Assessment for residual disease after pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension

Objectives Pulmonary endarterectomy (PEA) is recommended for eligible patients with chronic thromboembolic pulmonary hypertension (CTEPH) and is potentially curative. However, persistent/recurrent CTEPH post-PEA can occur. Here we describe symptom and diagnostic assessment rates for residual disease post-PEA and longitudinal diagnostic patterns before and after riociguat approval for persistent/recurrent CTEPH after PEA. Methods This US retrospective cohort study analysed MarketScan data (1 January 2002–30 September 2018) from patients who underwent PEA following a CTEPH/pulmonary hypertension (PH) claim with at least 730 days of continuous enrolment post-PEA. Data on pre-specified PH symptoms and the types and timings of diagnostic assessments were collected. Results Of 103 patients (pre-riociguat approval, n=55; post-riociguat approval, n=48), residual PH symptoms >3 months after PEA were reported in 89% of patients. Overall, 89% of patients underwent one or more diagnostic tests (mean 4.6 tests/patient), most commonly echocardiography (84%), with only 5% of patients undergoing right heart catheterisation (RHC). In the post- versus pre-riociguat approval subgroup, assessments were more specific for CTEPH with an approximately two-fold increase in 6-min walk distance and N-terminal prohormone of brain natriuretic protein measurements and ventilation/perfusion scans, and a four-fold increase in RHCs. Conclusions Low RHC rates suggest that many patients with PH symptoms post-PEA are not being referred for full diagnostic workup. Changes to longitudinal diagnostic patterns may indicate increased recognition of persistent/recurrent CTEPH post-PEA; however, there remains a need for greater awareness around the importance of continued follow-up for patients with residual PH symptoms post-PEA

Hypoxemia in patients with idiopathic or heritable pulmonary arterial hypertension.

The prevalence and prognostic implications of hypoxemia either at rest or during six-minute walk test (6MWT) in patients with idiopathic or heritable pulmonary arterial hypertension (IPAH or HPAH) have not been systemically studied.We sought to determine the prevalence, phenotypic and prognostic implications of hypoxemia in patients with IPAH and HPAH.Patients with IPAH or HPAH were identified from the Cleveland Clinic Pulmonary Hypertension Registry. Pulse oximetry (SpO2) at rest and during 6MWT was used to define hypoxemia at rest or during activities when measurements were lower than 90%, respectively.A total of 292 patients (age 50.6 ± 18.0 years, 73% females) with IPAH (88%) and HPAH (12%) were included. Of them, 143 (49%) had SpO2 >90% at rest and during 6MWT, 89 (31%) subjects had hypoxemia during 6MWT and 60 (20%) had hypoxemia at rest. Patients with hypoxemia had older age, greater body mass index, higher prevalence of cardiovascular risk factors, worse functional capacity and pulmonary function tests but less severe pre-capillary pulmonary hypertension. Individuals with hypoxemia either at rest or during the initial 6MWT had worse long-term survival when compared to subjects without hypoxemia, even when adjusting for a great number of potential confounders. (HR: 2.5 (95% CI: 1.54-3.98)).Hypoxemia in patients with IPAH and HPAH is associated with more comorbidities, less severe pre-capillary pulmonary hypertension and worse survival

Plasma levels of high density lipoprotein cholesterol and outcomes in chronic thromboembolic pulmonary hypertension.

BACKGROUND:High Density Lipoprotein Cholesterol (HDL-C) has various anti-inflammatory, anti-atherogenic, anti-oxidant and anti-coagulant properties that improve vascular function. The utility of HDL-C as a biomarker of severity and predictor of survival was described in patients with pulmonary arterial hypertension (PAH). No prior study has assessed the utility of HDL-C in patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH). OBJECTIVES:We aim to measure HDL-C levels in CTEPH patients and compare it to those in PAH patients and controls and determine HDL-C associations with markers of disease severity, hemodynamics and mortality in CTEPH. METHODS:We retrospectively included patients with CTEPH, identified from the Cleveland Clinic Pulmonary Hypertension Registry. All patients had right heart catheterization (RHC) and imaging studies consistent with CTEPH. We collected demographics, co-morbidities, baseline laboratory data including plasma HDL-C, six-minute walk test (6MWT), echocardiography and RHC. HDL-C levels were compared to a cohort of patients with cardiovascular risk factors and a previously published PAH cohort. RESULTS:HDL-C levels were available for 90 patients with CTEPH (age: 57.4±13.9 years; female 40%), 69 patients with PAH (age: 46.7±12.8 years; female 90%) and 254 control subjects (age: 56.7±13 years; female 48%). HDL-C levels in CTEPH patients were lower compared to controls and higher compared to PAH patients (median, IQR: CTEPH: 44, 34-57 mg/dl; PAH: 35.3, 29-39 mg/dl; Control: 49, 40-60 mg/dl; p < 0.01 for both pairwise comparisons). In CTEPH, higher HDL-C was associated with decreased prevalence of right ventricular dilation on echocardiography (p = 0.02). 57 patients with CTEPH underwent pulmonary thromboendarterectomy, higher HDL-C was associated with a larger decrement in postoperative pulmonary vascular resistance (PVR) (r = 0.37, p = 0.049). HDL-C was not associated with mortality or other markers of disease severity. CONCLUSIONS:HDL-C levels in CTEPH patients were lower compared to control subjects, but higher compared to PAH patients. Higher HDL-C in CTEPH was associated with less right ventricular dilation and greater decrement in postoperative PVR. These data suggest that HDL-C may be a useful marker of small vessel disease in CTEPH

Expression of the chemokine receptor CCR7 in prostate cancer presenting with generalized lymphadenopathy: Report of a case, review of the literature, and analysis of chemokine receptor expression

Generalized lymphadenopathy is a rare presentation of prostate cancer. We report a case and review reported cases in the literature. Because of the association of chemokine receptor expression with specific metastatic patterns, we tested for expression of chemokine receptors known to mediate migration to lymph nodes. We performed a MEDLINE (National Library of Medicine, Bethesda, MD) database search for case reports during the last 32 years using “prostate cancer,” “lymphadenopathy,” “metastatic to lymph nodes,” and “mimicking lymphoma” as keywords. Expression of the CXCR4 and CCR7 chemokine receptors was assessed by immunohistochemistry. Laser capture microdissection and reverse transcription polymerase chain reaction for CXCR4 were used to exclude nonspecific binding. Of 153 patients with prostate cancer presenting with lymphadenopathy (LAD) described in the literature, 67 (44%) presented with supraclavicular adenopathy, 29 (19%) retroperitoneal, 22 (14%) mediastinal, 15 (10%) cervical, 9 (6%) inguinal, and 2 (1%) axillary LAD. Only 9 patients presenting with generalized LAD have been previously reported. Monoclonal antibodies to CCR7 showed intense staining in the patient’s tumor epithelium. Little or no staining was observed for CXCR4. Reverse transcription polymerase chain reaction for chemokine receptors on ribonucleic acid (RNA) recovered from the patient’s sample failed to express messenger RNA for CXCR4 but did express messenger RNA for CCR1, CCR4, and CCR5. Prostate cancer may present on rare occasions with generalized adenopathy. Variable expression of chemokine receptors may be associated with organ specific patterns of metastasis. In this case, expression of CCR7 may have accounted for the unusual predilection of this patient’s prostate cancer for lymph nodes