Clinical Events After Deferral of LAD Revascularization Following Physiological Coronary Assessment.

BACKGROUND: Physicians are not always comfortable deferring treatment of a stenosis in the left anterior descending (LAD) artery because of the perception that there is a high risk of major adverse cardiac events (MACE). The authors describe, using the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) trial, MACE rates when LAD lesions are deferred, guided by physiological assessment using fractional flow reserve (FFR) or the instantaneous wave-free ratio (iFR). OBJECTIVES: The purpose of this study was to establish the safety of deferring treatment in the LAD using FFR or iFR within the DEFINE-FLAIR trial. METHODS: MACE rates at 1 year were compared between groups (iFR and FFR) in patients whose physiological assessment led to LAD lesions being deferred. MACE was defined as a composite of cardiovascular death, myocardial infarction (MI), and unplanned revascularization at 1 year. Patients, and staff performing follow-up, were blinded to whether the decision was made with FFR or iFR. Outcomes were adjusted for age and sex. RESULTS: A total of 872 patients had lesions deferred in the LAD (421 guided by FFR, 451 guided by iFR). The event rate with iFR was significantly lower than with FFR (2.44% vs. 5.26%; adjusted HR: 0.46; 95% confidence interval [CI]: 0.22 to 0.95; p = 0.04). This was driven by significantly lower unplanned revascularization with iFR and numerically lower MI (unplanned revascularization: 2.22% iFR vs. 4.99% FFR; adjusted HR: 0.44; 95% CI: 0.21 to 0.93; p = 0.03; MI: 0.44% iFR vs. 2.14% FFR; adjusted HR: 0.23; 95% CI: 0.05 to 1.07; p = 0.06). CONCLUSIONS: iFR-guided deferral appears to be safe for patients with LAD lesions. Patients in whom iFR-guided deferral was performed had statistically significantly lower event rates than those with FFR-guided deferral.

Aortic regurgitation after transcatheter aortic valve implantation (TAVI) - Angiographic, echocardiographic and hemodynamic assessment in relation to one year outcome.

BACKGROUND: Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) remains a relatively frequent and life-limiting complication. However, the most prognostically discriminative (and therefore preferred) technique of AR evaluation after TAVI is not yet clearly defined. The aim of this study was to compare angiographic, echocardiographic and hemodynamic assessment of AR after TAVI in relation to one year outcome. METHODS AND RESULTS: In this single center prospective cohort study, angiography (AR grading), echocardiography (AR quantification using color Doppler flow mapping) and invasive hemodynamics (AR index) were assessed before and after TAVI. All patients were followed up to at least one year. A total of 111 consecutive (very) high-risk patients with severe, symptomatic aortic valve stenosis underwent TAVI. No concordant relation could be demonstrated between angiographic, echocardiographic and invasive assessment of AR after TAVI. AR index <25 post TAVI was significantly influenced by left ventricular posterior wall thickness (odds ratio: 1.276, p=0.030) and AR index pre TAVI (odds ratio: 0.948, p=0.019). Neither angiographic nor hemodynamic AR assessments were able to discriminate between good or significantly decreased one year survival. In contrast, color Doppler flow mapping of AR after TAVI was highly reproducible, and able to differentiate between good or significantly decreased one year survival (AR grades 0-I: one year survival 87% vs. AR grades II-III-IV: one year survival 68%, p=0.035). CONCLUSION: Echocardiography using color Doppler flow mapping is the preferred technique to assess prognostically relevant AR after TAVI.

Bone matrix vesicle-bound alkaline phosphatase for the assessment of peripheral blood admixture to human bone marrow aspirates.

PURPOSE: Peripheral blood (PB) admixture should be minimized during numerical and functional, as well as cytokinetic analysis of bone marrow (BM) aspirates for research purposes. Therefore, purity assessment of the BM aspirate should be performed in advance. We investigated whether bone matrix vesicle (BMV)-bound bone alkaline phosphatase (ALP) could serve as a marker for the purity of BM aspirates. RESULTS: Total ALP activity was significantly higher in BM serum (97 (176-124)U/L, median (range)) compared to PB serum (63 (52-73)U/L, p < 0.001). Agarose gel electrophoresis showed a unique bone ALP fraction in BM, which was absent in PB. Native polyacrylamide gel electrophoresis revealed the high molecular weight of this fraction, corresponding with membrane-bound ALP from bone matrix vesicles (BMV), as evidenced by electron microscopy. A serial PB admixture experiment of bone cylinder supernatant samples, rich in BMV-bound ALP, confirmed the sensitivity of this proposed quality assessment method. Furthermore, a BMV ALP fraction of ≥ 15% is suggested as cut-off value for minimal BM quality. Moreover, the BM purity declines rapidly with larger aspirated BM volumes. CONCLUSION: The exclusive presence of BMV-bound ALP in BM could serve as a novel marker to assess purity of BM aspirates.

Cost-effectiveness of contemporary vascular closure devices for the prevention of vascular complications after percutaneous coronary interventions in an all-comers PCI population.

AIMS: The present observational case-control study assessed the cost-effectiveness of contemporary vascular closure devices (VCDs) for the prevention of vascular complications in an all-comers transfemoral percutaneous coronary intervention (PCI) population. METHODS AND RESULTS: A total of 8,292 consecutive PCI patients were enrolled from a single-centre prospective registry from January 2005 to December 2010. VCDs were available from July 2007 and, from that time point, VCDs were implanted in 1,780 of the 5,394 patients (33%). Vascular complications occurred in 221 (2.7%) patients. The use of VCDs was independently associated with a 53% risk reduction (OR 0.47, 95% CI: 0.3-0.7) in vascular complications (3.0% vs. 1.5%) and with a 65% risk reduction (IRR 0.37, 95% CI: 0.32-0.43) in the post-PCI length of hospital stay (LOS) (mean 2.8 vs. 1.5 days). Mainly due to the reduced LOS, the patients with VCDs accrued vascular direct medical costs (VCD, diagnosis and treatment of vascular complications, post-PCI LOS) that were on average 498€ less than those accrued by the non-VCD patients. The cost-effectiveness was present across all vascular risk profiles. CONCLUSIONS: In this large, all-comers transfemoral PCI population, the use of VCDs was independently associated with a reduction in the rate of vascular complications and the post-PCI length of hospital stay and proved to be cost-saving across all vascular risk profiles.

Automatic assessment of stent neointimal coverage by intravascular optical coherence tomography.

AIMS: This study aimed to validate automatic intravascular optical coherence tomography (IVOCT) analysis for the evaluation of neointimal coverage in response to stent implantation. METHODS AND RESULTS: Fourteen stented segments in common iliac arteries, acquired from a total of seven adult male New Zealand White rabbits, were interrogated in vivo by IVOCT. Durable polymer everolimus-eluting stents (EES; Xience V, Abbott Vascular, Santa Clara, CA, USA) were used exclusively. Comparison with histology was made in a total of 63 pairs of images, where neointimal thickness over corresponding individual stent struts was assessed. A high correlation coefficient (R = 0.85, P < 0.001) was obtained by comparing automatic IVOCT analysis with histology. Moreover, Bland-Altman statistics showed good limits of agreement (LOAs) of ±45 µm, with an average difference of -10 µm. In addition, manual IVOCT assessment presented very similar results when compared with histology (R = 0.83, P < 0.001 and LOA = ±48 µm with an average difference of -8 µm). Therefore, a very high correlation value was found, comparing manual to automatic IVOCT measurements (R = 0.95, P < 0.001) together with good LOAs (±27 µm) and an average difference of -2 µm. CONCLUSION: The results of the study suggest that automatic IVOCT analysis is a reliable and accurate tool able to speed up current IVOCT analysis procedures. This would potentially allow for a better integration of IVOCT in clinical practice and clinical studies assessing vascular response to stent implantation in a large series of patients.

Assessment of left ventricular volumes and primary mitral regurgitation severity by 2D echocardiography and cardiovascular magnetic resonance.

BACKGROUND: Two-dimensional transthoracic echocardiography (2DTTE) remains the first-line diagnostic imaging tool to assess primary mitral regurgitation although cardiovascular magnetic resonance (CMR) has proven to establish left ventricular function more accurately and might evaluate mitral regurgitation severity more reliably. We sought to compare routine evaluation of left ventricular function and mitral regurgitation severity by 2DTTE with assessment by CMR in moderate to severe primary mitral regurgitation without overt left ventricular dysfunction. METHODS: We prospectively included 38 patients (79% of male, age 57 ± 14 years) with at least moderate primary mitral regurgitation, a left ventricular ejection fraction ≥60% and a left ventricular end-systolic diameter ≤45 mm. Patients with evidence of coronary artery disease, arrhythmias or significant concomitant valvular disease were excluded. All patients were scheduled for 2DTTE and CMR. RESULTS: Left ventricular end-diastolic and end-systolic volumes were significantly underestimated by 2DTTE in comparison with CMR, although there was a strong correlation (Pearson r = 0.81, p < 0.00001 and r = 0.7, p < 0.00001, respectively). Measurement of the regurgitant orifice was similar between 2DTTE PISA method and planimetry by CMR (47 ± 24 vs. 42 ± 16 mm2, p = 0.12) with a strong correlation between both imaging techniques (Pearson r = 0.76, p < 0.0001). By contrast, assessment of the regurgitant volume by 2DTTE and by phase contrast velocity mapping by CMR showed poor agreement. CONCLUSIONS: In moderate to severe primary mitral regurgitation without overt left ventricular dysfunction, 2DTTE significantly underestimates left ventricular remodelling in comparison to CMR. Measurement of the regurgitant orifice with planimetry by CMR shows good agreement with the PISA method by 2DTTE and thus may be a valuable alternative to assess mitral regurgitation severity.

Assessment of endothelial dysfunction in childhood obesity and clinical use.

The association of obesity with noncommunicable diseases, such as cardiovascular complications and diabetes, is considered a major threat to the management of health care worldwide. Epidemiological findings show that childhood obesity is rapidly rising in Western society, as well as in developing countries. This pandemic is not without consequences and can affect the risk of future cardiovascular disease in these children. Childhood obesity is associated with endothelial dysfunction, the first yet still reversible step towards atherosclerosis. Advanced research techniques have added further insight on how childhood obesity and associated comorbidities lead to endothelial dysfunction. Techniques used to measure endothelial function were further brought to perfection, and novel biomarkers, including endothelial progenitor cells, were discovered. The aim of this paper is to provide a critical overview on both in vivo as well as in vitro markers for endothelial integrity. Additionally, an in-depth description of the mechanisms that disrupt the delicate balance between endothelial damage and repair will be given. Finally, the effects of lifestyle interventions and pharmacotherapy on endothelial dysfunction will be reviewed.

Transesophageal echocardiography for cardiac thromboembolic risk assessment in patients with severe, symptomatic aortic valve stenosis referred for potential transcatheter aortic valve implantation.

Stroke is a devastating complication after transcatheter aortic valve implantation (TAVI) and might partially be related to cardiac embolization. The aim of this single-center prospective study was to determine the incidence of intracardiac thrombi and left atrial spontaneous echo contrast (SEC), both known predictors of cardiac embolic stroke, in patients referred for potential TAVI. One hundred four consecutive patients with severe symptomatic aortic valve stenosis and at high or very high risk for surgery were included and underwent transesophageal echocardiography. In 11 patients (10.6%), intracardiac thrombi were detected, and 25 patients (24%) showed dense grade 2 SEC. Atrial fibrillation (p <0.0001), diastolic dysfunction (p = 0.0005), and atrial size (p = 0.0038) were related to the presence of intracardiac thrombus and/or dense SEC on multivariate analysis. In conclusion, the incidence of intracardiac thrombi and dense SEC in (very) high-risk patients with severe aortic valve stenosis referred for potential TAVI is high and can accurately be detected using transesophageal echocardiography. Systematic thromboembolic evaluation using transesophageal echocardiography is thus recommended in patients referred for TAVI.

Endothelial microparticles (EMP) for the assessment of endothelial function: an in vitro and in vivo study on possible interference of plasma lipids.

BACKGROUND: Circulating endothelial microparticles (EMP) reflect the condition of the endothelium and are of increasing interest in cardiovascular and inflammatory diseases. Recently, increased numbers of EMP following oral fat intake, possibly due to acute endothelial injury, have been reported. On the other hand, the direct interference of lipids with the detection of EMP has been suggested. This study aimed to investigate the effect of lipid-rich solutions, commonly administered in clinical practice, on the detection, both in vitro and in vivo, of EMP. METHODS: For the in vitro assessment, several lipid-rich solutions were added to whole blood of healthy subjects (n = 8) and patients with coronary heart disease (n = 5). EMP (CD31+/CD42b-) were detected in platelet poor plasma by flow cytometry. For the in vivo study, healthy volunteers were evaluated on 3 different study-days: baseline evaluation, following lipid infusion and after a NaCl infusion. EMP quantification, lipid measurements and peripheral arterial tonometry were performed on each day. RESULTS: Both in vitro addition and in vivo administration of lipids significantly decreased EMP (from 198.6 to 53.0 and from 272.6 to 90.6/µl PPP, respectively, p = 0.001 and p = 0.012). The EMP number correlated inversely with the concentration of triglycerides, both in vitro and in vivo (r = -0.707 and -0.589, p<0.001 and p = 0.021, respectively). The validity of EMP as a marker of endothelial function is supported by their inverse relationship with the reactive hyperemia index (r = -0.758, p = 0.011). This inverse relation was confounded by the intravenous administration of lipids. CONCLUSION: The confounding effect of high circulating levels of lipids, commonly found in patients that receive intravenous lipid-based solutions, should be taken into account when flow cytometry is used to quantify EMP.

B-type natriuretic peptide and assessment of jeopardised myocardium in acute myocardial infarction.

BACKGROUND: B-type natriuretic peptide (BNP) is used as prognostic marker in acute coronary syndromes. It is unknown whether BNP reflects the amount of jeopardised myocardium in the initial phase of acute ST-elevation myocardial infarction (STEMI). METHODS: Patients admitted for percutaneous coronary intervention in the acute phase of STEMI were studied. Samples for BNP were taken at the time of coronary intervention and were correlated with the amount of jeopardised myocardium. This was defined on coronary angiography as the vascular region distal to the infarct-related lesion and was expressed by a vascular score. The extend of epicardial injury on ECG was evaluated by: summation of ST-segment elevation in the infarct-related leads, number of leads with > or = 1 mm ST-segment elevation and number of leads with > or = 1 mm ST-segment depression/elevation. RESULTS: A total of 113 patients (median age (25th, 75th percentile) 61 (54, 69)) were studied. Median BNP was 27 pg/ml (12, 62) and was assessed 225 min (150, 315) after onset of pain. There was no significant relation between BNP and vascular score (r=0.026, p=0.8). The only independent variable of BNP was time delay between onset of pain and sample collection. Stepwise regression identified the extent of ST-segment elevation as independent predictor of the vascular score. CONCLUSION: At initial presentation of STEMI, BNP measurement does not allow a correct prediction of jeopardised myocardium. In contrast, ST-segment analysis, in particularly the extent of ST-segment elevation, provides useful information about the extent of jeopardised myocardium.