What has intravascular ultrasound taught us about plaque biology?

Intravascular ultrasound (IVUS) has a defined role in the cardiac catheterization laboratory to assess lesion severity and the procedural success of vascular interventions. However, IVUS has also contributed to our understanding of the biology of atherosclerosis and restenosis. In acute coronary syndromes, IVUS has revealed varying degrees of stenosis, thrombosis, and plaque derangement typical of the plaque disruption seen in many pathologic studies of patients who have died of this condition. IVUS has demonstrated that the culprit lesions of patients surviving acute coronary syndromes also tend to be softer, with less calcium, and tend to have more plaque with positive arterial remodeling (compensatory enlargement) than lesions causing stable coronary syndromes. Arterial remodeling is also an important component of restenosis after coronary interventions. IVUS has suggested that interventions that reduce restenosis tend to have a greater impact on preventing negative remodeling (constriction) rather than reducing neointimal proliferation. Oxidant stress may be an important contributor to negative remodeling, as IVUS has demonstrated this anatomy at sites of coronary artery spasm. Positive remodeling seen by IVUS is also associated with impaired endothelial vasomotor dysfunction, and IVUS studies have demonstrated the contribution of vasomotor tone to arterial elasticity. Future directions include integrating IVUS with other imaging modalities, such as angiography, to study the interaction of anatomic and physiologic factors in atherosclerosis progression, and using the raw ultrasound signal to distinguish plaque components and differences in wall strain that may identify vulnerable plaques.     

Vascular brachytherapy: what have we learned from intravascular ultrasound?

With the advent of intravascular brachytherapy (IVBT), a striking reduction in the rate of restenosis has been observed. The use of intravascular ultrasound (IVUS) during IVBT trials has shown many aspects and relevant pathophysiologic mechanisms following this practical therapy. Specifically, IVUS quantitative assessments have demonstrated a drastic inhibition of both neointimal formation and negative remodeling to be the predominant vascular response to IVBT. Moreover, IVBT has shown promise for challenging high-risk restenosis cases, such as patients with diabetes mellitus and smaller caliber target vessels. However, unexpected radiation-induced complications have also been discovered, as more patients have been treated for a broad class of lesion subsets. Edge effect, induced by catheter-based radiation, was seen to be due to geographic miss of the radiation source, advocating a new concept known as "radiation edge". Furthermore, late thrombosis, which is known to be strongly associated with new stent implantation following IVBT, may be avoided with novel antiplatelet agents. Two additional complications, whose clinical significance remains unclear, are unhealed dissection and late stent malapposition featured by IVUS qualitative assessment. Unhealed dissection was observed in half of radiated dissections and late stent malapposition has been seen for all radiation sources in a small percentage of cases at 6-12 months follow-up. Radiation sources, dosimetry, and delivery methods continue to improve and should ultimately translate to more effective treatment for the patient with atherosclerotic coronary disease.     

Is intravascular ultrasound the gold standard surrogate for clinically relevant atherosclerosis progression?

Are progressive changes in intravascular ultrasound (IVUS)-derived indexes of plaque size sufficiently predictive of in-trial or future cardiovascular event risk that IVUS can serve as an efficient surrogate for clinical events in coronary disease trials? This question remains unanswered by clinical trials reported to date. Indeed, the answer may well be "yes." Nevertheless, there are enough concerns about the physical limitations, the fundamental assumptions, and the interpretation of the IVUS measurements that the answer cannot be taken for granted. Here, we review the evidence to date, discuss some of the concerns, and compare IVUS results with those of quantitative arteriography.     

The application of intravascular ultrasound on diagnosis and intervention of acute coronary syndromes

Objective To explore the application of intravascular ultrasound (IVUS) on diagnosis and intervention of acute coronary syndrom (ACS). Methods IVUS was performed in 41 patients with acute coronary syndrom and after coronary intervention (PLCA in 21 lesions,stent in 10 lesions).     

Using intravascular ultrasound with drug-eluting stents. What have we learned so far?

Drug-eluting stents (DES) promise to change the landscape of interventional cardiology, overcoming restenosis that is the major limitation of percutaneous coronary interventions. Intravascular ultrasound (IVUS) examination has been at the centre of our efforts to understand the mechanisms and define different treatment strategies during coronary interventions. IVUS interrogation and 3-dimensional IVUS measurements have been used to better define the mechanisms of benefit and potential drawbacks of DES. The findings of these studies are summarized in this article and the potential importance of IVUS in the era of DES is discussed. Evidence of neointimal hyperplasia (IH) suppression and assessment of any edge effect or vessel remodeling after implantation of DES has been evaluated by IVUS. The overall clinical importance of IVUS in the new era will depend on the amount and the clinical significance of any unsolved questions we will face and on its ability to provide answers to the evolving questions.     

Is chest tube insertion with ultrasound guidance safe in patients using clopidogrel?

Background and objective: Drainage of the pleural space is a common procedure. The safety of chest tube insertion in patients using clopidogrel has not been investigated. Methods: Ultrasound‐guided chest tube insertions performed on 24 patients who were being actively treated with clopidogrel were retrospectively reviewed. Results: No excessive bleeding occurred in any of these patients. Conclusions: Given the known effects of clopidogrel on platelet function, these results were interpreted as indicating that clopidogrel therapy is a relative but not an absolute contraindication to chest tube insertion, if an experienced operator places a small‐bore tube under ultrasound guidance.     

How does angioplasty work? Serial analysis of human iliac arteries using intravascular ultrasound.

BACKGROUND. Previous studies regarding the mechanism by which balloon angioplasty increases luminal patency have generally used animal models or postmortem specimens from occasional fatal cases of angioplasty performed in human patients. In either case, conclusions regarding participatory mechanisms have relied exclusively on nonserial, postangioplasty histopathological examination. METHODS AND RESULTS. In the present study, intravascular ultrasound examination was performed before and after balloon angioplasty in 40 consecutive patients with iliac artery stenoses. The areas of the arterial wall, plaque, lumen, and areas resulting from angioplasty-induced plaque fractures were measured immediately after angioplasty in vivo and compared with findings recorded immediately before angioplasty. Angioplasty increased luminal cross-sectional area (CSA) from 11.5 +/- 0.6 mm2 before angioplasty to 25.4 +/- 1.2 mm2 after angioplasty (p = 0.0001). CSA of the portion of the postangioplasty neolumen contained within angioplasty-induced plaque fractures measured 10.0 +/- 0.8 mm2; the neolumen excluding the area contributed by these plaque fractures measured 15.4 +/- 0.8 mm2. Thus, the area contained within plaque fractures accounted for 10.0 mm2 (71.9%) of the 13.9-mm2 increase in luminal CSA after angioplasty. Analysis of CSA occupied by atherosclerotic plaque disclosed that plaque CSA decreased from 33.8 +/- 1.8 mm2 before angioplasty to 22.5 +/- 1.5 mm2 after angioplasty (p = 0.0001). Plaque CSA was thus reduced ("compressed") by 11.3 +/- 1.1 mm2. Total artery CSA increased ("stretched") slightly from 45.3 +/- 2.6 mm2 before angioplasty to 47.8 +/- 2.0 mm2 after angioplasty (p = 0.0025). CONCLUSIONS. In vivo analysis of iliac stenoses by intravascular ultrasound immediately before and after angioplasty demonstrates that plaque fractures and "compression" of atherosclerotic plaque are the principal factors responsible for increased luminal patency resulting from balloon angioplasty. "Stretching" of the arterial wall provides an additional, but minor, contribution.     

Ten years after introduction of intravascular ultrasound in the catheterization laboratory: tool or toy?

Intravascular ultrasound (IVUS) represents the gold standard in the assessment of atherosclerotic disease. It has deeply affected our understanding of coronary artery disease and therapeutic strategies. We learned that a phenomenon described in pathologic series plays a very important role during life--that of vessel remodeling. The type of remodeling (positive or negative) cannot been assessed by angiography but is clinically relevant for optimal, procedural lumen gain. The modern stent implantation technique with a high balloon to artery ratio and high balloon pressure is the result of the IVUS finding that the majority of stents are not optimally deployed despite appropriate angiographic results. IVUS is essential in the clinical practice for the assessment of ambiguous angiography, left main stem disease, complex lesion and in-stent restenosis. Furthermore, IVUS has become an indispensable research tool in the analysis of new therapeutic strategies such as coronary brachytherapy.     

Does remodeling occur in the diseased human saphenous vein bypass grafts? An intravascular ultrasound study

Background: Coronary artery remodeling is a common phenomenon in human atherosclerotic arteries. Controversies exist concerning the presence of absence of the remodeling process in diseased human coronary saphenous vein bypass grafts. The purpose of the study was to observe the vessel and lumen dimensions in patients who had undergone saphenous vein grafting with intravascular ultrasound to find out whether the remodeling process exists in the diseased human saphenous vein bypass grafts. Methods: A total of 43 saphenous vein bypass grafts from 43 patients (39 males, 4 females, mean age 63 ± 8 years); 1–16 years (mean 9.3 ± 4.0 years) after grafting, who had not undergone previous catheter intervention, were studied using intravascular ultrasound. The vessel, lumen and plaque area were measured at the lesion segment as well as in the proximal and distal reference segments. The percent stenosis was calculated. Results: In 43 bypass grafts having severe stenosis before intervention, plaque was eccentric in 69.4% and concentric in 30.6%. No calcification was detected in 75% cases and 25% cases has mild-moderate intimal calcification. The vessel area in the lesion segment was 19.0 ± 9.7 mm², significantly larger than the proximal reference segment 12.8 ± 4.0 mm² as well as the distal reference segment 12.9 ± 3.6 mm² (p < 0.001). It was also larger than that of the average area of the proximal and distal reference segments (p < 0.001). The vessel area increased in accordance with plaque area (p < 0.001). A weak relationship existed between vessel area and percent stenosis (r = 0.37, p = 0.04). Conclusion: In contrary to previous findings, diseased human saphenous vein bypass grafts undergo focal compensatory enlargement (remodeling) in the presence of plaque formation. The underlying mechanism is probably similar to that in de novo atherosclerosis.     

Can ultrasound guidance reduce the risk of pneumothorax following thoracentesis?,

OBJECTIVE:

Thoracentesis is one of the bedside procedures most commonly associated with iatrogenic complications, particularly pneumothorax. Various risk factors for complications associated with thoracentesis have recently been identified, including an inexperienced operator; an inadequate or inexperienced support team; the lack of a standardized protocol; and the lack of ultrasound guidance. We sought to determine whether ultrasound-guided thoracentesis can reduce the risk of pneumothorax and improve outcomes (fewer procedures without fluid removal and greater volumes of fluid removed during the procedures). In our comparison of thoracentesis with and without ultrasound guidance, all procedures were performed by a team of expert pulmonologists, using the same standardized protocol in both conditions.

METHODS:

A total of 160 participants were randomly allocated to undergo thoracentesis with or without ultrasound guidance (n = 80 per group). The primary outcome was pneumothorax following thoracentesis. Secondary outcomes included the number of procedures without fluid removal and the volume of fluid drained during the procedure.

RESULTS:

Pneumothorax occurred in 1 of the 80 patients who underwent ultrasound-guided thoracentesis and in 10 of the 80 patients who underwent thoracentesis without ultrasound guidance, the difference being statistically significant (p = 0.009). Fluid was removed in 79 of the 80 procedures performed with ultrasound guidance and in 72 of the 80 procedures performed without it. The mean volume of fluid drained was larger during the former than during the latter (960 ± 500 mL vs. 770 ± 480 mL), the difference being statistically significant (p = 0.03).

CONCLUSIONS:

Ultrasound guidance increases the yield of thoracentesis and reduces the risk of post-procedure pneumothorax. (Chinese Clinical Trial Registry identifier: ChiCTR-TRC-12002174 [http://www.chictr.org/en/])     

Is routine ultrasound guidance really necessary for closure of patent foramen ovale using the Amplatzer PFO occluder?

Objectives:

The aim of the study was to evaluate safety, efficacy, and long‐term clinical outcome of percutaneous closure of patent foramen ovale (PFO closure) in a low volume center using the Amplatzer PFO occluder without echocardiographic guidance.

Background:

Most centers perform PFO closure either by transesophageal echocardiography (TEE) or intracardiac echocardiography (ICE) guidance for optimal device selection. As TEE is poorly tolerated by patients in supine position and ICE is a costly alternative that increases vascular access complications, we wanted to assess the safety and efficacy of PFO closure by fluoroscopic guidance only.

Methods:

Before PFO closure, all patients had a diagnostic contrast‐TEE and morphological classification of PFO. All PFO closures were performed using the 25‐mm Amplatzer PFO occluder with fluoroscopic guidance only. Intraprocedural echocardiography was replaced by right atrial opacification using contrast angiography. Contrast TEE was done after 6 weeks, contrast TTE after 3, 6, and 12 months postprocedural.

Results:

In all 92 patients (52.4 ± 1.5 years), a 25‐mm Amplatzer PFO occluder was implanted in the correct position. Total fluoroscopic time was 8.4 ± 0.6 minutes and the application of contrast medium was 122.5 ± 5.8 mL. By contrast‐TEE, 12 patients (13 %) showed a small residual shunt (grade 1). During follow‐up (2.09 ± 0.13 years) two patients (2.1%) suffered from a recurrent event (TIA in both cases).

Conclusions:

Percutaneous closure of PFO using the 25‐mm Amplatzer PFO occluder guided by fluoroscopy only is a safe and efficacious intervention for nearly all patients. © 2009 Wiley‐Liss, Inc.     

Does the specific intravascular ultrasound criterion used to optimize stent expansion have an impact on the probability of stent restenosis?

Intravascular ultrasound (IVUS) imaging has been used to optimize stent implantation in coronary arteries, but the criteria used were chosen on an empiric basis. The aim of this study was to determine whether any of these criteria have an independent role in predicting the probability of freedom from restenosis. The study population consisted of 425 patients (496 lesions) who underwent angiographically successful IVUS-guided stenting. Five IVUS criteria were studied: (1) intrastent minimal lumen cross-sectional area (ISMLCSA) > or =9 mm2; (2) ISMLCSA (> or =9 mm2 and > or =80% of average reference lumen cross-sectional area [CSA]); (3) ISMLCSA > or =90% of average reference lumen CSA; (4) ISMLCSA > or =90% of distal reference lumen CSA; and (5) ISMLCSA > or =55% of average reference vessel CSA. These criteria were met in 33%, 29%, 68%, 82%, and 69% of lesions, respectively. Angiographic follow-up was performed in 335 of 421 eligible patients (80%) at 5.3 +/- 2.7 months. An absolute ISMLCSA > or =9 mm2 was associated with the lowest restenosis, but this criterion was primarily achieved in large vessels. The only criterion that was associated with higher probability of freedom from restenosis independently from vessel size was an ISMLCSA > or =55% of average reference vessel CSA. Therefore, when IVUS is used to guide stent implantation an effort should be made to achieve the largest lumen safely possible. An ISMLCSA > or =55% of the average reference vessel CSA seems to be the most appropriate criterion in terms of frequency of achievement and in terms of increasing the probability of freedom from restenosis.