[Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension].

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. METHODS AND RESULTS: Plasma BNP was measured in 60 patients with primary pulmonary hypertension 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 (> or = 150 pg/ml) had a significantly lower survival rate than those with an inframedian level, according to Kaplan-Meier survival curves (p < 0.05). Plasma BNP in survivors decreased significantly during the follow-up (217 +/- 38 to 149 +/- 30 pg/ml, p < 0.05), whereas that in nonsurvivors increased (365 +/- 77 to 544 +/- 68 pg/ml, p < 0.05). Thus, survival was strikingly worse for patients with a supramedian value of follow-up BNP (> or = 180 pg/ml) than for those with an inframedian value (p < 0.0001). 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 in patients with primary pulmonary hypertension.

Mode of onset of ventricular fibrillation in patients with Brugada syndrome detected by implantable cardioverter defibrillator therapy.

OBJECTIVES: We sought to demonstrate the mode of spontaneous onset of ventricular fibrillation (VF) in patients with Brugada syndrome. BACKGROUND: The electrophysiologic mechanisms of VF in Brugada syndrome have not been fully investigated. METHODS: Nineteen patients (all male, mean age 47 +/- 12 years) with Brugada syndrome were treated with an implantable cardioverter defibrillator (ICD). The implanted devices were capable of storing electrograms during an arrhythmic event. We investigated the mode of spontaneous onset of VF according to the electrocardiographic features during the episode of VF, which were obtained from stored electrograms of ICDs and/or electrocardiographic (ECG) monitoring. RESULTS: During a follow-up of 34.7 +/- 19.4 months (range 14 to 81 months), 46 episodes of spontaneous VF attacks were documented in 7/19 (37%) patients. The event-free period between ICD implantation and the first spontaneous occurrence of VF was 14.6 +/- 12.1 months (range 3.7 to 27.4 months). We investigated 33/46 episodes of VF, for which electrocardiographic features (10 to 20 s before and during VF) were obtained from ICDs and/or ECG monitoring in five patients. A total of 22/33 episodes of VF were preceded by premature ventricular contractions (PVCs), which were almost identical to the initiating PVCs of VF. Furthermore, in three patients who had multiple VF episodes, VF attacks were always initiated by the same respective PVC. The coupling interval of the initiating PVCs of VF was 388 +/- 28 ms. CONCLUSIONS: Spontaneous episodes of VF in patients with Brugada syndrome were triggered by specific PVCs. These findings may provide important insights into the pathophysiological mechanisms causing VF in Brugada syndrome.

Plasma brain natriuretic peptide as a prognostic indicator in patients with primary pulmonary hypertension.

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 (>/=150 pg/mL) had a significantly lower survival rate than those with an inframedian level, according to Kaplan-Meier survival curves (P<0.05). Plasma BNP in survivors decreased significantly during the follow-up (217+/-38 to 149+/-30 pg/mL, P<0. 05), whereas that in nonsurvivors increased (365+/-77 to 544+/-68 pg/mL, P<0.05). Thus, survival was strikingly worse for patients with a supramedian value of follow-up BNP (>/=180 pg/mL) than for those with an inframedian value (P<0.0001). 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.

The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome.

AIMS: Brugada syndrome is considered to be a distinctive subgroup of idiopathic ventricular fibrillation. Identification of the circadian pattern of ventricular fibrillation would contribute to the elucidation of its underlying pathophysiology, but this pattern remains unknown in patients with Brugada syndrome. METHODS: and Results A total of 12 consecutive Brugada syndrome patients (46+/-14 years, all male) who underwent implantation of an implantable cardioverter defibrillator were studied. The distribution of the time of ventricular fibrillation detection was examined and classified into four 6-hour time periods of the day. The mean follow-up period following implantation was 777+/-535 days. In six out of the 12 patients, ventricular fibrillation occurred during follow-up. The data logs revealed that ventricular fibrillation was detected 30 times (range, 3-9). Ventricular fibrillation was observed more frequently at night ( 1800 h to 0600 h) than in the day (0600 h to 1800 h) (93.3% [28/30] vs 6.7%[2/30], P<0.001), and during sleep than while awake (86.7% [26/30] vs 13.3%[4/30], P<0.001). Ventricular fibrillation occurred most frequently between midnight and 0600 h in patients with ventricular fibrillation episodes during sleep (76.9% [20/26] vs 23.1%[6/26], P<0.01). CONCLUSION: These results suggest that increased nocturnal vagal activity and withdrawal sympathetic activity may play an important role in the arrhythmogenesis of the Brugada syndrome.

Increased plasma levels of adrenomedullin in patients with pulmonary hypertension.

Adrenomedullin, a potent hypotensive peptide, reduces blood pressure and pulmonary vascular resistance, and increases pulmonary blood flow. The mRNA for adrenomedullin and its receptor is highly expressed in the lung, suggesting a regulatory role for adrenomedullin in the pulmonary circulation. To investigate the clinical significance of adrenomedullin in patients with pulmonary hypertension, we studied the relationship between plasma levels of adrenomedullin and pulmonary haemodynamics. Venous, arterial and pulmonary arterial blood samples were obtained during cardiac catheterization and plasma levels of adrenomedullin were measured by specific radioimmunoassay in 33 consecutive patients with severe pulmonary hypertension (12 cases of primary pulmonary hypertension, 21 with chronic thromboembolic pulmonary hypertension; age 49+/-16 years, mean pulmonary arterial pressure 50+/-15mmHg). In addition, plasma levels of adrenomedullin were measured before and after acute nitric oxide inhalation. The changes in plasma adrenomedullin during the follow-up period of 10.3+/-4.3 months were also evaluated (n=5). Sixty-two healthy subjects served as the control group. Adrenomedullin was measured in an antecubital vein in the controls. Plasma levels of adrenomedullin were significantly higher in the patients with pulmonary hypertension than in the control subjects (10.1+/-8.7 versus 4.9+/-1.1pmol/l, P<0.01). Plasma levels of adrenomedullin, expressed as their natural logarithm, were significantly correlated with mean right atrial pressure (r=0.71, P<0.01), stroke volume (r=-0.63, P<0.01), total pulmonary resistance (r=0.60, P<0.01), mean pulmonary arterial pressure (r=0.37, P<0.05), and the natural logarithm of plasma atrial natriuretic peptide (r=0. 63, P<0.01). Plasma levels of adrenomedullin did not change significantly after nitric oxide inhalation, but significantly increased in association with the elevation of the total pulmonary resistance during the long-term follow-up period. These results suggest that plasma levels of adrenomedullin increase in proportion to the extent of pulmonary hypertension.

Plasma brain natriuretic peptide levels increase in proportion to the extent of right ventricular dysfunction in pulmonary hypertension.

OBJECTIVES: This study sought to investigate the influence of right ventricular (RV) hemodynamic variables and function on the secretion of brain natriuretic peptide (BNP) in patients with isolated RV overload. BACKGROUND: Plasma BNP is known to increase in proportion to the degree of left ventricular (LV) overload. However, whether BNP secretion is also regulated in the presence of RV overload remains unknown. METHODS: Plasma BNP and atrial natriuretic peptide (ANP) levels in the pulmonary artery were measured in 44 patients with RV overload: 18 with RV volume overload (RVVO) due to atrial septal defect and 26 with RV pressure overload (RVPO) due to primary or thromboembolic pulmonary hypertension. Right heart catheterization was performed in all patients. RV and LV ejection fraction, myocardial mass and volume of the four chambers were determined by using electron beam computed tomography. RESULTS: Although both plasma BNP and ANP levels were significantly elevated in patients with RV overload compared with values in control subjects, plasma BNP and the BNP/ANP ratio were significantly higher in patients with RVPO than with RVVO (BNP 294 +/- 72 vs. 48 +/- 14 pg/ml; BNP/ANP 1.6 +/- 0.2 vs. 0.8 +/- 0.2, both p < 0.05). Plasma BNP correlated positively with mean pulmonary artery pressure (r = 0.73), total pulmonary resistance (r = 0.79), mean right atrial pressure (r = 0.79), RV end-diastolic pressure (r = 0.76) and RV myocardial mass (r = 0.71); it correlated negatively with cardiac output (r = -0.33) and RV ejection fraction (r = -0.71). Plasma BNP significantly decreased from 315 +/- 120 to 144 +/- 54 pg/ml with long-term vasodilator therapy (total pulmonary resistance decreased from 23 +/- 4 to 15 +/- 3 Wood U). CONCLUSIONS: Plasma BNP increases in proportion to the extent of RV dysfunction in pulmonary hypertension.

Thoracic esophageal carcinoma: evaluation in the sagittal section with magnetic resonance imaging.

Among 54 patients with thoracic esophageal carcinoma (53 squamous cell carcinoma, 1 adenosquamous carcinoma), the usefulness of MR sagittal imaging for evaluating local extent (T factor) was examined by measuring the anteroposterior (AP) diameter of the tumor. The MR examination was performed using ECG gated scans with a 3 mm slice at 1.5 Tesla. T1-weighted sagittal images were obtained. In 10 patients the appearance of the esophagus was normal, and in 44 patients a tumor was detected in the sagittal section. Thirty-seven lesions were histologically proved (Tis, 1; T1, 3; T2, 3; T3, 15; T4, 15). Lesions classified as 30 mm were resected. They were located in the lower esophagus. It is concluded that lesions detected in MR sagittal images might be T3 or T4 tumors, and masses of >30 mm might extend to adjacent organs, although two tumors with an AP diameter < 25 mm also invaded the trachea.

Effect of regional myocardial perfusion abnormalities on regional myocardial early diastolic function in patients with hypertrophic cardiomyopathy.

Nonuniform hypertrophy of the left ventricle is an important factor in regional diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM). However, the effect of myocardial perfusion abnormalities on regional diastolic dysfunction has not been established in patients with HCM. We investigated the relationship between regional myocardial perfusion abnormalities and regional early diastolic function in 31 patients with HCM and 8 control patients. Short-axis images of the left ventricle recorded by cine magnetic resonance imaging were divided into ten blocks. The time-to-peak-wall-thickness-thinning rate (TPWR) and the wall thickness were measured in each block. Of the 310 blocks from the patients with HCM, 242 (78%) showed normal thallium-201 uptake (group 1), 40 (13%) showed slightly decreased uptake (group 2), and 28 (9%) showed markedly decreased uptake (group 3). There was no difference in the regional wall thickness among the three groups. The TPWR was longer in patients with HCM than in control patients. It was significantly longer in group 3 (190+/-45ms) than in group 1 (167+/-36 ms) and group 2 (160+/-31 ms). (P < 0.01). The linear regression slope of the relationship between the TPWR and the regional wall thickness was significantly steeper in group 3 than in groups 1 and 2 (P < 0.05). In conclusion, abnormalities in regional myocardial perfusion, in addition to regional hypertrophy, contributed to the regional early diastolic dysfunction in patients with HCM.

Discordant technetium-99m HMPAO and thallium-201 chloride distribution in brain tumors.

We present four cases of primary brain tumors in which both Tc-99m HMPAO and Tl-201 chloride localized in the tumors, but with discordant distribution. Larger accumulation with Tc-99m HMPAO than Tl-201 chloride was observed in two patients (one astrocytoma and one meningioma). This was related to localization of the tracer in the tumor as well as in the adjacent hyperemic region as compared with the MRI findings. In one patient with pituitary adenoma, Tc-99m HMPAO localized in nearly the entire tumor, similar to the result with Tl-201 chloride. In one patient with astrocytoma, Tc-99m HMPAO showed partial tumor accumulation, less than that shown by Tl-201 chloride. Tc-99m HMPAO uptake by brain tumors does not always reflect the viable tumor burden as compared with the distribution of Tl-201 chloride and MRI or CT findings.

Use of MR angiography in a pregnant patient with thalamic AVM.

A 32-year-old pregnant woman at 29 gestational weeks suffered from the acute onset of severe headache. Brain CT, MRI, and MR angiography (MRA) showed intraventricular and thalamic hemorrhage, ruptured from a thalamic AVM. Based on these findings, conservative treatment was continued until delivery. After cesarean delivery at 34 gestational weeks, conventional cerebral angiography was performed, followed later by gamma-knife therapy. In pregnant patients with suspected cerebrovascular disorders, MRI and MRA should be the first of choice method to evaluate information on the diseased vessels and associated lesions since there is no radiation risk or side effects of contrast medium.

Normal appearance of the esophagus in sagittal section; measurement of the anteroposterior diameter with ECG gated MR imaging.

Sagittal images are valuable for determining the location and local extent of esophageal tumors. However, the normal appearance of the esophagus in sagittal section has not yet been analyzed well, although there have been a few reports on normal esophagus in the axial plane. In this study, the anteroposterior (AP) diameter of normal thoracic esophagus was measured in sagittal images using ECG gated magnetic resonance (MR) imaging, and compared with that of cadavers. In 78 subjects, 222 of 234 portions (95%) were depicted well when the esophagus was divided into three portions (upper thoracic, middle thoracic, and lower thoracic and abdominal). Almost all the AP diameters (96%) were within 15-16 mm. The data correlated well with the measurements in cadavers. The AP diameter of normal thoracic esophagus in sagittal section was considered to be up to 16 mm. These results might be of clinical use to evaluate the location and extent of esophageal tumors.

Brain SPECT of Creutzfeldt-Jakob disease.

SPECT imaging with I-123 IMP or Tc-99m HMPAO was performed in two patients with Creutzfeldt-Jakob disease to evaluate abnormalities in brain perfusion. In the first patient, there was decreased perfusion of the left frontal, parietal, and temporal lobes. CT and MRI were negative. In the second patient, there was patchy perfusion and slightly decreased perfusion of the right hemisphere. MRI revealed slight brain atrophy and bilateral high intensity areas in the basal ganglia on T2 weighted images. Subsequent SPECT imaging revealed severely decreased perfusion of the entire brain. Subsequent MRI demonstrated severe brain atrophy.

Simultaneous assessment of regional adrenergic activity and perfusion with 123I-MIBG and 201Tl in congestive heart failure.

Simultaneous assessment of regional adrenergic activity and perfusion with 123I-meta-iodobenzylguanidine (123I-MIBG) and 201Tl in various organs was performed in 13 patients with congestive heart failure (CHF) and 13 subjects without heart failure. In order to reduce the crosstalk of 201Tl to the 123I energy window to less than 5%, a dose of 123I-MIBG more than five times greater than that of 201Tl was administered following 201Tl scintigraphy. Regional uptake of 201Tl (%dose) was significantly increased in the heart (left ventricle) and lung (both P < 0.01) in the patients with CHF. The increased global cardiac uptake could have been related to the enlarged left ventricle. The patterns of regional uptake of 123I-MIBG (% dose) at 15 min were similar to those of 201Tl, suggesting that early 123I-MIBG uptake could in part depend on regional perfusion in both groups. At 3 h, regional uptake of 123I-MIBG was significantly increased in the heart, lung and kidney (all P < 0.01) in the patients with CHF. The delayed 123I-MIBG uptake indicates the degree of neuronal accumulation of the tracer, and therefore reflects adrenergic activity. Interestingly, the cardiac 123I-MIBG (adrenergic activity) to 201Tl (unit of perfusion) ratio decreased significantly in the heart (P < 0.01) but increased significantly in the kidney (P < 0.01) in the patients with CHF compared with the control group. Cardiac 123I-MIBG washout was also significantly increased in the CHF patients. Moreover, the cardiac 123I-MIBG:201Tl ratio was negatively correlated with plasma norepinephrine concentration (r = -0.74, P < 0.01), but positively correlated with LVEF (r = 0.60, P < 0.01). These data suggest that there may be impairment of both the neuronal uptake function and the vesicular storage function in the failing heart, and an increment in neuronal uptake function in the kidneys in patients with CHF. We suggest that dual-tracer scintigraphy is a useful non-invasive method for the simultaneous assessment of adrenergic activity and perfusion in various organs in patients with heart failure.

Scintigraphic study of malignant melanoma with 123I-iodoamphetamine.

N-isopropyl-p-I-123-iodoamphetamine (123I-IMP) is extracted by the brain in proportion to regional blood flow. It is particularly useful in the clinical assessment of various pathological conditions related to altered cerebral flow. Moreover, it has been reported that 123I-IMP is avidly incorporated into melanin and melanotic melanoma. We evaluated 123I-IMP scintigraphy using either planar or single photon emission tomography (SPET) studies in 10 patients with malignant melanoma. The patients were classified into two groups according to the tumour site: Group A, six patients with primary or metastatic cutaneous malignant melanoma of the extremity with planar scintigraphy; Group B, four patients with primary malignant melanoma of other organs with planar scintigraphy and SPET. In Group A, tumour uptake was demonstrated in four of six patients; in Group B, three of four patients had tumour accumulation on SPET and planar scintigraphy. SPET revealed the exact tumour localization, even in the case of a tumour located in the lung. These results suggest that planar scintigraphy using 123I-IMP is useful in the detection of malignant melanoma. Furthermore, more clear tumour localization is possible with SPET, even in the case of a tumour located in the lung.

Extensive soft-tissue involvement of dermatomyositis detected by whole-body scintigraphy with 99mTc-MDP and 201TL-chloride.

The authors present a case of extensive soft-tissue radioactivity visualized on both 99mTc-MDP and 201Tl-chloride scintigrams in a patient with dermatomyositis and colon cancer. Incidentally, diffuse and intense uptake of 99mTc-MDP was observed in the shoulder girdles, anterior chest wall, psoas muscles, both proximal thighs and right lower limb, corresponding to the sites of symptomatic muscles, even though skin lesions were limited and no calcification was detected on radiographs. Moreover, 201Tl-chloride was also intensely accumulated in nearly the same sites as the symptomatic muscles as shown on the 99mTc-MDP bone scintigrams. Whole-body scintigraphy with 99mTc-MDP and 201Tl-chloride is a useful tool to detect occult muscle lesions with dystrophic calcification and hyperemia in dermatomyositis.

Assessment of treatment response in irradiated lung cancer by sequential thallium-201 SPECT: comparison with tumor volume change and survival time.

We carried out a study to evaluate treatment response and residual mass in irradiated lung cancer with single photon emission computed tomography (SPECT) using 201TI, and investigated the relation among 201TI uptake ratio, tumor volume, and patient survival time. 201TI uptake ratios and tumor volume measured before and after radiotherapy were compared in 14 patients. We divided them into a complete response (CR) group (n = 5) and partial response + no change (PR + NC) group (n = 9) according to the tumor volume response determined by CT, and a longer survival (LS) group (n = 7) and shorter survival (SS) group (n = 7) according to the survival time. The CR group showed smaller 201TI uptake ratios after irradiation (5.3 +/- 6.0%) than the PR + NC group (52.0 +/- 27.4%) (p < 0.01), but there were no significant differences in 201TI uptake ratio before irradiation or survival time in the other two groups. The LS group showed a smaller 201TI uptake ratio before (107.8 +/- 48.3%) and after (17.0 +/- 14.4%) irradiation than the SS group (126.6 +/- 34.4% p < 0.01, 52.6 +/- 27.5% p < 0.05), but there were no significant differences in tumor volume before or after irradiation in the other two groups. We concluded that 201TI SPECT is very useful to evaluate treatment response in irradiated lung cancer and can play a supplementary role in evaluating prognosis.

Doppler spectral analysis of blood flow velocities in common femoral artery: age-related changes in healthy subjects and characteristics of abnormal hemodynamics in obstructive arterial disease.

Flow velocity patterns in the common femoral artery were analyzed in 66 lower extremities of 33 healthy subjects and 18 lower extremities of 12 patients with arteriosclerosis obliterans (ASO) by Doppler ultra-sonography. In a phantom study, Doppler flow velocity showed a close correlation with actual flow velocity: y = 1.02x - 1.22 (r = 0.995). In clinical trials, 33 healthy subjects were classified into three groups: group I (20-40 years), group II (41-60 years) and group III (61-80 years). Starting time of acceleration (STA) was shortened as age increased. Peak reverse velocity (PRV), maximum deceleration rate (MDR), and pulsatility index (PI) were significantly decreased in group III as compared with groups I and II. In patients with ASO, STA was prolonged, and PFV, PRV, MAR, MDR, PI, VSA, and FV were significantly decreased (p < 0.001) as compared with healthy control group III. Consequently, marked characteristic changes such as flattening of curves and disappearance of reverse flow in Doppler flow wave-form were observed. These data obtained by Doppler ultrasonography are thought to be useful for the early diagnosis and follow-up of patients with ASO.

Qualitative evaluation of chronic diffuse liver disease by STIR MRI.

OBJECTIVE: The purpose of our study was to characterize the relationship between signal intensity on STIR MRI, histology, and liver function. MATERIALS AND METHODS: MRI was performed in 39 patients with chronic liver diseases [chronic persistent hepatitis (CPH), chronic active hepatitis (CAH), liver cirrhosis (LC)] and 11 patients without liver dysfunction (normal). RESULTS: On STIR images, very low signal intensities compared with those of the spleen were seen in all 11 normal livers (100%), and brighter intensities were seen in chronic diffuse liver diseases (10 patients with CPH, 11 patients with CAH, and 18 patients with LC) (100%). The higher the signal grade on STIR images (moderate, marked), the more advanced was the chronic diffuse liver disease (p < 0.02). The levels of serum glutamic-oxaloacetic and glutamic-pyruvic transaminase increased in parallel with increasing signal intensity on STIR images (both p < 0.01). CONCLUSION: We found that the signal intensity of liver on STIR images appeared to be associated with the degree of histologic and/or clinical severity in patients with chronic liver disease.

Sequential subtraction scintigraphy with 99mTc-RBC for the early detection of gastrointestinal bleeding.

To improve the early detectability of gastrointestinal (GI) bleeding, we have developed a new subtraction scintigraphic technique using in vivo labeled 99mTc red blood cells (RBC). Use of this new sequential subtraction method every 5 min makes it possible to detect early the bleeding site and calculate the bleeding rate. In phantom experiments, focal activity was detected on subtraction images at pump rates of more than 0.20 ml/min at any urethane thickness, but was negative on conventional scintigrams. The calculated pump rate by the subtraction method correlated well with the actual syringe pump rate (y = 1.07x - 0.02, r = 0.99, p < 0.01) in the case of an 8-cm urethane board as an abdominal wall. Twenty-four of 50 patients with suspected GI bleeding were confirmed to be positive within 24 hr. The subtraction method showed 15 true positive and 2 false positive cases within 60 min. On the other hand, the conventional scintigraphic method showed only 7 true positive and 1 false positive cases. Sensitivity of the subtraction method was 62.5%, which was significantly higher (p < 0.05) than that of the conventional scintigraphic method (29.2%). These results suggest that sequential subtraction scintigraphy with 99mTc-RBC is an effective method for the early detection of GI bleeding and shortening the examination time as compared with conventional scintigraphy.