Right Ventricular Failure in Idiopathic Pulmonary Arterial Hypertension Is Associated With Inefficient Myocardial Oxygen Utilization

Wong, Yeun Ying; Ruiter, Gerrina; Lubberink, Mark; Raijmakers, Pieter; Knaapen, Paul; Marcus, J. Tim; Boonstra, Anco; Lammertsma, Adriaan A.; Westerhof, Nico; Laarse, Willem J. van der; Vonk‐Noordegraaf, Anton

doi:10.1161/circheartfailure.111.962381

Cited by 72 publications

(91 citation statements)

References 42 publications

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“…First, the decrease in β1-adrenergic receptor density in chronic RV pressure overload could explain, in part, the decrease in responsiveness to dobutamine. Secondly, the decrease in capillary density in the presence of a hypertrophied ventricle could contribute to perfusion abnormalities and inefficient myocardial oxygen utilisation leading to impaired contractile reserve [22][23][24][25][26]. Thirdly, a metabolic shift from fatty acid to glucose oxidation has been further described in the stressed right ventricle [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Right ventricular reserve in a piglet model of chronic pulmonary hypertension

et al. 2014

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Right ventricular (RV) response to exercise or pharmacological stress is not well documented in pulmonary hypertension (PH). We investigated the relationship between RV reserve and ventricular-arterial coupling.Surgical ligation of the left pulmonary artery was performed in 13 Large White piglets (PH group), thereafter weekly embolisations of the right lower lobe were performed for 5 weeks. A control group of six piglets underwent sham procedures. Right heart catheterisation and echocardiography were performed at week 6. Pressure-volume loops were recorded before and after dobutamine infusion.Induction of experimental PH resulted in a higher mean±SD pulmonary artery pressure (34±9 versus 14±2 mmHg; p<0.01) and in a lower ventricular-arterial coupling efficiency (0.66±0.18 versus 1.24±0.17; p<0.01) compared with controls at 6 weeks. Dobutamine-induced relative changes in RV stroke volume index (SVI) and end-systolic elastance were lower in the PH group (mean±SD 47±5% versus 20±5%, p<0.01, and 81±37% versus 32±14%, p<0.01, respectively). Change in SVI was strongly associated with resting ventricular-arterial coupling (R 2 =0.74; p<0.01). RV reserve was associated with ventricular-arterial coupling in a porcine model of chronic pressure overload. @ERSpublications Dobutamine testing in right ventricular pressure overload: a potentially useful method to assess contractile reserve

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Section: Discussionmentioning

confidence: 99%

Right ventricular reserve in a piglet model of chronic pulmonary hypertension

et al. 2014

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“…To assess clinical and hemodynamic characteristics, they underwent a 6-minute walk test and right heart catheterization 2 days prior to the PET study. 8 In addition, 18 FDG scans from 7 patients who had a myocardial infarction (MI) were included as a comparison group. Pulmonary hypertension secondary to pulmonary venous congestion after MI was excluded by echocardiography in these patients.…”

Section: Patientsmentioning

confidence: 99%

“…8 Briefly, patients had to fast overnight, and 2 and 1 hours prior to 18 FDG injection they received a single oral dose of 250 mg of acipimox (Nycomed, Hoofddorp, Netherlands) and a carbohydrate-and protein-enriched meal for glucose loading. 9 All scans were performed using an ECAT EXACT HR+ scanner (Siemens/CTI, Knoxville, TN) in 3D acquisition mode.…”

Section: Data Acquisitionmentioning

confidence: 99%

Pulmonary 2‐Deoxy‐2‐[¹⁸F]‐Fluoro‐D‐Glucose Uptake is Low in Treated Patients with Idiopathic Pulmonary Arterial Hypertension

et al. 2013

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Glucose metabolism measurement using 2-deoxy-2-[ FDG uptake in idiopathic pulmonary arterial hypertension (IPAH) patients changes and, if so, to determine whether the change is related to disease severity and survival. Sixteen IPAH patients who were treated with IPAH-specific therapy and 7 patients who had a myocardial infarction (MI) without pulmonary hypertension were included. IPAH disease severity was determined using the 6-minute walk test and right heart catheterization 2 days before 18 FDG PET. Regions of interest were defined for left and right lungs, and standardized uptake values (SUVs), normalized to body weight, injected dose, and plasma glucose level, were derived. Mean SUVs for IPAH left and right lungs were 0:40 AE 0:26 and 0:44 AE 0:18 (P ¼ 0:32), respectively. In MI patients, SUVs were 0:38 AE 0:13 and 0:35 AE 0:10 (P ¼ 0:24) in left and right lungs, respectively. Total lung SUVs were similar in IPAH and MI patients (0:41 AE 0:19 vs. 0:37 AE 0:11; P ¼ 0:56). There was no correlation between SUV and IPAH disease severity parameters. In addition, lung SUV did not predict survival in IPAH patients (hazard ratio, 1.155; 95% confidence interval, 0.16-8.26; P ¼ 0:88). In conclusion, pulmonary 18 FDG uptake in treated IPAH patients is low and is not associated with disease severity and survival, thereby limiting its clinical use in patient care.

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“…After a light breakfast 2 h before the first scan, patients fasted until the end of the scanning protocol. The 15 O scan protocol has been described previously (5,11,12), and a brief description can be found in the supplemental material (available online at http://jnm.snmjournals.org). After the last 15 O PET scan and a 2-h break, the patients were repositioned on the scanner bed for a 48-min dynamic emission scan (29 frames) after an intravenous injection of 300 MBq of 11 C-acetate in 3-dimensional acquisition mode (7).…”

Section: Pet Scanning Protocolmentioning

confidence: 99%

“…Therefore, the purpose of the present study was to assess whether the RV clearance rates of 11 C-acetate correlate with RV RPP and the MVO 2 (in standard units) of the hypertrophied right ventricle in IPAH patients. The MVO 2 data have been presented previously to determine RV efficiency (5,11,12). …”

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¹¹C-Acetate Clearance as an Index of Oxygen Consumption of the Right Myocardium in Idiopathic Pulmonary Arterial Hypertension: A Validation Study Using ¹⁵O-Labeled Tracers and PET

et al. 2013

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Idiopathic pulmonary arterial hypertension (IPAH) results in increased right ventricular (RV) workload and oxygen demand. It has been shown that myocardial oxygen consumption (MVO 2 ) of the hypertrophied right ventricle of IPAH patients can be measured using PET and 15 O-labeled tracers. This method is, however, not very suitable for routine clinical practice. The purpose of the present study was to assess whether MVO 2 can also be determined in the right ventricle of IPAH patients from the clearance of 11 C-acetate, a simple method that is in use for MVO 2 measurements of the left myocardium. Methods: Seventeen of 26 IPAH patients performed the total PET study. Nine other patients were scanned only for 11 Cacetate. 15 O-H 2 O, 15 O-O 2 , and 15 O-CO scans were used to derive RV flow, oxygen extraction fraction, and blood volume, respectively, from which RV MVO 2 was calculated. The rate of clearance determined by monoexponential curve fitting (K mono ) and the efflux rate constant k 2 were derived from the 11 C-acetate scan. The RV ratepressure product was also determined by means of right heart catheterization, as an index of the RV MVO 2 , and was calculated as the product of systolic pulmonary artery pressure and heart rate. Results: Both 11 C-acetate clearance rates, K mono (R 2 5 0.41, P 5 0.006) and k 2 (R 2 5 0.45, P 5 0.003), correlated with RV MVO 2 . They also correlated with RV rate-pressure product (K mono , R 2 5 0.41, P 5 0.0005; k 2 , R 2 5 0.48, P , 0.0001). Conclusion: 11 C-acetate clearance rates correlated moderately with quantitative RV MVO 2 measurements in IPAH. Therefore, 11 C-acetate PET can be used only as an index of RV oxidative metabolism in IPAH patients. The oxygen consumption (MVO 2 ) of the normal right myocardium is less than that of the left heart as a result of a lower afterload (1). In idiopathic pulmonary arterial hypertension (IPAH), elevated pulmonary vascular resistance causes right ventricular (RV) hypertrophy and ultimately fatal RV failure. To gain insight on the pathophysiology of reduced pump function in the failing heart, quantification of MVO 2 is important. A noninvasive method using state-of-the-art PET and 15 O-labeled tracers has been validated as a means to measure MVO 2 accurately (2-4). Using this method, it was recently demonstrated that the right ventricle consumes more oxygen in patients with severe IPAH than in those with mild PAH for generating similar RV power output (5). This method is, however, extensive and time-consuming (4), requiring 3 consecutive PET scans ( 15 O-H 2 O, 15 O-CO, and 15 O-O 2 ) and an on-site cyclotron to produce the short-lived 15 O tracers (6). PET using 11 C-acetate has been proposed as a more practical method to estimate MVO 2 . With 11 C-acetate being the precursor of acetyl-CoA in the tricarboxylic acid cycle, the rate of 11 C-acetate clearance determined by monoexponential curve fitting (K mono ) is closely related to MVO 2 of the left heart (4,7-10).It is not known, however, whether 11 C-acetate can also be used to esti...

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Right Ventricular Failure in Idiopathic Pulmonary Arterial Hypertension Is Associated With Inefficient Myocardial Oxygen Utilization

Abstract: Background-In idiopathic pulmonary arterial hypertension (IPAH), increased right ventricular (RV)

Cited by 72 publications

References 42 publications

Right ventricular reserve in a piglet model of chronic pulmonary hypertension

Right ventricular reserve in a piglet model of chronic pulmonary hypertension

Pulmonary 2‐Deoxy‐2‐[¹⁸F]‐Fluoro‐D‐Glucose Uptake is Low in Treated Patients with Idiopathic Pulmonary Arterial Hypertension

¹¹C-Acetate Clearance as an Index of Oxygen Consumption of the Right Myocardium in Idiopathic Pulmonary Arterial Hypertension: A Validation Study Using ¹⁵O-Labeled Tracers and PET

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Right Ventricular Failure in Idiopathic Pulmonary Arterial Hypertension Is Associated With Inefficient Myocardial Oxygen Utilization

Abstract: Background-In idiopathic pulmonary arterial hypertension (IPAH), increased right ventricular (RV)

Cited by 72 publications

References 42 publications

Right ventricular reserve in a piglet model of chronic pulmonary hypertension

Right ventricular reserve in a piglet model of chronic pulmonary hypertension

Pulmonary 2‐Deoxy‐2‐[18F]‐Fluoro‐D‐Glucose Uptake is Low in Treated Patients with Idiopathic Pulmonary Arterial Hypertension

11C-Acetate Clearance as an Index of Oxygen Consumption of the Right Myocardium in Idiopathic Pulmonary Arterial Hypertension: A Validation Study Using 15O-Labeled Tracers and PET

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Pulmonary 2‐Deoxy‐2‐[¹⁸F]‐Fluoro‐D‐Glucose Uptake is Low in Treated Patients with Idiopathic Pulmonary Arterial Hypertension

¹¹C-Acetate Clearance as an Index of Oxygen Consumption of the Right Myocardium in Idiopathic Pulmonary Arterial Hypertension: A Validation Study Using ¹⁵O-Labeled Tracers and PET