bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of serum lipoprotein(a) levels in bioprosthetic aortic valve degeneration
Authors: Farina J , Chao C J , Pereyra M , Roarke M , Said E , Barry T , Alsidawi S , Sell-Dottin K , Sweeney J P , Fortuin D , Ayoub C , Lester S , Oh J K , Arsanjani R , Marcotte F 
Published: November 2023

Abstract

Introduction
Lipoprotein(a) [Lp(a)] is associated with an increased incidence of aortic stenosis. Bioprosthetic aortic valve degeneration and native aortic stenosis share similar pathological mechanisms. Evidence regarding the role of serum Lp(a) concentrations in bioprosthetic aortic valve degeneration is lacking.

Purpose
To evaluate the association between serum Lp(a) concentrations and bioprosthetic aortic valve degeneration.

Methods
In this retrospective multicenter study, consecutive patients who underwent a bioprosthetic aortic valve replacement between Jan-2010 and Dec-2020 and had a preoperatory serum Lp(a) measurement were included. A baseline transthoracic echocardiography (TTE) was performed following the aortic valve replacement and a follow-up TTE was performed at least 24 months after the baseline study to determine the presence of bioprosthetic valve degeneration. Significant degeneration was defined as: (a) an increase &gt;10 mmHg in mean bioprosthetic aortic valve gradient from baseline status + a decrease in effective orifice area + a decrease in Doppler velocity index + exclusion of clinically thrombotic leaflet thickening, OR (b) new moderate or severe prosthetic aortic regurgitation (if the main component was periprosthetic, then it was not considered). Lp(a) concentrations were compared between patients with and without degeneration and regression analysis was conducted to investigate the association between bioprosthetic valve degeneration and Lp(a) levels.

Results
In total, 211 cases were included (mean age 74.1 ±9.4 years, 72.0% males, 29.9% transcatheter aortic valve replacements) (Figure 1). Median time between baseline and follow-up TTE was 5.0 (IQR 3.7) years. Bioprostheses degeneration was observed in 33 (15.6%) patients at follow-up. Median serum levels of Lp(a) were significantly higher in the patients affected by degeneration versus non-affected cases (50.0 vs 15.7 mg/dl, p=0.003). In the regression analysis, high Lp(a) levels (≥30 mg/dl) were associated with degeneration both in a univariate analysis (OR 4.8, 95%CI 2.2-10.9, p&lt;0.001) and multivariate analysis adjusted by other risk factors for bioprostheses degeneration (age, sex, hypertension, smoking, patient prosthesis mismatch, creatinine levels, and body surface area) (OR 5.2, 95%CI 2.1-12.8, p&lt;0.001).

Conclusion
Serum Lp(a) concentrations seem to be a risk factor for bioprosthetic aortic valve degeneration (Figure 2). There is an increasing need to accurately predict bioprosthetic aortic valve degeneration and to develop novel methods and treatments to increase their durability. Prospective studies are needed to confirm these findings and to investigate whether lowering Lp(a) could slow bioprostheses degradation.Population characteristicsLp(a) and bioprostheses degeneration
The expression of selected microRNAs enables identification of patients with functional atrial tricuspid regurgitation. New insights into TR pathophysiology
Authors: Hinojar Baydes R , Moreno-Gomez-Toledano R , Gonzalez-Gomez A , Garcia-Martin A , Rivas S , Sanroman M , Fernandez-Golfin C , Zaragoza C , Zamorano J L 
Published: November 2023

Abstract

Background
Functional tricuspid regurgitation (FTR) is a powerful and independent predictor of patients’ morbidity and mortality. Atrial FTR (A-FTR) is a recently defined phenotype associated with permanent atrial fibrillation. In A-FTR, the underlying pathophysiological factors behind tricuspid annulus (TA) enlargement and the subsequent development of atrial TRF are still unclear, given that despite RA enlargement, a significant fraction of patients presenting long-term persistent atrial fibrillation (AF) will fail to develop significant TR during follow-up. Different microRNAs (miRNAs) have been studied as regulators and diagnostic biomarkers in mitral and aortic valve disease, but no study has been focus on FTR so far.

Purpose
Our current study aims to identify and validate a selection of circulating miRNAs as potential regulators of A-FTR

Methods
Consecutive patients with severe A-FTR and patients with non-valvular permanent atrial fibrillation (AF without TR) undergoing anticoagulant therapy were prospectively recruited. The experimental design included a first screening phase in 16 subjects ((8 A-FTR and 8 AF controls) to identify candidate miRNAs differentially expressed in a miRNA qPCR panel containing 192 specific miRNAs, and a second validation phase in which selected miRNAs were screened for further validation by qRT-PCR in 80 additional patients (40 TR and 40 AF).

Results
The initial screening revealed 16 differentially expressed miRNAs in atrial FTR vs. AF subjects matched by age, gender and atrial dimensions (figure 1). In the validation phase, the expression of miR-29b-3p, miR-152-3p, miR-30e-5p, miR-186-5p, miR-126-5p and miR-148a-3p (p&lt;0.05) were significantly different in A-FTR compared to AF.
Among all, miR-186-5p, miR-152-3p and miR-30e-5p yielded the highest predictive values for the detection of A-FTR with areas under the curve of 0.96 (0.92-0.99), 0.90 (0.83-0.97) and 0.87 (0.79-0.95) respectively (p&lt;0,001 for all, figure 2).

Conclusions
Patients with atrial FTR exhibited different miRNA fingerprint compared to patients with permanent AF without TR but similar degree of atrial enlargement. Additionally, our study identified 3 novel miRNAs as potential diagnostic biomarkers of A-FTR: miR-186-5p, miR-152-3p and miR-30e-5p which excellent accuracy. Whether the differential expression of such miRNAs precedes or follows the development of FTR or the subsequent leaflet adaptation or growth, will be further explored in future studies.Table and volcano plot of miRNAmiRNA ROC curves in A-FTR
Introducing a novel ex-vivo calcification model for human aortic valves
Authors: El Ouraoui M , Wu H W , Palmen M , Hjortnaes J , Jukema J W , Ajmone Marsan N , Kruithof B P T 
Published: November 2023

Abstract

Background
Aortic stenosis (AS) is a narrowing of the aortic valve opening due to calcification and thickening of the leaflets. There are currently no effective pharmacological treatments for AS, and surgery or percutaneous interventions are the only therapeutic options. The cellular and molecular mechanisms underlying AS are complex and not fully understood due to the complexity and multi-factorial nature of AS and the absence of suitable test systems. In the current in-vitro models to study valvular calcification, isolated valvular interstitial cells (VICs) are cultured in 2D and in the absence of its native extracellular matrix. In addition, other cell types like valvular endothelial cells (VECs) and macrophages, which have been shown to impact the behavior of VICs, are absent.

Purpose
Our goal is to establish an ex-vivo calcification model for human aortic valves which maintains the original valve structure and cellular components.

Methods
Diseased aortic valves were harvested from patients undergoing aortic valve replacement. A 5mm x 7mm piece of this aortic valve tissue was dissected and embedded in agarose, then cut into 300 mm slices using a vibratome (Figure 1). In this way VICs remained in their valvular environment allowing the most native response of VICs to stimuli. The use of multiple slices from a single patient ensured proper internal controls. The slices were placed on a cell culture insert and cultured for 14 days. To induce calcification, the slices were cultured in the presence of 3 mM phosphate (n=23). As a control, valvular slices were cultured in the absence of 3mM phosphate (n=12). To validate if the calcification induced in the ex vivo culture system can be molecularly modulated the glucocorticoid dexamethasone was added to cultures containing 3mM phosphate (n=8). The slices were assessed for the presence of calcification using Alizarin Red staining and for the presence of osteogenic and inflammatory markers using (Immuno) histochemistry.

Results
In the presence of 3mM Phosphate, 74% of the slices demonstrated calcification, whereas no calcification was observed in all slices cultured without 3mM Phosphate (p&lt;0.0001; Figure 2a). Furthermore, osteogenic genes such as Runx and alkaline phosphatase-1, as well as the inflammation marker NFkb were expressed in the calcified slices (Figure 2a). Dexamethason inhibited the calcification in the slices treated with 3 mM phosphate (Figure 2b).

Conclusions
We developed a novel ex-vivo calcification model for human aortic valves in which the initiation and progression of aortic valve calcification can be studied. In addition, the calcification can be modulated at a molecular level providing a unique opportunity to uncover the molecular signaling pathways involved in valvular calcification and to test compounds facilitating pre-clinical translational studies.Figure 1Figure 2
5-year outcome comparison among aortic stenosis patients underwent transcatheter aortic valve implantation with or without permanent pacemaker
Authors: Liu D , Hu K , Sokalski V , Lau K , Lengenfelder B , Ertl G , Frantz S , Nordbeck P 
Published: November 2023

Abstract

Background
The occurrence of atrioventricular block due to local damage to the atrioventricular and infranodul tissues, requiring permanent pacemaker (PMI), is one of major complications of transcatheter aortic valve implantation (TAVI). Previous studies show conflicting results regarding impact of PMI on outcomes in TAVI patients.

Purpose
The purpose of this study was to compare the 5-year survival rate and CV mortality of TAVI patients without PM, patients with PMI before TAVI, and patients underwent PMI after TAVI. In addition, we also assessed the influence of early- and new-generation prostheses on the prevalence of PMI after TAVI and related outcomes.

Methods
A total of 778 patients who underwent TAVI in our hospital between 2009 and 2021 were included in this study (mean age 81.4±5.7 years, 50.9% male). Patients were divided into 3 groups: no PMI (n=614), PMI before TAVI (n=76), and PMI after TAVI (n=88). Primary endpoints were defined as all-cause death and cardiovascular (CV) death up to 5 years after TAVI.

Results
The prevalence of PMI after and before TAVI were 11.3% (88/778) and 9.8% (76/778), respectively. During a median follow-up time of 30 (18-49) months, the survival rate at 1, 2, and 5 years was 90.7%, 83.1%, and 69.2% in the no PMI group, 92.0%, 86.4%, and 76.1% in the PMI after TAVI group, and 89.5%, 86.8%, and 75.0% in the PMI before TAVI group. There was no significant difference in survival rate and CV mortality among the 3 groups (P&gt;0.05, Figure 1).
Of 778 patients, 251 (32.3%) patients received early-generation prostheses (Edwards SAPIEN or SAPIEN XT), 527 (67.7%) patients received new-generation prostheses (Edwards SAPIEN 3, SAPIEN 3 Ultra, or ACURATE neo). As compared with TAVI patients who received early-generation prostheses, the prevalence of PMI after TAVI was significantly higher (13.3% vs. 7.2%, P=0.012), while the 5-year all-cause mortality (20.7% vs. 47.8%, P&lt;0.001) or CV mortality (14.8% vs. 31.1%, P&lt;0.001) was significantly lower in those who received new-generation prostheses. TAVI patients with new-generation prostheses was associated with a better 5-year survival rate as compared with early-generation prostheses, irrespective of age, sex, and PMI (hazard ratio=0.654, 95% CI 0.500-0.855, P=0.002, Figure 2).
New-generation prostheses (relative risk=1.784, 95% CI=1.089-2.922, P=0.022) and greater prostheses diameter (per 1 mm increase, relative risk=1.144, 95% CI=1.017-1.287, P=0.025) were independently associated with increased risk of PMI after TAVI.

Conclusion
There is no significant difference in survival rate and CV mortality between patients who underwent PMI after or before TAVI and those who did not. New-generation prostheses is related to higher risk of PMI and better 5-year survival in TAVI patients.Figure 1Figure 2
Sex influence in the etiology and long-term prognosis of significant tricuspid regurgitation
Authors: Alegre Garcia G , Rodriguez Capitan J , Segovia Reyes J , Soler Gonzalez M , Marquez Camas P , Carmona Carmona J , Garcia Rodriguez L , Rodriguez Cordoba A , Gonzalez Aguado N , Diaz Exposito A , Angullo Gomez M , Luna Morales M , Palma Marti L , Gomez Doblas J J , Jimenez Navarro M 
Published: November 2023

Abstract

Introduction
It is widely recognized that significant tricuspid regurgitation is more frequent in women, but there is practically no information on the prognostic differences according to sex in the different etiological groups. Our objective was to analyze the impact of sex on the frequency and prognosis according to the etiological group.

Methods
Retrospective multicenter study that included consecutive patients with significant tricuspid regurgitation (moderate-severe degree or greater) diagnosed between 2002 and 2017 in 3 referral hospitals. We retrospectively classified the patients according to sex and type of tricuspid regurgitation based on clinical and echocardiographic data. The type of tricuspid regurgitation was defined in the first step that met the established criteria, differentiating between congenital and organic etiology (structural tricuspid disease), left valve disease (mild mitral stenosis or another at least moderate valve disease), ventricular dysfunction, associated with pulmonary hypertension, or atrial (by not fulfilling any of the above and presenting atrial dilatation). Subsequently, we compared prevalence and mortality from all causes according to sex for each etiology.

Results
A total of 778 patients were included, 71% women. The median follow-up was 40.2 months (interquartile range 11.2-80.9). When comparing the frequency of each etiological group according to sex, we only found significant differences in tricuspid regurgitation associated with ventricular dysfunction (9.7% men vs 3.1% women, p &lt;0.001). In terms of survival, we found significant differences with higher survival in women with organic etiologies (92.4 months in women vs 54.1 in men, p=0.021), secondary to valve disease (79.6 months in women vs 54.1 in men, p&lt;0.001) or pulmonary hypertension (58.9 months in women vs 28.7 in men, p=0.01). In the rest of the etiological groups, differences were not statistically significant. Figure shows Kaplan-Meier survival curves based on each etiology for each gender.

Conclusions
Significant tricuspid regurgitation was observed in a higher percentage of women (71%). Regarding the frequency for each type of tricuspid regurgitation, only significant differences were found in the etiology secondary to ventricular dysfunction, being more frequent in men. Regarding the survival curves, significant differences were found with greater survival in the group of women in organic tricuspid regurgitation, secondary to valve disease and secondary to pulmonary hypertension.Kaplan Meier survival curves
Predictors of major adverse cardiovascular events in patients with severe aortic stenosis awaiting aortic valve replacement
Authors: Fialho I , Mateus C , Passos M , Lima-Lopes J , Gerardo F , Miranda I , Madeira M , Marques M , Augusto J , Santos M , Baptista S , Farto-E-Abreu P , Morais C , Neves J 
Published: November 2023

Abstract

Background
Severe aortic stenosis (AS) is a progressive disease associated with an increased risk of heart failure (HF) and mortality if left untreated. Aortic valve replacement (AVR) is the treatment of choice. However, it is not always immediately available, and some patients have experienced major cardiovascular events (MACE) while waiting for AVR. The identification of reliable predictors of MACE can help clinicians risk-stratify severe AS patients and tailor their management to prevent adverse outcomes.

Purpose
We aimed to evaluate predictors of MACE in real-world patients with severe AS who are waiting for AVR.

Methods
We conducted a prospective registry of consecutive patients discussed in the Heart Team meeting of a single centre, between January 2018 and June 2021. All patients with severe AS were included. For each patient we recorded demographic data, blood test results, echocardiogram parameters, and MACEs (a composite of death, HF hospitalization, non-fatal acute myocardial infarction, and non-fatal stroke). MACEs were recorded until the patient underwent AVR. The median follow-up time was 187 days (IQR 59-352).

Results
Overall, 235 patients were included (mean age 76.7±10.7 years, 48.1% male). Previous HF hospitalization (HR 2.77, 95% CI 1.66 – 4.62), HF symptoms with New York Heart Association (NHYA) class ≥3 (HR 2.64, 95% CI 1.58–4.39), and the presence of left ventricular dysfunction (HR 2.86, 95% CI 1.71–4.78) were independent predictors of MACE (Figure 1). The presence of pulmonary hypertension (HR 2.16, 95CI 1.27–3.66), but not right ventricular dysfunction (HR 2.34, 95CI 0.45–12.08, p=0.31), was associated with MACE until AVR. Concomitant moderate to severe tricuspid regurgitation (HR 10.88, 95CI 1.41–83.94) and moderate to severe mitral regurgitation (HR 5.91, 95CI 1.50–23.34) were associated with a worse prognosis, even when adjusted for other relevant MACE predictors. Laboratory data such as serum creatinine, haemoglobin, and NT-proBNP levels were not associated with the occurrence of MACE in this population (HR 1.00). Past medical history of hypertension, diabetes, chronic kidney disease, and chronic obstructive pulmonary disease were not associated with MACE. Age was a limited predictor of MACE (HR 1.03, 95CI 1.00 – 1.06, p=0.04).

Conclusion
Previous HF hospitalization, NYHA class ≥3 symptoms, left ventricular dysfunction, and pulmonary hypertension were independent predictors of MACE in patients with severe AS awaiting AVR. Additionally, concomitant moderate to severe tricuspid and mitral regurgitation were also associated with worse prognosis. These findings may help identify those at high risk of MACE who would benefit most from early intervention and close monitoring.
Degenerative or rheumatic: after all, what is the most prevalent etiology of mitral regurgitation in developing countries?
Authors: Vicente Pereira Lipari L F , Fernandes J R C , Ziotti S V , Nazzetta D C , Tessari F C , Pessoa R S , Haussauer Jr H V , Rosa V E E , Pires L J N T , Accorsi T A D , Lopes M P , De Santis A S , Spina G S , Sampaio R O , Tarasoutchi F 
Published: November 2023

Abstract

Introduction
Mitral regurgitation (MR) is the most prevalent valve disease in Europe, mostly degenerative. In Brazil, on the other hand, there are few recent epidemiological data and previous studies show a higher prevalence of rheumatic disease.
However, a change in the epidemiological profile of valve disease has recently been observed, largely due to the increase in life expectancy and decrease in the incidence of rheumatic fever.
This study aims to evaluate patients with MR in a tertiary hospital in Brazil, emphasizing the etiological analysis.

Methods
Patients with moderate or severe MR on echocardiogram performed between 07/01/2018 and 06/30/2020 in a Brazilian Cardiology hospital were retrospectively evaluated, including 2,017 cases. Clinical data (age, sex, symptoms and comorbidities) were analyzed, in addition to complementary tests, such as electrocardiogram and echocardiogram.

Results
A total of 2,017 cases were included, of which 1,966 (97.5%) had severe MR. The mean age was 65 years and 52% were female.
In this cohort, 924 patients (45.8%) had primary MR, while 1093 (54.2%) had secondary causes. Among the primary etiologies (N=1093), degenerative was the most prevalent, responding to 51.3% (n=474), followed by rheumatic disease, present in 34.5% of the patients (n=319). The other primary etiologies observed were calcific (94 patients = 4.7%), infective endocarditis (15 patients = 0.7%) and congenital (10 patients = 0.5%).
In the comparative analysis between degenerative and rheumatic MR, a statistically significant difference was observed in age and gender. Patients diagnosed with rheumatic MR were younger - mean age: 58 years (standard deviation 49-68) compared to 67 years in patients with degenerative mitral disease (standard deviation 58-76 years). Most patients with rheumatic disease were female (N=255, 79.9%), with percentages almost twice as high as those observed in degenerative MR (N=192 - 40.5%).
Secondary causes (N=1,093) were composed of dilated etiology in 859 patients (78.6%), ischemic (140 patients - 12.8%) and atrial functional (55 patients - 5%).

Conclusion
In agreement with the current epidemiological change in valvular heart disease, we could also observe an important change in the etiology of MR in Brazil, with a reduction in the burden of rheumatic disease and greater expressiveness of mitral prolapse.
Derivation and validation of risk score to predict mortality or heart failure-related hospitalisation based on clinical and echocardiographic factors in moderate or severe aortic stenosis
Authors: Sen J , Wahi S , Marwick T 
Published: November 2023

Abstract

Background
Multiple studies from echocardiographic databases have investigated association between moderate or severe aortic stenosis (AS) and poor cardiovascular outcomes. However, outcomes and treatment response are also dependent on the clinical picture.

Purpose
To improve prognostication and management response of patients with moderate or severe AS by development and validation of a new risk score algorithm that combines clinical and echocardiographic parameters to predict 5-year all-cause mortality or heart failure (HF)-related hospitalisation.

Methods
3,452 consecutive patients diagnosed with moderate or severe AS [aortic valvular area &lt;1.5 cm2, peak velocity &gt; 3 m/s or dimensionless severity index &lt; 1.5] were included in this observational cohort study. The least absolute shrinkage and selection operator (LASSO) and logistic regression was used to develop a risk score. This score provided an estimated probability of 5-year composite outcomes of all-cause mortality or HF-related hospitalisation in moderate or severe AS patients. The risk score was then validated with a geographically separate independent test cohort (n=1,788).

Results
Among 3,452 patients with at least moderate AS with median follow up of 7.3 years, 41 variables were important predictive parameters to be included in risk score (Figure 1). The most significant independent predictors were non-cardiac (Table 1). Areas under the receiver operating characteristic curves for the score were 0.80 (95% CI: 0.79-0.82) in the training set and 0.76 (95% CI: 0.73-0.80) in the test dataset, demonstrating good discrimination.

Conclusions
A risk score algorithm based on demographics, echocardiography, and clinical features was developed and validated with over 1000 patients. This risk score can be useful to predict outcomes beyond conventional echocardiographic parameters in patients with moderate or severe AS.Fig 1.Score vs 5-yr composite outcomesTable 1.OR for predictors in risk score