The six-minute walk test is a submaximal exercise test that can be performed even by a patient with heart failure not tolerating maximal exercise testing. To elucidate the clinical significance and prognostic value of the six-minute walk test in patients with primary pulmonary hypertension (PPH), we sought (1) to assess the relation between distance walked during the six-minute walk test and exercise capacity determined by maximal cardiopulmonary exercise testing, and (2) to investigate the prognostic value of the six-minute walk test in comparison with other noninvasive parameters. The six-minute walk test was performed in 43 patients with PPH, together with echocardiography, right heart catheterization, and measurement of plasma epinephrine and norepinephrine. Symptom-limited cardiopulmonary exercise testing was performed in a subsample of patients (n = 27). Distance walked in 6 min was significantly shorter in patients with PPH than in age- and sex-matched healthy subjects (297 +/- 188 versus 655 +/- 91 m, p < 0. 001). The distance significantly decreased in proportion to the severity of New York Heart Association functional class. The distance walked correlated modestly with baseline cardiac output (r = 0.48, p < 0.05) and total pulmonary resistance (r = -0.49, p < 0. 05), but not significantly with mean pulmonary arterial pressure. In contrast, the distance walked correlated strongly with peak V O(2) (r = 0.70, p < 0.001), oxygen pulse (r = 0.57, p < 0.01), and V E-VCO(2) slope (r = -0.66, p < 0.001) determined by cardiopulmonary exercise testing. During a mean follow-up period of 21 +/- 16 mo, 12 patients died of cardiopulmonary causes. Among noninvasive parameters including clinical, echocardiographic, and neurohumoral parameters, only the distance walked in 6 min was independently related to mortality in PPH by multivariate analysis. Patients walking < 332 m had a significantly lower survival rate than those walking farther, assessed by Kaplan-Meier survival curves (log-rank test, p < 0.01). These results suggest that the six-minute walk test, a submaximal exercise test, reflects exercise capacity determined by maximal cardiopulmonary exercise testing in patients with PPH, and it is the distance walked in 6 min that has a strong, independent association with mortality.

Background-Plasma brain natriuretic peptide (BNP) level increases in proportion to the degree of right ventricular dysfunction in pulmonary hypertension. We sought to assess the prognostic significance of plasma BNP in patients with primary pulmonary hypertension (PPH). Methods and Results-Plasma BNP was measured in 60 patients with PPH at diagnostic catheterization, together with atrial natriuretic peptide, norepinephrine, and epinephrine. Measurements were repeated in 53 patients after a mean follow-up period of 3 months. Forty-nine of the patients received intravenous or oral prostacyclin. During a mean follow-up period of 24 months, 18 patients died of cardiopulmonary causes. According to multivariate analysis, baseline plasma BNP was an independent predictor of mortality. Patients with a supramedian level of baseline BNP (Ն150 pg/mL) had a significantly lower survival rate than those with an inframedian level, according to Kaplan-Meier survival curves (PϽ0.05). Plasma BNP in survivors decreased significantly during the follow-up (217Ϯ38 to 149Ϯ30 pg/mL, PϽ0.05), whereas that in nonsurvivors increased (365Ϯ77 to 544Ϯ68 pg/mL, PϽ0.05). Thus, survival was strikingly worse for patients with a supramedian value of follow-up BNP (Ն180 pg/mL) than for those with an inframedian value (PϽ0.0001). Conclusions-A high level of plasma BNP, and in particular, a further increase in plasma BNP during follow-up, may have a strong, independent association with increased mortality rates in patients with PPH. (Circulation. 2000;102:865-870.)

Background-Pluripotent

Background-Ghrelin is a novel growth hormone-releasing peptide that also induces vasodilation, inhibits sympathetic nerve activity, and stimulates feeding through growth hormone-independent mechanisms. We investigated the effects of ghrelin on left ventricular (LV) function, exercise capacity, and muscle wasting in patients with chronic heart failure (CHF). Methods and Results-Human synthetic ghrelin (2 g/kg twice a day) was intravenously administered to 10 patients with CHF for 3 weeks. Echocardiography, cardiopulmonary exercise testing, dual x-ray absorptiometry, and blood sampling were performed before and after ghrelin therapy. A single administration of ghrelin elicited a marked increase in serum GH (25-fold). Three-week administration of ghrelin resulted in a significant decrease in plasma norepinephrine (1132Ϯ188 to 655Ϯ134 pg/mL; PϽ0.001). Ghrelin increased LV ejection fraction (27Ϯ2% to 31Ϯ2%; PϽ0.05) in association with an increase in LV mass and a decrease in LV end-systolic volume. Treatment with ghrelin increased peak workload and peak oxygen consumption during exercise. Ghrelin improved muscle wasting, as indicated by increases in muscle strength and lean body mass. These parameters remained unchanged in 8 patients with CHF who did not receive ghrelin therapy. Conclusions-These preliminary results suggest that repeated administration of ghrelin improves LV function, exercise capacity, and muscle wasting in patients with CHF.

Disruption of the dystrophin–glycoprotein complex caused by genetic defects of dystrophin or sarcoglycans results in muscular dystrophy and/or cardiomyopathy in humans and animal models. However, the key early molecular events leading to myocyte degeneration remain elusive. Here, we observed that the growth factor–regulated channel (GRC), which belongs to the transient receptor potential channel family, is elevated in the sarcolemma of skeletal and/or cardiac muscle in dystrophic human patients and animal models deficient in dystrophin or δ-sarcoglycan. However, total cell GRC does not differ markedly between normal and dystrophic muscles. Analysis of the properties of myotubes prepared from δ-sarcoglycan–deficient BIO14.6 hamsters revealed that GRC is activated in response to myocyte stretch and is responsible for enhanced Ca2+ influx and resultant cell damage as measured by creatine phosphokinase efflux. We found that cell stretch increases GRC translocation to the sarcolemma, which requires entry of external Ca2+. Consistent with these findings, cardiac-specific expression of GRC in a transgenic mouse model produced cardiomyopathy due to Ca2+ overloading, with disease expression roughly parallel to sarcolemmal GRC levels. The results suggest that GRC is a key player in the pathogenesis of myocyte degeneration caused by dystrophin–glycoprotein complex disruption.

Large eccentric plaque containing an echolucent zone by IVUS can be at increased risk for instability even though the lumen area is preserved at the time of initial study. Compensatory enlargement of vessel wall due to remodeling may contribute to the relatively small degree of stenosis by angiography.

These results indicate that the present system accurately represents tissue velocity and can create two-dimensional color images that facilitate visual assessment of ventricular wall motion.

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