bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostically distinct phenotypes of metabolic health beyond obesity in aortic stenosis
Authors: Chew N , Zhang A , Kong G , Lee K L , Ng C H , Chong B , Ngiam N , Loh P H , Kuntjoro I , Wong R , Kong W , Yeo T C , Poh K K 
Published: October 2022

Abstract

Background
Whilst current evidence are in favour of metabolic health and non-obesity in the reduction of incident cardiovascular disease, little is known regarding the prognosis across the metabolic phenotypes once cardiovascular disease occurs. This study examined the prognosis of patients with significant aortic stenosis (AS) based on the presence of metabolic health and obesity.

Methods
This retrospective cohort on consecutive patients presenting with moderate-to-severe AS to a tertiary hospital between 2010 and 2015. Patients were allocated into 4 groups based on obesity and metabolic health: metabolically healthy obese (MHO), metabolically healthy non-obese (MHNO), metabolically unhealthy obese (MUO) and metabolically unhealthy non-obese (MUNO). Metabolic health was defined in accordance to Program Adult Treatment Panel III criteria. The primary outcome was all-cause mortality. Cox regression examined independent associations between mortality and metabolic phenotypes, adjusting for aortic valve area, ejection fraction, age, sex, chronic kidney disease and AVR as a time-dependent covariate.

Results
Of 727 patients, the majority (51.6%) were MUNO, followed by MUO (32.7%), MHNO (11.4%), and MHO (4.3%). MHNO had the highest mortality (43.0%), followed by the MUNO (37.5%), MUO (30.0%) and MHO (6.9%) groups (p=0.001). Compared to MHNO, MHO (HR 0.159, 95% CI 0.038–0.668, p=0.012) and MUO (HR 0.614, 95% CI 0.403–0.937, p=0.024) were independently associated with lower all-cause mortality rates, after adjusting for confounders. In obese patients, metabolic health had favourable survival compared to metabolically unhealthy (p=0.015), but this protective impact of metabolic health was not observed in overweight or normal weight individuals. Obesity had favourable survival compared to overweight and normal weight, in both metabolically health (p=0.002) and unhealthy (p=0.007) patients,

Conclusion
MHO patients with AS have the most favourable prognosis whilst the seemingly healthy MHNO group had the worst survival. There should be a paradigm shift towards prioritising metabolic health rather than weight reduction in patients with significant AS.

Funding Acknowledgement
Type of funding sources: None.
Albuminuria predicts worsening renal function at 1 month after transcatheter aortic valve implantation
Authors: Tobe A , Tanaka A , Tokuda Y , Shirai Y , Yamamoto T , Tokoro M , Furusawa K , Ishii H , Usui A , Murohara T 
Published: October 2022

Abstract

Background
Worsening renal function (WRF) at short term after transcatheter aortic valve replacement (TAVR) is reportedly associated with subsequent poor clinical outcomes. We previously reported preoperative albuminuria predicted mid-term WRF after TAVR. However, the impact of albuminuria on short-term WRF after TAVR is unknown.

Methods
Overall, 206 patients who underwent TAVR for severe aortic stenosis were investigated retrospectively. Patients were divided into two groups according to the preoperative urinary albumin-to-creatinine ratio (ACR): high (ACR ≥30 mg/g) and low (ACR &lt;30 mg/g). The incidence of 1-month WRF, defined as a decrease in estimated glomerular filtration rate (eGFR) ≥10% from baseline after TAVR, was investigated.

Results
More than half of the examined patients (n=106/206 [51.5%]) had a high ACR. Patients with a high ACR had significantly lower eGFR at baseline than those with a low ACR (49.3 [32.5–57.8] vs. 51.4 [37.7–65.8] mL/min/1.73 m2, p=0.03). Patients with a high ACR more frequently had acute kidney injury (8.5% vs. 1.0%, p=0.01) and 1-month WRF than those with a low ACR (29.2% vs. 12.0%, p=0.002). Multivariate analysis showed a high ACR was independently associated with 1-month WRF (odds ratio, 3.72; 95% confidence interval, 1.72–8.08; p&lt;0.001). Meanwhile, eGFR &lt;60 mL/min/1.73 m2 was not an independent predictor of 1-month WRF (odds ratio, 0.48; 95% confidence interval, 0.22–1.04, p=0.06).

Conclusions
Patients with preoperative albuminuria (ACR ≥30 mg/g) more frequently developed AKI and 1-month WRF after TAVR. Albuminuria was independently associated with 1-month WRF, suggesting albuminuria to be a universal predictor of deterioration of renal function at various time points.

Funding Acknowledgement
Type of funding sources: None.
Prevalence and prognostic implications of discordant grading and flow-gradient patterns in moderate aortic stenosis
Authors: Stassen J , Ewe S , Singh G K , Amanullah M R , Hirasawa K , Butcher S , Sin K Y K , Ding Z P , Sia C H , Chew N W S , Kong W K F , Poh K K , Delgado V , Marsan N A , Bax J J B 
Published: October 2022

Abstract

Background
The prognostic implications of discordant grading in severe aortic stenosis (AS) are well known. However, the prevalence of different flow-gradient patterns and their prognostic implications in moderate AS are unknown.

Purpose
To investigate the occurrence and prognostic implications of different flow-gradient patterns in patients with moderate AS.

Methods
Patients with moderate AS (aortic valve area 1.0–1.5 cm2) were divided in 4 groups, based on transvalvular mean gradient (MG), stroke volume index (SVi) and left ventricular ejection fraction (LVEF): concordant moderate AS (MG ≥20 mmHg); normal-flow, low-gradient discordant moderate AS (MG &lt;20 mmHg, SVi ≥35 ml/m2); “classical” low-flow, low-gradient discordant moderate AS (MG &lt;20 mmHg, SVi &lt;35 ml/m2 and LVEF &lt;50%) and “paradoxical” low-flow, low-gradient discordant moderate AS (MG &lt;20 mmHg, SVi &lt;35 ml/m2 and LVEF ≥50%). The primary endpoint was all-cause mortality.

Results
Of 1974 patients (age 73±10 years, 51% men) with moderate AS, 788 (40%) had discordant grading. Patients with discordant grading showed significantly higher mortality rates than patients with concordant grading (p&lt;0.001), even in the subgroup of patients having preserved LVEF (p=0.028) or preserved SVi (p=0.002). Of the patients with discordant grading, 71% had normal-flow, low-gradient moderate AS, 14% had “classical” low-flow, low-gradient moderate AS, and 14% had “paradoxical” low-flow, low-gradient moderate AS (Figure 1). Patients with normal-flow, low-gradient moderate AS, “classical” low-flow, low-gradient moderate AS, and “paradoxical” low-flow, low-gradient moderate AS had worse survival rates than patients with concordant grading (p&lt;0.001) (Figure 2). On multivariable analysis “paradoxical” low-flow, low-gradient (HR: 1.533; 95% CI: 1.133–2.075; p=0.006) and “classical” low-flow, low-gradient (HR: 1.926; 95% CI: 1.442–2.572; p&lt;0.001) but not normal-flow, low-gradient moderate AS were independently associated with all-cause mortality.

Conclusion
Discordant grading is frequently (40%) observed in patients with moderate AS. Low-flow, low-gradient patterns account for an important proportion of the discordant cases and are associated with increased mortality. These findings underline the need for better phenotyping patients with discordant moderate AS.

Funding Acknowledgement
Type of funding sources: Other. Main funding source(s): ESC Training Grant App000064741
Hypoattenuated leaflet thickening is associated with silent brain injury
Authors: Nagy A I , Bartykowszki A , Apor A , Suhai F , Varga A , Manouras A , Szilveszter B , Panajotu A , Jermendy A , Turani M , Molnar L , Papp R , Merkely B , Maurovich-Horvat P 
Published: October 2022

Abstract

Background
The association between hypoattenuated leaflet thickening (HALT) following transcatheter aortic valve implantation (TAVI) and stroke remains contradictory. Whether HALT carries an increased risk of subclinical brain injury (SBI) has not been investigated.

Purpose
We investigated whether HALT is associated with SBI on MRI. Furthermore, we assessed whether post-TAVR SBI impacts the patients' cognition and outcome.

Methods
153 patients undergoing TAVR were prospectively enrolled. Brain MRI was performed shortly post-TAVR and 6 months (6M) later to assess the occurrence of acute silent cerebral ischaemic lesions (SCIL) and chronic white matter hyperintensities (WMH). HALT was screened by cardiac CT angiography 6M post-TAVR. Neurocognitive evaluation was performed before, shortly after and 6M following TAVR.

Results
At 6M, 115 patients had diagnostic CTA and 10 had HALT. HALT status, baseline and follow-up MRIs were available in 91 cases. At 6M, new SCIL was evident in 16%, new WMH in 66%. New WMH was more frequent (100% vs 62%; p=0.047) with higher median volume (319 vs 50 mm3; p=0.039) among HALT-patients. In uni- and multivariate analysis, HALT was associated with new WMH volume (beta: 0.72; 95% CI: 0.2–1.39; p=0.009).
The patients' cognitive trajectory from pre-TAVR to 6M showed significant association with the 6M SCIL volume (beta: −4.69; 95% CI: −9.13 to −027; p=0.038), but was not related to the presence or volume of new WMH. During a 3.1-year follow-up neither HALT, nor the related WMH burden was related with increased mortality (HALT HR: 0.86, 95% CI: 0,202–3,687; p=0.84; new WMH HR: 1.09; 95% CI: 0,701–1,680; p=0.71).

Conclusions
6M post-TAVR, HALT was linked with greater WMH burden, but did not carry an increased risk of cognitive decline or mortality over a 3.1-year follow-up.

Funding Acknowledgement
Type of funding sources: Public Institution(s). Main funding source(s): János Bolyai Scholarship of the Hungarian Academy of Sciences
Incidence and predictors of transthyretin cardiac amyloidosis in patients with degenerative aortic stenosis
Authors: Abadie B , Held M , Puri R , Krishnaswamy A , Yun J , Hanna M , Reed G , Kapadia S , Jaber W 
Published: October 2022

Abstract

Background
The approval of new therapies for treating transthyretin (TTR) cardiac amyloidosis has led to significant interest in identifying patients at high risk for this disease. Investigators have identified a correlation between severe degenerative aortic stenosis (AS) and TTR cardiac amyloidosis in older patients, with several studies finding up to 20% of patients who undergo transcatheter aortic valve replacement (TAVR) having TTR cardiac amyloidosis. These initial TAVR studies were conducted when TAVR was performed almost exclusively in high surgical risk populations. Therefore, the true incidence of TTR cardiac amyloidosis in an all-comers with severe degenerative AS referred for TAVR is unknown.

Purpose
To identify the true burden of TTR cardiac amyloidosis in a contemporary population of severe degenerative AS undergoing TAVR screening.

Methods
All patients ≥70 years with severe native valve degenerative AS seen in a multidisciplinary valve clinic were referred for technetium-99m pyrophosphate cardiac scintigraphy (PYP scan) for evaluation of cardiac amyloidosis. Diagnosis was made via combination of planar grade and heart to contralateral lung ratio, confirmed on single positron emission computed tomography/computed tomography (SPECT/CT). Patients with a positive PYP scan were referred to a heart failure clinic where they underwent testing for AL amyloidosis.

Results
Over a 10 month period, 247 patients seen in valve clinic underwent a PYP scan. Of this cohort, 203 patients ultimately underwent TAVR, 15 surgical aortic valve replacement, and 2 balloon valvuloplasty with 27 patients having not yet undergone a procedure. The positivity rate was 4% (10/247) with 1 patient having an equivocal result. The patients with a positive PYP scan had higher rate of low-flow low-gradient (LFLG) AS (64% vs 29%, p=0.006) and classical LFLG AS (27% vs 8%, p=0.02). Echocardiographic measures associated with a positive PYP scan include a lower global longitudinal strain (−10.0% vs −16.1%, p=0.008), lower average e' (4.5 vs 6.5, p=0.003), and an increased E/A ratio (1.8 vs 1.1, p=0.018).

Conclusions
The incidence of TTR amyloidosis in a contemporary, severe AS population ≥70 years undergoing TAVR screening appears much lower than previously described in the literature. Echocardiographic traits may be able to predict which patients with severe AS should undergo evaluation for TTR cardiac amyloidosis.

Funding Acknowledgement
Type of funding sources: None.
Leukocyte extracellular vesicles as the first biomarkers to predict outcomes in patients undergoing percutaneous aortic valve replacement
Authors: Gasecka A , Van Der Pol E , Kochman J , Huczek Z , Wilimski R , Grabowski M , Filipiak K J , Nieuwland R 
Published: October 2022

Abstract

Background
Transcatheter aortic valve implantation (TAVI) is a novel treatment for aortic stenosis (AS), associated with better outcomes than surgical aortic valve replacement in high-risk patients. However, up to 29% of patients annually experience major adverse cardiac and cerebrovascular events (MACCE) after TAVI. MACCE are mostly caused by atherothrombosis, i.e. formation of platelet aggregates (thrombi) on ruptured atherosclerotic plaques. Because platelets release extracellular vesicles (EVs) during thrombus formation, we hypothesized that EVs are a biomarker to predict MACCE after TAVI.

Methods
This was a multicentre, prospective clinical study. Venous blood was collected 1 day before TAVI and at hospital discharge (n=57, mean age 79.9+6.4 years, 49% male). Flow cytometry (Apogee A60-Micro) was used to determine concentrations of plasma EVs labelled with markers for endothelial cells (CD146), leukocytes (CD45), platelets and megakaryocytes (CD61) and activated platelets (CD62p). Analysis of flow cytometry data files was fully automated. Rosetta Calibration (Exometry) and Flow-SR were used for diameter and refractive index determination. Wilcoxon signed rank test was used to compare EV concentrations before and after TAVI. The predictive value of EVs for MACCE and the cut-offs were calculated using a receiver operating characteristic curve. Logistic regression model incorporating EV concentrations and clinical characteristics was used to determine the best model for MACCE prediction.

Results
Concentrations of EVs from activated platelets increased, whereas from leukocytes decreased after TAVI, compared to the measurement before (p=0.06, p=0.04, respectively). Among 55 patients discharged from the hospital, 14 patients experienced MACCE (25%) during the median 15 months of observation. Increased baseline concentration of leukocyte EVs and male gender were the only independent predictors of MACCE in multivariable analysis (OR 4.01, 95% CI 0.77–23.77, p=0.04 for leukocyte EVs; OR 6.84, 95% CI 1.41–33.17, p=0.03 for male gender).

Conclusions
We identified increased concentrations of leukocyte EVs as new candidate biomarkers to predict MACCE after TAVI. Leukocyte EVs could be used to augment risk stratification in this patient cohort. The next step is to validate the clinical applicability of EVs to predict post-TAVI MACCE in a large-scale clinical trial.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Young Investigator Grant of the Polish Society of Cardiology
Early intervention versus conservative management of asymptomatic severe aortic stenosis: a systematic review and meta-analysis
Authors: Costa G , Cardoso J , Goncalves L , Teixeira R 
Published: October 2022

Abstract

Background
Aortic stenosis (AS) is the most common valvular disease in developed countries. However, the specific timing of intervention for asymptomatic patients with severe AS remains controversial.

Purpose
To compare the outcomes of early aortic valve replacement (AVR) versus watchful waiting (WW) in asymptomatic patients with AS.

Methods
We systematically searched PubMed, Embase and Cochrane databases, in December 2021, for both interventional or observational studies comparing early AVR with WW in the treatment of asymptomatic severe AS. Random-effects meta-analysis was performed.

Results
Thirteen studies were included in which two were randomised clinical trials. A total of 4,679 patients were included, providing a 1,268 pooled death events (327 in early AVR and 941 in WW). Our meta-analysis showed a significantly lower all-cause mortality for the early-AVR compared with WW group, although with a moderate amount of heterogeneity between studies in the magnitude of the effect (pooled odds ratio [OR], 0.41; 95% confidence interval [CI] 0.34, 0.50, P&lt;0.01; I2=60%). An early surgery strategy displayed a significantly lower cardiovascular mortality (pooled OR, 0.33; 95% CI [0.19, 0.56], P&lt;0.01; I 2=64%) and heart failure hospitalisations (pooled OR 0.19; 95% CI [0.10, 0.39], P&lt;0.01, I2=7%). However, both groups had similar rates of stroke (pooled OR 1.30; 95% CI [0.73, 2.29], P=0.36, I2=0%) and myocardial infarction (pooled OR 0.49; 95% CI [0.19, 1.27], P=0.14, I2=0%).

Conclusions
Our pooled data suggest that an early-AVR strategy is preferable for asymptomatic patients with severe AS.

Funding Acknowledgement
Type of funding sources: None.
Early aortic valve replacement improves exercise capacity in truly asymptomatic patients with severe aortic stenosis
Authors: Banovic M , Boskovic N , Bojanic M , Nedeljkovic I , Jovanovic M , Penicka M , Bartunek J 
Published: October 2022

Abstract

Background
Exercise capacity is a strong predictor of morbidity and mortality overall. In severe aortic stenosis (AS) ustained pressure overload during watchful waiting is associated with LV structural and functional deterioration and impaired clinical outcome both pre- and post aortic valve replacement (AVR). The effect of early surgical aortic valve replacement (SAVR) in asymptomatic patients with severe AS and normal left ventricular function on exercise capacity in unknown.

Aim
We investigated whether the early surgical AVR in truly asymptomatic patients with severe aortic stenosis and normal LVEF improves the exercise capacity.

Methods
This is a sub-analysis or the AVATAR trial (NCT02436655), which is international prospective randomized controlled trial that evaluated the safety and efficacy of early SAVR in the treatment of asymptomatic patients with severe AS, according to common criteria (valve area ≤1 cm2 with aortic jet velocity &gt;4 m/s or a mean transaortic gradient ≥40 mm Hg), and with normal left ventricular function. Patients underwent cardiopulmonary exercise testing (supine bicycle, ramp protocol, 15 W/min) at the baseline and 12 months following the randomization. Patients who had positive exercise testing at baseline visit were excluded. We compared the value of workload (in WATs), VO2 max, VO2 AT, VE/VCO2 and PETCO2 slope at the inclusion and at 12 months.

Results
Total of 157 patients (mean age, 67 years; 57% men) were randomly allocated to early surgery (n=78) or conservative treatment (n=79). Mean LVEF and Vmax in early surgery and conservative treatment group were 70% and 4.5m/s and 69% and 4.5m/s, respectively. After 12 months in patients with conservative treatment there was a slight decrease in the values of workload, VO2 max, VO2 AT, VE/VCO2 and PETCO2 slope, but without statistical significance. However operated patients showed a significant increase in workload (115.4±38.4 watts at 12 months vs 104.8±42.2 at inclusion, p=0.038) and VO2 max (19.7±6.8 at 12 months vs 16.2±5.4 at the inclusion, p=0.048), while there was slight increase in the values of VO2 AT, VEVCO2 and PETCO2 but without statistical significance.

Conclusion
Early SAVR improve the functional capacity in asymptomatic patients with severe aortic stenosis and normal left ventricular ejection fraction

Funding Acknowledgement
Type of funding sources: None.
Single centre experience in transcatheter mitral valve implantation: valve in valve, valve in ring and valve in MAC
Authors: Alvarez H A , Joner M , Xhepa E , Erlebach M , Schunkert E , Kastrati A , Lange R , Ruge H 
Published: October 2022

Abstract

Background
Mitral valve replacement/repeair procedures increase year. Redo procedure and severely calcified mitral ring are risk factors for high mortality. Transmitral valve implantation (TMVI) represents a less invasive procedure in high-risk population, but still with increase mortality. We seek to evaluate a one single center experience the safety and efficacy in patients undergoing transeptal TMVI with degenerated bioprostheses or ring and high surgical risk candidates with heavily mitral anulus calcification (MAC).

Methods
One-single centre, retrospective observational analysis, included patientes from 2012 to 2021 treated with a valve in mitral position. Valve-in-valve (ViV), valve in ring (ViR) and valve in MAC were included. Periprocedural, and in-hospital complications were documented and analyzed.

Results
Seventy-nine patients were included. ViV was done in 59 patients, ViR in 8 patients, ViMAC in 10 patients and Valve in native anatomy in 2 patients. Baseline, procedural characteristics and complications and reported on table. No significant statistical difference was observed in baseline characteristics. STS Score was 7.77+5.37 in ViV patients, 5.77+3.02 in ViR patients, 8.70+4.47 in ViMAC patients and 6.29+0.55 in native anatomy (p=0.634). Procedural success was observed in 96.6% of ViV, 87.5% in ViR, 80% in ViMAC and 100% in native anatomy (p=0.124). Procedural related death was observed only in one ViV patient. Conversion to surgery and valve embolisation was observed in one ViV (1.7%) and ViR (12.5%) patient, respectively. In-hospital death was observed in 5.1% ViV patients, 12.5% ViR, 20% ViMAC and none of the native anatomy patients.

Conclusion
TMVI is still challenging but feasible and safe. Carefully planning and heart team approach in experiences centers is important to address this issue and reduce as much as possible any complication.

Funding Acknowledgement
Type of funding sources: None.