The Prognostic Value of a Validated and Automated Intravascular Ultrasound-Derived Calcium Score.

BACKGROUND: Coronary calcification has been linked to cardiovascular events. We developed and validated an algorithm to automatically quantify coronary calcifications on intravascular ultrasound (IVUS). We aimed to assess the prognostic value of an IVUS-calcium score (ICS) on patient-oriented composite endpoint (POCE). METHODS: We included patients that underwent coronary angiography plus pre-procedural IVUS imaging. The ICS was calculated per patient. The primary endpoint was a composite of all-cause mortality, stroke, myocardial infarction, and revascularization (POCE). RESULTS: In a cohort of 408 patients, median ICS was 85. Both an ICS ≥ 85 and a 100 unit increase in ICS increased the risk of POCE at 6-year follow-up (adjusted hazard ratio (aHR) 1.51, 95%CI 1.05-2.17, p value = 0.026, and aHR 1.21, 95%CI 1.04-1.41, p value = 0.014, respectively). CONCLUSIONS: The ICS, calculated by a validated automated algorithm derived from routine IVUS pullbacks, was strongly associated with the long-term risk of POCE.

Variation in Coronary Atherosclerosis Severity Related to a Distinct LDL (Low-Density Lipoprotein) Profile: Findings From a Familial Hypercholesterolemia Pig Model.

OBJECTIVE: In an adult porcine model of familial hypercholesterolemia (FH), coronary plaque development was characterized. To elucidate the underlying mechanisms of the observed inter-individual variation in disease severity, detailed lipoprotein profiles were determined. Approach and Results: FH pigs (3 years old, homozygous LDLR R84C mutation) received an atherogenic diet for 12 months. Coronary atherosclerosis development was monitored using serial invasive imaging and histology. A pronounced difference was observed between mildly diseased pigs which exclusively developed early lesions (maximal plaque burden, 25% [23%-34%]; n=5) and advanced-diseased pigs (n=5) which developed human-like, lumen intruding plaques (maximal plaque burden, 69% [57%-77%]) with large necrotic cores, intraplaque hemorrhage, and calcifications. Advanced-diseased pigs and mildly diseased pigs displayed no differences in conventional risk factors. Additional plasma lipoprotein profiling by size-exclusion chromatography revealed 2 different LDL (low-density lipoprotein) subtypes: regular and larger LDL. Cholesterol, sphingosine-1-phosphate, ceramide, and sphingomyelin levels were determined in these LDL-subfractions using standard laboratory techniques and high-pressure liquid chromatography mass-spectrometry analyses, respectively. At 3 months of diet, regular LDL of advanced-diseased pigs contained relatively more cholesterol (LDL-C; regular/larger LDL-C ratio 1.7 [1.3-1.9] versus 0.8 [0.6-0.9]; P=0.008) than mildly diseased pigs, while larger LDL contained more sphingosine-1-phosphate, ceramides, and sphingomyelins. Larger and regular LDL was also found in plasma of 3 patients with homozygous FH with varying LDL-C ratios. CONCLUSIONS: In our adult FH pig model, inter-individual differences in atherosclerotic disease severity were directly related to the distribution of cholesterol and sphingolipids over a distinct LDL profile with regular and larger LDL shortly after the diet start. A similar LDL profile was detected in patients with homozygous FH.

Percutaneous coronary interventions during ST-segment elevation myocardial infarction: current status and future perspectives.

The present article focuses on recent innovations and possible future perspectives in the reperfusion treatment of ST-segment elevation myocardial infarction (STEMI). Among these, the shift from the femoral to the radial vascular access, the recent availability of bioresorbable coronary scaffolds, other innovative forms of stent specifically designed for STEMI patients, the use of cardioprotective strategies, as well as the possibility of including autologous bone marrow stem cell transplantation as part of the treatment of patients with STEMI are described and commented on as a glance into the future.

Rationale and methods of the integrated biomarker and imaging study (IBIS): combining invasive and non-invasive imaging with biomarkers to detect subclinical atherosclerosis and assess coronary lesion biology.

Death or myocardial infarction, the most serious clinical consequences of atherosclerosis, often result from plaque rupture at non-flow limiting lesions. Current diagnostic imaging with coronary angiography only detects large plaques that already impinge on the lumen and cannot accurately identify those that have a propensity to cause unheralded events. Accurate evaluation of the composition or of the biomechanical characteristics of plaques with invasive or non-invasive methods, alone or in conjunction with assessment of circulating biomarkers, could help identify high-risk patients, thus providing the rationale for aggressive treatments in order to reduce future clinical events. The IBIS (Integrated Biomarker and Imaging Study) study is a prospective, single-center, non-randomized, observational study conducted in Rotterdam. The aim of the IBIS study is to evaluate both invasive (quantitative coronary angiography, intravascular ultrasound (IVUS) and palpography) and non-invasive (multislice spiral computed tomography) imaging techniques to characterize non-flow limiting coronary lesions. In addition, multiple classical and novel biomarkers will be measured and their levels correlated with the results of the different imaging techniques. A minimum of 85 patients up to a maximum of 120 patients will be included. This paper describes the study protocol and methodological solutions that have been devised for the purpose of comparisons among several imaging modalities. It outlines the analyses that will be performed to compare invasive and non-invasive imaging techniques in conjunction with multiple biomarkers to characterize non-flow limiting subclinical coronary lesions.

No change in endothelial-dependent vasomotion late after coronary irradiation.

PURPOSE: Mechanical injury from balloon angioplasty and stenting is known to cause prolonged endothelial dysfunction, even distal to the injured segment. Intravascular irradiation therapy is associated with delayed healing response and may therefore also impede endothelial functional recovery. This study was conducted to assess endothelial function late after the irradiation of atherosclerotic coronary arteries. METHODS AND MATERIALS: In 15 patients (8 with additional radiation and 7 with stenting only), directly after the intervention and at 6-month follow-up, endothelial function of the distal segment was studied by assessment of coronary diameter after intracoronary acetylcholine (Ach). Coronary flow reserve (CFR) and intravascular ultrasound (IVUS) investigation were performed for unequivocal interpretation of angiographic data. RESULTS: No significant different response to Ach could be detected at baseline nor at follow-up (-17 +/- 14% vs. -17 +/- 15% for radiation vs. nonradiation at baseline, P=1.0; -8 +/- 11% vs. -9 +/- 13% at follow-up, P=.8). IVUS data revealed more constrictive remodeling in the nonradiation patients, but a minimal increase in mean plaque area in the radiation patients compared with a significant decrease in nonradiation patients (+4% vs. -25%, P=.02). CONCLUSIONS: Irradiation of atherosclerotic coronary arteries does not affect endothelium-dependent vasodilatation acutely or at 6 months. Irradiated segments demonstrated less negative remodeling but higher plaque burden than the controls did.

The black hole: echolucent tissue observed following intracoronary radiation.

AIMS: Recent trials in humans have given us insight into some of the consequences of intracoronary radiation. The authors describe a new observation noted on intravascular ultrasound: that of intraluminal echolucent tissue, dubbed the 'black hole', noted at six-month follow-up. METHODS AND RESULTS: One hundred and twenty-eight consecutive patients enrolled in brachytherapy protocols were analyzed. The control group (C) consisted of individuals who underwent percutaneous transluminal coronary angioplasty with (n = 48) and without (n = 22) stent implantation. Radiation groups included those who underwent low activity (LA) (n = 18), high activity (HA) (n = 26) and cold-end (CE) (n = 18) radioactive stenting. The Novoste Betacath (n = 39) and Guidant (n = 27) catheter-based radiation systems were also employed. At six-month follow-up echolucent tissue was identified in a total of 28 cases (22%). Angiographic restenosis occurred in 17 cases (61%). No echolucent tissue was seen in the control group or in the LA group. HA and CE radioactive stents were most commonly associated with echolucent tissue. Echolucent tissue was seen in all groups treated with catheter-based radiation with and without stenting. Pathology after atherectomy demonstrated smooth muscle cells scattered in extracellular matrix containing abundant proteoglycans and an absence of elastin and mature collagen. CONCLUSIONS: Echolucent tissue is common after radioactive stenting. It is composed of tissue rich in proteoglycans while poor in mature collagen and elastin.

TAXUS III Trial: in-stent restenosis treated with stent-based delivery of paclitaxel incorporated in a slow-release polymer formulation.

BACKGROUND: The first clinical study of paclitaxel-eluting stent for de novo lesions showed promising results. We performed the TAXUS III trial to evaluate the feasibility and safety of paclitaxel-eluting stent for the treatment of in-stent restenosis (ISR). METHODS AND RESULTS: The TAXUS III trial was a single-arm, 2-center study that enrolled 28 patients with ISR meeting the criteria of lesion length < or =30 mm, 50% to 99% diameter stenosis, and vessel diameter 3.0 to 3.5 mm. They were treated with one or more TAXUS NIRx paclitaxel-eluting stents. Twenty-five patients completed the angiographic follow-up at 6 months, and 17 of these underwent intravascular ultrasound (IVUS) examination. No subacute stent thrombosis occurred up to 12 months, but there was one late chronic total occlusion, and additional 3 patients showed angiographic restenosis. The mean late loss was 0.54 mm, with neointimal hyperplasia volume of 20.3 mm3. The major adverse cardiac event rate was 29% (8 patients; 1 non-Q-wave myocardial infarction, 1 coronary artery bypass grafting, and 6 target lesion revascularization [TLR]). Of the patients with TLR, 1 had restenosis in a bare stent implanted for edge dissection and 2 had restenosis in a gap between 2 paclitaxel-eluting stents. Two patients without angiographic restenosis underwent TLR as a result of the IVUS assessment at follow-up (1 incomplete apposition and 1 insufficient expansion of the stent). CONCLUSIONS: Paclitaxel-eluting stent implantation is considered safe and potentially efficacious in the treatment of ISR. IVUS guidance to ensure good stent deployment with complete coverage of target lesion may reduce reintervention.

Inaccuracy in manual multisegmental irradiation in coronary arteries.

PURPOSE: Retrospective evaluation of the accuracy of manual multisegmental irradiation with a source train for irradiation of long (re)stenotic lesions in coronary arteries, following percutaneous transluminal coronary angioplasty (PTCA). MATERIAL AND METHODS: Thirty-six patients were treated with intracoronary irradiation following PTCA with manual multisegmental irradiation. These patients were included in the multicenter, multinational 'European Surveillance Registry with the Novoste Beta-Cath system' (RENO). In all 36 patients the target length (i.e. PTCA length plus 5-mm margin at each side) was too long for the available source train lengths (30 and 40 mm). In 33 patients the radiation delivery catheter was manually positioned twice and in three patients three times in series, trying to avoid any gap or overlap. The total number of junctions was 39. Following a successful PTCA procedure the site of angioplasty was irradiated using the Novoste Beta-Cath afterloader with a 5-F non-centered catheter which accommodates the sealed beta-emitting (90)Sr/(90)Y source train or dummy source train. Radiation was delivered first to the distal part of the target length. Fluoroscopic images of this source position were stored in the computer memory. For irradiation of the proximal part of the target length, the delivery catheter had to be retracted over a distance equal to the source length used for the distal part. This was done by a continuous overlay video loop with ECG-gated replay of the image stored in the computer memory. The dummy source was used to position the delivery catheter so that the junction between both source positions was as precise as possible. Measurements of gap or overlap between the source positions were performed retrospectively on printed images. Doses were calculated, in accordance with the Novoste study protocol, at a distance of 2 mm from the source axis (=dose prescription distance) in several points along the irradiated length. RESULTS: Interventional or PTCA length varied between 33 and 95 mm. The lesion sites were in the left anterior descending artery, (n=6), right coronary artery (n=20), left circumflex artery (n=6) and one vein graft. The administered radiation dose was determined by the vessel diameter and the presence of a stent. This dose, prescribed at a distance of 2 mm from the source axis, varied between 16 and 22 Gy. No gap or overlap was seen between the two source trains in only two out of 39 cases. In 16 cases there was a gap ranging between 0.6 and 9.6 mm and 18 cases showed an overlap of 0.5-14.4 mm. In three patients the measurement was not possible. In case of a gap the minimal dose calculated at 2 mm from the source axis varies between 0 and 87% of the prescribed dose, depending on the distance between both sources. In case of overlap the maximal dose varies between 110 and 200% of the prescribed dose at 2 mm from the source axis. CONCLUSIONS: The results show the inaccuracy of manual multisegmental irradiation using a source train in coronary arteries, causing unacceptable dose inhomogeneities at a distance of 2 mm from the source axis at the junction between both source positions. Moreover, a perfect junction will never be possible due to movement of the non-centered radiation delivery catheter in the vessel lumen, as applied in this study. Manual multisegmental irradiation is therefore not recommended. Using longer line sources or source trains or preferably an automated stepping source is a more reliable and safer technique for treatment of long lesions.