Taishiro Chikamori

Comparative value of brain perfusion SPECT and [123I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer’s disease

PurposeBoth decreased occipital perfusion on brain single-photon emission computed tomography (SPECT) and reduction in cardiac 123I-metaiodobenzylguanidine (MIBG) uptake are characteristic features of dementia with Lewy bodies (DLB), and potentially support the clinical diagnosis of DLB. The aim of this study was to compare the diagnostic value of these two methods for differentiation of DLB from Alzheimer’s disease (AD).MethodsThe study population comprised 19 patients with probable DLB and 39 patients with probable AD who underwent both SPECT with N-isopropyl-p-[123I]iodoamphetamine and MIBG myocardial scintigraphy. Objective and quantitative measurement of perfusion in the medial occipital lobe, including the cuneus and lingual gyrus, was performed by the use of three-dimensional stereotactic surface projections.ResultsMedial occipital perfusion was significantly decreased in the DLB group compared with the AD group. The mean heart/mediastinum ratios of MIBG uptake were significantly lower in the DLB group than in the AD group. Although SPECT failed to demonstrate significant hypoperfusion in the medial occipital lobe in five patients with DLB, marked reduction of MIBG uptake was found in all patients with DLB. Receiver operating characteristic analysis revealed that MIBG myocardial scintigraphy enabled more accurate discrimination between DLB and AD than was possible with perfusion SPECT.ConclusionMIBG myocardial scintigraphy may improve the sensitivity in the detection of DLB. In particular, this method may provide a powerful differential diagnostic tool when it is difficult to distinguish cases of DLB from AD using brain perfusion SPECT.

Mechanisms of exercise limitation in hypertrophic cardiomyopathy

To assess the relation of exercise capacity to indexes of systolic and diastolic function in hypertrophic cardiomyopathy, 81 patients underwent two-dimensional echocardiography, technetium-99m equilibrium radionuclide angiography acquired in list mode and maximal, symptom-limited, treadmill exercise testing with measurement of maximal oxygen consumption (VO2 max). VO2 max for the group was 13.9 to 49.3 (mean 25.4) ml/min per kg. Thirty-six patients (44%) achieved less than or equal to 70% of age-predicted VO2 max. Patients with such a degree of limitation were more likely to be in New York Heart Association functional class II or III (23 of 36 vs. 14 of 45; p = 0.005); there was no such relation between VO2 and the incidence and magnitude of rest left ventricular outflow tract pressure gradient greater than 30 mm Hg (11 of 36 vs. 11 of 45; p = NS and 58 +/- 24 vs. 65 +/- 19 mm Hg; p = NS). In the 22 patients with a left ventricular outflow tract gradient, the ratios of peak ejection to peak filling rate and of atrial contribution to left atrial dimension were related to percent of the age-predicted VO2 max (r = 0.49, p = 0.02 and r = 0.54, p less than 0.02). These ratios reflect impaired left ventricular systolic performance and atrial systolic failure, respectively. Stepwise discriminant analysis revealed these two ratios to be the two strongest predictors (p = 0.0001) of patients with a left ventricular outflow tract gradient whose VO2 max was less than or equal to 70% of the age-predicted value (sensitivity 90%, specificity 100%).(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired binding of ZASP/Cypher with phosphoglucomutase 1 is associated with dilated cardiomyopathy

AIMS Z-band alternatively spliced PDZ-motif protein (ZASP)/Cypher is a Z-disc component of which several dilated cardiomyopathy (DCM)-associated mutations have been reported. Most of the mutations were found in exons 4 and 10 of ZASP/Cypher gene LDB3 and both exons were expressed preferentially in the heart. The aim of this study was to investigate the functional alteration of ZASP/Cypher caused by the DCM-associated mutations. METHODS AND RESULTS The yeast-two-hybrid method was used to identify the protein bound to a domain encoded by exon 4 of LDB3. Interaction of ZASP/Cypher with the binding protein was investigated in relation to the functional alterations caused by LDB3 mutations. Localization of the ZASP/Cypher-binding protein was examined at the cellular level in rat cardiomyocytes. Phosphoglucomutase 1 (PGM1), a metabolic enzyme involved in glycolysis and gluconeogenesis, was identified as a protein interacting with ZASP/Cypher. PGM1 bound to ZASP/Cypher at the domains encoded by exons 4 and 10. Two LDB3 mutations in exon 4 (Ser189Leu and Thr206Ile) and another mutation in exon 10 (Ile345Met) reduced the binding to PGM1. PGM1 showed diffuse localization in the cytoplasm of rat cardiomyocytes under standard culture conditions, and distribution at the Z-discs was observed under stressed culture conditions. Binding of endogenous PGM1 and ZASP/Cypher was found to be enhanced by stress in rat cardiomyocytes. CONCLUSION ZASP/Cypher anchors PGM1 to Z-disc under conditions of stress. The impaired binding of PGM1 to ZASP/Cypher might be involved in the pathogenesis of DCM.

The role of 123I-metaiodobenzylguanidine myocardial scintigraphy in the diagnosis of Lewy body disease in patients with dementia in a memory clinic.

Reduction in cardiac 123I-metaiodobenzylguanidine (MIBG) uptake is a characteristic feature of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB), and is useful in distinguishing them from other neurodegenerative disorders. The aim of this study was to investigate the role of this method of scintigraphy in the differential diagnosis of dementia in our Memory Clinic. We performed MIBG scintigraphy in patients with dementia referred to the Memory Clinic and compared the heart-to-mediastinum (H/M) ratio of MIBG uptake. Thirty out of 32 patients with DLB and all 9 PD with dementia patients had reduced H/M ratios, whereas 37 out of 40 patients with Alzheimer’s disease had normal H/M ratios. Most patients with vascular dementia, frontotemporal dementia, and other dementias had normal H/M ratios. The overall sensitivity to positively identify patients with Lewy body disease (including DLB and PD with dementia) was 95%, and the specificity to distinguish them from patients with other types of dementias was 87%. MIBG scintigraphy showed a high sensitivity for the detection of Lewy body disease, and also a high specificity for discrimination from other types of dementia. The scintigraphy may provide a valuable and adjunctive method in the diagnosis of Lewy body disease and a differential diagnostic tool for patients with dementias.

Reliability of pressure-derived myocardial fractional flow reserve in assessing coronary artery stenosis in patients with previous myocardial infarction

In 167 patients with suspected coronary artery disease, 74 of whom had myocardial infarction (MI), measurement of myocardial fractional flow reserve (FFR) in previous infarction territories, using a cut-off point of 0.75, showed a sensitivity of 79% and a specificity of 79% for myocardial ischemia as demonstrated by thallium-201 myocardial imaging. This sensitivity and specificity were similar to a sensitivity of 79% and a specificity of 72% observed in territories not related to MI. In addition, a receiver-operating characteristic curve analysis revealed that the best predictability of FFR for myocardial ischemia was between 0.74 and 0.76, regardless of the presence or absence of MI.

Value of dipyridamole thallium-201 imaging in noninvasive differentiation of idiopathic dilated cardiomyopathy from coronary artery disease with left ventricular dysfunction

The purpose of this study was to noninvasively differentiate in patients with reduced global left ventricular function between those with idiopathic dilated cardiomyopathy (IDC) and coronary artery disease (CAD). Clinical features and findings of dipyridamole thallium-201 imaging in 55 consecutive patients with IDC were compared with those in 77 with CAD. Left ventricular ejection fraction was similar between the 2 groups (34 +/- 16% vs 39 +/- 7%). Patients with IDC had lower incidences of ischemic chest pain (11 vs 79%; p less than 0.0001), electrocardiographic evidence of myocardial infarction (24 vs 82%; p less than 0.0001), and reversible defects (4 vs 57%; p less than 0.0001) than did those with CAD. The lowest percent thallium uptake in the initial imaging was less with CAD than IDC (30 +/- 15% vs 59 +/- 10%; p less than 0.001). Patterns of perfusion defects were classified as: no defects, multiple small defects and large defects. Of patients with IDC, 15 had no defects, 19 had multiple small defects, and 21 had large defects, whereas all those with CAD had large defects (p less than 0.0001). Stepwise discriminant analysis, using chest pain and electrocardiography, revealed sensitivity of 89%, specificity of 87%, accuracy of 88%, and positive predictive value of 83% in the identification of patients with IDC.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular regulatory functions in elderly patients with hypertension.

To dissociate the effects of an elevated blood pressure on the cardiovascular regulatory functions from those of aging in the hypertensive elderly individual, resting hemodynamic measurements and circulatory autonomic functions in 30 elderly (mean age, 66 years) hypertensive (World Health Organization stages I and II) patients were compared with those in 30 healthy elderly (mean age, 65 years) normotensive volunteers. The elderly hypertensive group showed a significantly lower cardiac index and higher total peripheral resistance. beta-Receptor sensitivity, as determined by chronotropic dose of infused isoproterenol, and baroreceptor reflex sensitivity index, derived from phase II, but not phase IV, of Valsalvas maneuver, were only slightly but significantly reduced in the hypertensive group. The variability of heart rate at rest as an index of parasympathetic control of heart was similar between these two groups. Plasma norepinephrine level was significantly inversely related to resting mean blood pressure (r = -0.31, p less than 0.05) when analyzed as a whole group. Plasma renin activity, but not plasma aldosterone, was significantly decreased in the hypertensive group. To define the effects of age itself, these parameters in normotensive elderly subjects were also compared with those in 12 young normotensive subjects (mean age, 23 years). Although resting hemodynamic measurements did not differ, various circulatory autonomic functions were significantly different between these two age groups. The variability of heart rate in 24-hour ambulatory monitoring, beta-receptor responsiveness, resting vagal cardiac activity, and baroreceptor reflex sensitivity derived from phase IV of Valsalvas maneuver were significantly depressed in the elderly. Resting plasma norepinephrine level was elevated and renin-aldosterone system decreased in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence of Coronary Heart Disease in Patients With Aortic Aneurysm and/or Peripheral Artery Disease

Although the presence of coronary heart disease (CHD) was the major determinant of perioperative mortality and long-term prognosis in patients with aortic aneurysm (AA) and peripheral artery disease (PAD), the prevalence and severity of CHD in patients with individual vascular diseases was unknown. Adenosine triphosphate-loading myocardial single-photon emission computed tomography therefore was performed in 788 patients with vascular diseases of the aorta and peripheral arteries, with AA in 500, PAD localized in the lower-limb arteries in 183, and combined AA and PAD in 105. Patients with known CHD, such as those with previous myocardial infarction or revascularization procedures, were excluded. Myocardial single-photon emission computed tomography was analyzed using a 20-segment model, and summed stress scores and summed difference scores were calculated. Stress-induced myocardial ischemia was defined as a summed difference score >or=2. The presence of myocardial ischemia was highest in patients with combined PAD and AA (73%), followed by PAD (55%; p = 0.005), and the lowest in patients with AA (37%; p <0.0001). Summed stress score was also the highest in patients with combined PAD and AA (11.6 +/- 9.9), followed by PAD (7.8 +/- 8.8; p <0.0001), and the lowest in patients with AA (4.0 +/- 6.2; p <0.0001 for both). Similarly, summed difference score was the highest in patients with combined PAD and AA (6.4 +/- 6.1), followed by PAD (4.4 +/- 5.7; p = 0.001) and AA (2.3 +/- 4.0; p <0.0001 for both). In conclusion, the prevalence of CHD in patients with PAD was >50%, and although myocardial ischemia was observed in only (1/3) of patients with AA, its prevalence not only doubled, but also indicated extensive myocardial ischemia when combined with PAD. Thus, cardiac evaluation was particularly important in patients with combined AA and PAD.

Noninvasive identification of significant narrowing of the left main coronary artery by dipyridamole thallium scintigraphy

To evaluate the usefulness of dipyridamole thallium scintigraphy with low-level exercise for the identification of left main (LM) coronary artery disease (CAD), 466 consecutive patients with CAD were studied. Thirty-eight patients (8%) had LM stenosis (diameter narrowing greater than or equal to 50%). The LM scintigraphic pattern was present in 9 of 38 patients with LMCAD and 38 of 428 CAD patients without LMCAD (24 vs 9%; p less than 0.005). This pattern was present in 6 of 9 patients with LMCAD without right CAD and in only 3 of 29 patients with LM and right CAD (67 vs 10%; p = 0.0005). Patients with LMCAD had a higher incidence of premature cessation of low-level exercise (53 vs 21%; p less than 0.0001), chest pain (68 vs 48%; p less than 0.02), blood pressure decrease of greater than or equal to 20 mm Hg (44 vs 16%; p less than 0.002) and greater ST depression (0.17 +/- 0.13 vs 0.06 +/- 0.10 mV; p less than 0.001) during dipyridamole loading than patients without LMCAD. Stepwise discriminant analysis revealed that the LM scintigraphic pattern and markers of ischemia during dipyridamole loading best identified (p less than 0.0001) patients with LMCAD without right CAD (sensitivity 67%, specificity 91%), but this predictability is no better than the LM scintigraphic pattern alone. The combination of clinical markers of ischemia during dipyridamole loading and scintigraphic findings of diffuse slow washout, extensive fixed defects and the LM pattern best identified (p less than 0.0001) patients with LM and right CAD (sensitivity 72%, specificity 80%).(ABSTRACT TRUNCATED AT 250 WORDS)

Delayed recovery of postexercise blood pressure in patients with chronic heart failure

Thirty-four patients with idiopathic dilated and ischemic cardiomyopathy underwent a symptom-limited cardiopulmonary exercise testing to evaluate the significance of postexercise blood pressure (BP) response. The postexercise BP response was useful in assessing the impaired exercise capacity and increased sympathetic activity in patients with heart failure.