From Device to Debris

The recent problems of Medtronic's Fidelis leads in defibrillator-pacemakers reminded me of the sea change that has occurred in medical therapeutics.

Device therapeutics has fast become a major mode of treatment in a variety of fields including cardiology, as new targets for drug therapy have become limited. In the old days, if the physician observed an adverse drug effect, the antidote was easily accomplished by stopping the medication. That is not to say that there were no long-term effects of disastrous proportion associated with oral or intravenous therapy. Drug-induced hepatitis, agranulocytosis, and shock, to name a few, still are potential adverse effects with parenteral or oral drug administration.

But with the development of device therapy, dealing with adverse events has become much more complicated. The advent of the implantable pacemaker seems to be the watershed device that changed the therapeutic landscape. I recall talking to Dr. Bill Chardack, a surgeon and coinventor with Wilson Greatbach of the implantable transvenous pacemaker in the mid 1960s about the issue of removing the right ventricular catheter should the site become infected or the catheter cease to function. His response was “that the issue was getting them in, not getting them out.” Well, a lot of catheters have been implanted since then, and many have become dysfunctional and remain in patients and can now be classified as biological “debris.”

Artificial heart valves, particularly in their early developmental stages, had to be removed as a result of thrombus formation or structural failure. Many of these valve failures required emergency surgery. Later, cracks developed in some of the aortic valve struts, which again led to both urgent and prophylactic surgery when they were identified with special x-rays. The implantation of many and varied of coronary stents, which obviously cannot be removed, created a new mechanical disease superimposed onto naturally occurring coronary artery disease. Most recently, a host of new devices has emerged that remodel the left ventricle or defibrillate it depending upon the therapeutic target. Many of these are experimental, meaning that they may or may not be of therapeutic benefit, and are implanted into the heart without any “exit strategy” should they be shown to be ineffective or hazardous.

The most troubling among them are the defibrillators. Patients have been told that without such a device they are facing imminent death. Implantation of this device has been advised on the basis of guidelines that presume that the rate of adverse events is small and the benefit is large. The benefit remains the same, but now, in the face of increased adverse events, the equation has changed. It does appear that most of the 150,000 Fidelis leads need to be disconnected (“Removing Medtronic Heart Cables is Hard Choice,” New York Times, April 7, 2009, p. B1). The easiest method is to disconnect the lead from the box and reimplant another lead. Removal of the lead is precarious and can result in rupture of the right ventricle or atrium. According to recent advisories, it should be performed only in experienced hands, if at all. Replacement with another lead may require a different vein and possibly a new defibrillator box. All of this adds up to considerable surgery in an aging population with significant left ventricular disease.

The most recent device adventure is the Watchman atrial appendage occlusive device to prevent systemic emboli in atrial fibrillation. The recently concluded PROTECT-AF study compares the device with warfarin in a small noninferiority trial. Many of the patients were not actually candidates for anticoagulant therapy; with 68% of the patients having CHADS scores of 1–2, according to the FDA's briefing document. The study demonstrated in a highly select group of patients that the device was not inferior to warfarin therapy. The Food and Drug Administration's Circulatory System Devices Panel voted in favor of approving the device by a narrow margin of 7–5. The panel historically has approved devices if they “work” and not always if they benefit patients.

The remains of old pacemakers and devices implanted for clinical research in patients may be lifesaving and may indeed relieve symptoms, but they may also end up in “human space,” not unlike old space satellites that are circling our planet. Seemingly harmless, this “debris” may become an issue in the future.

The recent problems of Medtronic's Fidelis leads in defibrillator-pacemakers reminded me of the sea change that has occurred in medical therapeutics.

Device therapeutics has fast become a major mode of treatment in a variety of fields including cardiology, as new targets for drug therapy have become limited. In the old days, if the physician observed an adverse drug effect, the antidote was easily accomplished by stopping the medication. That is not to say that there were no long-term effects of disastrous proportion associated with oral or intravenous therapy. Drug-induced hepatitis, agranulocytosis, and shock, to name a few, still are potential adverse effects with parenteral or oral drug administration.

But with the development of device therapy, dealing with adverse events has become much more complicated. The advent of the implantable pacemaker seems to be the watershed device that changed the therapeutic landscape. I recall talking to Dr. Bill Chardack, a surgeon and coinventor with Wilson Greatbach of the implantable transvenous pacemaker in the mid 1960s about the issue of removing the right ventricular catheter should the site become infected or the catheter cease to function. His response was “that the issue was getting them in, not getting them out.” Well, a lot of catheters have been implanted since then, and many have become dysfunctional and remain in patients and can now be classified as biological “debris.”

Artificial heart valves, particularly in their early developmental stages, had to be removed as a result of thrombus formation or structural failure. Many of these valve failures required emergency surgery. Later, cracks developed in some of the aortic valve struts, which again led to both urgent and prophylactic surgery when they were identified with special x-rays. The implantation of many and varied of coronary stents, which obviously cannot be removed, created a new mechanical disease superimposed onto naturally occurring coronary artery disease. Most recently, a host of new devices has emerged that remodel the left ventricle or defibrillate it depending upon the therapeutic target. Many of these are experimental, meaning that they may or may not be of therapeutic benefit, and are implanted into the heart without any “exit strategy” should they be shown to be ineffective or hazardous.

The most troubling among them are the defibrillators. Patients have been told that without such a device they are facing imminent death. Implantation of this device has been advised on the basis of guidelines that presume that the rate of adverse events is small and the benefit is large. The benefit remains the same, but now, in the face of increased adverse events, the equation has changed. It does appear that most of the 150,000 Fidelis leads need to be disconnected (“Removing Medtronic Heart Cables is Hard Choice,” New York Times, April 7, 2009, p. B1). The easiest method is to disconnect the lead from the box and reimplant another lead. Removal of the lead is precarious and can result in rupture of the right ventricle or atrium. According to recent advisories, it should be performed only in experienced hands, if at all. Replacement with another lead may require a different vein and possibly a new defibrillator box. All of this adds up to considerable surgery in an aging population with significant left ventricular disease.

The most recent device adventure is the Watchman atrial appendage occlusive device to prevent systemic emboli in atrial fibrillation. The recently concluded PROTECT-AF study compares the device with warfarin in a small noninferiority trial. Many of the patients were not actually candidates for anticoagulant therapy; with 68% of the patients having CHADS scores of 1–2, according to the FDA's briefing document. The study demonstrated in a highly select group of patients that the device was not inferior to warfarin therapy. The Food and Drug Administration's Circulatory System Devices Panel voted in favor of approving the device by a narrow margin of 7–5. The panel historically has approved devices if they “work” and not always if they benefit patients.

The remains of old pacemakers and devices implanted for clinical research in patients may be lifesaving and may indeed relieve symptoms, but they may also end up in “human space,” not unlike old space satellites that are circling our planet. Seemingly harmless, this “debris” may become an issue in the future.

The recent problems of Medtronic's Fidelis leads in defibrillator-pacemakers reminded me of the sea change that has occurred in medical therapeutics.

Device therapeutics has fast become a major mode of treatment in a variety of fields including cardiology, as new targets for drug therapy have become limited. In the old days, if the physician observed an adverse drug effect, the antidote was easily accomplished by stopping the medication. That is not to say that there were no long-term effects of disastrous proportion associated with oral or intravenous therapy. Drug-induced hepatitis, agranulocytosis, and shock, to name a few, still are potential adverse effects with parenteral or oral drug administration.

But with the development of device therapy, dealing with adverse events has become much more complicated. The advent of the implantable pacemaker seems to be the watershed device that changed the therapeutic landscape. I recall talking to Dr. Bill Chardack, a surgeon and coinventor with Wilson Greatbach of the implantable transvenous pacemaker in the mid 1960s about the issue of removing the right ventricular catheter should the site become infected or the catheter cease to function. His response was “that the issue was getting them in, not getting them out.” Well, a lot of catheters have been implanted since then, and many have become dysfunctional and remain in patients and can now be classified as biological “debris.”

Artificial heart valves, particularly in their early developmental stages, had to be removed as a result of thrombus formation or structural failure. Many of these valve failures required emergency surgery. Later, cracks developed in some of the aortic valve struts, which again led to both urgent and prophylactic surgery when they were identified with special x-rays. The implantation of many and varied of coronary stents, which obviously cannot be removed, created a new mechanical disease superimposed onto naturally occurring coronary artery disease. Most recently, a host of new devices has emerged that remodel the left ventricle or defibrillate it depending upon the therapeutic target. Many of these are experimental, meaning that they may or may not be of therapeutic benefit, and are implanted into the heart without any “exit strategy” should they be shown to be ineffective or hazardous.

The most troubling among them are the defibrillators. Patients have been told that without such a device they are facing imminent death. Implantation of this device has been advised on the basis of guidelines that presume that the rate of adverse events is small and the benefit is large. The benefit remains the same, but now, in the face of increased adverse events, the equation has changed. It does appear that most of the 150,000 Fidelis leads need to be disconnected (“Removing Medtronic Heart Cables is Hard Choice,” New York Times, April 7, 2009, p. B1). The easiest method is to disconnect the lead from the box and reimplant another lead. Removal of the lead is precarious and can result in rupture of the right ventricle or atrium. According to recent advisories, it should be performed only in experienced hands, if at all. Replacement with another lead may require a different vein and possibly a new defibrillator box. All of this adds up to considerable surgery in an aging population with significant left ventricular disease.

The most recent device adventure is the Watchman atrial appendage occlusive device to prevent systemic emboli in atrial fibrillation. The recently concluded PROTECT-AF study compares the device with warfarin in a small noninferiority trial. Many of the patients were not actually candidates for anticoagulant therapy; with 68% of the patients having CHADS scores of 1–2, according to the FDA's briefing document. The study demonstrated in a highly select group of patients that the device was not inferior to warfarin therapy. The Food and Drug Administration's Circulatory System Devices Panel voted in favor of approving the device by a narrow margin of 7–5. The panel historically has approved devices if they “work” and not always if they benefit patients.

The remains of old pacemakers and devices implanted for clinical research in patients may be lifesaving and may indeed relieve symptoms, but they may also end up in “human space,” not unlike old space satellites that are circling our planet. Seemingly harmless, this “debris” may become an issue in the future.