Alexander Ijsselmuiden

Diastolic Stiffness of the Failing Diabetic Heart Importance of Fibrosis, Advanced Glycation End Products, and Myocyte Resting Tension

Background— Excessive diastolic left ventricular stiffness is an important contributor to heart failure in patients with diabetes mellitus. Diabetes is presumed to increase stiffness through myocardial deposition of collagen and advanced glycation end products (AGEs). Cardiomyocyte resting tension also elevates stiffness, especially in heart failure with normal left ventricular ejection fraction (LVEF). The contribution to diastolic stiffness of fibrosis, AGEs, and cardiomyocyte resting tension was assessed in diabetic heart failure patients with normal or reduced LVEF. Methods and Results— Left ventricular endomyocardial biopsy samples were procured in 28 patients with normal LVEF and 36 patients with reduced LVEF, all without coronary artery disease. Sixteen patients with normal LVEF and 10 with reduced LVEF had diabetes mellitus. Biopsy samples were used for quantification of collagen and AGEs and for isolation of cardiomyocytes to measure resting tension. Diabetic heart failure patients had higher diastolic left ventricular stiffness irrespective of LVEF. Diabetes mellitus increased the myocardial collagen volume fraction only in patients with reduced LVEF (from 14.6±1.0% to 22.4±2.2%, P<0.001) and increased cardiomyocyte resting tension only in patients with normal LVEF (from 5.1±0.7 to 8.5±0.9 kN/m2, P=0.006). Diabetes increased myocardial AGE deposition in patients with reduced LVEF (from 8.8±2.5 to 24.1±3.8 score/mm2; P=0.005) and less so in patients with normal LVEF (from 8.2±2.5 to 15.7±2.7 score/mm2, P=NS). Conclusions— Mechanisms responsible for the increased diastolic stiffness of the diabetic heart differ in heart failure with reduced and normal LVEF: Fibrosis and AGEs are more important when LVEF is reduced, whereas cardiomyocyte resting tension is more important when LVEF is normal.

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.)

Circulating white blood cells and platelets amplify oxidative stress in heart failure.

Background Mitochondria of circulating white blood cells (WBC) and platelets sense oxidative stress during capillary passage and react by producing reactive oxygen species (ROS). Although evidence indicates that congestive heart failure (CHF) is associated with oxidative stress, the role of WBC and platelets as mediators in CHF has not been investigated.Methods Patients with CHF (n = 15) and healthy volunteers (n = 9) were enrolled between 2006 and 2007 into this observational study. Arterial and venous blood samples from participants were incubated with probes to detect cytosolic and mitochondrial ROS. Fluorescence-activated cell sorting was used to measure the degree of fluorescence in WBC and platelets.Results Patients with CHF had a higher proportion of ROS-positive arterial WBC and platelets than did controls (67% ± 47% versus 16% ± 9%; P <0.005), as well as venous WBC and platelets (77% ± 43% versus 38% ± 13%; P <0.01). In the control group, the proportion of cytosolic ROS-positive arterial WBC and platelets was lower than that for ROS-positive venous WBC and platelets (16% ± 9% versus 38% ± 13%; P <0.005). CHF patients had a higher proportion of mitochondrial ROS-positive arterial and venous WBC and platelets than did controls.Conclusion In CHF, the proportion of WBC and platelets that are ROS-positive is raised, possibly because cytosolic ROS-positive WBC and platelets are normally cleared in the lungs; this function is deficient in CHF while mitochondrial ROS production is increased. The raised numbers of circulating ROS-positive WBC and platelets amplify oxidative stress in CHF.

Direct coronary stent implantation does not reduce the incidence of in-stent restenosis or major adverse cardiac events: six month results of a randomized trial.

STUDY OBJECTIVE To compare the long-term angiographic, clinical and economic outcome of direct stenting vs stenting after balloon predilatation. PATIENT POPULATION AND METHODS Four hundred patients with coronary stenoses in a single native vessel were randomized to direct stenting vs stenting after predilatation. A major adverse cardiac and cerebral event (MACCE) was defined as death, myocardial infarction, stent thrombosis, target restenosis, repeat target- and non-target vessel-related percutaneous coronary intervention, target lesion revascularization, coronary artery bypass surgery and stroke. RESULTS Stents were successfully implanted in 98.3% of patients randomized to direct stenting vs 97.8% randomized to stenting preceded by predilatation. The primary success rate of direct stenting was 88.3%, vs 97.8% for stenting preceded by balloon dilatation (P=0.01). The angiographic follow-up at 6 months included 333 of the 400 patients (83%). The binary in-stent restenosis rate was 23.1% of 163 patients randomized to direct stenting vs 18.8% of 166 patients randomized to balloon predilatation (P=0.32). By 185+/-25 days, MACCE had occurred in 31 of 200 (15.5%) patients randomized to direct stenting, vs 33 of 200 (16.5%) randomized to predilatation (P=0.89). At 6 months, costs associated with the direct stenting strategy (Euros 3222/patient) were similar to those associated with predilatation (Euros 3428/patient, P=0.43). However, procedural costs were significantly lower. It is noteworthy that, on multivariate analysis, a baseline C-reactive protein level >10 mg l(-1)was a predictor of restenosis (odds ratio: 2.10, P=0.025) as well as of MACCE (odds ratio: 1.94, P=0.045). CONCLUSIONS Compared to stenting preceded by balloon predilatation, direct stenting was associated with similar 6-month restenosis and MACCE rates. Procedural, but not overall 6-month costs, were reduced by direct stenting. An increased baseline CRP level was an independent predictor of adverse long-term outcome after coronary stent implantation.

A randomized comparison of manual versus mechanical thrombus removal in primary percutaneous coronary intervention in the treatment of ST-segment elevation myocardial infarction (TREAT-MI).

Objectives: The objective of this study was to compare the efficacy and long‐term clinical outcome of manual thrombus aspiration with the Export catheter (Medtronic, Minneapolis, MN) versus mechanical thrombus cutting/aspiration with the X‐sizer system (eV3, White Bear Lake, MN) in primary percutaneous coronary intervention (PPCI). Background: In PPCI for acute ST‐segment elevation myocardial infarction (STEMI), markers of myocardial reperfusion are improved with adjunctive thrombectomy. Previous studies of different devices showed a variability in performance, suitability, and short‐term clinical outcome. In current literature, no direct comparison is available. Methods: We prospectively randomized 201 patients admitted for PPCI for STEMI to either the Export catheter or the X‐sizer prior to stent deployment. Technical success in advancing to and across the lesion, improvement of flow, reduction of thrombus, and the effect on ST‐segment resolution were examined. The primary endpoint of the follow‐up study was the combined endpoint of cardiac death, recurrent myocardial infarction (MI), or target‐vessel revascularization (TVR) at 3 years. Results: Although the Export catheter was more successfully deployed, other procedural parameters were similar with a trend toward better ST‐segment resolution (56.6% vs. 44%; P = 0.06) as compared to the X‐sizer system. The occurrence of the primary clinical endpoint at 3 years was 22.2% and 18.6%, respectively (HR 1.20; 95% CI 0.65–2.22; P = 0.35). Conclusion: Despite shorter procedural times, better lesion crossing, and fewer complications, both surrogate endpoints as well as 3‐year clinical follow‐up were similar with the use of the Export catheter as compared to the X‐sizer system.

Magnetically navigated percutaneous coronary intervention in distal and/or complex lesions may improve procedural outcome and material consumption

AIMS Comparison of magnetic guidewire navigation in percutaneous coronary intervention (magnetic PCI) across distal and/or complex lesions versus conventional navigation (conventional PCI). METHODS AND RESULTS Forty-seven consecutive patients (age 61 +/- 10 yr) undergoing elective single vessel magnetic PCI for distal and/or complex lesions were matched by age and lesion location with 45 patients undergoing conventional PCI (age 63 +/- 10 yr). Technical success rate was defined as an intraluminal wire position distal to the stenosis. Procedural outcome and costs were evaluated. Baseline demographics and angiographic characteristics of the two groups were similar. The technical success rate did not differ between magnetic and conventional PCI (95.7 vs 97.8%; p = 1.00). Significantly shorter procedural and fluoroscopy time were observed for magnetic compared to conventional PCI (29.9 +/- 17.6 vs 41.1 +/- 21 min, p = 0.007; 7.5 +/- 7.3 vs 16.1 +/- 22.4 min, p = 0.02 respectively). Less contrast was used in the magnetic PCI group (58 ml/patient; P = 0.02). These advantages resulted in a mean estimated saving of 1400 euro per patient (P < 0.001). Advantages of procedural outcome were even more pronounced in the ACC/AHA lesion class C subgroup. CONCLUSIONS Magnetic compared to conventional PCI is an attractive novel technique that proved to be feasible and safe and might be faster in distal and especially complex lesions.

One-year clinical outcomes of the STENTYS Self-Apposing¨ coronary stent in patients presenting with ST-segment elevation myocardial infarction: results from the APPOSITION III registry.

AIMS The aim of APPOSITION III was to evaluate the feasibility and performance of the STENTYS Self-Apposing¨ stent (STENTYS S.A., Paris, France) in the setting of primary percutaneous coronary intervention (PCI). METHODS AND RESULTS APPOSITION III was an international, prospective, multicentre registry. The study population consisted of 965 patients. The rate of the primary endpoint major adverse cardiac events (MACE), defined as the composite of cardiac death, recurrent target vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularisation (CD-TLR), at one year was 9.3%. One-year cardiac death rate was 2.0%, TV-MI rate was 1.3%, CD-TLR rate was 7.4% and definite/probable stent thrombosis (ST) rate was 3.5% (definite ST 2.8%). An interim safety analysis of in-hospital outcomes in the first 400 patients showed higher event rates if post-dilation was not performed, and post-dilations became highly recommended in the remaining cohort. Patients undergoing post-dilation eventually showed a numerically lower one-year MACE rate (8.4% vs. 11.3%, p=0.137). One-year TV-MI (0.8% vs. 2.5%, p=0.027) and definite ST (1.9% vs. 5.0%, p=0.010) rates were significantly lower if post-dilation was performed, with the divergence occurring at <30 days. CONCLUSIONS The use of the STENTYS Self-Apposing¨ stent in the setting of primary PCI was feasible and associated with acceptable cardiovascular event rates which improved when post-dilation was performed.

STENTYS self-apposing® sirolimus-eluting STENT in ST-segment elevation myocardial infarction: Results from the randomised apposition IV trial

AIMS We sought to investigate the impact of the self-apposing, sirolimus-eluting STENTYS stent on midterm and long-term stent apposition and strut coverage compared with a zotarolimus-eluting balloon-expandable stent in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). METHODS AND RESULTS In the APPOSITION IV trial, 152 STEMI patients were randomised (3:2) to the self-apposing, sirolimus-eluting STENTYS stent or a commercially available zotarolimus-eluting balloon-expandable stent at 12 sites in five countries with angiographic follow-up and optical coherence tomography at four or nine months. At four months, a lower percentage of malapposed stent struts was observed in the STENTYS group (N=21; Nstruts=501) compared with controls (N=26; Nstruts=326; 0.07% vs. 1.16%; p=0.002) with significantly more covered struts, using a 20 µm cut-off (94.32% vs. 89.09%; p=0.003). At nine months, the primary endpoint (percentage malapposed stent struts) was similar in both groups (STENTYS, N=40; Nstruts=566; control, N=21; Nstruts=292), showing complete apposition (p=0.55) and near total (>96%) coverage (p=0.58). CONCLUSIONS In STEMI patients undergoing PPCI, the self-apposing, sirolimus-eluting STENTYS stent was equivalent to a conventional drug-eluting balloon-expandable stent with respect to late stent strut apposition and coverage at nine months. However, stent strut apposition and coverage at four months were significantly better in the STENTYS group.

Comparison of magnetically navigated and conventional wire percutaneous coronary intervention of a single discrete stenosis

The objective of this study is to compare magnetic guidewire navigation in percutaneous coronary intervention (MPCI) to conventional percutaneous coronary intervention (CPCI) for the elective treatment of a single discrete stenosis.

First-in-man evaluation of the novel balloon delivery system STENTYS Xposition S for the self-apposing coronary artery stent: impact on longitudinal geographic miss during stenting.

AIMS A novel balloon delivery system (BDS) for the self-apposing STENTYS sirolimus-eluting stent (SES) has been developed for highly precise longitudinal stent positioning and deployment. The aim of this first-in-man study is to report the quantitative coronary analysis (QCA) angiography and optical coherence tomography (OCT) results as well as the 30-day clinical outcomes of the STENTYS Xposition S SES. METHODS AND RESULTS We included 25 patients (mean age 66.1±10.7 years) with stable coronary artery disease (24%) or acute coronary syndrome (including STEMI in 40%). The device was successfully placed at the intended site in all cases (100%), without procedural complications. Longitudinal geographic miss (entire lesion length [on QCA] not completely covered by the stent) was not observed. Pre-procedural MLD on QCA was 1.30±0.74 mm and post-procedural MLD was 2.74±0.44 mm, p<0.001 (acute gain 1.44±0.70 mm). OCT analyses showed a low percentage of malapposed stent struts directly post stent placement (2.4%), which further decreased after post-dilatation (0.6%, p=0.013), while mean stent area increased (from 9.7 mm2 to 10.5 mm2, p<0.001). At 30-day clinical follow-up, one (4%) major adverse cardiac event (MACE) was observed. One acute stent thrombosis (ST) occurred immediately post procedure in a STEMI patient which was related to inadequate medication therapy. CONCLUSIONS This first-in-man study demonstrated that the use of the novel STENTYS Xposition S balloon delivery system is feasible with a high technical success rate without longitudinal geographical miss. Stent strut malapposition rate directly after STENTYS placement was low and improved further after post-dilatation.