Doctors are all familiar with marketing efforts to promote new drugs, but once the new drugs displace older drugs in the medical marketplace, who serves as advocates for the continued manufacture of older FDA-approved drugs?
In a short answer: no one.
For those of us dealing in cardiac arrhythmia management, this presents difficult challenges to patient care if people are unable to take the newer drugs due to side effects. These patients no longer have a fall-back option to turn to for medical therapy when the older drugs have become extinct on the marketplace.
Examples of antiarrhythmics that have reached extinction status in the US include many of our older antiarrhythmic drugs such as procainamide, mexilentine or quinaglute.
Take for instance a recent case: A older person with recurrent ventricular tachycardia and congestive heart failure and ICD implantation who has experienced several appropriate shocks for hemodynamically-significant ventricular tachycardia from their ICD. They were not in heart failure and had a consistent ideal body weight. Beta blocker medications have been maximized. This same person is pacemaker dependent and allergic to Amiodarone and iodine. Sotalol was not tolerated and dronedarone is contraindicated because of heart failure. Their creatinine clearance is 40. The patient was placed on mexilentine in the hospital and did well, only to find after discharge that no pharmacies could obtain the drug any longer. Oral procainamide, I have found, has suffered the same fate long ago. Few options remain: dofetilide as an inpatient?
Perhaps.
Still, the issue of drug extinction is a challenging one: not enough market to justify the drug's manufacture, yet still a rare patient out there who might need an older medication. Even generic drug manufacturers won't manufacture these niche drugs - there's just not enough of a market to justify their manufacture and the regulatory environment precludes a small start-up company from even trying to meet the very small demand.
I wish I had an answer to this conundrum. How do others handle this situation?
-Wes
Showing posts with label ventricular tachycardia. Show all posts
Showing posts with label ventricular tachycardia. Show all posts
Monday, May 03, 2010
Thursday, December 27, 2007
VT Ablation and the Ankle Swelling Index
I read with interest this week's lead article in the New England Journal of Medicine that evaluated whether prophylactic catheter ablation of ventricular tissue would reduce the incidence of later implantable cardioverter-defibrillator (ICD) shocks called "SMASH-VT:" Substrate Mapping and Ablation in Sinus Rhythm to Halt Ventricular Tachycardia.
"Substrate modification," for those unfamiliar, is a term used by electrophysiologists to change the underlying milleu of the heart to prevent arrhythmias. This is performed by using a three-dimentional mapping system (Biosense-Webster's Carto system was used in this study exclusively) to define where small-amplitude (i.e, less than 1.5 mV in amplitude and implicitely thought to be abnormal) electrogram signals were detected within the heart. These areas were labeled as "scar" within the interior of the heart. By ablating, or burning, areas within the scar, it is hoped to disrupt the potentially life-threatening reentrant circuits that cause the abnormal heart rhythms that cause ICDs to fire. Many ablation lesions are used to create the "lines" that disrupt these circuits.
But the process of determining where to ablate in these cases is laborious and time-consuming. First, not all ablation was performed in sinus rhythm, as the pseudonym of the trial would suggest. The authors did try to induce ventricular tachycardia in the patients, and even tried to have rapid arrhythmias slowed with a class Ic antiarrhythmic to define the predominant clinical ventricular arrhythmia to target. Adding to the complexity of the studies performed, fully 74 percent of the patients underwent both a transseptal (crossing a catheter from the right to the left atrium to access the left ventricle) and simultaneous retrograde aortic approach (reaching the left ventricle by passing the ablation catheter up the femoral artery backward through the aortic valve and into the left ventricle).
It is an impressive tour d' force to perform these procedures. All in the name of reducing ICD shocks in the patient with an indwelling ICD and a history of ventricular tachycardia. Electrophysiologists reading this study know this.
So I found it interesting that I could not estimate my own Ankle Swelling Index (ASI) accurately from this study. That's the index of how large my ankles will become after standing at the patient's bedside to perform this procedure. A one-hour procedure gives an Ankle Swelling Index of 1, a two-hour procedure gives an ASI of 2, and so on. You see the reason I could not estimate this accurately is because no ablation times or radiation exposure times were mentioned in this study. Why? Were they excessive?
Instead, I must estimate. So given the complexity of the ablation procedure described in this study, I estimate the procedure times for each of each of these patients to exceed four hours each: an ASI greater than 4. And I would not be surprised if several indexes were over 5.
Man. That's huge.
It's huge because, like it or not, to ever apply prophylactic ventricular ablation to prevent ICD shocks in a patient who has already received (or will receive) an ICD, the time spent for both the patient and the doctor has to be worth the risks involved in long procedures. The complexities of this ablation approach, while shown to be feasible and safe (at least in this small group of carefully-selected patients), it was by no means without risk (three of the ablation patients had some complications). Further, not reporting the time required to implement this approach has serious implications for recommending the type of anesthesia and estimating whether these patients with limited ventricular function can lie recumbent long enough to undergo the procedure.
So while there appears to be a role for substrate-based catheter ablation to prevent ICD shocks, careful evaluation for the Ankle Swelling Index as well as the risks inherent to the ablation approach used in this sick patient population should be considered carefully before applying this approach to every patient receiving an ICD for the indiction of ventricular tachycardia or ventricular fibrillation.
-Wes
References:
Reddy VY, Reynolds MR, Neuzil P, Richardson AW, Taborsky M, Jongnarangsin K, Kralovec S, Sediva L, Ruskin JN, Josephson ME. "Prophylactic Catheter Ablation for the Prevention of Defibrillator Therapy." N Engl J Med Dec 27, 2007: 357(26): 2657-2665.
Editorial: Estes NAM. "Ablation after ICD Implantation — Bridging the Gap between Promise and Practice." N Engl J Med Dec 27, 2007; 357(26): 2717-2719.
"Substrate modification," for those unfamiliar, is a term used by electrophysiologists to change the underlying milleu of the heart to prevent arrhythmias. This is performed by using a three-dimentional mapping system (Biosense-Webster's Carto system was used in this study exclusively) to define where small-amplitude (i.e, less than 1.5 mV in amplitude and implicitely thought to be abnormal) electrogram signals were detected within the heart. These areas were labeled as "scar" within the interior of the heart. By ablating, or burning, areas within the scar, it is hoped to disrupt the potentially life-threatening reentrant circuits that cause the abnormal heart rhythms that cause ICDs to fire. Many ablation lesions are used to create the "lines" that disrupt these circuits.
But the process of determining where to ablate in these cases is laborious and time-consuming. First, not all ablation was performed in sinus rhythm, as the pseudonym of the trial would suggest. The authors did try to induce ventricular tachycardia in the patients, and even tried to have rapid arrhythmias slowed with a class Ic antiarrhythmic to define the predominant clinical ventricular arrhythmia to target. Adding to the complexity of the studies performed, fully 74 percent of the patients underwent both a transseptal (crossing a catheter from the right to the left atrium to access the left ventricle) and simultaneous retrograde aortic approach (reaching the left ventricle by passing the ablation catheter up the femoral artery backward through the aortic valve and into the left ventricle).
It is an impressive tour d' force to perform these procedures. All in the name of reducing ICD shocks in the patient with an indwelling ICD and a history of ventricular tachycardia. Electrophysiologists reading this study know this.
So I found it interesting that I could not estimate my own Ankle Swelling Index (ASI) accurately from this study. That's the index of how large my ankles will become after standing at the patient's bedside to perform this procedure. A one-hour procedure gives an Ankle Swelling Index of 1, a two-hour procedure gives an ASI of 2, and so on. You see the reason I could not estimate this accurately is because no ablation times or radiation exposure times were mentioned in this study. Why? Were they excessive?
Instead, I must estimate. So given the complexity of the ablation procedure described in this study, I estimate the procedure times for each of each of these patients to exceed four hours each: an ASI greater than 4. And I would not be surprised if several indexes were over 5.
Man. That's huge.
It's huge because, like it or not, to ever apply prophylactic ventricular ablation to prevent ICD shocks in a patient who has already received (or will receive) an ICD, the time spent for both the patient and the doctor has to be worth the risks involved in long procedures. The complexities of this ablation approach, while shown to be feasible and safe (at least in this small group of carefully-selected patients), it was by no means without risk (three of the ablation patients had some complications). Further, not reporting the time required to implement this approach has serious implications for recommending the type of anesthesia and estimating whether these patients with limited ventricular function can lie recumbent long enough to undergo the procedure.
So while there appears to be a role for substrate-based catheter ablation to prevent ICD shocks, careful evaluation for the Ankle Swelling Index as well as the risks inherent to the ablation approach used in this sick patient population should be considered carefully before applying this approach to every patient receiving an ICD for the indiction of ventricular tachycardia or ventricular fibrillation.
-Wes
References:
Reddy VY, Reynolds MR, Neuzil P, Richardson AW, Taborsky M, Jongnarangsin K, Kralovec S, Sediva L, Ruskin JN, Josephson ME. "Prophylactic Catheter Ablation for the Prevention of Defibrillator Therapy." N Engl J Med Dec 27, 2007: 357(26): 2657-2665.
Editorial: Estes NAM. "Ablation after ICD Implantation — Bridging the Gap between Promise and Practice." N Engl J Med Dec 27, 2007; 357(26): 2717-2719.
Sunday, January 28, 2007
The Supplication
“Dear God,
I bet it is very hard to love all of every body in the world. There are only 4 people in our family and I could never do it.”
– Nan
***
“Dear God,
Thank you for my baby brother but what I prayed for was a puppy.”
- Joyce
***
"Dear God,
Instead of letting people die and having to make new ones, why don't you just keep the ones you got now?"
- Jane
***
She was a 38 year-old mother of two kids with a warm personality and delightful smile. She had been plagued much her life with asthma but she had otherwise been fairly healthy. Her heart, she disclosed to her internist, had this nasty propensity to race when she became upset, exercised, or used her inhaler often. She complained about this to her doctor who ordered an exercise stress test and this is what it showed after 5 minutes of exercise:
For those not used to seeing an EKG, this one’s not normal. It demonstrates a rapid, wide-complex ventricular tachycardia (rapid heart rhythm arising in the lower chambers of the heart). The left bundle branch, inferior axis morphology suggested the ventricular tachycardia arose from the right ventricular outflow tract, just beneath the pulmonary valve. Although the cardiologist performing the exercise stress test usually gets a bit nervous when this rhythm starts during a treadmill test, the nice thing about this heart rhythm disturbance is it usually occurs in people with structurally normal hearts and is curable with catheter ablation (cauterizing the focus from where the arrhythmia arises). Alternative therapy with beta-blockers was not attempted because of the patient’s history of asthma.
So after carefully discussing the various therapy options with the patient, she chose catheter ablation.
“I’ll pray for you, Dr. Fisher.”
I didn’t know what to say initially, but thanked her and told her I’d see her on her surgical date.
***
Two weeks later, she arrived in our pre-op holding area with her hospital gown, IV, and surgical cap in place. Her friends and family surrounded her. She smiled contently as we prepped her for the procedure.
“Are you ready?”
“Yes I am.”
“Any last questions before we take you in the room?”
“No. You went over it pretty well during our visit.”
“Great, then we’ll get started…”
“Oh, Dr. Fisher?”
“Yes?”
“I had a dream last night. You see I prayed that your hands were guided to the exact spot of my fast heart beats. You’re going to do fine, you know.”
“Uh, sure, Ms. C. Thank you. I’ll see you in the room.”
I went to change into my scrubs and surgical attire. I entered the room and the staff were ready. I chose a simple approach using two catheters at first to make sure I could initiate the rhythm while she was sedated on our lab table. The catheters (wires) went in fine and I positioned one in the right ventricular apex and the other steerable ablation wire in the right atrium while we tried to start her rhythm in the lab.
At first we were not successful, but with the addition of a bit of Isuprel (an adrenaline-like medication we use to increase the heart rate), her tachycardia became easy to induce and was stable enough the permit careful mapping. I reached to the ablation catheter in the right atrium and placed it in the right ventricular outflow tract. The very first place I laid it appeared to be an excellent site for ablation. I couldn’t believe it. I asked my technician to pace from the ablation catheter tip. The paced EKG identically matched the spontaneous arrhythmia in all leads, even to the finest detail. The signal recorded from the ablation catheter tip preceded the surface electrocardiogram onset by 40 milliseconds (usually 30 milliseconds or so would suffice). Could it be? I dared not move the catheter.
I told my technician to prepare to perform the ablation. Once the energy settings and temperature adjustments were to my satisfaction, we applied radiofrequency energy to the tip of the ablation catheter. Her arrhythmia stopped three seconds after we started the lesion. Energy was continued for 47 seconds, then discontinued.
We tried and tried to re-initiate her heart rhythm disturbance and were no longer capable of re-starting the arrhythmia, even when she was given the Isuprel. We waited and kept trying to re-start the arrhythmia. Nothing happened. She was cured.
Total procedure time: 22 minutes.
Was it divine intervention? I have no idea. Frankly, it felt like pure blind luck. But to this day I have never had such a short, uncomplicated ablation procedure and I think back to her prediction and faith and I wonder...
-Wes
References: Kids Pray to God
I bet it is very hard to love all of every body in the world. There are only 4 people in our family and I could never do it.”
– Nan
“Dear God,
Thank you for my baby brother but what I prayed for was a puppy.”
- Joyce
"Dear God,
Instead of letting people die and having to make new ones, why don't you just keep the ones you got now?"
- Jane
She was a 38 year-old mother of two kids with a warm personality and delightful smile. She had been plagued much her life with asthma but she had otherwise been fairly healthy. Her heart, she disclosed to her internist, had this nasty propensity to race when she became upset, exercised, or used her inhaler often. She complained about this to her doctor who ordered an exercise stress test and this is what it showed after 5 minutes of exercise:
For those not used to seeing an EKG, this one’s not normal. It demonstrates a rapid, wide-complex ventricular tachycardia (rapid heart rhythm arising in the lower chambers of the heart). The left bundle branch, inferior axis morphology suggested the ventricular tachycardia arose from the right ventricular outflow tract, just beneath the pulmonary valve. Although the cardiologist performing the exercise stress test usually gets a bit nervous when this rhythm starts during a treadmill test, the nice thing about this heart rhythm disturbance is it usually occurs in people with structurally normal hearts and is curable with catheter ablation (cauterizing the focus from where the arrhythmia arises). Alternative therapy with beta-blockers was not attempted because of the patient’s history of asthma.
So after carefully discussing the various therapy options with the patient, she chose catheter ablation.
“I’ll pray for you, Dr. Fisher.”
I didn’t know what to say initially, but thanked her and told her I’d see her on her surgical date.
Two weeks later, she arrived in our pre-op holding area with her hospital gown, IV, and surgical cap in place. Her friends and family surrounded her. She smiled contently as we prepped her for the procedure.
“Are you ready?”
“Yes I am.”
“Any last questions before we take you in the room?”
“No. You went over it pretty well during our visit.”
“Great, then we’ll get started…”
“Oh, Dr. Fisher?”
“Yes?”
“I had a dream last night. You see I prayed that your hands were guided to the exact spot of my fast heart beats. You’re going to do fine, you know.”
“Uh, sure, Ms. C. Thank you. I’ll see you in the room.”
I went to change into my scrubs and surgical attire. I entered the room and the staff were ready. I chose a simple approach using two catheters at first to make sure I could initiate the rhythm while she was sedated on our lab table. The catheters (wires) went in fine and I positioned one in the right ventricular apex and the other steerable ablation wire in the right atrium while we tried to start her rhythm in the lab.
At first we were not successful, but with the addition of a bit of Isuprel (an adrenaline-like medication we use to increase the heart rate), her tachycardia became easy to induce and was stable enough the permit careful mapping. I reached to the ablation catheter in the right atrium and placed it in the right ventricular outflow tract. The very first place I laid it appeared to be an excellent site for ablation. I couldn’t believe it. I asked my technician to pace from the ablation catheter tip. The paced EKG identically matched the spontaneous arrhythmia in all leads, even to the finest detail. The signal recorded from the ablation catheter tip preceded the surface electrocardiogram onset by 40 milliseconds (usually 30 milliseconds or so would suffice). Could it be? I dared not move the catheter.
I told my technician to prepare to perform the ablation. Once the energy settings and temperature adjustments were to my satisfaction, we applied radiofrequency energy to the tip of the ablation catheter. Her arrhythmia stopped three seconds after we started the lesion. Energy was continued for 47 seconds, then discontinued.
We tried and tried to re-initiate her heart rhythm disturbance and were no longer capable of re-starting the arrhythmia, even when she was given the Isuprel. We waited and kept trying to re-start the arrhythmia. Nothing happened. She was cured.
Total procedure time: 22 minutes.
Was it divine intervention? I have no idea. Frankly, it felt like pure blind luck. But to this day I have never had such a short, uncomplicated ablation procedure and I think back to her prediction and faith and I wonder...
-Wes
References: Kids Pray to God
Subscribe to:
Posts (Atom)