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 stents­ie, 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.

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 B(2), and tumor necrosis factor (TNF)α 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 B(2), and TNFα release into aspirate plasma increased by 1.9±0.2 µmol/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. TNFα 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 TNFα 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.

Lessons from human coronary aspirate.

The interventional implantation of a stent into an atherosclerotic coronary artery is a unique and paradigmatic scenario of plaque rupture in humans. The use of protection devices not only prevents the released plaque particles and the superimposed thrombotic material from being washed and embolized into the coronary microcirculation of the individual patient, but permits also the retrieval and ex vivo analysis of particulate plaque debris and soluble substances. The particulate debris comprises typical cholesterol crystals, foam cells, hyalin material and calcium deposits from the atheroma as well as platelets and coagulation material; soluble substances include vasoconstrictors, such as serotonin and thromboxane, as well as inflammatory mediators, such as TNFα which amplifies vasoconstriction by inducing endothelial dysfunction. The vasoconstriction observed in a bioassay ex vivo correlates to clinical symptoms, angiographic stenosis and plaque burden, as assessed by intravascular ultrasound. The release of TNFα into the aspirate correlates to restenosis. Detailed analysis of the human coronary aspirate may promote a better understanding of the pathophysiology of the vulnerable atherosclerotic plaque and help to better antagonize the microvascular consequences of coronary microembolization, including the no reflow phenomenon. This article is part of a Special Issue entitled "Coronary Blood Flow."

Saphenous vein aorto-coronary graft atherosclerosis in patients with chronic kidney disease: more plaque calcification and necrosis, but less vasoconstrictor potential.

Atherosclerotic coronary arteries are more calcified in patients with than without chronic kidney disease (CKD). We addressed the potential for coronary microvascular obstruction in patients with and without CKD during stenting for saphenous vein aorto-coronary graft (SVG) stenosis under protection with a distal occlusion/aspiration device. In patients with and without CKD (n = 20/20), SVG plaque composition was analyzed from virtual histology using intravascular ultrasound analysis before stent implantation. There was more dense calcium and more necrotic core in patients with than without CKD (14 ± 3 vs. 3 ± 1 % and 21 ± 3 vs. 12 ± 2 % of plaque volume, respectively). Coronary aspirate was retrieved during stent implantation and divided into particulate debris and plasma. Patients with CKD had more particulate debris and calcium release than patients without CKD. In contrast, the release of serotonin was less in patients with than without CKD (0.4 ± 0.1 vs. 1.2 ± 0.3 µmol/L), whereas that of catecholamines, endothelin, tissue factor, thromboxane, tumor necrosis factor α, and C reactive protein was not significantly different. Confirming the biochemical results, aspirate plasma from patients with CKD induced less vasoconstriction of rat mesenteric arteries than that from patients without CKD (with endothelium (+E), 26 ± 7 %; without endothelium (-E): 28 ± 7 % vs. +E, 68 ± 12 %; -E: 95 ± 16 % of maximum KCl-induced vasoconstriction). Graft atherosclerosis of patients with CKD is more degenerated and releases more particulate debris and calcium, but the aspirate has surprisingly less serotonin and vasoconstrictor potential.

Acute vasomotor paralysis and potential downstream effects of paclitaxel from stents implanted for saphenous vein aorto-coronary bypass stenosis.

Implantation of bare metal stents (BMS) induces the release not only of particulate debris, but also of soluble vasoconstrictors which contribute to microvascular impairment. So this study aimed at addressing the potential attenuation of such vasoconstriction using paclitaxel eluting stents (PES). Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stent [n = 14 BMS, n = 14 PES, n = 3 sirolimus eluting stents (SES)] implantation in patients with saphenous vein aorto-coronary bypass stenosis and analyzed for plasma serotonin and thromboxane B(2) concentrations. The vasoconstriction of rat mesenteric arteries with intact (+E) and denuded (-E) endothelium in response to coronary arterial or aspirate plasma was quantified and normalized to that by potassium chloride (KCl(max) = 100%). Coronary arterial plasma before stent implantation induced a vasoconstriction of 30-43%, which was independent of endothelial integrity. Serotonin-release was 2.2 ± 0.5 µmol/l with BMS and 2.0 ± 0.4 µmol/l with PES, thromboxane B(2)-release was 26 ± 5 pg/ml with BMS and 22 ± 8 pg/ml with PES. BMS- and SES-aspirate plasma induced a vasoconstriction of 68 ± 18% (+E)/93 ± 14% (-E) and 81 ± 17% (+E)/124 ± 14% (-E), respectively. In contrast, PES-aspirate plasma induced only minor vasoconstriction of 8 ± 3% (+E)/12 ± 5% (-E). Addition of paclitaxel to BMS-aspirate plasma attenuated vasoconstriction. PES-aspirate induced microtubular condensation in immunofluorescence microscopy. Results indicate that aspirate from PES implantation attenuates vasoconstriction, possibly secondary to microtubular stabilization. Such acute downstream vascular paralysis could be beneficial in preventing a no-reflow phenomenon in patients undergoing stenting.

Serial intravascular ultrasound assessment of changes in coronary atherosclerotic plaque dimensions and composition: an update.

This manuscript reviews the use of serial intravascular ultrasound (IVUS) examination of coronary atherosclerosis in recent observational studies and randomized trials that revealed the effects of cholesterol-lowering and lipid-modifying therapies and offered novel insight into plaque progression and regression. We discuss the value of plaque progression-regression as complementary imaging endpoint and potential surrogate marker of cardiovascular event risk. In addition, the progress in serial assessment of coronary plaque composition and plaque vulnerability by radiofrequency-based analyses is reviewed. Finally, we report on the evaluation of true vessel remodelling in recent serial IVUS trials and discuss the future perspective of serial invasive imaging of coronary atherosclerosis.

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.

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.

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 preliminary 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.

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.

Impact of atherosclerotic plaque composition on coronary microembolization during percutaneous coronary interventions.

BACKGROUND: Cardiac marker release after percutaneous coronary interventions (PCI) reflects myocardial necrosis which is usually the result of periprocedural (micro)embolization of atherothrombotic debris and associated with impaired left ventricular function and adverse outcome. METHODS: In this prospective study, we examined 55 patients treated by direct stenting of single de-novo lesions to assess the relationship between plaque composition, as determined by preinterventional intravascular ultrasound (IVUS) with radiofrequency data (IVUS-RF) analysis (so-called Virtual Histology) versus coronary microembolization, as determined by serial measurement of cardiac markers. IVUS was performed with an electronic system and 20-MHz IVUS catheters. Serum creatine kinase (CK) and cardiac troponin I (CTnI) were determined before PCI and after 6, 12, and 24 hours. RESULTS: Plaques had a volume of 99 +/- 63 mm(3) and were composed of fibrous (61 +/- 9%) and fibro-fatty tissue (27 +/- 12%), dense calcium (4 +/- 3%), and necrotic core (NC) (8 +/- 6%). NC volume per se, volume per 10 mm of segment length, and volume % were correlated (r = 0.64, 0.66, and 0.52 respectively; all P < 0.01) with the maximum increase in cardiac markers (CK 55.4 +/- 55.7 U/l; CTnI 0.49 +/- 0.68 ng/ml). Patients in the 4th quartile of NC volume (>10.8 mm(3)) had a particularly high increase in markers (P < 0.001). In contrast, total plaque volume and plaque components other than NC had no relation with cardiac markers (ns). CONCLUSIONS: Patients with large NC in culprit lesions may experience more myocardial injury from peri-interventional microembolization. IVUS-RF assessment before PCI has the potential to identify lesions at particular high risk which may help to tailor PCI.

Cardiac computed tomography in patients with symptomatic new-onset atrial fibrillation, rule-out acute coronary syndrome, but with intermediate pretest probability for coronary artery disease admitted to a chest pain unit.

BACKGROUND: Atrial fibrillation (AF) and coronary artery disease (CAD) may be encountered coincidently in a large portion of patients. However, data on coronary artery calcium burden in such patients are lacking. Thus, we sought to determine the value of cardiac computed tomography (CCT) in patients presenting with new-onset AF associated with an intermediate pretest probability for CAD admitted to a chest pain unit (CPU). METHODS: Calcium scores (CS) of 73 new-onset, symptomatic AF subjects without typical clinical, electrocardiographic, or laboratory signs of acute coronary syndrome (ACS) admitted to our CPU were analyzed. In addition, results from computed tomography angiography (CTA) were related to coronary angiography findings whenever available. RESULTS: Calcium scores of zero were found in 25%. Median Agatston score was 77 (interquartile range: 1-270) with gender- and territory-specific dispersal. CS scores above average were present in about 50%, high (> 400)-to-very high (> 1000) CS scores were found in 22%. Overall percentile ranking showed a relative accordance to the reference percentile distribution. Additional CTA was performed in 47%, revealing stenoses in 12%. Coronary angiography was performed in 22% and resulted in coronary intervention or surgical revascularization in 7%. On univariate analysis, CS > 50th percentile failed to serve as an independent determinant of significant stenosis during catheterization. CONCLUSIONS: Within a CPU setting, relevant CAD was excluded or confirmed in almost 50%, the latter with a high proportion of coronary angiographies and subsequent coronary interventions, underlining the diagnostic value of CCT in symptomatic, non-ACS, new-onset AF patients when admitted to a CPU.

Relation between plaque progression and low-density lipoprotein cholesterol during aging as assessed with serial long-term (> or =12 months) follow-up intravascular ultrasound of the left main coronary artery.

Because of the clinical benefit of lipid lowering in older patients, we hypothesized that the relation between low-density lipoprotein (LDL) cholesterol serum levels and coronary plaque progression may persist throughout aging. We analyzed serial intravascular ultrasound (IVUS) data of 60 left main stems (18 +/- 9 months apart) and evaluated the relation between LDL cholesterol levels and coronary plaque progression at different ages. The population (n = 60) was divided into 3 groups according to age: tertile 1 (n = 20) was a mean age of 48 +/- 6 years (median 51, range 33 to 55), tertile 2 (n = 20) was a mean age of 58 +/- 2 years (median 59, range 55 to 61), and tertile 3 (n = 20) was a mean age of 66 +/- 6 years (median 65, range 61 to 83). Between groups, there was no significant difference in non-age-related demographics, clinical data, lipid profiles, or medications (e.g., statins). There was a positive linear relation between LDL cholesterol and annual changes in plaque plus media area in all age tertiles, which was statistically significant in tertiles 2 and 3 (r = 0.56, p <0.01; r = 0.50, p <0.02) and showed a strong trend in tertile 1 (r = 0.41, p = 0.07). The estimated LDL cholesterol thresholds, which, as determined by regression analysis, would correspond to no plaque progression, were 74, 60, and 78 mg/dl, respectively, in tertiles 1, 2, and 3. In conclusion, serial IVUS data in left main coronary arteries suggest that the relation between LDL cholesterol serum levels and plaque progression persists during aging.

Coronary Artery Calcium as an Independent Surrogate Marker in the Risk Assessment of Patients With Atrial Fibrillation and an Intermediate Pretest Likelihood for Coronary Artery Disease Admitted to a German Chest Pain Unit.

BACKGROUND: About 10% of patients admitted to a chest pain unit (CPU) exhibit atrial fibrillation (AF). HYPOTHESIS: To determine whether calcium scores (CS) are superior over common risk scores for coronary artery disease (CAD) in patients presenting with atypical chest pain, newly diagnosed AF, and intermediate pretest probability for CAD within the CPU. METHODS: In 73 subjects, CS was related to the following risk scores: Global Registry of Acute Coronary Events (GRACE) score, including a new model of a frequency-normalized approach; Thrombolysis In Myocardial Infarction score; European Society of Cardiology Systematic Coronary Risk Evaluation (SCORE); Framingham risk score; and Prospective Cardiovascular Münster Study score. Revascularization rates during index stay were assessed. RESULTS: Median CS was 77 (interquartile range, 1-270), with higher values in men and the left anterior descending artery. Only the modified GRACE (ρ = 0.27; P = 0.02) and the SCORE (ρ = 0.39; P < 0.005) were significantly correlated with CS, whereas the GRACE (τ = 0.21; P = 0.04) and modified GRACE (τ = 0.23; P = 0.02) scores were significantly correlated with percentile groups. Only the CS significantly discriminated between those with and without stenosis (P < 0.01). CONCLUSIONS: Apart from modified GRACE score, overall correlations between risk scores and calcium burden, as well as revascularization rates during index stay, were low. By contrast, the determination of CS may be used as an additional surrogate marker in risk stratification in AF patients with intermediate pretest likelihood for CAD admitted to a CPU.

How rapid is rapid? Exemplary results of real-life rapid rule-out troponin timing in troponin-positive acute coronary syndromes without persistent ST-segment elevation in two contrasting German chest pain unit facilities.

AIM: To analyse the timing of cardiac troponin (cTn) measurements in high-risk and cTn-positive acute coronary syndromes without persistent ST-segment elevation (NSTE-ACS) in two structurally different German chest pain units (CPUs), contrasting an urban university maximum care and a rural regional primary care facility. METHODS: All patients encoded as NSTEMI during the year 2013 were retrospectively enrolled in two centres: site (I)--centre of maximum care in an urban university setting and site (II)--centre of primary care in a rural regional care setting. Data acquisition included time intervals from admission to baseline cTn and first and second cTn control as well as type and timing of invasive management. RESULTS: The median times (site I vs. site II) from admission to cTn result announcement were 26.5 vs. 33.0 min (p = 0.02) for baseline, 4 vs. 4 h (p = 0.43) for the first and 11.0 vs. 16.5 h (p = 0.03) for the second control. Timely announcement, as recommended by guidelines, was available in 86.9% at baseline, 59.4% for the first or 41.1% for the second cTn control. Rates and timing of invasive management were independent from the time point of positive cTn announcement (p = 0.51 and p = 0.68, respectively). CONCLUSIONS: German CPUs provide timely identification of cTn-positive patients in a narrow and guideline-adherent time frame using a rapid rule-out protocol. Especially, baseline and early cTn timing was comparable between the urban university maximum care and the rural regional primary care facility without relevant impact on guideline-conforming invasive management, underlining the high standard of care in those highly professional institutions.

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.

Association of plaque characterization by intravascular ultrasound virtual histology and arterial remodeling.

Positive remodeling is more often observed in lesions of patients who have acute coronary syndromes or vulnerable (rupture-prone) plaques. However, there are few data that correlate plaque morphology, composition, and arterial remodeling in vivo. We evaluated coronary plaque characterization of lesions with positive remodeling using intravascular ultrasound (IVUS) radiofrequency data analysis. Seventy-seven nonbifurcation native coronary lesions (in 50 patients) were imaged in vivo using 30-MHz IVUS transducers. Lesions were classified into 4 plaque types, fibrous, fibrofatty, dense calcium, and necrotic core, by using processing of the radiofrequency signal validated in vitro. The remodeling index was calculated as the lesion external elastic membrane area divided by the proximal reference external elastic membrane area. Lesions were divided into 2 groups: positive remodeling (remodeling index>1.0, 26 lesions) and intermediate/negative remodeling (remodeling index

Determinants of coronary blood flow in humans: quantification by intracoronary Doppler and ultrasound.

The direct determinants of coronary flow are lumen area and blood flow velocity; however, the precise mechanisms that control these factors are not fully understood. The aim of the present study was to assess by which mechanisms lumen area and coronary flow velocity interact with hemodynamic and morphometric factors, thereby influencing coronary flow. Intracoronary Doppler and ultrasound measurements were performed in 28 patients without coronary lumen irregularities. Flow velocity and lumen cross-sectional area were measured in the proximal segments of all three coronary arteries. Global lumen cross-sectional area and global flow were obtained by adding up the values of all three coronary arteries. Left ventricular mass was assessed by echocardiography. Stress-mass-heart rate and pressure-rate products reflecting myocardial oxygen demand were calculated. Global coronary flow increased during adenosine-induced hyperemia from 197 +/- 72 to 637 +/- 204 ml/min (P < 0.001). Global coronary flow closely correlated with the stress-mass-heart rate product (r = 0.62; P < 0.001). Looking at the two constituents of flow separately, global coronary cross-sectional area was closely related to left ventricular muscle mass (r = 0.61; P < 0.001), whereas mean coronary flow velocity at rest showed a strong linear relation with the pressure-rate product (r = 0.64; P < 0.001). There was no interaction between cross-sectional area and blood flow velocity in any of the coronary vessels. Coronary lumen size and flow velocity, the two determinants of coronary flow, are principally determined by different physiological factors. Long-term flow adaptation is achieved by an increase in coronary lumen size, whereas short-term myocardial oxygen requirements are met by changes in resting flow velocity.

[Coronary stents. From a simple idea to a medical high-tech device]. / Koronare Stents / Von der Idee zum High-Tech-Implantat.

BACKGROUND: Coronary stents were introduced in clinical cardiology in the middle of the 1980s, as balloon angioplasty was associated with a high incidence of acute vessel closure and restenosis. EVOLUTION OF CORONARY STENTS: However, primarily designed to counteract elastic recoil after angioplasty, initial results were complicated by acute and subacute stent thrombosis. With the introduction of drugs effectively inhibiting platelet aggregation like ticlopidine and clopidogrel, stent could exhibit its superiority in comparison to angioplasty. Although the incidence of restenosis could be decreased significantly by coronary stents, restenosis remained a major drawback of this interventional technique. Several modifications of stent design and stent material had been tested, but without a real breakthrough. The introduction of active stent coating with anti-inflammatory and antiproliferative drugs marks a milestone in the development of this technology. With this approach the restenosis problem could be, even though not solved, but essentially mitigated. Current developments address bioabsorbable materials to make stents compatible with new upcoming noninvasive imaging techniques. CONCLUSION: Introduced 20 years ago as a simple wire mesh, modified by new designs and materials, and coated by highly effective drugs, coronary stents have advanced to medical high-tech devices in interventional cardiology.