Dobutamine stress echocardiography during transcatheter edge-to-edge mitral valve repair predicts residual mitral regurgitation.

OBJECTIVES: The current study sought to determine whether low-dose dobutamine stress echocardiography (DSE) during transcatheter edge-to-edge mitral valve repair (TMVR) can predict residual mitral regurgitation (MR) at discharge. BACKGROUND: In most patients, TMVR can successfully reduce MR from severe to mild or moderate. However, general anesthesia during the intervention affects hemodynamics and MR assessment. At discharge transthoracic echocardiogram residual MR (>moderate) is present in 10%-30% of patients which is associated with worse clinical outcome. METHODS: In consecutive patients the severity of MR was determined at baseline, immediately after TMVR clip implantation and subsequently during low-dose DSE (both under general anesthesia) and at discharge. RESULTS: A total of 39 patients were included (mean age 76.1 ± 8.1 years, 39% male, 56% functional MR, 41% left ventricular ejection fraction < 45%). An increase of MR during DSE was seen in 11 patients, of whom 6 (55%) showed >moderate MR at discharge. None of the 28 patients without an increase of MR during DSE showed >moderate MR at discharge. The diagnostic performance of the test could be established at a sensitivity of 100% and a specificity of 85% in unselected patients. CONCLUSIONS: DSE during TMVR is a useful tool to predict residual MR at discharge. It could support procedural decision making, including implantation of additional clips and thus potentially improve clinical outcome.

Tricuspid regurgitation after transcatheter mitral valve repair: Clinical course and impact on outcome.

OBJECTIVES: The aim of this study was to determine the course of tricuspid regurgitation (TR) after transcatheter mitral valve repair (TMVR), identify predictors for severe TR after TMVR and determine the association of severe TR after TMVR with outcome. BACKGROUND: TR is often present in patients with symptomatic mitral regurgitation (MR) and is associated with increased morbidity and mortality. The clinical course of TR after TMVR has not been clearly determined. METHODS: Patients that underwent TMVR between 2009 and 2017 were included. Clinical data were compared between patients with and without severe TR at 6 months after TMVR. Multivariate logistic regression analysis was performed to identify predictors for severe TR after TMVR. Survival analysis was done for both groups, using the Kaplan-Meier method. RESULTS: A total of 146 patients were included (mean age 76 years, 51% male, 79% New York Heart Association class ≥3 and 29% severe TR at baseline). Advanced age, atrial fibrillation (AF), right ventricular (RV) dysfunction, and limited procedural MR reduction were revealed as independent predictors for severe TR after TMVR. Survival of patients with severe TR after TMVR was 58% after 2 years compared to 82% for those with non, mild or moderate TR. CONCLUSIONS: Severe TR after TMVR is common in patients at advanced age, those with AF, RV dysfunction and limited MR reduction during TMVR and is associated with impaired survival. As the associated parameters are indicators of longstanding MR, research investigating the benefits of earlier intervention in MR should be initiated.

Final five-year results of the REMEDEE Registry: Real-world experience with the dual-therapy COMBO stent.

OBJECTIVES: This final report from the REMEDEE Registry assessed the long-term safety and efficacy of the dual-therapy COMBO stent in a large unselected patient population. BACKGROUND: The bio-engineered COMBO stent (OrbusNeich Medical BV, The Netherlands) is a dual-therapy pro-healing stent. Data of long-term safety and efficacy of the this stent is lacking. METHODS: The prospective, multicenter, investigator-initiated REMEDEE Registry evaluated clinical outcomes after COMBO stent implantation in daily clinical practice. One thousand patients were enrolled between June 2013 and March 2014. RESULTS: Five-year follow-up data were obtained in 97.2% of patients. At 5-years, target lesion failure (TLF) (composite of cardiac death, target-vessel myocardial infarction, or target lesion revascularization) was present in 145 patients (14.8%). Definite or probable stent thrombosis (ST) occurred in 0.9%, with no additional case beyond 3-years of follow-up. In males, 5-year TLF-rate was 15.6 versus 12.6% in females (p = .22). Patients without diabetes mellitus (DM) had TLF-rate of 11.4%, noninsulin-treated DM 22.7% (p = .001) and insulin-treated DM 41.2% (p < .001). Patients presenting with non-ST segment elevation acute coronary syndrome (NSTE-ACS) had higher incidence of TLF compared to non-ACS (20.4 vs. 13.3%; p = .008), while incidence with STE-ACS was comparable to non-ACS (10.7 vs. 13.3%; p = .43). CONCLUSION: Percutaneous coronary intervention with the dual-therapy COMBO stent in unselected patient population shows low rates of TLF and ST to 5 years. Remarkably, no case of ST was noted beyond 3 years.

Sex differences in 1-year clinical outcomes after percutaneous coronary intervention with COMBO stents: From the COMBO collaboration.

BACKGROUND: The COMBO drug eluting stent is a novel device with luminal endothelial progenitor cell capture technology for rapid homogeneous endothelialization. METHODS AND RESULTS: We examined for sex differences in 1-year outcomes after COMBO stenting from the COMBO collaboration, a pooled patient-level dataset from the MASCOT and REMEDEE multicenter registries. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel-myocardial infarction (TV-MI), or clinically driven target lesion revascularization (CD-TLR). Secondary outcomes included stent thrombosis (ST). Adjusted outcomes were assessed using Cox regression methods. The study included 861 (23.8%) women and 2,753 (76.2%) men. Women were older with higher prevalence of several comorbidities including diabetes mellitus. Risk of 1-year TLF was similar in both sexes (3.8% vs. 3.9%, HR 0.92, 95% CI 0.59-1.42, p = .70), without sex differences in the incidence of cardiac death (1.6% vs. 1.5%, p = .78), TV-MI (1.5% vs. 1.1%, p = .32), or CD-TLR (2.0% vs. 2.2%, p = .67). Definite or probable ST occurred in 0.4% women and 1.0% men (HR 0.26, 95% CI 0.06-1.11, p = .069). CONCLUSIONS: Despite greater clinical risks at baseline, women treated with COMBO stents had similarly low 1-year TLF and other ischemic outcomes compared to men.

One-Year COMBO Stent Outcomes in Acute Coronary Syndrome: from the COMBO Collaboration.

PURPOSE: The COMBO biodegradable polymer sirolimus-eluting stent includes endothelial progenitor cell capture (EPC) technology for rapid endothelialization, which may offer advantage in acute coronary syndromes (ACS). We sought to analyze the performance of the COMBO stent by ACS status and ACS subtype. METHODS: The COMBO collaboration (n = 3614) is a patient-level pooled dataset from the MASCOT and REMEDEE registries. We evaluated outcomes by ACS status, and ACS subtype in patients with ST segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) versus unstable angina (UA). The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization. Secondary outcomes included stent thrombosis (ST). RESULTS: We compared 1965 (54%) ACS and 1649 (46.0%) non-ACS patients. ACS presentations included 40% (n = 789) STEMI, 31% (n = 600) NSTEMI, and 29% (n = 576) UA patients. Risk of 1-year TLF was greater in ACS patients (4.5% vs. 3.3%, HR 1.51 95% CI 1.01-2.25, p = 0.045) without significant differences in definite/probable ST (1.1% vs 0.5%, HR 2.40, 95% CI 0.91-6.31, p = 0.08). One-year TLF was similar in STEMI, NSTEMI, and UA (4.8% vs 4.8% vs. 3.7%, p = 0.60), but definite/probable ST was higher in STEMI patients (1.9% vs 0.5% vs 0.7%, p = 0.03). Adjusted outcomes were not different in MI versus UA patients. CONCLUSIONS: Despite the novel EPC capture technology, COMBO stent PCI was associated with somewhat greater risk of 1-year TLF in ACS than in non-ACS patients, without significant differences in stent thrombosis. No differences were observed in 1-year TLF among ACS subtypes.

Bioresorbable Scaffolds versus Metallic Stents in Routine PCI.

BACKGROUND: Bioresorbable vascular scaffolds were developed to overcome the shortcomings of drug-eluting stents in percutaneous coronary intervention (PCI). We performed an investigator-initiated, randomized trial to compare an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent in the context of routine clinical practice. METHODS: We randomly assigned 1845 patients undergoing PCI to receive either a bioresorbable vascular scaffold (924 patients) or a metallic stent (921 patients). The primary end point was target-vessel failure (a composite of cardiac death, target-vessel myocardial infarction, or target-vessel revascularization). The data and safety monitoring board recommended early reporting of the study results because of safety concerns. This report provides descriptive information on end-point events. RESULTS: The median follow-up was 707 days. Target-vessel failure occurred in 105 patients in the scaffold group and in 94 patients in the stent group (2-year cumulative event rates, 11.7% and 10.7%, respectively; hazard ratio, 1.12; 95% confidence interval [CI], 0.85 to 1.48; P=0.43); event rates were based on Kaplan-Meier estimates in time-to-event analyses. Cardiac death occurred in 18 patients in the scaffold group and in 23 patients in the stent group (2-year cumulative event rates, 2.0% and 2.7%, respectively), target-vessel myocardial infarction occurred in 48 patients in the scaffold group and in 30 patients in the stent group (2-year cumulative event rates, 5.5% and 3.2%), and target-vessel revascularization occurred in 76 patients in the scaffold group and in 65 patients in the stent group (2-year cumulative event rates, 8.7% and 7.5%). Definite or probable device thrombosis occurred in 31 patients in the scaffold group as compared with 8 patients in the stent group (2-year cumulative event rates, 3.5% vs. 0.9%; hazard ratio, 3.87; 95% CI, 1.78 to 8.42; P<0.001). CONCLUSIONS: In this preliminary report of a trial involving patients undergoing PCI, there was no significant difference in the rate of target-vessel failure between the patients who received a bioresorbable scaffold and the patients who received a metallic stent. The bioresorbable scaffold was associated with a higher incidence of device thrombosis than the metallic stent through 2 years of follow-up. (Funded by Abbott Vascular; AIDA ClinicalTrials.gov number, NCT01858077 .).

One-year clinical outcomes in patients with chronic kidney disease treated with COMBO stents: From the COMBO collaboration.

BACKGROUND: Chronic kidney disease (CKD) patients undergoing percutaneous coronary intervention (PCI) experience greater ischemic events including clinically driven target lesion revascularization (CD-TLR). Whether the COMBO biodegradable-polymer sirolimus-eluting stent promotes better outcomes in these patients by virtue of endothelial progenitor cell capture technology is unknown. OBJECTIVE: We examined one-year outcomes by CKD status from the COMBO collaboration. METHODS: The COMBO collaboration was a patient-level pooled dataset from the REMEDEE and MASCOT registries (3,614 patients) of all-comers undergoing attempted COMBO stent PCI. The primary endpoint was one-year target lesion failure (TLF), composite of cardiac death, target-vessel myocardial infarction (TV-MI) or CD-TLR. Secondary endpoints included stent thrombosis (ST). RESULTS: The study included 6.4% (n = 231) CKD and 93.6% (n = 3,361) non-CKD patients. CKD patients were older and included more women with greater prevalence of several comorbidities but similar rate of acute coronary syndrome (50.6% vs. 54.5%, p = .26). CKD patients underwent radial PCI less often (56.1% vs. 70.3%, p < .001) and received clopidogrel (78.6% vs. 68.3%) more often (p = .004). One-year TLF occurred in 7.9% CKD vs. 3.7% non-CKD patients, p = .001. CKD patients also demonstrated greater incidence of cardiac death (6.2% vs. 1.2%, p < .0001), TV-MI (2.7% vs. 1.1%, p = .04) but similar CD-TLR (2.7% vs 2.2%, p = .61) and definite/probable ST (1.4% vs. 0.8%, p = .42), compared to non-CKD patients. CONCLUSIONS: CKD patients treated with COMBO stents had significantly greater incidence of one-year TLF compared to non-CKD patients driven by cardiac death and to a lesser extent TV-MI but not CD-TLR. They had similar rates of definite/probable ST.

Clinical outcomes at 2 years of the Absorb bioresorbable vascular scaffold versus the Xience drug-eluting metallic stent in patients presenting with acute coronary syndrome versus stable coronary disease-AIDA trial substudy.

BACKGROUND: Patients with acute coronary syndrome (ACS) might represent a specific subgroup, in which bioresorbable scaffold implantation in percutaneous coronary intervention (PCI), might lead to better outcomes when compared to conventional treatment with metallic drug eluting stents. In this prespecified subgroup analysis of the Amsterdam Investigator-Initiated Absorb Strategy All-Comers (AIDA) trial, we evaluated the clinical outcomes of Absorb bioresorbable vascular scaffold (BVS) versus Xience everolimus eluting stent (EES) treated patients presenting either with or without ACS. METHODS AND RESULTS: We classified AIDA patients on the basis of clinical presentation of ACS or of no-ACS. The rate of the 2-year primary endpoint of target vessel failure (TVF) was similar after treatment with Absorb BVS or Xience EES in ACS patients (10.2% versus 9.0% respectively; P = 0.49) and in no-ACS patients (11.7% versus 10.7%, respectively; P = 0.67) Definite or probable device thrombosis occurred more frequently with Absorb BVS compared to Xience EES in ACS patients (4.3% versus 1.7%, respectively, P = 0.03) as well as in no-ACS patients (2.4% versus 0.2%, respectively; P = 0.002). There were no statistically significant interactions between clinical presentation and randomized device modality for TVF (P = 0.80) and for the endpoint of definite or probable device thrombosis (P = 0.17). CONCLUSION: In the AIDA trial, the 2-year outcomes of PCI with Absorb BVS versus Xience EES were consistent in ACS and no-ACS patients: similar rates for TVF and consistently higher rates of definite or probable stent thrombosis under Absorb BVS versus Xience EES. There were no statistically significant interactions between clinical presentation and randomized device modality.

A sirolimus-eluting bioabsorbable polymer-coated stent (MiStent) versus an everolimus-eluting durable polymer stent (Xience) after percutaneous coronary intervention (DESSOLVE III): a randomised, single-blind, multicentre, non-inferiority, phase 3 trial.

BACKGROUND: MiStent is a drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall. It was developed to overcome the limitation of current durable polymer drug-eluting stents eluting amorphous sirolimus. The clinical effect of MiStent sirolimus-eluting stent compared with a durable polymer drug-eluting stents has not been investigated in a large randomised trial in an all-comer population. METHODS: We did a randomised, single-blind, multicentre, phase 3 study (DESSOLVE III) at 20 hospitals in Germany, France, Netherlands, and Poland. Eligible participants were any patients aged at least 18 years who underwent percutaneous coronary intervention in a lesion and had a reference vessel diameter of 2·50-3·75 mm. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting bioresorbable polymer stent (MiStent) or an everolimus-eluting durable polymer stent (Xience). Randomisation was done by local investigators via web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint (DOCE)-cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation-between the groups at 12 months after the procedure assessed by intention-to-treat. A margin of 4·0% was defined for non-inferiority of the MiStent group compared with the Xience group. All participants were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02385279. FINDINGS: Between March 20, and Dec 3, 2015, we randomly assigned 1398 patients with 2030 lesions; 703 patients with 1037 lesions were assigned to MiStent, of whom 697 received the index procedure, and 695 patients with 993 lesions were asssigned to Xience, of whom 690 received the index procedure. At 12 months, the primary endpoint had occurred in 40 patients (5·8%) in the sirolimus-eluting stent group and in 45 patients (6·5%) in the everolimus-eluting stent group (absolute difference -0·8% [95% CI -3·3 to 1·8], pnon-inferiority=0·0001). Procedural complications occurred in 12 patients (1·7%) in the sirolimus-eluting stent group and ten patients (1·4%) in the everolimus-eluting stent group; no clinical adverse events could be attributed to these dislodgements through a minimum of 12 months of follow-up. The rate of stent thrombosis, a safety indicator, did not differ between groups and was low in both treatment groups. INTERPRETATION: The sirolimus-eluting bioabsorbable polymer stent was non-inferior to the everolimus-eluting durable polymer stent for a device-oriented composite clinical endpoint at 12 months in an all-comer population. MiStent seems a reasonable alternative to other stents in clinical practice. FUNDING: The European Cardiovascular Research Institute, Micell Technologies (Durham, NC, USA), and Stentys (Paris, France).

Myocardial fibrosis predicts adverse outcome after MitraClip implantation.

BACKGROUND: High-risk patients with mitral regurgitation (MR) may be treated by a percutaneous mitral valve repair with the MitraClip, but identification of patients who may benefit remains difficult. We aimed to determine whether myocardial fibrosis predicts outcome in MR patients undergoing MitraClip implantation and is beneficial in clinical decision making. METHODS: Preprocedural to the MitraClip implantation, myocardial fibrosis was analyzed with cardiovascular magnetic resonance (CMR) through late gadolinium enhancement. The CMR data were core-lab adjudicated measured before the MitraClip implantation. Adverse outcome was defined as New York Heart Association (NYHA) class III or IV after 1 month or death within 1 month after the MitraClip implantation. RESULTS: In total, 23 patients underwent preprocedural CMR, mean age 80 ± 9 years, 45% male, 64% atrial fibrillation and 73% NYHA class III or IV at baseline. Myocardial fibrosis was present in 55% of the patients with degenerative MR and in 64% of the patients with functional MR. An adverse outcome occurred in 69% of the patients with myocardial fibrosis and in 11% of the patients without myocardial fibrosis (P = 0.01). CONCLUSIONS: Our hypothesis-generating study showed that the presence of myocardial fibrosis predicts adverse outcome in patients undergoing MitraClip implantation. After confirmation with larger sample size, identification of myocardial fibrosis might contribute to assess prognosis and to clinical decision making.

Three-year clinical outcomes after dual-therapy COMBO stent placement: Insights from the REMEDEE registry.

BACKGROUND: The bio-engineered COMBO stent (OrbusNeich Medical BV, The Netherlands) is a dual-therapy pro-healing stent. This novel technology may allow a shorter duration of dual antiplatelet therapy (DAPT) after stenting. We present the first 3 year clinical outcomes of patients treated with COMBO stent. METHODS AND RESULTS: The prospective, multicenter, investigator-initiated, all-comers REMEDEE Registry evaluates clinical outcomes after COMBO stent treatment. A 1,000 patients were enrolled between June 2013 and March 2014. Patients had a mean of 65 years ±11, 26% of the patients were females and 18% diabetics. More than 50% of patients presented with acute coronary syndrome, 60% of treated lesions were AHA/ACC lesion type B2 or C. Target lesion failure (TLF) at 3 year follow-up occurred in 10.7% of patients (N = 105). The separate components cardiac death, target vessel myocardial infarction and target lesion revascularization occurred in 4.1%, 2.0%, and 7.1%, respectively of patients. Definite stent thrombosis (ST) was observed in 0.7% of all patients. At 3-year follow-up there were only 73 patients taking DAPT. CONCLUSIONS: At 3-year follow-up, patients treated with COMBO stent in the present large prospective all-comers cohort, continue to show good clinical outcomes. Clinicaltrials.gov identifier: NCT01874002. CONDENSED ABSTRACT: The COMBO stent is a sirolimus-eluting stent with a luminal anti-CD34-antibody layer, that binds endothelial progenitor cells. These cells can differentiate to endothelial cells and stimulate early endothelialization of the stent. The REMEDEE Registry is the first large, multicenter, prospective, cohort study evaluating the clinical outcomes of 1,000 all-comers patients treated with COMBO stent. Target lesion failure at 3 year follow-up was 10.7% and the rate of definite ST was 0.7%.

CT determined psoas muscle area predicts mortality in women undergoing transcatheter aortic valve implantation.

OBJECTIVES: The aim of this study was to assess the predictive value of PMA measurement for mortality. BACKGROUND: Current surgical risk stratification have limited predictive value in the transcatheter aortic valve implantation (TAVI) population. In TAVI workup, a CT scan is routinely performed but body composition is not analyzed. Psoas muscle area (PMA) reflects a patient's global muscle mass and accordingly PMA might serve as a quantifiable frailty measure. METHODS: Multi-slice computed tomography scans (between 2010 and 2016) of 583 consecutive TAVI patients were reviewed. Patients were divided into equal sex-specific tertiles (low, mid, and high) according to an indexed PMA. Hazard ratios (HR) and their confidence intervals (CI) were determined for cardiac and all-cause mortality after TAVI. RESULTS: Low iPMA was associated with cardiac and all-cause mortality in females. One-year adjusted cardiac mortality HR in females for mid-iPMA and high-iPMA were 0.14 [95%CI, 0.05-0.45] and 0.40 [95%CI, 0.15-0.97], respectively. Similar effects were observed for 30-day and 2-years cardiac and all-cause mortality. In females, adding iPMA to surgical risk scores improved the predictive value for 1-year mortality. C-statistics changed from 0.63 [CI = 0.54-0.73] to 0.67 [CI: 0.58-0.75] for EuroSCORE II and from 0.67 [CI: 0.59-0.77] to 0.72 [CI: 0.63-0.80] for STS-PROM. CONCLUSIONS: Particularly in females, low iPMA is independently associated with an higher all-cause and cardiac mortality. Prospective studies should confirm whether PMA or other body composition parameters should be extracted automatically from CT-scans to include in clinical decision making and outcome prediction for TAVI.

Five-year follow-up of the endothelial progenitor cell capturing stent versus the paxlitaxel-eluting stent in de novo coronary lesions with a high risk of coronary restenosis.

OBJECTIVES: To assess the long-term safety and clinical efficacy of the Genous endothelial progenitor cell capturing stent (ECS) compared with the TAXUS Liberté paclitaxel-eluting stent (PES) in lesions with a high risk of restenosis. BACKGROUND: Instead of the use of cytotoxic or cytostatic drugs in drug-eluting stents, a "pro-healing" approach in ECS may overcome impeded healing response due to delayed functional endothelialization of the stent struts. METHODS: In the prospective, randomized TRIAS pilot study 193 patients with coronary artery lesions carrying a high risk of restenosis were included (ECS: n = 98, PES: n = 95). The primary focus of this analysis was target vessel failure (TVF) at 5 years. Dual antiplatelet therapy was prescribed for ≥1 month after ECS and for ≥6 months after PES. RESULTS: At 5 years follow-up, no significant differences were found in TVF (ECS 24% vs. PES 29%, risk difference 95% confidence interval (RDCI) -17.3% to 7.4%). Between 2 and 5 years after the index procedure, low numbers of TVF were observed in ECS compared with PES (ECS 4% vs. PES 16%, RDCI -20.8% to -2.3%). There was no definite stent thrombosis in ECS compared with four patients in the PES group. CONCLUSION: This is the first randomized study providing very long-term clinical efficacy and safety of the ECS in lesions carrying a high risk of restenosis. At 5 years follow-up, TVF rates in ECS group are numerically lower compared with PES due to an increase of events between 2 and 5 years after the index procedure.

What is the best ST-segment recovery parameter to predict clinical outcome and myocardial infarct size? Amplitude, speed, and completeness of ST-segment recovery after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.

AIMS: ST-segment recovery (STR) is a strong mechanistic correlate of infarct size (IS) and outcome in ST-segment elevation myocardial infarction (STEMI). Characterizing measures of speed, amplitude, and completeness of STR may extend the use of this noninvasive biomarker. METHODS AND RESULTS: Core laboratory continuous 24-h 12-lead Holter ECG monitoring, IS by single-photon emission computed tomography (SPECT), and 30-day mortality of 2 clinical trials of primary percutaneous coronary intervention in STEMI were combined. Multiple ST measures (STR at last contrast injection (LC) measured from peak value; 30, 60, 90, 120, and 240min, residual deviation; time to steady ST recovery; and the 3-h area under the time trend curve [ST-AUC] from LC) were univariably correlated with IS and predictive of mortality. After multivariable adjustment for ST-parameters and GRACE risk factors, STR at 240min remained an additive predictor of mortality. Early STR, residual deviation, and ST-AUC remained associated with IS. CONCLUSIONS: Multiple parameters that quantify the speed, amplitude, and completeness of STR predict mortality and correlate with IS.

Older coronary thrombus is an independent predictor of 1-year mortality in acute myocardial infarction.

BACKGROUND: We have previously shown that older thrombus is associated with a twofold higher long-term mortality in ST-segment elevation myocardial infarction (STEMI) patients after primary percutaneous coronary intervention (pPCI). We evaluated whether the addition of the presence of older thrombus to a multimarker model would result in increased predictive power for 1-year mortality in STEMI patients. METHODS: The study population (n = 1442) consists of STEMI patients treated with thrombus aspiration during pPCI. Patients were included if aspirated thrombus material could histopathologically be classified according to thrombus age (n = 870) and laboratory measurements of biomarkers (cardiac troponin T, glucose, N-terminal pro-brain natriuretic peptide, estimated glomerular filtration rate and C-reactive protein) were available. The additional prognostic value of the presence of older thrombus beyond multiple biomarkers and established clinical risk factors was evaluated using multivariate Cox regression models. RESULTS: Serum biomarker concentrations were similar between patients with fresh and older thrombus. Sixty patients (7%) died within 1 year. The presence of older thrombus remained strongly associated with mortality at 1 year after multivariable adjustment for multiple biomarkers and established clinical risk factors. Addition of older thrombus to either a model including clinical risk factors and biomarkers or a model including solely biomarkers resulted in significant increases in the discriminative value, evidenced by net reclassification improvement and integrated discriminative improvement. CONCLUSIONS: The presence of older thrombus provides independent complementary information to a multimarker model including established clinical risk factors and multiple biomarkers for predicting 1-year mortality in STEMI patients treated with pPCI and thrombus aspiration.

Influence of chronic kidney disease on anticoagulation levels and bleeding after primary percutaneous coronary intervention in patients treated with unfractionated heparin.

Unfractionated heparin (UFH) plasma protein binding and elimination might be impaired in patients with chronic kidney disease (CKD-defined as creatinine clearance <60 ml/min). It is currently unknown at which UFH bolus dose persistent prolongation of activated partial thromboplastin time (aPTT) occurs in ST-segment elevation myocardial infarction (STEMI) patients with CKD. We investigated the effect of different UFH bolus doses on the first aPTT measured within 6 and 12 h after PPCI in 1071 STEMI patients with and without CKD undergoing primary percutaneous coronary intervention (PPCI) between 1-1-2003 and 31-07-2008. In the first 6 h after PPCI, aPTT ratio was 5.1 for patients with CKD versus 3.4 for those without (p < 0.001). The proportion of patients with markedly high aPTTs (aPTT ratio ≥ 4 times control) increased with increasing heparin bolus and beyond 130 IU/kg there was a marked difference between patients with and without CKD (74.1 and 42.3 % respectively, p < 0.001). By multivariable analysis, CKD was associated with an increased risk of markedly high aPTTs (odds ratio (OR) 2.04; 95 % confidence interval (CI) 1.27-3.27), driven largely by an increased risk of aPTT prolongation in patients treated with UFH boluses ≥130 IU/kg (OR 3.69; 95 % CI 1.85-7.36; p for interaction = 0.009). In conclusion, CKD is associated with severe persistent aPTT prolongation in STEMI patients undergoing PPCI, possibly due to impaired plasma protein binding and reduced UFH elimination. A lower heparin bolus dose might result in lower aPTTs and less bleeding complications in patients with CKD undergoing PPCI.

Ventricular arrhythmia burst is an independent indicator of larger infarct size even in optimal reperfusion in STEMI.

OBJECTIVE: We hypothesized that ventricular arrhythmia (VA) bursts during reperfusion phase are a marker of larger infarct size despite optimal epicardial and microvascular perfusion. METHODS: 126 STEMI patients were studied with 24h continuous, 12-lead Holter monitoring. Myocardial blush grade (MBG) was determined and VA bursts were identified against subject-specific background VA rates in core laboratories. Delayed-enhancement cardiovascular magnetic resonance imaging was used to determine infarct size. RESULTS: In the group with MBG 3 no significant differences were found for baseline characteristics between burst versus no burst (102 vs. 24). In those with optimal epicardial and microvascular reperfusion (TIMI 3, stable ST-recovery, and MBG 3), VA burst was associated with larger infarct size (N=102/126; median 11.0 vs. 5.1%; p=0.004). CONCLUSION: In the event of MBG 3, VA bursts were associated with significantly larger infarct size even if optimal epicardial and microvascular reperfusion was present.

Long-term ischaemic and bleeding outcomes after primary percutaneous coronary intervention for ST-elevation myocardial infarction in the elderly.

BACKGROUND: The population is ageing rapidly and the proportion of patients aged ≥ 80 years undergoing primary percutaneous coronary intervention (PCI) is rising, but clinical trials have primarily been performed in younger patients. METHODS: Patients undergoing primary PCI between 2003 and 2008 were subdivided into 3 groups: < 60, 60-79, and ≥ 80 years. Endpoints at 3-year follow-up included all-cause mortality, recurrent myocardial infarction (reMI), stent thrombosis, target lesion revascularisation (TLR), bleeding (BARC bleeding ≥ 3), stroke, and major adverse cardiovascular events (MACE, a composite of cardiac mortality, reMI, stroke and TLR). RESULTS: 2002 patients with ST-segment elevation myocardial infarction (STEMI) were included, 885 (44.2 %) aged < 60, 921 (46.0 %) 60-79, and 196 (9.7 %) ≥ 80 years. Comorbidities such as diabetes mellitus, prior stroke, malignant disease, anaemia, and chronic kidney disease were more prevalent in patients ≥ 80 years. The incidence of both ischaemic and bleeding events strongly increased with age. Age ≥ 80 years was an independent predictor of mortality (HR 2.56, 95 % CI1.69-3.87, p < 0.001), a borderline non-significant predictor of overall bleeding (HR 1.38, 95 %CI 0.95-2.00, p = 0.088), and a significant predictor of non-access site bleeding (HR 2.26, 95 %CI 1.46-3.51, p < 0.001). CONCLUSION: Patients ≥ 80 years experienced high rates of ischaemic and bleeding complications; especially in this high-risk patient group individualised therapy is needed to optimise clinical outcomes.

APPOSITION V: STENTYS coronary stent system clinical trial in subjects with ST-segment elevation myocardial infarction--rationale and design.

BACKGROUND: Primary percutaneous coronary intervention (PCI) has considerably improved clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) when compared with thrombolytic therapy. Prognosis after primary PCI might be further improved by decreasing stent-related complications such as stent thrombosis. The STENTYS self-apposing stent has been shown to be superior compared with balloon-expandable stents with regard to stent apposition. The current prospective randomized trial was designed to evaluate whether the superior stent apposition of the STENTYS stent results in clinical outcomes that are at least noninferior to a conventional balloon-expandable stent. METHODS: The APPOSITION V is a prospective, multicenter, international, single-blinded, randomized controlled trial in STEMI patients. Randomization will be performed in a 2:1 ratio between the self-apposing nitinol bare-metal STENTYS stent and the balloon-expandable bare-metal MULTI-LINK. The primary end point is defined as target vessel failure, which is a composite of cardiac death, target vessel-related recurrent myocardial infarction, or clinically driven target vessel revascularization, at 1-year follow-up. Baseline intravascular ultrasound and optical coherence tomography (OCT) substudies will be performed in 212 and 60 subjects, respectively, and a repeat angiography at 12 to 13 months will be performed in 105 subjects, including intravascular ultrasound and OCT (in the 60 OCT patients). This study is registered on ClinicalTrials.gov with number NCT01732341. CONCLUSION: APPOSITION V will be the first randomized trial powered on clinical end points that directly compares the STENTYS self-apposing stent with a conventional balloon-expandable stent in patients presenting with STEMI undergoing primary PCI.

Amsterdam Investigator-initiateD Absorb strategy all-comers trial (AIDA trial): a clinical evaluation comparing the efficacy and performance of ABSORB everolimus-eluting bioresorbable vascular scaffold strategy vs the XIENCE family (XIENCE PRIME or XIENCE Xpedition) everolimus-eluting coronary stent strategy in the treatment of coronary lesions in consecutive all-comers: rationale and study design.

BACKGROUND: The Absorb everolimus-eluting bioresorbable vascular scaffold (AbsorbBVS) is a completely resorbable device engineered to overcome the limitations of permanent metallic stents, providing temporary scaffolding and antiproliferative drug delivery for the treatment of obstructive coronary artery disease. METHODS: The objective of the AIDA trial is to evaluate the efficacy and performance in an contemporary all-comer population of the AbsorbBVS strategy vs the XIENCE family everolimus-eluting metallic coronary stent system in the treatment of coronary lesions. The AIDA trial is a prospective, randomized (1:1), active-control, single-blinded, all-comer, noninferiority trial. A total of 2,690 subjects will be enrolled with broad inclusion and limited exclusion criteria according to the "Instructions for Use" of the AbsorbBVS strategy. The study population includes both simple and complex lesions, in patients with stable and acute coronary syndrome. The follow-up continues for 5years. The primary end point of the trial is target vessel failure, defined as the composite of cardiac death, myocardial infarction, and target vessel revascularization, at 2years. This study is registered on ClinicalTrials.gov with number NCT01858077. CONCLUSION: The AIDA trial will provide the first randomized direct comparison between the everolimus-eluting bioresorbable vascular scaffold and the everolimus-eluting metallic stent in contemporary percutaneous coronary intervention practice.