Comparison of 18F‐FDG uptake by Right Ventricular Myocardium in Idiopathic Pulmonary Arterial Hypertension and Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Fang, Wei; Zhao, Lan; Xiong, Changming; Ni, Xin‐Hai; He, Zhaoyi; He, Jian‐Guo; Wilkins, Martin R.

doi:10.4103/2045-8932.101651

Cited by 55 publications

(35 citation statements)

References 19 publications

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“…174 However, studies in animal models suggest that the origin of the signal is in the vasculature, correlating with histology, hemodynamics, and metabolism. 85 Increased RV FDG uptake has also been described in patients [175][176][177] and rats with PAH, 103 and the signal was reduced by therapies. Because the biology of both the pulmonary vessels and the RV myocardium is important for the prognosis and treatment of patients with PAH, the ability of positron emission tomography imaging to potentially simultaneously image the metabolic shifts in both tissues (Figure 2) makes this technique attractive although its cost and availability may restrict its use as an end point in clinical trials for now.…”

Section: Metabolic Biomarkers In Pahmentioning

confidence: 98%

The Metabolic Theory of Pulmonary Arterial Hypertension

Paulin

Michelakis

2014

Circulation Research

268

243

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A lthough traditionally pulmonary arterial hypertension (PAH) has been described as a disease exclusively of the pulmonary arteries, there is now evidence that PAH involves many other organs (Figure 1). For example, the hearts (right ventricle [RV]) of patients with PAH decompensate and fail at a much faster rate compared with what one would expect extrapolating from the left ventricle, suggesting that there may be mechanisms intrinsic to the RV that promote RV failure in PAH. Even patients with idiopathic PAH, without coexistent autoimmune disorders, have circulating immune cells that are activated, producing a strong inflammatory environment and potentially contributing to the malaise and weakness that patients with PAH have. Recent evidence suggests that, perhaps, their skeletal muscles (the target organs in the metabolic syndrome) have abnormalities similar to patients with diabetes mellitus, obesity, and

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Section: Metabolic Biomarkers In Pahmentioning

confidence: 98%

The Metabolic Theory of Pulmonary Arterial Hypertension

Paulin

Michelakis

2014

Circulation Research

268

243

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“…109 Inconsistent results have been reported when it comes to the correlation between quantitative changes in glucose metabolism and changes in RV load and function. 105,[108][109][110][111][112] The differences between study results However, the RV remodeling pattern has changed (B1 and B2). RV end-diastolic volume (RVEDV) showed a progressive increase from 140 to 449 mL after 7 years of follow-up.…”

Section: Rv Metabolic Remodelingmentioning

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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“…The 6-minute walk test was performed with a standardized protocol. 21 Patients recruited from Hammersmith Hospital in London (10 with IPAH) were receiving evidence-based PAH targeted treatments (Table 1). Patients recruited from Fuwai Hospital in Beijing (8 with IPAH and 2 with connective tissue disease) were taking symptomatic relief medications (such as diuretics) at the time of the scan.…”

Section: Patient Populationmentioning

confidence: 99%

Heterogeneity in Lung ¹⁸ FDG Uptake in Pulmonary Arterial Hypertension

et al. 2013

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P ulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling characterized by dysregulated growth of pulmonary vascular cells and inflammation. [1][2][3][4] In the search for new medicines, the focus is moving toward therapies targeting these mechanisms, drawing on approved oncology interventions, such as tyrosine kinase inhibitors (eg, imatinib) 5,6 and metabolic modulators (eg, dichloroacetate), 7,8 and antiinflammatory treatments. 9 The evaluation of these antiremodeling and anti-inflammatory strategies in PAH patients poses a considerable challenge that may hamper their development. Background-Pulmonary arterial hypertension (PAH) is a disease of progressive vascular remodeling, characterizedby dysregulated growth of pulmonary vascular cells and inflammation. A prevailing view is that abnormal cellular metabolism, notably aerobic glycolysis that increases glucose demand, underlies the pathogenesis of PAH. Increased lung glucose uptake has been reported in animal models. Few data exist from patients with PAH. Methods and Results-Dynamic positron emission tomography imaging with fluorine-18-labeled 2-fluoro-2-deoxyglucose ( Clinical Perspective on p 1224Noninvasive molecular imaging with the use of positron emission tomography (PET) offers enormous potential for monitoring cellular and biochemical events in otherwise inaccessible tissue and has been used in oncology to assess antiproliferative therapeutics. Specifically, fluorine-18-labeled 2-fluoro-2-deoxyglucose ( 18 FDG), a glucose analogue, is widely used for the detection and staging of a variety of malignant lesions and can provide a quantitative assessment of response to treatment.10-13 18 FDG PET exploits the "Warburg effect," 14,15 the observation that many cancers use aerobic cytoplasmic glycolysis as opposed to mitochondrial glucose oxidation as a major energy source, a process that requires increased cellular glucose uptake.Aerobic glycolysis is also a characteristic of nonmalignant proliferating cells and is observed in human pulmonary endothelial cells isolated and cultured from idiopathic PAH (IPAH) patient lungs, 16 as well as in pulmonary arterial smooth muscle cells from rodent PAH models.17 Lung parenchymal glucose uptake, measured by 18 FDG PET, has been reported to be increased in IPAH patients compared with healthy controls. 16,18 Recently, Marsboom et al 19 showed an increased lung 18 FDG PET signal in animal PAH models that is reduced by treatment with imatinib and dichloroacetate. These data provide the foundation for further investigation of the utility of 18 FDG PET as a tool in the assessment of patients with PAH. We set out to explore 3 questions: (1) the utility of dynamic 18 FDG PET acquisition in discriminating between PAH patients and healthy controls; (2) the feasibility of 18 FDG PET in tracking the pathology of pulmonary hypertension in in vivo PAH models and their response to treatment; and (3) the impact of treatments on cellular 18 FDG uptake with the use of IPAH-derived cells in vitro. Our da...

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Comparison of 18F‐FDG uptake by Right Ventricular Myocardium in Idiopathic Pulmonary Arterial Hypertension and Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Cited by 55 publications

References 19 publications

The Metabolic Theory of Pulmonary Arterial Hypertension

The Metabolic Theory of Pulmonary Arterial Hypertension

Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit

Heterogeneity in Lung ¹⁸ FDG Uptake in Pulmonary Arterial Hypertension

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Comparison of 18F‐FDG uptake by Right Ventricular Myocardium in Idiopathic Pulmonary Arterial Hypertension and Pulmonary Arterial Hypertension Associated with Congenital Heart Disease

Cited by 55 publications

References 19 publications

The Metabolic Theory of Pulmonary Arterial Hypertension

The Metabolic Theory of Pulmonary Arterial Hypertension

Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit

Heterogeneity in Lung 18 FDG Uptake in Pulmonary Arterial Hypertension

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Heterogeneity in Lung ¹⁸ FDG Uptake in Pulmonary Arterial Hypertension