Late Heart-to-mediastinum Ratio Research Articles

The prognostic impact of cardiac Metaiodobenzylguanidine imaging related to left ventricular geometry in patients with acute decompensated heart failure: a prospective study

Abstract Background It is known that changes in the geometry of the left ventricle (LV), such as dilation or hypertrophy, are associated with cardiovascular events. The sympathetic nervous system also plays a crucial role in exacerbating these changes. Cardiac iodine-123 metaiodobenzylguanidine (MIBG) imaging can evaluate cardiac sympathetic neuronal activity and has been strongly associated with poor clinical outcomes in heart failure (HF). However, the prognostic significance of cardiac MIBG imaging related to LV geometry is still unclear, particularly in patients admitted for acute decompensated HF (ADHF). Methods We studied consecutive 575 patients admitted for ADHF and echocardiography were performed just before discharge. In cardiac MIBG imaging, the heart-to-mediastinum ratio (HMR) was measured on the delayed image. We divided the patients into four groups according to the relative wall thickness (RWT) and LV mass index (LVMI) based on the ASE/EACVI classification as follows: normal (n=75), normal RWT and LVMI; concentric remodeling (n=56), high RWT and normal LVMI; eccentric hypertrophy (n=298), normal RWT and high LVMI; and concentric hypertrophy (n=146), high RWT and LVMI. The endpoint of this study was all cause death (ACD). Results During a follow-up period of 4.2 ± 2.5 years, 272 patients had ACDs (normal [n=32], concentric remodeling [n=28], eccentric hypertrophy [n=137] and concentric hypertrophy [n=75]). There was no significant association between LV geometry and ACDs. At univariate Cox analysis, late HMR was significantly and independently associated with ACDs in the subgroup of patients with eccentric hypertrophy (p=0.0004). However, there was no significant association between late HMR and ACDs in those with other subgroups of LV geometry. At multivariate Cox analysis, late HMR was also significantly associated with ACDs even after adjusting for major HF confounders in the subgroup of patients with eccentric hypertrophy (p=0.0042). Furthermore, Kaplan-Meier analysis revealed that patients with lower late HMR (<1.524: determined by ROC curve analysis) had a significantly higher risk of ACDs in the subgroup with eccentric hypertrophy (61% vs 37%, p<0.0001). Conclusions LV geometry has an impact on the prognostic value of cardiac MIBG imaging in patients admitted for ADHF.

Remote ischemic peri-conditioning suppressed the activation of cardiac sympathetic nervous system in patients with acute myocardial infarction: a randomized controlled trial

Abstract Background The activation of cardiac sympathetic nervous system is associated with poor prognosis in patients with acute myocardial infarction (AMI). Remote ischemic peri-conditioning (RIPC) is reported to improve clinical outcome in patients with AMI. However, there is not fully clarified whether RIPC could have an effect on cardiac sympathetic activity. Purpose The purpose of this study is to investigate the effect of RIPC on cardiac sympathetic activity in patients with AMI. Methods We randomly assigned 157 patients with suspected AMI undergoing emergent percutaneous coronary intervention to receive transient limb ischemia (by inflating a cuff at 200 mmHg for 4×5 minutes: RIPC group, n=77) or no procedure (control group, n=80) upon arrival to the cardiac catheterization laboratory. After excluding inappropriate patients such as those who were diagnosed with other than AMI, we analyzed 122 patients (62 patients in RIPC and 60 in control group). The primary endpoint was cardiac sympathetic activity assessed by the cardiac MIBG imaging washout rate (WR) at discharge and 1 year after discharge. WR and late heart-to-mediastinum ratio (HMR) in cardiac MIBG was calculated from the chest anterior view images obtained at 20 and 200 min after isotope injection. Results Patients in RIPC and control group had similar demographic and clinical characteristics at baseline. There was no significant difference in WR between two groups at discharge. Although WR was significantly decreased 1 year after the discharge in both groups, patients in RIPC group showed significantly lower WR than those in control group (22.0 [15.1-30.6]% and 26.5 [18.4-34.4]%, p=0.0269) 1 year after the discharge. Late HMR significantly decreased during 1-year follow-up in patients only in RIPC group (p=0.0133) and patients in RIPC group tended to show higher late HMR compared to those in control group (2.01 [1.79-2.25] and 1.92 [1.72-2.11], p=0.0581) 1 year after the discharge. Conclusion(s) Remote ischemic peri-conditioning could suppress the augmented cardiac sympathetic activity in patients with acute myocardial infarction during 1-year follow-up.

Endovascular renal sympathetic denervation to improve heart failure with reduced ejection fraction: the IMPROVE-HF-I study.

IntroductionThe aim of the present study was to assess the safety and efficacy of renal sympathetic denervation (RDN) in patients with heart failure with reduced ejection fraction (HFrEF).MethodsWe randomly assigned 50 patients with a left ventricular ejection fraction (LVEF) ≤ 35% and NYHA class ≥ II, in a 1:1 ratio, to either RDN and optimal medical therapy (OMT) or OMT alone. The primary safety endpoint was the occurrence of a combined endpoint of cardiovascular death, rehospitalisation for heart failure, and acute kidney injury at 6 months. The primary efficacy endpoint was the change in iodine-123 meta-iodobenzylguanidine (123I‑MIBG) heart-to-mediastinum ratio (HMR) at 6 months.ResultsMean age was 60 ± 9 years, 86% was male and mean LVEF was 33 ± 8%. At 6 months, the primary safety endpoint occurred in 8.3% vs 8.0% in the RDN and OMT groups, respectively (p = 0.97). At 6 months, the mean change in late HMR was −0.02 (95% CI: −0.08 to 0.12) in the RDN group, versus −0.02 (95% CI: −0.09 to 0.12) in the OMT group (p = 0.95) whereas the mean change in washout rate was 2.34 (95% CI: −6.35 to 1.67) in the RDN group versus −2.59 (95% CI: −1.61 to 6.79) in the OMT group (p-value 0.09).ConclusionRDN with the Vessix system in patients with HFrEF was safe, but did not result in significant changes in cardiac sympathetic nerve activity at 6 months as measured using 123I‑MIBG.Supplementary InformationThe online version of this article (10.1007/s12471-021-01633-z) contains supplementary material, which is available to authorized users.

Prognostic value of myocardial MIBG scintigraphy in acute ischemic stroke

Abstract Funding Acknowledgements Type of funding sources: None. Background Autonomic dysfunction is a common complication of acute ischemic stroke and has been associated with poor functional outcome and increased mortality. We investigated the potential relation between the myocardial washout rate (WOR) of 123I-meta-iodobenzylguanidine (123I-mIBG), as a measure of cardiac sympathetic activity, and functional outcome in acute ischemic stroke. Methods 38 patients with ischemic stroke (11 females, 72 years old [61-81)), underwent myocardial 123I-mIBG scintigraphy within the first week after stroke onset. Early (10 minutes post-injection (pi)) and late (4 hours pi) planar scans of the thoracic region were made. Regions of interest (ROI) were drawn over the mediastinum and the heart, and heart-to-mediastinum ratio (HMR) was calculated. Myocardial WOR was calculated as follows: (ROI heart early – ROI heart late)/ (ROI heart early) x 100%. Counts were corrected for background and counts in ROI heart late were corrected for decay. Patients were divided in 2 groups: those with a good functional outcome, defined as modified Rankin Scale (mRS) ≤ 2 at 3 months after stroke (i.e., patient is functionally independent), and those with a poor functional outcome, defined as a mRS > 2. Results Median WOR was 27,4 % (IQR 10,4-43,6). In univariate analysis, poor functional outcome after stroke was associated with age, stroke severity on admission (measured by the National Institutes of Health Stroke Scale (NIHSS)), beta-blocker use before and during hospitalization, WOR and late HMR. In subsequent multivariate analysis WOR (OR 1.087; 95% CI 1.003-1.177, p = 0.042) was an independent predictor of poor stroke outcome even after adjustment for age and NIHSS. Conclusions In patients with acute ischemic stroke, myocardial washout of 123I-mIBG predicts stroke outcome, even after adjustment for age and stroke severity on admission.

5 years follow-up of patients with heart failure and cardiac resynchronization: baseline variables associated to death

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Chronic Heart Failure (HF) has proven to be an increasing challenge for the global health management. Prognosis is affected by pharmacological optimization, comorbidities and risk factors control, lifestyle changes and invasive treatments like resynchronization (CRT) and transplant. Purpose To evaluate the association of baseline variables in HF patients, before CRT, with death event at 5 years follow up (FU). Methods Single center, post-hoc analysis of a prospective cohort of consecutive HF patients referred to CRT (2013-2015). Demographic data, HF etiology and NYHA class were evaluated at baseline as well as plasmatic of natriuretic peptide (BNP), heart to mediastinum ratio (HMR), left ventricular ejection fraction (LVEF) and volumes. Mortality was evaluated at 5 years. Patients were divided in two groups: "non survivors" and "survivors". Data were analyzed using descriptive statistics. Spearman test was used to evaluate the correlation between baseline variables and death. Results 102 patients were included (age 68.8 ± 10 years), 68.6% male, 29% ischemic cardiomyopathy, 74% NYHA III/IV, baseline LVEF 26 ± 7. 27% were CRT non-responders. At 5 years follow up 43% died, with 1.96% lost FU. Baseline variables in the two groups are displayed in table 1. Statistical analysis correlating baseline variables with death (Spearman test) showed weak correlation, with the strongest correlation obtained: late HMR with negative correlation 0.34; LV tele-diastolic volume with positive correlation 0.26. Conclusion The mortality at 5 years of HF patients with CRT was high (43%). Baseline variables (late HMR, LV tele-diastolic volume) were associated to death. These results should call early attention for a possible worst prognosis in severe HF patients to CRT. Table 1 "Non survivors" vs "Survivors" “Non Survivors”(n = 44) “Survivors”(n = 56) Age 67,11 ± 11,17 68,14 ± 10,51 Male 35 (80%) 35 (63%) NYHA III/IV 31 (70%) 43 (77%) Ischemic 15 (34%) 14 (25%) BNP 640,95 ± 606,23 370,41 ± 353,36 Late HMR 1,35 ± 0,16 1,47 ± 0,17 LVEF 27 ± 6,77 26 ± 7,47 Non responders 16 (36%) 12 (21%) LVTdV 225 ± 73,28 191 ± 58,5 PCR 10,33 ± 22,85 5,02 ± 9,27

Abdominal obesity, and not general obesity, is associated with a lower 123I MIBG heart-to-mediastinum ratio in heart failure patients with preserved ejection fraction.

The relationship between general obesity or abdominal obesity (abdominal circumference of ≥85cm in men and ≥ 90cm in women) and the heart-to-mediastinum ratio (HMR), a measure of cardiac sympathetic innervation, on cardiac iodine-123-metaiodobenzylguanidine scintigraphy (MIBG) in patients with heart failure with preserved ejection fraction (HFpEF) has not been clarified. A total of 239 HFpEF patients with both MIBG and abdominal circumference data were examined. We divided these patients into those with abdominal obesity and those without it. In the cardiac MIBG study, early phase image was acquired 15-20min after injection, and late phase image was acquired 3h after the early phase. A HMR obtained from a low-energy type collimator was converted to that obtained by a medium-energy type collimator. Early and late HMRs were significantly lower in those with abdominal obesity, although washout rates were not significantly different. The incidence of patients with early and late HMRs <2.2 was significantly higher in those with abdominal obesity. Multivariate linear regression analysis revealed that abdominal obesity was independently associated with early HMR (standardized β = -0.253, P = 0.003) and late HMR (standardized β = -0.222, P = 0.010). Multivariate logistic regression analysis revealed that abdominal obesity was independently associated with early (odds ratio [OR] [95% confidence interval {CI}] = 4.25 [2.13, 8.47], P < 0.001) and late HMR < 2.2 (OR [95% CI] = 2.06 [1.11, 3.83], P = 0.022). Elevated BMI was not significantly associated with low early and late HMR. The presence of abdominal obesity was significantly associated with low early and late HMR even in patients without elevated BMI values. Abdominal obesity, but not general obesity, in HFpEF patients was independently associated with low HMR, suggesting that visceral fat may contribute to decreased cardiac sympathetic activity in patients with HFpEF. UMIN000021831.

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.

Paradoxical Prognostic Implications of Visceral Adiposity for Lethal Cardiac Events in Association with Impaired Cardiac Sympathetic Innervation in Chronic Heart Failure

Background: Obesity increases the risk for development of heart failure (HF) but, when present is likely to be related to better outcomes in patients with HF. This study aimed to clarify the paradoxical prognostic values of visceral obesity in association with cardiac sympathetic function in HF patients. Methods and Results: A total of 653 consecutive patients with systolic HF who underwent visceral adiposity area (VAA) measurements using a computed tomographic technique were divided into 3 groups: VAA 1, area <80 cm2; VAA 2, area 80-140 cm2; VAA 3, area >140 cm2. Sympathetic innervation was quantified by 123I-MIBG cardiac activity. Patients were followed up for an average of 22 months with a primary endpoint of lethal cardiac events (CE). The CE group (n=200) had a lower late heart-to mediastinum ratio (HMR) and a smaller VAA than those in the non-CE group. Rates of overall CE/HF death were inversely correlated with VAA: 39.2% ± 6.2% for VAA 1, 27.4% ± 19.9% for VAA 2 and 24.1% ± 15.3% for VAA 3. In addition to sudden cardiac death rate, lethal arrhythmic event rate increased in association with visceral fat obesity: 3.0% for VAA 1, 7.5% for VAA 2 and 8.8% for VAA 3. Late HMR identified high-risk sub-populations in each group. Conclusion: Visceral obesity has paradoxical prognostic implications in terms of HF mortality and lethal arrhythmic/sudden cardiac death events. Cardiac sympathetic denervation and quantitative visceral adiposity are synergistically associated with overall cardiac mortality, contributing to better risk stratification of HF patients.

Imaging cardiac innervation in hereditary transthyretin (ATTRm) amyloidosis: A marker for neuropathy or cardiomyopathy in case of heart failure?

BackgroundNuclear imaging modalities using 123Iodine-metaiodobenzylguanidine (123I-MIBG) and bone seeking tracers identify early cardiac involvement in ATTRm amyloidosis patients. However, little is known whether results from 123I-MIBG scintigraphy actually correlate to markers for either cardiac autonomic neuropathy or cardiomyopathy. MethodsAll TTR mutation carriers and ATTRm patients who underwent both 123I-MIBG and 99mTechnetium-hydroxymethylene diphosphonate (99mTc-HDP) scintigraphy were included. Cardiomyopathy was defined as NT-proBNP > 365 ng/L, and cardiac autonomic neuropathy as abnormal cardiovascular reflexes at autonomic function tests. Late 123I-MIBG heart-to-mediastinum ratio (HMR) < 2.0 or wash-out > 20%, and any cardiac 99mTc-HDP uptake were considered as abnormal. Results39 patients (13 carriers and 26 ATTRm patients) were included in this study. Patients with cardiomyopathy, with or without cardiac autonomic neuropathy, had lower late HMR than similar patients without cardiomyopathy [median 1.1 (range 1.0-1.5) and 1.5(1.2-2.6) vs 2.4 (1.4-3.8) and 2.5 (1.5-3.7), respectively, P < 0.001]. Late HMR and wash-out (inversely) correlated with NT-proBNP r = − 0.652 (P < 0.001) and r = 0.756 (P < 0.001), respectively. Furthermore, late HMR and wash-out (inversely) correlated with cardiac 99mTc-HDP uptake r = − 0.663 (P < 0.001) and r = 0.617 (P < 0.001), respectively. ConclusionIn case of heart failure, 123I-MIBG scintigraphy reflects cardiomyopathy rather than cardiac autonomic neuropathy in ATTRm patients and TTR mutation carriers. 123I-MIBG scintigraphy may already be abnormal before any cardiac bone tracer uptake is visible.

Simultaneous dual-isotope 123I/99mTc acquisition using CZT-based cameras: Toward a one-stop-shop SPECT in heart failure patients

The CZT-cameras (DNM 530c and DSPECT) have only recently been introduced, and the impact of the increased energy resolution remains unknown. This paper summarizes the evidence on the assessment of: (i) the left ventricular function, (ii) the 123I/99mTc mismatch, and (iii) the heart-to-mediastinum ratio (HMR) of 123I-metaiodobenzylguanidine (MIBG) uptake under dual-isotope conditions (99mTc and 123I) using cadmium-zinc-telluride (CZT) technology. The diagnostic accuracy of CZT cameras for myocardial sympathetic innervation imaging, left ventricular function and perfusion assessment using perfusion-gated SPECT have only been established in a few studies, under single-isotope conditions. Limited evidence is available regarding simultaneous dual-isotope acquisition using CZT-cameras. However, recently reported data have shown that CZT cameras allow, in dual-isotope (123I and 99mTc) acquisitions and under routine conditions: (i) a simultaneous and accurate segmental study of myocardial innervation and perfusion (match and mismatch), (ii) the ventricular function assessment (EDV, ESV and LVEF), and (iii) the determination of the late HMR of cardiac 123I-MIBG uptake in patients with heart failure. However, this latter should be performed using transaxial reconstructed images and a linear correction based on phantom data acquisitions. ConclusionWith an increased energy resolution, the CZT cameras should become the one-stop shop SPECT for simultaneous dual-isotope 123I/99mTc acquisitions in heart failure patients, permitting to perform LV function, myocardial perfusion and innervation.

Relationship of left ventricular global longitudinal strain with cardiac autonomic denervation as assessed by 123I-mIBG scintigraphy in patients with heart failure with reduced ejection fraction submitted to cardiac resynchronization therapy: Assessment of cardiac autonomic denervation by GLS in patients with heart failure with reduced ejection fraction submitted to CRT

BackgroundHeart failure (HF) is associated with cardiac autonomic denervation (AD), which can be non-invasively assessed by 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy and has prognostic implications. We aimed to study the relationship between myocardial contractility assessed by global longitudinal strain (GLS) and AD assessed by 123I-mIBG scintigraphy in advanced HF. Methods/ResultsBETTER-HF is a prospective randomized clinical trial including HF patients (pts) submitted to cardiac resynchronization therapy (CRT) who are submitted to a clinical, echocardiographic, and scintigraphic assessment before and 6 months after CRT. 81 pts were included. An echocardiographic response (absolute increase in left ventricular ejection fraction ≥ 10%) was observed in 73.7% of pts. A higher baseline late heart-to-mediastinum ratio (HMR) was associated with a better echocardiographic response. There was a significant association between late HMR and GLS at baseline and 6 months. At baseline, GLS had an AUC of 0.715 for discrimination for a late HMR < 1.6. A GLS cut-off of − 9% maximized the likelihood of correctly classifying a pt as having severe AD (HMR < 1.6). ConclusionMyocardial contractility as assessed by GLS is moderately correlated with AD as assessed by 123I-mIBG scintigraphy and has a good discrimination for the identification of severe cardiac denervation. GLS may allow for a more readily accessible estimation of the degree of AD in advanced HF pts.

Investigation into cardiac sympathetic innervation during the commencement of haemodialysis in patients with chronic kidney disease

BackgroundPatients with chronic kidney disease (CKD) who undergo chronic haemodialysis (HD) show altered sympathetic tone, which is related to a higher cardiovascular mortality. The purpose of this study was to investigate the effect of transition from pre-HD to HD on cardiac sympathetic innervation.MethodsEighteen patients aged 58 ± 18 years (mean ± standard deviation [SD]), 13 males and five females, with stage 5 CKD and nine healthy control subjects aged 52 ± 17 (mean ± SD), three males and six females, were included in this prospective study between May 2010 and December 2013. All patients underwent 123I-labelled meta-iodobenzylguanidine (123I-MIBG) scintigraphy for cardiac sympathetic innervation and electrocardiographically gated adenosine stress and rest 99mTc-labelled tetrofosmin single-photon emission computed tomography for myocardial perfusion imaging prior to (pre-HD) and 6 months after the start of HD. Results of 123I-MIBG scans in patients were compared to controls. Impaired cardiac sympathetic innervation was defined as late heart-to-mediastinum ratio (HMR) < 2.0.ResultsMean late HMR was lower in patients during HD (2.3) than in controls (2.9) (p = 0.035); however, in patients it did not differ between pre-HD and after the start of HD. During HD, two patients showed new sympathetic innervation abnormalities, and in three patients innervation abnormalities seemed to coincide with myocardial perfusion abnormalities.ConclusionsCKD patients show cardiac sympathetic innervation abnormalities, which do not seem to progress during the maintenance HD. The relationship between sympathetic innervation abnormalities and myocardial perfusion abnormalities in HD patients needs further exploration.

Determination of the Heart-to-Mediastinum Ratio of 123I-MIBG Uptake Using Dual-Isotope (123I-MIBG/99mTc-Tetrofosmin) Multipinhole Cadmium-Zinc-Telluride SPECT in Patients with Heart Failure.

The aim of this retrospective study was to compare the heart-to-mediastinum ratio (HMR) of 123I-metaiodobenzylguanidine (123I-MIBG) uptake obtained using a multipinhole cadmium-zinc-telluride (CZT) camera with that obtained using conventional planar imaging. Methods: Forty consecutive heart failure patients underwent planar acquisition 4 h after 123I-MIBG injection (191 ± 41 [mean ± SD] MBq). To localize the heart using the CZT camera, 99mTc-tetrofosmin (358 ± 177 MBq) was administered and dual-isotope acquisition was performed. The HMRs were calculated with conventional planar imaging (HMRplanar), with anterior reprojection images using the CZT camera (HMRreproj), and with transaxial reconstructed images using the CZT camera (HMRtransaxial). In a phantom study, we estimated a linear model fitting the CZT camera data to the planar data, and we applied it to provide corrected CZT camera-determined HMRs in patients (cHMRreproj and cHMRtransaxial). Results: Thirty-four men and 6 women (71 ± 9 y old) with ischemic (22 patients) and nonischemic (18 patients) heart failure completed the study. For 22 of the 40 patients (55%), the New York Heart Association classification was class II and the ejection fraction was 35% ± 9%. HMRreproj (1.12 ± 0.19) and HMRtransaxial (1.35 ± 0.34) were lower than HMRplanar (1.44 ± 0.14) (P < 0.0001 and P < 0.01, respectively). cHMRreproj (1.54 ± 0.09) and cHMRtransaxial (1.45 ± 0.14) were significantly different (P < 0.0001). Lin concordance correlation and Bland-Altman analysis demonstrated an almost perfect concordance and a high agreement between HMRplanar and cHMRtransaxial (P was not significant) but not between HMRplanar and cHMRreproj (P < 0.0001). Conclusion: This study demonstrated that determination of the late HMR of cardiac 123I-MIBG uptake using dual-isotope (123I and 99mTc) acquisition on a multipinhole CZT camera was feasible in patients with heart failure. However, this determination should be performed using transaxial reconstructed images and linear correction based on phantom data acquisitions.

Synergistic prognostic implications of left ventricular mechanical dyssynchrony and impaired cardiac sympathetic nerve activity in heart failure patients with reduced left ventricular ejection fraction

Impairment of cardiac sympathetic innervation is a potent prognostic marker in heart failure, while left ventricular mechanical dyssynchrony (LVMD) has recently been noted as a novel prognosis determinant in heart failure patients with reduced LV ejection fraction (HFrEF). This study was designed to determine the correlation between cardiac sympathetic innervation quantified by metaiodobenzylguanidine (MIBG) activity and LVMD measured by electrocardiogram-gated myocardial perfusion imaging and to evaluate their incremental prognostic values in HFrEF patients. A total of 570 consecutive HFrEF patients were followed up for 19.6 months with a primary endpoint of lethal cardiac events (CE) such as sudden cardiac death, death due to pump failure and appropriate ICD shock against life-threatening ventricular tachyarrhythmias. Cardiac sympathetic function and innervation were quantified as heart-to-mediastinum ratio (HMR) and washout kinetics of cardiac MIBG activity. LVMD was assessed by a standard deviation (SD) of systolic phase angle in gated myocardial perfusion imaging. Patients with CE (n = 166, 29%) had a significantly lower HMR and a significantly greater phase SD than did non-CE patients: 1.46 ± 0.28 vs. 1.63 ± 0.29, P < 0.0001 and 39.1 ± 11.6 vs. 33.1 ± 10.1, P < 0.0001, respectively. Compared to the single use of optimal cut-offs of late HMR (1.54) and phase SD (38), their combination more precisely discriminated high-risk or low-risk patients from others with log rank values from 7.78 to 65.2 (P = 0.0053 to P ≤ 0.0001). Among significant univariate variables, multivariate Cox proportional hazards model identified NYHA functional class, estimated glomerular filtration rate (eGFR), HMR 1.54 and phase SD 60 as significant determinants of CE with hazard ratios of 3.108 (95% CI, 2.472-3.910; P < 0.0001), 0.988 (95% CI, 0.981-0.996; P = 0.0021), 0.257 (95% CI, 0.128-0.498; P < 0.0001) and 1.019 (95% CI, 1.019-1.037; P = 0.0228), respectively. By combining the four independent determinants, the prognostic powers synergistically (P < 0.0001) increased maximally to 263.8. Left ventricular mechanical dyssynchrony and impairment of cardiac sympathetic innervation are synergistically related to lethal cardiac events, contributing to better stratification of lethal cardiac event-risks and probably to optimization of therapeutic strategy in patients with HFrEF.

Iodine-123 metaiodobenzylguanidine scintigraphy for the assessment of cardiac sympathetic innervation and the relationship with cardiac autonomic function in healthy adults using standardized methods.

Global iodine-123 metaiodobenzylguanidine (I-MIBG) uptake is predictive of cardiovascular events and mortality in patients with heart failure. Normal variations in global and regional uptake, however, are not well defined and few studies have addressed the functional relevance of I-MIBG uptake and distribution in healthy individuals. We performed I-MIBG scintigraphy and cardiac autonomic function testing using the standardized methodology in 15 healthy individuals (mean age 54.6±5.3 years, male : female 10 : 5) with no evidence of previous myocardial infarction or ischaemic heart disease. Early heart to mediastinum ratio (HMR) was 1.67±0.13, late HMR was 1.73±0.16 and washout rate was 19.09±7.63% (4.20-31.30). Regional analysis showed reduced tracer uptake at the apex, base and inferior wall in all individuals. Early and late HMR correlated negatively with RFa (r=-0.603; P=0.05 and r=-0.644; P=0.033) and expiration and inspiration ratio (r=-0.616; P=0.043 and r=-0.676; P=0.022) and positively with LFa/RFa (r=0.711; P=0.014 and r=0.784; P=0.004). Washout rate correlated only with RFa (r=0.642; P=0.033). Healthy adults show a heterogeneous pattern of cardiac innervation with reduced regional uptake of I-MIBG. Furthermore, HMR correlates with indices of cardiac sympathetic function, suggesting that it might not only be a useful prognostic marker but may also provide insight into the functional integrity of the cardiac autonomic nervous system.

O11-5 - Cardiac Sympathetic Nerve Activity and Left Ventricular Dyssynchrony Can Predict Long-Term Prognosis in Heart Failure Patients with Systolic Dysfunction

Backgrounds: Left ventricular (LV) dyssynchrony is said to be involved in prognosis of heart failure (HF) patient with reduced LV ejection fraction(rLVEF). But it is not demonstrated the relationship between the prognosis of HF and LV dyssynchrony quantifiable by cardiac scintigraphy.This study aimed to investigate whether autonomic innervation quantified by metaiodobenzylguanidine(MIBG) and LV dyssynchrony measured by Phase SD of rest 99mTc (Tetrofosmin) have an independent and additive prognostic value in HF patients. Methods: Consecutive 478 HF patients with rLVEF were followed up for 22.6 months after quantification of MIBG activity as a heart-to-mediastinum ratio(HMR) and washout-rate,and LV dyssynchrony as Phase SD of 99mTc were compared with cardiac event(CE) group and non-CE group. Results: During a follow-up,CE was documented only in 132 of HF patients.The CE patient group had a greater washout-rate(29.8% VS 27.1% P = .0059)and a lower earlyHMR(1.60 VS 1.75 P < .0001)and a lower lateHMR(1.42 VS 1.63 P < .0001)and higher Phase SD(39.1 VS 33.3 P < .0001)than non-CE group.HF patients with late HMR < 1.60 demonstrated a significant greater CE rate compared with those without(P < .0001).HF patients with Phase SD > 37 demonstrated a significant greater CE rate compared with those without(P < .0001).HF patients with both late HMR < 1.60 and Phase SD > 37 showed a significant greater CE rate compared with the other patients(P < .0001). Conclusions: LV dyssynchrony as Phase SD of 99mTc and impaired cardiac sympathetic innervation defined as a lateHMR independently predict cardiac mortality risk in HF patients with rLVEF.

Individuals with impaired glucose tolerance demonstrate normal cardiac sympathetic innervation using I-123 mIBG scintigraphy

BackgroundImpaired glucose tolerance (IGT) is associated with an increased risk of type 2 diabetes (T2DM) and cardiovascular disease. Some but not all studies have reported cardiac autonomic dysfunction in subjects with IGT and there is only one direct study of cardiac innervation in subjects with IGT. The purpose of this study was to assess global and regional cardiac sympathetic innervation and cardiac autonomic function in individuals with IGT. Methods and ResultsWe undertook 123I-mIBG scintigraphy and cardiac autonomic function in 15 subjects with IGT and 15 age and sex-matched healthy controls. Early heart to mediastinum ratio (HMR) (1.71 ± 0.17 vs 1.67 ± 0.13, P = .49), late HMR (1.73 ± 0.18 vs 1.73 ± 0.16, P = .97) and washout rate (WR) (18.6 ± 4.2 vs 19.1 ± 7.6%, P = .84), did not differ between subjects with IGT and control subjects. More detailed regional analysis revealed reduced tracer uptake at the apex, base and inferior wall in all subjects and the anterior wall in a minority of subjects. There were no differences in total score (56.6 ± 4.0 vs 53.3 ± 8.4, P = .193), modified score (48.5 ± 3.3 vs 46.2 ± 6.0, P = .215), anterior wall score (10.2 ± 1.3 vs 10.1 ± 1.6, P = .898), inferior wall score (8.9 ± 1.9 vs 7.7 ± 2.6, P = .163), basal score (18.7 ± 1.9 vs 18.2 ± 3.3, P = .636) and tests of cardiac autonomic function between the groups. ConclusionGlobal and regional measures of MIBG uptake and washout as well as cardiac autonomic function did not differ between subjects with IGT and healthy controls.

First determination of the heart-to-mediastinum ratio using cardiac dual isotope (¹²³I-MIBG/⁹⁹mTc-tetrofosmin) CZT imaging in patients with heart failure: the ADRECARD study.

Cardiac innervation is assessed using the heart-to-mediastinum ratio (HMR) of metaiodobenzylguanidine (MIBG) on planar imaging using Anger single photon emission computed tomography (A-SPECT). The aim of the study was to determine the HMR of MIBG obtained using a CZT-based camera (D-SPECT; Spectrum Dynamics, Israel) in comparison with that obtained using conventional planar imaging. The ADRECARD study prospectively evaluated 44 patients with heart failure. They underwent planar acquisition using the A-SPECT camera 4 h after (123)I-MIBG injection (236.4 ± 39.7 MBq). To localize the heart using D-SPECT, (99m)Tc-tetrofosmin (753 ± 133 MBq) was administered and dual isotope acquisition was performed using the D-SPECT system. HMR was calculated using both planar A-SPECT imaging and front view D-SPECT cine data. In a phantom study, we estimated a model fitting the A-SPECT and the D-SPECT data that was further applied to correct for differences between the cameras. A total of 44 patients (39 men and 5 women, aged 60 ± 11 years) with ischaemic (31 patients) and nonischaemic (13 patients) cardiomyopathy completed the study. Most patients (28 of 44) were NYHA class II, and the mean left ventricular ejection fraction was 33 ± 7 %. The mean HMR values were 1.34 ± 0.15 and 1.45 ± 0.27 from A-SPECT and D-SPECT, respectively (p < 0.0001). After correction, Lin's concordance correlation showed an almost perfect concordance between corrected D-SPECT HMR and A-SPECT HMR, and Bland-Altman analysis demonstrated a high agreement between the two measurements. The ADRECARD study demonstrated that determination of late HMR during cardiac MIBG imaging using dual isotope ((123)I and (99m)Tc) acquisition on a CZT camera (D-SPECT) is feasible in patients with heart failure. A linear correction based on the phantom study yielded a high agreement between (123)I MIBG HMR obtained using a CZT camera and that from conventional planar imaging.

A Pooled Analysis of Multicenter Cohort Studies of 123I-mIBG Imaging of Sympathetic Innervation for Assessment of Long-Term Prognosis in Heart Failure

The study objectives were to create a cardiac metaiodobenzylguanidine (mIBG) database using multiple prospective cohort studies and to determine the quantitative iodine-123-labeled mIBG indices for identifying patients with chronic heart failure (HF) at greatest and lowest risk of lethal events. Although the prognostic value of cardiac mIBG imaging in patients with HF has been shown, clinical use of this procedure has been limited. It is required to define universally accepted quantitative thresholds for high and low risk that could be used as an aid to therapeutic decision-making using a large cohort database. Six prospective HF cohort studies were updated, and the individual datasets were combined for the present patient-level analysis. The database consisted of 1,322 patients with HF followed up for a mean interval of 78 months. Heart-to-mediastinum ratio (HMR) and washout rate of cardiac mIBG activity were the primary cardiac innervation markers. The primary outcome analyzed was all-cause death. Lethal events were observed in 326 patients, and the population mortality rate was 5.6%, 11.3%, and 19.7% at 1, 2, and 5 years, respectively. Multivariate Cox proportional hazard model analysis for all-cause mortality identified age (p < 0.0001), New York Heart Association (NYHA) functional class (p < 0.0001), late HMR of cardiac mIBG activity (p < 0.0001), and left ventricular ejection fraction (LVEF) (p = 0.0029) as significant independent predictors. Analysis of the 512-patient subpopulation with B-type natriuretic peptide (BNP) results showed BNP (p < 0.0001), greater NYHA functional class (p = 0.0002), and late HMR (p = 0.0011) as significant predictors, but LVEF was not. The receiver-operating characteristic-determined threshold of HMR (1.68) identified patients at significantly increased risk in any LVEF category. Survival rates decreased progressively with decreasing HMR, with 5-year all-cause mortality rates >7% annually for HMR <1.25, and <2% annually for HMR ≥1.95. Addition of HMR to clinical information resulted in a significant net reclassification improvement of 0.175 (p < 0.0001). Pooled analyses of independent cohort studies confirmed the long-term prognostic value of cardiac mIBG uptake in patients with HF independently of other markers, such as NYHA functional class, BNP, and LVEF, and demonstrated that categoric assessments could be used to define meaningful thresholds for lethal event risk.

123I-Labelled metaiodobenzylguanidine for the evaluation of cardiac sympathetic denervation in early stage amyloidosis

PurposeCardiac amyloidosis is a rare disorder, but it may lead to potentially life-threatening restrictive cardiomyopathy. Cardiac manifestations frequently occur in primary amyloidosis (AL) and familial amyloidosis (ATTR), but are uncommon in secondary amyloidosis (AA). Echocardiography is the method of choice for assessing cardiac amyloidosis. Amyloid deposits impair the function of sympathetic nerve endings. Disturbance of myocardial sympathetic innervations may play an important role in the remodelling process. 123I-MIBG can detect these innervation changes.MethodsPatients with biopsy-proven amyloidosis underwent general work-up, echocardiography and 123I-MIBG scintigraphy. Left ventricular internal dimensions and wall thickness were measured, and highly refractile cardiac echoes (sparkling) were analysed. Early (15 min) and late (4 h) heart-to-mediastinum ratio (HMR) and wash-out rate were determined after administration of MIBG.ResultsIncluded in the study were 61 patients (30 women and 31 men; mean age 62 years; 39 AL, 11 AA, 11 ATTR). Echocardiographic parameters were not significantly different between the groups. Sparkling was present in 72 % of ATTR patients, in 54 % of AL patients and in 45 % of AA patients. Mean late HMR in all patients was 2.3 ± 0.75, and the mean wash-out rate was 8.6 ± 14 % (the latter not significantly different between the patient groups). Late HMR was significantly lower in patients with echocardiographic signs of amyloidosis than in patients without (2.0 ± 0.70 versus 2.8 ± 0.58, p < 0.001). Wash-out rates were significantly higher in these patients (−3.3 ± 9.9 % vs. 17 ± 10 %, p < 0.001). In ATTR patients without echocardiographic signs of amyloidosis, HMR was lower than in patients with the other types (2.0 ± 0.59 vs. 2.9 ± 0.50, p = 0.007).ConclusionMIBG HMR is lower and wash-out rate is higher in patients with echocardiographic signs of amyloidosis. Also, 123I-MIBG scintigraphy can detect cardiac denervation in ATTR patients before signs of amyloidosis are evident on echocardiography.