Effects of mineralocorticoid receptor antagonist eplerenone on cardiac sympathetic nerve activity and left ventricular remodeling after reperfusion therapy in patients with first ST-segment elevation myocardial infarction.

PURPOSE: The activation of the renin-angiotensin-aldosterone system prevents the uptake of norepinephrine and promotes structural remodeling of the heart. The mineralocorticoid receptor antagonist (MRA) eplerenone prevents left ventricular (LV) remodeling in patients with acute myocardial infarction, but its influence on cardiac sympathetic nerve activity (CSNA) has not been determined. METHODS: We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Eighty-four STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients who treated with MRA (N = 42), and those who did not (N = 42). The LV end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography, and plasma procollagen type III amino terminal peptide (PIIINP) was measured before and 3 weeks after treatment. The delayed total defect score (TDS), delayed heart/mediastinum count (H/M) ratio, and washout rate (WR) were determined using 123I-MIBG scintigraphy after 3 weeks. RESULTS: Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the MRA group showed significantly lower TDS and WR values (TDS: 22.8 ± 8.1 vs 32.2 ± 11.5, P < 0.005; WR: 31.1 ± 9.0% vs 42.7 ± 9.9%, P < 0.001) and a significantly higher H/M ratio (2.23 ± 0.41 vs 2.03 ± 0.36, P < 0.05) than the non-MRA group. The degree of change in LV parameters, and PIIINP were more favorable in the MRA group than in the non-MRA group. Moreover, multiple linear regression analyses revealed that both WR and not MRA treatment were significant predictor for LV remodeling, along with PIIINP concentrations. CONCLUSION: Administration of eplerenone improves CSNA and prevents LV remodeling in patients with a first STEMI.

Efficacy of Add-on Therapy with Carvedilol and the Direct Renin Inhibitor Aliskiren for Improving Cardiac Sympathetic Nerve Activity, Cardiac Function, Symptoms, Exercise Capacity and Brain Natriuretic Peptide in Patients with Dilated Cardiomyopathy.

Purpose/Method: Aliskiren is a direct renin inhibitor that has been reported to be effective for CHF, but the usefulness of combined therapy with carvedilol and aliskiren has not been reported. Forty-four patients with dilated cardiomyopathy (DCM) were randomized into a group receiving add-on therapy with carvedilol plus aliskiren and another group receiving carvedilol alone for 6 months. Nuclear imagings with 123I-Metaiodobenzylguanidine (MIBG) and 99mTc-Sestamibi were performed. Exercise capacity using a specific activity scale (SAS) and the New York Heart Association (NYHA) class were evaluated. Cardiac sympathetic nerve activity was evaluated by 123I-MIBG imaging, with the delayed heart-to-mediastinum activity ratio (H/M), delayed total defect score (TDS), and washout rate (WR). Results: Combined add-on therapy with carvedilol and aliskiren improved several parameters much more than carvedilol alone (p<0.05) with respect to TDS, ejection fraction (EF), NYHA, SAS on 6 months and the changes in TDS, EF, end-diastolic volume and brain natriuretic peptide (BNP). Conclusion: Add-on therapy with carvedilol and aliskiren is more effective than carvedilol alone for improving cardiac sympathetic nerve activity, cardiac function, symptoms, exercise capacity, and brain natriuretic peptide in patients with DCM.

A 2-Year Prospective Study on the Differences in Prognostic Factors for Major Adverse Cardiovascular, Cerebrovascular and Renal Events Between Patients with Mild and Severe Chronic Kidney Disease.

Purpose/Method: No studies have reported on prognostic markers in patients with chronic kidney disease (CKD) according to the severity of the disease. Therefore, in this multicenter, prospective trial performed as part of the Gunma CKD SPECT Multicenter Study, we recruited 311 patients with CKD (eGFR < 60 min/mL/1.73 m2) including 50 patients on hemodialysis and followed them for 2 years. The study sample underwent stress 99mTc-tetrofosmin SPECT for suspected or possible ischemic heart disease. We evaluated the summed stress score (SSS), summed rest score (SRS), summed difference score (SDS) and cardiac function with electrocardiogram-gated SPECT. Then, we compared the differences in prognostic markers for major adverse cardiac, cerebrovascular, and renal events (MACCRE) between patients with mild CKD (30 min/mL/1.73 m2 ≤ eGFR <60 min/mL/1.73 m2; n=184) and those with severe CKD (eGFR <30 min/mL/1.73 m2; n=97). Results: Of 281 patients available for analysis, 91 experienced MACCRE. In a multivariate Cox proportional hazards analysis of factors related to MACCRE, in patients with mild CKD the significant prognostic markers were SDS (P=0.002) and end-systolic volume (ESV, P=0.034); and in the patients with severe CKD, they were eGFR (P=0.03) and diabetes-mellitus (DM, P=0.023). Conclusions: Our findings indicate that SDS and ESV are significant prognostic markers for MACCRE in patients with mild CKD and eGFR and DM are significant prognostic markers in patients with severe CKD.

Assessment of therapeutic effects of statin on cardiac sympathetic nerve activity after reperfusion therapy in patients with first ST-segment elevation myocardial infarction and normal low-density lipoprotein cholesterol.

BACKGROUND: Statin treatment reduces enhanced cardiac sympathetic nerve activity (CSNA) in patients with heart disease, and reduces adverse cardiac events in patients with coronary artery disease. METHODS: We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients and low-density lipoprotein cholesterol < 120 mg/dL in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Sixty STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients treated with strong statin (n = 30), and those who did not (n = 30). Moreover, echocardiographic left ventricular (LV) parameters were determined, and plasma procollagen type III amino terminal peptide (PIIINP) was also measured before and 3 weeks after treatment. RESULTS: Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the statin group showed significantly lower delayed total defect score and washout rate evaluated by 123I-MIBG scintigraphy (22.4 ± 8.1 vs. 29.6 ± 10.5; P < 0.01, and 30.4 ± 8.9% vs. 40.1 ± 11.4%; P < 0.005, respectively) and higher delayed heart/mediastinum count ratio (2.17 ± 0.38 vs. 1.96 ± 0.30, P < 0.05) compared with the non-statin group. Moreover, the degree of change in LV parameters and PIIINP was more favorable in the statin group than in the non-statin group. CONCLUSIONS: Administration of statin improves CSNA after reperfusion therapy in patients with first STEMI.

Most Important Prognostic Values to Predict Major Adverse Cardiovascular, Cerebrovascular, and Renal Events in Patients with Chronic Kidney Disease Including Hemodialysis for 2 Years.

Patients with chronic kidney disease (CKD) have an increased risk of adverse cardiovascular/cerebrovascular events. The aim of this study is to clarify whether stress myocardial perfusion single-photon emission computed tomography (SPECT) could predict cardiovascular/cerebrovascular events. In the Gunma-CKD SPECT Study, a multicenter prospective cohort trial, 311 patients with CKD (estimated glomerular filtration rate < 60 min/mL/1.73 m2) including 50 patients on hemodialysis underwent stress 99mTc-tetrofosmin SPECT for suspected ischemic heart disease and were followed for 2 years. The primary endpoint was the occurrence of cardiac death (CD), while the secondary endpoint was major adverse cardiovascular/cerebrovascular and renal events (MACCRE). MACCRE occurred in 91 out of 286 patients (CD in 13 and other MACCRE in 78 patients). According to a multivariate Cox analysis, hemoglobin (Hb) and end-systolic volume (ESV) were associated with CD (p < 0.05), while the summed difference score, diabetes mellitus (DM), and Hb were associated with MACCRE (p < 0.05). Kaplan-Meier analysis showed that the CD-free rate was higher in patients with ESV < 105 mL (log-rank, p = 0.0013), Hb > 12 g (log-rank, p = 0.0036), and a summed stress score < 6 (log-rank, p = 0.0058). The MACCRE-free rate was higher in patients with SDS = 0 (log-rank, p = 0.0097), without DM (log-rank, p = 0.0091), and with Hb > 12 g (log-rank, p = 0.0023). Myocardial perfusion SPECT parameters as well as renal anemia and DM can be reliable prognostic markers in patients with CKD including hemodialysis.

Assessment of therapeutic effects of statin on cardiac sympathetic nerve activity and cardiac events in patients with ischemic cardiomyopathy and mild to moderate heart failure.

INTRODUCTION: We determined whether statin therapy improved cardiac sympathetic nerve activity as evaluated using iodine-123-metaiodobenzylguanidine (I-MIBG) scintigraphy, and whether this therapy affects prognosis in patients with ischemic cardiomyopathy. PATIENTS AND METHODS: This study was a subanalysis of our previous report of the result that the serial I-MIBG scintigraphic studies were the most useful prognostic indicator in patients with heart failure. Patients with heart failure [left ventricular ejection fraction (LVEF) <45%] but no cardiac events for at least 5 months before the study were identified according to their history of decompensated acute heart failure requiring hospitalization. The patients underwent I-MIBG scintigraphy and echocardiography immediately before hospital discharge and after 6 months. The % denervation, heart/mediastinum count ratio, and washout rate were determined from the I-MIBG scintigraphy, and the left ventricular end-diastolic volume, left ventricular end-systolic volume, and LVEF were also determined from echocardiography. We selected 76 patients with old myocardial infarction without active ischemia and used propensity score matching to compare patients who received oral statin (n=38) with those who did not (n=38). The patients were followed up for a median of 4.74 years, with the primary and secondary study end points defined as incidences of fatal cardiac events and major adverse cardiac events (MACEs), respectively. RESULTS: After treatment, the I-MIBG scintigraphic and echocardiographic parameters were improved in the statin and nonstatin groups. However, the extent of change in the % denervation was -12.3±10.3 and -6.2±9.6 (P<0.01), whereas that in the heart/mediastinum count ratio was 0.19±0.14 and 0.08±0.15 (P<0.01), and that in washout rate was -8.1±7.2 and -0.5±9.2% (P<0.01). The extent of change in left ventricular end-diastolic volume, left ventricular end-systolic volume, and LVEF in the statin group tended to exceed than in the nonstatin group, but these changes were not statistically significant. Of the 76 patients, 18 experienced fatal cardiac events and 32 experienced MACEs during the study. Multivariate Cox regression analyses revealed that the nonstatin therapy was a significant predictor of both cardiac death and MACEs in our patients. On Kaplan-Meier analysis, the rates of freedom from cardiac death or MACEs were significantly higher in the statin group than those in the nonstatin group (all, P<0.05). CONCLUSION: Statin therapy improved cardiac sympathetic nerve activity in patients with ischemic cardiomyopathy and mild to moderate heart failure. Furthermore, statin is potentially effective for reducing cardiac events in these patients.

Quantitative Analysis of Iodine Image of Dual-energy Computed Tomography at Rest: Comparison With 99mTc-Tetrofosmin Stress-rest Single-photon Emission Computed Tomography Myocardial Perfusion Imaging as the Reference Standard.

PURPOSE: Dual-energy computed tomography (DECT) can be used for visual determination of iodine distribution in the myocardium (iodine image); however, the accuracy and reproducibility of the process remains debatable. Because of the low contrast-to-noise ratio of CT, we hypothesized that quantitative measurement may be more accurate for detecting myocardial ischemia. In this study, we evaluated our quantitative method by comparing it with visual analysis using Tc-tetrofosmin (TF) stress-rest single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) as the reference standard. MATERIALS AND METHODS: Forty-three patients who had a significant stenosis on cardiac rest DECT and had received Tc-TF stress-rest SPECT MPI within 1 month were retrospectively analyzed. The regions of interest were set on iodine images in accordance with the American Heart Association (AHA) 17-segment model (a total of 731 segments). The regions of interest values were divided by the amount of iodine (mg) per unit weight (kg) and defined as perfusion value (perfusion value analysis). All segments were also visually analyzed and receiver operating characteristic curve analysis performed to identify the superior analysis. RESULTS: The receiver operating characteristic curve analysis showed that perfusion value analysis is significantly superior to visual analysis [the area under the curve: 0.921 (95% confidence interval, 0.860-0.981) versus 0.685 (95% confidence interval, 0.580-0.791), respectively, P<0.05], with 93.8% sensitivity, 99.1% specificity, 98.9% accuracy, 83.3% positive predictive value, and 99.7% negative predictive value (P<0.01). CONCLUSIONS: Quantitative analysis of the iodine image of rest DECT, called perfusion value analysis, is more accurate than visual analysis when compared with Tc-TF SPECT MPI as the reference standard.

Comparative effects of long and short-acting loop diuretics on mortality in patients with chronic heart failure.

BACKGROUND: We previously reported that the long-acting loop diuretic azosemide improves cardiac sympathetic nerve activity (CSNA) in patients with chronic heart failure (CHF), compared with short-acting furosemide. However, its influence on mortality has not been determined. METHODS: The present study was a further analysis of our previously published study in which azosemide showed improved 123I-metaiodobenzylguanidine scintigraphic findings compared with furosemide in CHF patients with reduced left ventricular ejection fraction (LVEF). Patients with CHF were identified according to their histories of acute decompensated heart failure requiring hospitalization. A total of 108 patients were selected and propensity score matching was used to compare patients treated with azosemide (n=54) or furosemide (n=54). RESULTS: During the median follow-up period of 5.22years, 24 out of 108 patients experienced cardiac death events. In multivariate Cox regression analysis (adjusted for age, non-beta-blocker treatments, and impaired CSNA), furosemide treatment was an independent predictor of cardiac death events (p=0.034, hazard ratio 2.624, 95% confidence interval 1.074 to 6.047). On Kaplan-Meier analysis, the cardiac death-free rate in the azosemide group was significantly higher than that in the furosemide group (p<0.05). CONCLUSIONS: These findings indicate the superior effectiveness of azosemide in reducing mortality compared with furosemide.

Adaptive servo-ventilation therapy improves cardiac sympathetic nerve activity, cardiac function, exercise capacity, and symptom in patients with chronic heart failure and Cheyne-Stokes respiration.

PURPOSE: Adaptive servo-ventilation (ASV) therapy has been reported to be effective for improving central sleep apnea (CSA) and chronic heart failure (CHF). The purpose of this study was to clarify whether ASV is effective for CSA, cardiac sympathetic nerve activity (CSNA), cardiac symptoms/function, and exercise capacity in CHF patients with CSA and Cheyne-Stokes respiration (CSR-CSA). METHODS: In this study, 31 CHF patients with CSR-CSA and a left ventricular ejection fraction (LVEF) ≤ 40% were randomized into an ASV group and a conservative therapy (non-ASV) group for 6 month. Nuclear imagings with 123I-Metaiodobenzylguanidine (MIBG) and 99mTc-Sestamibi were performed. Exercise capacity using a specific activity scale (SAS) and the New York Heart Association (NYHA) class were evaluated. CSNA was evaluated by 123I-MIBG imaging, with the delayed heart/mediastinum activity ratio (H/M), delayed total defect score (TDS), and washout rate (WR). RESULTS: The ASV group had significantly better (P < .05) results than the non-ASV group with respect to the changes of AHI (-20.8 ± 14.6 vs -0.5 ± 8.1), TDS (-7.9 ± 4.3 vs 1.4 ± 6.0), and H/M(0.16 ± 0.16 vs -0.04 ± 0.10) on 123I-MIBG imaging, as well as the changes of LVEF (5.3 ± 3.9% vs 0.7 ± 32.6%), SAS (1.6 ± 1.4 vs 0.3 ± 0.7), and NYHA class (2.2 ± 0.4 vs 2.7 ± 0.5) after 6-month therapy. CONCLUSIONS: Performing ASV for 6 months achieved improvement of CSR-CSA, CSNA, cardiac symptoms/function, and exercise capacity in CHF patients with CSR-CSA.

Usefulness of Cardiac Sympathetic Nerve Imaging Using (123)Iodine-Metaiodobenzylguanidine Scintigraphy for Predicting Sudden Cardiac Death in Patients With Heart Failure.

The autonomic nervous system plays an important role in the human heart. Activation of the cardiac sympathetic nervous system is a cardinal pathophysiological abnormality associated with the failing human heart. Myocardial imaging using (123)I-metaiodobenzylguanidine (MIBG), an analog of norepinephrine, can be used to investigate the activity of norepinephrine, the predominant neurotransmitter of the sympathetic nervous system. Many clinical trials have demonstrated that (123)I-MIBG scintigraphic parameters predict cardiac adverse events, especially sudden cardiac death, in patients with heart failure. In this review, we summarize results from published studies that have focused on the use of cardiac sympathetic nerve imaging using (123)I-MIBG scintigraphy for risk stratification of sudden cardiac death in patients with heart failure.

Comparative effects of long-acting and short-acting loop diuretics on cardiac sympathetic nerve activity in patients with chronic heart failure.

OBJECTIVE: Short-acting loop diuretics are known to enhance cardiac sympathetic nerve activity (CSNA) in patients with chronic heart failure (CHF). The effects of two loop diuretics-long-acting azosemide and short-acting furosemide-on CSNA were evaluated using (123)I-metaiodobenzylguanidine (MIBG) scintigraphy in patients with CHF. METHODS: The present study was a subanalysis of our previously published study, which had reported that serial (123)I-MIBG studies were the most useful prognostic indicator in patients with CHF. Patients with CHF (n=208, left ventricular ejection fraction <45%) but no history of cardiac events for at least 5 months prior to the study were identified according to their histories of acute decompensated heart failure requiring hospitalisation. Patients underwent (123)I-MIBG scintigraphy immediately before hospital discharge and at a 6-month follow-up. The delayed % denervation, delayed heart/mediastinum count (H/M) ratio and washout rate (WR) were determined using (123)I-MIBG scintigraphy. A total of 108 patients were selected, and propensity score matching was used to compare patients treated with either oral azosemide (n=54) or furosemide (n=54). RESULTS: After treatment, (123)I-MIBG scintigraphic parameters improved in both groups. However, the degree of change in % denervation was -13.8±10.5 in the azosemide group and -5.7±12.7 in the furosemide group (p<0.01), the change in H/M ratio was 0.20±0.16 in the azosemide group and 0.06±0.19 in the furosemide group (p<0.01), and the change in WR was -11.3±9.2% in the azosemide group and -3.0±12.7% in the furosemide group (p<0.01). Moreover, multivariate analysis showed an independent and significant positive relationship between furosemide and δ-WR from hospital discharge to 6 months after treatment in patients with CHF (p=0.001). CONCLUSIONS: These findings indicate that azosemide suppresses CSNA compared with furosemide in patients with CHF. TRIAL REGISTRATION NUMBER: UMIN000000626 (UMIN-CTR Clinical Trial).

Diastolic Stunning as a Marker of Severe Coronary Artery Stenosis: Analysis by Speckle Tracking Radial Strain in the Resting Echocardiogram.

BACKGROUND: Two-dimensional speckle tracking (2DST) stress echocardiography detects postischemic myocardial diastolic stunning. However, the use of 2DST at rest for detecting diastolic stunning in ischemia is unclear. RESULTS: Thirty-nine patients (age = 65 ± 12 years; male/female = 34/5) with effort angina pectoris that was confirmed by stress myocardial perfusion scintigraphy were enrolled. Ischemic area (I) was determined in the middle LV short axial view using stress myocardial scintigraphy. The area opposite to it was defined as nonischemic area (non-I). Midventricular parasternal short-axis (SAX) radial strains were estimated using 2DST at rest on the following day. LV diastolic function was evaluated using diastolic index (DI, changes in the regional LV radial strain during diastole) and radial strain rate (SR) during early diastolic period. These parameters were compared between I and non-I before and 1 month after percutaneous coronary intervention (PCI) in the I of 3 coronary vessels. For the I, the DI was lower (38 ± 27 vs. 55 ± 27; P = 0.003) and SR was higher (-1.6 ± 0.6 vs. -1.9 ± 0.8; P = 0.007) than in non-I before PCI. One month after PCI, the DI and SR recovered to 53 ± 27 (P = 0.008) and -2.1 ± 0.8 (P = 0.006), respectively. Furthermore, the DI of the LAD and LCX significantly improved (P = 0.0004 and 0.002, respectively); the RCA area showed tendency to improve (P = 0.092), and the SR also improved (P < 0.05) in all areas after PCI. CONCLUSION: Diastolic stunning in ischemic areas can be detected using 2DST at rest and recover 1 month after PCI.

Prognostic value of myocardial perfusion single photon emission computed tomography for major adverse cardiac cerebrovascular and renal events in patients with chronic kidney disease: results from first year of follow-up of the Gunma-CKD SPECT multicenter study.

PURPOSE: Patients with chronic kidney disease (CKD) have an increased risk of adverse cardio-cerebrovascular events. We examined whether stress myocardial perfusion single photon emission computed tomography (SPECT) provides reliable prognostic markers for these patients. METHODS: In this multicenter, prospective cohort trial from the Gunma-CKD SPECT study protocol, patients with CKD [estimated glomerular filtration rate (eGFR) < 60 min/ml per 1.73 m(2)] undergoing stress (99m)Tc-tetrofosmin SPECT for suspected or possible ischemic heart disease were initially followed for 1 year, with the following study endpoints: primary, the occurrence of cardiac deaths (CDs), and secondary, major adverse cardiac, cerebrovascular, and renal events (MACCREs). The summed stress score (SSS), summed rest score, and summed difference score (SDS) were estimated with the standard 17-segment, 5-point scoring model. Left ventricular end-diastolic volume, end-systolic volume (ESV), and ejection fraction were measured using electrocardiogram-gated SPECT. RESULTS: During the first year of follow-up, 69 of 299 patients experienced MACCREs (CD, n = 7; non-fatal myocardial infarction, n = 3; hospitalization for heart failure, n = 13; cerebrovascular accident, n = 1; need for revascularization, n = 38; and renal failure, i.e., hemodialysis initiation, n = 7). ESV and SSS were associated with CDs (p < 0.05), and eGFR and SDS were associated with MACCREs (p < 0.05), in multivariate logistic analysis. Patients with high ESV and high SSS had a significantly higher CD rate during the first year than the other CKD patient subgroups (p < 0.05). Patients with low eGFR and high SDS had a significantly higher MACCRE rate than the other subgroups (p < 0.05). CONCLUSION: Myocardial perfusion SPECT can provide reliable prognostic markers for patients with CKD.

Effects of adding intravenous nicorandil to standard therapy on cardiac sympathetic nerve activity and myocyte dysfunction in patients with acute decompensated heart failure.

PURPOSE: Nicorandil, an adenosine triphosphate-sensitive potassium channel opener, improves cardiac sympathetic nerve activity (CSNA) in ischemic heart disease or chronic heart failure. However, its effects on CSNA and myocyte dysfunction in acute heart failure (AHF) remain unclear. We investigated the effects of adding intravenous nicorandil to standard therapy on CSNA and myocyte dysfunction in AHF. METHODS: We selected 70 patients with mild to moderate nonischemic AHF who were treated with standard conventional therapy soon after admission. Thirty-five patients were assigned to additionally receive intravenous nicorandil (4-12 mg/h; group A), whereas the remaining patients continued their current drug regimen (group B). Delayed total defect score (TDS), delayed heart to mediastinum count (H/M) ratio, and washout rate (WR) were determined by (123)I-metaiodobenzylguanidine (MIBG) scintigraphy within 3 days of admission and 4 weeks later. High sensitivity troponin T (hs-TnT) level was also measured at the same time points. RESULTS: After treatment, MIBG scintigraphic parameters significantly improved in both groups. However, the extent of the changes in these parameters in group A significantly exceeded the extent of the changes in group B [TDS -11.3 ± 4.3 in group A vs -4.0 ± 6.0 in group B (p < 0.01); H/M ratio 0.31 ± 0.16 vs 0.14 ± 0.16 (p < 0.01); WR -13.8 ± 7.8 % vs -6.1 ± 8.9 % (p < 0.01)]. The hs-TnT level decreased significantly from 0.052 ± 0.043 to 0.041 ± 0.033 ng/ml (p < 0.05) in group A, but showed no significant change in group B. Moreover, in both groups, no relationships between the extent of changes in MIBG parameters and hs-TnT level were observed. CONCLUSION: Adding intravenous nicorandil to standard therapy provides additional benefits for CSNA and myocyte dysfunction over conventional therapy alone in AHF patients. Furthermore, the mechanisms of improvement in CSNA and myocyte dysfunction after nicorandil treatment in AHF patients were distinct.

Effects of statin therapy on cardiac sympathetic nerve activity and left ventricular remodeling in patients with chronic heart failure: a propensity score-matched analysis.

Statin therapy reduces enhanced cardiac sympathetic nerve activity (CSNA) in patients with heart disease, and prevents left ventricular (LV) remodeling in chronic heart failure (CHF) patients. We sought to evaluate the effects of statin therapy on CSNA, as evaluated by I-metaiodobenzylguanidine (MIBG) scintigraphy, and LV remodeling in CHF patients. This study was sub-analysis of our previous report of the result that the serial I-MIBG studies were the most useful prognostic indicator in CHF patients. Patients with CHF (n = 208; left ventricular ejection fraction <45%) but no cardiac events for at least 5 months before the study, were identified according to their history of decompensated acute heart failure requiring hospitalization. The patients underwent I-MIBG scintigraphy and echocardiography immediately before hospital discharge and after 6 months. The delayed % denervation, delayed heart/mediastinum count (H/M) ratio, and washout rate (WR) were determined by I-MIBG scintigraphy. The LV end-diastolic volume (EDV) and end-systolic volume (ESV) were also determined by echocardiography. We selected 164 patients and used propensity score matching to compare patients who received oral statin (n = 82), and those who did not (n = 82).The changes in I-MIBG scintigraphic parameters improved, and in echocardiographic LVEDV and LVESV reduced in the statin group compared with those in the non-statin group. Moreover, there were significant correlations between changes in the I-MIBG scintigraphic findings and those in the LVEDV (% denervation, r = 0.534, P < 0.001; H/M ratio, r =  -0.516, P < 0.001; and WR, r = 0.558, P < 0.001); or the LVESV (% denervation, r = 0.479, P < 0.001; H/M ratio, r =  -0.450, P < 0.001; and WR, r = 0.520, P < 0.001) in the statin group. In contrast, there was no relationship between these parameters in the non-statin group.Statin therapy not only improved CSNA, but also reduced LV volume, in other wards, prevented LV remodeling in CHF patients.

Coronary vasospasm during CT angiography.

A 71-year-old man, a heavy smoker, was admitted for evaluation of "chest oppression" after every dinner. Cardiac CT with a beta-blocker showed coronary stenosis in the left circumflex. Although adenosine triphosphate-stress perfusion single-photon emission CT revealed no ischemia, Holter electrocardiography belatedly indicated an ST elevation associated with his symptoms while smoking. He was diagnosed to have vasospastic angina. Cardiac CT without a beta-blocker showed thin diffuse plaque and negative remolding without any significant stenosis at the same site. Asian patients have a tendency to develop vasospastic angina. Although beta-blockers are recommended for cardiac CT, the routine administration of beta-blockers in cardiac CT may have some risk for such cases.

Coronary artery calcification as a new predictor of non-target lesion revascularization during the chronic phase after successful percutaneous coronary intervention.

In the drug-eluting stent era, the outcome of patients undergoing percutaneous coronary intervention (PCI) has remarkably improved. Nevertheless, non-target lesion revascularization (non-TLR) is often performed even after successful PCI and optimized medical therapy. This study aimed to determine the predictor of non-TLR. In all, 125 consecutive patients with stable angina pectoris underwent intravascular ultrasound (IVUS)-guided PCI and were followed up for 3.3 ± 0.5 years. We performed oral glucose-tolerance tests in patients with no history of known diabetes mellitus (DM) to investigate glucose tolerance. To evaluate the severity of coronary artery calcification (CAC), we calculated CAC score by multiplying the arc (degree) with the length (mm) of the superficial calcium deposit detected by IVUS. Fourteen patients underwent non-TLR (non-TLR group); the remaining 111 did not (reference group). Glycosylated hemoglobin (HbA1c; %) and prevalence of known DM were similar in both groups, but the non-TLR group had higher fasting blood glucose (103 ± 16 vs. 94 ± 11 mg/dl, p = 0.04) and blood glucose (196 ± 60 vs. 149 ± 48 µU/ml, p = 0.01) and insulin at 2 h (184 ± 241 vs. 67 ± 49 µU/ml, p < 0.01) than did the reference group. CAC score was significantly higher in the non-TLR group (788 ± 585 vs. 403 ± 466, p = 0.01). Multiple logistic analysis indicated that CAC score is an independent predictor of non-TLR (p = 0.008). Non-TLR-free rate was significantly higher for patients with CAC score ≥400 than for those with CAC score <400 (p = 0.01). Non-TLR is associated with abnormal glucose tolerance and CAC score; CAC score is an independent predictor of non-TLR. Secondary prevention is especially important in patients with high CAC scores.

Evaluation of cardiac sympathetic nerve activity and aldosterone suppression in patients with acute decompensated heart failure on treatment containing intravenous atrial natriuretic peptide.

PURPOSE: Aldosterone prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide (ANP), a circulating hormone of cardiac origin, inhibits aldosterone synthase gene expression in cultured cardiocytes. We evaluated the effects of intravenous ANP on cardiac sympathetic nerve activity (CSNA) and aldosterone suppression in patients with acute decompensated heart failure (ADHF). METHODS: We studied 182 patients with moderate nonischemic ADHF requiring hospitalization and treated with standard therapy containing intravenous ANP and 10 age-matched normal control subjects. ANP was continuously infused for >96 h. In all subjects, delayed total defect score (TDS), heart to mediastinum ratio, and washout rate were determined by 123I-metaiodobenzylguanidine (MIBG) scintigraphy. Left ventricular (LV) end-diastolic volume, end-systolic volume, and ejection fraction were determined by echocardiography. All patients with acute heart failure (AHF) were examined once within 3 days and then 4 weeks after admission, while the control subjects were examined only once (when their hemodynamics were normal). Moreover, for 62 AHF patients, plasma aldosterone concentrations were measured at admission and 1 h before stopping ANP infusion. RESULTS: 123I-MIBG scintigraphic and echocardiographic parameters in normal subjects were more favorable than those in patients with AHF (all p < 0.001). After treatment, all these parameters improved significantly in AHF patients (all p < 0.001). We also found significant correlation between percent changes of TDS and aldosterone concentrations (r = 0.539, p < 0.001) in 62 AHF patients. CONCLUSION: The CSNA and LV performance were all improved in AHF patients. Furthermore, norepinephrine uptake of myocardium may be ameliorated by suppressing aldosterone production after standard treatment containing intravenous ANP.