EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS

SNOWMASS, COLO. (FRONTLINE MEDICAL NEWS) – Ultraslow infusion of a very-low-dose thrombolytic agent for treatment of mechanical prosthetic valve thrombosis appears to be as effective as surgery – the former first-line therapy – and sports a far lower stroke risk, Rick A. Nishimura, MD, said at the Annual Cardiovascular Conference at Snowmass.

“I’m not saying you have to use this, but I think it’s reasonable to consider it, especially if the patient is at high risk for surgery and low risk for thrombolysis,” according to Dr. Nishimura , professor of cardiovascular diseases and hypertension at the Mayo Clinic in Rochester, Minn.

He added that he and his Mayo colleagues have begun using the novel therapy and are favorably impressed with the resultant complete normalization of valve gradients and low complication rate.

Dr. Nishimura was cochair of the writing committee for the current American College of Cardiology/American Heart Association guidelines for management of valvular heart disease ( Circulation. 2014 Jun 10;129[23]:e521-643 ). Those guidelines state that emergency surgery is the treatment of choice for thrombosis of a left-sided mechanical heart valve. That strong recommendation was based on a dozen nonrandomized studies reported prior to 2013 which showed a 95% success rate with surgery compared with 75% with conventional large-bolus thrombolytic therapy, a high 10%-12% mortality with either form of therapy, and a stroke risk of 12%-14% with thrombolytic therapy, substantially higher than for surgery.

Since release of the ACC/AHA guidelines, however, there’s been an important new development: Three groups outside of the United States have pioneered ultraslow thrombolytic therapy for mechanical prosthetic valve thrombosis. The supporting evidence comes from cohort studies, with no randomized trials done to date. But the collective reported experience from these three research teams shows a 90%-95% success rate – comparable to surgery – along with stroke and mortality rates in the low single digits.

The Turkish group waits until the patient’s international normalized ratio (INR) is below 2.5, then administers 25 mg of tissue plasminogen activator guided by transesophageal echocardiography (TEE) over 25 hours.

“We traditionally give 90 mg over 1 hour, so this is very, very slow therapy,” Dr. Nishimura observed.

After the 24-hour infusion, TEE is repeated. If imaging shows the clot is not resolved, another 25 mg of tissue plasminogen activator is given over 24 hours. This process is repeated for up to 8 days as needed ( Am Heart J. 2015 Aug;170[2]:409-18 ).

Dr. Nishimura advised reserving ultraslow thrombolytic therapy for patients who are hemodynamically stable; this treatment takes a while to work, so patients in severe heart failure should be sent straight away to surgery. The novel therapy is best suited for patients with recent-onset mechanical valve thrombosis, a low INR, TEE evidence that the clot isn’t huge, and/or when surgical expertise isn’t readily available.

Before you can treat a prosthetic mechanical valve thrombosis, however, you have to make the diagnosis. Here’s what Dr. Nishimura recommends: First, suspect the condition on the basis of clinical symptoms of heart failure and dull, muffled S1 and S2 sounds on auscultation, especially in a patient who presents with a low INR.

Next, prove that obstruction is present via Doppler echocardiographic evidence of an abnormal gradient across the mechanical valve.

Finally, determine if the mechanical valve shows abnormal disc motion with sticking leaflets. TEE is excellent for visualizing a mechanical mitral valve but isn’t helpful if it’s a mechanical aortic valve.

“Old-fashioned fluoroscopy is the best approach for looking at leaflet motion in the atrial valve and mitral valve. We’ve got 3-D cine now that provides beautiful images, but if you can get the same information with a quick fluoroscopy, go with the fluoroscopy,” the cardiologist suggested.

He reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

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