Fasting 2-Deoxy-2-[<sup>18</sup>F]fluoro-<scp>d</scp>-glucose Positron Emission Tomography to Detect Metabolic Changes in Pulmonary Arterial Hypertension Hearts over 1 Year

Lundgrin, Erika L.; Park, Margaret M.; Sharp, Jacqueline; Tang, W.H. Wilson; Thomas, James D.; Asosingh, Kewal; Comhair, Suzy; DiFilippo, Frank P.; Neumann, Donald R.; Davis, Laura; Graham, Brian B.; Tuder, Rubin M.; Dostanic, Iva; Erzurum, Serpil C.

doi:10.1513/annalsats.201206-029oc

Cited by 92 publications

(79 citation statements)

References 42 publications

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“…The main finding of the present study, namely decrease of RVGU after the training, seems to be a positive adaptation to training compared with opposite shift of increasing glucose metabolism in the disease state, which is thought to result from increased myocardial workload due to disease (2,22,23,28,44). In a recent review regarding physiological and pathophysiological changes in RV of athletes (4), authors speculated whether nuclear imaging could provide the means to differentiate these two conditions.…”

Section: Discussionmentioning

confidence: 64%

“…Cardiac metabolism can be measured noninvasively using positron emission tomography (PET). However, RV metabolism has been studied previously using PET only in the context of diseases, such as pulmonary artery hypertension and heart failure (2,22,23,28,44). These studies indicated that RV glucose utilization is increased when the workload of the RV increases due to a disease.…”

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confidence: 99%

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Right ventricular metabolic adaptations to high-intensity interval and moderate-intensity continuous training in healthy middle-aged men

Heiskanen

Leskinen

Heinonen

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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Heiskanen MA, Leskinen T, Heinonen IH, Löyttyniemi E, Eskelinen JJ, Virtanen K, Hannukainen JC, Kalliokoski KK. Right ventricular metabolic adaptations to high-intensity interval and moderate-intensity continuous training in healthy middle-aged men. Am J Physiol Heart Circ Physiol 311: H667-H675, 2016. First published July 22, 2016; doi:10.1152/ajpheart.00399.2016Despite the recent studies on structural and functional adaptations of the right ventricle (RV) to exercise training, adaptations of its metabolism remain unknown. We investigated the effects of short-term, high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on RV glucose and fat metabolism. Twenty-eight untrained, healthy 40 -55 yr-old-men were randomized into HIIT (n ϭ 14) and MICT (n ϭ 14) groups. Subjects performed six supervised cycle ergometer training sessions within 2 wk (HIIT session: 4 -6 ϫ 30 s all-out cycling/4-min recovery; MICT session: 40 -60 min at 60% peak O 2 uptake). Primary outcomes were insulin-stimulated RV glucose uptake (RVGU) and fasted state RV free fatty acid uptake (RVFFAU) measured by positron emission tomography. Secondary outcomes were changes in RV structure and function, determined by cardiac magnetic resonance. RVGU decreased after training (Ϫ22% HIIT, Ϫ12% MICT, P ϭ 0.002 for training effect), but RVFFAU was not affected by the training (P ϭ 0.74). RV end-diastolic and endsystolic volumes, respectively, increased ϩ5 and ϩ7% for HIIT and ϩ4 and ϩ8% for MICT (P ϭ 0.002 and 0.005 for training effects, respectively), but ejection fraction mildly decreased (Ϫ2% HIIT, Ϫ4% MICT, P ϭ 0.034 for training effect). RV mass and stroke volume remained unaltered. None of the observed changes differed between the training groups (P Ͼ 0.12 for group ϫ training interaction). Only 2 wk of physical training in previously sedentary subjects induce changes in RV glucose metabolism, volumes, and ejection fraction, which precede exercise-induced hypertrophy of RV.Listen to this article's corresponding podcast at http://ajpheart.podbean. com/e/right-ventricular-metabolic-adaptations-to-exercise-training/. EXERCISE-INDUCED HYPERTROPHY of the left ventricle (LV), socalled athlete's heart, is generally associated with excellent health outcomes. Right ventricle (RV) has remained less studied, and for a long time it was considered merely as "a passive conduit" (8,14,42). Recently, RV adaptations to exercise training have gained increased research interest. While previous studies concerning the effects of training on the RV have reported balanced hypertrophy with the LV (21, 35-37), other studies have reported RV dysfunction following intense endurance exercise (3,9,10,25,26,40). A recent meta-analysis further confirmed that prolonged intense exercise leads to reduction of RV function, while LV function remains unaffected (6), underlining the need for further studies specifically on RV adaptations.As an alternative for traditional moderate-intensity continuous training (MICT), high-intensity interval training (H...

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Section: Discussionmentioning

confidence: 64%

mentioning

confidence: 99%

Right ventricular metabolic adaptations to high-intensity interval and moderate-intensity continuous training in healthy middle-aged men

Heiskanen

Leskinen

Heinonen

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…104 RV myocardial glucose uptake can be quantified by PET with the use of 18 F-2-deoxy-2-fluoro-dglucose ( 18 F-FDG) tracers, 105 and some studies have demonstrated an increase in the ratio of RV to LV glucose uptake in PAH. However, it remains unclear whether this increased ratio is explained by an increased RV glucose uptake [106][107][108] or a decreased LV uptake. 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.…”

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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“…Emerging pathophysiological concepts for the basis of the maladaptive phenotype include quantitative and qualitative differences in reactivation of the fetal gene package, RV ischemia (macro-and/or microvascular), chamber-specific activation of the adrenergic system (48), RV-specific dysregulation of key enzymes (e.g., phosphodiesterase-5 [49] and pyruvate dehydrogenase [13]), metabolic changes that favor glycolysis over glucose oxidation (50), and RV fibrosis.…”

Section: Maladaptive Rv Hypertrophymentioning

confidence: 99%

“…and hemodynamic characteristics (i.e., mean pulmonary artery pressure [mPAP] and pulmonary vascular resistance [PVR] (3)(4)(5)(6) offer an opportunity to define PH phenotypes more precisely on the basis of pathobiology, which is crucial in such a heterogeneous syndrome. This Statement gives examples of PH phenotypes, identifies gaps in our knowledge regarding phenotypes, and describes the need for research to delineate phenotypes and to detect the association of phenotypes with prognosis and/or response to management.…”

Section: Introduction and Rationalementioning

confidence: 99%

An Official American Thoracic Society Statement: Pulmonary Hypertension Phenotypes

Dweik¹,

Rounds²,

Erzurum³

et al. 2014

Am J Respir Crit Care Med

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Background: Current classification of pulmonary hypertension (PH) is based on a relatively simple combination of patient characteristics and hemodynamics. This limits customization of treatment, and lacks the clarity of a more granular identification based on individual patient phenotypes. Rapid advances in mechanistic understanding of the disease, improved imaging methods, and innovative biomarkers now provide an opportunity to define PH phenotypes on the basis of biomarkers, advanced imaging, and pathobiology. This document organizes our current understanding of PH phenotypes and identifies gaps in our knowledge.

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Fasting 2-Deoxy-2-[¹⁸F]fluoro-d-glucose Positron Emission Tomography to Detect Metabolic Changes in Pulmonary Arterial Hypertension Hearts over 1 Year

Abstract: PAH hearts have pathologic glycolytic metabolism that is quantitatively related to cardiac dysfunction over time, suggesting that metabolic imaging may be useful in therapeutic monitoring of patients.

Cited by 92 publications

References 42 publications

Right ventricular metabolic adaptations to high-intensity interval and moderate-intensity continuous training in healthy middle-aged men

Right ventricular metabolic adaptations to high-intensity interval and moderate-intensity continuous training in healthy middle-aged men

Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit

An Official American Thoracic Society Statement: Pulmonary Hypertension Phenotypes

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Fasting 2-Deoxy-2-[18F]fluoro-d-glucose Positron Emission Tomography to Detect Metabolic Changes in Pulmonary Arterial Hypertension Hearts over 1 Year

Abstract: PAH hearts have pathologic glycolytic metabolism that is quantitatively related to cardiac dysfunction over time, suggesting that metabolic imaging may be useful in therapeutic monitoring of patients.

Cited by 92 publications

References 42 publications

Right ventricular metabolic adaptations to high-intensity interval and moderate-intensity continuous training in healthy middle-aged men

Right ventricular metabolic adaptations to high-intensity interval and moderate-intensity continuous training in healthy middle-aged men

Noninvasive Imaging in the Assessment of the Cardiopulmonary Vascular Unit

An Official American Thoracic Society Statement: Pulmonary Hypertension Phenotypes

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Product

Resources

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Fasting 2-Deoxy-2-[¹⁸F]fluoro-d-glucose Positron Emission Tomography to Detect Metabolic Changes in Pulmonary Arterial Hypertension Hearts over 1 Year