Cardiac Sympathetic Nerve Function Research Articles

Association between sebum secretion and cardiac sympathetic dysfunction in Parkinson's disease

BackgroundPatients with Parkinson's disease (PD) have α-synuclein (α-Syn) deposition in the skin, and decreased sebum secretion due to epidermal dysfunction. However, the relationship between sebum secretion and autonomic neuropathies is unknown. MethodsUsing the medical records in our facility, we identified patients newly diagnosed with PD on admission from August 2020 to December 2023. We analyzed whether sebum secretory ability at multiple sites was associated with cardiac sympathetic nerve function that was assessed by cardiac 123I-metaiodobenzylguanidine scintigraphy. ResultsForty patients were included. Their sebum secretion ability positively correlated with the ratio of the average pixel count in the heart to that in the mediastinum (H/M ratio) in the posterior neck, the anterior chest, the arms, and the abdomen. In the multiple regression analysis, those in the arms (β, 8.8; 95 % CI, 4.4–13.2; P < 0.001) and abdomen (β, 1.3; 95 % CI, 0.1–2.5; P = 0.032) were associated with the H/M ratio after controlling for age, sex, and UPDRS part III. ConclusionThis study revealed an association between sebum secretion in the arms and the abdomen, and cardiac sympathetic nerve function in PD patients. The site of the sebum secretory disturbance associated with cardiac sympathetic nerves closely resembled the gradient of α-Syn deposition in the skin, corroborating its deposition pattern. Our findings suggest that noninvasive sebum measurement may serve as an adjunctive diagnostic tool of α-Syn deposition in the skin for PD and provide insights into sympathetic nerve damage alongside cardiac sympathetic nerve assessments.

Cardiac Sympathetic Nerve Function in Patients with Severe Aortic Stenosis Prior and After Transcatheter Aortic Valve Implantation: Evaluation by 5-Year Risk Model.

Background: While the non-invasive assessment of cardiac sympathetic nerve dysfunction is readily accessible, its applicability in invasive intervention for structural heart disease has received limited investigation. Our study aimed to clarify the cardiac sympathetic nerve function in patients with severe Aortic stenosis (AS) and its postoperative changes after transcatheter aortic valve implantation (TAVI) using 123I-metaiodobenzylguanidine scintigraphy (MIBG) in combination with 5-year mortality prediction model. Methods: Consecutive 26 patients (83±5ys, male 4) with severe AS who underwent MIBG prior TAVI procedures were retrospectively enrolled. Of those, 15 patients underwent postoperative-follow up MIBG. The early and delayed heart-to-mediastinum ratio (e- and d-H/M), and washout rate (WR) were obtained from MIBG planner imaging. The MIBG 5-year mortality prediction model was employed to compare pre and after TAVI. Cardiac function and wall thickness were evaluated with transthoracic echocardiography. Results: Preoperative e-H/M, d-H/M, and WR were 2.4±0.5, 2.3±0.4, and 29±14% respectively, and WR showed significant correlation to left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) (r=-0.4 and 0.6; p=0.03, and 0.001 for LVEF and BNP, respectively). 102±28 days after TAVI, either H/M or WR did not show significant improvement among enrolled patients (2.5±0.3, 2.3±0.4, and 30±11% for e-, d-H/M, and WR for after TAVI), while the BNP level was significantly reduced (128±691 and 94±194 pg/dl, for pre vs. after, p=0.008). Five patients showed a significant recovery in WR (37.0±13.8 and 28.8±8.5% for pre and post, p=0.04), and left ventricular wall thickness was significantly thinner compared to those who did not recover (15.2±3.2 vs 11.2±2.4, p=0.02; 14.2±2.9 vs 10.8±1.8, p=0.02 for intraventricular septum and posterior wall, respectively). In 5-year prediction risk model, 7 patients showed a significant reduction in mortality risk, and the patients who did not show risk reduction had significantly reduced renal function (eGFR 57.5±18.8 vs. 38.2±11.3 ml/min/1.73m2, p=0.03 for recovered vs. not recovered). Conclusion: After a 3-month follow-up after TAVI, diverse response in cardiac MIBG parameters were observed among patients with severe AS, despite successful valve replacement. Cardiac MIBG serves as a non-invasive tool that can comprehensively evaluate and surrogate the severity of heart failure resulting from a multi-factorial condition.

Left-atrial volume reduction reflects improvement of cardiac sympathetic nervous function in patients with severe aortic stenosis after transcatheter aortic valve replacement.

Trans-catheter aortic valve replacement (TAVR) is an excellent alternative intervention for surgical aortic valve replacement. Cardiac sympathetic nervous (CSN) function and left atrial (LA) volume are both important prognostic factors in patients with aortic stenosis (AS) after TAVR. The relationship between the two clinical factors is unknown, however. This retrospective observational study aimed to assess the correlation between CSN function and LA volume in 48 symptomatic patients with severe AS (median age: 85years, IQR 82-88years; 81% female) before and after TAVR. CSN function was assessed by performing 123I-metaiodobenzylguanidine (MIBG) scintigraphy before and 6months after TAVR, and the delayed heart-to-mediastinum ratio (dHMR) and washout rate (WR) were calculated. We also performed transthoracic echocardiography near the same time. TAVR improved the dHMR, WR, and LA volume index (LAVI) (dHMR: median 2.89 [IQR 2.62-3.23] vs. 2.98 [2.49-3.25], p = 0.0182; WR: 28% [24-38] vs. 23% [16-32], p < 0.0001; LAVI: 47.7mL/m2 [37.8-56.3] vs. 41.2mL/m2 [33.7-56.1], p = 0.0024). In multiple linear regression analysis, the percentage change in LAVI from baseline to post-TAVR (∆LAVI%) was an independent predictor of change in dHMR from baseline to post-TAVR (β = - 0.35, p = 0.0110). In conclusion, LA volume reduction reflected CSN functional improvement after TAVR. In patients with TAVR, ∆LAVI% might be a valuable parameter for evaluating CSN functional recovery.

Serial changes in cardiac sympathetic nervous function after transcatheter aortic valve replacement: A prospective observational study using 123I-meta-iodobenzylguanidine imaging

BackgroundTranscatheter aortic valve replacement (TAVR) can rapidly improve cardiac sympathetic nervous function (CSNF) within 2 weeks in patients with aortic stenosis (AS). However, whether such short-term improvements will be sustained thereafter remains unclear. MethodsPatients with severe AS who underwent TAVR between October 2017 and June 2019 were enrolled in this single-center, prospective, observational study. 123I-meta-iodobenzylguanidine imaging was performed at baseline, within 2 weeks after TAVR, and at 6 to 12 months post-TAVR to evaluate the heart–mediastinum ratio (H/M) and washout rate. ResultsOf 183 consecutive patients, 75 (19 men; median age: 86 years) were evaluated. The late H/M significantly improved within 2 weeks after TAVR (P = .041) and further improved over 6 to 12 months after TAVR (P = .041). Multivariate analysis revealed that the baseline mean aortic valve pressure gradient (mPG) was an independent predictor of mid-term improvement in the late H/M (> 0.1) (P = .037). Patients with a high baseline mPG (≥ 58 mmHg) exhibited a significantly greater increase in the late H/M than those with a low baseline mPG (< 42 mmHg) (0.24 vs 0.01; P = .029). ConclusionCSNF demonstrated sustained improvement from within 2 weeks after TAVR until 6 to 12 months later. Such improvement was related to baseline hemodynamic AS severity.

Assessment of Exhaustive Exercise under Internet of Things Exercise Monitoring System and Mechanism Analysis of Cardiovascular Endothelial Cell Apoptosis Induced by Oxidative Stress

To investigate the effect of high-intensity exhaustive exercise on body and the molecular mechanism of oxidative stress regulating apoptosis of cardiovascular endothelial cells (CVECs), 70 college students who took an aerobics course were recruited as the research subjects, all of which were divided into the high-intensity group (35 students) and the moderate-intensity group (35 students). The Internet of Things- (IoT-) based human exercise information monitoring system was employed to collect the electrocardiogram, serum indexes, and oxidative stress indexes of the two groups of subjects after exercise. Moreover, 30 clean male SD rats were divided into exhaustive exercise group ( n = 10 ), routine exercise group ( n = 10 ), and blank control group ( n = 10 ) using treadmill exercise as stress source, and various physiological indexes of the three groups were compared. In human experiments, the time-domain indexes of heart rate variability (HRV), 50 ms in the total number of sinus heartbeats (PNN50), the standard deviation of all NN intervals (SDNN), standard deviation of mean NN interval (SDANN), standard deviation of difference between adjacent NN intervals (SDSD), root mean square (RMSSD) in the high intensity group were lower than those in the moderate intensity group ( P &lt; 0.05 ). The levels of T-sensitive troponin I (Tnl-ultra), cortisol (COR), high-sensitive troponin T (TnT-hs), high-sensitive C-reactive protein (hs-CRP), and human heart-type fatty acid binding protein (HUMAN H-FABP) in high intensity group were higher than those in moderate intensity group ( P &lt; 0.05 ). Experiments on animals found that SOD content and mRNA expression of fork-head box 03A (FOX03A) and silencing-information regulator 1 (Sirtl) in serum of rats in exhaustion exercise group were lower than those in the routine exercise group and blank control group, while lactate dehydrogenase (LDH) and malondialdehyde (MDA) contents were opposite ( P &lt; 0.05 ). In short, strenuous exercise made the body in the state of acute stress, leading to the disturbance of cardiac autonomic nervous function and sympathetic nervous function, and increasing the risk of malignant arrhythmia. Oxidative stress induced by exhaustive exercise may promote the apoptosis of CVECs by reducing the expression of Sirtl and FOX03A and locating FOX03A to the nucleus.

Factors Influencing Cardiac Sympathetic Nervous Function in Patients With Severe Aortic Stenosis: Assessment by 123I-Metaiodobenzylguanidine Myocardial Scintigraphy

Numerous studies have shown that 123I-metaiodobenzylguanidine (MIBG) scintigraphy, an index of cardiac sympathetic nervous (CSN) activity, is useful for predicting prognosis in patients with heart failure. However, the factors influencing the CSN activity of patients with severe aortic stenosis (AS) remain unclear. We enrolled 91 patients with severe AS who underwent 123I-MIBG scintigraphy, coronary computed tomography (CCT), and transthoracic echocardiography. When CCT angiography (CCTA) showed an obstructive epicardial artery, invasive coronary angiography was performed within 1 week of CCTA. There were 21 male and 70 female patients with a mean age of 84±5 years. Eighty-five (85) patients (93%) had hypertension and 13 patients (14%) had diabetes. Two (2) patients (2%) had previous myocardial infarction and eight (9%) had a previous coronary intervention. All patients had severe AS: aortic valve area was 0.63±0.18 cm2 and the mean pressure gradient was 56±19 mmHg. Regarding 123I-MIBG parameters, early heart-to-mediastinum (H/M) ratio was 3.1±0.5, delayed H/M ratio was 2.8±0.6, and the washout rate (WR) was 35%±13%. Multivariable linear regression analysis showed that coronary artery disease (β=-0.30, p=0.002) was an independent predictor of delayed H/M ratio, and that aortic valve area (β=-0.20, p=0.048) was an independent predictor of WR. Our findings suggest that coronary artery disease is an independent predictor of delayed H/M ratio, and aortic valve area is an independent predictor of WR in patients with severe AS.

Changes in cardiac sympathetic nerve activity on 123 I-metaiodobenzylguanidine scintigraphy after MitraClip therapy.

AimsIn patients with heart failure, over‐activation of the cardiac sympathetic nerve (CSN) function is associated with severity of heart failure and worse outcome. The effects of MitraClip therapy on the CSN activity in patients with mitral regurgitation (MR) remained unknown. In this study, we evaluated the impact of the MitraClip therapy on CSN activity assessed by 123I‐metaiodobezylguanidine (MIBG) scintigraphy.Methods and resultsWe enrolled consecutive patients with moderate‐to‐severe (3+) or severe (4+) MR who were scheduled to undergo MitraClip procedure in this prospective observational study. MIBG scintigraphy was performed at baseline and 6 months after the MitraClip procedure to evaluate the heart–mediastinum ratio and washout rate (WR). Changes in these MIBG parameters were analysed. Of the 13 consecutive patients, 10 were successfully treated with MitraClip procedure and completed follow‐up assessment. With regard to the MIBG parameters, changes in the early and delayed heart–mediastinum ratio from baseline to 6 months were not significant (2.16 ± 0.42 to 2.06 ± 0.34, P = 0.38 and 1.87 ± 0.39 to 1.83 ± 0.39, P = 0.43, respectively), whereas WR was significantly decreased (38.6 ± 3.9% to 32.6 ± 3.94%, P = 0.002).ConclusionsThe CSN activity of the WR on MIBG imaging was improved 6 months after MitraClip therapy in patients with 3+ or 4+ MR.

Prognostic value of cardiac 123 I-metaiodobenzylguanidine imaging for predicting cardiac events after transcatheter aortic valve replacement.

AimsIn patients with aortic valve stenosis (AS), cardiac sympathetic nervous (CSN) dysfunction and its improvement after transcatheter aortic valve replacement (TAVR) have been reported. The prognostic impact of CSN function remains unclear. This study investigated the prognostic value of cardiac 123I‐metaiodobenzylguanidine (MIBG) imaging for predicting cardiac events after TAVR.Methods and resultsThis single‐centre prospective observational study enrolled patients with AS between July 2017 and May 2019. MIBG scintigraphy was performed before and soon after TAVR to evaluate the late heart–mediastinum ratio (L‐H/M). Patients were classified into three pairs of groups based on the baseline and post‐TAVR L‐H/M (≥2.0 or <2.0) and on the presence of TAVR‐related improvement in L‐H/M. The study endpoint was the occurrence of major adverse cardiac events (MACE), defined as a composite of all‐cause death, non‐fatal myocardial infarction, and hospitalization due to heart failure. Among the 187 consecutive patients who underwent TAVR, 107 (27 men; median age: 86 years) were evaluated. Over a median follow‐up of 366 days, 15 (14.0%) patients had MACE. The incidence of MACE was significantly low in patients with L‐H/M improvement and/or high post‐TAVR L‐H/M (≥2.0). Baseline L‐H/M and frailty were associated with poor response of L‐H/M to TAVR treatment. TAVR‐related improvement in L‐H/M had significant effects on MACE, with an adjusted hazard ratio of 0.233 (95% confidence interval, 0.064–0.856; P = 0.028).ConclusionsTAVR‐related improvement in L‐H/M was an independent predictor of cardiac events, 1 year after TAVR. Cardiac MIBG imaging is useful for predicting cardiac events after TAVR.

Abstract 14945: Prognostic Value of Cardiac 123 I-MIBG Imaging for Predicting Cardiac Events After Transcatheter Aortic Valve Replacement

Introduction: In patients with aortic valve stenosis (AS), cardiac sympathetic nervous (CSN) dysfunction and its improvement after transcatheter aortic valve replacement (TAVR) have been reported; however, the prognostic impact of CSN function remains unclear. This study investigated the prognostic value of cardiac 123 I-metaiodobenzylguanidine (MIBG) imaging for predicting cardiac events after TAVR. Hypothesis: We hypothesized that the improvement in MIBG parameter with TAVR treatment can be an indicator of better prognosis. Methods: This single-center prospective observational study enrolled patients with AS between July 2017 and May 2019. MIBG scintigraphy was performed before and after TAVR to evaluate the delayed heart-mediastinum ratio (d-H/M). Patients were classified into three pairs of groups based on the baseline and post-TAVR d-H/M (≥2.0 or &lt;2.0) and on the presence of TAVR-related improvement in d-H/M (i.e. Δ d-H/M [post-TAVR – baseline] &gt;0 or ≤0). The study endpoint was the occurrence of major adverse cardiac events (MACE), defined as a composite of all-cause death, non-fatal myocardial infarction, and hospitalization due to heart failure. Results: Among the 187 consecutive patients who underwent TAVR, 107 (27 men; median age: 86 years) were evaluated. Over a median follow-up of 366 days, 15 (14.0%) patients had MACE. The incidence of MACE was significantly low in patients with d-H/M improvement and/or high post-TAVR d-H/M (≥2.0). Baseline d-H/M and frailty were associated with poor response of d-H/M to TAVR treatment. Moreover, post-TAVR d-H/M had significant effects on MACE, with an adjusted hazard ratio of 1.264 (95% confidence interval, 0.034-2.480; p=0.04). Conclusions: Both d-H/M improvement and high post-TAVR d-H/M were associated with better prognosis in patients who underwent TAVR. Cardiac MIBG imaging is useful for predicting cardiac events after TAVR.

Impact of Prosthesis-Patient Mismatch After Transcatheter Aortic Valve Replacement on Changes in Cardiac Sympathetic Nervous Function.

The impact of prosthesis-patient mismatch (PPM) after transcatheter aortic valve replacement (TAVR) on changes in cardiac sympathetic nervous (CSN) function remains unclear. Using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, we investigated the impact of PPM after TAVR on CSN activity.We enrolled 44 of 117 patients with severe aortic stenosis who underwent TAVR for analysis in the present study. We conducted 123I-MIBG scintigraphy at baseline and at about 9 months after TAVR. Differences between baseline and post-TAVR 123I-MIBG parameters were compared between cases with and without PPM.There were 17 and 27 patients with and without PPM, respectively. Those without PPM exhibited significantly decreased left ventricular mass index (122 ± 36 g/m2 versus 108 ± 30 g/m2, P < 0.001) following TAVR, whereas those with PPM did not (117 ± 21 g/m2 versus 110 ± 17 g/m2, P = 0.09). Significant improvements in delayed heart-to-mediastinum (H/M) ratio (2.8 ± 0.4 versus 3.0 ± 0.4, P = 0.004) and washout rate (WR) (33% ± 10% versus 24% ± 12%, P < 0.001) were observed after TAVR in patients without PPM but not in those with PPM. Multivariable linear regression analysis revealed PPM to be a negative predictor of improvements in delayed H/M ratio and WR.Delayed H/M ratio and WR improve significantly after TAVR in the absence of PPM, whereas these improvements are not observed in patients with PPM. Hence, the presence of PPM is a negative predictor of improvements in delayed H/M ratio and WR in patients undergoing TAVR.

Prognostic value of cardiac 123I-metaiodobenzylguanidine imaging for predicting cardiac events after transcatheter aortic valve replacement

Abstract Background In patients with aortic valve stenosis (AS), cardiac sympathetic nervous (CSN) dysfunction and its improvement after TAVR have been reported; however, the prognostic impact of CSN function remains unclear. This study investigated the prognostic value of cardiac 123I-metaiodobenzylguanidine (MIBG) imaging for the prediction of cardiac events after transcatheter aortic valve replacement (TAVR). Methods This study was a single-center prospective observational study that enrolled patients with AS or failed surgical bioprostheses between July 2017 and May 2019. MIBG scintigraphy was performed before and after TAVR to evaluate the delayed heart–mediastinum ratio (d-H/M). Patients were classified into three pairs of groups based on the baseline and post-TAVR d-H/M (≥2.0 or &amp;lt;2.0) and on the presence of TAVR-related improvement of d-H/M. The study endpoints were major adverse cardiac events (MACE), including all-cause death, myocardial infarction, and hospitalization due to heart failure. The association of d-H/M with MACE following TAVR was based on a Cox proportional hazards ratio model adjusted for multiple prognostic variables. Results Of 187 consecutive patients who underwent TAVR, 111 (31 men; median age: 86 years) were evaluated. Over a median follow-up of 366 days, 16 (14.4%) patients had MACE. The incidence of MACE was significantly lower in patients with d-H/M improvement and/or the high post-TAVR d-H/M (≥2.0). Post-TAVR d-H/M had significant impacts on MACE, with an adjusted hazard ratio of 1.326 (95% confidence interval, 0.139–2.515; p=0.027). Conclusions Both d-H/M improvement and high post-TAVR d-H/M were associated with better prognosis in patients who underwent TAVR. Cardiac MIBG imaging was useful for predicting cardiac events after TAVR. Funding Acknowledgement Type of funding source: None

New Conditioning Evaluation Method Using Heart Autonomic Function In Competitive Archery Athletes

PURPOSE: Archery is mainly an outdoor sport that involves shooting arrows from a standing position at a target 70 meters away. It is a relatively static sport that requires less physical activity than most other sports, but extremely fine control over movements. In the present study we investigated a new method of evaluating the condition of athletes in target sports, such as archery, for improving performance from the perspective of autonomic function, i.e., heart rate and heart rate variability (HRV) and respiratory sinus arrhythmia (RSA). METHODS: The participants were members of the Japanese women’s national archery team (athlete A: age, 30 years, height, 180.0 cm, weight, 69.0 kg; athlete B: age, 18 years, height, 157.5 cm, weight, 50.0 kg). HRV was measured 1) at rest in the supine position for 5-min, 2) at rest in the supine position for 3-min, after having five deep breaths, then, 3) in the standing position for 3-min and finished the measurement with five deep breaths. The ECG data were derived from the chest II leads using the Biopac MP36 data acquisition system (Santa Barbara, CA, USA) and input at a sampling frequency of 1 kHz, and heart rate and HRV were measured from the R-R interval. RESULTS: The HRV results for athletes A and B are shown in Table 1. In the present study, athletes A and B were both asked about their subjective feelings of fatigue and their archery performance (scores) at the time of the HRV measurements. Athlete A reported subjective feelings of fatigue at the time of the measurement. Athlete B had no subjective feelings of fatigue, but the inability to achieve high scores. CONCLUSION: The results suggest that even when there are no subjective feelings of fatigue, but the heart rate is high, LF/HF is high, HF is low, or RSA is low, in that case, cardiac sympathetic nervous function will be predominant, and poorer performance may be expected.

Prognostic effect and modulation of cardiac sympathetic function in heart failure patients treated with cardiac resynchronization therapy

BackgroundCardiac autonomic dysfunction as assessed by 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy is associated with poor prognosis in heart failure (HF) patients. Although cardiac resynchronization therapy (CRT) has emerged as an effective therapy in improving outcomes on HF patients, its effect on cardiac sympathetic nervous function is still not fully understood. We aimed to study the value of pre-implantation 123I-mIBG late heart-to-mediastinum ratio (HMR) as a predictor of response and outcomes after CRT and to correlate modification in this parameter with CRT response and functional improvement. Methods and ResultsBETTER-HF (Benefit of exercise training therapy and cardiac resynchronization in HF patients) is a prospective randomized clinical trial including HF patients submitted CRT (mean LVEF 24 ± 8%, 74% NYHA class ≥ III) who underwent a clinical, echocardiographic, and scintigraphic assessment before and 6 months after CRT. One-hundred and twenty-one patients were included. Echocardiographic response was observed in 54% and composite outcome of cardiac mortality, cardiac transplant or heart failure hospitalization in 24% of patients. Baseline late HMR was an independent predictor of CRT response (regression coefficient 2.906, 95% CI 0.293-3.903, P .029) and outcomes (HR 0.066 95% CI 0.005-0.880, P .040). At follow-up, 123I-mIBG imaging showed positive changes in cardiac sympathetic nerve activity only in responders to CRT (1.36 ± 0.14 prior vs. 1.42 ± 0.16 after CRT, P .039). There was a significant correlation between improvement in late HMR and improvement in peak oxygen consumption (r 0.547, P < .001). ConclusionIn our study, baseline cardiac denervation predicted response and clinical outcomes after CRT implantation. Cardiac sympathetic function was improved only in patients who responded to CRT and these positive changes were correlated with improvement in functional capacity.

The NADPH oxidase inhibitor apocynin improves cardiac sympathetic nerve terminal innervation and function in heart failure.

What is the central question of this study? Does NADPH oxidase activation mediate cardiac sympathetic nerve denervation and dysfunction in heart failure. What is the main findings and its importance? Cardiac sympathetic nerve terminal density and function were reduced in heart failure after myocardial infarction in rabbits. The NADPH oxidase inhibitor apocynin prevented the reduction in cardiac sympathetic nerve terminal density and function in heart failure. This suggest that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in heart failure. NADPH oxidase may be a potential therapeutic target for cardiac sympathetic denervation and dysfunction in heart failure. Congestive heart failure (CHF) is characterized by cardiac sympathetic nerve terminal abnormalities, as evidenced by decreased noradrenaline transporter (NAT) density and cardiac catecholaminergic and tyrosine hydroxylase (TH) profiles. These alterations are associated with increased reactive oxygen species (ROS). NADPH oxidase is a major source of ROS in CHF. In this study, we tested the hypothesis that NADPH oxidase activation mediates cardiac sympathetic nerve terminal abnormalities in CHF. CHF was produced by myocardial infarction (MI) in rabbits. Rabbits with MI or a sham operation were randomized to orally receive an NADPH oxidase inhibitor, apocynin (6mgkg-1 day-1 ), or placebo for 30days. MI rabbits exhibited left ventricular dilatation, systolic dysfunction, and increases in NADPH oxidase activity and 4-hydroxynonenal expression in the remote non-infarcted myocardium, all of which were prevented by treatment with apocynin. Cardiac catecholaminergic histofluorescence profiles and immunostained TH and PGP9.5 expression were decreased, and the decreases were ameliorated by apocynin treatment. NAT, TH and PGP9.5 protein and mRNA expression were reduced and the reduction was mitigated by apocynin treatment. The effects of apocynin were confirmed by utilizing the NADPH oxidase inhibitor diphenyleneiodonium in a separate experiment. In conclusion, the NADPH oxidase inhibitor apocynin attenuated increased myocardial oxidative stress and decreased cardiac sympathetic nerve terminals in CHF after MI in rabbits. These findings suggest that the activation of NADPH oxidase mediates cardiac sympathetic nerve terminal abnormalities in CHF, and the inhibition of NADPH oxidase may be beneficial for the treatment of heart failure.

P1221Effect of transcatheter aortic valve implantation on cardiac sympathetic nervous function assessed by 123I-metaiodobenzylguanidine scintigraphy in patients with severe aortic stenosis

Abstract Background Cardiac sympathetic nervous (CSN) function assessed by 123I-metaiodobenzylguanidine (MIBG) scintigraphy is associated with poor prognosis in patients with heart failure. Purpose The aim of this study was to investigate the effects of transcatheter aortic valve implantation (TAVI) on CSN function in patients with severe aortic stenosis (AS) using MIBG scintigraphy. Methods This was a single-center prospective observational study that enrolled patients between July 2017 and July 2018. Among 77 registered patients who scheduled to undergo TAVI, 35 patients (7 men; mean age: 87 years) were evaluated. The MIBG scintigraphy was performed at baseline and 6 months after TAVI procedure to evaluate the heart-mediastinum ratio (H/M) and washout rate (WR). The MIBG parameter changes were compared with B-type natriuretic peptide (BNP) levels and echocardiographic parameters, including aortic valve area (AVA), peak velocity (Vmax), mean pressure gradient (PG), and left ventricular ejection fraction (LVEF). Results All patients successfully underwent TAVI with improved BNP level (388±341 pg/mL vs. 167±118 pg/mL, p&lt;0.001). The AVA, Vmax, mean PG and LVEF improved after TAVI (0.6±0.2 cm2 vs. 1.6±0.5 cm2, p&lt;0.001; 4.6±0.8 m/s vs. 2.1±0.3 m/s, p&lt;0.001; 54±20 mmHg vs. 9±3 mmHg, p&lt;0.001; 58±11% vs. 63±9%, p=0.01, respectively). In the MIBG imaging, the delayed H/M significantly increased (2.5±0.6 vs. 2.6±0.7, p=0.03), and the WR decreased (32±8% vs. 29±8%, p=0.047) after TAVI. There was a correlation between the changes in the MIBG parameters and the change in mean PG from baseline to 6 months (delayed H/M: r=0.391, p=0.02; WR: r=0.347, p=0.04). Multivariate logistic regression analysis showed that baseline mean PG was an independent predictor of improved both delayed H/M and WR (odds ratio=1.062; 95% confidence interval: 1.009–1.137; p=0.042). Conclusions TAVI can improve the CSN function in patients with AS. Such CSN improvement was related with hemodynamic changes. Acknowledgement/Funding None

Early effects of transcatheter aortic valve replacement on cardiac sympathetic nervous function assessed by 123I-metaiodobenzylguanidine scintigraphy in patients with severe aortic valve stenosis.

The effects of transcatheter aortic valve replacement (TAVR) on cardiac sympathetic nervous (CSN) function have not been fully explored. This study aimed to investigate the early (within 2weeks) effects of TAVR on CSN function in patients with severe aortic valve stenosis (AS) using 123I-metaiodobenzylguanidine (MIBG) scintigraphy. Of 143 consecutive patients who were scheduled to undergo TAVR, 67 (18 men; median age 86years) were evaluated in this single-centre prospective observational study. MIBG scintigraphy was performed at baseline and 3-14days after the TAVR procedure to evaluate the heart-mediastinum ratio (H/M) and washout rate (WR). Differences between baseline and post-TAVR MIBG parameters were analysed. MIBG parameter changes were compared with echocardiographic parameters. Furthermore, factors involved in the improvement in MIBG parameters were investigated. All patients successfully underwent TAVR with improved echocardiographic parameters, including aortic valve area (AVA; 0.6cm2 vs. 1.6cm2), peak velocity (4.5m/s vs. 2.0m/s), mean pressure gradient (50mmHg vs. 9mmHg), and left ventricular ejection fraction (56% vs. 62%) (all p < 0.001). On MIBG imaging, delayed H/M significantly increased (2.57 vs. 2.68, p < 0.001), whereas WR decreased (32.2% vs. 26.8%, p < 0.001). In multivariate analysis, higher baseline WR was associated with improvement in WR (> 3%). Female sex, Clinical Frailty Scale score ≤ 5, baseline estimated glomerular filtration rate, and baseline AVA were predictors of improvement in delayed H/M (> 0.1). Baseline AVA and E/E' were independent predictors of improvement in both WR and delayed H/M. The CSN function was impaired in patients with AS, as assessed using MIBG scintigraphy. WR and delayed H/M improved immediately after TAVR. Improvement in CSN function may be related to echocardiographic AS severity at baseline before TAVR.

Late gadolinium enhancement on cardiac magnetic resonance combined with 123I- metaiodobenzylguanidine scintigraphy strongly predicts long-term clinical outcome in patients with dilated cardiomyopathy.

Late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is limited in its ability to detect diffuse interstitial fibrosis, which is commonly found in idiopathic dilated cardiomyopathy (DCM). On the other hand, Washout rate (WR) by cardiac 123I- metaiodobenzylguanidine (123I-MIBG) scintigraphy which evaluates cardiac sympathetic nervous function, is a useful tool for predicting the prognosis in DCM. We investigated the predictive value of the combination of two different types of examinations, LGE on CMR and WR by 123I-MIBG scintigraphy for outcomes in DCM compared with LGE alone. One-hundred forty-eight DCM patients underwent CMR and 123I-MIBG scintigraphy. Patients were divided into 4 groups according to the presence or absence of LGE and WR cut-off value of 45% for predicting prognosis based on receiver operating characteristic curve analysis. Cardiac deaths, re-hospitalization for heart failure, implantation of a left ventricular assist device, and life-threatening ventricular arrhythmias were defined as clinical events. Forty-two DCM patients reached the clinical events during the median follow-up for 9.1 years (interquartile range, 8.0–9.2 years).Multivariable Cox regression analysis identified WR≥45%+LGE positive group as an independent predictor of cardiac events (HR 3.18, 95%CI 1.36–7.45, p = 0.008). Notably, there was no significance in the cardiac event-free survival rate between the WR<45%+LGE positive and WR≥45%+LGE negative groups (p = 0.89). The combination of WR by 123I-MIBG scintigraphy and LGE on CMR, which evaluate different type of cardiac deterioration, serves as a stronger predictor of long-term outcomes in DCM patients than LGE alone.

192Early effect of transcatheter aortic valve implantation on cardiac sympathetic nervous function assessed by 123i-metaiodobenzylguanidine scintigraphy in patients with severe aortic stenosis

192Early effect of transcatheter aortic valve implantation on cardiac sympathetic nervous function assessed by 123i-metaiodobenzylguanidine scintigraphy in patients with severe aortic stenosis

Effect of Switching from Cilnidipine to Azelnidipine on Cardiac Sympathetic Nerve Function in Patients with Heart Failure Preserved Ejection Fraction.

Cardiac sympathetic nerve activity is known to play a key role in the development and progression of heart failure (HF). Azelnidipine, an L-type calcium channel blocker (CCB), inhibits the sympathetic nerve activity of the central system. In contrast, cilnidipine, an N-type CCB, inhibits the sympathetic nerve activity of the peripheral system. CCBs are recommended as class IIa in patients with HF preserved ejection fraction (HFpEF); however, there are no comparative data on the difference in effect of cilnidipine and azelnidipine in patients with HFpEF and hypertension. We investigated the difference in effect of azelnidipine compared with cilnidipine in patients with HFpEF. Twenty-four consecutive HF patients who received angiotensin II type1a receptor blocker and beta blocker from April 2013 to January 2015 were enrolled. Cilnidipine was switched to azelnidipine during the follow-up period. Blood pressures, heart rate, blood tests, echocardiography, and 123I-metaiodobenzylguanidine (MIBG) cardiac-scintigraphy were measured before and after 6 months from azelnidipine administration. B-type natriuretic peptide tended to decrease after switching to azelnidipine; however, there were no significant differences between the pre-state and post-state (pre-state: 118.5 pg/mL and post-state: 78.4 pg/mL, P = 0.137). Other laboratory findings, including catecholamine, also did not change significantly. In echocardiography, there were no significant differences in systolic and diastolic functions at the pre-state and post-state. As for MIBG, there were no significant changes in heart/mediastinum ratio. However, washout rate was significantly reduced (pre-state: 42.9 and post-state: 39.6, P = 0.030). Azelnidipine improved the dysfunction of cardiac sympathetic nerve activity compared with cilnidipine in patients with HFpEF.

Early therapeutic effects of adaptive servo-ventilation on cardiac sympathetic nervous function in patients with heart failure evaluated using a combination of 11C-HED PET and 123I-MIBG SPECT

RationaleAdaptive servo-ventilation (ASV), a novel respiratory support therapy for sleep disorders, may improve cardiac function in heart failure (HF). However, the reasons that ASV improves cardiac function have not been fully studied especially in sympathetic nervous function (SNF). The purpose of the present study was to investigate the effects of ASV therapy on cardiac SNF in patients with HF. MethodsWe evaluated ASV therapeutic effects before and 6 months after ASV therapy in 9 HF patients [57.3 ± 17.3 years old, left ventricular ejection fraction (LVEF) 36.1 ± 16.7%]. We performed echocardiography, polysomnography, biomarkers, 11C-hydroxyephedrine (HED) PET as a presynaptic function marker and planar 123I-metaiodobenzylguanidine (MIBG) to evaluate washout rate. ResultsASV therapy reduced apnea-hypopnea index (AHI) and improved plasma brain natriuretic peptide (BNP) concentration. In 123I-MIBG imaging, the early heart/mediastinum (H/M) ratio increased after ASV therapy (2.19 ± 0.58 to 2.40 ± 0.67; P = 0.045). Washout rate did not change (23.8 ± 7.3% to 23.8 ± 8.8%; P = 0.122). Global 11C-HED retention index (RI) improved from 0.068 ± 0.033/s to 0.075 ± 0.034/s (P = 0.029). ConclusionsASV reduced AHI and improved BNP. ASV might initially improve presynaptic cardiac sympathetic nervous function in HF patients after 6 months of treatment.