[Show abstract][Hide abstract] ABSTRACT: Objectives:
Mitral regurgitation (MR) is a common entity in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR), but its influence on outcomes remains controversial. The purpose of this meta-analysis was to assess the clinical impact of and changes in significant (moderate-severe) MR in patients undergoing TAVR, overall and according to valve design (self-expandable (SEV) vs balloon-expandable (BEV)).
All national registries and randomised trials were pooled using meta-analytical guidelines to establish the impact of moderate-severe MR on mortality after TAVR. Studies reporting changes in MR after TAVR on an individual level were electronically searched and used for the analysis.
Eight studies including 8015 patients (SEV: 3474 patients; BEV: 4492 patients) were included in the analysis. The overall 30-day and 1-year mortality was increased in patients with significant MR (OR 1.49, 95% CI 1.16 to 1.92; HR 1.32, 95% CI 1.12 to 1.55, respectively), but a significant heterogeneity across studies was observed (p<0.05). The impact of MR on mortality was not different between SEV and BEV in meta-regression analysis for 30-day (p=0.360) and 1-year (p=0.388) mortality. Changes in MR over time were evaluated in nine studies including 1278 patients. Moderate-severe MR (SEV: 326 patients; BEV: 192 patients) improved in 50.5% of the patients at a median follow-up of 180 (30-360) days after TAVR, and the degree of improvement was greater in patients who had received a BEV (66.7% vs 40.8% in the SEV group, p=0.001).
Concomitant moderate-severe MR was associated with increased early and late mortality following TAVR. A significant improvement in MR severity was detected in half of the patients following TAVR, and the degree of improvement was greater in those patients who had received a BEV.
[Show abstract][Hide abstract] ABSTRACT: Collateral growth in patients with coronary artery disease (CAD) is highly heterogeneous. Although multiple factors are thought to play a role in collateral development, the contribution of genetic factors to coronary collateral circulation (CCC) is largely unknown. The goal of this study was to assess whether functional single nucleotide polymorphisms (SNPs) in genes involved in vascular growth are associated with CCC.
677 consecutive CAD patients were enrolled in the study and their CCC was assessed by the Rentrop method. 22 SNPs corresponding to 10 genes involved in postischemic neovascularization were genotyped and multivariate logistic regression models were adjusted using clinically relevant variables to estimate odds ratios and used to examine associations of allelic variants, genotypes and haplotypes with CCC.
Statistical analysis showed that the HIF1A rs11549465 and rs2057482; VEGFA rs2010963, rs1570360, rs699947, rs3025039 and rs833061; KDR rs1870377, rs2305948 and rs2071559; CCL2 rs1024611, rs1024610, rs2857657 and rs2857654; NOS3 rs1799983; ICAM1 rs5498 and rs3093030; TGFB1 rs1800469; CD53 rs6679497; POSTN rs3829365 and rs1028728; and LGALS2 rs7291467 polymorphisms, as well as their haplotype combinations, were not associated with CCC (p < 0.05).
We could not validate in our cohort the association of the NOS3 rs1799983, HIF1A rs11549465, VEGFA rs2010963 and rs699947, and LGALS2 rs7291467 variants with CCC reported by other authors. A validated SNP-based genome-wide association study is required to identify polymorphisms influencing CCC.
[Show abstract][Hide abstract] ABSTRACT: Background Little evidence exists of the burden and predictors of cardiac death after transcatheter aortic valve replacement (TAVR). Objectives The purpose of this study was to assess the incidence and predictors of cardiac death from advanced heart failure (HF) and sudden cardiac death (SCD) in a large patient cohort undergoing TAVR. Methods The study included a total of 3,726 patients who underwent TAVR using balloon (57%) or self-expandable (43%) valves. Causes of death were defined according to the Valve Academic Research Consortium-2. Results At a mean follow-up of 22 ± 18 months, 155 patients had died due to advanced HF (15.2% of total deaths, 46.1% of deaths from cardiac causes) and 57 had died due to SCD (5.6% of deaths, 16.9% of cardiac deaths). Baseline comorbidities (chronic obstructive pulmonary disease, atrial fibrillation, left ventricular ejection fraction ≤40%, lower mean transaortic gradient, pulmonary artery systolic pressure >60 mm Hg; p < 0.05 for all) and 2 procedural factors (transapical approach, hazard ratio [HR]: 2.38, 95% confidence interval [CI]: 1.60 to 3.54; p < 0.001; presence of moderate or severe aortic regurgitation after TAVR, HR: 2.79, 95% CI: 1.82 to 4.27; p < 0.001) independently predicted death from advanced HF. Left ventricular ejection fraction ≤40% (HR: 1.93, 95% CI: 1.05 to 3.55; p = 0.033) and new-onset persistent left bundle-branch block following TAVR (HR: 2.26, 95% CI: 1.23 to 4.14; p = 0.009) were independently associated with an increased risk of SCD. Patients with new-onset persistent left bundle-branch block and a QRS duration >160 ms had a greater SCD risk (HR: 4.78, 95% CI: 1.56 to 14.63; p = 0.006). Conclusions Advanced HF and SCD accounted for two-thirds of cardiac deaths in patients after TAVR. Potentially modifiable or treatable factors leading to increased risk of mortality for HF and SCD were identified. Future studies should determine whether targeting these factors decreases the risk of cardiac death.
Journal of the American College of Cardiology 02/2015; 65(5):437-48. DOI:10.1016/j.jacc.2014.11.027 · 16.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Primary percutaneous coronary intervention with stent implantation is the recommended treatment for patients with ST elevation myocardial infarction (STEMI). Date from randomized trial showed a good performance of titanium--nitro--oxide coated stent in this context. The aim of this study was to confirm these data in an all comers population.
A multicentre registry was performed in 23 hospitals in Spain. We selected patients with STEMI from a global TITAN AMI registry that included patients with acute coronary syndrome. Primary end point was the composite of cardiac death, non-fatal myocardial infarction, stent thrombosis and target lesions revascularization, at 12--month follow-up.
We included 893 patients with STEMI. We included all possibilities for PCI: 86,6% primary, 5,0% facilitated after successful fibrinolysis and 8,4% rescue PCI after failed fibrinolysis. The primary end point was observed in 8,4% of the patients: cardiac death 2,7%, reinfarction 3,4%, target lesion revascularization 3,5% and definite or probable stent thrombosis 2,8%. The majority of stent thrombosis presented in the first 30 days after PCI.
BioActive stent (Titanium--nitro--oxide coated stent) can be an alternative for the treatment of patients with STEMI. One--year follow--up showed better results than those presented by regular bare---metal stent or first---generation drug eluting stent in terms of stent thrombosis.
[Show abstract][Hide abstract] ABSTRACT: To evaluate the usefulness of the information obtained with SPECT, coronary angio-CT and fusion images, in patients with stable ischemic disease who need invasive coronary angiography (IA).
Revista Española de Medicina Nuclear e Imagen Molecular 12/2014; 34(3). DOI:10.1016/j.remn.2014.11.004 · 0.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: -This study aimed to evaluate the prevalence of previously undiagnosed arrhythmias in candidates for TAVR and to determine its impact on therapy changes and arrhythmic events following the procedure.
-A total of 435 candidates for TAVR underwent 24-hour continuous electrocardiographic (ECG) monitoring the day before the procedure. Newly diagnosed arrhythmias were observed in 70 patients (16.1%) before TAVR: paroxysmal atrial fibrillation (AF)/atrial tachycardia (AT) in 28, advanced atrio-ventricular block (AVB) or severe bradycardia in 24, non-sustained ventricular tachycardia in 26, and intermittent left bundle branch block (LBBB) in 3 patients. All arrhythmic events but one were asymptomatic, and led to a therapy change in 43% of patients. In patients without known AF/AT, the occurrence of AF/AT during 24-hour ECG recording was associated with a higher rate of 30-day cerebrovascular events (7.1% vs 0.4%, P=0.030). Among the 53 patients with new-onset AF/AT after TAVR, 30.2% had newly diagnosed paroxysmal AF/AT before the procedure. In patients who needed permanent pacemaker implantation following the procedure (n=35), 31.4% had newly diagnosed advanced AVB or severe bradycardia before TAVR. New-onset persistent LBBB following TAVR occurred in 37 patients, 8.1% of whom had intermittent LBBB before the procedure.
-Newly diagnosed arrhythmias were observed in about a fifth of TAVR candidates, led to a higher rate of cerebrovascular events and accounted for a third of arrhythmic events following the procedure. This high arrhythmia burden highlights the importance of an early diagnosis of arrhythmic events in such patients in order to implement the appropriate therapeutic measures earlier on.
[Show abstract][Hide abstract] ABSTRACT: The Working Group on Cardiac Catheterization and Interventional Cardiology presents its yearly report on the data from the registry of the activity in Spain corresponding to 2013.Methods
The centers introduce their data online voluntarily and the information is analyzed by the Steering Committee of the Working Group on Cardiac Catheterization.ResultsIn 2013, 104 hospitals sent their data (72 public centers and 32 private). In all, 136 715 diagnostic studies were performed (120 358 coronary angiograms), with a slight decrease with respect to 2012, a reduction that was also observed in the rate, which was 2944 diagnostic studies per million population. A total of 65 912 interventional procedures were carried out during a phase of stability, for a rate of 1419 interventions per million population. Other techniques included the implantation of 99 417 stents and 1384 biodegradable intracoronary devices (64% of them drug-eluting devices). There were 18 337 procedures in acute myocardial infarction, for an increase of 7% with respect to 2012 and representing 27.8% of all the percutaneous coronary interventions. Radial access was the approach used in 71% of the diagnostic procedures and in 65% of the interventional procedures. The performance of renal denervation has nearly doubled with respect to 2012. For the first time, more than 1000 transcatheter aortic valve implantation procedures were carried out in 1 year, although the frequency increased only slightly (23%).Conclusions
There continued to be a slight increase in the activity in cardiac catheterization in association with ST-segment elevation myocardial infarction, whereas, with the exception of recently introduced, highly specific procedures, the use of the remainder of the procedures, among them transcatheter aortic valve implantation, leveled off.Full English text available from: www.revespcardiol.org/en
Revista Espa de Cardiologia 11/2014; 66(11). DOI:10.1016/j.recesp.2014.08.005 · 3.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
It is unknown if lack of polymer can provoke a different edge response in drug-eluting stents. The aim of this study was to compare edge vascular response between polymer-free paclitaxel-eluting stent (PF-PES) and polymer-based paclitaxel-eluting stents (PB-PES). METHODS AND RESULTS: A total of 165 eligible patients undergoing percutaneous coronary intervention were prospectively randomized 1:1 to receive either PF-PES or PB-PES. Those patients with paired intravascular ultrasound (IVUS) after procedure and at 9-month follow-up were included in this analysis.Seventy-six patients with 84 lesions, divided into PB-PES (38 patients, 41 lesions) and PF-PES groups (38 patients, 43 lesions) had paired post-procedure and 9-month follow-up IVUS and were therefore included in this substudy. There was a significant lumen decrease at the proximal edge of PF-PES (from 9.02±3.06 mm(2)to 8.47±3.05 mm(2); P=0.040), and a significant plaque increase at the distal edges of PF-PES (from 4.39±2.73 mm(2)to 4.78±2.63 mm(2); P=0.004). At the distal edge there was a significant plaque increase in the PF-PES compared to PB-PES (+8.0% vs. -0.6%, respectively; P=0.015) with subsequent lumen reduction (-5.2% vs. +6.0%, respectively; P=0.024).
PF-PES had significant plaque increase and lumen reduction at the distal edge as compared to PB-PES, probably due to difference in polymer-based drug-release kinetics between the 2 platforms.
[Show abstract][Hide abstract] ABSTRACT: Aims: This study will compare the efficacy of drug-eluting balloons (DEB) and everolimus-eluting stents (EES) in patients with drug-eluting stent (DES) in-stent restenosis (ISR). Methods and results: This is a prospective, multicentre, randomised clinical trial comparing DEB and EES in patients with DES-ISR. The study is an investigator-driven initiative generated within the RIBS study programme. A total of 310 patients with DES-ISR will be included and randomised (1:1) to DEB or EES. Angiographic follow-up has been scheduled at six to nine months. Quantitative coronary analyses will be performed in a centralised core lab by blinded personnel. The primary endpoint of the study is minimal lumen diameter at angiographic follow-up. Other secondary angiographic endpoints include % diameter stenosis, late loss, net gain and binary restenosis rate. An independent clinical events committee will adjudicate clinical events after reviewing source documents. The main clinical outcome measure is a combined endpoint of cardiac death, myocardial infarction and target vessel revascularisation at one year. Individual components of the combined clinical endpoint and rates of target lesion revascularisation and stent thrombosis will also be compared. Conclusions: This randomised clinical trial will determine the relative efficacy of EES versus DEB in patients presenting with DES-ISR. (ClinicalTrials.gov Identifier: NCT01239940).
EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology 09/2014; 11(3). DOI:10.4244/EIJY14M09_07 · 3.77 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Intravenous antagomir-92a based-therapy enhanced neoangiogenesis and improved left ventricular contractility in a mouse model of acute myocardial infarction (MI), but its effect on postMI remodeling is unknown and clinical translation limited by the need of repeated administration and potential systemic adverse effects (AE). We investigated whether a single intracoronary administration of antagomir-92a encapsulated in microspheres (Antag92aME) could prevent deleterious myocardial remodeling one month (1mo) after MI.
Methods and results: We developed poly-d,-lactide-co-glycolide 9 μm ME with 7-10% loads of 3 mg Antag92a. In a first phase, ME were injected in the LAD coronary artery of healthy pigs. Repetitive injections to a total dose of 240 mg were used (n=3) to rule out persistent effects in myocardial contraction (intramyocardial piezoelectric crystals), LAD flow (Doppler probe) or necrosis (histology), and fluorescence labeled ME injection (n=4) showed no ME content in myocardium outside the LAD territory or in lung, spleen or liver (fluorescence microscopy). Finally, miR-92a expression was quantified by RT-PCR in 3 pigs euthanized at 1, 3 and 10 days after Antag92aME injection demonstrating local and sustained miR-92a inhibition (>8× and >4× fold at 1 and 10 days). In a second phase, MI was induced inflating a 2.5/12 mm balloon (49 min) in LAD of 27 closed-chest minipigs, randomly to blind receive Antag92aME, placeboME or saline administration, 5 minutes after reperfusion. Intravascular echocardiography was performed during ischemia, reperfusion and repeated 1mo later immediately before the animals were euthanized and the hearts excised, ex-vivo MRI was performed (maximum necrotic wall thickness (Tmax), largest diameter (D) between remodeled and contralateral wall (DR) and its largest perpendicular D between unaffected walls (DN) were measured in short-axis transverse ventricular slices) and ventricle histologic sections were obtained. Mortality was 23% (1, 2, 3 died in Antag92aME, placeboME and saline). Antag92aME induced vessel growth (161.57±58.71 vessels/cm2, 68.49±23.56, 73.91±24.97; p=0.001) reduced regional wall motion dysfunction (28.6% and 76.9% of dyskinesia in treated vs non-treated p=0.03) and prevented adverse remodeling 1mo after injury (Tmax: 9.01±0.6, 5.61±0.5, 6.07±0.9 p=0.006, DR/DN: 1.29±0.1, 2.02±0.2, 1.93±0.2 p=0.03).
Conclusions: Early intracoronary administration of Antag92aME in a pig model of reperfused MI prevents ventricular remodeling with no local or distant AE emerging as a promising therapeutic approach to translate to patients that suffer a large MI.
European Heart Journal 09/2014; 3(5). DOI:10.1161/JAHA.114.000946 · 15.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives
The aim of this study was to determine the impact of the degree of residual aortic regurgitation (AR) and acuteness of presentation of AR after transcatheter aortic valve replacement (TAVR) on outcomes.
The degree of residual AR after TAVR leading to excess mortality remains controversial, and little evidence exists on the impact of the acuteness of presentation of AR.
A total of 1,735 patients undergoing TAVR with balloon-expandable or self-expanding valves were included. The presence and degree of AR were evaluated by transthoracic echocardiography; acute AR was defined as an increase in AR severity of ≥1 degree compared with pre-procedural echocardiography.
Residual AR was classified as mild in 761 patients (43.9%) and moderate to severe in 247 patients (14.2%). The presence of moderate to severe AR was an independent predictor of mortality at a mean follow-up of 21 ± 17 months compared with none to trace (adjusted hazard ratio [HR]: 1.81, 95% confidence interval [CI]: 1.32 to 2.48; p < 0.001) and mild AR (adjusted HR: 1.68, 95% CI: 1.27 to 2.24; p < 0.001) groups. There was no increased risk in patients with mild AR compared with those with none to trace AR (p = 0.393). In patients with moderate to severe AR, acute AR was observed in 161 patients (65%) and chronic AR in 86 patients (35%). Acute moderate to severe AR was independently associated with increased risk of mortality compared with none/trace/mild AR (adjusted HR: 2.37, 95% CI: 1.53 to 3.66; p < 0.001) and chronic moderate to severe AR (adjusted HR: 2.24, 95% CI: 1.17 to 4.30; p = 0.015). No differences in survival rate were observed between patients with chronic moderate to severe and none/trace/mild AR (p > 0.50).
AR occurred very frequently after TAVR, but an increased risk of mortality at ∼2-year follow-up was observed only in patients with acute moderate to severe AR.
Journal of the American College of Cardiology 09/2014; 7(9):1022–1032. DOI:10.1016/j.jcin.2014.04.012 · 16.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introducción y objetivos
El gen PLAU, que codifica para el activador del plasminógeno tipo urocinasa, desempeña un papel destacado en el crecimiento colateral. Se ha investigado si el polimorfismo PLAU P141L (C > T), que causa una mutación en el dominio kringle de la proteína, se asocia con la circulación colateral coronaria en una cohorte de 676 pacientes con enfermedad arterial coronaria.
Se genotipificó el polimorfismo de muestras de sangre mediante prueba basada en TaqMan, y la circulación colateral se evaluó por el método Rentrop. Las asociaciones de las variantes alélicas y los genotipos con la circulación colateral se examinaron mediante modelos de regresión logística multivariable ajustados por las variables clínicamente relevantes.
Los pacientes con circulación colateral deficiente (Rentrop 0-1; n = 547) presentaron mayor frecuencia del genotipo TT que aquellos con buena circulación colateral (Rentrop 2-3; n = 129; p = 0,020). Por otra parte, el alelo T fue más frecuente en los pacientes con circulación deficiente (p = 0,006). La odds ratio de los portadores del alelo T de presentar una circulación colateral deficiente (ajustada por variables clínicamente relevantes) fue estadísticamente significativa en el modelo dominante (odds ratio = 1,83 [intervalo de confianza del 95%, 1,16-2,90]; p = 0,010) o el aditivo (odds ratio = 1,73 [intervalo de confianza del 95%, 1,14-2,62]; p = 0,009).
Se demuestra una asociación entre la circulación colateral coronaria y el polimorfismo PLAU P141L. Los pacientes con la variante 141L tienen mayor riesgo de sufrir una circulación colateral deficiente.
Revista Espanola de Cardiologia 07/2014; 67(7). DOI:10.1016/j.rec.2013.11.022 · 3.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction and objectives
Urokinase-type plasminogen activator, which is encoded by the PLAU gene, plays a prominent role during collateral arterial growth. We investigated whether the PLAU P141L (C > T) polymorphism, which causes a mutation in the kringle domain of the protein, is associated with coronary collateral circulation in a cohort of 676 patients with coronary artery disease.
The polymorphism was genotyped in blood samples using a TaqMan-based genotyping assay, and collateral circulation was assessed by the Rentrop method. Multivariate logistic regression models adjusted by clinically relevant variables to estimate odds ratios were used to examine associations of PLAU P141L allelic variants and genotypes with collateral circulation.
Patients with poor collateral circulation (Rentrop 0-1; n = 547) showed a higher frequency of the TT genotype than those with good collateral circulation (Rentrop 2-3; n = 129; P = .020). The T allele variant was also more common in patients with poor collateral circulation (P = .006). The odds ratio of having poorly developed collaterals in patients bearing the T allele (adjusted for clinically relevant variables) was statistically significant under the dominant model (odds ratio =1.83 [95% confidence interval, 1.16-2.90]; P = .010) and the additive model (odds ratio =1.73 [95% confidence interval, 1.14-2.62]; P = .009).
An association was found between coronary collateral circulation and the PLAU P141L polymorphism. Patients with the 141L variant are at greater risk of developing poor coronary collateral circulation.
Full English text available from: www.revespcardiol.org/en
Revista Espa de Cardiologia 07/2014; 67(7). DOI:10.1016/j.recesp.2013.11.022 · 3.79 Impact Factor