Heart Failure

Compromising Combinations

As disturbing as it might be to me, it appears that the FDA does not read my blog. I have written several times about the controversy concerning the combination of the drugs Plavix and the proton pump inhibitors. I and many other more prominent and learned cardiologists than I thought the controversy was resolved by the publication of the articles mentioned in my last blog on the subject.On November 17 during the American Heart Association meeting in Orlando, the FDA issued a public health warning on the "possible interaction" between Plavix and one proton pump inhibitor Prilosec.

Apparently the FDA was not swayed by the data from COGENT which I have reviewed in previous blogs. Maybe they know something that we have not been told. They have required the manufacturers to update the label of Plavix. The "label" is that piece of folded up tissue paper that you sometimes get with new drug prescriptions that is written in micro type and reads like Greek.

It should be noted that although no other members of the proton pump inhibitor class were mentioned, the drugs that the FDA recommended to use with Plavix are the H2 antagonists such as Pepcid or Zantac. Tagamet cannot be used as it is metabolized the same pathway that Plavix is and will have the same consequences that the use of Prilosec will.

If you are taking Plavix and need help with the risk of GI bleeding your doctor will be the person to ask what you should do. The "safest" decision may be to take the H2 blockers mentioned and forget about it. If doctors other than your primary doctor or cardiologist try to put you on other medication, it is your responsibility to help us and tell us all the medications you are on. It is always a wise idea to check with your primary doctor when any changes are made to your medications.

I can guarantee you that this is not the last we have heard on this topic. I will continue this discussion as data is presented.

Weighing Your Surgical Options

I have over the last several blogs pointed out how ideas, when they come to medicine, need to be rigorously tested. I want to travel back to the original question which is "who needs coronary bypass or angioplasty to manage their coronary artery disease?" It is important to remember as I have blogged before that management of this illness is medically based. Patients need to stop smoking, manage their cholesterol with statins and diet, exercise, control diabetes and high blood pressure. At times, it becomes necessary to provide revascularization because primarily chest pain or angina is life limiting. This means that your lifestyle is hindered. This equation is different for a 45 year old man than an 85 year old man and realistic goals need to be put in place.

Angioplasty can often be easily done but does not provide a mortality benefit or a prevention of myocardial infarction. It is a treatment of symptoms that do not respond to medical management. Surgery is much the same. However, if you have left main disease or poor heart function with three vessel disease you will live longer if you have bypass surgery instead of medical management alone.

The method of surgery should be discussed with your surgeon and depends on the placement of your arteries, and the condition of the segments needed for bypass targets and other technical concerns. Also important is the surgeon's case level and whether he or she is comfortable with the procedures required.

The concept of "minimally invasive surgery" and robotic surgery is untested at this time and is purely a variation that requires a good hard look. It was widely felt that off pump surgery would be better but that is not the case. Robots are very expensive and it remains to be seen whether the whole idea is worth the trouble and expense.

One further point about the ROOBY study is that it again proved the point about getting a complete operation. What I mean by that is that all the vessels that need to be fixed need to be fixed. Although that sounds silly, angioplasty will often target only certain arteries and "manage" the others. Off pump did a poorer job of bypassing all the vessels needed. This approach leads to worse outcomes with increased need for reoperation, angina and death. As always you should have a thorough understanding of what is wrong and what your options are. If you don't get the answers you need continue to ask until you do.

Off Pump Study Results Recently Revealed

Published in the New England Journal of Medicine earlier this month were the findings of the ROOBY study (NEJM 2009; 361:1827-37). The Randomized On/Off Bypass study group was comprised of 18 VA medical centers and was conducted from February 2002 to May 2008. More than 9,600 patients were screened for entry into the study; 7,460 were excluded because they had poor target vessels, would not give consent, or their surgeons were not a participant; 2,203 were randomized and 1,104 were assigned to off pump, while 1,099 were assigned to on pump randomly. Of the1,104 randomized patients to off pump, 137 needed the bypass machine for the operation to be completed. Interestingly, of the 1,099 patients who were randomized to on pump operations, 43 were converted to off pump.

The results showed there was no significant difference in the 30 day composite outcome--7.0% for off pump and 5.6% for on pump. The composite was death or the complications of reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure.

Further, the results for the one year outcome were worse: off pump 9.9% vs. 7.4 % for on pump. The 1-year composite was death from any cause, repeat revascularization procedure, or a nonfatal myocardial infarction.

Follow up angiograms revealed the overall patency rate of the bypass grafts was 82.6% in the off pump group and 87.8% in the on pump group. The off pump group had a higher proportion of arteries not able to be bypassed 17.8% vs. 11.1%. There were no differences in neurocognitive outcomes or short term use of major resources.

Overall, this study showed that patients who had the standard operation did better. This result is similar to the findings of a recent Meta analysis and of several other smaller studies. Single center and single surgeon studies fare better and reflect different surgical abilities but do not reflect "real world" outcomes. In this study, you needed to have done at least 20 off pump cases to be considered an investigator.

There are several problems with this study -- the most glaring is that it is almost exclusively an all-male study. Remember it was done at the VA and in spite of the different composition of our armed forces at the present time most women who are veterans are not at the age to need this type of medical care. These results can not be generalized to women who often have poorer bypass targets and would be expected to have poorer outcomes.

Next...putting this information in context.

Off the Beating Path

Off-pump coronary artery bypass surgery was developed during the 1990s. The reason that the heart-lung machine is necessary during the operation is that it provides blood and oxygen to the body and brain while the heart is stopped. The heart needs to be still so that the surgeons can sew the veins and arterial conduits on to the arteries that need to be bypassed. In the best of circumstances this is complicated. The heart arteries are buried under the pericardial fat on the surface of the heart. They are 1-2 mm in diameter without blood. Surgeons wear special glasses called loops to provide powerful magnification so they can see these structures to sew to. The surgery requires the area to be motionless so this can be accomplished. This is why the heart is stopped.Off-pump surgery was promoted as a way to possibly manage some of the consequences of coronary bypass surgery using a bypass machine. These, in theory, included better operative mortality, improved late mortality, less perioperative morbidity, better neurocognitive outcomes, less resource utilization and the ability to operate on high risk patients with improved outcomes.

The technique was originally the brainchild of an ah-ha moment. A surgeon realized that when one small area of the heart was touched that it did not move. He basically took a spoon and cut a hole in the center of it, pressed it over the area of artery that he wanted to operate on and it was still enough to accomplish the sewing that needed to be done.

The medical device companies put their best minds on it and soon a wide variety of devices were available to do this work. All, I might add, significantly more complicated and expensive than a spoon with a hole cut in it. Most involve some degree of suction on the heart to stabilize and position it while it is allowed to beat. There is a learning curve to this and not all surgeons do it. Some started doing it exclusively and some never do it. Some operations are done both ways to lessen the amount of time on the bypass machine.

But does it matter? Does it provide any benefit? This is where research comes in. A comparison study between the two techniques was performed and reported recently. In my next blog, I will again point out that if you ask a question you may be surprised at the answer.

The Libby Zion Law

Sidney Zion who died recently began a crusade against what he felt was his daughter’s death due to inadequate staffing and negligence.  The doctors had mixed two drugs that can have unfortunate consequences and in this case death.  This is known as the serotonin syndrome.  This occurred through lack of knowledge or by mistake because the levels of training were not adequate.  The 36 hour shift became a flash point in the case.

In 1986 a grand jury was impaneled to consider murder charges.  The grand jury declined to indict them for murder.   There were trials both malpractice and civil.  There were multiple state medical board hearings.  At the conclusion the doctor’s insurance company paid $375,000 for “pain and suffering” to the family.  The two residents were censured for acts of gross negligence.  This did not affect their right to practice.  One of them, Gregg Stone, is a prominent cardiovascular researcher who still is at Columbia in New York.

As a direct result of this case and the crusading efforts of Sidney Zion, the New York State Department of Health Code, Section 405, became known as the Libby Zion law.  It limits the amount of resident work to 80 hrs per week.  In 2003, The Accreditation Council for Graduate Medical Education adopted similar regulations for all medical training programs in the United States.

This change has led to unintentional consequences.  It has led to a different philosophy among medical graduates that while not wrong is different than the philosophy of those that came before Libby.  Many graduates now want limited work hours in private practice and extensive time off that older physicians find alarming.  This limitation of work leads to the worsening of an already acute lack of physicians at times.  This coupled with the momentous changes that confront us as we move to health care reform and the decreasing numbers of new physicians may led to doctor shortages especially in those areas of the United States that are chronically underserved.

Next…what about doctors in private practice?

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The Case of Libby Zion and What She Means to the Medical Community

Sometimes the death of an individual has long lasting permanent consequences far removed from the tragedy for the family.  Physicians who presently are in practice are dated from either before or after the death of this individual.  Who was Libby Zion and why does she mean so much to physicians?

There is now a profound difference in the way all doctors are trained that can be dated to after Libby Zion’s death.  Although there is a touch of “when I was a child, I walked to school through 10-foot high snow drifts in the sub-zero temperature” when doctors my age trained we worked until we were finished.  What did that mean?  I worked for thirty-six hours and was off 12 hours.  The off 12 occurred if you were finished with your patient care responsibilities.  This was not all the time but it was when you were on primary hospital training and could last for three months at a time before you were rotated to another service with less time requirements.

In practice this prepared us for what can sometimes happen.  That is having to work through the night and then the next day.  Whether this was sound theory or practice was never really questioned.  It was the “way it had always been done.”

Libby Zion was an 18 year old freshman at Bennington College with a history of depression.  She was admitted to the New York Hospital Cornell Medical Center on March 4, 1984 during the evening shift.  She had a history of ongoing depression and was complaining of fever, agitation and jerking motions of her body.  No diagnosis was provided but she was admitted to the ward and cared for by two new physicians, one with eight months of experience and one with twenty months.  She was given a pain killer and a sedative and was felt to have a viral syndrome and that “she was acting out.”

At 3:00 am , she became more agitated and the doctor ordered restraints and an antipsychotic to be injected.  She was not seen again.  At 6:30am in the morning, her temperature was 107.6 and soon after she suffered a cardiac arrest and died.  It might have ended there except Libby’s father was Sidney Zion, a journalist.

Next…the long battle.

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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...

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.