Multi-biomarker analysis in patients after transcatheter aortic valve implantation (TAVI)

Abstract

Background: In this study we sought to examine whether transcatheter aortic valve implantation (TAVI) is followed by a change in the plasma levels of novel cardiovascular biomarkers.

Methods: We collected blood samples of 79 patients with severe aortic valve stenosis undergoing TAVI before and at 7 days, 1 month, 3 months and 6 months post TAVI and analyzed the plasma concentrations of GDF-15, H-FABP, fetuin-A, galectin 3, sST2 and suPAR by means of ELISA.

Results: There was a significant increase in the concentration of fetuin-A (median: 52.44 mg/ml to 113.2 mg/ml, p?<?0.001) and a significant decrease of H–FABP after TAVI (median: 4.835 ng/ml to 2.534 ng/ml, p?<?0.001). The concentrations of suPAR and sST2 showed an initial increase (suPAR median: 2755 pg/ml 3489 pg/ml, p?<?0.001; sST2 median: 5832 pg/ml to 7137 pq/ml, p?<?0.001) and subsequently decreased significantly.

Conclusion: We hypothesize that the decrease of H-FABP and the increase of fetuin-A could be due to a hemodynamic improvement after valve replacement. The initial increase of suPAR could indicate an inflammatory stimulus and the significant increase in sST2 could be due to the mechanical strain caused by implantation of the valve.     

Report on outcomes of valve-in-valve transcatheter aortic valve implantation and redo surgical aortic valve replacement in the Netherlands

Netherlands Heart Journal - We sought to investigate real-world outcomes of patients with degenerated biological aortic valve prostheses who had undergone valve-in-valve transcatheter aortic valve...     

Determinants of elevated carbohydrate antigen 125 in patients with severe symptomatic aortic valve stenosis referred for transcatheter aortic valve implantation

Purpose: Elevated carbohydrate antigen 125 (CA125) predicts adverse outcome after transcatheter aortic valve implantation (TAVI). While known underlying pathophysiological mechanisms of elevated CA125 include serosal effusions and inflammatory stimuli, clinical determinants associated with elevated CA125 in patients referred for TAVI remain unknown. Therefore, we investigated clinical, laboratory and echocardiographic determinants of elevated CA125 in patients with severe aortic valve stenosis referred for TAVI.

Methods: This study includes 650 patients with severe aortic stenosis referred for TAVI. Baseline CA125 was determined by an immunoassay and dichotomized (elevated versus normal) based on the manufacturer cutoff value (>35?U/mL).

Results: CA125 elevation was present in 28% (181/650). Patients with elevated CA125 had an overall worse clinical profile and were more symptomatic with a higher rate of NYHA class III/IV (80% versus 58%; p?Conclusion: Elevated CA125 levels in patients referred for TAVI summarize a subset of patients with an overall worse clinical profile who are more symptomatic.     

Body mass index and all-cause mortality in a large Chinese cohort

Background

Obesity is known to be associated with an increased risk of death, but current definitions of obesity are based on data from white populations. We examined the association between body mass index (BMI) and the risk of death in a large population of adult Chinese people.

Methods

We examined the association between body mass index (BMI) and all-cause mortality prospectively among 58 738 men and 65 718 women aged 20 years and older enrolled in 1998–1999 from four national health screening centres in Taiwan. We used Cox proportional hazards regression analyses to estimate the relative risks of all-cause mortality for different BMI categories during a maximum follow-up of 10 years.

Results

A total of 3947 participants died during the follow-up period. The lowest risk of death was observed among men and women who had a BMI of 24.0–25.9 (mean 24.9). After adjustment for age, smoking status, alcohol intake, betel-nut chewing, level of physical activity, income level and education level, we observed a U-shaped association between BMI and all-cause mortality. Similar U-shaped associations were observed when we analyzed data by age (20–64 or ≥ 65 years), smoking (never, < 10 pack-years or ≥ 10 pack-years) and presence of a pre-existing chronic disease, and after we excluded deaths that occurred in the first three years of follow-up.

Interpretation

BMI and all-cause mortality had a U-shaped association among adult Chinese people in our study. The lowest risk of death was among adults who had a BMI of 24.0–25.9 (mean 24.9). Our findings do not support the use of a lower cutoff value for overweight and obesity in the adult Chinese population.The prevalence of obesity has dramatically increased in past decades in both developed and developing countries. The World Health Organization (WHO) reported that 1.6 billion adults are overweight and at least 400 million are obese.¹ The WHO further predicted that by the year 2015, about 2.3 billion adults will be overweight and more than 700 million will be obese.¹ In Taiwan, according to a national survey performed between 1993–1996 and 2005–2008, the prevalence of overweight and obesity (defined as body mass index [BMI] ≥ 24 kg/m²) had increased dramatically, from 33.4% to 50.8% among men and from 31.7% to 36.9% among women.²Overweight and obesity have been recognized as important and independent risk factors for many chronic diseases such as diabetes mellitus, hypertension, stroke, cardiovascular diseases and malignant diseases.^3–7 Substantial epidemiologic evidence shows that obesity is associated with an increased risk of cardiovascular-related and all-cause mortality.^8,9 Therefore, obesity has become a major public health problem around the world.Current definitions of obesity and overweight in adults are based on data from white populations. The WHO has proposed another definition for Asian people, but most of the data it used were from cross-sectional studies.¹⁰ One study showed that, for a given BMI, Asian people had higher body fat than white people.¹¹ Furthermore, the association between BMI and all-cause mortality has been reported to be J-shaped or U-shaped. Most of the studies involved white people, with only a few involving Asian populations. Gu and colleagues reported a U-shaped association between BMI and all-cause mortality among Chinese people.¹² However, they included only middle-aged adults over 40 years old and not all adults over 20 years.We designed a large prospective cohort study to assess the association between BMI and all-cause mortality in a nationwide representative sample of Chinese adults over 20 years old in Taiwan. We also intended to find the optimal BMI cutoff values for overweight and obesity among Chinese adults.     

Simulation of transcatheter aortic valve implantation through patient-specific finite element analysis: Two clinical cases

Transcatheter aortic valve implantation (TAVI) is a minimally invasive procedure introduced to treat aortic valve stenosis in elder patients. Its clinical outcomes are strictly related to patient selection, operator skills, and dedicated pre-procedural planning based on accurate medical imaging analysis. The goal of this work is to define a finite element framework to realistically reproduce TAVI and evaluate the impact of aortic root anatomy on procedure outcomes starting from two real patient datasets. Patient-specific aortic root models including native leaflets, calcific plaques extracted from medical images, and an accurate stent geometry based on micro-tomography reconstruction are key aspects included in the present study. Through the proposed simulation strategy we observe that, in both patients, stent apposition significantly induces anatomical configuration changes, while it leads to different stress distributions on the aortic wall. Moreover, for one patient, a possible risk of paravalvular leakage has been found while an asymmetric coaptation occurs in both investigated cases. Post-operative clinical data, that have been analyzed to prove reliability of the performed simulations, show a good agreement with analysis results. The proposed work thus represents a further step towards the use of realistic computer-based simulations of TAVI procedures, aiming at improving the efficacy of the operation technique and supporting device optimization.     

Influence of permanent pacemaker implantation after transcatheter aortic valve implantation with new-generation devices

Objective

Permanent pacemaker implantation (PPMI) after transcatheter aortic valve implantation (TAVI) is the most common complication after the procedure. PPMI rates remain high with the new-generation TAVI devices despite improved outcomes concerning paravalvular aortic regurgitation and vascular access complications. However, the impact of PPMI on mortality and clinical outcome is still a matter of debate, and data with new-generation devices on this matter are scarce. Therefore, we sought to analyse the influence of PPMI in patients treated with the new-generation devices on one-year outcome.

Methods

We enrolled 612 consecutive patients without prior pacemaker undergoing transfemoral TAVI with the new-generation devices. Patients with or without PPMI were compared with respect to clinical outcome within one year.

Results

PPMI was performed in 168 patients (24.4% of the overall study population). There was no significant difference in one-year outcome concerning all-cause mortality (PPMI vs. no-PPMI: 12.2% vs. 12.5%, p?=?0.94), rate of major adverse events including cardiac, cerebral or valve-related events and bleeding complications (22.1% vs. 24.5%, p?=?0.55) or need for rehospitalisation due to cardiac symptoms (16.1% vs. 18.1%, p?=?0.63). In patients with reduced ejection fraction (<45%) there was also no impact of PPMI on one-year mortality (14.3% vs. 15.7%, p?=?0.86). Furthermore, multivariate analysis did not reveal PPMI to be independently associated with one-year mortality (odds ratio 0.94, 95% confidence interval 0.50–1.74, p?=?0.83).

Conclusions

In this large all-comers TAVI population with new-generation devices the need for postprocedural PPMI did not show a statistical significant impact on survival or combined endpoint of major adverse events within one year.

     

Supra-annular Valve-in-Valve implantation reduces blood stasis on the transcatheter aortic valve leaflets

Leaflet thrombosis following transcatheter aortic valve replacement (TAVR) and Valve-in-Valve (ViV) procedures has been increasingly recognized. This study aimed to investigate the effect of positioning of the transcatheter aortic valve (TAV) in ViV setting on the flow dynamics aspect of post-ViV thrombosis by quantifying the blood stasis in the intra-annular and supra-annular settings. To that end, two idealized computational models, representing ViV intra-annular and supra-annular positioning of a TAV were developed in a patient-specific geometry. Three-dimensional flow fields were then obtained via fluid-solid interaction modeling to study the difference in blood residence time (BRT) on the TAV leaflets in the two settings. At the end of diastole, a strip of high BRT ($⩾1.2s$) region was observed on the TAV leaflets in the ViV intra-annular positioning at the fixed boundary where the leaflets are attached to the frame. Such a high BRT region was absent on the TAV leaflets in the supra-annular positioning. The maximum value of BRT on the surface of non-, right, and left coronary leaflets of the TAV in the supra-annular positioning were 53%, 11%, and 27% smaller compared to the intra-annular positioning, respectively. It was concluded that the geometric confinement of TAV by the leaflets of the failed bioprosthetic valve in ViV intra-annular positioning increases the BRT on the leaflets and may act as a permissive factor in valvular thrombosis. The absence of such a geometric confinement in the ViV supra-annular positioning leads to smaller BRT and subsequently less likelihood of leaflet thrombosis.     

Incidence and outcome of prosthetic valve endocarditis after transcatheter aortic valve replacement in the Netherlands

Background

Transcatheter aortic valve replacement (TAVR) is increasingly being used as an alternative to conventional surgical valve replacement. Prosthetic valve endocarditis (PVE) is a rare but feared complication after TAVR, with reported first-year incidences varying from 0.57 to 3.1%. This study was performed to gain insight into the incidence and outcome of PVE after TAVR in the Netherlands.

Methods

A multicentre retrospective registry study was performed. All patients who underwent TAVR in the period 2010–2017 were screened for the diagnosis of infective endocarditis in the insurance database and checked for the presence of PVE before analysis of general characteristics, PVE parameters and outcome.

Results

A total of 3968 patients who underwent TAVR were screened for PVE. During a median follow-up of 33.5 months (interquartile range (IQR) 22.8–45.8), 16 patients suffered from PVE (0.4%), with a median time to onset of 177 days (IQR 67.8–721.3). First-year incidence was 0.24%, and the overall incidence rate was 0.14 events per 1000 person-years. Overall mortality during follow-up in our study was 31%, of which 25% occurred in hospital. All patients were treated conservatively with intravenous antibiotics alone, and none underwent a re-intervention. Other complications of PVE occurred in 5 patients (31%) and included aortic abscess (2), decompensated heart failure (2) and cerebral embolisation (1).

Conclusion

PVE in patients receiving TAVR is a relatively rare complication and has a high mortality rate.

     

Pre-procedural elevated cardiac troponin predict risk of long-term all-cause mortality after transcatheter aortic valve replacement: a meta-analysis of prospective studies

Abstract

Background: The purpose of this meta-analysis was to evaluate the relationship between elevated cardiac troponin pre-transcatheter aortic valve replacement (TAVR) and long-term all-cause mortality.

Methods: Prospective studies with the endpoint of all-cause mortality were included. We primarily used the fixed-effect model weighted by inverse variance. Meta-regression and subgroup analyses were conducted to explore the potential sources of heterogeneity by specified study characteristics.

Results: Seven prospective studies comprising of 3049 subjects were included in our meta-analysis. Pre-procedural elevated cardiac troponin was associated with increased risk of long-term mortality post TAVR [hazard ratio (HR) 2.25, 95% CI 1.83–2.78, p?=?0.000, I² = 30.3%, p for heterogeneity 0.197]. In addition, subgroup analyses have shown that the group with an younger age (<82?y) seemed to have a higher risk of all-cause mortality than the group with older age (≥82?y) [HR 4.08 (2.41 to 6.89) VS 2.01 (1.60 to 2.53), p?=?0.016 for subgroup difference].

Conclusions: Pre-procedural elevated cardiac troponin was associated with increased long-term all-cause mortality in patients undergoing TAVR.     

Risk evaluation of adverse aortic events in patients with non-circular aortic annulus after transcatheter aortic valve implantation: a numerical study

Biomechanics and Modeling in Mechanobiology - Transcatheter aortic valve implantation (TAVI) is a micro-invasive surgery used to treat patients with aortic stenosis (AS) efficiently. However, the...     

Echocardiographic evaluation of delayed outcome of artificial valve implantation in patients with aortic semilunar valve insufficiency]

An average follow-up period of 16 patients was 28 months following an implantation of the artificial aortic valve for its insufficiency. In 10 operated patients who were able to continue their occupation exercise tolerance increased by two classes, according to NYHA. Blood pressure gradient decreased significantly from 61.8 to 37.5 mmHg, cardiac volume index decreased from 639 to 602 ml/m2. Echocardiographically measured muscle mass of the left ventricle, end-diastolic and end-systolic volumes, and the left atrial dimensions decreased significantly following surgery. A significance of the relation of the left ventricle volume to its mass <4 as a prognostic factor in aortic valve replacement has also been confirmed.     

Simulation of transcatheter aortic valve implantation: a patient-specific finite element approach

Until recently, heart valve failure has been treated adopting open-heart surgical techniques and cardiopulmonary bypass. However, over the last decade, minimally invasive procedures have been developed to avoid high risks associated with conventional open-chest valve replacement techniques. Such a recent and innovative procedure represents an optimal field for conducting investigations through virtual computer-based simulations: in fact, nowadays, computational engineering is widely used to unravel many problems in the biomedical field of cardiovascular mechanics and specifically, minimally invasive procedures. In this study, we investigate a balloon-expandable valve and we propose a novel simulation strategy to reproduce its implantation using computational tools. Focusing on the Edwards SAPIEN valve in particular, we simulate both stent crimping and deployment through balloon inflation. The developed procedure enabled us to obtain the entire prosthetic device virtually implanted in a patient-specific aortic root created by processing medical images; hence, it allows evaluation of postoperative prosthesis performance depending on different factors (e.g. device size and prosthesis placement site). Notably, prosthesis positioning in two different cases (distal and proximal) has been examined in terms of coaptation area, average stress on valve leaflets as well as impact on the aortic root wall. The coaptation area is significantly affected by the positioning strategy ( ? 24%, moving from the proximal to distal) as well as the stress distribution on both the leaflets (+13.5%, from proximal to distal) and the aortic wall ( ? 22%, from proximal to distal). No remarkable variations of the stress state on the stent struts have been obtained in the two investigated cases.     

Postoperative analysis of the mechanical interaction between stent and host tissue in patients after transcatheter aortic valve implantation

The analysis is based on a finite element procedure to extract the contact forces between an implanted Nitinol stent and the surrounding host tissue using postoperative CT images. The methodology was applied for patients (N=46) which have undergone a TAVI procedure with the Medtronic CoreValve Revalving System (MCRS) to obtain corresponding deformation and force maps. The postoperative CT data were recorded for each patient in both systolic and diastolic phase of the heart cycle. Scalar parameters were defined, which map deformed geometry and contact force field to mechanically relevant quantities: radial dilatation, radial shape distortion, non-convex points, mean force, a force deviation measure and a pressure equivalent. The latter demonstrates that in the area of the aortic root, the added circumferential loading is of the same order as the baseline average blood pressure, thus leading to a doubling of the local mechanical load. Generally the force distribution along the stent is non-homogeneous. A comparison of systolic and diastolic data revealed slightly higher contact forces during the diastole, indicating that the stent has to carry more load in this phase. The geometrical and mechanical parameters were compared for two types of clinical complication: para-valvular leakage (PVL) and permanent pacemaker requirement (PPM). It was found that an increase in mean force can be associated with both complications; significantly for PVL and as a trend for PPM.     

Concomitant transapical transcatheter aortic valve implantation and minimally invasive direct coronary artery bypass

We represent a successful minimally invasive combined off-pump procedure consisting of a transapical aortic valve implantation and a direct coronary artery bypass grafting in a woman with a severe aortic stenosis and a critical coronary artery disease. Due to her comorbidities, she was classified as a high-risk patient qualifying for a transcatheter procedure. We performed this combined procedure in a hybrid operation room, starting with the coronary bypass to maintain a coronary blood flow during the transapical valve implantation. The operation processed without any complications and she was discharged at the seventh postoperative day into the allocating hospital.     

The rationale of using cerebral embolic protection devices during transcatheter aortic valve implantation

Aortic valve stenosis is one of the most common valvular abnormalities, which can manifest as angina, syncope, dyspnoea and sudden cardiac death. Transcath     

A new body shape index predicts mortality hazard independently of body mass index

Background

Obesity, typically quantified in terms of Body Mass Index (BMI) exceeding threshold values, is considered a leading cause of premature death worldwide. For given body size (BMI), it is recognized that risk is also affected by body shape, particularly as a marker of abdominal fat deposits. Waist circumference (WC) is used as a risk indicator supplementary to BMI, but the high correlation of WC with BMI makes it hard to isolate the added value of WC.

Methods and Findings

We considered a USA population sample of 14,105 non-pregnant adults () from the National Health and Nutrition Examination Survey (NHANES) 1999–2004 with follow-up for mortality averaging 5 yr (828 deaths). We developed A Body Shape Index (ABSI) based on WC adjusted for height and weight: ABSI had little correlation with height, weight, or BMI. Death rates increased approximately exponentially with above average baseline ABSI (overall regression coefficient of per standard deviation of ABSI [95% confidence interval: –]), whereas elevated death rates were found for both high and low values of BMI and WC. (–) of the population mortality hazard was attributable to high ABSI, compared to (–) for BMI and (–) for WC. The association of death rate with ABSI held even when adjusted for other known risk factors including smoking, diabetes, blood pressure, and serum cholesterol. ABSI correlation with mortality hazard held across the range of age, sex, and BMI, and for both white and black ethnicities (but not for Mexican ethnicity), and was not weakened by excluding deaths from the first 3 yr of follow-up.

Conclusions

Body shape, as measured by ABSI, appears to be a substantial risk factor for premature mortality in the general population derivable from basic clinical measurements. ABSI expresses the excess risk from high WC in a convenient form that is complementary to BMI and to other known risk factors.     

Prevalence of blood type A and risk of vascular complications following transcatheter aortic valve implantation

Objectives

To assess the prevalence of blood type A among patients referred for transcatheter aortic valve implantation (TAVI) and whether it is related to vascular complications.

Backgrounds

Vascular complications following TAVI are associated with adverse outcomes. Various blood types, particularly type A, have been shown to be more prevalent in cardiovascular diseases and to be related to prognosis.

Methods

The prevalence of various blood types in a cohort of 491 consecutive patients who underwent TAVI was compared with a control group of 6500 consecutive hospitalised patients. The prevalence and predictors of vascular complications and bleeding events were evaluated in the blood type A group and were compared with non-type A patients.

Results

The mean age of TAVI patients was 83?±?6 years, and 40?% were males. Patients were divided into two groups: blood type A (n?=?220) and non-type A (n?=?271). Type A was significantly more prevalent in the TAVI group than in the control group (45 vs. 38?%, p?=?0.023). Compared with the non-type A group, patients with blood type A had more major and fatal bleeding (14.5 vs. 8.1?%, p?=?0.027) and more vascular complications (any vascular complication: 24.5 vs. 15.9?% p?=?0.016; major vascular complications: 12.3 vs. 7?% p?=?0.047). In a multivariable analysis, blood type A emerged as a significant and independent predictor for vascular complications and bleeding events.

Conclusions

Blood type A is significantly more prevalent in TAVI patients than in the general population and is related to higher rates of vascular and bleeding complications.