George Chandy

Usefulness of Beta-Blocker Therapy and Outcomes in Patients With Pulmonary Arterial Hypertension

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 β-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 β-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 β-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, β-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 β-blocker use in patients with PAH.

Worsening renal function and prognosis in pulmonary hypertension patients hospitalized for right heart failure.

Increased central venous pressures have been associated with the development of worsening renal function (WRF), an important marker of prognosis. We sought to determine the incidence and prognostic significance of WRF in pulmonary hypertension patients (PH) with isolated right HF. A prospective study of PH clinic patients admitted to hospital for right HF. WRF was defined as a rise in creatinine of 26 μmol/L (0.3 mg/dL) within the first 48 hours of admission. A total of 32 patients were enrolled in this study, 67% of patients had moderate-severe chronic kidney disease with an eGFR ≤ 60 mL/min and 34% (n=11) developed WRF during their admission. The mean right atrial pressure was higher in patients with WRF (19 ± 7 mm Hg vs 12 ± 6 mm Hg, P=.05). A total of 36% of patients with WRF died in hospital compared to 5% in the group that did not develop WRF (OR for hospital death 13.3 ± 16, P=.03). The combined endpoint of death or readmission at 6 months was 45% in the WRF group and 43% in the group without WRF (P=.89). Significant renal dysfunction is common in patients with PH and an acute decline in renal function is an important marker of in hospital death and short term mortality in right heart failure.

Shifts in myocardial fatty acid and glucose metabolism in pulmonary arterial hypertension: a potential mechanism for a maladaptive right ventricular response.

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.

Reversible pulmonary arterial hypertension associated with interferon-beta treatment for multiple sclerosis.

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.

Pulmonary hypertension associated with parenchymal lung disease

Pulmonary arterial hypertension (PAH) is a disorder of poor prognosis and significant mortality. Patients with concurrent parenchymal lung disease are classified as group 3 pulmonary hypertension (PH). The evaluation of this particular group of patients is complicated and the therapeutic options are limited. Diagnosis of PH must be confirmed by right heart catheterization, and the extent of lung disease should be investigated by a combination of pulmonary function testing and by thoracic high-resolution computed tomography scanning. Therapy is fraught with potential problems because the use of PAH-specific therapy potentially results in worsening hypoxemia. Currently, there are very limited data demonstrating the efficacy and safety of the use of such vasoactive medications within this population. Further randomized clinical trials (focusing on patients with PH out of proportion to the underlying parenchymal lung disease) are needed to evaluate the benefits and potential side effects of PAH-specific therapy in patients with parenchymal lung disease.

EVALUATION OF LUNG GLUCOSE UPTAKE WITH FLUORINE-18 FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY/CT IN PATIENTS WITH PULMONARY ARTERY HYPERTENSION AND PULMONARY HYPERTENSION DUE TO LEFT HEART DISEASE

Pulmonary arterial hypertension (PAH) is characterized by remodeling of the media with proliferation of smooth muscle cells in pulmonary arteries and arterioles. In contrast, pulmonary hypertension (PH) associated with left heart disease (group 2 PH) is caused by passive transmission of elevated

Pulmonary Hypertension due to Fibrosing Mediastinitis Treated Successfully With Stenting of Pulmonary Vein Stenoses

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.

EVALUATION OF PULMONARY GLUCOSE METABOLISM WITH FDG-PET/CT IN PATIENTS WITH PULMONARY ARTERY HYPERTENSION AND PULMONARY HYPERTENSION DUE TO LEFT HEART DISEASE

BACKGROUND: Pulmonary arterial hypertension (PAH; WHO group 1) is a progressive disease characterized by profound vascular remodeling of the media with proliferation of smooth muscle cells in pulmonary arteries and arterioles. In contrast, pulmonary hypertension (PH) associated with left heart disease (WHO group 2) is caused largely by passive transmission of elevated pulmonary venous pressures into the lung arterial system. Recent studies showed increased glucose metabolism in the lung parenchyma in animal models or small PAH patient cohorts, and may reflect underlying metabolic abnormalities in the remodeled pulmonary vasculature. However, there is no study to compare lung FDG uptake in patients with PAH with those with PH due to left heart disease (group 2 PH), in which the same metabolic abnormalities may not be evident. The aim of this study was to compare lung FDG uptake among three groups including PAH groups, group 2 PH and control subjects. METHOD AND RESULTS: Twenty-two patients with PAH (13 patients with idiopathic PAH and 9 patients with connective tissue disease), 8 patients with group 2 PH, as well as 14 control subjects (no lung disease, no uncontrolled diabetes or PH) were included. There were no significant differences in the mean age between cohorts (PAH 55.6 14.0 vs control 55.9 17.1 vs group 2 PH 59.4 14.5 yrs, p1⁄40.83). Mean pulmonary arterial pressure (mPAP) was assessed with right heart catheterization and was not significantly different between PAH and group 2 PH (45.0 12.1 vs 42.1 mmHg, p1⁄40.56). All subjects underwent FDG-PET/CT imaging. Regions of interest (ROIs) were drawn manually to include the lateral one-third of the lungs on the sagittal images to avoid including obvious pulmonary vessels or non-specific fibrosis. The mean standard uptake value (SUV g/cc) of FDG in each lung was obtained and average values of both lungs were calculated as mean lung FDG SUV. The correlation between mPAP and mean lung FDG SUV was also analyzed in PAH and group 2 PH. PAH patients demonstrated significantly increased mean lung FDG SUV compared with control subjects and group 2 PH (PAH: 0.79 0.27 vs control: 0.53 0.19 vs group 2 PH: 0.35 0.20, p<0.0001). The mean lung FDG SUV did not correlate with mPAP either in PAH or group 2 PH. CONCLUSION: PAH is associated with increased pulmonary FDG uptake indicating increased glucose metabolism in the lung. This may represent active inflammation and requires further study. 414 SEX AND AGE NORMALIZATION OF TYPE-B NATRIURETIC PEPTIDE FOR RISK STRATIFICATION IN ORGANIC MITRAL REGURGITATION