Advances in Cardiovascular Diagnosis and Treatment

LINDA HARDER | PHOTOGRAPHY TRACEY BROWN

Studies show there’s new hope for treating paroxysmal atrial fibrillation and ischemic strokes, and demonstrate that depression is an independent risk factor for coronary artery disease. Our Maryland experts explain.

Clearer Data on Managing Ischemic Strokes

New clinical trials across the world are providing fresh evidence about the effectiveness of both emerging and existing interventions for ischemic strokes. Treatment advances may be why stroke has dropped to fourth place as the major cause of death in the U.S., but with nearly 800,000 Americans affected by a new or recurrent stroke each year, that guidance is critically needed.

tPA Window of Effectiveness Expands

According to the National Institutes of Neurological Disorders and Stroke, patients receiving intravenous tissue-type plasminogen activator (tPA) within three hours of stroke onset are 33%  more likely to recover with little or no disability than those who don’t. While administering tPA within 90 minutes is still preferable, first demonstrated by three large trials in the 1990s, researchers have found that its window of effectiveness is longer than previously believed. Recent clinical trials in Europe have demonstrated that thrombolysis can be effective for some patients up to four-and-a-half hours after stroke symptom onset; after that time, the risks may outweigh the benefits.

When Thrombolysis is Contra-indicated

Thrombolysis is contraindicated in patients who are pregnant or who have had major surgery or serious trauma within 14 days, or gastrointestinal or urinary tract hemorrhage, history of stroke or serious head trauma within 21 days. It also is contraindicated for patients with a history of intracranial hemorrhage, brain tumor or known cranial aneurysm.amir

“The average patient has a 3-6% risk of intracranial hemorrhage with tPA,” Amir Zangiabadi, M.D., director of Neuroscience and Stroke Services at Washington Adventist Hospital, says. “Those with high blood pressure, advanced age, a large stroke or a delay in receiving tPA, however, are at higher risk. Patients older than age 80 or patients with diabetes should not receive a thrombolytic more than three hours after a stroke. A common myth about thrombolytics is that those aged 50 or younger are at higher risk, whereas they are actually at lower risk (only about 2%).”

Intracranial Ultrasound as Potential Adjunct

The results from CLOTBUST-HF – an initial trial of 20 patients receiving high-frequency intracranial ultrasound – published October 2013, were promising. “Physicians placed a circular helmet on the patient’s head that provided 2-megahertz pulse-waves for two hours, in conjunction with tPA. The ultrasound may stir up the blood near the clot or help bind the drug to the clot. It is also possible that ultrasound waves will help shake up the clot,” Dr. Zangiabadi explains. “The recanalization rates for the middle cerebral artery were higher than with tPA alone, but it’s a small trial and we don’t yet know the impact on disability rates.”

A Phase III trial of this approach, called CLOTBUST-ER, is underway, with results expected in the next two to three years.

Stenting vs. Carotid Endarterectomy

The Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST), published in the New England Journal of Medicine in 2010, found that carotid endarterectomy was safer than stenting in patients older than 70. However, for those under age 70, stenting was marginally safer.

“Endarterectomy decreases the risk of stroke but the use of anesthesia possibly increases the risk of myocardial infarct,” says Dr. Zangiabadi. “The implication is that patients with a history of myocardial infarct may do better with stent placement.”

The American Academy of Neurology provides the following treatment guidelines:

  • Symptomatic patients that have >70% stenosis or those with 50% – 69% stenosis, a life expectancy > 5 years and risk of stroke or death <6% should be treated with stent or endarterectomy. For stenosis <50%, mitigate risk factors only.
  • Asymptomatic patients with 60% – 99% occlusion, 40 –75 years old, > 5 year life expectancy, and risk of stroke or death < 3% should have an interdisciplinary team determine if stent or endarterectomy is warranted.

“Anyone with greater than 60% stenosis should have additional imaging beyond an ultrasound,” Dr. Zangiabadi advises. “MR angiography (MRA) usually doesn’t require contrast and can be appropriate for older patients with lots of calcification or those with kidney problems. CT angiography (CTA) requires contrast. Carotid angiography is the gold standard but carries about a 1% risk of stroke, so it’s only recommended when MRA or CTA are inconclusive.”

Interventional Thrombolysis Controversial

Interventional thrombolysis, where a catheter is inserted through the groin to directly deliver a clot-disrupting or retrieval device, is controversial. Newer generations of this approach may improve outcomes, and may be appropriate when pharmaceutical tPA is not effective.

“The proven clinical benefit is only in a small population,” notes Dr. Zangiabadi. “The problem is that it takes time to transfer patients to tertiary centers performing this procedure, and it must be performed within six hours. All studies report good recanalization results but the clinical results are less clear. I refer selected patients, such as those with basilar artery thrombosis, where there’s about a 90% chance of mortality, but it should be evaluated on a case-by-case basis.”

Stenting Intracranial Arterial Stenosis

The Stenting and Aggressive Medical Management for Preventing Recurrent stroke in Intracranial Stenosis (SAMMPRIS) study for intracranial arterial stenosis showed that stenting is not effective for treating intracranial carotid, basilar or middle cerebral artery stenosis. Dr. Zangiabadi concludes, “Stenting does more harm than good, and these patients tend to re-stenose. They should instead have their risk factors aggressively controlled.”

Depression: An Independent Cardiac Risk Factor

kaplinAdam Kaplin, M.D., PhD, assistant professor of Psychiatry and Neurology, The Johns Hopkins Hospital, is frustrated by the lack of awareness of the key role depression plays in cardiovascular disease. “Studies show that depression is an independent risk factor for cardiac morbidity and mortality as large as, or greater than, any other risk factor, including diabetes, hypertension and smoking,” he exclaims. “And in the 12 months following a cardiac catheterization, it’s the single greatest predictor of having a major cardiovascular event.”

“Depression affects the brain, which in turn impacts the autonomic nervous system, and that affects the heart,” he adds. “Yet, in most residency programs, physicians get three years of internal medicine training without a single day of psychiatric training. We need to increase awareness of the importance of mental health on cardiovascular health.”

Mechanisms Behind the Linkage

The relationship between depression and coronary artery disease isn’t completely understood. A 2011 article in Vascular Health Risk Management noted the following contributing factors:

  • Interleukin-6, an inflammatory biomarker associated with heart disease, was found in a small study to be significantly higher in those with major depression than in a control group.
  • Depression creates an imbalance of the sympathetic and parasympathetic systems, which is associated with great morbidity and mortality.
  • Platelet reactivity is higher with depressed patients, affecting atherosclerosis and thrombosis.
  • Genetic polymorphism in the serotonin transport promoter region gene was associated with a higher risk of depression and CAD.

Screen for Depression

Dr. Kaplin advises primary care physicians to screen for depression as they would screen for hypertension or any other risk factors. He suggests that physicians can use Patient Health Questionnaire 2 (PHQ-2), the first two questions from the well-documented and highly effective Patient Health Questionnaire 9 (PHQ-9) to provide quick insight.

“Using PHQ-2, you can ask patients two quick questions related to their mood over the past two weeks,” he says. “First, ‘how often have you felt little interest or pleasure in doing things?’ And second, ‘how often have you felt down, depressed or hopeless?’ If the patient answers ‘not at all’ to both questions (for a score of 0), no further follow-up is needed. If they indicate that either has been an issue, however, ideally the next step is to administer the full PHQ-9 or another depression screening tool.”

A July/August 2010 study in the Annals of Family Medicine found that a score of 2 to 6 in the PHQ-2 had a specificity of 50% and a sensitivity of 90%.

“Ideally, all of your patients should be screened for depression, using any of your favorite tools,” Dr. Kaplin recommends. “At the very least, physicians should screen everyone who has had a myocardial infarct.” He cites the rise in U.S. suicide rates, and the finding that two-thirds of individuals who go on to commit suicide visited their primary care physician in the month prior to their demise.

Clinicians need to monitor patients’ moods outside the office, too,” he adds. “Once you learn about treating depression, it’s incredibly rewarding, because it has such a positive impact on their overall health.”

Mood 24/7 App

As an adjunct to in-person counseling, Dr. Kaplin worked with Health Central and Remedy Health to develop Mood 24/7, a simple mobile phone app to help physicians track their patients’ moods. Patients can also use this app to track their own moods. The app sends patients a daily text message that asks them to assess their mood on a scale of 1 to 10, then reports the data to approved providers. The goal is to better inform treatment decisions and improve patient compliance. For more information, visit www.mood247.com.

Barriers to Treatment

Dr. Kaplin notes that it’s challenging to demonstrate a statistically significant cardiovascular benefit to treating depression. “The problem is that, like investing money in the stock market, if you lost 50% of your money in Year 1, you have to increase your earnings by 100% in Year 2 to get back to zero. Similarly, it’s harder to demonstrate that a treatment for depression improves cardiovascular health (and thereby decreases risk by a certain percentage) than it is to prove that something is a risk factor, with the resulting increased risk. The SADHART study [Sertraline Antidepressant Heart Attack Randomized Trial] found that this antidepressant could safely treat patients with a recent MI or unstable angina, but it wasn’t statistically significant because the numbers were so small.”

Another barrier to effective treatment is the lack of coordinated care between providers. While Dr. Kaplin believes electronic medical records are important to improving care coordination, he laments the small percent of hospitals that are storing psychiatric records electronically. “We did a study last year of the top 18 hospitals in the country, and found that only four of them stored their psychiatric records electronically. Those who did, however, saw a 40% drop in readmission rates among psychiatric patients.”

Yet another major barrier to proper mental health treatment is the lack of compensation for time spent on those issues. The push for more accountable and coordinated care provides some hope that these barriers will be better addressed going forward.

Newer Techniques Improve Atrial Fibrillation Outcomes

If there’s one point to take away from a conversation with Jeffrey Banker, M.D., an bankerelectrophysiologist and heart rhythm specialist at the Heart Center at Sinai, it’s that paroxysmal atrial fibrillation is more dangerous than most physicians appreciate. “Most don’t realize that the five-year mortality rate reported in the AFFIRM trial that studied the pharmacologic management of atrial fibrillation in 4000 patients was about 24%,” he cautions. “Anti-arrhythmic drugs maintain the sinus rhythm only about 10% to 20% of the time. The good news is that newer ablation techniques significantly improve the maintenance of sinus rhythm and therefore limit the progression of the condition, which carries a significant risk of stroke and worsening heart failure.

PAF is believed caused by irregular electrical signals originating in the pulmonary veins. Ablating the tissue in these veins was found to stop or reduce these abnormal rhythms that then cause the atria to pump erratically and inefficiently.

Fire and Ice

Catheter ablation is appropriate for many symptomatic afib patients who have failed cardioversion and anti-arrhythmia medications. The original radiofrequency (RF) approach, available for more than a decade, uses a catheter that emits radiofrequency energy that renders atrial tissue participating in the afib no longer electrically active. Dr. Banker notes that this technique has drawbacks. “A limitation of the ‘fire’ approach to ablation is that it creates a set of tiny dots in a circle that are like Pointillism – from far away, they look complete, but when you get close, you see that the dots don’t connect.”

That issue, plus the fact that the burned tissue may heal over time, allows the faulty electrical signal to resume in 10% to 20% of cases within 24 months, and in half the cases within five years. And the procedure is time consuming, typically taking four to five hours.

In contrast, a newer technique utilizes ‘ice’ rather than ‘fire’ to ablate tissue. Physicians insert a cardiac cryoablation catheter through the groin into the atria, where they deploy a balloon that freezes tissue in the pulmonary veins.

“It’s like inserting an inflatable ping pong ball that fully covers the opening of the pulmonary veins,” Dr. Banker explains. “The cryoablation takes only about three minutes to get to minus-30-40 degrees Celsius and freeze a ring of tissue around the pulmonary vein. Experience has shown that tissue should be frozen and thawed twice to ensure tissue death. The whole procedure takes only about an hour.”

For patients who have failed a cardioversion and two trials of anti-arrhythmia drugs, it’s better to do the ablation procedure sooner rather than later. He remarks, “PAF can end up causing heart failure, and the cumulative risk of stroke, even with anti-coagulants, is 1% per year.

Ablation Far Safer Today

Dr. Banker notes that the evidence for the safety and efficacy of both types of ablation procedures has been mounting in the past 10 years. “The cryoballoon approach is proving to be highly effective and safe. The STOP AF [Sustained Treatment of Paroxysmal Atrial Fibrillation] trial found it effective in nearly 70% of cases, while anti-arrhythmia drugs were only 7% effective. However, there’s no good long-term data yet to suggest that ‘fire’ is better than ‘ice’ or vice versa. A new European trial will be the first head-to-head trial. A laser and new RF device also will soon be available.”

New techniques employed during ablation also make it far safer than it was a decade ago. “We now use intracardiac echo to avoid perforation and subsequent cardiac tamponade. We also avoid injuring the esophagus, which lies directly posterior to the left atrium, by inserting a temperature probe into it. We pace extensively so we can delineate and avoid injuring the phrenic nerve, which can cause diaphragmatic paralysis. Lastly, harm to the pulmonary veins can be minimized by ablating well outside them.”

As a result, morbidity and mortality rates experienced from 2001 to 2010 have fallen significantly. “It takes extensive training to do these procedures well,” acknowledges Dr. Banker, “but patients who undergo PAF ablation now have a risk of stroke, heart failure and death that’s comparable to a similar population that does not have PAF.”

Amir Zangiabadi, M.D., director of Neuroscience and Stroke Services at Washington Adventist Hospital

Adam Kaplin, M.D., PhD, assistant professor of Psychiatry and Neurology, The Johns Hopkins Hospital

Jeffrey Banker, M.D., electrophysiologist and heart rhythm specialist, The Heart Center at Sinai


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