Peripheral arterial tonometry cannot detect patients at low risk of coronary artery disease.

BACKGROUND: Endothelial dysfunction precedes coronary artery disease (CAD) and can be measured by peripheral arterial tonometry (PAT). We examined the applicability of PAT to detect a low risk of CAD in a chest pain clinic. METHODS: In 93 patients, PAT was performed resulting in reactive hyperaemia (RHI) and augmentation (AIx) indices. Patients were risk classified according to HeartScore, Diamond and Forrester pretest probability (DF), exercise testing (X-ECG), and computed tomography calcium scoring (CCS) and angiography (CTA). Correlations, risk group differences and prediction of revascularisation within 1 year were calculated. RESULTS: RHI correlated with HeartScore (r = - 0.21, p = 0.05), AIx with DF (r = 0.26, p = 0.01). However, both were not significantly different between normal and ischaemic X-ECG groups. In addition RHI and AIx were similar between low risk as compared with intermediate-to-high risk, based on risk algorithms (RHI: 1.98 (0.67) vs 1.94 (0.78); AIx: 0.0 (21) vs 5.0 (25); p = NS), or CCS and CTA (RHI: 1.99 (0.58) vs 1.89 (0.82); AIx: - 2.0 (24) vs 4.0 (25); p = NS). Finally, RHI and AIx failed to predict revascularisation (RHI: OR 1.42, CI 0.65-3.1; AIx: OR 1.02, CI 0.98-1.05). CONCLUSIONS: PAT cannot detect a low risk of CAD, possibly because RHI and AIx versus X-ECG, CCS and CTA represent independent processes.

Successful stenting of catheter-induced unprotected left main coronary artery dissection.

Catheter-induced left main coronary artery (LMCA) dissection is a dramatic, although uncommon complication of diagnostic coronary angiography and requires prompt treatment. We describe a case of iatrogenic occlusive dissection of the LMCA during coronary angiography, treated by subsequent percutaneous recanalisation.

Thrombotic complication during intracoronary imaging.

Intracoronary imaging with intracoronary ultrasound and coherence tomography is often used in the follow-up of coronary stent implantation. The present case shows an infrequent complication of these procedures, suggesting our continued attention to the selective use of these invasive procedures.

New drug-eluting stents with biodegradable polymers.

Current drug-eluting stents (DES) perform well compared to bare metal stents. However, long-term rates of major adverse events and in particular repeat revascularization by PCI are still an issue. In this concise review we will discuss the possibilities of biodegradable coatings to improve biocompatibility of DES. Among the various members of the synthetic biodegradable polymer family, polyesters are widely used and attractive for their ease of degradation, with degradation products often being resorbed through general metabolic pathways. A new development is surface functionalization of polyesters to improve endothelialization.

Postconditioning against ischaemia-reperfusion injury: ready for wide application in patients?

Ischaemic postconditioning (IPOC) is an intervention in which brief, intermittent periods of reocclusion at the onset of reperfusion (i.e. stuttering reperfusion) protect myocardium from lethal reperfusion injury. The mechanism underlying the cardioprotective effects of IPOC is incompletely understood. However, it is perceived that IPOC begins with specific cell-surface receptors responsible for activating a number of signalling pathways, many of which appear to converge at the mitochondrial level. IPOC has been demonstrated both in animal models and in patients with acute myocardial infarction (AMI) in small proof-of-concept trials. This intervention offers the possibility of further limiting infarct size in patients undergoing primary percutaneous coronary intervention (PCI). Here, we provide a brief overview of the concept of IPOC and the mechanisms underlying this phenomenon. (Neth Heart J 2010;18:389-93.).

Endothelial dysfunction after drug eluting stent implantation.

Endothelial dysfunction has been implicated in the pathological process of coronary artery disease as well as an adverse event after coronary drug eluting stent (DES) implantation. In this review, an overview will be given of the evidence to date regarding the effects of coronary DES on endothelial function obtained from both clinical and experimental studies. Stenting in general and DES seem to impair several aspects of endothelial function: provision of a permeable barrier function; modulation of adhesion, thrombosis and inflammation; and regulation of vascular tone. However, new insights show that the effects of DES can extend beyond the stent and peri-stent area: the vascular bed distal to the stent, starting with the distal conduit vessels up to the distal microvasculature, might be at risk. In addition, insight into the mechanism of DES induced endothelial dysfunction has been gained. To finalize this review, clinical complications and solutions of DES associated endothelial dysfunction will be discussed.

Late stent thrombosis, endothelialisation and drug-eluting stents.

Drug-eluting stents (DES) significantly reduce the risk of restenosis after percutaneous coronary revascularisation, but an increased risk of late stent thrombosis (LST) has been put forward as a major safety concern. Meta-analysis of clinical trials, however, does not support this caveat. Even so, many interventional cardiologists think that LST is associated with DES and related to delayed endothelialisation. This hypothesis is based on autopsy studies and clinical intracoronary angioscopy. In autopsy studies, differences between endothelialisation of DES and baremetal stents (BMS) have been reported. Most preclinical studies, however, have failed to show any significant differences in endothelialisation between DES and BMS. Our own studies, using the porcine coronary artery model, also suggest that DES show no differences in re-endothelialisation. However, DES do delay vascular healing and induce endothelial dysfunction. This paper will review clinical and animal studies which consider re-endothelialisation and LST. (Neth Heart J 2009;17:177-81.).

Cell transplantation for cardiac regeneration: where do we stand?

During the last decade transplantation of cells into the heart has emerged as a novel therapy for the prevention and treatment of heart failure. Although various cell types have been used, most experience has been obtained with the progenitor cells of skeletal muscle, also called myoblasts, and a wide array of bone marrow-derived cell types. The first preclinical studies demonstrated an improvement in global and regional heart function that was attributed mainly to a direct contractile effect of the transplanted cells. Furthermore, it was suggested that multiple cell types are able to form true cardiomyocytes and truly 'regenerate' the myocardium. More recent studies have questioned these early findings. Other mechanisms such as paracrine effects on the infarct and remote myocardium, a reduction in adverse remodelling and improvement of mechanical properties of the infarct tissue likely play a more important role. On the basis of encouraging preclinical studies, multiple early-phase clinical trials and several randomised controlled trials have been conducted that have demonstrated the feasibility, safety and potential efficacy of this novel therapy in humans. This review summarises the available evidence on cardiac cell transplantation and provides an outlook on future preclinical and clinical research that has to fill in the remaining gaps. (Neth Heart J 2008;16:88-95.).

Bone marrow cell therapy after acute myocardial infarction: the HEBE trial in perspective, first results.

During the last decennium, the role of bone marrow mononuclear cells (BMMC) has been underscored in the healing process after acute myocardial infarction (AMI). Although these cells improve left ventricular recovery after AMI in experimental studies, results from large-scale randomised trials investigating BMMC therapy in patients with AMI have shown contradictory results. To address this issue the HEBE study was designed, a multicentre, randomised trial, evaluating the effects of intracoronary infusion of BMMCs and the effects of intracoronary infusion of peripheral blood mononuclear cells after primary percutaneous coronary intervention. The primary endpoint of the HEBE trial is the change in regional myocardial function in dysfunctional segments at four months relative to baseline, based on segmental analysis as measured by magnetic resonance imaging. The results from the HEBE trial will provide detailed information about the effects of intracoronary BMMC therapy on post-infarct left ventricular recovery. In addition, further analysis of the data and material obtained may provide important mechanistic insights into the contribution of BMMCs to natural recovery from AMI as well as the response to cell therapy. This may significantly contribute to the development of improved cell-based therapies, aiming at optimising post-infarct recovery and preventing heart failure. (Neth Heart J 2008;16:436-9.).

Reduction in infarct size, but no functional improvement after bone marrow cell administration in a porcine model of reperfused myocardial infarction.

AIMS: Stem cell therapy after myocardial infarction (MI) has been studied in models of permanent coronary occlusion. We studied the effect of intracoronary administration of unselected bone marrow (BM) and mononuclear cells (MNC) in a porcine model of reperfused MI. METHODS AND RESULTS: In 34 swine, the left circumflex coronary artery was balloon-occluded for 2 h followed by reperfusion. Ten swine without MI served as controls. All swine underwent magnetic resonance imaging (MRI) 1 week post-MI. The next day, 10 of the 30 surviving MI swine received BM, 10 other MI swine received MNC, and the remaining MI swine received medium intracoronary. Four weeks later, all swine underwent a follow-up MRI. One week after MI, end-diastolic volume (92+/-16 mL) and left ventricular (LV) weight (78+/-12 g) were greater, whereas ejection fraction (40+/-8%) was lower than in controls (69+/-11 mL, 62+/-13 g, and 53+/-6%). Injection of BM or MNC had no effect on the MI-induced changes in global or regional LV-function. However, there was a significant reduction in infarct size 4 weeks after MNC injection (-6+/-3%) compared with the medium (-3+/-5%). CONCLUSION: Intracoronary injection of BM or MNC in swine does not improve regional or global LV-function 4 weeks after injection. However, a reduction in infarct-size was noted after MNC injection.

Neointimal hyperplasia and endothelial function after percutaneous coronary intervention.

Percutaneous coronary revascularisation has become much safer and efficacious since its introduction more than 25 years ago. Currently, the need for surgical backup is small and the rate of late complications is lower than 10%. Further improvements are being studied, especially directed towards more biocompatible stents, using pharmacological principles with wider therapeutic windows and enhancing the vascular healing response/reendothelialisation. This article reviews several activities within the ICIN theme group `Vessel Wall'.

One year clinical follow up of paclitaxel eluting stents for acute myocardial infarction compared with sirolimus eluting stents.

OBJECTIVE: To compare clinical outcome of paclitaxel eluting stents (PES) versus sirolimus eluting stents (SES) for the treatment of acute ST elevation myocardial infarction. DESIGN AND PATIENTS: The first 136 consecutive patients treated exclusively with PES in the setting of primary percutaneous coronary intervention for acute myocardial infarction in this single centre registry were prospectively clinically assessed at 30 days and one year. They were compared with 186 consecutive patients treated exclusively with SES in the preceding period. SETTING: Academic tertiary referral centre. RESULTS: At 30 days, the rate of all cause mortality and reinfarction was similar between groups (6.5% v 6.6% for SES and PES, respectively, p = 1.0). A significant difference in target vessel revascularisation (TVR) was seen in favour of SES (1.1% v 5.1% for PES, p = 0.04). This was driven by stent thrombosis (n = 4), especially in the bifurcation stenting (n = 2). At one year, no significant differences were seen between groups, with no late thrombosis and 1.5% in-stent restenosis (needing TVR) in PES versus no reinterventions in SES (p = 0.2). One year survival free of major adverse cardiac events (MACE) was 90.2% for SES and 85% for PES (p = 0.16). CONCLUSIONS: No significant differences were seen in MACE-free survival at one year between SES and PES for the treatment of acute myocardial infarction with very low rates of reintervention for restenosis. Bifurcation stenting in acute myocardial infarction should, if possible, be avoided because of the increased risk of stent thrombosis.

Residual angina pectoris after percutaneous coronary intervention for acute coronary syndrome.

Fractional flow reserve (FFR) is an important diagnostic tool to guide decision-making in the cardiac catheterisation laboratory and for evaluation of percutaneous coronary interventions (PCI). Especially the pressure pullback curve at maximal hyperaemia is convincing in demonstrating the exact location and severity of a coronary stenosis. This pressure pullback curve can also demonstrate the presence of diffuse disease. We present a case in which FFR with pressure pullback curve seven days after a PCI, which did not result in complete symptom relief, indicates the presence of diffuse disease. Based on this result the patient was treated medically.

Routine sirolimus eluting stent implantation for unselected in-stent restenosis: insights from the rapamycin eluting stent evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry.

OBJECTIVE: To assess the effectiveness of routine sirolimus eluting stent (SES) implantation for unselected patients with in-stent restenosis and to provide preliminary information about the angiographic outcome for lesion subgroups and for different in-stent restenosis patterns. DESIGN: Prospective, single centre registry. SETTING: Tertiary referral centre. PATIENTS: 44 consecutive patients (53 lesions) without previous brachytherapy who were treated with SES for in-stent restenosis were evaluated. Routine angiographic follow up was obtained at six months and the incidence of major adverse cardiovascular events was evaluated. RESULTS: At baseline, 42% of the lesions were focal, 21% diffuse, 26% proliferative, and 11% total occlusions. Small vessel size (reference diameter < or = 2.5 mm) was present in 49%, long lesions (> 20 mm) in 30%, treatment of bypass grafts in 13%, and bifurcation stenting in 18%. At follow up, post-SES restenosis was observed in 14.6%. No restenosis was observed in focal lesions. For more complex lesions, restenosis rates ranged from 20-25%. At the one year follow up, the incidence of death was 0, myocardial infarction 4.7% (n = 2), and target lesion revascularisation 16.3% (n = 7). The target lesion was revascularised because of restenosis in 11.6% (n = 5). CONCLUSIONS: Routine SES implantation is highly effective for focal in-stent restenosis and appears to be a promising strategy for more complex patterns of restenosis.

Sonotherapy, antirestenotic therapeutic ultrasound in coronary arteries: the first clinical experience.

We studied the safety and feasibility of intracoronary sonotherapy (IST) and its effect on the coronary vessel at 6 months. Thirty-seven patients with stable or unstable angina were included (40 lesions). The indication was de novo lesion (n = 26), restenosis (n = 2), in-stent restenosis (n = 11), and a total occlusion of a venous bypass graft. After successful angioplasty, IST was performed using a 5 Fr catheter with three serial ultrasound transducers operating at 1 MHz. IST was successfully performed in 36 lesions (success rate, 90%). IST exposure time per lesion was 718 +/- 127 sec. During hospital stay, one patient died due to a bleeding complication. At 6-month follow-up, one patient experienced acute myocardial infarction, eight patients underwent repeat PTCA. No patient underwent CABG. Late lumen loss was 1.05 +/- 0.70 mm with a restenosis rate of 25%. IVUS analysis revealed a neointima burden of 25% +/- 11%. IST can be applied safely and with high acute procedural success. Sonotherapy-related major adverse events were not observed. Late lumen loss and neointimal growth were similar to conventional PTCA approaches. These results justify the initiation of randomized clinical efficacy studies.