Prognostic Utility of Biomarkers in Predicting of One-Year Outcomes in Patients with Aortic Stenosis Treated with Transcatheter or Surgical Aortic Valve Implantation

Objectives

The aim of the work was to find biomarkers identifying patients at high risk of adverse clinical outcomes after TAVI and SAVR in addition to currently used predictive model (EuroSCORE).

Background

There is limited data about the role of biomarkers in predicting prognosis, especially when TAVI is available.

Methods

The multi-biomarker sub-study included 42 consecutive high-risk patients (average age 82.0 years; logistic EuroSCORE 21.0%) allocated to TAVI transfemoral and transapical using the Edwards-Sapien valve (n = 29), or SAVR with the Edwards Perimount bioprosthesis (n = 13). Standardized endpoints were prospectively followed during the 12-month follow-up.

Results

The clinical outcomes after both TAVI and SAVR were comparable. Malondialdehyde served as the best predictor of a combined endpoint at 1 year with AUC (ROC analysis) = 0.872 for TAVI group, resp. 0.765 (p<0.05) for both TAVI and SAVR groups. Increased levels of MDA, matrix metalloproteinase 2, tissue inhibitor of metalloproteinase (TIMP1), ferritin-reducing ability of plasma, homocysteine, cysteine and 8-hydroxy-2-deoxyguanosine were all predictors of the occurrence of combined safety endpoints at 30 days (AUC 0.750–0.948; p<0.05 for all). The addition of MDA to a currently used clinical model (EuroSCORE) significantly improved prediction of a combined safety endpoint at 30 days and a combined endpoint (0–365 days) by the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI) (p<0.05).Cystatin C, glutathione, cysteinylglycine, asymmetric dimethylarginine, nitrite/nitrate and MMP9 did not prove to be significant. Total of 14.3% died during 1-year follow-up.

Conclusion

We identified malondialdehyde, a marker of oxidative stress, as the most promising predictor of adverse outcomes during the 30-day and 1-year follow-up in high-risk patients with symptomatic, severe aortic stenosis treated with TAVI. The development of a clinical “TAVIscore” would be highly appreciated. Such dedicated scoring system would enable further testing of adjunctive value of various biomarkers.     

Transfemoral Aortic Valve Implantation with the New Edwards Sapien 3 Valve for Treatment of Severe Aortic Stenosis—Impact of Valve Size in a Single Center Experience

Aims

The third generation Edwards Sapien 3 (Edwards Lifesciences Inc., Irvine, California) system was optimized to reduce residual aortic regurgitation and vascular complications.

Methods and Results

235 patients with severe symptomatic aortic stenosis were prospectively enrolled. Transcatheter aortic valve implantations (TAVI) were performed without general anesthesia by transfemoral approach. Patients were followed for 30 days. Patients received 23mm (N = 77), 26mm (N = 91) or 29mm (N = 67) valve based on pre-procedural 256 multislice computer tomography. Mean oversizing did not differ between the 3 valves. There was no residual moderate or severe aortic regurgitation. Rate of mild aortic regurgitation and regurgitation index did not differ between groups. There was no switch to general anesthesia or conversion to surgery. Rate of major vascular complication was 3.0% with no difference between valve and delivery sheath sizes. Within 30 days rates of all cause mortality (2.6%) and stroke (2.1%) were low.

Conclusions

In patients with severe aortic stenosis transfemoral TAVI with the Edwards Sapien 3 valve without general anesthesia was associated with a high rate of device success, no moderate or severe residual aortic regurgitation, low rates of major vascular complication, mortality and stroke within 30 days with no difference between the 3 valve sizes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02162069","term_id":"NCT02162069"}}NCT02162069     

C-Reactive protein reactions to glucose-insulin-potassium infusion and relations to infarct size in patients with acute coronary syndromes

Little is known about preoperative predictors of resource utilization in the treatment of high-risk patients with severe symptomatic aortic valve stenosis. We report results from the prospective, medical-economic “TAVI Calculation of Costs Trial”. In-hospital resource utilization was evaluated in 110 elderly patients (age ≥ 75 years) treated either with transfemoral (TF) or transapical (TA) transcatheter aortic valve implantation (TAVI, N = 83), or surgical aortic valve replacement (AVR, N = 27). Overall, 22 patient-specific baseline parameters were tested for within-group prediction of resource use. Baseline characteristics differed between groups and reflected the non-randomized, real-world allocation of treatment options. Overall procedural times were shortest for TAVI, intensive care unit (ICU) length of stay (LoS) was lowest for AVR. Length of total hospitalization since procedure (THsP) was lowest for TF-TAVI; 13.4 ± 11.4 days as compared to 15.7 ± 10.5 and 21.2 ± 15.4 days for AVR and TA-TAVI, respectively. For TAVI and AVR, EuroScore I remained the main predictor for prolonged THsP (p <0.01). Within the TAVI group, multivariate regression analyses showed that TA-TAVI was associated with a substantial increase in THsP (55 to 61 %, p <0.01). Additionally, preoperative aortic valve area (AVA) was identified as an independent predictor of prolonged THsP in TAVI patients, irrespective of risk scores (p <0.05). Our results demonstrate significant heterogeneity in patients baseline characteristics dependent on treatment and corresponding differences in resource utilization. Prolonged ThsP is not only predicted by risk scores but also by baseline AVA, which might be useful in stratifying TAVI patients. German Clinical Trial Register Nr. DRKS00000797     

Transcatheter aortic valve implantation and surgical aortic valve replacement among hospitalized patients with and without type 2 diabetes mellitus in Spain (2014–2015)

Background

Type 2 diabetes mellitus (T2DM) is strongly related to the in-hospital and short-term prognosis in patients with cardiovascular diseases needing surgical or invasive interventions. How T2DM might influence the treatment of aortic stenosis (AS) has not been completely elucidated for surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI). The aims of this study were: (1) to describe the use of aortic valve replacement procedures (TAVI and SAVR) among hospitalized patients with and without T2DM; and (2) to identify factors associated with in hospital mortality (IHM) among patients undergoing these procedures.

Methods

We analyzed data from the Spanish National Hospital Discharge Database between January 1, 2014 and December 31, 2015 for patients aged ≥ 40 years. We selected patients whose medical procedures included TAVI (ICD-9-CM codes 35.05, 35.06) and SAVR (ICD-9-CM codes 35.21, 35.22). We stratified each cohort by diabetes status: T2DM (ICD-9-CM codes 250.x0, 250.x2) and no diabetes. We retrieved data about specific comorbidities, risk factors, procedures, and specific in-hospital postoperative complications. Hospital outcome variables included IHM, and length of hospital stay (LOHS).

Results

We identified a total of 2141 and 16,013 patients who underwent TAVI (n = 715; 33.39% with T2DM) and SAVR (n = 4057; 25.33% with T2DM). In patients who underwent TAVI we found no differences in IHM (3.64% in T2DM vs. 5.12% in non-T2DM, p = 0.603). In the cohort of SAVR, mean LOHS was significantly lower in patients with T2DM than in non-diabetic patients (13.77 vs. 17.27 days). IHM was lower in patients with T2DM (4.36% vs. 6.31%, p < 0.01). After multivariable adjustment for both procedures, patients with T2DM had significantly lower IHM than patients without diabetes (adjusted OR 0.60; IC 95% 0.37–0.99 for TAVI and adjusted OR 0.80; IC 95% 0.66-0-96 for SAVR).

Conclusions

T2DM diabetic patients with AS undergoing a valvular replacement procedure through SAVR or TAVI did not have a worse prognosis compared to non-diabetic patients during hospitalization, showing lower IHM after multivariable adjustment. However, given the limitations of administrative data more prospective studies and clinical trials aimed at evaluating the influence of these procedures in diabetic patients with AS are needed.

     

The Nordic Aortic Valve Intervention (NOTION) trial comparing transcatheter versus surgical valve implantation: study protocol for a randomised controlled trial

Background

Degenerative aortic valve (AV) stenosis is the most prevalent heart valve disease in the western world. Surgical aortic valve replacement (SAVR) has until recently been the standard of treatment for patients with severe AV stenosis. Whether transcatheter aortic valve implantation (TAVI) can be offered with improved safety and similar effectiveness in a population including low-risk patients has yet to be examined in a randomised setting.

Methods/Design

This randomised clinical trial will evaluate the benefits and risks of TAVI using the transarterial CoreValve System (Medtronic Inc., Minneapolis, MN, USA) (intervention group) compared with SAVR (control group) in patients with severe degenerative AV stenosis. Randomisation ratio is 1:1, enrolling a total of 280 patients aged 70 years or older without significant coronary artery disease and with a low, moderate, or high surgical risk profile. Trial outcomes include a primary composite outcome of myocardial infarction, stroke, or all-cause mortality within the first year after intervention (expected rates 5% for TAVI, 15% for SAVR). Exploratory safety outcomes include procedure complications, valve re-intervention, and cardiovascular death, as well as cardiac, cerebral, pulmonary, renal, and vascular complications. Exploratory efficacy outcomes include New York Heart Association functional status, quality of life, and valve prosthesis and cardiac performance. Enrolment began in December 2009, and 269 patients have been enrolled up to December 2012.

Discussion

The trial is designed to evaluate the performance of TAVI in comparison with SAVR. The trial results may influence the choice of treatment modality for patients with severe degenerative AV stenosis.

Trial registration

ClinicalTrials.gov: NCT01057173     

Clinical outcome of high-risk patients with severe aortic stenosis and reduced left ventricular ejection fraction undergoing medical treatment or TAVI

Introduction

Reduced left ventricular function in patients with severe symptomatic valvular aortic stenosis is associated with impaired clinical outcome in patients undergoing surgical aortic valve replacement (SAVR). Transcatheter Aortic Valve Implantation (TAVI) has been shown non-inferior to SAVR in high-risk patients with respect to mortality and may result in faster left ventricular recovery.

Methods

We investigated clinical outcomes of high-risk patients with severe aortic stenosis undergoing medical treatment (n = 71) or TAVI (n = 256) stratified by left ventricular ejection fraction (LVEF) in a prospective single center registry.

Results

Twenty-five patients (35%) among the medical cohort were found to have an LVEF≤30% (mean 26.7±4.1%) and 37 patients (14%) among the TAVI patients (mean 25.2±4.4%). Estimated peri-interventional risk as assessed by logistic EuroSCORE was significantly higher in patients with severely impaired LVEF as compared to patients with LVEF>30% (medical/TAVI 38.5±13.8%/40.6±16.4% versus medical/TAVI 22.5±10.8%/22.1±12.8%, p <0.001). In patients undergoing TAVI, there was no significant difference in the combined endpoint of death, myocardial infarction, major stroke, life-threatening bleeding, major access-site complications, valvular re-intervention, or renal failure at 30 days between the two groups (21.0% versus 27.0%, p = 0.40). After TAVI, patients with LVEF≤30% experienced a rapid improvement in LVEF (from 25±4% to 34±10% at discharge, p = 0.002) associated with improved NYHA functional class at 30 days (decrease ≥1 NYHA class in 95%). During long-term follow-up no difference in survival was observed in patients undergoing TAVI irrespective of baseline LVEF (p = 0.29), whereas there was a significantly higher mortality in medically treated patients with severely reduced LVEF (log rank p = 0.001).

Conclusion

TAVI in patients with severely reduced left ventricular function may be performed safely and is associated with rapid recovery of systolic left ventricular function and heart failure symptoms.     

Evaluation of the Valve Academic Research Consortium-2 Criteria for Myocardial Infarction in Transcatheter Aortic Valve Implantation: A Prospective Observational Study

Objective

To evaluate the relevance of the individual components of the Valve Academic Research Consortium (VARC)-2 criteria for periprocedural myocardial infarction (MI) in transcatheter aortic valve implantation (TAVI). The association between biomarkers and adverse procedural outcome has been established. However, the additive prognostic importance of signs and symptoms are more uncertain.

Methods

A total of 125 consecutive TAVI patients were prospectively included in this study. Biomarkers for MI were analyzed and signs and symptoms according to VARC-2 criteria were collected from clinical records.

Results

The criteria of elevated biomarkers and of signs or symptoms were found in 27 (22%) and 32 (26%) of the patients, respectively. According to VARC-2 definition, 12 (10%) had MI. VARC-2 definition of MI, Troponin T (TnT) > 600 ng/L, and presence of signs or symptoms correlated with 6 months mortality, prolonged ICU stay, elevation of N-terminal prohormone brain natriuretic peptide, and renal impairment. No signs or symptoms were found in 7 (44%) of the patients who fulfilled the criterion of elevated TnT > 600 ng/L. In the group with positive TnT criterion, there were no significant differences between those with and without signs or symptoms in respect to levels of TnT (1014 [585–1720] ng/L versus 704 [515–905] ng/L, p = 0.17) or creatine kinase-MB (36 [25–52] μg/L versus 29 [25–39] μg/L, p = 0.32). In the multivariate Cox regression analysis, TnT > 600 ng/L was the only significant independent variable associated with 6-months postprocedural mortality.

Conclusions

Myocardial injury in TAVI, measured with biomarkers, correlates well with adverse procedural outcome. In this study it is also the strongest predictor for early postprocedural mortality. The additional requirement of signs or symptoms for the diagnosis of MI results in omission of a considerable number of clinically significant MI.     

Patients with aortic stenosis referred for TAVI: treatment decision, in-hospital outcome and determinants of survival

Aims

To assess treatment decision and outcome in patients referred for transcatheter aortic valve implantation (TAVI) in addition to predictive factors of mortality after TAVI.

Methods

Three-centre prospective observational study including 358 patients. Endpoints were defined according to the Valve Academic Research Consortium.

Results

Of the 358 patients referred for TAVI, TAVI was performed in 235 patients (65%), surgical aortic valve replacement (AVR) in 24 (7%) and medical therapy (MT) in 99 (28%). Reasons to decline TAVI in favour of AVR/MT were patient preference (29%), peripheral vascular disease (15%) and non-severe aortic stenosis (11%). The logistic EuroSCORE was significantly higher in patients who underwent TAVI and MT in comparison with those undergoing AVR (19 vs. 10%, p = 0.007). At 30 days, all-cause mortality and the combined safety endpoint were 9 and 24% after TAVI and 8 and 25% after AVR, respectively. All-cause mortality was significantly lower in the TAVI group compared with the MT group at 6 months, 1 year and 2 years (12% vs. 22%, 21% vs. 33% and 31% vs. 55%, respectively, p < 0.001). Multivariable analysis revealed that blood transfusion (HR: 1.19; 95% CI: 1.05–1.33), pre-existing renal failure (HR: 1.18; 95% CI: 1.06–1.33) and STS score (HR: 1.06; 95% CI: 1.02–1.10) were independent predictors of mortality at a median of 10 (IQR: 3–23) months after TAVI.

Conclusions

Approximately two-thirds of the patients referred for TAVI receive this treatment with gratifying short- and long-term survival. Another 7% underwent AVR. Prognosis is poor in patients who do not receive valve replacement therapy.     

CT-Angiography–Based Evaluation of the Aortic Annulus for Prosthesis Sizing in Transcatheter Aortic Valve Implantation (TAVI)–Predictive Value and Optimal Thresholds for Major Anatomic Parameters

Background/Objectives

To evaluate the predictive value of CT-derived measurements of the aortic annulus for prosthesis sizing in transcatheter aortic valve implantation (TAVI) and to calculate optimal cutoff values for the selection of various prosthesis sizes.

Methods

The local IRB waived approval for this single-center retrospective analysis. Of 441 consecutive TAVI-patients, 90 were excluded (death within 30 days: 13; more than mild aortic regurgitation: 10; other reasons: 67). In the remaining 351 patients, the CoreValve (Medtronic) and the Edwards Sapien XT valve (Edwards Lifesciences) were implanted in 235 and 116 patients. Optimal prosthesis size was determined during TAVI by inflation of a balloon catheter at the aortic annulus. All patients had undergone CT-angiography of the heart or body trunk prior to TAVI. Using these datasets, the diameter of the long and short axis as well as the circumference and the area of the aortic annulus were measured. Multi-Class Receiver-Operator-Curve analyses were used to determine the predictive value of all variables and to define optimal cutoff-values.

Results

Differences between patients who underwent implantation of the small, medium or large prosthesis were significant for all except the large vs. medium CoreValve (all p’s<0.05). Furthermore, mean diameter, annulus area and circumference had equally high predictive value for prosthesis size for both manufacturers (multi-class AUC’s: 0.80, 0.88, 0.91, 0.88, 0.88, 0.89). Using the calculated optimal cutoff-values, prosthesis size is predicted correctly in 85% of cases.

Conclusion

CT-based aortic root measurements permit excellent prediction of the prosthesis size considered optimal during TAVI.     

The Self-Expanding Symetis Acurate Does Not Increase Cerebral Microembolic Load When Compared to the Balloon-Expandable Edwards Sapien Prosthesis: A Transcranial Doppler Study in Patients Undergoing Transapical Aortic Valve Implantation

Objectives

The aim of this study was to quantify potential differences in count, frequency and pattern of high-intensity transient signals (HITS) during transapical transcatheter aortic valve implantation (TA-TAVI), by comparing the Symetis Acurate TA (SA) with the balloon-expandable Edwards Sapien XT (ES) system.

Background

Recently, the Symetis Acurate TA revalving system has been introduced for TA-TAVI. The Symetis Acurate TA aortic bioprosthesis is self-expanding and is deployed by a specific two-step implantation technique. Whether this novel method increases the load of intraprocedural emboli, detected by transcranial Doppler ultrasound (TCD) as HITS, or not is not clear.

Methods

Twenty-two patients (n = 11 in each study arm, median logistic EuroScore 20%, median STS score 7%) displayed continuous TCD signals of good quality throughout the entire TA-TAVI procedure and were included in the final analysis. Data are presented as median with interquartile ranges.

Results

No significant differences were detected in total procedural or interval-related HITS load (SA: 303 [200; 594], ES: 499 [285; 941]; p = 0.16). With both devices, HITS peaked during prosthesis deployment (PD), whereas significantly fewer HITS occurred during instrumentation (SA: p = 0.002; ES: <0.001) or post-implantation PI (SA: p = 0.007; ES: <0.001). PD-associated HITS amounted to almost half of the total HITS load. One patient suffered new disabling stroke at 30 days. Thirty-day mortality amounted to 13.6% (3 of 22 patients).

Conclusions

Simplified transapical delivery using the self-expanding SA device does not increase HITS, despite of a two-step deployment technique with more interactions with the native aortic valve, when compared to the balloon-expandable ES valve. The similarity in HITS count, frequency and pattern with the two systems suggests a common mechanism for the release of cerebral microemboli.     

High Spinal Anesthesia Enhances Anti-Inflammatory Responses in Patients Undergoing Coronary Artery Bypass Graft Surgery and Aortic Valve Replacement: Randomized Pilot Study

Background

Cardiac surgery induces many physiologic changes including major inflammatory and sympathetic nervous system responses. Here, we conducted a single-centre pilot study to generate hypotheses on the potential immune impact of adding high spinal anaesthesia to general anaesthesia during cardiac surgery in adults. We hypothesized that this strategy, previously shown to blunt the sympathetic response and improve pain management, could reduce the undesirable systemic inflammatory responses caused by cardiac surgery.

Methods

This prospective randomized unblinded pilot study was conducted on 14 patients undergoing cardiac surgery for coronary artery bypass grafting and/or aortic valve replacement secondary to severe aortic stenosis. The primary outcome measures examined longitudinally were serum pro-inflammatory (IL-6, IL-1b, CCL2), anti-inflammatory (IL-10, TNF-RII, IL-1Ra), acute phase protein (CRP, PTX3) and cardiovascular risk (sST2) biomarkers.

Results

The kinetics of pro- and anti-inflammatory biomarker was determined following surgery. All pro-inflammatory and acute phase reactant biomarker responses induced by surgical stress were indistinguishable in intensity and duration between control groups and those who also received high spinal anaesthesia. Conversely, IL-10 levels were markedly elevated in both intensity and duration in the group receiving high spinal anesthesia (p = 0.005).

Conclusions

This hypothesis generating pilot study suggests that high spinal anesthesia can alter the net inflammatory response that results from cardiac surgery. In appropriately selected populations, this may add incremental benefit by dampening the net systemic inflammatory response during the week following surgery. Larger population studies, powered to assess immune, physiologic and clinical outcomes in both acute and longer term settings, will be required to better assess potential benefits of incorporating high spinal anesthesia.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00348920","term_id":"NCT00348920"}}NCT00348920     

Endothelial-Derived Oxidative Stress Drives Myofibroblastic Activation and Calcification of the Aortic Valve

Aims

Oxidative stress is present in and contributes to calcification of the aortic valve, but the driving factors behind the initiation of valve oxidative stress are not well understood. We tested whether the valve endothelium acts as an initiator and propagator of oxidative stress in aortic valve disease.

Methods and Results

Calcified human aortic valves showed side-specific elevation of superoxide in the endothelium, co-localized with high VCAM1 expression, linking oxidative stress, inflammation, and valve degeneration. Treatment with inflammatory cytokine TNFα increased superoxide and oxidative stress and decreased eNOS and VE-cadherin acutely over 48 hours in aortic valve endothelial cells (VEC) and chronically over 21 days in ex vivo AV leaflets. Co-treatment of VEC with tetrahydrobiopterin (BH₄) but not apocynin mitigated TNFα-driven VEC oxidative stress. Co-treatment of ex vivo AV leaflets with TNFα+BH₄ or TNFα+peg-SOD rescued endothelial function and mitigated inflammatory responses. Both BH₄ and peg-SOD rescued valve leaflets from the pro-osteogenic effects of TNFα treatment, but only peg-SOD was able to mitigate the fibrogenic effects, including increased collagen and αSMA expression.

Conclusions

Aortic valve endothelial cells are a novel source of oxidative stress in aortic valve disease. TNFα-driven VEC oxidative stress causes loss of endothelial protective function, chronic inflammation, and fibrogenic and osteogenic activation, mitigated differentially by BH₄ and peg-SOD. These mechanisms identify new targets for tailored antioxidant therapy focused on mitigation of oxidative stress and restoration of endothelial protection.     

Antithrombotic therapy in patients undergoing TAVI: an overview of Dutch hospitals

Purpose

To assess current antithrombotic treatment strategies in the Netherlands in patients undergoing transcatheter aortic valve implantation (TAVI).

Methods

For every Dutch hospital performing TAVI (n = 14) an interventional cardiologist experienced in performing TAVI was interviewed concerning heparin, aspirin, thienopyridine and oral anticoagulation treatment in patients undergoing TAVI.

Results

The response rate was 100 %. In every centre, a protocol for antithrombotic treatment after TAVI was available. Aspirin was prescribed in all centres, concomitant clopidogrel was prescribed 13 of the 14 centres. Duration of concomitant clopidogrel was 3 months in over two-thirds of cases. In 2 centres, duration of concomitant clopidogrel was based upon type of prosthesis: 6 months versus 3 months for supra-annular and intra-annular prostheses, respectively.

Conclusions

Leaning on a small basis of evidence and recommendations, the antithrombotic policy for patients undergoing TAVI is highly variable in the Netherlands. As a standardised regimen might further reduce haemorrhagic complications, large randomised clinical trials may help to establish the most appropriate approach.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-013-0496-6) contains supplementary material, which is available to authorized users.     

Microparticle-Induced Coagulation Relates to Coronary Artery Atherosclerosis in Severe Aortic Valve Stenosis

Background

Circulating microparticles (MPs) derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification.

Methods

In a cross-sectional study of 55 patients with severe aortic valve stenosis, we assessed the coronary calcification score (CAC) as indicator of total coronary atherosclerosis burden, and aortic valve calcification (AVC) by computed tomography. Thrombin-antithrombin complex (TATc) levels were measured as a marker for thrombin formation. Circulating MPs were characterized by flow cytometry according to the expression of established surface antigens and by measuring MP-induced thrombin generation.

Results

Patients with CAC score below the median were classified as patients with low CAC, patients with CAC Score above the median as high CAC. In patients with high CAC compared to patients with low CAC we detected higher levels of TATc, platelet-derived MPs (PMPs), endothelial-derived MPs (EMPs) and MP-induced thrombin generation. Increased level of PMPs and MP-induced thrombin generation were independent predictors for the severity of CAC. In contrast, AVC Score did not differ between patients with high and low CAC and did neither correlate with MPs levels nor with MP-induced thrombin generation.

Conclusion

In patients with severe aortic valve stenosis MP-induced thrombin generation was independently associated with the severity of CAC but not AVC indicating different pathomechanisms involved in coronary artery and aortic valve calcification.     

Dietary Inflammatory Index and Incidence of Cardiovascular Disease in the SUN Cohort

Background

Diet is known to play a key role in atherogenesis and in the development of cardiovascular events. Dietary factors may mediate these processes acting as potential modulators of inflammation. Potential Links between inflammatory properties of diet and the occurrence of cardiovascular events have not been tested previously.

Objective

We aimed to assess the association between the dietary inflammatory index (DII), a method to assess the inflammatory potential of the diet, and incident cardiovascular disease.

Methods

In the prospective, dynamic SUN cohort, 18,794 middle-aged, Spanish university graduates were followed up for 8.9 years (median). A validated 136-item food-frequency questionnaire was used to calculate the DII. The DII is based on scientific evidence about the relationship between diet and inflammatory biomarkers (C-reactive protein, IL-1β, IL-4, IL-6, IL-10 and TNF-α). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between the DII and incident cardiovascular disease (myocardial infarction, stroke or cardiovascular death).

Results

The risk for cardiovascular events progressively increased with each increasing quartile of DII (p_trend = 0.017). The multivariable-adjusted HR for participants in the highest (most pro-inflammatory) vs. the lowest quartile of the DII was 2.03 (95% CI 1.06–3.88).

Conclusions

A pro-inflammatory diet was associated with a significantly higher risk for developing cardiovascular events.     

IL-6 Transsignaling in Patients with Chronic Spontaneous Urticaria

Background

IL-6 trans-signaling is critically involved in the initiation and promotion of inflammatory and autoimmune diseases. Therefore, we investigated the clinical relevance of soluble members of IL-6 trans-signaling system in chronic spontaneous urticaria (CSU).

Methods

IL-6, interleukin 6 soluble receptor (IL-6 sR) and soluble gp130 (sgp130) were measured by ELISA method in plasma from CSU patients and the healthy subjects. The data were related to activation of the acute phase response as indicated by serum C-reactive protein (CRP) concentration and compared between patients stratified by the disease activity.

Results

Concentrations of IL-6, IL-6 sR, sgp130 in plasma and CRP in serum were significantly elevated in CSU patients compared with the healthy controls. CRP correlated significantly with IL-6 and sgp130, similarly IL-6 correlated significantly with sgp130. By contrast, CRP and IL-6 did not correlate significantly with IL-6 sR. However, significant correlation was noted between IL-6 sR and sgp130.

Conclusions

Concentrations of IL-6 and its soluble receptors were significantly elevated in patients with CSU, suggesting upregulation of the IL-6 trans-signaling in the disease. In addition, our results support the concept that the system may be involved in pathogenesis of the systemic inflammatory activation in CSU patients.     

Clinical course of patients diagnosed with severe aortic stenosis in the Rotterdam area: insights from the AVARIJN study

Objective

To prospectively evaluate the clinical course of patients with severe aortic stenosis (AS) and identify factors associated with treatment selection and patient outcome.

Methods

Patients diagnosed with severe AS in the Rotterdam area were included between June 2006 and May 2009. Patient characteristics, echocardiogram, brain natriuretic peptide (NT-proBNP), and treatment strategy were assessed at baseline, and after 6, 12, and 24 months. Endpoints were aortic valve replacement (AVR) / transcatheter aortic valve implantation (TAVI) and death.

Results

The study population comprised 191 patients, 132 were symptomatic and 59 asymptomatic at study entry. Two-year cumulative survival of symptomatic patients was 89.8 % (95 % CI 79.8–95.0 %) after AVR/TAVI and 72.6 % (95 % CI 59.7–82.0 %) with conservative treatment. Two-year cumulative survival of asymptomatic patients was 91.5 % (95 % CI 80.8–96.4 %). Two-year cumulative incidence of AVR/TAVI was 55.9 % (95 % CI 47.5–63.5 %) in symptomatic patients. Sixty-eight percent of asymptomatic patients developed symptoms, median time to symptoms was 13 months; AVR/TAVI cumulative incidence was 38.3 % (95 % CI 23.1–53.3 %). Elderly symptomatic patients with multiple comorbidities were more likely to receive conservative treatment.

Conclusions

In contemporary Dutch practice many symptomatic patients do not receive invasive treatment of severe AS. Two-thirds of asymptomatic patients develop symptoms within 2 years, illustrating the progressive nature of severe AS. Treatment optimisation may be achieved through careful individualised assessment in a multidisciplinary setting.     

Comparison of Aortic Annulus Diameter Measurement between Multi-Detector Computed Tomography and Echocardiography: A Meta-Analysis

Background and Purpose

Accurate measurement of aortic annulus diameter is crucial for choosing suitable prosthetic size for transcatheter aortic valve implantation (TAVI). Several imaging methods are available for the measurement, but significant variability between different modalities has been observed. The purpose of this study was to systematically compare the measurements of aortic annulus diameter between multi-detector computed tomography (MDCT), transthoracic echocardiography (TTE), and transesophegeal echocardiography (TEE).

Methods

PubMed and EMBASE databases between January 2000 and January 2012 were searched. We extracted data from eligible studies evaluating the aortic annulus diameter by MDCT and echocardiography (TTE, TEE, or both). We performed a random-effects meta-analysis to calculate the weighted mean differences of aortic annulus diameter measurement between MDCT, TTE, and TEE.

Results

A total of 10 eligible studies involving 581 subjects with aortic valve stenosis were included. Aortic annulus diameter measured on coronal view by MDCT (25.3±0.52 mm) was respectively larger than that measured on sagittal view by MDCT (22.7±0.37 mm), TTE (22.6±0.28 mm), and TEE (23.1±0.32 mm). The weighted mean difference of aortic annulus diameter between coronal view by MDCT and TTE these two methods was 2.97 mm, followed by the weighted mean difference of 2.53 mm between coronal view and sagittal view by MDCT, and the mean difference of 1.74 mm between coronal view on MDCT and TEE (P<0.0001 for all). The weighted mean difference of aortic annulus diameter measurement between TEE and TTE was significant but somewhat small (0.45 mm, P = 0.007).

Conclusion

Aortic annulus diameter measured on coronal view by MDCT was robustly and significantly larger than that obtained on sagittal view by MDCT, TTE, or TEE. Such variability of aortic annulus diameter measurement by different imaging modalities cannot be ignored when developing optimal strategies for selection of prosthetic valve size in TAVI.     

The Relationship between Zinc Status and Inflammatory Marker Levels in Rural Korean Adults Aged 40 and Older

Background

Serum cytokines and C-reactive protein (CRP) are known as one of the major risk factors in atherosclerosis. The antioxidant and anti-inflammatory properties of zinc have been suggested, but few data are available on the relationship between zinc status and inflammatory markers in epidemiological studies.

Objective

The present study aims to investigate the cross-sectional relationships of serum cytokines and CRP with dietary zinc intake and serum zinc levels in healthy men and women aged 40 and older in rural areas of South Korea.

Materials and Methods

A group of 1,055 subjects (404 men, 651 women) was included in dietary zinc analysis while another group of 695 subjects (263 men, 432 women) was included in serum zinc analysis. Serum IL-6, TNF-α, and CRP were measured as inflammatory markers.

Results

There was no significant inverse relationship between dietary zinc intake and inflammatory markers. We found a significant inverse relationship between serum zinc levels and all three inflammatory markers in women (P for trend = 0.0236 for IL-6; P for trend = 0.0017 for TNF-α; P for trend = 0.0301 for CRP) and between serum zinc levels and a single inflammatory marker (IL-6) in men (P for trend = 0.0191), although all R2 values by regression were less than 10%.

Conclusion

In conclusion, serum zinc levels may be inversely related to inflammatory markers (IL-6, TNF-α, and CRP), particularly in women.