Tadashige Fujii

Iodine-123 Metaiodobenzylguanidine Scintigraphic Assessment of Myocardial Sympathetic Innervation in Patients With Familial Amyloid Polyneuropathy☆

OBJECTIVES This study attempted to assess myocardial sympathetic innervation using iodine-123 (I-123) metaidobenzylguanidine (MIBG) imaging in patients with familial amyloid polyneuropathy. BACKGROUND Signs and symptoms of cardiac autonomic dysfunction are commonly seen in patients with cardiac amyloidosis. However, the incidence and magnitude of abnormalities in myocardial sympathetic nerve function by means of I-123 MIBG imaging and their relation to clinical findings, cardiac function and the results of thallium-201 (Tl-201) and technetium-99m pyrophosphate (Tc-99m PYP) myocardial scanning have not yet been clarified. METHODS We performed M-mode, two-dimensional and Doppler echocardiography and I-123 MIBG, Tl-201 and Tc-99m PYP imaging of the heart in 12 patients with familial amyloid polyneuropathy and biopsy-proved cardiac amyloidosis. RESULTS Ten of 12 patients had no clinical evidence of overt heart disease, but left ventricular (LV) wall thickening was observed in 4 of these 10. Left ventricular percent fractional shortening and Doppler transmitral flow velocity patterns were found to be normal in all 12 patients. Eight of 12 patients showed no myocardial MIBG accumulation, with limited uptake in the remaining 4 demonstrated only in the LV anterior wall. Diffuse but mild myocardial uptake of Tc-99m PYP occurred in only 4 of 12 patients, and all 12 had normal results on Tl-201 myocardial scanning. Complete defects on myocardial MIBG scans were found in five of eight patients with negative findings on Tc-99m PYP myocardial scanning. The incidence and magnitude of myocardial uptake of MIBG were independent of clinical findings, extent of endomyocardial amyloid deposition, electrocardiographic QRS voltage and ventricular wall thickness. CONCLUSIONS Patients with familial amyloid polyneuropathy show a high incidence of myocardial adrenergic denervation with viable myocardium that can be identified very early in cardiac amyloidosis, before the development of clinically apparent heart disease, ventricular wall thickening, significant LV systolic and diastolic dysfunction and positive findings on Tc-99m PYP myocardial scanning.

Early identification of amyloid heart disease by technetium-99m-pyrophosphate scintigraphy: A study with familial amyloid polyneuropathy

To determine whether technetium-99m-pyrophosphate (Tc-99m-PYP) scanning or two-dimensional echocardiography can detect amyloid heart disease in an earlier stage of familial amyloid polyneuropathy, 15 patients were examined. Although 10 of the 15 patients had no clinical evidence of congestive heart failure, as well as normal ventricular wall thickness and normal values for left ventricular systolic function, five (50%) of them showed mild or moderate myocardial uptake. On the other hand, none had characteristic highly refractile myocardial echoes on the two-dimensional echocardiographic images (p less than 0.01), and values for diastolic function were reduced in four of the five and normal in the remaining one. In 85 control subjects, diffuse positive pyrophosphate scans of the heart were found in four (5%) of them (three with dilated cardiomyopathy and one with sarcoidosis), and highly refractile granular sparkling echoes were observed in nine (11%) (five with hypertrophic cardiomyopathy, three with aortic stenosis, and one with hypereosinophilic syndrome). We conclude that Tc-99m-PYP scanning is a more sensitive and specific method and may have the potential ability to detect amyloid heart disease in the earlier stage of familial amyloid polyneuropathy than two-dimensional echocardiography.

Hypoxia-Induced Pulmonary Blood Redistribution in Subjects With a History of High-Altitude Pulmonary Edema

BACKGROUND Pulmonary hypertension has been suggested to play an important role in development of high-altitude pulmonary edema (HAPE), and individual susceptibility has been suggested to be associated with enhanced pulmonary vascular response to hypoxia. We hypothesized that much greater pulmonary vasoconstriction would be induced by acute alveolar hypoxia in HAPE-susceptible (HAPE-s) subjects and that changes in pulmonary blood flow distribution could be demonstrated by radionuclide study. METHODS AND RESULTS We performed ventilation-perfusion scintigraphy in 8 HAPE-s subjects and 5 control subjects while each was in the supine position and acquired functional images of pulmonary blood flow and ventilation under separate normoxic and hypoxic (arterial oxygen saturation, 70%) conditions. We also measured acceleration time/right ventricular ejection time (AcT/RVET) with Doppler echocardiography under each condition in both groups. Moreover, we assayed human leukocyte antigen (HLA) alleles serologically in the HAPE-s group. Pulmonary blood flow was significantly shifted from the basal lung region to the apical lung region under hypoxia in HAPE-s subjects, although no significant change in regional ventilation was observed. With Doppler echocardiography, HAPE-s subjects showed increased pulmonary arterial pressure during hypoxia compared with control subjects. The magnitude of cephalad redistribution of lung blood flow was significantly higher in the HLA-DR6-positive than in HLA-DR6-negative HAPE-s subjects. CONCLUSIONS These findings suggest that acute hypoxia induces much greater cephalad redistribution of pulmonary blood flow that results from exaggerated vasoconstriction in the basal lung in HAPE-s subjects. Furthermore, pulmonary vascular hyperreactivity to hypoxia may be associated with HLA-DR6.

Radionuclide angiographic assessment of left ventricular diastolic filling in amyloid heart disease: A study of patients with familial amyloid polyneuropathy

To assess left ventricular diastolic filling in amyloid heart disease, 17 patients with familial amyloid polyneuropathy and 20 normal subjects were examined by radionuclide angiography. None of the patients showed clinical evidence of restrictive cardiomyopathy. All but two patients had normal left ventricular ejection fraction. Peak filling rate was significantly lower and time to peak filling rate was significantly greater in patients than in normal subjects (2.60 +/- 0.52 versus 3.10 +/- 0.44 EDV/s, p less than 0.001, and 215 +/- 53 versus 147 +/- 18 ms, p less than 0.001, respectively). The mean left ventricular filling volume during rapid diastolic filling and atrial systole in patients was 54.5 +/- 19.5% and 44.2 +/- 21.6% of the stroke volume, respectively, compared with 83.8 +/- 6.6% (p less than 0.001) and 20.0 +/- 6.0% (p less than 0.001), respectively, in normal subjects. Although 10 of the 14 patients without clinical evidence of overt heart disease had normal ventricular wall thickness as well as normal ejection fraction, 8 of the 10 showed abnormal diastolic filling. In patients with familial amyloid polyneuropathy, indexes of diastolic filling were significantly related to ventricular wall thickness alone. The incidence and magnitude of abnormalities in time to peak filling rate and contribution of rapid filling as well as atrial systole to ventricular filling increased with age and duration of illness. Thus, abnormal diastolic filling can be seen even in the early stage of familial amyloid polyneuropathy and may be related to myocardial amyloid deposition as well as to fibrosis. Careful consideration should be given to age and duration of illness when diastolic filling is assessed in this disorder.

Reduced lung uptake of Iodine‐123 metaiodobenzylguanidine in high‐altitude pulmonary oedema

Background and objective:  Iodine‐123 metaiodobenzylguanidine (123I‐MIBG) uptake in the lungs is a potentially suitable marker of pulmonary endothelial function because MIBG behaviour in the pulmonary circulation is quantitatively similar to that of norepinephrine. In addition, hypoxia reduces 123I‐MIBG transport in pulmonary endothelial cells in vitro. The present study was undertaken to evaluate 123I‐MIBG uptake in the lungs of patients with high‐altitude pulmonary oedema (HAPE).

Estimation of pulmonary hypertension by perfusion lung scintigraphy: gravitational effect of postural changes between the lateral decubitus positions.

To estimate pulmonary hypertension in patients with various heart diseases, we devised a new method using perfuison lung scintigraphy with technetium-99m-labelled macroaggregated albumin. In this method, changes in the distribution of pulmonary perfusion caused by gravitational effects, namely, changes in the total count ratios of the right lung against the left lung between right and left lateral decubitus positions (rt/lt), were assessed in 62 patients and in 10 normal subjects. The rt/lt ratios were calculated as indices of the above changes. They correlated significantly with mean pulmonary arterial pressure (mPAP) (γ= −0.62,P < 0.001), pulmonary capillary wedge pressure (γ = −0.63,P < 0.001) and pulmonary arteriolar resistance (γ = 0.50,P < 0.001) in all subjects. In 17 patients with valvular heart diseases, the ratio correlated significantly with mPAP (γ = − 0.84,P < 0.001). In 10 patients with various heart diseases, the U/S ratio, i.e. the index of changes in the count ratios of the upper field against the lower field for the right lung following postural change from the upright to the supine position, was also obtained as well as the rt/lt ratio. The latter evidenced a better correlation with mPAP (γ = −0.90,P < 0.001) than the former (γ=−0.64,P < 0.05). We conclude that this method is valuable as a noninvasive approach for the estimation of pulmonary hypertension.

Iodine‐123 metaiodobenzylguanidine scintigraphic assessment of pulmonary vascular status in patients with chronic obstructive pulmonary disease

Background and objective:  Lung uptake of iodine‐123 metaiodobenzylguanidine (123I‐MIBG) is used as an indicator of pulmonary endothelial function. Decreased lung uptake of 123I‐MIBG has been demonstrated in patients with COPD as compared with normal subjects. The present study was performed to examine the relationship between lung uptake of 123I‐MIBG and pulmonary artery pressure (Ppa) at rest and during exercise, in patients with COPD.

Pulmonary Endothelial Impairment During Gefitinib Therapy: A Preliminary Assessment with Iodine-123-Metaiodobenzylguanidine (123IMIBG) Scintigraphy

Iodine-123-metaiodobenzylguanidine ( 123 I-MIBG) kinetics in the lung could serve as a novel diagnostic tool to evaluate endothelial damage. Interstitial lung disease (ILD) associated with gefitinib, an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI), has been reported as a serious adverse effect. This study was performed to examine the possibility that gefitinib induces pulmonary endothelial damage. Serial 123 I-MIBG scintigraphy was performed in 5 patients with non-small cell lung cancer before and one month after initiation of gefitinib treatment. Anterior planar images were acquired 15 min after injection of 123 I-MIBG and the total lung to upper mediastinum ratio (L/M) was calculated in both lungs. None of the patients developed ILD during the study. There were no significant differences in the values of L/M before and after gefitinib therapy. These findings suggest that gefitinib has little influence on the pulmonary endothelium in patients with no signs of ILD.

Study of the Ventilatory Lung Motion Imaging in Primary Lung Cancer.

TC-99m MAAによる肺血流シンチグラフィを応用して, 換気に伴う肺・胸郭系の動きを描画・定量する独自の方法, 肺換気運動イメージングを考案・利用し, 原発性肺癌84例における本法の臨床的意義を検討した.本法により, 肺内および肺辺縁の動きが描出され, 肺門型, 胸水型, T3+T4において, 肺の動きは担癌肺で低値, 両肺で低値の傾向を示した.局所肺における動きと肺血流分布の一致, 解離など多様な関係も示され, 胸膜病変, 横隔膜神経麻痺を含む種々の呼吸運動 (換気) の異常が描出された.本法は本症において肺の動きと肺血流を同時に把握でき, 病変の広がり・進展度および病態の評価に役立ち, 補助診断法として利用しうる方法である.

Early Detection of Amyloid Heart Disease by Technetium-99M-Pyrophosphate Single-Photon Emission-Computed Tomography : A Study with Familial Amyloid Polyneuropathy

Eighteen patients with familial amyloid polyneuropathy (FAP) were studied to determine whether technetium-99m-pyrophosphate (Tc-99m-PYP) scintigraphy or two-dimensional echocardiography (2-DE) can detect myocardial involvement in an earlier stage. Thirteen of them were considered to be in the early stage of myocardial amyloid infiltrative process because they showed no clinical evidence of overt heart disease, as well as normal ventricular wall thickness and normal values for left ventricular systolic function. Although planner scintigraphy showed mild or moderate myocardial uptake in six (46 %) of the 13 patients, single-photon emission-computed tomography, performed in 12 of them, demonstrated an unevenly distributed biventricular uptake in ten (83 %), including four who were judged to be negative by the planner scanning. On the other hand, none had characteristic highly refractile myocardial echoes on the 2-DE images. In additional 95 control patients with nonischemic heart disease, planner scintigraphy showed diffuse positive pyrophosphate scans of the heart in five (4%) of them and 2-DE demonstrated granular sparkling echoes in 10 (10%). In conclusion, (1) planner Tc-99m-PYP scanning is a more sensitive and specific procedure to detect amyloid heart disease in the earlier stage of FAP than 2-DE and (2) single-photon emission-computed tomography may be more sensitive for diagnosing this condition.