Subsequent invasive angiography was less likely to show normal coronary arteries in patients diagnosed with coronary CT angiography results in lieu of stress testing data (0.96% versus 2.70% with stress testing, hazard ratio 0.39, 95% confidence interval 0.23-0.68). This group was also more likely to have confirmed obstructive coronary artery disease (CAD, 13.65% versus 11.10%, HR 1.29, 95% CI 1.08-1.55).

In addition, coronary CT angiography led to more use of preventive therapies (13.65% versus 3.57%, HR 4.03, 95% CI 3.12-5.20), David E. Newby, MD, of University of Edinburgh in the U.K., and colleagues reported online in the Journal of the American College of Cardiology.

Following-up 50 days after imaging, which was the median time for starting preventive drugs, the myocardial infarction rate in coronary CT angiography patients was half that seen in the control group (0.82% versus 1.64%, HR 0.50, 95% CI 0.28-0.88).

“We believe this reduction in events is consistent with the anticipated effect size attributable to initiation of preventive therapies together with potential benefits from lifestyle modification and coronary revascularization,” Newby and colleagues wrote.

“This suggests better use of invasive angiography, especially as the rate of coronary revascularization was high in those for whom coronary CT angiography had changed the initial diagnosis and suggested the presence of obstructive disease,” they wrote.

James K. Min, MD, of Weill Cornell Medical College in New York, and colleagues deemed the SCOT-HEART results the “highest-quality evidence to date for the comparative benefit of coronary CT angiography over standard-of-care approaches.”

“Not only may coronary CT angiography be considered a reasonable alternative to stress testing for initial diagnostic CAD evaluation, but it may actually be preferred,” they wrote in an accompanying editorial.

Coronary CT angiography now offers non-invasive fractional flow reserve measurements and thus may become “the oft-discussed ‘one-stop shop’ of coronary evaluation,” according to Min and colleagues.

Newby’s group concluded that “given the potentially greater hazards and costs of invasive angiography, our findings indicate that coronary CT angiography is as an effective and readily applicable gatekeeper for the conduct of invasive coronary angiography.”

The SCOT-HEART substudy included 4,146 patients who were randomized to receive standard care with or without coronary CT angiography.

Cumulative costs were higher in the CT group, with a mean difference of $462 at 6 months. The added expenses were directly attributable to the cost of coronary CT angiography itself, the investigators suggested, as downstream costs were the same between groups.

Min’s group noted that the earlier PROMISE trial had failed to show superiority for coronary CT angiography. That, they suggested, was due to “a follow-up period too short to enable realization of the salutary effects of preventive therapy, particularly in the trial’s population with a low prevalence of CAD.”

They argued that there is a gradient to CAD, which gives CT angiography an edge over stress testing.

“The ability to identify, quantify, and characterize atherosclerosis may be a distinguishing feature of coronary CT angiography that allows transcending beyond traditional lumen-based CAD assessments,” the editorialists wrote.

Newby and colleagues acknowledged that they were limited to a modest number of events in their study group of over 4,000 patients. “The majority of subjects had no or minimal CAD and therefore were not at risk,” they wrote, adding that longer-term study is underway to accrue more analyzable events.

Regardless, they concluded that “in patients with suspected angina due to coronary heart disease, coronary CT angiography leads to more appropriate use of invasive angiography and alterations in preventative therapies that were associated with a halving of fatal and non-fatal myocardial infarction.”

The Massachusetts General Hospital Neuroradiology Division employed an experience and evidence based approach to develop a neuroimaging algorithm to best select patients with severe ischemic strokes caused by anterior circulation occlusions (ACOs) for intravenous tissue plasminogen activator and endovascular treatment.

Methods found to be of value included the National Institutes of Health Stroke Scale (NIHSS), non-contrast CT, CT angiography (CTA) and diffusion MRI. Perfusion imaging by CT and MRI were found to be unnecessary for safe and effective triage of patients with severe ACOs. An algorithm was adopted that includes: non-contrast CT to identify hemorrhage and large hypodensity followed by CTA to identify the ACO; diffusion MRI to estimate the core infarct; and NIHSS in conjunction with diffusion data to estimate the clinical penumbra.

Read full article: The Massachusetts General Hospital acute stroke imaging algorithm (PDF)

• Superior reduction of ischemic and hemorrhagic stroke vs warfarin
• Similar rate of major bleeds^‡ with PRADAXA vs warfarin
• PRADAXA is the ONLY anticoagulant to demonstrate superior reduction of ischemic stroke vs warfarin
• PRADAXA also demonstrated a lower rate of intracranial bleeding vs warfarin

Additional 35% risk reduction of stroke/systemic embolism vs warfarin. Protect the brain by reducing the risk of ischemic stroke.

Learn more at pradaxapro.com

In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-totreat analysis. Treatment differences were assessed with the use of a Cox proportional- hazards model, with study center as a random effect.

Stroke occurred in 8.2% of patients in the clopidogrel–aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel–aspirin group and in eight (0.3%) in the aspirin group (P = 0.73); the rate of hemorrhagic stroke was 0.3% in each group.

Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage.

Original Article

Stroke is a major cause of death and disability worldwide, and the third or fourth most common cause of death in the USA.^[1] Therefore, stroke is an extremely common and potentially devastating disease. Acute recognition is critical to timely therapeutic intervention, which has evolved over time due to research including intravenous recombinant tissue plasminogen activator for ischemic stroke.^[2] However, the management of the stroke patient after the initial few hours and over the next few days – including blood pressure management, development of raised intracranial pressure (ICP) and management of seizures, fever and medical complications – are critical to patient outcomes.^[3] The evolution of bedside intensive care unit (ICU) techniques to monitor unstable brain tissue has developed in parallel to the ongoing research in acute stroke therapeutics.^[4] For example, the avoidance of hypoglycemia or hypotension after acute ischemic stroke might improve patient outcomes.^[5] However, after acute stroke, long-term hypertension control is important to preventing secondary stroke.^[6,7] Prevention and treatment of fever after stroke can also potentially improve outcome.^[5] This article briefly describes standard ICU bedside stroke monitoring techniques and expands upon them with newer ICU stroke monitoring techniques.

Perhaps one of the oldest methods of monitoring the acute stroke patient is the measurement of ICP. Since cerebral perfusion pressure (CPP) = mean arterial pressure – ICP, the measurement and management of ICP has profound cerebral physiology management implications.^[8] Without detection of raised ICP, CPP will be compromised and can cause secondary focal or global ischemia. The Monroe–Kellie hypothesis explains how three volumes of brain, blood and cerebrospinal fluid relate to intracranial pressure–volume relationship. The adult skull contains a finite volume, as compared with pediatric populations (<2 years of age), which contain a soft, expansive fontanel. Since the skull is a closed intracranial vault in adults, an increased ‘total’ intracranial volume such as adding a hematoma must be reciprocally compensated by a decrease in cerebral blood volume (e.g., more venous outflow) or decreased cerebrospinal fluid volume in order to maintain normal ICP and preserve CPP. When intracranial compensatory mechanisms can no longer accommodate additional increases in intracranial volume, ICP rises precipitously and CPP trends towards 0. Normal ICP values are defined as <20 mmHg.^[9–14] CPP in a normal ‘autoregulated’ state varies across a range of mean arterial pressure values to maintain a constant cerebral blood flow (CBF) (Figure 1). Injury to brain tissue results in disturbed pressure autoregulation, meaning CBF becomes linearly dependent upon CPP. Therefore, ICP monitoring is often necessary to first measure ICP, and secondarily calculate CPP. CBF can be assumed but not directly measured from ICP alone, which is problematic, especially if it is not known whether autoregulation is present or absent. However, newer complex ‘multimodal monitoring’ (MMM) computers can calculate via a Pearson moving correlation coefficient method,^[9] whether pressure autoregulation is present or absent, which adds value to the bedside management of critical patients.

External ventricular drain (EVD) is perhaps one of the most common methods to invasively measure ICP via an intraventricular catheter, which allows for diagnosis and treatment of raised ICP. Ventricular ICP measurement is considered a ‘gold-standard’ means for assessing elevations in global ICP,^[4,11] but it is invasive. EVDs also carry the risk of CNS infection such as meningitis/ventriculitis, like any other invasive brain probe, as well as risk of brain hemorrhage with EVD placement within the parenchyma. Antibiotic and silver-coated catheters are now in clinical use and may reduce the risk of infection.

Over the last 100 years, an ever-increasing number of ICU bedside monitoring techniques have been discovered and researched to aid the stroke patient. Newer and noninvasive methods are emerging such as NIRS, nICP and MMM computer help provide a ‘unified’ graphical display to help manage complex physiological relationships. Such MMM ability, while it remains mostly at advanced or academic neuroscience ICUs across the world, may prove in future research to derive specific physiological parameters for intervention, similar to directed therapy targets in sepsis.

Key Issues

• Stroke is a devastating disease, ranking fourth among leading causes of death in the USA, and is a global disease with similar mortality and morbidity.
• Management of blood pressure, intracranial pressure, fever and seizures in critical care patients after the onset of a stroke is vital to patient outcomes.
• The recent advancements in neuromonitoring and interventional therapy have been linked to an overall decrease in the rates of morbidity and mortality among patients suffering from stroke-related illnesses.
• Monitoring of intracranial pressure (ICP) has profound implications to the status of a patient’s cerebral autoregulation, and the direction of necessary neurotherapeutics.
• Understanding the mixed venous O₂saturation provided by jugular venous oxygen saturation and near-infrared spectroscopy (NIRS) offers insights into the ‘supply and demand’ physiology of the injured brain, and may help detect previously undiagnosed ‘cerebral desaturations’ and secondary ischemia.
• Currently, invasive methods of ICP measurement such as the external ventricular drain are seen as the gold standard for assessing elevations in ICP, but may place the patient at risk of infection, especially with prolonged monitoring.
• Noninvasive monitoring devices such as EEG, transcranial Doppler and NIRS provide alternative methods for indirectly measuring cerebral metabolic function without the risks of invasive probes and devices (e.g., Licox^TM).
• Newer modalities such as NIRS and cerebral Hemedex^TM require validation against gold-standard methods of brain oxygenation and blood flow, respectively, before they receive widespread implementation.

Full Article at Medscape Neurology

These guidelines were put together by an expert panel and touch on many aspects of acute stroke care, with a focus on ischemic stroke. The guidelines include dozens of recommendations. I am not going to talk about all of them today, but I would like to highlight some that are particularly important to treating clinicians.

First, the guidelines come out very strongly in favor of transporting patients with acute stroke to the nearest primary or comprehensive stroke center. This is a great idea because we know from numerous studies and analyses that care at these certified stroke centers really does make a difference in terms of improving outcomes and reducing complications. That is a very strong positive recommendation. In addition, the guidelines now say that these stroke centers should be certified by an independent body or agency, so we are moving away from the paradigm of self-certification [toward independent, objective certification], which is also a positive move.

Next is a curious recommendation about patients with intracranial stenosis: If you want to confirm that someone has an intracranial stenosis, the guidelines now recommend catheter angiography rather than noninvasive studies such as CTA (computerized tomographic angiography) or MRA (magnetic resonance angiography). That is curious, because I think a lot of folks have moved away from doing catheter angiography, but in these recommendations they really come down in favor of doing a catheter angiogram to confirm an intracranial stenosis. We will have to see where that goes in terms of altering routine care.

As you might imagine, a fairly extensive section [is dedicated to] using IV tPA (tissue plasminogen activator), and the recommendations come down very strongly in favor of a door-to-needle time of 60 minutes, which is emerging as a national quality metric by the National Quality Forum. This is a good timeframe to aim for, although, again, in a clinical context I think we have all had the experience or occasion when we do have to delay giving the IV tPA as we try to get more clinical information. I think we need to have some flexibility here. The new guidelines do recommend treatment up to the 4.5-hour time window, with exclusion criteria in terms of age, oral anticoagulation, diabetes, and stroke, similar to [the criteria in] the ECASS 3 study. What is curious is that if you talk to our stroke colleagues in Europe who actually conducted ECASS 3, they do not follow their own exclusion criteria. They treat everybody [with IV tPA] up to 4.5 hours except those who have had a massive stroke with significant early changes. Our new guidelines, the 2013 guidelines, do have the ECASS 3 exclusion criteria similar to what the scientific statement said several years ago. However, these new guidelines now say that it is reasonable to treat people with mild strokes, or improving symptoms, if the benefits outweigh the risks. They also say that it may be reasonable to treat patients even if they had surgery within the past 3 months, assuming that there is no active bleeding and the benefits outweigh the risks.

Finally, on the vexing issue of using IV tPA in patients taking [one of the] new oral anticoagulants, the guidelines say do not treat these patients with IV tPA unless you are sure that their clotting studies are normal or you are certain that they have not taken any of these oral anticoagulants for the past 2 days.

Dr. Mark Alberts is a Vice-Chair of Clinical Affairs in the Department of Neurology at University of Texas Southwestern Medical Center in Dallas.

“The findings of this study suggest that the blood pressure lowering and lipid effects of plain dark chocolate could represent an effective and cost effective strategy for the prevention of cardiovascular disease in people with metabolic syndrome (and no diabetes),” the researchers, with senior author Christopher M. Reid, PhD, CCRE Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, The Alfred Centre, Melbourne, Victoria, Australia, conclude.

“Chocolate benefits from being by and large a pleasant and, hence sustainable, treatment option,” they write. “Evidence to date suggests that the chocolate would need to be dark and of at least 60-70% cocoa, or formulated to be enriched with polyphenols.”

Dark chocolate, derived from coca beans, is rich in polyphenols, specifically flavonoids that exhibit antihypertensive, anti-inflammatory, antithrombotic, and metabolic effects, all of which may contribute to cardio-protection.

Long-Term Effects

Previous studies have shown that dark chocolate consumption may lower blood pressure, but they have been relatively short, only up to a maximum of 18 weeks. Studies have also shown that dark chocolate may decrease total and low-density lipoprotein cholesterol and increase high-density lipoprotein cholesterol, but again, these changes have been explored only in short-term trials.

To determine potential long-term effects of consuming dark chocolate every day, as well as the cost-effectiveness of this strategy, Australian researchers used statistical modeling techniques, particularly a Markov model to which health states (“alive without cardiovascular disease,” “alive with cardiovascular disease,” “dead from cardiovascular disease,” “dead from other causes”) and decision analysis (no dark chocolate [control], or with dark chocolate [treatment]) were added.

With each annual cycle, the researchers used risk prediction algorithms and population life tables to estimate how eating dark chocolate every day for 10 years would affect patients with metabolic syndrome.

The study used data on 2013 participants from the Australian Diabetes Obesity and Lifestyles study who had metabolic syndrome, did not have a diagnosis of cardiovascular disease or frank diabetes, and who were not receiving antihypertensive medications.

The patients were relatively young (mean age, 53.6 years) and considered at high risk: They had a mean systolic blood pressure of 141.1 mmHg, mean total cholesterol level of 6.1 mmol/L, mean hemoglobin A1c of 34.4 mmol/mol, and mean waist circumference of 100.4 cm.

The researchers concluded that under the best-case scenario, in which all these patients ate dark chocolate daily for a decade, 70 nonfatal cardiovascular events, including nonfatal stroke and nonfatal myocardial infarction per 10,000 population, as well as 15 cardiovascular related deaths per 10,000 population, could be prevented.

The estimated incremental cost-effectiveness ratio was $52,500 per years of life saved when $42 per person per year was assumed to have been spent on a prevention strategy using dark chocolate.

Even if only 80% of individuals with metabolic syndrome adhered to daily consumption of dark chocolate over 10 years, preventing only 55 nonfatal and 10 fatal events per 10,000, it would still be considered an effective and cost-effective intervention strategy, the authors write.

Prevention Strategy

A dark chocolate prevention strategy of $42 per person per year in a high-risk population would be cost-effective “based on the commonly accepted, albeit arbitrary, threshold of $50,000 per years of life saved,” said the authors.

The $42 per person per year could be devoted to advertising, education campaigns, or, potentially, subsidization of dark chocolate in this high-risk population, they said.

The authors point out that they did not assess the potential effectiveness of dark chocolate consumption on cardiovascular events other than nonfatal stroke and nonfatal myocardial infarction, such as heart failure.

They also stressed that the effects of dark chocolate consumption on blood pressure and total cholesterol, although beneficial, are not as profound as those of drug interventions.

The authors have disclosed no relevant financial relationships.

BMJ. Published online May 31, 2012.

Atrial fibrillation occurs in about 1 percent of adults in their 60s. The incidence rate rises with age after that, with about 10 to 12 percent of people in their 80s having atrial fibrillation.

Atrial fibrillation may or may not cause symptoms. Either way, it can lead to development of blood clots in the heart that can break off and travel to the brain, where they can disrupt blood supply and cause a stroke.

About 15 percent of strokes are attributed to atrial fibrillation — and that number may be higher as undetected atrial fibrillation may be responsible for some of the roughly 25 percent of strokes that have no identifiable cause.

Whether you feel symptoms or not, it’s important to follow through with recommended treatments. These may include medications or surgery designed to help control or reset your heart rhythm, in addition to anti-clotting medications to prevent stroke.

Mixed signals

A heartbeat starts with an electric signal from the heart’s natural pacemaker, the sinoatrial (SA) node. This signal passes through the heart’s upper chambers (atria). The signal causes the atria to contract, squeezing blood into the heart’s two lower chambers (ventricles). A split second later, the signal passes through an electrical checkpoint — the atrioventricular (AV) node — that connects the atria and ventricles. This causes the ventricles to contract, pumping blood to the body.

Atrial fibrillation occurs when chaotic electrical signals in the heart’s atria cause the atria to beat irregularly and fast — so fast that they don’t really beat. Instead, they quiver (fibrillate) as they race at 300 to 400 beats a minute. The heart can still pump blood to the rest of the body, but less efficiently.

The chaotic electrical signals from the atria bombard the AV node. The AV node blocks many of the extra signals from reaching the ventricles, but often some get through. This causes the ventricles to beat faster than normal. The average resting heart rate is 60 to 100 beats a minute. People with atrial fibrillation may have an irregular heartbeat in the range of 100 to 175 beats a minute.

Atrial fibrillation can cause lightheadedness, decreased blood pressure, weakness, shortness of breath, heart palpitations, confusion and chest pain. Symptoms may occur in periodic episodes lasting for a few minutes to a week before stopping on their own. They can also occur more persistently or even continually. This is more likely to occur in those with some sort of underlying heart disease.

Diagnosis of atrial fibrillation involves one or more tests to measure the electrical impulses given off by your heart. Imaging tests of your heart may be done to look for structural problems — such as damage from heart disease or heart failure.

Blood tests, a physical exam and other testing may be done to look for any underlying medical conditions — such as excessive thyroid hormone production — that may be triggering the heart rhythm problem.

Treatment for atrial fibrillation often starts with medication to prevent blood clots. Additional treatment decisions involve consideration of factors such as how long you’ve had atrial fibrillation, what the underlying causes may be and how bothersome symptoms are. The worse the symptoms, the more aggressive your treatment may be.

Sometimes, treating an underlying condition can return the rhythm to normal. Otherwise, the main nonsurgical choices are:

• Resetting your heart’s rhythm (cardioversion) — This is the ideal treatment because it resets the heart rhythm to normal, which also means that your heart rate will normalize as well. About 30 to 40 percent of people treated with cardioversion retain heart rhythm control for at least one year. This may not seem like a great success rate, but it’s often worth a try, especially if you have symptoms or if it’s the first time you’ve had the problem. The longer you’ve had atrial fibrillation, the less likely cardioversion will work.Cardioversion to restore normal sinoatrial rhythm can be attempted using anti-arrhythmic drugs. Electrical cardioversion can also be performed. In this brief procedure an electrical shock is delivered to your heart. The shock stops your heart’s electrical activity momentarily. When your heart begins beating again, the hope is that it resumes its normal rhythm.

  If your heart rhythm returns to normal with either method, doctors often prescribe oral anti-arrhythmic drugs to help maintain a normal rhythm. Commonly used drugs include amiodarone (Cordarone, Pacerone), dofetilide (Tikosyn), dronedarone (Multaq), flecainide (Tambocor), propafenone (Rythmol) and sotalol (Betapace).

  These drugs can cause side effects, such as nausea, dizziness and fatigue. Side effects are sometimes serious enough to prompt taking a different direction with therapy.

• Controlling your heart rate — When your atrial fibrillation can’t be converted to a normal rhythm, the goal may switch to improving symptoms by slowing the rate at which your ventricles are beating. This can be done with medications, such as digoxin (Lanoxin), calcium channel blockers or beta blockers. Heart rate control is done in conjunction with taking anti-clotting medications.

Surgical options

Sometimes, using a drug to maintain a normal heart rhythm or heart rate doesn’t work well — or side effects of a drug aren’t tolerable. An alternative option may be a surgical procedure called radiofrequency ablation.

In this, one or more tubes (catheters) are inserted in a vessel near your groin, threaded up to your heart and used to burn areas of tissue within the atria. This causes scarring of the tissue that disrupts and stops erratic electrical signals. In some cases, other types of catheters that can freeze areas of heart tissue are used.

Radiofrequency ablation stops atrial fibrillation for at least one year in about 75 to 85 percent of people who have occasional episodes. It decreases it in about 10 to 20 percent of people whose atrial fibrillation is continual.

A surgical maze procedure is another way to achieve a similar result, but it requires open-heart surgery. Several precise incisions — or areas of burned or frozen tissue — are made in the atria. This results in scar tissue that disrupts and blocks extra electrical signals. It’s usually reserved for people who don’t respond to other treatments — or it may be done during another open-heart surgery such as a coronary artery bypass procedure or heart valve repair.

When it comes to controlling heart rate — but not atrial rhythm — the main surgical option involves destroying the AV node. This procedure is done using catheters inserted through a leg vein. With the AV node destroyed, electrical signals don’t pass to the ventricles. The atria continue to fibrillate, which makes it necessary to take anti-clotting drugs to prevent stroke. A pacemaker is implanted to establish a normal ventricle rhythm.

April 20, 2012 (Dubai, United Arab Emirates) — An international study is confirming what many cardiologists have known for a while–many smokers around the globe know that smoking can cause lung cancer, but far fewer are aware that their habit has adverse effects on the heart. Even more striking, smokers were largely unaware that secondhand smoke increases the risk of heart disease and stroke among nonsmokers.

The new numbers, unveiled by Dr Geoffrey T Fong (University of Waterloo, ON) at the World Congress of Cardiology (WCC) 2012, come from the International Tobacco Control (ITC) Policy Evaluation and the Global Tobacco Surveillance System (GTSS). Both, Fong noted to heartwire , provide strikingly similar snapshots of smokers’ perceptions of their own disease risk.

“We know the science–that smoking or tobacco use and secondhand smoke are significant causes of CVD, as well as lung cancer and other forms of cancer–and then the question becomes, do people know the facts about the relationship between tobacco use, secondhand smoke, and CVD, and to what extent does this differ across different countries?” Fong told heartwire . “This is important because well-informed people are more capable of making a decision about tobacco use: for those who don’t use it, will they start? or for those who are using tobacco, would it give them reason to quit?”

Smokers, Fong points out, are much more likely to die of heart disease than they are from lung cancer.

Unawareness Around the Globe

In both data sets, lack of awareness that smoking causes heart disease, or heart attacks, and stroke was highest in China, at over 70% for stroke and ranging from 46% to 62% for heart disease between the ITC and GTSS surveys. By contrast, lack of awareness that smoking causes lung cancer among Chinese smokers was under 20% in both data sets.

Other countries with striking unawareness of smoking’s effects on the heart (25% or higher) were the Netherlands, Bangladesh, Thailand, India, Russia, and Vietnam in at least one of the surveys, with ignorance about stroke even higher. And that lack of awareness did not reach zero even in countries where tobacco-control efforts have been in place for years. In France, for example, almost 14% of smokers surveyed said they were unaware that smoking could cause stroke, a number that reached 17% in New Zealand and Brazil.

Across all countries surveyed, smokers are more aware of the risks of lung cancer than they are about the risks of CVD.

“Generally speaking, in low- and middle-income countries, there is less awareness of the harms of tobacco generally, but even in higher-income countries, heart-attack awareness was not as good as you’d expect,” Fong said. “In the US, for example, where there have been 50 years of awareness campaigns, smoking is still by far the leading cause of death,” yet lack of awareness that smoking causes heart disease among US smokers surveyed was almost 13%, rising to 24% for stroke.

In every country surveyed by the ITC, lack of awareness among smokers that secondhand smoke could cause heart attacks was typically double the awareness that this kind of “passive” exposure could cause lung cancer. That number jumped even higher when the same question was asked of nonsmokers. In Vietnam, for example, 88% of nonsmokers said they did not believe or did not know that secondhand smoke could cause heart disease.

“Across all countries surveyed, smokers are more aware of the risks of lung cancer than they are about the risks of cardiovascular disease,” Fong said. “People’s knowledge that secondhand smoke exposure causes cardiovascular disease is alarming low compared with their knowledge that secondhand smoke causes lung cancer.”

Where There’s Doubt, There’s a Market

To heartwire , Fong drew an analogy with global warming, pointing out that “creation of doubt” has been a tobacco-company marketing strategy, which underscores the importance of collecting these kinds of data on people’s beliefs and knowledge.

“If the tobacco industry or those who would argue against tobacco-control policies are successful, then the knowledge of or belief in the proven science linking smoking and heart disease, stroke, and cancer will erode. And there are forces that want to erode that.”

Physicians need to be aware of these kinds of forces, Fong stressed, and step up their efforts to educate patients and to help smokers quit. His presentation included other data collected by the ITC showing that only 50% of US smokers who visited a doctor were advised to quit, a number that fell to 16% in France, and 7% in the Netherlands.

Of note, the Netherlands, once a leader in implementing smoke-free policies, has in recent years partially repealed smoke-free legislation and had announced plans to end government-supported antismoking media campaigns.

In Canada, the new budget announced by the ruling Conservative party includes axing $15 million from its antismoking media programs.

Yet a recent National Cancer Institute monograph also showed that mass media have a profound impact “on knowledge, awareness, belief, and motivation for quitting and actual quitting,” Fong said.

“The ITC project has also published numerous studies showing the effectiveness of warning labels,” Fong said, and these new data support ongoing efforts to have all tobacco-product packaging have large, visible labels that include graphics, he said.

Of note, few countries have implemented pictorial health warnings on tobacco products that inform smokers about the cardiovascular risks of tobacco use, and no country has used pictorial health warnings to remind smokers that secondhand smoke causes cardiovascular disease.

Dr Georges Saade (Lebanese University, Beirut), who spoke during a WCC press conference, noted that tobacco use and secondhand-smoke exposure are major causes of cardiovascular disease globally and account for approximately 10% of all cardiovascular deaths. He also cited a US Surgeon General’s report from 2010 noting that secondhand smoke increases the risk of acute coronary syndromes by 25% to 30%.

Background and aim Identification of ischaemic stroke subtype currently relies on clinical evaluation supported by various diagnostic studies. The authors sought to determine whether specific diffusion-weighted MRI (DWI) patterns could reliably guide the subsequent work-up for patients presenting with acute ischaemic stroke symptoms.

Methods 273 consecutive patients with acute ischaemic stroke symptoms were enrolled in this prospective, observational, single-centre NIH-sponsored study. Electrocardiogram, non-contrast head CT, brain MRI, head and neck magnetic resonance angiography (MRA) and transoesophageal echocardiography were performed in this prespecified order. Stroke neurologists determined TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification on admission and on discharge. Initial TOAST stroke subtypes were compared with the final TOAST subtype. If the final subtype differed from the initial assessment, the diagnostic test deemed the principal determinant of change was recorded. These principal determinants of change were compared between a CT-based and an MRI-based classification schema.

Results Among patients with a thromboembolic DWI pattern, transoesophageal echocardiography was the principal determinant of diagnostic change in 8.8% versus 0% for the small vessel group and 1.7% for the other group (p Conclusions DWI patterns appear to predict stroke aetiologies better than conventional methods. The study data suggest an MRI-based diagnostic algorithm that can potentially obviate the need for echocardiography in one-third of stroke patients and may limit the number of secondary extracranial vascular imaging studies to approximately 10%.
Introduction

The accurate diagnosis of stroke subtype is important for the acute management of cerebral ischaemia and for the prognosis and secondary prevention of stroke. Currently, a variety of diagnostic tests exist for the evaluation of acute ischaemic stroke patients. A sequential choice of diagnostic tests should be made to optimise diagnostic yield, reduce the risk of harm to the patient and minimise cost. Challenges may arise when the practitioner is limited by either availability of diagnostic methods or cost-containment policies.[1] The introduction of powerful diagnostic imaging modalities and aggressive therapeutic strategies requires the need to streamline diagnostic protocols while maintaining standards of care that are well founded, cost-effective and readily available. This has improved accuracy but increased the complexity of clinical decision-making.

Conflicting data exist regarding the diagnostic utility of hospital-based testing in the evaluation of acute ischaemic stroke. The comprehensive in-hospital evaluation of ischaemic stroke patients is performed to accurately determine stroke aetiology. Presumably, knowledge of stroke aetiology leads to better treatment of patients and improved prevention of recurrence. For example, there is clear benefit in evaluating patients for risk factors such as carotid stenosis and atrial fibrillation, which have a distinct treatment path. However, some believe that the standard diagnostic studies do not yield results that warrant prolonged hospitalisation.[2]

We tested the hypothesis that specific diffusion-weighted MRI (DWI) patterns can more efficiently and accurately identify stroke aetiologies than conventional diagnostic methods. Our aim was to establish whether a comprehensive MRI evaluation has the potential to limit the need for other diagnostic studies and provide a more cost-effective approach to stroke diagnosis. We sought to determine whether MRI could be reliably used as the pivotal study to guide the subsequent diagnostic approach for patients presenting with symptoms of acute ischaemic stroke.
Materials and Methods

Two hundred and seventy-three consecutive adult patients admitted within 48 h of onset of ischaemic stroke symptoms and able to comply with MRI and transoesophageal echocardiography were included in this prospective NIH-sponsored study. All patients, or their designated representative, signed an informed consent to participate in this study. Patients who were intoxicated, who had a severe terminal illness, HIV/AIDS, symptoms referable to an alternative diagnosis such as migraine, seizure or psychiatric disorder, who were in coma or from whom consent was not obtainable were excluded. Patients with a known history of atrial fibrillation were excluded, as their stroke aetiology was presumed to be self-evident; patients who subsequently developed atrial fibrillation were enrolled. Patients who received intravenous tissue plasminogen activator were excluded, as we postulated that thrombolytics could influence the appearance of DWI lesions.[3] Patients enrolled in other investigational drug studies were also excluded. Transient ischaemic attacks (TIAs) were defined as clinical symptoms suggestive of stroke lasting less than 24 h. The attending stroke neurologist determined a modified Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification on both admission and discharge.[4]

Patients were to undergo CT, MRI, intracranial and cervical magnetic resonance angiography (MRA) and transoesophageal echocardiography, in this prespecified order. Not all patients underwent all diagnostic testing. Two hundred and fifteen (78.7%) patients had a cervical MRA. Two hundred and forty-one (88.3%) patients had an echocardiogram during their hospitalisation and 196 (81.3%) had transoesophageal echocardiography. No statistically significant difference existed between the rates of acquisition of MRI, MRA or transoesophageal echocardiography for all three groups. All patients had an MRI and MRA of the brain. MRI scans were acquired using the 1.5 GE Signa Horizon scanners (GE Medical Systems, Waukesha, Wisconsin, USA). The MRI sequences that were obtained included: spin echo-echoplanar imaging DWI, fast spin echo, fast spin echo fluid attenuated inversion recovery, gradient echo and multiplanar gradient echo. Apparent diffusion coefficient maps were created from the DWI. Contrast-enhanced MRA (ce-MRA) and three-dimensional time-of-flight MRA (tof-MRA) of the intracranial cerebral circulation and cervical internal carotid arteries were obtained.

The attending stroke neurologist classified each patient’s presumed stroke subtype according to TOAST criteria on admission, after initial clinical assessment (history, examination and baseline laboratory studies) and review of the admission head CT (initial TOAST). The initial TOAST classification was determined prior to acquisition of the MRI scan. The attending stroke neurologist performed the same classification on hospital discharge after all diagnostic tests were completed and final diagnostic assessments were made (final TOAST).

A CT-based classification scheme was compared with an MRI-based one. The initial TOAST subtype was converted to a CT-based classification schema as follows: initial TOAST subtypes 1 and 2 (large artery and cardioembolic) were designated CT-based thromboembolic, initial TOAST group 3 (small-vessel disease) was designated CT-based small-vessel disease and the remaining TOAST groups 4 and 5 (other determined or undetermined) were designated CT-based other. The DWI pattern of the MRI was classified into one of three patterns: (1) thromboembolic, (2) small vessel or (3) other. The thromboembolic pattern was defined as either single or multiple acute ischaemic lesions, in a unilateral or bilateral distribution. Single lesions had to measure greater than 1.5 cm in diameter. The small-vessel pattern was defined as a single small (50% stenosis (North American Symptomatic Carotid Endarterectomy Trial criteria) ipsilateral to a symptomatic hemisphere. The interstudy agreement in the per cent stenosis measurement from the tof-MRA, ce-MRA and carotid ultrasound was compared using Cohen’s κ statistic.

Attending stroke physicians chose one diagnostic test: MRI, MRA, transoesophageal echocardiography, other test or ‘none’ as the principal determinant of change if the final TOAST classification differed from the initial TOAST classification. Other tests included: ECG/telemetry, EEG, catheter angiogram, transcranial Doppler ultrasound, ophthalmological examination, clinical examination, and serological tests of hypercoagulability and peripheral blood smear. If two tests were equally likely to result in the diagnosis, then physicians were to choose ‘none’ as the principal determinant of change. When the initial and final TOAST classes were the same, no test was considered the principal determinant, as no change was made. The tests that constituted the ‘principal determinant of change’ were evaluated for both CT-based and MRI-based approaches. Proportions of the groups were compared using χ2 or Fisher exact tests. All tests were two-tailed and significant at level αResults

The demographic characteristics of the cohort are detailed in Table 1. One hundred and seventy-three patients had positive lesions on DWI, compatible with acute ischaemia. Correspondence between the initial and final TOAST classification is shown for the entire cohort in Table 2. The sensitivity and positive predictive value of the initial TOAST score were 60.8% and 47.0% for large artery atherosclerosis, respectively, 40.4% and 67.9% for cardioembolism and 94.0% and 61.8% for small-vessel disease.

One hundred and fifty-three (56.0%) patients had the same diagnosis on discharge as they had on admission. Of the 120 patients who had a change in their diagnosis, transoesophageal echocardiography was the principal determinant of change in 11%, MRI in 13% and MRA in 16% (Table 3). Of the 13 patients for whom transoesophageal echocardiography was the principal determinant of change, 3 had high-risk lesions (left atrial appendage thrombus, aortic valve vegetation and left ventricular thrombus), 6 had medium-risk lesions (5 patent foramen ovale (PFO) and atrial septal aneurysm and 1 mobile atheromatous plaque of the aortic arch) and 4 had low-risk lesions (1 left atrial spontaneous echogenic contrast and PFO, 1 PFO and 2 regional wall motion abnormalities). Of the 19 patients for whom MRA was the principal determinant of change, 11 had culprit lesions in the cervical vessels, 6 had intracranial lesions and 2 had evidence of both. For 55 patients, no test was identified as the principal determinant of change. Of those, eight had more than one possible stroke aetiology. Thirty-three of the 55 patients had no lesion on DWI and a negative diagnostic evaluation.

Stroke is a pathologically heterogeneous disease. A comprehensive approach to the determination of stroke aetiology may be prohibitively costly; alternatively, a cursory evaluation may not adequately prevent recurrence. Our data support the use of a new a diagnostic algorithm for the evaluation of patients presenting with an acute stroke (figure 3). Algorithms can reduce practice variation, limit delays in care, curtail hospital length of stay and minimise patient morbidity.

The proposed model includes initial stratification based on pattern of DWI abnormality after acquisition of the brain MRI/MRA. In the model, the DWI pattern is classified into one of three groups: thromboembolic (includes a unilateral or bilateral distribution of acute ischaemic lesion), small-vessel disease or other. Patients in the thromboembolic category are further stratified according to the presence or absence of ipsilateral arterial atherosclerosis. Our results indicate that the utility of transoesophageal echocardiography is particularly high in the select group of stroke patients who are considered to have a thromboembolic MRI pattern and negative cervical MRA and particularly low in patients with the small-vessel pattern. This approach may obviate the need for transoesophageal echocardiography in patients with a presumed diagnosis of a small-vessel (lacunar) stroke following MRI/MRA.

This study demonstrates a poor correlation between the initial CT-based diagnostic impression and final stroke subtype classification, even among trained vascular neurologists. Sensitivity and positive predictive value were low for all stroke subtypes; the exception was a high sensitivity for small-vessel disease. The diagnosis of small-vessel disease was overestimated; more than one-third of patients initially considered to have small-vessel disease subsequently had a different final diagnosis.

Significant controversy exists regarding the diagnostic utility of echocardiography in the evaluation of acute ischaemic stroke. Yu and colleagues suggest that its low yield, coupled with lack of evidence for urgent anticoagulation, render it a poor screening tool for stroke patients.[2] They cite a yield of 3.8% for transoesophageal echocardiography and a yield of 1.5% for transthoracic echocardiography. Other authors believe that echocardiography, especially via the transoesophageal route, strongly influences secondary prevention strategies.[6–8] An MRI-based diagnostic approach may allow doctors to selectively obtain transoesophageal echocardiography examinations in the subgroup of patients who are most likely to benefit.

In patients with a change in diagnosis, MRA was the key determinant of change in 16%. Sixty per cent of these changes were based on cervical MRA findings and 40% were based on the results of the intracranial MRA. In the subgroup analysis of cervical MRAs, there was excellent agreement between tof-MRA, ce-MRA and ultrasound in patients with minimal atheromatous disease. However, there was considerably less agreement when disease was present. Our findings corroborate previously published results regarding the sensitivity and specificity of MRA in the identification of cervical and intracranial atherosclerosis.[9–13] We found that MRA had a high negative predictive value and could obviate the need for further vascular imaging if the study was normal; this applied to about 90% of our patients. By contrast, the poor agreement with carotid ultrasound in patients with a positive MRA supports the need for additional diagnostic studies (such as CT angiography or ultrasound).

TIAs were more commonly classified by MRI into the other group (65%) compared with thromboembolic (35.2%) and the small-vessel disease (27.3%) groups (p≤0.001). Most of the TIA patients had negative DWI scans and, therefore, our diagnostic algorithm may not be ideally suited for the diagnostic work-up of TIA patients. The addition of perfusion-weighted MRI (PWI) may detect a lesion in one-third of the DWI-negative TIA patients as suggested by Mlynash et al, although there is insufficient evidence to support its routine use.[14 15] Mlynash found that the combination of DWI and PWI, when performed within 48 h of symptom onset, identified evidence of brain ischaemia in half of the patients admitted with stroke symptoms lasting less than 24 h. Furthermore, long-term Holter monitoring may be more revealing than echocardiography in this subset of patients. A recent study of 24 h Holter monitoring for patients with stroke or TIA found that of the patients with documented paroxysmal atrial fibrillation, 41% presented with TIA.[16]

This study has some limitations. Our use of the modified TOAST classification at the time of the initial assessment differs from the traditional use of the TOAST classification, which is based on an assessment of all available data from the complete diagnostic evaluation. However, in order to determine the additive benefit of each diagnostic test, pretest assessment was required; we chose a modification of the TOAST classification for its ease of comparison with the final TOAST determination. Moreover, we applied TOAST criteria to patients admitted with TIA; this was also not part of the standard TOAST criteria. However, studies of DWI have demonstrated that many ischaemic episodes with symptoms lasting

These data represent a clinical approach to the determination of stroke aetiology, and not the true ‘yield’ of diagnostic testing. This highlights a key difference between our study and many other investigations assessing the diagnostic utility of specific tests. We assessed which tests led to a change in the diagnosis, that is, the principal determinant of change. We feel that this may be a more clinically relevant approach to determine the optimal evaluation for acute ischaemic stroke patients, as opposed to the traditional notion of diagnostic yield. The diagnostic yield of a study is defined as how often a test is positive, whether or not it has a bearing on the final diagnosis. For example, although moderate and high-risk lesions were noted by echocardiography in 53/241 (22.0%) patients, physicians chose transoesophageal echocardiography as the principal determinant of diagnostic change in only 13/241 (5.4%) patients. The concept of the principal determinant of change was chosen to be a more relevant notion in the clinical work-up.

In conclusion, DWI patterns appear to predict stroke aetiologies better than conventional diagnostic methods. Early MRI/MRA can help tailor the stroke diagnostic evaluation and may limit the need for other studies including transoesophageal echocardiography and carotid ultrasound thereby providing a more cost-effective approach to stroke diagnosis, improved patient satisfaction and decreased length of hospital stay. This algorithm may not be applicable to MRI-negative TIAs as it is based on DWI patterns; the addition of PWI may increase diagnostic sensitivity. Future studies are required to validate this algorithm.
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