bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4115543: Safety and Efficacy of a Novel Technique for Extraction of Micra
TM
Leadless Pacemaker with Aveir
TM
Retrieval Catheter System: An Eight Case series.
Authors: Maldonado Noel , Doty Brandon , Gabrah Kirollos , Cain Jonathan , Lee Bridget , Mahtani Arun , Al-Hindi Feross , Brider Jamarcus , Nair Devi
Published: November 2024

Background:
Leadless cardiac pacemakers (LCP) have evolved as an excellent alternative to transvenous pacemaker (TVPM) for bradycardia therapy with excellent safety and efficacy outcomes. Micra
TM
was the first commercially available LCP. The device attaches to the right ventricular myocardium with four Nitinol FlexFix™tines. Its inherent design poses problems with retrievability. This leads to many devices being turned off and left behind in the right ventricle at the end of its life. The Aveir retrieval catheter was recently launched as part of the Aveir family of LCP and has a tri-loop snare re-docking mechanism, steerability, and protective sleeve.

Goals:
We aim to show the safety and efficacy of using this novel retrieval catheter for extraction of the Micra™ LCP in lieu of abandoning the LCP in the right ventricle.

Results:
We present a case series of 8 successful retrievals of Micra™ LCP using the Aveir™ retrieval catheter. Four patients had the LCP removed during upgrade to cardiac resynchronization therapy and the other four had the LCP removed at the time of replacement of the LCP at device end-of-life. The mean age of the cohort was 72.6±9.4 years (62.5% female). The average age of the retrieved LCP was 4 years and 4 months with the oldest device being in place for 7 years and 7 months. Median retrieval time, defined as time from retrieval catheter in to retrieval catheter out, was 4.8±2.4 minutes. In 100% of the cases the LCP was successfully retrieved in its entirety via femoral venous access. There were no intra- or post-procedural complications, including vascular complications, pericardial effusions, right ventricular dysfunction or worsening tricuspid regurgitation. At six months follow up, patients continued to remain free of the above complications.

Conclusion:
This case series demonstrates the safety and feasibility of using the Aveir™ retrieval catheter for extraction of the Micra™ LCP device in lieu of abandonment. Additional studies should be considered to assess the risk and benefits of abandoning the device in the right ventricle extraction of the LCP with this novel technique. The authors acknowledge the steep learning curve associated with this procedure. Further multicenter analysis of this technique is necessary to determine its generalizability.
Abstract 4115634: Potential Role for Circadian Disruption in Acute Kidney Injury-driven Cardiovascular Disease
Authors: Segal Mark , Diao Yanpeng , Douma Lauren , Crislip Gene , Lu Yuanqing , Han Shuhong , Clapp William , Gumz Michelle
Published: November 2024

Background/Hypothesis:
Circadian disruption and AKI, even if kidney function recovers, are linked to an increased risk of CVD and death. We explored the hypothesis that AKI was associated with CVD through circadian disruption.

Approach:
Sixteen ~25-week-old PER2::Luciferase (a real-time reporter of circadian rhythm) C57BL/6J male mice had micro-clamps applied to both renal pedicles for ~26 minutes to produce a recoverable AKI. Three animals underwent a sham procedure. Three animals had to be euthanized all others had serum creatinine (Scr) measured on day 2. Twelve weeks after surgery, all animals (n=13) were euthanized.

Results:
The sham group's day 2 Scr (n=3; mean 0.10 [range 0.08 - 0.15]) was unchanged from baseline (0.11 [0.07 - 0.18]). Based on the day 2 Scr, 3 mice were classified as having mild/moderate AKI (Scr increased ≤ 3-fold) (0.16 [0.08 - 0.20]) and 7 as having severe AKI (Scr increased > 3-fold) (0.98 [0.26 - 1.93]). By 12 weeks post-AKI, the Scr (0.16 [0.1 - 0.2 mg/dl]) of all animals returned to a level statistically similar to baseline. Immunohistochemistry demonstrated that 6 of 7 mice with severe AKI had atherosclerotic-like lesions in the aortic root (A), sinus, or coronaries (B): 4 mice had lesions averaging 9,754.7 µm
2
and 2 mice had coronary artery lumen narrowing averaging 56.2%. Similar lesions were found in 1 of 3 mice with mild/moderate AKI, but
no lesions
were found in the sham animals (C). The lesions had CD45+ cells on their surface and in the adventitia (A inset), but were devoid of CD68+ and SMC alpha-actin+ cells. In the neointima, SMC alpha-actin+ cells predominated (B inset). Mouse liver, lung, adrenal gland, renal cortex, outer and inner medulla were collected at 15:00 and analyzed for 5 days by Lumicycle. Circadian rhythms were evaluated with JTK_CYCLE. No apparent AKI-dependent differences were observed in the liver, lung, adrenal, or renal outer medulla. However, the amplitude of renal inner medulla rhythms decreased with AKI (P = 0.008), while the amplitude of renal cortex increased with AKI (P = 0.01, E&F).

Conclusions:
This is the first report of an AKI model resulting in atherosclerosis-like lesions in wild-type mice without the need for a high-fat diet, genetic manipulation, or further provocation. The lesions were associated with a disruption of the intrarenal circadian rhythms. We will discuss the implications of this research as well as the metabolic consequences of the circadian disruption.
Abstract 4115654: Assessing Diagnostic Performance: A Systematic Review and Meta-Analysis of Machine Learning-Based Fractional Flow Reserve versus Traditional Invasive Fractional Flow Reserve for Coronary Artery Stenosis Evaluation
Authors: Jain Shubhika , Panchal Viraj , Adams Mariah , Singh Mansunderbir , Goyal Samarth , Joshi Divya Dinesh , Vyas Rahul , Thotamgari Sahith Reddy , Brar Vijaywant
Published: November 2024

Introduction:
Fractional Flow Reserve (FFR) is a stenosis-specific index for coronary artery stenosis (CAS) detection and its effect on myocardial perfusion. Visualizing stenosis through an invasive coronary angiography (iFFR) lacks consistency and is highly subjective. Recently, non-invasive techniques have been developed using artificial intelligence (AI) and Machine learning (ML) to measure FFR (ML-FFR). We aimed to analyze the diagnostic performance of ML-FFR in comparison to iFFR in the detection of CAS.

Methods:
A search was carried out in PubMed, IEEE Xplore digital library, and clinicaltrials.gov where studies evaluating the risk of CAS in patients undergoing ML-FFR and iFFR were considered in terms of FFR values from 2014 to 2024. OpenMetaAnalyst was used to evaluate the diagnostic performance in terms of pooled Sensitivity(SN), Specificity(SP), Negative Likelihood Ratio(NLR), Positive Likelihood Ratio(PLR), and Diagnostic Odds Ratio(DOR) at 95% confidence interval (CI). P<0.05 was considered significant.

Results:
A total of 9 studies including 1358 vessel lesions were analyzed. The pooled SN, SP, NLR, and PLR were 81.1%(74.3%-86.4,p=0.014), 91.8%(84.9%-95.7%, p<0.001), 0.187 (0.151-0.232, p=0.575) and 9.898(5.492-17.839,p<0.001), respectively with >75% heterogeneity in SP and PLR. After excluding two studies, a “leave-out” analysis showed pooled SN, SP, NLR, and PLR as 79.9% (71.4%-86.3%, p=0.007), 94.4% (90.2%-96.9%, p=0.002), 0.187 ( 0.140-0.250, p=0.540) and 14.307 (8.094-25.289, p=0.004) with <70% heterogeneity. The pooled DOR was 53.42 (28.26-100.99, p=0.005) at random effect model.

Conclusion:
ML-FFR showed significant diagnostic values signifying that it can be used as a potential non-invasive alternative to iFFR for detecting lesion severity and guiding clinical decision-making in patients with suspected CAD, especially for those who are considered high-risk or ineligible for invasive angiography.
Abstract 4115801: Assessing Prevalence of Cardiac Amyloidosis at the Time of Spinal Laminectomy for Spinal Stenosis
Authors: Sul Lidiya , Ives Lauren , Schlenk Richard , Kalfas Iain , Mroz Thomas , Orr Doug , Benzel Edward , Krishnaney Ajit , Pelle Dominic , Cotta Claudiu , Nakashima Megan , Steinmetz Michael , Kilpatrick Scott , Reith John , Hanna Mazen
Published: November 2024

Introduction:
Cardiac amyloidosis (CA) involves deposition of amyloid fibrils within cardiac myocardium, resulting in heart failure. Recent studies have shown an association between amyloid deposition in the ligamentum flavum (LF) and development of CA. Our study aims to investigate the prevalence of CA in patients identified with amyloid deposition in their LF at the time of spinal laminectomy for spinal stenosis, employing a comprehensive approach integrating multi-modality imaging and laboratory testing.

Methods:
This is a retrospective study of patients age >50 years old who underwent spinal laminectomy for non-congenital spinal stenosis or spondyloarthropathy. LF tissue samples obtained during surgery were examined histologically for amyloid deposition. Patients with positive findings underwent testing, including serum markers, echocardiography, and 99mtechnetium pyrophosphate (99mTcPYP) scintigraphy. Additionally, cardiac magnetic resonance imaging (cMRI) was obtained when clinically appropriate to assess for CA.

Results:
Among the 197 enrolled patients, 39 (19.3%) exhibited amyloid deposition in LF tissue. Patient demographics and clinical characteristics did not significantly differ between the positive and negative groups (Table 1). Of the 39 amyloid positive specimens, subtyping using mass spectrometry identified 1 (3%) light-chain, 28 (72%) transthyretin (TTR), and 10 (25%) were unable to be subtyped. Of the 28 TTR positive patients, 8 were of the wild type genotype. Furthermore, 18 of the 28 TTR patients underwent 99mTcPYP scintigraphy, of which none had cardiac uptake consistent with TTR amyloidosis; the other 10 declined work up. Of the 10 untyped patients, 6 had 99mTcPYP scintigraphy with none of the patients having cardiac uptake. Adjunctive cMRI in select positive patients showed findings inconsistent with amyloid deposition. Serum NT-proBNP, Troponin T, and serum pre-albumin levels were similar between groups.

Conclusion:
Amyloid deposition in LF tissue did not correlate with cardiac manifestations of amyloidosis at the time of surgery. Longitudinal investigation is ongoing to better understand the relationship between amyloid deposition in LF tissue and the development of CA over time.
Abstract 4115947: Empagliflozin Inhibits the Mobilization of CCR2+ Monocyte-Derived Macrophages by Reducing CCL2 Expression in Fibroblasts and Slows the Progression of Heart Failure After Pressure Overload.
Authors: Morishita Shun , Horitani Keita , Shiojima Ichiro
Published: November 2024

Background:
The positive effects of sodium glucose co-transporter-2 (SGLT2) inhibitors on reducing cardiovascular mortality and hospitalizations due to heart failure have been well established. Although numerous theories propose explanations for the cardioprotective actions of SGLT2 inhibitors, these hypotheses primarily rely on initial findings and require further validation. Studies have shown that immune cells, particularly macrophages marked by C-C chemokine receptor type 2 (CCR2), contribute to the progression of heart failure by infiltrating the myocardium and inducing detrimental structural changes following myocardial infarction or pressure overload.

Purpose:
This study aims to investigate whether SGLT2 inhibitors can mitigate heart damage by inhibiting the migration of CCR2+ monocyte-derived macrophages.

Methods:
In this experiment, male B6 mice were subjected to transverse aortic constriction (TAC) to induce heart failure. Two weeks post-TAC, with heart function confirmed as equal across all groups by echocardiography, one group began receiving daily oral doses of empagliflozin, while another served as the control. At four weeks post-TAC, cardiac function was reassessed. The animals were then euthanized, and their hearts were analyzed using flow cytometry, staining, and qPCR to evaluate heart failure and the involvement of immune cells. Additionally, isolated cardiac fibroblasts were subjected to cyclic stretching to mimic post-TAC mechanical stress.

Results:
Treatment with empagliflozin resulted in improved cardiac function and reduced congestion in the heart and lungs, indicating alleviation of heart failure. The treatment notably decreased myocardial fibrosis, evident from Picrosirius-red staining and reduced expression of fibrosis-related mRNA. Importantly, empagliflozin specifically reduced the number of CCR2-positive macrophages in the heart, without affecting other types of immune cells. In cardiac fibroblasts that underwent cyclic stretching, empagliflozin pre-treatment diminished the expression of C-C motif chemokine ligand 2 (CCL2), the ligand for CCR2.

Conclusion:
Empagliflozin’s ability to suppress CCL2 expression in fibroblasts and curtail the recruitment of CCR2+ macrophages may represent a potential strategy to decelerate heart failure progression. These findings advance our understanding of the cardioprotective mechanisms of SGLT2 inhibitors and propose novel therapeutic avenues for heart failure management.
Abstract 4116281: Improvement in Valvular Regurgitation Severity with Atrioventricular Junction Ablation: Conduction System and Biventricular Devices
Authors: Krayem Hussein , Nation Charles , Peddibhotla Bharath , Prabhu Sagar , Shaikh Rafae , GADELA VAISHNAVI , Kolominsky Jeffrey , Kontos Michael , Naz Naveed , Bhardwaj Hem , Trankle Cory , Turlington Jeremy , Kron Jordana , Shepard Richard , Mankad Pranav , Koneru Jayanthi , Ellenbogen Kenneth , Pillai Ajay , Gertz Zachary
Published: November 2024

Background:
Ablate-and-pace strategies for permanent atrial fibrillation (AF) have shown mortality benefit with biventricular pacemakers (BiV). The mechanism of benefit is not well understood, but may involve cardiac remodeling. We sought to characterize the effects of AV junction ablation (AVJA) in patients receiving BiV or conduction system pacing (CSP) devices on valvular regurgitation.

Objective:
To evaluate the effects of AVJA in permanent AF on valvular regurgitation as measured by standard 2D echocardiography.

Methods:
Consecutive patients undergoing BiV/CSP after AVJA for permanent AF with tricuspid regurgitation (TR) and/or mitral regurgitation (MR) between January 2018 and January 2023 at our institution were analyzed. Ejection fraction (EF), TR severity, and MR severity were compared pre-AVJA and post-AVJA.

Results:
A total of 102 patients met the above criteria. Median clinical follow up time was 902 days (IQR 578-1537 days) from AVJA. In patients with at least 1+ MR at baseline (N=65), there was significant improvement in MR severity post-AVJA (p=0.003). At baseline, 51% of patients had 1+ MR, 36% of patients had 2+ MR, 10% of patients had 3+, and 3% of patients had 4+ MR. Post AVJA, 45% (29 patients) had improvement in MR severity, 40% (26 patients) had no change, and 15% (10 patients) worsened. The greatest improvement was seen in patients with reduced baseline EF(defined as EF<50%). All 3+ and 4+ MR improved to at least 2+ MR post-AVJA in this subset. In patients with at least 2+ TR at baseline (N=28), there was also significant improvement in TR severity (p=0.029).

Conclusion:
AVJA with physiologic pacing in patients with permanent AF is associated with improvement in MR and TR severity.
Abstract 4116300: Valvular Abnormalities and Risk of Abdominal Aortic Aneurysm Associated with Fluoroquinolone Use; A Retrospective Cohort Study
Authors: Shahin Hania , Seylani Allen , Haile Yohannes , Lowe Catherine , Vo Carolynne
Published: November 2024

Introduction:
Fluoroquinolones (FQ) are efficacious antibiotics whose antimicrobial effect is achieved through bacterial DNA gyrase inhibition. However, there is evidence suggesting that FQ may cause impaired collagen synthesis and an increase in tissue collagen degradation. Collagen serves as a predominant structural constituent of the aortic wall and heart valves. These structures undergo tissue maintenance, which necessitates the regulated expression of MMPs and TGF-β. In this study, we hypothesized that prolonged usage of FQs may increase risk of valvular abnormalities and abdominal aortic aneurysm.

Methods:
We conducted a retrospective cohort study utilizing de-identified patient data from the TriNetX platform, an extensive electronic health records (EHR) system. The cohorts consisted of smoker patients who used FQs for more than two consecutive weeks, Cohort A, N= 352,215 and smoker patients without a history of FQ use, Cohort B, N=350,912. Propensity score matching balanced baseline characteristics between cohorts: age, sex, ethnicity, and comorbidities.

Results:
The risk of developing AAA among smokers with a history of FQ use was 1.222% while the risk was 0.806% among smokers without history of FQ use (P< 0.0001, 95% CI (0.63,0.691), Risk Ratio (RR)= 0.66). The risk of developing nonrheumatic (NR) aortic insufficiency among smokers with history of FQ use was 1.479% while smokers with no history of fluoroquinolone use had a 0.95% risk (P<<0.0001, 95% CI (0.616,0.67), RR= 0.643). The risk of developing NR mitral insufficiency in smokers with history of FQ use was 3.873% versus their smoker FQ naive counterparts risk of 2.317% (P< 0.0001, 95% CI (0.582,0.615), RR= 0.598). NR tricuspid insufficiency in smokers with FQ usage was also increased versus their smoker FQ naive counterparts at 3.089% and 1.758%, respectively (P< 0.0001, 95% CI (0.552,0.587), RR =0.569).

Conclusions:
This study uncovered a significant association between FQ use, risk of AAA, and NR-valvular insufficiencies among smokers. In particular, male smokers are at highest risk of developing AAA. This same population is at risk for prostatitis that would likely need treatment with FQs, further increasing their risk. Despite the efficacy of this class of antibiotics, caution is paramount when prescribing FQs in individuals who are actively smoking or have any connective tissue pathologies.
Abstract 4116340: The Effect of Periprocedural Statin Therapy on Mortality and Cardiovascular Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis
Authors: Goyal Aman , Mashkoor Yusra , Abbasi Haleema Qayyum , Khan Rozi , Jain Hritvik , Rathore Sawai Singh , Puttaswamy Darshan , Moeed Abdul , Sulaiman Samia , Belur Agastya
Published: November 2024

Background:
Transcatheter aortic valve replacement (TAVR) stands as a notable alternative to surgery for severe aortic stenosis (AS). Despite the established benefits of statins in cardiovascular pathologies, their specific impact in patients with severe AS undergoing TAVR remains uncertain. Our study aims to assess whether perioperative statin use improves survival and outcomes post-TAVR.

Methods:
A search was conducted across various databases to retrieve studies comparing perioperative statin use versus no statin use in patients undergoing TAVR. The primary outcome of interest was all-cause mortality (ACM). Secondary outcomes included stroke, acute kidney injury (AKI), 30-day mortality, myocardial infarction (MI), cardiovascular complications, and in-hospital mortality. Comprehensive Meta-Analysis Software (v. 3) was used to pool odds ratio (OR) under a random-effects model, with statistical significance set at p < 0.05.

Results:
Our analysis encompassing 20663 patients from 15 observational studies found that perioperative statin use was associated with a significant reduction in ACM (OR= 0.71, 95% CI: 0.61-0.83,

I
2

= 50.3%, p<0.001). Although not statistically significant, perioperative statin use demonstrated a trend towards a decreased risk of stroke (OR= 0.90, 95% CI: 0.68-1.19,

I
2

= 0%, p= 0.455), AKI (OR= 0.99, 95% CI: 0.75-1.31,

I
2

= 49%, p= 0.968), and 30-day mortality (OR= 0.71, 95% CI: 0.46-1.10,

I
2

= 0%, p= 0.126), and no difference was seen in the risk of MI (OR= 1.72, 95% CI: 0.73-4.04,

I
2

= 0%, p= 0.214), cardiovascular complications (OR= 1.12, 95% CI: 0.91-1.37,

I
2

= 0%, p= 0.297), and in-hospital mortality (OR= 0.42, 95% CI: 0.13-1.38,

I
2

= 65.8%, p= 0.151) (Figure 1 and 2).

Conclusion:
Perioperative statin therapy reduces all-cause mortality in TAVR patients but shows limited impact on other outcomes. Further large-scale prospective studies and trials are necessary to corroborate our findings.
Abstract 4116603: Interleukin-33 from Necrotic Tunica Media Plays a Key Role in the Exacerbations of Coronary Arteritis in Kawasaki Disease
Authors: Okada Seigo , Sakai Aiko , Ohnishi Yuji , Yasudo Hiroki , Motonaga Takahiro , Fukano Reiji , Waniishi Takako , Sugiyama Masaya , HASEGAWA Shunji
Published: November 2024

Objective:
Alarmins resulting from cell death or oxidative stress have been shown to be involved in the development of Kawasaki disease (KD) vasculitis. In our previous study, we demonstrated the potential role of (IL)-33 as an alarmin in the development of KD vasculitis. Although edematous dissociation (necrotic change) of the tunica media is thought to be a major source of IL-33 in KD vasculitis, it has not yet been elucidated.

Methods:
We investigated the impact of IL-33 released from necrotic human coronary artery smooth muscle cells (HCASMCs) on human coronary artery endothelial cells (HCAECs) by a co-culture assay using the Transwell
®
cell culture insert system. Subsequently, we evaluated the anti-inflammatory effects of anti-IL-33 and anti-ST2 antibodies compared to the conventional therapies of KD, such as high-dose IgG or anti-tumor necrosis factor (TNF)-α antibody.

Results:
Primary necrosis of HCASMCs induced significant release of IL-33. In co-cultures of necrotic HCASMCs with HCAECs, necrotic HCASMCs significantly induced the production of various proinflammatory cytokines in HCAECs. Anti-IL-33 and anti-ST2 antibodies exhibited unique inhibitory effects on the production of platelet-derived growth factor-BB or IL-12(p70) in HCAECs.

Conclusion:
The results of the present study suggest the potential involvement of edematous dissociation of the tunica media in the development of KD vasculitis. Furthermore, the distinctive anti-inflammatory effects of the anti-IL-33/ST2 axis drugs suggest novel therapeutic options for patients with refractory KD.
Abstract 4116639: Efficacy of Transcatheter Aortic Valve Replacement for Severe Pure Native Aortic Valve Regurgitation: A Meta-Analysis
Authors: Jha Mayank , Harikrishna Arya , Mal Madho , Jain Hritvik , Daga Pawan , Hanif Muhammad , Aamir Muhammad , Rajeswaran Yasotha , Zacks Jerome
Published: November 2024

Background:
Surgical aortic valve replacement (SAVR) is the preferred treatment option for patients with severe aortic regurgitation (AR). Recently, several patients with mixed aortic valve disease, comprising severe aortic stenosis (AS) and at least moderate AR, have been successfully treated with TAVR. However, the treatment of severe native aortic valve regurgitation (NAVR) without AS remains a matter of contention, and the efficacy of TAVR remains uncertain.

Aims:
The primary outcomes were 30-day mortality and the incidence of device success. The secondary outcomes included incidence of myocardial infarction (MI), stroke, major bleeding, acute kidney injury (AKI) ≥ stage 2, moderate-to-severe paravalvular leak (PVL), permanent pacemaker implantation (PPM), and post-procedural moderate-to-severe AR.

Methods:
We systematically searched PubMed, Cochrane Library, Scopus and ClinicalTrials.gov for published articles from inception until 2nd April 2024 to evaluate clinical outcomes of TAVR in patients with NAVR. The statistical analysis was conducted using R-Studio 5.3.3. The rates of events with 95% confidence intervals (CI) and the heterogeneity was assessed using p-value and I
2
statistics.

Results:
A total of 23 published articles with 4,397 patients were included. All-cause mortality at 30 days was 12% (95% CI: 6% to 23%), while device success was 86% (95% CI: 81% to 92%). The incidence of complications such as MI (3%, 95% CI: 2% to 4%), stroke (3%, 95% CI: 2% to 3%), major bleeding (8%, 95% CI: 5% to 11%), AKI ≥ stage 2 (8%, 95% CI: 5% to 12%), and major vascular complications were relatively low (6%, 95% CI: 4% to 7%). PPM was required for 15% of patients (95% CI: 11% to 18%). PVL was observed in 10% of patients (95% CI: 2% to 41%) and post-procedural moderate-to-severe AR occurred in 9% of patients (95% CI: 4% to 20%).

Conclusion:
TAVR is a viable and reasonable option for a specific population with NAVR. Nevertheless, it is imperative to conduct larger studies with a longer duration of follow-up to obtain more robust evidence of the feasibility of TAVR in patients with NAVR.
Abstract 4116692: Cardiovascular Safety of Fertility Therapy: A Systematic Review and Meta-Analysis
Authors: Pivato Carlo Andrea , INVERSETTI ANNALISA , Condorelli Gianluigi , Chieffo Alaide , LEVI SETTI PAOLO , LATINI ALESSIA , BUSNELLI ANDREA , MESSA MARTINA , CRISTODORO MARTINA , Bragato Renato , Francone Marco , ZUCCOLO LUISA , IEVA FRANCESCA , DI ANGELANTONIO EMANUELE , Stefanini Giulio
Published: November 2024

Background and Aims:
The increasing use of assisted reproductive technology (ART) has raised concerns regarding its long-term cardiovascular safety due to potential hormonal imbalances and pro-thrombotic states. This study aimed to assess the long-term cardiovascular risk associated with fertility treatments in women.

Methods:
Following PRISMA guidelines, a systematic review and meta-analysis was conducted via MEDLINE (Pubmed) from inception to January 2024. Randomized, cohort or case-control studies were included if fulfilling the following criteria: the association between fertility therapy and the subsequent cardiovascular outcome was reported and conditioned on confounding factors (at least age); the presence of a control group; minimum one-year follow-up. Effect size (ES) estimates of the association between fertility therapy and subsequent cardiovascular disease were pooled using the DerSimonian and Laird random-effects model. Heterogeneity was assessed with the I
2
index. This study is registered with PROSPERO (CRD42024505605).

Results:
Of 7,298 articles screened, eleven studies were included, encompassing 606,912 women undergoing ART and 70,562,486 controls. The analysis found no increase in the long-term risk of major adverse cardiovascular events (ES=0.97, 95% CI=0.81-1.16, I
2
=89.55%, p=0.73), coronary heart disease (ES=0.88, 95% CI=0.71-1.10, I
2
=24.36%, p=0.26), stroke (ES=1.20, 95% CI=0.96-1.49, I
2
=48.33%, p=0.11), heart failure (ES=0.74, 95% CI=0.60-0.94, I
2
=0.00%, p=0.01), venous thromboembolism (ES=1.03, 95% CI=0.78-1.34, I
2
=54.41%, p=0.85), hypertension (ES=1.08, 95% CI=0.88-1.326, I
2
=94.63%, p=0.46), or diabetes (ES=1.03, 95% CI=0.86-1.22, I
2
=78.44%, p=0.77).

Conclusions:
ART does not increase the long-term risk of cardiovascular diseases in women. These results support the cardiovascular safety of fertility treatments, though further research into specific ART techniques and extended follow-up is recommended.
Abstract 4117454: PCSK9 Inhibitors for ASCVD Risk Reduction in Asian Populations — a meta-analysis of efficacy and safety profiles
Authors: Hariyanto Jesslyn , Setiawan Jessica Anastasia , Hardi Catherine Jillian , Ng Sunanto
Published: November 2024

Background:
Dyslipidemia is increasingly prevalent in the Asia-Pacific region, correlating with higher mortality rates for ASCVD among this population. Statins, the cornerstone for dyslipidemia management, face higher intolerance in Asians compared to other races. PCSK9 inhibitors have emerged as a promising therapeutic additive to other lipid-lowering therapies. However, current trials predominantly involve caucasian populations, emphasizing the need for efficacy data across other ethnic groups. This meta-analysis aims to analyze the efficacy and safety profile of PCSK9i in Asian populations at high risk for ASCVD.

Methods:
We searched PubMed, Scopus, and Cochrane for RCTs from the past 10 years on PCSK9i vs. placebo in Asian populations at risk for ASCVD. Efficacy was measured by the mean difference in LDL levels from baseline. Safety parameters included ALT/AST, CK levels, and binding antibodies. Analysis was done with Review Manager, assessing heterogeneity with I^2 statistics.

Results:
Eleven studies in Singapore, Japan, the Philippines, India, South Korea, China, and Taiwan included 5443 patients (73% male, mean age 60.6, mean baseline LDL 114 mg/dL) with follow-up from 12 weeks to 16 months. Inclisiran was used in 3 studies, evolocumab in 5, alirocumab in 2, and tafolecimab in 1, alongside statins or ezetimibe.

PCSK9i reduced LDL by -74.21 mg/dL and increased the likelihood of >50% LDL reduction compared to placebo (RR: 37.41, 95% CI: 16.31-85.82, P < 0.00001; I^2: 0%). PCSK9i significantly improve the achievement of LDL levels <70 mg/dL compared to placebo (RR: 15.77; 95% CI: 7.12 - 34.91, P < 0.00001; I^2: 82%)

Adverse events showed a non-significant risk of >3x ULN increase in ALT/AST
(
RR 0.58; 95% CI: 0.33-1.05; P = 0.78, I^2: 0%) and >5x ULN increase in creatine kinase (RR 0.32; 95% CI: 0.07-1.49; P = 0.97; I^2 = 0%). No significant difference in binding antibodies was observed (RR: 2.50, 95% CI: 0.13-49.47, P = 0.55; I^2 = 65%)

Conclusion:
In Asian populations, PCSK9 inhibitors effectively lower LDL levels without significant adverse events. The considerable heterogeneity in LDL reduction may result from variations in dosing, different agents used, baseline LDL levels, and geographical diversity. Future research should explore effects across more ethnicities to enhance generalizability.
Abstract 4117640: Thirty-Year Prevalence and Prognosis of the Cardiovascular-Kidney-Metabolic Syndrome in U.S. Females and Males
Authors: Ji Hongwei , sabanayagam charumathi , Matsushita Kunihiro , Cheng Ching-Yu , Rim Tyler Hyungtaek , Sheng Bin , Li Huating , Tham Yih Chung , Cheng Susan , Wong Tien
Published: November 2024

Background:
The American Heart Association recently published guidelines on how to clinically identify and categorize individuals with cardiovascular-kidney-metabolic (CKM) syndrome. The extent to which CKM syndrome prevalence and prognosis differ by sex remain unknown. This study aimed to examine the impact of sex on trends in prevalence over 30 years and long-term prognosis of the CKM syndrome in the US.

Methods:
We analyzed nationally representative NHANES 1988-2018 data collected from 33,868 US adults (age ≥20 years) who were under surveillance for all-cause mortality through December 31, 2019. We examined sex-specific prevalence of CKM syndrome, and sex-specific CKM associations with all-cause mortality.

Results:
Of the 33,868 adults studied, the mean±SD age was 48.4±18.3 years with 52% female and 56% non-White. Overall prevalence of CKM syndrome increased steadily from 1988 to 2018 in both sexes, with a larger temporal rise in prevalent Stage 3 CKM seen for males (from 18.9% to 22.4%) compared to females (from 13.9% to 15.2%) (
Figure 1
). Over a median follow-up of 13.3 years, there were 8745 deaths. In multivariable cox-regression analysis, worsening CKM severity was associated with all-cause mortality (P<0.001 for both sexes), with greater magnitudes of risk seen in females (HR=1.24 to 3.33) compared to males (HR=0.85 to 2.60) across all stages (LRT χ
2
=19.0, P
interaction
<0.001); results were similar for cardiovascular mortality (LRT χ
2
=22.3, P
interaction
<0.001) (
Table 1
).

Conclusions:
Females, compared with males, exhibited a lower prevalence of CKM stage 3 but experienced excess mortality risk across the spectrum of multi-system CKM dysfunction. These findings underscore the importance of identifying mechanisms underlying joint cardiovascular, renal, and metabolic systems pathophysiology to close a potentially widening sex disparities gap in multi-organ disease risk.
Abstract 4117645: Ischemic Heart Disease Trends in Canada: A 30-Year Epidemiological Study
Authors: Wang Valerie , Hou Neo , Gajjar Avi , Wang Herbert
Published: November 2024

Introduction:
Ischemic heart disease (IHD) results from coronary artery blockages that impede myocardial blood flow. We aim to examine the temporal trends of IHD in Canada from 1990 to 2019, assessing age-standardized mortality, disability-adjusted life years (DALYs), and other health indicators.

Methods:
We analyzed data from the 2019 Global Burden of Disease study on Canadian IHD cases over three decades. The study investigated age-standardized deaths, DALYs, years lived with disability (YLDs), years of life lost (YLLs), prevalence, and incidence across both sexes. We performed statistical analyses using Microsoft Excel 16.63.1.

Results:
Over the period from 1990 to 2019, Canadian men and women experienced notable decreases in IHD incident rates [-45.11%], overall mortality [-60.64%], YLLs [-62.824%], prevalence [-26.778%], YLDs [-48.729%], and DALYs [-50.467%]. Detailed analysis revealed a reduction in death rates by 61.311% in men and 61.119% in women, while YLLs decreased by 63.115% for men and 63.808% for women. Similarly, DALYs showed a decline of 62.67% for men and 63.25% for women. Prevalence rates fell by 25.417% in women and 29.594% in men, whereas YLDs decreased by 51.148% for women and 49.172% for men. The 2019 data confirmed a per 100,000 population count of 48.78 YLDs, 1020.28 YLLs, and 1069.06 DALYs across both sexes.

Conclusions:
This study illustrates a significant decrease in ischemic heart disease (IHD) metrics in Canada from 1990 to 2019, highlighting notable reductions in mortality, prevalence, and disability rates among both genders. The findings underscore the effectiveness of healthcare improvements and public health initiatives and IHD. Despite these advancements, IHD continues to pose a substantial health challenge, indicating the need for ongoing efforts in medical care, policy-making, and lifestyle modifications to further alleviate the disease's burden in Canada.
Abstract 4117657: Targeting GPR39 for Hypoxia-induced Pulmonary Hypertension in Mice
Authors: Methner Carmen , Liu Lijuan , Kaul Sanjiv
Published: November 2024

Background:
Primary pulmonary arterial hypertension (PAH) is a disease affecting young subjects. It has very poor prognosis and optimal treatment is not available. 15-hydroxyeicosatetraenoic acid (15-HETE), a potent vasoconstrictor, has been implicated in the pathogenesis of PAH. Elevated levels of 15-HETE have been shown to be associated with worse prognosis in patients with PAH. Oral ingestion of 15-HETE leads to development of PAH in rodents. We recently showed that 15-HETE is the endogenous agonist for the G-protein coupled receptor 39 (GPR39) present in vascular smooth muscle cells.

Hypothesis:
We, therefore, hypothesized that global deletion of GPR39 (knock-out [KO] mice) would protect from PAH by removing the receptor through which 15-HETE causes vasoconstriction.

Methods:
Accordingly, 13 wild-type (WT) and 16 KO mice were placed in a hypoxia chamber (10% O
2
). Litter-mate controls (7 WT and 13 KO) were subjected to normoxia (room air, 21% O
2
). At the end of 4 weeks heart rate as well as aortic and right ventricular (RV) pressures were measured (latter using micromanometer-tipped catheter), and the animals were then euthanized for measurement of RV wall thickness and RV size from which RV wall stress was calculated.

Results:
Heart rate and systolic blood pressure were not different between the 4 groups
.
WT hypoxic animals developed PAH with peak RV systolic pressures (RVSP) being significantly higher than normoxic WT and hypoxic WT and hypoxic KO mice. (Figure 1) Similar results were noted for RV end-diastolic pressure (Figure 2) and RV wall stress (Figure 3).

Conclusions:
By deleting GPR39, the target for 15-HETE, we were able to prevent hypoxia induced PAH and RV dysfunction. Pharmacological inhibition of GPR39 may open new frontiers in the treatment of PAH.
Abstract 4117767: Interplay Between ST2 Gene Downregulation and Inflammatory Processes in Hypertrophic Cardiomyopathy
Authors: Sun Huang , Guo Xiying , Cao Xingyu , Diao Haixia , Ang Yan
Published: November 2024

Introduction:
Hypertrophic Cardiomyopathy (HCM) is an inherited heart disease and the pathogenesis of HCM involves genetic mutations, hemodynamic stress, and metabolic factors, with myocardial fibrosis playing a crucial role in severe clinical events. IL-33/ST2 signaling pathway known for its roles in immune response and tissue repair, participates in cardiac protection and anti-cardiac fibrosis in heart failure. The role of ST2 in HCM remains unclear, and IL-33/ST2 pathway and broader inflammatory responses may be critical in HCM.

Hypothesis:
ST2 gene downregulation and dysregulation of inflammatory pathways represent a novel mechanism in HCM.

Methods:
We re-analyzed the raw whole transcriptome sequencing data using a comprehensive bioinformatics pipeline from 9 GEO datasets. After removing low-quality samples, myocardial tissue samples from 109 HCM patients and 210 non-HCM controls were included. HTSeq-count was used to obtain the read count of each gene. Differential expression analyses were conducted using DESeq2. Spearman correlation analysis was performed for ST2 with all other protein-coding genes. Gene set enrichment analysis (GSEA) was performed to explore the biological significance of ST2 related genes. CIBERSORTx was used to estimate the immune cell composition of heart tissues. Additionally, network analyses and statistical correlations were conducted.

Results:
Our analysis identified significant downregulation of the ST2 gene in HCM patients compared to controls (log2FC = -5.0, p = 2.7E-147). In total, 5,180 upregulated and 741 downregulated genes were detected. Additionally, 208 genes were significantly correlated with the expression of ST2. GSEA based on the correlation coefficients revealed a significant increase in immune response, inflammation, and IFN-γ pathway activity, along with a decrease in the expression of genes related to sarcomeric function, cardiac morphogenesis, and metabolism in HCM. Notably, the significant inverse correlation between ST2 expression and regulatory T cells (r = -0.34) and a positive correlation with neutrophils (r = 0.39) suggest that ST2 may modulate immune cell populations in HCM. Pathway analysis indicated ST2's central role in networks involving inflammatory and fibrotic responses.

Conclusion:
The interplay between ST2 and inflammatory pathways may drive myocardial remodeling and fibrosis in HCM. This study paves a new way for investigating pathogenic mechanisms and therapeutic strategies for HCM.
Abstract 4118086: Doxorubicin Induces a Cytotoxic T-cell Inflammatory Response That Contributes to Cardiac Fibrosis and Systolic Dysfunction
Authors: Bayer Abraham , Zambrano Maria , Smolgovsky Sasha , Robbe Zachary , Ariza Abul , kaur Kuljeet , Sawden Machlan , Avery Anne , London Cheryl , Asnani Aarti , Alcaide Pilar
Published: November 2024

Background:
Doxorubicin (DR), the most commonly used chemotherapy, results in dose-dependent cardiotoxicity in part by causing oxidative stress, cardiomyocyte death, and cardiac fibrosis. Whether these elicit a cardiac immune response that contributes to DR cardiomyopathy and could be targeted for cardio-protection is unknown. We
hypothesized
that an aberrant T-cell immune response secondary to cardiac damage contributes to DR cardiomyopathy.

Methods:
We treated wild type (WT) mice and CD8
+
T-cell antigen restricted OTI mice with 5.0 mg/kg of DR or PBS weekly for 4 or 8 weeks and performed targeted antibody depletion of CD8
+
and CD4
+
T-cells. Primary mouse T-cells and cardiac fibroblasts (CFB) were used for mechanistic studies. Whole blood was analyzed by flow cytometry and proteomics in human and canine lymphoma patients before and after DR initiation.

Results:
DR treated mice exhibited cardiac CD8
+
T-cell infiltration alongside hallmarks of DR cardiomyopathy, including declined ejection fraction (EF) measured by echocardiography, cardiac cell death, and fibrosis determined by TUNEL and picrosirius red stain. Cardiac CD8
+
T-cells co-localized with αSMA
+
CFB and had enhanced expression of the degranulation marker CD107a and IFNγ in DR compared to PBS treated mice. DR hearts also showed increased gene and protein expression of the IFNγ inducible chemokines
Cxcl9
and
Cxcl10
. DR resulted in increased circulating CD8
+
T-cells and the frequency of activated CD8
+
cells in the cardiac draining lymph nodes. Targeted antibody depletion of CD8
+
but not CD4
+
T-cells in the onset of DR treatment improved EF and decreased cardiac fibrosis. OTI mice were protected from DR induced EF decline, cardiac T-cell infiltration, and cardiac fibrosis, indicating an antigen-specific CD8
+
T-cell response
.
Mechanistically, DR induced ICAM-1 expression on CFB and ICAM-1 dependent adhesion of activated CD8
+
T-cells, which in turn increased CFB αSMA expression. Contact between CD8
+
T-cells and DR-treated CFB caused CD8
+
T-cell degranulation and Granzyme B release that contributed to CFB activation. Human and canine cancer patients followed longitudinally had increased circulating CD8
+
T-cells after anthracycline treatment, and human plasma levels of CXCL9/CXCL10 correlated with decreased EF post DR.

Conclusion:
Our data demonstrate a novel role for cytotoxic T-cells in DR cardiomyopathy across 3 species, through CXCL9/10-dependent cardiotropism and CD8
+
T-cell dependent fibrosis.
Abstract 4118410: The Effect of Positive Tilt Table Tests on Long QT Syndrome Diagnosis: A Cross-Sectional Perspective
Authors: Mohammadi Abbas , Nikoo Mohammad Hossein , Fatemian Hossein
Published: November 2024

Background:
The tilt table test (TTT) serves as a widely adopted diagnostic tool for evaluating syncope of undetermined etiology, with a positive result often indicative of parasympathetic overstimulation. This excessive activation of the parasympathetic system holds the potential to influence QTc measurement not only through rate modulation but also by impacting potassium ionic channels, given that muscarinic activation inwardly rectifies the K+ current.

Methods:
In this cross-sectional study, 478 patients experiencing syncope of unknown origin underwent evaluation with TTT and 24-hour Holter electrocardiogram monitoring. The Schwartz Score, utilized for diagnosing Long QT syndrome, was computed for all participants. Those with secondary causes of long QT were excluded from the analysis. The association between positive TTT results and Schwartz Score was then examined.

Results:
A total of 478 patients were enrolled in the study, comprising 208 (43.4%) males and 270 (56.4%) females. The mean age of the patients was 42.43±17.979 years. TTT results were positive in 289 (60.46%) patients and negative in 189 (39.54%) patients. Patients with positive TTT results exhibited a significantly higher mean Schwartz Score compared to those with negative results (2.77±0.08 vs. 1.99±0.12) (P<0.001) (Figure 1). The odds ratio for higher Schwartz scores in the presence of positive TTT results was 4.547.

Conclusion:
Caution is warranted when diagnosing long QT syndrome as a potential cause of syncope solely based on the Schwartz Score. This study underscores the necessity for potential modifications to the scoring system, acknowledging the impact of tilt table test outcomes on its predictive accuracy. These findings contribute to the ongoing discourse on refining diagnostic approaches for Long QT syndrome in the context of syncope, promoting more accurate and nuanced clinical decision-making.
Abstract 4118425: Prevalence and Spectrum of Pathogenic Genetic Variants in Korean Cardiomyopathy Patients: Insights from Next-Generation Sequencing
Authors: Park Jinoh , Choi Jung Hyun , Lee Sun Hack , Kim Min Sun , Kim Soo-Jin
Published: November 2024

Background and Aim:
Next-generation sequencing (NGS) is increasingly used to identify genetic variants associated with cardiomyopathies, which can aid in precise diagnosis and management. This study aimed to elucidate the prevalence and spectrum of pathogenic and likely pathogenic genetic variants in a cohort of Korean population diagnosed with different forms of cardiomyopathy.

Methods:
This retrospective study analyzed 122 patients diagnosed with cardiomyopathy at three tertiary hospitals in Korea, all of whom underwent NGS to identify genetic variants between December 2017 and October 2023. Detailed patient records, including clinical diagnoses, imaging results, and family histories, were reviewed to correlate genetic findings with phenotypic data.

Results:
Of the patients, 35 (28.7%) were found to have pathogenic or likely pathogenic variants, and 43 (35.2%) were found to have only variants of uncertain significance. Of the patients with pathogenic or likely pathogenic variants, 16 had hypertrophic cardiomyopathy (HCM) and 16 had dilated cardiomyopathy (DCM), while 3 remained with an uncertain clinical phenotype. In the HCM group, 16 patients exhibited variants predominantly in MYBPC3 (62.5%), followed by MYH7 (12.5%), and others such as TPM1, TNNI3, PRKAG2, and SCN5A (each 6.3%). Additionally, 43.8% of the HCM group had a familial history of sudden cardiac death or cardiomyopathy, with a mean left ventricular mass index (LVMi) of 148.3 ± 70.4 g/m2 and a mean maximal wall thickness of 17.7 ± 3.9 mm. The DCM group showed a different pattern, with TTN variants in 43.8%, LMNA in 18.8%, and others including MYBPC3, RBM20, TTN2, and KCNQ1 (each 6.3%). This group had a mean left ventricular ejection fraction (LVEF) of 27% and a LVMi of 119.7 g/m2.

Conclusion:
Our findings highlight significant genetic diversity in cardiomyopathies among Korean patients, with distinct genetic backgrounds observed in HCM and DCM. The high prevalence of specific mutations such as MYBPC3 in HCM and TTN in DCM could guide targeted genetic testing and personalized treatment strategies in these populations.
Abstract 4118611: Blood Pressure Lowering Effectiveness of Ultrasound Renal Denervation: A Systematic Review and Meta-analysis.
Authors: Guerrero Hernandez Juan Miguel , Nuñez-Gil Ivan , Garcia-Mena Lissette , Palomino Ojeda Cristian
Published: November 2024

Background:
Ultrasound Renal Denervation (uRDN) has emerged as an innovative therapeutic modality for resistant hypertension. However, there is uncertainty regarding the effectiveness of this procedure compared to other renal denervation techniques. We aimed to evaluate the effectiveness of uRDN especially on ambulatory and daytime blood pressure.

Objectives:
given the need for clarity in treatment approaches, our study aimed to evaluate the impact of ultrasound renal denervation particularly on ambulatory and daytime blood pressure in patients with hypertension.

Methods:
we conducted a systematic search of Embase, PubMed, and Cochrane Library databases up to March 2024 to identify randomized controlled trials (RCT) evaluating the effectiveness of uRDN. Statistical analyses were performed using RevMan 6.3 software, utilizing the mean and standard deviation method to calculate mean differences (MD) with a 95% confidence interval (CI).

Results:
four studies were included in the final analysis, involving 648 patients. Ultrasound renal denervation reduced daytime ambulatory SBP (5.12 mmHg; 95% CI -6.07 to -4.16, p = < 0.00001), 24 hours SBP (-4.87 mmHg; 95% CI 6.53 to -3.20, p = < 0.00001), office SBP (-5.03 mmHg; 95% CI -6.27 to -3.79, p = < 0.00001) at 2 months after the procedure and showed a decrease in patient medication at 6 months after the procedure.

Conclusions:
the use of uRND decreases the blood pressure among patients within 2-3 months following the procedure. However, after 6-months of procedure, there is no further significant reduction in blood pressure, although there is a notable decrease in medication. With this data, it is reassuring to conclude that endovascular uRDN using upgraded catheter technologies with the refinement of contemporary procedural techniques has improved the BP-lowering efficacy and safety of RDN during a 3 to 6-month follow-up, with decrease short-term need in medications. The impact of uRDN on the long term deserves further investigation.