Archive for month: August, 2020

Cardiovascular disease is the most frequent cause of mortality globally, with cancer the second most frequent cause: CVD accounts for over 30percent, and cancer around 17percent, of deaths worldwide. In the more affluent western countries, because of the enormous improvements in diagnosis and management of CVD, cancer has overtaken CVD as the leading cause of death. However as populations age the two conditions frequently coexist. Of course many of the modifiable risk factors are shared, but CVD is also a known complication of cancer therapy and recent robust population studies have shown that patients with some forms of CVD have an increased risk of cancer.
Most of the modifiable risk factors for both conditions are well known, and include tobacco smoking, physical inactivity, unhealthy dietary habits and obesity. There are also well established risk factors for CVD that recent studies suggest may also be risk factors for cancer, such as Type 2 diabetes, and hypertension and hyperlipidaemia, both prevalent in cancer survivors. Alcohol consumption, a known risk factor for cancers including those of the alimentary tract, liver and breast, is also a risk factor for CVD (unless consumption is light, which is still considered protective against CVD).
As the number of patients surviving cancer continues to increase, more and more data are available demonstrating that the risk of morbidity and mortality from CVD in these individuals is greater than in subjects without a history of cancer. For instance, a robust analysis involving over a million female survivors of breast cancer compared with control women who had not had cancer reported that the risk of CVD mortality was significantly lower in the control group. Cancer itself can cause local and systemic cardiovascular conditions such as effusions and arrhythmias, and in addition many of the drugs and drug combinations used in cancer chemotherapy can be cardiotoxic, such as anthracyclines, trastuzumab and most of the approved tyrosine kinase inhibitors. Radiation therapy can affect the pericardium, valves and myocardium long term.
Recently a Danish group of over 9000 cancer-free chronic heart failure (HF) patients were compared over time with the general Danish population and a significantly increased risk of cancer was demonstrated in the HF group. Over a thousand US cancer-free survivors of myocardial infarction followed by HF were also shown to have a significantly higher risk of developing cancer compared with patients who did not have HF.
It is surely prudent that all healthcare providers as well as CVD and cancer patients are informed about this bidirectional relationship.

Although not commonplace, carotid artery stenting (CAS) is occasionally accompanied by the protrusion of plaque into the stent lumen, and a variety of ischemic complications during intra- and post-operative periods. Among these complications, plaque protrusion (PP) into the stent and thrombus on the stent after CAS are some of the most worrying for clinicians.
The correction of PP is achieved by additional post-dilations or stent-in-stent implantation.

First noticed in mid-1990s
The first observations of PP date over two decades and provided the impetus for embolic protection devices. In a paper published in the mid-1990s, a team led by Frank Veith, M.D (from the Mayo Clinic) suggested that restoration of flow and removal of protection devices might lead to the continuing break off of protrusions and provoke some delayed strokes.
Today, apart from PP, key causes of late in-stent stenosis seen in CAS include neo-intimal proliferation due to self-expanding stents as well as restricted post-procedural stent dimensions from inefficient balloon dilation.

The covered stent
One way to prevent PP is by covering the plaque with a stent graft. Covered stents also offer advantage in usability, without the need for distal protection devices in difficult internal carotid arteries, where a protection filter may be near-impossible to place. However, covered stents are accompanied by a high rate of restenosis. In one randomized trial in the mid-2000s, researchers at Vienna Medical University reported a 38% restenosis rate in patients treated with covered stents for carotid artery stenosis, while restenosis was absent in the bare stent group. The precise causes of high restenosis rates with stent grafts require further research. One suspected factor is the buckling of a covered stent’s proximal and distal ends and the prevention of endothelization.

Both symptomatic and asymptomatic events
During stent implantation, plaque disruption and distal migration of plaque particles may cause symptomatic or asymptomatic ischemic events, in spite of protection devices. These can be viewed on diffusion-weighted (DW) magnetic resonance imaging (MRI).
In some CAS cases, physicians encounter plaque particles filling filters leading to symptomatic cerebral embolism. This is particularly true with ulcerated plaque and severe stenosis.  What is now of growing concern is that, after stent implantation, plaque protrusion into the lumen can lead to peri-procedural stent thrombosis, 30-day stroke, and late in-stent stenosis.

Stroke biggest complication
The biggest complication with carotid artery stenting is stroke. This can occur during CAS and for up to 30 days after the procedure. Although the cause of late stroke after CAS remains unknown, PP is generally suspected to be a key cause.
PP incidence is evaluated by IVUS (intra-venous ultrasound) and angiography, although as we shall see, there are variations in results based on methodology. The prognosis of PP (over a 30-day period) and the incidence of ischemic lesions (48 hours after CAS) are usually assessed by diffusion-weighted images.

The Tokai study
In recent years, one oft-cited report concerns a study by the Department of Cardiology at Tokai University School of Medicine (Isehara). The findings were published in October 2014 by the ‘Journal of Stroke and Cerebrovascular Disorders’. During their study, the Tokai researchers evaluated 77 CAS procedures, which were performed consecutively with IVUS between May 2008 and December 2012. All cases were distally protected with filter devices. The rate of PP was assessed at the end of each procedure using IVUS and angiography.
Six plaque protrusions (7.8%) through the stent struts were detected by IVUS but only two (2.6%) by angiography. One of the major predictors of PP was pre-procedural severe stenosis with flow delay.   Overall stroke rate was 2.6% (major 0%, minor 2.6%), and these occurred in the catheterization laboratory. However, no late stroke was observed at 30 days after procedure.
One of the key outcomes of the Tokai study was that IVUS seems to detect plaque protrusion better than angiography. Since the adequate management of plaque protrusion is considered as a means to reduce stroke complications, IVUS usage is worth considering.

The Yao-Nara study
In 2017, results of another, broader Japanese effort by researchers at Ishinkai Yao General Hospital (Yao) and Nara Medical University (Nara) suggested different conclusions. The study, which was published in the April 17 issue of ‘JACC: Cardiovascular Interventions’, sought to clarify the frequency and prognosis of plaque protrusions in CAS by analysing data on 328 patients treated under IVUS guidance in the period 2007-2016, using different types of stents and embolic protection devices.
At 30 days, the rate of ipsilateral ischemic stroke was 2.8% and the rate of transient ischemic attack was 2.6%. There were no patient deaths. Moreover, in most stroke cases, symptoms were observed immediately after dilatation.  New ischemic lesions were found in 35.7% of patients within 48 hours of the procedure, based on diffusion-weighted imaging (DWI).

Lack in lesion variation, but stent type matters, as does evaluation method
One of the most intriguing conclusions was the lack of difference in the incidence of new ischemic lesions, in terms of stable versus unstable plaques. Analysis by stent type, however, did indicate difference. There were more ipsilateral ischemic lesions with open-cell stents as compared to closed-cell stents.
The authors suggest the findings indicate a necessity to minimize PP “to prevent periprocedural ischemic stroke” and that the placement of open-cell stents with high radial force may disintegrate unstable plaque, causing protrusions. One strategy mentioned by the authors to manage PP is to perform IVUS to check for large-volume protrusions. The latter are then sought to be differentiated as being either ‘convex’ or ‘non-convex’. For the former, stent-in-stent placement is performed using closed-cell stents until the disappearance of the protrusion. In the case of ‘nonconvex’ protrusions, the authors recommend 5-10 minutes of observation, followed again by stent-in-stent placement should the protrusion enlarge, or clinical follow-up within 30 days after CAS in case of no enlargement.

As we observed previously, there are differences in PP incidence based on whether it is evaluated by angiography or IVUS. One of the most significant limitations of the Japanese study above was the occurrence of 27 cases of plaque protrusion on IVUS, but just nine cases on angiography. The study protocol required confirmation by both modalities.

Limitations to Yao-Nara study
In an editorial accompanying the study, William A. Gray, MD (Lankenau Heart Institute, Wynnewood, PA), cautioned that this two thirds difference “will clearly affect many of the subsequent associations and conclusions.” Gray also underlined that by treating plaque protrusion with stent-in-stent placement in approximately half of the cases, the researchers might have potentially changed the clinical and imaging outcomes. Furthermore, he cautioned, the study was not core-lab controlled, with no routine use of MRI before and after procedures, and that the assessors were not blinded. Finally, they did not mandate use of specific stents or perform independent neurological assessment of clinical outcomes.
As a result, the association between stent type and plaque protrusion is ‘likely’. However, it may not be as strong as the authors contend.

Such shortcomings are likely to be addressed when the Japanese effort is paired with emerging data showing reductions in both plaque protrusion and ischemic lesions via the use of mesh-covered stents. Gray agrees that this is strengthening the case for “improvements in stent design.” Indeed, emerging micromesh stent designs are expected to contribute greatly to prevention of plaque protrusion and may become a new standard for CAS.

SCAFFOLD trial
In the United States, the SCAFFOLD trial, led by Peter A. Schneider, MD, of Kaiser Foundation Hospital at Honolulu (Hawaii) is completing evaluation of a mesh-covered, open-cell heparin coated stent in patients at high surgical risk. The objectives are to make the first 30 days safer, with the understanding that reduced cell size equates to less plaque prolapse and fewer delayed events.
Other similar trials using different mesh technologies are also under way, and more are imminent. In Italy, for instance, University of Roma La Sapienza has begun a positive-control study to analyze and compare the rate of off-table subclinical neurological events in two groups of patients submitted to CAS with a close-cell stent, and a new mesh-covered carotid stent called C-Guard.
Overall, new parameters are coming into place, via stents with differences in pore size, flexibility etc. The drivers for such efforts range from new materials to a broad range of cardiovascular conditions. In France, for example, University Hospital Grenoble is conducting trials with Mguard, a stainless-steel closed cell stent covered with an ultra-thin polymer mesh sleeve, to prevent distal embolization during percutaneous coronary intervention in ST-segment-elevation myocardial infarction.

Case selection and stenting success
One of the observations of SCAFFOLD was that case selection for stenting was a key “to good clinical results.”
So far, patient selection criteria for CAS is largely based on surgical risk related to other co-morbidities. The morphology of the atherosclerotic plaque is given little attention, although studies have demonstrated the existence of extensive variability, which in turn confers specific risks for plaque vulnerability. Overall, the detection of unstable plaque on MR plaque imaging and the use of open cell stent are considered to be significant predictive factors of PP.

In recent years, there have been growing calls for devising best practices in peri-procedural management and follow-up, and for continuous feedback from clinicians to industry to improve stent design.
In general, achieving better outcomes of CAS is seen as the best method to solidify its place as a frontline treatment of carotid vascular disease. 

One promising approach for patient selection and identification of plaque, has been the use of virtual histology intravascular ultrasound imaging (VH IVUS). Researchers have suggested a strong correlation between VH IVUS plaque characterization and the true histological examination of plaque following endarterectomy, especially in ‘vulnerable’ plaque types.
The results of one of the earliest efforts in this area were published in October 2007 in ‘The Journal of Endovascular Therapy’. This followed a prospective, two-arm study by the Arizona Heart Hospital & Translational Research Center. The researchers enrolled 30 patients.
In the first arm of the study, 15 patients underwent VH IVUS examination of carotid plaque with a cerebral protection device. This was immediately followed by carotid endarterectomy (CEA), and the comparison of ‘virtual’ with true histology (classifying plaque type by VH IVUS and histopathology in a blinded study).
In the second arm, 15 patients undergoing CAS had a preliminary VH IVUS scan performed with cerebral protection. Debris collected from the filter following stenting was examined histologically and compared with the VH IVUS data.
The diagnostic accuracy of VH IVUS to agree with true histology in different carotid plaque types was 99.4% in thin-cap fibroatheroma, 96.1% for calcified thin-cap fibroatheroma, 85.9% in fibroatheroma, 85.5% for fibrocalcific, 83.4% in pathological intimal thickening, and 72.4% for calcified fibroatheroma.

The march of healthcare technology is not always even. Benefits on one front can often be outweighed by problems on another. Radiology is no exception to this rule.
Like other medical professionals, radiologists have begun using portals and social media to connect to patients and join the move towards personal healthcare.

Websites and radiology
Today, websites staffed by imaging professionals seek to directly address the public about radiology. Such a trend is especially pronounced in the US. Examples include radiology Q&A portals at the University of Texas’ John P. and Kathrine G. McGovern Medical School, Northwest Radiology Consultants in Atlanta, Georgia, and a host of others. One of the best known is the RSNA/ACR public information website, RadiologyInfo.org, which offers a library of resources for patients including information on how various imaging procedures are performed. In Europe, the ESR has a Website page dedicated to ‘Radiation and Patients’ and an ‘Ask EuroSafe Imaging’ Q&A page, split into three sections (CT, interventional radiology and pediatric imaging), with answers provided by radiologists from across the continent.

Radiologists and social media
Radiologists have also sought to use social media to build and continuously strengthen interactive relationships with patients outside a formal hospital or physician office setting. Such approaches have spilt over into tackling concerns after widespread reports in the media about the ‘over-use’ of medical radiation. In the US, for example, the Health Physics Society has a site dedicated largely to addressing such risk perceptions in the general public. The UK too has seen such a step with the British Institute of Radiology and the Institute of Physics and Engineering in Medicine endorsing Ask for Evidence, as part of which a panel of radiologists and medical physicists respond to questions from the public on radiation safety.

Technology versus patient downtime
These are clearly significant and laudable developments. Informed patients are increasingly regarded to be better patients by several physicians. However, other recent developments in technology, above all electronic medical/health records (EMR/EHR), are placing a growing burden on clinicians to update medical documentation, in order to facilitate real-time sharing and reduce errors. This results in less time for patient care.  A key driver here, in the US, consists of federal government meaningful use (MU) requirements, which provides physicians with financial incentives to use EHRs.
For radiologists, these incentives are hardly negligible and range from 44,000 to 63,750 dollars (39,000 to 56,735 Euros) over a 5-or 6-year period via Medicare and Medicaid, respectively.
On the other hand, MU also requires 10% of patients viewing, downloading or transmitting their electronic health information, with over 40% of all imaging scans to be made accessible via certified EHR technology.
The above requirements are hardly a testimonial to efficiency. One study on MU published by the Radiological Society of North America (RSNA) in 2012 found that medical residents reported having to spend the bulk of their time updating charts and documentation, and that EHR adoption correlated directly to reduced time for direct patient care.

Radiology strives to remain at technology cutting edge
This is a profound challenge. Radiology has traditionally been the medical speciality at the cutting edge of technical advancement. It was radiology which first moved away from paper to digital technology. As a result, radiologists and industry are currently seeking to fast track solutions for increasing patient downtime and improving workflow.

Data use
In the first stage, the focus was on enhancing use of available data. Ironically, illustrating the unevenness and asynchronicity in the progress of technology, efforts were concentrated on getting more usable data out of electronic records, which did not always trickle down to radiologists. One reason was the lack of skills. Referring physicians often left responsibility to get approval for imaging to office staff, many of of who lacked the clinical knowledge required to seek such approval.

Automation: From CPOE to CDS
Soon after, the effort shifted to automation, especially in the shape of decision support (and so-called assistant clinical reasoning) tools. Such a process continues, with evolution from static to dynamic, patient-centred tools. A good example of this is the computerized order entry (CPOE) system. In 2012, a study in the ‘Journal of the American College of Radiology’ proved the clinical viability of combining radiology CPOE with imaging decision support, including pathways and algorithms, as well as classification for actionable findings.
One of the longest-used clinical decision support systems is ACR Assist from the American College of Radiology, which is designed to blend in seamlessly with radiology workflow. Clinical data is encoded in vendor-neutral ways, in order to quickly build commercial applications. The ACR has since created guidelines for radiologists and referring physicians to proceed after clinical findings. Others are also stepping in with new initiatives to enhance automation and decision support. Massachusetts General Hospital, for example, has developed Procedure Order Entry (PrOE), a surgical appropriateness system to help identify whether a procedure is necessary, and the implications of this for radiology are under active investigation. By utilizing evidence-based guidelines rather than have a less-informed entity authorize diagnostic imaging, CPOE in radiology not only enhances efficiency, but also the quality of care.

IPads and speed
One unexpected finding cited in the 2012 RSNA study on meaningful use was that residents using iPads were able to enter and update data more rapidly. Indeed, a majority of those surveyed found that iPads led to significant increases in work efficiency.
This was an opportune moment, given that a year previously, the US Food and Drug Administration had cleared the first mobile app to allow physicians to make diagnoses using iPads or iPhones.
Currently, radiology imaging applications for mobile platforms allow remote monitoring and control for a PACS administrator. Fuelled by standard tools such as DICOM viewers, these impact directly on quality control, data management and workflow efficiency.

The implications of teleradiology connectivity are especially dramatic in emergency settings. About five years ago, Mayo Clinic physicians deployed smartphones in order to assess their utility in a telemedicine stroke-management network which connected radiologists to neurologists and emergency physicians at a remote facility. The findings were encouraging, with over 90% of agreement on the key radiological findings. In the future, smartphone-based teleradiology systems are likely to become commonplace among first responders.

Image management and automation
Image management is also being used as a means to automate processes. The fast growth of technology has also necessitated unprecedented collaborations between specialists. Oncologists, for example, have been working with radiologists to analyse datasets for tumour detection and monitoring, and some studies report sharp reduction in the time required to study suspicious tissue.
On its part, Massachusetts General has also developed QPID (Queriable Patient Interface Dossier) to integrate electronic records and streamline providers’ abilities to access details in a patient’s medical history.
Other areas for attention include voice-enabled documentation, accompanied by structured reporting and data sets that pre-populate a radiology report. These not only reduce human error when inputting data but also enables radiologists to interpret and diagnose a study when a referring physician is most in need of the information – while meeting a patient.

From automation to deep machine learning
The greatest benefit of automation is to maximize the use of available data. This enhances the  ability to provide not just personal but precision medicine, too. When interfaced to an appropriate radiology-focused IT platform, individual radiologists and the broader radiology (as well as clinical) community will be empowered to benefit from feedback loops that reinforce positive lessons, de-emphasize negative ones and continuously build appropriateness and best-practice guidelines. Based on the templated information in a report, colleagues (real and virtual) would be able to rapidly offer second opinions and perspectives on how to best serve a specific patient-case.
Further down the road are deep machine learning tools which will provide sophisticated, structured and in-depth data on a patient, to enable increasingly informed decisions in the context of specific and individual challenges – influenced by factors ranging from pharmacogenomics to disease staging, age and lifestyle. Such knowledge, which would create highly actionable reports, are expected to dramatically impact upon patient outcomes.

Radiology and public perception
It is no secret that professional radiological societies strongly believe there is a need to improve patient (and public) perception of the role played by radiologists in healthcare, and that this necessitates closer contact with patients. Patients after all seldom choose a radiologist. This choice is made by a referring physician or health plan.
Though radiology is essential to patient care, radiological services often seem inconvenient, a threat to privacy, sometimes mysterious and scary. The connect between a radiologist and patient is intermediated by nurses and assistants (e.g. for injecting contrast material or preparing them for the imaging procedure), or by technologists seen as managers of machines. Various studies have shown that radiologists are not always present during performance of a study and seldom introduce themselves to a patient.
As a result, patients increasingly consider radiologists to be supervisors of a technological process. The clinician requesting the examination and receiving the radiology report is considered to be the one interpreting the study and making the decision.

Patient at the core
To sum up, the core value proposition in transforming and keeping radiology up to date involves the patient. Although the growing digitization of healthcare pushes radiologists away from patients, there is a need to make these interactions more prominent. Some radiologists warn that otherwise, there is a risk of their services becoming commoditized. For such a process, there is clearly a need to draw more patient data into decision-making.  One of the most ambitious efforts on this count was launched at the turn of the decade by RSNA, with funding from the National Institute of Biomedical Imaging and Bioengineering. The project, which promotes patient access to self-management tools, is known as Image Share, and consists of a secure network based on open-standards architecture. Images are exchanged between servers at radiology departments and imaging centres via the Cloud. A two-year pilot began in 2011 at Mount Sinai Medical Center in New York, followed by university hospitals in several states. In 2016, RSNA introduced a validation programme for the project, to test vendor system compliance with standards for exchange of medical images. To date, results have been satisfying.

Although initiatives like this will continue to grow in importance, they are unlikely to do more than enhance the efficiency of radiologists – and their professional judgement – in improving patient care.