Maxwell Afari

Neointimal patterns obtained by optical coherence tomography correlate with specific histological components and neointimal proliferation in a swine model of restenosis

AIMS Although optical coherence tomography (OCT) is capable to detect microscopic peri-strut changes that seem to be related to neointimal inhibition and healing, its ability to characterize these components is still limited. In this study, we aimed to compare different OCT morphological characteristics with different in-stent neointimal tissue types analysed by histology. METHODS A total of 69 stents (39 drug eluting and 30 bare metal stents) were implanted in coronary arteries of 27 swine. By OCT, neointimal type was classified as homogeneous, heterogeneous, or layered according to its pattern of backscatter and optical intensity. The resulting optical patterns were correlated with several histological findings [external elastic lamina (EEL) disruption, fibrin deposition, circumferential rim of peri-strut inflammatory cell infiltration, and fibrous connective deposition] in every single cross-section (CS) analysed. RESULTS A total of 197 matched OCT and histological CS were analysed. The heterogeneous (0.44 ± 0.21 mm) and layered (0.65 ± 0.16 mm) patterns had a significantly higher degree of neointimal thickness compared with the homogeneous pattern (0.25 ± 0.16 mm, P < 0.001). Fibrous connective tissue deposition was more frequently present in the homogeneous pattern (71.6%, P < 0.001), whereas significant fibrin deposits were more commonly seen in the heterogeneous pattern (56.9%, P = 0.007). Peri-strut inflammation was less frequently found in the homogeneous pattern (19.8%, P < 0.001) in comparison with the layered (73.9%) or heterogeneous patterns (43.1%). The presence of EEL rupture was also more commonly seen in layered (73.9%) and heterogeneous (46.6%) patterns than in the homogeneous pattern (22.4%, P < 0.001). CONCLUSION The optical characteristics of neointimal formation seen in OCT properly correlated with the presence of several histological findings involved in stent healing. The biological implications of these findings in clinical outcomes require further investigation.

Evaluation of Efficacy and Dose Response of Different Paclitaxel-Coated Balloon Formulations in a Novel Swine Model of Iliofemoral In-Stent Restenosis

OBJECTIVES The authors aimed to validate a novel iliofemoral in-stent restenosis (ISR) model for the efficacy evaluation of paclitaxel-coated balloons (PCB) using the familial hypercholesterolemic swine (FHS). BACKGROUND Most of the validation work regarding PCB technologies has been performed in the coronary territory of juvenile domestic swine. Although invaluable for safety evaluation, this model is not suited for the evaluation of the efficacy of peripheral PCB technologies. METHODS Twenty-four iliofemoral segments in 12 FHS underwent balloon injury and self-expanding stent placement. After 21 days, the resulting ISR lesions were treated with either 1 μg/mm(2) dose (n = 8), or 3 μg/mm(2) dose (n = 8) PCB (Cotavance, Bayer Pharma AG/MEDRAD, Indianola, Pennsylvania), or with an identical uncoated control balloon (n = 8). RESULTS At termination (28 days after treatment), the percent diameter stenosis by quantitative vascular analysis in the control group was higher (31.2 ± 13.7%) compared with the 1 μg/mm(2) (19.3 ± 14.0%, 38% reduction) and 3 μg/mm(2) (8.6 ± 10.7%, 72% reduction) PCB groups. Intravascular ultrasound analysis showed 36% (1 μg/mm(2) dose, p = 0.04) and 55% (3 μg/mm(2) dose, p < 0.01) reductions in neointimal volume stenosis. In the histological analysis, the control group showed the highest degree of percent area stenosis (65 ± 14.3%). The reductions in percent area stenosis was 13.2% (p = 0.5) and 26% (p = 0.04) in the 1 μg/mm(2) and 3 μg/mm(2) dose groups, respectively. CONCLUSIONS The FHS model of iliofemoral ISR demonstrated a dose-dependent effect on the inhibition of neointimal proliferation of a clinically validated PCB technology. This model represents a positive step toward the efficacy evaluation of PCB in the peripheral vascular territory.

Correlation of Angiographic Late Loss With Neointimal Proliferation in Stents Evaluated by OCT and Histology in Porcine Coronary Arteries

OBJECTIVES We aimed to evaluate the correlation of angiographic late loss (LL) with the degree of in-stent neointimal proliferation assessed by optical coherence tomography (OCT) and histology. BACKGROUND Angiographic LL is the most common endpoint used in clinical trials for the evaluation of the efficacy of drug-eluting stents (DES). However, there are few data in regards to the accuracy of angiographic LL in the evaluation of DES displaying lower degrees of neointimal proliferation. METHODS A total of 49 stents (36 DES and 13 bare-metal stents) were deployed in coronary arteries of 23 domestic swine and followed up for 28 or 90 days, thus obtaining different degrees of neointimal proliferation. Each stent was divided into 8 to 9 segments along the longitudinal axis to match corresponding histological cross sections. Angiographic LL was calculated at each segment throughout the entire length of the stent and compared with in-stent neointimal thickness (NT) obtained by OCT and histology. RESULTS A total of 382 angiographic segments were suitable for matched comparison with both OCT and histological findings. The mean LL at follow-up was 0.60 ± 0.57 mm (range: -0.46 to 2.3 mm) for all segments. Approximately 13.9% of stent segments had a LL between -0.5 and 0 mm, and 22.5% had a LL greater than 1.0 mm. The correlation between OCT and histology for the evaluation of NT was adequate regardless the level of angiographic LL. In addition, overall correlations between angiographic LL and NT by OCT or histology were adequate (R = 0.77 and 0.63, respectively). However, angiographic LL showed a poor correlation with NT by OCT or histology at a value <0.55 mm (R = 0.38 and 0.15, respectively). CONCLUSIONS Angiographic LL below a threshold value of 0.55 mm correlates poorly with NT obtained by OCT and histology. These results suggest a cautious interpretation is needed to evaluate angiographic endpoints in DES trials in which LL values below this threshold are reported.

Peri-strut low-intensity areas in optical coherence tomography correlate with peri-strut inflammation and neointimal proliferation: an in-vivo correlation study in the familial hypercholesterolemic coronary swine model of in-stent restenosis.

BackgroundPeri-strut low-intensity area (PLI) is a common imaging finding during the evaluation of in-stent neointima using optical coherence tomography (OCT). We aimed to determine the biological significance of PLI by comparing in-vivo OCT images with the corresponding histological sections obtained from the familial hypercholesterolemic swine model of coronary stenosis. MethodsA total of 26 coronary vessels of nine familial hypercholesterolemic swine were injured with 30% balloon overstretch and then immediately followed by everolimus eluting or bare metal stent placement at 20% overstretch. At 30 days, all stented vessels were subjected to in-vivo OCT analysis and were harvested for histological evaluation. For OCT analysis, stent cross-sections (three per stent) were categorized into presence (PLI+) or absence (PLI−) of PLI. In histology, inflammation and fibrin deposition were scored semiquantitatively from 0 (none) to 3 (severe). ResultsPLI was found in 64.9% of stent sections. Peri-strut inflammation was more frequently observed in OCT sections PLI (+) compared with PLI (−) (56.0 vs. 7.4%, P=0.01). In contrast, peri-strut fibrin deposits was similar in both groups (PLI+=58.0% vs. PLI−=59.3%, P=0.94). Histological neointimal thickness was significantly higher in PLI (+) sections (mean±SE: 0.68±0.06 vs. 0.34±0.02 mm; P<0.01), yielding a higher percent area stenosis compared with PLI (–) (mean±SE: 59.0±4.4 vs. 34.1±2.2%, P<0.01). The PLI diagnostic sensitivity and specificity for inflammation were 80 and 76.1%, respectively (>56% PLI, area under the curve=0.86, P<0.01), whereas for fibrin deposition, the sensitivity and specificity were 42.2 and 76.1%, respectively (area under the curve=0.56, P=NS). Area under the receiver operating characteristic curve was significantly higher for identifying inflammation than fibrin (0.86 vs. 0.56, P<0.01). The severity of PLI correlated with the neointimal thickness when assessed by OCT (R=0.79, P<0.001). ConclusionThe presence of PLI in OCT correlates with neointimal thickness and appears to have a diagnostic value in the recognition of peri-strut inflammation, therefore possibly serving as a surrogate for in-vivo assessment of stent efficacy.

Stent healing response following delivery of paclitaxel via durable polymeric matrix versus iopromide-based balloon coating in the familial hypercholesterolaemic swine model of coronary injury

AIMS The routine use of paclitaxel-coated balloons (PCB) in combination with bare metal stents (BMS) in de novo coronary lesions has been questioned. In this study, we aimed to compare the vascular response of BMS implanted using a second-generation PCB (BMS+PCB) with the TAXUS stent (PES) and a BMS control (BMS) in the familial hypercholesterolaemic swine (FHS) model of coronary injury. METHODS AND RESULTS A total of 17 stents (PES=6, BMS+PCB=6, and BMS=5) were implanted in the coronary territory of 10 FHS using a 20% overstretch injury ratio. Imaging evaluation (QCA and IVUS) was conducted in all animals at baseline and 28 days following stent implantation. Following terminal imaging all animals were euthanised and stented coronary segments harvested for histological evaluation. At 28 days, the lowest degree of percentage diameter stenosis by QCA was achieved by the PES (2.9 ± 9%) followed by the BMS+PCB (9.5 ± 16.4%) and the BMS group (25.65 ± 18.7%, p<0.05). In histology, percentage area of stenosis (BMS+PCB=29.6 ± 6.4% vs. PES=21.5 ± 3.3% vs. BMS=55.2 ± 12.9%; p<0.01) and neointimal thickness (BMS+PCB=0.26 ± 0.1 mm vs. PES=0.21 ± 0.1 mm vs. BMS=0.59 ± 0.2 mm; p<0.01) were significantly reduced in both paclitaxel groups in comparison to BMS controls. Both BMS+PCB and BMS groups had higher endothelialisation scores (PES=1.50 ± 0.9 vs. BMS+PCB=2.73 ± 0.4 vs. BMS=3.00; p<0.05) and lower peri-strut inflammatory scores (PES=0.83 ± 0.4 vs. BMS+PCB=0.20 ± 0.2 vs. BMS=0.43 ± 0.6, p<0.05) when compared to PES. Neointima maturity (PCB+BMS: 2.00 [2-2.4] vs. PES: 1.00 [0.3-1] vs. BMS: 3.00, p<0.05) and fibrin deposition (PCB+BMS: 1.40 ± 0.3 vs. PES: 2.17 ± 0.7 vs. BMS: 0.27 ± 0.3, p<0.05) scores in PCB+BMS appeared to fall between the PES and the BMS ranges. CONCLUSIONS In the FHS coronary injury model, BMS implantation using a PCB yields a degree of neointimal inhibition comparable to the PES. The BMS+PCB combination presented lower degrees of inflammation and fibrin deposition; however, signs of delayed healing were still present.

Multimodal Imaging after Sudden Cardiac Arrest in an 18-Year-Old Athlete.

We report the case of a previously healthy 18-year-old male athlete who twice presented with sudden cardiac arrest. Our use of electrocardiography, echocardiography, cardiac magnetic resonance, coronary angiography, coronary computed tomographic angiography, and nuclear stress testing enabled the diagnoses of apical hypertrophic cardiomyopathy and anomalous origin of the right coronary artery. We discuss the patients treatment and note the useful role of multiple cardiovascular imaging methods in cases of sudden cardiac arrest.

TCT-598 Luminal Fibrin as a Key Component in Mechanism of Action in Drug Coated Balloon Technologies

The mechanism of action of Drug Coated Balloons (DCB) is not fully understood. Its suggested that following balloon dilatation, Paclitaxel is deposited on the vascular luminal surface and serves as a natural drug delivery system. We hypothesize that fibrin acts as a biological glue covering

Refractory Hypotension as an Initial Presentation of Bilateral Subclavian Artery Stenosis

Bilateral subclavian stenosis is a rare clinical condition. An interbrachial pressure difference of 15 mm Hg can raise suspicion for unilateral subclavian artery stenosis, but the diagnosis of bilateral subclavian artery stenosis can be challenging. We present a case of a 75-year-old woman who presented with refractory hypotension after surgery. Initial vitals revealed blood pressure in the 60s/50s mm Hg in both arms. Cardiopulmonary examination was remarkable for diminished pulses in all 4 extremities and audible carotid bruits. She continued to be hypotensive despite aggressive fluid resuscitation. Troponin T peaked at 0.24 ng/mL (reference < 0.04), and an echocardiogram revealed a reduction in ejection fraction (37% from 50%). Left and right heart catheterization demonstrated normal filling pressures and cardiac output. During the procedure, however, it was noted that the patients central blood pressure was 70–80 mm Hg higher than cuff pressures obtained in either arm. Selective angiography revealed 90% left subclavian ostial stenosis as well as 70% stenosis of the right subclavian artery.

Lyme Carditis: An Interesting Trip to Third-Degree Heart Block and Back

Carditis is an uncommon presentation of the early disseminated phase of Lyme disease. We present the case of a young female who presented with erythema migrans and was found to have first-degree heart block which progressed to complete heart block within hours. After receiving ceftriaxone, there was complete resolution of the heart block in sequential fashion. Our case illustrates the importance of early recognition and anticipation of progressive cardiac conduction abnormalities in patients presenting with Lyme disease.

MULTIMODALITY IMAGING IN EXERCISE INDUCED SUDDEN CARDIAC ARREST

Sudden cardiac death in a young athlete is considered a paradoxical tragedy because athletes are expected to be the healthiest in the community. In this era of technological advancement, the collaborative use of diverse imaging tools could potentially improve our understanding of sudden cardiac