Archive for October, 2009
More on Implantable Defribrillators
Despite all odds, no financial backing or grants, the three men mentioned in my previous blog developed the implantable defibrillator in Baltimore. After animal testing, the first device was implanted in a patient at Johns Hopkins Hospital by Dr. Levi Watkins, Jr. in February 1980. A patent was issued on May 13, 1980 entitled “Method and Apparatus for Monitoring Heart Activity, Detecting Abnormalities, and Cardioverting a Malfunctioning Heart.” The FDA approved the device in 1985 and it was commercialized in the late 1980s. Dr. Mirowski died in March 1990 at the age of 65 of multiple myeloma. He lived to see the device accepted with nearly 10,000 implants by then. He would not be surprised to find out that from 1990 to 2002 more than 416,000 implants were performed.
These devices have been the subject of numerous studies in an attempt to find the optimal patient selection and to avoid the burden that these devices do impose on patients. We are looking for the “sweet spot” — making sure that the right people get the devices and will benefit the most from them.
The early devices were shock only. Since then, all ICDs as they are now called provide pacing as well and the devices can provide various types of therapy in an attempt to terminate the rhythm and only shock as a last resort. Many patients can have their arrhythmias terminated by pacing or small shocks and these changes in therapy allow for longer battery life. These devices cost upwards of $50,000 and have other features’ that will be discussed in other blogs.
Dr. Luceri of this institution who sits on our Clinical Advisory Committee participated in the seminal trial documenting these devices value. The Sudden Cardiac Death in Heart Failure Trial also known as SCD-HeFT was published in the NEJM January 2005. Twenty-five years after the first ICD was implanted, this study proved once and for all that ICDs were superior to medical management and saved lives.
Dr. Mirowski’s insight and determination has saved hundred’s of thousands of patients. One person can make an enormous difference.
The Genesis of Implantable Cardiac Defibrillators
The vast majority of people who die from sudden cardiac death are not being monitored in a coronary care unit. Two individuals in particular are responsible for saving the lives of millions of people. One in particular has a truly inspiring story.
Michel Mirowski was born Mordechai Frydman in Warsaw, Poland, in 1924. This was not the time or place to be born Jewish. His father changed his name to Mieczyskaw Mirowski and he blended into the Polish population. He escaped with other Poles to the Ukraine and fought alongside them in the Polish Army. After the war, he returned to Poland, but his family had all been murdered and all his possessions lost. He, like many others, was displaced and he was able to go to Israel. He wanted to become a doctor and as there was no training in Israel, he went to Lyon, France, and entered medical school. He knew neither French nor English but learned both. He was taught in French and studied medical books in English. He married a French women and she called him Michel.
He then studied cardiology in Mexico City, teaching himself Spanish and then went on to Johns Hopkins, where he studied with the great Helen Taussig. When he completed this journey, he went back to Tel Aviv and was the only cardiologist in the hospital. He had a great mentor and teacher in another physician in the hospital. About five years after Mirowski returned, this individual became ill with ventricular tachycardia. Although he was urged to remain in the hospital under observation, he elected to go home and two weeks later he died suddenly during dinner with his family.
Heartbroken, Mirowski began to conceptualize a device that would be implanted in a person to monitor and treat these fatal rhythms. As with most new ideas, everyone said it couldn’t be done. He soon realized that it was not possible to do in Israel and again arrived back in America at Sinai Hospital in Baltimore, Maryland. Here he met Dr. Morton Mower who was the head of the cardiac care unit. Along with Alois Langer, an expert in electrocardiographic signal analysis, these three men went on to develop a device that could be implanted in a patient which would monitor the heartbeat continuously and, if needed, provide life-saving therapy.
Next…why this is so important.
Cardiac Care through the Years
Take a journey with me. It is a journey of progress and inspiration, of concept and life. It is the journey of science in the service of mankind and how the building blocks of discovery are pieced together to make a whole.
Sudden cardiac death is the unheralded cause of death of roughly 500,000 people a year in the United States alone. Sometimes it occurs with acute myocardial infarctions, sometime in people at risk for it, as I will discuss. It can happen without warning and is almost uniformly fatal. Tim Russert of NBC news is a recent example. It is generally a rhythm known as ventricular tachycardia or ventricular fibrillation. Sometimes the rhythm starts as ventricular tachycardia but “degenerates” into ventricular fibrillation. Alternately, it starts as ventricular fibrillation.
This rhythm can be terminated in different ways but the most effective is by shocking the heart back to a normal rhythm. The sooner the shock is administered the more likely the patient will survive.
Two developments in the 1960s together became the first real improvement in cardiac care. The development of an external defibrillator by Dr. Frank Pautridge in Belfast Ireland gave doctors a mechanism to shock the heart. The first devices weighed in over 50 lbs. The second development was the placing of all patients with unstable cardiac issues in a specialized unit which was called a coronary care unit. This was first described in July 1961 by a British physician Dr. Desmond Julian in the British Thoracic Society Journal. This concept soon spread world wide and the first in the United States was opened in Bethany Medical Center in Kansas City, Kansas by Dr Hughes Day. He was also the first to organize all the tools and drugs needed for cardiac arrest in one place and it became known as a “crash cart.”
What about the majority of people who are not being monitored? How should we help them? That’s next…
Fractional Flow Reserve
At the recent Transcatheter Catheter Therapeutics conference in San Francisco a report was given on the two year follow up of the FAME study. This study included 1,005 patients with multivessel disease and randomized them to angiography-or- FFR guided angioplasty.
What is FFR? FFR stands for fractional flow reserve. It is a technique that is easy to perform in the cath lab. A special wire is place beyond the lesion in the coronary artery and then the drug adenosine is given to the patient through an intravenous line. This is the same drug that is often used to simulate the exercise portion of nuclear stress tests. It is a benign drug that disappears instantly when the infusion is stopped. It causes a pressure difference from the arterial pressure before and after the lesion. If the pressure difference is .75 then the lesion is significant.
The study randomized people to angiography or the group that had all lesions angioplastied at the decision of the doctor or FFR where the lesions were not dilated if the pressure was >.75. 500 lesions were deferred. Only one myocardial infarction occurred in that group two years later, a rate of 0.2%. At two years, 22.2% of the group randomized to angioplasty had an end point compared to 17.7% in the FFR-guided treatment group.
This follow up gives those of us that practice Interventional Cardiology a powerful tool to determine whether an indeterminate lesion should be intervened upon. This simple test saves time, valuable health care dollars, radiation and contrast use which in turn preserves renal function. This device is available to us at Holy Cross in the Jim Moran Heart and Vascular labs and is often used. It helps us make the right decision for patients so that medical care can be optimized.
Different Paths Lead to the Cath Lab
It might seem that using angiography to determine whether a coronary lesion is significant would be easy. Sometimes it is; sometimes it is not.
Patients arrive in the cath lab by different routes. Some come from the hospital because of unstable angina or myocardial infarctions. Some come because of classic symptoms of angina and multiple risk factors. Some come because of a positive stress test, stress echo test, or nuclear stress test.
The problem occurs because coronary arteries are three dimensional and they are being represented in two dimensions. To get around this, multiple views are obtained during the exam by rotating the camera around during the catheterization to obtain multiple angles. Heavy calcification and overlap often obscure vessels.
Confounding this problem further if you take a cath film to multiple doctors there is significant inter-observer variation in reporting of the severity of a stenosis in an artery. In fact if you ask the same doctor at different times the reports can vary.
This is a critical problem. The stenting of a coronary artery that is not significant can produce long lasting poor consequences for a patient. As I have written about in other blogs, medical management is an excellent way to treat much of what we find in the cath lab. Regardless of the extent of disease in one’s coronary arteries, management of the illness is medical and life long. Angioplasty is for those patients that have failed medical management and had life limiting angina. Surgery is for patients that can not have angioplasty or have poor heart function.
There is a way to discriminate coronary lesions that are considered “indeterminate.” Sometimes, even lesions that correspond to nuclear stress test results do not appear significant.
Next…what’s a doctor to do?
Is Your Medicine Making You Sick to your Stomach?
Gastrointestinal side effects such as reflux and bleeding are common in patients who take aspirin and Plavix. As I have written in other blogs, the effect of aspirin is local and systemic so that enteric coated aspirin does not lessen this risk. The importance of the drugs in preventing sudden coronary stent thrombosis led to the guideline recommendation that proton pump inhibitors be given along with aspirin and Plavix to lessen the risk.
Proton pump inhibitors such as Nexium and Protonix are drugs used to decrease the amount of acid in the stomach leading to a significant reduction in ulcers and reflux. They are used along with another class of drugs called H2 antagonists which are Zantac, Pepcid and Tagamet.
On May 6, 2009, a study was released at the Society for Cardiovascular Angiography and Interventions from researchers at Medco, a large pharmaceutical distributor. The study looked at the data from 16,690 patients and their conclusions were that instead of lowering the risk of major adverse cardiovascular events, this combination of drugs increased the risk from 17.9% to 25.1 %. Their data showed that all PPI’s were the same as far as risk of events.
As I have written before, this is the wonder and frustration of medicine. How can something which appears so logical be so wrong? Is it wrong? Why is it wrong? Researchers went to work to discover the problem. It seems that these drugs share a metabolic enzyme pathway and much like cars on a busy street, not all the traffic can travel at the same time. As Plavix needs to be metabolized, this interferes with the levels of the active drug, which in turn lessens the drug’s effectiveness.
But is it true? The Principle-TIMI 44 trial examined this problem and the study was released on line before publication. They found that no association was found between PPI use and increased risk for major cardiovascular events. This study used twice the normal dose of Plavix. In a similar study using twice the dose of Plavix (150mg a day), the PACA trial (Proton Pump Inhibitors and Clopidogrel Association) found that Protonix was better than Prilosec in preserving the necessary effect of Plavix.
What to do? I am recommending to my patients that if they must take these drugs they should increase the dose of Plavix. A better choice is probably to use the H2 blockers instead of these drugs for prophylaxis of GI bleeding. If PPI’s must be used, Protonix may be the best choice in the class. More information will be presented at the American Heart Association meeting in November. Individuals who are on these combinations should discuss this with their cardiologists.
The Plavix Puzzle
It is frustrating to our patients and to practicing doctors when a wealth of contradictory information becomes available. This is primarily because medical progress advances by fits and starts and only time and further study lead to progress.One such problem is Plavix and its use as a medication to prevent sudden coronary stent closure. Even though we have been putting in drug eluting stents for a number of years, cardiologists still don’t know how long to continue antiplatelet medication with Plavix. Just to remind you, antiplatelet medication with aspirin is indefinite.
When drug eluting stents first came on the market, the recommended time for the maintenance of Plavix therapy was 3 months for sirolimus stents (Cypher) and six months for paclitaxel (Taxus) stents. Current guidelines state the need for therapy for a minimum of one year for both and consideration should be given for indefinite therapy if feasible.
We are participating in two trials which will attempt to answer this question by enrolling people into a large cohort and after one year randomizing them to Plavix or placebo and see if there is a difference in outcomes. This study, known as DAPT or Dual Antiplatelet Trial, is being led by Harvard University.
Further confusing the picture is the recent news that certain combinations of medication can interfere with Plavix absorption and metabolism. This can lead to poor outcomes with increasing abrupt stent closure even with people taking all of their medication consistently. Even worse, these medications are used together to lessen the gastrointestinal bleeding problems with Plavix and aspirin combination.
Next… Studies of proton pump inhibitors and Plavix: where do we go from here?
At low risk for cardiovascular events? Aspirin still recommended
Aspirin has long held a place in the secondary prevention of heart attack and death. In other words, there is no controversy about aspirin’s use if you have the diagnosis of atherosclerotic disease. In fact, this is a Class 1A (the highest level) indication in Cardiovascular Guidelines for practice.The controversy is: can we prevent heart attacks and death in patients who have no knowledge of their atherosclerotic burden. This is not a small group of people. It is estimated that 50 million Americans use low dose aspirin regularly for cardioprophylaxis.
Multiple trials have been done with the seminal trial being the Physicians Health Study that started in the mid 1980’s. Basically 22,071 male physicians who were age 40-84 were enrolled. The first problem was they were all men so no knowledge of women’s benefit was gained. They were randomized to take 325mg of aspirin every other day or placebo. Since even physicians are limited, they took the pills from a blister pack and in the aspirin group every other pill was a placebo.
The trial was stopped early because if you were over 50 years of age and a male you had a 44% reduction in heart attacks. A small group had chronic stable angina (i.e. secondary prevention). Although they were “enrolled improperly” the risk reduction of heart attack was 87%. Reduction of stroke and cardiovascular death were found to be inconclusive because of very low rates of occurrence.
Women got their chance in the Women’s Health Study a 40,000 patient trial that showed low dose aspirin did not lower the risk of MI but did lower the risk of stroke.
In 1994 the Antiplatelet Trialist Group published their overview of 174 randomized trials of antiplatet agents. This study included 70,000 high risk patients and 30,000 low risk patients. Again the number of females was unknown. The findings were that long-term antiplatet therapy in patients at high risk of vascular disease offers significant protection against MI, stroke and death. Cardiovascular Guidelines state that among patients with a 10-year cardiovascular risk greater than or equal to 10% this therapy is warranted. See 09/04/09 blog regarding calculating your risk.
Low dose aspirin is used. This is defined as 75-325mg a day. The use of enteric coated does not appear to reduce the risk of GI bleeding complications contrary to common belief. The lower the dose of aspirin used the lower the risk of GI bleeding.
Confused yet? Most doctors are. The best summary is that if patients who are at low risk for cardiovascular events take aspirin for an average of 6.4 years three cardiovascular events are prevented per 1000 women and four cardiovascular events are prevented for men. 2.5 major bleeding events per 1000 occurred among woman and 3.0 per 1000 men.
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