Wall stress modulates brain natriuretic peptide production in pressure overload cardiomyopathy.

OBJECTIVES: We postulated that both diastolic and systolic load modulate B-type natriuretic peptide (BNP) production in human pressure overload hypertrophy/failure. BACKGROUND: In isolated myocytes, diastolic stretch induces BNP messenger ribonucleic acid expression. However, the mechanism of the BNP release in human hypertrophy remains controversial. METHODS: In 40 patients with symptomatic aortic stenosis (AS), left ventricular (LV) performance and systolic and diastolic wall stress were calculated from combined invasive and echocardiographic data. Plasma BNP was determined by the rapid point-of-care bedside analyzer (Biosite Triage, Biosite Diagnostics Inc., San Diego, California). RESULTS: A significant relationship was observed between plasma BNP and pulmonary capillary wedge pressure (p < 0.001), fractional shortening (p = 0.001), and aortic valve area (p = 0.006). Furthermore, a significant correlation was noted between BNP and LV mass index (p = 0.005) as well as between BNP and markers of diastolic load such as LV end-diastolic wall stress (p = 0.011), indexed LV end-diastolic volume (p < 0.001), and isovolumic relaxation time (p = 0.02). Preoperative BNP levels were elevated in patients with AS compared with patients without AS. Plasma BNP was higher in AS patients with impaired versus normal preload reserve (297 +/- 56 pg/ml vs. 168 +/- 44 pg/ml; p = 0.017) and in AS patients with clinical deterioration after valve replacement compared with those without (399 +/- 82 pg/ml vs. 124 +/- 41 pg/ml; p = 0.011). CONCLUSIONS: In patients with AS, BNP appears to be regulated not only by systolic but also by diastolic load. This supports the hypothesis that myocardial stretch modulates BNP production in human pressure overload hypertrophy/failure.

Hyperdynamic myocardial response to beta-adrenergic stimulation in patients with chest pain and normal coronary arteries.

OBJECTIVES: The goal of this study was to test the hypothesis that an abnormal response to beta-adrenergic stimulation may play a role in the pathophysiology of chest pain in patients with normal coronary arteries. BACKGROUND: The mechanism of angina-like (AL) chest pain in patients with angiographically normal coronary arteries remains controversial. METHODS: Fifty-eight patients with AL pain and a normal coronary angiogram underwent dobutamine echocardiography (DE) to evaluate regional wall motion and intraventricular flow velocities (IFV). Control patients consisted of 22 matched patients free of angina and coronary artery disease. Abnormal IFV were defined as dagger-shaped Doppler spectrum > or =3 m/s. RESULTS: Dobutamine-induced regional wall motion abnormalities did not develop in any of the patients. An IFV > or = 3 m/s was found in 28 patients (48%) with AL pain but in only 4 (18%) control patients (p < 0.05). In the subgroup of patients with AL pain and IFV > or =3 m/s, plasma renin concentration (PRC) was higher as compared with those with IFV <3 m/s (18 +/- 17 pg/ml vs. 9 +/- 6 pg/ml, p < 0.05). There were no differences in plasma ADR, NADR, or angiotensin-converting enzyme levels. Fourteen patients with angina and IFV > or =3 underwent control DE and blood sampling after 6 weeks treatment with 10 mg of bisoprolol. In these patients, a decrease in IFV (from 3.4 +/- 0.35 m/s to 2.46 +/- 0.64 m/s, p < 0.001) and a decrease in angina score (from 5.4 +/- 1.5 to 0.6 +/- 1.4, p < 0.001) were observed at follow-up. CONCLUSIONS: The present data suggest that an exaggerated myocardial response to beta-adrenergic stimulation plays a role in the mechanisms of chest pain in some patients with normal coronary arteries.