To Infuse or Not?

Abstract

Heart failure continues to be one of the few problems in cardiovascular medicine that is increasing in frequency. It is a major public health problem in the United States. Approximately five million people in this country have heart failure. There are about a half of a million patients who receive a diagnosis of heart failure for the first time each year. Heart failure is responsible for approximately 12 to 15 million office visits and approximately 6.5 million hospital days each year. Nearly 300,000 patients die of heart failure as a primary or contributory cause each year, and the number of deaths has increased steadily despite advancements in treatment. It is primarily a disease of the elderly. Approximately 5 to 10% of people > 65 years old have heart failure. It is the most common Medicare diagnosis-related group, and more Medicare dollars are spent for the diagnosis and treatment of heart failure than for any other diagnosis. In the United States, approximately five million dollars are spent annually on drugs for the treatment of heart failure.1Hunt SA Baker DW Chin MH et al.ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure).J Am Coll Cardiol. 2001; 38: 2101-2113Abstract Full Text Full Text PDF PubMed Scopus (1212) Google ScholarAs we use new developments and innovations in the treatment of coronary artery disease and valvular heart disease, patients tend to live longer and subsequently develop heart failure. End-stage congestive heart failure is a disease that has a very poor prognosis, with mortality rates > 50% in severe cardiomyopathies. Our understanding of the pathophysiology of heart failure has come quite a long way since the 1960s and 1970s when it was thought that it was primarily a “pump problem.” We now know that heart failure is a neurohormonal syndrome; as research continues, we have come a long way in using medications such as β-blockers and angiotensin-converting enzyme inhibitors in the treatment of this disease. Much controversy has existed in the use of long-term intermittent inotropic infusions in patients with end-stage congestive heart failure. There is some belief that long-term infusions may even shorten the patient's life span, but many clinicians have seen the beneficial effects of long-term intermittent inotropic infusions. In the past, there was a very small study done whereby patients who were receiving dobutamine experienced sudden death with increased frequency vs the control group. This study, in my opinion, was flawed because of the fact that it was a small study; in addition, the patients who were infused at the time had potassium levels that were low. The concern is that dobutamine and inotropic infusions may increase the incidence of arrhythmogenic death.2Steiness E Olesen KH Cardiac arrhythmias induced by hypokalaemia and potassium loss during maintenance digoxin therapy.Br Heart J. 1976; 38: 167-172Crossref PubMed Scopus (102) Google Scholar This has been the controversial issue that has separated the different schools of thought of the physicians who treat heart failure. Some advocate the use of inotropic infusions intermittently as a way for symptomatic improvement, as well as for care of the patient and improving their quality of life, while others argue that this method of treatment may shorten the patient's life span and may not be beneficial.In this issue of CHEST (see page 1198), Nanas and colleagues present a study of long-term intermittent dobutamine infusion combined with oral amiodarone for end-stage heart failure. This randomized, double-blinded, placebo-control study included 30 patients with congestive heart failure who were refractory to standard therapy. The patients were receiving digoxin, enalapril, spironolactone, and diuretics, and then were subsequently randomized to intermittent dobutamine infusion vs placebo. All patients had a radionuclide left ventricular ejection fraction of < 35%, and all patients received amiodarone therapy orally. Their hypothesis was that dobutamine would improve the hemodynamics of these patients and amiodarone would counteract the possible serious proarrhythmic effect of dobutamine. The patients were subsequently followed up by the same team of physicians in the same ICUs. It was then subsequently noted that the patients who were receiving biweekly dobutamine infusions along with amiodarone had a 57% relative reduction in death rate during the first year of follow-up and a 41% absolute reduction in mortality at 1 year. This was better than the placebo group.Obviously, this study by no means will settle the controversy of “to infuse or not” in end-stage heart failure. Nonetheless, this is a novel pilot study that is well designed and does show an improved survival benefit with dobutamine infusion. The good news from this study is that it does not show that it decreases the patient's life span. This study sets the stage for future studies that are desperately needed in this ever-evolving arena of heart failure. New therapeutic measures such as maximizing angiotensin-converting enzyme inhibition and using carvedilol3Packer M Bristow MR Cohn JN et al.The effect of carvedilol on morbidity and mortality in patients with heart failure: U.S. Cardveidol Heart Failure Study Group.N Engl J Med. 1996; 334: 1349-1355Crossref PubMed Scopus (4168) Google Scholar need to be included in future studies that are done with patients receiving inotropic outpatient intermittent infusions. The data that we have collected and the lessons that we have learned from implantable cardiac defibrillator trials, as well as biventricular pacing in patients with severe cardiomyopathy and heart failure, have to be included in future trials with or without inotropic infusions in end-stage heart failure. As this disease continues to increase in frequency, especially as the population continues to increase in age, physicians who care for these patients must continue to keep up with this rapidly advancing and changing field of heart failure.In summary, this study shows that at least we do not decrease the life span of the patient, and this can be used as a model for future studies. Obviously, it is advisable that when the physician decides to infuse, the patient should be adequately informed about the possibility that infusion therapy may shorten his/her life span. Nonetheless, it has been shown that patients who have a severe cardiomyopathy with significant heart failure that is refractory and with multiple hospitalizations may benefit symptomatically from inotropic infusions and their quality of life seems to improve. Whether this improvement is solely the result of the inotropic infusions or secondary to the fact that the physician carefully follows up the patient after every infusion and then adjusts the medical therapy, is a question that remains to be answered. Heart failure continues to be one of the few problems in cardiovascular medicine that is increasing in frequency. It is a major public health problem in the United States. Approximately five million people in this country have heart failure. There are about a half of a million patients who receive a diagnosis of heart failure for the first time each year. Heart failure is responsible for approximately 12 to 15 million office visits and approximately 6.5 million hospital days each year. Nearly 300,000 patients die of heart failure as a primary or contributory cause each year, and the number of deaths has increased steadily despite advancements in treatment. It is primarily a disease of the elderly. Approximately 5 to 10% of people > 65 years old have heart failure. It is the most common Medicare diagnosis-related group, and more Medicare dollars are spent for the diagnosis and treatment of heart failure than for any other diagnosis. In the United States, approximately five million dollars are spent annually on drugs for the treatment of heart failure.1Hunt SA Baker DW Chin MH et al.ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure).J Am Coll Cardiol. 2001; 38: 2101-2113Abstract Full Text Full Text PDF PubMed Scopus (1212) Google Scholar As we use new developments and innovations in the treatment of coronary artery disease and valvular heart disease, patients tend to live longer and subsequently develop heart failure. End-stage congestive heart failure is a disease that has a very poor prognosis, with mortality rates > 50% in severe cardiomyopathies. Our understanding of the pathophysiology of heart failure has come quite a long way since the 1960s and 1970s when it was thought that it was primarily a “pump problem.” We now know that heart failure is a neurohormonal syndrome; as research continues, we have come a long way in using medications such as β-blockers and angiotensin-converting enzyme inhibitors in the treatment of this disease. Much controversy has existed in the use of long-term intermittent inotropic infusions in patients with end-stage congestive heart failure. There is some belief that long-term infusions may even shorten the patient's life span, but many clinicians have seen the beneficial effects of long-term intermittent inotropic infusions. In the past, there was a very small study done whereby patients who were receiving dobutamine experienced sudden death with increased frequency vs the control group. This study, in my opinion, was flawed because of the fact that it was a small study; in addition, the patients who were infused at the time had potassium levels that were low. The concern is that dobutamine and inotropic infusions may increase the incidence of arrhythmogenic death.2Steiness E Olesen KH Cardiac arrhythmias induced by hypokalaemia and potassium loss during maintenance digoxin therapy.Br Heart J. 1976; 38: 167-172Crossref PubMed Scopus (102) Google Scholar This has been the controversial issue that has separated the different schools of thought of the physicians who treat heart failure. Some advocate the use of inotropic infusions intermittently as a way for symptomatic improvement, as well as for care of the patient and improving their quality of life, while others argue that this method of treatment may shorten the patient's life span and may not be beneficial. In this issue of CHEST (see page 1198), Nanas and colleagues present a study of long-term intermittent dobutamine infusion combined with oral amiodarone for end-stage heart failure. This randomized, double-blinded, placebo-control study included 30 patients with congestive heart failure who were refractory to standard therapy. The patients were receiving digoxin, enalapril, spironolactone, and diuretics, and then were subsequently randomized to intermittent dobutamine infusion vs placebo. All patients had a radionuclide left ventricular ejection fraction of < 35%, and all patients received amiodarone therapy orally. Their hypothesis was that dobutamine would improve the hemodynamics of these patients and amiodarone would counteract the possible serious proarrhythmic effect of dobutamine. The patients were subsequently followed up by the same team of physicians in the same ICUs. It was then subsequently noted that the patients who were receiving biweekly dobutamine infusions along with amiodarone had a 57% relative reduction in death rate during the first year of follow-up and a 41% absolute reduction in mortality at 1 year. This was better than the placebo group. Obviously, this study by no means will settle the controversy of “to infuse or not” in end-stage heart failure. Nonetheless, this is a novel pilot study that is well designed and does show an improved survival benefit with dobutamine infusion. The good news from this study is that it does not show that it decreases the patient's life span. This study sets the stage for future studies that are desperately needed in this ever-evolving arena of heart failure. New therapeutic measures such as maximizing angiotensin-converting enzyme inhibition and using carvedilol3Packer M Bristow MR Cohn JN et al.The effect of carvedilol on morbidity and mortality in patients with heart failure: U.S. Cardveidol Heart Failure Study Group.N Engl J Med. 1996; 334: 1349-1355Crossref PubMed Scopus (4168) Google Scholar need to be included in future studies that are done with patients receiving inotropic outpatient intermittent infusions. The data that we have collected and the lessons that we have learned from implantable cardiac defibrillator trials, as well as biventricular pacing in patients with severe cardiomyopathy and heart failure, have to be included in future trials with or without inotropic infusions in end-stage heart failure. As this disease continues to increase in frequency, especially as the population continues to increase in age, physicians who care for these patients must continue to keep up with this rapidly advancing and changing field of heart failure. In summary, this study shows that at least we do not decrease the life span of the patient, and this can be used as a model for future studies. Obviously, it is advisable that when the physician decides to infuse, the patient should be adequately informed about the possibility that infusion therapy may shorten his/her life span. Nonetheless, it has been shown that patients who have a severe cardiomyopathy with significant heart failure that is refractory and with multiple hospitalizations may benefit symptomatically from inotropic infusions and their quality of life seems to improve. Whether this improvement is solely the result of the inotropic infusions or secondary to the fact that the physician carefully follows up the patient after every infusion and then adjusts the medical therapy, is a question that remains to be answered.