Iodine-123-metaiodobenzylguanidine imaging can predict future cardiac events in heart failure patients with preserved ejection fraction

Katoh, Shigehiko; Shishido, Tetsuro; Kutsuzawa, Daisuke; Arimoto, Takanori; Netsu, Shunsuke; Funayama, Akira; Ishino, Mitsunori; Niizeki, Takeshi; Nishiyama, Satoshi; Takahashi, Hiroki; Miyashita, Takehiko; Miyamoto, Takuya; Nitobe, Joji; Watanabe, Tetsu; Kubota, Isao

doi:10.1007/s12149-010-0409-3

Cited by 46 publications

(36 citation statements)

References 32 publications

(44 reference statements)

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“…A diabetic heart is also likely to have impaired 123 I-MIBG activity (low HMR and 123 I-MIBG defect) in association with disease progression (14). Table 1 summarizes major investigations that prospectively monitored patients with chronic HF for more than 2 y with an endpoint of cardiac death (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). (26).…”

Section: Clinical Use Of 123 I-mibg Studies Leading To Japanese Nuclementioning

confidence: 99%

Cardiac ¹²³I-MIBG Imaging for Clinical Decision Making: 22-Year Experience in Japan

Nakajima

Nakata

2015

J Nucl Med

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Cardiac neuroimaging with 123 I-metaiodobenzylguanidine ( 123 I-MIBG) has been officially used in clinical practice in Japan since 1992. The nuclear cardiology guidelines of the Japanese Circulation Society, revised in 2010, recommended cardiac 123 I-MIBG imaging for the management of heart failure (HF) patients, particularly for the assessment of HF severity and prognosis of HF patients. Consensus in North American and European countries regarding incorporation into clinical practice, however, has not been established yet. This article summarizes 22 y of clinical applications in Japan of 123 I-MIBG imaging in the field of cardiology; these applications are reflected in cardiology guidelines, including recent methodologic advances. A standardized cardiac 123 I-MIBG parameter, the heartto-mediastinum ratio (HMR), is the basis for clinical decision making and enables common use of parameters beyond differences in institutions and studies. Several clinical studies unanimously demonstrated its potent independent roles in prognosis evaluation and risk stratification irrespective of HF etiologies. An HMR of less than 1.6−1.8 and an accelerated washout rate are recognized as high-risk indicators of pump failure death, sudden cardiac death, and fatal arrhythmias and have independent and incremental prognostic values together with known clinical variables, such as left ventricular ejection fraction and brain natriuretic peptide. Another possible use of this imaging technique is the selection of therapeutic strategy, such as pharmacologic treatment and nonpharmacologic treatment with an implantable cardioverter-defibrillator or cardiac resynchronization device; however, this possibility remains to be investigated. Recent multiple-cohort database analyses definitively demonstrated that patients who were at low risk for lethal events and who were defined by an HMR of greater than 2.0 on 123 I-MIBG studies had a good long-term prognosis. Future investigations of cardiac 123 I-MIBG imaging will contribute to better risk stratification of low-risk and high-risk populations, to the establishment of costeffective use of this imaging technique for the management of HF patients, and to worldwide acceptance of this imaging technique in clinical cardiology practice.

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Section: Clinical Use Of 123 I-mibg Studies Leading To Japanese Nuclementioning

confidence: 99%

Cardiac ¹²³I-MIBG Imaging for Clinical Decision Making: 22-Year Experience in Japan

Nakajima

Nakata

2015

J Nucl Med

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“…Furthermore, patients with the lowest uptake, as reflected by the heart-to-mediastinal ratio, or with the fastest washout from the heart tend have the poorest prognosis (8,9). Multiple studies suggest that 123 I-MIBG can be used as an independent predictor of HF progression and cardiac mortality (11)(12)(13).…”

Section: Hear T Failure (Hf) Is a Growing Health Problem In The Unitedmentioning

confidence: 99%

Biodistribution and Radiation Dosimetry of LMI1195: First-in-Human Study of a Novel ¹⁸F-Labeled Tracer for Imaging Myocardial Innervation

et al. 2014

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A novel 18 F-labeled ligand for the norepinephrine transporter (N-[3-bromo-4-(3-18 F-fluoro-propoxy)-benzyl]-guanidine [LMI1195]) is in clinical development for mapping cardiac nerve terminals in vivo using PET. Human safety, whole-organ biodistribution, and radiation dosimetry of LMI1195 were evaluated in a phase 1 clinical trial. Methods: Twelve healthy subjects at 3 clinical sites were injected intravenously with 150-250 MBq of LMI1195. Dynamic PET images were obtained over the heart for 10 min, followed by sequential whole-body images for approximately 5 h. Blood samples were obtained, and heart rate, electrocardiogram, and blood pressure were monitored before and during imaging. Residence times were determined from multiexponential regression of organ region-ofinterest data normalized by administered activity (AA). Radiation dose estimates were calculated using OLINDA/EXM. Myocardial, lung, liver, and blood-pool standardized uptake values were determined at different time intervals. Results: No adverse events due to LMI1195 were seen. Blood radioactivity cleared quickly, whereas myocardial uptake remained stable and uniform throughout the heart over 4 h. Liver and lung activity cleared relatively rapidly, providing favorable target-to-background ratios for cardiac imaging. The urinary bladder demonstrated the largest peak uptake (18.3% AA), followed by the liver (15.5% AA). The mean effective dose was 0.026 ± 0.0012 mSv/MBq. Approximately 1.6% AA was seen in the myocardium initially, remaining above 1.5% AA (decay-corrected) through 4 h after injection. The myocardium-to-liver ratio was approximately unity initially, increasing to more than 2 at 4 h. Conclusion: These preliminary data suggest that LMI1195 is well tolerated and yields a radiation dose comparable to that of other commonly used PET radiopharmaceuticals. The kinetics of myocardial and adjacent organ activity suggest that cardiac imaging should be possible with acceptable patient radiation dose.

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“…As outlined above, although previous studies have already reported similar relationships with 123 I-mIBG planar scintigraphic indices in HFpEF patients (18,19), the novelty of this study relates to use of 11 C-HED PET imaging, which allows for improved global and regional quantification of SNS innervation due to better spatiotemporal resolution and more quantitative image analysis than conventional 123 I-mIBG planar imaging. In this study, 11 C-HED-derived indices of cardiac sympathetic function were related to transthoracic echocardiographic indices of diastolic dysfunction as established in the 2009 recommendations of the American Society of Echocardiography (ASE) and European Association of Echocardiography (EAE) (21).…”

mentioning

confidence: 75%

“…Along these lines, decreased global 11 C-HED RI is independently predictive of worse cardiovascular prognosis and all-cause mortality in patients with HFrEF (23,24). More relevant to the topic at hand, other studies have reported that the 123 I-mIBG heart-to-mediastinal ratio and washout rate can discriminate between HF severity and can predict worse prognosis and future cardiac events in HFpEF patients (18,19).…”

mentioning

confidence: 96%

“…Other human studies have observed similar findings with respect to the relationship between SNS activity and HFpEF (15), although many of these studies are limited by the small sample sizes, and not all of these studies report on diastolic parameters. Interestingly, albeit in a limited number of studies, it has been shown that indices of sympathetic presynaptic nerve function derived from planar 123 I-mIBG scintigraphy correlate with the severity of diastolic dysfunction, exercise capacity, LV remodeling, response to therapy, and HF severity and are able to predict adverse cardiovascular events in patients with HFpEF (17)(18)(19). More specifically, the 123 I-mIBG heart-to-mediastinal ratio and 123 I-mIBG washout rate have proved to be the most useful indices in these studies.…”

mentioning

confidence: 99%

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Imaging of the Cardiac Sympathetic Nervous System Has Potential Value in the Evaluation of Patients with Heart Failure with Preserved Ejection Fraction

Boutagy

Sinusas

2017

J Nucl Med

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See the associated article on page 784.Hear t failure (HF) is a major public health problem that affects more than 5.8 million people in the United States and 23 million people worldwide (1). HF is a clinical syndrome, rather than a disease, and can occur in patients with reduced and preserved left ventricular (LV) ejection fraction. Community-based studies indicate that approximately 50% of patients with the clinical diagnosis of HF have preserved EF (HFpEF), whereas the remaining patient population presents with HF with reduced EF (HFrEF) (2,3). The values used to define preserved EF range in the literature from 40% to 55%, but current guidelines recommend an EF of more than 50% with elevated natriuretic peptide (BNP or NTproBNP) levels and relevant structural heart disease, such as left atrial enlargement or LV diastolic dysfunction, as criteria for HFpEF (4,5). Although clinical symptoms and mortality are similar among patients with HFpEF and HErEF, there are pronounced differences between these HF phenotypes in patient demographics, responses to therapy, and underlying pathophysiology of LV remodeling (6,7). Importantly, the prevalence of HFpEF relative to HFrEF is rising at a rate of 1% per year and will thus dominate as the prevalent HF phenotype over the next decade (8). Despite the rising prevalence, there are limited data to support effective therapies for HFpEF, and the role of diagnostic strategies and prognostic biomarkers remain ambiguous (4,9).Excessive cardiac sympathetic nervous system (SNS) activation is a hallmark of HF progression in patients with HFrEF (10-12). A compensatory increase in adrenergic drive causes desensitization/ downregulation of the norepinephrine transporter (or uptake-1 mechanism) on the cardiac presynaptic nerve terminal due to excess norepinephrine in the synaptic cleft. The downregulation of uptake-1 exposes the heart and postsynaptic adrenergic receptors to greater concentrations of norepinephrine, which in turn causes desensitization/downregulation of b-adrenergic receptors, cardiac remodeling, and worsening of HF and prognosis (10). Importantly, in vivo noninvasive assessment of sympathetic innervation with SPECT and PET imaging using radiolabeled analogs of norepinephrine have provided valuable prognostic information in patients with HFrEF beyond currently available biomarkers, such as BNP and LV ejection fraction. The most commonly used SPECT tracer to assess cardiac sympathetic innervation is 123 Imetaiodobenzylguanadine ( 123 I-mIBG), whereas the most commonly used PET tracer is 11 C-hydroxyephedrine ( 11 C-HED). Both of these tracers are norepinephrine radioanalogs, and their uptake primarily represents presynaptic nerve function (or density) in the heart.LV diastolic dysfunction is a characteristic finding in patients with HFpEF, and increasing severity of diastolic dysfunction is related to HF progression and a worse prognosis in these patients (13,14). Several lines of evidence suggest that dysregulated SNS activity plays an important role in the pathophysiol...

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Iodine-123-metaiodobenzylguanidine imaging can predict future cardiac events in heart failure patients with preserved ejection fraction

Abstract: (123)I-MIBG imaging provides independent prognostic information in patients with HFPEF.

Cited by 46 publications

References 32 publications

Cardiac ¹²³I-MIBG Imaging for Clinical Decision Making: 22-Year Experience in Japan

Cardiac ¹²³I-MIBG Imaging for Clinical Decision Making: 22-Year Experience in Japan

Biodistribution and Radiation Dosimetry of LMI1195: First-in-Human Study of a Novel ¹⁸F-Labeled Tracer for Imaging Myocardial Innervation

Imaging of the Cardiac Sympathetic Nervous System Has Potential Value in the Evaluation of Patients with Heart Failure with Preserved Ejection Fraction

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Iodine-123-metaiodobenzylguanidine imaging can predict future cardiac events in heart failure patients with preserved ejection fraction

Abstract: (123)I-MIBG imaging provides independent prognostic information in patients with HFPEF.

Cited by 46 publications

References 32 publications

Cardiac 123I-MIBG Imaging for Clinical Decision Making: 22-Year Experience in Japan

Cardiac 123I-MIBG Imaging for Clinical Decision Making: 22-Year Experience in Japan

Biodistribution and Radiation Dosimetry of LMI1195: First-in-Human Study of a Novel 18F-Labeled Tracer for Imaging Myocardial Innervation

Imaging of the Cardiac Sympathetic Nervous System Has Potential Value in the Evaluation of Patients with Heart Failure with Preserved Ejection Fraction

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Cardiac ¹²³I-MIBG Imaging for Clinical Decision Making: 22-Year Experience in Japan

Cardiac ¹²³I-MIBG Imaging for Clinical Decision Making: 22-Year Experience in Japan

Biodistribution and Radiation Dosimetry of LMI1195: First-in-Human Study of a Novel ¹⁸F-Labeled Tracer for Imaging Myocardial Innervation