Reduced myocardial carbon-11 hydroxyephedrine retention is associated with poor prognosis in chronic heart failure

Pietilä, Mikko; Malminiemi, Kimmo; Ukkonen, Heikki; Saraste, Markku; Någren, Kjell; Lehikoinen, Pertti; Voipio‐Pulkki, Liisa‐Maria

doi:10.1007/s002590000449

Cited by 85 publications

(41 citation statements)

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“…Likewise, a reduced density of β-adrenoceptors, as reflected by a decreased uptake of the tracers 11 C-CGP-12177 and 11 C-CGP-12388, was associated with worse survival of patients with LV failure. [123][124][125] The increased renin-angiotensin-aldosterone system activity in PAH reflects disease severity. 126 PET imaging with 11 C-KR31173 tracers could allow the quantification of cardiac angiotensin receptor density 127 and may provide important pathophysiological data in patients with PAH.…”

Section: Rv Neurohormonal Systemmentioning

confidence: 99%

Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit

et al. 2015

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899N oninvasive imaging plays a key role in both the diagnosis and management of patients with pulmonary hypertension (PH). In recent years, there have been 2 major changes in perspective of imaging in PH. The first was the realization that imaging should focus on the evaluation of not only the pulmonary pressures but also the cardiopulmonary unit ( Figure 1). 1,2The second was the emergence of multimodality imaging with a complementary role for echocardiography, magnetic resonance (MRI), computed tomography, and positron emission tomography (PET).2-7 These techniques not only help in the diagnosis of PH but also help identify factors that determine risk and prognosis and gauge therapeutic effects on right ventricular (RV) function in patients with pulmonary arterial hypertension (PAH). Although echocardiography is the mainstay in the assessment of hemodynamic and ventricular function in PH, MRI has emerged as the gold standard for quantifying volumes, function, and flow in the right side of the heart. 2-7 PET is also offering novel insights into perfusion and blood flow, metabolism, neurohormonal activation, and other molecular processes in the right side of the heart but is used mainly for research at this time. Catheterization of the right side of the heart remains the gold standard for defining PH and assessing hemodynamics both at rest and with exercise. Invasive assessment of cardiac output (CO) may, however, have limited accuracy when assumed instead of measured oxygen consumption is used to derive CO (eg, using the Fick method) or when thermodilution is used in the setting of a low-CO state. [8][9][10] This review covers RV imaging studies performed in the field of PH and discusses recent advances in echocardiography and cardiac MRI and PET imaging for detailed assessment of RV function. The review starts with a discussion of important physiological considerations and unmet needs in imaging research of the right side of the heart in PH. Computed tomography angiography, which plays an important role in evaluating chronic thromboembolic PH, is not discussed extensively in this review. Physiological ConsiderationsAlthough PH is a syndrome affecting the pulmonary vasculature, survival of patients with PH is closely related to RV function. 1,[11][12][13][14] The RV initially adapts to the increased afterload by increasing its wall thickness and contractility. These mechanisms are, however, often insufficient, and RV dysfunction eventually occurs. After the recent Fifth World Symposium on Pulmonary Hypertension, a definition of failure of the right side of the heart secondary to PH was adopted: "Right heart failure in the setting of PH can be defined as a complex clinical syndrome due to a suboptimal delivery of blood or elevated systemic venous pressure at rest or exercise as a consequence of elevated RV afterload."2 The proposed definition takes into account both the systolic and diastolic characteristics of function of the right side of the heart, as well as physiological demands such as exercise.In underst...

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Section: Rv Neurohormonal Systemmentioning

confidence: 99%

Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit

et al. 2015

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“…These findings are new. Previous studies of presynaptic function alone, using either methoxyisobutylisonitrile (MIBG) uptake and clearance or 11 C-mHED retention fraction (RF) in CHF populations have suggested that those with the fastest MIBG washout or an RF , 0.18 have a higher SCD or transplant event rate (37,38). In our population, RF (not shown) and heterogeneity of presynaptic function (by RF or PS nt ) were not predictive.…”

Section: Discussionmentioning

confidence: 47%

“…The other endpoint of ventricular arrhythmia leading to ICD discharge in 1 and death in the other are objective events, as was the 1 death from progressive CHF. Similar criteria were used by Pietila et al (38).…”

Section: Discussionmentioning

confidence: 82%

Evidence for Pre- to Postsynaptic Mismatch of the Cardiac Sympathetic Nervous System in Ischemic Congestive Heart Failure

et al. 2008

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Pre-and postsynaptic cardiac sympathetic function is altered in ischemic congestive heart failure (CHF). Whether there is a presynaptic-to-postsynaptic mismatch or whether mismatch is related to adverse cardiac events is unknown. Methods: In 13 patients with ischemic CHF and 25 aged-matched healthy volunteers, presynaptic function was measured by PET of 11 Cmeta-hydroxyephedrine ( 11 C-mHED), a norepinephrine (NE) analog. Postsynaptic function, b-adrenergic receptor (BAR) density (B9 max ), was measured by imaging 11 C-CGP12177. Myocardial blood flow (MBF) was measured by imaging 15 O-water. Each heart was analyzed both globally and regionally, excluding infarcted regions, and a mismatch score, defined as the ratio of B9 max to NE uptake (PS nt ) , was used to indicate mismatch of post-and presynaptic function. Results: Global and regional MBF was not different between CHF and healthy subjects. The global measure of PS nt was lower in CHF (0.32 6 0.34) than that in healthy subjects (0.81 6 0.33, P , 0.0001) and in all 12 regions. Global B9 max tended to be lower in CHF than that in healthy subjects (10.0 6 6.4 pmol/mL vs. 13.4 6 4.2, P 5 0.056) and in all 12 regions. The global mismatch score (B9 max :PS nt ) in CHF patients was significantly greater than that in healthy subjects (50.3 6 50.7 vs. 19.3 6 9.7, P 5 0.005) and also greater in 11 of 12 regions. After 1.5 y of follow-up, 4 individuals had an adverse outcome (CHF death, new or recurrent sudden death, or progressive CHF leading to transplantation). Three of the 4 had mismatch scores . 3 times that of the healthy subjects or the CHF patients without an adverse outcome. Conclusion: Mismatch between pre-and postsynaptic left ventricular sympathetic function is present in patients with severe CHF and may be more marked in those with adverse outcomes.

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“…On the other hand, the relation between dysfunctional SNS innervation to diastolic dysfunction may not be as important as the relationship between global 11 C-HED uptake to cardiovascular prognosis and mortality in these HFpEF patients. 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: 86%

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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Reduced myocardial carbon-11 hydroxyephedrine retention is associated with poor prognosis in chronic heart failure

Cited by 85 publications

References 4 publications

Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit

Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit

Evidence for Pre- to Postsynaptic Mismatch of the Cardiac Sympathetic Nervous System in Ischemic Congestive Heart Failure

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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