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Natriuretic Peptides in Aortic Stenosis
Abstract & Commentary
Synopsis: Since natriuretic peptide levels are elevated in symptomatic patients with moderate-severe aortic stenosis, they may be useful in the management of asymptomatic patients.
Source: Gerber IL, et al. Circulation. 2003;107: 1884-1890.
The development of symptoms and the need for other cardiac surgery are the only class I indications for valve replacement in aortic stenosis. However, in many patients with echocardiographic evidence of severe aortic stenosis, symptom status is unclear due to inactivity or concomitant diseases. Thus, a biological marker of early left ventricular decompensation would be of value. Plasma natriuretic peptide levels are related to disease severity in aortic stenosis, but their relationship to symptom status has not been reported. Gerber and colleagues studied 74 patients with isolated aortic stenosis (peak velocity > 2.5 m/s). Independent clinical evaluation revealed that 45 were symptomatic and 29 were asymptomatic. Aortic valve area by echocardiography was smaller in symptomatic patients (0.77 vs 0.99 cm2; P < .0001). Plasma natriuretic peptides were also higher in symptomatic patients (amino-terminal brain natriuretic peptide [N-BNP] 112 vs 33 pmol/L; P = .0002). After adjustment for age, sex, creatinine, and other compounders, N-BNP levels remained higher in symptomatic patients by 1.74 times (95% CI; 1.12-2.69, P = .014). Natriuretic peptide levels were also progressively higher for each NYHA class (mean N-BNP = 13, 34, 105, and 202 pmol/L, respectively). However, symptoms such as angina or syncope did not correlate with natriuretic peptide levels within each NYHA class. Angina was highly predictive of coronary artery disease at catheterization. Natriuretic peptide levels and peak aortic velocity were more predictive of symptoms (sensitivities 73-78%) than were measures of left ventriculation size and performance (sensitivities 43-70%). Gerber et al concluded that since natriuretic peptide levels are elevated in symptomatic patients with moderate-severe aortic stenosis, they may be useful in the management of asymptomatic patients.
Comment by Michael H. Crawford, MD
Physicians often feel uneasy with patients who have severe aortic stenosis by echocardiography but deny symptoms. We know prognosis is related to valve area, and when it drops to 0.7 cm2 or less, we fear sudden cardiac death will be the first symptom the patient has. In an effort to convince reluctant patients to consider surgery by bringing out symptoms, we consider a carefully monitored low-level exercise test. However, this is dangerous, time intensive for the physician, and may not convince the patient to have surgery. Clearly, a blood test would be simpler and perhaps more persuasive.
Natriuretic peptides are a good candidate for a blood test approach since they correlate with symptoms and prognosis, including sudden death, in patients with heart failure. In this study, natriuretic peptide levels were significantly different between class I and II patients with moderate-to-severe aortic stenosis (34 vs 105 pmol/L; P < .001). This suggests they may be useful for decting patients with early left ventricular dysfunction before overt or recogniziable symptoms develop. Interestingly, in this study, once NYHA class was taken into consideration, there was no realtionship between natriuretic peptide levels and symptoms of angina or syncope. This suggests that natiuretic peptide levels are related to the development of dyspnea due to left ventricular dysfunction. Interpreting natriuretic peptide levels is complicated because age and sex affect the values. Thus, it is likely that natriuretic peptides will be part of our decision-making process in aortic stenosis but not the sole criterion for surgery.
Dr. Crawford if Professor of Medicine, Mayo Medical School; Consultant in Cardiovascular Diseases, and Director of Research, Mayo Clinic, Scottsdale, AZ.