Total Defect Score Research Articles

Usefulness of 201TlCl/123I-BMIPP dual-myocardial SPECT for patients with non-ST segment elevation myocardial infarction

Earlier studies suggested that elevated cardiac troponin T (cTnT) might be useful for detecting less severe types of myocardial injury (i.e., non-ST segment elevation myocardial infarction). The objective of this study is to elucidate the usefulness of (201)thallous chloride ((201)TlCl) and (123)I-betamethyl-p-iodophenyl-pentadecanoic acid ((123)I-BMIPP) dual-single-photon emission computed tomography (SPECT) imaging for patients with myocardial infarction (MI) without ST segment elevation. Consecutive 86 patients (56 men and 30 women; mean age 66 +/- 12 years) clinically diagnosed with acute myocardial infarction (AMI) were divided into two groups according to serum creatine kinase MB (CK-MB) and cTnT levels. Group A consisted of 53 patients with increased serum CK-MB and cTnT levels, and Group B, 33 patients with increased serum cTnT without increased serum CK-MB. All patients underwent (201)TlCl and (123)I-BMIPP dual-SPECT about 8 days following the onset. The left ventricular myocardium was divided into 20 segments on each SPECT image, and tracer accumulation in those segments was scored on a five-point scoring system. The total defect scores (TDS) were calculated by summing the scores for all 20 segments, and compared between groups A and B. Group B patients were subdivided into two groups according to the TDS on (123)I-BMIPP images as groups B(S) (severe; TDS > or = 8) and B(M) (mild; TDS < or = 7), and we compared the prognosis over a period of 2 years from the onset between the three groups. The TDS of group A derived from (201)TlCl and (123)I-BMIPP images was significantly higher than those of group B (14.5 +/- 10.8 vs. 1.5 +/- 2.4 and 20.8 +/- 13.3 vs. 9.1 +/- 6.2, respectively; P < 0.0001). The sensitivities of (201)TlCl and (123)I-BMIPP images were 94.3% (50/53) and 96.2% (51/53) to detect the culprit coronary lesions in group A (no significant difference). In contrast, the sensitivity of (123)I-BMIPP images (72.7%, 24/33) was higher than that of (201)TlCl images (27.3%, 9/33) in group B (P < 0.05). At 2 years of follow-up, the incidence of hard cardiac events in groups A, B(S), and B(M) was 24.5%, 27.8%, and 6.7%, respectively. The rate of group BS, as well as that of group A, was significantly higher than that of group B(M) (P < 0.05). Of those with a clinical diagnosis of AMI accompanied by increased cTnT, the CK-MB negative patients accounted for 38% (33/86) of all patients as having non-ST segment elevation myocardial infarction such as NTMI. For such patients, (123)I-BMIPP imaging is useful not only for the detection of the culprit lesions but also for the prediction of the prognosis.

Scintigraphic studies on the etiology of Ampulla Cardiomyopathy

Although there are many reports on Ampulla Cardiomyopathy, its etiologic mechanisms are not well known. Etiology of Ampulla Cardiomyopathy was investigated by myocardial scintigraphy with various nuclear tracers. In nine patients with Ampulla Cardiomyopathy, myocardial scintigraphy was performed at acute, subacute and chronic phases. Total defect score (TDS) of tallium-201 (Tl) or technetrium-99m sestamibi (MIBI) myocardial perfusion and iodine-123-beta-methyl-p-iodophenyl penta-decanoic acid (BMIPP) scintigraphies was calculated. Cardio-mediastinal ratio (H/M) and washout rate (WR) of early and delayed images of iodine-123-meta-iodobenzylguanidine (MIBG) scintigraphy were also calculated. The patients in whom TDS of myocardial perfusion scintigraphy at acute phase was 0, were classified into group N (n = 5) and those with TDS > or = 1 into group D (n = 4). TDS of BMIPP at acute, subacute and chronic phases was higher in D than in N; 28.8 +/- 10.3 vs. 7.2 4.7 (p = 0.0039), 15.5 +/- 2.1 vs. 1.0 +/- 0.8 (p < 0.0001) and 2.7 +/- 1.2 vs. 0 (p = 0.05), respectively. WR of MIBG at acute phase was also higher in D (50.3 +/- 5.7% vs. 36.6 +/- 10.5%, p = 0.05). H/M (dH/M) on the delayed images and WR at chronic phase were not different between the two groups. H/M (eH/M) on the early images was lower in D. Blood noradrenaLine (ng/ml) at acute phase was higher in D than in N (1.21 +/- 0.55 vs. 0.45 +/- 0.33, p < 0.05). Left ventricular ejection fraction (LVEF) was decreased in both at acute phase but it was lower in D than in N (48.1 +/- 3.7% vs. 69.9 +/- 9.7%, p < 0.05) at subacute phase. These findings suggest that the etiology of Ampulla Cardiomyopathy is neurologically stunned myocardium induced by coronary microcirculatory disorder. Due to the significant amount of time that was necessary for normalization of wall motion in the D group, myocardial scintigraphy is believed to be also useful in assessment of severity.

Effect of angiotensin-converting enzyme inhibitors on systemic inflammation and myocardial sympathetic innervation in normotensive patients with type 2 diabetes mellitus

Diabetes mellitus (DM) may cause an increase in the inflammatory status and oxidative stress as well as sympathetic nervous system overactivity, even in the absence of any other organic heart disease. We investigated the effect of perindopril, an angiotensin-converting enzyme inhibitor (ACE-i), on indexes of systemic inflammation and oxidative stress in normotensive patients with type 2 DM. We also examined the effect of the drug on the disturbances of left ventricular myocardial adrenergic innervation that may be seen in these patients. We studied 62 normotensive patients with type 2 DM, who were randomized to receive perindopril (n=32) or placebo (n=30). At the start of the study and after 6 months' therapy blood samples were taken to evaluate total peroxides (TP), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), and the patients underwent a (123)I-metaiodobenzylguanidine myocardial scintigraphy study. ACE-i caused a significant reduction in levels of cytokines and TP (P<0.001 for IL-6 and TNF-alpha, P=0.001 for TP). There was also a reduction in total defect score (P<0.001) and the heart to mediastinum ratio at 10 min and 4 h was improved (P<0.001 for both). No significant alterations were observed in the placebo group. Our data indicate that the addition of ACE-i to the medication of normotensive diabetic type 2 patients may improve the disturbed myocardial adrenergic innervation, the systemic inflammatory status and oxidative stress. Our findings indicate the cardioprotective action of ACE-i and suggest that earlier treatment might be appropriate in those patients.

Combined therapy with carvedilol and amiodarone is more effective in improving cardiac symptoms, function, and sympathetic nerve activity in patients with dilated cardiomyopathy: Comparison with carvedilol therapy alone

Carvedilol therapy has been reported to be more effective than other beta-blockers in patients with chronic heart failure (CHF). Amiodarone is an anti-arrhythmic medicine that has also been reported to be effective in patients with CHF. But the usefulness of combined therapy with carvedilol and amiodarone has not been reported. We compared 15 patients (M/F = 3/12, age = 57 +/- 8 y) with dilated cardiomyopathy (DCM) receiving carvedilol and amiodarone with 15 patients (M/F = 3/12, age = 61 +/- 9 y) receiving carvedilol alone. Patients were studied before and after 1 year of treatment (1Y). NYHA class and exercise capacity based on the specific-activity-scale (SAS), were assessed. Cardiac sympathetic nerve activity was estimated using total defect score (TDS), H/M ratio and washout rate (WR) of 123I-MIBG imaging. Cardiac function was evaluated using 99mTc-MIBI QGS. Combined therapy improved several parameters much more than carvedilol alone (p < 0.05) including delta-TDS (15.0 +/- 8.6 vs. 7.6 +/- 7.2) and delta-WR (15.9 +/- 11.0% vs. 7.3 +/- 10.0%) for 123I-MIBG imaging, delta-LVEF (26.1 +/- 11.4% vs. 15.5 +/- 13.8%), delta-end-systolic volume (100 +/- 63.8 ml vs. 58.9 +/- 47.3 ml), 1Y NYHA class (1.5 +/- 0.5 vs. 1.9 +/- 0.5), 1Y SAS (7.3 +/- 0.7 Mets vs. 6.2 +/- 1.0 Mets), and delta-SAS (3.4 +/- 0.8 Mets vs. 2.6 +/- 1.1 Mets). Combined therapy with carvedilol and amiodarone is more effective in improving cardiac symptoms, exercise capacity, cardiac function and cardiac sympathetic nerve activity in patients with DCM.

Prediction of cardiac events in patients with dilated cardiomyopathy using 123I-BMIPP and 201Tl myocardial scintigraphy

Various clinical trials for dilated cardiomyopathy (DCM) have demonstrated that the prognosis as well as cardiac function is improved by the administration of beta-blocker therapy. On the other hand, 123I-betamethyl-p-iodophenyl-pentadecanoic acid (BMIPP) reflects myocardial fatty acid metabolism and is considered to be a more sensitive tracer than perfusion tracers. In this study, the efficacy of DCM for the evaluation of myocardial damage and the prediction of cardiac events was studied using 123I-BMIPP and 201TI (Tl) myocardial scintigraphy. Study subjects comprised 33 DCM patients, divided into a cardiac event group (event, n = 9) and an event-free group (event free, n = 24). An extent score (ES) and severity score (SS) were calculated for each BMIPP image. BMIPP and Tl images were divided into 17 segments, and total defect scores (TDS) were calculated for each. The TDS of the BMIPP and Tl images were compared with score differences greater than or equal to 4 and less than 4 defined as mismatch and non-mismatch, respectively. The TDS of BMIPP was significantly higher in the event group than in the event-free group (P < 0.05). The ES and SS were significantly higher in the event group than in the event-free group (P < 0.01). The comparison in the 2 x 2 contingency tables showed that the occurrence of non-mismatch was significantly higher in the event-free group (chi2 test; P < 0.01). The ES of BMIPP was a significant predictor of cardiac events in the multivariate analysis (P < 0.01). These results suggest that the ES for BMIPP is useful as a predictor of cardiac events in DCM.

Long-Term Nicorandil Therapy Improves Cardiac Sympathetic Nerve Activity After Reperfusion Therapy in Patients with First Acute Myocardial Infarction

Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, reduces plasma norepinephrine concentration in patients with ischemic heart disease. However, long-term effects on cardiac sympathetic nerve activity (CSNA) as evaluated by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy have not been determined for patients with acute myocardial infarction (AMI). We studied 40 patients with their first AMI who were treated with intravenous nicorandil before and after primary coronary angioplasty. After suspension of the initial intravenous nicorandil treatment, 20 patients were randomized to receive oral nicorandil (15 mg/d) (group A) and the other 20 patients received a placebo (group B). All patients were also treated with an angiotensin-converting enzyme (ACE) inhibitor or beta-blockers. The delayed heart-to-mediastinum count ratio (H/M ratio), delayed total defect score (TDS), and washout rate (WR) were determined from (123)I-MIBG scintigraphy 3 wk and 6 mo after angioplasty. The left ventricular (LV) end-diastolic volume (EDV), LV end-systolic volume (ESV), and LV ejection fraction (EF) were determined by contrast left ventriculography, whereas plasma procollagen type III amino-terminal peptide (PIIINP) concentrations were also measured at the same time points. Three weeks after angioplasty, TDS, H/M ratios, WR, LVEDV, LVESV, and LVEF were similar in both groups. After 6 mo, all of these parameters had improved in both groups. However, the extent of change in TDS was -9 +/- 6 in group A and -5 +/- 6 in group B (P < 0.05), whereas that in the H/M ratio was 0.15 +/- 0.13 and 0.07 +/- 0.11 (P < 0.05) and that in the WR was -12% +/- 8% and -5% +/- 11% (P < 0.05). The extent of change in LVEDV, LVESV, and LVEF in group A tended to exceed that in group B, but these changes were not statistically significant. We found significant correlations between the percent change in PIIINP and that of TDS from baseline to 6 mo in group A (r = 0.456, P < 0.05). Long-term nicorandil therapy can be more beneficial for CSNA and LV remodeling than short-term therapy in patients with AMI.

Evaluation of cardiac sympathetic nerve activity and left ventricular remodelling in patients with dilated cardiomyopathy on the treatment containing carvedilol

It has been reported that carvedilol improves cardiac sympathetic nerve activity (CSNA) in patients with dilated cardiomyopathy (DCM). However, the influence of carvedilol on cardiac (123)I-meta-iodobenzylguanidine (MIBG) scintigraphic findings and left ventricular (LV) remodelling has not been determined in DCM patients. In 30 patients with DCM and 10 normal controls, the delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined by (123)I-MIBG scintigraphy. In addition, the left ventricular end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), and LV ejection fraction (LVEF) were calculated by echocardiography. In the DCM patients, the regional defect score index (RDSI), regional washout rate index (RWRI), and wall motion score index (WMSI) were also determined to evaluate regional adrenergic dysfunction and wall motion. Examinations were repeated in all DCM patients after standard treatment containing carvedilol at a dose of 10-20 mg/day (mean dose: 16 +/- 4 mg/day) for a mean of 12 +/- 1 months. Both the (123)I-MIBG scintigraphic and echocardiographic parameters were significantly worse in the DCM patients than the normal control subjects. After treatment, all of these parameters improved significantly in the DCM patients. There was a significant correlation between the changes of (123)I-MIBG findings and changes of the LVEDV and LVESV after treatment. Moreover, there was a significant correlation between changes of the WMSI and those of the RDSI or RWRI in DCM patients. Both (123)I-MIBG scintigraphic parameters and echocardiographic parameters were improved in the DCM patients. There was a significant correlation between the changes of (123)I-MIBG scintigraphic and echocardiographic findings after treatment. These findings implicate that long-term, including carvedilol, therapy can improve both CSNA and LV remodelling in patients with DCM.

Effects of Intravenous Atrial Natriuretic Peptide on Cardiac Sympathetic Nerve Activity and Left Ventricular Remodeling in Patients With First Anterior Acute Myocardial Infarction

We sought to evaluate the effects of atrial natriuretic peptide (ANP) on cardiac sympathetic nerve activity (CSNA) and left ventricular (LV) remodeling in patients with first anterior acute myocardial infarction (AMI) after primary coronary angioplasty. The activation of the renin-angiotensin-aldosterone system (RAAS) prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide, a circulating hormone of cardiac origin, has vasodilatory and diuretic properties, and can inhibit the RAAS. We studied 50 patients with first anterior AMI who were randomly assigned to receive ANP (group A) or isosorbide dinitrate (group B) before and after primary coronary angioplasty. The ANP or ISDN was continuously infused >48 h. The extent score (ES) was determined from 99mTc-pyrophosphate scintigraphy to evaluate the area of initial myocardial damage 3 to 5 days after primary angioplasty. The LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined from 123I-meta-iodobenzylguanidine scintigraphy after 3 weeks. After primary angioplasty, age, gender, risk factors, peak serum creatine phosphokinase concentration, recanalization time, and ES were similar in the 2 groups. However, in group A (n = 25), the TDS was significantly lower (34 +/- 8 vs. 41 +/- 8; p < 0.05), the H/M ratio was significantly higher (1.96 +/- 0.18 vs. 1.74 +/- 0.23; p < 0.05), and the WR was significantly lower (35 +/- 8% vs. 44 +/- 12%; p < 0.005) than in group B (n = 25). Moreover, the LVEDV and LVEF in group A were better than in group B (LVEDV: 85.5 +/- 28.5 ml vs. 106.3 +/- 39.4 ml [p < 0.05]; LVEF: 47.9 +/- 10.2% vs. 41.5 +/- 11.8% [p < 0.05]). Intravenous ANP improves CSNA and prevents LV remodeling in patients with first anterior AMI.

Usefulness of Biventricular Pacing to Improve Cardiac Symptoms, Exercise Capacity and Sympathetic Nerve Activity in Patients With Moderate to Severe Chronic Heart Failure

Although cardiac resynchronization using biventricular pacing (BVP) results in significant clinical improvement in patients with chronic heart failure (CHF), there is no evidence of improvement in sympathetic nerve activity (SNA). Eighteen patients with CHF (dilated cardiomyopathy/ischemic cardiomyopathy =14/4) and left ventricular (LV) ejection fraction <40%, QRS duration >160 ms and dyssynchronous LV wall motion were classified into 2 groups based on the findings of (99m)Tc-methoxyisobutyl isonitrile (MIBI) quantitative gated single-photon emission computed tomography (SPECT) (QGS). Resynchronization was considered to be present when the difference between the QGS frame number for end-systole for the LV septal and lateral walls (dyssynchrony index) disappeared. Group A achieved resynchronization after BVP, but not Group B. In group A, New York Heart Association functional class (p=0.0002), specific activity scale (p=0.0001), total defect score (p<0.05), and the heart/mediastinum ratio of delayed (123)I-metaiodobenzylguanidine imaging (p<0.05) were significantly improved after resynchronization. However, there was no significant change in group B. Cardiac resynchronization after BVP can improve cardiac symptoms, exercise capacity, and SNA in patients with moderate to severe CHF.

Brief Episode of Myocardial Ischemia Before Prolonged Ischemia Attenuates Cardiac Sympathetic Nerve Injury

The aim of this study was to investigate the effects of brief ischemia before prolonged ischemia on cardiac sympathetic neural function. Brief ischemia inhibits the sympathetic neural release of norepinephrine (NE) during subsequent sustained ischemia. However, whether it can attenuate the neural function after sustained ischemia remains unknown. Sympathetic neural function was assessed using 123I-metaiodobenzylguanidine (MIBG) in patients who with (Group I) or without angina (Group II) within 3 days prior to acute myocardial infarction. In the rat experiment, cardiac interstitial NE (iNE) with or without pretreatment of 5-min coronary ligation was determined during a 30-min occlusion. Differences between MIBG and Thallium-201 for the total defect score were significantly greater in Group II than in Group I (6.1 +/- 4.0 vs 0.4 +/- 4.4). Levels of iNE were less in rats with a 5-min pretreatment (7.3 +/- 2.3 vs 18.6 +/- 5.9 x 10(3) pg/ml, p < 0.01) and MIBG uptake of ischemic region was greater (0.061 +/- 0.029 vs 0.031 +/- 0.011 %kg dose/g, p < 0.05) compared with rats without the pretreatment. A brief episode of ischemia attenuates the sympathetic neural injury caused by subsequent prolonged ischemia and this protective effect is associated with attenuation of NE release during the prolonged ischemia.

Comparative effects of nicorandil with isosorbide mononitrate on cardiac sympathetic nerve activity and left ventricular function in patients with ischemic cardiomyopathy

Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves left ventricular (LV) remodeling after myocardial infarction in rat models. However, the effects of chronic nicorandil therapy on cardiac sympathetic nerve activity in patients with ischemic cardiomyopathy have not been determined. Thirty-six patients with ischemic cardiomyopathy (LV ejection fraction [LVEF] < 40%) who underwent successful revascularization procedure before 6 months were treated by standard conventional therapy. Eighteen patients were randomized to additionally receive nicorandil (15 mg/d), whereas the other 18 patients received isosorbide mononitrate (40 mg/d). The delayed heart-to-mediastinum count ratio (H/M ratio), delayed total defect score (TDS), and washout rate (WR) were determined from (123)I-meta-iodobenzylguanidine (MIBG) scintigraphy before and 6 months after treatment. Left ventricular end-diastolic volume (LVEDV) and LVEF were determined by echocardiography. Total defect score, H/M ratio, WR, LVEDV, and LVEF at baseline were similar for both groups. After treatment, in patients receiving nicorandil, TDS decreased from 50 +/- 6 to 40 +/- 11 (P < .005), H/M ratio increased from 1.68 +/- 0.23 to 1.79 +/- 0.26 (P = .005), and WR decreased from 46% +/- 9% to 40% +/- 12% (P < .005). In addition, LVEDV decreased from 178 +/- 31 to 157 +/- 30 mL (P < .0005), and LVEF increased from 33% +/- 6% to 39% +/- 7% (P < .05). In patients receiving isosorbide mononitrate, no significant changes were observed in these parameters. Moreover, there was a significant correlation between the percent change of LVEF and that of TDS from baseline to 6 months in the patients receiving nicorandil (r = -0.569, P < .05). The present study demonstrates improvements in cardiac (123)I-MIBG scintigraphic and echocardiographic parameters with nicorandil treatment. These findings indicate that nicorandil can improve cardiac sympathetic nerve activity and LV function in patients with ischemic cardiomyopathy.

The clinical correlates of articular cartilage defects in symptomatic knee osteoarthritis: a prospective study

To determine whether articular cartilage defects are associated with cartilage loss and joint replacement in subjects with symptomatic knee osteoarthritis (OA). One hundred and seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of their dominant knee at baseline and 2 yr later. Cartilage defects were identified as prevalent (defect score > or =2) in each knee compartment. Occurrence of joint replacement by 4 yr was documented. Cartilage defects were present in 81% of medial, 64% of lateral tibiofemoral compartments and 55% of patellar cartilages. Annual patellar cartilage loss was highest in those with defects compared with no defects (5.5% vs 3.2%, P = 0.01). Tibial cartilage loss was not associated with defects in the medial (4.6% vs 5.8%, P = 0.42) or lateral (4.7% vs 6.5%, P = 0.21) tibial cartilages. Higher total cartilage defect scores (8-15) were associated with a 6.0-fold increased risk of joint replacement over 4 yr compared with those with lower scores (2-7) (95% confidence interval 1.6, 22.3), independently of potential confounders. Articular cartilage defects are associated with disease severity in knee OA and predict patellar cartilage loss and knee replacement.

Effects of perindopril on cardiac sympathetic nerve activity in patients with congestive heart failure: comparison with enalapril

The production of aldosterone in the heart is suppressed by the angiotensin-converting enzyme (ACE) inhibitor perindopril in patients with congestive heart failure (CHF). Moreover, perindopril has been reported to have more cardioprotective effects than enalapril. Forty patients with CHF [left ventricular ejection fraction (LVEF) <45%; mean 33+/-7%] were randomly assigned to perindopril (2 mg/day; n = 20) or enalapril (5 mg/day; n = 20). All patients were also treated with diuretics. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS) and washout rate (WR) were determined from 123I-meta-iodobenzylguanidine (MIBG) images, and plasma brain natriuretic peptide (BNP) concentrations were measured before and 6 months after treatment. The left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and LVEF were also determined by echocardiography. After treatment, in patients receiving perindopril, TDS decreased from 39+/-10 to 34+/-9 (P < 0.01), H/M ratios increased from 1.62+/-0.27 to 1.76+/-0.29 (P < 0.01), WR decreased from 50+/-14% to 42+/-14% (P < 0.05) and plasma BNP concentrations decreased from 226+/-155 to 141+/-90 pg/ml (P < 0.0005). In addition, the LVEDV decreased from 180+/-30 to 161+/-30 ml (P < 0.05) and the LVESV decreased from 122+/-35 to 105+/-36 ml (P < 0.05). Although the LVEF tended to increase, the change was not statistically significant (from 33+/-8% to 36+/-12%; P = NS). On the other hand, there were no significant changes in these parameters in patients receiving enalapril. Plasma BNP concentrations, 123I-MIBG scintigraphic and echocardiographic parameters improved after 6 months of perindopril treatment. These findings indicate that perindopril treatment can ameliorate the cardiac sympathetic nerve activity and the left ventricular performance in patients with CHF.

Effects of candesartan on cardiac sympathetic nerve activity in patients with congestive heart failure and preserved left ventricular ejection fraction

We sought to evaluate the effects of angiotensin receptor blocker (ARB) on cardiac sympathetic nerve activity (CSNA) in patients with congestive heart failure (CHF) with a preserved left ventricular ejection fraction (LVEF). Approximately 50% of patients with CHF have preserved LVEF. It is reported that ARB therapy improves CSNA in CHF patients and reduced LVEF. However, the effect of ARB therapy on CSNA evaluated by iodine-123 meta-iodobenzylguanidine ((123)I-MIBG) scintigraphy has not been determined in CHF patients with preserved LVEF. We selected 50 patients with nonischemic CHF and LVEF >40% who were treated with standard therapy. Twenty-five patients were randomized to also receive candesartan, whereas the remaining 25 patients received placebo. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined by (123)I-MIBG scintigraphy before and six months after treatment. The LV end-diastolic volume and LVEF were determined by echocardiography, and the plasma brain natriuretic peptide (BNP) concentration was also measured. In patients receiving candesartan, (123)I-MIBG scintigraphic and echocardiographic parameters were significantly improved after treatment. In contrast, there were no significant changes in these parameters in patients receiving placebo. There was a significant correlation between the changes in (123)I-MIBG scintigraphic findings and the percent change in BNP from baseline to six months in patients receiving candesartan (TDS: r = 0.587, p < 0.005; H/M ratio: r = -0.509, p < 0.01; WR: r = 0.602, p < 0.005). Adding candesartan to standard therapy can improve CSNA and LV performance in CHF patients with preserved LVEF.

Knee cartilage defects: association with early radiographic osteoarthritis, decreased cartilage volume, increased joint surface area and type II collagen breakdown

To generate hypotheses regarding the associations between knee cartilage defects and knee radiographic osteoarthritis (ROA), cartilage volume, bone size and type II collagen breakdown in adults. A cross-sectional convenience sample of 372 male and female subjects (mean age 45 years, range 26-61) was studied. Knee cartilage defect score (0-4) and prevalence (a defect score of > or =2), cartilage volume, and bone surface area were determined using T1-weighted fat saturation MRI. Urinary levels of C-terminal crosslinking telopeptide of type II collagen (U-CTX-II) were measured by enzyme-linked immunosorbent assay. Height, weight and ROA were measured by standard protocols. In multivariate analysis, the severity and prevalence of knee cartilage defects were significantly and independently associated with tibiofemoral osteophytes (regression coefficient (beta): +0.86 to +1.31/unit, odds ratio (OR): 2.97-3.68/unit, all P<0.05 with the exception of OR in lateral tibiofemoral compartment) and tibial bone area (beta: +0.11 to +0.25/cm2; OR: 1.33-1.58/cm2, all P<0.01). Knee cartilage defects were inconsistently associated with joint space narrowing after adjustment for osteophytes but consistently with knee cartilage volume (beta: -0.27 to -0.70/ml; OR: 0.16-0.56/ml, all P<0.01 except for OR at lateral tibial cartilage site P=0.06). Lastly, knee cartilage defect severity was significantly associated with U-CTX-II (Partial r=+0.18, P<0.001 for total cartilage defect score). Osteophytes and increasing knee bone size may be causally related to knee cartilage defects. Furthermore, knee cartilage defects may result in increased cartilage breakdown leading to decreased cartilage volume and joint space narrowing suggesting an important role for knee cartilage defects in early knee OA.

Spontaneous Anterograde Flow of the Infarct Artery Preserves Myocardial Perfusion and Fatty Acid Metabolism in Patients With Anterior Acute Myocardial Infarction

It remains unclear whether spontaneous anterograde flow preserves myocardial fatty acid metabolism in patients with acute myocardial infarction (AMI). The present study comprised 129 patients with a first anterior AMI in whom Thrombolysis in Myocardial Infarction (TIMI) 3 flow was obtained on the final angiogram: 28 patients with spontaneous anterograde flow and 101 patients with total occlusion on the initial angiogram. Thallium-201 (201Tl) and iodine-123-beta-methyl-p-iodophenyl penta-decanoic acid (123I-BMIPP) dual-isotope myocardial single-photon emission computed tomography (SPECT) was performed at 6.5+/-4.2 days after onset. The SPECT image was divided into 17 segments, and each segment was graded with scores between 0 and 4 (0, normal uptake; 4, defective). The sum of each score was defined as the total defect score (TDS). TDS values for 201Tl (9.0 +/-7.4 vs 16.8+/-12.2, p < 0.01) and 123I-BMIPP (19.3+/-11.6 vs 24.1 +/-10.4, p < 0.05) were significantly lower in patients with spontaneous anterograde flow than in those with total occlusion. These results suggest that spontaneous anterograde flow of the infarct artery preserves not only myocardial perfusion but also fatty acid metabolism in patients with AMI. 123I-BMIPP SPECT image may underestimate the area at risk especially in patients with spontaneous anterograde flow.

Effects of nicorandil on cardiac sympathetic nerve activity after reperfusion therapy in patients with first anterior acute myocardial infarction

Ischaemic preconditioning (PC) is a cardioprotective phenomenon in which short periods of myocardial ischaemia result in resistance to decreased contractile dysfunction during a subsequent period of sustained ischaemia. Nicorandil, an ATP-sensitive potassium channel opener, can induce PC effects on sympathetic nerves during myocardial ischaemia. However, its effects on cardiac sympathetic nerve activity (CSNA) and left ventricular remodelling have not been determined. In this study, we sought to determine whether nicorandil administration improves CSNA in patients with acute myocardial infarction (AMI). We studied 58 patients with first anterior AMI, who were randomly assigned to receive nicorandil (group A) or isosorbide dinitrate (group B) after primary coronary angioplasty. The nicorandil or isosorbide dinitrate was continuously infused for >48 h. The extent score (ES) was determined from 99mTc-pyrophosphate scintigraphy, and the total defect score (TDS) was determined from 201Tl scintigraphy 3-5 days after primary angioplasty. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed TDS and washout rate (WR) were determined from 123I-meta-iodobenzylguanidine (MIBG) images 3 weeks later. The left ventriculography results were re-examined 6 months after treatment. Fifty patients originally enrolled in the trial completed the entire protocol. After treatment, no significant differences were observed in ES or left ventricular parameters between the two groups. However, in group A (n=25), the TDSs determined from 201Tl and 123I-MIBG were significantly lower (26+/-6 vs 30+/-5, P<0.01, and 32+/-8 vs 40+/-6, P<0.0001, respectively), the H/M ratio significantly higher (1.99+/-0.16 vs 1.77+/-0.30, P<0.005) and the WR significantly lower (36%+/-8% vs 44%+/-12%, P<0.005) than in group B (n=25). Moreover, 6 months after treatment, LVEDV and LVEF were better in group A than in group B. These findings indicate that nicorandil can have beneficial effects on CSNA and left ventricular remodelling in patients with first anterior AMI.

Interventricular conduction delay is associated with myocardial fatty acid metabolic abnormalities in dilated cardiomyopathy

Background: Interventricular conduction delay (IVCD) is an important prognostic indicator in dilated cardiomyopathy (DCM). Abnormalities in glucose metabolism are related to prolonged QRS duration in patients with severe heart failure, and improvement after resynchronization therapy is also reported. However, an association between IVCD and abnormal myocardial fatty acid metabolism has not been well understood in DCM patients. Methods: To investigate the association of the metabolic abnormalities with IVCD, I-123 beta-methyliodophenylpentadecanoic acid (BMIPP) and thallium-201 (Tl) single photon emission computed tomography (SPECT) were performed in 62 non-ischemic DCM patients. The uptake was scored visually from 0 (normal) to 3 (defect) in 17 segments of the left ventricle (LV), and a total defect score in all 17 segments was calculated. Results: Seventeen patients with prolonged QRS duration (<130 msec) showed greater LV end-diastolic diameter (70±13 versus 64±7mm, p=0.007) and lowere LV ejection fraction (25 ± 10 versus 31 ± 10%, p = 0.04) as compared with the other 44 without IVCD. The total defect score of BMIPP was greater in the patients with IVCD (22 ± 6 versus 16 ± 8, p = 0.009), although that of Tl was similar. Multiple logistic regression analysis for 10 clinical variables including scintigraphic parameters demonstrated a strong association of the BMIPP score with IVCD (odds ratio: 1.19/ 1 increase, p = 0.02). Conclusions: IVCD in DCM patients is strongly associated with myocardial fatty acid metabolic abnormalities.

Efficacy of amiodarone treatment on cardiac symptom, function, and sympathetic nerve activity in patients with dilated cardiomyopathy: comparison with β-blocker therapy

Background Amiodarone, which is an antiarrhythmic drug used to treat life-threatening arrhythmias, is effective in patients with chronic heart failure. However, its effectiveness compared with β-blockers has not yet been reported. Methods and results In 30 patients (mean age, 57 ± 13 years) with dilated cardiomyopathy, we compared 15 patients receiving amiodarone (group A) with 15 patients receiving metoprolol (group B). Before and after 1 year of treatment, cardiac iodine 123 metaiodobenzylguanidine uptake was assessed from the total defect score, heart-to-mediastinum activity ratio based on delayed images, and washout rate. New York Heart Association class and echocardiographic left ventricular ejection fraction were also assessed. In both groups the total defect score decreased (from 25 ± 11 to 16 ± 10 in group A, P < .01; from 26 ± 10 to 18 ± 11 in group B, P < .01), the heart-to-mediastinum activity ratio increased (from 1.63 ± 0.16 to 1.81 ± 0.29 in group A, P < .01; from 1.63 ± 0.21 to 1.85 ± 0.3 in group B, P < .01), and the washout rate decreased (from 51% ± 12% to 38% ± 14% in group A, P < .01; from 48% ± 11% to 37% ± 8% in group B, P < .01). Left ventricular ejection fraction increased (from 30% ± 9% to 42% ± 11% in group A, P < .01; from 26% ± 7% to 46% ± 16% in group B, P < .01) and New York Heart Association functional class improved (from 3.1 ± 0.5 to 1.8 ± 0.7 in group A, P < .01; from 2.9 ± 0.5 to 1.7 ± 0.6 in group B, P < .01). Conclusion Amiodarone treatment can improve cardiac symptom, function, and sympathetic nerve activity, as evaluated by I-123 metaiodobenzylguanidine imaging in patients with dilated cardiomyopathy, which improves to a similar extent with β-blocker treatment.

Is I-123-beta-methyl-p-iodophenyl-methylpentadecanoic acid imaging useful to evaluate asymptomatic patients with hypertrophic cardiomyopathy? I-123 BMIPP imaging to evaluate asymptomatic hypertrophic cardiomyopathy.

Myocardial imaging with I-123-beta-methyl-p-iodophenyl-methylpentadecanoic acid (BMIPP) is useful for predicting the outcome of patients with hypertrophic cardiomyopathy (HCM). But its usefulness in asymptomatic patients is unclear. Eighteen patients with asymptomatic HCM were examined with BMIPP and exercise stress perfusion imaging and then followed for 4.0 +/- 0.8 years. Extent of the defect (total defect score, TDS) and myocardial uptake of BMIPP (%uptake) were calculated to evaluate the BMIPP images. In the first study abnormal findings in the BMIPP and perfusion images were detected of 67 and 22% of the patients, respectively. In the second BMIPP study, the TDS had increased (2.1 +/- 2.7 to 4.1 +/- 4.9, p < 0.005) and the %uptake had decreased (5.67 +/- 0.88% to 4.81 +/- 0.91%, p < 0.001), but there were no differences in myocardial perfusion between the first and second study. Exertional dyspnea developed in 17% of the patients, and they were among the one third of the patients with the greatest reduction of %uptake. This group also showed deterioration of left ventricular (LV) %fractional shortening and LV volume in the second study. Abnormal findings on BMIPP images were frequently observed in patients with asymptomatic HCM, and these abnormal findings progressed with time. The greater reduction of %uptake during the follow-up period reflects the deterioration of the LV function.