bluuebunny/crossref_metadata_2025_split huggingface dataset:
4069From first in man transcatheter aortic valve implantation, a 15-year experience
Authors: Avinee G , Durand E , Levesque T , Litzler P Y , Dacher J N , Bauer F , Tron C , Cribier A , Eltchaninoff H 
Published: October 2019

Abstract

Background
Since the first-in-man transcatheter aortic valve implantation (TAVI) performed in 2002, the number of procedures has dramatically increased. However, long-term data regarding outcome and valve durability remain poor.

Purpose
We aimed to evaluate the evolution of 30-day outcomes over years and long-term mortality and valve durability after TAVI.

Methods
All consecutive patients presenting with severe symptomatic aortic stenosis treated by TAVI in our center were included prospectively. Clinical and echocardiographic follow-up was performed at 30 days and annually thereafter. Survival curves were constructed using Kaplan-Meier analysis. We also evaluated valve durability according to the European standardized definition of structural valve deterioration.

Results
Between 2002 and 2018, 1530 consecutive patients underwent TAVI including 1285 (84.0%) patients via a femoral approach. A balloon-expandable transcatheter heart valve was predominantly used (1421 patients; 92.9%). The annual transfemoral approach rate increased progressively to reach 93.3%. Age of patients remained stable over time with a global mean age of 83.7±6.5 years old. Logistic EuroSCORE decreased from 49.2±8.2% to 14.3±8.6% (p<0.0001). Thirty-day mortality dramatically decreased below 3% since 2015 and was 0% in 2018. Similarly, major vascular complications decreased from 50.0% in the first year to less than 1% since 2017 (p=0.001). The length of hospital-stay progressively shortened up to a median of 2 days in 2018. The Kaplan-Meier survival estimation was 82.3%, 60.3%, 33.0%; 11.7% and 8.9% respectively at 1, 3, 5, 8 and 10 years. On long-term follow-up the mean aortic gradient remained unchanged (Figure), and only five patients presented a severe prosthetic valve deterioration. Among them, four patients successfully benefited from a valve in valve TAVI procedure. The competing risk analysis at 10 years estimates risk for severe and moderate-or-severe valve deterioration of 1.9±0.9% and 4.3±1.3% respectively.
TEE mean transaortic gradient

Conclusions
Long-term (up to 10 years) follow-up of our large pioneer series of patients treated by TAVI shows a dramatic improvement of outcomes and no warning signs of valve deterioration suggesting very encouraging valve durability, using predominantly, a balloon expandable prosthesis. Further studies are warranted to study valve durability after TAVI before extension to lower risk patients.
4078Lipoprotein(a) and clinical outcomes in patients after revascularization of peripheral arteries
Authors: Tmoyan N A , Ezhov M V , Afanasieva O I , Klesareva E A , Afanasieva M I , Pokrovsky S N 
Published: October 2019

Abstract

Background
Randomized trials have proved the reduction of cardiovascular events due to LDL-cholesterol level decrease. However, despite high-intensity statin therapy, there is a residual risk, that could be associated with lipoprotein(a) [Lp(a)]. It has been shown that there is an association between elevated Lp(a) level and cardiovascular outcomes in patients with coronary heart disease. Data about the role of Lp(a) in the development of cardiovascular events after revascularization of peripheral arteries are scarce.

Purpose
To evaluate the relationship of Lp(a) level with cardiovascular outcomes after revascularization of carotid and lower limbs arteries.

Methods
The study included 258 patients with severe carotid and/or lower extremity artery disease, who underwent successful elective revascularization. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The secondary endpoint was the composite of transitory ischaemic attack, limb amputation, hospitalization for unstable angina, or revascularization surgery.

Results
During 36 months follow-up 29 (11%) primary and 113 (44%) secondary endpoints were registered. It was noted greater rate of primary (21 [8%] vs. 8 [3%]; hazard ratio [HR], 3.0; 95% confidence interval [CI] 1.5–6.3; p<0.01) and secondary endpoints (72 [28%] vs. 41 (16%], HR, 2.5; 95% CI 1.7–3.7; p<0.01) in patients with elevated Lp(a) level (≥30 mg/dl) compared to patients with Lp(a) <30 mg/dl (Picture). Multivariable-adjusted Cox regression analysis revealed that Lp(a) was independently associated with incidence of cardiovascular outcomes.

Conclusions
Patients with peripheral artery diseases have a high risk of cardiovascular events and the level of Lp(a) ≥30 mg/dl is an independent predictor of cardiovascular events in prospective 3-year follow-up after revascularization of carotid and lower limbs arteries.
4090Maximum standardized uptake value of pericardial fat for prediction of ventricular arrhythmias in patients with cardiac sarcoidosis
Authors: Ishii Y , Yufu K , Kira S , Miyoshi M , Abe I , Oniki T , Kondo H , Saito S , Fukui A , Okada N , Akioka H , Shinohara T , Teshima Y , Nakagawa M , Takahashi N 
Published: October 2019

Abstract

Background
Cardiac sarcoidosis is a cause of epicarditis and sustained life-threatening ventricular arrhythmias. These arrhythmias occasionally arise from epicardial. Positron emission tomogramphy-comututed tomography (PET-CT) is useful for diagnosis with sarcoidosis. However, the usefulness for prediction of ventricular arrhythmias in patients with cardiac sarcoidosis is unknown.

Objective
We hypothesized that the evaluation of pericardial fat inflammation could identify high-risk sarcoidosis patients for ventricular arrhythmias.

Methods
We enrolled 20 consecutive patients with cardiac sarcoidosis performed PET-CT between August 2016 and December 2018. In each case, we measured the maximum standardized uptake value (SUVmax) of pericardial fat around the left atrium, both ventricules, atrioventricular groove, and left main coronary.

Results
Seven patients experienced ventricular tachycardia (VT) or ventricular fibrillation (VF). VT/VF patients had significantly more complete right bundle branch block (P=0.035), larger left atrial dimension (P=0.021), larger left ventricular end-diastolic dimension (P=0.005), lower ejection fraction (P=0.007), and higher E/e' (P=0.004). SUVmax of pericardial fat in the roof of left atrium (LA) and left ventricular (LV) with VT/VF patients were significantly higher than non-VT/VF patients (LA: 1.63 vs 1.32, P=0.0311; LV: 1.84 vs 1.26, P=0.045). The cut-off values of SUVmax derived from the ROC curve in the roof of LA and LV are 1.47 and 1.59 respectively. The Kaplan Meire estimator showed that high SUVmax patients in the roof of LA had significantly more detection of NSVT.

Conclusions
Our results suggest the relationship between SUVmax and VT/VF occurrence in patients with cardiac sarcoidosis. The evaluateon of SUVmax may be useful for VT/VF risk stratification.
4092Magnetic resonance imaging of Fabry disease cardiomyopathy in patients receiving oral chaperone therapy
Authors: Muentze J , Gensler D , Cairns T , Maniuc O , Oder D , Wanner C , Frantz S , Nordbeck P 
Published: October 2019

Abstract

Background
Fabry disease is a lysosomal storage disorder with multiple organ involvement. Renal and cardiac symptoms can lead to dialysis and myocardial hypertrophy with fibrosis, responsible for heart failure with preserved ejection fraction (HFpEF). Enzyme replacement therapy (ERT) is available for all patients with Fabry disease since 2001, requiring infusions every other week. Since May 2016, the chaperone migalastat represents a novel form of specific therapy as the first oral therapy available for certain Fabry patients. Through this molecule the function of the mutated enzyme α-galactosidase A can be restored. Recent trials have shown positive cardiac effects of chaperone therapy using echocardiography; however, MRI investigations further evaluating these findings are not available yet.

Objective
To evaluate cardiac effects of migalastat therapy in patients with amenable α-galactosidase A mutations in the prospective monocentric HEAL-FABRY registry (NCT03362164).

Methods and results
Comprehensive clinical investigations including serial MRI were conducted at baseline before initiation of migalastat therapy and at least one year thereafter in all patients without contraindications such as pacemakers or ICDs. Out of 29 patients included in the study (mean age at start of therapy 52.8±14 years, total range 20–74 years), until then 12 patients with MRI data completed the 1-year follow-up. At 1 year, enzyme activity in leucocytes increased from 0.06 to 0.21 nmol/min/mg protein (p=0.001). Distinctive changes over time were observed not only in diastolic but also systolic parameters. The systolic myocardial mass index was reduced by 2.39% (p=0.10). In the AHA segment number 5, most important for classification of severe myocardial damage in Fabry patients, late gadolinium enhancement was reduced by 8.58% in all 5 patients with verified progressive fibrosis (p=0.14). One patient stopped migalastat therapy due to personal reasons. No significant side effects were observed.
Analysis of LGE (systolic phase)

Conclusion
These preliminary MRI data show positive effects of migalastat therapy in patients with Fabry disease and cardiac involvement. Compared to echocardiography, MRI has the potential to allow for comprehensive additional analyses regarding both cardiac morphology and function.
4093Beyond global longitudinal strain: early impairment of apical function after antracyclines therapy
Authors: Manganaro R , Longobardo L , Cusma' Piccione M , Bava A , Costantino R , Guarneri M C , Ferrazzo G , Vaccaro V , Laterra G , Aliibani L , Daffina' M G , Di Nunzio D , Altavilla G , Carerj S , Zito C 
Published: October 2019

Abstract

Purpose
To confirm GLS diagnostic sensitivity as parameter for the evaluation of LV systolic function in women with breast cancer who underwent chemotherapy including anthracyclines and to identify a pattern of decreased 2D speckle tracking regional longitudinal strain through the analysis of polar maps obtained with AFI technology.

Methods
We enrolled 60 female patients (age with 56.5±12 years) with breast cancer before the beginning of chemotherapy. The study protocol included clinical examination, ECG with QTc calculation, lab test (BNP and troponin I) and echocardiography with TDI and speckle tracking analysis (STI), that were performed before the beginning of the chemotherapy (basal) and after 3, 6 and 12 months. Echocardiography evaluation included the following parameters: LV end-diastolic and end-systolic volumes, LV ejection fraction (EF), average TDI S' at the mitral annulus, Global Longitudinal Strain (GLS), regional longitudinal strain, E/A ratio, E/E' ratio and sPAP. For each patient we analyzed the bull's eye maps before the beginning of the therapy (basal value) and when GLS showed the lowest values during the FU (FU value), to identify the pattern of regional longitudinal strain alterations. We compared basal and FU strain values for each of the 17 LV segments and the difference between them (delta) was calculated according to the formula [(FU LS –basal LS, (%)].

Results
During the FU, systolic blood pressure, systolic pulse pressure and BNP values increased from the basal assessment to the 3 and 6 months FU. Similarly, a progressive worsening of GLS values has been observed (basal −20.4±2.6%, 3 months FU −18.2±2.5%, 6 months FU −17.7±2.9, 12 months FU −17.6±3, p value <0.001). Through the analysis of polar maps, we observed that regional strain values worsened significantly in all the LV segments but the most evident impairment was reported in the apical cap (−22.8±3.9 vs −17.1±3.8; p<0.001, Δ=−5,78%) and in the apical segment of the anterior interventricular septum (−23.4±4.5 vs −17±6.3; p<0.001, Δ=−6,2%), as reported in Figure.

Conclusion
GLS is able to identify LV systolic dysfunction that EF is not able to detect. However, since that it describes the global function of LV, GLS could result as normal (18–20%) when strain impairment of some LV segments is counterbalanced by the compensatory strain increase of other segments, determining an misdiagnosis of myocardial damage. Regional strain and particularly the Δ-strain, seem to suggest that anthracyclines induce a damage more evident in the apical cap and in the apical segment of the interventricular septum and this pattern could be typical in these patients. Thus, polar maps analysis could be provide additional information about cardiac damage in this population.
4120Anti-tumor activity of a nanoliposomal anti-PCSK9 vaccine in BALB/c mice bearing 4T1 breast cancer
Authors: Momtazi-Borojeni A A , Nik M E , Jaafari M R , Banach M , Sahebkar A 
Published: October 2019

Abstract

Background
Although suppression of proprotein convertase subtilisin/kexin 9 (PCSK9) has been known to be an effective lipid-lowering approach, the efficacy and safety of PCSK9 inhibitors in non-cardiovascular diseases, particularly cancer, are yet unknown.

Purpose
The present study aimed to evaluate effect of PCSK9 inhibition on cancer behavior and endpoints in mice model of breast tumor, using a nanoliposomal anti-PCSK9 vaccine.

Methods
The nanoliposomal anti-PCSK9 vaccine was formulated via conjugation of immunogenic PCSK9 peptide to the surface of nanoliposome particles by using DSPE-PEG-Maleimide lipid. The prepared vaccine was adsorbed to Alum adjuvant (L-IFPTA+) and immunized subcutaneously four times with a bi-weekly interval in BALB/c mice.Two weeks after the last immunization, the vaccinated and unvaccinated mice were subcutaneously inoculated with 4T1 breast carcinoma cells into the right flank. After tumor mass was palpable, the mice were randomly divided into four groups and subjected to different treatment protocols: (1) PBS (untreated control), (2) vaccine group, (3) the combination group which involved vaccinated tumor-bearing mice who received single tail vein injection of Doxil®, and (4) Doxil® (positive control) group which involved unvaccinated tumor-bearing mice who received Doxil®. To evaluate therapeutic efficacy, mouse body weight, tumor size, and survival were monitored every other day for 60 days.

Results
The vaccine was found to efficiently generate specific antibodies against PCSK9 in BALB/c mice, and thereby reduce concentration of plasma PCSK9 and impede its function. Evaluation of tumor size demonstrated that time to reach endpoint (TTE) of the vaccine, combination, Doxil, and control groups was 47±10, 57±4, 60±4, 39±9 days, respectively. Rate of tumor growth in vaccine, combination, and Doxil groups was decreased by 21, 48, 53%, respectively, when compared with the control group (Figure). In the vaccine group life span was increased by 4.2%, while the survival in the combination and Doxil group was significantly lower than the control group.
Figure 1. Anti-PCSK9 vaccine efficacy.

Conclusions
Our results reveal that PCSK9 inhibition not only exerts no harmful effects, but also can moderately improve breast cancer behavior in animal model.
4181Prognosis of patients with mid-range left ventricular ejection fraction treated with PCI: insight from the global leaders study
Authors: Chichareon P , Modolo R , Kogame N , Tomaniak M , Teiger E , Quintella E F , Almeida M , Hamm C , Steg G , Juni P , Vranckx P , Valgimigli M , Windecker S , Onuma Y , Serruys P W 
Published: October 2019

Abstract

Background
Heart failure with mid-range ejection fraction (left ventricular ejection fraction between 40 to 49%) was introduced in the 2016 European Society of Cardiology guidelines for heart failure. The prognosis of the mid-range of left ventricular ejection fraction (LVEF) was less well assessed in patients treated with percutaneous coronary intervention (PCI).

Purpose
We aimed to assess the 2-year outcomes of patients with mid-range ejection fraction (LVEF between 40 to 49%) after PCI compared with reduced LVEF (<40%) and preserved LVEF (≥50) in the GLOBAL LEADERS study.

Methods
The GLOBAL LEADERS study was a multicenter, randomized trial comparing the efficacy and safety of two antiplatelet strategies in all-comers patients undergoing PCI with biolimus-A9 eluting stent.
Patients with available information of LVEF were eligible in the present analysis. Patients were classified according to their LVEF into three groups; preserved (LVEF ≥50), mid-range (LVEF 40–49%) and reduced (LVEF <40%) left ventricular ejection fraction. Clinical outcomes at 2 years after PCI were compared among three groups in the multivariable Cox regression analysis.
The primary outcome of present study was all-cause mortality at 2 years after PCI. The secondary outcomes were patient-oriented composite endpoint (POCE). Individual components of the composite endpoint, definite or probable stent thrombosis and bleeding academic research consortium (BARC) type 3 or 5 were also reported.

Results
Out of 15968 patients included in the GLOBAL LEADERS study, information of LVEF was available in 15008 patients (93.99%); 12,128 patients (80.81%) were in the group of preserved LVEF, 1,737 patients (11.57%) were in the mid-range LVEF group and 1,143 patients (7.62%) were in the reduced LVEF group.
The risk of all-cause mortality and POCE at 2 years were significantly different among the three groups. In an adjusted model, compared with the group of preserved LVEF, the hazard ratio for the all-cause mortality at 2 years rose from 1.89 (95% CI, 1.46–2.45) to 3.72 (95% CI, 2.95–4.70) in the group of mid-range and reduced LVEF respectively. Similar rises were observed for the POCE at 2 years from 1.27 (95% CI, 1.11–1.44) in the group of mid-range LVEF to 1.63 (95% CI, 1.42–1.87) in the group of reduced LVEF.
The risk of stroke, myocardial infarction, and definite or probable stent thrombosis in patients with mid-range LVEF was not different from patients with reduced LVEF (see figure). A similar risk of revascularization was observed among the three groups.
Outcomes among three LVEF categories

Conclusion
Patients with mid-range LVEF undergoing PCI had a different prognosis from patients with reduced LVEF and preserved LVEF in term of survival and composite ischemic endpoints at 2 years.
4223Income level and the prevalence of ischemic coronary heart disease in a low-mid-income country with high social inequalities. Influence of neighborhood walkability
Authors: Cerci R J , Baena C P , Vitola J V , Cerci J J , Pereira Neto C C , Masukawa M , Gracia A P W , Silvello L L , Prado P , Hino A A F , Fernades Silva M M 
Published: October 2019

Abstract

Background
The greater burden of coronary heart disease (CHD) comes from low-middle income countries (LMIC). Socioeconomic status, environmental factors, poor access to healthcare, physical inactivity and excess consumption of carbohydrates, have explained part of this burden. However, the association between income level and CHD in LMIC with marked social inequalities is not fully understood, and whether there is influence of neighborhood walkability (walking-promoting potential of the residential built environment for daily activities) in this association requires further investigation.

Purpose
To investigate to what level income is associated with ischemic CHD in a LMIC with great social inequalities and to explore the potential role of neighborhood walkability in this association.

Methods
We evaluated patients referred for myocardial perfusion imaging with SPECT (SPECT-MPI) from February 2010 to August 2017 at a reference imaging center in our city, Brazil. Each patient was georeferenced and the exposure variable was the average income in Brazilian currency (Real) per month, from the patient's residential census block. Ischemic CHD was defined by an abnormal myocardial perfusion (summed stress score >3) during a SPECT-MPI study. Walkability was measured by a score combining street connectivity, residential density, commercial density and mixed land use. We used mixed effects models to evaluate the association between income level and ischemic CHD, adjusted for potential confounders, and performed a mediation analysis to measure the percentage of this association mediated by walkability.

Results
From 26,810 participants, those living in the lowest tertile income neighborhoods were younger (61±12 vs 63±13 vs 65±12 yrs old); with higher body mass index (28.4±5 vs 27.7±5 vs 27.4±4 kg/m2); more likely to be women (52 vs 49 vs 47%), current smokers (10 vs 9 vs 8%), sedentary (79 vs 76 vs 73%), having diabetes (27 vs 24 vs 23%), hypertension (65 vs 62 vs 60%) and with known CHD (21 vs 20 vs 19%) when compared to the second and the highest tertiles respectively, all with p<0.001. After adjusting for these potential confounders, income level was inversely associated with ischemic CAD (Figure). Neighborhoods with higher income levels were associated with better walkability scores (R = 0.34eta; p<0.001), but walkability did not mediate the association between income level and ischemic CHD (percent mediated = −0.3%).
Figure 1. Association of income and CHD

Conclusions
In this large registry from a LMIC population, living in a lower-income neighborhood was associated with higher prevalence of ischemic CHD. Even though neighborhood walkability was directly associated with neighborhood income, it did not explain the association between income level and ischemic CHD.
4258Re-evaluating the genetic contribution of monogenic dilated cardiomyopathy
Authors: Mazzarotto F , Tayal U , Buchan R , Midwinter W , Wilk A , Whiffin N , Watkins H , Funke B , O'regan D , Olivotto I , Barton P J , Prasad S K , Cook S A , Ware J S , Walsh R 
Published: October 2019

Abstract

Background
Dilated cardiomyopathy (DCM) is genetically heterogeneous, with >100 purported disease genes tested in clinical laboratories. However, many genes were originally identified based on candidate-gene studies that did not adequately account for background population variation. Here we define the frequency of rare variation in 2538 DCM patients across protein-coding regions of 56 commonly tested genes and compare this to both 912 confirmed healthy controls and a reference population of 60,706 individuals.

Purpose
To identify clinically interpretable genes robustly associated with dominant monogenic DCM.

Methods
We used the TruSight Cardio sequencing panel to evaluate the burden of rare variants in 56 putative DCM genes in 1040 DCM patients and 912 healthy volunteers processed with identical sequencing and bioinformatics pipelines. We further aggregated data from 1498 DCM patients sequenced in diagnostic laboratories and the ExAC database for replication and meta-analysis.

Results
Specific variant classes in TTN, DSP, MYH7 and LMNA were associated with DCM in all comparisons. Variants in BAG3, TNNT2, TPM1, NEXN and VCL were significantly enriched specific patient subsets, with the last 3 genes likely contributing primarily to early-onset forms of DCM. Overall, rare variants in these 9 genes potentially explained 19–26% of cases. Whilst the absence of a significant excess in other genes cannot preclude a role in disease, such genes have limited diagnostic value since novel variants will be uninterpretable and therefore non-actionable, and their diagnostic yield is minimal.

Conclusion
In the largest sequenced DCM cohort yet described, we observe robust disease association only with a limited number of genes, highlighting their importance in DCM and translating into high interpretability in diagnostic testing. The other genes evaluated have limited value in diagnostic testing in DCM. This data will contribute to community gene curation efforts, and will reduce erroneous and inconclusive findings in diagnostic testing.

Acknowledgement/Funding
Wellcome Trust (107469/Z/15/Z), BHF (SP/10/10/28431), MRC (MR/M003191/1), Fondation Leducq (11-CVD01), Italian Ministry of Health (RF-2013-02356787)