Evangelia Karvouni

Transcoronary transplantation of autologous mesenchymal stem cells and endothelial progenitors into infarcted human myocardium.

The aim of the study was to investigate whether a combination of mesenchymal stem cells (MSCs) capable of differentiating into cardiac myocytes and endothelial progenitors (EPCs) that mainly promote neoangiogenesis might be able to facilitate tissue repair in myocardial scars. Previous studies have shown that intracoronary transplantation of autologous bone marrow stem cells results in improvement of contractility in infracted areas of human myocardium. Eleven patients with an anteroseptal myocardial infarction (MI) underwent transcoronary transplantation of bone marrow‐derived MSCs and EPCs to the infarcted area through the left anterior descending artery. Eleven age‐ and sex‐matched patients served as controls. Wall motion score index was significantly lower at follow‐up in the transplantation (P = 0.04) but not in the control group. On stress echocardiography, there was improvement of myocardial contractility in one or more previously nonviable myocardial segments in 5 out of 11 patients (all with recent infarctions) and in none of the controls (P = 0.01). Restoration of uptake of Tc99m sestamibi in one or more previously nonviable myocardial scars was seen in 6 out of 11 patients subjected to transplantation and in none of the controls (P = 0.02). Cell transplantation was an independent predictor of improvement of nonviable tissue. Intracoronary transplantation of MSCs and EPCs is feasible, safe, and may contribute to regional regeneration of myocardial tissue early or late following MI.

Mortality risk conferred by small elevations of creatine Kinase-MB isoenzyme after percutaneous coronary intervention

OBJECTIVES The aim of this study was to assess whether small creatine kinase-MB isoenzyme (CK-MB) elevations after percutaneous coronary intervention (PCI) affect the subsequent mortality risk. BACKGROUND Several studies have evaluated the relationship of CK-MB levels after PCI with the subsequent risk of death. While there is consensus that elevations exceeding 5 times the upper limit of normal increase mortality significantly, there is uncertainty about the exact clinical impact of smaller CK-MB elevations. METHODS We performed a meta-analysis of seven studies with CK-MB measurements and survival outcomes on 23230 subjects who underwent PCI. Data were combined with random effects models. RESULTS Mean follow-up was 6 to 34 months per study. By random effects, 19% (95% confidence interval [CI], 16% to 23%) had one- to five-fold CK-MB elevations, while only 6% (95% CI, 5% to 9%) had >5-fold elevations. Compared with subjects with normal CK-MB, there was a dose-response relationship with relative risks for death being 1.5 (95% CI, 1.2 to 1.8, no between-study heterogeneity) with one- to three-fold CK-MB elevations, 1.8 (95% CI, 1.4 to 2.4, no between-study heterogeneity) with three- to five-fold CK-MB elevations, and 3.1 (95% CI, 2.3 to 4.2, borderline between-study heterogeneity) with over five-fold CK-MB elevations (p < 0.001 for all). CONCLUSIONS Any increase in CK-MB after PCI is associated with a small, but statistically and clinically significant, increase in the subsequent risk of death.

Recombinant Apolipoprotein A-IMilano Infusion Into Rabbit Carotid Artery Rapidly Removes Lipid From Fatty Streaks

Apolipoprotein A-IMilano (AIM), a natural variant of human apolipoprotein A-I, confers to carriers a significant protection against vascular disease. In previous studies, administration of recombinant AIM-phospholipid (AIM-PL) complexes to hypercholesterolemic rabbits markedly inhibited neointimal formation after arterial injury; moreover, repeated injections of AIM-PL in apoE-deficient mice significantly reduced atherosclerosis progression. The objective of the present study was to determine if a single localized infusion of AIM-PL complexes administered directly to atheromatous lesions could promote plaque regression. Lipid-rich, atheromatous plaques were generated at both common carotid arteries of 25 rabbits by applying a perivascular electric injury, followed by 1.5% cholesterol diet for 90 days. Rabbits were infused with either saline, phospholipid vesicles, or 3 different AIM-PL doses (250, 500, or 1000 mg of protein) delivered through an intravascular ultrasound (IVUS) catheter positioned at the origin of the right carotid. The lesions at the left carotid artery were therefore exposed to the agents systemically. Infusion of AIM-PL at the 2 highest doses caused reduction of right carotid artery plaque area by the end a 90-minute infusion as assessed by IVUS analysis. Plaque area regression was confirmed by histology in carotid arteries receiving direct (500 and 1000 mg doses) and systemic (500 mg dose) delivery, 72 hours after the start of the treatment. Plaque lipid content was associated with significant and similar decreases in Oil Red O staining in both arteries. These results suggest AIM-PL complexes enhanced lipid removal from arteries is the mechanism responsible for the observed plaque changes.

Intravenous glycoprotein IIb/IIIa receptor antagonists reduce mortality after percutaneous coronary interventions.

OBJECTIVES We sought to evaluate the impact of intravenous antagonists of the platelet IIb/IIIa receptor on the survival of patients undergoing percutaneous coronary interventions (PCIs). BACKGROUND Several trials have shown that intravenous antagonists of the platelet glycoprotein (GP) IIb/IIIa receptor reduce the incidence of myocardial infarction (MI) and composite cardiac outcomes (death, MI, or revascularization) in patients undergoing PCI. However, individual studies have not had adequate power to examine differences in mortality. METHODS We performed a meta-analysis of 19 randomized, placebo-controlled trials (20 comparisons, n = 20,137). Death was the primary outcome. Secondary outcomes included MI, composite cardiac outcomes, and major bleeding. RESULTS Mortality was significantly reduced at 30 days (risk ratio [RR] 0.69 [95% confidence interval [CI] 0.53 to 0.90]), at six months (RR 0.79 [95% CI 0.64 to 0.97]), and including longer follow-up (RR 0.79 [95% CI 0.66 to 0.94]), with no significant between-study heterogeneity. The relative risk reduction was largely similar in trials of patients with or without acute myocardial infarction (AMI), in trials continuing or discontinuing heparin after the procedure, and in trials using stents or another PCI as the intended primary procedure. Myocardial infarction and composite outcomes were significantly reduced (p < 0.001 for all) at 30 days and six months. Major bleeding was significantly increased only in trials where heparin infusion was continued after the procedure (RR 1.70 [95% CI 1.36 to 2.14]), although there was no excess bleeding when heparin was discontinued (RR 1.02 [95% CI 0.85 to 1.24]). CONCLUSIONS In patients undergoing PCI, GP IIb/IIIa receptor antagonists confer a significant and sustained decrease (20% to 30%) in the risk of death.

Biodegradable Stents “Fulfilling the Mission and Stepping Away”

In 458 BC, a prominent Roman leader named Lucius Quintius Cincinnatus was unique in his behavior. Cincinnatus served his country when he was needed and, after fulfilling his duty, he returned to his private life.1 We now see a new medical device, a biodegradable stent, that mimics this historical figure. The 2 main functions of a stent, treatment of dissection and prevention of restenosis, refer to 2 events that occur and progress in a set frame of time. Coronary dissections are effectively contained by stent insertion and undergo a healing process, with the majority of cardiac events occurring in the first 6 months.2 In-stent restenosis also occurs within the first 6 months.3 Therefore, a permanent prosthesis that is in place beyond this initial period has no clear function. Besides lacking a well-defined function, are there any negative aspects related to the presence of a permanent coronary implant? Zidar et al4 stated that one of the main reasons to develop a biodegradable stent was the short-term need for a stent and the potential long-term complications of metal stents. Kimura et al3 demonstrated, with an extended angiographic follow-up of 3 years, that the presence of a metallic stent does not seem to be associated with lesion progression or accelerated atherosclerosis of the treated site after 6 months. In fact, late improvement in luminal diameter seems to occur between 6 months and 3 years. The Belgian Netherlands Stent Study (BENESTENT I) recently extended its follow-up to 5 years and demonstrated a sustained and persistent benefit of the stent.5 If no demonstrable complications exist with a permanent intracoronary implant, can the question be turned around by asking, “What are the benefits of not having a permanent coronary implant?” Two answers can be given. 1. Coronary stenting freezes recoil, …

Intravascular ultrasound-guided percutaneous transluminal coronary angioplasty with provisional spot stenting for treatment of long coronary lesions

OBJECTIVES The purpose of this study was to evaluate the approach of intravascular ultrasound (IVUS)-guided percutaneous transluminal coronary angioplasty (PTCA) with spot stenting (SS) for the treatment of long coronary lesions. BACKGROUND Treating long coronary lesions with balloon angioplasty results in suboptimal short- and long-term outcomes. Full lesion coverage with traditional stenting (TS) has been associated with a high restenosis rate. METHODS We prospectively evaluated a consecutive series of 130 long lesions (>15 mm) in 101 patients treated with IVUS-guided PTCA and SS. The results were compared with those of TS in a matched group of patients. Coronary angioplasty was performed with a balloon to vessel ratio of 1:1, according to the IVUS media-to-media diameter of the vessel at the lesion site, to achieve prespecified IVUS criteria: lumen cross-sectional area (CSA) > or =5.5 mm(2) or > or =50% of the vessel CSA at the lesion site. The stents were implanted only in the vessel segment where the criteria were not met. RESULTS In the SS group, stents were implanted in 67 of 130 lesions, and the mean stent length was shorter than that of lesions in the matched TS group (10.4 +/- 13 mm vs. 32.4 +/- 13 mm, p < 0.005). The 30-day major adverse cardiac event (MACE) rate was similar (5%) for both groups. Angiographic restenosis was 25% with IVUS-guided SS, as compared with 39% in the TS group (p < 0.05). Follow-up MACE and target lesion revascularization rates were lower in the SS group than in the TS group (22% vs. 38% [p < 0.05] and 19% vs. 34% [p < 0.05], respectively). CONCLUSIONS Intravascular ultrasound-guided SS for the treatment of long coronary lesions is associated with good acute outcome. Angiographic restenosis and follow-up MACE rates were significantly lower than those with TS.

Cutting Balloon angioplasty for the treatment of in-stent restenosis

The results using the Cutting Balloon for the treatment of in‐stent restenosis may be superior to those of conventional percutaneous transluminal coronary angioplasty (PTCA) or even the combination of PTCA preceded by rotational atherectomy. The reasons for these possible differences are not yet well defined. The case we report suggests that the Cutting Balloon achieves a better final result than conventional PTCA, by making the tissue more amenable to being pushed outward through the stent struts. Cathet. Cardiovasc. Intervent. 50:452–459, 2000.

Medical personnel and patient dosimetry during coronary angiography and intervention.

Percutaneous coronary interventions are associated with increased radiation exposure compared to most radiological examinations. This prospective study aimed at (1) measuring entrance doses for all in-room personnel, (2) performing an assessment of patient effective dose and intracoronary doses, (3) investigating the contribution of each projection to kerma-area product (KAP) and irradiation time, (4) comparing results with established DRL values in this clinical setting and (5) estimating the risk for fatal cancer to patients and operators. Measurements were performed during 40 consecutive procedures of coronary angiography (CA), half of which were followed by ad hoc coronary angioplasty (PTCA). KAP measurements were used for patients and thermoluminescent dosimetry for the in-room personnel. The mean KAP value per procedure for CA was 29 +/- 9 Gy cm2. Thirty four per cent of KAP was due to fluoroscopy, whereas the remainder (66%) was due to digital cine. Accordingly, the mean KAP value per PTCA procedure was 75 +/- 30 Gy cm2, and contribution of fluoroscopy is 57%. Effective dose per year was estimated to be 0.04-0.05 mSv y(-1) for the primary operator, and 0.03-0.04 mSv y(-1) for those assisting. Corresponding measurements for radiographer and nurse were below detectable level, implying minimal radiation hazards for them. Regarding radiation exposure, coronary intervention is considered a quite safe procedure for both patients and personnel in laboratories with modern equipment and experienced operators as long as standard safety precautions are considered. Exposure optimization though should be constantly sought through continuous review of procedures.

New recipes for in-stent restenosis: cut, grate, roast, or sandwich the neointima?

In-stent restenosis is set to become a large part of our interventional practice in the new millennium. Stent implantation has grown so much that it now comprises 60–70% of all percutaneous coronary revascularisation interventions, and assuming a conservative 25% restenosis rate for a total of around one million percutaneous transluminal coronary angioplasty (PTCA) procedures this year, more than 150 000 lesions will need treatment because of in-stent restenosis. The increasing popularity of stent implantation is because of improvements in immediate gain, in tackling dissections, in preventing recoil after PTCA, and in reducing late restenoses, which have been documented in many randomised trials where results have been compared with PTCA. However, despite excellent immediate results, stents have not eliminated restenosis, especially in complex lesions with diffuse coronary disease or in small vessels.1-4 Furthermore, the mechanism of in-stent restenosis is very different from that of restenosis after conventional percutaneous treatment (PTCA, directional, rotational, or laser atherectomy). Lumen narrowing after these latter interventions is mainly caused by late wall recoil, and this negative remodelling of the treated segment can easily be treated with a new PTCA or by stent implantation.5 6 The stent, on the other hand, maintains the expansion it reaches after the procedure and all the reduction in lumen diameter is caused by intimal hyperplasia.7 The challenge to the interventionist in the coming years is how to prevent and treat this condition. Recently the Washington group suggested an angiographic classification of in-stent restenosis according to lesion length and geographical distribution of intimal hyperplasia in relation to the implanted stent. Four patterns of in-stent restenosis were suggested (table 1), with different impacts on the late outcome after a new revascularisation procedure.8 View this table: Table 1 Angiographic patterns of in-stent restenosis (ISR) Repeat balloon angioplasty for in-stent restenosis is an easy and safe procedure …

Conduction patterns in the cardiac veins: Electrophysiologic characteristics of the connections between left atrial and coronary sinus musculature

AbstractIntroduction: Fractionated electrograms and double potentials have been well described within the coronary sinus (CS) in humans. The pattern of circumferential activation in the CS has not been investigated. Furthermore, no data exist on conduction characteristics within the great cardiac vein (GCV) or the middle cardiac vein (MCV). Methods and Results: Twenty patients underwent catheter mapping of the CS, the MCV, and the GCV. Anatomical areas were verified by cannulation of the left superior pulmonary vein. The pattern of circumferential muscle activation within the proximal CS was also studied with a circular mapping catheter (Lasso 12 mm). At conventional mapping during sinus rhythm and high right atrial pacing, discrete double potentials or fractionated electrograms were recorded during left, right atrial and CS pacing at the CS ostium, mid-CS, and distal CS-ligament of Marshall area, in 2 (10%), 1 (5%), and 9 (45%) patients, respectively, whereas no patient displayed such signals in the MCV or GCV (p < 0.001). Proximal CS mapping with the Lasso was accomplished in 10 patients, 7 of whom had no evidence of multicomponent potentials in the CS at conventional mapping. Specific CS potentials dissociated from the atrial electrograms were recorded in all patiens with the use of circumferential mapping. The perimetric distribution of electrograms within the CS suggested an oblique course of conduction across the CS musculature. Conclusion: Potentials representing activation of the CS musculature, with an oblique course of conduction across the CS, can be recorded in human CS but not in the GCV or MCV. This is compatible with anatomical observations of sinus venosus musculature covering the CS but not other cardiac veins, and supports the rationale for the role of CS musculature in the generation of atrial arrhythmias.