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Abstract & Commentary
Source: Knot UN, et al. Nitroprusside in critically ill patients with left ventricular dysfunction and aortic stenosis. N Engl J Med 2003;348:1756-1763.
For decades, conventional teaching has dictated that patients with aortic stenosis and congestive heart failure should not be treated with vasodilators because of the concern of life-threatening hypotension.
In this prospective observational study, 25 patients with severe aortic stenosis and left ventricular systolic dysfunction were treated with intravenous nitroprusside (NTP). Patients were included who met the following criteria: admitted to the intensive care unit (ICU) for invasive monitoring of heart failure; ejection fraction of 35% or less, severe aortic stenosis with a valve area of 1 cm2 or less on echocardiogram; and a depressed cardiac index of 2.2 L/min/m2 or less. The only exclusion criterion was hypotension, which was defined as the need for any inotropic or vasopressor agent, or a mean systemic arterial pressure of less than 60 mmHg.
After baseline variables were recorded, the patients were treated with intravenous NTP in a dose titrated to a mean arterial pressure between 60-70 mmHg. The cardiac index and other variables then were measured at six and 24 hours after initiation of NTP. At baseline, the mean cardiac index was 1.60 ± 0.35 L/min/m2. After six hours of NTP at a mean dose of 103 ± 67 ug/min, the cardiac index had increased to 2.22 ± 0.44 L/min/m2 (p < 0.001). After 24 hours, the cardiac index had increased further to 2.52 ± 0.55L/min/m2 (p < 0.001). The increase in cardiac index was found in patients with both high-gradient and low-gradient aortic stenosis. NTP was well tolerated and had minimal side effects. All patients continued to receive NTP until surgery, conversion to medical therapy, or death. There were five in-hospital deaths and one death after discharge; all were reviewed and did not appear related to NTP.
Commentary by Stephanie B. Abbuhl, MD, FACEP
Another long-standing dictum gets put to the test and challenged with scientific data. This study shows that even with a severely stenotic aortic valve, the failing heart can increase cardiac output when afterload is reduced. NTP rapidly and markedly improved cardiac function in patients with severe left ventricular dysfunction and severe aortic stenosis.
What we don’t know from this study is if the findings can be generalized to patients with aortic stenosis who have normal left ventricular function. The authors suggest that since the normal ventricle is much less sensitive to afterload than the failing ventricle, the benefits of NTP may not outweigh the potential risks. However, given the results of this study, this certainly is an area that needs reexamination and further research.
We also don’t have a head-to-head comparison of NTP with a positive inotropic agent, so it remains unclear how an agent such as dobutamine would compare. The authors note that dobutamine has been studied and appears safe in similar patients with no coronary artery disease. However, in patients with coronary disease (as in the majority of patients in this study), there are increased complications with dobutamine, including arrhythmias and ischemia.
Patients with aortic stenosis and heart failure have an especially high risk of death and present a challenge to the emergency physician. While the use of NTP was successful in this study with invasive monitoring, its use in the emergency department without a Swan-Ganz catheter would be ill-advised. However, if more studies replicate and possibly broaden this experience, we may find ourselves considering vasodilator in patients with aortic stenosis in the near future.
Dr. Abbuhl, Medical Director, Department of Emergency Medicine, The Hospital of the University of Pennsylvania; Associate Professor of Emergency Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, is on the Editorial Board of Emergency Medicine Alert.