated LDL-C ≥250 mg/dL, or ACS at any age with back-calculated LDL-C ≥330 mg/dL. T3HLP was based upon non-HDL-C:apolipoprotein (apo)B ratio >2.6, which was validated using the UK Biobank database. Additionally, a pharmacogenomics (PGx) subgroup (n=11,880) was studied for variants in genes causing HeFH and for apoE genotypes (T3HLP).

Results:
Clinical HeFH was identified in 6.7% of the full trial cohort and 5.9% of the PGx subgroup. In the PGx subgroup, 295 patients (2.5%) had genetically confirmed HeFH, 45.8% of whom also qualified as clinical HeFH. Baseline LDL-C was higher in patients with vs without clinical or genetic HeFH (
Table
). Percent LDL-C-lowering was lower but absolute LDL-C lowering and hazard ratio for major adverse CV events (MACE) with alirocumab were similar in patients with versus without clinical or genetic HeFH. Only 0.09% of subjects in the UK Biobank carried the T3HLP biomarker ratio, with 89% of these carrying the apoE2/2 homozygote genotype. Only 30 of 18,924 patients (0.16%) in the trial were classified as T3HLP. Of these, 13 were in the PGx subgroup of whom 7 (53.8%) were apoE2/2 homozygotes. Lipid responses to alirocumab in patients with T3HLP were comparable with those in the overall population (>50% LDL-C lowering and numerically lower MACE rate).

Conclusions:
In this post hoc analysis of ODYSSEY OUTCOMES, individuals with HeFH were common and those with T3HLP were rare. Carriers of either genetic condition benefited from alirocumab in terms of lipid response and clinical outcomes.
Abstract 4140508: Adaptive Cardiac Arrest Training Curriculum for Capacity Building in Northern Ghana: Addressing Contextual Challenges for Sustainability
Authors: Ahadzi Dzifa , Leung Claudia , Al-Hassan Rahma , Baba Yabasin Iddrisu , Yakubu Abdul-Subulr , Cournooh Annette , IKEDA SCOTT , Alomatu Samuel , Sakeah Patience , Boateng Laud , Hernandez Odalys Rivera , Akanbong Prosper
Published: November 2024

Background:
Structured institutional cardiac resuscitation response training is critical to prepare healthcare workers to respond in emergencies. Best practices require context-adapted training while maintaining quality and fidelity. Resource-limited settings face unique challenges, including deficiencies in basic life support training, limited resources, and a lack of certified trainers. An approach to contextualize training, build capacity, and ensure long-term sustainability is needed.

Objective:
To describe the adaptive approaches used to implement and scale up in-hospital cardiac arrest response training at a teaching hospital in northern Ghana, addressing specific challenges and focusing on long-term sustainability.

Methods:
Leveraging an international academic partnership known as AMPATH Ghana, a multidisciplinary team designed an adapted cardiovascular life support training program inspired by the American Heart Association ACLS training. The program was tailored to local challenges, such as resource limitations, knowledge gaps, and institutional capacity (Table 1). Trainers used a combination of didactic learning, hands-on practice, simulations, and structured feedback. Participant surveys assessed the program’s impact and guided subsequent training iterations.

Results:
198 healthcare workers were trained over four iterations (74% nurses, 35% medical officers, 1% pharmacists). Before the training, 23.4% of trainees felt very confident in their ability to work effectively in a code situation. This increased to 75.3% post-training (p<0.001). With each iteration, adaptations enhanced training quality and fidelity. Medical officers (general practitioner level) were trained as co-facilitators after the first iteration, and additional resources were developed with institutional support to enhance fidelity and sustainability.

Conclusion:
Through a bilateral academic partnership, an adaptive approach to contextually appropriate cardiac arrest response training has improved knowledge and healthcare worker confidence in a teaching hospital in northern Ghana. This adaptive approach may be replicated in similar resource-limited settings to effectively and sustainably scale up training and enhance healthcare capacity.
Abstract 4140565: Chimpanzee Induced Pluripotent Stem Cells (iPSCs)-derived Cardiomyocytes as Surrogates for Human iPSCs in Cardiomyocyte Research and Cross-Species Chimeric Embryo Development
Authors: Roodgar Morteza , Parham Maryam , Suchi Fabian , Bajpai Vivek , Nakauchi Hiromitsu , Wu Joseph , Snyder Michael
Published: November 2024

Induced pluripotent stem cells (iPSCs) provide valuable insights into early tissue and organ development, with potential applications in cross-species comparative studies. Nonhuman primate (NHP) iPSCs, particularly those derived from chimpanzees (Pan troglodytes), which share the closest evolutionary relationship with humans, offer a unique opportunity to study cardiomyocyte comparative developmental physiology. Given the limitations of using human cells, chimpanzee iPSCs can serve as an effective surrogate in earliest stages of embryonic development.

In this study, we derived and maintained chimpanzee iPSCs under novel optimized conditions. We investigated the compatibility of human and chimpanzee iPSCs and their derived cardiomyocytes by co-culturing and differentiating these cells into cardiomyocytes. Our results demonstrate that mixed colonies of human and chimpanzee iPSCs can form homologous intermix colonies and differentiate into synchronized beating cardiomyocyte layers. This high level of compatibility suggests similar differentiation pathways in both species.

Utilizing chimpanzee iPSCs as surrogates for human iPSCs, we assessed their potential in forming primate cross-species chimeric preimplantation embryos. When injected into early rhesus macaque blastocysts, chimpanzee iPSCs were able to survive and proliferate near the inner cell mass. Our study not only introduces a new resource of NHP iPSCs with detailed transcriptome and proteomics characterizations but also highlights the high compatibility of chimpanzee and human iPSC-derived cardiomyocytes, evidenced by the formation of synchronized beating layers during co-culture experiments. These findings hold significant implications for advancing our understanding of cardiomyocyte development and potential therapeutic applications.
Abstract 4140574: Echoes of Danger: A Case of Recurrent Atrial Myxoma with Cerebral Embolization
Authors: Kholoki Obada , Sahi Akshita , Kaufmann Julian
Published: November 2024

Introduction:
Atrial myxomas are cardiac tumors that can cause arterio-occlusive diseases due to embolization of myxomatous fragments. Treatment is through prompt surgical resection, with recurrence rates relatively rare. Herein, we present a case of recurrent left atrial myxoma with hemorrhagic, cerebral embolization.

Case Report:
A 34-year-old male presented with acute onset numbness and tingling of the left arm. He was vitally stable with unremarkable physical examination or bloodwork. CT Head showed multifocal brain metastases in the bilateral parietal and left frontal lobes. Brain MRI demonstrated multiple hemorrhagic masses throughout the cerebral hemispheres with vasogenic edema. The patient’s past medical history was pertinent for bilateral occlusion of the femoral and popliteal arteries, with workup revealing a left atrial myxoma that was surgically resected in 2005. The patient presented again in 2021 with right facial paresthesia and arm weakness. Brain MRI showed bilateral cortical and subcortical MCA ischemic strokes. TEE confirmed the recurrence of a left atrial myxoma, requiring a repeat sternotomy and resection.

Since then, the patient was frequently hospitalized with seizures and strokes. Surveillance brain MRIs consistently demonstrated hemorrhagic masses of varying sizes and vasogenic edema, localized to the watershed territories of the cerebral arteries. The patient underwent left frontal craniotomy and resection of a left frontal lobe lesion in 2023, with pathology specimens representing organizing cerebral hemorrhage of unclear etiology. Repeat echocardiograms did not show recurrence of a myxoma. The overwhelming clinical opinion states that these are myxomatous metastasis from before the patient’s last cardiac surgery. Given the tumor burden and progressive nature of the disease, the patient was deemed inappropriate for neurosurgery or chemotherapy.

Discussion:
Recurrence after surgical resection of atrial myxomas is rare, with 0.5 cases reported per 1000-person years, and is mainly attributed to inadequate surgical resection. Limited research exists regarding malignant atrial myxomas. The prevailing hypothesis points to the neoplastic transformation of myxomatous emboli into malignant lesions. Our patient is a unique case of a recurrent atrial myxoma with symptomatic cerebral metastasis. This case highlights the importance of adequate resection of cardiac myxomas to prevent the malignant transformation of an otherwise benign tumor.
Abstract 4140591: Impact of Mitral Annular Calcification on Cardiovascular Outcomes in Patients with Diastolic Heart Failure
Authors: Isaacs Evan , Idowu Abiodun , Pressman Gregg
Published: November 2024

Background:
Mitral annular calcification (MAC) may be a marker of biological age; its impact on outcomes in patients with heart failure with preserved ejection fraction remains unclear.

Methods:
A retrospective propensity-matched cohort analysis of patients ages > 18 years hospitalized with diastolic heart failure with and without MAC in the TriNetX database. Cohorts were balanced on socio-demographics, and medications (anticoagulants, antiplatelet, beta-blockers, diuretics, anti-arrhythmic, lipid-lowering agents, and SGLT2i). Patients with rheumatic valve disease were excluded. Adjusted odds ratios (aOR) were calculated for outcomes and Kaplan-Meier survival analysis curves with log-rank tests over five-year follow-up were analyzed using R software.

Results:
There were 11384 participants matched to each cohort; the average age at diagnosis was 72.5 + 11.6 years, 76.2% were Caucasian, and 56.9% were female. Left ventricular ejection fractions were similar in both MAC (58.3 + 11.9) vs non-MAC (58.2 + 12.6). Median follow-up was 423 days (MAC group) and 575 days (non-MAC group). All-cause hospitalization (HR: 2.31, 95%CI: 2.04 – 2.62, p<0.001), heart failure hospitalization (HR: 2.22, 95%CI: 1.92 – 2.55, p<0.001), acute myocardial infarction (HR: 2.06, 95%CI: 1.79 – 2.35, p<0.001), unstable angina (HR: 2.28, 95%CI: 1.72-3.04, p<0.001), and stroke (HR: 1.70, 95%CI: 1.45 – 2.00, p<0.001) were all higher in MAC patients than non-MAC patients (table 1).

Conclusion:
Among patients hospitalized with ‘diastolic heart failure’ MAC is associated with worse cardiovascular outcomes.
Abstract 4140600: Safety and Efficacy of Left Atrial Appendage Occlusion Procedure for Patients with Nonvalvular Atrial Fibrillation and Prior Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis
Authors: Chanda Veda , Bittar Vinicius , Carvalho Pedro , Garot Philippe
Published: November 2024

Background:
Patients with nonvalvular atrial fibrillation (AF) and a history of intracranial bleeding while on anticoagulant therapy commonly undergo left atrial appendage occlusion (LAAO) to prevent thromboembolic events. Despite being suitable candidates for LAAO, treatment for this patient population is underrepresented in clinical trials.

Methods:
PubMed, Cochrane, and Embase databases were systematically searched for studies reporting clinical outcomes after LAAO in patients with prior intracranial bleeding. Pooled incidence data were presented as mean percentages with 95% confidence intervals (CI) using a random-effects model.

Results:
A total of 20 observational studies were included comprising 1,945 patients with nonvalvular AF and prior intracranial bleeding receiving LAAO. The mean age was 73.2 years, 35.2% were women, 49.8% received Watchman device. The mean CHA
2
DS
2
-VASc was 4.48 and the mean HAS-BLED was 3.74. In patients with prior intracranial bleeding, the LAAO procedure was associated with an all-cause mortality pooled incidence rate of 4.42% (95% CI 2.40-8.02; I
2
=81%, Figure 1A), major bleeding rate of 3.93% (95% CI 2.43-6.30; I
2
=54%, Figure 1B), device-related thrombosis rate of 1.46% (95% CI 0.83-2.66; I
2
=0%), peri device leak rate of 4.70% (95% CI 1.61-12.97; I
2
=86%), and stroke rate of 3.48% (95% CI 2.14-5.63; I
2
=47%).

Conclusion:
This meta-analysis of 20 studies found that, in patients with history of intracranial bleeding receiving LAAO, the incidence of clinical outcomes is comparable to the overall population undergoing LAAO.