Heart of the Matter

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.

There is mounting frustration for both clinical trialists and the pharmaceutical industry with the difficulty of moving clinical trial results to patient care. Over the past 10 years, there has been a paucity of new cardiac drugs approved by the Food and Drug Administration. This drought follows a flood of drugs that came into clinical care in the previous 2 decades.

The increasing difficulty and expense of carrying out clinical trials in the United States has led to reliance on patient recruitment in Eastern Europe and Asia.

As a result, a number of the large pharmaceutical companies have withdrawn from the development of new cardiac drugs and have moved to other more fertile disease systems. At the same time, because of the current economic environment, it has been difficult to obtain venture capital funding to initiate studies of new drugs.

Nevertheless, some areas that remain “hot” targets of cardiovascular disease are receiving continued interest and support by Big Pharma. This has been particularly true in acute coronary syndromes: Although long-term mortality rates have changed dramatically, new interventional procedures and change in diagnostic criteria have provided a ready supply of patients available for recruitment.

The area of heart failure, where the 60-day mortality rate for hospitalized patients exceeds 25% in spite of advances with ACE inhibitors and beta-blockers, has also been an appealing target of research.

Although the interest in these areas is welcome, it raises some interesting issues for the clinician when interpreting the results of intervention.

In acute coronary syndromes, for which a decrease in mortality had been the major therapeutic target, mortality now represents less than 25% of all combined events in some clinical trials. As mortality became a smaller part of the end point measurement, troponin-defined reinfarction increased in both statistical and clinical significance. As we all know, reinfarction is subject to significant variation and interpretation as more sensitive biomarkers reflect smaller degrees of infarction which may be of questionable clinical importance.

The clinical relevance of reinfarction has come into special prominence as we develop more potent antithrombotic and antiplatelet agents that are associated with an increased potential for major bleeding. The benefit of achieving this combined end point, dominated by myocardial infarction determined using a biomarker, weighed against the potential of increased bleeding risk, is less obvious.

The investigation of new drugs for the treatment of heart failure, particularly in an aging population, has resulted in a search for relevant measures that truly impact a patient's life. In addition to mortality, rehospitalization is the most commonly-used measure of therapeutic success, reflecting both the clinical and economic burdens of the disease.

In young heart failure patients, subsequent hospitalization could result from a cardiac event. But as our population ages and we apply new therapies to older patients, total hospitalization has become much more heterogeneous. Rehospitalization in octogenarians, who increasingly dominate our heart failure population, may have different implications. The readmissions may be a result of noncardiac concerns such as cancer, pulmonary disease, trauma, or debilitating neurologic events.

In addition, the increasing reliance on patients from Eastern Europe and Asia to participate in clinical trials, because of economic and legal restrictions, has made the use of rehospitalization a less certain end point when applying trial results to Western Europe and North America.

The increased reliance upon these patients in both heart failure and ACS trials has become a necessity for sufficient recruitment. A recent analysis of the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) trial revealed considerable baseline and mortality differences between patients randomized in Eastern Europe and those participants from the United States and Western Europe (J. Am. Coll. Cardiol. 2008;52:1640-8).

All of these issues have challenged designers of clinical trials to create a study that is relevant to local societal requirements. The world has not become so flat that studies in India and China can have complete relevancy to Americans when we stray from hard core end points such as mortality.

There is mounting frustration for both clinical trialists and the pharmaceutical industry with the difficulty of moving clinical trial results to patient care. Over the past 10 years, there has been a paucity of new cardiac drugs approved by the Food and Drug Administration. This drought follows a flood of drugs that came into clinical care in the previous 2 decades.

The increasing difficulty and expense of carrying out clinical trials in the United States has led to reliance on patient recruitment in Eastern Europe and Asia.

As a result, a number of the large pharmaceutical companies have withdrawn from the development of new cardiac drugs and have moved to other more fertile disease systems. At the same time, because of the current economic environment, it has been difficult to obtain venture capital funding to initiate studies of new drugs.

Nevertheless, some areas that remain “hot” targets of cardiovascular disease are receiving continued interest and support by Big Pharma. This has been particularly true in acute coronary syndromes: Although long-term mortality rates have changed dramatically, new interventional procedures and change in diagnostic criteria have provided a ready supply of patients available for recruitment.

The area of heart failure, where the 60-day mortality rate for hospitalized patients exceeds 25% in spite of advances with ACE inhibitors and beta-blockers, has also been an appealing target of research.

Although the interest in these areas is welcome, it raises some interesting issues for the clinician when interpreting the results of intervention.

In acute coronary syndromes, for which a decrease in mortality had been the major therapeutic target, mortality now represents less than 25% of all combined events in some clinical trials. As mortality became a smaller part of the end point measurement, troponin-defined reinfarction increased in both statistical and clinical significance. As we all know, reinfarction is subject to significant variation and interpretation as more sensitive biomarkers reflect smaller degrees of infarction which may be of questionable clinical importance.

The clinical relevance of reinfarction has come into special prominence as we develop more potent antithrombotic and antiplatelet agents that are associated with an increased potential for major bleeding. The benefit of achieving this combined end point, dominated by myocardial infarction determined using a biomarker, weighed against the potential of increased bleeding risk, is less obvious.

The investigation of new drugs for the treatment of heart failure, particularly in an aging population, has resulted in a search for relevant measures that truly impact a patient's life. In addition to mortality, rehospitalization is the most commonly-used measure of therapeutic success, reflecting both the clinical and economic burdens of the disease.

In young heart failure patients, subsequent hospitalization could result from a cardiac event. But as our population ages and we apply new therapies to older patients, total hospitalization has become much more heterogeneous. Rehospitalization in octogenarians, who increasingly dominate our heart failure population, may have different implications. The readmissions may be a result of noncardiac concerns such as cancer, pulmonary disease, trauma, or debilitating neurologic events.

In addition, the increasing reliance on patients from Eastern Europe and Asia to participate in clinical trials, because of economic and legal restrictions, has made the use of rehospitalization a less certain end point when applying trial results to Western Europe and North America.

The increased reliance upon these patients in both heart failure and ACS trials has become a necessity for sufficient recruitment. A recent analysis of the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) trial revealed considerable baseline and mortality differences between patients randomized in Eastern Europe and those participants from the United States and Western Europe (J. Am. Coll. Cardiol. 2008;52:1640-8).

All of these issues have challenged designers of clinical trials to create a study that is relevant to local societal requirements. The world has not become so flat that studies in India and China can have complete relevancy to Americans when we stray from hard core end points such as mortality.

There is mounting frustration for both clinical trialists and the pharmaceutical industry with the difficulty of moving clinical trial results to patient care. Over the past 10 years, there has been a paucity of new cardiac drugs approved by the Food and Drug Administration. This drought follows a flood of drugs that came into clinical care in the previous 2 decades.

The increasing difficulty and expense of carrying out clinical trials in the United States has led to reliance on patient recruitment in Eastern Europe and Asia.

As a result, a number of the large pharmaceutical companies have withdrawn from the development of new cardiac drugs and have moved to other more fertile disease systems. At the same time, because of the current economic environment, it has been difficult to obtain venture capital funding to initiate studies of new drugs.

Nevertheless, some areas that remain “hot” targets of cardiovascular disease are receiving continued interest and support by Big Pharma. This has been particularly true in acute coronary syndromes: Although long-term mortality rates have changed dramatically, new interventional procedures and change in diagnostic criteria have provided a ready supply of patients available for recruitment.

The area of heart failure, where the 60-day mortality rate for hospitalized patients exceeds 25% in spite of advances with ACE inhibitors and beta-blockers, has also been an appealing target of research.

Although the interest in these areas is welcome, it raises some interesting issues for the clinician when interpreting the results of intervention.

In acute coronary syndromes, for which a decrease in mortality had been the major therapeutic target, mortality now represents less than 25% of all combined events in some clinical trials. As mortality became a smaller part of the end point measurement, troponin-defined reinfarction increased in both statistical and clinical significance. As we all know, reinfarction is subject to significant variation and interpretation as more sensitive biomarkers reflect smaller degrees of infarction which may be of questionable clinical importance.

The clinical relevance of reinfarction has come into special prominence as we develop more potent antithrombotic and antiplatelet agents that are associated with an increased potential for major bleeding. The benefit of achieving this combined end point, dominated by myocardial infarction determined using a biomarker, weighed against the potential of increased bleeding risk, is less obvious.

The investigation of new drugs for the treatment of heart failure, particularly in an aging population, has resulted in a search for relevant measures that truly impact a patient's life. In addition to mortality, rehospitalization is the most commonly-used measure of therapeutic success, reflecting both the clinical and economic burdens of the disease.

In young heart failure patients, subsequent hospitalization could result from a cardiac event. But as our population ages and we apply new therapies to older patients, total hospitalization has become much more heterogeneous. Rehospitalization in octogenarians, who increasingly dominate our heart failure population, may have different implications. The readmissions may be a result of noncardiac concerns such as cancer, pulmonary disease, trauma, or debilitating neurologic events.

In addition, the increasing reliance on patients from Eastern Europe and Asia to participate in clinical trials, because of economic and legal restrictions, has made the use of rehospitalization a less certain end point when applying trial results to Western Europe and North America.

The increased reliance upon these patients in both heart failure and ACS trials has become a necessity for sufficient recruitment. A recent analysis of the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) trial revealed considerable baseline and mortality differences between patients randomized in Eastern Europe and those participants from the United States and Western Europe (J. Am. Coll. Cardiol. 2008;52:1640-8).

All of these issues have challenged designers of clinical trials to create a study that is relevant to local societal requirements. The world has not become so flat that studies in India and China can have complete relevancy to Americans when we stray from hard core end points such as mortality.

This column has in the past commented on the shortcomings of guidelines in a number of clinical situations, including the expanded use of coronary interventional procedures and the implantation of automatic defibrillators in heart failure.

Guidelines designed as advisory to clinicians have achieved almost biblical, or, if you will, Koranic, status in the care of patients.

As a result, many physicians young and old have developed a state of mental paralysis, unable to make clinical decisions based on pathophysiology, pharmacology, or social status of the patient. They go through a maze of decision trees that often lead to a clinical judgment without fully considering the patient's status.

The process is reminiscent of the Yogi Berra aphorism, “When you come to a fork in the road, take it.”

The recent analysis by the Duke Clinical Research Institute of the ACC/AHA Clinical Practice Guidelines process over the last 25 years provides an incisive examination of the weakness of this otherwise well meaning process (JAMA 2009;301:831-41).

Guidelines were created largely to incorporate the results of randomized clinical trials (RCTs) into clinical care. Such trials, designed to prove the efficacy of new drugs and devices, represent major investments by pharmaceutical companies, which are focused on testing their products in the most advantageous environment. As a result, many patients with comorbid illnesses are excluded to provide a clear message about the drugs' specificity in a given illness.

Those of us who straddle the clinical research world and clinical practice know very well patients included in trials bear little resemblance to those we treat at the bedside or in the clinic. Most Medicare beneficiaries have multiple comorbidities that affect both therapy and outcome. Nevertheless, the guidelines have used RCT results when available.

Unfortunately, RCTs cover only a small fraction of clinical practice. In lieu of RCT data, “expert opinion and standard of care” were used to fill the gaps in evidence, which comprise most of the clinical decision process.

This reliance on expert opinion in guideline committees also has been challenged as a potential source of bias. Industry has had such profound impact on clinical research and trials that it is almost impossible to find physicians with expertise who do not have some potential bias as a result of research support, advisory committees, speakers' bureaus, and consulting fees. Many of these experts included in guideline panels have honest scientific investment in therapeutic concepts, which also have the potential to cloud their judgment.

Unfortunately, there is a paucity of guidelines that are even supported by RCTs. According to the Duke analysis, with a class I recommendation, defined as when “there is evidence and/or general agreement that a given procedure is useful and effective” only 19% had a class A level of evidence, defined as being supported with RCT data. In 36% of the class I recommendations, “expert opinion, case studies or standard of care” —class C evidence level—was the support. The analysis further suggested that as guidelines expanded over time, the use of class II recommendations, where there is “conflicting evidence and/or a diversion of opinion” has increased.

To put this in the context of current clinical practice, the report cited data from the ACC National Registry showing that 30% of all the percutaneous coronary interventions and 39% of those performed after an acute MI fell under class II indications. This represented 115,000 and 45,000 procedures, respectively.

The development of standards for medical therapy is important for the care of our patients, and RCTs are crucial to understanding the safety and benefit of new therapies. Much of the success in reducing the mortality in heart disease has been the result of the incorporation of RCT results into bedside care.

Nevertheless, our current process needs to be improved. We need to develop a mechanism for testing therapy in the real world dominated by an increasingly aging patient population with myriad comorbid diseases.

The current attempts by the Centers for Medicare and Medicaid Services to assess the efficacy and safety of new therapies have been inadequate. The development of registries such as the ACC's ICD Registry, has not met the full potential of this process.

We need randomized trial data of real patients as a new therapy is introduced in clinical care. In the absence of that, the collection of registry data must be strengthened and the analyses made available to the medical community as soon as possible.

This column has in the past commented on the shortcomings of guidelines in a number of clinical situations, including the expanded use of coronary interventional procedures and the implantation of automatic defibrillators in heart failure.

Guidelines designed as advisory to clinicians have achieved almost biblical, or, if you will, Koranic, status in the care of patients.

As a result, many physicians young and old have developed a state of mental paralysis, unable to make clinical decisions based on pathophysiology, pharmacology, or social status of the patient. They go through a maze of decision trees that often lead to a clinical judgment without fully considering the patient's status.

The process is reminiscent of the Yogi Berra aphorism, “When you come to a fork in the road, take it.”

The recent analysis by the Duke Clinical Research Institute of the ACC/AHA Clinical Practice Guidelines process over the last 25 years provides an incisive examination of the weakness of this otherwise well meaning process (JAMA 2009;301:831-41).

Guidelines were created largely to incorporate the results of randomized clinical trials (RCTs) into clinical care. Such trials, designed to prove the efficacy of new drugs and devices, represent major investments by pharmaceutical companies, which are focused on testing their products in the most advantageous environment. As a result, many patients with comorbid illnesses are excluded to provide a clear message about the drugs' specificity in a given illness.

Those of us who straddle the clinical research world and clinical practice know very well patients included in trials bear little resemblance to those we treat at the bedside or in the clinic. Most Medicare beneficiaries have multiple comorbidities that affect both therapy and outcome. Nevertheless, the guidelines have used RCT results when available.

Unfortunately, RCTs cover only a small fraction of clinical practice. In lieu of RCT data, “expert opinion and standard of care” were used to fill the gaps in evidence, which comprise most of the clinical decision process.

This reliance on expert opinion in guideline committees also has been challenged as a potential source of bias. Industry has had such profound impact on clinical research and trials that it is almost impossible to find physicians with expertise who do not have some potential bias as a result of research support, advisory committees, speakers' bureaus, and consulting fees. Many of these experts included in guideline panels have honest scientific investment in therapeutic concepts, which also have the potential to cloud their judgment.

Unfortunately, there is a paucity of guidelines that are even supported by RCTs. According to the Duke analysis, with a class I recommendation, defined as when “there is evidence and/or general agreement that a given procedure is useful and effective” only 19% had a class A level of evidence, defined as being supported with RCT data. In 36% of the class I recommendations, “expert opinion, case studies or standard of care” —class C evidence level—was the support. The analysis further suggested that as guidelines expanded over time, the use of class II recommendations, where there is “conflicting evidence and/or a diversion of opinion” has increased.

To put this in the context of current clinical practice, the report cited data from the ACC National Registry showing that 30% of all the percutaneous coronary interventions and 39% of those performed after an acute MI fell under class II indications. This represented 115,000 and 45,000 procedures, respectively.

The development of standards for medical therapy is important for the care of our patients, and RCTs are crucial to understanding the safety and benefit of new therapies. Much of the success in reducing the mortality in heart disease has been the result of the incorporation of RCT results into bedside care.

Nevertheless, our current process needs to be improved. We need to develop a mechanism for testing therapy in the real world dominated by an increasingly aging patient population with myriad comorbid diseases.

The current attempts by the Centers for Medicare and Medicaid Services to assess the efficacy and safety of new therapies have been inadequate. The development of registries such as the ACC's ICD Registry, has not met the full potential of this process.

We need randomized trial data of real patients as a new therapy is introduced in clinical care. In the absence of that, the collection of registry data must be strengthened and the analyses made available to the medical community as soon as possible.

This column has in the past commented on the shortcomings of guidelines in a number of clinical situations, including the expanded use of coronary interventional procedures and the implantation of automatic defibrillators in heart failure.

Guidelines designed as advisory to clinicians have achieved almost biblical, or, if you will, Koranic, status in the care of patients.

As a result, many physicians young and old have developed a state of mental paralysis, unable to make clinical decisions based on pathophysiology, pharmacology, or social status of the patient. They go through a maze of decision trees that often lead to a clinical judgment without fully considering the patient's status.

The process is reminiscent of the Yogi Berra aphorism, “When you come to a fork in the road, take it.”

The recent analysis by the Duke Clinical Research Institute of the ACC/AHA Clinical Practice Guidelines process over the last 25 years provides an incisive examination of the weakness of this otherwise well meaning process (JAMA 2009;301:831-41).

Guidelines were created largely to incorporate the results of randomized clinical trials (RCTs) into clinical care. Such trials, designed to prove the efficacy of new drugs and devices, represent major investments by pharmaceutical companies, which are focused on testing their products in the most advantageous environment. As a result, many patients with comorbid illnesses are excluded to provide a clear message about the drugs' specificity in a given illness.

Those of us who straddle the clinical research world and clinical practice know very well patients included in trials bear little resemblance to those we treat at the bedside or in the clinic. Most Medicare beneficiaries have multiple comorbidities that affect both therapy and outcome. Nevertheless, the guidelines have used RCT results when available.

Unfortunately, RCTs cover only a small fraction of clinical practice. In lieu of RCT data, “expert opinion and standard of care” were used to fill the gaps in evidence, which comprise most of the clinical decision process.

This reliance on expert opinion in guideline committees also has been challenged as a potential source of bias. Industry has had such profound impact on clinical research and trials that it is almost impossible to find physicians with expertise who do not have some potential bias as a result of research support, advisory committees, speakers' bureaus, and consulting fees. Many of these experts included in guideline panels have honest scientific investment in therapeutic concepts, which also have the potential to cloud their judgment.

Unfortunately, there is a paucity of guidelines that are even supported by RCTs. According to the Duke analysis, with a class I recommendation, defined as when “there is evidence and/or general agreement that a given procedure is useful and effective” only 19% had a class A level of evidence, defined as being supported with RCT data. In 36% of the class I recommendations, “expert opinion, case studies or standard of care” —class C evidence level—was the support. The analysis further suggested that as guidelines expanded over time, the use of class II recommendations, where there is “conflicting evidence and/or a diversion of opinion” has increased.

To put this in the context of current clinical practice, the report cited data from the ACC National Registry showing that 30% of all the percutaneous coronary interventions and 39% of those performed after an acute MI fell under class II indications. This represented 115,000 and 45,000 procedures, respectively.

The development of standards for medical therapy is important for the care of our patients, and RCTs are crucial to understanding the safety and benefit of new therapies. Much of the success in reducing the mortality in heart disease has been the result of the incorporation of RCT results into bedside care.

Nevertheless, our current process needs to be improved. We need to develop a mechanism for testing therapy in the real world dominated by an increasingly aging patient population with myriad comorbid diseases.

The current attempts by the Centers for Medicare and Medicaid Services to assess the efficacy and safety of new therapies have been inadequate. The development of registries such as the ACC's ICD Registry, has not met the full potential of this process.

We need randomized trial data of real patients as a new therapy is introduced in clinical care. In the absence of that, the collection of registry data must be strengthened and the analyses made available to the medical community as soon as possible.

Vast changes are about to occur in health insurance in America. Some will occur as a result of economic necessities, others by political action. The election of President Barack Obama signaled at least the willingness of Americans to look for change.

Whether the new president can negotiate through the minefield of doctors, insurers, labor unions, and industry to find an amicable solution is, to say the least, uncertain. He has framed the issue of health insurance no longer as an American's right but more importantly as an economic necessity. Health insurance is a way to get Americans back to work.

Glenn Beck of CNN has likened the solution of the economic problems facing Social Security, Medicare, and Medicaid to the cost of stopping an asteroid aimed at this country, due to strike in 2019, at a cost of $53 trillion. According to the Social Security and Medicare trustees, only a 122% increase in Medicare tax and a 26% increase in Social Security tax can avert it. In 2007, health care expenditures increased by 6.1% to $2.2 trillion, or $7,421 per person. Total private and federally funded health costs represent 16.2% of the gross domestic product, compared with 16% in 2006 (Health Affairs 2009;28;246–61). Well, those are issues for the next generation. Forget about them for now and let's just consider some of the issues facing health care tomorrow.

To provide the universality of health insurance, major changes will occur in how we pay, what we pay, and who does the paying. As physicians and hospitals are squeezed in the current economic environment, it might be a chance to look at what is going on in the health insurance world. Private insurers are coming under significant pressure as unemployment and health costs increase (AMNews, Nov. 24, 2008). Insurers are having increasing difficulty providing dividends to their stockholders without raising premiums. This is an issue as membership falls and the burden is placed on fewer subscribers. At the same time, investment income that had been used to support services has taken a beating in the stock market.

In Michigan, where many current and former auto workers are losing some or all of their health insurance coverage, Blue Cross and Blue Shield of Michigan is talking of increasing premiums for single contracts and Medicare supplemental coverage up to 55% (Detroit Free Press, Jan. 17, 2009). Such a hike will be sure to force even more people to join the ranks of the uninsured.

President Obama's proposal during the run-up to the election called for supplementing private job-based health plans with a federal plan. Faced with increasing unemployment, employer-based health insurance may not provide much of a support and may not be depended on for long. It is possible that in this economic environment, the public may be more interested in moving more fully to a government-funded program. Before withdrawing his nomination for Secretary of Health and Human Services, Tom Daschle had been talking about starting a federal insurance plan fashioned after Medicare and running it in competition with the private insurers. Congress already is enlarging federally supported health plans by expanding the SCHIP program by adding 4 million children under age 18 at an upgraded poverty level. The Massachusetts health insurance plan, which mandates a combination of industry- and state-funded health insurance plans, is being held up as a potential model. It has decreased the percentage of uninsured in Massachusetts to the single-digit level.

Regardless of the plan chosen, it is certain that impact on the total cost of health care will not be achieved without physicians giving up part of or the entire traditional fee-for-service payment system. That system has resulted in excess use of procedures and specialists. Historically, as fees were decreased, the volume of services increased to compensate.

The quality care guidelines of the American College of Cardiology and the American Heart Association have had no measurable effect on the utilization and cost of health care. How fee-for-service payment will be modified is uncertain, but it will likely lead to something more than just decreasing fees.

Some suggest that the current economic environment will not permit major changes; other suggest that the mounting need to provide health insurance to the uninsured will force congressional action. Stay tuned.

Vast changes are about to occur in health insurance in America. Some will occur as a result of economic necessities, others by political action. The election of President Barack Obama signaled at least the willingness of Americans to look for change.

Whether the new president can negotiate through the minefield of doctors, insurers, labor unions, and industry to find an amicable solution is, to say the least, uncertain. He has framed the issue of health insurance no longer as an American's right but more importantly as an economic necessity. Health insurance is a way to get Americans back to work.

Glenn Beck of CNN has likened the solution of the economic problems facing Social Security, Medicare, and Medicaid to the cost of stopping an asteroid aimed at this country, due to strike in 2019, at a cost of $53 trillion. According to the Social Security and Medicare trustees, only a 122% increase in Medicare tax and a 26% increase in Social Security tax can avert it. In 2007, health care expenditures increased by 6.1% to $2.2 trillion, or $7,421 per person. Total private and federally funded health costs represent 16.2% of the gross domestic product, compared with 16% in 2006 (Health Affairs 2009;28;246–61). Well, those are issues for the next generation. Forget about them for now and let's just consider some of the issues facing health care tomorrow.

To provide the universality of health insurance, major changes will occur in how we pay, what we pay, and who does the paying. As physicians and hospitals are squeezed in the current economic environment, it might be a chance to look at what is going on in the health insurance world. Private insurers are coming under significant pressure as unemployment and health costs increase (AMNews, Nov. 24, 2008). Insurers are having increasing difficulty providing dividends to their stockholders without raising premiums. This is an issue as membership falls and the burden is placed on fewer subscribers. At the same time, investment income that had been used to support services has taken a beating in the stock market.

In Michigan, where many current and former auto workers are losing some or all of their health insurance coverage, Blue Cross and Blue Shield of Michigan is talking of increasing premiums for single contracts and Medicare supplemental coverage up to 55% (Detroit Free Press, Jan. 17, 2009). Such a hike will be sure to force even more people to join the ranks of the uninsured.

President Obama's proposal during the run-up to the election called for supplementing private job-based health plans with a federal plan. Faced with increasing unemployment, employer-based health insurance may not provide much of a support and may not be depended on for long. It is possible that in this economic environment, the public may be more interested in moving more fully to a government-funded program. Before withdrawing his nomination for Secretary of Health and Human Services, Tom Daschle had been talking about starting a federal insurance plan fashioned after Medicare and running it in competition with the private insurers. Congress already is enlarging federally supported health plans by expanding the SCHIP program by adding 4 million children under age 18 at an upgraded poverty level. The Massachusetts health insurance plan, which mandates a combination of industry- and state-funded health insurance plans, is being held up as a potential model. It has decreased the percentage of uninsured in Massachusetts to the single-digit level.

Regardless of the plan chosen, it is certain that impact on the total cost of health care will not be achieved without physicians giving up part of or the entire traditional fee-for-service payment system. That system has resulted in excess use of procedures and specialists. Historically, as fees were decreased, the volume of services increased to compensate.

The quality care guidelines of the American College of Cardiology and the American Heart Association have had no measurable effect on the utilization and cost of health care. How fee-for-service payment will be modified is uncertain, but it will likely lead to something more than just decreasing fees.

Some suggest that the current economic environment will not permit major changes; other suggest that the mounting need to provide health insurance to the uninsured will force congressional action. Stay tuned.

Vast changes are about to occur in health insurance in America. Some will occur as a result of economic necessities, others by political action. The election of President Barack Obama signaled at least the willingness of Americans to look for change.

Whether the new president can negotiate through the minefield of doctors, insurers, labor unions, and industry to find an amicable solution is, to say the least, uncertain. He has framed the issue of health insurance no longer as an American's right but more importantly as an economic necessity. Health insurance is a way to get Americans back to work.

Glenn Beck of CNN has likened the solution of the economic problems facing Social Security, Medicare, and Medicaid to the cost of stopping an asteroid aimed at this country, due to strike in 2019, at a cost of $53 trillion. According to the Social Security and Medicare trustees, only a 122% increase in Medicare tax and a 26% increase in Social Security tax can avert it. In 2007, health care expenditures increased by 6.1% to $2.2 trillion, or $7,421 per person. Total private and federally funded health costs represent 16.2% of the gross domestic product, compared with 16% in 2006 (Health Affairs 2009;28;246–61). Well, those are issues for the next generation. Forget about them for now and let's just consider some of the issues facing health care tomorrow.

To provide the universality of health insurance, major changes will occur in how we pay, what we pay, and who does the paying. As physicians and hospitals are squeezed in the current economic environment, it might be a chance to look at what is going on in the health insurance world. Private insurers are coming under significant pressure as unemployment and health costs increase (AMNews, Nov. 24, 2008). Insurers are having increasing difficulty providing dividends to their stockholders without raising premiums. This is an issue as membership falls and the burden is placed on fewer subscribers. At the same time, investment income that had been used to support services has taken a beating in the stock market.

In Michigan, where many current and former auto workers are losing some or all of their health insurance coverage, Blue Cross and Blue Shield of Michigan is talking of increasing premiums for single contracts and Medicare supplemental coverage up to 55% (Detroit Free Press, Jan. 17, 2009). Such a hike will be sure to force even more people to join the ranks of the uninsured.

President Obama's proposal during the run-up to the election called for supplementing private job-based health plans with a federal plan. Faced with increasing unemployment, employer-based health insurance may not provide much of a support and may not be depended on for long. It is possible that in this economic environment, the public may be more interested in moving more fully to a government-funded program. Before withdrawing his nomination for Secretary of Health and Human Services, Tom Daschle had been talking about starting a federal insurance plan fashioned after Medicare and running it in competition with the private insurers. Congress already is enlarging federally supported health plans by expanding the SCHIP program by adding 4 million children under age 18 at an upgraded poverty level. The Massachusetts health insurance plan, which mandates a combination of industry- and state-funded health insurance plans, is being held up as a potential model. It has decreased the percentage of uninsured in Massachusetts to the single-digit level.

Regardless of the plan chosen, it is certain that impact on the total cost of health care will not be achieved without physicians giving up part of or the entire traditional fee-for-service payment system. That system has resulted in excess use of procedures and specialists. Historically, as fees were decreased, the volume of services increased to compensate.

The quality care guidelines of the American College of Cardiology and the American Heart Association have had no measurable effect on the utilization and cost of health care. How fee-for-service payment will be modified is uncertain, but it will likely lead to something more than just decreasing fees.

Some suggest that the current economic environment will not permit major changes; other suggest that the mounting need to provide health insurance to the uninsured will force congressional action. Stay tuned.

Dr. George Burch, one of the great leaders in cardiology in the mid-20th century, wrote in a 1954 monograph that “the patient with moderate or severe congestive heart failure should be placed at bed rest immediately.” As a result, many patients were kept in bed for many weeks. This was the considered recommendation of many cardiologists, who had at the time little else to offer to their patients.

In the half century that followed, we learned a great deal about exercise physiology and its role in rehabilitating patients after an acute myocardial infarction. It is now part of the standard care of such patients.

More recently, a large body of clinical data has emerged providing insight into the role of exercise in the patient with heart failure. These studies suggest that, contrary to previous concerns, exercise training may be safe and can lead to improved cardiac physiology. There is now significant evidence that exercise training improves exercise performance, increases peak oxygen consumption, reduces both muscle and systemic sympathetic activity, and favorably modifies systemic and tissue inflammatory markers.

On the basis of these physiologic studies, several clinical trials were performed in the past decade and reported clinical benefits associated with exercise training in heart failure. Although most of the studies have been small, they tended to reinforce the safety and physiologic benefits of exercise training. These studies were designed to include a broad spectrum of patients with varying degrees of heart failure, such as elderly patients, who are becoming an increasingly large part of the heart failure population.

As a result of the progress in this field, in 2002 the National Heart, Lung, and Blood Institute embarked on HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training). The trial, involving more than 2,300 patients with New York Heart Association class I-IV heart failure with ejection fractions of less than 35%, tested the relative morbidity and mortality benefit of exercise training in those who also were receiving optimal medical therapy.

Patients were randomized to usual care or a supervised exercise program for a concentrated 3-month period of exercise 3 days a week for 4 months, followed by home exercise 5 days a week for 2 years (CARDIOLOGY NEWS, Dec. 2008, p. 24).

Although the trial did not achieve statistical significance in its primary goal of decreasing all-cause mortality or all-cause hospitalization, it did demonstrate a significant 14% decrease in the disease-specific clinical outcome of cardiovascular mortality or heart failure hospitalization. This effect on outcome is similar to that achieved with angiotensin receptor blockade when added to de novo heart failure patients. In addition, the trial further supported the safety of exercise therapy in heart failure.

Many institutions have cardiac rehabilitation programs that include patients with heart failure. In some programs, the therapy is paid for by a third party. In light of the outcomes of HF-ACTION, an important question arises as to whether this therapy, with an expense that might be similar to the cost of providing cardiac rehabilitation for acute myocardial infarction patients, should become part of our standard reimbursement for Medicare and all third parties as an intrinsic part of heart failure therapy. This will be an important issue at a time when the escalating cost of health care is under increasing scrutiny.

Nevertheless, the result of HF-ACTION provides an important additional modality of treatment for heart failure patients and answers the question regarding the safety of exercise. The HF-ACTION investigators will need to provide the information, and some guidance, as to which patients with heart failure can benefit the most from exercise therapy.

It's time to consider making exercise therapy a standard, reimbursable treatment for heart failure. ©Pavel

Dr. George Burch, one of the great leaders in cardiology in the mid-20th century, wrote in a 1954 monograph that “the patient with moderate or severe congestive heart failure should be placed at bed rest immediately.” As a result, many patients were kept in bed for many weeks. This was the considered recommendation of many cardiologists, who had at the time little else to offer to their patients.

In the half century that followed, we learned a great deal about exercise physiology and its role in rehabilitating patients after an acute myocardial infarction. It is now part of the standard care of such patients.

More recently, a large body of clinical data has emerged providing insight into the role of exercise in the patient with heart failure. These studies suggest that, contrary to previous concerns, exercise training may be safe and can lead to improved cardiac physiology. There is now significant evidence that exercise training improves exercise performance, increases peak oxygen consumption, reduces both muscle and systemic sympathetic activity, and favorably modifies systemic and tissue inflammatory markers.

On the basis of these physiologic studies, several clinical trials were performed in the past decade and reported clinical benefits associated with exercise training in heart failure. Although most of the studies have been small, they tended to reinforce the safety and physiologic benefits of exercise training. These studies were designed to include a broad spectrum of patients with varying degrees of heart failure, such as elderly patients, who are becoming an increasingly large part of the heart failure population.

As a result of the progress in this field, in 2002 the National Heart, Lung, and Blood Institute embarked on HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training). The trial, involving more than 2,300 patients with New York Heart Association class I-IV heart failure with ejection fractions of less than 35%, tested the relative morbidity and mortality benefit of exercise training in those who also were receiving optimal medical therapy.

Patients were randomized to usual care or a supervised exercise program for a concentrated 3-month period of exercise 3 days a week for 4 months, followed by home exercise 5 days a week for 2 years (CARDIOLOGY NEWS, Dec. 2008, p. 24).

Although the trial did not achieve statistical significance in its primary goal of decreasing all-cause mortality or all-cause hospitalization, it did demonstrate a significant 14% decrease in the disease-specific clinical outcome of cardiovascular mortality or heart failure hospitalization. This effect on outcome is similar to that achieved with angiotensin receptor blockade when added to de novo heart failure patients. In addition, the trial further supported the safety of exercise therapy in heart failure.

Many institutions have cardiac rehabilitation programs that include patients with heart failure. In some programs, the therapy is paid for by a third party. In light of the outcomes of HF-ACTION, an important question arises as to whether this therapy, with an expense that might be similar to the cost of providing cardiac rehabilitation for acute myocardial infarction patients, should become part of our standard reimbursement for Medicare and all third parties as an intrinsic part of heart failure therapy. This will be an important issue at a time when the escalating cost of health care is under increasing scrutiny.

Nevertheless, the result of HF-ACTION provides an important additional modality of treatment for heart failure patients and answers the question regarding the safety of exercise. The HF-ACTION investigators will need to provide the information, and some guidance, as to which patients with heart failure can benefit the most from exercise therapy.

It's time to consider making exercise therapy a standard, reimbursable treatment for heart failure. ©Pavel

Dr. George Burch, one of the great leaders in cardiology in the mid-20th century, wrote in a 1954 monograph that “the patient with moderate or severe congestive heart failure should be placed at bed rest immediately.” As a result, many patients were kept in bed for many weeks. This was the considered recommendation of many cardiologists, who had at the time little else to offer to their patients.

In the half century that followed, we learned a great deal about exercise physiology and its role in rehabilitating patients after an acute myocardial infarction. It is now part of the standard care of such patients.

More recently, a large body of clinical data has emerged providing insight into the role of exercise in the patient with heart failure. These studies suggest that, contrary to previous concerns, exercise training may be safe and can lead to improved cardiac physiology. There is now significant evidence that exercise training improves exercise performance, increases peak oxygen consumption, reduces both muscle and systemic sympathetic activity, and favorably modifies systemic and tissue inflammatory markers.

On the basis of these physiologic studies, several clinical trials were performed in the past decade and reported clinical benefits associated with exercise training in heart failure. Although most of the studies have been small, they tended to reinforce the safety and physiologic benefits of exercise training. These studies were designed to include a broad spectrum of patients with varying degrees of heart failure, such as elderly patients, who are becoming an increasingly large part of the heart failure population.

As a result of the progress in this field, in 2002 the National Heart, Lung, and Blood Institute embarked on HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training). The trial, involving more than 2,300 patients with New York Heart Association class I-IV heart failure with ejection fractions of less than 35%, tested the relative morbidity and mortality benefit of exercise training in those who also were receiving optimal medical therapy.

Patients were randomized to usual care or a supervised exercise program for a concentrated 3-month period of exercise 3 days a week for 4 months, followed by home exercise 5 days a week for 2 years (CARDIOLOGY NEWS, Dec. 2008, p. 24).

Although the trial did not achieve statistical significance in its primary goal of decreasing all-cause mortality or all-cause hospitalization, it did demonstrate a significant 14% decrease in the disease-specific clinical outcome of cardiovascular mortality or heart failure hospitalization. This effect on outcome is similar to that achieved with angiotensin receptor blockade when added to de novo heart failure patients. In addition, the trial further supported the safety of exercise therapy in heart failure.

Many institutions have cardiac rehabilitation programs that include patients with heart failure. In some programs, the therapy is paid for by a third party. In light of the outcomes of HF-ACTION, an important question arises as to whether this therapy, with an expense that might be similar to the cost of providing cardiac rehabilitation for acute myocardial infarction patients, should become part of our standard reimbursement for Medicare and all third parties as an intrinsic part of heart failure therapy. This will be an important issue at a time when the escalating cost of health care is under increasing scrutiny.

Nevertheless, the result of HF-ACTION provides an important additional modality of treatment for heart failure patients and answers the question regarding the safety of exercise. The HF-ACTION investigators will need to provide the information, and some guidance, as to which patients with heart failure can benefit the most from exercise therapy.

It's time to consider making exercise therapy a standard, reimbursable treatment for heart failure. ©Pavel

Among individuals who experience an acute myocardial infarction, approximately half will die of sudden death, and it often occurs outside of the hospital. The benefit of automatic implantable cardioverter defibrillators (ICDs) in high-risk patients with left ventricular dysfunction with chronic ischemic heart failure has focused our attention on ways of preventing sudden death.

Unfortunately, ICDs have been found to be ineffective and perhaps dangerous in the first 30 days after an acute MI, when such patients are at the greatest risk of sudden death (N. Engl. J. Med. 2004;351:2481–8).

A recent epidemiologic study from the Mayo Clinic of the population in Olmsted County, Minn., examined the occurrence of sudden death in the 30 days after an acute MI. It provides some interesting insight into the change in the frequency of sudden death during the last 25 years and underscores the importance of β-blocker therapy in patients experiencing an acute MI (JAMA 2008;300:2022–9).

In the Mayo Clinic study, sudden death was the cause of 24% of all deaths that occurred in acute MI patients between 1987 and 2005. Of the 59 sudden deaths that occurred in the first year after an acute MI, 35 (59%) occurred in the first 30 days after the MI. However, during the 27 years of the study, the incidence of sudden death decreased significantly. Compared with the period of 1979 to 1987, the risk of sudden death was reduced by 20% during 1988–1997, and by 38% during 1998–2005. The concomitant occurrence of heart failure doubled the rate of sudden death.

Many changes in the therapy of patients experiencing an acute myocardial infarction have occurred since that study began in 1979, including the use of thrombolytics, percutaneous coronary intervention, and coronary artery bypass surgery. All of these interventions have had an important impact on decreasing post-acute MI mortality. However, the only intervention initiated in that period that has been shown to affect sudden death is β-blocker therapy.

First reported in 1981, β-blocker therapy in large multicenter clinical trials both in the United States and Europe indicated that these drugs have a profound effect on total mortality after an acute MI and are particularly effective in preventing sudden death.

In the Beta-Blocker Heart Attack Trial (BHAT), β-blockers initiated within 7 days of hospitalization for an acute myocardial infarction decreased all mortality by 26% and sudden death by 28%. In BHAT patients with heart failure, therapy with β-blockers resulted in a 47% decrease in sudden death. Propranolol was used in BHAT, initiated at a dose of 120 mg daily and increased to 160–180 mg at 4 weeks.

Despite these reported effects, β-blocker therapy was poorly accepted for the routine treatment after an acute MI. Well into the 1990s, fewer than 50% of patients who had experienced an acute myocardial infarction received that therapy. It was not until the incorporation of β-blocker therapy as a quality measure by the National Committee for Quality Assurance (NCQA) in 1996 and the subsequent inclusion in American Heart Association-American College of Cardiology guidelines in 2000 that they were more widely used. Now, well over 90% of patients discharged from the hospital after an acute myocardial infarction are treated with β-blockers. It is often a low dose, but they are receiving some therapy nonetheless.

Although we cannot be certain what led to the decrease in sudden death in Olmsted County, it is tempting to presume that at least it can be attributed in part to the temporal changes in β-blocker usage.

Quality improvement programs provide a measure of whether or not a drug is ordered, but they do not measure the dose used. Equating the propranolol doses in BHAT to the contemporary β-blockers carvedilol and metoprolol succinate, both of which have been shown to provide benefits similar to that of propranolol, calls for daily doses up to 50 mg and 200 mg, respectively. The NCQA has recently introduced a new measure to ensure continuing therapy after 6 months, after a study in 2006 indicated that only 71% of patients after an acute myocardial infarction were still receiving β-blockers.

The observations from Olmsted County place in perspective the success of the quality improvement process in mitigating mortality in acute myocardial infarction. They also should provide an important encouragement for the practitioner to use full doses of contemporary β-blockers and to continue therapy.

Among individuals who experience an acute myocardial infarction, approximately half will die of sudden death, and it often occurs outside of the hospital. The benefit of automatic implantable cardioverter defibrillators (ICDs) in high-risk patients with left ventricular dysfunction with chronic ischemic heart failure has focused our attention on ways of preventing sudden death.

Unfortunately, ICDs have been found to be ineffective and perhaps dangerous in the first 30 days after an acute MI, when such patients are at the greatest risk of sudden death (N. Engl. J. Med. 2004;351:2481–8).

A recent epidemiologic study from the Mayo Clinic of the population in Olmsted County, Minn., examined the occurrence of sudden death in the 30 days after an acute MI. It provides some interesting insight into the change in the frequency of sudden death during the last 25 years and underscores the importance of β-blocker therapy in patients experiencing an acute MI (JAMA 2008;300:2022–9).

In the Mayo Clinic study, sudden death was the cause of 24% of all deaths that occurred in acute MI patients between 1987 and 2005. Of the 59 sudden deaths that occurred in the first year after an acute MI, 35 (59%) occurred in the first 30 days after the MI. However, during the 27 years of the study, the incidence of sudden death decreased significantly. Compared with the period of 1979 to 1987, the risk of sudden death was reduced by 20% during 1988–1997, and by 38% during 1998–2005. The concomitant occurrence of heart failure doubled the rate of sudden death.

Many changes in the therapy of patients experiencing an acute myocardial infarction have occurred since that study began in 1979, including the use of thrombolytics, percutaneous coronary intervention, and coronary artery bypass surgery. All of these interventions have had an important impact on decreasing post-acute MI mortality. However, the only intervention initiated in that period that has been shown to affect sudden death is β-blocker therapy.

First reported in 1981, β-blocker therapy in large multicenter clinical trials both in the United States and Europe indicated that these drugs have a profound effect on total mortality after an acute MI and are particularly effective in preventing sudden death.

In the Beta-Blocker Heart Attack Trial (BHAT), β-blockers initiated within 7 days of hospitalization for an acute myocardial infarction decreased all mortality by 26% and sudden death by 28%. In BHAT patients with heart failure, therapy with β-blockers resulted in a 47% decrease in sudden death. Propranolol was used in BHAT, initiated at a dose of 120 mg daily and increased to 160–180 mg at 4 weeks.

Despite these reported effects, β-blocker therapy was poorly accepted for the routine treatment after an acute MI. Well into the 1990s, fewer than 50% of patients who had experienced an acute myocardial infarction received that therapy. It was not until the incorporation of β-blocker therapy as a quality measure by the National Committee for Quality Assurance (NCQA) in 1996 and the subsequent inclusion in American Heart Association-American College of Cardiology guidelines in 2000 that they were more widely used. Now, well over 90% of patients discharged from the hospital after an acute myocardial infarction are treated with β-blockers. It is often a low dose, but they are receiving some therapy nonetheless.

Although we cannot be certain what led to the decrease in sudden death in Olmsted County, it is tempting to presume that at least it can be attributed in part to the temporal changes in β-blocker usage.

Quality improvement programs provide a measure of whether or not a drug is ordered, but they do not measure the dose used. Equating the propranolol doses in BHAT to the contemporary β-blockers carvedilol and metoprolol succinate, both of which have been shown to provide benefits similar to that of propranolol, calls for daily doses up to 50 mg and 200 mg, respectively. The NCQA has recently introduced a new measure to ensure continuing therapy after 6 months, after a study in 2006 indicated that only 71% of patients after an acute myocardial infarction were still receiving β-blockers.

The observations from Olmsted County place in perspective the success of the quality improvement process in mitigating mortality in acute myocardial infarction. They also should provide an important encouragement for the practitioner to use full doses of contemporary β-blockers and to continue therapy.

Among individuals who experience an acute myocardial infarction, approximately half will die of sudden death, and it often occurs outside of the hospital. The benefit of automatic implantable cardioverter defibrillators (ICDs) in high-risk patients with left ventricular dysfunction with chronic ischemic heart failure has focused our attention on ways of preventing sudden death.

Unfortunately, ICDs have been found to be ineffective and perhaps dangerous in the first 30 days after an acute MI, when such patients are at the greatest risk of sudden death (N. Engl. J. Med. 2004;351:2481–8).

A recent epidemiologic study from the Mayo Clinic of the population in Olmsted County, Minn., examined the occurrence of sudden death in the 30 days after an acute MI. It provides some interesting insight into the change in the frequency of sudden death during the last 25 years and underscores the importance of β-blocker therapy in patients experiencing an acute MI (JAMA 2008;300:2022–9).

In the Mayo Clinic study, sudden death was the cause of 24% of all deaths that occurred in acute MI patients between 1987 and 2005. Of the 59 sudden deaths that occurred in the first year after an acute MI, 35 (59%) occurred in the first 30 days after the MI. However, during the 27 years of the study, the incidence of sudden death decreased significantly. Compared with the period of 1979 to 1987, the risk of sudden death was reduced by 20% during 1988–1997, and by 38% during 1998–2005. The concomitant occurrence of heart failure doubled the rate of sudden death.

Many changes in the therapy of patients experiencing an acute myocardial infarction have occurred since that study began in 1979, including the use of thrombolytics, percutaneous coronary intervention, and coronary artery bypass surgery. All of these interventions have had an important impact on decreasing post-acute MI mortality. However, the only intervention initiated in that period that has been shown to affect sudden death is β-blocker therapy.

First reported in 1981, β-blocker therapy in large multicenter clinical trials both in the United States and Europe indicated that these drugs have a profound effect on total mortality after an acute MI and are particularly effective in preventing sudden death.

In the Beta-Blocker Heart Attack Trial (BHAT), β-blockers initiated within 7 days of hospitalization for an acute myocardial infarction decreased all mortality by 26% and sudden death by 28%. In BHAT patients with heart failure, therapy with β-blockers resulted in a 47% decrease in sudden death. Propranolol was used in BHAT, initiated at a dose of 120 mg daily and increased to 160–180 mg at 4 weeks.

Despite these reported effects, β-blocker therapy was poorly accepted for the routine treatment after an acute MI. Well into the 1990s, fewer than 50% of patients who had experienced an acute myocardial infarction received that therapy. It was not until the incorporation of β-blocker therapy as a quality measure by the National Committee for Quality Assurance (NCQA) in 1996 and the subsequent inclusion in American Heart Association-American College of Cardiology guidelines in 2000 that they were more widely used. Now, well over 90% of patients discharged from the hospital after an acute myocardial infarction are treated with β-blockers. It is often a low dose, but they are receiving some therapy nonetheless.

Although we cannot be certain what led to the decrease in sudden death in Olmsted County, it is tempting to presume that at least it can be attributed in part to the temporal changes in β-blocker usage.

Quality improvement programs provide a measure of whether or not a drug is ordered, but they do not measure the dose used. Equating the propranolol doses in BHAT to the contemporary β-blockers carvedilol and metoprolol succinate, both of which have been shown to provide benefits similar to that of propranolol, calls for daily doses up to 50 mg and 200 mg, respectively. The NCQA has recently introduced a new measure to ensure continuing therapy after 6 months, after a study in 2006 indicated that only 71% of patients after an acute myocardial infarction were still receiving β-blockers.

The observations from Olmsted County place in perspective the success of the quality improvement process in mitigating mortality in acute myocardial infarction. They also should provide an important encouragement for the practitioner to use full doses of contemporary β-blockers and to continue therapy.

Treatment of acute coronary syndromes has come a long way since 1969, when Dr. Arthur Moss and I held a symposium at the University of Rochester titled, The Prehospital Phase of Acute Myocardial Infarction. It was one of the first such events focused on the early pathophysiologic events and care of patients with symptoms of an acute myocardial infarction (Am. J. Card. 1969;24:609–11).

This meeting was held about 4 years after Prof. Desmond Julian in Edinburgh proposed the concept of a coronary care unit and a few years after Dr. Frank Partridge had organized the first mobile coronary care unit in Belfast, Northern Ireland, and Dr. Hughes Day established the first CCU in Bethany, Kan. These seminal efforts showed that patients with an acute MI were best cared for in the setting of a unit dedicated to the treatment of the pathophysiologic events associated with acute myocardial ischemia. Prior to the development of CCUs, patients with acute MIs were hospitalized in the general hospital ward without any special monitoring.

We became interested at that time in the prodromal symptoms leading up to the event and factors that lead to the decision to come to the hospital. We observed that approximately 3.5 hours elapsed from the onset of symptoms to hospital arrival (Circulation 1970;41:737–42). More than half of that time was taken up with the patient and or family making a decision to come to the hospital. It is more than likely that many patients who experienced an acute MI could have died in that time.

To deal with hospital delay, we among others urged for the first time that patients come promptly to the emergency department without consulting their physicians. This was a sharp departure from the standard of practice at that time. The rest, of course, is history. The floodgates were opened and the emergency departments (EDs) were deluged with the myriad of medical causes of chest pain, real and fancied. The emergency physicians were left to sort it all out.

Fast forward to the development of biomarkers, exercise technology, and imaging that developed from the need to define and identify the individual with an acute coronary event. Today there are approximately 8 million visits to the ED for chest pain and related symptoms. Of these, approximately 20% are defined as an acute coronary syndrome (ACS) event. Of the estimated 1.1 million myocardial infarctions annually in the United States, about half the patients survive and make it to the ED for care. Recent studies indicate that the diagnosis of acute MI is missed in 2.1% of them (N. Engl. J. Med. 2000;342:1163–70). Similarly, 2.3% of patients seen in the ED for unstable angina are discharged and their diagnosis is missed. The risk-adjusted mortality rate in those patients in whom the diagnosis was missed is associated with an increased mortality risk.

In response to this deluge of patients coming to EDs, more than 1,500 chest pain units have been established, most of them attached to an ED where patients can be monitored and evaluated outside of the hurly-burly atmosphere characteristic of emergency departments. These units were first established by the American College of Cardiovascular Administrators in 1991, which later merged into the Society of Chest Pain Centers and Providers (SCPCP). The organization is made up predominately of ED physicians and bridges the fields of emergency medicine, cardiology, and critical care nursing. Although often located within emergency facilities, they provide an atmosphere where patients can be evaluated using current diagnostic facilities at a cost less than that of the traditional CCU. They also expedite early therapy for patients with ACS by shortening door-to-needle time and by early administration of thrombolytic and pharmacologic therapy to minimize ischemia. The chest pain centers are now undergoing an accreditation process under the direction of the SCPCP.

To deal with this increased volume of patients coming to the ED for evaluation of chest pain, hospitals have modified emergency department facilities and procedures. The establishment of chest pain centers has provided a model of how chest pain patients can be expeditiously managed and treated in the face of increasing patient volume in an era of decreasing numbers of EDs nationwide.

Treatment of acute coronary syndromes has come a long way since 1969, when Dr. Arthur Moss and I held a symposium at the University of Rochester titled, The Prehospital Phase of Acute Myocardial Infarction. It was one of the first such events focused on the early pathophysiologic events and care of patients with symptoms of an acute myocardial infarction (Am. J. Card. 1969;24:609–11).

This meeting was held about 4 years after Prof. Desmond Julian in Edinburgh proposed the concept of a coronary care unit and a few years after Dr. Frank Partridge had organized the first mobile coronary care unit in Belfast, Northern Ireland, and Dr. Hughes Day established the first CCU in Bethany, Kan. These seminal efforts showed that patients with an acute MI were best cared for in the setting of a unit dedicated to the treatment of the pathophysiologic events associated with acute myocardial ischemia. Prior to the development of CCUs, patients with acute MIs were hospitalized in the general hospital ward without any special monitoring.

We became interested at that time in the prodromal symptoms leading up to the event and factors that lead to the decision to come to the hospital. We observed that approximately 3.5 hours elapsed from the onset of symptoms to hospital arrival (Circulation 1970;41:737–42). More than half of that time was taken up with the patient and or family making a decision to come to the hospital. It is more than likely that many patients who experienced an acute MI could have died in that time.

To deal with hospital delay, we among others urged for the first time that patients come promptly to the emergency department without consulting their physicians. This was a sharp departure from the standard of practice at that time. The rest, of course, is history. The floodgates were opened and the emergency departments (EDs) were deluged with the myriad of medical causes of chest pain, real and fancied. The emergency physicians were left to sort it all out.

Fast forward to the development of biomarkers, exercise technology, and imaging that developed from the need to define and identify the individual with an acute coronary event. Today there are approximately 8 million visits to the ED for chest pain and related symptoms. Of these, approximately 20% are defined as an acute coronary syndrome (ACS) event. Of the estimated 1.1 million myocardial infarctions annually in the United States, about half the patients survive and make it to the ED for care. Recent studies indicate that the diagnosis of acute MI is missed in 2.1% of them (N. Engl. J. Med. 2000;342:1163–70). Similarly, 2.3% of patients seen in the ED for unstable angina are discharged and their diagnosis is missed. The risk-adjusted mortality rate in those patients in whom the diagnosis was missed is associated with an increased mortality risk.

In response to this deluge of patients coming to EDs, more than 1,500 chest pain units have been established, most of them attached to an ED where patients can be monitored and evaluated outside of the hurly-burly atmosphere characteristic of emergency departments. These units were first established by the American College of Cardiovascular Administrators in 1991, which later merged into the Society of Chest Pain Centers and Providers (SCPCP). The organization is made up predominately of ED physicians and bridges the fields of emergency medicine, cardiology, and critical care nursing. Although often located within emergency facilities, they provide an atmosphere where patients can be evaluated using current diagnostic facilities at a cost less than that of the traditional CCU. They also expedite early therapy for patients with ACS by shortening door-to-needle time and by early administration of thrombolytic and pharmacologic therapy to minimize ischemia. The chest pain centers are now undergoing an accreditation process under the direction of the SCPCP.

To deal with this increased volume of patients coming to the ED for evaluation of chest pain, hospitals have modified emergency department facilities and procedures. The establishment of chest pain centers has provided a model of how chest pain patients can be expeditiously managed and treated in the face of increasing patient volume in an era of decreasing numbers of EDs nationwide.

Treatment of acute coronary syndromes has come a long way since 1969, when Dr. Arthur Moss and I held a symposium at the University of Rochester titled, The Prehospital Phase of Acute Myocardial Infarction. It was one of the first such events focused on the early pathophysiologic events and care of patients with symptoms of an acute myocardial infarction (Am. J. Card. 1969;24:609–11).

This meeting was held about 4 years after Prof. Desmond Julian in Edinburgh proposed the concept of a coronary care unit and a few years after Dr. Frank Partridge had organized the first mobile coronary care unit in Belfast, Northern Ireland, and Dr. Hughes Day established the first CCU in Bethany, Kan. These seminal efforts showed that patients with an acute MI were best cared for in the setting of a unit dedicated to the treatment of the pathophysiologic events associated with acute myocardial ischemia. Prior to the development of CCUs, patients with acute MIs were hospitalized in the general hospital ward without any special monitoring.

We became interested at that time in the prodromal symptoms leading up to the event and factors that lead to the decision to come to the hospital. We observed that approximately 3.5 hours elapsed from the onset of symptoms to hospital arrival (Circulation 1970;41:737–42). More than half of that time was taken up with the patient and or family making a decision to come to the hospital. It is more than likely that many patients who experienced an acute MI could have died in that time.

To deal with hospital delay, we among others urged for the first time that patients come promptly to the emergency department without consulting their physicians. This was a sharp departure from the standard of practice at that time. The rest, of course, is history. The floodgates were opened and the emergency departments (EDs) were deluged with the myriad of medical causes of chest pain, real and fancied. The emergency physicians were left to sort it all out.

Fast forward to the development of biomarkers, exercise technology, and imaging that developed from the need to define and identify the individual with an acute coronary event. Today there are approximately 8 million visits to the ED for chest pain and related symptoms. Of these, approximately 20% are defined as an acute coronary syndrome (ACS) event. Of the estimated 1.1 million myocardial infarctions annually in the United States, about half the patients survive and make it to the ED for care. Recent studies indicate that the diagnosis of acute MI is missed in 2.1% of them (N. Engl. J. Med. 2000;342:1163–70). Similarly, 2.3% of patients seen in the ED for unstable angina are discharged and their diagnosis is missed. The risk-adjusted mortality rate in those patients in whom the diagnosis was missed is associated with an increased mortality risk.

In response to this deluge of patients coming to EDs, more than 1,500 chest pain units have been established, most of them attached to an ED where patients can be monitored and evaluated outside of the hurly-burly atmosphere characteristic of emergency departments. These units were first established by the American College of Cardiovascular Administrators in 1991, which later merged into the Society of Chest Pain Centers and Providers (SCPCP). The organization is made up predominately of ED physicians and bridges the fields of emergency medicine, cardiology, and critical care nursing. Although often located within emergency facilities, they provide an atmosphere where patients can be evaluated using current diagnostic facilities at a cost less than that of the traditional CCU. They also expedite early therapy for patients with ACS by shortening door-to-needle time and by early administration of thrombolytic and pharmacologic therapy to minimize ischemia. The chest pain centers are now undergoing an accreditation process under the direction of the SCPCP.

To deal with this increased volume of patients coming to the ED for evaluation of chest pain, hospitals have modified emergency department facilities and procedures. The establishment of chest pain centers has provided a model of how chest pain patients can be expeditiously managed and treated in the face of increasing patient volume in an era of decreasing numbers of EDs nationwide.

As this column is being written, America's quadrennial self-flagellation over choosing a new president is underway, and by the time it arrives in your mailbox, a new president will have been elected.

That president will be facing numerous problems, one of which is providing health care to the 300 million Americans in the face of a failing economy, a huge budget deficit, and increasing unemployment, particularly in the manufacturing sector. Because employers laid the foundation upon which health insurance has been built, economic collapse, particularly of the auto industry and its related support industries, would leave thousands of workers without health insurance. Those who are employed will face increasing personal costs to participate in their coverage. In this environment, our ability as physicians to meet the standards of cardiac care will become increasingly difficult.

How either candidate meets the expectations in the next 4 years remains uncertain regardless of who becomes president. If we have a Democratic president along with the presumed ascendancy of a Democratic majority in Congress, it is possible but not certain that significant changes will occur. Sen. Barack Obama has promised a $2,500 decrease in insurance premiums and providing health care to everyone by achieving efficiencies in care.

With a Republican president, it is more than likely we will continue to deal with a stalemate in the face of a Democratic Congress. Nevertheless, Sen. John McCain plans to provide a tax credit for each individual of $2,500 and $5,000 to every family. Those who are uninsured can take their tax credit and apply it to the insurance of their choice when they become insured.

It is clear, however, that no one is totally happy with how health care is provided at the present. There is considerable anxiety about our individual ability to pay for health insurance as the cost of these plans continues to increase. At the same time, the number of uninsured remains unacceptably large—almost 45 million Americans are without health insurance. There has been a slight decrease in the number of Americans without insurance as more families are turning to Medicare and Medicaid as incomes decrease and the population ages. In 2008, as unemployment has risen and individuals have lost their employer-supported insurance, there has been a 2.1% nationwide increase in patients going into Medicaid. In Michigan, where unemployment is approximately 10%, Medicaid enrollment increased by 3.8%. As unemployment increases, we can anticipate this expansion of government coverage to increase.

The recent huge advances made in clinical science with its resultant increase in expensive drugs and devices represent a paradox in an atmosphere of diminishing economic resources. The calls for more aggressive preventive measures to decrease the incidence of coronary heart disease, hypertension, and diabetes is occurring in the face of an expanding population of uninsured patients and decreasing financial resources. Preventive medicine is lacking even for insured Americans.

However, throughout the country, alternative ways to pay and organize health insurance and provide a more inclusive system are emerging.

The Massachusetts health plan is one of those alternatives. It requires that each resident be enrolled in a private, state, or federal insurance program. It mandates universal coverage to those with lower incomes, using a sliding scale of premiums for families who are earning less than three times the poverty level or $63,000. Many of the insured have purchased private insurance, participate in the subsidized plan, or have enrolled in Medicaid. By providing state-sponsored health insurance programs, Massachusetts has seen the uninsured rate decrease to about 5% (N. Engl. J. Med. 2008:358;2757–60). This program, which relies on funding from the Centers for Medicare and Medicaid Services, provides a foundation upon which preventive medicine can be built, as well as an opportunity to mitigate the forces that lead to annually increasing acute care expenses. Whether or not this model can be applied to a larger population, particularly in view of the problematic national economy, our next president faces a significant challenge indeed.

As this column is being written, America's quadrennial self-flagellation over choosing a new president is underway, and by the time it arrives in your mailbox, a new president will have been elected.

That president will be facing numerous problems, one of which is providing health care to the 300 million Americans in the face of a failing economy, a huge budget deficit, and increasing unemployment, particularly in the manufacturing sector. Because employers laid the foundation upon which health insurance has been built, economic collapse, particularly of the auto industry and its related support industries, would leave thousands of workers without health insurance. Those who are employed will face increasing personal costs to participate in their coverage. In this environment, our ability as physicians to meet the standards of cardiac care will become increasingly difficult.

How either candidate meets the expectations in the next 4 years remains uncertain regardless of who becomes president. If we have a Democratic president along with the presumed ascendancy of a Democratic majority in Congress, it is possible but not certain that significant changes will occur. Sen. Barack Obama has promised a $2,500 decrease in insurance premiums and providing health care to everyone by achieving efficiencies in care.

With a Republican president, it is more than likely we will continue to deal with a stalemate in the face of a Democratic Congress. Nevertheless, Sen. John McCain plans to provide a tax credit for each individual of $2,500 and $5,000 to every family. Those who are uninsured can take their tax credit and apply it to the insurance of their choice when they become insured.

It is clear, however, that no one is totally happy with how health care is provided at the present. There is considerable anxiety about our individual ability to pay for health insurance as the cost of these plans continues to increase. At the same time, the number of uninsured remains unacceptably large—almost 45 million Americans are without health insurance. There has been a slight decrease in the number of Americans without insurance as more families are turning to Medicare and Medicaid as incomes decrease and the population ages. In 2008, as unemployment has risen and individuals have lost their employer-supported insurance, there has been a 2.1% nationwide increase in patients going into Medicaid. In Michigan, where unemployment is approximately 10%, Medicaid enrollment increased by 3.8%. As unemployment increases, we can anticipate this expansion of government coverage to increase.

The recent huge advances made in clinical science with its resultant increase in expensive drugs and devices represent a paradox in an atmosphere of diminishing economic resources. The calls for more aggressive preventive measures to decrease the incidence of coronary heart disease, hypertension, and diabetes is occurring in the face of an expanding population of uninsured patients and decreasing financial resources. Preventive medicine is lacking even for insured Americans.

However, throughout the country, alternative ways to pay and organize health insurance and provide a more inclusive system are emerging.

The Massachusetts health plan is one of those alternatives. It requires that each resident be enrolled in a private, state, or federal insurance program. It mandates universal coverage to those with lower incomes, using a sliding scale of premiums for families who are earning less than three times the poverty level or $63,000. Many of the insured have purchased private insurance, participate in the subsidized plan, or have enrolled in Medicaid. By providing state-sponsored health insurance programs, Massachusetts has seen the uninsured rate decrease to about 5% (N. Engl. J. Med. 2008:358;2757–60). This program, which relies on funding from the Centers for Medicare and Medicaid Services, provides a foundation upon which preventive medicine can be built, as well as an opportunity to mitigate the forces that lead to annually increasing acute care expenses. Whether or not this model can be applied to a larger population, particularly in view of the problematic national economy, our next president faces a significant challenge indeed.

As this column is being written, America's quadrennial self-flagellation over choosing a new president is underway, and by the time it arrives in your mailbox, a new president will have been elected.

That president will be facing numerous problems, one of which is providing health care to the 300 million Americans in the face of a failing economy, a huge budget deficit, and increasing unemployment, particularly in the manufacturing sector. Because employers laid the foundation upon which health insurance has been built, economic collapse, particularly of the auto industry and its related support industries, would leave thousands of workers without health insurance. Those who are employed will face increasing personal costs to participate in their coverage. In this environment, our ability as physicians to meet the standards of cardiac care will become increasingly difficult.

How either candidate meets the expectations in the next 4 years remains uncertain regardless of who becomes president. If we have a Democratic president along with the presumed ascendancy of a Democratic majority in Congress, it is possible but not certain that significant changes will occur. Sen. Barack Obama has promised a $2,500 decrease in insurance premiums and providing health care to everyone by achieving efficiencies in care.

With a Republican president, it is more than likely we will continue to deal with a stalemate in the face of a Democratic Congress. Nevertheless, Sen. John McCain plans to provide a tax credit for each individual of $2,500 and $5,000 to every family. Those who are uninsured can take their tax credit and apply it to the insurance of their choice when they become insured.

It is clear, however, that no one is totally happy with how health care is provided at the present. There is considerable anxiety about our individual ability to pay for health insurance as the cost of these plans continues to increase. At the same time, the number of uninsured remains unacceptably large—almost 45 million Americans are without health insurance. There has been a slight decrease in the number of Americans without insurance as more families are turning to Medicare and Medicaid as incomes decrease and the population ages. In 2008, as unemployment has risen and individuals have lost their employer-supported insurance, there has been a 2.1% nationwide increase in patients going into Medicaid. In Michigan, where unemployment is approximately 10%, Medicaid enrollment increased by 3.8%. As unemployment increases, we can anticipate this expansion of government coverage to increase.

The recent huge advances made in clinical science with its resultant increase in expensive drugs and devices represent a paradox in an atmosphere of diminishing economic resources. The calls for more aggressive preventive measures to decrease the incidence of coronary heart disease, hypertension, and diabetes is occurring in the face of an expanding population of uninsured patients and decreasing financial resources. Preventive medicine is lacking even for insured Americans.

However, throughout the country, alternative ways to pay and organize health insurance and provide a more inclusive system are emerging.

The Massachusetts health plan is one of those alternatives. It requires that each resident be enrolled in a private, state, or federal insurance program. It mandates universal coverage to those with lower incomes, using a sliding scale of premiums for families who are earning less than three times the poverty level or $63,000. Many of the insured have purchased private insurance, participate in the subsidized plan, or have enrolled in Medicaid. By providing state-sponsored health insurance programs, Massachusetts has seen the uninsured rate decrease to about 5% (N. Engl. J. Med. 2008:358;2757–60). This program, which relies on funding from the Centers for Medicare and Medicaid Services, provides a foundation upon which preventive medicine can be built, as well as an opportunity to mitigate the forces that lead to annually increasing acute care expenses. Whether or not this model can be applied to a larger population, particularly in view of the problematic national economy, our next president faces a significant challenge indeed.

Let's face it: Diabetes management has been off the radar screen of most cardiologists. But the recent report of two major randomized clinical trials should reenergize research in the pathogenesis of macrovascular atherosclerotic disease in diabetes and increase our efforts in the prevention of cardiovascular sequelae of this disease.

These two trials, ACCORD (Action to Control Cardiovascular Risk in Diabetes) and ADVANCE (Action in Diabetes and Vascular Disease) (N. Engl. J. Med. 2008:358;2545-72), explored the role of intensive glucose control in the development of macrovascular and microvascular disease in type 2 diabetic patients with established cardiovascular disease or additional risk factors. Since previous clinical studies showed that hyperglycemic control modulated microvascular disease in diabetics, it seemed reasonable to further modify glucose control to prevent macrovascular disease. Both studies achieved a significant decrease in blood glucose levels, although researchers used different drug protocols to achieve their targets.

In addition to more precise insulin therapy, ACCORD used the thiazolidinedione rosiglitazone as additive therapy to achieve the target, whereas ADVANCE used the sulfonylurea gliclazide in addition to perindopril and indapamide.

Both studies were negative in their unique ways. ACCORD failed to have a positive effect on the primary outcome of a composite of nonfatal myocardial infarction and stroke in addition to cardiovascular mortality. Although the study showed a significant decrease in nonfatal myocardial infarction, this decrease was associated with an increase in all-cause mortality and morbidity due to cardiovascular disease, which led to the study's premature termination.

In contrast, ADVANCE observed a nonsignificant 10% reduction in a composite of micro- and macrovascular end points. In regard to the macrovascular end points, the major emphasis of these studies, there was no benefit observed as to nonfatal myocardial infarction, stroke, or death. The failure of the intensive glucose control strategy to limit the expression of macrovascular disease emphasizes the importance of a more aggressive approach to secondary prevention.

Diabetes continues to be a growing problem in cardiology and most certainly will increase in its incidence as our population ages and becomes more obese. The pathogenesis of the process that accelerates the deposition of cholesterol in the arterial wall in diabetes continues to elude our understanding. It is clear, however, that diabetic patients are at increased risk of atherosclerosis and coronary artery disease.

Many of the medications that have been shown to be effective in preventing the expression and progression of coronary artery disease in the general population are equally effective in diabetes patients, and are underutilized. It is estimated that fewer than 10% of diabetic patients are being treated to target for hypertension and hyperlipidemia (JAMA 2004;291:335-42). For example, ACE inhibitors were underutilized in ACCORD. And in the ADVANCE trial, fewer than 50% of the patients randomized to that study were receiving statins, and fewer than 60% were receiving aspirin. These therapies were much more widely used in ACCORD, and this increased use was associated with a lower mortality and morbidity in ACCORD than in ADVANCE.

It is possible that other targets for intervention in the diabetic patient will be developed from the further analysis of these two very important studies and subsequent research. However, it is clear from these studies that diabetic patients should be considered at high risk for the development of atherosclerosis, even if they have not expressed a clinical event. It is therefore imperative that we become more effective in instituting preventive therapies—proved effective in cardiac patients—in our diabetic patients. Even in well-organized clinical centers such as those used in these studies, these goals are difficult to achieve and are not being met.

Let's face it: Diabetes management has been off the radar screen of most cardiologists. But the recent report of two major randomized clinical trials should reenergize research in the pathogenesis of macrovascular atherosclerotic disease in diabetes and increase our efforts in the prevention of cardiovascular sequelae of this disease.

These two trials, ACCORD (Action to Control Cardiovascular Risk in Diabetes) and ADVANCE (Action in Diabetes and Vascular Disease) (N. Engl. J. Med. 2008:358;2545-72), explored the role of intensive glucose control in the development of macrovascular and microvascular disease in type 2 diabetic patients with established cardiovascular disease or additional risk factors. Since previous clinical studies showed that hyperglycemic control modulated microvascular disease in diabetics, it seemed reasonable to further modify glucose control to prevent macrovascular disease. Both studies achieved a significant decrease in blood glucose levels, although researchers used different drug protocols to achieve their targets.

In addition to more precise insulin therapy, ACCORD used the thiazolidinedione rosiglitazone as additive therapy to achieve the target, whereas ADVANCE used the sulfonylurea gliclazide in addition to perindopril and indapamide.

Both studies were negative in their unique ways. ACCORD failed to have a positive effect on the primary outcome of a composite of nonfatal myocardial infarction and stroke in addition to cardiovascular mortality. Although the study showed a significant decrease in nonfatal myocardial infarction, this decrease was associated with an increase in all-cause mortality and morbidity due to cardiovascular disease, which led to the study's premature termination.

In contrast, ADVANCE observed a nonsignificant 10% reduction in a composite of micro- and macrovascular end points. In regard to the macrovascular end points, the major emphasis of these studies, there was no benefit observed as to nonfatal myocardial infarction, stroke, or death. The failure of the intensive glucose control strategy to limit the expression of macrovascular disease emphasizes the importance of a more aggressive approach to secondary prevention.

Diabetes continues to be a growing problem in cardiology and most certainly will increase in its incidence as our population ages and becomes more obese. The pathogenesis of the process that accelerates the deposition of cholesterol in the arterial wall in diabetes continues to elude our understanding. It is clear, however, that diabetic patients are at increased risk of atherosclerosis and coronary artery disease.

Many of the medications that have been shown to be effective in preventing the expression and progression of coronary artery disease in the general population are equally effective in diabetes patients, and are underutilized. It is estimated that fewer than 10% of diabetic patients are being treated to target for hypertension and hyperlipidemia (JAMA 2004;291:335-42). For example, ACE inhibitors were underutilized in ACCORD. And in the ADVANCE trial, fewer than 50% of the patients randomized to that study were receiving statins, and fewer than 60% were receiving aspirin. These therapies were much more widely used in ACCORD, and this increased use was associated with a lower mortality and morbidity in ACCORD than in ADVANCE.

It is possible that other targets for intervention in the diabetic patient will be developed from the further analysis of these two very important studies and subsequent research. However, it is clear from these studies that diabetic patients should be considered at high risk for the development of atherosclerosis, even if they have not expressed a clinical event. It is therefore imperative that we become more effective in instituting preventive therapies—proved effective in cardiac patients—in our diabetic patients. Even in well-organized clinical centers such as those used in these studies, these goals are difficult to achieve and are not being met.

Let's face it: Diabetes management has been off the radar screen of most cardiologists. But the recent report of two major randomized clinical trials should reenergize research in the pathogenesis of macrovascular atherosclerotic disease in diabetes and increase our efforts in the prevention of cardiovascular sequelae of this disease.

These two trials, ACCORD (Action to Control Cardiovascular Risk in Diabetes) and ADVANCE (Action in Diabetes and Vascular Disease) (N. Engl. J. Med. 2008:358;2545-72), explored the role of intensive glucose control in the development of macrovascular and microvascular disease in type 2 diabetic patients with established cardiovascular disease or additional risk factors. Since previous clinical studies showed that hyperglycemic control modulated microvascular disease in diabetics, it seemed reasonable to further modify glucose control to prevent macrovascular disease. Both studies achieved a significant decrease in blood glucose levels, although researchers used different drug protocols to achieve their targets.

In addition to more precise insulin therapy, ACCORD used the thiazolidinedione rosiglitazone as additive therapy to achieve the target, whereas ADVANCE used the sulfonylurea gliclazide in addition to perindopril and indapamide.

Both studies were negative in their unique ways. ACCORD failed to have a positive effect on the primary outcome of a composite of nonfatal myocardial infarction and stroke in addition to cardiovascular mortality. Although the study showed a significant decrease in nonfatal myocardial infarction, this decrease was associated with an increase in all-cause mortality and morbidity due to cardiovascular disease, which led to the study's premature termination.

In contrast, ADVANCE observed a nonsignificant 10% reduction in a composite of micro- and macrovascular end points. In regard to the macrovascular end points, the major emphasis of these studies, there was no benefit observed as to nonfatal myocardial infarction, stroke, or death. The failure of the intensive glucose control strategy to limit the expression of macrovascular disease emphasizes the importance of a more aggressive approach to secondary prevention.

Diabetes continues to be a growing problem in cardiology and most certainly will increase in its incidence as our population ages and becomes more obese. The pathogenesis of the process that accelerates the deposition of cholesterol in the arterial wall in diabetes continues to elude our understanding. It is clear, however, that diabetic patients are at increased risk of atherosclerosis and coronary artery disease.

Many of the medications that have been shown to be effective in preventing the expression and progression of coronary artery disease in the general population are equally effective in diabetes patients, and are underutilized. It is estimated that fewer than 10% of diabetic patients are being treated to target for hypertension and hyperlipidemia (JAMA 2004;291:335-42). For example, ACE inhibitors were underutilized in ACCORD. And in the ADVANCE trial, fewer than 50% of the patients randomized to that study were receiving statins, and fewer than 60% were receiving aspirin. These therapies were much more widely used in ACCORD, and this increased use was associated with a lower mortality and morbidity in ACCORD than in ADVANCE.

It is possible that other targets for intervention in the diabetic patient will be developed from the further analysis of these two very important studies and subsequent research. However, it is clear from these studies that diabetic patients should be considered at high risk for the development of atherosclerosis, even if they have not expressed a clinical event. It is therefore imperative that we become more effective in instituting preventive therapies—proved effective in cardiac patients—in our diabetic patients. Even in well-organized clinical centers such as those used in these studies, these goals are difficult to achieve and are not being met.

I am sure that many of you have been asked the same question that I have this summer. It typically occurred at a cocktail party, when a 50-something woman, upon learning that I am a cardiologist, sidled up and motioned toward a portly gentleman hovering over the appetizers. “That's my husband. He saw his doctor last week and was told that his blood pressure was a little high, but that he shouldn't worry. They'll check him again next year. What should he do to prevent a heart attack like Tim Russert's?”

Mr. Russert's untimely death sent shivers through millions of middle-aged men and their families. Here was a guy seemingly getting the best preventive care, yet he died from an acute myocardial infarction. Despite our efforts, sudden death remains the most common outcome of heart disease. It is estimated that at least a third of all heart attacks lead to sudden death, often the first expression of coronary heart disease. After resuscitation, patients often admit to symptoms they attributed to anything but a myocardial infarction.

Sudden death can occur as the first expression of coronary heart disease, in the setting of known coronary heart disease or in patients with advanced heart failure. Early evaluation, either by stress or by electrophysiologic testing or more sophisticated imaging with fast CT or MRI, can help in identifying patients at increased risk, but it provides little help in establishing timing of the mortality event.

It is likely that Mr. Russert's event occurred as a result of a plaque rupture and thrombus formation. The development of that plaque can be modified with statin therapy—although little is known about the effect of statins on sudden death.

Acceleration of plaque formation can occur with a variety of stimuli, including cigarette smoking, hypertension, and diabetes. The aggressive treatment of hypertension—a major step on the road to acute MI and heart failure—is critical. I am convinced that calcium entry blockers, particularly dihydropyridines, are the most effective treatment of hypertension. But since most patients with hypertension require more than one drug, β-blockers also are essential for preventing the long-term mortality and morbidity of hypertension, which include sudden death and heart failure. These drugs mitigate the adrenergic surge that occurs with an acute MI or ischemic stress. However, I admit that achieving adequate treatment of hypertension is one of the most difficult therapeutic challenges I face.

Sudden death as an expression of heart failure probably is related to a complex relation between interstitial fibrosis and increased circulating catecholamines leading to the development of micro reentry circuits that then degenerate into ventricular fibrillation. In patients with heart failure and those who have experienced a MI, β-blockers significantly decrease the risk of sudden death.

It is therefore distressing that in studies of implantable cardioverter defibrillators in heart failure, β-blockers are underutilized. Implantable cardioverter defibrillators do play an important role in the prevention of sudden death in heart failure, but as noted in previous columns, we still do not have a good understanding of which patients are best suited for ICD use.

Lastly, a comment about aspirin. Widely used in the general population, therapy with this ubiquitous drug has a paradoxical effect, as reported in the Physicians' Health Study (N. Engl. J. Med. 1989;321:129–35), by decreasing MI mortality but increasing sudden death. Guidance for aspirin therapy for primary prevention has been based in part on Framingham risk scores (N. Engl. J. Med. 2002;346:1468–74). In my opinion, aspirin has benefit in high-risk patients with ischemic heart disease and particularly in those patients who have experienced an acute coronary syndrome. But for primary prevention, the evidence is not very supportive for its use.

This leads us to the continued quandary posed by my cocktail party questioner. Unfortunately, it is almost impossible to predict the timing of sudden death, but we have been successful in decreasing the likelihood of experiencing an event in the unknown future. Its occurrence is a little like playing Russian roulette: Sometimes, the gun is loaded.

I am sure that many of you have been asked the same question that I have this summer. It typically occurred at a cocktail party, when a 50-something woman, upon learning that I am a cardiologist, sidled up and motioned toward a portly gentleman hovering over the appetizers. “That's my husband. He saw his doctor last week and was told that his blood pressure was a little high, but that he shouldn't worry. They'll check him again next year. What should he do to prevent a heart attack like Tim Russert's?”

Mr. Russert's untimely death sent shivers through millions of middle-aged men and their families. Here was a guy seemingly getting the best preventive care, yet he died from an acute myocardial infarction. Despite our efforts, sudden death remains the most common outcome of heart disease. It is estimated that at least a third of all heart attacks lead to sudden death, often the first expression of coronary heart disease. After resuscitation, patients often admit to symptoms they attributed to anything but a myocardial infarction.

Sudden death can occur as the first expression of coronary heart disease, in the setting of known coronary heart disease or in patients with advanced heart failure. Early evaluation, either by stress or by electrophysiologic testing or more sophisticated imaging with fast CT or MRI, can help in identifying patients at increased risk, but it provides little help in establishing timing of the mortality event.

It is likely that Mr. Russert's event occurred as a result of a plaque rupture and thrombus formation. The development of that plaque can be modified with statin therapy—although little is known about the effect of statins on sudden death.

Acceleration of plaque formation can occur with a variety of stimuli, including cigarette smoking, hypertension, and diabetes. The aggressive treatment of hypertension—a major step on the road to acute MI and heart failure—is critical. I am convinced that calcium entry blockers, particularly dihydropyridines, are the most effective treatment of hypertension. But since most patients with hypertension require more than one drug, β-blockers also are essential for preventing the long-term mortality and morbidity of hypertension, which include sudden death and heart failure. These drugs mitigate the adrenergic surge that occurs with an acute MI or ischemic stress. However, I admit that achieving adequate treatment of hypertension is one of the most difficult therapeutic challenges I face.

Sudden death as an expression of heart failure probably is related to a complex relation between interstitial fibrosis and increased circulating catecholamines leading to the development of micro reentry circuits that then degenerate into ventricular fibrillation. In patients with heart failure and those who have experienced a MI, β-blockers significantly decrease the risk of sudden death.

It is therefore distressing that in studies of implantable cardioverter defibrillators in heart failure, β-blockers are underutilized. Implantable cardioverter defibrillators do play an important role in the prevention of sudden death in heart failure, but as noted in previous columns, we still do not have a good understanding of which patients are best suited for ICD use.

Lastly, a comment about aspirin. Widely used in the general population, therapy with this ubiquitous drug has a paradoxical effect, as reported in the Physicians' Health Study (N. Engl. J. Med. 1989;321:129–35), by decreasing MI mortality but increasing sudden death. Guidance for aspirin therapy for primary prevention has been based in part on Framingham risk scores (N. Engl. J. Med. 2002;346:1468–74). In my opinion, aspirin has benefit in high-risk patients with ischemic heart disease and particularly in those patients who have experienced an acute coronary syndrome. But for primary prevention, the evidence is not very supportive for its use.

This leads us to the continued quandary posed by my cocktail party questioner. Unfortunately, it is almost impossible to predict the timing of sudden death, but we have been successful in decreasing the likelihood of experiencing an event in the unknown future. Its occurrence is a little like playing Russian roulette: Sometimes, the gun is loaded.

I am sure that many of you have been asked the same question that I have this summer. It typically occurred at a cocktail party, when a 50-something woman, upon learning that I am a cardiologist, sidled up and motioned toward a portly gentleman hovering over the appetizers. “That's my husband. He saw his doctor last week and was told that his blood pressure was a little high, but that he shouldn't worry. They'll check him again next year. What should he do to prevent a heart attack like Tim Russert's?”

Mr. Russert's untimely death sent shivers through millions of middle-aged men and their families. Here was a guy seemingly getting the best preventive care, yet he died from an acute myocardial infarction. Despite our efforts, sudden death remains the most common outcome of heart disease. It is estimated that at least a third of all heart attacks lead to sudden death, often the first expression of coronary heart disease. After resuscitation, patients often admit to symptoms they attributed to anything but a myocardial infarction.

Sudden death can occur as the first expression of coronary heart disease, in the setting of known coronary heart disease or in patients with advanced heart failure. Early evaluation, either by stress or by electrophysiologic testing or more sophisticated imaging with fast CT or MRI, can help in identifying patients at increased risk, but it provides little help in establishing timing of the mortality event.

It is likely that Mr. Russert's event occurred as a result of a plaque rupture and thrombus formation. The development of that plaque can be modified with statin therapy—although little is known about the effect of statins on sudden death.

Acceleration of plaque formation can occur with a variety of stimuli, including cigarette smoking, hypertension, and diabetes. The aggressive treatment of hypertension—a major step on the road to acute MI and heart failure—is critical. I am convinced that calcium entry blockers, particularly dihydropyridines, are the most effective treatment of hypertension. But since most patients with hypertension require more than one drug, β-blockers also are essential for preventing the long-term mortality and morbidity of hypertension, which include sudden death and heart failure. These drugs mitigate the adrenergic surge that occurs with an acute MI or ischemic stress. However, I admit that achieving adequate treatment of hypertension is one of the most difficult therapeutic challenges I face.

Sudden death as an expression of heart failure probably is related to a complex relation between interstitial fibrosis and increased circulating catecholamines leading to the development of micro reentry circuits that then degenerate into ventricular fibrillation. In patients with heart failure and those who have experienced a MI, β-blockers significantly decrease the risk of sudden death.

It is therefore distressing that in studies of implantable cardioverter defibrillators in heart failure, β-blockers are underutilized. Implantable cardioverter defibrillators do play an important role in the prevention of sudden death in heart failure, but as noted in previous columns, we still do not have a good understanding of which patients are best suited for ICD use.

Lastly, a comment about aspirin. Widely used in the general population, therapy with this ubiquitous drug has a paradoxical effect, as reported in the Physicians' Health Study (N. Engl. J. Med. 1989;321:129–35), by decreasing MI mortality but increasing sudden death. Guidance for aspirin therapy for primary prevention has been based in part on Framingham risk scores (N. Engl. J. Med. 2002;346:1468–74). In my opinion, aspirin has benefit in high-risk patients with ischemic heart disease and particularly in those patients who have experienced an acute coronary syndrome. But for primary prevention, the evidence is not very supportive for its use.

This leads us to the continued quandary posed by my cocktail party questioner. Unfortunately, it is almost impossible to predict the timing of sudden death, but we have been successful in decreasing the likelihood of experiencing an event in the unknown future. Its occurrence is a little like playing Russian roulette: Sometimes, the gun is loaded.