bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of atrial fibrillation in clinical outcomes of low gradient aortic stenosis
Authors: Kolluri N , Oguz D , Scott C G , Crestanello J A , Nkomo V T 
Published: October 2022

Abstract

Introduction
Aortic stenosis (AS) is the most common significant valvular heart disease in developed countries. A significant portion of the AS populations have low-gradient AS (LGAS), defined as aortic valve area ≤1.0 cm2 and a trans-aortic mean systolic gradient and peak velocity &lt;40 mmHg and &lt;4 m/s, respectively. LGAS has been shown previously to have worse mortality compared to high-gradient AS (HGAS). Atrial fibrillation (AF) is associated with LGAS and AF has been associated with worse outcomes compared to sinus rhythm (SR) in HGAS. The prognostic impact of AF in LGAS is not well described in previous literature.

Hypothesis
AF will be associated with worse clinical outcomes compared to SR in patients with LGAS.

Methods
3400 patients diagnosed with LGAS from 2010–2020 were retrospectively identified and analyzed. Their electrical rhythm was analyzed at the time of their echocardiographic diagnosis of LGAS and patients were split into 3 separate groups: SR (n=2036), SR with history of AF (n=519), and AF (n=845). After adjustment for age, sex, and Charlson Comorbidity Index (CCI), primary endpoints of overall mortality and cardiac mortality were assessed for patients.

Results
Compared to those with SR, patients with AF and history of AF had significantly higher overall mortality (HR 1.52, p&lt;0.0001 and HR 1.22, p=0.004, respectively) and cardiac mortality (HR 2.05, p&lt;0.0001 and HR 1.37, p=0.03, respectfully) (Figure 1). On further sub group analysis, AF seemed to be most importantly associated with mortality and cardiac mortality in patients with preserved ejection fraction (EF &gt;50%, normal flow LGAS) compared to those patients with reduced EF (classical low-flow LGAS), where there was no statistically significant difference in outcomes between AF and SR (Figure 2).

Conclusions
Atrial fibrillation, compared to sinus rhythm, is associated with worse overall mortality and cardiac mortality in patients with LGAS and preserved EF. Specifically, this association was strongest in patients with preserved EF &gt;50%. Given these findings, the presence of AF should be factored into clinical decision making regarding LGAS management given the higher risk of age, sex, and CCI adjusted overall and cardiac mortality. Further research needs to be done to see if earlier aortic valve intervention in these patients would improve mortality compared to their SR counterparts.

Funding Acknowledgement
Type of funding sources: None.
Clinical characteristics, echocardiographic features and long-term outcomes of patients with ischaemic versus non-ischaemic left ventricular thrombus
Authors: Goh F Q , Sim J J L , Ling R R , Neo V S Q , Ng E S T , Leow A S T , Tan B Y Q , Kong W K F , Sharma V K , Poh K K , Wong R C , Yeo L L L , Chai P , Yeo T C , Sia C H 
Published: October 2022

Abstract

Background
Left ventricular thrombus (LVT) may develop in patients following myocardial infarction (MI), as well as in ischaemic and non-ischaemic cardiomyopathies, and may result in acute ischaemic stroke. Smaller studies comparing LVT associated with ischaemic and non-ischaemic aetiologies only reported 1-year outcomes or focused on specific subpopulations. We aimed to compare the clinical and echocardiographic characteristics and longer-term outcomes in a large population of patients with ischaemic versus non-ischaemic LVT.

Methods
This was a retrospective study of 552 consecutive patients with echocardiographically-identified LVT from March 2011 to January 2021 at a tertiary centre. Ischaemic LVT included LVT associated with MI and ischaemic cardiomyopathy. Non-ischaemic LVT included cases without evidence of ischaemia. Echocardiographic images were interpreted by trained cardiologists. We studied thrombus resolution as well as 5-year rates of ischaemic stroke and all-cause mortality.

Results
Of the 552 patients, mean age was 59.9 years and 84.4% were male. 492 patients had ischaemic LVT and 60 patients had non-ischaemic LVT. Ischaemic LVT was associated with older age (60.4 versus 55.3 years), male sex (86.8% versus 65.0%), smoking (49.2% versus 25.0%) and hyperlipidaemia (54.3% versus 28.3%). Left ventricular ejection fraction (LVEF) was lower in non-ischaemic LVT (28.9% versus 31.9%). LVEF ≤35% was associated with increased mortality in ischaemic LVT (HR 2.11, 95% CI 1.32–3.38). Rates of thrombus resolution, stroke and all-cause mortality were similar in the 2 groups. Anticoagulation was associated with a lower risk of stroke in ischaemic LVT (HR 0.32, 95% CI 0.16–0.66) and lower mortality in both ischaemic (HR 0.44, 95% CI 0.26–0.72) and non-ischaemic LVT (HR 0.14, 95% CI 0.03–0.61).

Conclusion
Patients with ischaemic LVT were more often older, male, smokers and had cardiovascular co-morbidities compared to those with non-ischaemic LVT. Thrombus resolution, stroke and all-cause mortality rates were similar in both groups. Anticoagulation was associated with lower mortality but this needs to be investigated in future prospective studies.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): CHS was supported by the National University of Singapore Yong Loo Lin School of Medicine's Junior Academic Faculty Scheme
Systemic proinflammatory-profibrotic response in aortic stenosis patients with diabetes and its relationship with myocardial remodeling and clinical outcome
Authors: Lee H J , Park C S , Lee S , Park J B , Kim H K , Park S J , Kim Y J , Lee S P 
Published: October 2022

Abstract

Background
It is unclear whether and how diabetes mellitus may aggravate myocardial fibrosis and remodeling in the pressure-overloaded heart. We investigated the impact of diabetes on the prognosis of aortic stenosis (AS) patients and its underlying mechanisms using comprehensive noninvasive imaging studies and plasma proteomics.

Methods
Severe AS patients undergoing both echocardiography and cardiovascular magnetic resonance (CMR) (n=253 of which 66 had diabetes) comprised the imaging cohort. The degree of replacement and diffuse interstitial fibrosis by late gadolinium enhancement (LGE) and extracellular volume fraction (ECV) was quantified using CMR. Plasma samples were analyzed with the multiplex proximity extension assay for 92 proteomic biomarkers in a separate biomarker cohort of severe AS patients (n=100 of which 27 had diabetes).

Results
In the imaging cohort, diabetic patients were older (70.4±6.8 vs. 66.7±10.1 years) and had a higher prevalence of ischemic heart disease (28.8% vs. 9.1%), with more advanced ventricular diastolic dysfunction. On CMR, diabetic patients had increased replacement and diffuse interstitial fibrosis (LGE% 0.3 [0.0–1.6] versus 0.0 [0.0–0.5], p=0.009; ECV% 27.9 [25.7–30.1] versus 26.7 [24.9–28.5], p=0.025) (Figure 1).
Plasma proteomics analysis of the biomarker cohort revealed that 9 proteins (E-selectin, interleukin-1 receptor type 1, interleukin-1 receptor type 2, galectin-4, intercellular adhesion molecule 2, integrin beta-2, galectin-3, growth differentiation factor 15, and cathepsin D) are significantly elevated in diabetic AS patients (Figure 2). Pathway over-representation analyses of the plasma proteomics with Gene Ontology terms indicated that pathways related to inflammatory response and extracellular matrix components were enriched, suggesting that diabetes is associated with systemic effects that evoke proinflammatory and profibrotic response to the pressure-overloaded myocardium.
During follow-up (median 6.3 years [IQR 5.2–7.2]) of the imaging cohort, 232 patients received aortic valve replacement (AVR) with 53 unexpected heart failure admissions or death. Diabetes was a significant predictor of heart failure and death, independent of clinical covariates and AVR (hazard ratio 1.88, 95% confidence interval 1.06–3.31, p=0.030).

Conclusion
Plasma proteomic analyses indicate that diabetes potentiates the systemic proinflammatory and profibrotic milieu in AS patients. These systemic biological changes underlie the increase of myocardial fibrosis, diastolic dysfunction, and worse clinical outcomes in severe AS patients with concomitant diabetes.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): National Research Foundation of Korea
Association of left ventricular myocardial work with all-cause mortality after transcatheter aortic valve implantation
Authors: Nussbaum S , Anwer S , Erhart L , Zurcher D , Walther A L , Winkler N , Rumpf P M , Tsiourantani G , Tanner F C 
Published: October 2022

Abstract

Introduction
Echocardiography is an important modality for peri-interventional assessment of patients undergoing transcatheter aortic valve implantation (TAVI). Left ventricular (LV) global longitudinal strain measures ventricular deformation at end-systole, while myocardial work parameters determine LV deformation throughout the cardiac cycle and correct for afterload.

Aims
To evaluate LV deformation by myocardial work efficiency (GWE) and index (GWI) in early post-TAVI echocardiography and explore its association with all-cause mortality.

Methods
We analyzed 144 patients with severe aortic stenosis and an echocardiography study within two weeks after TAVI. All echocardiographic analyses were performed using GE EchoPac v2.6. Follow-up data was obtained from medical records until September 2021. All-cause mortality was the primary endpoint.

Results
During a median follow-up duration of 625 [IQR: 511.0–769.8] days, 25 (17.5%) patients died. No significant differences in the baseline characteristics were found between non-survivors and survivors. GWE (Figure 1A) and GWI (Figure 1B) were significantly lower among non-survivors than survivors. Both myocardial work parameters differentiated non-survivors from survivors with a cut-off value of −85% for GWE and 990 mmHg% for MWI (Figure 2; both p&lt;0.001).

Conclusions
In this study, GWE and GWI were lower among non-survivors than survivors and were associated with an increased risk of all-cause mortality after TAVI.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss Heart Foundation
Phenotyping patients with aortic stenosis using cluster analysis to determine mortality and suitability for transcatheter aortic valve replacement
Authors: Sen J , Pires D , De Sa A , Ascher D , Wahi S , Marwick T 
Published: October 2022

Abstract

Background
Current classification of aortic stenosis (AS) is based on guideline-recommended echocardiographic criteria. Heterogeneity of patients with AS is increasingly recognised. Clinical and demographic factors in addition to echocardiographic parameters can determine those who may derive the greatest benefit from transcatheter aortic valvular replacement (TAVR) and influence patient outcomes.

Purpose
Our study aims to define distinct AS echocardiographic and clinical phenotypes and to accurately identify patients most likely to die or benefit from TAVR.

Methods
Patients diagnosed with at least mild AS between 2009 and 2021 (pre-TAVR) from a multicentre echocardiographic database at a quaternary referral centre included. Unsupervised clustering analysis was performed using K-means, partitioning around medoids, density-based spatial clustering, hierarchical clustering algorithms on 56 demographic, echocardiographic and clinical variables. Associations between AS clusters and clinical outcomes (all-cause mortality, cardiovascular death, AS-related death), and effect of TAVR on clinical outcomes were assessed using Cox proportional hazards models.

Results
Four AS clusters were identified amongst 2,456 patients with median follow up of 4.7 years (median age: 77 years, male: 66%).
Cluster 1 (n=542) had the lowest aortic valvular area (AVA, mean 0.89 cm2), highest peak velocity (Vmax) (4.3 m/s), mean gradient (45 mmHg), and the most bicuspid valves (12.7%). Cluster 2 (n=827) had 50% women, mostly in sinus rhythm and less severe echo findings. Cluster 3 (n=592) had predominantly males (85%) with a mean AVA of 1.65 cm2 and the most cardiovascular risk factors (hypertension, diabetes, hyperlipidaemia, stable angina, acute coronary syndrome, and atherosclerosis). Cluster 4 (n=495) had the highest left atrial size (mean 32 cm2), the most atrial fibrillation (82%), heart failure (80%), rheumatic heart disease (26%) and chronic kidney disease (55.8%), but only moderate AS (AVA 1.3 cm2, Vmax 3 m/s). All-cause mortality was highest in Cluster 4 (Hazard ratio (HR) 1.57, 95% CI: 1.33–1.85) and AS-related death was highest in Cluster 1 (HR 3.96, 95% CI: 2.61–5.99, Figure 1A). TAVR reduced AS-related death in only Cluster 1 (HR 0.22, 95% CI: 0.05–0.88, p=0.033, Figure 1B).

Conclusions
We demonstrated that phenotypic classification via a combination of demographics, echocardiography and comorbidities can significantly improve management of AS. This personalised approach can be implemented to identify patients most likely to die and most likely to benefit from TAVR.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): National Heart Foundation of Australia (ID: 102578)National Health and Medical Research Council of Australia (ID: 1191044)
To compare efficacy and safety of direct oral anticoagulants in patients with concurrent atrial fibrillation and bioprosthetic heart valve repair or replacement: a systematic review and meta-analysis
Authors: Kaur A , Dhaliwal A , Khandait H , Konje S , Bhatia K , Sohal S , Turagam M , Gwon Y , Mamas M , Dominguez A , Bhatt D , Velagapudi P 
Published: October 2022

Abstract

Background
Use of direct oral anticoagulants (DOACs) is contraindicated in patients with mechanical valves. However data on their use in patients with atrial fibrillation (AF) and bioprosthetic valves (BV) is still limited.

Purpose
To assess the safety and efficacy of DOACs versus Vitamin K antagonist (VKA) in patients with AF after BV repair or replacement.

Methods
We performed a comprehensive review of electronic databases (PubMed, Embase, Scopus, Cochrane) using MeSH terms and keywords for DOACs, AF and BVs from inception through December 2021. Randomized clinical trials (RCT) or observational studies that reported clinical outcomes comparing DOACs versus VKA in patients with AF and BVs were eligible for inclusion. Ten articles were reviewed for full text. Primary outcome was a composite of all cause stroke or systemic embolic event.
Secondary outcomes included major bleeding and all-cause mortality. Subgroup analysis stratified by study design was performed. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using Mantel-Haenszel method with DerSimonian-Laird estimator for tau2 for random effects model.
Interstudy heterogeneity was assessed using the Higgins I 2 value. All statistical analysis was performed using RevMan 5.4.1 software.

Results
Ten studies (5 RCTs, 5 observational studies) with a total of 5,333 patients (DOACs n=2434; VKA n=2899) were included. Aortic, mitral and mixed BV repair or replacement were 74.2%, 25.6% and 0.02% respectively. The mean age was 72.6±11.9 years. The mean follow-up was 15.7±12.9 months. Type of DOACs included apixaban (n=553, 22.7%), rivaroxaban (n=893, 36.7%), dabigatran (n=151, 6.2%) and edoxaban (n=837, 34.4%). There was no significant difference in primary outcome of stroke or systemic embolic event (RR: 0.79; CI: 0.56–1.11; p&gt;0.05; I2=12%) or secondary outcomes of major bleeding (RR: 0.84; CI: 0.64–1.11; p&gt;0.05; I2=45%), and all-cause mortality (RR: 0.84; CI: 0.64–1.11; p&gt;0.05; I2=29%) between DOACs compared with VKA.

Conclusion
In patients with AF and BV, DOACs are non-inferior to VKA for risk of stroke or systemic embolism, major bleeding, and all-cause mortality. Thus, DOACs can serve as a viable alternative to VKAs which have a narrow therapeutic index, multiple drug interactions, and require frequent monitoring.

Funding Acknowledgement
Type of funding sources: None.
Comparing direct oral anticoagulants versus vitamin K antagonist in patients with atrial fibrillation after transcatheter aortic valve replacement: an updated meta-analysis
Authors: Dhaliwal A , Kaur A , Konje S , Bhatia K , Sohal S , Rawal H , Turagam M , Gwon Y , Mamas M , Dominguez A , Bhatt D , Velagapudi P 
Published: October 2022

Abstract

Background
Oral anticoagulation therapy is indicated for patients undergoing transcatheter aortic valve replacement (TAVR) with concomitant or new onset atrial fibrillation (AF). However the data on optimal anticoagulation regimen in this population remains unclear.

Purpose
To compare efficacy and safety outcomes of direct oral anticoagulants (DOACs) versus Vitamin K antagonists (VKA) in patients with AF post TAVR.

Methods
We searched electronic databases (PubMed, Embase, Scopus, Cochrane) from inception to February28th, 2022 using MeSH terms and keywords for DOACs, AF or TAVR. Primary outcome of interest was all-cause stroke or systemic embolic event. Secondary safety outcomes were major bleeding and all-cause mortality. Pooled risk ratio (RR) and 95% confidence interval (CI) were calculated using a random-effects model. Interstudy heterogeneity was assessed using the Higgins I 2 value. All statistical analysis were performed using RevMan 5.4.1 software.

Results
We identified five eligible studies (1RCT, 4 observational) including 3694 patients (DOAC n=1581, VKA n=2113). The mean age was 81.4±0.9 years. The mean follow-up was 12.4±14.3 months. Type of DOACs included apixaban (n=394, 24.9%), rivaroxaban (n=354, 22.4%), dabigatran (n=119, 7.5%) and edoxaban (n=714, 45.2%).There was no significant difference in primary outcome of stroke or systemic embolic event (RR: 0.93; CI: 0.65–1.33; p&gt;0.05; I2=5%), or in secondary outcomes of major bleeding (RR: 1.02; CI: 0.78–1.34; p&gt;0.05; I2=44%) and all-cause mortality (RR: 0.87; CI: 0.59–1.27; p&gt;0.05; I2=56%) between DOACs and VKA groups.

Conclusion
This meta-analysis shows anticoagulation therapy with DOACs has similar safety and efficacy outcomes compared to VKA in patients with AF undergoing TAVR.

Funding Acknowledgement
Type of funding sources: None.
Do valve type and post-ballooning affect transprosthetic gradients in patients undergoing transcatheter aortic valve-in-valve procedure?
Authors: Fusini L , Muratori M , Tamborini G , Gripari P , Ghulam Ali S , Cefalu' C , Fabbiocchi F , Galli S , Roberto M , Agrifoglio M , Pontone G , Bartorelli A L , Pepi M 
Published: October 2022

Abstract

Introduction
Valve-in-Valve transcatheter aortic valve implantation (ViV-TAVI) is an appealing treatment option for patients with degenerated aortic bioprosthetic valves. However, high post-procedural transprosthetic gradients are very common after ViV-TAVI than after TAVI for native-valve aortic stenosis.

Aim
We sought to evaluate transprosthetic gradients (ΔP) and hemodynamic outcome in patients undergoing ViV-TAVI according to valve type and balloon post-dilation (balloon-expandable vs self-expandable with and without post-dilation).

Material and methods
We retrospectively analyzed 111 patients undergoing ViV-TAVI. A balloon-expandable valve was used in 35 patients (32%, Group 1), a self-expandable valve in 76 cases of which 39 (35%, Group 2) without balloon post-dilation and 37 (33%, Group 3) with balloon post-dilation. A comprehensive transthoracic echocardiography (TTE) was performed in all patients at baseline, at discharge and at 6-months follow-up.

Results
Successful ViV-TAVI was performed in 110 patients (99%). Baseline peak and mean ΔP, left ventricular volumes, ejection fraction, and pulmonary artery systolic pressure were similar among groups. A significant improvement in all echocardiographic parameters was observed in all groups over time (Table 1). In particular, a significant reduction in postprocedural gradients was observed at discharge and at 6-months follow-up compared to baseline in all groups. Immediately after ViV-TAVI procedure, the lowest value of mean ΔP was observed in Group 3 (12±7 mmHg) compared to both Group 1 (20±9 mmHg) and Group 2 (17±8 mmHg, p=0.001). This result was confirmed at 6-months follow-up (p=0.012). Rate of small valve size (≤23 mm) implanted was similar among groups (Group 1: 78%, Group 2: 60%, Group 3: 62%, p=0.123). Similar 1-year all-cause mortality was observed among groups (9%, 13%, 0%, respectively, p=0.135).

Conclusions
In patients with failed surgical aortic prosthesis, ViV-TAVI is an effective option and is associated with sustained improved hemodynamics in all patients. Anyway, the choice of prosthetic valve type and implantation technique are relevant on residual transprosthetic gradients and should be taken into account for a better long-term outcome.

Funding Acknowledgement
Type of funding sources: None.
Yield of echocardiographic screening of first-degree relatives of children with bicuspid aortic valve
Authors: Norsk J , Sillesen A S , Raja A A , Paerregaard M , Dannesbo S , Hansson V M , Kock T , Voegg R O B , Vejlstrup N , Iversen K , Bundgaard H 
Published: October 2022

Abstract

Background
Bicuspid aortic valve (BAV) is the most common congenital heart defect, affecting 0.8% of new-borns. BAV is associated with valve dysfunction, as well as an increased risk of aortopathy. The prevalence of BAV in first-degree relatives of symptomatic BAV patients, is reported to be 5–10%. First-degree relatives also have an increased risk of aortic dilatation, independently of aortic valve morphology.

Purpose
The purpose of the study was to determine the prevalence of BAV, associated valve dysfunction and aortopathy in first-degree relatives to children diagnosed with BAV neonatally in a population-based study.

Methods
Between April 2016 and October 2018 all expecting parents at three major maternity centres were offered inclusion in a large-scale population study with focus on congenital heart disease (N≥25,000). A total of 197 children, in 196 families, were diagnosed with BAV. All first-degree relatives, including half-siblings, were offered inclusion in the follow-up study with standardized transthoracic echocardiography. Adults were also examined with transoesophageal echocardiography. Aorta diameters were measured at the AV annulus, sinuses of Valsalva, sino-tubolare junction and in the proximal ascending aorta. Aortic dilatation in children were defined as any aortic root or ascending aorta diameter ≥2 standard deviations (SD) from the expected mean, calculated as z-score using formulas from the Paediatric Heart Network Echocardiogram Database. In adults, aortic dilatation was defined as aortic root and/or ascending aorta diameters indexed to body surface area (BSA) exceeding normal reference values established by the European Association of Cardiovascular Imaging.

Results
In total, 352 first-degree relatives (242 adults [35.3 years SD 5.5] and 110 children [4.5 years, SD 3.5] were included. BAV was diagnosed in 24 relatives (6.8%). BAV could not be conclusively ruled out in 52 relatives (14.8%), who are awaiting further examination with transoesophageal echocardiography. Dilatation of the aortic root was observed in 8 adult relatives and in 17 children (7.1%). Aortic valve regurgitation was observed in 23 relatives (6.5%). In total 58 relatives (16.2%) were diagnosed with either BAV, dilated aorta, or aortic regurgitation.

Conclusion
One in fifteen first-degree relatives to children diagnosed with BAV neonatally, also had BAV, corresponding to &gt;8 fold increase in prevalence compared with the background population. One in six relatives had BAV, dilated aorta, or aortic regurgitation. These findings are of importance for family-screening programs of BAV.

Funding Acknowledgement
Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Danish Children's Heart Association