Dirk Böse

Temporary scaffolding of coronary arteries with bioabsorbable magnesium stents: a prospective, non-randomised multicentre trial

BACKGROUND Coronary stents improve immediate and late results of balloon angioplasty by tacking up dissections and preventing wall recoil. These goals are achieved within weeks after angioplasty, but with current technology stents permanently remain in the artery, with many limitations including the need for long-term antiplatelet treatment to avoid thrombosis. We report a prospective multicentre clinical trial of coronary implantations of absorbable magnesium stents. METHODS We enrolled 63 patients (44 men; mean age 61.3 [SD 9.5 years]) in eight centres with single de novo lesions in a native coronary artery in a multicentre, non-randomised prospective study. Follow-up included coronary angiography and intravascular ultrasound at 4 months and clinical assessment at 6 months and 12 months. The primary endpoint was cardiac death, non-fatal myocardial infarction, or clinically driven target lesion revascularisation at 4 months FINDINGS 71 stents, 10-15 mm in length and 3.0-3.5 mm in diameter, were successfully implanted after pre-dilatation in 63 patients. Diameter stenosis was reduced from 61.5 (SD 13.1%) to 12.6 (5.6%) with an acute gain of 1.41 mm (0.46 mm) and in-stent late loss of 1.08 mm (0.49 mm). The ischaemia-driven target lesion revascularisation rate was 23.8% after 4 months, and the overall target lesion revascularisation rate was 45% after 1 year. No myocardial infarction, subacute or late thrombosis, or death occurred. Angiography at 4 months showed an increased diameter stenosis of 48.4 (17.0%). After serial intravascular ultrasound examinations, only small remnants of the original struts were visible, well embedded into the intima. Neointimal growth and negative remodelling were the main operating mechanisms of restenosis. INTERPRETATION This study shows that biodegradable magnesium stents can achieve an immediate angiographic result similar to the result of other metal stents and can be safely degraded after 4 months. Modifications of stent characteristics with prolonged degradation and drug elution are currently in development.

Coronary Microembolization From Bedside to Bench and Back to Bedside

Coronary microembolization from the erosion or rupture of a vulnerable atherosclerotic plaque occurs spontaneously in acute coronary syndromes and iatrogenically during percutaneous coronary interventions. Typical consequences of coronary microembolization are microinfarcts with an inflammatory response, contractile dysfunction, and reduced coronary reserve. Apart from transient elevations of creatine kinase and troponin, microemboli can be visualized by intracoronary Doppler and the resulting microinfarcts by late-enhancement nuclear magnetic resonance. Statins, antiplatelet agents, and coronary vasodilators protect against microembolization and microinfarction when started before percutaneous coronary interventions. Distal protection devices can retrieve atherothrombotic debris and prevent its embolization into the microcirculation, but their effect on clinical outcome has been disappointing so far, except for saphenous vein bypass grafts. Devices for aspiration of thrombi and thrombus-derived vasoconstrictor, thrombogenic, and inflammatory substances, however, reduce thrombus burden, improve perfusion, and provide protection in patients with acute myocardial infarction.

Safety and performance of the drug-eluting absorbable metal scaffold (DREAMS) in patients with de-novo coronary lesions: 12 month results of the prospective, multicentre, first-in-man BIOSOLVE-I trial

BACKGROUND Bioabsorbable vascular scaffolds were developed to overcome limitations of permanent bare-metal or drug-eluting coronary stents—ie, stent thrombosis (despite prolonged dual antiplatelet therapy), the life-long presence of a caged vessel segment that does not allow vasomotion or remodelling, and chronic vessel wall inflammation. We assessed the safety and performance of a new magnesium-based paclitaxel-eluting absorbable metal scaffold in symptomatic patients with de-novo coronary lesions. METHODS We did a prospective, multicentre, first-in-man trial (BIOSOLVE-1) of the drug-eluting absorbable metal scaffold (DREAMS). 46 patients with 47 lesions were enrolled at five European centres. The primary endpoint was target lesion failure, a composite of cardiac death, target vessel myocardial infarction, and clinically driven target lesion revascularisation, at 6 and 12 months. Clinical follow-up was scheduled at 1, 6, 12, 24, and 36 months. Patients were consecutively assigned to angiographic and intravascular ultrasonographic follow-up at 6 months or 12 months. Optical coherence tomography was done in some patients. All patients were recommended to take dual antiplatelet therapy for at least 12 months. This trial is registered with ClinicalTrials.gov, number NCT01168830. FINDINGS Overall device and procedural success was 100%. Two of 46 (4%) patients had target lesion failure at 6 months (both clinically driven target lesion revascularisations), which rose to three of 43 (7%) at 12 months (one periprocedural target vessel myocardial infarction occurred during angiography at the 12 month follow-up visit). We noted no cardiac death or scaffold thrombosis. INTERPRETATION Our results show feasibility, a good safety profile, and promising clinical and angiographic performance results up to 12 months for DREAMS. Our promising clinical results show that absorbable metal scaffolds might be an alternative to polymeric absorbable scaffolds. FUNDING Biotronik.

Relationship Between Cardiovascular Risk as Predicted by Established Risk Scores Versus Plaque Progression as Measured by Serial Intravascular Ultrasound in Left Main Coronary Arteries

Background—Intravascular ultrasound (IVUS) is increasingly used as an end point in studies aimed at reducing progression or inducing regression of coronary artery disease. However, data linking serial changes by IVUS with clinical outcomes are scarce. Methods and Results—In the absence of a validated risk score for secondary prevention, we compared 3 established risk scores for primary prevention—PROCAM, SCORE, and Framingham—with plaque progression and lumen reduction as assessed with serial IVUS (follow-up, 18±9 months) in atherosclerotic left main coronary arteries of 56 patients with established atherosclerosis. For all 3 algorithms, patients at highest estimated risk of events showed greater plaque progression than patients at lowest risk (P<0.05 to <0.01). There were positive linear relationships between the risk of clinical events and plaque progression (r=0.41 to 0.60; P<0.002 to <0.0001). This translated into a greater decrease in lumen dimensions with increasing risk (P<0.05, PROCAM and SCORE). Risk prediction using the PROCAM algorithm showed the strongest relation with serial IVUS. During follow-up, 18 patients suffered from adverse cardiovascular events; these patients had an annual plaque progression that was significantly greater than other patients (25.2±19.4% versus 5.9±15.6%, P<0.001). Conclusions—There was a positive linear relationship between the estimated risk of clinical events derived from all 3 established risk-score algorithms and the extent of plaque progression measured by serial IVUS. This translated into stenosis progression (reduction in lumen dimensions) with increasing clinical risk.

Early- and Long-Term Intravascular Ultrasound and Angiographic Findings After Bioabsorbable Magnesium Stent Implantation in Human Coronary Arteries

OBJECTIVES This study aimed to evaluate the degradation rate and long-term vascular responses to the absorbable metal stent (AMS). BACKGROUND The AMS demonstrated feasibility and safety at 4 months in human coronary arteries. METHODS The PROGRESS-AMS (Clinical Performance and Angiographic Results of Coronary Stenting) was a prospective, multicenter clinical trial of 63 patients with coronary artery disease who underwent AMS implantation. Angiography and intravascular ultrasound (IVUS) were conducted immediately after AMS deployment and at 4 months. Eight patients who did not require repeat revascularization at 4 months underwent late angiographic and IVUS follow-up from 12 to 28 months. RESULTS The AMS was well-expanded upon deployment without immediate recoil. The major contributors for restenosis as detected by IVUS at 4 months were: decrease of external elastic membrane volume (42%), extra-stent neointima (13%), and intra-stent neointima (45%). From 4 months to late follow-up, paired IVUS analysis demonstrated complete stent degradation with durability of the 4-month IVUS indexes. The neointima was reduced by 3.6 +/- 5.2 mm(3), with an increase in the stent cross sectional area of 0.5 +/- 1.0 mm(2) (p = NS). The median in-stent minimal lumen diameter was increased from 1.87 to 2.17 mm at long-term follow-up. The median angiographic late loss was reduced from 0.62 to 0.40 mm by quantitative coronary angiography from 4 months to late follow-up. CONCLUSIONS Intravascular ultrasound imaging supports the safety profile of AMS with degradation at 4 months and maintains durability of the results without any early or late adverse findings. Slower degradation is warranted to provide sufficient radial force to improve long-term patency rates of the AMS.

Vasoconstrictor Potential of Coronary Aspirate From Patients Undergoing Stenting of Saphenous Vein Aortocoronary Bypass Grafts and Its Pharmacological Attenuation

Rationale: Stent implantation into atherosclerotic plaques releases, apart from particulate debris, soluble substances that contribute to impaired microvascular perfusion. Objective: To quantify the release of vasoconstrictors and to determine the efficacy of coronary dilators to attenuate their action. Methods and Results: Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stenting in 22 patients with severe saphenous vein aorto-coronary bypass stenoses. The release of catecholamines, endothelin, serotonin, thromboxane B2, and tumor necrosis factor (TNF)&agr; was measured. The response of rat mesenteric arteries with intact (+E) and denuded (−E) endothelium to aspirate plasma was normalized to that by KCl. Responses to selective receptor blockade, adenosine, nitroprusside, and verapamil against the aspirate-induced constriction were determined. The coronary arterial plasma withdrawn before stenting induced 21±5% and the aspirate plasma after stenting induced 95±8% of maximum KCl-induced vasoconstriction. Serotonin, thromboxane B2, and TNF&agr; release into aspirate plasma increased by 1.9±0.2 &mgr;mol/L, 25.6±3.1 pg/mL, and 19.7±6.1 pg/mL, respectively, during stenting. The aspirate-induced vasoconstriction was largely antagonized by selective serotonin receptor blockade, with little further antagonism by additional thromboxane receptor blockade. TNF&agr; did not induce constriction per se but potentiated the constriction with serotonin and the thromboxane-analog U-46619 in arteries +E. The concentrations to induce half-maximal vasodilation were comparable for nitroprusside (+E, 3.3×10−8; −E, 1.9×10−8 mol/L) and verapamil (+E, 8.3×10−8; −E, 7.8×10−8 mol/L), and the vasoconstriction was eventually eliminated. The vasodilator response to adenosine was dependent on functional endothelium and weaker. Conclusion: Serotonin is the main coronary vasoconstrictor after stenting, and thromboxane and TNF&agr; somewhat potentiate the serotonin response. Nitroprusside and verapamil are more potent than adenosine to attenuate the aspirate plasma-induced vasoconstriction, and they are not dependent on functional endothelium.

Guidance of percutaneous transcatheter aortic valve implantation by real-time three-dimensional transesophageal echocardiography – A single-center experience

Percutaneous transcatheter aortic valve implantation (TAVI) is an evolving interventional therapy for high-risk, non-surgical patients with severe, symptomatic aortic valve stenosis (AS). As a standard procedure, 2D transesophageal echocardiography has been used for the preinterventional assessment of the native valve and measurement of the aortic annulus as well as for intraprocedural guidance. Recently, a new matrix array, transesophageal probe for real-time three-dimensional echocardiography (RT3D-TEE) has been introduced. We applied this new technique to monitor percutaneous aortic valve implantation and described our initial experiences with this method in patients undergoing TAVI. We hypothesized that RT3D-TEE provides improved evaluation of the native aortic valve and annulus dimension due to unlimited scan plane orientation. This new technology should also enable accurate guiding of percutaneous cardiac interventions by providing immediate information on prosthesis position and function in real-time. In our preliminiary clinical experience real-time three-dimensional transesophageal echocardiography (RT3D TEE) was demonstrated to provide improved guiding of percutaneous aortic valve replacement by superior spatial visualisation of the cardiac structures and facilitated the detection of procedure-related complications. Due to the advantages of real-time 3D TEE monitoring, this technique might improve the outcome of patients treated with percutaneous aortic valve replacement.

Do systemic risk factors impact invasive findings from virtual histology? Insights from the international virtual histology registry

AIMS Cardiovascular risk factors such as elevated serum lipid levels are important in the development of coronary atherosclerosis. Radiofrequency (RF) analysis of intravascular ultrasound [IVUS, Virtual histology (VH)] offers a unique tool to study the composition of coronary atherosclerotic plaque in vivo. We used data from the multicentre VH registry to assess the association between cardiovascular risk factors and coronary plaque volume and composition. METHODS AND RESULTS Between August 2004 and July 2006, 990 patients in 42 centres were enrolled in a prospective, multicentre, non-randomized global VH registry. Coronary artery imaging was performed by conventional IVUS and RF-IVUS. The four RF-IVUS plaque components [dense calcium (DC), necrotic core (NC), fibrous (F) tissue, and fibro fatty (FF)] were analysed in every recorded frame. The results were expressed as mean cross-sectional areas, absolute volume, and percentage of total plaque volume. Risk factor assessment included evaluation of family history of previous myocardial infarction (MI), past or current smoking, diabetes mellitus, hypertension, and the laboratory measurements. Patients with diabetes had an increased relative proportion of NC (6.47 +/- 0.28 vs. 5.86 +/- 0.14%, P = 0.037) and DC (4.58 +/- 0.27 vs. 3.90 +/- 0.14%, P = 0.017), and patients with hypertension had an increased relative proportion of FF, DC (4.35 +/- 0.16 vs. 3.57 +/- 0.17%, P = 0.02) and NC (6.24 +/- 0.17 vs. 5.60 +/- 0.19%, P = 0.01). Compared with patients with LDL-C <100 mg/dL, patients with LDL-C >160 mg/dL had higher plaque volume (342.1 +/- 26.2 vs. 318.6 +/- 10.7 mm(3)). Linear regression analysis showed a correlation between the level of HDL-C and F (r = -0.149, P < 0.01), FF (r = -0.106, P < 0.01), and NC (r = -0.90, P < 0.05). The level of LDL correlated with F (r = 0.110, P < 0.01). Patients with prior MI have an increased percentage of F (30.03 +/- 0.59 vs. 28.20 +/- 0.37%, P = 0.009). Smoking had no relevant effect on plaque composition. Treatment with acetylsalicylacid and statins reduced FF with altering plaque volume. CONCLUSION Radiofrequency-IVUS detects marked differences in coronary plaque composition related to the risk factor profile with particular focus on lipid levels. Greater amounts of NC were associated with diabetes, hypertension, MI, and low HDL-C. The effects of treatment of changes related to plaque composition are underway.

Images in cardiovascular medicine. Novel magnetic resonance-compatible coronary stent: the absorbable magnesium-alloy stent.

A 54-year-old male patient with known 2-vessel coronary artery disease and stable angina presented for elective percutaneous coronary intervention of a proximal right coronary artery stenosis (Figure 1). Previously, the patient had undergone intervention of mid-left anterior descending coronary artery stenosis by sirolimus-eluting stent implantation. Figure 1. Preinterventional coronary angiogram showing the high-grade stenosis in the proximal segment of the right coronary …A 54-year-old male patient with known 2-vessel coronary artery disease and stable angina presented for elective percutaneous coronary intervention of a proximal right coronary artery stenosis (Figure 1). Previously, the patient had undergone intervention of mid-left anterior descending coronary artery stenosis by sirolimus-eluting stent implantation. Figure 1. Preinterventional coronary angiogram showing the high-grade stenosis in the proximal segment of the right coronary …

Novel Magnetic Resonance-Compatible Coronary Stent The Absorbable Magnesium-Alloy Stent

A 54-year-old male patient with known 2-vessel coronary artery disease and stable angina presented for elective percutaneous coronary intervention of a proximal right coronary artery stenosis (Figure 1). Previously, the patient had undergone intervention of mid-left anterior descending coronary artery stenosis by sirolimus-eluting stent implantation. Figure 1. Preinterventional coronary angiogram showing the high-grade stenosis in the proximal segment of the right coronary …A 54-year-old male patient with known 2-vessel coronary artery disease and stable angina presented for elective percutaneous coronary intervention of a proximal right coronary artery stenosis (Figure 1). Previously, the patient had undergone intervention of mid-left anterior descending coronary artery stenosis by sirolimus-eluting stent implantation. Figure 1. Preinterventional coronary angiogram showing the high-grade stenosis in the proximal segment of the right coronary …