I have invited Dr. Kluger to respond to points made in my letter to him below. When I receive his comments, I will post them here.
Jeffrey Kluger, M.D.
Director of Heart Rhythm Management
Department of Cardiology Practice
Hartford Hospital / Cardiology
PO Box 5037
Hartford, CT 06102-5037
Dear Dr. Kluger:
On June 29, 2010, I was prescribed amiodarone for asymptomatic non-life-threatening premature ventricular contractions (PVCs) by electrophysiologist Dr. Stephen Prater of Atlanta. Local doctors, including Dr. Prater who prescribed the drug, say the amiodarone caused my pulmonary fibrosis (PF), a disease that developed within five months after the drug was prescribed. PF is progressive and fatal, usually within two to four years.
You were asked by Jennifer Motley, M.D., of Atlanta, to provide an expert opinion on whether the amiodarone was an appropriate standard of medical care, or if it was inappropriately prescribed. You were paid for your opinion by the Warshauer Group of Atlanta, with which Dr. Motley is affiliated. In a letter to me, Dr. Motley summarized your analysis as follows: “Our consulting expert, Dr. Kluger, is an electrophysiologist who has done research with Amiodarone. He reviewed your records and found the care you received was lacking in one main respect. Dr. Kluger felt that prescribing you amiodarone initially was a judgment call by Dr. Prater and not outside of the standard of care. However, he felt it was inappropriate for Dr. Katz not to stop the amiodarone in December and evaluate you for pulmonary toxicity at that time, as symptoms had already developed. That being said, he pointed out that you had a pulmonary process that predated the amiodarone. There is clearly evidence of this pulmonary condition in 2002…”
It’s particularly interesting that Dr. Prater, in January 2011 immediately after Dr. Katz in December 2010 took no action, also declined to stop the amiodarone. He also saw no particular need to evaluate me himself or arrange for an accelerated appointment with a pulmonologist in that appointment.
As you no doubt know, medical mistakes in the U.S. account for an estimated 200,000 fatalities per year, and suffering without immediate death for hundreds of thousands more. Medical mistakes are the third leading cause of death in the nation, after only heart disease and cancer. Little to no progress has been made by the medical profession in these deplorable statistics in the past ten years.
Since your opinion is counter to that of a number of local doctors, I hope you’ll clarify it. I’m collecting information about amiodarone for a book. I spent much of my life as a newspaper reporter and editor, and journalism professor at the Universities of Wisconsin and Georgia. Over the years, I’ve had thousands of articles and 17 books published. Five of the books deal with medical subjects, cancer in particular. I’m a past state director of the American Cancer Society, the American Lung Association, and several other health charities.
My goal in writing about amiodarone, if I live long enough to finish it, is to alert the public to the damage being done by cardiologists and electrophysiologists unnecessarily prescribing this dangerous drug. I hope to make the public more aware of how amiodarone entered the American medical scene without clinical trials overseen by the Food and Drug Administration.
You were likely unaware of my particular circumstances when you rendered your paid opinion. So let me provide those details, please, and invite your further comment. I want to get the story right. If anything I say below is incorrect, please let me know promptly so I can include your corrections in my account. If, on the other hand, I’m right and your opinion is wrong, there’s only one way for you to repair that - and that’s by correcting your initial opinion. If you agree that you were wrong after reading this, you will know the right and ethical thing is to do.
First, let me cover how the amiodarone came to be prescribed for me. I had a quintuple bypass in July 2009. The surgery was successful, and the surgeon who performed it said it should give me another ten years of life expectancy - out to the year 2019.
In the spring of 2010, I began a cardiac rehabilitation program at Piedmont Hospital in Atlanta. While taking the course, my heart was monitored for two hours twice weekly.
After several of these cardiac classes, a nurse named Joann Gorrell of Piedmont Hospital on May 10, 2010, notified my cardiologist, Dr. Stuart Katz, that I was having asymptomatic premature ventricular contractions. Note the nurse’s use of the word asymptomatic - I had no life-threatening symptoms such as dizziness or blacking out. She wanted the cardiologist to see me before I went further in the course. Dr. Katz referred me to the electrophysiologist, Dr. Prater.
In my first visit with Dr. Prater on June 2, 2010, he said the PVCs were not life-threatening and required no action. The PVCs were some doubles and an occasionally triple when I exerted myself on exercise machines. I had no quintuples or above, which Dr. Prater said could be life-threatening. So Dr. Prater, the electrophysiologist who eventually prescribed the amiodarone for me, himself admits that prescribing it was inappropriate in my case, and contrary to reasonable care. As I usually do at meetings with physicians, I taped the session on a microcassette with Dr. Prater’s permission, and my wife was present with me at the appointment, as she is at almost all my medical appointments.
Unfortunately for me, the nurses at Piedmont insisted that I go back to Dr. Prater because I continued to have the minor PVCs during exercise. I had my second appointment with Dr. Prater on June 30, 2010. This time he prescribed 200 mg of amiodarone for me “to improve my quality of life.”
Based on my research to date, amiodarone is most appropriately prescribed in cases of atrial fibrillation, not the non-life-threatening PVCs I was experiencing. It seems pretty obvious to me that the prescription was to blow me off so the nurses at Piedmont Cardiology would stop sending me to bother him. I also taped this session with Dr. Prater, and my wife was present.
No baseline testing as recommended by the FDA, not even the taking of a chest x-ray, was done at the time the amiodarone was prescribed. Nor was I given any warning by the doctor of the dangerous side effects of the drug.
My quality of life before the amiodarone was prescribed was great - I was something of a gym rat, and I was working out regularly not only at Piedmont Cardiac Rehab but at the Bally’s near my home. Aside from gym exercise like swimming, weight lifting and machine aerobics at Bally’s, I was mowing the grass at home and cutting down trees with my chain saws. I was traveling when and where I wanted. But that would not go on for long.
By Thanksgiving in November 2010, only five months after I began taking the amiodarone, I was beginning to have trouble breathing.
In December 2010, I had an annual physical with cardiologist Dr. Stuart Katz. At the time, I pointed out to him and his nurse Lisa not only my breathing difficulties, but the blueness (cyanosis) around my fingers. I specifically asked him if the amiodarone could be the cause of my breathing difficulties and cyanosis. He didn’t think so. It turned out, he told me later, that he didn’t know the symptoms of amiodarone poisoning even though he bills himself as a cardiologist. He ordered no appropriate tests to determine if I was suffering from amiodarone toxicity, and so far as I know, he did not notify Dr. Prater who was in the same practice at the Piedmont Heart Institute. I taped the session with the permission of Dr. Katz.
Between the December 16, 2010, appointment with Dr. Katz, and the January 17, 2011, appointment with Dr. Prater, my wife and I began talking about our concerns with two well respected nurses who live in our neighborhood.
At the January 17, 2011, appointment, I informed Dr. Prater about the shortness of breath and cyanosis, asking if amiodarone could be at fault. Dr. Prater was still in denial about the amiodarone. He thought it was still good for me, despite the drug’s history of causing life-threatening pulmonary, thyroid, vision and other problems. He suggested that I reduce the dosage from 200 to 100 mg. daily. Thinking that something else might be the cause of my pulmonary problems (such as congestive heart disease, which I did not have - an echocardiogram indicated my rebuilt heart was as good as an astronaut’s), he suggested that I see a pulmonologist. I made an appointment with Dr. Kenneth Melby of the Atlanta Pulmonary Group for January 31, 2011.
In his report on my January 31 appointment with him, Dr. Melby says I had no prior history of lung disease before the appointment. Dr. Melby took two x-rays on January 31, and showed me shadows in the lower quadrants of my lungs indicating significant fibrotic damage to the lower part of both my lungs. He was not sure what had caused the anomalies, but wanted me to come back to see him.
On February 7-8, three nurses - one from our neighborhood, one the nurse for Dr. Victor E. Corrigan (Dr. Corrigan did the catheterization before my bypass surgery), the third Dr. Prater’s own assistant, ganged up on him, saying I had all the symptoms of amiodarone poisoning. On February 8, I received a phone call from Dr. Prater’s assistant Michell saying Dr. Prater wanted me to discontinue the amiodarone. By that time, the damage was done. I’d been unnecessarily given a death sentence to quiet down an anxious cardiac rehab nurse.
Now, let’s consider the interstitial lung disease dating to 2002 that you mention.
I’ve had annual chest x-rays plus other x-rays and CT scans over the years from 2002 through 2010. Not once did a physician ever mention that I was showing any signs of lung disease. Not until I saw Dr. Leslie Watters of the Atlanta Pulmonary Group on July 26, 2011, did any doctor ever mention any symptoms of pulmonary disease dating to 2002. Dr. Watters was the first. Dr. Katz, who would have received the analysis of my annual physical chest x-rays, never once mentioned any signs of interstitial lung disease on my annual physical and other chest x-rays. His partner, Dr. Steinberg, who I occasionally saw, never mentioned it. Dr. Victor E. Corrigan, who did two heart catheterizations on me over the years, never mentioned it. Dr. John Gott, the surgeon who did the quintuple bypass on me in July 2009, and who had access to extensive chest x-rays and other scans taken before and after the surgery, never mentioned it. The logical conclusion is that none of these doctors thought I had any pulmonary symptoms worthy of mention in the period 2002-2010.
In an appointment I had with pulmonologist Dr. Kenneth Melby on August 11, 2011, Dr. Melby told me that he and Dr. Prater were in agreement that my pulmonary fibrosis was the result of amiodarone toxicity. By this time, Dr. Melby had left the Atlanta Pulmonology Group and joined another practice. I was continuing to see him, but also began seeing Dr. Leslie Watters of the Atlanta Pulmonology Group.
As you know, Dr. Kluger, there is no treatment or cure for pulmonary fibrosis. The only possible action is a lung transplant. Drs. Melby and Watters referred me to the Emory University McKelvey Center for Lung Transplantation in Atlanta, the only institution in Georgia that does lung transplants. I had my first appointment with Dr. David Neujahr of the transplant center on October 4, 2011. The upshot was that Emory has never done a transplant on anyone over seventy years of age because of low life expectancy following the transplant(s). I’m seventy-four. However, Dr. Neujahr did indicate that Emory considers amiodarone as a dangerous drug that should only be prescribed in extenuating circumstances. My circumstances were not extenuating.
I wanted validation from a second electrophysiologist about the appropriateness of amiodarone being prescribed for me. I checked with a number of resources, and the name that came up as someone I could trust was Dr. David Wilson, an electrophysiologist who practices in Lawrenceville, Georgia., and at St. Joseph’s Hospital in Atlanta, where the Atlanta Pulmonology Group offices are located. I had my first appointment with him on October 12, 2011. At that appointment, which I taped, and at which my wife was present, Dr. Wilson emphasized that he would not have prescribed amiodarone for me based on the EKG strips from my sessions at the Cardiac Rehabilitation Program at the Piedmont Hospital Fuqua Heart Center. So we have a respected electrophysiologist who disagrees with you that Dr. Prater’s prescription of amiodarone was appropriate for me and within the standard of care. You say that it is your opinion that “prescribing you amiodarone initially was a judgment call by Dr. Prater and not outside of the standard of care.” At least one of your peers disagrees with your conclusion.
One of the unfortunate things about amiodarone is that cardiologists are freely prescribing this dangerous drug for many off-label, non-life-threatening conditions, and failing to warn the people who get the prescriptions of the dangerous side effects of the drug. That leaves the pulmonologists having to clean up the messes created by these physicians prescribing amiodarone for all sorts of off-label conditions .
On February 21, 2012, I had an opportunity to attend a two-hour discussion with Dr. Remzi Bag, M.D., who is now medical director of lung transplantation at Emory University Hospitals’ McKelvey Center. Before coming to Emory, Dr. Bag served as chief of the lung transplant and pulmonary hypertension division of INTEGRIS Baptist Medical Center in Oklahoma City, Oklahoma. He also has served as the director, lung and heart-lung transplant programs, at St. Luke’s Episcopal Hospital, and as director, pulmonary transplant program, at Baylor College of Medicine and The Methodist Hospital in Houston.
Asked about amiodarone at that session, Dr. Bag responded that cardiologists and electrophysiologists like you seem to think the drug is harmless and a great boon, but it is the pulmonologists who are left with no option other than lung transplants to repair the damage often unnecessarily done by amiodarone. It would appear that Dr. Bag’s credentials are at least equal to if not considerably in excess of your own expertise. So when you conclude in my case that “prescribing you amiodarone initially was a judgment call by Dr. Prater and not outside of the standard of care,” you will forgive me for questioning the accuracy of your statement. It sounds to me - my opinion, admittedly - that you are trying to protect the rear end of another electrophysiologist.
Let me conclude with various FDA recommendations and warnings to physicians prescribing amiodarone - recommendations and warnings that are being widely ignored either deliberately or out of ignorance by physicians.
· There have been post-marketing reports of acute-onset (days to weeks) pulmonary injury in patients treated with oral amiodarone with or without initial I.V. therapy. Findings have included pulmonary infiltrates and/or X-ray, pulmonary alveolar hemorrhage, pleural effusion, bronchospasm, wheezing, fever, dyspnea, cough, hemoptysis, and hypoxia. Some cases have progressed to respiratory failure and/or death. Post-marketing reports describe cases of pulmonary toxicity in patients treated with low doses of amiodarone; however, reports suggest that the use of lower loading and maintenance doses of amiodarone are associated with a decreased incidence of amiodarone-induced pulmonary toxicity.
· Amiodarone hydrochloride tablets may cause a clinical syndrome of cough and progressive dyspnea accompanied by functional, radiographic, gallium-scan, and pathological data consistent with pulmonary toxicity, the frequency of which varies from two to seven percent in most published reports, but is as high as ten to seventeen percent in some reports. Therefore, when amiodarone therapy is initiated, a baseline chest X-ray and pulmonary-function tests, including diffusion capacity, should be performed. The patient should return for a history, physical exam, and chest X-ray every three to six months. (None of these underlined recommendations were observed in my case.)
· Patients with preexisting pulmonary disease have a poorer prognosis if pulmonary toxicity develops. (I was never told I had any pre-existing pulmonary condition - but surely if it was there, Dr. Prater would have been aware of it, is that not correct?)
· Interstitial/alveolar pneumonitis may result from the release of oxygen radicals and/or phospholipidosis and is characterized by findings of diffuse alveolar damage, interstitial pneumonitis or fibrosis in lung biopsy specimens. Phospholipidosis (foamy cells, foamy macrophages), due to inhibition of phospholipase, will be present in most cases of amiodarone-induced pulmonary toxicity; however, these changes also are present in approximately fifty percent of all patients on amiodarone therapy. These cells should be used as markers of therapy, but not as evidence of toxicity. A diagnosis of amiodarone-induced interstitial/alveolar pneumonitis should lead, at a minimum, to dose reduction or, preferably, to withdrawal of the amiodarone to establish reversibility, especially if other acceptable antiarrhythmic therapies are available. Where these measures have been instituted, a reduction in symptoms of amiodarone-induced pulmonary toxicity was usually noted within the first week, and a clinical improvement was greatest in the first two to three weeks. Chest X-ray changes usually resolve within two to four months. According to some experts, steroids may prove beneficial. Prednisone in doses of 40 to 60 mg/day or equivalent doses of other steroids have been given and tapered over the course of several weeks depending upon the condition of the patient.
· In a patient receiving amiodarone, any new respiratory symptoms should suggest the possibility of pulmonary toxicity, and the history, physical exam, chest X-ray, and pulmonary-function tests (with diffusion capacity) should be repeated and evaluated. A fifteen percent decrease in diffusion capacity has a high sensitivity but only a moderate specificity for pulmonary toxicity; as the decrease in diffusion capacity approaches thirty percent, the sensitivity decreases but the specificity increases. A gallium-scan also may be performed as part of the diagnostic workup.
· Fatalities, secondary to pulmonary toxicity, have occurred in approximately ten percent of cases. However, in patients with life-threatening arrhythmias (I did not have life-threatening arrhythmia), discontinuation of amiodarone therapy due to suspected drug-induced pulmonary toxicity should be undertaken with caution, as the most common cause of death in these patients is sudden cardiac death. …
· If a diagnosis of amiodarone-induced hypersensitivity pneumonitis is made, amiodarone should be discontinued, and treatment with steroids should be instituted. If a diagnosis of amiodarone-induced interstitial/alveolar pneumonitis is made, steroid therapy should be instituted and, preferably, amiodarone discontinued or, at a minimum, reduced in dosage. Some cases of amiodarone-induced interstitial/alveolar pneumonitis may resolve following a reduction in amiodarone dosage in conjunction with the administration of steroids. In some patients, rechallenge at a lower dose has not resulted in return of interstitial/alveolar pneumonitis; however, in some patients (perhaps because of severe alveolar damage) the pulmonary lesions have not been reversible.
I eagerly await your comments
Sincerely,
/s/ Noel L. Griese
Noel L. Griese
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