ABSTRACT
Aim: Previous studies have demonstrated increased glucose uptake by 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in lung parenchyma in animal models or small pulmonary arterial hypertension (PAH) cohorts. However, it is not well known whether increased FDG uptake in the lung is a unique phenomenon in PAH or whether elevated pulmonary artery pressure (PAP) induces FDG uptake. Methods and results: Nineteen patients with PAH, 8 patients with pulmonary hypertension due to left heart disease (PH-LHD), and 14 age matched control subjects were included. All PH patients underwent right heart catheterization and FDG-PET. The mean standard uptake value (SUV g/mL) of FDG in each lung was obtained and average values of both lungs were calculated as mean lung FDG SUV. The correlation between hemodynamics and mean lung FDG SUV was also analyzed in PH patients. Mean PAP (mPAP) was not significantly different between PAH and PH-LHD (45±11 vs 43±5 mmHg, p=0.51). PAH patients demonstrated significantly increased mean lung FDG SUV compared with PH-LHD and controls (PAH: 0.76±0.26 vs PH-LHD: 0.51±0.12 vs controls: 0.53±0.16, p=0.0025). The mean lung FDG SUV did not correlate with mPAP either in PAH or PH-LHD. Conclusion: PAH is associated with increased lung FDG uptake indicating increased glucose utilization in the lung. This may represent metabolic shift to glycolysis and/or active inflammation in the remodeled pulmonary vasculature, and is observed to a greater extent in PAH than in patients with PH secondary to LHD and control subjects without PH.
ABSTRACT
AIMS: We investigated the role of metabolic alterations in the development of a maladaptive right ventricular (RV) response in pulmonary arterial hypertension (PAH), which has not previously been undertaken. This study evaluated relationships between glucose and fatty acid metabolism obtained using PET with invasive pulmonary haemodynamics, RV measurements, and RV function to gain insight into the mechanism of RV maladaptation. METHODS AND RESULTS: Seventeen consecutive PAH patients (mean age 56 ± 15) who underwent right heart catheterization [mean pulmonary arterial pressure (mPAP) 43 ± 12 mmHg] had cardiac 18F-fluoro-2-deoxyglucose (FDG) and (18)F-fluoro-6-thioheptadecanoic acid (FTHA) PET imaging. RV and left ventricular (LV) FDG and FTHA uptake standard uptake values (SUVs) were measured. The SUV was corrected for the partial volume effect (SUVPVE) based on cardiac magnetic resonance imaging (CMR). Right ventricular ejection fraction (RVEF) was determined by CMR. There was a significant positive correlation between mPAP and RV/LV FDG SUVPVE (r = 0.68, P = 0.003), and the ratio of RV/LV FDG SUV : RV/LV FTHA SUV (r = 0.60, P = 0.02). RVEF was negatively correlated with RV/LV FDG SUVPVE uptake (r = -0.56, P = 0.02) and RV/LV FTHA SUVPVE (r = -0.62, P = 0.019). CONCLUSION: Increased pulmonary arterial pressures are associated with increases in the ratio of FDG/FTHA uptake in the RV. Inverse correlation between the uptake of the metabolic tracers and RV function may reflect a shift towards increased fatty acid oxidation and glycolysis associated with RV failure in maladaptive remodelling.
Subject(s)
Fatty Acids/metabolism , Fluorodeoxyglucose F18 , Glucose/metabolism , Hypertension, Pulmonary/diagnostic imaging , Positron-Emission Tomography/methods , Ventricular Dysfunction, Right/diagnostic imaging , Academic Medical Centers , Adaptation, Physiological , Adult , Aged , Cohort Studies , Female , Humans , Hypertension, Pulmonary/physiopathology , Magnetic Resonance Imaging, Cine/methods , Male , Middle Aged , Myocardial Perfusion Imaging/methods , Ontario , Prospective Studies , Pulmonary Circulation/physiology , Ventricular Dysfunction, Right/physiopathology , Ventricular Remodeling/physiologyABSTRACT
Interferon (IFN) therapy has an important role in the treatment of multiple sclerosis and chronic hepatitis C infection. A few case reports have described an association between IFN therapy and the development of irreversible pulmonary arterial hypertension (PAH), and it is currently listed as a possible drug-induced cause of PAH in the most recent classification of pulmonary hypertension. A causal link between IFN use and PAH remains to be elucidated; many reports of PAH resulting from IFN occur in individuals with some other risk factor for PAH. The authors present a case involving a patient with multiple sclerosis with no known risk factors for PAH, who developed severe PAH after exposure to IFN therapy. The patient experienced significant clinical and hemodynamic improvement, with normalization of her pulmonary pressures after the initiation of combination therapy for PAH. At 28 months after diagnosis, she remains asymptomatic with no hemodynamic evidence of PAH and has been off all PAH therapy for 10 months.
Subject(s)
Hypertension, Pulmonary/chemically induced , Immunologic Factors/adverse effects , Interferon-beta/adverse effects , Multiple Sclerosis/drug therapy , Antihypertensive Agents/therapeutic use , Drug Therapy, Combination , Female , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/drug therapy , Immunologic Factors/therapeutic use , Interferon-beta/therapeutic use , Middle Aged , Multiple Sclerosis/complications , Phenylpropionates/therapeutic use , Pyridazines/therapeutic use , Tadalafil/therapeutic useABSTRACT
We describe a patient with fibrosing mediastinitis after childhood histoplasmosis who presented with severe pulmonary hypertension secondary to pulmonary vein stenoses. Stenting of 2 stenosed pulmonary veins via a transseptal approach resulted in an immediate decrease in systolic pulmonary artery pressure from 90 to 68 mm Hg and improvement in dyspnea and cardiac index, which was sustained at 6 months. This case highlights the importance of routinely assessing the pulmonary veins during workup for pulmonary hypertension.
Subject(s)
Blood Vessel Prosthesis Implantation/methods , Hypertension, Pulmonary/etiology , Mediastinitis/complications , Pulmonary Veins/surgery , Pulmonary Veno-Occlusive Disease/complications , Sclerosis/complications , Stents , Adult , Follow-Up Studies , Humans , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/surgery , Male , Mediastinitis/diagnosis , Pulmonary Veno-Occlusive Disease/diagnosis , Pulmonary Veno-Occlusive Disease/surgery , Radiography, Thoracic , Sclerosis/diagnosis , Tomography, X-Ray ComputedABSTRACT
Pulmonary arterial hypertension (PAH) is a disorder in which pulmonary arterial remodeling and vasoconstriction progressively lead to right heart failure (HF), exercise intolerance, and high mortality. Beta-blockers have been shown to decrease mortality in left-sided HF, but their efficacy in isolated right HF associated with PAH is uncertain. Patients with PAH may have cardiac co-morbidities for which ß-blocker therapy is indicated, and the relative risk benefit of this therapy remains to be proved. This is a prospective cohort study of 94 consecutive patients with PAH divided into 2 groups with and without ß-blocker use at baseline. Rate of all-cause mortality, PAH-related hospitalization, change in 6-minute walk test, right ventricular structure and function measured by echocardiography, and hemodynamics measured by right heart catheterization were determined between subjects with and without ß-blocker use. Beta-blocker use was common (28%) in this cohort. After a median follow-up of 20 months, changes in pulmonary hemodynamics and right ventricular size and function were similar between groups. There were no statistically significant differences in adverse events including PAH-related hospitalization or all-cause mortality (p = 0.19), presence of right HF by last visit (p = 0.75), or change in last 6-minute walk distance (p = 0.92). In conclusion, ß-blocker use is not uncommon in a select group of patients with PAH and cardiac co-morbidities and did not appear to exert detrimental effects in clinical, functional, and hemodynamic outcomes. Further randomized data are needed to evaluate the potential benefits and risks of ß-blocker use in patients with PAH.
